Bienvenidos a todos los que hoy nos acompañan en este seminario organizado por la IGCS. Yo soy el Dr. Clemente Arab, profesor de la Facultad de Medicina de la Universidad de Chile, bajo en el Hospital Dr. Luis T. Negruz y en el Instituto Oncológico FAL, y soy presidente saliente, o podría decirse, paspresidente de la Sociedad Chilena de Ginecología Oncológica. En esta moderación de hoy me acompaña la Dra. Magali Malka. Ella es ginecóloga-oncóloga del Hospital Edgardo Raveagliati del Perú y miembro de la Sociedad Peruana de Ginecología Oncológica. En este seminario de hoy se tocan temas y tópicos muy interesantes que parece que estaban resueltos hasta hace poco. En cirugía de cáncer de ovario avanzado, neoyuancia versus cirugía primaria, a partir de los datos del Scorpio y lo que hoy estamos esperando con el estudio TRASA. Y pareciera que el tema de la neoyuancia en cáncer de cuello hubiese estado solucionado tras el randomizado de VUCTA, pero hoy tenemos las presentaciones de neoyuancia en cáncer de cuello uterino y cómo usted hace un engranaje de aquello con el embarazo y con la cirugía de preservación reproductiva. Y por supuesto que se tocan los temas de vacunas que son también fundamentales en prevención. Pero además este seminario tiene un sentido pedagógico y es como la IGCES es capaz de llegar con la docencia a los distintos rincones del planeta. Y es por eso que con ustedes dejo al profesor Robert Coleman, presidente de la IGCES, quien les dará un saludo inicial. Buenos dias, and welcome to all the delegates attending the Latin American Conference, Selected Topics in Gynecologic Oncology. I'm honored to have the opportunity to open this Congress and welcome the almost 600 registrants. Over the past three and a half years, the IGCS along with many regional societies in Latin America have enjoyed a strategic and synergistic relationship. This started when then president of the IGCS, Roberto Angioli and our CEO, Mary Aiken, attended a meeting with society leaders here in Houston. The impact of that overwhelmingly positive meeting has been far reaching since Latin America represents a large proportion of our membership. For that, I thank you. Your participation is very much appreciated and needed. In the true spirit of collaboration, I'm so proud that IGCS could partner with all of you on this outstanding program. Thank you to all of the speakers and moderators and of course, Renee Pereja, my good friend, who has done such an amazing job as your IGCS council representative. Over the coming months, I look forward to continuing to enhance our partnership and finding additional ways to build on our momentum. IGCS has many programs and member benefits, including our early career and mentoring program, the gynecologic oncology training series and our ever popular virtual tumor boards. All of us at IGCS continue to be so excited about the opportunities that lie ahead. Please feel free to reach out to me or our CEO, Mary Aiken at any point in time. Thank you for making IGCS the international organization for gynecologic oncology. I look forward to this meeting. I hope you enjoy it. Thank you so much. Gracias a todos por ser parte del IGCS. Thank you. Muchas gracias, doctor. Gracias por sus palabras. Vamos a dar inicio al módulo de cáncer de ovario con la ponencia novedad en el tratamiento quirúrgico de cáncer de ovario a cargo del profesor Pedro Ramírez. El profesor Pedro Ramírez es ginecólogo oncólogo del Anderson Center de Texas, de la Universidad de Texas. Adelante, profesor Ramírez, con su presentación. Buenos días a todos. Muchísimas gracias, Clemente, por la introducción. Gracias de nuevo a René, mi gran amigo al IGCS por apoyar este congreso. Gracias a todos los otros ponentes por participar en este congreso. Muchísimas gracias al doctor Robert Coleman, el presidente de la sociedad. Rob, your Spanish continues to get better and better every day. So, so, so impressed. Congratulations. La primera charla va a ser un tema que, claro, todos nosotros día a día vemos pacientes con cáncer de ovario avanzado. Y es un tema que sería fácil si todas las pacientes con cáncer de ovario avanzado al ser evaluadas inicialmente se pudieran llevar a cirugía o sería fácil también si todas las pacientes pudieran proceder a un tratamiento de neoadjuvancia, pero no es así. Y por tal entonces, cada día tratamos de entender aún más cómo es que podemos definitivamente evaluar esas pacientes adecuadamente para determinar cuáles son los pacientes ideales que se someten a una cirugía primaria y cuáles son los pacientes que son ideales para un tratamiento de neoadjuvancia. Así que en el curso de estos 20, 25 minutos, quisiera compartir con ustedes algunos de los detalles de los trabajos que tenemos hasta hoy en día con la evaluación de la cirugía primaria contra la neoadjuvancia, hablando específicamente de estos estudios que pueden ver acá, pero también recalcar cuáles son los métodos que usamos hoy en día para determinar esas pacientes, esas pacientes las cuales son ideales para cirugía o ideales para un tratamiento con neoadjuvancia. Y las herramientas que usamos hoy en día, claro, todos entendemos el factor de las imágenes y la evaluación de las imágenes, pero lo que quisiera compartir acá con ustedes es algunos de los detalles que hoy estamos usando en nuestra institución con respecto a lo que se llama un reporte estructurado de radiología. Quiere decir una colaboración que tenemos con los radiólogos para que ellos nos den información más adecuada acerca de lo que nosotros como cirujanos estamos buscando en esos reportes. Claro, también tenemos el factor de la laparoscopía, una evaluación que muchas instituciones ya ha incorporado como la parte estándar del manejo de las pacientes, donde se hace una evaluación laparoscópica para determinar cuáles son las pacientes que se deben someter a una citorreducción primaria. Y en este factor hemos tenido algunos cambios recientemente en términos de cuáles son las definiciones que usamos hoy en día para considerar una paciente ideal para una cirugía primaria. Muchos en ciertas instituciones tienen cierto interés en este índice, el índice llamado Peritoneal Carcinomatosis Index. En muchas instituciones ya se usa ordinariamente. Hablaré acerca de las potenciales ventajas y desventajas de ese índice. Voy solamente a recalcar que hay un nuevo estudio en la cirugía de intervalo, pero el Dr. Rao Jain va a hablar acerca de todos los detalles de esto, porque el Dr. Rao Jain, que está en nuestro panel, es el investigador principal para ese estudio. Brevemente también hablaré de algo que casi ya se había olvidado en el manejo de las pacientes de cáncer de ovario, lo que se llamaba el Second Look Surgery. Esto por muchos años ya no se consideraba parte rutinaria, aún no se considera parte rutinaria, pero en nuestra institución tenemos varios estudios donde las pacientes se someten a un second look y depende con los resultados de ese second look, entonces así se toman decisiones acerca de cómo manejar a estas pacientes. Y finalmente hablar acerca de la publicación reciente que se hizo evaluando los indicadores de calidad de una cirugía de cáncer de ovario. Por tanto, entonces comenzamos con los estudios que ya muchos ya conocemos, y obvio no vamos a entrar en detalles de estos estudios, pero como sabemos ya hay cuatro estudios prospectivos randomizados haciendo una evaluación de la quimioterapia neoadjuvante con la cirugía primaria. Y este fue el primer estudio de Vergote que se publicó en el New England Journal of Medicine, donde por primera vez en un estudio prospectivo randomizado, pacientes, número de pacientes adecuado, se nota que no hay diferencia entre el tiempo libre de enfermedad y la sobrevivencia global cuando se hace la evaluación o la comparación de cirugía primaria contra una cirugía de intervalo. Un segundo estudio, el estudio Corus, que se publicó ya hace cinco años, es el segundo estudio que compara la misma pregunta, y en este estudio de nuevo se demuestra que no hay diferencia cuando se evalúa el tiempo libre de enfermedad y la sobrevivencia global entre estos dos grupos de pacientes, los pacientes tratados con quimioterapia neoadjuvante y la citorreducción primaria. Y como sabemos, ya se han hecho varias críticas de estos dos estudios, considerando que la tasa de citorreducción óptima no era ideal, que quizás las pacientes, particularmente las pacientes que se incluyeron en el estudio Corus, son pacientes de edad avanzada, pacientes en las cuales un gran porcentaje no se trataron con el tratamiento estándar que se considera el carboplatino y taxol. Y entonces, por tal, derivando varios estudios que, esto, varias críticas que demuestran que quizás estos estudios no son la población ideal para tomar esta evaluación, pero no por tanto, claro, tenemos ya dos estudios que demuestran que no hay diferencia. Un tercer estudio que fue publicado este año de la Sociedad del Grupo Clínico de Oncología de Japón, donde de nuevo hacen la misma evaluación, la misma pregunta, la evaluación del tratamiento neoadjuvante contra la cirugía primaria. Y de nuevo, un tercer estudio demuestra que no hay diferencia. Estudios prospectivos randomizados, tres que demuestran que no hay diferencia ninguna. Y lo que ven acá en la franja de la derecha es claro, lo que sí se ha demostrado que la sobrevivencia, si una paciente se somete a cirugía, la sobrevivencia es ideal si el residuo es R0. Y obvio, no es lo mejor cuando un residuo es más de un centímetro. Pero no obstante eso, neoadjuvancia contra citoreducción primaria no hay diferencia. Y este es el último estudio que se publica por la doctora Ana Fagotti, publicada en nuestra revista del International Journal of Gynecological Cancer. Y en este estudio, de nuevo, un estudio prospectivo randomizado, donde en este estudio incorporan el factor de la laparoscopia para hacer una evaluación de estas pacientes. Y de nuevo, un cuarto estudio demostrándonos que no hay diferencia entre la citoreducción primaria y la quimioterapia neoadjuvante. Entonces ya tenemos varios estudios, cuatro estudios que no demuestran ninguna diferencia. Y claro, estamos en anticipación de los resultados del Trust. Los dos ponentes que siguen esta presentación van a explorar este estudio y los potenciales resultados de este estudio y las implicaciones de los resultados de este estudio. Pero de nuevo, es interesante como seguimos evaluando esta misma pregunta porque en realidad consideramos que como ginecólogos, obvio nos gusta operar, pero cuando no vemos la respuesta que queremos, entonces continuamos haciendo estos estudios y claro, veremos cuáles serán los resultados del Trust y también, claro, veremos cuáles será la implicación de esos resultados en nuestra práctica. Ahora, una de las preguntas que recientemente se hace en este artículo que considero un artículo muy interesante, un artículo de Alex Melamed y su grupo, como ven, un artículo de miles de pacientes, pacientes evaluados de una base de datos, donde se hace la pregunta, si la neoadjuvancia no beneficia a las pacientes y idealmente la citoreducción primaria es el tratamiento adecuado para estas pacientes, entonces si aumenta la tasa de neoadjuvancia, deberíamos ver una disminución en la sobrevivencia. Y en este estudio, lo que ellos demuestran es que desde el 2004 hasta el 2016, en los Estados Unidos, la tasa de pacientes que se someten a neoadjuvancia continúa aumentando. Hoy por hoy, un 50% o 60% de pacientes de ovario avanzado en los Estados Unidos se tratan con quimioterapia neoadjuvante. Y lo que vemos acá es que a medida que se ha incorporado un aumento en la neoadjuvancia, no hemos visto una disminución en la sobrevivencia de esas pacientes. Entonces, por tal reafirmando que por tratar a una paciente con un tratamiento neoadjuvante, uno no está perjudicando a esa paciente. Este es un estudio que no se ha publicado todavía. Es un estudio que va a salir en la revista de Gynecologic Oncology. Y es un estudio donde hicieron lo que se llama propensity score matching. Y en ese sistema, lo que se hace es se hace una evaluación de las pacientes, las cuales tienen comparación de riesgos muy similares. Y de nuevo, a la izquierda, antes de hacer el propensity matching, lo que se había demostrado en los estudios retrospectivos es que las pacientes que se someten a una cito reducción primaria tienen mejor sobrevivencia que las pacientes que van en neoadjuvancia. De nuevo, es una evaluación retrospectiva como todos los otros estudios retrospectivos demostrando lo mismo. Pero cuando ellos hacen el propensity matching, que quiere decir que igualan los grupos de riesgo de esas pacientes, no se ve diferencia ninguna. De nuevo, entonces, reafirmando los resultados de los cuatro estudios que se han publicado hasta ahora. Ahora, lo importante es que, bueno, ya sabemos, claro, que hay este factor de que la paciente tiene que ser idealmente escogida para llevar a cirugía. Pero lo que no hemos respondido es cómo escogemos a una paciente idealmente para someterse a una cirugía. Y la radiología es sumamente importante, claro, porque todos, cuando vemos a una paciente, usualmente hoy tenemos una tomografía o una resonancia magnética o un PET, y de ahí determinamos, llevamos a esta paciente a cirugía o tomamos una biopsia y procedemos a un tratamiento neoadjuvante. Acá quería enseñarles un ejemplo de lo que se llama el reporte estructurado de radiología en nuestra institución. Y esto es un trabajo que el equipo del Anderson ha estado trabajando ya por varios meses, varios años, quizás, con los radiólogos para, en realidad, pedirle a los radiólogos, no me de un reporte donde es un resumen global. Nosotros queremos información específica de los detalles anatómicos, de dónde hay enfermedad y dónde no hay enfermedad. Y entonces acá, como ustedes ven, en la evaluación de la tomografía del pulmón, específicamente describen lo que hay en el pulmón, los nódulos torácicos, la pleura, el corazón, el pericardio. Cuando vamos a la evaluación del abdomen, acá específicamente nos dicen cuándo hay enfermedad, cuáles son las características de esa enfermedad, el hígado, el vaso, el páncreas, qué es lo que se ve en cada región del abdomen. Y así nosotros tenemos un informe muchísimo más detallado. Es prácticamente como tener el score de la laparoscopía, pero en un reporte radiólogo. Y esto considero y consideramos que nos va a añadir muchísima información y nos va a añadir un factor que nos puede ayudar a determinar si una paciente se somete a cirugía o una paciente se somete a tratamiento de neoadjuvancia. Porque con un reporte tan detallado, ya esto va a disminuir también la cantidad de pacientes que se van a llevar a una laparoscopía, porque ya sabemos la información detallada de los aspectos anatómicos del abdomen. Claro, sabemos del factor de la laparoscopía, la introducción, esto fue en el año 2005, la doctora Ana Fagotti. Y sabemos la evaluación que se hace donde se determina un score, un score de 2 o 0, basado en el nivel de involucración de enfermedad en el abdomen. Y es lo que en muchas instituciones, incluyendo nuestras instituciones, usamos rutinariamente, no en todas las pacientes, pero en selectos números de pacientes. Recientemente, en el 2015, se publica este artículo de Marco Petrillo, que era uno de los fellows de Ana Fagotti, donde ellos ya reconocen que han pasado 10 años desde su primera publicación. La cirugía de citorreducción se hace muchísima más agresiva hoy que se hacía en el 2005. Se hace citorreducción primaria muchísimo más agresiva en el abdomen superior. Entonces ellos hicieron una reevaluación de su sistema laparoscópico, porque antes de este artículo, se consideraba que si una paciente tenía un score de 8 o menos, se sometía a cirugía, o 8 o más, se sometía al tratamiento de neoadjuvancia. Ellos hicieron una evaluación de la población entera y entonces consideraron el número de pacientes que caía en cada uno de esos scores que se daban con la laparoscopía. Y lo que demostraron es que cuando se introduce este concepto de una citorreducción mucho más agresiva, una citorreducción donde se incorpora la citorreducción primaria del abdomen superior, entonces no se debe usar un score de 8, pero si no se debe usar un score de 10. Y por tal concluyen que ahora, hoy por hoy, una paciente con un score de más de 10 o igual a 10, la posibilidad de llegar a un R0 es cero. Y por tal entonces se considera que menos de 10 es lo que se debería someter para una paciente que va a una citorreducción primaria. Y lo que también demuestran es que cuando el score es menos de 10, 33% de las pacientes tampoco se pudieron llegar a un R0. Interesantemente, y podemos hablar de eso en la discusión, la mayoría de estas pacientes, este 33% donde el score era menos de 10, una de las preguntas que surge es que, bueno, si me dices que ahora el score es menos de 10, ¿por qué es que no puedo hacer una citorreducción R0? De ese 33% donde no se pudo hacer una citorreducción R0, 43% era porque tenían nódulos paraórticos positivos que la laparoscopia no podía determinar. Este concepto de la laparoscopia y la evaluación antes de la cirugía primaria, se evaluó prospectivamente en un estudio prospectivo randomizado donde las pacientes se sometían a la evaluación laparoscópica o la citorreducción primaria. Y lo que demostraron es que si se somete la paciente a una laparoscopia antes de la cirugía, la cantidad de laparotomías que no eran necesarias se disminuye. Como ven acá, 57% laparotomías que eran innecesarias, inútiles, quiere decir que entraron a la laparotomía y, obvio, dejaron más de R0 a un 27%. Entonces, lo que nos dice es que por el método de la laparoscopia quizás podemos disminuir la cantidad de pacientes que se van a someter, abrir y cerrar porque no se puede hacer esta cirugía. Ahora, una de las cosas que muchos han considerado, dice, bueno, en realidad, como cirujano, como ginecólogo, oncólogo, yo en realidad no necesito un radiólogo. Yo puedo mirar las imágenes y así determinar si basado en mi evaluación de esas imágenes, como cirujano, yo puedo proceder con una cirugía. Y este fue un estudio que se hizo acá en el MD Anderson por Nicole Fleming. Y lo que demostró es que la correlación entre la evaluación quirúrgica y la evaluación del cirujano de esa radiología es aproximadamente un 50%. Así que quiere decir que tenemos que obtener los detalles de la radiología. Y importar también el concepto de la carcinomatosis, el índice peritoneal de carcinomatosis. Este es un concepto que se usó o se usa en misothelioma, un concepto que se usa en cáncer del colon. En cáncer del ovario se ha publicado, pero no ha sido adaptado. Es un proceso complejo donde se divide el abdomen en 13 secciones, donde se hace una evaluación, un score basado en el tamaño del tumor en esas secciones del abdomen. Y por tal, se toma una decisión. Es prácticamente otro concepto de la evaluación laparoscópica. Ahora, la crítica de este concepto es que no hay un valor ideal donde se dice, más de 20 no se hace cirugía y menos de 20 se hace. Hay artículos que nos dicen menos y más de 20. Otros artículos que nos dicen menos y más de 25. Otros más de 30. No todos los pacientes que se han publicado son pacientes de estadios 3. No todos los pacientes se le ha hecho una citorreducción. Y en ningún estudio ha demostrado que este índice aporta a la sobrevivencia de estas pacientes. Tampoco esta evaluación es muy limitada por si se va a hacer por la laparoscopía. Y también tenemos que tomar en cuenta la evaluación de el tamaño del tumor. Muchas veces no se puede determinar con exactitud entre dos cirujanos o entre grupos de cirujanos. Y claro, las variaciones, como vemos acá en este caso, cómo determinamos que una sección 4 para mí es la misma sección 4 para René Pareja o una sección 4 para Rob Coleman. Y por tal, entonces, no se ha incorporado definitivamente. Esto es acá una aplicación, un score que estamos evaluando, donde se va a introducir, esto va a ser una aplicación que va a ser gratis, la vamos a distribuir. Y en esta aplicación, como ven acá, usted puede incorporar esta aplicación al teléfono y marcar estos detalles de lo que se ve durante la cirugía. Y entonces, así, esta aplicación le va a decir si usted debe proceder con una cirugía o si debe ir inmediatamente a una citurreducción, porque a medida que va evaluando los detalles de la evaluación intraperitoneal, le dice si se debe proceder a una cirugía o no. Como había dicho, la cirugía de intervalo, el doctor Raúl Jaim va a hablar de este estudio. Y es un estudio prospectivo, randomizado, comparando la laparotomía con la cirugía mínima invasiva. ¿Qué es lo que hacemos después que la paciente termina el tratamiento inicial, después que la paciente completa el tratamiento de la quimioterapia? En nuestra institución tenemos un estudio donde las pacientes que son BRCA y homologous recombination deficient negativas, basado en lo que se encuentre en la segunda cirugía, en el second look. Entonces, las pacientes, si tienen un second look positivo, entran a un estudio. Un second look negativo solamente es seguimiento. Y si tienen BRCA positivo o homologous recombination positivo, entonces, si tienen una second look positiva o si tienen una second look negativa entra en un estudio de PARP inhibitors. Y finalmente, les pido que también consideren ver y estudiar este artículo que se publicó en el International Journal, donde se habla acerca de los indicadores de calidad con respecto al manejo de las pacientes de cáncer de ovario avanzado. Juntos a considerar, finalmente sabemos que las pacientes que se someten a quimioterapia neoadjuvantes usualmente son pacientes de un perfil muy bajo, pacientes ya de edad avanzada, pacientes de las cuales malnutridas, las cuales idealmente, claro, no son las mejores candidatas para cirugía. Los estudios que han evaluado a las pacientes que son operables, quiere decir, evaluando una paciente a la cual se puede operar y no operar esa paciente y darle neoadjuvantes, son los estudios prospectivos y en esos no se ha demostrado ninguna diferencia. Reconociendo la calidad de las tomografías, tenemos variedades en términos de esa calidad. Hay variedad en términos de la calidad de los radiólogos en estos centros. Tenemos aún limitaciones por la laparoscopía, como decía anteriormente, pacientes las cuales tienen un gran grado de nódulos paraórticos en la vena cava. Usualmente esas pacientes no se pueden evaluar laparoscópicamente idealmente. El índice del peritoneo carcinomatosis no es aceptado en muchas instituciones y no se ha demostrado que por usar eso se aumenta la sobrevivencia de esas pacientes. Y claro, el factor de la experiencia del cirujano y la calidad de esos indicadores, sabremos a ver qué resultados tenemos en el estudio TRUST. Por tal entonces, la conclusión de esta presentación es que los estudios prospectivos, randomizados en este tema, no nos demuestran ninguna diferencia. La evaluación antes de la cirugía primaria debe incorporar un reporte estructurado de radiología. Consideramos que la laparoscopía también aumenta la posibilidad de determinar quiénes son los pacientes ideales. Y también vamos a incorporar el factor de usar otros métodos e incorporar estos métodos. Y invito a todos a que usen esta aplicación que vamos a diseminar ya pronto. Así que muchísimas gracias a todos. Gracias por su atención. Y gracias a la IGCES. Muchas gracias, profesor Ramírez, por su excelente y pedagógica presentación. Voy a dar dos avisos. Primero, esta ponencia, este seminario se está grabando y será subido siguientemente a las plataformas de la IGCES. Y segundo, que todas las preguntas las pueden hacer en inglés o en español por intermedio del chat y serán respondidas en la mesa de discusión. Muy bien. Buenos días a todos los participantes. Vamos a continuar con esta presentación que creo que ha tenido un muy buen comienzo. Vamos a continuar para comprender qué pasaría si el TRAS tiene un resultado positivo. Y para esta ponencia tenemos con nosotros al doctor Reitan Ribeiro. Él es cirujano-oncólogo del Hospital Erasmo Gardner de Curitiba, Brasil. Ya muy conocido por todas las sociedades de ginecología oncológica. Él es director científico de la Sociedad Brasileña de Cirugía Oncológica. Vamos, le damos pase, doctor. Bienvenido. Buenos días. Muchas gracias, Magaly. Muchas gracias a la IGCES por la invitación. Y todos los amigos, René, Pedro, Robert. Entonces, muchas gracias por estar con ustedes. Gracias, Pedro, porque ya presentaste toda mi clase. Entonces, bueno, voy a intentar hablar un poco, una forma un poco distinta acerca del tópico. Y creo que eso, bueno, es una pregunta que es más fácil de lo que parece, pero no es la respuesta que Pedro está esperando o Robert y otros. Va a ser un poco distinta. Bueno, no tengo conflictos para esta charla. Y, bueno, ¿qué es el TRAS? El TRAS es el acrónimo para hablar. El TRAS es el estudio de upfront. Entonces, cirugía primaria en el cáncer de ovario avanzado. Bueno, no solo cirugía primaria. Claro, hay que tener quimioterapia como parte importante del TRAS, que es básicamente el objetivo es ver si la cirugía de situación primaria es superior a la cirugía situadora de intervalo después de quimioterapia en términos de supervivencia general. Y esto es un objetivo muy, muy audacioso porque ahora los estudios en general trabajan con supervivencia libre de enfermedad. Y acá un estudio como ese para que cirugía sea mejor en términos de supervivencia, esto no va a ser una cosa muy fácil. Bueno, solo para que entiendan, creo que Pedro explicó muy bien de cómo todo empezó. Nosotros sabemos que es muy importante la situación como un factor prognóstico muy, el más importante para las pacientes con carcinoma epithelial de ovario. Pero también sabemos que hay un bias muy fuerte de esa lesión, que obviamente es mucho más fácil sacar toda la enfermedad de todas las pacientes con poca enfermedad que las pacientes que tienen mucho. Y así es. Entonces es un bias muy grande. Pero hace décadas que nosotros tratamos todas las pacientes con la idea de que se debe sacar todo el tumor y que si no lo está haciendo, está haciendo algo malo. Bueno, entonces estaba todo muy bien hasta que Bergo até en 2010 publicó el estudio con la de neuadjuvancia, el primer estudio como Pedro, que nos mostró una diferencia interna de supervivencia y las pacientes desde la cirugía primaria tuvieron más complicaciones. Bueno, en general nosotros que nos gusta muchísimo operar, lo que decimos nosotros, bueno, es que la cirugía no fue buena, que solo 41% de los pacientes tuvieron situaciones óptimas y menos de 20% situaciones completas. Entonces lo que decimos nosotros, no. Mila los estudios con situaciones completas en tumores avanzados, como este de anesthesia del memorio, que bueno, mismo cuando tiene un tumor, mucho tumor en el abdomen superior, si quita todo el tumor, la supervivencia de las pacientes es muy similar a las pacientes que tienen menos enfermedad. Entonces sería una de las pruebas que quitar el tumor sigue siendo el tratamiento estándar. Bien, claro que eso hay que considerar que hay un bias porque es un centro que ni siempre es una cosa reproducible, pero ese es el argumento que nosotros siempre usamos acerca de la neuadjuvancia. Bueno, entonces en 2011 el NICN incorporó las indicaciones en el tratamiento. Bueno, el NICN pasó a incluir la opción de neuadjuvancia en el tratamiento del cáncer de ovario. Bien, ¿para quién? Para los pacientes que no se puede reducir los primarios. Bueno, después como también Pedro tuvimos el CORUS, que es el otro estudio. Bueno, este es un estudio con centros de ingleses y de Nueva Zelanda. Nueva Zelanda entonces también el mismo que pasó sin una diferencia de supervivencia. Y que decimos nosotros, bueno, la tasa de resecciones óptimas no fue buena, fue cerca de 41% cuando nosotros queríamos algo entre 60-70, 50-70. Y entonces no sería bueno. Pero en verdad nosotros sabemos que son pacientes que tienen más tumor. Entonces esos son casos más difíciles. Y la tasa de situación óptima es muy cercana del estudio de Bergot. Bueno, después de eso el estudio de Japón, el mismo. Y bueno, acá antes nosotros decíamos, bueno, quizás son los cirujanos de Inglaterra. Bueno, ahora son también los cirujanos de Japón. Y ahora en los últimos años tenemos más dos estudios con resultados. El discordo que no voy a hablar porque eso no es importante porque Italia no tiene buenos cirujanos. Entonces voy a mostrar cómo el Trust Trial puede cambiar todo. O no. Bueno, ¿cuál es la idea del Trust? Bueno, muy simple. Comparar a los pacientes que van a la situación primaria contra los pacientes que hacen carbotaxol, el esquema padrón que todos nosotros usamos, y la situación de intervalo. Bueno, hasta acá nada de nuevo. ¿Qué sería la cosa nueva del Trust? Es que solo centros cualificados pueden incluir pacientes. Bueno, entonces eso es porque ustedes no tienen pacientes reclutando en el Trust. Es porque solo el cirujano bueno puede incluirlos. Bueno, el estudio empezó en 2016 y ahora ya cerró el ejecutamiento y los resultados son esperados en abril del 2023. Y si el estudio tiene un resultado positivo, entonces mira, un resultado positivo en términos de supervivencia general. Bueno, la primera cosa es que vamos a hacer una fiesta de tres días. Acá en Brasil están todos invitados porque no sé si eso va a pasar. Pero mira, lo que vamos a hacer es básicamente lo que hacemos hoy con los pacientes, seleccionando los casos y los casos en que es posible hacer la situación completa. Y los pacientes que tienen condiciones generales que no son buenas o que tienen un score muy alto de carcinomatosis con Fagot o con PCI, que a Pedro no le gusta mucho. Pero voy a hablar muy poco sobre PCI. Bueno, la vamos a referir a la neoadjuvancia. Sí, Reitan, pero ¿por qué no vamos a operar más si el estudio es positivo? Bueno, porque ya tenemos una evidencia que muy poco probablemente vamos a conseguir operar todos los pacientes y hacer cirugía muy grandes. Y aquí sí, el Scorpion trial nos enseña una cosa muy, muy importante. Creo que es la mayor contribución del estudio. Bueno, que fue publicada en el International Journal este año. Y también que tiene resultados muy contundentes sin una diferencia significativa en términos de supervivencia y también de tiempo libre de enfermedad. Pero acá hay una información muy importante que creo que, bueno, no es el objetivo primario del estudio, pero está muy claro que al principio de las curvas hay una queda muy fuerte en el grupo de la cirugía. Y acá, mira, siempre nosotros estamos diciendo, no el problema de los estudios es que los cirujanos no son buenos, no están haciendo cirugía muy largas, el tiempo cirúrgico es muy poco, las pacientes no sangran, no quitan órganos, no está buena la cirugía. Bueno, ahora que nosotros tenemos un centro italiano que vivimos nosotros, es que cuando hacemos las cirugías radicales en pacientes con mucho volumen de enfermedad, con cirugía muy grande, tenemos muchas complicaciones. Entonces, cuando vemos los resultados, mira, más del 50% de los pacientes que hacen cirugía primaria tienen complicaciones graves. Eso no son complicaciones de brandas, son complicaciones graves. Bueno, y 8.3% de mortalidad cirúrgica. Entonces, casi uno en cada 10 pacientes va a morir de la cirugía. Claro que, ¿cómo hacer para compensarlo? Bueno, pocos tratamientos tienen una diferencia de 10% en términos de supervivencia y las pacientes están muriendo muy temprano en la curva. Esto no se puede recuperar. Bueno, acá cuando comparamos con las pacientes en la neoadjuvancia, no van a morir casi nadie. Bueno, otra cosa que es, cuando se ve la complejidad de cirugía, se queda muy obvio que la mayoría de los pacientes en el brazo de la cirugía tuvieron cirugías muy complejas, muy largas, con sangrado, con resecciones múltiplas. Y procedimientos, por ejemplo, del abdomen superior, casi todos, 100%. Claro, por supuesto, son pacientes que tienen enfermedad 3D o más, entonces hay que mantener la enfermedad en el abdomen superior. Mira, claro, acá, bueno, Italia solo tiene cuatro copas del mundo, entonces solo quedó Brasil como un time bueno para hacer cirugía, porque el resto del mundo no sabe hacerlo. Entonces, claro que la culpa no es de los italianos, el centro que hizo los procedimientos de referencia mundial son muchísimo especializados, haciendo cirugía muy buena, mucha ciencia envolvida y todo. Entonces no hay cómo decir ahora que el problema son los cirujanos o los centros. Sí, pero ahora el punto es que, bueno, solo es un centro. Y que eso no va a funcionar en nosotros. Claro que no, por supuesto, intentamos todas las formas y el resultado es el mismo. Pero una información que creo que es muy importante acerca del centro de Italia, que es probablemente uno de los mejores del mundo, es, claro, la definición, cómo seleccionan los pacientes que van a cirugía o no. Y como Pedro también, esta es la publicación de Petrillo, la revisión del score de Fagotti. Y bueno, usan un score para seleccionar a los pacientes, hasta 10, hasta 8 se puede reducirlos. El problema es que cuando vemos los parámetros, lo mental que es la carcinomatosis espiritual, el compromiso del diafragma, del intestino, bueno, hay que ser mucha enfermedad, no es poca. Por ejemplo, si hay compromiso del recto, el recto no es un compromiso significativo. Bueno, si hay compromiso del diafragma, hay que ser mucho. Entonces, mira, hay que ser doenza confluente o implantes más grandes, como 5 o 6 centímetros. Y así, los implantes pequeños no puntúan en la clasificación. Entonces, mira, para tener un paciente 8, usted necesita una enfermedad muchísimo grave, muy intensa. En general, son cirugías muy largas. Bueno, si nosotros vamos a incluir estos pacientes, una cosa que está faltando, la información que debería, que es una cosa que tenemos que ver, es cuál es la morbilidad y la mortalidad por cada score. Creo que eso es muy importante, porque vamos a tener que trazar una línea y separar dónde está el punto en que la mortalidad y la morbilidad es aceptable. ¿Por qué? Porque la paciente que muere, bueno, eso va a obviamente impactar la curva de supervivencia, pero también las pacientes que tienen complicaciones graves, bueno, no van a hacer quimioterapia. Y como ustedes saben, si hago una cirugía de cáncer de ovario y la paciente se queda con complicaciones por 3 meses y empieza la quimioterapia después de 4 meses, ya está con enfermedad. Entonces se perdió como 4 meses del tratamiento, solo eso que pasó. Eso es una cosa que nosotros quisimos ver, dónde está la línea. Yo no sé, acá yo puse en el 4, que eso es una cosa sin una evidencia, pero que me parece que es probablemente el punto en que las cosas van a cambiar significativamente. Bueno, y ahora, Reita, mira, pero usted me dice que va a pasar si el estudio es positivo. Bueno, después de la fiesta, el NCCN va a cambiar la definición y creo que no va a ser el de booking, va a ser un punto, nosotros vamos a necesitar un punto. No sé si el PAGUAT va a ser 4, 6, o si el PSI, que a Pedro no le gusta mucho, pero a nosotros que hacemos cirugía oncológica, nos gusta muchísimo, porque es mucho más claro acerca de la información. No va a cambiar el tratamiento, la paciente, eso no. De facto, no hay un impacto en la supervivencia, pero es solo una forma de comunicación entre nosotros. Al final, probablemente los cirujanos con sus experiencias y cada centro van a necesitar definir cuál es el punto en que se puede hacerlo. Y acá nosotros también hacemos, ahora estamos empezando a hacer resonancia con difusión para determinar las secciones que van a ser necesarias. Pero seguimos haciendo la paroscopía porque esto es la forma más precisa de seleccionar a los pacientes. Bueno, entonces eso va a cambiar, que creo que los pacientes que van a cirugía primaria van a tener menos enfermedad y un PCI que sea más bajo, que sea 20, es un PCI con habitualmente una cirugía que es más tranquila. Bueno, y los pacientes que antes decimos que pacientes sin condiciones de cirugía, creo que eso también va a cambiar. La definición sería una cosa más, si hay un riesgo de complicaciones que van a causar un retraso de la quimioterapia. Al final es eso que es muy importante. Los pacientes pueden hacer cirugía. Si no tienen complicaciones, los pacientes van muy bien. Pero si tienen complicaciones, entonces la cirugía no va a ayudar a los pacientes. Al contrario, va a ser una causa de mayor mortalidad y morbididad. Bueno, ¿y tiene evidencia acerca de eso? No, no tenemos una evidencia. Pero mira, acá es muy importante cuando intentamos decir lo que va a pasar con las cosas. Es que nosotros no seguimos solo la evidencia. Eso siempre pasó. Y probablemente son muy pocos los cirujanos que solo hacen cosas baseadas en la evidencia. Y mira como eso es importante. Acá no estamos hablando del tratamiento después de estos pacientes que van a la neoadvance. Ese es el NCCM de este año. Y mira, no hay citación a HIPEC. Bueno, hay un estudio fase 3, el único, que es un sitio de reducción de intervalo. Y esta no hay duda que es la mejor evidencia. Bueno, pero hay una citación solo muy pequeña en la parte inferior como eso es una cosa opcional. Pero en verdad, mira, es el único estudio randomizado. Entonces es la mejor evidencia. Y nosotros sabemos como eso. Ni siempre las personas aceptan. Bueno, entonces hay que considerar. Y que las personas van a seguir haciendo cosas que están muy raizadas y que ni siempre son la mejor evidencia. Solo un poquito, filla. Disculpa. Bueno, voy a finalizar y voy a dar un poco, salir un segundito. Bueno, y si el estudio 3 tiene un resultado negativo, bueno, entonces vamos a hacer lo que hacemos bien. Vamos a tirar los tomates y procurar problemas en el estudio, que es la cosa que hacemos mejor. Bien, muchas gracias. Y me gustaría invitarlos también para ver online el maratón de cirugía que va a ser en la próxima semana. Y muchas gracias. Sí, Reytan, you agree with me. Muchas gracias, Dr. Reytan. Suele suceder cuando uno tiene hijos, pues, ¿no? Son cosas que pasan, no hay ningún problema. Magali. Si tenemos problemas, sí, René, dime. I would like to say that we are having some problems with English translation, but we are doing our best to solve it as soon as possible, okay? Thank you. Sí, se están solucionando los problemas de traducción. Pueden enviar sus preguntas, de todas maneras, al chat de preguntas y respuestas, por favor. Por ahí las estamos recibiendo. Y, bueno, continuamos. Le doy el pase, Dr. Arac. Sí. Ahora se va a presentar la contrapartida. ¿Qué pasa si el estudio 3 tiene un resultado negativo? La ponencia está a cargo del Dr. Alejandro Raujaín. El Dr. Raujaín es ginecólogo colo, trabaja en el MDV Cancer Center de Houston, Texas. Adelante, Alejandro, por favor, con tu presentación. Good morning, thank you very much to the IUCS for the opportunity to present today. It is a bit of a complicated exercise to try to discuss a study that has not been published and to try to predict what will happen in the future, but I think it is an exercise that is worth starting to plan the future. I am not going to discuss with Reitan the number of World Cups because in Mexico we did not even pass the round of 16. So it is something that is impossible for me to compete with Brazil or Italy in soccer. I have nothing to discuss. As Reitan and Pedro mentioned, there have been many retrospective studies that have shown that primary cytoreduction increases survival in those patients with advanced ovarian cancer. And this has been published one after another after other retrospective studies. I think many have seen this figure of a study published by Bristol and NSG almost 20 years ago. And this has been perpetuated as Reitan and Pedro discussed earlier. This is a study that we published about 4 or 5 years ago, in which we used the National Cancer Database database in the United States, in which we took all those patients in the database that had advanced ovarian cancer studies, and we compared neoadjuvant therapy with primary surgery. And like all retrospective studies, we showed that those patients who had primary surgery had better survival than those patients who had neoadjuvant therapy. So everything was going very well. What is very important, as Reitan mentioned earlier, is that all retrospective studies have a very important bias of selection. So what is important in this study is not the fact that we show that apparently primary surgery has better survival, but the fact that when we take some variables that are not included in the database, for example, the number of diseases, how serious is the disease that the patient has, the performance status, if we had that information available and included it in the statistical analysis, what would happen? So, for example, in this study, what we did is, by means of statistical formulas, what would happen if the prevalence of a worse performance status in patients who received neoadjuvant therapy is compared to those who had primary therapy? And as we know, those patients who have a worse performance status have a worse survival than those who have a zero performance status. So if we had that information available and we changed the prevalence, and we said that performance status is much more prevalent in patients who receive neoadjuvant therapy than those who have primary surgery, what we see is that that study that seemed that patients who had primary surgery had better survival, that effect disappears. And in fact, when we make the prevalence of performance status of 1 or 2 be 90% in patients who receive neoadjuvant therapy, compared to 40% in primary surgery, in fact, it seems that patients who receive neoadjuvant therapy have better survival. Obviously, these numbers are hypothetical, but the importance of this exercise and this publication is that when you take into account what we call unmeasured confounders, variables that are not available in the databases and you include them in the analysis, these effects of patients who have better survival in primary surgery disappear. So it is very likely that many of those previous retrospective studies would have included these analysis of unmeasured confounders. Many of those studies would have been negative. So, in addition, as Pedro and Raytan mentioned earlier, there are four randomized studies that have shown that those patients who receive neoadjuvant therapy have the same survival rate as those patients who receive primary surgery. These are the first studies, the study of Evergoat and the CORUS trial. This is probably the most important slide in the entire presentation. These are the four studies, and as you can see in the columns to the right, all the studies are very consistent in showing that those patients who receive neoadjuvant therapy have the same survival rate as those patients who receive primary surgery. Obviously, we all know that there have been many criticisms about the ERTC, the CORUS, about the type of surgery, the time of surgery, if it was an optimal resuscitation, if it was not an optimal resuscitation, the type of chemotherapy they received. But the important thing is that everything is very consistent. The other part that I want to draw your attention to is the SCORPION trial. And as Raytan mentioned earlier, the SCORPION is very important for two reasons that I think are fundamental. One is that in the SCORPION trial, patients with a score of 8 to 12 were included. Those patients are patients who had a super, super high volume of disease. They are not patients who only have peritoneal disease or a little bit of disease in the rectum. They are patients who really have peritoneal carcinoma, liver disease, liver disease, stomach disease, or mental caking. In other words, patients with really advanced disease. The other important part of the SCORPION trial is when it comes to optimal resuscitation rates and R0 resection. These are really rates that you would expect in any center that has a very high volume. That is, they are patients who really received ultra-radical surgeries with optimal surgery rates that would be expected in any high-performance center in the United States. Probably, to be honest, higher than in centers like Memorial Sloan, MD Anderson. In other words, again, super, super radical surgeries. And when you take that study, there really was no difference in survival between those patients who had primary surgery and adjuvant therapy. These are the graphs of Keppel-Meyer, which I think are important to show again. As Rayton mentioned, it is very important in all these adjuvant therapy studies to see the first part of the curve. And that is the mortality that happens in the first 30 to 60 days of surgery that is seen in all the studies that compare primary surgery with adjuvant therapy. There is always that dip in mortality in those who feel they receive primary surgery. But again, I think the SCORPION trial has received a lot of criticism because it is a superiority analysis, because the number of patients may not be so high. But the curves, despite all those criticisms, the truth is that the curves do not separate at all. And it can give you a very good idea, in my opinion, of what we can expect from the TRUST trial. And based on this information, I suppose that the TRUST trial will be negative. But hey, what is happening in the United States? And I want to put an idea that if the TRUST trial were to be positive, what would we expect in an analysis across the United States or in a population analysis? So what we have seen in the United States is that the rate of adjuvant therapy has increased over the years and the rate of primary reduction has decreased over the years. And this is a study that we published in BMJ a couple of years ago. And what we tried to do is, what happens at the United States level with the adoption of adjuvant therapy? If the adoption of adjuvant therapy really changes survival in the United States? What we did was a quasi-experimental study, which means that if you do this quasi-experimental study well, it is very similar to a randomized study. You can do causal inference analysis, which can give you results very similar to a randomized study. So what we did in this study is that we divided the United States into different areas. And what we saw is that there were two areas in the United States in particular in which there was a significant increase in adjuvant therapy between 2010 and 2011 and from 2011 to 2012. The absolute number does not matter, what matters is the change or the delta between one year and the other year. And as I said, there are two areas in particular in England and in the southeastern part of the United States where there was a dramatic increase in the use of adjuvant therapy. We also found three areas in which there was almost no increase or very little increase in the use of adjuvant therapy, or in fact there was a decrease in the use of adjuvant therapy and that serve as controls. That is, we want to compare those areas in which in those particular years there was a dramatic increase in adjuvant therapy with those areas in which it was established or decreased in the use of adjuvant therapy. And that serves as cases and controls or it is a population analysis. This is to show how in these two areas in the United States and just in that year that we are seeing between 2011 and 2012, there was a significant increase of more than 40% in the use of adjuvant therapy compared to the other areas that will serve as controls. And this is the most important slide. What you would expect in this line, in this graph you can see the mortality per year per person, what happens between 2011 and 2012, what happens in the places that are of interest, which are the cases. As you can see, the mortality was decreasing, as expected, the temporal analysis is decreasing, but just in the year between 2011 and 2012, this, you would expect that the point would be here for the secular trends, but it really decreased even more due to the use of adjuvant therapy. And when you compare that in the areas that are controls, there really was no decrease in mortality, and maybe it increased a little. And you can transfer that to the curves of Kaplan-Meier, what happens in 2011 and what happens in 2012. And as you can see, in the year in which there was more use of adjuvant therapy, patients in these areas had a better survival in those compared to 2011 when there was not so much use of adjuvant therapy. And what is even more interesting is that in those places that are the controls, in 2011 and 2012, there was not at all any difference in mortality among the groups. What you can say with this natural experiment that happens in the United States is that the use of adjuvant therapy, again, not what happens in an institution, but what happens in population analysis, in fact, instead of increasing mortality, what seems to be is that the use of adjuvant therapy decreased mortality in these areas. So, what are the possible mechanisms of this study? One is that, as we see constantly, in those areas that received adjuvant therapy more frequently, a decrease in mortality at 30 to 90 days. The other part that is important that we do not forget is that if you have a patient who receives primary surgery and has complications, it is a patient that you may have to dilate, give chemotherapy, or there are a number of frequent patients who, due to so many complications they have, will never receive chemotherapy. So, these are the possible mechanisms. What is important in this study is that it does not tell us what is happening in a center like MD Anderson, Memorial Sloan, Duke, it is telling us what is happening in population analysis. This means that if we adopt Trust Trial throughout the United States or throughout the country, what we would probably see is that mortality would possibly increase instead of decrease. This is another separate study that Pedro also mentioned, which was done by my colleague and friend Alex Melamed, in which what he did was to see what has happened with the increase of adjuvant therapy in the United States. This is also a study of the National Cancer Database, and what you can see is that as adjuvant therapy has increased over time in the United States, survival has also increased. Obviously, there are many other things that have made survival increase over the years, better chemotherapies, better access to health, better intensive therapies, better support, more knowledge, but what is important is that this dramatic increase in adjuvant therapy has not caused this survival to stabilize or decrease. This gives us an idea that in population analysis, the use of adjuvant therapy has benefited instead of causing negative effects in the population. So, what are my concerns with Trust Trial? I think it is an important study, but what worries me about Trust Trial is if we find it positive, and how people will interpret it. This is a study that was published in Guidon recently, in which researchers are looking at what survival is one year and three years in different countries, in patients with advanced liver cancer. And what is important is that, as we all expect, survival in liver cancer is really different in different countries, and it is probably different in different institutions. What I mean by this in the Trust Trial is that one of the main problems of the Trust Trial is that it will not be a study that will be able to be generalized to all institutions. The researchers, the patients that are being included in the Trust Trial are in centers that have high specialization, with surgeons who do a high volume, but in addition to all this, they are centers that have the ability that if a patient has a complication, to be able to rescue them and put them at an optimal level so that they receive the same type of chemotherapy. They have access to other specialties such as vascular surgeons, oncologists, pancreas liver surgeons, and they can do all these radical surgeries and try to reduce complications. And the point of all this is that if the Trust Trial becomes positive, it will not be able to be generalized to all institutions around the world. The other important part of primary surgery, if the Trust Trial becomes positive, it is very important, as Reitan mentioned, to see what the complications are. This is a somewhat old table, but what is important is that doing primary surgery really has a very high risk of leading to severe complications and that it can dilate the chemotherapy, and we also saw that with Reitan in the Scorpion Trial. And this is another important slide. In this study, what we were trying to do is try to see if there is an optimal point in the patient's age as to whether it is more worthwhile to do primary surgery. So, in blue are the patients who received primary surgery and in yellow are the patients who received adjuvant therapy, and what we are seeing is mortality in the first three months after surgery. And as you can see, around 55 years, mortality in those patients who received primary surgery dramatically increases in those patients who are 55 or 60 years old, and when you see patients who are 70 years old, mortality at 90 days is almost 10%, and in those patients who are 80 years old, mortality at 90 days is 20%, and it is significantly higher in those patients who received primary surgery compared to those who received adjuvant therapy. Obviously, age is a proxy, and we have patients who are 80 years old who are super healthy, and we have patients who are 50 years old who have a lot of comorbidities, but at least it gives you an idea of how age affects this decision in terms of mortality in the first 90 days after surgery. I think this study is super important to take into account. On the other hand, if the Trust Trial were positive, I think a lot of people will try to... There has been an argument for many years to try to decentralize ovarian cancer treatment, and how and what would happen if this were to happen? This is a study that was published recently, this is a study in Sweden, in which they tried to see what happens before centralizing ovarian cancer treatment, before 2011 and after 2011, and what they showed is that after they adopted this centralization of ovarian cancer, the survival seems to have increased, suggesting that centralizing ovarian cancer treatment is a good idea. And the other part is what they saw in this, they tried to see if the patient received complete sedation or if they had residual disease, and it is quite consistent that those patients who received care after this centralization of ovarian cancer treatment had better survival. The problem with this study is that this is a study that was done in a country with little volume, with few inhabitants, and how this would translate in other countries with much more volume, like the United States, it is difficult to know, and what would be the logistics of centralizing ovarian cancer treatment, I think it is much more complicated and it is something that is not solved in this study, and in my opinion I think it is something that would be very complicated, at least in the United States, to be able to achieve. There are many interests that would compete, where would patients with ovarian cancer go. The other part that is very important to take into account for the TRUST trial is that the TRUST trial was done before the PARP individuals were included, and as all of you know, the PARP individuals have radically changed the treatment in the first line in patients with ovarian cancer. These are the four studies that have been published in the first line with ovarian cancer, SOLO1, PRIMA, PAOLA, and VILIA, and all of them have consistently shown, in particular, that in those patients who have a mutation in BRCA, or have a deficiency in HRV, those patients who received a PARP unit have a significantly longer survival than those patients who did not receive the PARP, and this is also very consistent in this population. So it is difficult to know what is going on and how TRUST changes all of this, and if the PARP individuals, at some point, if there is a difference in PARP, in TRUST trial, if the PARP individuals will be able to reduce the difference today, and today we are seeing how the PARPs are being included more and more in the first line, there are studies that are being included before chemotherapy, so I think it is very interesting what is going to happen with the PARP individuals. Today it is difficult to think that they are everywhere in the world, but eventually they are chemotherapies that are going to be available, in my opinion, everywhere in the world, and the costs are going to reduce significantly so that they can be used again in all countries. So how do I see the future of ovarian cancer treatment? As I mentioned before, I believe that the rates of therapy will continue to increase despite the TRUST trial, and I believe that the most important thing and what is not yet, the most critical question, in my opinion, in the management of patients with ovarian cancer in the first line, is to try to decide which patients will benefit from primary surgery or non-adjuvant therapy. I believe that more and more places will incorporate laparoscopy or phagotic score for this. This is the study that was conducted in the Netherlands, it is a randomized study of minimally invasive surgery, and those patients who received minimally invasive surgery with a modified score had less risk of having a futile laparotomy than those patients who received primary surgery. This is a study that we did at MD Anderson, which is also consistent, in which we saw that those patients who had a laparoscopy risk of having an optimal laparotomy significantly, it is very, very high. And as we have seen the other part that has increased non-adjuvant therapy, what we have also seen is that it has increased the use of minimally invasive surgery for ovarian cancer after non-adjuvant therapy. Today, around 20-25% of patients in the United States who receive non-adjuvant therapy have a reduction of interval by minimally invasive surgery. There are several studies that have shown that this approach is feasible. This is the first study published by Aleti in which they took 30 patients. What is important in this study is that those patients who had minimally invasive surgery in 96% of them had a residual disease of R0 and practically all of them had an optimal reduction of less than 1 cm, showing that this approach is feasible. We are in the 3 minutes, Alejandro, please. This is a study that we published a couple of years ago in which in population analysis in the United States, we showed that doing this minimally invasive approach in patients with interval surgery does not change the survival compared to those who had open surgery. And again, very consistent studies that this residual disease was very similar to laparotomy and laparoscopy. And this is the International Trial by Anna Fagotti which also again shows that this approach is feasible. Obviously in these studies there is a selection bias that is quite important and that is why we are doing this randomized study, the LANS trial, comparing those patients who receive therapy in the adjuvant comparing open surgery with minimally invasive surgery. This study is open and we are starting to do the enrollment and those who are interested in participating please send us an email. The primary goal of the study is to compare minimally invasive surgery with open surgery in terms of disease pre-survival and these are the secondary objectives. What is important in this study is the inclusion criteria. These are patients with advanced high-degree cancer such as 3C or 4 who receive therapy in the adjuvant and what is super important is that they have to have normalization of the CA125 after 3 or 4 cycles, and that based on the imaging studies, the surgeon thinks that he can do the surgery by means of paroscopy or by robot. This is the study scheme, it is very simple. The patients are randomized after the inclusion criteria are met, and they are randomized to laparotomy or minimally invasive surgery, either laparoscopy or laparotomy, and if they receive more chemotherapy, then we follow them for 5 more years. These are the criteria to select the centers. What is important is that we are looking for centers that have experience in randomized studies, and that can give chemotherapy, and that have experience doing minimally invasive surgery. And the study is separated into two phases. The first phase is a pilot study, which are the first 100 patients. We are now enrolling patients in this pilot part, and the objective of the pilot part is to make sure that the study is feasible to do. So we have to make sure that we can enroll enough patients, that the crossover means that it is less than 25%, that the conversion rate of minimally invasive surgery to laparotomy is less than 25%, and that there is not a very big difference between the number of ER0 receptions between the two groups. We are looking to include 550 patients in the study for this non-inferiority study. And these are the institutions that are participating in the pilot part, and I want to thank all of them who have helped us include patients. And since the pilot study is open, the objective is to include up to 30 centers around the world to reach 580 patients. So if you are interested in participating, please send an email to me or Pedro or René to be able to participate. And I want to thank all of our collaborators, Ana Fagori, who is the co-PI in this study, Pedro, Rob and René, who have been great mentors in this study, and Alex Melamed, who has been my collaborator for many years. Thank you very much. Muchas gracias, Alejandro, por la completa presentación. A continuación iniciaremos la sesión de preguntas y respuestas. Hemos intentado seleccionar algunas que de alguna forma convocan las distintas inquietudes. La primera, que me gustaría dejársela al profesor Ramírez, ¿se deben hacer cito reducciones masivas durante la pandemia o es mejor indicar quimioterapia neoayuante? Nosotros en nuestra institución, cuando comenzó la pandemia, obvio, en los Estados Unidos, en una manera ya más avanzada, más fuerte, que fue aproximadamente en marzo, tomamos una decisión como institución de no proceder con cito reducciones primarias y todas las pacientes se sometían a un tratamiento de quimioterapia neoayuante. Ahora, hoy en día, ya tenemos un proceso en el cual todas las pacientes que se llevan a cirugía, cualquier tipo de cirugía, se le hace un examen y antes de la cirugía, obvio, tiene que tener un examen confirmado negativo y, por tal, entonces, el manejo es igual que antes de la pandemia. Muy bien. Esta pregunta también es para el doctor Ramírez. Bueno, como en toda Latinoamérica, hemos tenido el problema también de la disposición de sala de hospitalizaciones, sala de operaciones, afluencia de pacientes y, bueno, lo más lamentable, lo del COVID-19. Entonces, hemos también tenido esas opciones de dar primero quimioterapia o tratar de reservar a esas pacientes que no pueden operarse para la quimioterapia neoayuante. Entonces, hay una pregunta que nos envían y dice, ¿vale la pena llevar a cabo una cirugía cito reductora en pacientes que han recibido ya seis cursos de quimioterapia? Efectivamente, por COVID-19 y que las imágenes nos demuestran de que hay respuesta completa. Esa es la pregunta. Sí, es una pregunta buenísima y, en realidad, es una pregunta que hemos tenido mucho antes que existía la pandemia. El concepto del tiempo ideal a hacer una cito reducción de intervalo después de tres o cuatro ciclos o después de seis ciclos. En el International Journal of Gynecologic Cancer se acaba de publicar un artículo del Memorial Sloan-Kettering donde hicieron una evaluación de las pacientes que recibían cuatro ciclos de quimioterapia neoayuante en comparación a más de cuatro ciclos de quimioterapia neoayuante. Y lo que se demostró fue que la sobrevivencia de las pacientes que tenían más de cuatro ciclos tenían un factor de sobrevivencia peor que las que se le daba hasta cuatro ciclos. Ahora, es importante recalcar que esos estudios son estudios retrospectivos donde no se hizo una evaluación de las pacientes que llegan a cuatro con una respuesta perfecta, una respuesta ideal, y la decisión se hace de seguir a seis o seguir a siete. Típicamente, una paciente que llega a cuatro y la decisión es, bueno, vamos a seguir a cinco o vamos a seguir a seis, es porque esa paciente no está respondiendo muy bien. Son las pacientes típicas que hacemos una evaluación de las imágenes y decimos, bueno, en realidad es como una respuesta estable, quizás un poquitico mejor, pero todavía tiene metástasis en el mesenterio, tiene metástasis en los ganglios, tiene metástasis en la cerosa, y entonces por eso vamos a seguir a seis. Entonces, yo creo que hay que tener muchísimo cuidado cómo interpretamos estos artículos que nos dicen que hacer seis es peor que cuatro, porque no se usan pacientes en las cuales después de cuatro le está yendo perfecto y hubieran podido ir a cirugía y entonces por tal hacer una comparación así. ¿Qué por tal entonces? Bueno, lo que hacemos en práctica, una paciente que o por la pandemia o porque no ha respondido muy bien, después de seis ciclos, obvio, si una paciente tiene una respuesta completa, el estándar es hacer una cirugía, aunque claro, ya muchas pacientes, como Alejandro dijo, cada cirugía tiene su morbilidad. Teniendo una respuesta correcta, una respuesta completa, lo más probable es que la morbilidad va a ser menos de una cirugía de intervalo, pero una paciente que tiene 85 años, si le han dado seis ciclos de quimioterapia y ha tenido una respuesta completa, puede ser que esa paciente le diga, en realidad, ¿por qué necesito cirugía si ahora tengo una tomografía que dice que está completamente normal y un CEA 125 que está normal, me encanta jugar golf, ¿por qué voy a hacer una cirugía ahora que ya he respondido completamente? Pero claro, el estándar es después de cuatro o seis, si hay una respuesta completa, hacer una citoreducción o una cirugía. Muchas gracias, Dr. Ramírez. Para Reitan, ¿cuál es la diferencia en morbilidad operatoria entre la cirugía ultra radical del cáncer lobario y la quimioterapia neoayuante en tu centro o a nivel internacional, los centros con experiencia en esto? ¿La diferencia en la mortalidad? Sí, bueno, en los estudios, el estudio, por ejemplo, de Italia es cerca del 10%, porque la mortalidad cirúrgica de los pacientes de intervalos es muy baja, es cerca de cero, casi cero. Y bueno, en general, en los centros que hacen citoreducciones grandes, bueno, el estudio 3C o 4, con metástasis secales, entre 3 y 5%. Eso es la mortalidad de la cirugía primaria, y la mortalidad de citoreducción de intervalo en general es muy baja, porque las citoreducciones son mucho menores, entonces no pasa tanto. Entonces, claro, hay que considerarlas. Acá nosotros aquí, bueno, creo que hasta como dos o tres, dos años, un poco menos, hacíamos citoreducciones a todo costo, muy grandes. Bueno, tenemos pacientes que se quedaron internados por tres meses, cuatro meses, con muchas complicaciones, pacientes que murieron en la cirugía, y en verdad ahora, bueno, tenemos un conflicto interno, pero en verdad yo estoy haciendo casos mucho más seleccionados. Si la citoreducción es muy grande, entonces no. Hacemos, en general, si es posible hacer, por ejemplo, una cirugía en cuatro, seis horas, inspecciones intestinales, pero no múltiples intestinales, por ejemplo, no. Antes hacíamos, por ejemplo, colectomía derecha, colectomía izquierda, colectomía y cosas así, no lo hacemos más. Y las secciones peritoneales del diafragma, si son pequeñas, bien, pero si hay que hacer muy grandes, o como se dice, espesura total del diafragma, entonces ahora hacemos muy poco, solo si son muy pequeñas. Y, por ejemplo, no hacemos más pancreatectomías, no hacemos más. Entonces no es solo el score, es la impresión del equipo. Entonces si es una cirugía muy mórbida, no las referimos a quimioterapia. Entonces la impresión que tenemos nosotros ahora es que las pacientes que tienen que estar prontas para empezar quimioterapia en 15 días, 15 o 30 máximo, no más que eso. Si eso no va a pasar, las referimos. En otras palabras, la edad aumenta la sabiduría. Eso yo no sé porque sigo muy joven, entonces no. Para el doctor Alejandro, según todo lo que hasta ahora estamos conversando y en relación a su ponencia, ¿cuál cree que es la causa para rechazar la evidencia de cuatro ensayos clínicos que demuestran que hay equivalencia entre la quimioterapia en ayuvantes y la cirugía cito-reductora primaria? Yo no creo que haya que rechazar la evidencia. Yo creo que la evidencia es súper clara de que terapia en ayuvantes es equivalente a cirugía primaria. Yo creo que a pesar de que si el trust trial llegara a ser positivo, lo único que va a demostrar el trust trial es de que si llegara a ser positivo, que tengo la sospecha personal de que no va a ser positivo, pero bueno, si llegara a ser positivo, lo único que va a demostrar es de que en centros muy específicos con cirujanos de alto volumen, y no solamente son los cirujanos, también hay que tomar en cuenta la institución donde está el cirujano, que en esos centros, en esas situaciones en particular, la cirugía cito-reductora primaria puede ser mejor que terapia en ayuvantes, pero también la otra cosa que hay que ver del trust trial que no sabemos es de que a pesar de que sea positivo, ¿qué tan robustos son las diferencias? Si es una diferencia entre tres y cuatro meses en sobrevida, realmente eso vale la pena a someter a pacientes, cuando estás viendo esos promedios en mediano, esa mediana diferencia, o sea que yo creo que esperar los resultados, pero en personal, o sea, yo creo que la, para mí, la evidencia es muy clara de que cirugía primaria y terapia en ayuvantes son equivalentes. Lo que Alejandro acaba de decir, porque lo que Alejandro dice es muy importante, ese factor de cuando hablamos de los centros centralizados y los centros de alto volumen, inmediatamente el cirujano ginecólogo-oncólogo traduce eso en su mente a que en esos centros hay mejores cirujanos, y se han demostrado en varios estudios que lo que hace la diferencia es que esos centros siguen las guías de manejo de una paciente con cáncer, no quiere decir que solo sea el cirujano, quiere decir que esos centros, eso se ha demostrado en varios estudios, que cuando se hace la evaluación de estos centros, estos centros son los que más siguen las guías del NCCN, son los centros donde tienen equipos multidisciplinarios donde se discuten a estas pacientes, son centros donde se incorpora la evaluación radiológica, son centros donde en realidad se siguen las reglas, no es porque el centro sea que en ese centro hay un supercirujano, lo que hace la diferencia es que esos centros siguen las reglas del juego. Y puede ser que esos centros también tengan acceso, no solamente a todo lo que dijo Pedro, que creo que es superimportante, pero además esos pacientes pueden tener acceso a mejores trials, acceso a terapias nuevas, a quimioterapias nuevas, o sea que es difícil saber, tratar de generalizar los estudios que va a pasar con el TRUST, y esto yo creo que va a ser la limitación más importante. Y una cosa que creo que es muy interesante es que el TRUST empezó después que ya existía un estudio randomizado con un resultado significativo, sin diferencia, entonces eso muestra también que nosotros siempre hay una tendencia a no aceptar cambios, siempre queremos o nuestras creencias, eso es una cosa que pasa. Y en verdad hoy la pregunta es ¿será que quimioterapia neoadjuvante para pacientes con 3A o 2 es mejor que hacer cirugía? Esta es la pregunta, porque la pregunta para pacientes con tumores más grandes no tenemos dudas. Y mismo si el trial es positivo, el TRUST, ¿será que las pacientes que tenían mucha enfermedad que fueron operadas, si estas pacientes estuvieran en el grupo de neoadjuvancia, probablemente el grupo que fue operado tendría resultados mucho mejores. Entonces hay que definir quiénes son los pacientes que necesitan cirugía. Eso es importante. Probablemente mismo los 3A, no sé. Eso es súper crítico. Lo que Raytan acaba de decir también es súper importante. En el TRUST están incluyendo pacientes con estradiol 3B que son pacientes que, todos esos pacientes creo que todos aquí estamos conscientes de que esos pacientes en general van a recibir cirugía primaria, no tienen enfermedad alta. Entonces van a incluir pacientes con 3B, 3A y 4 que es diferente a lo que incluyeron Scorpion. Scorpion son pacientes que tenían enfermedad difusa, peritoneal de alto, alto volumen. Entonces, si el TRUST llegara a ser positivo puede ser que también en parte es de que la sobrevida está aumentado por esos pacientes que son 3B que definitivamente se van a beneficiar por o se pueden beneficiar por cirugía primaria potencialmente. Estoy 100% de acuerdo con eso. . I completely agree, Professor Ramírez, with what you point out. And in that same sense, there is a question for Reitan. Something that Professor Ramírez answered regarding the positive tract. Do you believe that these results are reproducible in centers that do not meet European standards, the quality of bowel cancer, and in Latin America? Yes, I think Pedro already answered very well. I don't think so. It's the same thing that happens with HIPEC. Look, HIPEC, you also have to have a very specialized center, and when they say that the complications are manageable or are few, that's not true. And the same thing will happen with TREST. And, well, there is no chance that TREST is positive. This is not going to happen. I don't know. It's recording, right? Well, this is going to be a very, very big surprise. But I don't think this is going to happen. Magaly, I think we have time for one more question. Yes, we only have two minutes left. I think we have to make the most of it. And we still have a lot of things left. How complicated. Well, in bowel cancer, we always need the joint management of medical oncology and chemotherapy. Even though we are surgeons, I think it's the truth. So, the question for Dr. Coleman is sent to us here. What do you think about the use of PAR inhibitors in patients with non-muted BRCA? Oh, a non-muted BRCA. So, in patients, so it really depends on what you have available to you. So, remember, the way that we assess whether or not a tumor is a good candidate for a PAR inhibitor is that it has a deficiency in the ability to repair a double-strand break in DNA. So, unlike a lot of the drugs we use, which are direct targets to the cancer biology, this is something that has to be given in a state where the tumor is vulnerable. The best way that we can assess that is by testing the tumor for BRCA mutation. It's the most reliable factor that can reflect on the ability of the cancer cell to repair itself. In those patients, PAR inhibitors have demonstrated very consistently, but not 100%, efficacy. So, the step down from that is what happens in a tumor that has evidence of homologous recombination deficiency, but is not BRCA. Those patients appear to have some benefit to the use of a PAR inhibitor, particularly in the frontline setting, and there is approval for it. But if you don't have access to testing or access to PAR inhibitors, this information is purely prognostic. And it provides at least some guidance as to whether there are genetic risks for other diseases, like breast cancer, and familial risks to the rest of the family. The third part is, what do we do in the patient in whom there is no evidence of homologous recombination deficiency? And this is assessed by a test that is trying to determine whether or not this is present in the tumor. We do have approval in that scenario, but it's been not directly tested in the frontline setting. However, we do have data in this setting in the recurrent situation. And I can tell you that the response rate, a tumor that's this size, getting a PAR inhibitor where it's a homologous recombination deficiency test negative, those patients have a very low chance of responding, which speaks to the biology, which is how I started this question. So I personally do not recommend PAR inhibitors in patients that are annotated, meaning they had testing done that showed that they did not have a BRCA mutation or did not have homologous recombination deficiency in non-BRCA states. And I prefer to use bevacizumab or make the decision about bevacizumab in the frontline setting in that group of patients. Muchas gracias, doctor. Muchas gracias. A continuación... Doctor, tenemos una última pregunta, creo. Sí. Esta pregunta es para el doctor Ramírez. ¿Cree que estamos en el renacimiento del second look? ¿Y si tiene algún tipo de potencial para convertirse en el standard of care? No, no considero que estamos en ese momento, porque tenemos ya evidencia que la incorporación del second look no impactaba la sobrevivencia de las pacientes. Pero claro, esa era evidencia de la literatura que se había publicado en los años 90, porque en realidad no teníamos buenos tratamientos y no teníamos una percepción exacta del concepto molecular. No la tenemos hoy tampoco, pero tenemos muchísima más información de los aspectos moleculares de estas pacientes. Tenemos ya tratamientos que nos ofrecen una ventaja en términos de la sobrevivencia, en términos de tratamiento adyuvante después del tratamiento primario. Entonces, lo que se está explorando con el second look, que es solamente para determinar y saber y aprender muchísimo más acerca de estos tumores, para determinar si en realidad las pacientes que tienen un second look positivo se benefician de estos factores como los inhibidores de PARP. En cada cirugía que hacemos en este estudio de second look, y de nuevo es bajo un estudio, no lo hacemos rutinariamente, solamente bajo un estudio, cada biopsia que se toma no solo va a patología, pero cada biopsia se le hace una evaluación molecular también a ese tejido. Entonces, es una manera de aprender un poco si nos provee información adicional para determinar un triage de las pacientes. Después que se termine el tratamiento, cuáles se beneficiarían de continuación de Abastin, cuáles se beneficiarían de continuación de los inhibidores de PARP, y así aprender más acerca de este grupo de pacientes. Muchas gracias, Dr. Ramírez. A continuación, vamos a seguir con la sesión de cáncer de cervix. Les damos las gracias a los ponentes, al profesor Ramirez, al Dr. Reitan Rivero y a Alejandro Reujaín, por el excelente nivel de las presentaciones y discusión. Muy bien. A continuación, ingresamos al momento, módulo de cervix, de cáncer de cervix, y vamos a iniciar con la ponencia de la Dra. Miriam Perrota. La Dra. Miriam Perrota es jefa de ginecología oncológica del Hospital Italiano de Buenos Aires. Es profesora de ginecología de la Universidad de Buenos Aires. Y vamos a empezar con el primer tema que tiene a cargo ella sobre el impacto de la vacuna de BPH en la mortalidad por cáncer de cervix. Bienvenida, doctora. Su micro, doctora, está apagado. Perdón, perdón. Buenos días. Primero, es un placer para mí compartir este día con todos ustedes, con este panel tan calificado. Mi agradecimiento al IGCS, a su presidente, al doctor Colma, y por supuesto a René Pareja, que tanto hace por la ginecología oncológica de nuestro continente. Vamos a dejar un poquito el bisturí y vamos a dedicarnos unos minutos a la prevención del cáncer cervical y cuál es el rol que tienen las vacunas contra el HPV en la prevención de este tumor. No declaro conflictos de interés. Dado que es la primera presentación, voy a hacer un breve recuerdo respecto a la epidemiología del cáncer, a la actual declaración de la ONS para prevenir el cáncer cervical en los próximos años, cómo fue el proceso de desarrollo de vacunas profilácticas contra el HPV, cuáles fueron los endpoints primarios que han demostrado ser la vacuna efectiva, y por último nos vamos a dedicar a ver si la vacunación contra el HPV impacta en la incidencia y mortalidad por el cáncer de cuello invasor. Todos sabemos y recordamos los datos del Globocan 2018, 570.000 casos por año y 311.000 muertes, a pesar de que el cáncer de cuello uterino es una enfermedad prevenible. La distribución de esta neoplasia también es tan conocida y tan difícil de modificar, y podemos ver cifras de incidencia y de mortalidad tan dispares, tan bajas como menos de 7 por 100.000 mujeres, y tan altas como mortalidades de superior a 13 por 100.000 mujeres en los países pobres o en vías de desarrollo. Y siempre me gusta mostrar este slide del Globocan, en donde vemos en las barras celestes la incidencia y en las barras rojas la mortalidad según los diferentes países, en donde claramente se evidencia de que el cáncer de cuello uterino es un tumor de la inequidad, que afecta a aquellas mujeres pobres con pocos recursos. Y es por eso que la OMS y la OPS ha lanzado el plan de acción sobre la prevención y el control del cáncer de cuello uterino. Y sencillamente porque si no se toman las medidas que corresponden, se espera un incremento muy importante en la incidencia y en la mortalidad de esta neoplasia. Y además, más del 85% de mujeres afectadas serán, como decía, mujeres pobres de países pobres, madres de hijos cuyas vidas se ven truncadas con la pérdida de sus madres. Y esto no es un golpe bajo, sino que simplemente implica de que el cáncer de cuello uterino no solamente es un problema de salud pública, es un problema afectivo, es un problema social y un problema laboral muy serio, que ojalá se pueda resolver. Por eso, el plan de acción se refiere a mejorar la organización y el manejo de los programas de cáncer cérvico uterino, mejorar la información y los registros de cáncer, que todos sabemos que en aquellos países en donde la incidencia es mayor, es donde más fallamos en estas áreas. Fortalecer la prevención primaria por medio de las vacunas, mejorar el tamizaje y el tratamiento de las lesiones precursoras con estrategias actualizadas e innovadoras y mejorar el acceso a los servicios de diagnóstico y tratamiento cuando las mujeres ya presentan la enfermedad. La visión de la OMS es un mundo sin cáncer de cuello y el objetivo es lograr para el 2030 cuatro casos por 100.000 mujeres por año. Para lograr esto, las acciones deben ser muy fuertes. Vacunar a más del 90% de las niñas a los 15 años. Que el 70% de las mujeres tengan un screening entre los 35 y 40 años utilizando una metodología sensible como es el test de BPH y que el 90% de ellas puedan ser manejadas apropiadamente si es que realmente tienen la enfermedad pre-invasora o invasora. Como vemos entonces, uno de los pilares fundamentales de las acciones que nos propone la OMS es lograr una vacunación universal. Este cuadro que parece un poco complicado pero que no lo es, nos muestra la perspectiva histórica de los estudios de BPH y cáncer cervical. Y ustedes ven que con la incorporación de una metodología molecular adecuada en un periodo de tiempo que no fue muy largo, se pudo determinar la relación entre los virus oncogénicos de HPV y el cáncer cervical. Y a partir de allí, numerosos estudios epidemiológicos se realizaron en todo el mundo. Estudios de casos y controles sobre HPV y cáncer, estudios de historia natural y progresión de las lesiones, la determinación de la prevalencia del HPV y la distribución de los tipos de HPV en el cáncer y en las mujeres normales, los trials que determinaron cuál es la utilidad clínica de la tipificación viral, fundamentalmente en el screening y en el triage de citologías anormales, y por supuesto, más o menos a mediados de los 90, los trials de vacunas que siguieron todas las fases que requiere la aprobación de un fármaco hasta lograr la cuadrivalente, su aprobación en el año 2016, y la bivalente en el 2017. Entonces, ¿cuáles fueron los principios para el desarrollo de las vacunas? Que la etiología del cáncer de cuello uterino era infecciosa, el conocimiento de la patogénesis de la enfermedad, la prevalencia de los tipos de HPV en los cánceres de cuello en todo el mundo, porque esto fue fundamental para determinar cuáles iban a ser los tipos virales que iban a ser incluidos en las fórmulas vacunales, y por supuesto, la identificación de una respuesta inmune. Estos fueron los ensayos por todos conocidos, los ensayos de eficacia, que fueron estudios multicéntricos, fase 2 y fase 3, que evaluaron la eficacia de las vacunas, la tetravalente en los estudios Future, la bivalente en el estudio Patricia, el de Costa Rica y el Vivian, y la nonavalente, estudios de fase 3, de inmunogenicidad, eficacia y seguridad. Y como vemos acá remarcado en rojo, ya la vacuna bivalente, el Future, mostró efectividad para el desarrollo de lo que era en ese momento el endpoint, que era el sin dos más, cercanos al 100%, lo mismo en el estudio Patricia para la vacuna bivalente. Y este es el estudio randomizado internacional y multicéntrico, fase 3 sobre 14.000 mujeres, que también demostró que la vacuna nonavalente, al ser comparada con la cuadrivalente, tenía altos índices de eficacia para el desarrollo de lesiones precursoras. Hoy en día, para diciembre de este año, 124 países han incorporado la vacunación contra el HPV en sus calendarios. Y si nosotros vemos los datos de nuestro continente sacados de la OPS, 40 países ya han incorporado la vacunación, lo cual realmente es sumamente auspicioso en nuestro continente de Latinoamérica. Quiero contarles que en nuestro país, en la Argentina, la vacunación es gratuita y obligatoria para niñas de 11 años. Ha sido incorporada al calendario en el 2011, en el 2015 se pasó a dos dosis en lugar de tres, y en el 2017 se incorporó a los varones de 11 años al calendario de vacunación. Y tenemos la suerte, dentro de lo que es la salud pública de nuestro país, de que los programas de vacunación se cumplen bastante bien, y si vemos en el gráfico de la derecha, tenemos en las barras naranjas y en las barras celestes los varones, un porcentaje muy elevado de cobertura, sobre todo en la primera dosis, y no es muy baja también para la segunda dosis de la vacunación. Lo importante que sepamos es que una vez que los programas fueron incorporados, hay que monitorizar estos programas. ¿Y cómo se hace el seguimiento de las pacientes vacunadas? Hay un seguimiento que es temprano, que dura años, en donde lo que hay que evaluar es la prevalencia del HPV en el grupo vacunado y las verrugas genitales. Un seguimiento intermedio que lleva años o décadas, que es determinar el impacto en el precursor del cáncer. Y un seguimiento tardío, que lleva décadas, que es de qué manera las vacunas impactan en la prevención del cáncer invasor de coeluterito. Australia, como todos sabemos, fue, diría, de los primeros países que incorporó al calendario la vacunación con altos índices de cumplimiento y altos índices de cobertura. Y fue el primer país que empezó a publicar los resultados del seguimiento. Son muchos los estudios que evalúan el impacto de las vacunas. Y este es un review sistemático que realizó Susan Garland sobre 58 estudios de varios países. Y demuestra que hubo, después de 10 años de incorporación, una reducción del 90% de las infecciones por los virus de la fórmula vacunal, un 90% de disminución de las verrugas genitales, un 45% de disminución de los cambios histológicos menores, y un 85% de disminución de las anomalías histológicas de alto grado. Y esta es una revisión Cochrane de Mark Arvin, en donde ustedes pueden ver que en la primera línea no hay reportes respecto al impacto en el cáncer invasor, pero sí ven de qué manera las vacunas impactan en la disminución del precursor del cáncer, SIN2+, SIN3+, AIS, e incluso SIN2+, con virus que no están incluidos dentro de la fórmula de la vacuna. Por lo tanto, lo que hoy sabemos es que las vacunas contra el HPV, aparte de ser seguras, han demostrado ser eficaces para prevenir las lesiones de alto grado, las infecciones y las verrugas genitales. Pero no hay datos, o hay muy pocos datos, respecto al impacto de la vacunación en el riesgo de desarrollar cáncer invasor. Este es un estudio finlandés que se realizó revisando la corte de mujeres finlandesas que formaron parte de los estudios de eficacia Future y Patricia, y pudieron demostrar una eficacia en el grupo vacunada de un 100% y un desarrollo solamente de 10 casos de cánceres asociados al HPV, de los cuales eran 8 cánceres de cuello uterino, uno orofaringio y otro de uvulva. Este es otro estudio, también con revisiones, es un estudio americano que revisó la base de datos SIR, es un estudio de corte seccional, en donde determinó la incidencia de cáncer cervical en el 2011 al 2014, que decaía en un 29% cuando se comparaba con el periodo previo a la vacuna en las mujeres de 15 a 24 años. Y este fue un poco el artículo recientemente publicado en el New England que nos convoca con esta presentación, que es un estudio de corte basado en registros que se sigue entre el 2006 y el 2017. Los registros utilizados en Suecia fue el registro poblacional sueco, el registro nacional de vacunación, el registro de prescripción de drogas, y el registro sueco de cáncer. Es decir, todos conocemos los registros de los países nórdicos europeos, de tal manera que pudieron tener la data bastante cercana a la realidad. Y ellos concluyen que en la población sueca de niñas y mujeres de 10 a 30 años, la vacuna cuadrivalente se asocia con una sustancial reducción en el riesgo de cáncer a nivel poblacional. Para atender el trabajo, algunos datos de Suecia. La vacunación en Suecia se inició en el 2007 con vacuna tetravalente casi exclusivamente. Es subsidiada para mujeres de 3 a 17 años. Se utilizó primero un esquema de tres dosis y a partir del 2015 el esquema de dos dosis. El screening en Suecia incluye a mujeres de entre 23 y 64 años con una periodicidad que varía entre 3 y 7 años según la edad de las pacientes. Los criterios de inclusión, pacientes sin antecedentes de cáncer, sin vacunación previa contra YPV, y que no hayan emigrado a Suecia luego del 1 de enero del 2006, porque si no, no se conocía el estado vacunal previo. Se inició el seguimiento el 1 de enero del 06 o en el cumpleaños número 10, lo que ocurriera último, y se finalizó el seguimiento, lo que ocurriera primero, el 31 de diciembre del 17, el cumpleaños 31, el diagnóstico de cáncer, el fallecimiento, emigración, utilización de la vacuna vivalente o pérdida en el seguimiento. Se incorporaron o cumplieron los criterios de inclusión Gracias. Un millón seiscientas mil pacientes vacunados, prácticamente medio millón, es el grupo de pacientes vacunados al menos con una dosis. Esta es la tabla en donde se considera a la edad como un factor muy importante. También dividieron a las pacientes en cortes de nacimiento para ver si de alguna manera esto tenía algún impacto en tanto en la recepción de la vacuna como en el riesgo de cáncer. Y también utilizaron algunos factores correctores como yo llamaría el estado parental o familiar o social de las pacientes para ver qué impacto podía tener esto en las vacunas. Esto es la incidencia acumulada o riesgo de cáncer, que como ustedes ven, aumenta en la curva, se ve a partir de los 23 años, que es cuando empieza la vacunación en Suecia. Y se dan cuenta de qué manera la incidencia baja sustancialmente y llega a cuatro por cien mil mujeres en el grupo de pacientes vacunadas antes de los 17 años, que sabemos que es la edad ideal para que las pacientes reciban la vacuna. Esta es la razón de la tasa de incidencia, en donde ustedes pueden ver que en el grupo no vacunado se diagnosticaron 538 casos y 19 en el grupo de vacunas, con una protección realmente muy importante. Y el rate ratio, cuando se ajusta por edad y por los otros factores también de ajustes independientes de la edad, baja en forma considerable. Y una de las cosas que creo importante resaltar es la edad de vacunación. Solamente dos cánceres en el grupo de pacientes vacunadas antes de los 17 años. Por lo tanto, la conclusión es que la vacuna tetravalente se asoció a un riesgo sustancialmente menor de desarrollar cáncer invasor, la reducción fue más pronunciada en aquellas mujeres vacunadas en edades tempranas, en mujeres naif, antes del inicio de sus relaciones sexuales. Los resultados coinciden con lo que hasta hoy está publicado, también apoyan entonces la recomendación de vacunar a las niñas y tiene limitaciones aceptadas por los mismos autores. El sesgo de voluntariado sano, no se puede estimar el riesgo de carcinoma cervical invasor en relación al número de dosis, dado el bajo número de eventos cáncer. La alta tasa de screening que tiene esta población puede detectar cánceres asintomáticos y subestimar la reducción del riesgo. Y yo agregaría que la población evaluada es una población muy joven, no es la población target del cáncer de cuello uterino y el periodo de seguimiento aún es corto. No se consideraron otros factores epidemiológicos de riesgo conocidos. No hay relación del desarrollo del cáncer y el número de dosis. Creo que también puede tener que ver, aunque los autores lo desestiman, el hecho de que las pacientes hayan tenido lesiones precursoras durante el seguimiento y que hayan sido tratadas. Los autores dicen que en esencia esto no puede modificar los resultados. Así que para terminar, creo que el monitoreo de los programas de las vacunas tienen que seguir. Ya tenemos datos del seguimiento temprano e intermedio y tenemos que seguir todas estas cortes de pacientes vacunadas en seguimiento tardío para poder definir si el impacto de la vacuna disminuye el cáncer, que es el objetivo final de la prevención primaria y secundaria de este tumor. Bueno, yo les agradezco mucho la atención y les quiero mostrar esta foto, que es un atardecer en el río Paraná, en el norte de nuestro país donde yo nací, y que, bueno, ojalá puedan visitarla. Muchas gracias a todos. Muchas gracias, doctora, por su ponencia. A continuación, la doctora Juliana Rodríguez nos presentará quimioterapia en el adyuvante en embarazada con cáncer de cervez. La doctora Rodríguez es ginecóloga-oncóloga de la Fundación Santa Fe y del Instituto Nacional de Cancerología de Bogotá, Colombia. Adelante, doctora Rodríguez, por favor. Bueno, buenos días a todos. Es un gran placer estar en un auditorio tan selecto. Y a todos los asistentes, muchas gracias por asistir a esta presentación. Como les decía, en el día de hoy, les voy a hablar un poco de la quimioterapia en adyuvante en cáncer cervical y paciente que está gestando. Para esta charla, no tengo ningún conflicto de interés. Vamos a manejar una agenda muy breve, pero muy precisa, para que ustedes lleven elementos importantes sobre la epidemiología del cáncer cervical, el cáncer y embarazo, cuál es el impacto que nos genera una paciente que está en gestación respecto a su patología oncológica, cuál es la evaluación de estas pacientes, qué nos ofrece la evidencia de estrategias de tratamiento, y ya específicamente vamos a hablar de quimioterapia en adyuvante en cáncer cervical y embarazo, cuáles son los lineamientos específicos que existen, y unas pequeñas conclusiones respecto a los desenlaces oncológicos, maternos, obstétricos, e incluso de la primera infancia. ¿Por qué es importante hablar de cáncer cervical? Sabemos que esta patología aporta cerca de 500.000 nuevos casos, según datos de la OCAN 2018, y cerca de 300.000 muertes. Pero además de esto, sabemos que esta enfermedad tiene una distribución muy desigual a lo largo del mundo, y vemos cómo cerca del 84% de los casos ocurren en países que están en vía de desarrollo o que tienen un índice human development index below 0.8. And from there, many Latin American countries, as you know, there is even inequality between countries in specific regions. And this is also very important to note, the risk of malignancy in women according to their age group changes according to age. When we have patients between 20 and 24 years old, the risk of malignancy per se, only by age, is about 36 in 10,000 women. But in patients who are older, between 40 and 45 years old, this risk even doubles, up to nine times more. What has this generated? That women are more and more exposed to maternity leave. We see that about 37% of cervical cancer cases are diagnosed in patients with reproductive age. And this generates more cases with cervical cancer, even cancers of other origins, that are going to be pregnant and that we should definitely know what their handling is. And a generalization regarding pregnancy cancer. Let's remember that cancer is diagnosed in pregnant women in society developed close to one in a thousand pregnancies. The incidence rate of invasive cervical cancer in pregnancy is heterogeneous among publications, but it approaches close to 0.1%. And something very important to highlight is that definitely pregnancy generates an opportunity for us to certify this pathology. And this gives us an advantage to make appropriate diagnoses and adequate handling in these patients. According to data from the INCIP, which is an international registry of pregnancy cancer and infertility led by Dr. Amant, basically we have data and records of this cancer that occurs in gestation. They also talk about fertility preservation and postnatal diagnoses. According to these records, basically we have that the most commonly diagnosed neoplasia in pregnancy is breast cancer, close to 41%, followed by hematological neoplasia, 12%. And we see that cervical cancer has a non-expressible load of disease of 10%. Regarding gynecological neoplasia, we must know that cervical cancer is the most frequently diagnosed pathology. And we see an incidence rate of 1.4 to 4.6, according to this data. And these incidences also vary at the time the pregnancy diagnosis is made and the load of specific disease in each region. That is, this neoplasia definitely competes with us during the gestation. And as I mentioned, by making an early detection, by being a tamization opportunity, we see that about 80% of patients will be diagnosed with this neoplasia in early stages or surgical. A very common question is to see how the pregnancy impacts specifically in the prognosis of neoplasia. This is a macho cohort of Dr. Alaska and collaborators where basically what they do is match patients by age and stages, including 132 pregnant women with a control of 256 patients in relation to 1 to 2. And 80% of the patients in this study were in stages 1 to 1 to 1 to 2. And why do I think it is important to highlight this? When you look at the oncological impact of being pregnant and having cervical cancer versus having cervical cancer by stage, there is no statistically significant difference. And when you look at it as an independent factor in the multivariate analysis, we see that there were no differences either. That is to say that apparently we have a neoplasia that being or not being pregnant has similar oncological results. Regarding the evaluation, this point is very important. It is in our hands to definitively certify the patients. We must do a very careful physical exam, include histopathological documentation, either by colposcopy or biopsy, all biochemistry, but I also want to make a special emphasis on this aspect and it is the images, which in addition to not only generating fear in patients for the risks of teratogenicity of ionizing radiation, it also sometimes generates many expectations, concerns in doctors that we have to prohibit these diagnostic tests. This is a consensus of the American College of Obstetrics and Gynecology. They are specific guides for the diagnosis by images during pregnancy. I want to emphasize that we understand that as the pregnancy is earlier and when the baby is in full organogenesis, the threshold of damage will be important to take into account, but when you compare, here on the right side of the graph, the approximate threshold is 100 milligrams and when we see even the ionizing radiation of any diagnostic test, including x-ray or tomography, it does not even reach a significant part of this threshold of teratogenicity. And it is very important to emphasize that it is unacceptable to delay these images in pregnant patients. I can't offer therapy to my patient if I don't know what their true extent of the disease is. So, we will always consider the risk of teratogenicity. Let's remember that the resonance is safe, no negative impact has been shown in any trimester of the pregnancy. We know that gadolinium is category C, that is, that the specific use should outweigh the benefit versus the risk, so there is no specific consensus, or a recommendation based on level 1, but the ideal thing is not to use gadolinium and this will allow us to look at the local extent of the disease and see the ganglion commitment that these patients have. The thorax study, if necessary, if we have patients who deserve it, ideally do a thorax x-ray, but if I have high suspicion of a high-risk disease with an important metastatic-pulmonary commitment, ideally I can do a tomography. The important thing is that we are selective and do these tests and always, always give advice to patients explaining what the potential risks and benefits of these tests are. Let's not forget, and less importantly, we have to do ultrasound studies because it is always necessary to evaluate the fetal viability in the context of the management of these patients. Specifically, cervical cancer treatment, in general, oncological management is favored over the termination of the pregnancy. Let's understand that giving birth is an elective term, in order to seek standard management for these patients will have an impact on birth health. The treatment must adhere to protocols similar to those of non-pregnant patients, as I mentioned, basically the evidence we have are retrospective studies, expert advice, but it is what there is, it is what we must adhere to. So, what are we going to evaluate for the treatment during the pregnancy? We are going to take into account five fundamental aspects. Pregnancy diagnosis, the figo stadium, histology, the ganglion commitment of this patient, and, no less important, the desire of this patient to continue his or her pregnancy. We must always do an obstetric oncological balance. We seek to impact on the survival of these patients by trying live neonates and without comorbidities. However, it is definitely a challenge. Let's not forget that we have a team and we are not going to treat mothers isolated from fetuses. That is, we have to try to find strategies that offer the best benefits to this baby. What options are there during the pregnancy? An elective preterm birth, postpone the treatment until the baby is born, non-adjuvant chemotherapy, surgery, or terminate the pregnancy electively to be able to give the standard management. This is a consensus published in 2019 in the Annals of Oncology, led by Dr. Amant, but basically what it shows us is what we are going to offer to these patients according to the state, to the gestational age. I want to highlight here how chemotherapy has different roles throughout this, and we are going to see it in the chat. But is chemotherapy useful in cervical cancer? Definitely yes. You know that it is endorsed in different scenarios, in chemoradiation, adjuvant management in high-risk patients, even in metastatic diseases. So we know that there is a direct benefit of the use of these agents. And why give it as a non-adjuvant therapy in cervical cancer? What are the principles? Basically, controlling the tumor volume, generating a better radio sensitivity, the control of micrometastases in distant places has also been argued, and how this high concentration of medication will improve the response in terms of oncological impact. When has chemotherapy been used, and it is not the subject of this talk, and we will see it below, in patients who want early-stage or locally advanced reservation surgery for fertility. The first report on cervical cancer and pregnancy in which non-adjuvant chemotherapy was used was published in 1998, by Dr. Teguari, and there were two patients where the results were obstetric and maternal favorable, even oncological. This has generated, this advent, this knowledge of pathology has generated an increase in the use of chemotherapy. We see that definitely in a temporal trend, this tool is increasingly used. As I mentioned, we have several scenarios where we can use non-adjuvant chemotherapy. Patients with 1 to 2, 1v1 states of more than 22 weeks, I can offer them non-adjuvant chemotherapy or delay the state management until birth. Patients with 1v2 states with less than 22 weeks and are taken to pelvic lymphadenectomy and this is negative, I can also offer this therapy. Patients with less than 22 weeks without taking them to pelvic lymphadenectomy, I can give them ischemia. Patients with more than 22 weeks or patients with large tumors, this is according to the FIGO 2018 classification, more than 4 centimeters, who have less than 22 weeks and a firm desire to continue the pregnancy or even more than 22 weeks to do this disease control. It is very important to understand the objectives, as I mentioned, what I want by giving this therapy during pregnancy is to reduce the size of the tumor, but above all, prevent the dissemination to the point where it reaches a fetal viability. We should not ignore the different physiological changes that pregnant women have. There is an increase in plasma volume, there is a decrease in albumin, especially in the second and third trimester. There is a greater hepatic and renal clearance and this means that we have to be very selective and very careful when giving these therapies to patients. This is also very interesting to understand and it is that the agents can use the placental barrier. This is going to be related to the type of therapy and basically all these physiological changes that pregnancy has. The decision to use chemotherapy during pregnancy must be balanced with this fetal risk, as I had already mentioned. Regarding this transplacental step, there is a very interesting work by Dr. Kohler. He included 21 cases, 20 patients received cisplatin and one received a combination with carboplatin. The average number of cycles was three. And what was basically done was that at the time of birth, samples of umbilical cord and amniotic liquid were taken, in addition to the blood sample, to see this cisplatin concentration. And it was interesting to see that up to 65% of the patients had a concentration of this agent at the umbilical level and 42% in the amniotic fluid. In other words, we definitely cannot ignore this transplacental step that chemotherapy agents do. There are specific guidelines. This recommendation consensus that I mentioned earlier gives us specific guidelines for systemic therapy in patients who will receive it during pregnancy. Important things to highlight, the same dose will be given with respect to a non-pregnant patient, according to the current weight, not the ideal weight. It is important to understand that it is indicated in the first trimester and if I am going to give this patient therapy, I must wait until week 14 to start this treatment due to the high risk of organogenesis that I already mentioned, of doing a theratogenicity. And it is also very important to understand that the ideal thing is not to prolong this chemotherapy beyond 35 weeks and I must leave a window for a fetal-maternal medullary recovery of at least three to four weeks before getting pregnant. That is, if I am going to get my patient pregnant from week 35 to week 31, ideally 32, I must suspend the treatment. The recommended regimen is the combination of platelet-rich plasma, weekly or every three weeks for cervical cancer. To highlight the evidence regarding the oncological safety of neonatal and early childhood results, the evidence is really scarce and I want to highlight that in pregnant patients, there is a lot of limitation to do prospective studies for the ethical component. When we summarize more or less what there is of evidence for this specific aspect, there are less than 100 cases published and we have different reviews that tell us about this topic. We have a very interesting review carried out by Dr. Song's group, published in 2019. It is a systematic review with meta-analysis that included 39 studies. 88 patients were included, handled with non-adjuvant chemotherapy based on platinum and I am going to highlight some specific aspects to take them into account. The diagnosis of cervical cancer was 32 years old. 84% were diagnosed in the second quarter. The highest histology of the diagnosis was stem cell in 73% and we see that 87.5% of the patients had early stages in this review. The agents used were cisplatin only in monotherapy 62.5% and combination 35.2%. As I told you, if one evaluates the heterogeneity of these studies, it is quite broad because there are no specific consensus. At least in this review, they included patlitaxel, mipistina, doxorubicin, 5-fluoracylo, bleomicin, and we see that the combination of carbotaxol in 1.1%. Regarding the response rates, of chemotherapy, the progression was 2.9%. It was interesting to highlight that the maternal toxicity was low and really the most specific related effects were tombocytopenia, anemia, reaction to patlitaxel, nausea, and vomiting. There were also obstetrics like miscarriage hemorrhage, previous placenta, and oligodendroids not necessarily related to therapy. Regarding the life of the birth, according to the study, they were similar to how they are handled in non-pregnant women and we see that the recurrence in this systematic review was 19.8% and 13.5% of death. From the study of Dr. Alaska, little evidence in the sense that there were only 22 patients with similar clinical characteristics. And this is also very interesting to highlight how chemotherapy was not an independent prognostic factor to worsen the outcome of free survival in pregnancy. The fetal results, I insist, definitely at the time of conception of the organogenesis, we are going to have deleterious effects. There is even the theory of all or nothing, and it is how chemotherapeutic agents or even radiotherapy are going to eliminate an imminent fetal death. And as in the second and third quarters, it has been specifically related to small fetuses, membrane rupture, and entry into the uterus. The study of Dr. Koller basically showed that all children had no link to morbidity. The study of Dr. Song showed 80.7% of healthy neonates and 17 neonates that presented respiratory difficulty syndrome, elevated creatinine, anemia, and something very interesting to highlight is that there was a loss of bilateral hearing, that is, an associated autotoxicity. It has really been the only case as reported. There have been other revisions that have not shown this effect, but we must take into account the use of cisplatin. And as for the outcome, already in early childhood, at 5 years old, a rapid retoperitoneal sarcoma and a leukemia at 22 months. However, the causal association was not direct, and I want to insist that long-term monitoring of these neonates or these children requires more studies. Regarding the oncological links, in this part of the INCIP, we see that 37 cases of cervix were included. And basically to show you that 37% of the patients received taxanos and platino. And when we see the only statistically significant association was that the patients who received taxano had two more small fetuses for gestational age and those who received platino three more times. In addition to this, more income to the ICU, 2.37 times more than those who used taxanos. These are two studies to finish. Basically, the long-term results in early childhood. This had a fairly extensive follow-up until the age of 18, where no deterioration was shown in general health, cardiac function or neurodevelopment. And of patients exposed during pregnancy. And this was a study of multicentric case control, children who were paired with children of mothers who received care during pregnancy for cancer and other children who did not receive these chemotherapies. And there was no difference in neurological or cardiac development at 36 months. When the association was specifically measured by the agent, the taxanos and platinos that we use in cervical cancer, there was no statistically significant difference. And that if we have evidence in Latin America, we have it. I want to present the largest series published to date, which included two institutions from six Latin American countries with 33 patients. This study was led by Dr. Aldo López from Peru, to whom I thank for this information. And basically what we did was a characterization of patients with cervical cancer and pregnancy who had live children. The main histology was scamosa in 90%. 60% were diagnosed in the second quarter. The most used agent was in combination carbotaxol 60.6%. The number of cycles, the median was three. And we had a progression rate of 3% of these patients. As for the obstetric disease, we cannot define, a multivariate analysis was not done to see specifically that it was by the chemotherapy agent, but we had postpartum hemorrhage, two restrictions of growth, which we must also take into account. The birth disease, what we saw basically were two neonates with low weight, 6.1% in our cohort. And I want to emphasize that the follow-up was somewhat short and that has also been a limitation of the studies. 26, the median follow-up, 26 months. Here we characterize the oncological treatments. We had radical hysterectomy in 33% of the patients, chemotherapy in 57%. And in the middle we did hysterectomy at the time of the cesarean section and postpartum in 50% of the patients. Regarding the oncological results, I also want to emphasize that our recurrence rate was 26.7%. However, three quarters of these patients, or 75%, had a locally advanced disease. And the death rate was 13.3% of this population. Here we basically characterize the relapses according to the state and it was a little higher than the literature, these oncological outcomes. Never forget, and to finish, it is essential when we have these patients with cervical cancer and pregnancy, to do multidisciplinary management. We must include a whole staff and always work hand in hand, not only in the medical group, but with the patients, explaining the entire oncological panorama. To conclude, the option of delaying the birth to fetal maturity using non-adjuvant chemotherapy is feasible. We must evaluate the maternal efficacy and safety, understand that the studies available, the scope is still scarce and we lack evidence that it will be a little difficult to do it prospectively. It is necessary to guarantee greater follow-up in childhood, in neonates, to ensure these cognitive and functional links, and that a multidisciplinary team is definitely required. I thank you very much for this invitation. Thank you very much, Dr. Rodríguez, for your explanatory presentation. We continue with the presentation of Dr. Fabio Martinelli from Italy. The doctor is an oncologist at the National Institute of Tumors in Milan, in Italy. The doctor is going to talk to us about non-adjuvant chemotherapy in pregnancy... Sorry, non-adjuvant chemotherapy in cervical cancer, state of the art. Go ahead, doctor. Good morning, everyone. Thank you very much for the invitation. I hope I get a good Spanish, so you can understand what I'm going to say. Let's start. We have to talk about non-adjuvant therapy in cervical cancer. I have no conflict of interest. What are the theoretical foundations for non-adjuvant therapy in cervical cancer? Reducing the tumor size, thus making the surgery less complex when performing the surgery. Eliminating micro-metastases, trying to reduce systemic relapses, trying to avoid doing radiotherapy, especially in young patients, and preserving it in the event of a subsequent relapse. And above all, it is a treatment option where radiotherapy teams are not suitable to achieve a radiotherapy suitable for the treatment of this cancer. Historically, the candidates for this therapy are patients with locally advanced cervical cancer, 1B-2B of the old classification, which represents about 35-36% of the patients. But we have non-adjuvant therapy. Why? Let's see how the treatment has evolved over time. Non-adjuvant therapy has radiotherapy compared to radiotherapy. Non-adjuvant therapy has surgery compared to surgery, with radiotherapy and chemotherapy. And in the end, non-adjuvant therapy has chemotherapy compared to chemotherapy. Let's start with non-adjuvant therapy before radiotherapy. We have this cochrane, which is based on data from individual patients, more than 2,000 patients. There is a lot of variability, but there is no statistically significant difference between doing non-adjuvant therapy or not doing it before radiotherapy. What emerges from this study is that if you have cycles every more than two weeks or a dose of cisplatin less than 25 mg per square meter, there is a precondition for survival. So you have to do cycles every less than two weeks with more than 25 mg per square meter. What happened with non-adjuvant therapy before surgery compared to surgery. Here we also have a Cochrane with more than 1,000 patients. And what happened is that the general survival and the survival of disease is statistically better in the group that has done neodymphagy. Why is that? Because the patients who have neodymphagy have a significant decrease in positive ganglia and positive parameters. There is a trend that is not significant of a reduction in local and remote relapses. It does not have a particular benefit for the type of surgery that has to be done later. And unlike what happened with radiotherapy, there is no effect on the dose or time between cycles. Now that we have seen that doing neodymphagy before radiotherapy does not change anything, there are no differences. Neodymphagy before surgery makes a difference. So the community has compared neodymphagy before surgery with radiotherapy. Here in the Cochrane of before, there are more than 800 patients, a lot of variability. And what happened is that doing neodymphagy before surgery has an improvement in survival, free of disease, general survival, and a reduction in local or remote relapses between 13% and 15%. But you have to take into account some factors. These are the studies included in the review. Between 23% and 90% of the patients who were in the neodymphagy group received auxiliary radiotherapy. And the Italian study of Benedetti from 2002, which has the highest weights, in the radiotherapy group, 28% of the patients did not receive bariatric therapy. And the average gray administered was only 61 gray, with a time of more than 8 weeks of radiotherapy. So it can be said that the radiotherapy was not adequate enough to control the disease. In addition, radiotherapy is no longer the standard of treatment. Because in 1999, the NCI issued a statement where it defined chemotherapy as the standard, based on cisplatin, as the standard for treating locally advanced cervical cancer. So we did a comparison between neodymphagy plus surgery, which we have seen is superior to radiotherapy alone, compared to chemotherapy. And we are going to see two randomized studies that have been published and presented recently. This is a study from India with more than 600 patients. The groups included are the first BES-2 to 2B TOROS-FAMOS. The patients did Carbotaxol as a neodymphagy chemotherapy, and the endpoint was the Disease-Free Survival of the study. Here are the graphs. We can see that the Disease-Free Survival of patients with radiotherapy is significantly better than patients who did neodymphagy. There are no differences in the survival value. It should be borne in mind, however, that adverse events in patients who do chemotherapy are better than in patients who do neodymphagy, in terms of rectal, vehicular, and vaginal dysfunction. And in the short term, and especially in the long term, there is a vaginal dysfunction that remains for more than two years. This, for young patients, must be taken into account. A sub-analysis of this study shows us that, if you evaluate the first BES-2 and the second TOROS-FAMOS, there is no significant difference in the survival of disease-free patients. But if you evaluate the 2B TOROS-FAMOS, there is a significant difference, so this is a stage that does not have to be treated with neodymphagy chemotherapy. However, it should be borne in mind that 32% of patients who did neodymphagy decided to resort to any type of radiotherapy. The European study, which has not yet been published, but has been presented in ICS, Neurotics, etc., is more or less similar to the planning. It compares neodymphagy plus surgery, putting cisplatin with a minimum dose of 225 mgmq, to chemotherapy. Here, the primary endpoint was the overall survival at 5 years. Here, the curves are more or less like those of the Indian study, where there is no difference in the intention to treat and overall survival. There is a significant difference in favor of chemotherapy for disease-free progression. Here they have also done a sub-analysis, where it is seen that patients with 2B cancer have a prejudicial effect in neodymphagy plus surgery, while patients who have a smaller tumor size and have a stage of 1B-2 can benefit from this. Also in this study, 27% of patients in the neodymphagy group received adjuvant radiotherapy. The authors conclude, as I said before, that there is a better result in the neodymphagy plus surgery group in stage 1B-2. However, it must be taken into account when analyzing the history and statistical data. Both the Indian study and the European study were planned to have an increase of 10% of disease-free and survival in favor of neodymphagy chemotherapy. So both studies are negative, because they did not reach the planned endpoint. In the end, we will see something about neodymphagy before chemotherapy. There is a recently published study, the CIRCE study of a group from Brazil, which here in the planning of the study, was supposed to put neodymphagy with gencitabine cisplatin before doing chemotherapy, and it was planned as a positive study. In the end, it turned out to be a very negative study. So neodymphagy is prejudicial to chemotherapy and chemotherapy performs better than adding neodymphagy. There is another ongoing study, the Interlace Phase 2 Trial, and we are waiting for the results of this study to understand whether neodymphagy has a place here before chemotherapy or we have to leave it. To summarize what we have seen so far, neodymphagy before radiotherapy compared to rapid radiotherapy has no differences. Neodymphagy before surgery compared to surgery favors neodymphagy because you have a reduction of the positive ganglion and positive parameters. Neodymphagy before surgery compared to radiotherapy favors neodymphagy, but you have to keep in mind that radiotherapy does not meet the standard of care for locally advanced cervical cancer. Neodymphagy before surgery compared to chemotherapy, which is the standard now, favors chemotherapy, but if you analyze the data, you can see that there is a favorable trend in patients with a tumor size that is a stage of 1 to 2. Neodymphagy before chemotherapy can be prejudicial, but we have to wait for the Interlace Phase 3 Trial. What are the open questions about neodymphagy? The doses of chemo, how many, which drugs to use, and what happens between cancer tumors and tumors. For the dose, here is a review of the recent publication by Prof. Gadducci, he is an Italian colleague who specializes in this topic. We are going to see how, analyzing conventional chemotherapy, which has cisplatin with other mechanisms, they can be vincristina, bleumicina, taxolic, posfamide, athenes, objective response rate, and pathological response rate, very good, with a survival rate, free from disease or global, comparable to what emerges from chemotherapy. And also, in recent studies, more than Phase 2, different chemotherapy regimes are being tried, with the dose dense, with carboplatin, taxol, or cisplatin, and we have results that are good, but we have to take into account that here the stages are a little smaller than in the conventional studies. For what happens to the tumors versus the others, there is this review of 11 trials with more than 1,500 patients, which does not see significant differences in the short term on survival, but in the long term, patients with this type of non-tumor have a survival rate that is lower than patients with this type of tumors. So, for the types of chemotherapy that can be said, there are no definitive conclusions. We know that taxol and platinum fosfamide, which is the combination of drugs tested in the SNAP study in Italy, has the best pathological response rate, but it has a high toxicity in terms of neutropenia, thrombocytopenia, and anemia. For what happens to this type, we do not have definitive conclusions. To conclude, let's see a little what the guidelines say. In Europe, the European Society for Oncological Genetics together with the Society for Radiotherapy and Pathology considers neodymia in the handling of locally advanced primary B2-2A2 cancer, but it is also controversial. If we go to see the American guidelines, they tell us that only outside of America is neodymia used in the primary B3-2B stage of the 2012 figure, and the panelists do not recommend the use of neodymia outside of clinical trials. In conclusion, chemotherapy is the standard treatment in the locally advanced cancer of the cervix. Neodymium chemotherapy before surgery can be a treatment option in selected patients. In other words, patients with a primary B3 tumor located in the cervix of a size greater than 4 cm, or patients with a primary B2-2A1 tumor with an external ring of interest. Why is that? Because if you are going to do a primary surgery on this patient, it will most likely also be radiotherapy. This is the only indication to try to avoid radiotherapy, which we have seen, as in Gupta's study, has a long-term effect on sexual and vaginal function. We still have to define which are the best drugs for neurodegenerative diseases. We have seen in the presentation before Juliana how in pregnant patients, carboplatin and Taxol are the most used. Surely the patients I answer are neodymium. The answer is a survival predictor. This derives from an Italian prospective study, but we have seen that the patients I answer do not have to do neodymium radiotherapy or chemotherapy. They have a very wide survival rate. We have to personalize the treatment for each patient because, as I said before, the standard is chemotherapy. If there is a suitable team for radiotherapy, we have to do new studies if we want to try to see if neodymium has any place in the cancer. Thank you very much for your attention. I hope I have been quite clear with my Spanish. Thank you very much, Doctor. Very clear. Thank you very much, Dr. Araf. I have the last presentation today. Before I start, I want to thank IGCS, represented by its President, Rob Coleman, who has accompanied us throughout the session, its CEO, Mary Aiken, the staff team behind all this editing, Cathy Fearing and Susan Ralph, and REN TV, which is providing us with translation services in English. So, without further ado, let's start talking a little about non-adjuvant chemotherapy in the preservation of fertility in patients with early-stage uterine cancer, particularly tumors larger than 2 and smaller than 4 centimeters. I have no conflict of interest to offer this presentation impartially. The management guides of the NCCN do not even mention non-adjuvant chemotherapy as part of what we can offer patients. They refer to trachelectomy and clarify that radical trachelectomy has been validated mainly in tumors smaller than 2 centimeters. The European guides go a little further and say that it should not be offered the preservation of fertility in patients with tumors larger than 2 centimeters in the usual clinical scenario, because this is a treatment that should be considered experimental. We know, as Juliana explained, as Fabio explained in his complete talk, that uterine cancer is sensitive to chemotherapy. And we also know that the preservation of fertility today is a very important issue for patients. So, in the real life of our hospitals, we are going to have patients with tumors larger than 2 centimeters who are going to want to preserve fertility, and we as a treatment team have to offer them health. In the literature, we basically have 24 articles. There are 8 case reports, there are 7 small series between 2 and 8 patients, where the largest would have 28 patients, at least in the initial attempt. All these series include different approximations, radical vaginal trachelectomy, paroscopic, robotic, abdominal, conization, and basically with ganglion sampling, with lymphadenectomy, and there are at least 20 different combinations of chemotherapy. In other words, the information is quite heterogeneous. What I am going to do is a recount of what is in the information. Unfortunately, we do not have data to do a kind of meta-analysis, and what you are going to hear is the interpretation given by those who are talking about this available literature, but it does not intend to be a truth that you have to believe completely. What I am going to talk about is based on the knowledge of 180 patients who have been published in the literature and who were able to maintain fertility after chemotherapy in the assistant. What we know is based on less than 200 patients. Most of these studies, as I said before, are retrospective, except for Vincenzo's, which I will talk about shortly. The methodological images are different in all of them, the chemotherapy agents, the number of cycles, the moment when the lymphadenectomy is done, if before or after, the type of surgery that is done, the indications, the follow-up cycles according to each institution, and, of course, not all the information is available. I want to answer some questions throughout the talk, which are the questions that worry us the most. The first is whether it is safe to offer primary tracheotomy to patients with tumors greater than 2 cm. About five years ago, we published this review where we did a recount of what was in the literature, and taking into account almost 200 publications we were able to get up front for tumors greater than 2 cm the recurrence rate of 6%, which is what we more or less understand as the recurrence rate of tracheotomy. So, from the oncological point of view, it seems safe to offer tracheotomy to these patients. The death rate is less than 1%, and fertility could be preserved in a significant percentage in this series. What is the problem? The problem is that when we operate these patients with tumors greater than 2 cm, in this study in memory of the Sloan-Kettering Cancer Center, the rate of fertility preservation by doing primary tracheotomy in this size is 30%. This is a rate that I cannot offer to a family that comes to me as a doctor to preserve the reproductive function, and then I go out with the fact that I only preserve it to 30% of the patients that come to me. A similar rate in this study of the group that described the radical abdominal tracheotomy by Dr. Laszlo Ungar, because the risk factors are increasing, both the risk-intermediate factors and the risk-heavy factors, such as ganglion compromise, and many of these patients end up requiring help, and fertility cannot be preserved. That is why the help chemotherapy arises. These are some photos of some of the articles published, where we see some large tumors before and after chemotherapy. This is one of our publications, a patient who had a tumor of 4 cm, and we gave him help chemotherapy, and he had a complete response. This is a publication by Dr. Marchiole, where he shows us the photo of the physical exam, the photo of the ultrasound, and the photo of the resonance, how the tumor responds completely after chemotherapy. We have to offer something to our patients. When patients are pregnant and have cancer, and those cancers are surgical, when patients want to preserve fertility, there are several options. Tracheotomy in its various forms, simple chemotherapy with lymphadenectomy or determination of the ganglion state, even laconization plus determination of the ganglion state, as demonstrated by the CONSERVE study, and help chemotherapy plus surgery. The first case was reported 14 years ago by Dr. Marie Plante, where she tells us the result with two patients, and there is a controversy that Fabio mentioned something about it. Help chemotherapy reduces the tumor size and makes the cases that were not operable, they were after chemotherapy, it seems that it increases the sensitivity network, and it seems that it also fights or treats the nodal micrometastatic disease, that is, it prevents an important amount of recurrences, and it has been identified as an important prognostic factor in some publications. Within the CONS, within the adverse things for help chemotherapy, patients who do not respond to chemotherapy are making a delay in their treatment, and that help chemotherapy could select some clones that could become later radio-resistant. The second question would be if help chemotherapy does a downstaging of ganglion disease, and recently this meta-analysis was published, this is from November, where they take into account studies of help chemotherapy not for fertility preservation, but for radical hysterectomy, and they look at the difference in ganglion commitment in patients who received chemotherapy versus those who were operated on initially. And look, in this study of CAI, the percentage of ganglion commitment is 9% in those who received chemotherapy versus almost 30%, three times more in those who were operated on initially. This is 25% against 42%, 32% against 39%, 8% in this Argentine study of Juan Sardi, 8% after chemotherapy versus 31% before chemotherapy, almost four times more, 17% versus 34%. In other words, at least in these clinical trials, it has been seen that patients who receive help chemotherapy exhibit a lower ganglion commitment. If you think logically, they probably had the same ganglion commitment as those who were operated on, but they had the ability to reduce that ganglion commitment. And what is the rate of ganglion commitment in tumors of 2 to 4 centimeters? It depends on where we look. Let's look at this study, this is from Vietnam, this is from Thailand, which puts more than 1,200 patients subjected to radical hysterectomy published in 2010, and for the 1V1 of 2009, that is, tumors smaller than 4 centimeters, the rate of ganglion commitment is 17%. And for tumors larger than 4 centimeters, the rate of ganglion commitment is almost 25%. I think the most important study that considers this incidence of risk factors by tumor size was published by PARC in 2010, and I always show it because I love it. And here we have how, for tumors, this study includes more than 1,400 patients. In tumors of less than 2 centimeters, the pelvic cancer compromise rate is 6%, shown in the CONSERV with 5.4%, in tumors of 2 to 4 centimeters, which is the size that matters to us, 18 to 4 centimeters. When tumors exceed 4 centimeters, it doubles and the cancer compromise rate can go up to 36%. And what is the cancer compromise rate that we have in patients who have received chemotherapy with the purpose of preserving fertility? Well, basically, out of 180 patients, 8. In other words, the cancer compromise rate in these patients reported in the literature after chemo is 4.2%. So it seems that this cancer compromise after chemotherapy will adapt to the tumor size that remains after chemotherapy. It is not the 18% that we would originally have, 2 to 4 centimeters. It goes down to 4%. So the main question and the main reason for controversy is, is it mandatory to have a pelvic lymphadenectomy before giving chemotherapy? Because these patients are more likely to have cancer compromise. And let's say the controversy began with this study by Dr. Berselino. This was published in Gynecological Oncology in 2012. It is a retrospective, although they say that the oncological links were looked at in a prospective way, and it included 18 patients. And of those 18 patients with tumors greater than 2 centimeters, 12 had cancer compromise. In other words, the cancer compromise rate is 67%, 2 out of 3. They say in this paper that, for this observation, in this retrospective study of these 18 patients, pelvic lymphadenectomy should always be done before giving chemotherapy to the adjuvant. By dissecting the study a little, we see that of these 12 patients, 4 had tumors greater than 4 centimeters, where the cancer compromise is greater. And then I invite you to look at the number of ganglions obtained in pelvic lymphadenectomy, 1 out of 48, 2 out of 49, 11 out of 48. In other words, today, who extracts 48 pelvic ganglions? Let's say it seems that there was a notable effort by the doctors to demonstrate ganglion disease, to find a 66% ganglion compromise, different from everything else shown in the literature. And they unfortunately do not report how those lymphatic ganglions were processed. The European guide, then, based on this study, says that pelvic lymphadenectomy must be done to all patients, that a fertility preservative surgery will be done. And this then has become almost as if it were the eleventh commandment. We are going to do pelvic lymphadenectomy to all patients before giving chemotherapy. And probably this could not be true. And it is more an opinion of experts than a data supported by the literature, as I am going to show you. Look at this 67%, based on 18 patients against 18% based on more than 615 patients. I think there is an important bias in the information that this study gives us. And to top it off, I'm going to ask you this question. Think about the radical hysterectomies that you have done to patients with tumors between two and four centimeters. Think about how many of those were sent to radiotherapy for ganglions. With all certainty, they are not 66%. Because if that were the ganglion commitment rate, then we would have to rethink what we do to patients who do not want to preserve fertility with tumors of two to four centimeters. And we would have to do a different strategy, the one we do today, which is to take them to surgery. Going back then, we have 24 articles. I already explained to you that there are only nine major series. Of those nine, I selected for the purposes of the presentation and for the purposes of time, seven that report recurrences. Here is the one from the NOSCA, which is from the series of Dr. Kohler in Germany. Sostercil and Tesfai are from the Netherlands. This is from Dr. David Zivula's group, Dr. Slama. This is from Elena Roa, from the group of Dr. Lukas Ropp. And this is from Vincenzo, from the group of Dr. Ana Fagotti and Dr. Giovanni Scambia. These are studies that have between nine and 28 patients. And I also want to highlight this one, which is the largest study. It was recently published in the International Journal of Gynecological Cancer. It is a work led by Gabriel Rendon from Colombia. It has 23 patients. It is a retrospective analysis. It becomes the study that has the most patients in literature with fertility preserved with 23. We see, these are the studies included that have recurrences. And we see that, for example, in the series of Marchiol, of Tesfai, and in this study, they put patients in which lymphadenectomy is done before or in which lymphadenectomy is done later. And this leads to some medical oncologists of the teams demanding that patients have lymphadenectomy because they are not very convinced that one should give chemotherapy before without certifying the ganglion state. Even the Rendon study has patients who had trachelectomy, abdominal radical trachelectomy, paroscopic radical trachelectomy and cold cone after chemotherapy. And this one from Vincenzo is the only prospective in the literature of adjuvant chemotherapy and surgery. And the surgery that was done later was a conization. So he put 11 patients at the end with a 9% recurrence rate. I'm going to show you. First 25 patients were seen. 13 patients were selected for adjuvant chemotherapy. Of those, 11 responded because two had a stable disease, progressed, and according to the protocol, something else was done. And of these 11 patients, all were adjuvant chemotherapy. And of those 11 who went to conization, a 6% radical tracheectomy. And in the end, from the analysis for recurrence, they were a recurrence. Of the 11 patients, a recurrence. And characteristically, that patient did not recur locally, he recurred at a distance in the liver. And in this study, also for the first time, they consider the detection of ganglion as a strategy to determine the ganglion commitment in these patients. All these patients were adjuvant chemotherapy before surgery. What is there then in the literature regarding the moment of adjuvant chemotherapy? Because if you have to do adjuvant chemotherapy before, we would have to have better results. When adjuvant chemotherapy is done before surgery, and this was in 45 patients, the recurrence rate is 13%. When adjuvant chemotherapy is done later, the recurrence rate is 16% and there seems to be no difference. I'm sorry I can't show you a P value because it would not be legal with different inclusion criteria, different methodologies, to put a P. I'm just going to show you absolute values and each one will take it, will adopt this information as soon as they have it. Regarding the type of surgery, there are 89 patients who were given some form of radicality, either abdominal, vaginal, laparoscopic or robotic. And there are 44 patients who were given simple or conical trachelectomy because they exhibited a good, adequate response after chemotherapy. The general recurrence rate is 13%. When we compare the patients who were given radicality, the recurrence rate is 11%. And the patients who were not given radicality, the recurrence rate is 22%. I clarify again that I don't know if there is a statistically significant difference because this comparison is not legal. However, the recurrence rate is twice as high, at least when we do conization in patients who responded completely. The recurrence rate is unparalleled compared to the other forms of 1% for non-adjuvant chemotherapy and surgery. In the most complete review made to date, which was published by Enrica Ventibeña, it has two publications, an enlistment of oncological detachment in fertility preservation and this one in fertility and sterility and obstetric detachment, tells us that there is a 77% pregnancy rate and a 76% birth rate for non-adjuvant chemotherapy. What do we know so far about this problem? That there is no apparently significant difference in the oncological detachment. If one does the lymphadenectomy first and then the chemo, or first gives the chemo and then does the lymphadenectomy in patients with negative images. What we know is based on 180 patients in 24 articles. There is a lot of heterogeneity regarding chemotherapy agents and the time the agents are given and the number of cycles, the surgical treatment after non-adjuvant chemotherapy and there is a variable response rate, both pathological, imaginological and complete responses and those definitions vary between studies. And of course there is controversy regarding the moment of doing the lymphadenectomy. So what do we need? To do a clinical trial perspective where hopefully all patients have the same surgical approach and personally I think that we have to give some form of radicality for the data of this retrospective review that all patients receive the same chemotherapy, the role of the previous lymphadenectomy has to be still defined. How are we going to process these lymphatic ganglions if we are going to consider sentinel or not? What is the best imaging study we have? And it is very difficult, very difficult to get these patients. The clinical prospective trial that is being carried out is led by Dr. Marie Plante from Quebec in Canada, she is the countess. We publish the protocol in the International Journal of Gynecological Cancer. Basically, they are looking for older patients with uterine cancer, older than 2 centimeters and younger than 4, scamoso adenovirus and non-scamoso. All of them are going to have a previous lymphadenectomy and only patients with negative ganglion are going to be administered an adjuvant chemotherapy. There are some criteria for preservative fertility surgery and there are also some criteria for neoadjuvant therapy. After the three cycles, a nuclear magnetic resonance will be made and if it does not respond, there is no progression, they are going to be removed from the study. If there is a complete or partial response, they can be offered in simple or conical trachelectomy or simple or conical trachelectomy and adjuvant therapy will be done according to the findings. And if there is a suboptimal response, the tumor is greater than 2 centimeters, it will be removed from the study. It is noteworthy that radical trachelectomy is not considered because we see that at least in retrospect, the recurrence rates of conical trachelectomy and simple trachelectomy can reach 22%. As conclusions, I mean that the preservation of fertility after neoadjuvant chemotherapy reaches 90% and is comparable to all other forms of preservative surgery for cancer of the uterine neck. The D-cycle and the survival are equivalent to all other types of preservative fertility surgery. The ideal regime has not been determined, basically they are based on platinum, either cisplatin or carpoplatin, usually with Paclitaxel, but in some protocols they have given hemsitabine and other drugs. There is no agreement between the best surgical approach, there is no agreement between whether to do the lymphadenectomy first or do it later in those patients who do not require ganglion commitment in the images. And obviously we need the countess and other studies that can be done on this to answer all these questions. And that was my message. Thank you very much. Thank you very much, René, for the excellent presentation. Next, the questions of this next cancer module of service. A question for Dr. Miriam Perrota. Currently, with the frequency of intraepithelial neoplasms, the NIC1 or NIC3 treated, the question they ask us is, should these patients be vaccinated with NIC1 or NIC3 that have been treated? Well, the first thing we need to know is that the vaccine is prophylactic, it is not a curative vaccine. And that the NIC1 or the SYN1 is not treated, they are patients that must be controlled. With respect to the intraepithelial neoplasm 3 or 2+, SYN2, P16 positive, that is, the true precursor of cancer, there are studies indicating the vaccine, but with the aim of reducing the recurrence of the disease. That is, the vaccine is not used to cure the established virus or the lesion that the virus originated in the uterus. For SYN3, as a subsequent treatment, in order to avoid recurrence, yes. In SYN1, no. Anyway, we have to consider that there may be a scenario to vaccinate older patients. In that case, the doctor will have to assess the risk and the correct indication, but that clearly the vaccines are prophylactic and that to reduce uterine cancer, it is necessary to vaccinate the ideal target population, which are naive girls. I don't know if that was answered. For Dr. Perrota, also another question. Of the three components of the initiative to eliminate neck cancer of the World Health Organization, which do you think is the most difficult to implement or the most ambitious? Well, I think the three legs are ambitious. Vaccines in our continent, in Latin America, are already incorporated in the vast majority of countries. The important thing is to achieve adequate coverage in each country. But when we saw the distribution map, there are many countries with high incidence of cancer that still do not have the vaccines incorporated. So that is a challenge. It seems to me like a very important challenge to achieve a screening and a screening with a BPH test, which, as we all know, is the screening method par excellence today, because it is clearly much more sensitive than cytology. So I think that is a challenge that is quite difficult to achieve, to screen at least once with a BPH test for women over 35 and 40 years old. And the third leg, which is to give an adequate treatment to the sick patient. This is also a challenge. But I think that in our countries, the big drawback is that we do not have centralization of treatments. Because if we could have centers of derivation to treat neck cancer, I think that if we analyze in our countries, this is feasible. However, other components are already entering here, other situations that are out of the reach of doctors. But I think that to provide an adequate treatment, we need to center the treatment and the management of patients with cervical cancer. And finally, I want to say that another very important challenge for our countries is to have records. If we do not have adequate records, it will be very difficult for us to reach the objectives proposed by WHO. We all know that in our records they say uterine cancer. It is difficult to define the real incidence and mortality that we have. Thank you, doctor. You touched on a fundamental issue, the records. The one who does not tabulate, fabulates. Totally. It is like that. It is like that, absolutely. And that is a very difficult challenge. Very good. For Dr. Juliana, when we talk about cancer and breastfeeding, it is very difficult to manage both the mother and the child. So there is a question that they ask us, regardless of the moment or the situation we are in, what is going to be the determining factor that tells us when to end the gestation, regardless of the gestational age? Perfect. As I mentioned, the evidence is scarce. However, there are some aspects that are common in all the evidence. Basically, patients who have surgical stages that have been taken to pelvic lymphadenectomy and that we document metastatic disease in those glands, it is an indication of termination of the pregnancy. Patients who initially debut with a 4B stage, we already know the basis of their disease prognosis, so it is not recommended to continue the pregnancy. Patients who have progression during non-adjuvant chemotherapy management have potentially also been placed as candidates. In any case, I want to emphasize that although we have strong oncological decisions to advise the patient, in the end it is she who decides what management she wants to receive and whether or not to continue the gestation. I think that is very important to emphasize. Correct. For Dr. Rodríguez, Juliana asks the following, in the setting of uterine cancer and pregnancy, a patient with indication of radiotherapy, which is given neoadjuvant chemotherapy during pregnancy, and that later, at the time of cesarean section and radical hysterectomy, there is no disease in the residual piece, does it have, under your criteria, indication of subsequent radiotherapy? Well, it's a super interesting question, and I also want to clarify that with those less than 100 published cases, the specific scenario is not delimited, as they are asking me. In the larger series, in the review, in fact, there was a complete answer of 8%. So, what all the authors point out is, give her the adjuvant chemotherapy and give her the standard or primary management. If that patient already received primary management, discuss it in a multidisciplinary meeting, make the best decision. Personally, I think that if she does not have additional factors for adjuvancy in that piece, then she would not need that radiotherapy. I want to tell you about the Latin American experience of the series. There was a specific case, and very similar to what they are asking in the auditorium, and it was for a meeting and a consensus of all the experts of that clinic that it was defined to give adjuvant radiotherapy for the benefit of this patient. But let's say that finally the answer is left to the discussion of the multidisciplinary group. There is no evidence that any of the two alternatives are valid. Very good. For Dr. Fabio, we basically have, for example, in institutions like the ones I work in, there is a lot of control in what studies or trials are with people. Descriptive studies do not have much value if you do not compare them with others. So, doing adjuvancy in cancer in women who are gestating is difficult, unlike other institutions where they can have that freedom. So, there is a question that tells us in Milan, to which patient is adjuvant chemotherapy administered today in cases that are not associated with gestation? Before surgery. So, you have to do it in a clinical study, because, as I said, the evidence from the three clinical trials of phase 3 says that you have to do chemotherapy. And they are young patients, here I have a cousin B3, or I have a cousin B2, 2A1, with an extremally interrupted ring, which are the patients who are going to be operated on in the first instance, for sure they will have an adjuvant radiotherapy. What we try to do is to avoid radiotherapy in young patients, because, as we have also seen in the study of Gupta, there are vaginal sexual collateral effects that are achieved up to two years or more after the treatment. These are the patients that I have to do. First of all, the patients have to do a dissonance and a PET to evaluate that they do not have a distance disease or a nodal disease. Thank you very much, Dr. For Fabio, a question, what is your opinion on the dense dose schemes based on platinum taxol? And if it is required, do the patients pass the Leuven schemes? And if the patients undergo a preoperative radiological study or a previous laparoscopy? As I said before, the patients have to do a radiological study with resonance to see the size, something reproducible of the size of the neck, and a PET or a TAC to see that there is no distance disease. On the neoadjuvant regimen, there is data from phase 2 studies that put every week the taxol and the platinum, it can be the carb, the cisplatin. There are different schedules in different studies. There is not yet a certain data of what is the best. For sure, we know that what was the conventional, before the three-seminar manual, taxol and possibly platinum, which was tested here in Italy in the SNAP, is the best in terms of pathological response, complete on the body, but it is the most toxic. So now, here in Italy, what I do in neoadjuvance, I make a scheme of two dens with carb or taxol, every six or nine cycles, it depends on the response of what you have to do. The goal is to try to avoid doing a trimodality, doing neoadjuvance, surgery and radiotherapy. This is the best it can be, which is what we have seen in the previous studies, in Sardi, up to 90% received that, and in the other studies, more or less 30%. We have to select the patients who can do a different treatment from what is the standard, but we have to be sure that it will not end with a trimodality. Thank you very much. And to finish, because we are a little out of time, but we are still, I think, for Dr. René Pareja. Dr. René Pareja, is it necessary to know the ganglion state prior to the study of fertility preservation? And if it is considered, because you spoke of simple or radical tracheotomy, is this considered an adequate option? Rene? I think he got out. I think he has problems with his... Yes, he got out. I think he got out of the internet. Let's continue. There is a question that I don't know, while René gets informed. Yes. It could also be for René or for the doctor, for Fabio. If there is a complete pathological response after neo-adjuvant chemotherapy in a cone, does it offer a less radical surgery, a type A, type B stereotomy? There is no data about what to do after neo-adjuvant. I personally believe that you can do a less radical surgery. You can offer a type B and take into account the initial stage. Because if the patient had an initial interest in a parameter you can do a type C on one side and a type B on the other. You have to personalize the treatment. This, as I said before, is not the standard. The standard is chemotherapy. So everything you do with neo-adjuvant in cervical cancer, you have to personalize and you can get the patient used to it. We hope to see the data of the Shape study to see if we can do a less radical surgery also in initial cancers. We will see, because for sure neo-adjuvant will reduce the data of micrometastases and positive ganglions as you have seen in my presentation of DNA. So doing an extra radical surgery does not make much sense if you do not express the philosophy of the Germans who do only a super radical surgery without doing anything else after. I leave it to him. Doctor Ara, can I ask a question while we wait for René? Yes, Doctor Ara. Hello, what a pity. René is not here, so we leave it. René, there was a question for you about the preservation of fertility. Is it necessary to conclude that ganglion study is necessary before this strategy? And if so, when we talk about tracheotomy, the simple radical, which do you consider an option? It is the opposite. Today we do not know if we have to remove the ganglions before or not, because if the images do not say that there is a ganglion commitment, there is a very high chance that chemotherapy sterilizes those ganglions. So today we do not know if that has to be done that way. Probably the countess, if it is carried out and the patients who are going to be recruited are recruited, can give us information about it. But we do not have with the current evidence a way to certify that this must be done to all patients, because in fact more than half of the patients have been done the opposite and the recurrence rates are similar. And at least, according to what has been shown, the retrospective analysis seems to have more recurrences when conization is done in patients who had a complete response. The countess should also give us information in perspective about that aspect. But unfortunately with what is available in the literature, it is impossible to determine what is the best behavior in these patients. If you ask me personally, I believe that patients, if the images are negative, one can proceed with chemotherapy, do the cleaning and should give some degree of radicality in their surgery. That is my personal answer. Thank you very much. In the spirit of time, I believe we have fulfilled the goal of the morning. We have had a very high-level event. Our thanks from Latin America to the organization led by Dr. Ramirez and all the IGCS. A thank you also to all the speakers who have had the time, the dedication to make their best presentation and especially in Spanish, because we have had a great audience. We have reached almost 300 participants. From there, thank you to all. A special thank you to René, because he has been the one who has had us there organizing us and the truth is that it has come out, in my opinion, it has come out very well. A thank you to all. We hope that this will be repeated. The commitment from Peru and I think that it is very important for Latin America to be able to participate in these events. Thank you very much for your participation. See you. Thank you all. Thank you. Goodbye.

gynecologic oncology

cervical cancer during pregnancy

surgical treatment advancements

neoadjuvant therapy

TRUST trial

treatment approaches efficacy

treatment approaches safety

evaluation in gynecologic oncology

imaging techniques

structured radiology reports

chemotherapy as adjuvant therapy

individualized treatment plans

pregnancy stage and treatment

tumor characteristics

cisplatin and platinum-based chemotherapy