Eficacia y seguridad de olaparib como terapia de mantenimiento en pacientes con cáncer de ovario, de trompas de falopio, o peritoneal primario, recurrente, sensible a la quimioterapia basada en platino / Efficacy and safety of olaparib as maintenance therapy in patients with primary, recurrent ovarian, fallopian tube, or peritoneal cancer sensitive to platinum-based chemotherapy

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen, el que expone la evaluación de la eficacia y seguridad de olaparib como terapia de mantenimiento en pacientes con cáncer de ovario, de trompas de Falopio, o peritoneal primario, recurrente, sensible a la quimioterapia basada en platino. Así, el Dr. Miguel Ángel Ticona Castro, médico especialista en oncología del Servicio de Oncología del Hospital Nacional Edgardo Rebagliati Martins de la Red Prestacional Rebagliati, siguiendo la Directiva N° 003-IETSI-ESSALUD-2016, envió al Instituto de Evaluación de Tecnologías en Salud e Investigación ­ IETSI la solicitud de uso por fuera del petitorio del producto farmacéutico olaparib. ASPECTOS GENERALES: En el 2019, en Perú se diagnosticaron aproximadamente 1237 nuevos casos de cáncer de ovario, con 771 muertes atribuidas a la enfermedad (Institute for Health Metrics and Evaluation 2022). El cáncer de ovario epitelial seroso es la histología que se encuentra con más frecuencia en los cánceres de ovario avanzados, y entre 20 % y 30 % de los cánceres de ovario serosos de alto grado tienen la mutación del gen del cáncer de mama 1 o 2 (BRCA 1/2). El tratamiento estándar para el cáncer de ovario, de trompas de Falopio, o peritoneal primario (en lo sucesivo denominados colectivamente como cáncer de ovario) incluye la cirugía y la quimioterapia basada en platino. A pesar de las altas tasas de respuesta esperadas (75 % al 85 %), la recurrencia es probable en la mayoría de las mujeres. Si esta recurrencia ocurre seis meses o más después de la última quimioterapia basada en platino, los pacientes se clasifican como sensibles al platino. Tras la respuesta a la quimioterapia basada en platino, la estrategia de tratamiento estándar actual a nivel internacional es "observar y esperar" si se vuelve a dar una progresión de la enfermedad (CADTH 2017; Ray-coquard et al. 2020). METODOLOGÍA: Se realizó una búsqueda sistemática utilizando las bases de datos PubMed, Cochrane Library y LILACS. Además, se realizó una búsqueda dentro de bases de datos pertenecientes a grupos que realizan evaluaciones de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), incluyendo el Scottish Medicines Consortium (SMC), el National Institute for Health and Care Excellence (NICE), la Canadian Agency for Drugs and Technologies in Health (CADTH), la Haute Autorité de Santé (HAS), el Institute for Quality and Efficiency in Health Care (IQWiG), el Instituto de Evaluación Tecnológica en Salud de Colombia (IETS), la Comissáo Nacional de Incorporacáo de Tecnologias no Sistema Único de Saúde (CONITEC), entre otros. Asimismo, se revisó la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA) y páginas web de sociedades especializadas en el manejo del cáncer como la National Comprehensive Cancer Network (NCCN), la European Society for Medical Oncology (ESMO), la American Society of Clinical Oncology (ASCO), y la Sociedad Española de Oncología Médica (SEOM). Adicionalmente, se hizo una búsqueda en las páginas web del registro de ensayos clínicos administrado por la Biblioteca Nacional de Medicina de los Estados Unidos (https://clinicaltrials.gov/) y de la International Clinical Trial Registry Platform (ICTRP) (https://apps.who.int/trialsearch/), para identificar ensayos clínicos en curso o cuyos resultados no hayan sido publicados. La búsqueda de literatura se limitó a GPC, ETS, revisiones sistemáticas con metaanálisis de ensayos clínicos aleatorizados (ECA) y ECA que abordaran la pregunta PICO del presente dictamen. Se incluyeron las publicaciones en inglés y español. Se excluyeron los ensayos clínicos no aleatorizados, los estudios observacionales, las series de casos, los reportes de casos, las cartas al editor, los comentarios, las editoriales y los resúmenes de congresos. Teniendo en cuenta que los datos finales de los estudios SOLO2 y Studyl9 (estudios pivotales de olaparib en cáncer de ovario recurrente) se publicaron recientemente, en marzo de 2021 y octubre de 2018, respectivamente, solo se incluyeron las revisiones sistemáticas con meta-análisis si incluían los datos finales de ambos estudios. En cuanto a las GPC, se priorizaron aquellas que utilizaron sistemas de gradación para el nivel de evidencia y el grado de las recomendaciones brindadas. RESULTADOS: La búsqueda de literatura permitió identificar 13 publicaciones que aportan información de relevancia para fines de la presente actualización: cuatro GPC realizadas por la NCCN (NCCN 2022), la SEOM (Redondo et al. 2021), la ASCO (Tew et al. 2020), y la ESMO (ESMO 2020); cinco ETS elaboradas por el NICE de Inglaterra y Gales (NICE 2020), el IQWiG de Alemania (IQWiG 2018), la CADTH de Canadá (CADTH 2017), el SMC de Escocia (SMC 2016), y la HAS de Francia (HAS 2015); y cuatro publicaciones de ECA: dos publicaciones del ECA de fase II Studyl9 (Ledermann et al. 2012; Friedlander et al. 2018) y dos publicaciones del ECA de fase III SOLO2 (Pujade-lauraine et al. 2017; Poveda et al. 2021). CONCLUSIÓN: Por todo lo expuesto, el IETSI no aprueba el uso de olaparib como terapia de mantenimiento para pacientes con cáncer de ovario, con o sin mutación BRCA, recurrente, sensible a la quimioterapia basada en platino, que hayan recibido al menos 2 líneas previas de quimioterapia basada en platino, con respuesta completa o parcial a su régimen más reciente.

Eficacia y seguridad de olaparib como terapia de mantenimiento en mujeres adultas con cáncer de ovario epitelial avanzado, de trompas de falopio o peritoneal primario con mutación de brca de línea germinal o somática que presentan respuesta completa o parcial a la quimioterapia basada en platino de primera línea que no recibieron bevacizumab / Efficacy and safety of olaparib as maintenance therapy in adult women with somatic or germline BRCA-mutated advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer who have a complete or partial response to first-line platinum-based chemotherapy who did not receive bevacizumab

ANTECEDENTES: En el marco de la metodología ad hoc para evaluar solicitudes de tecnologías sanitarias, aprobada mediante Resolución de Instituto de Evaluación de Tecnologías en Salud e Investigación N° 111-IETSI-ESSALUD-2021, se ha elaborado el presente dictamen, el cual expone la evaluación de la eficacia y seguridad de olaparib como terapia de mantenimiento en mujeres adultas con cáncer de ovario epitelial avanzado, de trompas de Falopio o peritoneal primario con mutación de BRCA de línea germinal o somática que presentan respuesta completa o parcial a la quimioterapia basada en platino de primera línea que no recibieron bevacizumab. Así, el Dr. Miguel Ticona Castro, médico oncólogo del Hospital Nacional Edgardo Rebagliati Martins, siguiendo la Directiva N° 003-IETSI-ESSALUD-2016, envía al Instituto de Evaluación de Tecnologías en Salud e Investigación ­ IETSI, la solicitud de uso fuera del petitorio del producto olaparib. METODOLOGÍA: Se realizó una búsqueda bibliográfica exhaustiva en las bases de datos PubMed, The Cochrane Library y LILACS. Asimismo, se realizó una búsqueda manual dentro de las páginas web pertenecientes a grupos que realizan evaluaciones de tecnologías sanitarias (ETS) y guías de práctica clínica (GPC), incluyendo la National Institute for Health and Care Excellence (NICE), Canadian Agency for Drugs and Technologies in Health (CADTH), Scottish Medicines Consortium (SMC), Instituto de Calidad y Eficiencia en la Atención de la Salud (IQWiG, por sus siglas en alemán), Haute Autorité de Santé (HAS), el Instituto de Evaluación Tecnológica en Salud (IETS), el Instituto de Efectividad Clínica y Sanitaria (IECS), Comissão Nacional de Incorporação de Tecnologias no Sistema Único de Saúde (CONITEC), la Base Regional de Informes de Evaluación de Tecnologías en Salud de las Américas (BRISA), el Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI), Centro Nacional de Excelencia Tecnológica en Salud (CENETEC) , Agency for Healthcare Research and Quality (AHRQ), Scottish Intercollegiate Guidelines Network (SIGN), Guidelines International Network (GIN), National Health and Medical Research Council (NHMRC), New Zealand Guidelines Group (NZGG), European Society for Medical Oncology (ESMO), National Comprehensive Cancer Network (NCCN). Además, se realizó una búsqueda de GPC de las principales sociedades o instituciones especializadas en oncología y ginecología oncológica, tales como: la American Society of Clinical Oncology (ASCO), Sociedad Española de Oncología Médica (SEOM), y la International Federation of Gynecology and Obstetrics (FIGO). Finalmente, se realizó una búsqueda adicional en la página web de registro de ensayos clínicos (EC) www.clinicaltrials.gov, para identificar EC en curso o que no hayan sido publicados aún. La búsqueda de literatura se limitó a GPC, ETS, revisiones sistemáticas (RS) con metaanálisis de ECA de fase III y ECA de fase III. RESULTADOS: Luego de la búsqueda bibliográfica (hasta diciembre de 2021), se incluyeron 5 GPC desarrolladas por la NCCN (National Comprehensive Cancer Network 2021), la ASCO (Tew et al. 2020), la Cancer Care Ontario (Hirte et al. 2021), la ESMO (Colombo et al. 2019) y la SEOM (Redondo et al. 2021); así como 3 ETS realizadas por CADTH, NICE e IQWiG (Institute for Quality and Efficiency in Health Care 2019, The CADTH pan- Canadian Oncology Drug Review (pCODR) 2019, The National Institute for Health and Care Excellence 2019), y un ensayo clínico aleatorizado (ECA) de fase III de doble ciego denominado SOLO-1 (NCT01844986) con tres publicaciones de un análisis interino (Moore et al. 2018), de calidad de vida (Friedlander et al. 2021) y una con seguimiento hasta cinco años de seguimiento (Banerjee et al. 2021). CONCLUSIÓN: Por lo expuesto, el Instituto de Evaluación de Tecnologías en Salud e Investigación aprueba el uso de olaparib como terapia de mantenimiento en mujeres adultas con cáncer de ovario epitelial avanzado, de trompas de Falopio o peritoneal primario con mutación de BRCA de línea germinal o somática que presentan respuesta completa o parcial a la quimioterapia basada en platino de primera línea que no recibieron bevacizumab. La vigencia del presente dictamen es de un año y se debe asegurar un sistema de farmacovigilancia intensiva de los pacientes que lleguen a usar olaparib, según lo establecido en el Anexo N° 1. Asimismo, la continuación de dicha aprobación estará sujeta a la evaluación de los resultados obtenidos y de mayor evidencia que pueda surgir en el tiempo.

Artificial intelligence-based image analysis can predict outcome in high-grade serous carcinoma via histology alone.

High-grade extrauterine serous carcinoma (HGSC) is an aggressive tumor with high rates of recurrence, frequent chemotherapy resistance, and overall 5-year survival of less than 50%. Beyond determining and confirming the diagnosis itself, pathologist review of histologic slides provides no prognostic or predictive information, which is in sharp contrast to almost all other carcinoma types. Deep-learning based image analysis has recently been able to predict outcome and/or identify morphology-based representations of underlying molecular alterations in other tumor types, such as colorectal carcinoma, lung carcinoma, breast carcinoma, and melanoma. Using a carefully stratified HGSC patient cohort consisting of women (n = 30) with similar presentations who experienced very different treatment responses (platinum free intervals of either ≤ 6 months or ≥ 18 months), we used whole slide images (WSI, n = 205) to train a convolutional neural network. The neural network was trained, in three steps, to identify morphologic regions (digital biomarkers) that are highly associating with one or the other treatment response group. We tested the classifier using a separate 22 slide test set, and 18/22 slides were correctly classified. We show that a neural network based approach can discriminate extremes in patient response to primary platinum-based chemotherapy with high sensitivity (73%) and specificity (91%). These proof-of-concept results are novel, because for the first time, prospective prognostic information is identified specifically within HGSC tumor morphology.

Health Care Provider Adherence to Surgical Guidelines for Risk-Reducing Salpingo-Oophorectomy.

OBJECTIVE: To evaluate health care provider adherence to the surgical protocol endorsed by the National Comprehensive Cancer Network and the American College of Obstetricians and Gynecologists at the time of risk-reducing salpingo-oophorectomy and compare adherence between gynecologic oncologists and obstetrician-gynecologists (ob-gyns). METHODS: In this multicenter retrospective cohort study, women were included if they had a pathogenic BRCA mutation and underwent risk-reducing salpingo-oophorectomy between 2011 and 2017. Adherence was defined as completing all of the following: collection of washings, complete resection of the fallopian tube, and performing the Sectioning and Extensively Examining the Fimbriated End (SEE-FIM) pathologic protocol. RESULTS: Of 290 patients who met inclusion criteria, 160 patients were treated by 18 gynecologic oncologists and 130 patients by 75 ob-gyns. Surgery was performed at 10 different hospitals throughout a single metropolitan area. Demographic and clinical characteristics were similar between groups. Overall, 199 cases (69%) were adherent to the surgical protocol. Gynecologic oncologists were more than twice as likely to fully adhere to the full surgical protocol as ob-gyns (91% vs 41%, P<.01). Specifically, gynecologic oncologists were more likely to resect the entire tube (99% vs 95%, P=.03), to have followed the SEE-FIM protocol (98% vs 82%, P<.01), and collect washings (94% vs 49%, P<.01). Complication rates did not differ between groups. Occult neoplasia was diagnosed in 11 patients (3.8%). The incidence of occult neoplasia was 6.3% in gynecologic oncology patients and 0.8% in obstetrics and gynecology patients (P=.03). CONCLUSION: Despite clear surgical guidelines, only two thirds of all health care providers were fully adherent to guidelines. Gynecologic oncologists were more likely to follow surgical guidelines compared with general ob-gyns and more likely to diagnose occult neoplasia despite similar patient populations. Rates of risk-reducing surgery will likely continue to increase as genetic testing becomes more widespread, highlighting the importance of health care provider education for this procedure. Centralized care or referral to subspecialists for risk-reducing salpingo-oophorectomy may be warranted.

Morbidity after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with carboplatin used for ovarian, tubal, and primary peritoneal cancer.

BACKGROUND AND OBJECTIVES: Hypertherm intraperitoneal chemotherapy (HIPEC) is increasingly used in the treatment of ovarian, tubal, and primary peritoneal cancer (OC). The aim was to evaluate short-term morbidity of cytoreductive surgery (CRS) and carboplatin HIPEC. METHODS: Prospective feasibility study performed from January 2016 to December 2017. Twenty-five patients with primary OC (FIGO III-IV) received upfront or interval CRS combined with carboplatin HIPEC at dose 800 mg/m 2 . Primary outcome measurements: grade 3 to 5 adverse events within 30 days according to Common Terminology Criteria for Adverse Events. Secondary outcome measurements: reoperation rate, length of hospital stay, readmission rate, and time from surgery to systemic chemotherapy administration. RESULTS: No deaths (grade 5) or grade 4 adverse events were observed. Eleven patients (44.0%) experienced at least one grade 3 adverse event, the most common being an infection (28.0%) and neutropenia (12.0%). The reoperation rate was 8.0%. The median hospital stay was 14 days (range 9-25 days), and five patients (25.0%) were readmitted within 30 days after surgery. Median time from surgery to the administration of the first dose of systemic chemotherapy was 41 days (range 24-81 days). CONCLUSION: Our small-scale prospective study supports that CRS and carboplatin HIPEC used for primary advanced-stage OC is feasible with acceptable morbidity.

Management of epithelial cancer of the ovary, fallopian tube, primary peritoneum. Long text of the joint French clinical practice guidelines issued by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY, endorsed by INCa. (Part 2: systemic, intraperitoneal treatment, elderly patients, fertility preservation, follow-up).

Adjuvant chemotherapy by carboplatin and paclitaxel is recommended for all high-grade ovarian and tubal cancers (FIGO stages I-IIA) (grade A). After primary surgery is complete, 6 cycles of intravenous chemotherapy (grade A) are recommended, or a discussion with the patient about intraperitoneal chemotherapy, according to her risk-benefit ratio. After complete interval surgery for FIGO stage III, hyperthermic intraperitoneal chemotherapy (HIPEC) can be proposed, in accordance with the modalities of the OV-HIPEC trial (grade B). In cases of postoperative tumor residue or in FIGO stage IV tumors, chemotherapy associated with bevacizumab is recommended (grade A).

[Management of epithelial ovarian cancer. Short text drafted from the French joint recommendations of FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa]. / Texte court rédigé à partir de la recommandation nationale de bonnes pratiques cliniques « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa ¼.

Faced to an undetermined ovarian mass on ultrasound, an MRI is recommended and the ROMA score (combining CA125 and HE4) can be proposed (grade A). In case of suspected early stage ovarian or fallopian tube cancer, omentectomy (at least infracolonic), appendectomy, multiple peritoneal biopsies, peritoneal cytology (grade C) and pelvic and para-aortic lymphadenectomy are recommended (grade B) for all histological types, except for the expansive mucinous subtype where lymphadenectomy may be omitted (grade C). Minimally invasive surgery is recommended for early stage ovarian cancer, if there is no risk of tumor rupture (grade B). Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). In case of ovarian, Fallopian tube or primitive peritoneal cancer of FIGO III-IV stages, thoraco-abdomino-pelvic CT scan with injection (grade B) is recommended. Laparoscopic exploration for multiple biopsies (grade A) and to evaluate carcinomatosis score (at least using the Fagotti score) (grade C) are recommended to estimate the possibility of a complete surgery (i.e. no macroscopic residue). Complete medial laparotomy surgery is recommended for advanced cancers (grade B). It is recommended in advanced cancers to perform para-aortic and pelvic lymphadenectomy in case of clinical or radiological suspicion of metastatic lymph node (grade B). In the absence of clinical or radiological lymphadenopathy and in case of complete peritoneal surgery during an initial surgery for advanced cancer, it is possible not to perform a lymphadenectomy because it does not modify the medical treatment and the overall survival (grade B). Primary surgery is recommended when no tumor residue is possible (grade B). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A).

[Malignant epithelial ovarian cancer: Role of intra peritoneal chemotherapy and hyperthermic intra peritoneal chemotherapy (HIPEC): Article drafted from the French Guidelines in oncology entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY under the aegis of CNGOF and endorsed by INCa]. / Tumeurs épithéliales malignes de l'ovaire : place de la chimiothérapie intrapéritonéale et de la chimiothérapie hyperthermique intrapéritonéale (CHIP). Article rédigé sur la base de la recommandation nationale de bonnes pratiques cliniques en cancérologie intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY sous l'égide du CNGOF et labellisée par l'INCa.

Intraperitoneal drug delivery in first-line treatment of advanced ovarian cancer have been widely studied. After a complete primary surgery or with residual disease<1cm, intraperitoneal chemotherapy significantly improves disease-free and overall survival (NP1), but with more local and systemic toxicities. Whenever this therapeutic option is under consideration, the ratio efficacy/toxicity must be carefully discussed. Intraperitoneal chemotherapy has to be considered after complete or optimal primary surgery in ovarian, tubal or primitive peritoneal carcinomatosis FIGO IIIC. This treatment must be performed by trained teams and after an assessment of the ratio efficacy/toxicity. In one randomized study, hyperthermic intraperitoneal chemotherapy (HIPEC) using cisplatinum at interval surgery demonstrated an improvement in recurrence free and overall survival compared to surgery alone, in patients initially not resectable and with residual tumor less than 1cm (complete or optimal surgery) (NP1). HIPEC has to be considered after a complete or optimal interval surgery (residu<10mm) in patients with ovarian, tubal or primitive carcinomatosis FIGO IIIC, initially not resectable (Grade B).

[Part II drafted from the short text of the French guidelines entitled "Initial management of patients with epithelial ovarian cancer" developed by FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY and endorsed by INCa. (Systemic and intraperitoneal treatment, elderly, fertility preservation, follow-up)]. / Partie 2 rédigée à partir de la synthèse de la recommandation nationale de bonnes pratiques cliniques intitulée « Conduites à tenir initiales devant des patientes atteintes d'un cancer épithélial de l'ovaire ¼ élaborée par FRANCOGYN, CNGOF, SFOG, GINECO-ARCAGY et labélisée par l'INCa. (Traitement systémique et intrapéritonéal, personnes âgées, préservation de la fertilité et suivi).

Adjuvant chemotherapy with carboplatin and paclitaxel is recommended for all high-grade ovarian or Fallopian tube cancers, stage FIGO I-IIA (grade A). After a complete first surgery, it is recommended to deliver 6 cycles of intravenous (grade A) or to propose intraperitoneal (grade B) chemotherapy, to be discussed with patient, according to the benefit/risk ratio. After a complete interval surgery for a FIGO III stage, the hyperthermic intra peritoneal chemotherapy (HIPEC) can be proposed in the same conditions of the OV-HIPEC trial (grade B). In case of tumor residue after surgery or FIGO stage IV, chemotherapy associated with bevacizumab is recommended (grade A). For BRCA mutated patient, Olaparib is recommended (grade B).

Development and Validation of Ovarian Symptom Index-18 and Neurotoxicity-4 for Korean Patients with Ovarian, Fallopian Tube, or Primary Peritoneal Cancer.

PURPOSE: The purpose of this study was to develop Korean versions of the National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy (NCCN-FACT) Ovarian Symptom Index-18 (NFOSI-18) and FACT/Gynecologic Oncology Group (FACT-GOG) Neurotoxicity 4-item (NTX-4), evaluating their reliability and reproducibility. MATERIALS AND METHODS: In converting NFOSI-18 and NTX-4, the following steps were performed: forward translation, backward translation, expert review, pretest of preliminary format, and finalization of Korean versions (K-NFOSI-18 and K-NTX-4). Patients were enrolled from six institutions where each had completed chemotherapy for ovarian, tubal, or peritoneal cancer at least 1 month earlier. In addition to demographics obtained by questionnaire, all subjects were assessed via K-NFOSI-18, K-NTX-4, and a Korean version of the EuroQoL-5 Dimension. Internal structural validity and reliability were evaluated using item internal consistency, item discriminant validity, and Cronbach's α. To evaluate test-retest reliability, K-NFOSI-18 and K-NTX-4 were readministered after 7-21 days, and intraclass correlation coefficients (ICCs) were calculated. RESULTS: Of the 250 women enrolled during the 3-month recruitment period, 13 withdrew or did not respond, leaving 237 (94.8%) for the analyses. Mean patient age was 54.3±10.8 years. Re-testing was performed in 190 patients (80.2%). The total K-NFOSI-18 and K-NTX-4 scores were 49 (range, 20 to 72) and 9 (range, 0 to 16), respectively, with high reliability (Cronbach's α=0.84 and 0.89, respectively) and reproducibility (ICC=0.77 and 0.84, respectively) achieved in retesting. CONCLUSION: Both NFOSI-18 and NTX-4 were successfully developed in Korean with minimal modification. Each Korean version showed high internal consistency and reproducibility.

Population-based study of survival for women with serous cancer of the ovary, fallopian tube, peritoneum or undesignated origin - on behalf of the Swedish gynecological cancer group (SweGCG).

OBJECTIVE: The aim of the study was to determine survival outcome in patients with serous cancer in the ovary, fallopian tube, peritoneum and of undesignated origin. METHODS: Nation-wide population-based study of women≥18years with histologically verified non-uterine serous cancer, included in the Swedish Quality Registry for primary cancer of the ovary, fallopian tube and peritoneum diagnosed 2009-2013. Relative survival (RS) was estimated using the Ederer II method. Simple and multivariable analyses were estimated by Poisson regression models. RESULTS: Of 5627 women identified, 1246 (22%) had borderline tumors and 4381 had malignant tumors. In total, 2359 women had serous cancer; 71% originated in the ovary (OC), 9% in the fallopian tube (FTC), 9% in the peritoneum (PPC) and 11% at an undesignated primary site (UPS). Estimated RS at 5-years was 37%; for FTC 54%, 40% for OC, 34% for PPC and 13% for UPS. In multivariable regression analyses restricted to women who had undergone primary or interval debulking surgery for OC, FTC and PPC, site of origin was not independently associated with survival. Significant associations with worse survival were found for advanced stages (RR 2.63, P<0.001), moderate (RR 1.90, P<0.047) and poor differentiation (RR 2.20, P<0.009), neoadjuvant chemotherapy (RR1.33, P<0.022), residual tumor (RR 2.65, P<0.001) and platinum single (2.34, P<0.001) compared to platinum combination chemotherapy. CONCLUSION: Survival was poorer for serous cancer at UPS than for ovarian, fallopian tube and peritoneal cancer. Serous cancer at UPS needs to be addressed when reporting and comparing survival rates of ovarian cancer.

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for gynecological malignancies: a single center experience.

INTRODUCTION: The objective of this study was to assess the outcome of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) plus early postoperative intraperitoneal chemotherapy (EPIC) in patients with advanced gynecological malignancies. MATERIALS AND METHODS: A retrospective series of 51 patients with advanced gynecologic cancer, evaluated between May 2008 to February 2014. Peritoneal Cancer Index (PCI) and Completeness of Cytoreduction (CCR) score were used in the study group. The study group consisted of the cancers of ovarian, fallopian tube, endometrial, and uterine sarcomas. RESULTS: Mean PCI score of the study group was 18, and the postoperative complications were similar with the literature. Patients were followed in a period of 15 days to 64 months and the mean survival time was 22.8 months. Fifty-two percent of the patients were alive without evidence of the disease and overall one-year survival was found 56%. CONCLUSIONS: The authors concluded that CRS, HIPEC, EPIC, and peritonectomy are a crucial options in patients with advanced gynecological cancers.

Effect of Prophylactic Extended-Infusion Carboplatin on Incidence of Hypersensitivity Reactions in Patients with Ovarian, Fallopian Tube, or Peritoneal Carcinomas.

STUDY OBJECTIVE: To determine whether extended-infusion carboplatin, initiated at approximately the eighth cumulative carboplatin cycle and prior to development of carboplatin hypersensitivity, reduces the incidence of carboplatin hypersensitivity reactions in patients with ovarian, fallopian tube, or peritoneal cancer. DESIGN: Retrospective chart review. SETTING: Large integrated health system. PATIENTS: A total of 326 patients with ovarian, fallopian tube, or primary peritoneal cancer who received at least eight cumulative cycles of carboplatin between January 2007 and September 2014 were included. Of these, 161 patients received all doses of carboplatin infused over 30 or 60 minutes (standard-infusion group [total of 1317 carboplatin cycles]), and 165 patients received the 3-hour extended infusion of carboplatin administered at approximately the eighth cumulative cycle and prior to development of a hypersensitivity reaction (extended-infusion group [total of 1527 carboplatin cycles]). MEASUREMENTS AND MAIN RESULTS: Baseline characteristics were similar between the groups, except significantly more patients in the extended-infusion group received triple premedication therapy prior to infusion (p<0.001). Hypersensitivity reactions occurred in 64 patients (40%) who received standard-infusion carboplatin and 40 patients (24.2%) who received extended-infusion carboplatin (p=0.0027). The median cycle of hypersensitivity reaction development did not differ significantly between the groups: 9 cycles in patients who received standard-infusion versus 11 cycles in patients who received extended-infusion carboplatin (p=0.06). Through regression analysis, the premedication regimen received prior to carboplatin infusion was the only variable significantly associated with hypersensitivity reactions (odds ratio 0.59, 95% confidence interval 0.36-0.97, p=0.038). CONCLUSION: Patients who received extended-infusion carboplatin experienced a lower incidence of hypersensitivity reactions than patients who received standard-infusion carboplatin, which may be attributed to the triple premedication regimen received more frequently in patients in the extended-infusion group.

Patterns of First Recurrence in African American Patients with High Grade Epithelial Ovarian Carcinoma.

BACKGROUND/AIMS: The aim of this study is to compare the distribution of anatomic sites of first recurrence in African American (AA) patients with ovarian carcinoma compared to Caucasians. METHODS: Patients diagnosed with high-grade epithelial ovarian, fallopian tube or peritoneal carcinoma from 2007 to 2013 were identified. Patterns of recurrence were compared for AA and Caucasian patients. Progression-free survival (PFS) and overall survival (OS) were compared. RESULTS: A total of 238 patients were included - 210 Caucasians and 28 AAs. At a follow-up time of 28 months, AAs were more likely to have multiple anatomic sites of recurrence rather than a single site when compared to Caucasians (63.6 vs. 35.5%, p = 0.01). Time to first recurrence was shorter for AA patients (12 vs. 18 months, p < 0.01). PFS and OS did not differ. AA patients with multiple sites of first recurrence had a significantly shorter OS than Caucasian patients with multiple sites of first recurrence (24 vs. 30 months, p = 0.022). CONCLUSION: Patterns of first recurrence differ between AAs and Caucasians. AAs have shorter times to first recurrence and are more likely to have multiple anatomic sites involved. AA patients with multiple sites of recurrence have a shorter OS than Caucasian patients with multiple sites.

Carcinosarcoma of the fallopian tube with disappearance of carcinoma cells by neoadjuvant chemotherapy: case study.

The authors report a case of carcinosarcoma (CS) of the fimbria of the fallopian tube in which carcinoma cells disappeared with neoadjuvant chemotherapy (NAC). A 74-year-old woman visited the present hospital with a large pelvic mass and pleural effusion. A magnetic resonance image of the tumor was highly suggestive of ovarian carcinoma. Due to the presence of both serous.adenocarcinoma cells in pleural effusion and pulmonary thrombosis, the patient was given NAC consisting of carboplatin plus paclitaxel (TC) and anticoagulant therapy with warfarin potassium. With six courses of NAC, the pleural effusion and pulmonary thrombosis disappeared, and the tumor decreased 36.2% in greatest diameter. Maximum debulking surgery was then performed. The tumor was found to be located in the fimbria of the right fallopian tube. Hysterectomy and bilateral salpingo-oophorectomy were performed, and histologic examination revealed chondrosarcoma with the presence of necrotic epithelial cells. The necrotic areas were interspersed with papillary structures, and immunohistochemical study showed positivity for CK7 and negativity for CK20, p53, and estrogen receptor (ER), indicating serous adenocarcinoma. Thus, heterologous CS with disappearance of viable carcinoma cells by NAC was diagnosed. The patient was given adjuvant chemotherapy consisting of three courses of TC, and there has been no evidence of disease for 20 months. The authors' experience in this case of gynecologic CS indicates that a serous adenocarcinomatous component of tubal CS can be well cured by TC-based NAC.

Clinical outcomes in patients with isolated serous tubal intraepithelial carcinoma (STIC): A comprehensive review.

OBJECTIVE. Serous tubal intraepithelial carcinoma (STIC) is currently considered the precursor lesion of pelvic (i.e., ovarian or peritoneal) high-grade serous carcinoma. The incidence of STIC has been reported to range from 0.6% to 7% in BRCA mutations carriers. However, the clinical outcome of patients with 'isolated' STIC remains elusive. The aim of this study is to review the published literature on isolated STIC to determine outcomes of these ients and present a summary of management strategies. METHODS. A systematic English-language literature search was conducted in PubMed, MEDLINE-Ovid, Scopus, EBSCO host, Cochrane Library of articles published from February 2006 to April 2015. Study inclusion criteria for review were the following: risk-reducing salpingo-oophorectomy (RRSO), BRCA mutation carriers, non-BRCA mutation carriers, and benign surgical indication. Exclusion criteria were as follows: the presence of synchronous gynecological cancers, concurrent non-gynecological malignancies, the presence of ovarian intraepithelial lesions, and articles that did not include any clinical information and were restricted to pathology information only. RESULTS. A total of 78 patients with isolated STIC were included in our analysis. The median age for all patients was 53.7 years (range; 37-83). Surgical indication was RRSO in 67 patients with BRCA mutations or high-risk personal or family history. In the other 11 patients, an incidental STIC was detected after surgery for non-cancerous indications. Eleven (16.4%) patients received chemotherapy after the diagnosis of STIC. The follow-up time ranged from 2 to 150 months. Three (4.5%) patients with BRCA mutations were diagnosed with primary peritoneal carcinoma (PPC) during the follow-up at 43, 48 and 72 months after RRSO. CONCLUSIONS. The rate of primary peritoneal carcinoma in patients with BRCA mutations and isolated STIC is 4.5%. The role of adjuvant therapy remains elusive and routine surveillance with tumor markers and imaging is not warranted.

Adherence patterns to National Comprehensive Cancer Network (NCCN) guidelines for referral to cancer genetic professionals.

OBJECTIVE: Genetic predisposition is responsible for 5-10% of breast cancer, 10% of ovarian cancer and 2-5% of uterine cancer. The study objective was to compare genetic counseling and testing referral rates among women with breast cancer that met NCCN referral guidelines to the referral rates among women with gynecologic cancers and determine predictors of referral. METHODS: Utilizing an institutional tumor registry database, patients from an academic women's oncology program were identified who met a subset of NCCN guidelines for genetic referral between 2004 and 2010. Patients diagnosed with ovarian cancer, breast cancer ≤50years of age, or uterine cancer <50years of age were included. A retrospective electronic chart review was conducted to evaluate for a genetic referral and uptake of genetic testing. RESULTS: 820 women were included (216 uterine, 314 breast, and 290 ovarian cancer). The overall genetic referral rate was 21.7%. 34% of eligible breast cancer patients were referred compared to 13.4% of uterine cancer and 14.5% of ovarian cancer patients (p<0.0001). Younger age, breast cancer diagnosis, family history and earlier stage were all significant referral predictors. The odds of being referred increased with the number of affected family members. 70.8% of referred patients, consulted with genetics. Among those who consulted with genetics, 95.2% underwent testing. CONCLUSIONS: Although increasing, genetic counseling remains underutilized across cancer diagnosis. Women with breast cancer are more likely to be referred than women with gynecologic cancers. Younger age, earlier stage and positive family history appear to be predictive of referral for genetic evaluation.

Targeting those with decreased meaning and peace: a supportive care opportunity.

PURPOSE: To evaluate if an individual's level of meaning/peace (M/P) predicts various quality of life (QOL) and mental well-being measures. To identify targets that might enhance the overall spiritual well-being and QOL of ovarian cancer patients. METHODS: Multi-site analysis of women with newly diagnosed stages II-IV ovarian, primary peritoneal, or fallopian tube cancer. Patients completed the following surveys: Functional Assessment of Chronic Illness Therapy-Ovarian (FACT-O), Functional Assessment of Chronic Illness Therapy-Spiritual (FACIT-Sp), Edmonton Symptom Assessment System (ESAS), Hospital Anxiety and Depression Scale (HADS), Templer's Death Anxiety Scale (DAS), Herth Hope Index (HHI), and Brief Multidimensional Measure of Religiousness/Spirituality (BMMRS). Linear regression models were created to examine the effect of M/P (FACIT-Sp) upon QOL, symptoms, and other measures of mental well-being. These models adjusted for the effect of site, race, age, stage, anaphylaxis to chemotherapy, and partner status as potential confounders. RESULTS: This study enrolled 104 patients from three separate sites. After adjusting for potential confounders, it was found that higher M/P predicted better QOL (FACT-O) (p < 0.0001). Higher M/P also predicted decreased death anxiety, depression, and anxiety (p ≤ 0.005). Finally, higher M/P predicted increased hope and coping scores (p ≤ 0.0005). CONCLUSIONS: Level of M/P is associated with several important mental and physical health states. This information may allow providers to identify patients at increased risk for mental/physical distress and may facilitate early referral to targeted psychotherapy interventions focused on improving patient QOL and decreasing anxiety and depression.

Clinical characteristics and outcomes of patients with stage I epithelial ovarian cancer compared with fallopian tube cancer.

OBJECTIVE: The purpose of this study was to compare clinical characteristics and survival between patients with stage I epithelial ovarian cancer and fallopian tube cancer. STUDY DESIGN: We identified women with stage I epithelial ovarian cancer and fallopian tube cancer who underwent treatment from 2000-2010. Correlation between categoric variables was assessed with χ2 test. The Kaplan-Meier survival analysis was used to generate overall survival data. Factors predictive of outcome were compared with the use of the log-rank test and Cox proportional hazards model. RESULTS: The study group consisted of 385 women with epithelial ovarian cancer and 43 women with fallopian tube cancer. Patients with fallopian tube cancer had a higher rate of stage IA disease (65% vs 48%; P=.02) and grade 3 tumors (60.4% vs 30.9%; P<.001). Patients with fallopian tube cancer had a significantly higher rate of breast cancer (25.6% vs 5.7%; P<.001) and BRCA 1 mutations (45.8% vs 9.1%; P<.001). There was no difference in the rates of platinum-based and paclitaxel chemotherapy between the groups. Women with fallopian tube cancer were more likely to have received ≥6 cycles of chemotherapy (58.1% vs 44.1%; P=.02). The 5-year disease-free survival rates were 100% in women with fallopian tube cancer and 93% in patients with epithelial ovarian cancer (P=.04). The 5-year overall survival rates were 100% and 95% for fallopian tube cancer and epithelial ovarian cancer, respectively (P=.7). CONCLUSION: We found a higher rate of stage IA, grade 3, and serous carcinoma in fallopian tube cancer. Women with fallopian tube cancer had a higher rate of breast cancer. There was no difference in overall survival between the groups.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for recurrent ovarian carcinoma: analysis of 30-day morbidity and mortality.

PURPOSE: The aim of this study was to evaluate morbidity and mortality associated with cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with ovarian, fallopian tube, and primary peritoneal cancer. METHODS: A retrospective review of patients undergoing cytoreductive surgery plus HIPEC from 1 January 2007 to 29 July 2013 at two academic medical centers was performed. Grade 3/4 complications (National Cancer Institute's Common Toxicity Criteria version 4.0) from day of surgery until 30 days postoperatively were recorded. RESULTS: Thirty-two patients were identified, with 27 cases of ovarian cancer, three primary peritoneal cancers, and two fallopian tube cancers. Indications included 24 at the time of cancer recurrence, six at interval surgical resection, and two in the consolidative setting. Hyperthermic chemotherapeutic regimens included carboplatin (n = 21), cisplatin (n = 4), oxaliplatin (n = 2), oxaliplatin + intravenous 5-fluorouracil (n = 1), doxorubicin (n = 1), and cisplatin + doxorubicin (n = 1). Infusion time ranged from 30 to 90 min, with a maximum temperature range of 41-43 °C. The combined grade 3/4 morbidity rate was 65.6 %, and the most frequent morbidities included grade 3 anemia (40.6 %), infection (15.6 %), and pleural effusion (12.5 %). Six patients required readmission (18.8 %), and two patients required reoperation (6.2 %). Full-thickness diaphragm resection/peritoneal stripping had a significant association with grade 3/4 pleural effusions (p = 0.0007). CONCLUSIONS: Cytoreductive surgery plus HIPEC is feasible in patients with ovarian cancer with 65.6 % grade 3/4 morbidity and no deaths. Balancing these complications with potential survival benefits is important in centers considering implementing HIPEC protocols.