The relationship of C-Reactive Protein to Albumin Ratio and interval debulking surgery outcome after neoadjuvant chemotherapy in ovarian cancer patients.

OBJECTIVE: To investigate the relationship between the changes of C-reactive protein to Albumin Ratio (CAR) levels and Interval Debulking Surgery (IDS) outcome after Neoadjuvant Chemotherapy (NAC) in ovarian cancer patients. METHODS: A nested case-control study for 209 patients with ovarian cancer who received NAC-IDS therapy from the First Affiliated Hospital of Bengbu Medical College between 2015‒2021 was conducted. Demographic data, laboratory indicators, and imaging examinations were collected. The outcome was regarded as optimal IDS in this study. Univariate and multivariate logistic regression analyses were performed to assess the relationship of CAR before NAC, CAR after NAC and ∆CAR with optimal IDS. The authors also performed the subgroup analysis based on menopausal state. RESULTS: The end time of follow-up was January 24, 2022. A total of 156 patients had been treated with optimal IDS, and 53 with suboptimal IDS. After adjusting age, body mass index, menopausal state, NAC drug, peritoneal perfusion and CAR before NAC, the result showed that CAR after NAC (Odds Ratio [OR = 3.48], 95% Confidence Interval [95% CI 1.28‒9.48], p = 0.015) and ∆CAR (OR = 0.29, 95% CI 0.11‒0.78, p = 0.015) were associated with optimal IDS, respectively. Additionally, the authors found a significant correlation between CAR after NAC and optimal IDS (OR = 3.16, 95% CI 1.07‒9.35, p = 0.038), and ∆CAR and optimal IDS (OR = 0.32, 95% CI 0.11‒0.94, p = 0.038) among ovarian cancer patients with menopause. CONCLUSION: CAR after NAC and ∆CAR were independent prognostic markers of optimal interval debulking surgery for ovarian cancer patients.

Expert consensus: Profiling and management of advanced or metastatic epithelial ovarian cancer / Consenso de expertos basado en la evidencia: perfilamiento y manejo del carcinoma epitelial de ovario de alto grado avanzado.

Introduction and objective: The approach to patients with advanced or metastatic high-grade epithelial ovarian cancer (EOC) has evolved over time with the advent of new therapies and multimodal strategies. The objective of this consensus of experts is to generate national recommendations for the profiling and management of advanced or metastatic high-grade OEC, defined as stages III and IV of the "The International Federation of Gynecology and Obstetrics (FIGO) classification at the time of diagnosis to base on the literature review that included international evidence-based clinical practice guidelines (CPG). Material and methods: Eleven panelists (oncologists and gynecological oncologists) answered 8 questions about the profiling and management of advanced or metastatic ovarian epithelial carcinoma. The panelists were chosen for their academic profile and influence in national health institutions. Guidelines from the "ESMO Standardized Operating Procedures Consensus Conference" were used to develop the consensus. It was agreed that the level of agreement to accept a recommendation should be ≥ 80%. The document was peer reviewed. Results: Eight general recommendations are made, which are presented into five domains. Some of these recommendations are subdivided into specific recommendations. Initial treatment Recommendation 1.1 Complete primary cytoreduction (PCS) surgery is suggested as the initial therapy of choice for patients with high-grade or metastatic EOC, which should ideally be carried out in centers with experience, followed by adjuvant therapy. 1.2 Neoadjuvant chemotherapy followed by interval cytoreduction surgery (ICS) is suggested in those who are unlikely to achieve a complete cytoreduction in PCS either due to unresectable metastatic disease or who present unresectability criteria (imaging, laparoscopic and/or by laparotomy) and that have been defined by a gynecological oncologist and patients with poor functional status and comorbidities according to the criteria of the multidisciplinary team (clinical oncology, gynecological oncology, radiology, etc.). Recommendation 2. In patients with high-grade epithelial ovarian cancer (EOC), in stage III locally advanced or metastatic, who received neoadjuvant chemotherapy and achieved a complete or partial response (cytoreduction with tumor residue < 2.5 mm), the use of Hyperthermic IntraPeritoneal Chemotherapy (HIPEC) could be considered as an alternative to standard platinum-based adjuvant intravenous chemotherapy during interval cytoreductive surgery, after discussion in a multidisciplinary tumor board, at a center experienced in treating this type of patients. Use of genetic testing. Recommendation 3. It is suggested at the time of diagnosis to offer molecular genetic testing to all patients with high-grade advanced or metastatic EOC regardless of family history. Recommendation 4. It is suggested to offer genetic counseling, by qualified personnel, to all patients with high-grade advanced or metastatic EOC who are ordered genetic testing. Recommendation 5. It is suggested that all patients with advanced or metastatic high-grade EOC undergo a germ panel that includes the Breast Cancer Susceptibility Genes 1/2 genes (BRCA 1/2) and the other susceptibility genes according to with institutional protocols and the availability of genetic testing panels; If it is negative, then somatic testing should be performed that includes the homologous recombination deficiency (HRD) status, regardless of family history. Adjuvant Therapy Recommendation 6. 6.1. It is suggested that all patients with advanced stage III/IV EOC, with PSC of (0-2), got adjuvant intravenous chemotherapy as standard treatment within six weeks after Prc. It is suggested paclitaxel/carboplatin. Recommendation 6.2. It is suggested to use standard chemotherapy base on platinum plus Bevacizumab as adjuvant chemotherapy to patients with high-risk disease (EOC stage IV or stage III with suboptimal tumor cytoreduction), following by bevacizumab as maintenance. The use of bevacizumab as maintenance therapy is not recommended if bevacizumab was not included in the first line of treatment. We suggested the dose used in GOG-0218 and ICON7 trials. Recommendation 6.3 It is suggested combined intravenous/intraperitoneal chemotherapy only for selected patients, with optimal cytoreduction (residual lesions < 1 cm), especially those without residual disease (R0) and who are evaluated in a multidisciplinary meeting. It is not considered standard treatment. Recommendation 6.4. 6.4.1 It is suggested to use Poly ADP ribose polymerase (PARP) inhibitors such as olaparib or niraparib as maintenance after receiving first-line chemotherapy in patients with stage III/IV BRCA1/2 positive EOC who received platinumbased chemotherapy and obtained complete response/partial response (CR/PR), 6.4.2 It is suggested to use olaparib alone or in combination with bevacizumab or niraparib in patients with stage III/IV BRCA1/2 positive EOC who received platinum-based chemotherapy plus bevacizumab and achieved CR/PR. 6.4.3 It is suggested to use niraparibin patients with stage III/IV BRCA1/2 negative or unknown EOC who received platinum-based chemotherapy and achieved CR/PR. 6.4.4 It is suggested to use bevacizumab or olaparib plus bevacizumab in patients with EOC stage III/IV BRCA1/2 negative or unknown (HRD positive) who received platinum-based chemotherapy plus bevacizumab and obtained CR/PR. Treatment of disease relapse Recommendation 7. Secondary cytoreductive surgery followed by chemotherapy is suggested for selected patients with high-grade advanced EOC in first relapse, platinum-sensitive (platinum-free interval ≥ 6 months), positive "Arbeitsgemeinschaft Gynäkologische Onkologie ­ AGO" score or "I-model" positive (< 4.7) with a potential resection to R0 in centers with access to optimal surgical and postoperative support. Note: Platinum-free interval and AGO score have only been developed as positive predictors of complete resection and not to exclude patients from surgery. Recommendation 8. 8.1 For patients with relapse advanced high-grade EOC platinum-sensitive, the following is suggested: Platinum-based combination chemotherapy: carboplatin/liposomal doxorubicin or carboplatin/paclitaxel or carboplatin/nab-paclitaxel or carboplatin/docetaxel or carboplatin/gemcitabine) for six cycles. If combination therapy is not tolerated, give carboplatin or cisplatin alone. Combination chemotherapy (carboplatin/gemcitabine or carboplatin/paclitaxel or carboplatin/doxorubicin liposomal) plus bevacizumab followed by bevacizumab as maintenance (until progression or toxicity). Recommendation 8.2 For patients with relapsed advanced high-grade EOC platinum-resistant, it is suggested: Sequential treatment with chemotherapy, preferably with a non-platinum single agent (weekly paclitaxel or pegylated liposomal doxorubicin or docetaxel or oral etoposide or gemcitabine or trabectidine or, topotecan). Weekly paclitaxel or pegylated liposomal doxorubicin or topotecan could be administrate with or without bevacizumab. Other agents are considered potentially active (capecitabine, cyclophosphamide, ifosfamide, irinotecan, oxaliplatin, pemetrexed, vinorelbine, cyclophosphamide) could be recommended for later lines. Hormone receptor-positive patients who do not tolerate or have no response to cytotoxic regimens may receive hormone therapy with tamoxifen or other agents, including aromatase inhibitors (anastrozole and letrozole) or leuprolide acetate, or megestrol acetate. Patients with a performance score ≥ 3 should be considered only for best supportive care. Recommendation 8.3 Maintenance therapy with PARP inhibitors: It is suggested in patients with relapse advanced high-grade EOC stage III/IV BRCA1/2 (positive, negative or unknown) who have received two or more lines of platinum-based chemotherapy and have achieved CR/PR, use olaparib, niraparib or rucaparib. Niraparib could be useful in BRCA 1/2 +/-/unknown patients, as rucaparib, however, the latter does not yet have approval from the regulatory office in Colombia. Conclusions: It is expected that the recommendations issued in this consensus will contribute to improving clinical care, oncological impact, and quality of life of these women.

Introducción y objetivo: el abordaje de pacientes con cáncer epitelial de ovario (CEO) de alto grado avanzado o metastásico ha ido evolucionando a través del tiempo con el advenimiento de nuevas terapias y estrategias multimodales. El objetivo de este consenso de expertos es generar recomendaciones nacionales para el perfilamiento y manejo del CEO de alto grado avanzado o metastásico, definido como estadios III y IV de la clasificación de la Federación Internacional de Ginecología y Obstetricia (FIGO) al momento del diagnóstico, a partir de la revisión de la literatura que incluyó guías de práctica clínica (GPC) internacionales basadas en la evidencia. Materiales y métodos: once panelistas (oncólogos y ginecólogos oncólogos) respondieron ocho preguntas sobre el perfilamiento y manejo del carcinoma epitelial de ovario avanzado o metastásico. Los panelistas fueron escogidos por su perfil académico e influencia en instituciones de salud nacionales. Para el desarrollo del consenso se utilizaron los lineamientos de la "Conferencia de consenso de procedimientos operativos estandarizados de ESMO". Se definió que el nivel de acuerdo para aceptar una recomendación debía ser ≥ 80%. El documento fue revisado por pares. Resultados: Se hacen 8 recomendaciones generales, presentadas en cinco dominios; algunas de ellas se subdividen en recomendaciones específicas. Tratamiento inicial Recomendación 1 1.1. Como terapia inicial de elección para pacientes con CEO de alto grado o metastásico se sugiere la cirugía de citorreducción primaria (Cpr) completa que, idealmente, debe realizarse en centros con experiencia, seguida de terapia adyuvante. 1.2. Se sugiere quimioterapia neoadyuvante seguida de cirugía de citorreducción de intervalo (Cint) en quienes sea improbable alcanzar una citorreducción completa en la Cpr, bien sea por enfermedad metastásica no resecable o que presenten criterios de irresecabilidad (imagenológicos, laparoscópicos o por laparotomía) que hayan sido definidos por un ginecólogo oncólogo. También en pacientes con un pobre estado funcional y comorbilidades de acuerdo con el criterio del equipo multidisciplinario (oncología clínica, ginecología oncológica, radiología, etc.). Recomendación 2. En pacientes con CEO de alto grado, en estadio III localmente avanzado o metastásico, que recibieron quimioterapia neoadyuvante y alcanzaron respuesta completa o parcial (citorreducción con residuo tumoral < 2,5 mm), se podría evaluar el uso de la quimioterapia intraperitoneal hipertérmica (Hyperthermic IntraPeritoneal Chemotherapy - HIPEC) como alternativa a la quimioterapia IV adyuvante estándar basada en platinos durante la Cint, previa discusión en junta multidisciplinaria, en un centro de experiencia en este tipo de pacientes. Uso de pruebas genéticas Recomendación 3. Al momento del diagnóstico, se sugiere ofrecer testeo molecular genético a toda paciente con CEO de alto grado avanzado o metastásico, independientemente de la historia familiar. Recomendación 4. Se sugiere ofrecer asesoramiento genético, por parte de personal calificado, a toda paciente con CEO de alto grado avanzado o metastásico a quien se le ordene un testeo genético. Recomendación 5. Se sugiere que a toda paciente con CEO de alto grado avanzado o metastásico se le realice panel germinal que incluya los genes de susceptibilidad al cáncer de mama 1/2 (BRCA 1/2) y los otros genes de susceptibilidad de acuerdo con los protocolos institucionales y la disponibilidad de paneles de testeo genético; si es negativo entonces se debería realizar testeo somático que incluya el estatus de deficiencia de la recombinación homóloga (homologous recombination deficiency - HRD), independientemente de la historia familiar. Terapia adyuvante Recomendación 6 6.1. Se sugiere que a toda paciente con CEO estadios III/IV avanzado o metastásico, con estatus de desempeño (performance score care - PSC) de 0-2 se le administre como tratamiento estándar quimioterapia intravenosa (IV) adyuvante dentro de las seis semanas posteriores a la Cpr. Se sugiere administrar paclitaxel/carboplatino. 6.2. Se sugiere utilizar quimioterapia estándar basada en platino más bevacizumab como adyuvancia en pacientes con enfermedad de alto riesgo (CEO estadios IV o III con citorreducción tumoral subóptima), continuando con bevacizumab como mantenimiento. No se recomienda el uso de bevacizumab como terapia de mantenimiento si no se incluyó en la primera línea de tratamiento. Se sugiere seguir los esquemas de los estudios Gynecologic Oncology Group Study (GOG-0218) e International Collaborative Ovarian Neoplasm (ICON7). 6.3. Se sugiere la quimioterapia combinada IV/intraperitoneal (IP) solo para pacientes seleccionadas, con una citorreducción óptima (lesiones residuales < 1 cm), en especial aquellas sin enfermedad residual (R0) y que sean evaluadas en junta multidisciplinaria. La quimioterapia combinada IV/IP no se considera como tratamiento estándar. 6.4. 6.4.1. Se sugiere utilizar inhibidores de poli(ADP-ribosa) polimerasa (PARP) tales como olaparib o niraparib como mantenimiento después de recibir una primera línea de quimioterapia en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino y obtuvieron respuesta completa/respuesta parcial (RC/RP). 6.4.2. Se sugiere utilizar olaparib solo o en combinación con bevacizumab o niraparib en pacientes con CEO estadios III/IV BRCA1/2 positivo que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. 6.4.3. Se sugiere utilizar niraparib en pacientes con CEO estadio III/IV BRCA1/2 negativo o desconocido que recibieron quimioterapia basada en platino y obtuvieron RC/RP. 6.4.4. Se sugiere utilizar bevacizumab u olaparib más bevacizumab en pacientes con CEO estadios III/IV BRCA1/2 negativo o desconocido (HRD positivo) que recibieron quimioterapia basada en platino más bevacizumab y obtuvieron RC/RP. Tratamiento de la recaída de la enfermedad Recomendación 7. Se sugiere la realización de la cirugía de citorreducción secundaria (Csec), seguida de quimioterapia, a pacientes seleccionadas con CEO de alto grado avanzado o metastásico en primera recaída, platino-sensibles (intervalo libre de platinos ≥ 6 meses), puntuación Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) positiva o Integrate model (I-Model) positivo (< 4,7), y con una potencial resección a R0, en centros con acceso a soporte quirúrgico y posoperatorio óptimo. Nota: el intervalo libre de tratamiento con platinos y la puntuación AGO solo se han desarrollado como predictores positivos de resección completa y no para excluir a las pacientes de la cirugía. Recomendación 8 8.1. Para pacientes con CEO de alto grado avanzado o metastásico en recaída platino-sensibles se sugiere: Quimioterapia combinada basada en platino: carboplatino/doxorrubicina liposomal o carboplatino/paclitaxel o carboplatino/ nab-paclitaxel o carboplatino/docetaxel o carboplatino/gemcitabina, por seis ciclos. Si no se tolera la terapia combinada, dar carboplatino o cisplatino solo. Quimioterapia combinada: carboplatino/gemcitabina o carboplatino/paclitaxel o carboplatino/doxorubicina liposomal, más bevacizumab, seguida de bevacizumab como mantenimiento (hasta progresión o toxicidad). 8.2. Para pacientes con CEO de alto grado avanzado o metastásico en recaída, platino-resistentes, se sugiere: Tratamiento secuencial con quimioterapia, preferiblemente con un agente único que no sea un platino (paclitaxel semanal o doxorrubicina liposomal pegilada o docetaxel o etopósido oral o gemcitabina o trabectidina o topotecan). El paclitaxel semanal o la doxorrubicina liposomal pegilada o el topotecan pueden ser administrados con o sin bevacizumab. Existen otros agentes que se consideran potencialmente act ivos (capecitabina, ciclofosfamida, ifosfamida, irinotecán, oxaliplatino, pemetrexed, vinorelbina, ciclofosfamida), que se podrían recomendar para líneas posteriores. Las pacientes con receptores hormonales positivos que no toleran o no tienen respuesta a los regímenes citotóxicos pueden recibir terapia hormonal con tamoxifeno u otros agentes, incluidos los inhibidores de la aromatasa (anastrozol y letrozol) o acetato de leuprolide o acetato de megestrol. Pacientes con PSC ≥ 3 deberían ser consideradas solo para el mejor cuidado de soporte. 8.3. Terapia de mantenimiento con inhibidores PARP. Para pacientes con CEO de alto grado avanzado o metastásico en recaída estadios III/IV BRCA1/2 (positivo, negativo o desconocido), que hayan recibido dos o más líneas de quimioterapia basada en platino y hayan alcanzado RC/RP, se sugiere utilizar olaparib, niraparib o rucaparib. El niraparib podría ser útil en pacientes BRCA 1/2 +/-/desconocido, al igual que el rucaparib, sin embargo, este último no tiene aún aprobación del ente regulador en Colombia. Conclusiones: se espera que las recomendaciones emitidas en este consenso contribuyan a mejorar la atención clínica, el impacto oncológico y la calidad de vida de estas mujeres.

SEOM-GEICO clinical guideline on epithelial ovarian cancer (2023).

In recent years, the incorporation of new strategies to the therapeutic armamentarium has completely changed the outcomes of epithelial ovarian cancer (EOC). The identification of new predictive and prognostic biomarkers has also enabled the selection of those patients more likely to respond to targeted agents. Nevertheless, EOC is still a highly lethal disease and resistance to many of these new agents is common. The objective of this guideline is to summarize the most relevant strategies to manage EOC, to help the clinician throughout the challenging diagnostic and therapeutic processes and to provide evidence-based recommendations.

OCEANIA: real-world study of ovarian cancer treatment patterns across multiple lines of therapy in Argentina and Brazil.

Aim: To evaluate real-world data on treatment patterns in Argentina and Brazil in patients with ovarian cancer.Methods: This study evaluated de-identified antineoplastic exposure data from a private healthcare provider in Argentina and health claims database (Orizon) in Brazil from 2010 to 2019 and 2015 to 2020, respectively.Results: Platinum-based chemotherapy was the most common first-line therapy (Argentina: n =311 [87.6%]; Brazil: n = 1142 [79.3%]). The proportion of patients receiving platinum-based chemotherapy declined across both populations from first- to second-line, while use of non-platinum-based, targeted, and hormone therapies increased. Duration of platinum-based treatment and time to next treatment decreased from first- to fourth-line.Conclusion: There is an unmet need for effective therapies that can prolong time to next treatment in ovarian cancer in Argentina and Brazil.

[Box: see text].

The every woman study™ low- and middle-income countries edition protocol: A multi-country observational study to assess opportunities and challenges to improving survival and quality of life for women with ovarian cancer.

BACKGROUND: Ovarian cancer is a challenging disease to diagnose and treat effectively with five-year survival rates below 50%. Previous patient experience research in high-income countries highlighted common challenges and opportunities to improve survival and quality of life for women affected by ovarian cancer. However, no comparable data exist for low-and middle-income countries, where 70% of women with the disease live. This study aims to address this evidence gap. METHODS: This is an observational multi-country study set in low- and middle-income countries. We aim to recruit over 2000 women diagnosed with ovarian cancer across multiple hospitals in 24 countries in Asia, Africa and South America. Country sample sizes have been calculated (n = 70-96 participants /country), taking account of varying national five-year disease prevalence rates. Women within five years of their diagnosis, who are in contact with participating hospitals, are invited to take part in the study. A questionnaire has been adapted from a tool previously used in high-income countries. It comprises 57 multiple choice and two open-ended questions designed to collect information on demographics, women's knowledge of ovarian cancer, route to diagnosis, access to treatments, surgery and genetic testing, support needs, the impact of the disease on women and their families, and their priorities for action. The questionnaire has been designed in English, translated into local languages and tested according to local ethics requirements. Questionnaires will be administered by a trained member of the clinical team. CONCLUSION: This study will inform further research, advocacy, and action in low- and middle-income countries based on tailored approaches to the national, regional and global challenges and opportunities. In addition, participating countries can choose to repeat the study to track progress and the protocol can be adapted for other countries and other diseases.

Microcosting Analysis of Advanced Ovarian Cancer: Real-World Evidence From the Perspective of a Reference Public Brazilian Hospital.

OBJECTIVES: Evaluate the cost of advanced ovarian cancer, using the microcosting technique, based on real-world evidence from the perspective of a reference Brazilian public hospital. METHODS: Retrospective cohort study of patients newly diagnosed with advanced ovarian cancer in 2017 and followed-up for up to 5 years. A bottom-up microcosting method was applied, using the activity-based cost approach, which evaluates service costs based on activity consumption throughout patients' journey. RESULTS: The results indicate a median overall survival of 35.3 months and a median age of 57 years (33-80 years old). The average cost per patient was USD 34 991.595 over a period of 35.3 months, with admissions because of the disease progression and end-of-life care being the most relevant. CONCLUSIONS: The results show that the costs of activities currently involved in the treatment of advanced ovarian cancer represent an important economic impact for the public health system. These data can support future analyses on the impact of incorporating new technologies for the treatment of ovarian cancer and on the financing and sustainability of the Brazilian public healthcare system.

High Financial Hardship among Patients with Advanced Ovarian Cancer.

Ovarian cancer is considered the most fatal and costly gynecologic cancer. Although personalized therapies have improved ovarian cancer prognosis, they have resulted in increased financial toxicity concerns among this population. This study evaluated financial toxicity in patients with advanced ovarian cancer. Using secondary data from a study of barriers to palliative care, financial toxicity (FT) was measured through the Comprehensive Score for Financial Toxicity scale. Univariate and bivariate analyses were used to assess the relationship between selected demographic (i.e., age, race, ethnicity, education, place of birth, insurance type, yearly household income, employment status) and treatment-specific variables (i.e., years since diagnosis, surgery, chemotherapy, radiation, hormonal and targeted therapy) with clinically relevant financial toxicity. Characteristics were compared using Fisher's exact or chi squared tests. A total of 38 participants with advanced ovarian cancer were included in this study; 24% (n = 9) reported clinically significant FT. Income (p = .001), place of birth (p = .048) and employment status (p = .001) were related to FT. Study findings highlight that advanced ovarian cancer patients experience high FT, particularly those with low income, who are not able to work and were born outside the US. Further research using larger datasets and more representative samples is needed to inform intervention development and implementation.

Delivery of hereditary cancer genetics services to patients newly diagnosed with ovarian and endometrial cancers at three gynecologic oncology clinics in the USA, Brazil, and Mexico.

OBJECTIVE: Three gynecologic oncology clinics located in the USA, Brazil, and Mexico collaborated to evaluate their delivery of hereditary cancer genetics services. This descriptive retrospective review study aimed to establish baseline rates and timeliness of guideline-recommended genetics service delivery to patients with ovarian, fallopian tube, primary peritoneal (ovarian), and endometrial cancers at each clinic. METHODS: Patients who were newly diagnosed with ovarian and endometrial cancers between September 1, 2018 and December 31, 2020 were identified from the medical records of the clinics. Genetics service delivery metrics included the rates of mismatch repair deficiency tumor testing for patients with endometrial cancer (microsatellite instability/immunohistochemistry, MSI/IHC), referral to genetics services for patients with ovarian cancer, completed genetics consultations, and germline genetic testing for patients with ovarian and endometrial cancers. Timeliness was calculated as the average number of days between diagnosis and the relevant delivery metric. Descriptive statistics were used to analyze data. RESULTS: In total, 1195 patients (596 with ovarian cancer, 599 with endometrial cancer) were included in the analysis, and rates of genetics service delivery varied by clinic. For patients with ovarian cancer, referral rates ranged by clinic from 32.6% to 89.5%; 30.4-65.1% of patients completed genetics consultation and 32.6-68.7% completed genetic testing. The timeliness to genetic testing for patients with ovarian cancer ranged by clinic from 107 to 595 days. A smaller proportion of patients with endometrial cancer completed MSI/IHC testing (10.0-69.2%), with the average time to MSI/IHC ranging from 15 to 282 days. Rates of genetics consultation among patients with endometrial cancer ranged by clinic from 10.8% to 26.0% and 12.5-16.6% completed genetic testing. CONCLUSIONS: All clinics successfully established baseline rates and timeliness of delivering hereditary cancer genetics services to patients with ovarian and endometrial cancers. Lower rates of delivering genetics services to patients with endometrial cancer warrant additional research and quality improvement efforts.

In Vitro and In Vivo Efficacy of a Stroma-Targeted, Tumor Microenvironment Responsive Oncolytic Adenovirus in Different Preclinical Models of Cancer.

More than one million women are diagnosed annually worldwide with a gynecological cancer. Most gynecological cancers are diagnosed at a late stage, either because a lack of symptoms, such as in ovarian cancer or limited accessibility to primary prevention in low-resource countries, such as in cervical cancer. Here, we extend the studies of AR2011, a stroma-targeted and tumor microenvironment responsive oncolytic adenovirus (OAdV), whose replication is driven by a triple hybrid promoter. We show that AR2011 was able to replicate and lyse in vitro fresh explants obtained from human ovarian cancer, uterine cancer, and cervical cancer. AR2011 was also able to strongly inhibit the in vitro growth of ovarian malignant cells obtained from human ascites fluid. The virus could synergize in vitro with cisplatin even on ascites-derived cells obtained from patients heavily pretreated with neoadjuvant chemotherapy. AR2011(h404), a dual transcriptionally targeted derived virus armed with hCD40L and h41BBL under the regulation of the hTERT promoter, showed a strong efficacy in vivo both on subcutaneous and intraperitoneally established human ovarian cancer in nude mice. Preliminary studies in an immunocompetent murine tumor model showed that AR2011(m404) expressing the murine cytokines was able to induce an abscopal effect. The present studies suggest that AR2011(h404) is a likely candidate as a novel medicine for intraperitoneal disseminated ovarian cancer.

Development of handheld induction heaters for magnetic fluid hyperthermia applications andin-vitroevaluation on ovarian and prostate cancer cell lines.

Objective:Magnetic fluid hyperthermia (MFH) is a still experimental technique found to have a potential application in the treatment of cancer. The method aims to reach around 41 °C-47 °C in the tumor site by exciting magnetic nanoparticles with an externally applied alternating magnetic field (AMF), where cell death is expected to occur. Applying AMFs with high spatial resolution is still a challenge. The AMFs from current and prospective MFH applicators cover relatively large areas; being not suitable for patients having metallic implants near the treatment area. Thus, there will be a clinical need for smaller magnetic field applicators. To this end, a laparoscopic induction heater (LIH) and a transrectal induction heater (TRIH) were developed.Methods:Miniature 'pancake' coils were wound and inserted into 3D printed enclosures. Ovarian (SKOV-3, A2780) and prostate (PC-3, LNCaP) cancer cell lines were used to evaluate the instruments' capabilities in killing cancer cellsin vitro, using Synomag®-D nanoparticles as the heat mediators. NIH3T3 normal cell lines were also used with both devices to observe if these cells tolerated the conditions applied.Results:Magnetic field intensities reached by the LIH and TRIH were 42.6 kA m-1at 326 kHz and 26.3 kA m-1at 303 kHz, respectively. Temperatures reached in the samples were 41 °C by the LIH and 43 °C by the TRIH. Both instruments successfully accomplished killing cancer cells, with minimal effects on normal cells.Conclusion:This work presents the first line of handheld medical induction heaters and have the potential to be a complement to existing cancer therapies.Significance:These instruments could enable the development of MFH modalities that will facilitate the clinical translation of this thermal treatment.

Treatment delay and treatment pattern modifications among epithelial ovarian cancer patients during the COVID-19 pandemic: A retrospective cohort study.

BACKGROUND AND OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic disrupted healthcare access and medical treatment, including oncological care. Treatment delay in ovarian cancer could impact survival. We aimed to assess if there were delays and treatment changes in a cohort of epithelial ovarian cancer patients. METHODS: A retrospective cohort of epithelial ovarian cancer patients included cases diagnosed during the first 22 months of the COVID-19 pandemic in the state of Sao Paulo and those diagnosed in the 22 months preceding the outbreak. Time-to-treat was measured in days. In each group, surgery and chemotherapy proportions were assessed according to healthcare insurance status. RESULTS: A 56.2% reduction in epithelial ovarian cancer diagnosis was identified during the pandemic group compared to the prepandemic group; fewer patients were diagnosed in stage I (p < 0.01). Time-to-treat increased from 18.9 to 23 days (p < 0.01). Surgery in the public sector fell from 74.6% to 65.3% during the pandemic, compared to 87.1% to 68.8% in the private sector. CONCLUSION: There were fewer overall diagnoses, reduced stage I diagnosis, increased time-to-treat, and a reduction in the proportion of patients submitted to surgery. Brazil's public healthcare system demonstrated a higher resiliency to treatment change than the private sector.

Ovarian squamous cell carcinoma.

Ovarian squamous cell carcinoma is a rare and aggressive ovarian neoplasm, where most of the cases arise from mature teratoma, which represents up to 20% of all ovarian tumors. Moreover, primary squamous cell carcinoma is considered to be related to human papillomavirus infection. The diagnosis is difficult and metastasis from bladder, genital tract, lung, and digestive tract cancers must be ruled out. There are no guidelines for treatment, however, radical surgery combined with adjuvant chemotherapy and radiation therapy, are the most common approach. We present the case of a young women diagnosed with a de novo ovarian squamous cell carcinoma, as well as the treatment and follow-up that she received.

Interval cytoredutive surgery and HIPEC in advanced ovarian cancer with small-bowel disease: results and reflections.

INTRODUCTION: Small-bowel involvement in patients with ovarian cancer has been strongly correlated with the possibility of cytoreduction and thus with survival. The main objective of this study was to evaluate the prognostic significance of small-bowel involvement in patients undergoing optimal-complete interval cytoreductive surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC). METHODS: We included a series of patients diagnosed with stage IIIC-IVA (pleural effusion) high-grade serous epithelial ovarian cancer and in whom CRS + HIPEC was indicated after neoadjuvant systemic chemotherapy (NACT). The study period extended from January 2008 to January 2020, with a minimum follow-up of 12 months from the inclusion of the last patient. A multivariate analysis using Cox regression allowed us to identify the variables that were independently related to disease-free survival. RESULTS: A total of 144 patients were selected, 13 (9%) of whom were excluded from the analysis, because their disease was considered unresectable. The study included a series of 131 patients with a median age of 62 years (34-79 years) and a median Peritoneal Cancer Index (PCI) calculated during surgery of 9 (1-35). The median PCI of bowel areas 9-12 (SB-PCI) was 3 (1-10). Performance of a CC-1 cytoreduction (HR: 1.93, 95% CI: 1.02-3.64, p = 0.042) and SB-PCI greater than 3 (HR: 2.25, 95%CI: 1.13-4.48, p = 0.21) were independent factors associated with shorter disease-free survival. CONCLUSION: Small-bowel involvement, even in patients with a macroscopically complete resection, showed a correlation with worse prognostic outcomes and could be considered as a variable in the postoperative management of these patients.

Case Report of Small Cell Carcinoma of the Ovary, Hypercalcemic Type (Ovarian Rhabdoid Tumor) with SMARCB1 Mutation: A Literature Review of a Rare and Aggressive Condition.

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and aggressive condition that is associated with the SMARCA4 mutation and has a dismal prognosis. It is generally diagnosed in young women. Here, we report a case of a young woman with SCCOHT harboring a rare molecular finding with a highly aggressive biological behavior. The patient had a somatic SMARCB1 mutation instead of an expected SMARCA4 alteration. Even though the patient was treated with high-dose chemotherapy followed by stem cell transplantation, she evolved with disease progression and died 11 months after her first symptoms appeared. We present a literature review of this rare disease and discuss the findings in the present patient in comparison to expected molecular alterations and options for SCCOHT treatment.

[Treatment of advanced epithelial ovarian tumor. Hospital Italiano de Buenos Aires experience]. / Tratamiento de tumores malignos epiteliales de ovario en estadios avanzados. Experiencia del Hospital Italiano de Buenos Aires.

Ovarian cancer represents the third gynecological cancer in frequency in Argentina. There is a lack of information on this pathology in our country regarding the treatment and evolution of patients who suffer it. The aim of this study was to evaluate the perioperative and oncological results in patients with advanced epithelial ovarian tumor. We present a retrospective cohort in which we evaluated disease-free survival and overall survival in patients with epithelial ovarian tumor treated at the Hospital Italiano de Buenos Aires between June 2009 and June 2017. Of 170 patients included in the study, 72 (42.4%) received primary debulking surgery (CCP), while 98 (57.6%) received neoadjuvant therapy and interval surgery (CI). The optimal cyto-reduction rate was 75% and 79% respectively. No differences were found in perioperative outcomes, or in severe complications between the two groups. The median disease-free survival in the CCP group was 2.5 years (95% CI 1.6-3.1) while in the CI group it was 1.4 (95% CI 1.2-1.7) p < 0.001. The median overall survival was 5.8 years in CPP, and 3.5 years in CI. Faced with a meticulous selection by a group of experts, patients with advanced ovarian cancer treated with CCP present better oncological results than those who received neoadjuvant therapy and CI.

El cáncer de ovario ocupa el tercer lugar en frecuencia entre los cánceres ginecológicos en Argentina. Existe un déficit de información de esta enfermedad en nuestro país respecto al tratamiento y evolución oncológica de las pacientes. El objetivo de nuestro trabajo fue evaluar los resultados perioperatorios y oncológicos, en pacientes con tumor epitelial de ovario con estadios avanzados. Presentamos una cohorte retrospectiva en la que se evaluó la supervivencia libre de enfermedad y la supervivencia global en pacientes con tumores epiteliales de ovario tratadas en el Hospital Italiano de Buenos Aires entre junio del 2009 a junio del 2017. De 170 pacientes incluidas en el estudio, 72 (42.4%) fueron tratadas con una cirugía de citorreducción primaria (CCP), mientras que 98 (57.6%) recibieron neoadyuvancia y luego cirugía del intervalo (CI). La tasa de citorreducción óptima fue de 75% y de 79% respectivamente. No se encontraron diferencias en los resultados perioperatorios, ni en las complicaciones graves entre ambos grupos. La mediana de SLE en el grupo de CCP fue de 2.5 años (IC 95% 1.6-3.1) mientras que en el grupo de CI fue de 1.4 (IC 95% 1.2-1.7) p < 0.001. La mediana de supervivencia global fue de 5.8 años en CCP, y de 3.5 años en CI. En pacientes adecuadamente seleccionadas la CCP presenta mejores resultados oncológicos a la neoadyuvancia y CI. La selección correcta de las pacientes para tratamiento primario es fundamental para definir la conducta terapéutica.

Tratamiento de tumores malignos epiteliales de ovario en estadios avanzados. Experiencia del Hospital Italiano de Buenos Aires / Treatment of advanced epithelial ovarian tumor. Hospital Italiano de Buenos Aires experience

Resumen El cáncer de ovario ocupa el tercer lugar en frecuencia entre los cánceres ginecológicos en Argentina. Existe un déficit de información de esta enfermedad en nuestro país respecto al tratamiento y evolución oncológica de las pacientes. El objetivo de nuestro trabajo fue evaluar los resultados perioperatorios y oncológicos, en pacientes con tumor epitelial de ovario con estadios avanzados. Presentamos una cohorte retrospectiva en la que se evaluó la supervivencia libre de enfermedad y la supervivencia global en pacientes con tumores epiteliales de ovario tratadas en el Hospital Italiano de Buenos Aires entre junio del 2009 a junio del 2017. De 170 pacientes incluidas en el estudio, 72 (42.4%) fueron tratadas con una cirugía de citorreducción primaria (CCP), mientras que 98 (57.6%) recibieron neoadyuvancia y luego cirugía del intervalo (CI). La tasa de citorreducción óptima fue de 75% y de 79% respectivamente. No se encontraron diferencias en los resultados perioperatorios, ni en las complicaciones graves entre ambos grupos. La mediana de SLE en el grupo de CCP fue de 2.5 años (IC 95% 1.6-3.1) mientras que en el grupo de CI fue de 1.4 (IC 95% 1.2-1.7) p < 0.001. La mediana de supervivencia global fue de 5.8 años en CCP, y de 3.5 años en CI. En pacientes adecuadamente seleccionadas la CCP presenta mejores resultados oncológicos a la neoadyuvancia y CI. La selección correcta de las pacientes para tratamiento primario es fundamental para definir la conducta terapéutica.

Abstract Ovarian cancer represents the third gynecological cancer in frequency in Argentina. There is a lack of information on this pathology in our country regarding the treatment and evolution of patients who suffer it. The aim of this study was to evaluate the perioperative and oncological results in patients with advanced epithelial ovarian tumor. We present a retrospective cohort in which we evaluated disease-free survival and overall survival in patients with epithelial ovarian tumor treated at the Hospital Italiano de Buenos Aires between June 2009 and June 2017. Of 170 patients included in the study, 72 (42.4%) received primary debulking surgery (CCP), while 98 (57.6%) received neoadjuvant therapy and interval surgery (CI). The optimal cyto-reduction rate was 75% and 79% respectively. No differences were found in perioperative outcomes, or in severe complications between the two groups. The median disease-free survival in the CCP group was 2.5 years (95% CI 1.6-3.1) while in the CI group it was 1.4 (95% CI 1.2-1.7) p < 0.001. The median overall survival was 5.8 years in CPP, and 3.5 years in CI. Faced with a meticulous selection by a group of experts, patients with advanced ovarian cancer treated with CCP present better oncological results than those who received neoadjuvant therapy and CI.

Ovarian metastasis from colorectal adenocarcinoma / Metástase ovariana de adenocarcinoma colorretal

Introduction: Ovarian metastases of gastrointestinal origin, also called Krukenberg tumors, have a guarded prognosis. Physicians need to look for alternatives in diagnosis and treatment for this clinical condition in order to improve the outcome of the patients. Objectives: To report the experience of the authors in the treatment of these patients, and to perform a review of the literature on the epidemiology, clinical presentation, diagnosis, treatment, and prognosis for ovarian metastases from colorectal cancer. Methods: We collected clinical information regarding the patients treated for ovarian metastasis from colorectal adenocarcinoma at our coloproctology service, and performed a search on the PubMed database using the terms colorectal cancer, ovarian metastasis, Krukenberg tumor and surgery. Conclusion: Large abdominal tumors are the most frequent presentation of ovarian metastasis from colorectal cancer. The diagnosis is based on a histopathological analysis, levels of carcinoembryonic antigen (CEA) and cancer antigen 125 (CA-125), and immunohistochemical studies for the cytokeratin 20 (CK20), caudal-type homeobox 2 (CDX2) and vilina markers. Citoreductive surgical procedures are the most promising approach to treatment, with the highest impact on overall survival. The prognosis is negatively influenced by the extent of the metastasis, by citoreductive surgical procedures with persistence of macro- or microscopic foci of the disease, and by low scores on the general well-being index of the patient. (AU)

Introdução: As metástases ovarianas de tumores gastrointestinais, também chamadas de tumores de Krukenberg, são neoplasias de prognóstico reservado. Exigem conhecimento de alternativas diagnósticas e terapêuticas para garantir melhora da sobrevida das pacientes. Objetivos: Relatar a experiência dos autores no tratamento dessas pacientes, e fazer uma revisão da literatura sobre a epidemiologia, apresentação clínica, diagnóstico, tratamento e prognóstico das metástases ovarianas do câncer colorretal. Métodos: Foi realizada uma coleta de informações clínicas de pacientes tratados por metástases ovarianas de adenocarcinoma colorretal em nosso serviço de coloproctologia, em conjunto com uma pesquisa na base de dados PubMed com os termos colorectal cancer, ovarian metastasis, Krukenberg tumor, e surgery. Conclusão: Volumosas massas abdominais constituem a principal apresentação clínica da doença. As alternativas diagnósticas incluem a avaliação histopatológica, a identificação dos níveis de antígeno cárcino-embriônico (ACE) e de antígeno de câncer 125 (CA-125), e exame imunoistoquímico de espécimes cirúrgicos para os marcadores citoqueratina 20 (CK20), homeobox 2 do tipo caudal (CDX2), e vilina. O tratamento citorredutor completo demonstrou o maior impacto na sobrevida dos pacientes. O prognóstico é influenciado negativamente pela extensão da doença metastática, por cirurgia citorredutiva com persistência focos microscópicos ou macroscópicos da doença, e baixo escore de índice de bem-estar geral do paciente. (AU)