Management of patients with recurrent/metastatic endometrial cancer: Consensus recommendations from an expert panel from Brazil.

Background: Endometrial cancer is of increasing concern in several countries, including Brazil, in part because of an ageing population, declines in fertility, and the increasing prevalence of obesity. Although endometrial tumors had lagged behind other cancer types in terms of treatment improvements, molecular characterization of these tumors is paving the way for novel therapies and an expansion of the therapeutic arsenal. We aimed to help medical oncologists who manage patients with recurrent or metastatic endometrial cancer in the Brazilian healthcare setting. Methods: The panel, composed of 20 medical oncologists, convened in November 2021 to address 50 multiple-choice questions on molecular testing and treatment choices. We classified the level of agreement among panelists as (1) consensus (≥75% choosing the same answer), (2) majority vote (50% to <75%), or (3) less than majority vote (<50%). Results: Consensus was present for 25 of the 50 questions, whereas majority vote was present for an additional 23 questions. Key recommendations include molecular testing for every patient with recurrent/metastatic endometrial cancer; choice of first-line treatment according to microsatellite instability and HER2, with the addition of programmed death ligand 1 (PD-L1) and hormone receptors (HRs) for second-line therapy; carboplatin and paclitaxel as the preferred option in first-line treatment of HER2-negative disease, with the addition of trastuzumab in HER2-positive disease; pembrolizumab plus lenvatinib as a key option in second line, regardless of HER2, PD-L1 or HRs; and various recommendations regarding treatment choice for patients with distinct comorbidities. Conclusion: Despite the existing gaps in the current literature, the vast majority of issues addressed by the panel provided a level of agreement sufficient to inform clinical practice in Brazil and in other countries with similar healthcare environments.

Recommendations for the treatment of vulvar cancer in settings with limited resources: Report from the International Gynecological Cancer Society consensus meeting.

Introduction: Due to scant literature and the absence of high-level evidence, the treatment of vulvar cancer is even more challenging in countries facing limited resources, where direct application of international guidelines is difficult. Recommendations from a panel of experts convened to address some of these challenges were developed. Methods: The panel met in Rio de Janeiro in September 2019 during the International Gynecological Cancer Society congress and was composed of specialists from countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East. The panel addressed 62 questions and provided recommendations for the management of early, locally advanced, recurrent, and/or metastatic vulvar cancer. Consensus was defined as at least 75% of the voting members selecting a particular recommendation, whereas a majority vote was considered when one option garnered between 50.0% and 74.9% of votes. Resource limitation was defined as any issues limiting access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or funding for the provision of contemporary medical care. Results: Consensus was reached for nine of 62 (14.5%) questions presented to the panel, whereas a majority vote was reached for 29 (46.7%) additional questions. For the remaining questions, there was considerable heterogeneity in the recommendations. Conclusion: The development of guidelines focusing on areas of the world facing more severe resource limitations may improve medical practice and patient care.

Clinical Course, Genetic, and Immunohistochemical Characterization of Solid Pseudopapillary Tumor of the Pancreas (Frantz Tumors) in a Brazilian Cohort.

Frantz tumors or solid pseudopapillary pancreatic neoplasm (SPN) are rare exocrine neoplasms that carry a favorable prognosis; they represent up to 3% of all tumors located in the region of the pancreas and have specific age and gender predispositions. In recent years, the rising curve of diagnosis is entitled to the evolution and access of diagnostic imaging. In this paper, we have retrospectively reviewed and described the clinical course of 40 patients with SPN from three institutions in Brazil, who had their diagnosis between 2005 and 2020, and analyzed the clinicopathological, genetic, and surgical aspects of these individuals. In accordance with the literature, most patients were women, 60% with unspecified symptoms at diagnosis, with tumors mainly located in the body and tail of the pancreas, of whom 70% underwent a distal pancreatectomy with sparing splenectomy as a standard procedure, and none of the cases have experienced recurrence to date. Surgery still remains the mainstay of treatment given the low metastatic potential, but more conservative approaches as observed in this cohort are evolving to become the standard of care. Herein, we present an in-depth analysis of cases focusing on the latest literature and report some of the smallest tumor cases in the literature. To our knowledge, this is the first report evaluating germline genetic testing and presenting a case of detected Li-Fraumeni syndrome.

Recommendations for the prevention, screening, diagnosis, staging, and management of cervical cancer in areas with limited resources: Report from the International Gynecological Cancer Society consensus meeting.

Introduction: Nearly 85% of cervical cancer new cases are diagnosed in limited resources countries. Although several strategies have been proposed to reduce the disease burden, challenges remain to provide the best possible care. We report recommendations from an expert consensus meeting convened to address from prevention to management of cervical cancer in limited resources countries. Methods: The expert panel, composed by invited specialists from 38 developing countries in Africa, Asia, Eastern Europe, Latin America, and the Middle East, convened in Rio de Janeiro in September 2019, during the Global Meeting of the International Gynecological Cancer Society (IGCS). Panel members considered the published scientific evidence and their practical experience on the topics, as well as the perceived cost-effectiveness of, and access to, the available interventions. The focus of the recommendations was on geographic regions rather than entire countries because medical practice varies considerably in the countries represented. Resource limitation was qualified as limited access to qualified surgeons, contemporary imaging or radiation-oncology techniques, antineoplastic drugs, or overall funding for provision of state-of-the-art care. Consensus was defined as at least 75% of the voting members selecting a particular answer of the multiple-choice questionnaire, whereas the majority vote was considered as 50% to 74.9%. Results: Consensus was reached for 25 of the 121 (20.7%) questions, whereas for 54 (44.6%) questions there was one option garnering between 50% to 74.9% of votes (majority votes). For the remaining questions, considerable heterogeneity in responses was observed. Discussion: The implementation of international guidelines is challenging in countries with resource limitations or unique health-care landscapes. The development of guidelines by the health care providers in those regions is more reflective of the reality on the ground and may improve medical practice and patient care. However, challenges remain toward achieving that goal at political, economic, social, and medical levels.

Ovarian small cell carcinoma in one of a pair of monozygous twins.

One of a pair of monozygous twins was diagnosed and died of small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) at the age of 30 years. Her sister remained unaffected and was very concerned about her risk for developing SCCOHT. By performing comprehensive molecular analysis using whole exome sequencing (WES) approach, we showed that the deceased twin's tumour has bi-allelic somatic genetic defects (a pathogenic frameshift deletion in SMARCA4 and LOH on chr19p). Results of WES of constitutional DNA from her unaffected sister were confirmatory. Based on our findings, we concluded that the living twin is not at risk for SCCOHT and does not need to consider preventive oophorectomy.

Incidental Findings in Reduction Mammoplasty Specimens in Patients with No Prior History of Breast Cancer. An Analysis of 783 Specimens.

Breast reduction surgery is a common procedure and the rate of incidental findings in the removed specimens varies between 0% and 4.6%. There are no guidelines about pathological evaluation of breast reduction surgery. We reviewed all pathology reports of patients undergoing breast reduction surgery in a single tertiary institution in Brazil from January 2008 to August 2014. Exclusion criteria were a personal history of breast cancer, unclear reason for mastectomy and incomplete data on the pathology report. We considered "relevant findings" flat epithelial atypia, atypical hyperplasia, carcinomas in situ and invasive carcinoma. Of 1672 specimens from breast reduction surgery, 783 met inclusion criteria. Median patient age was 40 (8-77), 91% underwent bilateral mastectomy and 57% of the specimens weighted less than 200 g. In 55% of cases, 4 or more paraffin blocks were sampled. There were 40 (5.1%) relevant findings and the most common was atypical lobular hyperplasia (16-2%). There were 3 invasive carcinomas (0.38%). In multivariate analysis, the only variables associated with a higher odds of relevant pathological findings were patient age ≥ 40 (OR 4.73 CI95% 1.98-11.3 p < 0.001) and sampling of ≥4 paraffin blocks from each specimen (OR 6.69 95% CI 2.25-19.9 p < 0.001). The incidence of pre-malignant and malignant lesions in specimens from breast reduction surgery is around 5%, but this risk is significantly higher for patients older than 40 years-old. Sampling at least 4 paraffin blocks from each specimen significantly increases detection rates.

Predictive Value of Serum Carbohydrate Antigen 19-9 (CA19-9) for Early Mortality in Advanced Pancreatic Cancer.

INTRODUCTION: Levels of carbohydrate antigen 19-9 (CA19-9) in metastatic pancreatic cancer are used in daily practice as a marker of response to chemotherapy. The association between CA19-9 levels and mortality remains uncertain. This study sought to determine the most accurate level of CA19-9 associated with early mortality, both at diagnosis and during the course of metastatic disease. METHODS: This research is a retrospective analysis of 64 patients with metastatic adenocarcinoma of the pancreas evaluated from January 2010 to December 2015. A receiver-operating characteristic (ROC) curve analysis was performed to evaluate the CA19-9 value and the association with early death (death within 2 months after diagnosis of advanced disease). The survival analysis was estimated by the Kaplan-Meier method, and variables of interest were assessed by proportional hazards regression Cox models. RESULTS: The mortality rate was 92.2%, and the estimated median survival was 11.0 months. For the ROC curve analysis of initial CA19-9, an area under the curve of 0.868 (95% confidence interval 0.782 to 0.954) was obtained; the cutoff of 2504 U/ml had a sensitivity of 100% and specificity of 82.8% for early death. The effect of initial CA19-9 and chemotherapy contributed independently to the survival time, and every increase of 1000 CA19-9 units increased the risk of death by 9% (p = 0.0003). CONCLUSION: CA19-9 levels in advanced pancreatic adenocarcinoma are associated independently with worse prognosis and early death. CA19-9 levels could be considered as a stratification factor for future clinical trials.

Project ECHO: A Telementoring Program for Cervical Cancer Prevention and Treatment in Low-Resource Settings.

Cervical cancer incidence and mortality rates are significantly higher in low- and middle-income countries compared with the United States and other developed countries. This disparity is caused by decreased access to screening, often coupled with low numbers of trained providers offering cancer prevention and treatment services. However, similar disparities are also found in underserved areas of the United States, such as the Texas-Mexico border, where cervical cancer mortality rates are 30% higher than in the rest of Texas. To address these issues, we have adopted the Project ECHO (Extension for Community Healthcare Outcomes) program, a low-cost telementoring model previously proven to be successful in increasing local capacity, improving patient management skills, and ultimately improving patient outcomes in rural and underserved areas. We use the Project ECHO model to educate local providers in the management of cervical dysplasia in a low-resource region of Texas and have adapted it to inform strategies for the management of advanced cervical and breast cancer in Latin America and sub-Saharan Africa. This innovative approach, using ECHO, is part of a larger strategy to enhance clinical skills and develop collaborative projects between academic centers and partners in low-resource regions.

Minimizing the uncertainties regarding the effects of delaying radiotherapy for Glioblastoma: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Previous studies have provided no clear conclusions regarding the effects of delaying radiotherapy (RT) in GBM patients. We present a systematic review and meta-analysis to address the effect of delayed RT on the overall survival (OS) of GBM patients. METHODS: A systematic search retrieved 19 retrospective studies published between 1975 and 2014 reporting on the waiting time (WT) to RT for GBM patients. The meta-analysis was performed by converting WT to RT studies intervals into a regression coefficient (ß) and standard error expressing the effect size on OS per week of delay. RESULTS: Data required to calculate the effect size on OS per week of delay were available for 12 studies (5212 patients). A non-adjusted model and a meta-regression model based on well-recognized prognostic factors were performed. No association between WT to RT, per week of delay, and OS was found (HR=0.98; 95% CI 0.90-1.08; p=0.70). The meta-regression adjusted for prognostic factors weighted by the inverse-variance (1/SE(2)) showed no clear evidence of the effect of WT to RT, per week of delay, on OS. CONCLUSIONS: This meta-analysis, despite limitations, provided no evidence of a true effect on OS by delaying RT in GBM patients.

Radiotherapy for recurrent small cell carcinoma of the ovary: A case report and review of the literature.

•Small cell carcinoma of the ovary is a rare and aggressive malignant tumor.•No effective treatment for recurrent disease has yet been described.•Patients with recurrent disease may respond to salvage surgery, chemotherapy, radiotherapy or a combination of these modalities.

Waiting time to radiotherapy as a prognostic factor for glioblastoma patients in a scenario of medical disparities.

OBJECTIVE: To evaluate the effect of waiting time (WT) to radiotherapy (RT) on overall survival (OS) of glioblastoma (GBM) patients as a reliable prognostic variable in Brazil, a scenario of medical disparities. METHOD: Retrospective study of 115 GBM patients from two different health-care institutions (one public and one private) in Brazil who underwent post-operative RT. RESULTS: Median WT to RT was 6 weeks (range, 1.3-17.6). The median OS for WT ≤ 6 weeks was 13.5 months (95%CI , 9.1-17.9) and for WT > 6 weeks was 14.2 months (95%CI, 11.2-17.2) (HR 1.165, 95%CI 0.770-1.762; p = 0.470). In the multivariate analysis, the variables associated with survival were KPS (p < 0.001), extent of resection (p = 0.009) and the adjuvant treatment (p = 0.001). The KPS interacted with WT to RT (HR 0.128, 95%CI 0.034-0.476; p = 0.002), showing that the benefit of KPS on OS depends on the WT to RT. CONCLUSION: No prognostic impact of WT to RT could be detected on the OS. Although there are no data to ensure that delays to RT are tolerable, we may reassure patients that the time-length to initiate treatment does not seem to influence the control of the disease, particularly in face of other prognostic factors.

Waiting time to radiotherapy as a prognostic factor for glioblastoma patients in a scenario of medical disparities / Tempo de espera para a radioterapia como um fator prognóstico em pacientes com glioblastoma em um cenário de disparidades médicas

Objective To evaluate the effect of waiting time (WT) to radiotherapy (RT) on overall survival (OS) of glioblastoma (GBM) patients as a reliable prognostic variable in Brazil, a scenario of medical disparities. Method Retrospective study of 115 GBM patients from two different health-care institutions (one public and one private) in Brazil who underwent post-operative RT. Results Median WT to RT was 6 weeks (range, 1.3-17.6). The median OS for WT ≤ 6 weeks was 13.5 months (95%CI , 9.1-17.9) and for WT > 6 weeks was 14.2 months (95%CI, 11.2-17.2) (HR 1.165, 95%CI 0.770-1.762; p = 0.470). In the multivariate analysis, the variables associated with survival were KPS (p < 0.001), extent of resection (p = 0.009) and the adjuvant treatment (p = 0.001). The KPS interacted with WT to RT (HR 0.128, 95%CI 0.034-0.476; p = 0.002), showing that the benefit of KPS on OS depends on the WT to RT. Conclusion No prognostic impact of WT to RT could be detected on the OS. Although there are no data to ensure that delays to RT are tolerable, we may reassure patients that the time-length to initiate treatment does not seem to influence the control of the disease, particularly in face of other prognostic factors. .

Objetivo Avaliar o efeito do tempo de espera (TE) até radioterapia na sobrevida global de pacientes com glioblastoma como um fator prognóstico confiável. Método Estudo retrospectivo de 115 pacientes com glioblastoma, que foram submetidos à radioterapia pós-operatória, em dois serviços diferentes no Brasil (um público e outro privado). Resultados Mediana de TE para radioterapia foi de 6 semanas (variação, 1,3-17,6). A mediana de sobrevida para TE ≤ 6 semanas foi de 13,5 meses (IC95%, 9,1-17,9) e para TE > 6 semanas foi de 14,2 meses (IC95%, 11,2-17,2) (HR 1,165, 0,770-1,762; p = 0,470). Na análise multivariada, as variáveis associadas à sobrevida foram perfomance status (p < 0,001), extensão da ressecção (p = 0,009) e tratamento adjuvante (p = 0,001). Conclusão Não se observou impacto prognóstico para TE até a radioterapia na sobrevida. Diante de outros fatores prognósticos, é possível assegurar de que o espaço de tempo até a radioterapia não parece influenciar o controle da doença. .

Sustained complete response after maintenance therapy with topotecan and erlotinib for recurrent cervical cancer with distant metastases.

INTRODUCTION: Recurrent cervical cancer is associated with a poor prognosis. Most treatment responses are partial and of short duration. The development of new therapies is vital to improve treatment for recurrent disease. Epidermal growth factor receptor (EGFR) inhibitors may have a role in this setting. CASE DESCRIPTION: A 53-year-old woman with stage IB2 squamous cell carcinoma of the cervix was initially treated with chemoradiation. Six months after completing treatment, she developed a recurrence in the common iliac and para-aortic lymph nodes above the previous radiation field and was treated with additional radiation therapy. Two years later, she developed recurrent disease in the left supraclavicular lymph nodes and was treated with chemoradiation followed by 3 cycles of adjuvant cisplatin and topotecan. She had a complete response and was placed on maintenance therapy with topotecan and erlotinib, which was well tolerated and produced minimal side effects. After 20 months of maintenance therapy, it was discontinued given the long interval without evidence of disease. The patient is currently without evidence of disease 5 years after completing the topotecan-erlotinib treatment. CONCLUSION: We noted a sustained response in a patient with recurrent metastatic cervical cancer treated with radiotherapy, cisplatin, and topotecan followed by maintenance therapy with topotecan and erlotinib. Further evaluation of the role of EGFR inhibitors in this setting should be considered given their favorable toxicity profile and biological relevance.

Initial care and outcome of glioblastoma multiforme patients in 2 diverse health care scenarios in Brazil: does public versus private health care matter?.

BACKGROUND: The aim of this study was to describe the epidemiological and survival features of patients with glioblastoma multiforme treated in 2 health care scenarios--public and private--in Brazil. METHODS: We retrospectively analyzed clinical, treatment, and outcome characteristics of glioblastoma multiforme patients from 2003 to 2011 at 2 institutions. RESULTS: The median age of the 171 patients (117 public and 54 private) was 59.3 years (range, 18-84). The median survival for patients treated in private institutions was 17.4 months (95% confidence interval, 11.1-23.7) compared with 7.1 months (95% confidence interval, 3.8-10.4) for patients treated in public institutions (P < .001). The time from the first symptom to surgery was longer in the public setting (median of 64 days for the public hospital and 31 days for the private institution; P = .003). The patients at the private hospital received radiotherapy concurrent with chemotherapy in 59.3% of cases; at the public hospital, only 21.4% (P < .001). Despite these differences, the institution of treatment was not found to be an independent predictor of outcome (hazard ratio, 1.675; 95% confidence interval, 0.951-2.949; P = .074). The Karnofsky performance status and any additional treatment after surgery were predictors of survival. A hazard ratio of 0.010 (95% confidence interval, 0.003-0.033; P < .001) was observed for gross total tumor resection followed by radiotherapy concurrent with chemotherapy. CONCLUSIONS: Despite obvious disparities between the hospitals, the medical assistance scenario was not an independent predictor of survival. However, survival was directly influenced by additional treatment after surgery. Therefore, increasing access to resources in developing countries like Brazil is critical.

Is there publication bias towards Brazilian articles on cancer?

OBJECTIVE: To investigate whether Brazilian articles on cancer are published in journals with an impact factor and/or repercussion (measured by the number of citations) inferior to those that come from foreign organizations. METHODS: A search was carried out in PubMed for the MeSH term "neoplasm" with the limits clinical trial, affiliation of the Brazilian author(s), and interval from July 1st, 2009 to June 30, 2010. Selected for matching were non-Brazilian related articles published from three months prior to three months after the date of publication of the Brazilian study. The numbers of citations were obtained from two databases, as well as the impact factor for the journals in which the articles were published. RESULTS: Forty-three national and 876 related international articles were identified. The Brazilian publications had a mean impact factor of 3.000 versus 3.430 of the international ones (p=0.041). There was no statistically significant difference as to the number of citations between the two groups. The affiliation of the first author with a Brazilian or foreign organization did not significantly influence the number of citations or the impact factor. CONCLUSION: Brazilian articles are significantly less accepted in journals with higher impact factors, although it does not compromise its repercussion on the scientific community.

Existe viés de publicação para artigos brasileiros sobre câncer? / Is there publication bias towards Brazilian articles on cancer?

OBJETIVO: Investigar se artigos brasileiros sobre câncer são publicados em periódicos de fator impacto e/ou repercussão (medida pelo número de citações) inferiores aos oriundos de instituições estrangeiras MÉTODOS: Pesquisou-se, no PubMed, o MeSH Term "neoplasm" com os limitadores: clinical trial, afiliação de autor(es) brasileira e intervalo de 1º de julho de 2009 a 30 de junho de 2010. Foram selecionados para pareamento artigos relacionados, não brasileiros, publicados entre três meses antes e três meses depois da data de publicação do estudo brasileiro. Foram obtidos os números de citações, em duas bases de dados, assim como o fator de impacto para as revistas nas quais os artigos foram publicados. RESULTADOS: Identificaram-se 43 artigos nacionais e 876 internacionais relacionados. Os brasileiros apresentaram fator de impacto médio de 3.000 contra 3.430 dos internacionais (p=0,041). Não houve diferença estatisticamente significativa quanto ao número de citações entre os grupos. A afiliação do primeiro autor à instituição brasileira ou estrangeira também não influenciou significativamente no número de citações nem no fator de impacto. CONCLUSÃO: Artigos brasileiros são significativamente menos aceitos em revistas de maior impacto sem aparente comprometimento de sua repercussão na comunidade científica.

OBJECTIVE: To investigate whether Brazilian articles on cancer are published in journals with an impact factor and/or repercussion (measured by the number of citations) inferior to those that come from foreign organizations. METHODS: A search was carried out in PubMed for the MeSH term "neoplasm" with the limits clinical trial, affiliation of the Brazilian author(s), and interval from July 1st, 2009 to June 30, 2010. Selected for matching were non-Brazilian related articles published from three months prior to three months after the date of publication of the Brazilian study. The numbers of citations were obtained from two databases, as well as the impact factor for the journals in which the articles were published. RESULTS: Forty-three national and 876 related international articles were identified. The Brazilian publications had a mean impact factor of 3.000 versus 3.430 of the international ones (p=0.041). There was no statistically significant difference as to the number of citations between the two groups. The affiliation of the first author with a Brazilian or foreign organization did not significantly influence the number of citations or the impact factor. CONCLUSION: Brazilian articles are significantly less accepted in journals with higher impact factors, although it does not compromise its repercussion on the scientific community.