Search

Background: Hepatocellular carcinoma (HCC) accounts for approximately 90% of liver cancer cases. Sorafenib, the first drug to demonstrate survival benefits for advanced HCC, was validated through the SHARP randomized clinical trial (RCT). While RCTs are essential for assessing new therapies, real-world studies provide additional insights into their effectiveness in routine clinical practice. This study aimed to evaluate sorafenib’s real-world effectiveness by analyzing overall survival (OS) and the time to radiological and symptomatic progression. Methods: Data from 368 patients treated with sorafenib at a Brazilian Cancer Center between 2009 and 2020 were retrospectively reviewed. Results: The median OS was 9.6 months, and the time to radiological progression was 5.3 months, similar to the SHARP trial. However, the time to symptomatic progression was shorter (2.3 months) than the SHARP study (4.1 months). In terms of safety, 27.4% of patients presented clinically relevant toxicities, and 24.5% needed to discontinue treatment due to toxicity. Conclusions: Overall, sorafenib demonstrated effectiveness in the studied population, with OS and radiological progression times comparable to SHARP study results. The difference in symptomatic progression may be due to the study’s retrospective nature and limitations.

Abstract Endometrial carcinoma (EC) is the most common gynecologic malignancy in high-income countries, with its incidence and mortality rising globally, particularly in countries undergoing rapid socioeconomic transitions. Over the past decade, the management of EC has shifted towards molecular classification and biomarker-driven therapies. This shift began in 2013 with the discovery of the 4 prognostic and molecular EC subgroups by The Cancer Genome Atlas (TCGA). Following the TCGA discovery, the Proactive Molecular Risk Classifiers for Endometrial Cancer (ProMisE) and the TransPORTEC initiative have provided 4 pragmatic molecular classifiers by combining next-generation sequencing (NGS) and surrogate immunohistochemical markers to TCGA’s categorization: Mismatch Repair Deficient (MMRd); p53-abnormal (p53abn); No Specific Molecular Profile (NSMP); and POLE-mutant (POLEmut). These subgroups not only provide insights into the biological behavior of EC but also have strong clinical relevance and prognostic implications. In line with these advancements, the World Health Organization (WHO) endorsed molecular classification in 2020, advocating for its integration into EC pathology reports. In 2023, the Federation of International Gynecology and Obstetrics (FIGO) proposed a new staging system that integrates histological parameters and molecular profiles into routine pathology practice. The use of complete molecular classification surrogates in all EC cases, whenever resources permit, is intended to promote prognostic risk-group stratification, data collection, Lynch Syndrome (LS) screening, and potentially influence adjuvant and systemic treatment decisions, as well as predict the efficacy of Immune Checkpoint Inhibitors (ICI). Consequently, the evolving landscape of predictive biomarkers in EC has gained importance in daily oncology practice, profoundly changing the role of pathologists. Pathologists are now crucial in interpreting molecular information and participating as members of multidisciplinary teams in therapeutic decisions. This review article aims to emphasize the importance of molecular classification in EC and encourage pathologists to become familiar with the use of predictive biomarkers in their daily anatomical pathology practice.

Abstract We evaluated the prevalence of pathogenic/likely pathogenic germline variants (PGV) in Brazilian pancreatic adenocarcinoma (PC) patients, that represent a multiethnic population, in a cross-sectional study. We included 192 PC patients unselected for family history of cancer. We evaluated a panel of 113 cancer genes, through genomic DNA sequencing and 46 ancestry-informative markers, through multiplex PCR. The median age was 61 years; 63.5% of the patients presented disease clinical stages III or IV; 8.3% reported personal history of cancer; 4.7% and 16.1% reported first-degree relatives with PC or breast and/or prostate cancer, respectively. Although the main ancestry was European, there was considerable genetic composition admixture. Twelve patients (6.25%) were PGV carriers in PC predisposition genes (ATM, BRCA1, BRCA2, CDKN2A, MSH2, PALB2) and another 25 (13.0%) were PGV carriers in genes with a limited association or not previously associated with PC (ACD, BLM, BRIP1, CHEK2, ERCC4, FANCA, FANCE, FANCM, GALNT12, MITF, MRE11, MUTYH, POLE, RAD51B, RAD51C, RECQL4, SDHA, TERF2IP). The most frequently affected genes were CHEK2, ATM and FANC. In tumor samples from PGV carriers in ACD, BRIP1, MRE11, POLE, SDHA, TERF2IP, which were examined through exome sequencing, the main single base substitutions (SBS) mutational signature was SBS1+5+18, probably associated with age, tobacco smoking and reactive oxygen species. SBS3 associated with homologous repair deficiency was also represented, but on a lower scale. There was no difference in the frequency of PGV carriers between: (a) patients with or without first-degree relatives with cancer; and (b) patients with admixed ancestry versus those with predominantly European ancestry. Furthermore, there was no difference in overall survival between PGV carriers and non-carriers. Therefore, genetic testing should be offered to all Brazilian pancreatic cancer patients, regardless of their ancestry. Genes with limited or previously unrecognized associations with pancreatic cancer should be further investigated to clarify their role in cancer risk.

IntroductionWe conducted an extensive, sex-oriented real-world data analysis to explore the impact and safety of non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors (coxibs) on cancer treatment outcomes. This is particularly relevant given the role of the COX-2/PGE2 pathway in tumor cell resistance to chemotherapy and radiotherapy.MethodsThe study applied a retrospective cohort design utilizing the TriNetX research database consisting of patients receiving cancer treatment in 2008-2022. The treated cohorts included patients who were prescribed with coxibs, aspirin or ibuprofen, while individuals in the control cohort did not receive these medicines during their cancer treatment. A 1:1 propensity score matching technique was used to balance the baseline characteristics in the treated and control cohorts. Then, Cox proportional hazards regression and logistic regression were applied to assess the mortality and morbidity risks among patient cohorts in a 5-year follow-up period.ResultsUse of coxibs (HR, 0.825; 95% CI 0.792-0.859 in females and HR, 0.884; 95% CI 0.848-0.921 in males) and ibuprofen (HR, 0.924; 95% CI 0.903-0.945 in females and HR, 0.940; 95% CI 0.917-0.963 in males) were associated with improved survival. Female cancer patients receiving aspirin presented increased mortality (HR, 1.078; 95% CI 1.060-1.097), while male cancer patients also had improved survival when receiving aspirin (HR, 0.966; 95% CI 0.951-0.980). Cancer subtype specific analysis suggests coxibs and ibuprofen correlated with survival, though ibuprofen and aspirin increased emergency department visits’ risk. Secondary analyses, despite limited by small cohort sizes, suggest that COX inhibition post-cancer diagnosis may benefit patients with specific cancer subtypes.DiscussionSelective COX-2 inhibition significantly reduced mortality and emergency department visit rates. Further clinical trials are needed to determine the optimal conditions for indication of coxibs as anti-inflammatory adjuvants in cancer treatment.

PURPOSEMost patients with cancer will be hospitalized throughout the disease course. However, most evidence on the causes and outcomes of these hospitalizations comes from administrative data or small retrospective studies from high-income countries.METHODSThis study is a retrospective cohort of patients with solid tumors hospitalized from February 1, 2021, to December 31, 2021, in a tertiary cancer center in São Paulo, Brazil. We collected data on cancer diagnosis, symptoms at admission, hospitalization diagnosis, and survival clinical outcomes during in-hospital stay (in-hospital mortality) and after discharge (readmission rates and overall survival [OS]). Progressive disease (PD) diagnosis during admission was retrieved from manual chart review if explicitly stated by the attending physician. We modeled in-hospital mortality and postdischarge OS with logistic regression and Cox proportional hazards models, respectively.RESULTSA total of 3,726 unique unplanned admissions were identified. The most common symptoms at admission were pain (40.6%), nausea (16.8%), and dyspnea (16.1%). PD (34.0%), infection (31.1%), and cancer pain (13.4%) were the most frequent reasons for admission. The in-hospital mortality rate was 18.9%. Patients with PD had a high in-hospital mortality rate across all tumor groups and higher odds of in-hospital death (odds ratio, 3.5 [95% CI, 3.0 to 4.2]). The 7-, 30-, and 90-day readmission rates were 11.9%, 33.5%, and 54%, respectively. The postdischarge median OS (mOS) was 12.6 months (95% CI, 11.6 to 13.7). Poorer postdischarge survival was observed among patients with PD (mOS, 5 months v 18 months; P < .001; hazard ratio, 2.4 [95% CI, 2.1 to 2.6]).CONCLUSIONPD is a common diagnosis during unplanned hospitalizations and is associated with higher in-hospital mortality rates and poorer OS after discharge. Oncologists should be aware of the prognostic implications of PD during admission and align goals of care with their patients.

Borderline ovarian tumors typically exhibit indolent behavior and boast a favorable prognosis; however, a subset of patients experiences disease recurrence and progression to low-grade ovarian carcinoma. The complex biology underlying these phenomena has been illuminated through molecular analyses. KRAS and BRAF mutations have emerged as recurrent ?ndings in borderline ovarian tumors. Speci?cally, KRAS mutations have been linked to a higher risk of recurrence and progression to low-grade ovarian carcinoma, while BRAF mutations seem to confer a protective e?ect, inducing a senescent state that mitigates the likelihood of progression. In this comprehensive review, we explore the biology and the molecular pro?le of borderline ovarian tumors, shedding light on recent discoveries that have enriched our comprehension. Additionally, we discuss the current state of borderline ovarian tumors management. Surgery remains the cornerstone of treatment. While cytotoxic therapies role is limited so far, molecular characterization emphasizes the imminent potential for personalized therapeutic approaches.

Introduction: Breast cancer (BC) is the most common type of cancer in premenopausal women with germline TP53 pathogenic variants (mTP53) (Li Fraumeni syndrome - LFS). However, little is known about the BC prognosis in these patients. This study analyzed the BC-related oncologic outcomes of patients with LFS. Methods: We evaluated a cohort of LFS patients with BC in comparison with a control cohort of BC patients with no pathogenic variant in a hereditary cancer panel. The primary endpoint was recurrence-free survival (RFS). Due to the risk of second malignancies in LFS, only locoregional and distant recurrences were considered events for RFS. Secondary endpoints included rates of contralateral BC, overall survival (OS), and breast cancer-specific survival (BCSS). Results: Forty-one patients were evaluated in the mTP53 group and 82 in the control group. Median age at BC diagnosis was 40 and 41 years, respectively. The mTP53 group received less adjuvant radiotherapy than the control group (63.4% vs 93.9%, P

Introdução/Objetivo: Aeromonas spp. são microrganismos ubíquos, frequentemente encontrados em ambientes aquáticos, e podem causar infecções graves em pacientes imunossuprimidos. Este estudo tem como objetivo avaliar as características clínicas e microbiológicas de pacientes oncológicos com bacteremia por este microrganismo. Métodos: Estudo retrospectivo, envolvendo pacientes com Aeromonas spp. isolado em hemoculturas no período de janeiro de 2013 a maio de 2023 em um hospital oncológico. As características clínicas e demográficas dos pacientes foram analisadas. A identificação e o perfil de sensibilidade das cepas de Aeromonas aos antimicrobianos foram determinadas por métodos automatizados (VITEK2). Resultados: Foram identificados 56 pacientes com bacteremia por Aeromonas spp. A maioria era do sexo masculino (32; 57,1%) e portador de tumor sólido (41; 73,2%), principalmente câncer de pâncreas (14; 25,0%) e de vias biliares (8; 14,3%). Quinze (26,8%) pacientes tinham doença onco-hematológica (10; 17,9% tinham leucemia mieloide aguda). Vinte (35,7%) pacientes eram neutropênicos e 37 (66,1%) receberam quimioterapia nos 30 dias antes do diagnóstico. Maioria das infecções foram identificadas na admissão (34; 60,7%) e o sitio primário de infeção foi o trato biliar na maior parte dos casos (23; 41,1%), mas 21 pacientes (37,5%) apresentaram infecção primária da corrente sanguínea. A maioria dos casos (30;53,6%) foram considerados como infecção polimicrobiana; E. coli (15; 26,8%) e K. pneumoniae (14; 25%) foram os microrganismos mais isolados. Mais de 90% das cepas de Aeromonas eram sensíveis aos aminoglicosídeos, cefalosporinas de 3ª e 4ª gerações, piperacilina-tazobactam, carbapenêmicos e fluorquinolonas. Meropenem (26; 46,4%) e piperacilina-tazobactam (19; 33,9%) foram os antimicrobianos mais utilizados para o tratamento. A mortalidade em 7 e 30 dias foi de 41,1% e 60,7%, respectivamente. Conclusão: Pacientes com câncer podem apresentar infecções intra e extra-abdominais por Aeromonas, com elevada mortalidade. A maioria das infecções eram admissionais e polimicrobianas. Os beta-lactâmicos (cefalosporinas de 3ª e 4ª gerações; piperacilina-tazobactam e carbapenêmicos), os aminoglicosídeos e as quinolonas continuam ativos contra este microrganismo.

PURPOSEPatients with cancer are at increased risk for unfavorable outcomes from COVID-19. Knowledge about the outcome determinants of severe acute respiratory syndrome coronavirus 2 infection in this population is essential for risk stratification and definition of appropriate management. Our objective was to evaluate prognostic factors for all-cause mortality in patients diagnosed with both cancer and COVID-19.METHODSAll consecutive patients with cancer hospitalized at our institution with COVID-19 were included. Electronic medical records were reviewed for clinical and laboratory characteristics potentially associated with outcomes.RESULTSFive hundred seventy-six consecutive patients with cancer and COVID-19 were included in the present study. An overall in-hospital mortality rate of 49.3% was demonstrated. Clinical factors associated with increased risk of death because of COVID-19 were age over 65 years, Eastern Cooperative Oncology Group performance status > 0 zero, best supportive care, primary lung cancer, and the presence of lung metastases. Laboratory findings associated with a higher risk of unfavorable outcomes were neutrophilia, lymphopenia, and elevated levels of D-dimer, creatinine, C-reactive protein, or AST.CONCLUSIONA high mortality rate in patients with cancer who were diagnosed with COVID-19 was demonstrated in the present study, emphasizing the need for close surveillance in this group of patients, especially in those with unfavorable prognostic characteristics.

PURPOSEThe objective of this review is to address the barriers limiting access to treatment of advanced metastatic breast cancer (mBC) in Brazil, specifically for patients in the public health care system, arguably those with the least access to innovation.MATERIALS AND METHODSA selected panel of Brazilian experts in BC were provided with a series of relevant questions to address in a multiday conference. During the conference, responses were discussed and edited by the entire group through numerous drafts and rounds of discussion until a consensus was achieved.RESULTSThe authors propose specific and realistic recommendations for implementing access to new drugs in cancer care in Brazil. Moreover, in creating these recommendations and framework, the authors strive to address the most important barriers and impediments for technology incorporation. A feasible and specific multidisciplinary process is proposed, which is based on the collective participation of all involved stakeholders.CONCLUSIONGiven the current benefits and likely future developments, there is a great need to expand treatments for mBC not only in Brazil but also in most other countries in the world where access issues remain an unresolved demand. Adapting the current framework is essential for accomplishing this goal. The recommendations in this review can serve as a framework for adoption of new technologies in countries with limited resources.

Abstract Young breast cancer (BC) patients carrying a germline BRCA pathogenic variant (mBRCA) have similar outcomes as non-carriers. However, the impact of the type of gene (BRCA1 vs. BRCA2) and hormone receptor status (positive [HR+] vs. negative [HR−]) on clinical behavior and outcomes of mBRCA BC remains largely unknown. This is an international, multicenter, hospital-based, retrospective cohort study that included mBRCA patients diagnosed, between January 2000 and December 2012, with stage I–III invasive early BC at age ≤40 years. From 30 centers worldwide, 1236 young mBRCA BC patients were included. Among 808 and 428 patients with mBRCA1 or mBRCA2, 191 (23.6%) and 356 (83.2%) had HR+tumors, respectively (P

Resumo O desafio imposto ao sistema de saúde pela pandemia da COVID-19 faz com que haja uma necessidade de readequações de rotinas e serviços de saúde, com os objetivos de controlar a disseminação do vírus e preservar a saúde. Torna-se ainda mais importante o manejo seguro e correto dos pacientes dos grupos de risco, como os pacientes idosos, os portadores de doenças cardiovasculares e os pacientes com câncer. Dessa forma, a cardio-oncologia ganha novo dimensionamento, no intuito de se adequar às necessidades dos pacientes diante de uma pandemia, reestruturando o sistema de atendimento de forma a oferecer qualidade e segurança na assistência à saúde.

BackgroundIn recent years, the potential of multi-criteria decision analysis (MCDA) in the health field has been discussed widely. However, most MCDA methodologies have given little attention to the aggregation of different stakeholder individual perspectives.ObjectiveTo illustrate how a paraconsistent theory-based MCDA reusable framework, designed to aid hospital-based Health Technology Assessment (HTA), could be used to aggregate individual expert perspectives when valuing cancer treatments.MethodsAn MCDA methodological process was adopted based on paraconsistent theory and following ISPOR recommended steps in conducting an MCDA study. A proof-of-concept exercise focusing on identifying and assessing the global value of first-line treatments for metastatic colorectal cancer (mCRC) was conducted to foster the development of the MCDA framework.ResultsOn consultation with hospital-based HTA committee members, 11 perspectives were considered in an expert panel: medical oncology, oncologic surgery, radiotherapy, palliative care, pharmacist, health economist, epidemiologist, public health expert, health media expert, pharmaceutical industry, and patient advocate. The highest weights were assigned to the criteria "overall survival" (mean 0.22), "burden of disease" (mean 0.21) and "adverse events" (mean 0.20), and the lowest weights were given to "progression-free survival" and "cost of treatment" (mean 0.18 for both). FOLFIRI and mFlox scored the highest global value score of 0.75, followed by mFOLFOX6 with a global value score of 0.71. mIFL was ranked last with a global value score of 0.62. The paraconsistent analysis (para-analysis) of 6 first-line treatments for mCRC indicated that FOLFIRI and mFlox were the appropriate options for reimbursement in the context of this study.ConclusionThe Paraconsistent Value Framework is proposed as a step beyond the current MCDA practices, in order to improve means of dealing with individual expert perspectives in hospital-based HTA of cancer treatments.

Poly (ADP-ribose) polymerase (PARP) inhibitors constitute an important treatment option for ovarian cancer nowadays. The magnitude of benefit from PARP inhibitors is influenced by the homologous recombination status, with greater benefit observed in patients with BRCA mutated or BRCA wild-type homologous recombination deficient (HRD) tumors. Although some PARP inhibitor activity has been shown in homologous recombination proficient (HRP) ovarian tumors, its clinical relevance as a single agent is unsatisfactory in this population. Furthermore, even HRD tumors present primary or secondary resistance to PARP inhibitors. Strategies to overcome treatment resistance, as well as to enhance PARP inhibitors’ efficacy in HRP tumors, are highly warranted. Diverse combinations are being studied with this aim, including combinations with antiangiogenics, immunotherapy, and other targeted therapies. This review discusses the rationale for developing therapy combinations with PARP inhibitors, the current knowledge, and the future perspectives on this issue.

ABSTRACT BACKGROUND: Management of rectal cancer has become more complex with multimodality therapy (neoadjuvant chemoradiotherapy and surgery) and this has led to the need to organize multidisciplinary teams. The aim of this study was to report on the planning, implementation and evaluation of an integrated care pathway for neoadjuvant treatment of middle and lower rectal cancer. DESIGN AND SETTING: This was a cross-sectional post-implementation study that was carried out at a public university cancer center. METHODS: The Framework for Program Evaluation in Public Health of the Centers for Disease Control and Prevention (CDC) was used to identify resources and activities; link results from activities and outcomes with expected goals; and originate indicators and outcome measurements. RESULTS: The logic model identified four activities: stakeholders’ engagement, clinical pathway development, information technology improvements and training programs; and three categories of outcomes: access to care, effectiveness and organizational outcomes. The measurements involved 218 patients, among whom 66.3% had their first consultation within 15 days after admission; 75.2% underwent surgery < 14 weeks after the end of neoadjuvant treatment and 72.7% completed the treatment in < 189 days. There was 100% adherence to the protocol for the regimen of 5-fluorouracil and leucovorin. CONCLUSIONS: The logic model was useful for evaluating the implementation of the integrated care pathways and for identifying measurements to be made in future outcome studies.

OBJECTIVES: In breast cancer (BC) patients, the frequency of germline BRCA mutations (gBRCA) may vary according to the ethnic background, age, and family history of cancer. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the second most common somatic mutated gene in BC; however, the association of mutations in both genes with cancer has not been thoroughly investigated. Thus, our aims were to investigate gBRCA mutation frequency in a cohort of postmenopausal Brazilian BC patients and the association of gBRCA1/BRCA2 and PIK3CA somatic mutations. METHODS: Forty-nine postmenopausal (>55 years) and forty-one young (≤35 years) BC patients were included in this study. The postmenopausal group included patients who reported a positive family history of cancer. For these patients, gBRCA1/BRCA2 were sequenced using next-generation sequencing (NGS) or Sanger sequencing. Data for gBRCA in young patients were already available from a previous study. DNA from formalin-fixed, paraffin-embedded (FFPE) tumors was obtained from 27 postmenopausal and 41 young patients for analyzing exons 9 and 20 of PIK3CA. The association between gBRCA1/BRCA2 and somatic mutations in PIK3CA was investigated. RESULTS: The overall frequency of gBRCA1/BRCA2 among the 49 postmenopausal patients was 10.2%. The frequencies of somatic mutations in PIK3CA in the postmenopausal and young patients were 37% and 17%, respectively (ns). The most common PIK3CA mutation was found to be E454A. Nonsense and frameshift mutations, which may counteract the oncogenic potential of PIK3CA were also detected. Regardless of age, 25% of BRCA1/BRCA2 mutation carriers and non-carriers , each, had PIK3CA somatic mutations. CONCLUSIONS: Data obtained indicate that BRCA1/BRCA2 gene testing may be considered for postmenopausal patients with BC who have a family history of cancer. Although some of them are not considered pathogenic, somatic variants of PIK3CA are frequently observed in BC patients, especially in postmenopausal patients.

Purpose: The purpose of this new resource-stratified guideline is to provide expert guidance to clinicians and policymakers on implementing palliative care of patients with cancer and their caregivers in resource-constrained settings and is intended to complement the Integration of Palliative Care Into Standard Oncology Care: American Society of Clinical Oncology Clinical Practice Guideline Update of 2016. Methods: ASCO convened a multidisciplinary, multinational panel of experts in medical oncology, family medicine, radiation oncology, hematology/oncology, palliative and/or hospice care, pain and/or symptom management, patient advocacy, public health, and health economics. Guideline development involved a systematic literature review, a modified ADAPTE process, and a formal consensus-based process with the Expert Panel and additional experts (consensus ratings group). Results: The systematic review included 48 full-text publications regarding palliative care in resource-constrained settings, along with cost-effectiveness analyses; the evidence for many clinical questions was limited. These provided indirect evidence to inform the formal consensus process, which resulted in agreement of ≥ 75% (by consensus ratings group including Expert Panel). Recommendations: The recommendations help define the models of care, staffing requirements, and roles and training needs of team members in a variety of resource settings for palliative care. Recommendations also outline the standards for provision of psychosocial support, spiritual care, and opioid analgesics, which can be particularly challenging and often overlooked in resource-constrained settings. Additional information is available at www.asco.org/resource-stratified-guidelines.It is the view of ASCO that health care providers and health care system decision makers should be guided by the recommendations for the highest stratum of resources available. The guideline is intended to complement but not replace local guidelines.

Purpose: The best adjuvant treatment in high-risk endometrial cancer remains unclear. Although adjuvant chemotherapy seems to improve overall survival (OS) in locally advanced disease, the role of adding radiotherapy is not certain. We evaluated the outcomes of patients with high-risk endometrial cancer treated with adjuvant chemotherapy followed by radiotherapy. Patients and Methods: We performed a retrospective analysis of patients with high-risk endometrial cancer (endometrioid histology stages III to IVA or carcinosarcoma, clear cell, or serous histology stages I to IVA) treated with adjuvant carboplatin and paclitaxel, followed by radiotherapy, from 2010 to 2017 at a Brazilian cancer center. The Kaplan-Meier method was used for survival analysis, and prognostic factors were analyzed using the Cox proportional hazards model. Results: One hundred forty-six consecutive patients were evaluated. The OS rates were 86.2% at 3 years and 75.4% at 5 years. OS was significantly affected by pelvic lymphadenectomy (P = .001) and positive peritoneal cytology (P < .001). Three- and 5-year disease-free survival (DFS) rates were 78.3% and 69.5%, respectively. The initial site of recurrence was limited to the pelvis in 4.1% of patients, within the abdomen in 1.3%, and extra-abdominal in 11.6%. Patients with grade 1 or 2 endometrioid carcinoma had better prognosis than patients with endometrioid carcinoma grade 3 or nonendometrioid histology (3-year DFS, 93.67% v 68.5%, respectively; P = .0017). Conclusion: Adjuvant carboplatin and paclitaxel, followed by radiotherapy, is effective in high-risk endometrial cancer and associated with low rates of pelvic recurrence, which might be explained by the addition of radiotherapy. The high-risk group is heterogeneous, and the benefit of adjuvant treatment in patients with grade 1 or 2 endometrioid carcinoma is less clear.

Abstract Hereditary cancer risk assessment is a multidisciplinary and dynamic process, with the purpose of estimating probabilities of germline mutations in cancer susceptibility genes and assessing empiric risks of cancer based on personal and family histories, in order to offer clinical and molecular diagnoses and clinical management based on these risks. Genetic tests are available and most of them are reimbursed by insurance companies, although they are generally not covered by the public health systems of developing countries. More recently, molecular diagnosis of hereditary cancer is feasible through next-generation sequencing (NGS) panels. Here we review the benefits and limitations of NGS technologies in the clinical practice.

ABSTRACT OBJECTIVE: To analyze the cost effectiveness of the diagnostic program for the germline mutation in BRCA1/2 genes and of preventative strategies for the relatives of patients diagnosed with ovarian cancer associated with this mutation. METHODS: The study analyzed the cost effectiveness by developing an analysis of the Markov decision process from the perspective of the National Health System. The strategies compared reflect upon the adoption of genetic testing and preventative strategies for relatives or the usual care currently proposed. The incremental cost-effectiveness ratio was expressed in terms of cost per case avoided. The sensitivity analysis was performed in a univariate and deterministic manner. RESULTS: The study showed increments for effectiveness and for costs when performing genetic testing and adopting prophylactic measures for family members. The incremental cost-effectiveness ratio was estimated at R$908.58 per case of cancer avoided, a figure considered lower than the study's cost-effectiveness threshold (R$7,543.50). CONCLUSIONS: The program analyzed should be considered a cost-effective strategy for the national situation. Studies in various other countries have reached similar conclusions. One possible ramification of this research might the need to perform a budgetary-impact analysis of making the program one of the country's health policies.

Ovarian cancer patients with homologous recombination deficiencies exhibit specific clinical behaviors, and improved responses to treatments, such as platinum-based chemotherapy and poly (ADP-ribose) polymerase (PARP) inhibitors, have been observed. Germline mutations in the BRCA 1/2 genes are the most well-known mechanisms of homologous recombination deficiency. However, other mechanisms, such as germline and somatic mutations in other homologous recombination genes and epigenetic modifications, have also been implicated in homologous recombination deficiency. The epidemiology and implications of these other mechanisms need to be better understood to improve the treatment strategies for these patients. Furthermore, an evaluation of various diagnostic tests to investigate homologous recombination deficiency is essential. Comprehension of the role of homologous recombination deficiency in ovarian cancer also allows the development of therapeutic combinations that can improve the efficacy of treatment. In this review, we discuss the epidemiology and management of homologous recombination deficiency in ovarian cancer patients.

Background: A large number of health economic evaluation (HEE) studies have been published in developed countries. However, Brazilian HEE literature in oncology has not been studied. Objective: To investigate whether the scientific literature has provided a set of HEE in oncology capable of supporting decision making in the Brazilian context.Methods: A systematic review was conducted to identify and characterize studies in this field. We searched multiple databases selecting partial and full HEE studies in oncology (1998-2013).Results: Fifty-five articles were reviewed, of these, 33 (60%) were full health economic evaluations. Type of cancers most frequently studied were: breast (38.2%), cervical (14.6%), lung (10.9%) and colorectal (9.1%). Procedures (47.3%) were the technologies most frequently evaluated. In terms of the intended purposes of the technologies, most (63.6%) were treatments. The majority of the incremental cost-effectiveness ratios (ICERs) reported have been below the cost-effectiveness threshold suggested by the World Health Organization (WHO).Conclusions: There has been an increase in the number of HEEs related to cancer in Brazil. These studies may support decision-making processes regarding the coverage of and reimbursement of healthcare technologies for cancer treatment in Brazil.

Resumo: O câncer de mama é a principal causa de morte por câncer em mulheres no Brasil. As novas diretrizes para detecção precoce no Brasil foram elaboradas com base em revisões sistemáticas da literatura sobre riscos e possíveis benefícios de diversas estratégias de detecção precoce. O objetivo do presente artigo é apresentar as recomendações e atualizar a síntese de evidências, discutindo as principais controvérsias existentes. As recomendações para o rastreamento do câncer de mama (mulheres assintomáticas) foram: (i) recomendação contrária forte ao rastreamento com mamografia em mulheres com menos de 50 anos; (ii) recomendação favorável fraca ao rastreamento com mamografia em mulheres com idades entre 50 e 69 anos; (iii) recomendação contrária fraca ao rastreamento com mamografia em mulheres com idades entre 70 e 74 anos; (iv) recomendação contrária forte ao rastreamento com mamografia em mulheres com 75 anos ou mais; (v) recomendação favorável forte de que o rastreamento nas faixas etárias recomendadas seja bienal, quando comparada às periodicidades menores do que a bienal; (vi) recomendação contrária fraca ao ensino do autoexame das mamas para rastreamento; (vii) ausência de recomendação favorável ou contrária ao rastreamento com exame clínico das mamas; e (viii) recomendação contrária forte ao rastreamento com ressonância nuclear magnética, ultrassonografia, termografia ou tomossíntese, seja isoladamente, seja como complemento à mamografia. As recomendações para o diagnóstico precoce do câncer de mama (mulheres com sinais ou sintomas suspeitos) foram: (i) recomendação favorável fraca à implementação de estratégias de conscientização para o diagnóstico precoce do câncer de mama; (ii) recomendação favorável fraca ao uso de sinais e sintomas selecionados nas presentes diretrizes como critério de referência urgente para serviços de diagnóstico mamário; e (iii) recomendação favorável fraca de que toda a avaliação diagnóstica do câncer de mama, após a identificação de sinais e sintomas suspeitos na atenção primária, seja feita em um mesmo centro de referência.

Small-cell ovarian carcinoma (SCOC) is a rare and aggressive neoplasia, predominantly affecting young women who are frequently first diagnosed with advanced stage disease. Platinum-based chemotherapy (ChT) can provide high response rates and rapidly ameliorate symptoms in this scenario. However, progression after chemotherapy usually occurs quickly, leading to high mortality rates. In addition, ChT complications, such as tumor lysis syndrome (TLS) can also occur, jeopardizing the patient’s outcome. We present a case of metastatic SCOC in a 47-year-old patient who achieved tumor response after platinum-based chemotherapy and developed TLS, from which she recovered with supportive treatment. After the second ChT cycle, she developed febrile neutropenia and died 8 weeks after the diagnosis of SCOC. Although SCOC is a chemo-sensitive tumor, short-lived responses and frequent chemotherapy complications lead to a dismal prognosis.

Teratomas are the most commonly diagnosed germ cell tumors and occur primarily in testes and ovaries. Platinum-based therapy followed by surgical resection of the residual lesion is generally the recommended treatment. In contrast, immature uterine teratomas are rare, with few cases reported in the literature. Moreover, there is no standard treatment for these tumors. Non-puerperal uterine inversion is also rare in women younger than 45 years of age, and neoplastic lesions are responsible for this condition. Here, we report a case of an immature uterine teratoma associated with uterine inversion. The patient underwent surgery followed by adjuvant chemotherapy and continues to be monitored.

Primary choriocarcinoma of the ovary is rare. Furthermore, this tumor can arise from gestational tissue or pure germ cells of the ovary, with the latter resulting in non-gestational choriocarcinoma. While the clinical characteristics and histology of both tumor types are identical, differentiation of these tumors is necessary for effective treatment. One strategy for the differentiation of these tumors types is to assay for the presence of paternal DNA. Accordingly, in the present case, a patient with primary choriocarcinoma of the ovary with a non-gestational origin was confirmed by DNA analysis. The patient subsequently exhibited an excellent response to chemotherapy, and following surgery, achieved complete remission. A pathological analysis of surgical specimens further confirmed the absence of tumor.