Filomena Marino Carvalho

Management of endometrial cancer in Latin America: raising the standard of care and optimizing outcomes

Molecular characterization of endometrial cancer is allowing for increased understanding of the natural history of tumors and paving a more solid pathway for novel therapies. It is becoming increasingly apparent that molecular classification is superior to histological classification in terms of reproducibility and prognostic discrimination. In particular, the Proactive Molecular Risk Classifier for Endometrial Cancer allows classification of endometrial cancer into groups very close to those determined by the Cancer Genome Atlas Research Network—that is, DNA polymerase epsilon-mutated, mismatch repair-deficient, p53 abnormal, and non-specific molecular profile tumors. The transition from the chemotherapy era to the age of targeted agents and immunotherapy, which started later in endometrial cancer than in many other tumor types, requires widespread availability of specialized pathology and access to novel agents. Likewise, surgical expertise and state-of-the-art radiotherapy modalities are required to ensure adequate care. Nevertheless, Latin American countries still face considerable barriers to implementation of international guidelines. As we witness the dawn of precision medicine as applied to endometrial cancer, we must make continued efforts towards improving the quality of care in this region. The current article discusses some of these challenges and possible solutions.

Role of systematic pelvic and para‐aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy cycles for high‐grade serous ovarian carcinoma

AbstractIntroductionWe analyzed the role of systematic pelvic and para‐aortic lymphadenectomy in delayed debulking surgery after six neoadjuvant chemotherapy (NACT) cycles for advanced high‐grade serous ovarian carcinoma.Materials and MethodsWe retrospectively reviewed patients with advanced ovarian carcinoma who underwent NACT with carboplatin‐paclitaxel between 2008 and 2016. Patients were included only if they had FIGO IIIC‐IVB high‐grade serous carcinoma with clinically negative lymph nodes after six NACT cycles (carboplatin‐paclitaxel) and underwent complete or near complete cytoreduction. Patients with partial lymphadenectomy or bulky nodes were excluded. Patients who underwent systematic pelvic and aortic lymphadenectomy and those who did not undergo lymph node dissection were compared. Progression‐free and overall survivals were analyzed using the Kaplan–Meier method.ResultsTotally, 132 patients with FIGO IIIC‐IVB epithelial ovarian carcinoma were surgically treated after NACT. Sixty patients were included (39 and 21 in the lymphadenectomy and nonlymphadenectomy group, respectively); 40% had suspicious lymph nodes before NACT. Patient characteristics, blood transfusion numbers, and complication incidence were similar between the groups. In the lymphadenectomy group, 12 patients (30.8%) had histologically positive lymph nodes and the surgical time was longer (229 vs. 164 min). The median overall survival in the lymphadenectomy and nonlymphadenectomy groups, respectively, was 56.7 (95% CI 43.4–70.1) and 61.2 (21.4–101.0) months (p = 0.934); the corresponding disease‐free survival was 8.1 (6.2–10.1) and 8.3 (5.1–11.6) months (p = 0.878). Six patients exclusively presented with lymph node recurrence.ConclusionsSystematic lymphadenectomy after six NACT cycles may have no influence on survival.

L1 cell adhesion molecule (L1CAM) in stage IB cervical cancer: distinct expression in squamous cell carcinomas and adenocarcinomas

Aims L1 cell adhesion molecule (L1CAM) has been shown to be correlated with tumour progression, attributed to its possible association with epithelial-mesenchymal transition (EMT), characterised by the expression of vimentin and loss of e-cadherin. Herein, we investigate the associations between L1CAM and clinicopathological parameters, as well as the expression of vimentin and e-cadherin, in carcinomas restricted to the cervix. Methods The study was retrospective observational and included 45 squamous cell carcinomas (63.4%) and 26 adenocarcinomas (36.6%) submitted to primary surgical treatment. Patient age, FIGO (International Federation of Gynecology and Obstetrics) stage, tumour size and follow-up were obtained from the medical records. All the slides were revised to evaluate histological differentiation, lymphovascular space invasion, depth of infiltration, disease-free cervical wall thickness, pattern of invasion front, Silva pattern (for adenocarcinomas) and the percentage of tumour-infiltrating lymphocytes. Tissue microarrays were constructed for immunohistochemical staining for L1CAM, e-cadherin and vimentin. Results Adenocarcinomas were associated with lower disease-free and overall survival. L1CAM and vimentin expressions were more frequent among adenocarcinomas, although loss of e-cadherin expression was more common among squamous carcinomas. L1CAM expression was associated with larger tumours, vimentin expression and lower disease-free survival. No association was observed between the expression of either L1CAM or vimentin and loss of e-cadherin. High levels of tumour-infiltrating lymphocytes were more frequent in squamous cell carcinoma, high-grade tumours, destructive pattern at front of invasion and loss of e-cadherin expression. Conclusions Our results confirm the prognostic role of L1CAM in cervical carcinomas, but suggest a role for mechanisms other than EMT.