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

INTRODUCTION: We 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 METHODS: We 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. RESULTS: Totally, 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. CONCLUSIONS: Systematic lymphadenectomy after six NACT cycles may have no influence on survival.

Adjuvant Carboplatin and Paclitaxel Chemotherapy Followed by Radiotherapy in High-Risk Endometrial Cancer: A Retrospective Analysis.

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.

Management of Para-aortic Lymph Node Disease in Patients With Cervical Cancer: What Is the Best Approach?

Cervical cancer remains a prevalent and deadly disease in low-income countries, especially among young and otherwise healthy women. Multimodality treatment has led to a significant improvement in outcomes for patients with locally advanced disease, and this is mainly because of the incorporation of platinum-based chemoradiotherapy in current treatment protocols. However, locally advanced tumors are associated with a greater risk for para-aortic lymph node (PALN) involvement, which is an important adverse prognostic factor. Most staging techniques have low accuracy for detection of disease in this area, which could lead to understaging and undertreatment. Meanwhile, patients with PALN disease are underrepresented in trials addressing the treatment of advanced cervical cancer and a few studies have been directed at this population. The aim of this review is to analyze the current data regarding staging and treatment of cervical cancer with PALN disease to determine which strategy is best when managing these patients.

Carboplatin-based chemoradiotherapy in advanced cervical cancer: an alternative to cisplatin-based regimen?

OBJECTIVE: To evaluate the results of treatment with cisplatin or carboplatin concomitant with radiotherapy (RT) in cases of locally advanced cervical cancer (CC). METHODS: This study is a retrospective analysis of medical records of 184 patients with cervical cancer stage IIB-IVA who were treated at Instituto do Câncer do Estado de São Paulo from May 2008 to December 2012. All patients received complete pelvic region external-beam RT with weekly cisplatin (cis-RT, 40mg/m(2); n=159) or carboplatin (carbo-RT, AUC 2; n=25), followed by high-dose-rate intracavitary brachytherapy (HDR-ICBT). Primary endpoint was progression free survival; secondary endpoints were overall survival and overall response rate, which includes complete and partial responses. RESULTS: Five or more chemotherapy cycles were administered to 87.3% and 84% of the cis-RT- and carbo-RT- treated patients, respectively (p=0.749). Estimated 3-years progression free survival was 59% in the cis-RT group vs 40% in the carbo-RT group (p=0.249). Estimated 3-years overall survival was 70% in the cis-RT group vs 68% in the carbo-RT group (p=0.298). Overall response rate (95.3% cis-RT vs 95.4% carbo-RT; p=0.911) and grade ≥3 toxic effects (8.5% cis-RT vs 11.8% carbo-RT; p=0.757) were similar. In multivariate analysis, only the overall response rate was a significant predictor of survival. CONCLUSIONS: Patients with advanced cervical cancer who are treated with carbo-RT have similar 3-years overall survival, progression free survival, overall response rate, and toxic effects when compared to cis-RT-treated patients. Carbo-RT may be an alternative treatment in patients that cannot receive cisplatin.

Oncologic Concerns regarding Laparoscopic Cytoreductive Surgery in Patients with Advanced Ovarian Cancer Submitted to Neoadjuvant Chemotherapy.

BACKGROUND: Presently, the use of laparoscopy in advanced ovarian cancer (AOC) is extremely controversial. In the era of neoadjuvant chemotherapy (NACT), endoscopic debulking surgery could be a reasonable alternative for selected patients with primarily unresectable disease. OBJECTIVES: To evaluate the feasibility as well as the operative and oncologic safety of laparoscopic debulking surgery in patients with AOC submitted to NACT. METHODS: This is a pilot observational study on initially unresectable, high-grade serous ovarian cancer treated with a sequence of 6 cycles of carboplatin and paclitaxel followed by debulking surgery performed by laparoscopy (group 1) or laparotomy (group 2). The inclusion criteria were clinical complete response, CA-125 normalization, imaging without disease in critical areas, and optimal cytoreduction. RESULTS: From January 2011 to March 2014, 21 patients were included. Ten women underwent laparoscopy and 11 laparotomy. No epidemiological or oncologic differences were observed between the groups. No surgery-related casualties, intraoperative complications, conversion to laparotomy, or excessive blood loss or transfusion was detected in the laparoscopic procedures. The mean time of operation was 292 min. The length of hospital stay averaged 3.6 days. Two women in group 1 developed relevant complications. After a mean follow-up of 20 months, the recurrence rates were similar, i.e. 80% in group 1 versus 88% in group 2. Although statistical significance was not reached, the mortality related to cancer was considerably higher (20 vs. 0%; p = 0.086) and the mean chemotherapy-free interval was markedly shorter in group 1 (13.3 vs. 20.5 months; p = 0.288). CONCLUSION: Laparoscopic optimal debulking surgery after NACT is feasible and effective in selected patients. Nevertheless, laparoscopy was substantially associated with inferior oncologic results. Endoscopic cytoreduction in AOC should be cautiously suggested until larger prospective trials confirm the observed results.

ERCC1 in advanced biliary tract cancer patients treated with chemotherapy: prognostic and predictive roles.

BACKGROUND: In oncology, we tend to look for factors that reflect better prognosis or predict response to treatments in order to make a selection from which patients will derive the benefit, avoiding futile therapies and/or toxicities. Definitive prognostic and predictive factors in advanced biliary cancer remain unknown. METHODS: We retrospectively analyzed all consecutive patients in our institution with advanced biliary tract cancer treated with palliative cisplatin plus gemcitabine. We evaluated the prognostic and predictive role of the immunohistochemistry (IHC) expression of ERCC1 (excision cross-complementing gene-1) on tumor response and also examined several clinical and laboratory prognostic factors for overall survival. RESULTS: From January 2009 to July 2011, 72 patients were identified; their median overall survival was 9.5 months. Independent variables associated with shorter survival identified by the multivariable Cox regression analysis were ECOG 2-3 (HR 8.4; 95% CI 3.4 to 20.7; p < 0.001) and Charlson Comorbidity Index >1 (HR 9.5; 95% CI 1.6 to 55.3; p = 0.012). Pathology slides were available from 44 patients: 23 (52%) stained positive for ERCC1 on IHC (score ≥0.5). In this subgroup, expression of ERCC-1 was not prognostic and was not associated with either clinical benefit (partial response and stable disease) or tumor response (partial response only) to chemotherapy. CONCLUSIONS: In this cohort of unselected patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin, IHC expression of ERCC1 was not either predictive or prognostic. Patients with ECOG 2-3 and/or multiple comorbidities had worse survival.

Neoadjuvant chemotherapy with six cycles of carboplatin and paclitaxel in advanced ovarian cancer patients unsuitable for primary surgery: Safety and effectiveness.

OBJECTIVE: Three cycles of neoadjuvant chemotherapy (NACT) followed by interval debulking (ID) surgery is an alternative for patients with advanced ovarian cancer unresectable disease. This study aimed to determine the efficacy and safety of six cycles of NACT followed by cytoreduction. METHODS: Retrospective analysis of all patients with advanced epithelial ovarian cancer, tubal carcinoma, or primary peritoneal carcinoma treated with platinum based NACT between January 2008 and February 2012. RESULTS: Eighty-two patients underwent NACT; 78% and 18.2% had extensive stage IIIC or IV disease at diagnosis, respectively. Their median age was 60 years (41-82). On histology, serous adenocarcinoma was found in 90.2%. Patients did not receive chemotherapy after debulking surgery. 35.4% suffered grade 3/4 toxicity; the most commonly observed toxicities were hematologic and nausea. After NACT, 23.1% experienced clinical complete response, 57.4% partial response, and 12.1% disease progression. Complete resection of all macroscopic and microscopic disease (R0) was performed in 63.7%. Surgical complications were uncommon; however, four (6.2%) patients needed a second procedure due to operative complications and 18 (27.3%) needed blood transfusion after debulking. Over a median follow-up period of 19.2 months, median overall survival and chemotherapy-free interval were 37.5 months (confidence interval not reached) and 16 months, respectively. CONCLUSION: Six cycles of neoadjuvant carboplatin and paclitaxel was safe and effective and did not increase perioperative or postoperative complications in patients with stage IIIC/IV disease who were unsuitable for optimal PDS. The overall survival of this cohort was higher than that of those treated with ID surgery.

Effectiveness of guaraná (Paullinia cupana) for postradiation fatigue and depression: results of a pilot double-blind randomized study.

CONTEXT AND OBJECTIVE: Guaraná (Paullinia cupana) has been used medicinally for centuries. The aim of this study is evaluate the effectiveness of guaraná in the treatment of postradiation depression and fatigue. DESIGN AND SETTING: This study had a double-blind randomized design with crossover between experimental arms, at Faculdade de Medicina da Fundação do ABC. METHODS: We conducted a randomized double-blind crossover trial with 36 patients with breast cancer undergoing adjuvant radiation therapy. We randomized patients to either guaraná 75 mg daily p.o. or to placebo. Patients were switched to the other experimental arm at the middle of the radiation treatment, which consisted of 28 daily fractions of 180 cGy. Evaluations were conducted at the beginning, at the middle, and at the end of radiation therapy. RESULTS: We were unable to show any statistically significant differences between the guaraná and the placebo-treated group with any of the measured scores. Also, within the same group, we did not see any statistically significant associations during either the guaraná- or placebo-treated periods with any of the aforementioned measures. CONCLUSIONS: We were unable to show that patients with breast cancer undergoing radiation therapy derive any advantage with guaraná over placebo for both fatigue and depressive symptoms.

Prevalence of the burnout syndrome among Brazilian medical oncologists.

INTRODUCTION: Burnout syndrome which is prevalent among oncologists is characterized by three aspects: emotional exhaustion, depersonalization and low personal accomplishment. The purpose was to evaluate prevalence of the burnout syndrome among Brazilian medical oncologists and the variables that correlate with its presence. METHODS: A survey was conducted with members of the Brazilian Society of Medical Oncology (SBOC) who received three questionnaires (general, Maslach burnout questionnaire and an opinion survey) mailed to all 458 members. RESULTS: Response rate was of 22.3%. According to the criteria proposed by Grunfeld, which consider burnout present when at least one of the aspects is severely abnormal, prevalence of this syndrome was 68.6% (95% confidence interval, CI: 58.68% to 77.45%). By multivariate analysis having a hobby/physical activity, a religious affiliation, older age, living with a companion and rating vacation time as sufficient were correlated significantly and independently with burnout syndrome. CONCLUSIONS: The burnout syndrome is prevalent among Brazilian oncologists. Oncologists having sufficient personal and social resources to engage in a hobby, physical activity, have enough vacation time and religious activities are at lower risk of developing burnout.