EROS 2.0 study: evaluation of two interventional radiotherapy (brachytherapy) schedules for endometrial cancer: a comparison of late vaginal toxicity rates.

BACKGROUND: To compare the late toxicity rates after two different high dose rate (HDR) adjuvant intravaginal interventional radiotherapy (IRT-brachytherapy) dose schedules in stage I-II endometrial cancer. METHODS: Stage I-II patients with endometrial cancer treated with surgery (with or without lymphadenectomy) and adjuvant HDR-IRT between 2014 and 2020 were included in this analysis. Patients were treated with two schedules. In the first cohort (C1), 21 Gy were delivered in three weekly fractions (7 Gy) prescribed 0.5 cm from the applicator surface. In the second cohort (C2), 24 Gy were delivered in four weekly fractions (6 Gy). The clinical target volume was the upper third of the vagina for C1 and the upper 3 cm for C2. HDR-IRT technique and point prescription (5 mm depth from the applicator surface) were the same for all patients. Vaginal toxicity was scored according to the CTCAE 5.0 scale in terms of the presence versus absence of any toxicity grade. The correlation among toxicity and clinical covariates (age, lymphadenectomy, fractionation, stage) was tested by Pearson correlation test (univariate) and by logistic regression (multivariable). RESULTS: 114 stage I and three stage II patients, median age 62 (range: 32-85) years, were included in this analysis. The mean follow-up was 56.3 months in C1 (40-76) and 20 months in C2 (8-42). Vaginal late toxicity was recorded in 40 and 15 patients in C1 and 2, respectively. Age, lymphadenectomy, and fractionation were significantly correlated with toxicity at univariate analysis (p value = 0.029, 0.006, and 0.002, respectively), while stepwise logistic regression confirmed only age and fractionation as significantly correlated parameters (p value = 0.02 and 0.001, respectively). Three-year local relapse-free, distant metastasis-free and cause-specific survival rates were 96.6%, 94.8%, and 99.1%, respectively. CONCLUSIONS: This analysis showed lower vaginal late toxicity rate in C2 compared to C1.

Randomized trial of primary debulking surgery versus neoadjuvant chemotherapy for advanced epithelial ovarian cancer (SCORPION-NCT01461850).

OBJECTIVE: To investigate whether neoadjuvant chemotherapy followed by interval debulking surgery is superior to primary debulking surgery in terms of perioperative complications and progression-free survival, in advanced epithelial ovarian, fallopian tube or primary peritoneal cancer patients with high tumor load. METHODS: Patients with advanced epithelial ovarian, fallopian tube or primary peritoneal cancer (stage IIIC-IV) underwent laparoscopy. Patients with high tumor load assessed by a standardized laparoscopic predictive index were randomly assigned (1:1 ratio) to undergo either primary debulking surgery followed by adjuvant chemotherapy (arm A), or neoadjuvant chemotherapy followed by interval debulking surgery and adjuvant chemotherapy (arm B). Co-primary outcome measures were progression-free survival and post-operative complications; secondary outcomes were overall survival, and quality of life. Survival analyses were performed on an intention-to-treat population. RESULTS: 171 patients were randomly assigned to primary debulking surgery (n=84) versus neoadjuvant chemotherapy (n=87). Rates of complete resection (R0) were different between the arms (47.6% in arm A vs 77.0% in arm B; p=0.001). 53 major postoperative complications were registered, mainly distributed in arm A compared with arm B (25.9% vs 7.6%; p=0.0001). All patients were included in the intent-to-treat analysis. With an overall median follow-up of 59 months (95% CI 53 to 64), 142 (83.0%) disease progressions/recurrences and 103 deaths (60.2%) occurred. Median progression-free and overall survival were 15 and 41 months for patients assigned to primary debulking surgery, compared with 14 and 43 months for patients assigned to neoadjuvant chemotherapy, respectively (HR 1.05, 95% CI 0.77 to 1.44, p=0.73; HR 1.12, 95% CI 0.76 to 1.65, p=0.56). CONCLUSIONS: Neoadjuvant chemotherapy and primary debulking surgery have the same efficacy when used at their maximal possibilities, but the toxicity profile is different.

Emerging drugs for endometrial cancer.

INTRODUCTION: From the dualistic classification that divides endometrial cancer (EC) into two types with distinct underlying molecular profiling, histopathology and clinical behavior, arises a deeper understanding of the carcinogenesis pathways. EC treatment comprises different and multimodal therapeutic approaches, such as chemotherapy, radiation therapy or combinations of novel drugs; however, few of these regimens have truly improved progression-free or survival rates in advanced and metastatic settings. AREAS COVERED: We reviewed the main molecular pathways involved in EC carcinogenesis through a wide literature search of novel compounds that alone or in combination with traditional drugs have been investigated or are currently under investigation in randomized clinical trials. EXPERT OPINION: The molecular therapies mainly discussed in this review are potential therapeutic candidates for more effective and specific treatments. In the genomic era, a deeper knowledge about molecular characteristics of cancer provides the hope for the development of better therapeutic approaches. Targeting both genetic and epigenetic alterations, attacking tumor cells using cell-surface markers overexpressed in tumor tissue, reactivating antitumor immune responses and identifying predictive biomarkers represent the emerging strategies and the major challenges.

The Role of Multimodal Imaging in Pathological Response Prediction of Locally Advanced Cervical Cancer Patients Treated by Chemoradiation Therapy Followed by Radical Surgery.

PURPOSE: This study aimed to develop predictive models for pathological residual disease after neoadjuvant chemoradiation (CRT) in locally advanced cervical cancer (LACC) by integrating parameters derived from transvaginal ultrasound, MRI and PET/CT imaging at different time points and time intervals. METHODS: Patients with histologically proven LACC, stage IB2-IVA, were prospectively enrolled. For each patient, the three examinations were performed before, 2 and 5 weeks after treatment ("baseline", "early" and "final", respectively). Multivariable logistic regression models to predict complete vs. partial pathological response (pR) were developed and a cost analysis was performed. RESULTS: Between October 2010 and June 2014, 88 patients were included. Complete or partial pR was found in 45.5% and 54.5% of patients, respectively. The two most clinically useful models in pR prediction were (1) using percentage variation of SUVmax retrieved at PET/CT "baseline" and "final" examination, and (2) including high DWI signal intensity (SI) plus, ADC, and SUVmax collected at "final" evaluation (area under the curve (95% Confidence Interval): 0.80 (0.71-0.90) and 0.81 (0.72-0.90), respectively). CONCLUSION: The percentage variation in SUVmax in the time interval before and after completing neoadjuvant CRT, as well as DWI SI plus ADC and SUVmax obtained after completing neoadjuvant CRT, could be used to predict residual cervical cancer in LACC patients. From a cost point of view, the use of MRI and PET/CT is preferable.