A multi-institutional analysis of sequential versus ‘sandwich’ adjuvant chemotherapy and radiotherapy for stage IIIC endometrial carcinoma

Abstract

ObjectiveTo analyze the outcomes of sequential or sandwich chemotherapy (ChT) and radiotherapy (RT) in patients with node-positive endometrial cancer (EC).MethodsData from 4 centers were collected retrospectively for 179 patients with stage IIIC EC treated with postoperative RT and ChT (paclitaxel and carboplatin). Patients were either treated with 6 cycles of ChT followed by RT (sequential arm; 96 patients) or with 3 cycles of ChT, RT, and an additional 3 cycles of ChT (sandwich arm; 83 patients). Prognostic factors affecting overall survival (OS) and progression-free survival (PFS) were analyzed.ResultsThe 5-year OS and PFS rates were 64% and 59%, respectively, with a median follow-up of 41 months (range, 5–167 months). The 5-year OS rates were significantly higher in the sandwich than sequential arms (74% vs. 56%; p=0.03) and the difference for 5-year PFS rates was nearly significant (65% vs. 54%; p=0.05). In univariate analysis, treatment strategy, age, International Federation of Gynecology and Obstetrics (FIGO) stage, pathology, rate of myometrial invasion, and grade were prognostic factors for OS and PFS. In multivariate analysis, non-endometrioid histology, advanced FIGO stage, and adjuvant sequential ChT and RT were negative predictors for OS, whereas only non-endometrioid histology was a prognostic factor for PFS.ConclusionPostoperative adjuvant ChT and RT for stage IIIC EC patients, either given sequentially or sandwiched, offers excellent clinical efficacy and acceptably low toxicity. Our data support the superiority of the sandwich regimen compared to the sequential strategy in stage IIIC EC patients for OS.

Immunohistochemical biomarkers are prognostic relevant in addition to the ESMO-ESGO-ESTRO risk classification in endometrial cancer

“…There is an ongoing debate about routine surgical staging with LN dissection or sampling in EC, especially after the introduction of molecular profiling. Yet, LN status as determined by either lymphadenectomy or SLN remains an important prognosticator for survival and guiding adjuvant treatment in the current ESMO-ESGO-ESTRO risk classification [5,[30][31][32][33]. The study of Ouldamer et al concluded, that even patients within the 'high-intermediate' risk group should receive systematic nodal staging for a significant better survival [34].…”

Predictors of Survival in Women with High-Risk Endometrial Cancer and Comparisons of Sandwich versus Concurrent Adjuvant Chemotherapy and Radiotherapy

“…To our knowledge, there was no article mentioned about the comparison between sandwich and concurrent CRTs. Similarly, Onal et al reported a superiority of sandwich CRT in PFS and OS, compared with sequential CRT or radiotherapy only [ 8 , 9 ]. The underlying mechanism explaining the finding about the superiority of sandwich CRT is unknown.…”

“…Similarly, Young et al reported that positive lymph node metastasis was associated with worse PFS (HR = 3.37, p = 0.03) and OS (HR = 2.96, p = 0.04) in FIGO 1988 stage III EC patients [ 12 ]. Onal et al also found that paraaortic lymph node metastasis was a predictor for worse OS (HR = 2.01, 95% CI = 1.15–3.53, p = 0.02) compared with pelvic lymph node metastasis [ 9 ]. Thus, patients with paraaortic lymph node metastasis might be treated with a more intensive therapy to prevent EC recurrence.…”

Preclinical Efficacy and Involvement of AKT, mTOR, and ERK Kinases in the Mechanism of Sulforaphane against Endometrial Cancer

“…Approximately 57% of all endometrial cancer cases are related to obesity or being overweight [3]. Although patients with early-stage endometrial cancer are efficaciously treated with surgery, with or without chemo-radiotherapy, resulting in five-year survival rates of 80-85% [4], these therapeutic options are limited in younger patients due to the desire to preserve fertility and in obese patients due to poor hormonal sensitivity and surgical outcomes and higher cost of surgical care [5]. Twenty percent to 30% of endometrial cancer patients are diagnosed with the late-stage disease 2 of 22 at the time of surgery, with an estimated five-year survival rate of 40-70% for stage III patients, and a very poor five-year survival of 0-10% for stage IV patients [6].…”