Dataset Information

Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial.

ABSTRACT:

SUBMITTER: Glynne-Jones R

PROVIDER: S-EPMC5337624 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial.

Glynne-Jones Robert R Sebag-Montefiore David D Meadows Helen M HM Cunningham David D Begum Rubina R Adab Fawzi F Benstead Kim K Harte Robert J RJ Stewart Jill J Beare Sandy S Hackshaw Allan A Kadalayil Latha L

The Lancet. Oncology 20170211 3

<h4>Background</h4>Guidelines for anal cancer recommend assessment of response at 6-12 weeks after starting treatment. Using data from the ACT II trial, we determined the optimum timepoint to assess clinical tumour response after chemoradiotherapy.<h4>Methods</h4>The previously reported ACT II trial was a phase 3 randomised trial of patients of any age with newly diagnosed, histologically confirmed, squamous cell carcinoma of the anus without metastatic disease from 59 centres in the UK. We rand ...[more]

PMID: 28209296

Similar Datasets

Project description:BackgroundIn the EC-CRT-001 phase II study, the combination of toripalimab (an anti-programmed death-1 antibody) and definitive chemoradiotherapy (CRT) has shown promising efficacy in patients with locally advanced oesophageal squamous cell carcinoma (ESCC). Here, we reported the long-term outcomes and post-hoc exploratory analyses.MethodsThis single-arm, phase II trial enrolled 42 patients diagnosed with unresectable stage I-IVA ESCC was conducted at Sun Yat-sen University Cancer Center between November 2019 and January 2021. Treatment consisted of chemotherapy (weekly 50 mg/m2 of paclitaxel and 25 mg/m2 of cisplatin for five cycles), concurrent radiotherapy (50.4 Gy in 28 fractions), and toripalimab (240 mg every 3 weeks for up to 1 year). The primary endpoint was clinical complete response (CR) rate at 3 months after CRT completion. The 3-year overall survival (OS) and progression-free survival (PFS) rates were evaluated. Additionally, the exploratory objectives included analysing recurrence patterns, assessing the associations between immune-related adverse events (irAEs) and efficacy, and identifying potential predictors for irAEs. The trial was registered with ClinicalTrials.gov (NCT04005170).FindingsWith a median follow-up of 44.3 months (IQR 40.8-46.1), the 3-year OS and PFS rates were 44.8% (95% CI 31.9-62.8) and 35.7% (95% CI 23.8-53.6), respectively. Patients who failed to achieve a clinical complete response (CR) demonstrated significantly worse OS (hazard ratio [HR] = 13.73, 95% CI 4.43-42.54, P < 0.0001) and PFS (HR = 32.08, 95% CI 8.57-120.10, P < 0.0001). Disease recurrence occurred in 23 of 42 patients (55%), with recurrences being earlier and more frequent in the non-CR group compared to the CR group. Patients experiencing irAEs showed a significantly higher CR rate (72% vs. 39%, P = 0.082) and better PFS (HR = 0.43, 95% CI 0.19-0.93, P = 0.027) than those without irAEs. GON4L mutation was associated with a lower incidence of irAEs (P = 0.036).InterpretationThe updated survival outcomes confirmed the efficacy of toripalimab plus definitive CRT in locally advanced ESCC. Moreover, the development of irAEs may predict a more favourable prognosis.FundingNational Natural Science Foundation of China, Beijing Xisike Clinical Oncology Research Foundation, and Sci-Tech Project Foundation of Guangzhou.

Project description:ObjectivesPost-chemoradiotherapy (CRT) FDG PET is a useful prognosticator of esophageal cancer. However, debate on the diverse criteria of previous publications preclude worldwide multicenter comparisons, and even a universal practice guide. We aimed to validate a simple qualitative interpretation criterion of post-CRT FDG PET for outcome stratification and compare it with other criteria.MethodsThe post-CRT FDG PET of 114 patients with esophageal squamous cell carcinoma (ESCC) were independently interpreted using a qualitative 4-point scale (Qual4PS) that identified focal esophageal FDG uptake greater than liver uptake as residual tumor. Cohen's κ coefficient (κ) was used to measure interobserver agreement of Qual4PS. The Kaplan-Meier method and Cox proportional hazards regression analyses were used for survival analysis. Other criteria included a different qualitative approach (QualBK), maximal standardized uptake values (SUVmax3.4, SUVmax2.5), relative change of SUVmax between pre- and post-CRT FDG PET (ΔSUVmax), mean standardized uptake values (SUVmean), metabolic volume (MV) and total lesion glycolysis (TLG).ResultsOverall interobserver agreement on the Qual4PS criterion was excellent (κ: 0.95). Except the QualBK, SUVmax2.5, and TLG, all the other criteria were significant predictors for overall survival (OS). Multivariable analysis showed only Qual4PS (HR: 15.41; P = 0.005) and AJCC stage (HR: 2.47; P = 0.007) were significant independent variables. The 2-year OS rates of Qual4PS(‒) patients undergoing CRT alone (68.4%) and patients undergoing trimodality therapy (62.5%) were not significant different, but the 2-year OS rates of Qual4PS(+) patients undergoing CRT alone (10.0%) were significantly lower than in patients undergoing trimodality therapy (42.1%).ConclusionsThe Qual4PS criterion is reproducible for assessing the response of ESCC to CRT, and valuable for predicting survival. It may add value to response-adapted treatment for ESCC patients, and help to decide whether surgery is warranted after CRT.

Dataset Information

Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial.

Publications

Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets