Dataset Information

Icotinib With Concurrent Radiotherapy vs Radiotherapy Alone in Older Adults With Unresectable Esophageal Squamous Cell Carcinoma: A Phase II Randomized Clinical Trial.

ABSTRACT: Importance:Palliative radiotherapy (RT) is generally recommended for older patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis. A new combination treatment is therefore needed. Objective:To assess the efficacy and toxicity of RT plus icotinib vs RT alone in older patients with ESCC. Design, Setting, and Participants:This randomized, multicenter, open-label, phase II clinical trial was conducted in China, with enrollment between January 1, 2015, and October 31, 2016. Patients aged 70 years or older with clinical stage T2 to T4, N0/1, M0/1a unresectable (because of comorbidities, T4 disease, unresectable lymph node, or refused surgery) ESCC were randomized 1:1 to receive RT plus icotinib or RT alone. Radiation was prescribed at 60 Gy in 30 fractions in both groups, and icotinib was administered at a dosage of 125 mg 3 times a day in the RT plus icotinib group. The last follow-up was completed on June 30, 2019, and data were analyzed from July 1 to September 30, 2019. Interventions:Patients were randomized to either RT plus icotinib or RT alone. Main Outcomes and Measures:The primary end point was overall survival (OS). Treatment-related toxic effects were evaluated. Immunohistochemistry was performed to analyze epidermal growth factor receptor (EGFR) expression if available. Results:A total of 127 patients (median age, 76 years [range, 70-91 years]; 76 men [59.8%]) were enrolled and were eligible for survival analysis. Median OS was 24.0 (95% CI, 22.2-25.8) months in the RT plus icotinib group vs 16.3 (95% CI, 13.8-18.8) months in the RT group (hazard ratio, 0.53; 95% CI, 0.33-0.87; P?=?.008). No difference was observed in grades 3 or 4 adverse events. Patients with EGFR overexpression had a significantly better median overall survival (not reached vs 16.3 months [range, 2.6-45.1 months]; P?=?.03) in the RT plus icotinib group. Conclusions and Relevance:In this randomized clinical trial, icotinib plus RT was well tolerated and improved OS in older patients with ESCC relative to RT alone. Patients with EGFR overexpression benefitted more from icotinib with RT. Trial Registration:ClinicalTrials.gov Identifier: NCT02375581.

SUBMITTER: Luo H

PROVIDER: S-EPMC7542309 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Icotinib With Concurrent Radiotherapy vs Radiotherapy Alone in Older Adults With Unresectable Esophageal Squamous Cell Carcinoma: A Phase II Randomized Clinical Trial.

Luo Honglei H Jiang Wei W Ma Li L Chen Peng P Fang Min M Ding Lingyu L Hua Yuhui Y Du Dexi D Jing Zhao Z Xie Ruifei R Song Yaqi Y Wang Jiayang J Zhou Rongjing R Tian Zhifeng Z Wu Shixiu S

JAMA network open 20201001 10

<h4>Importance</h4>Palliative radiotherapy (RT) is generally recommended for older patients with esophageal squamous cell carcinoma (ESCC) with poor prognosis. A new combination treatment is therefore needed.<h4>Objective</h4>To assess the efficacy and toxicity of RT plus icotinib vs RT alone in older patients with ESCC.<h4>Design, setting, and participants</h4>This randomized, multicenter, open-label, phase II clinical trial was conducted in China, with enrollment between January 1, 2015, and O ...[more]

PMID: 33026449

Similar Datasets

Project description:Purpose: The reported data of elderly ESCC are rather limited and there is a lack of information to guide treatment decisions for elderly patients with esophageal cancer. This study aims to identify the efficacy and factors for optimal treatment approaches for elderly esophageal squamous cell carcinoma (ESCC) treated with radiotherapy (RT) alone or concurrent chemoradiation (CCRT). Methods: This study included 184 I-III elderly ESCC patients aged ≥70 years treated by oral single agent CCRT (sCCRT) or double agents CCRT (dCCRT) or RT alone at a single institution in China. RT was delivered with Intensity Modulated Irradiation Therapy (IMRT) or Volumetric-Modulated Arc Therapy (VMAT). Sequential or simultaneous integrated boost (SIB) approach was applied for GTV dose escalation. Toxicities were evaluated by criteria of Radiation Therapy Oncology Group. Statistical analyses were performed on survival and failure patterns. Results: At a median follow-up time of 15.5 months, the 2- and 3-year estimated overall survival (OS) were 43.5% and 35.2%, respectively. T and N stage, GTV dose (cutoff value 56Gy), simultaneous integrated boost (SIB) technique and CCRT were significant predictors for the outcomes. sCCRT was significantly associated with higher OS, LRFS, and DFS when compared with RT alone and no difference was observed between sCCRT and dCCRT. 44% patients experienced treatment failure, among whom 65.4% developed local failure. 81.3% local failure occurred in GTV and 70.6% regional failures occurred out of radiation field. dCCRT was the only independent prediction factor for grade ≥ 2 neutropenia and gastrointestinal reactions compared with sCCRT and RT alone. No significant difference of toxicities was observed between sCCRT and RT alone. Conclusions: Our results demonstrated that CCRT in elderly patients had significant survival benefit compared to RT alone, especially using Single oral agent. sCCRT had less toxicities compared to dCCRT, and the toxicity was similar to RT alone. GTV dose ≥ 56 Gy and SIB technique were optimal approaches for radiotherapy.

Project description:ImportanceMost older patients with esophageal cancer cannot complete the standard concurrent chemoradiotherapy (CCRT). An effective and tolerable chemoradiotherapy regimen for older patients is needed.ObjectiveTo evaluate the efficacy and toxic effects of CCRT with S-1 vs radiotherapy (RT) alone in older patients with esophageal cancer.Design, setting, and participantsA randomized, open-label, phase 3 clinical trial was conducted at 23 Chinese centers between June 1, 2016, and August 31, 2018. The study enrolled 298 patients aged 70 to 85 years. Eligible participants had histologically confirmed esophageal cancer, stage IB to IVB disease based on the 6th edition of the American Joint Committee on Cancer (stage IVB: only metastasis to the supraclavicular/celiac lymph nodes) and an Eastern Cooperative Oncology Group performance status of 0 to 1. Data analysis was performed from August 1, 2020, to March 10, 2021.InterventionsPatients were stratified according to age (<80 vs ≥80 years) and tumor length (<5 vs ≥5 cm) and randomly assigned (1:1) to receive either CCRT with S-1 or RT alone.Main outcomes and measuresThe primary end point was the 2-year overall survival rate using intention-to-treat analysis.ResultsOf the 298 patients enrolled, 180 (60.4%) were men. The median age was 77 (interquartile range, 74-79) years in the CCRT group and 77 (interquartile range, 74-80) years in the RT alone group. A total of 151 patients (50.7%) had stage III or IV disease. The CCRT group had a significantly higher complete response rate than the RT group (41.6% vs 26.8%; P = .007). Surviving patients had a median follow-up of 33.9 months (interquartile range: 28.5-38.2 months), and the CCRT group had a significantly higher 2-year overall survival rate (53.2% vs 35.8%; hazard ratio, 0.63; 95% CI, 0.47-0.85; P = .002). There were no significant differences in the incidence of grade 3 or higher toxic effects between the CCRT and RT groups except that grade 3 or higher leukopenia occurred in more patients in the CCRT group (9.5% vs 2.7%; P = .01). Treatment-related deaths were observed in 3 patients (2.0%) in the CCRT group and 4 patients (2.7%) in the RT group.Conclusions and relevanceIn this phase 3 randomized clinical trial, CCRT with S-1 was tolerable and provided significant benefits over RT alone in older patients with esophageal cancer.Trial registrationClinicalTrials.gov Identifier: NCT02813967.

Project description:BackgroundThe literature regarding esophageal fistula after definitive concurrent chemotherapy and intensity modulated radiotherapy (IMRT) for esophageal squamous cell carcinoma (ESCC) remains lacking. We aimed to investigate the risk factors of esophageal fistula among ESCC patients undergoing definitive concurrent chemoradiotherapy (CCRT) via IMRT technique.MethodsA total of 129 consecutive ESCC patients receiving definitive CCRT with IMRT between 2008 and 2018 were reviewed. The cumulative incidence of esophageal fistula and survival of patients were estimated by the Kaplan-Meier method and compared between groups by the log-rank test. The risk factors of esophageal fistula were determined with multivariate Cox proportional hazards regression analysis.ResultsMedian follow-up was 14.9 months (IQR, 7.0-28.8). Esophageal perforation was identified in 20 (15.5%) patients, resulting in esophago-pleural fistula in nine, esophago-tracheal fistula in seven, broncho-esophageal fistula in two, and aorto-esophageal fistula in two patients. The median interval from IMRT to the occurrence of esophageal fistula was 4.4 months (IQR, 3.3-10.1). Patients with esophageal fistula had an inferior median overall survival (10.0 vs. 17.2 months, p = 0.0096). T4 (HR, 3.776; 95% CI, 1.383-10.308; p = 0.010) and esophageal stenosis (HR, 2.601; 95% CI, 1.053-6.428; p = 0.038) at baseline were the independent risk factors for esophageal fistula. The cumulative incidence of esophageal fistula was higher in patients with T4 (p = 0.018) and pre-treatment esophageal stenosis (p = 0.045). There was a trend toward better survival after esophageal fistula among patients receiving repair or stenting for the fistula than those only undergoing conservative treatments (median survival, 5.9 vs. 0.9 months, p = 0.058).ConclusionsT4 and esophageal stenosis at baseline independently increased the risk of esophageal fistula in ESCC treated by definitive CCRT with IMRT. There existed a trend toward improved survival after the fistula among patients receiving repair or stenting for esophageal perforation.

Project description:BACKGROUND:Preoperative chemoradiotherapy (CRT) followed by surgery is the most common approach for patients with resectable esophageal cancer. Nevertheless, considerable numbers of esophageal-cancer patients undergo surgery as the first treatment. The benefit of neoadjuvant therapy might only be for patients with a pathologic complete response, so stratified research is necessary. Postoperative treatments have important roles because of the poor survival rates of patients with stage-IIB/III disease treated with resection alone. Five-year survival of patients with stage-IIB/III thoracic esophageal squamous cell carcinoma (TESCC) after surgery is 20.0-28.4%, and locoregional lymph-node metastases are the main cause of failure. Several retrospective studies have shown that postoperative radiotherapy (PORT) and postoperative chemoradiotherapy (POCRT) after radical esophagectomy for esophageal carcinoma with positive lymph-node metastases and stage-III disease can decrease locoregional recurrence and increase overall survival (OS). Using intensity-modulated RT, PORT reduces locoregional recurrence further. However, the rate of distant metastases increases to 30.7%. Hence, chemotherapy may be vital for these patients. Therefore, a prospective randomized controlled trial (RCT) is needed to evaluate the value of PORT and concurrent POCRT in comparison with surgery alone (SA) for esophageal cancer. METHOD:This will be a phase-II/III RCT. The patients with pathologic stage-IIB/III esophageal squamous cell carcinoma will receive concurrent POCRT or PORT after radical esophagectomy compared with those who have SA. A total of 120 patients in each group will be recruited. POCRT patients will be 50.4 Gy concurrent with paclitaxel (135-150 mg/m2) plus cisplatin or nedaplatin (50-75 mg/m2) treatment every 28 days. Two cycles will be required for concurrent chemotherapy. The prescription dose will be 54 Gy for PORT. The primary endpoint will be disease-free survival (DFS). The secondary endpoint will be OS. Other pre-specified outcome measures will be the proportion of patients who complete treatment, toxicity, and out-of-field regional recurrence rate between PORT and POCRT. DISCUSSION:This prospective RCT will provide high-level evidence for postoperative adjuvant treatment of pathologic stage-IIB/III esophageal squamous cell carcinoma. TRIAL REGISTRATION:clinicaltrials.gov (NCT02279134). Registered on October 26, 2014.

Dataset Information

Icotinib With Concurrent Radiotherapy vs Radiotherapy Alone in Older Adults With Unresectable Esophageal Squamous Cell Carcinoma: A Phase II Randomized Clinical Trial.

Publications

Icotinib With Concurrent Radiotherapy vs Radiotherapy Alone in Older Adults With Unresectable Esophageal Squamous Cell Carcinoma: A Phase II Randomized Clinical Trial.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets