Prospective Randomized Phase 2 Study of Concurrent Chemoradiation Therapy (CCRT) Versus Chemotherapy Alone in Stage IV Esophageal Squamous Cell Carcinoma (ESCC)

Abstract

Purpose/Objective(s): Stage IV ESCC carries a poor prognosis with a median survival of 6-9 months. The standard treatment has traditionally been chemotherapy. Palliative radiation therapy was used for symptom relief. The optimal treatment for stage IV ESCC has not yet been established. The aim of this study was to compare the efficacy and safety of CCRT versus chemotherapy alone in patients with stage IV ESCC. Materials/Methods: Patients with stage IV ESCC were randomly assigned to the CCRT group and the chemotherapy group. Both groups of patients received at least 2 cycles of chemotherapy with cisplatin and docetaxel every 3 weeks. Patients in CCRT group received 50-60 Gy/ 25-30 fractions/ 5-6 weeks of concurrent radiation therapy to the esophageal primary tumor. The primary end point was overall survival (OS). The secondary end points were progression-free survival (PFS), object response rate (ORR) of primary tumor and toxicity. Results: Between August 2013 and October 2015, 60 patients were enrolled and divided into the CCRT group (n Z 30) and the chemotherapy group (n Z 30). The 60 patients were comprised of 48 male and 12 female patients, with a median age of 56 years (range 36-70 years). The baseline clinical characteristics of the 2 groups were similar. Patients in the CCRT group received a mean 54.7 Gy of radiation therapy and a mean 3.6 cycles of chemotherapy, whereas patients in the chemotherapy group received a mean 3.8 cycles. The ORR of the primary tumor was higher in the CCRT group than in the chemotherapy group (83.3% vs. 46.7%, P Z 0.001). At a median follow-up of 18 months, median PFS (9.3 vs. 4.7 months, P Z 0.021) and median OS (18.3 vs. 10.2 months, P Z 0.001) were significantly longer in the CCRT than that in the chemotherapy group. Overall survival rates at 1and 2 years were 73.3% and 43.3% respectively, in the CCRT group, and 46.6%and 26.7% respectively in chemotherapy group (P Z 0.030) Although grade 3 neutropenia was significantly more frequent in the CCRT group than that in the chemotherapy group (33.3% vs. 20.0%, P < 0.05), the rates of other toxicities did not differ. Conclusion: Concurrent chemoradiation therapy was well tolerated and associated with longer PFS and OS than chemotherapy alone in patients with stage IV ESCC. Controlled randomized, multi-center trials are required to determine whether CCRT is a primary treatment option for patients with stage IV ESCC.

Chemoradiotherapy Versus Chemotherapy Alone for Advanced Esophageal Squamous Cell Carcinoma: The Role of Definitive Radiotherapy for Primary Tumor in the Metastatic Setting

“…In a large cohort of 12,683 patients with metastatic EC, Guttmann et al ( 13 ) reported that definitive-dose (≥50.4 Gy) CRT was associated with superior survival compared to CT alone (median OS 8.3 vs. 11.3 months). As shown in Table 2 , the clinical survival outcomes of the metastatic population in this study were highly consistent with those of previous studies ( 13 , 18 – 21 ).…”

“…In terms of metastatic EC, extended survival after definitive CRT has been reported by several previous studies. A prospective randomized phase 2 study demonstrated that the CRT was associated with significantly improved median PFS (9.3 vs. 4.7 months, p = 0.021) and median OS (18.3 vs. 10.2 months, p = 0.001) than CT alone ( 18 ). Moreno et al ( 19 ) also suggested that additional RT could derive better survival compared to CT alone with extended 2- and 5-year OS of 6.4% and 2.7%, respectively (p <.001).…”

Utilization and Outcomes of Radiation in Stage IV Esophageal Cancer

“…The survival benefit of definitive-dose radiotherapy in stage IV esophageal cancer has been suggested by several previous studies evaluating concurrent chemoradiotherapy when compared with chemotherapy alone. 30 , 46 , 47 , 48 Our study extends these findings, using a more contemporary patient population with multivariable models that adjust for metastatic pattern at presentation (nodal only, single organ, multiorgan) and exclude patients in the control arm that were felt not to be healthy enough to be irradiated.…”

Survival benefit of radiotherapy in metastatic esophageal cancer: a population-based study

“…( 13 ) found that combining surgery with radiotherapy could improve survival in metastatic EC, it based on older populations, older methods of radiotherapy, and did not analyze the clinical benefits of chemotherapy combined with radiation therapy. A phase II study compared concurrent chemoradiation therapy (CCRT) with chemotherapy alone in stage IV esophageal squamous cell carcinoma, demonstrating that CCRT significantly prolonged median progression-free survival (mPFS, 9.3 vs. 4.7 months, P=0.021) and mOS (18.3 vs. 10.2 months, P=0.001) ( 14 ). This study challenged the status of standard treatment modality for metastatic EC treated with chemotherapy alone.…”