Elective lymph node irradiation late course accelerated hyper-fractionated radiotherapy plus concurrent cisplatin-based chemotherapy for esophageal squamous cell carcinoma: a phase II study

Abstract

Background: In this phase II study, we evaluated the efficacy, toxicity, and patterns of failure of elective lymph node irradiation (ENI) late course accelerated hyper-fractionated radiotherapy (LCAHRT) concurrently with cisplatin-based chemotherapy (CHT) for esophageal squamous cell carcinoma (ESCC).

Methods: Patients with clinical stage II-IVa (T1-4N0-1M0 or M1a) ESCC were enrolled between 2004 and 2011. Radiation therapy (RT) comprised two courses: The first course of radiation covered the primary and metastatic regional tumors and high risk lymph nodal regions, given at 2 Gy per fraction for a dose of 40 Gy. In the second course, LCAHRT was delivered to the boost volume twice a day for an additional 19.6 Gy in 7 treatment days, using 1.4 Gy per fraction. Two cycles of CHT were given at the beginning of RT.

Results: The median age and Karnofsky performance status were 63 years and 80, respectively. The American Joint Committee on Cancer stage was II in 14 (20.6%) patients, III in 32 (47.1%), and IVa in 22 (32.3%). With a median follow-up of 18.5 months, the overall survival at 1-, 3-, 5-year were 75.5%, 46.5%, 22.7% for whole group patients, versus 78.6%, 49.4%, 39.9% for patients with stage II-III. The patterns of first failure from local recurrence, regional failure, and distant metastasis were seen in 20.6%, 17.6%, and 19.1%, respectively. The most frequent acute high-grade (≥ 3) toxicities were esophagitis and leucopenia, occurred in 26.4% and 32.4%.

Conclusions: ENI LCAHRT concurrently with CHT was appeared to be an effective regimen for ESCC patient with a favorable and tolerated profile. Further observation with longer time and randomized phase III trial is currently underway.

Trial registration: ChiCTR-TRC-09000568.

Figure 1

TNM stage distribution in 68 patients. The American Joint Committee TNM stage was II in 14 (20.6%) patients, III in 32 (47.1%), and IV_a in 22 (32.3%), respectively.

Figure 2

Kaplan-Meier curve of overall survival (OS) for whole group patients treated with late course accelerated hyper-fractionated radiotherapy plus concurrent chemotherapy. With a median follow-up of 18.5 months, the median survival was 34.4 months (95% confidence interval: 19.1–49.6 months), and the 1-, 3-, 5-year OS were 75.5%, 46.5%, 22.7%, respectively.

Figure 3

Kaplan-Meier curves of overall survival (OS) were compared in patients with TNM stage II-III and IV_a. For patients with stage II–III, the 1-, 3-, and 5-year OS were 78.6%, 49.4%, and 39.9%, respectively, versus 68.3%, 41.0%, and 15.4% for IV_a patients, respectively, however, no statistically significant difference was observed in our limited sample size (p=0.671).

Figure 4

Kaplan-Meier curves of overall survival (OS) were compared in patients receiving different chemotherapy regimens. Our data did not show statistically significant difference in OS rates between the three groups (p=0.690).