Sequential boost of intensity-modulated radiotherapy with chemotherapy for inoperable esophageal squamous cell carcinoma: A prospective phase II study

Abstract

Purpose: This prospective phase II study aimed to determine the efficacy and tolerability of sequential boost of intensity-modulated radiation therapy (IMRT) with chemotherapy for patients with inoperable esophageal squamous cell carcinoma (ESCC).

Methods: Patients with histologically or cytologically proven inoperable ESCC were enrolled in this study (ChiCTR-OIC-17010485). A larger target volume for subclinical lesion was irradiated with 50 Gy, and then, a smaller target volume only including gross tumor was boosted to 66 Gy. The fraction dose was 2 Gy, and no elective node was irradiated. Concurrent and consolidation chemotherapy of fluorouracil (600 mg/m² , days 1-3) plus cisplatin (25 mg/m² , days 1-3) was administered every 4 weeks, for 4 cycles in total. The primary endpoint was 2-year progression-free survival (PFS).

Results: Eighty-eight patients were enrolled in this study. The median age was 65 years (range: 45-75 years), and 69 patients (78.4%) were men. With the median follow-up of 26 (range: 3-95) months, the 2- and 5-year PFS were 39.3% and 36.9%, respectively, and overall survival (OS) were 57.1% and 39.2%, respectively. Tumor stage and concurrent chemotherapy were independent OS predictors. Major acute adverse events were myelosuppression and esophagitis, most of which were grades 1-2. Nine percent and 2.3% of patients had grade 3 acute esophagitis and late esophageal strictures, respectively.

Conclusions: Sequential boost to 66 Gy by IMRT with chemotherapy was safe and effective for inoperable ESCC. A randomized phase III study to compare with standard dose of 50 Gy is warranted.

Keywords: chemoradiotherapy; esophageal squamous cell carcinoma; intensity-modulated radiotherapy.

Figure 1

The survival of 88 esophageal cancer patients. (A) progression‐free survival. (B) overall survival

Figure 2

Survival and relapse according to concurrent chemotherapy. (A) progression‐free survival. (B) overall survival. (C) local‐regional recurrence. (D) distant metastasis

Figure 3

One example for lymph node recurrence outside the PTV. (A) pretreatment, the short diameter of subcarinal lymph node (orange arrow) was 6 mm. (B) the radiotherapy target and radiation dose coverage. The subcarinal lymph node was out of plan tumor volume (PTV). Red area, gross tumor volume; blue area, PTV‐2; green area, PTV‐1; purple line, radiation dose of 66 Gy; yellow line, radiation dose of 50 Gy. (C) the volume of subcarinal lymph node (orange arrow) increased significantly 3 months after radiotherapy