27: Radiation Therapy in the Management of Esophageal Cancer

Introduction

Radiation therapy plays an important role in the multimodality treatment of esophageal cancer. Only 30% to 40% of patients with esophageal cancer have potentially resectable disease at presentation. In combination with chemotherapy in the neoadjuvant setting, radiation has been shown to improve survival over surgery alone. Radiation also can be very effective in the palliative setting. In this chapter, we discuss the general background and data on the use of radiation in the management of esophageal cancer.

Radiation Alone

There are few studies of radiation alone for esophageal cancer, and these have generally had poor outcomes. Historically, radiation was used for patients with extensive disease or those unfit for surgery. In a review of 49 early series of patients treated with radiation alone for esophageal squamous cell carcinoma, the overall survival rate at 5 years was 6%.¹ In a British study of 101 patients with clinically localized esophageal cancer, who received definitive radiation doses of 45 to 53 Gray (Gy, unit of absorbed radiation dose), the 5-year survival rate was 21%.² In a randomized trial (Radiation Therapy Oncology Group [RTOG] 85-01) of combined chemoradiation versus radiation alone to 64 Gy for 121 patients with mostly esophageal squamous cell carcinoma, 5-year overall survival in the radiation alone arm was 0.^3,4 For this reason, radiation alone for esophageal cancer is generally considered palliative rather than curative in intent. However, there are some studies exploring whether early-stage (stage I) esophageal cancer could be effectively treated with radiation alone.⁵

Definitive Chemoradiation

Definitive concurrent chemotherapy and radiation therapy have been studied as an alternative to operative management for esophageal cancer, particularly for patients who are not good surgical candidates. RTOG 85-01 was a prospective, randomized phase III trial of patients with nondisseminated adenocarcinoma or squamous cell carcinoma of the thoracic esophagus.^3,4,6 Patients were randomized between radiation alone (64 Gy in 32 fractions over 6.5 weeks) versus concurrent chemoradiation (2 cycles of infusional 5-FU plus cisplatin and radiation [50 Gy in 25 fractions over 5 weeks]). The trial closed early because a planned interim analysis showed a significant survival advantage for chemoradiation (5-year survival 27% vs. 0%) as well as a reduction in locoregional and distant failures. However, 46% of patients in the chemoradiation arm had persistent or locally recurrent disease in the esophagus at 12 months. Severe acute but not late toxicity was significantly higher in the chemoradiation arm.

The follow-up trial to RTOG 85-01 asked the question whether radiation dose escalation may improve local control rates. In the Intergroup 0123 study (RTOG 94-05), 236 patients with nonmetastatic squamous cell carcinoma or adenocarcinoma of the thoracic esophagus received concurrent cisplatin and 5-FU, and the patients were randomized between two different radiation doses: 50.4 Gy in 28 fractions or 64.8 Gy in 36 fractions.⁷ Radiation treatment was given daily, ...