Clinical Investigation
Late Toxicity After Definitive Concurrent Chemoradiotherapy for Thoracic Esophageal Carcinoma

https://doi.org/10.1016/j.ijrobp.2008.10.075Get rights and content

Purpose

To evaluate late cardiopulmonary toxicities after concurrent chemoradiotherapy (CCRT) for esophageal carcinomas.

Methods and Materials

From February 2002 through April 2005, 74 patients with clinical Stage I–IVB carcinoma of the esophagus were treated with CCRT. Sixty-nine patients with thoracic squamous cell carcinoma were the core of this analysis. Patients received 60 Gy of radiation therapy in 30 fractions over 8 weeks, including a 2-week break, and received 2 cycles of fluorouracil/cisplatin chemotherapy concomitantly. Initial radiation fields included primary tumors, metastatic lymph nodes, and supraclavicular, mediastinal, and celiac nodes areas. Late toxicities were assessed with the late radiation morbidity scoring scheme of the Radiation Therapy Oncology Group/European Organiation for Research and Treatment of Cancer.

Results

The median age was 67 years (range, 45–83 years). The median follow-up time was 26.1 months for all patients and 51.4 months for patients still alive at the time of analysis. Five cardiopulmonary toxic events of Grade 3 or greater were observed in 4 patients, Grade 5 heart failure and Grade 3 pericarditis in 1 patient, and Grade 3 myocardial infarction, Grade 3 radiation pneumonitis, and Grade 3 pleural effusion. The 2-year cumulative incidence of late cardiopulmonary toxicities of Grade 3 or greater for patients 75 years or older was 29% compared with 3% for younger patients (p = 0.005).

Conclusion

The CCRT used in this study with an extensive radiation field is acceptable for younger patients but is not tolerated by patients older than 75 years.

Introduction

Concurrent chemoradiotherapy (CCRT) has become a standard treatment for patients with unresectable or medically inoperable esophageal carcinoma. A prospective randomized trial (Radiation Therapy Oncology Group [RTOG] 85-01) has demonstrated a significant survival advantage compared with radiotherapy alone 1, 2, 3. Although chemoradiotherapy is more effective than radiotherapy alone, treatment-related late toxicities are reported to be severe 4, 5. Furthermore, the survival rates are not satisfactory: the median survival duration is 12.5 to 21 months, and the 5-year survival rate is 14% to 29% 1, 2, 3, 4, 5. One reason why the late toxicities of CCRT are severe is that the radiation fields for esophageal cancer are extensive for prophylactic lymph node irradiation. Lymph node metastases are found at autopsy in approximately 70% of patients with esophageal cancer (6). Moreover, Sannohe et al. have reported that the incidence of supraclavicular node metastases is higher than 15% in patients with thoracic esophageal carcinoma (7). Therefore, initial radiation fields tend to be extensive to involve the prophylactic lymph node area. An unresolved issue is which patients are the best candidates for such intensive chemoradiotherapy.

In Japan, the incidence of esophageal cancer has increased significantly during the past decades 8, 9, 10, and squamous cell carcinoma is predominant, unlike in Western countries. Since 1999, we have performed CCRT with a total dose of 60 Gy for patients with esophageal carcinoma. The initial radiation fields extended from the supraclavicular fossa to the area of the celiac lymph nodes. Here we report the results of definitive CCRT for esophageal carcinomas.

Section snippets

Patient eligibility and pretreatment evaluation

All patients had histologically confirmed squamous cell carcinoma of the thoracic esophagus and were treated with definitive CCRT at our hospital between February 2002 and April 2005. Patients eligible for this study included those with an Eastern Cooperative Oncology Group performance status of 0 to 2, adequate organ functions, and clinical Stage I to IVA. Patients with Stage IVB disease were eligible if only supraclavicular lymph nodes were involved but were not eligible if they had other

Patient characteristics and radiation techniques

Between February 2002 and April 2005, a total of 74 patients with carcinoma of the esophagus received definitive chemoradiotherapy. Five patients were excluded from this analysis for cervical esophageal carcinoma (3 patients) or small-cell carcinoma (2 patients). The characteristics of the other 69 patients are shown in Table 1. The median age was 67 years (range, 45–83 years), and 14 patients were 75 years or older (20%). Of the patients, 63 (91%) completed the planned radiation therapy. The

Discussion

Chemoradiotherapy has become a standard therapy for patients with inoperable esophageal carcinoma, but severe toxicities are a matter of great concern for CCRT. One manifestation of severe early toxicity is esophageal fistula. Tracheo-esophageal fistulas developed in 4 of our patients. Because all 4 patients had bulky primary lesions infiltrated neighboring organs through the esophageal wall, the esophageal fistulas were related to the destructive tumor characteristics rather than the

Conclusion

In conclusion, the CCRT used in this study with extensive radiation fields is acceptable for younger patients but is not tolerated by patients older than 75 years.

References (20)

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Conflict of interest: none.

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