Factors influencing the development of ulcers and strictures in carcinoma of the esophagus treated with radiotherapy with or without concurrent chemotherapy

Purpose: To ascertain factors that could influence the development of ulcers and strictures in the definitive management of squamous cell carcinoma (SCC) of esophagus treated with external beam radiotherapy (EBRT), high-dose-rate (HDR) intralumenal radiotherapy (ILRT) with or without concurrent weekly cisplatin (CDDP @ 35 mg/m2) chemotherapy (CT).
Materials and Methods: Between 1990-2005, 244 patients with inoperable SCC of esophagus were identified from our database and grouped into one of the following: those receiving at least 60Gy EBRT (Gp E, n=44); EBRT followed by HDR-ILRT (Gp E+I, n=98); at least 50Gy EBRT with CT (Gp E+C, n=68); EBRT+HDR-ILRT + CT (Gp E+I+C, n=34). Ulcers (discovered on endoscopy) and strictures evident on a barium swallow (which needed dilatations) were scored as treatment induced, if the biopsy was negative. Factors likely to influence their outcome were analyzed.
Results: The groups were matched for all patient and disease characteristics except pretreatment hemoglobin and Karnofsky performance score (KPS), which were lower in Gp E. The incidence of ulcers was 7%, 8%, 6% and 21% ( P =0.08) while that of strictures was 14%, 9%, 21% and 41% ( P =0.00) for the groups E, E+I, E+C and E+I+C respectively. On univariate analysis, patients with better KPS ( P =0.03), treated with narrow applicators (6 mm vs. 10 mm, P =0.00), received CT ( P =0.00) or assigned to Gp E+I+C ( P =0.00) were more likely to develop strictures, with a trend for development of ulcers in Gp. E+I+C ( P =0.08). Logistic regression retained only Gp E+I+C for development of ulcers (OR 10.36, 95% CI 1.2-89.1, P =0.03) and strictures (OR 4.2, 95% CI 1.4-12.6, P =0.00).
Conclusion: Treatment intensification as in Gp E+I+C results in about a three-fold increase in treatment induced late morbidity which can adversely impact on swallowing function and therefore emphasizes the need for optimisation of HDR-ILRT when used in a CT+RT protocol.

Keywords
Brachytherapy, chemotherapy, esophageal neoplasms, late morbidity, radiotherapy