We pooled the data from seven studies of second cancer risk after treatment of Hodgkin's disease (HD) and estimated the relative risks (RR) of solid cancers (SC) for the following two treatment groups: (1) radiotherapy, with or without chemotherapy; and (2) chemotherapy alone. For all treatment groups combined, the RR of SC was 2.1 (95% confidence limits: 1.8 to 2.4). In the radiotherapy group, statistically significant RR were found for SC for all anatomic sites (RR: 2.2; 95% confidence limits: 1.9 to 2.6) and for SC of the bones and joints (RR: 20.0), soft tissues (RR: 18.3), non-HD lymphomas (RR: 8.1), melanomas of the skin (RR: 6.7), buccal cavity and pharynx (RR: 4.1), nervous system (RR: 3.6), respiratory system (RR: 2.5), and digestive system (RR: 1.8). In the chemotherapy alone group, none of the RR differed significantly from unity, and the RR for SC of all sites was 1.1 (95% confidence limits: 0.5 to 1.9). The average duration of follow-up for patients with chemotherapy was shorter than the duration of follow-up for patients with radiotherapy. This may explain the general absence of elevated RR after chemotherapy.

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The purpose of this report is to analyze the role and optimum integration of chemotherapy for invasive carcinoma of the esophagus in the combined modality setting. The charts of 157 patients with primary invasive nonmetastatic carcinoma of the esophagus treated with curative intent between 1984 and 1998 were reviewed. Various combinations of chemotherapy (C), radiotherapy (R), and surgery (S) were used. Chemotherapy was multiagent (typically 5-fluorouracil [5-FU]/cisplatin/hydroxyurea, 5-FU/cisplatin/leucovorin, or docetaxel/cisplatin) for all but seven patients treated with single agents. The clinical endpoints examined were overall survival (OS) and cause-specific survival (CSS). Multivariate analyses and pairwise comparisons were made for determination of the benefit of chemotherapy. On the multivariate analyses, only American Joint Committee on Cancer stage and chemotherapy were statistically significant determinants of both OS and CSS. Following are the results of the pairwise analyses: 3-year OS: (no C) versus (any C): 16% versus 27% (p = 0.02); (S) versus (C+S): 19% versus 34% (p = 0.35); (R) versus (C+R): 0% versus 13% (p = 0.05); (R + S) versus (C + R + S): 18% versus 33% (p = 0.03). The administration of adjuvant chemotherapy can improve survival in patients with invasive nonmetastatic esophageal carcinoma. This benefit appears to be greater when chemotherapy is given with radiotherapy (with or without surgery) than in the absence of radiotherapy, perhaps because of a radiosensitizing effect not possible when using surgery is the only local control modality.

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