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Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease
Journal article   Open access   Peer reviewed

Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease

Lois B Travis, Mary Gospodarowicz, Rochelle E Curtis, E Aileen Clarke, Michael Andersson, Bengt Glimelius, Timo Joensuu, Charles F Lynch, Flora E van Leeuwen, Eric Holowaty, …
JNCI : Journal of the National Cancer Institute, Vol.94(3), pp.182-192
02/06/2002
DOI: 10.1093/jnci/94.3.182
PMID: 11830608
url
https://doi.org/10.1093/jnci/94.3.182View
Published (Version of record) Open Access

Abstract

Lung cancer is a frequent cause of death in patients cured of Hodgkin's disease, but the contributions of chemotherapy, radiotherapy, and smoking are not well described. We quantified the risk of treatment-associated lung cancer, taking into account tobacco use. Within a population-based cohort of 19 046 Hodgkin's disease patients (diagnosed from 1965 through 1994), a case-control study of lung cancer was conducted. The cumulative amount of cytotoxic drugs, the radiation dose to the specific location in the lung where cancer developed, and tobacco use were compared for 222 patients who developed lung cancer and for 444 matched control patients. All statistical tests were two-sided. Treatment with alkylating agents without radiotherapy was associated with increased lung cancer risk (relative risk [RR] = 4.2; 95% confidence interval [CI] = 2.1 to 8.8), as was radiation dose of 5 Gy or more without alkylating agents (RR = 5.9; 95% CI = 2.7 to 13.5). Risk increased with both increasing number of cycles of alkylating agents and increasing radiation dose (P for trend <.001). Among patients treated with mechlorethamine, vincristine, procarbazine, and prednisone (MOPP), risk increased with cumulative amounts of mechlorethamine and procarbazine (P<.001) when evaluated separately. Statistically significantly elevated risks of lung cancer were apparent within 1-4 years after treatment with alkylating agents, whereas excess risk after radiotherapy began 5 years after treatment and persisted for more than 20 years. Risk after treatment with alkylating agents and radiotherapy together was as expected if individual excess risks were summed. Tobacco use increased lung cancer risk more than 20-fold; risks from smoking appeared to multiply risks from treatment. Past treatments with alkylating agents and radiation therapy for Hodgkin's disease were associated with an increased risk of lung cancer in a dose-dependent and additive fashion. The precise risk estimates, however, should be interpreted cautiously, given the possible residual and enhancing effects of tobacco.
 Smoking - adverse effects Humans Middle Aged Risk Factors Male Radiotherapy - adverse effects Hodgkin Disease - complications Case-Control Studies Lung Neoplasms - complications Neoplasms, Second Primary - etiology Dose-Response Relationship, Drug Neoplasms, Second Primary - complications Disease-Free Survival Hodgkin Disease - radiotherapy Lung Neoplasms - etiology Antineoplastic Agents - adverse effects Hodgkin Disease - therapy Adolescent Hodgkin Disease - drug therapy Adult Female Aged Child Dose-Response Relationship, Radiation

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