Lung cancer following chemotherapy and radiotherapy for Hodgkin's disease.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Travis
Lois B
LB
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA. travisl@epndce.nci.nih.gov
Gospodarowicz
Mary
M
Curtis
Rochelle E
RE
Clarke
E Aileen
EA
Andersson
Michael
M
Glimelius
Bengt
B
Joensuu
Timo
T
Lynch
Charles F
CF
van Leeuwen
Flora E
FE
Holowaty
Eric
E
Storm
Hans
H
Glimelius
Ingrid
I
Pukkala
Eero
E
Stovall
Marilyn
M
Fraumeni
Joseph F
JF
Boice
John D
JD
Gilbert
Ethel
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects; D016022:Case-Control Studies; D002648:Child; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006689:Hodgkin Disease / Q000150:complications* / Q000188:drug therapy / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D008175:Lung Neoplasms / Q000150:complications* / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000150:complications* / Q000209:etiology*; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D000970:Antineoplastic Agents