Roles of radiotherapy and smoking in lung cancer following Hodgkin's disease.

BACKGROUND: Several studies have shown that survivors of Hodgkin's disease have increased risk of lung cancer, but the factors responsible for this excess risk are not well known. PURPOSE: This study was undertaken to investigate the effects of radiation dose, chemotherapy, and smoking on the risk of lung cancer following treatment of Hodgkin's disease. METHODS: We conducted a case-control study in a cohort of 1939 patients treated for Hodgkin's disease from 1966 through 1986 in The Netherlands. Detailed treatment information was collected from the medical records for 30 case patients with lung cancer following Hodgkin's disease and 82 matched control subjects who had not developed lung cancer. Multiple sources were used to obtain as complete smoking histories of the study participants as possible. For each case-control set, the radiation dose received by the area of the lung where the case patient developed the tumor was estimated on the basis of radiotherapy charts and experimental simulations of treatments. The estimates of relative risk (RR) for lung cancer associated with specific exposures were obtained from logistic regression methods, and all tests of statistical significance were two-sided. RESULTS: A statistically significant increase in risk of lung cancer was observed with increasing radiation dose (P for trend = .01) with an RR of 9.6 (95% confidence interval [CI] = 0.93-98) for patients who received 9 Gy or more compared with those who received less than 1 Gy. Patients who smoked more than 10 pack-years after the diagnosis of Hodgkin's disease had a sixfold increase in the risk of lung cancer compared with patients who smoked less than 1 pack-year (P = .03). Positive interaction on a multiplicative scale was observed between the carcinogenic effects of smoking and radiation. The increase in risk of lung cancer with increasing radiation dose was much greater among the patients who smoked after diagnosis of Hodgkin's disease than among those who refrained from smoking (P = .04). There was no increase in lung cancer risk in relation to the number of cycles of chemotherapy or the cumulative doses of the drugs mechlorethamine and procarbazine. CONCLUSIONS: The excess risk of lung cancer in Hodgkin's disease patients treated with radiotherapy is related to the radiation dose received by the affected area of the lung. Smokers experience a significantly greater risk attributable to radiotherapy than nonsmokers. IMPLICATIONS: Physicians in charge of patient treatment should make a special effort to dissuade Hodgkin's disease patients from smoking after receiving radiotherapy.

Second cancer risk following Hodgkin's disease: a 20-year follow-up study.

PURPOSE: To determine risk factors for the development of second primary cancers during long-term follow-up of patients with Hodgkin's disease (HD). PATIENTS AND METHODS: We assessed the risk of second cancers (SCs) in 1939 HD patients, who were admitted to the Netherlands Cancer Institute (NKI; Amsterdam) or the Dr Daniel den Hoed Cancer Center (DDHK; Rotterdam) between 1966 and 1986. For 97% of the cohort, we obtained a medical status up to at least January 1989. The median follow-up duration of the patients was 9.2 years; for 17% of the patients, follow-up was longer than 15 years. For more than 98% of all second tumors, the diagnosis was confirmed through a pathology report. RESULTS: In all, 146 patients developed a SC, compared with 41.9 cases expected on the basis of incidence rates in the general population (relative risk [RR], 3.5; 95% confidence interval [CI], 2.9 to 4.1). The mean 20-year actuarial risk of all SCs was 20% (95% CI, 17% to 24%). Significantly increased RRs were observed for leukemia (RR, 34.7; 95% CI, 23.6 to 49.3), non-Hodgkin's lymphoma (NHL) (RR, 20.6; 95% CI, 13.1 to 30.9), lung cancer (RR, 3.7; 95% CI, 2.5 to 5.3), all gastrointestinal cancers combined (RR, 2.0; 95% CI, 1.2 to 3.1), all urogenital cancers combined (RR, 2.4; 95% CI, 1.4 to 3.7), melanoma (RR, 4.9; 95% CI, 1.6 to 11.3), and soft tissue sarcoma (RR, 8.8; 95% CI, 1.8 to 25.8). As compared with the general population, the cohort experienced an excess of 63 cancer cases per 10,000 person-years. Cox-model analysis indicated the following as significant risk factors for developing leukemia: first-year treatment with chemotherapy (CT), follow-up treatment with CT, age at diagnosis of HD greater than 40 years, splenectomy, and advanced stage. Patients treated with CT in the 1980s had a substantially lower risk of leukemia than patients treated in the 1970s (10-year actuarial risks of 2.1% and 6.4%, respectively; P = .07). Significant risk factors for NHL were older age, male sex, and combined modality treatment as compared with either modality alone. Risk of lung cancer was strongly related to radiotherapy (RT), while an additional role of CT could not be demonstrated. After more than 15 years of follow-up, women treated with mantle-field irradiation before age 20 years had a greater than forty-fold increased risk of breast cancer (P < .001). CONCLUSION: While the long-term consequences of HD treatment as administered in the 1960s and 1970s are still evolving, it is promising that patients who received the new treatment regimens introduced in the 1980s have a much lower leukemia risk than patients treated in earlier years. Beginning 10 years after initial RT, the follow-up program of women who received mantle-field irradiation before age 30 years should routinely include breast palpation and yearly mammography.

Long-term risk of second malignancy in survivors of Hodgkin's disease treated during adolescence or young adulthood.

PURPOSE: To quantify the long-term risk of second primary cancers (SCs) in patients diagnosed with Hodgkin's disease (HD) during adolescence or young adulthood. PATIENTS AND METHODS: The risk of SCs was assessed in 1,253 patients diagnosed with HD before the age of 40 years and treated in two Dutch cancer centers between 1966 and 1986. The median follow-up duration was 14.1 years. RESULTS: In all, 137 patients developed SCs, compared with 19.4 cases expected on the basis of incidence rates in the general population (relative risk [RR] = 7.0; 95% confidence interval, 5.9 to 8.3). The 25-year actuarial risk of SC overall was 27.7%. The RR of solid tumors increased greatly with younger age at the first treatment of HD, not only for breast cancer but also for all other solid tumors, with RRs of 4.9, 6.9, and 12.7 for patients first treated at ages 31 to 39 years, 21 to 30 years, and

Risks of second primary breast and urogenital cancer following female breast cancer in the south of The Netherlands, 1972-2001.

A cohort of 9919 breast cancer patients from the population-based Eindhoven Cancer Registry was followed for vital status and development of second cancer. Person-year analysis was applied to determine the risk of second primary breast or urogenital cancer among breast cancer patients and to assess its correlation with age, treatment and time since the first breast cancer diagnosis. Women with previous breast cancer have an elevated risk of overall second breast or urogenital cancer. The largest relative risk was observed for second breast cancer (SIR (standardised incidence ratio) 3.5; 95% confidence interval (CI) 3.2-3.8) and second ovarian cancer (SIR 1.7; 95% CI 1.2-2.3). The absolute excess risk was highest for second breast cancer (64/10,000 patients/year). However, breast cancer has an inverse relationship to risk of cervical cancer. Changes in behavioural risk factors are important for lowering the risk of second cancer after breast cancer.

[Second primary tumors in patients treated at an early age for Hodgkin's disease; consequences for the follow-up]. / Tweede primaire tumoren bij mensen die op jonge leeftijd behandeld zijn voor de ziekte van Hodgkin; consequenties voor de follow-up.

As curative treatment is now available for a substantial group of cancer patients, it is increasingly important to evaluate how late complications of treatment affect their long-term survival. Two recent publications summarize the second malignancies in survivors of Hodgkin's disease treated during adolescence or young adulthood. After more than 20 years' follow-up, the risk of solid tumours is still much greater in survivors of Hodgkin's disease than in the population at large. Age at treatment has a major effect on the occurrence of second malignancy. Reassuringly, the increased risk of solid tumours in patients who were less than 20 years of age seems to decrease as these patients grow older. The data of these studies suggest that chemotherapy may increase the risk of solid tumours from radiotherapy. Special alertness to symptoms of second malignancies is advised during follow-up after treatment for Hodgkin's disease, especially in patients treated below the age of 20.

Primary malignancy after primary female breast cancer in the South of the Netherlands, 1972-2001.

OBJECTIVES: To assess the risk of second primary cancers among women with previous breast cancer and calculate the excess burden of second cancer in the population. METHODS: A population-based longitudinal study was conducted using the Eindhoven cancer registry data on 9919 breast cancer patients diagnosed in the period 1972-2000 and followed until 2001. Standardised incidence ratios (SIR) and absolute excess risks (AER) were calculated. RESULTS: In total, 1298 (13%) women developed a second primary cancer. The risk of overall second cancer was higher among breast cancer patients compared to the general population (SIR: 2.8; 95% CI: 2.6-2.9), with an AER of 115 second cancers for every 10,000 breast cancer patients per year. High SIR and AER were observed for breast cancer (SIR: 4.1; 95% CI: 3.8-4.4; AER: 64/10,000 patients/year) and ovarian cancer (SIR: 2.0; 95% CI: 1.5-2.7; AER: 4.5/10,000 patients/year). CONCLUSIONS: Our recent data show that women with previous breast cancer have an elevated risk of developing a second cancer compared to the general population. Excess burden for the population is especially high for second cancers of the breast, ovary and colon. Screening may only be justified for breast, ovary and colon cancer in certain groups of patients.

Excess mortality from breast cancer 20 years after diagnosis when life expectancy is normal.

In a population-based study, causes of death were traced of 418 deceased breast cancer patients diagnosed in 1960-1979 who survived at least 10 years after diagnosis. The pattern of causes of death in these patients was compared with the general female population using standardized mortality ratios (SMRs). Of 418 patients surviving at least 10 years, 196 (47%) died from breast cancer and 50 (12%) died from another cancer. The SMR for breast cancer was 15.8 (95% CI: 13.1-18.8) 10-14 years after diagnosis; it was still 4.7 (95% CI: 2.6-7.8) after 20 years. Overall mortality was higher than expected 10-14 years after diagnosis (SMR: 1.3; 95% CI: 1.1-1.5), but lower after more than 20 years (SMR: 0.6; 95% CI: 0.4-0.7). Despite a normal (or even improved) life expectancy for breast cancer patients 20 years after diagnosis the risk of dying from this disease remained elevated.