Roles of radiation dose and chemotherapy in the etiology of stomach cancer as a second malignancy.

PURPOSE: To evaluate the roles of radiation dose, chemotherapy, and other factors in the etiology of stomach cancer in long-term survivors of testicular cancer or Hodgkin lymphoma. METHODS AND MATERIALS: We conducted a cohort study in 5,142 survivors of testicular cancer or Hodgkin lymphoma treated in the Netherlands between 1965 and 1995. In a nested case-control study, detailed information on treatment, smoking, gastrointestinal diseases, and family history was collected for 42 patients with stomach cancer and 126 matched controls. For each subject, the mean radiation dose to the stomach was estimated. Relative risks (RRs) of stomach cancer and the radiation-related excess relative risk (ERR) per gray were calculated by conditional logistic regression analysis. RESULTS: The risk of stomach cancer was 3.4-fold increased compared with the general population. The risk increased with increasing mean stomach dose (p for trend, <0.001), at an ERR of 0.84 per Gy (95% confidence interval [CI], 0.12-15.6). Mean stomach doses of more than 20 Gy were associated with a RR of 9.9 (95% CI, 3.2-31.2) compared with doses below 11 Gy. The risk was 1.8-fold (95% CI, 0.8-4.4) increased after chemotherapy and 5.4-fold (95% CI, 1.2-23.9) increased after high doses of procarbazine (>or=13,000 mg) vs. <10,000 mg. The RR of smoking more than 10 cigarettes per day vs. no smoking was 1.6 (95% CI, 0.6-4.2). CONCLUSIONS: Stomach cancer risk is strongly radiation dose dependent. The role of chemotherapy, particularly of procarbazine and related agents, needs further study, because of the relatively small numbers of chemotherapy-treated subjects.

An overview of prognostic factors for long-term survivors of breast cancer.

BACKGROUND: Numerous studies have examined prognostic factors for survival of breast cancer patients, but relatively few have dealt specifically with 10+-year survivors. METHODS: A review of the PubMed database from 1995 to 2006 was undertaken with the following inclusion criteria: median/mean follow-up time at least 10 years; overall survival and/or disease-specific survival known; and relative risk and statistical probability values reported. In addition, we used data from the long-standing Eindhoven Cancer Registry to illustrate survival probability as indicated by various prognostic factors. RESULTS: 10-year breast cancer survivors showed 90% 5-year relative survival. Tumor size, nodal status and grade remained the most important prognostic factors for long-term survival, although their role decreased over time. Most studies agreed on the long-term prognostic values of MI (mitotic index), LVI (lymphovascular invasion), Her2-positivity, gene profiling and comorbidity for either all or a subgroup of breast cancer patients (node-positive or negative). The roles of age, socioeconomic status, histological type, BRCA and p53 mutation were mixed, often decreasing after correction for stronger prognosticators, thus limiting their clinical value. Local and regional recurrence, metastases and second cancer may substantially impair long-term survival. Healthy lifestyle was consistently related to lower overall mortality. CONCLUSIONS: Effects of traditional prognostic factors persist in the long term and more recent factors need further follow-up. The prognosis for breast cancer patients who have survived at least 10 years is favourable and increases over time. Improved long-term survival can be achieved by earlier detection, more effective modern therapy and healthier lifestyle.

Treatment-specific risks of second malignancies and cardiovascular disease in 5-year survivors of testicular cancer.

PURPOSE: To compare radiotherapy and chemotherapy effects on long-term risks of second malignant neoplasms (SMNs) and cardiovascular diseases (CVDs) in testicular cancer (TC) survivors. PATIENTS AND METHODS: In our nationwide cohort comprising 2,707 5-year TC survivors, incidences of SMNs and CVDs were compared with general-population rates by calculating standardized incidence ratios (SIRs) and absolute excess risks (AERs). Treatment effects on risks of SMN and CVD were quantified in multivariable Cox regression and competing risks analyses. RESULTS: After a median follow-up time of 17.6 years, 270 TC survivors developed SMNs. The SIR of SMN overall was 1.7 (95% CI, 1.5 to 1.9), with an AER of 32.3 excess occurrences per 10,000 person-years. SMN risk was 2.6-fold (95% CI, 1.7- to 4.0-fold) increased after subdiaphragmatic radiotherapy and 2.1-fold (95% CI, 1.4- to 3.1-fold) increased after chemotherapy, compared with surgery only. Subdiaphragmatic radiotherapy increased the risk of a major late complication (SMN or CVD) 1.8-fold (95% CI, 1.3- to 2.4-fold), chemotherapy increased the risk of a major late complication 1.9-fold (95% CI, 1.4- to 2.5-fold), and smoking increased the risk of a major late complication 1.7-fold (95% CI, 1.4- to 2.1-fold), compared with surgery only. The median survival time was 1.4 years after SMN and 4.7 years after CVD. CONCLUSION: Radiotherapy and chemotherapy increased the risk of developing SMN or CVD to a similar extent as smoking. Subdiaphragmatic radiotherapy strongly increases the risk of SMNs but not of CVD, whereas chemotherapy increases the risks of both SMNs and CVDs. Prolonged follow-up after chemotherapy is needed to reliably compare the late complications of radiotherapy and chemotherapy after 20 years.