Doxorubicin Exposure and Breast Cancer Risk in Survivors of Adolescent and Adult Hodgkin Lymphoma.

PURPOSE: Female Hodgkin lymphoma (HL) survivors treated with chest radiotherapy (RT) at a young age have a strongly increased risk of breast cancer (BC). Studies in childhood cancer survivors have shown that doxorubicin exposure may also increase BC risk. Although doxorubicin is the cornerstone of HL chemotherapy, the association between doxorubicin and BC risk has not been examined in HL survivors treated at adult ages. METHODS: We assessed BC risk in a cohort of 1,964 female 5-year HL survivors, treated at age 15-50 years in 20 Dutch hospitals between 1975 and 2008. We calculated standardized incidence ratios, absolute excess risks, and cumulative incidences. Doxorubicin exposure was analyzed using multivariable Cox regression analyses. RESULTS: After a median follow-up of 21.6 years (IQR, 15.8-27.1 years), 252 women had developed invasive BC or ductal carcinoma in situ. The 30-year cumulative incidence was 20.8% (95% CI, 18.2 to 23.4). Survivors treated with a cumulative doxorubicin dose of >200 mg/m2 had a 1.5-fold increased BC risk (95% CI, 1.08 to 2.1), compared with survivors not treated with doxorubicin. BC risk increased 1.18-fold (95% CI, 1.05 to 1.32) per additional 100 mg/m2 doxorubicin (Ptrend = .004). The risk increase associated with doxorubicin (yes v no) was not modified by age at first treatment (hazard ratio [HR]age <21 years, 1.5 [95% CI, 0.9 to 2.6]; HRage ≥21 years, 1.3 [95% CI, 0.9 to 1.9) or chest RT (HRwithout mantle/axillary field RT, 1.9 [95% CI, 1.06 to 3.3]; HRwith mantle/axillary field RT, 1.2 [95% CI, 0.8 to 1.8]). CONCLUSION: This study shows that treatment with doxorubicin is associated with increased BC risk in both adolescent and adult HL survivors. Our results have implications for BC surveillance guidelines for HL survivors and treatment strategies for patients with newly diagnosed HL.

Position shifts and volume changes of pelvic and para-aortic nodes during IMRT for patients with cervical cancer.

BACKGROUND AND PURPOSE: To evaluate volume changes and position shifts and their contribution to treatment margins of pelvic and para-aortic lymph nodes during Intensity Modulated Radiation Therapy (IMRT) for advanced cervical cancer. MATERIALS AND METHODS: Seventeen patients with visible nodes on MR images underwent T2-weighted MR scans before and weekly during the course of IMRT. Thirty-nine pelvic and para-aortic nodes were delineated on all scans. Margins accommodating for volume and position changes were taken from the boundaries of the nodal volumes in the six main directions. RESULTS: Nodal volume regression from the pre-treatment situation to week 4 was 58% on average (range: 11.7% increase to 100% decrease). Nodal volumes partly increased between the pre-treatment scans and the scans in weeks 1-3, but in week 4 all nodes except one had regressed. Around the nodal volumes manually derived ITV margins accounting for volume changes and position shifts of 7.0, 4.0, 7.0, 8.0, 7.0 and 9.0mm to the medial, lateral, anterior, posterior, superior and inferior directions were needed to cover 95% of all nodes. CONCLUSIONS: We used weekly MR scans to derive inhomogeneous margins that accommodate for nodal volume and position changes during treatment. These margins should be taken into consideration when planning external beam radiotherapy (EBRT) boosts, especially for highly conformal boosting techniques.