Yvonne M. Geurts

Background: Few studies examined treatment-specific long-term risks of cardiovascular diseases (CVD) in diffuse large B-cell lymphoma survivors treated with potentially cardiotoxic radiotherapy and/or chemotherapy with or without rituximab after the 1990s. Methods: Long-term CVD risk was examined in a multicenter cohort comprising 2356 diffuse large B-cell lymphoma survivors who survived at least 5 years and who were treated at ages 15-61 years in 1989-2012. CVD data were acquired from medical records, general practitioners, and disease registries. Observed CVD numbers were compared with expected CVD incidence in the Dutch population to estimate standardized incidence ratios (SIRs) and absolute excess risks (10 000 person-years). Treatment-specific CVD risks were assessed using multivariable Cox regression. Results: During a median follow-up of 14.2 years (IQR = 10.1-18.9 years), 312 survivors were diagnosed with a first CVD at least 5 years after treatment. Compared with the general population, diffuse large B-cell lymphoma survivors had increased risks of heart failure ([HF]; SIR = 3.9, 95% confidence interval [CI] = 3.4 to 4.6; absolute excess risk = 62.8) and cerebrovascular accident (SIR = 1.3, 95% CI = 1.0 to 1.7; absolute excess risk = 9.8), while risk of coronary artery disease was decreased (SIR = 0.7, 95% CI = 0.5 to 0.9; absolute excess risk = −30.9). HF risk was higher among females (SIR = 5.3, 95% CI = 4.2 to 6.5) than males (SIR = 3.2, 95% CI = 2.6 to 4.0, P for heterogeneity < .001), and among survivors aged 40 years and younger at diffuse large B-cell lymphoma treatment (SIR = 10.5, 95% CI = 7.2 to 14.8; P for trend < .001). Exposure to more than 300 mg/m2 doxorubicin was associated with a 2.8-fold (95% CI = 1.7 to 4.5) increased risk of cardiomyopathy or HF, while radiotherapy involving the heart was associated with a 1.9-fold (95% CI = 1.1 to 3.1) increased risk of valvular heart disease. Conclusion: Those surviving at least 5 years after diffuse large B-cell lymphoma have increased risks of developing CVDs, especially HF. Physicians and patients should recognize this risk, and individualized cardiac screening should be considered.

Purpose: Standardized patient-reported outcomes (PRO) monitoring during and after rectal cancer treatment provides insight into treatment-related toxicities patients experience and improves health-related quality-of-life as well as overall survival. We aimed to select a subset of the PRO version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) for standardized monitoring of treatment-related symptomatic toxicities in rectal cancer. Methods: We used a mixed methods approach including a literature review, and semi-structured interviews with health care providers (HCPs) involved in rectal cancer care and rectal cancer patients. Results from literature and interviews were summarized and used in a modified Delphi procedure to select a PRO-CTCAE subset specific for rectal cancer. Results: Twenty-six PRO-CTCAE symptomatic toxicities were identified from literature. Fifteen HCPs from multiple disciplines (medical, radiation and surgical oncology), and a heterogeneous group of fifteen rectal cancer patients treated with chemotherapy and/or radiotherapy and/or surgery, participated in semi-structured interviews. Ten HCPs (67%) and nine patients (90%) participated in the first Delphi round. The final selected PRO-CTCAE core-subset contained 16 symptomatic toxicities: ‘diarrhea’, ‘fecal incontinence’, ‘constipation’,‘bloating of the abdomen’, ‘pain in the abdomen’, ‘vomiting’, ‘decreased libido’, ‘pain during vaginal sex’, ‘ability to achieve and maintain erection’, ‘fatigue’, ‘anxiety’, ‘feeling that nothing could cheer you up’, ‘urinary incontinence’, ‘painful urination’, ‘general pain’, and ‘hand-foot syndrome’. Conclusion: Based on a comprehensive mixed methods study, a PRO-CTCAE subset for standardized treatment-related symptomatic toxicity monitoring in rectal cancer was identified. Assessment of the effectiveness and compliance of symptomatic toxicity monitoring using this subset is recommended.

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 ( P_trend = .004). The risk increase associated with doxorubicin (yes v no) was not modified by age at first treatment (hazard ratio [HR]_{age , 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.}