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BACKGROUND: Hodgkin lymphoma (HL) occurs at young ages, with the highest incidence between 20 and 40 years. While cure rates have improved to 80%-90% over the past decades, survivors of HL are at substantial risk of late treatment-related complications, such as cardiovascular diseases, breast cancer, severe infections, and hypothyroidism. To reduce morbidity and mortality from late treatment effects, the Dutch Better care after lymphoma, Evaluation of long-term Treatment Effects and screening Recommendations (BETER) consortium developed a survivorship care program for 5-year survivors of HL that includes risk-based screening for and treatment of (risk factors for) late adverse events. Even though several cancer survivorship care programs have been established worldwide, there is a lack of knowledge about their effectiveness in clinical practice. OBJECTIVE: The Improving Nationwide Survivorship care Infrastructure and Guidelines after Hodgkin lymphoma Treatment (INSIGHT) study evaluates whether Dutch BETER survivorship care for survivors of HL decreases survivors' burden of disease from late adverse events after HL treatment and associated health care costs and improves their quality of life. METHODS: The INSIGHT study is a multicenter retrospective cohort study with a quasi-experimental design and prospective follow-up, embedded in the national BETER survivorship care infrastructure. The first BETER clinics started in 2013-2016 and several other centers started or will start BETER clinics in 2019-2024. This allows us to compare survivors who did and those who did not receive BETER survivorship care in the last decade. Survivors in the intervention group are matched to controls (n=450 per group) based on sex, age at diagnosis (±5 years), age in 2013 (±5 years), and treatment characteristics. The primary outcome is the burden of disease in disability-adjusted life years from cardiovascular disease, breast cancer, severe infections, and hypothyroidism. In a cost-effectiveness analysis, we will assess the cost of BETER survivorship care per averted or gained disability-adjusted life year and quality-adjusted life year. Secondary outcomes are BETER clinic attendance, adherence to screening guidelines, and knowledge and distress about late effects among survivors of HL. Study data are collected from a survivor survey, a general practitioner survey, medical records, and through linkages with national disease registries. RESULTS: The study was funded in November 2020 and approved by the institutional review board of the Netherlands Cancer Institute in July 2021. We expect to finalize recruitment by October 2024, data collection by early 2025, and data analysis by May 2025. CONCLUSIONS: INSIGHT is the first evaluation of a comprehensive survivorship program using real-world data; it will result in new information on the (cost-)effectiveness of survivorship care in survivors of HL in clinical practice. The results of this study will be used to improve the BETER program where necessary and contribute to more effective evidence-based long-term survivorship care for lymphoma survivors. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/55601.
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PURPOSE: Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular disease (CVD) due to former lymphoma treatment. In 2013, cardiovascular screening for 5-year HL survivors according to national guidelines was implemented in Dutch survivorship clinics. We aim to assess the following: (1) adherence to screening guidelines and (2) the yield of (risk factors for) CVD in the screening program. METHODS: The study population consisted of 5-year HL survivors who received survivorship care at three University Medical Centers from 2013 to 2016 through 2021. Patient characteristics, cardiovascular screening procedures, and outcomes were collected from the medical records. RESULTS: In 186 survivors eligible for cardiovascular screening (mean age 47.8 years, 60.8% female), the following diagnostics were performed: complete blood tests (81.0%, median frequency: yearly instead of advised 5-yearly evaluation), electrocardiogram (93.0%), echocardiography (94.6%). Fifty-five percent of survivors had at least one modifiable cardiovascular risk factor (i.e., current smoking, overweight, new/insufficiently controlled hypertension, dyslipidemia, or diabetes). Screening detected ≥ 1 CVD in 31.1% of survivors. Among survivors with available echocardiography report (n = 106), screening detected new aortic and/or mitral valve dysfunction(s) in 51.0% (with grades 3-4 in 4.9%) and impaired left ventricular ejection fraction in 10.3%. CONCLUSIONS: Adherence to the screening guidelines in the Dutch HL survivorship care program was reasonable to good and a substantial number of actionable (risk factors for) CVD were diagnosed. IMPLICATIONS FOR CANCER SURVIVORS: Our findings inform HL survivors at high risk of late cardiotoxicity about cardiovascular screening findings and demonstrate appropriate therapeutic actions after diagnosis of (risk factors for) CVD.
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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.