Impact of Risk-Adapted Therapy for Pediatric Hodgkin Lymphoma on Risk of Long-Term Morbidity: A Report From the Childhood Cancer Survivor Study

Abstract

PURPOSE To determine the incidence of serious chronic health conditions among survivors of pediatric Hodgkin lymphoma (HL), compare by era of therapy and by selected cancer therapies, and provide estimates of risks associated with contemporary therapy. METHODS Assessing 2,996 5-year HL survivors in the Childhood Cancer Survivor Study diagnosed from 1970 to 1999, we examined the cumulative incidence of severe to fatal chronic conditions (grades 3-5) using self-report conditions, medically confirmed subsequent malignant neoplasms, and cause of death based on the National Death Index. We used multivariable regression models to estimate hazard ratios (HRs) per decade and by key treatment exposures. RESULTS HL survivors were of a mean age of 35.6 years (range, 12-58 years). The cumulative incidence of any grade 3-5 condition by 35 years of age was 31.4% (95% CI, 29.2 to 33.5). Females were twice as likely (HR, 2.1; 95% CI, 1.8 to 2.4) to have a grade 3-5 condition compared with males. From the 1970s to the 1990s, there was a 20% reduction (HR, 0.8; 95% CI, 0.7 to 0.9) in decade-specific risk of a grade 3-5 condition ( P trend = .002). In survivors who had a recurrence and/or hematopoietic cell transplant, the risk of a grade 3-5 condition was substantially elevated, similar to that of survivors treated with high-dose, extended-field radiotherapy (HR, 1.2; 95% CI, 0.9 to 1.5). Compared with survivors treated with chest radiotherapy ≥ 35 Gy in combination with an anthracycline or alkylator, a contemporary regimen for low-intermediate risk HL was estimated to lead to a 40% reduction in risk of a grade 3-5 condition (HR, 0.6; 95% CI, 0.4 to 0.8). CONCLUSION This study demonstrates that risk-adapted therapy for pediatric HL has resulted in a significant reduction in serious long-term outcomes.

The forgotten survivor: A comprehensive review on Non‐Hodgkin lymphoma survivorship

“…Furthermore, HSCT was shown to increase the incidence of serious health conditions (grade 3-5) in survivors with pediatric HL in a way equivalent to the risk of patients who received high-dose, extendedfield radiotherapy. 93 These findings highlight the importance of NRM post HSCT and necessitate greater attention. 94 Given the unique and complex late effects of HSCT, we suggest following the American Society for Transplantation and Cellular Therapy (ASTCT) guidelines for further recommendations.…”

“…The reported main causes of NRM included infection (30‐year cumulative incidence: 10.7%; SMR: 52.0), subsequent malignancy (30‐year cumulative incidence: 7.0%; SMR: 4.8), CVD (30‐year cumulative incidence: 4.6%; SMR: 4.1), and pulmonary disease (30‐year cumulative incidence: 2.7%; SMR: 13.9). Furthermore, HSCT was shown to increase the incidence of serious health conditions (grade 3–5) in survivors with pediatric HL in a way equivalent to the risk of patients who received high‐dose, extended‐field radiotherapy 93 . These findings highlight the importance of NRM post HSCT and necessitate greater attention 94 …”

Mitigating, monitoring, and managing long-term chemotherapy- and radiation-induced cardiac toxicity

“…Although the past 70 years have seen a dra matic improve ment in the cure rates of most child hood can cers, in many instances, this has required sig nifi cant inten si fi ca tion of ther a pies, including the use of radio ther apy, anthracycline che mo ther apy, and hema to poi etic cell trans plan ta tion. 1 While refine ments over the past sev eral decades have led to a reduc tion in spe cific cardiotoxic expo sures such as radio ther apy for many patients with acute lym pho blas tic leu ke mia (Table 1) and Hodgkin lym phoma (Table 2), 7,8 the empha sis on anthracycline and hema to poi etic cell trans plan ta tion for AML and relapsed hema to logic malig nan cies may con trib ute to increased car dio vas cu lar mor bid ity in those sur vi vors. 9 The devel op ment of newer molec u lar targeted ther apies may reduce reli ance on con ven tional cyto toxic chemotherapies, and refine ments in radio ther apy may reduce dam age to the heart and great ves sels.…”

Primary Mediastinal B Cell Lymphoma in the Positron-Emission Tomography Era Executive Summary of the American Radium Society Appropriate Use Criteria

“…Survivors of lymphoma treated with anthracycline-based chemotherapy and mediastinal RT are at risk for developing secondary cancers within the radiation field and cardiotoxicity from both the anthracycline and radiation. [26][27][28] When RT is recommended, best practices should be considered to minimize the radiation dose to the organs at risk (OARs) while maintaining appropriate target coverage. Studies have demonstrated a linear dose-response relationship between radiation dose and risk of cardiac disease and also various second cancers (eg, breast cancer, lung cancer, gastrointestinal cancer, sarcoma, but not thyroid cancer), [29][30][31] suggesting that minimizing the dose to the OARs will help to reduce the risk of these second cancers.…”