Hodgkin lymphoma accounts for approximately 16% of all malignancies in adolescents and young adults (between ages 15 and 39 years).1, 2 Its 5-year survival expectations currently exceed 90%.3 However, the most pressing current challenge in the management of this malignancy is to reduce both acute and late toxicity and balance the goal of achieving high overall survival rates in tandem with the avoidance of long-term morbidity and mortality.4
The introduction of combination anthracycline-containing chemotherapy and high-energy radiation therapy in the early 1970s changed the outcome of Hodgkin disease from that of an almost automatic death sentence to one frequently associated with cure. It is one of our best contemporary success stories. However, this transformation has come at a price, as treatment-related malignancies and other serious late effects now pose considerable threats to Hodgkin survivors. Two major reviews shed light on the nature of these risks.
The long-term dual jeopardy of chest irradiation and anthracycline use was targeted by researchers from St. Jude Children’s Research Hospital. They analyzed two large patient databases of longitudinal clinical data and health outcomes to determine the magnitude of cardiovascular (CV) morbidity in pediatric, adolescent, and young adult survivors of Hodgkin lymphoma.5
Researchers focused on those who survived beyond 10 years and had reached at least 18 years of age. Both age- and sex-matched community controls were used for comparison. Of note was the researchers’ intent to discern the cumulative burden of CV disease versus cumulative incidence. This metric was devised to quantify the added magnitude and trajectory of total CV mortality by counting the number and severity of CV health conditions, and their recurrences in relation to age and time from diagnosis.
CV conditions were identified as myocardial infarction, arrhythmias, CV dysfunction (i.e., cardiomyopathy, cor pulmonale, and pulmonary hypertension), structural defects (i.e., heart valve disorder, pericarditis), vascular disease, and essential hypertension. At age 50, the cumulative incidence of survivors’ who experienced at least one grade 3-5 CV condition was nearly 50% (45.4%) as compared with 15.7% of community controls. Myocardial infarction and structural heart defects were the major etiology of excessive cumulative burden in survivors and was associated with high cardiac radiation dose (>35 Gy) more so than anthracycline dose.
Another study was from the Netherlands Cancer Institute of nearly 4,000 5-year survivors of Hodgkin lymphoma.6 Patients who received treatment between the ages of 15-50 years of age were compared to the general population for their risk of developing a second cancer. Of particular note was the finding that the cumulative incidence of second solid malignancies did not differ by treatment decade (i.e., 1965-1976, 1977-1988, and 1989-2000). Despite a transition in therapies used that included smaller radiation treatment volumes, lower radiation doses, less anthracycline-containing chemotherapy regimens, lower doses of alkylating agents, and less frequency of infradiaphragmatic irradiation in more recent years, solid tumor risk remained constant.7, 8 Also consider the following findings:
At 30 years after starting treatment of Hodgkin lymphoma, the cumulative incidence of developing a second cancer was 33.2%; at 40 years “out,” the cumulative incidence was 48.5%;
Forty percent of the excess risk of being diagnosed with a second cancer was attributed to the development of breast cancer;
Smoking increased the risk of a second diagnosis of lung cancer in female patients who had received supradiaphragmatic irradiation.
The risk for developing second, third, and even four subsequent primary cancers remains a critical theme in Hodgkin lymphoma survivorship. Oncologists remain burdened by the difficult task of balancing optimum decision-making for the control of primary disease with the potential long-term risks of both radiation and chemotherapy late toxicity.6
As oncology nurses, our role is to remain apprised of research findings and to incorporate them into our teaching and patient follow-up. This Hodgkin lymphoma exemplar characterizes our pressing agenda to keep our eyes focused on the long-term prize—how to live on free of cancer, but not be relegated to a compromised quality-of-life status. The search continues.
Barr RD, Ries LA, Lewis DR, et al. Incidence and incidence trends of the most frequent cancers in adolescent and young adult Americans, including "nonmalignant/noninvasive" tumors. Cancer. 2016 Apr 1;122(7):1000-8.
Ward E, DeSantis C, Robbin A, et al. Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin. 2014 Mar-Apr;64(2):83-103.
National Cancer Institute: Surveillance, Epidemiology, and End Results (SEER) Program. Cancer Incidence and Survival Among Children and Adolescents: United States SEER Program 1975–1995.
Brugieres L, Brice P. Tumors in Adolescents and Young Adults. Prog Tumor Res. 2016;43:101-114.
Bhaka N, Liu Q, Yeo F, et al. Cumulative burden of cardiovascular morbidity in paediatric, adolescent, and young adult survivors of Hodgkin’s lymphoma: An analysis from the St. Jude Lifetime Cohort Study. Lancet Oncol. 2016 Sep;17(9):1325-34.
Schaapveld M, Aleman BM, van Eggermond AM, et al. Second Cancer Risk up to 40 Years after Treatment for Hodgkin’s Lymphoma. N Engl J Med. 2015 Dec 24;373(26):2499-511.
Specht L, Yahalom J, Illidge T, et al. Modern radiation therapy for Hodgkin lymphoma: Field and dose guidelines from the International Lymphoma Radiation Oncology Group (ILROG).Int J Radiat Oncol Biol Phys. 2014 Jul 15;89(4):854-62.
Diehl V, Thomas R, Re D. Part II: Hodgkin’s lymphoma—diagnosis and treatment. Lancet Oncol. 2004 Jan;5(1):19-26.
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