In a Swedish study reported in the Journal of Clinical Oncology, Lagerlöf et al identified rates of long-term morbidity in a more contemporary cohort of patients with stage I to IIA classical Hodgkin lymphoma treated with ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) and the more modern technique of limited-field radiotherapy.

As stated by the investigators, “Available data on long-term toxicity after radiotherapy for classical Hodgkin lymphoma mostly refer to radiotherapy techniques no longer in use…. Treatments before 2000 resulted in a high degree of disease control, but also in long-term toxicity with increased risks for diseases of the circulatory system, secondary cancers, and diseases of the respiratory system.”

Study Details

The study included all 215 patients with classical Hodgkin lymphoma treated with two or four cycles of ABVD and 30-Gy limited-field radiotherapy from 1999 to 2005 in Sweden. Patients were matched 1:4 with 860 comparators from the Total Population Register for age, sex, and region of residence at the time of diagnosis of classical Hodgkin lymphoma for the corresponding patient. Patients and comparators were cross-checked against national health registries for malignancies, diseases of the circulatory system, and diseases of the respiratory system from the day of diagnosis of classical Hodgkin lymphoma.

Key Findings

Median follow-up was 16 years (range = 12­–19 years).

Patients had a nonsignificantly increased risk for secondary malignancy (hazard ratio [HR] = 1.5, 95% confidence interval [CI] = 1.0–2.4) and significantly increased risks for diseases of the circulatory system (HR = 1.5, 95% CI = 1.1–2.0) and diseases of the respiratory system (HR = 2.6, 95% CI = 1.6–4.3).

Among individual diseases of the circulatory system diagnoses (hypertension, coronary heart disease, heart failure, ischemic cerebrovascular disease, and venous thromboembolism [VTE]), only VTE was significantly increased among patients (HR = 3.7, 95% CI = 1.9–7.2). In analysis excluding events from the first 6 months after diagnosis of classical Hodgkin lymphoma and censoring patients and comparators at time of malignancy or relapse of classical Hodgkin lymphoma, the hazard ratio for VTE was no longer significant (2.2, 95% CI = 0.9–5.5).

Among individual diseases of the respiratory system diagnoses (chronic obstructive pulmonary disease, asthma, radiation, and bleomycin-induced pneumonitis), only risk for asthma was significantly increased (HR = 3.5, 95% CI = 1.8–6.8). Diseases of the respiratory system were diagnosed at a significantly younger median age in patients vs comparators (46 vs 65 years, P = .03).

As related by the investigators, higher rates of long-term morbidity have been reported in earlier cohorts of patients using older radiotherapy techniques. For example, two studies showed standardized incidence ratios of 4.6 and 2.62 for malignancies; another study reported standardized incidence ratios of 3.2 for coronary heart disease and 6.8 for heart failure.

The investigators concluded, “Compared with toxicity from earlier radiotherapy techniques, excess morbidity was not eliminated, but lower than previously reported. The elevated risk of diseases of the respiratory system was driven by diagnosis of asthma, which could in part be explained by misdiagnosis of persisting pulmonary toxicity.”

Ingemar Lagerlöf, MD, of Uppsala University, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Stiftelsen Onkologiska Klinikens i Uppsala Forskningsfond and Swedish Cancer Society. For full disclosures of the study authors, visit ascopubs.org.