Among patients with classical Hodgkin lymphoma (cHL), limited-field radiotherapy (LF-RT) reduced toxicity but did not eliminate excess long-term morbidity, according to study findings published in the Journal of Clinical Oncology.

Patients treated with 2 or 4 cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) followed by 30 Gy LF-RT experienced excess morbidity from secondary cancers as well as diseases of the circulatory and respiratory systems, but to a lesser extent than what has been previously reported with standard involved-field (IF) RT.

Researchers investigated the long-term excess morbidity in a population-based cohort of patients with cHL who were uniformly treated with chemotherapy followed by RT with smaller irradiated volumes and reduced doses compared with earlier cohorts treated with standard IF-RT.

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The study cohort included 215 patients with cHL who were treated with 2 or 4 cycles of ABVD followed by 30 Gy LF-RT between 1999 and 2005. The analysis also included 860 comparators who were matched for age, sex, and region of residence.

All participants 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 cHL.

The median age of the patients was 34 years (range, 18 to 77 years) at diagnosis, 28% had stage I disease, and 72% had stage II disease. The median follow-up was 16 years (range, 12 to 19 years).

Relative to the comparators, patients had an increased risk of developing a second malignancy (hazard ratio [HR], 1.5; 95% CI, 1.0-2.4), as well as an elevated risk 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).

When researchers analyzed individual diseases of the circulatory system (hypertension, coronary heart disease, heart failure, ischemic cerebrovascular disease, and venous thromboembolism [VTE]), only VTE was significantly increased (HR, 3.7; 95% CI, 1.9-7.2).

However, if the first 6 months of active treatment were excluded and participants were censored at relapse or diagnosis of any malignancy, the increased HR for VTE was no longer significant (HR, 2.2; 95% CI, 0.9-5.5).

In analyses of individual diseases of the respiratory system (chronic obstructive pulmonary disease, asthma, and radiation- and bleomycin-induced pneumonitis), only the risk for asthma was significantly increased (HR, 3.5; 95% CI, 1.8-6.8). These patients were significantly younger (46 years [range, 22 to 85]) at diagnosis than the comparators (65 years [range, 22 to 90]; P =.03).

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

“As upfront therapy for patients with early-stage Hodgkin lymphoma is refined, treatment-related morbidity has decreased but not disappeared,” the researchers added. “These results should serve as a benchmark for future studies with long-term endpoints.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Lagerlöf I, Fohlin H, Enblad G, et al. Limited, but not eliminated, excess long-term morbidity in stage I-IIA Hodgkin lymphoma treated with doxorubicin, bleomycin, vinblastine, and dacarbazine and limited-field radiotherapy. J Clin Oncol. Published online January 25, 2022. doi: 10.1200/JCO.21.02407