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Excess Morbidity Is Reduced, Not Eliminated With Contemporary cHL Treatment

April 27, 2022

May 2022

The excess morbidity in early-stage classical Hodgkin lymphoma (cHL) is significantly reduced but not fully eliminated after treatment with radiotherapy plus doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD), according to a study published in the Journal of Clinical Oncology.

According to Ingemar Lagerlöf, MD, of Uppsala University in Sweden, and colleagues, relatively recent advances in cHL research and treatment have reduced toxicities associated with therapy while retaining high rates of cure. For instance, doses of radiotherapy have been decreased from 30-40 Gy to 20-30 Gy, with clinical risk factors driving dosing decisions. Chemotherapy has also been modified to include combinations with fewer toxicities, while the number of chemotherapy cycles have also been decreased based on clinical risk factors.

Despite advances in research and management, researchers stated that few publications have characterized the long-term toxicities associated with modern cHL-directed radiotherapy with limited fields and reduced doses. To investigate this research gap, they examined a cohort of Swedish patients with early-stage cHL who received two or four cycles of ABVD and 30 Gy limited-field radiotherapy between 1999 and 2005.

Anonymized patient data were obtained from a Nordic registry. The Total Population Register was used to identify comparators who were matched four to one for age, sex, and region of residence at the time of cHL diagnosis. Patients with cHL and comparators were cross-checked against several registers for morbidity and mortality.

The cohort included 215 patients with cHL whose median age was 34 years at time of diagnosis. Approximately 28% of patients (n=61) had stage I disease, with 16% of these patients (n=10) being allocated to four ABVD cycles. Another 72% of patients (n=154) had stage II disease, with most of these patients (72%) being allocated to four ABVD cycles. Approximately 96% of patients received treatment based on individual risk factors. There were 860 comparators in the study.

When evaluated against comparators (see FIGURE), patients had a trend toward a higher risk of second malignancy (hazard ratio [HR] = 1.5; 95% CI 1.0-2.4). Additionally, patients had a higher 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). The researchers found that the excess risk for respiratory disease primarily consisted of asthma (HR=3.5; 95% CI 1.8-6.8).

FIGURE. (A) Proportions of patients treated with ABVD ×2 or ×4 followed by 30Gy limited-field radiotherapy, for classical Hodgkin lymphoma stage IA-IIA in Sweden during 1999-2005, with any secondary Ca, DCS, DRS, and comorbidities. (B) Proportions of comparators with any Ca, DCS, DRS, and comorbidities.

Source: Lagerlöf et al. 2022. CC BY-NC-ND 4.0
ABVD = doxorubicin, bleomycin, vinblastine, and dacarbazine; Ca = cancer; DCS = diseases of the circulatory system; DRS = diseases of the respiratory system
Source: Lagerlöf et al. 2022. CC BY-NC-ND 4.0
ABVD = doxorubicin, bleomycin, vinblastine, and dacarbazine; Ca = cancer; DCS = diseases of the circulatory system; DRS = diseases of the respiratory system

Survival for patients was equivalent to the expected survival in the general population during the median 17 years of follow-up.

The researchers wrote that limitations of the study were related to the study’s lack of power and that the follow-up period of nearly two decades might not be long enough to see the relevant trends of excess morbidity.

“Our group is going to add follow-up time to this cohort by repeating data collection,” Dr. Lagerlöf said. He added that there is a need to further examine the type of combined modality treatment, in particular the effect of using intensity-modulated radiation therapy and volumetric modulated arc therapy, given that these techniques “reduce doses given to organs at risk but often increase the volume of healthy tissue in the field, which might change long-term excess morbidity.”

Any conflicts of interest declared by the authors can be found in the original article.

Reference

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 [published online ahead of print, 2022 Jan 25]. J Clin Oncol. doi: 10.1200/JCO.21.02407.

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