Presently, there is no well-defined standard of care for managing pediatric patients with early-stage Hodgkin lymphoma (HL). “Current treatments include chemotherapy alone or combined modality therapy (CMT) with chemotherapy and radiotherapy,” explains Rahul R. Parikh, MD. “CMT has been shown to be manageable for these patients but can this treatment can result in toxic side effects. More recently, there has been an increased emphasis on reducing radiotherapy in this patient population. This strategy, however, remains controversial.”

With disease control becoming more common for early-stage pediatric HL, greater attention is being paid to identifying the most appropriate patients for CMT versus chemotherapy alone and the subsequent effects on survival. “CMT has demonstrated efficacy, with event-free survival rates of 80% and higher and with overall survival (OS) rates that are greater than 95%,” says Dr. Parikh. “However, questions remain as to whether CMT benefits outweigh risks of long-term side effects.”

A Closer Look

For a study published in JAMA Oncology, Dr. Parikh and colleagues examined use of CMT in early-stage pediatric HL and its association with improved OS using data from the National Cancer Database. Study patients received definitive treatment with chemotherapy or CMT. Clinical features and survival outcomes were assessed in 5,657 pediatric patients (up to 21 years of age) with a diagnosis of stage I or II HL between 2004 and 2015. “Our work is the largest retrospective study to date involving this patient population,” Dr. Parikh says. The primary goal was to determine the association between use of CMT and OS. The authors also explored links between pathologic factors and OS.

“CMT was associated with improved OS at 5 years (97.3%) when compared with those receiving chemotherapy alone (94.5%),” says Dr. Parikh (Figure). “Our study also found that use of CMT was preferential in younger patients, male patients, those with stage II disease, and those with private insurance.” Several factors were significantly associated with OS in the study, including age, presence of B symptoms, use of transplant procedure, and type of health insurance. These OS findings remained significant in an intention-to-treat analysis and multivariate analysis.

In a sensitivity analysis, the low-risk cohort—those with stage I to stage IIA disease—and adolescent and young adult patients benefited the most from CMT. “Adolescents and young adult patients had the most impressive benefit with combined modality therapy versus chemotherapy alone,” Dr. Parikh says. “Conversely, the youngest patients—those aged 1 to 13 years—appeared to benefit the least from this combined form of treatment. This is an important finding because these patients are most vulnerable to the potential long-term effects of radiotherapy.”

The study also identified changes in national practice patterns. Use of CMT decreased by 24.8% from 2004 to 2015, dropping from 59.7% to 34.9% during this period. The most common physician-reported rationale for not using consolidation radiotherapy as part of the CMT program was that it was not part of the planned initial treatment strategy, accounting for more than 90% of cases. This finding may be due, in part, to chemotherapy alone being used as standard therapy in clinical trials. It could also reflect clinician bias against the use of radiotherapy, perhaps due to a lack of access to modern radiation treatment options (eg, proton therapy). 

Key Implications

Current radiotherapy techniques minimize the long-term effects of CMT, but researchers are continuing to establish which patients will truly benefit from CMT and seeking to determine if some patients can be identified as better candidates for consolidation radiotherapy. “Our study demonstrated an improvement in survival benefit for patients with early-stage pediatric HL,” says Dr. Parikh. “Clinicians should discuss CMT as a treatment option with these patients and their family and caregivers. Investigators should consider designing future clinical trials for this patient group to include CMT as a standard arm. In addition, research is needed on ways to improve access to care for all pediatric patients with this disease.”

References

Jhawar SR, Rivera-Nunex Z, Drachtman R, Cole PD, Hoppe BS, Parikh RR. Association of combined modality therapy vs chemotherapy alone with overall survival in early-stage pediatric Hodgkin lymphoma. JAMA Oncol. 2019;5(5):689-695. Available at: https://jamanetwork.com/journals/jamaoncology/fullarticle/2719758.

Parikh RR, Grossbard ML, Harrison LB, Yahalom J. Early-stage classic Hodgkin lymphoma: the utilization of radiation therapy and its impact on overall survival. Int J Radiat Oncol Biol Phys. 2015;93(3):684-693.

André MPE, Girinsky T, Federico M, et al. Early positron emission tomography response–adapted treatment in stage I and II Hodgkin lymphoma: final results of the Randomized EORTC/LYSA/FIL H10 Trial. J Clin Oncol. 2017;35(16):1786-1794.