JAMA: Limited RT strategy may suffice for some kids w/ Hodgkin lymphoma
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Nearly 90 percent of pediatric patients with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy who bypassed radiation therapy (RT) achieved two-year event-free survival, according to a study published June 27 in the Journal of the American Medical Association.

Although more than 90 percent of children with favorable-risk Hodgkin lymphoma achieve long-term survival, late toxic effects of therapy result in excess mortality among patients followed up beyond 10 years. This has spurred clinicians and researchers to consider treatment modifications.

Risk-adapted combined chemotherapy and radiotherapy has been employed to minimize adverse effects while maintaining outcomes. “Response-adapted therapies aim to identify patients for whom it would be safe to reduce radiation therapy dose, volume, or both,” wrote Monika L. Metzger, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., and colleagues. 

Metzger and colleagues designed a multi-institutional Phase 2 clinical trial to assess the efficacy of chemotherapy among patients with favorable-risk Hodgkin lymphoma who achieve a complete response as indicated by CT or PET imaging after two cycles of chemotherapy and do not undergo radiation therapy.

The researchers enrolled 88 patients; 47 patients who achieved a complete response after two cycles of chemotherapy underwent two additional chemotherapy cycles but did not receive radiation therapy. Among the other 41 patients who did not obtain a complete response, 39 received 25.5 Gy radiotherapy.

Metzger et al reported two-year event-free survival for patients who achieved early complete response (the non-radiation therapy cohort) at 89.4 percent. The corresponding rate for patients who underwent radiation therapy was 92.5 percent.

Five-year follow-up data were available for 56 patients. Among this group, overall event-free survival was 88.5 percent, and rates were similar for both groups at 89.4 percent for children who did not undergo radiation therapy and 87.5 percent for children who did. Five-year overall survival was 100 percent.

The five patients who did not undergo radiation therapy who experienced recurrence were successfully retrieved with chemotherapy and radiation therapy without stem cell transplant, according to Metzger and colleagues.

Previous research has suggested that patients with nodular lymphocyte predominant Hodgkin lymphoma may be cured with less therapy. However, Metzger et al described the outcome for these patients in the current study as “disappointing.”

They wrote, “None of the 10 patients with nodular lymphocyte predominant Hodgkin lymphoma who had undergone complete resection relapsed; thus is it possible that many of them could have been spared chemotherapy altogether. In contrast, patients with stage II (and unresected) nodular lymphocyte predominant Hodgkin lymphoma who did not receive radiotherapy are at increased risk of relapse.” The researchers suggested low-dose irradiation may be beneficial for such patients when they are treated with chemotherapy agents that omit alkylating agents.

Given the small sample size, Metzger and colleagues stressed the need to confirm the effectiveness of a risk-adapted response-based approach in a larger cohort.

Kimberly F. Whelan, MD, and Frederick D. Goldman, MD, both of University of Alabama at Birmingham, reinforced the need for additional research in an accompanying editorial, referring to the Children’s Oncology Group (COG) study AHOD0431. In this study, radiation therapy was omitted for patients based on complete response after three cycles of chemotherapy. However, a two-year event-free survival rate of 84 percent suggests “complete response status after three cycles of chemotherapy may not optimally identify patients for whom therapy may be decreased.” Other studies have raised similar questions, the editorialists noted.

Yet, Childhood Cancer Survivor Study reports have documented increased overall excess risk of death due in part to second malignant neoplasms and cardiovascular disease among survivors of childhood lymphoma. The study found that 70 percent of survivors reported at least one chronic health condition.

“The cumulative incidence of these late effects continues to increase without an apparent plateau…Thus, identifying a patient population in which radiation can be safely eliminated or minimized should decrease the risk of serious late complications and improve the quality of life.”

Two Phase 3 studies (AHOD0031 and AHOOD0831) initiated by COG will provide some of these data regarding the role of radiation therapy in patients with intermediate- and high-risk Hodgkin lymphoma and early favorable responses, wrote Whelan and Goldman.