Children with Favorable-risk Disease and Complete Response to Chemotherapy Have High Survival Rates without Radiotherapy

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Among children with favorable-risk Hodgkin lymphoma, those who achieved a complete response after two cycles of chemotherapy and received no radiotherapy had high rates of survival similar to those who had a less complete response to chemotherapy and received radiotherapy, according to a study in the Journal of the American Medical Association. “To our knowledge, this is the first trial in which a select group of children with favorable-risk Hodgkin lymphoma experienced a high rate of 2- and 5-year event-free survival without exposure to radiotherapy, alkylating agent, epipodophyllotoxin, or bleomycin chemotherapy and a relatively low cumulative dose of anthracyclines,” the researchers commented.

The multi-institutional, unblinded, nonrandomized phase II clinical trial included 88 patients with stage I/II Hodgkin lymphoma and a median age of 13.9 years (range, 4.4–20.6 years). The study was designed to evaluate the efficacy of four cycles of VAMP (vinblastine, doxorubicin, methotrexate, prednisone) in patients with favorable–risk Hodgkin lymphoma who had a complete response after two cycles and did not receive radiotherapy. The 47 patients who achieved a complete response after two cycles of VAMP completed therapy without involved-field radiotherapy.

“Among the 41 (47%) who did not achieve a complete response (39 partial responses, 2 stable diseases), 39 received radiotherapy according to protocol, 1 withdrew consent for participation and received radiotherapy elsewhere, and 1 had early disease progression prior to radiotherapy and received retrieval therapy,” the investigators reported.

Key Results

The 2-year event-free survival rate was 90.8% overall, 89.4% for those who achieved early complete response and did not receive involved-field radiotherapy, and 92.5% for those who did not achieve complete response and did require radiotherapy (P = .61). The estimated 5-year survival was 89.4% for patients who did not undergo irradiation and 87.5% for patients who did.

“Therapy was well tolerated without major complications. Delay or dose modifications due to adverse toxic effects were rare,” the investigators noted. “The most common adverse effects were neuropathic pain (2% of patients) and nausea and vomiting (3% of patients), all of which are readily managed with supportive care.”

Long-term adverse effects after radiotherapy included subclinical pulmonary dysfunction in 12 patients (14%), asymptomatic compensated hypothyroidism in 9 patients (10%), asymptomatic left-ventricular dysfunction in 4 patients (5%), and osteonecrosis and moderate osteopenia in 2 patients (2%). “No second malignant neoplasms were observed,” the authors added. Evaluation of quality of life during and after treatment will be reported in a future manuscript.

Study Implications

“Our results suggest that a risk-adapted response-based approach may be very effective and well-tolerated for a selected group of patients with favorable-risk Hodgkin lymphoma,” the authors concluded. “It would be important to confirm the results in a larger cohort,” they noted.

“These findings highlight the continued commitment to reduce complications in the treatment of childhood malignancies and add to the growing body of evidence detailing the utility of early response-adapted therapy,” according to an accompanying editorial. “The emphasis on minimizing therapy when possible is especially important in the treatment of childhood malignancies, for which the consequences of late complications [are] well documented. However, any attempt to decrease therapy to minimize late effects must be balanced with the risk of relapse because the primary cause of death the first 10 years after diagnosis remains recurrent disease,” the editorialists continued.

“Even though the outcomes reported by Metzger et al are encouraging, these results must be corroborated in larger, randomized studies because earlier attempts to decrease both the intensity of chemotherapy and to omit radiation in select low-risk patients have not been as promising,” they added.■

Metzger ML, et al: JAMA 307:2609-2616, 2012.

Whelan KF, Goldman FD: JAMA 307:2639-2641, 2012.