Limited RT, Complete Response to Chemo Leads to High Rate of Event-Free Survival in Children with Favorable-Risk Hodgkin Lymphoma

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(ChemotherapyAdvisor) – Use of limited radiotherapy in children with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy resulted in a high rate of 2-year event-free survival, investigators reported in the June 27 issue of JAMA.

“More than 90% of children with favorable-risk Hodgkin lymphoma can achieve long-term survival, yet many will experience toxic effects from radiation therapy. Pediatric oncologists strive for maintaining excellent cure rates while minimizing toxic effects,” wrote lead author Monika L. Metzger, MD, MSc, St Jude Children's Research Hospital, Memphis, TN. These include development of second malignant neoplasms and nonneoplastic complications of treatment.

The multicenter unblinded, nonrandomized single group phase 2 study evaluated the efficacy of 4 cycles of vinblastine, doxorubicin, methotrexate, and prednisone (VAMP) in patients with favorable-risk Hodgkin lymphoma and assessed the need for radiotherapy based on early response to chemotherapy.

A total of 88 patients with Hodgkin lymphoma stage I and II (<3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) were enrolled in the study between March 3, 2000, and December 9, 2008; data are reported as of March 12, 2012. Patients who achieved a complete response after 2 cycles received no radiotherapy (n=47) and those with less than a complete response received 25.5 Gy-involved-filed radiotherapy (n=41).

Two-year event-free survival, the primary outcome measure, was 90.8% (>90% was desired; 80% “was considered to be unacceptably low”), the investigators reported. The rate was 89.4% for those who did not require radiotherapy compared with 92.5% for those who did (P=0.61).

Neuropathic pain, nausea or vomiting, neutropenia, and febrile neutropenia were the most common acute adverse effects; 9 patients were hospitalized 11 times for febrile neutropenia or nonneutropenic infection. “Long-term adverse effects after radiotherapy were asymptomatic compensated hypothyroidism in 9 patients (10%), osteonecrosis and moderate osteopenia in 2 patients each (2%), subclinical pulmonary dysfunction in 12 patients (14%), and asymptomatic left ventricular dysfunction in 4 patients (5%). No second malignant neoplasms were observed,” they wrote.

At the time of analysis, all but 1 patient were alive. Median follow-up for survivors was 6.9 years (range, 2.5-11.4 years), excluding 1 patient who withdrew consent prior to radiotherapy. A total of 56 of 87 patients (64%) had at least 5 years of follow-up. For these patients, the 5-year event-free survival is 88.5%, and the 5-year overall survival, 100%; 1 patient died approximately 7.5 years after study enrollment.

“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 desire to avoid late treatment complications—particularly those resulting from high doses of irradiation—has motivated most treatment modifications for pediatric Hodgkin lymphoma,” the authors write. Confirming these results in a larger cohort is warranted.

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