Association between radiotherapy vs no radiotherapy based on early response to VAMP chemotherapy and survival among children with favorable-risk Hodgkin lymphoma

Abstract

Context: 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.

Objective: To evaluate the efficacy of 4 cycles of vinblastine, Adriamycin (doxorubicin), methotrexate, and prednisone (VAMP) in patients with favorable-risk Hodgkin lymphoma who achieve a complete response after 2 cycles and do not receive radiotherapy.

Design, setting, and patients: Multi-institutional, unblinded, nonrandomized single group phase 2 clinical trial to assess the need for radiotherapy based on early response to chemotherapy. Eighty-eight eligible patients with Hodgkin lymphoma stage I and II (<3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) enrolled between March 3, 2000, and December 9, 2008. Follow-up data are current to March 12, 2012.

Interventions: The 47 patients who achieved a complete response after 2 cycles received no radiotherapy, and the 41 with less than a complete response were given 25.5 Gy-involved-field radiotherapy.

Main outcome measures: Two-year event-free survival was the primary outcome measure. A 2-year event-free survival of greater than 90% was desired, and 80% was considered to be unacceptably low.

Results: Two-year event-free survival was 90.8% (95% CI, 84.7%-96.9%). For patients who did not require radiotherapy, it was 89.4% (95% CI, 80.8%-98.0%) compared with 92.5% (95% CI, 84.5%-100%) for those who did (P = .61). Most common acute adverse effects were neuropathic pain (2% of patients), nausea or vomiting (3% of patients), neutropenia (32% of cycles), and febrile neutropenia (2% of patients). Nine patients (10%) were hospitalized 11 times (3% of cycles) 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.

Conclusions: Among patients with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy, the use of limited radiotherapy resulted in a high rate of 2-year event-free survival.

Trial registration: clinicaltrials.gov Identifier: NCT00145600.

Conflict of interest statement

Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.

Figures

Figure 1

Overall survival (OS) and event-free survival (EFS) distributions for the whole cohort of children with favorable-risk Hodgkin lymphoma treated with VAMP (vinblastine, doxorubicin, methotrexate, and prednisone) with or without low-dose field radiotherapy (n=88). One patient with nodular lymphocyte predominant Hodgkin lymphoma died more than five years after original diagnosis and combined relapse with transformation to diffuse large B-cell lymphoma. Curves have been truncated at 8 years.

Figure 2

Event-free survival (EFS) distributions for children with favorable-risk Hodgkin lymphoma according to their early response to therapy: complete response (complete response, n=47) versus less than complete response (

Figure 3

Event-free survival (EFS) distributions for nodular lymphocyte predominant Hodgkin lymphoma (n=32) versus classical Hodgkin lymphoma (all other histologies, n=56) in children treated with VAMP (vinblastine, doxorubicin, methotrexate, and prednisone) with or without low-dose field radiotherapy. Curves have been truncated at 8 years. The p-value was derived using Cox proportional hazards regression.