NEW YORK (Reuters Health) – Children with Hodgkin lymphoma who achieve a complete response after two cycles of chemotherapy can achieve excellent event-free survival without radiotherapy, according to new findings.
“Before omitting radiotherapy, it is very important for physicians interested in this therapy to make sure that their patients meet all the criteria listed, particularly the clinical characteristics of patients and the response to therapy measures we used to determine who needed radiotherapy in addition to the chemotherapy,” said Dr. Monika L. Metzger, whose results are published in the June 27 issue of JAMA.
Dr. Metzger, from St. Jude Children’s Research Hospital and Health Sciences Center in Memphis, Tennessee, and colleagues investigated the efficacy of vinblastine, doxorubicin (Adriamycin), methotrexate, and prednisone (VAMP) chemotherapy with or without radiotherapy based on early response to chemotherapy for children with favorable-risk Hodgkin lymphoma.
Of the 88 children in the phase II study, 47 (53%) achieved a complete response after two cycles of VAMP and finished the remaining two cycles without receiving low-dose involved-field radiotherapy. Thirty-nine of the remaining 41 children received radiotherapy according to protocol.
After a median follow-up of 6.9 years, the estimated two-year event-free survival was 89.4% for patients who achieved early complete response and did not receive radiotherapy, compared to 92.5% for those who did (p=0.61).
The estimated five-year event-free survival was 89.4% among patients who did not get radiotherapy and 87.5% among patients who did. The five-year overall survival was 100%, but one patient died about 7.5 years after study enrollment.
All patients who were not irradiated and experienced recurrence did so at a previously involved site and were successfully treated with chemotherapy and radiotherapy without stem cell transplant.
Neither patient characteristics nor tumor features predicted treatment failure, and there was no evidence that early complete response was a significant predictor of event-free survival.
Long-term toxicity included asymptomatic compensated hypothyroidism in nine patients (all of whom had received radiotherapy to the neck), subclinical pulmonary dysfunction in 12 patients (all of whom received thoracic radiation), and asymptomatic left ventricular dysfunction in 4 patients.
“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 investigators conclude. “Future studies should consider further tailoring of radiotherapy reserving irradiation for patients who remain PET positive at early response evaluation.”
“We are continuing to look for the right backbone chemotherapy that will allow us to reduce the number of patients who undergo radiotherapy from about 53 percent in this study without compromising outcome or adding to the risk of long term toxicity,” Dr. Metzger told Reuters Health by email.
In an editorial published along with the findings, Dr. Kimberly F. Whelan and Dr. Frederick D. Goldman from the University of Alabama at Birmingham strike a cautionary note.
“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,” Drs. Whelan and Goldman write.
“The emphasis on minimizing therapy when possible is especially important in the treatment of childhood malignancies, for which the consequences of late complications is well documented,” they add. “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.”