PROBABLY OK TO SKIP RADIATION IN SOME CHILDREN WITH HODGKIN LYMPHOMA 

June 27, 2012 — Can the use of radiotherapy be limited in some children with Hodgkin lymphoma? Possibly, according to the results of a new study in the June 26 issue of the Journal of the American Medical Association. Children with favorable-risk Hodgkin lymphoma and a complete early response to chemotherapy had a high rate of 2-year event-free survival, without undergoing radiotherapy.

For patients who did not undergo radiotherapy, the 2-year event-free survival was 89.4%, compared with 92.5% for those who did (P = .61).

"This study adds to evidence that it is possible to omit radiation even in patients treated with a less intense chemotherapy regimen and still achieve excellent long-term survival," said first study author Monika Metzger, MD, an associate member at the department of oncology, St Jude Children's Research Hospital in Memphis, Tennessee. "I think there is enough data now to suggest that it is safe to omit radiotherapy in patients with the same features as those described in this study and who have the same early treatment response.

"We also gave a 5-year event-free survival, which is appropriate in this setting, since we had enough follow up," she told Medscape Medical News, adding that their previous work has also shown that event-free survival is very similar at 5 and 10 years (Clin Oncol. 2007;25:332-337).

Within their cohort of 87 patients, 64% had at least 5 years of follow-up. Patients who did not undergo radiation therapy achieved an estimated 5-year event-free survival of 89.4%, which was similar to the 87.5% observed among those who did.

Findings Encouraging But More Data Needed

"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," note Kimberly F. Whelan, MD, MSPH, and Frederick D. Goldman, MD, both of the University of Alabama in Birmingham.

However, they point out that even though these results are encouraging, they must be corroborated in larger, randomized studies. Previous attempts to decrease both the intensity of chemotherapy and to omit radiation in select low-risk patients have not achieved such promising outcomes.

The editorialists explain that the emphasis on minimizing therapy whenever possible is particularly important when treating childhood malignancies, as the consequences of late complications have been thoroughly 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," they write.

Drs. Whelan and Goldman add that the Children’s Oncology Group has recently completed phase 3 studies for patients with intermediate- (AHOD0031) and high-risk (AHOD0831) Hodgkin lymphoma that minimize or omit radiation therapy in patients with early favorable responses. "Data should be forthcoming shortly," they add.

Study Details

While more than 90% of children with favorable-risk Hodgkin lymphoma will achieve long-term survival, late toxic effects of therapy can cause a high rate of morbidity and mortality. This includes the development of second cancers, note the study authors. Thus, in order to help mitigate late toxic effects while maintaining excellent outcomes, "risk-adapted combined-modality therapy" (combined chemotherapy and radiotherapy according to predetermined risk stratification) has been individualized to minimize therapy while maintaining an excellent outcome.

They add that the aim of response-adapted therapies, which are tailored according to early initial response to treatment, is to identify patients "for whom it would be safe to reduce radiation therapy dose, volume, or both."

In this study, Dr. Metzger and colleagues conducted a multi-institutional, nonrandomized, single group phase 2 clinical trial to assess the need for radiotherapy based on early response to chemotherapy. The cohort included 88 patients with Hodgkin lymphoma stage I and II (<3 nodal sites, no B symptoms, mediastinal bulk, or extranodal extension) who were enrolled between March 2000 and December 2008.

Chemotherapy consisted of four 28-day cycles of VAMP: vinblastine, 6 mg/m²; doxorubicin, 25 mg/m²; and methotrexate 20 mg/m ², which was administered intravenously on days 1 and 15, and oral prednisone, 40 mg/m² on days 1 through 14. All patients were evaluated weekly during their treatment.

Within this group, 47 patients (53%) achieved a complete response after 2 cycles of VAMP and completed their treatment without radiotherapy. Of the 41 patients (47%) who did not achieve a complete response (39 partial responses, 2 stable diseases), 39 received radiotherapy according to protocol (1 received radiotherapy elsewhere, and 1 had early disease progression prior to radiotherapy and received retrieval therapy).

Follow-up data are current to March 12, 2012, and all except for 1 patient were alive at the time of the analysis, the authors note. The median follow-up was 6.9 years (range 2.5-11.4 years).

The estimated 2-year event-free survival was 90.8% for the whole cohort, and the 5-year event-free survival was 88.5%. The 5-year overall survival was 100%, with 1 patient dying about 7.5 years after study enrollment.

A total of 11 patients experienced treatment failure, including 5 who did not receive radiation therapy. All of the patients who experienced a recurrence and who did not receive radiation therapy did so at a previously involved site. Treatment with chemotherapy and radiation therapy was successful and none required a stem cell transplant.

The study was supported by a National Institutes of Health Cancer Support Core Grant and the American Lebanese Syrian Associated Charities. Dr. Metzger reports receiving funding for an international conference unrelated to the study from Seattle Genetics, Amgen, and Millennium. Several coauthors report conflicts of interest, as noted in the paper. The editorialists report no conflicts of interest.

JAMA. Published online June 26, 2012. Abstract