The study, conducted by Monika L. Metzger, M.D., of St. Jude Children’s Research Hospital, Memphis, Tenn., is published in the June 27 issue of JAMA. The researchers explained:
“Currently more than 90 percent of children with favorable-risk Hodgkin lymphoma will achieve long-term survival. However, studies demonstrate excess mortality among patients followed up beyond 10 years from their Hodgkin Lymphoma diagnosis as a result of late toxic effects of therapy, including the development of second malignant neoplasms and nonneoplastic treatment complications.
Risk-adapted combined-modality therapy (combined chemotherapy and radiotherapy according to predetermined risk stratification) has therefore been tailored to minimize therapy while maintaining excellent outcome. Response-adapted therapies (tailored according to early initial response) aim to identify patients for whom it would be safe to reduce radiation therapy dose, volume, or both.”
The researchers conducted the multi-center, Phase II, clinical trial in order to evaluate the need for radiotherapy based on early response to chemotherapy. The team evaluated the efficacy of 4 cycles of vinblastine, Adriamycin (doxorubicin) methotrexate, and prednisone (VAMP).
88 patients were enrolled between 2000 and 2008 with favorable-risk Hodgkin lymphoma who achieve a complete response after 2 cycles.
Two-year event-free survival was the primary outcome measure for the study. The team found that 47 participants who did not receive radiotherapy achieved complete response after two cycles. 41 Participants who did not achieve a complete response received 25.5 Gy-involved-field radiotherapy.
According to the researchers, a 2-year event-free survival of 80% was considered extremely low, and 90%+ was considered desirable.
The researchers found that 2-year event-free survival was 92.5% for participants who did not achieve complete response and required radiotherapy, versus 89.4% for those who did achieve complete response and no radiotherapy.
In addition, the team found that participants who did not receive irradiation had an estimate 5-year event-free survival of 89.4%, vs. 87.5% for participants who did receive irradiation.
The researchers explained: “Therapy was well tolerated without major complications. Delay or dose modifications due to adverse toxic effects were rare. The most common adverse effects were neuropathic pain (2 percent of patients) and nausea and vomiting (3 percent of patients), all of which are readily managed with supportive care. Neutropenia [lower-than-normal number of neutrophils (a type of white blood cell) in the blood] was observed in 60 percent of patients (32 percent of cycles), and febrile neutropenia in 2 percent of patients (0.9 percent of cycles).”
10% of patients were admitted to hospital 11 times for either febrile neutropenia or nonneutropenic infection.
Long-term side effects following radiotherapy included:
- asymptomatic left ventricular dysfunction – 4 patients
- asymptomatic compensated hypothyroidism – 9 patients
- subclinical pulmonary dysfunction – 12 patients
According to the researchers, no second malignant neoplasms were observed.
The team said:
“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.”
They conclude that a larger cohort would be important in order to verify these results.
In an associated report, Kimberly F. Whelan, M.D., M.S.P.H., and Frederick D. Goldman, M.D., of the University of Alabama at Birmingham, conclude:
“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.
Response-based regimens have been used for patients enrolled in studies of high-risk and low-risk Hodgkin lymphoma. With the advent of minimal residual disease testing, these regimens similarly play a large role in childhood leukemia treatment. 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. 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.”
Written by Grace Rattue
The Journal of The American Medical Association