Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2014-11-10
Dose-intensive response-based chemotherapy and radiation therapy for children and adolescents with newly diagnosed intermediate-risk hodgkin lymphoma: a report from the Children's Oncology Group Study AHOD0031.
Abstract
Purpose
The Children's Oncology Group study AHOD0031, a randomized phase III study, was designed to evaluate the role of early chemotherapy response in tailoring subsequent therapy in pediatric intermediate-risk Hodgkin lymphoma. To avoid treatment-associated risks that compromise long-term health and to maintain high cure rates, dose-intensive chemotherapy with limited cumulative doses was used.
Patients and methods
Patients received two cycles of doxorubicin, bleomycin, vincristine, etoposide, cyclophosphamide, and prednisone (ABVE-PC) followed by response evaluation. Rapid early responders (RERs) received two additional ABVE-PC cycles, followed by complete response (CR) evaluation. RERs with CR were randomly assigned to involved-field radiotherapy (IFRT) or no additional therapy; RERs with less than CR were nonrandomly assigned to IFRT. Slow early responders (SERs) were randomly assigned to receive two additional ABVE-PC cycles with or without two cycles of dexamethasone, etoposide, cisplatin, and cytarabine (DECA). All SERs were assigned to receive IFRT.
Results
Among 1,712 eligible patients, 4-year event-free survival (EFS) was 85.0%: 86.9% for RERs and 77.4% for SERs (P < .001). Four-year overall survival was 97.8%: 98.5% for RERs and 95.3% for SERs (P < .001). Four-year EFS was 87.9% versus 84.3% (P = .11) for RERs with CR who were randomly assigned to IFRT versus no IFRT, and 86.7% versus 87.3% (P = .87) for RERs with positron emission tomography (PET) -negative results at response assessment. Four-year EFS was 79.3% versus 75.2% (P = .11) for SERs who were randomly assigned to DECA versus no DECA, and 70.7% versus 54.6% (P = .05) for SERs with PET-positive results at response assessment.
Conclusion
This trial demonstrated that early response assessment supported therapeutic titration (omitting radiotherapy in RERs with CR; augmenting chemotherapy in SERs with PET-positive disease). Strategies directed toward improved response assessment and risk stratification may enhance tailoring of treatment to patient characteristics and response.
Related Questions
What areas do you treat with RT for an intermediate or high risk pediatric Hodgkin Lymphoma with a slow early response?
For pediatric Hodgkin lymphoma, radiation fields are really based according to the treatment protocol. If the patient was being treated per AHOD 0031, then the radiation fields would include all sites of initial involvement, assuming they don't meet the criteria for omission of RT (RER and then a CR...
What treatment would you recommend to effectively treat a pediatric patient newly diagnosed with low risk Hodgkin's lymphoma while minimizing the risk of late toxicity?
COG and we try to limit radiation whenever possible. The intermediate risk HD study show early responders (PET negative after 2 cycles of ABVE-PC) could skip radiation—personally I have a long discussion about the long term risks of radiation, particularly breast cancer, leukemia and heart damage, a...
Do you omit consolidative RT in pediatric patients with intermediate risk, non-bulky Hodgkin lymphoma who have a rapid early response to chemotherapy?
Yes, if the patients meet the rigid requirements for response, which include a rapid early response (Complete response or very good partial response) after 2 cycles of ABVE-PC chemotherapy AND have a complete response at the end of treatment then the data suggests similar outcomes whether or not the...