Dataset Information

Excellent Outcomes Following Response-based Omission of Radiotherapy in Children and Adolescents With Intermediate or High-risk Hodgkin Lymphoma.

ABSTRACT: Several pediatric Hodgkin lymphoma (HL) consortia have demonstrated safe omission of radiotherapy (RT) in early stage HL, whereas feasibility of omitting RT in advanced HL is still under investigation. This is a single institution retrospective analysis of 27 patients with intermediate-risk or high-risk HL (age 22?y and younger), treated with a modification of the dose-intensive OEPA-COPDAC (vincristine, etoposide, prednisone, doxorubicin-cyclophosphamide, vincristine, prednisone, dacarbazine) regimen, with radiation restricted to only sites of inadequate early response (Deauville ?3 and/or ?75% tumor shrinkage). Their outcome was compared with a historical cohort (n=42) treated with Stanford V or ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), who received consolidative involved-field RT. RT was omitted in 15 of 27 (56%) of patients treated with OEPA-COPDAC, majority of whom (67%) had high-risk disease. At a median follow-up of 3.1 years, the 3-year progression-free survival was 100% in patients who received OEPA-COPDAC, versus 83.3% (95% confidence interval, 68.2%-91.7%) in the historical cohort, P=0.03. Our analysis demonstrates excellent survival with omission of RT in more than 50% of patients with pediatric advanced HL, treated with a dose-intensive chemotherapy regimen. When administered, RT was restricted to only sites of inadequate early response. Results of large prospective studies are needed to validate these findings.

SUBMITTER: Ozuah NW

PROVIDER: S-EPMC6026082 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Excellent Outcomes Following Response-based Omission of Radiotherapy in Children and Adolescents With Intermediate or High-risk Hodgkin Lymphoma.

Ozuah Nmazuo W NW Marcus Karen J KJ LaCasce Ann S AS Billett Amy L AL

Journal of pediatric hematology/oncology 20180801 6

Several pediatric Hodgkin lymphoma (HL) consortia have demonstrated safe omission of radiotherapy (RT) in early stage HL, whereas feasibility of omitting RT in advanced HL is still under investigation. This is a single institution retrospective analysis of 27 patients with intermediate-risk or high-risk HL (age 22 y and younger), treated with a modification of the dose-intensive OEPA-COPDAC (vincristine, etoposide, prednisone, doxorubicin-cyclophosphamide, vincristine, prednisone, dacarbazine) r ...[more]

PMID: 29293187

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Project description: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.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.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.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.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.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.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.clinicaltrials.gov Identifier: NCT00145600.

Project description: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 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.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.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.

Dataset Information

Excellent Outcomes Following Response-based Omission of Radiotherapy in Children and Adolescents With Intermediate or High-risk Hodgkin Lymphoma.

Publications

Excellent Outcomes Following Response-based Omission of Radiotherapy in Children and Adolescents With Intermediate or High-risk Hodgkin Lymphoma.

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