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Children’s Oncology Group (COG) trial AHOD0431 reduced systemic therapy and used response-adapted involved-field radiotherapy (IFRT) in early-stage pediatric classic Hodgkin lymphoma. We investigated the impact of positron emission tomographic response after 1 cycle (PET1) and on IFRT outcomes and pattern of relapse. Patients in AHOD0431 underwent PET1 response assessment after AVPC (doxorubicin, vincristine, prednisone, and cyclophosphamide). “Rapid early responders” (RERs) had a negative PET1 (PET1−); “slow early responders” (SERs) had a positive PET1 (PET1+). Patients with a partial response by computed tomographic and functional imaging after 3 chemotherapy cycles received 21-Gy IFRT, whereas complete responders had no IFRT. Progression-free survival (PFS) was evaluated for RERs and SERs treated with or without IFRT. Recurrence sites were initial, new, or both. Relapses involving initial sites were characterized as “within the PET1+ site” or “initially involved but outside the PET1+ site.” Median follow-up was 118 months. The 10-year PFS rate among RERs was 96.6% with IFRT and 84.1% without IFRT (P = .10), whereas SERs were 80.9% with IFRT and 64.0% without IFRT (P = .03). Among 90 RERs who did not receive IFRT, all 14 relapses included an initial site. Among 45 SERs receiving no IFRT, 14 of 16 relapses were in the initial site (9 PET1+ site only). Among 58 patients receiving IFRT, 5 of 10 relapses were in the PET1+ site. After 3 cycles of AVPC alone, RERs showed favorable results. Conversely, SERs had unfavorable outcomes with AVPC alone, although they improved with 21-Gy IFRT. RT remains an important component of treatment for SERs. This trial was registered at www.clinicaltrials.gov as #NCT00302003.

PURPOSE Children with low-grade glioma often require long-term therapy and suffer from treatment morbidity. Although targeted agents are promising, tumor targets often encompass normal developmental pathways and long-term effects of inhibition are unknown. Lenalidomide is an immunomodulatory agent with wide-ranging properties. Phase I studies indicated greater tolerability of lenalidomide in children compared with adults and a potential dose-response effect. PATIENTS AND METHODS We performed a phase II trial of lenalidomide in children with pilocytic astrocytomas and optic pathway gliomas who failed initial therapy. Primary objectives included determination of objective response rate of children randomly assigned to regimen A, low-dose (20 mg/m2/dose), or regimen B, high-dose (115 mg/m2/dose) lenalidomide, and assessment for early progression. Secondary objectives included estimation of event-free survival, overall survival, incidence of toxic events, and assessment of plasma lenalidomide concentrations. Lenalidomide was administered once daily × 21 days of each 28-day cycle for each regimen. RESULTS Seventy-four eligible patients were enrolled (n = 37, each arm). The predefined activity level of interest was achieved for both arms. Four objective responses were observed in each arm, and the number of early progressors was low. Eighteen patients completed 26 cycles of therapy (regimen A, n = 12; regimen B, n = 6). The median number of cycles was 14 (range, 2-26) for regimen A and 11 for regimen B (range, 1-26). Of 74 eligible patients who received study drug, 30 required dose reduction for toxicity (regimen A, n = 6; regimen B, n = 24) and 16 discontinued because of toxicity (regimen A, n = 2; regimen B, n = 14). CONCLUSION Lenalidomide demonstrates a sufficient level of activity in children with low-grade glioma to warrant further exploration. Low-dose (20 mg/m2/dose administered once daily × 21 days of each 28-day cycle) lenalidomide appears to have better tolerability with comparable activity.

Purpose/Objective(s) COG AHOD0831 was a multi-center, prospective study that used a response-adapted approach for patients Materials/Methods Patients from AHOD0831 were identified who had baseline PET scans that were amenable to quantitative analyses. For each patient, metabolic tumor volume (MTV), total lesion glycolysis (TLG), maximum standardized uptake value (SUVmax), and peak SUV (SUVpeak) were obtained for mediastinal (m) and total body (t) disease. MTV was defined based on thresholds of SUV > 2.5 or > 40% SUVmax. TLG was defined as MTV * tumor SUVmean. EFS was assessed by Kaplan-Meier analyses. 2nd EFS was defined as the time to a second event, reflecting rates of successful salvage after a 1st relapse. Receiver operating characteristic analyses estimated the ability of PET parameters to predict EFS; optimized cutoff values were identified using a Youden index. Results Of 166 patients enrolled on AHOD0831, 94 (57%) had PET scans evaluable for quantitative analysis. For this subset: median age 15.5 years; 62% male; 67% white; 45% stage III, 55% stage IV; 86% bulk; 60% nodular sclerosis histology; 54% RER, 46% SER. These characteristics did not differ significantly from the complete AHOD0831 cohort. At a median follow-up of 49 months, 4-year EFS was 76% for the complete cohort (76% RERs, 75% SERs). Patients with high tMTVs and tTLGs, based on each threshold, were significantly more likely to be SERs (all P Conclusion RERs with a low baseline metabolic tumor burden experienced excellent EFS with less intensive therapy. Conversely, RERs with a high baseline tumor burden experienced poor EFS that was even worse than that of SERs. Thus, patients with a high metabolic tumor burden upfront may benefit from intensified therapy, even if they achieve a RER. PET-based measures of initial disease burden may contribute to risk-based treatment algorithms and improve outcomes in HL.