The aim of this study was to test the hypothesis that our 60-gene DNA/RNA ThyroSeq v2 next-generation sequence (NGS) assay would identify additional genetic markers, including gene fusions in sporadic pediatric differentiated thyroid carcinomas (DTC) that had no known molecular alterations. Sporadic pediatric DTCs with informative molecular testing (n = 18) were studied. We previously tested 15 cases by our standard 7-gene (BRAF, NRAS, HRAS, KRAS, RET/PTC1, RET/PTC3, PAX8/PPARg) mutation panel. Three cases were not tested previously. The standard 7-gene panel identified molecular alterations in 9 of 15 tumors (60%). Cases analyzed by ThyroSeq v2 NGS included the six previously negative cases by the standard 7-gene panel and three cases not previously tested. The NGS assay revealed new gene fusions in four of six previously negative cases (67%). These gene fusions included ETV6/NTRK3 (n = 3) and TPR/NTRK1 (n = 1). A point mutation (BRAF-V600E) was detected in one of three untested cases. While standard testing could identify only molecular alterations in 60% of cases, with the addition of the ThyroSeq v2 NGS, this increased to 87% (n = 13/15). Some cases with chromosomal rearrangements, including ETV6/NTRK3, appear to be associated with an aggressive histopathologic phenotype, but had no documented history of radiation exposure. Additional work is needed to investigate if pediatric DTCs could benefit from a reclassification based on molecular subtypes, which may better reflect their underlying biologic potential. Our data support the use of broad gene panels for the molecular diagnostics of pediatric thyroid nodules to aid future classification, treatment, and clinical management recommendations.

Clinical features, FNA cytology, and molecular genetics are valuable tools to discriminate benign from malignant nodules in pediatric patients. This information is important to direct subsequent clinical management.

Purpose: Radioimmunotherapy has been approved for relapsed follicular lymphoma (FL), including rituximab-refractory FL. This study was designed to determine the CR rate with shortcourse chemoimmunotherapy with cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab (CHOP-R) followed by 90-Y ibritumomab tiuxetan (RIT) with extended rituximab as first-line treatment. Experimental Design: Between March 2004 and February 2007, 60 patients with stage II to IV symptomatic or bulky FL from a single institution supported by a large community network entered this phase II trial. Patients received CHOP-R for three treatment cycles before RIT followed by four additional weekly treatments with rituximab. Response was determined using fusion [18 F] fluorodeoxyglucose-positron emission tomography (PET)-computed tomography (CT) imaging. Results: Of the 60 patients entering this trial, 55 patients completed all protocol therapy. The median follow up was 19.7 months (range, 0.26-35.9 months). For intent-to-treat analysis, the complete response (CR) rate after CHOP-R, as assessed by CT and PET imaging, was 40% and 46%, respectively. After RIT, the CR rate improved, as assessed by CTand PET imaging, to 82% and 89%, respectively. Ten patients have progressed, including eight from best response of CR. Seven of 18 patients who were PET positive after CHOP-R progressed compared with 3 of 37 patients who were PET negative (P = 0.010). Conclusions: In patients with previously untreated, symptomatic or bulky FL, short-course chemoimmunotherapy and consolidation RIT and extended rituximab resulted in a high CR rate. Failure to achieve an early PET CR after CHOP-R indicated high risk of relapse.After three decades with little advance in the outcome for patients with follicular lymphoma (FL), the addition of the anti-CD20 chimeric monoclonal antibody, rituximab, dramatically changed the overall response rates (ORR) and may be affecting survival (1). As a single agent, rituximab was shown in a nonrandomized pivotal trial of 166 patients with relapsed low-grade lymphoma to have an ORR of 48% and a complete response (CR) of 6% (2). Lacking significant myelosuppression, investigators immediately recognized that rituximab was an ideal agent to combine with chemotherapy. Phase II studies combining chemotherapy with rituximab in relapsed and previously untreated patients with FL showed impressive ORR and CR rates of 90% to 100% and 50% to 70%, respectively (3, 4). Subsequently, two large randomized trials confirmed the benefit of combining chemotherapy with immunotherapy with CR rates of 41% and 20% compared with 10% and 17% with chemotherapy alone, significantly longer duration of response, and possibly, a survival advantage (5, 6).Radioimmunotherapy is a promising new therapy demonstrating complete and partial responses in chemotherapy and rituximab refractory patients. As early as 1996, a phase II study using single agent 131-iodine (I) tositumomab (Bexxar; GlaxoSmithKline), in previously untreated patients with FL, resul...

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