BACKGROUND:The objective of this study was to evaluate local control for patients with intermediate-risk rhabdomyosarcoma (RMS) treated on Children's Oncology Group (COG) protocol ARST0531. METHODS: This study analyzed 424 patients with intermediate-risk RMS. Patients were randomized to chemotherapy with either vincristine, dactinomycin, and cyclophosphamide (VAC) or VAC alternating with vincristine and irinotecan. With the goal of improving local control, radiation therapy (RT) was delivered early at week 4 and was concurrent with irinotecan in the experimental arm. Individualized local control plans for children 24 months old or younger were allowed. Local failure on ARST0531 was compared with local failure on the preceding COG intermediate-risk study, D9803. RESULTS: For patients with group I/II alveolar RMS (n = 55), the 5-year cumulative incidence of local failure was 13.4%; for group III alveolar RMS (n = 141), it was 20.2%; and for group III embryonal RMS (n = 228), it was 27.9% (P = .03). Among patients with group III disease, local failure did not differ by histology, site, nodal status, RT modality, or treatment arm. Local failure was worse for a tumor size >5 cm (32.3% vs 16.7%; P = .001). Among patients with group III embryonal RMS, local failure was higher on ARST0531 than D9803 (27.9% vs 19.4%; P = .03). After the exclusion of patients 24 months old or younger or patients who did not receive radiation, local failure remained significantly increased on ARST0531 (P = .02). After adjustments for clinical prognostic factors, event-free survival and overall survival were worse on ARST0531 (P = .004 and P = .05, respectively). CONCLUSIONS: Despite interventions designed to enhance local control, local control was inferior on ARST0531 in comparison with D9803. The reason for this is unclear, but it could be the reduced cyclophosphamide dose on ARST0531. Cancer 2019;125:3242-3248.

Purpose/Objectives To examine the late effects of intensity modulated radiation therapy (IMRT) in pediatric patients with rhabdomyosarcoma of the head and neck. Materials/Methods All one-year survivors of pediatric head and neck rhabdomyosarcoma treated with IMRT at a single institution from 1999-2014 were assessed for long term complications. Late toxicities were graded according to CTCAE version 4.03. Results Among 30 patients, median age at IMRT was 7.4 (1.5-20.8) years, median follow-up was 7.7 (1.2-14.4) years, and median IMRT dose was 50.4 (36-50.4) Gy. Tumor subsites included parameningeal (80%), orbit (13%), and other (7%). Common late toxicities were facial disfigurement (n=23, 77%), growth hormone deficiency (n=11, 37%), cataract (n=10, 34%), and dental problems (n=10, 33%). Twenty-two patients (73%) had ≥ 2 late toxicities and fourteen patients (47%) had ≥ 3 late toxicities. Seventeen patients (57%) experienced grade 2 toxicity and ten patients (33%) had grade 3 toxicity. Grade 3 toxicities included visual disturbance, cataract, facial disfigurement, chronic sinusitis/otitis, and hearing loss. Severe facial deformity was noted in nine patients (30%), and three patients underwent cosmetic surgery. Patients with severe facial deformity were treated at younger ages (median 6.0 years versus 8.1 years for patients with no/non-severe facial deformity) and more likely to have infratemporal fossa tumors. There were no secondary solid malignancies. Conclusions Late radiation toxicities are common in survivors of pediatric head and neck rhabdomyosarcoma treated with IMRT. While the majority of late effects are mild-moderate, they can significantly impact quality of life, particularly facial disfigurement.

Over the last decade, immunotherapy has rapidly changed the therapeutic landscape and prognosis for many hematologic malignancies and adult solid tumors. Despite this success, immunotherapy for pediatric solid tumors remains in the early stages of development, and significant clinical benefit has yet to be realized, with anti-GD2 for neuroblastoma being the exception. The limited neoepitope expression and paucity of T-cell infiltration into the immunosuppressive tumor microenvironment have hampered current established immunotherapies. Emerging approaches to recruit T cells, to convert phenotypically "cold" into "inflamed" tumors, and to vastly improve therapeutic indices hold exceptional promise. Here, we review these approaches, highlighting the role of the tumor microenvironment and novel antibody platforms to maximize the full clinical potential of immunotherapy in pediatric oncology.

Purpose The optimal dose of radiation in high-risk neuroblastoma is unknown. We sought to evaluate local control following 21-Gy radiotherapy (RT) to the primary site in patients with high-risk neuroblastoma. Patients and Methods After receiving dose-intensive chemotherapy and gross total resection (GTR), 246 patients (ages 1.2–17.9, median 4.0 years) with high-risk neuroblastoma underwent RT to the primary site at xxx from 2000–2014. RT consisted of 21 Gy in twice-daily fractions of 1.5 Gy each. Local failure (LF) was correlated with biologic prognostic factors and clinical findings at the time of diagnosis and start of RT. Results Median follow-up of surviving patients was 6.4 years. Cumulative incidence of LF was 7.1% at 2 years post-RT and 9.8% at 5 years post-RT. The isolated LF rate was 3.0%. Eighty-six percent of all local failures were within the RT field. Local control was worse in patients who required more than one surgical resection to achieve GTR (22.4% vs 8.3%, p=0.01). There was also a trend towards inferior local control with MYCN-amplified tumors or serum LDH ≥1500 U/L (p=0.09 and p=0.06 respectively). Conclusion After intensive chemotherapy and maximal surgical debulking, hyperfractionated RT with 21 Gy in high-risk neuroblastoma results in excellent local control. Given the young patient age, concern for late effects, and local control >90%, dose-reduction may be appropriate for patients without MYCN amplification who achieve GTR.

No abstract