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Tenosynovial giant cell tumor (TGCT) is a rare proliferative disorder of synovial membrane that previously was known as pigmented villonodular synovitis (PVNS). Primary treatment involves surgical resection, however, complete removal of all disease involvement is difficult to achieve. Radiation may be useful to reduce the risk of recurrence. We report and update our institutional experience treating diffuse and recurrent TGCT with postsurgical external beam radiation therapy.We performed a retrospective chart review of 30 patients with TGCT from 2003-2019 treated with radiation therapy. Each patient was evaluated for demographics, radiation treatment parameters, surgical management, complications, and outcome.With mean follow-up of 82 months (range 3-211), 24 patients (80%) who underwent surgery followed by radiation therapy did not experience any further relapse, and all 30 patients achieved local control (100%) with additional salvage therapy following radiotherapy. The most common site of disease was the knee (n=22, 73%), followed by the ankle (n=5, 16%) and the hand (n=3, 10%). Seven patients (24%) presented at time of initial diagnosis while 23 (76%) presented with recurrent disease following surgical resection, with an average of 2.6 surgical procedures prior to radiotherapy. Following resection, 18/30 patients (67%) demonstrated residual TGCT by imaging. The median radiotherapy dose delivered was 36 Gy (range, 34-36 Gy) in 1.8-2.5 Gy/fractions over 4 weeks. In the assessment of post-treatment joint function, 26 sites (86%) exhibited excellent or good function, 2 (7%) fair, and 2 poor (7%) as determined by our scoring system. There were no cases of radiation-associated malignancy.Among patients with diffuse or recurrent TGCT, postsurgical external beam radiation therapy provided excellent local control and good functional status, with minimal treatment-related complications. Post-surgical radiation therapy is a well-tolerated noninvasive treatment that should be considered following maximal cytoreductive resection to prevent disease progression and recurrence.

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Background: Although ionizing radiation is an established environmental risk factor for thyroid cancer, the effect of chemotherapy drugs on thyroid cancer risk remains unclear. We evaluated the chemotherapy-related risk of thyroid cancer in childhood cancer survivors and the possible joint effects of chemotherapy and radiotherapy.Methods: The study included 12,547 five-year survivors of childhood cancer diagnosed during 1970 through 1986. Chemotherapy and radiotherapy information was obtained from medical records, and radiation dose was estimated to the thyroid gland. Cumulative incidence and relative risks were calculated with life-table methods and Poisson regression. Chemotherapy-related risks were evaluated separately by categories of radiation dose.Results: Histologically confirmed thyroid cancer occurred in 119 patients. Thirty years after the first childhood cancer treatment, the cumulative incidence of thyroid cancer was 1.3% (95% CI, 1.0–1.6) for females and 0.6% (0.4–0.8) for males. Among patients with thyroid radiation doses of 20 Gy or less, treatment with alkylating agents was associated with a significant 2.4-fold increased risk of thyroid cancer (95% CI, 1.3–4.5; P = 0.002). Chemotherapy risks decreased as radiation dose increased, with a significant decrease for patients treated with alkylating agents (Ptrend = 0.03). No chemotherapy-related risk was evident for thyroid radiation doses more than 20 Gy.Conclusions: Treatments with alkylating agents increased thyroid cancer risk, but only in the radiation dose range less than 20 Gy, in which cell sparing likely predominates over cell killing.Impact: Our study adds to the evidence for chemotherapy agent–specific increased risks of thyroid cancer, which to date, were mainly thought to be related to prior radiotherapy. Cancer Epidemiol Biomarkers Prev; 21(1); 92–101. ©2011 AACR.

PurposeThe Audio-Visual Assisted Therapeutic Ambience in Radiotherapy (AVATAR) system was the first published radiation therapy (RT)-compatible system to reduce the need for pediatric anesthesia through video-based distraction. We evaluated the feasibility of AVATAR implementation and effects on anesthesia use, quality of life, and anxiety in a multicenter pediatric trial.Methods and materialsPediatric patients 3 to 10 years of age preparing to undergo RT at 10 institutions were prospectively enrolled. Children able to undergo at least 1 fraction of RT using AVATAR without anesthesia were considered successful (S). Patients requiring anesthesia for their entire treatment course were nonsuccessful (NS). The PedsQL3.0 Cancer Module (PedsQL) survey assessed quality of life and was administered to the patient and guardian at RT simulation, midway through RT, and at final treatment. The modified Yale Preoperative Anxiety Scale (mYPAS) assessed anxiety and was performed at the same 3 time points. Success was evaluated using the χ2 test. PedsQL and mYPAS scores were assessed using mixed effects models with time points evaluated as fixed effects and a random intercept on the subject.ResultsEighty-one children were included; median age was 7 years. AVATAR was successful at all 10 institutions and with photon and proton RT. There were 63 (78%) S patients; anesthesia was avoided for a median of 20 fractions per patient. Success differed by age (P=.04) and private versus public insurance (P < .001). Both patient (P=.008) and parent (P=.006) PedsQL scores significantly improved over the course of RT for patients aged 5 to 7. Anxiety in the treatment room decreased for both S and NS patients over RT course (P < .001), by age (P < .001), and by S versus NS patients (P < .001).ConclusionsIn this 10-center prospective trial, anesthesia avoidance with AVATAR was 78% in children aged 3 to 10 years, higher than among age-matched historical controls (49%; P < .001). AVATAR implementation is feasible across multiple institutions and should be further studied and made available to patients who may benefit from video-based distraction.

PURPOSE Brentuximab vedotin, an effective anti-CD30 antibody-drug conjugate approved for use in adults with classical Hodgkin lymphoma (HL), was introduced in this frontline trial to reduce prescribed radiation in children and adolescents with classical HL. METHODS Open-label, single-arm, multicenter trial for patients (age ≤ 18 years) with stage IIB, IIIB, or IV classical HL was conducted. Brentuximab vedotin replaced each vincristine in the OEPA/COPDac (vincristine, etoposide, prednisone, and doxorubicin/cyclophosphamide, vincristine, prednisone, and dacarbazine) regimen according to GPOH-HD2002 treatment group 3 (TG3); two cycles of AEPA and four cycles of CAPDac. Residual node radiotherapy (25.5 Gy) was given at the end of all chemotherapy only to nodal sites that did not achieve a complete response (CR) at the early response assessment (ERA) after two cycles of therapy. Primary objectives were to evaluate the safety and efficacy (complete remission at ERA) of this combination and the 3-year event-free (EFS) and overall survival (OS). The trials are registered at ClinicalTrials.gov (identifier: NCT01920932 ). RESULTS Of the 77 patients enrolled in the study, 27 (35%) achieved complete remission at ERA and were spared radiation. Patients who were irradiated received radiation to individual residual nodal tissue. At a median follow-up of 3.4 years, the 3-year EFS was 97.4% (SE 2.3%) and the OS was 98.7% (SE 1.6%). One irradiated patient experienced disease progression at the end of therapy and now remains disease free more than 6 years following salvage therapy, and one unexpected death occurred. Only 4% of patients experienced grade 3 neuropathy. CONCLUSION The integration of brentuximab vedotin in the frontline treatment of pediatric high-risk HL is highly tolerable, facilitated significant reduction in radiation exposure, and yielded excellent outcomes.

Neurological paraneoplastic syndromes are exceedingly rare, and often difficult to recognize clinically. Paraneoplastic achalasia is a condition characterized by new-onset dysphagia that is unrelated to tumor burden, most often due to the development of auto-immune antibodies targeting esophageal tissue. Due to the rarity of this condition, diagnosis is often delayed, leading to increased time to treatment. Here we report a case of a rare paraneoplastic achalasia in a female child with EBV + Hodgkin lymphoma (HL), review literature describing paraneoplastic achalasia, and discuss treatment strategies for improving clinical outcome in these patients.

Purpose Pediatric radiation therapy (RT) requires optimal immobilization that often necessitates daily anesthesia. To decrease anesthesia use, we implemented a novel audiovisual-assisted therapeutic ambience in RT (AVATAR) system that projects video onto a radiolucent screen within the child's line of vision to provide attentional diversion. We investigated its reduction on anesthesia use, payer charges, and treatment time, in addition to its impact on radiation delivery. Methods and Materials A 6-year retrospective analysis was performed among children undergoing RT (n = 224) 3 years before and 3 years after the introduction of AVATAR. The frequency of anesthesia use before and after AVATAR implementation, in addition to RT treatment times, were compared. The number of spared anesthesia treatments allowed for a charge to payer analysis. To document the lack of surface dose perturbation by AVATAR, a phantom craniospinal treatment course was delivered both with and without AVATAR. Additionally, an ion chamber course was delivered to document changes to the dose at depth. Results More children were able to avoid anesthesia use entirely in the post-AVATAR cohort compared with the pre-AVATAR cohort (73.2% vs 63.4%; P = .03), and fewer required anesthesia for each treatment (18.8% vs 33%; P = .03). AVATAR introduction reduced anesthesia use for all ages studied. Treatment time per session was reduced by 38% using AVATAR compared with anesthesia. There were 326 fewer anesthesia sessions delivered over 3 years after AVATAR was introduced, with an estimated savings of >$500,000. Optically stimulated luminescent dosimeters revealed a small increase in dose of 0.8% to 9.5% with AVATAR, whereas the use of a thermomolded face mask increased skin dose by as much as 58%. Conclusions AVATAR introduction decreased anesthesia use in children undergoing RT. More children avoided anesthesia entirely, and fewer needed anesthesia for every treatment, resulting in a reduction in treatment time and savings of nearly $550,000 in approximately 3 years, with minimal perturbation of RT dose delivery.

The Children's Oncology Group (COG) uses Clinical Group (CG) and modified Tumor Node Metastasis (TNM) stage to classify rhabdomyosarcoma (RMS). CG is based on surgicopathologic findings and is determined after the completion of initial surgical procedure(s) but prior to chemotherapy and/or radiation therapy. The modified TNM stage is based on clinical and radiographic findings and is assigned prior to any treatment. These systems have evolved over several decades. We review the history, evolution, and rationale behind the current CG and modified TNM classification systems used by COG for RMS. Data from the seven most recently completed and reported frontline COG trials (D9602, D9802, D9803, ARST0331, ARST0431, ARST0531, ARST08P1) were analyzed, and confirm that CG and modified TNM stage remain relevant and useful for predicting prognosis in RMS. We propose updates based on recent data and discuss factors warranting future study to further optimize these classification systems.

Traditional management of metastatic sarcoma primarily relies on systemic therapy, with surgery often used for tumor control. We analyzed the rates of recurrence, overall survival, and treatment complications in patients undergoing either surgical resection or stereotactic body radiation therapy (SBRT) for metastatic sarcoma of the bone and/or soft tissue.The records of patients with metastatic sarcoma between 2009 and 2020 were reviewed. Local recurrence (LR) was defined as tumor growth or recurrence at the tumor site. Cumulative LR incidence was analyzed accounting for the competing risk of death, and groups were compared using the Gray test. Overall survival (OS) was assessed using the Kaplan-Meier method and log-rank test. Hazard ratios were determined using the Cox proportional hazards model.A total of 525 metastatic lesions in 217 patients were analyzed. The mean age of patients was 57 years (range, 4-88 years). The lung was the predominant site treated (50%), followed by intra-abdominal (13%) and soft tissue (11%). Two-year cumulative incidences of LR for surgery and SBRT were 14.8% (95% confidence interval [CI], 11.6%-18.5%) and 1.7% (95% CI, 0.1%-8.2%), respectively (P = .003). Local recurrence occurred in 72 (16.5%) of 437 tumors treated with surgery and 2 (2.3%) of 88 tumors treated with SBRT. The adjusted hazard ratio for LR of lesions treated surgically was 11.5 (P = .026) when controlling for tumor size and tumor site. Median OS was 29.8 months (95% CI, 25.6-40.9 months). There were 47 surgical complications among a total of 275 procedures (18%). Of 58 radiation treatment courses, radiation-related toxic effects were reported during the treatment of 7 lesions (12%), and none were higher than grade 2.We observed excellent local control among patients selected for treatment with SBRT for metastatic sarcoma, with no evidence of an increase in LR after SBRT compared with surgical management. Further investigation is necessary to better define the most appropriate local control strategies for metastatic sarcoma.

Children and adolescents with rhabdomyosarcoma (RMS) comprise a heterogeneous population with variable overall survival rates ranging between approximately 6% and 100% depending on defined risk factors. Although the risk stratification of patients has been refined across five decades of collaborative group studies, molecular prognostic biomarkers beyond FOXO1 fusion status have yet to be incorporated prospectively in upfront risk-based therapy assignments. This review describes the evolution of risk-based therapy and the current risk stratification, defines a new risk stratification incorporating novel biomarkers, and provides the rationale for the current and upcoming Children's Oncology Group RMS studies.

There are very few reported cases of stereotactic radiosurgery (SRS) delivered in children under 3 years of age. We report an 18-month-old boy with metastatic recurrence of undifferentiated round cell sarcoma to the brain which was treated with chemotherapy, resection and robotic frameless SRS. Frameless SRS was delivered without technical difficulties, acute adverse events, or clinical sequelae 1.5 months post-radiation. Longer term follow-up will be needed to evaluate local tumor control and effects on neurocognitive development, endocrine function and growth. This report adds to the literature of the few reported cases of successfully attempted SRS in very young children.

There is limited information addressing the occurrence of esophageal strictures among the growing population of survivors of childhood cancer. Using the Childhood Cancer Survivor Study, we analyzed data from 17,121 5-year survivors and 3400 siblings to determine the prevalence and risk factors for esophageal strictures. Prevalence among survivors was 2.0% (95% confidence interval [CI]: 1.8–2.2%), representing a 7.6-fold increased risk compared to siblings. Factors significantly associated with risk of esophageal stricture included diagnosis of Hodgkin lymphoma, greater chest radiation dose, younger age at cancer diagnosis, platinum chemotherapy, and hematopoietic stem cell transplantation. While uncommon, survivors are at risk for therapy-related esophageal strictures.

PurposeThe ARST0332 trial for pediatric and young adults with nonrhabdomyosarcoma soft tissue sarcoma (NRSTS) used risk-based treatment including primary resection with lower-than-standard radiation doses to optimize local control (LC) while minimizing long-term toxicity in those requiring radiation therapy (RT). RT for high-grade NRSTS was based on extent of resection (R0: negative margins, R1: microscopic margins, R2/U: gross disease/unresectable); those with >5 cm tumors received chemotherapy (CT; ifosfamide/doxorubicin). This analysis evaluates LC for patients assigned to RT and prognostic factors associated with local recurrence (LR).Methods and materialsPatients aged 5 cm tumor (arm C); or neoadjuvant RT (45 Gy)/CT plus delayed surgery, CT, and postoperative boost to 10.8 Gy R0

Limited data are available regarding radiation therapy in pediatric pleuropulmonary blastoma (PPB). We report the case of a 3-year-old girl with type II PPB successfully treated with trimodality therapy including multiagent chemotherapy, resection, and whole pleura radiation therapy. While longer follow-up is required to confirm ultimate local tumor control and long-term post-treatment sequelae, currently 3.5 years following therapy, she is well, without recurrent disease or observable toxicity. The goal of this report is to add our experience to the literature regarding PPB, its management, and treatment, as prospective randomized controlled trials are not feasible due to the rarity of this disease.

TPS11591 Background: Patients with high-risk rhabdomyosarcoma (HR-RMS) continue to have poor outcomes with 3-year event free survival (EFS) rates of 30% or less despite chemotherapy dose intensification on recent cooperative group RMS trials. Vinorelbine (VINO) has demonstrated clinical activity in RMS patients with relapsed/refractory disease and shown to provide a survival benefit when given with oral cyclophosphamide as maintenance chemotherapy for a select group of patients that achieved first complete remission. Methods: ARST2031 is a randomized Phase 3 trial with the primary aim to compare event-free survival (EFS) of patients with HR-RMS treated with vincristine, dactinomycin and cyclophosphamide (VAC) followed by maintenance with vinorelbine and oral cyclophosphamide (VINO-CPO) or vinorelbine, dactinomycin and cyclophosphamide (VINO-AC) followed by maintenance with VINO-CPO. Patients are stratified by histology and randomly assigned to VAC followed by VINO-CPO maintenance or VINO-AC followed by VINO-CPO maintenance. To be eligible, patients must be ≤ 50 years of age at the time of enrollment with newly diagnosed RMS except adult-type pleomorphic, based upon institutional histopathologic classification. All patients must have Stage 4 disease and patients diagnosed with embryonal RMS (ERMS) must be ≥ 10 years of age. Patients with malignant cytology in cerebrospinal fluid, intra-parenchymal brain metastases, or diffuse leptomeningeal disease are excluded. The study was activated on September 13, 2021 and is anticipated to enroll approximately 4 patients per month. The planned sample size is 100 patients, with approximately 50 patients randomized to each arm. Safety and feasibility of VINO-AC will be assessed in the first 8 patients prior to randomization. The study will have power of 0.8 to detect a hazard ratio of 0.61 (74 events in total) when the one-sided Type I error rate is 0.10, with 30 months of accrual and 2 years of follow-up. The hazard ratio of 0.61 was determined by assuming piecewise exponential distributions and specifying the 2-year EFS of 46% vs. 28% and long-term EFS of 32% vs. 16%, based on prior outcome data. Biospecimens will be collected and banked for future use. Clinical trial information: NCT04994132.

The use of radiotherapy as bridging therapy to chimeric antigen receptor T-cell therapy (CAR-T) in pre-B acute lymphoblastic leukemia (B-ALL) has been minimally explored. Here, we present a boy with B-ALL who relapsed after allogeneic bone marrow transplant with disseminated disease, including significant symptomatic cardiovascular and gastrointestinal (GI) involvement. The cardiac and GI leukemic infiltrates were successfully treated with bridging radiation therapy (BRT) prior to CAR-T infusion. Using this approach, he successfully tolerated CAR-T with no evidence of disease or sequelae on 3-month follow-up. This is the first reported case of safe and effective delivery of cardiac BRT in B-ALL.

Purpose We evaluated the impact of a virtual radiation oncology clerkship. Methods and Materials We developed a 2-week virtual radiation oncology clerkship that launched on April 27, 2020. Clerkship components included a virtual clinic with radiation oncology faculty and residents, didactic lectures, student talks, and supplemental sessions such as tumor boards and chart rounds. Medical students completed pre- and post-clerkship self-assessments. Faculty and resident participants also completed surveys on their experience with virtual lectures and clinics. Pre- and post-clerkship results were compared using a 2-sided paired t test. An analysis of variance model was used to analyze the clerkship components. Results Twenty-six medical students, including 4 visiting students, enrolled over 2 clerkship periods (4 weeks). All students completed the pre- and post-clerkship self-assessments and agreed that the clerkship improved their understanding of radiation oncology. Compared with 3 (11.5%) students who agreed that they understood the daily responsibilities of a radiation oncologist before the clerkship, 22 (84.6%) students agreed and 3 (11.5%) strongly agreed that they understood the daily responsibilities of a radiation oncologist after the clerkship (P < .0001). Although 15 students (57.7%) reported an increased interest in radiation oncology because of the clerkship, the mean level of interest in radiation oncology as a career remained the same, with pre- and post-clerkship scores of 3.0 (±0.9) and 3.0 (±1.1) on a 5-point scale, respectively (P = .7). Students found virtual clinic and didactic lectures to be the most valuable components of the clerkship. Most respondents agreed (30.8%) or strongly agreed (65.4%) to recommend the clerkship to their classmates. Conclusions Our virtual clerkship was effective in increasing medical student interest in and knowledge about radiation oncology. These data will help optimize a new paradigm of virtual radiation oncology education for medical students during COVID-19 and beyond.

This report by the Radiation Oncology Discipline of Children’s Oncology Group (COG) describes the practice patterns of pediatric image-guided radiotherapy (IGRT) based on a member survey and provides practice recommendations accordingly. The survey comprised of 11 vignettes asking clinicians about their recommended treatment modalities, IGRT preferences, and frequency of in-room verification. Technical questions asked physicists about imaging protocols, dose reduction, setup correction, and adaptive therapy. In this report, the COG Radiation Oncology Discipline provides an IGRT modality/frequency decision tree and the expert guidelines for the practice of ionizing image guidance in pediatric radiotherapy patients.

Purpose Our institution cancelled all in-person clerkships due to the COVID-19 pandemic. In response, we designed a virtual radiation oncology medical student clerkship. Methods and Materials We convened an advisory panel to design a virtual clerkship curriculum. We implemented clerkship activities using a cloud-based learning management system, video web conferencing systems and a telemedicine portal. Students completed assessments pre- and post-clerkship to provide data to improve future versions of the clerkship. Results The virtual clerkship spans 2 weeks and is graded pass or fail. Students attend interactive didactic sessions during the first week and participate in virtual clinic and give talks to the department during the second week. Didactic sessions include lectures, case-based discussions, treatment planning seminars and material adapted from the Radiation Oncology Education Collaborative Study Group curriculum. Students also attend virtual departmental quality assurance rounds, cancer center seminars and multi-disciplinary tumor boards. The enrollment cap was met during the first virtual clerkship period (April 27 through May 8, 2020), with a total of 12 students enrolling. Conclusions Our virtual clerkship can increase student exposure and engagement in radiation oncology. Data on clerkship outcomes are forthcoming., In response to cancelation of all in-person clerkships at our institution due to the COVID-19 pandemic, we designed a virtual radiation oncology clerkship. We fulfilled clerkship learning objectives using an array of digital education tools and were able to broaden our reach in educating medical students about our field.

Rhabdomyosarcoma is a heterogeneous disease both in presentation and histology. Improvements in a multimodality therapy resulted in the improved overall survival for patients with a low-risk and intermediate-risk disease but not for patients with a metastatic disease. We reviewed and contrasted the North American and European practice patterns, though ultimately the principles of staging, surgery, radiation therapy, and chemotherapy are similar in both Children's Oncology Group and International Society of Paediatric Oncology treatment approaches. Efforts are underway to investigate improved local control rates in higher risk patients using radiation dose escalation strategies, and delayed primary excision in select cases. The prognostic significance of imaging-based chemotherapy response, proton therapy, novel biomarkers, and targeted drugs will be determined in upcoming clinical trials.

Background: Brentuximab vedotin is an anti-CD30 antibody-drug conjugate approved for use in adults with newly diagnosed and relapsed/refractory high-risk classical Hodgkin lymphoma (HL). Methods: Open label, single-arm, multicenter trial for patients (age < 18 years) with stage IIB, IIIB or IV classical HL. One dose of brentuximab vedotin (AdcetrisO) replaced each vincristine in the OEPA [vincristine, etoposide, prednisone, and doxorubicin]/COPDac [cyclophosphamide, vincristine, prednisone, and dacarbazine] regimen (2 cycles of AEPA and 4 cycles of CAPDac) according to GPOH-HD2002 treatment group 3 [TG3]. 1 Residual node radiotherapy (25·5 Gy) was given at the end of all chemotherapy only to nodal sites that did not achieve a complete response (CR) at the early response assessment (ERA) after 2 cycles of therapy. Primary objectives were to evaluate the safety and efficacy (complete remission at ERA) of this combination and the 3-year event-free and overall survival. Findings: Of the 77 patients enrolled in the study, 27 (35%) achieved complete remission at ERA and were spared radiation. Patients who were irradiated received radiation to individual residual nodal tissue. At a median follow-up of 3·4 years, the 3 year event-free survival was 97·4% (SE 2·3%) and overall survival 98·7% (SE 1·6%). One irradiated patient experienced disease progression at the end of therapy and now remains disease free more than 6 years following salvage therapy, and one unexpected death occurred. Only 4% patients experienced Grade 3 neuropathy. Interpretation: The integration of brentuximab vedotin in the frontline treatment of pediatric high-risk HL is highly tolerable, facilitated reduction in radiation exposure, and yielded excellent outcomes. Trial Registration: IND (#118603), The trial is registered with www.clinicaltrials.gov, NCT01920932. Funding Statement: Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30CA021765. Declaration of Interests: None to declare. Ethics Approval Statement: The trial was approved by the institutional review board of each participating center and monitored by the SJCRH Data, Safety, and Monitoring Board. Informed consent was obtained as per institutional guidelines.

Purpose Our aim was to review the advances in radiation therapy for the management of pediatric cancers made by the Children's Oncology Group (COG) radiation oncology discipline since its inception in 2000. Methods and Materials The various radiation oncology disease site leaders reviewed the contributions and advances in pediatric oncology made through the work of the COG. They have presented outcomes of relevant studies and summarized current treatment policies developed by consensus from experts in the field. Results The indications and techniques for pediatric radiation therapy have evolved considerably over the years for virtually all pediatric tumor types, resulting in improved cure rates together with the potential for decreased treatment-related morbidity and mortality. Conclusions The COG radiation oncology discipline has made significant contributions toward the treatment of childhood cancer. Our discipline is committed to continuing research to refine and modernize the use of radiation therapy in current and future protocols with the goal of further improving the cure rates and quality of life of children with cancer.

Purpose/Objective(s) Late toxicity of treatment remains a major consideration among survivors of childhood leukemia. Pediatric patients with leukemia who receive fractionated total body irradiation (fTBI) as conditioning prior to stem cell transplantation (SCT) are frequently treated with a 4 Gy testicular boost in addition to fTBI to 12-13.2 Gy to reduce the risk of testicular relapse in this “sanctuary site.” However, total body irradiation can be associated with risk of impaired hormonal function; it is unclear if the 4 Gy testicular boost is needed to reduce risk of testicular relapse, and whether it contributes to the toxicity beyond that imparted by fTBI. This study investigated patients both with and without a boost for risk of recurrence, hormonal function, and fertility. Materials/Methods We retrospectively reviewed records of boys treated for leukemia with fTBI as part of conditioning for SCT at our institution from 1989-present. We included patients with both AML and ALL in our analysis. We excluded patients who died in the peri-transplant period. Cumulative incidence was tested using Gray's Test for Equality of Cumulative Incidence Functions. Endocrine outcomes were tested using chi square test. Results We identified 91 boys (age range 9 months – 22 years), 62 with ALL and 29 with AML. Median follow up was 43.4 months. In addition to fTBI to 12-13.2 Gy, 52 patients received a midplane testicular dose of 4 Gy (49 with ALL, 3 with AML), while 39 patients did not receive the testicular boost (13 with ALL, 26 with AML). There was no difference in time to first relapse or cumulative incidence of relapse between the boost and no-boost groups. There were 2 testicular relapses, one ALL patient who received boost and one AML patient who did not receive boost. The risk of abnormal luteinizing hormone (LH) was 65% in the boost group vs 26% in the non-boost group, P = 0.0063. Serum follicle-stimulating hormone, total testosterone, free testosterone, abnormal sperm studies did not differ between groups, nor did the percentage of patients who required endocrine or fertility treatments. We further investigated the subset of patients with ALL and similarly found no difference in risk of relapse between patients who had received a testicular boost and those who had not boost. Conclusion Omission of boost was associated with comparable risk of recurrence and improved endocrine outcomes, specifically LH levels. Our data suggest that omission of testicular boost in the fTBI program is oncologically safe and results in improved hormonal function.

Purpose Radiation therapy is an important component of treatment for many childhood cancers. Depending upon the age and maturity of the child, pediatric radiation therapy often requires general anesthesia for immobilization, position reproducibility, and daily treatment delivery. We designed and clinically implemented a radiation therapy–compatible audiovisual system that allows children to watch streaming video during treatment, with the goal of reducing the need for daily anesthesia through immersion in video. Methods and materials We designed an audiovisual-assisted therapeutic ambience in radiation therapy (AVATAR) system using a digital media player with wireless streaming and pico projector, and a radiolucent display screen positioned within the child's field of view to him or her with sufficient entertainment and distraction for the duration of serial treatments without the need for daily anesthesia. We piloted this system in 25 pediatric patients between the ages of 3 and 12 years. We calculated the number of fractions of radiation for which this system was used successfully and anesthesia avoided and compared it with the anesthesia rates reported in the literature for children of this age. Results Twenty-three of 25 patients (92%) were able to complete the prescribed course of radiation therapy without anesthesia using the AVATAR system, with a total of 441 fractions of treatment administered when using AVATAR. The median age of patients successfully treated with this approach was 6 years. Seven of the 23 patients were initially treated with daily anesthesia and were successfully transitioned to use of the AVATAR system. Patients and families reported an improved treatment experience with the use of the AVATAR system compared with anesthesia. Conclusions The AVATAR system enables a high proportion of children to undergo radiation therapy without anesthesia compared with reported anesthesia rates, justifying continued development and clinical investigation of this technique.

BACKGROUND Ewing sarcoma survivors (ESSs) are at increased risk for treatment-related complications. The incidence of treatment-related morbidity and late mortality with aging is unknown. METHODS This study reports survival probabilities, estimated with the Kaplan-Meier method, and the cumulative incidence of cause-specific mortality and chronic conditions among ESSs in the Childhood Cancer Survivor Study who were treated between 1970 and 1986. Piecewise exponential models were used to estimate relative rates (RRs) and 95% confidence intervals (CIs) for these outcomes. Chronic conditions were graded with the Common Terminology Criteria for Adverse Events (version 4.03). RESULTS Among 404 5-year ESSs (median age at last follow-up, 34.8 years; range, 9.1-54.8 years), the 35-year survival rate was 70% (95% CI, 66%-74%). Late recurrence (cumulative incidence at 35 years, 15.1%) was the most common cause of death, and it was followed by treatment-related causes (11.2%). There were 53 patients with subsequent neoplasms (SNs; cumulative incidence at 35 years, 24.0%), and 38 were malignant (14.3% at 35 years). The standardized incidence ratios were 377.1 (95% CI, 172.1-715.9) for osteosarcoma, 28.9 (95% CI, 3.2-104.2) for acute myeloid leukemia, 14.9 (95% CI, 7.9-25.5) for breast cancer, and 13.1 (95% CI, 4.8-28.5) for thyroid cancer. Rates of chronic conditions were highest for musculoskeletal (RR, 18.1; 95% CI, 12.8-25.7) and cardiac complications (RR, 1.8; 95% CI, 1.4-2.3). Thirty-five years after the diagnosis, the cumulative incidences of any chronic conditions and 2 or more chronic conditions were 84.6% (95% CI, 80.4%-88.8%) and 73.8% (95% CI, 67.8%-79.9%), respectively. CONCLUSIONS With extended follow-up, ESSs' risk for late mortality and SNs does not plateau. Treatment-related chronic conditions develop years after therapy, and this supports the need for lifelong follow-up. Cancer 2017;123:2551–60. © 2017 American Cancer Society.

Survivors of childhood cancer are at risk of long-term sequelae that arise as a consequence of cancer treatment. Radiation and chemotherapy treatment in pediatric female patients can have detrimental impacts on fertility, particularly in those with pelvic tumor involvement. We report 2 successful natural full-term pregnancies with vaginal delivery in a woman 12 years after biopsy, irradiation (55.5 Gy), and multi-agent chemotherapy for treatment of pelvic Ewing sarcoma. Both children were born healthy, with no complications in pregnancy or delivery. Fertility preservation and risk assessment following chemotherapy/radiation therapy is evolving, providing new data to effectively counsel and treat young women.

Background Few studies have addressed the efficacy of palliative radiotherapy (RT) for pediatric osteosarcoma (OS), a disease generally considered to be radioresistant. We describe symptom relief, local control, and toxicity associated with palliative RT among children with OS. Procedure Patients diagnosed with OS at age 18 and under and treated with RT for palliation of symptomatic metastases or local recurrence at the primary site from 1997 to 2017 were included. We retrospectively reviewed details of RT, symptom improvement, local control, survival, and toxicity. Results Thirty-two courses of palliative RT were given to 20 patients with symptomatic metastatic and/or locally recurrent primary disease. The median equivalent dose in 2 Gy fractions (EQD2) was 40.0 Gy (range, 20.0-60.4). The median number of fractions per course was 15 (range, 5-39). Symptom improvement occurred in 24 (75%) courses of RT at a median time of 15.5 days (range, 3-43). In nine courses (37.5%), symptoms recurred after a median duration of symptom relief of 140 days (range, 1-882). Higher EQD2 correlated with longer duration of response (r = 0.39, P = 0.0003). Imaging revealed local failure in 3 of 14 courses followed with surveillance imaging studies (21.4%). The median time to progression was 12.9 months (range, 4.4-21.8). The median follow-up time following the first course of palliative RT was 17.5 months (range, 1.74-102.24), and median time to overall survival was 19.4 months. Toxicity was mild, with grade 2 toxicity occurring in one course (3.1%). Conclusions RT is an effective method of symptom palliation for patients with recurrent or metastatic OS, with higher delivered dose correlating with longer symptom relief and with little associated toxicity.

Classic Hodgkin lymphoma post-transplant lymphoproliferative disorder (HL-PTLD) has been rarely reported in children, with limited data available to guide treatment decisions. We report a retrospective review of five children diagnosed with classic HL-PTLD following solid organ transplant between 2007 and 2013 at Stanford University. Patients were treated with Stanford V chemotherapy and involved field radiation therapy. With a median follow-up of 7.2 years (range, 4.7-10.5 years) since diagnosis, all patients remain in remission from HL-PTLD and free from graft failure. In this series, combined modality therapy with risk-adapted chemotherapy and radiation therapy was a successful strategy for the treatment of classic HL-PTLD.

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.

Radiation therapy is an effective treatment for pediatric cancers, yet requires immobilization and often anesthesia for precision treatment. Patients with Down syndrome are at increased risk for anesthesia-associated complications. We have implemented an audiovisual system (AVATAR) that enables patients to watch videos during daily radiation therapy. We report a unique experience eliminating the need for anesthesia during radiation in a child with Down syndrome who previously required sedation in order to tolerate chemotherapy. AVATAR is a feasible alternative to daily anesthesia and may be useful for patients with special difficulty tolerating treatment.

BACKGROUND Women treated with mantle irradiation for Hodgkin lymphoma (HL) are at an increased risk of developing breast cancer (BC). Current guidelines recommend screening breast magnetic resonance imaging (MRI) as an adjunct to mammography (M) in these patients. There are limited data, however, as to the impact of breast MRI on cancer detection rates. The aim of the current study is to evaluate the use of breast MRI in survivors of HL treated and followed at a single institution. MATERIALS AND METHODS We retrospectively reviewed 980 female patients treated with mantle irradiation for HL between 1961 and 2008. Records were reviewed to determine age at radiotherapy treatment, radiotherapy dose, breast imaging (including M and breast MRI), biopsy results if applicable, and incidence of BC. RESULTS A total of 118 patients had breast imaging performed at our institution. Median age at HL diagnosis was 28 years (range, 10 to 69 y). Median radiotherapy dose was 36 Gy (range, 20 to 45 Gy). Seventy-nine patients (67%) underwent M screening only, 1 (1%) breast MRI only, and 38 (32%) both M and breast MRI. Of these 38, 19 (50%) underwent 54 screening MRI studies (range per patient=1 to 8), 13 (34%) underwent preoperative MRI for workup of BC, and 6 (16%) initiated screening MRI of the contralateral breast only after diagnosed with BC. Fifty-nine biopsies were performed: 47 were prompted by suspicious M findings only, 10 by palpable findings on physical examination (PE), and 2 by suspicious breast MRI findings. Of the 47 biopsies prompted by M, 24 revealed malignant disease, whereas 23 proved to be benign. All 10 biopsies performed by palpation were malignant. Both biopsies prompted by MRI findings were benign. With M, there were 34 true-positive findings in 32 patients, 23 false-positive findings, and 1 false-negative finding. With screening MRI, there were 2 false-positive findings, 1 false-negative finding, and no true-positive findings. CONCLUSIONS The role of screening breast MRI in women previously irradiated for HL is evolving. Further education of patients and physicians is important to increase awareness of more sensitive BC screening modalities in this high-risk population. Future studies are necessary to determine the appropriate integration of screening breast MRI into the ongoing follow-up of these women.

As a diagnosis of exclusion, Undifferentiated Pleomorphic Sarcoma (UPS) has unclear clinical characteristics. The objective of this retrospective cohort study is to investigate which clinical and prognostic factors of primary lower-extremity UPS will determine failure.We retrospectively reviewed 55 primary lower-extremity UPS cases treated at Stanford between 1998 and 2015. Overall Survival (OS) and Disease-Free Survival (DFS) curves were calculated. Univariate Fisher's Exact Tests were used to examine relationships between disease recurrence, treatment, patient factors, tumor characteristics, and surgical margins.5-year DFS and OS rates were 60% (95% CI, 45%-72%) and 68% (95% CI, 53%-79%), respectively. The 5-year DFS rate for patients with positive margins was 33.3% (95% CI, 5%-68%) compared with 63% (95% CI, 47%-76%) for patients with negative margins. (Log-rank, P=0.03). The OS rate for those with disease recurrence was 42% % (95% CI, 16%-67%) compared with 76% (95% CI, 59%-87%) for patients who did not have disease recurrence (log-rank, P=0.021). Local failure occurred more frequently with omission of radiation therapy (Fisher's exact test, P=0.009).Positive surgical margins are an important prognostic factor for predicting relapse in UPS. Relapse of any kind led to worse OS. Radiation therapy improved local control of disease but had no statistically significant effect on DFS, highlighting the need for improved diagnostics to identify those at highest risk for hematogenous metastasis and for selection of patients for adjuvant systemic treatment.

Background The purpose of this study was to evaluate risk and response-based multi-agent therapy for patients with rhabdomyosarcoma (RMS) at first relapse. Methods Patients with RMS and measurable disease at first relapse with unfavorable-risk (UR) features were randomized to a 6-week phase 2 window with 1 of 2 treatment schedules of irinotecan with vincristine (VI) (previously reported). Those with at least a partial response to VI continued to receive 44 weeks of multi-agent chemotherapy including the assigned VI regimen. UR patients who did not have measurable disease at study entry, did not have a radiographic response after the VI window, or declined VI window therapy received 31 weeks of multi-agent chemotherapy including tirapazamine (TPZ) at weeks 1, 4, 10, 19, and 28. Favorable-risk (FR) patients received 31 weeks of the same multi-agent chemotherapy without VI and TPZ. Results One hundred thirty-six eligible patients were enrolled. For 61 patients not responding to VI, the 3-year failure-free survival (FFS) and overall survival (OS) rates were 17% (95% confidence interval [CI], 8%-29%) and 24% (13%-37%), respectively. For 30 UR patients not treated with VI, the 3-year FFS and OS rates were 21% (8%-37%) and 39% (20%-57%), respectively. FR patients had 3-year FFS and OS rates of 79% (47%-93%) and 84% (50%-96%), respectively. There were no unexpected toxicities. Conclusions Patients with UR RMS at first relapse or disease progression have a poor prognosis when they are treated with this multi-agent therapy, whereas FR patients have a higher chance of being cured with second-line therapy.

Here we describe the case of a 10-year-old boy with a history of chronic hepatitis B who was diagnosed with hepatocellular carcinoma (HCC) with a large central hepatic mass and metastatic disease in a celiac lymph node. His tumor was unresectable, due to location and lack of clear margins, and he could not receive chemotherapy due to elevated bilirubin. He was treated with stereotactic body radiotherapy (SBRT) to the primary site and involved nodal region. After completing radiotherapy, his total bilirubin level fell below 1.0 mg/dL, allowing him to begin systemic therapy with cisplatin and doxorubicin. At three months after SBRT, his bilirubin was 0.1 mg/dL, alpha-fetoprotein (AFP) was 88 ng/mL, and imaging demonstrated a decrease in tumor size (total volume 28.7 cc), with no evidence of local or distant disease progression. He then developed distant disease within the liver, but his disease remained controlled at the primary site and nodes that had been treated with SBRT. He underwent orthotopic liver transplantation (OLT) with an uneventful operative course and remains with no evidence of disease at seven months after OLT. This is one of the first reported cases of successful downstaging of pediatric HCC with nodal involvement to allow for OLT, and it argues for consideration of similar patients for OLT.

Purpose Intermediate-risk rhabdomyosarcoma (RMS) includes patients with either nonmetastatic, unresected embryonal RMS (ERMS) with an unfavorable primary site or nonmetastatic alveolar RMS (ARMS). The primary aim of this study was to improve the outcome of patients with intermediate-risk RMS by substituting vincristine and irinotecan (VI) for half of vincristine, dactinomycin, and cyclophosphamide (VAC) courses. All patients received a lower dose of cyclophosphamide and earlier radiation therapy than in previous trials. Patients and Methods Patients were randomly assigned at study entry to either VAC (cumulative cyclophosphamide dose, 16.8 g/m2) or VAC/VI (cumulative cyclophosphamide dose, 8.4 g/m2) for 42 weeks of therapy. Radiation therapy started at week 4, with individualized local control plans permitted for patients younger than 24 months. The primary study end point was event-free survival (EFS). The study design had an 80% power (5% one-sided α-level) to detect an improved long-term EFS from 65% (with VAC) to 76% (with VAC/VI). Results A total of 448 eligible patients were enrolled in the study. At a median follow-up of 4.8 years, the 4-year EFS was 63% with VAC and 59% with VAC/VI ( P = .51), and 4-year overall survival was 73% for VAC and 72% for VAC/VI ( P = .80). Within the ARMS and ERMS subgroups, no difference in outcome by treatment arm was found. Severe hematologic toxicity was less common with VAC/VI therapy. Conclusion The addition of VI to VAC did not improve EFS or OS for patients with intermediate-risk RMS. VAC/VI had less hematologic toxicity and a lower cumulative cyclophosphamide dose, making VAC/VI an alternative standard therapy for intermediate-risk RMS.

Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment.We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudinal follow-up of 5-year survivors of common childhood cancers (leukaemia, tumours of the CNS, Hodgkin lymphoma, non-Hodgkin lymphoma, Wilms tumour, neuroblastoma, soft tissue sarcoma, or bone tumours) who were diagnosed before the age of 21 years and from 1970 to 1999 in North America. We examined the cumulative incidence of severe to fatal chronic health conditions occurring up to 20 years post-diagnosis among survivors, compared by diagnosis decade. We used multivariable regression models to estimate hazard ratios per diagnosis decade, and we added treatment variables to assess whether treatment changes attenuated associations between diagnosis decade and chronic disease risk.Among 23 601 survivors with a median follow-up of 21 years (IQR 15-25), the 20-year cumulative incidence of at least one grade 3-5 chronic condition decreased significantly from 33·2% (95% CI 32·0-34·3) in those diagnosed 1970-79 to 29·3% (28·4-30·2; p0·0001) in 1980-89, and 27·5% (26·4-28·6; p=0·012 vs 1980-89) in 1990-99. By comparison, the 20-year cumulative incidence of at least one grade 3-5 condition in 5051 siblings was 4·6% (95% CI 3·9-5·2). The 15-year cumulative incidence of at least one grade 3-5 condition was lower for survivors diagnosed 1990-99 compared with those diagnosed 1970-79 for Hodgkin lymphoma (17·7% [95% CI 15·0-20·5] vs 26·4% [23·8-29·1]; p0·0001), non-Hodgkin lymphoma (16·9% [14·0-19·7] vs 23·8% [19·9-27·7]; p=0.0053), astrocytoma (30·5% [27·8-33·2] vs 47·3% [42·9-51·7]; p0·0001), Wilms tumour (11·9% [9·5-14·3] vs 17·6% [14·3-20·8]; p=0·034), soft tissue sarcoma (28·3% [23·5-33·1] vs 36·5% [31·5-41·4]; p=0·021), and osteosarcoma (65·6% [60·6-70·6] vs 87·5% [84·1-91·0]; p0·0001). By contrast, the 15-year cumulative incidence of at least one grade 3-5 condition was higher (1990-99 vs 1970-79) for medulloblastoma or primitive neuroectodermal tumour (58·9% [54·4-63·3] vs 42·9% [34·9-50·9]; p=0·00060), and neuroblastoma (25·0% [21·8-28·2] vs 18·0% [14·5-21·6]; p=0·0045). Results were consistent with changes in treatment as a significant mediator of the association between diagnosis decade and risk of grade 3-5 chronic conditions for astrocytoma (HR per decade without treatment in the model = 0·77, 95% CI 0·64-0·92; HR with treatment in the model=0·89, 95% CI 0·72-1·11; pOur results suggest that more recently treated survivors of childhood cancer had improvements in health outcomes, consistent with efforts over the same time period to modify childhood cancer treatment regimens to maximise overall survival, while reducing risk of long-term adverse events. Continuing advances in cancer therapy offer promise of further reducing the risk of long-term adverse events in childhood cancer survivors. However, achieving long-term survival for childhood cancer continues to come at a cost for many survivors, emphasising the importance of long-term follow-up care for this population.National Cancer Institute and the American Lebanese-Syrian Associated Charities.

Purpose For infants with localized rhabdomyosarcoma who were enrolled on Children's Oncology Group ARST0331 and ARST0531, local therapy guidelines were provided, but adherence was not mandated because of toxicity concerns. We examined adherence to protocol for local therapy guidelines, treatment variations, and outcomes for these patients. Methods Children aged ≤24 months who were enrolled on ARST0331 and ARST0531 were evaluated. Data were verified through radiologic, surgical, pathologic, and clinical records. Local therapy was assessed for adherence to protocol guidelines, with variations termed “individualized local therapy.” The subdistribution hazards model assessed local failure, the Kaplan-Meier product limit method assessed event-free survival (EFS) and overall survival, and the log-rank test was used to evaluate prognostic impact. Results The median age of the patients was 14 months, and 124 patients were eligible. Common primary sites were genitourinary (40%), parameningeal (14%), and the extremities (11%). Most patients had unresected disease (group 3, 64%) and embryonal histology (73%). Fifty-eight percent of patients received radiation therapy at a median of week 12 (weeks 1-45). The median radiation dose was 48.6 Gy (30.6-54 Gy). Forty-three percent of patients received individualized local therapy (outside protocol guidelines), typically omission or delay of radiation therapy. Delayed primary excision was performed in 28% at a median of week 14 (weeks 7-34). With a median follow-up of 5.6 years, the 5-year local failure, EFS, and overall survival rates were 24%, 68%, and 82%, respectively. Local failure was significantly higher (35%) in patients receiving individualized local therapy than in patients who received protocol-specified local therapy (16%; P = .02). The site of failure was local in 64% of patients, local and distant in 5%, and distant only in 23%. EFS was significantly higher among patients who were aged 12 to 24 months, had tumors ≤5 cm, had group 1/2 disease, and underwent protocol-specified therapy. Conclusions Local recurrence was the predominant pattern of failure and was more common in those receiving individualized local therapy. De-escalation of effective therapies because of concerns about treatment toxicity should be considered cautiously.

Background Radiation therapy (RT) remains a critical component of multimodality treatment for medulloblastoma. Traditionally, clinicians strive to start RT within 4-5 weeks of surgery, but the optimal timing after surgery remains unclear. Methods Using the National Cancer Database, we identified pediatric and adolescent patients with medulloblastoma treated with curative-intent surgery, RT, and chemotherapy. Factors associated with early or delayed RT were identified using Pearson chi-squared tests. Overall survival (OS) differences based on RT timing were compared using the Kaplan-Meier estimator with log-rank tests. Patient, tumor, and treatment characteristics associated with OS were analyzed with univariate and multivariate Cox proportional hazards models. Results Among the 1338 patients analyzed, early RT (defined as initiation ≤3 wk after surgery) was associated with younger age, M1-3 disease, and subtotal resection. Patients who initiated RT early had decreased 5-year OS compared with patients who initiated RT 3.1-4, 4.1-5, or >5 weeks after surgery (72.5% vs. 80.5%, 79.4%, and 77.8%, respectively; P = 0.019), but there was no significant difference in OS among the latter 3 groups (P = 0.788). On multivariate analysis, early RT versus the 3.1- to 4-week interval was significantly associated with poorer OS (adjusted hazard ratio, 1.72; 95% CI: 1.19-2.48; P = 0.004), while time to RT of >5 weeks but within 90 days of surgery did not adversely impact OS (P = 0.563). Conclusions In this large national database analysis, delaying RT within 90 days of surgery was not associated with inferior outcomes. Although clinical judgment remains paramount, postoperative RT timing should allow for healing and the development of an optimal treatment plan.

Purpose To determine local control according to clinical variables for patients with intermediate-risk rhabdomyosarcoma (RMS) treated on Children's Oncology Group protocol D9803. Patients and Methods Of 702 patients enrolled, we analyzed 423 patients with central pathology–confirmed group III embryonal (n=280) or alveolar (group III, n=102; group I-II, n=41) RMS. Median age was 5 years. Patients received 42 weeks of VAC (vincristine, dactinomycin, cyclophosphamide) or VAC alternating with VTC (T = topotecan). Local therapy with 50.4 Gy radiation therapy with or without delayed primary excision began at week 12 for group III patients. Patients with group I/II alveolar RMS received 36-41.4 Gy. Local failure (LF) was defined as local progression as a first event with or without concurrent regional or distant failure. Results At a median follow-up of 6.6 years, patients with clinical group I/II alveolar RMS had a 5-year event-free survival rate of 69% and LF of 10%. Among patients with group III RMS, 5-year event-free survival and LF rates were 70% and 19%, respectively. Local failure rates did not differ by histology, nodal status, or primary site, though there was a trend for increased LF for retroperitoneal (RP) tumors ( P =.12). Tumors ≥5 cm were more likely to fail locally than tumors P =.0004). Almost all (98%) RP tumors were ≥5 cm, with no difference in LF by site when the analysis was restricted to tumors ≥5 cm ( P =.86). Conclusion Local control was excellent for clinical group I/II alveolar RMS. Local failure constituted 63% of initial events in clinical group III patients and did not vary by histology or nodal status. The trend for higher LF in RP tumors was related to tumor size. There has been no clear change in local control over RMS studies, including IRS-III and IRS-IV. Novel approaches are warranted for larger tumors (≥5 cm).

Purpose To analyze treatment outcomes for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) at a single institution. Patients and Methods Patients with newly diagnosed NLPHL between 1996 and 2013 were reviewed retrospectively. Patients treated before 1996 were excluded because the majority received extended field radiation therapy (RT) alone. Results Fifty-five patients (22 ≤ 21 years old) were identified. The median follow-up time was 6.8 years. Among 37 patients with limited-stage (I-II) disease, treatments included involved field RT at a median dose of 36 Gy (n=9), rituximab monotherapy (n=9), observation (n=3), and response-adaptive therapy (n=16), in which the RT dose was reduced from 25.5 Gy to 15 Gy or was eliminated based on interim imaging after chemotherapy. The 5-year progression-free survival (PFS) was 76.4% (95% confidence interval [CI], 63.1-92.4). Nine patients experienced progression, including 5 receiving rituximab, 2 undergoing observation, and 2 receiving response-adaptive therapy. Rituximab was associated with an inferior PFS compared with RT alone ( P =.02). The difference in PFS between response-adaptive therapy and RT alone was not statistically significant ( P =.39). Among 18 patients with advanced-stage (III-IV) disease, treatments included chemotherapy alone (n=3), combined modality therapy (CMT) (n=2), response-adaptive therapy (n=2), rituximab (n=7), and observation (n=4). The 5-year PFS was 29.9% (CI, 13.3-67.4). Twelve patients experienced progression, including 1 receiving chemotherapy, 1 receiving CMT, 6 receiving rituximab, and 4 undergoing observation. There was no significant PFS difference between rituximab and non-rituximab therapies ( P =.19) within the caveat of small sample sizes. In the entire cohort, 9 patients (3 with limited disease, 6 with advanced disease) experienced large cell transformation (LCT). Seven patients died; of those, 5 died with LCT. Conclusions For limited disease, response-adaptive therapy demonstrated comparable outcomes with RT alone. Rituximab monotherapy resulted in inferior outcomes for limited disease and a high relapse rate for advanced disease.