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Purpose Primary mediastinal B cell lymphoma (PMBCL) is a highly curable subtype of non-Hodgkin lymphoma that is diagnosed predominantly in adolescents and young adults. Consequently, long-term treatment-related morbidity is critical to consider when devising treatment strategies that include different chemoimmunotherapy strategies with or without radiation therapy. Furthermore, adaptive approaches using the end-of-chemotherapy (EOC) positron emission tomography (PET)/computed tomography (CT) scanning may help to determine which patients may benefit from additional therapies. We aimed to develop evidence-based guidelines for treating these patients. Methods and Materials We conducted a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline using the PubMed database. The ARS expert committee, composed of radiation oncologists, hematologists, and pediatric oncologists, developed consensus guidelines using the modified Delphi framework. Results Nine studies met the full criteria for inclusion based on reporting outcomes on patients with primary mediastinal B cell lymphoma with EOC PET/CT response scored with the 5-point Deauville scale. These studies formed the evidence for these guidelines in managing patients with PMBCL according to the EOC PET response, including after a 5-point Deauville scale of 1 to 3, 4, or 5, and for patients with relapsed and refractory disease. The expert group also developed guidance on radiation simulation, treatment planning, and plan evaluation based on expert opinion. Conclusions Various treatment approaches exist in the management of PMBCL, including different chemoimmunotherapy regimens, the use of consolidative radiation therapy, and adaptive approaches based on EOC PET/CT response. These guidelines can be used by practitioners to provide appropriate treatment according to different disease scenarios.

Radiotherapy (RT) technology and utilization has considerably evolved over the last 50 years in the management of pediatric Hodgkin lymphoma (HL). In response to significant late effects from RT in HL survivors, clinical trials in the United States and Europe have evaluated ways to maintain high cure rates while reducing late toxicities from treatment. While numerous differences exist with respect to the RT guidelines embedded within therapeutic protocols across the cooperative groups, greater agreement is observed in the indications for RT, doses, volumes, and the incorporation of modern treatment modalities. This report provides an overview of RT delivery in pediatric HL protocols in the United States and Europe and examines areas of consensus on the utilization and delivery of RT in pediatric HL.

Purpose Early stage (stages I-II) classical Hodgkin lymphoma (cHL) is a highly curable disease typically diagnosed in adolescents and young adults (AYAs). Proton therapy can also reduce the late toxicity burden in this population, but data on its comparative efficacy with photon radiotherapy in this population are sparse. We assessed outcomes in AYAs with cHL in a multi-institution retrospective review. Materials and Methods We identified 94 patients aged 15 to 40 years with stages I and II cHL treated with radiotherapy as part of their initial treatment between 2008 and 2017. We used Kaplan-Meier analyses and log-rank testing to evaluate survival differences between groups of patients. Results A total of 91 patients were included in the analysis. The 2-year progression-free survival (PFS) rate was 89%. Of the 12 patients who experienced progression after radiotherapy, 4 occurred out-of-field, 2 occurred in-field, and 6 experienced both in- and out-of-field progression. There was no significant difference in 2-year PFS among AYA patients by radiotherapy dose received (≥ 30 Gy, 91%; Conclusion Our cohort of AYA patients had comparable outcomes regardless of radiotherapy dose or modality used. For patients with significant risk of radiation-induced late effects, proton therapy is a reasonable treatment modality.

Purpose The use of stereotactic body radiation therapy (SBRT) in pediatric patients has been underreported. We reviewed practice patterns, outcomes, and toxicity of SBRT in this population. Methods and Materials In this multi-institutional study, 55 patients with 107 non-central nervous system lesions treated with SBRT between 2010 and 2016 were reviewed. Treatment response was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST v1.1 criteria for soft-tissue and bone lesions, respectively. Patterns of local failure (LF) were assessed dosimetrically. The cumulative incidence of LF and toxicity were estimated accounting for the competing risk event of death. Predictors of LF were identified through joint frailty models for clustered competing risks. Results The median (range) dose/fraction was 7 (4.5-25) Gy, the total (range) dose/site was 35 (12-45), and the median (range) number of fractions was 5 (1-9). The radiographic response rates of bone and soft-tissue lesions were 90.6% and 76.7%, respectively. Symptom improvement was observed for 62% of symptomatic sites. A total of 27 LFs were documented, with 14 in-field, 9 marginal, and 4 out-of-field LFs. The 1-year estimated cumulative LF rate, progression-free survival, and overall survival were 25.2% (95% confidence interval [CI], 17.2%-36.1%), 17.5% (95% CI, 9.0%-34.1%), and 61% (95% CI, 48.9%-76.1%), respectively. Lesion type (soft tissue vs bone) was the only significant predictor of LF on multivariable analysis (P = .04), with increased hazard for soft-tissue lesions. No acute or late toxicity of grade 4 or higher was observed; the estimated 1-year cumulative incidence of late toxicity of any grade was 7.5% (95% CI, 3.6%-12.1%). Conclusions The SBRT was well tolerated and resulted in radiographic response and symptom palliation in most pediatric patients with advanced disease. The 1-year cumulative LF rate of 25% will serve as a benchmark for further modifications to radiation therapy indications, parameters, and combination therapy.

Little is known about the prevalence of pediatric radiation oncologists treating patients off study according to Children's Oncology Group (COG) trials before data are available regarding toxicity and efficacy of novel radiotherapy regimens. We conducted a 12-question survey of 358 pediatric radiation oncologists to characterize practice patterns regarding ongoing and completed COG protocols off study. With 130 responses (40.3%), the prevalence of providing treatment per protocol, but off study, before data are available in abstract or peer-reviewed form varied from 9.1% (for ACNS1422) to 88.1% (for AHOD1331). Future studies are needed to understand the effects of these practice patterns on outcomes.

Purpose: Patients with large, high-grade soft tissue sarcomas are commonly treated with aggressive limb preservation regimens. This study aimed to assess cancer control outcomes of patients treated with neoadjuvant chemoradiation (CRT) compared with radiation therapy (RT) alone. Methods: We reviewed records of patients with high-grade extremity or trunk soft tissue sarcomas ≥5 cm who were treated with neoadjuvant radiation with or without chemotherapy. Patient and disease characteristics were compared using t test and χ2 tests. Standardized mortality ratio weighted method was used to compare overall survival (OS), local control, and disease-free (DFS) survival. Acute radiation and surgical toxicity were reported. Results: In the study, 64 patients (34 CRT and 30 RT) treated between 1997 and 2015 were analyzed. In the RT group compared with the CRT group, the patient population was older, with a median age of 65 versus 50 years (P < .001), and more likely to have cardiovascular disease (CVD; 30% vs 0%, P < .001). At a median follow-up of 41 months, after adjusting for propensity score of receiving RT, the 3-year LC was 87.3% versus 86.1%, DFS was 58.5% versus 56.6%, and OS was 75.6% versus 69.0% for the CRT and RT groups, respectively (P > .05). Acute dermatitis occurred in 18% versus 3% and surgical complications occurred in 32% versus 17% of CRT and RT patients, respectively. Conclusions: In this study, patients receiving RT alone were more likely to be older and have comorbid cardiovascular disease. When controlling for baseline differences, neoadjuvant CRT and RT provided similar rates of LC, DFS, and OS.

Radiation therapy (RT) for the management of lymphoma has evolved over the past few decades. Large, extended, or involved fields have been replaced by smaller involved sites or nodal volumes. Currently, customized plans are created for each individual patient, and these plans encompass only the areas involved by disease. A critical factor that has enabled this shift in practice is the evolving use of imaging studies. Imaging plays a key role in patient selection and RT planning and delivery. The objective of this manuscript is to provide guidelines for best practice of use of imaging in pretreatment evaluation, treatment choice, RT target volume definition, and RT treatment verification and delivery.

Radiation therapy (RT) provides an effective and often rapid means to alleviate symptomatic progression in pediatric patients with advanced or metastatic cancer. As part of a comprehensive, multimodality approach to pediatric palliative care, RT can be a useful tool to manage pain, spinal cord compression, dyspnea, neurologic compromise, bleeding, and bowel or urinary obstruction. Whether such symptoms present earlier in the disease course or in children and adolescents approaching the end of life, they can significantly impact the quality of life of patients and caregivers. Control of symptoms is therefore an important aspect in maximizing end of life care. Outcomes for palliative RT in both children and adults are favorable. While RT has been widely adopted as a component of palliative oncologic care for many adult malignancies, it remains infrequently utilized in pediatric patients despite the relative radiosensitivity of many pediatric tumors. Potential barriers to palliative radiation for pediatric patients include insufficient understanding by care providers regarding the utility of RT for a given symptom, lack of comfort in discussing a transition away from definitive management, concern over radiation-related side effects, and hesitancy toward radiation treatment on the part of parents and caregivers. Delivery of palliative RT can also be impeded by logistical obstacles including lack of on-site radiation facilities, unavailability of radiation oncologists comfortable with pediatric treatments, and the potential need for specialized medical care such as pediatric anesthesia. The aim of this review is to foster a more complete understanding of the benefits and limitations of palliative RT in the pediatric oncology setting, including common symptoms experienced by children and adolescents with cancer that may be indications for the integration of RT into palliative care paradigms, as well as the expected efficacy of treatment. We describe the logistics, delivery, common doses for palliative radiation regimens, and management of potential side effects. While palliative RT is generally well tolerated in the pediatric population, we also discuss potential side effects of RT to various body sites and approaches for prevention or mitigation.

AIM AND BACKGROUND: We describe a successful implementation of a departmental incident learning system (ILS) across a regionally expanding academic radiation oncology department, dovetailing with a structured integration of the safety and quality program across clinical sites. MATERIALS AND METHODS M: Over 6 years between 2011 and 2017, a long-standing departmental ILS was deployed to 4 clinical locations beyond the primary clinical location where it had been established. We queried all events reported to the ILS during this period and analyzed trends in reporting by clinical site. The chi-square test was used to determine whether differences over time in the rate of reporting were statistically significant. We describe a synchronous development of a common safety and quality program over the same period. RESULTS: There was an overall increase in the number of event reports from each location over the time period from 2011 to 2017. The percentage increase in reported events from the first year of implementation to 2017 was 457% in site 1, 166.7% in site 2, 194.3% in site 3, 1025% in site 4, and 633.3% in site 5, with an overall increase of 677.7%. A statistically significant increase in the rate of reporting was seen from the first year of implementation to 2017 (p

Purpose The purpose of this study was to characterize and evaluate the clinical significance of volume changes of soft tissue sarcomas during radiation therapy (RT), prior to definitive surgical resection. Materials and methods Patients with extremity or pelvis soft tissue sarcomas treated at our institution from 2013 to 2016 with RT prior to resection were identified retrospectively. Tumor volumes were measured using cone-beam computed tomography obtained daily during RT. Linear regression evaluated the linearity of volume changes. Kruskal-Wallis tests, Mann-Whitney U tests, and linear regression evaluated predictors of volume change. Logistic and Cox regression evaluated volume change as a predictor of resection margin status, histologic treatment response, and tumor recurrence. Results Thirty-three patients were evaluated. Twenty-nine tumors were high grade. Prior to RT, median tumor volume was 189 mL (range, 7.2 to 4,885 mL). Sixteen tumors demonstrated significant linear volume changes during RT. Of these, 5 tumors increased and 11 decreased in volume. Myxoid liposarcoma (n = 5, 15%) predicted decreasing tumor volume (p = 0.0002). Sequential chemoradiation (n = 4, 12%) predicted increasing tumor volume (p = 0.008) and corresponded to longer times from diagnosis to RT (p = 0.01). Resection margins were positive in three cases. Five patients experienced local recurrence, and 7 experienced distant recurrence, at median 8.9 and 6.9 months post-resection, respectively. Volume changes did not predict resection margin status, local recurrence, or distant recurrence. Conclusion Volume changes of pelvis and extremity soft tissue sarcomas followed linear trends during RT. Volume changes reflected histologic subtype and treatment characteristics but did not predict margin status or recurrence after resection.

With the increasing use of advanced radiation techniques such as intensity modulated radiation therapy, stereotactic radiation therapy, and proton therapy, radiation oncologists now have the tools to mitigate radiation-associated toxicities. This is of utmost importance in the treatment of a pediatric patient. To best use these advanced techniques to mitigate radiation-induced growth abnormalities, the radiation oncologist should be equipped with a nuanced understanding of the anatomy of centers of growth. This article aims to enable the radiation oncologist to better understand, predict, and minimize radiation-mediated toxicities on growth. We review the process of bone development and radiation-induced growth abnormalities and provide an atlas for contouring important growth plates to guide radiation treatment planning. A more detailed recognition of important centers of growth may improve future treatment outcomes in children receiving radiation therapy.

Non-rhabdomyosarcoma soft-tissue sarcomas (NRSTS) comprise 4% of childhood cancers and consist of numerous histologic subtypes. Prognostic factors associated with poor outcome include high histologic grade, large tumor size, presence of metastases, and unresectability. Complete surgical resection is critical for the best oncologic outcomes and is prioritized in treatment algorithms. The use of radiation therapy (RT) and chemotherapy is based upon factors such as resectability, histologic grade, tumor size, and stage. North American and European trials are defining a risk-based approach to NRSTS to limit treatment-related toxicity and to maximize therapeutic efficacy. In this paper, we summarize the current roles of surgery, RT, and chemotherapy in NRSTS and describe ongoing research that is advancing the care of NRSTS patients.

PURPOSE/OBJECTIVE(S) To evaluate the relationship between total body irradiation (TBI) and other factors in the development of idiopathic pneumonia syndrome (IPS) in pediatric patients undergoing allogeneic hematopoietic cell transplantation (HCT) for acute leukemia. MATERIALS/METHODS Between 2006-2019, 121 pediatric patients with acute leukemia (84 lymphoblastic, 37 myeloid), ranging in age from 1 to 21 years (median 12), underwent allogeneic HCT at a single institution with matched sibling (n = 33), single unrelated cord blood (sUCB; n = 57), or double unrelated cord blood (dUCB; n = 31) donor. Pretransplantation conditioning included cyclophosphamide (100-120 mg/kg) with (n = 89) or without fludarabine (75 mg/m2) (n = 32). TBI was delivered in 8 b.i.d. fractions of 1.65 Gy over 4 days via opposed lateral beams of 6, 18, or 25 MV prescribed to midplane at umbilicus, with the patient in a semi-recumbent position, and without lung shielding. Aluminum lung compensator was utilized if predicted mid-lung point dose was ≥3% higher than prescription dose (n = 28). Dose rate was specified at 9-20 cGy/min and depended on linear accelerator availability. Patients were stratified by receipt of high-dose-rate (HDR; > 15 cGy/min; 36%) or low-dose-rate (LDR; ≤15 cGy/min; 64%) delivery. IPS was defined as pulmonary injury based on clinical symptoms, radiographic evidence, or pulmonary function testing within 100 days of HCT in the absence of concurrent infection. The association between treatment factors and IPS was examined. RESULTS Overall, IPS developed in 22 (18%) patients from day 6 to 83 (median 20) after HCT. On univariate analysis, factors associated with IPS included donor type (matched sibling 12%, sUCB 12%, dUCB 35%, P < 0.01), HDR TBI (35% vs 9% for LDR, P < 0.01), and lower beam energy (35% for 6 MV and 15% for 18/25 MV, P = 0.04). The finding of beam energy significance is likely the result of the 6 MV cohort having a greater dose rate (median 16 cGy/min) than the 18/25 MV cohort (11 cGy/min). On competing risk regression analysis, the pre-specified factors of dose rate, beam energy, lung compensator, age, HCT comorbidity index, and donor type were included in the model. All factors except age (hazard ratio [HR] 1.09, P = 0.20) and lung compensator (HR 1.8, P = 0.17) showed an independent statistically significant association with IPS. Kaplan-Meier estimated 1-year survival was 73% for the entire cohort. Time-dependent effect of IPS did not show an association with overall survival (HR 1.2, P = 0.76). CONCLUSION TBI dose rate is an important variable in the risk of pulmonary toxicity in children treated with allogeneic HCT. TBI dose rates ≤15 cGy/min reduced the risk of posttransplantation IPS and should be strongly considered as an easily implemented parameter in pre-transplantation TBI-based conditioning.

PURPOSE/OBJECTIVE(S) Renal dysfunction after hematopoietic cell transplantation (HCT) is a multi-factorial disorder. Studies have linked dose and fractionation with the incidence of late renal dysfunction in patients who underwent total body irradiation (TBI)-based myeloablative conditioning, but the effect of dose rate remains under studied. We conducted a single-institution retrospective study to elucidate the effect of TBI parameters and peri-HCT factors on late renal dysfunction among pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML) after allogeneic HCT. MATERIALS/METHODS 123 patients (age 1-22) with acute leukemia (38 AML, 85 ALL) underwent HCT using a TBI-based regimen at our institution from 2006-2019. HCT conditioning regimen included cyclophosphamide with or without fludarabine followed by TBI (13.2 Gy in 8 twice-daily fractions over 4 days). TBI dose rate was limited to 15 cGy/min; 35%) or low-dose-rate (LDR; ≤15 cGy/min; 65%) TBI. All patients received a calcineurin inhibitor to prevent graft-versus-host disease (GVHD). Serum creatinine (Cr) was recorded at baseline and trended post-HCT. Late renal dysfunction was defined as persistent increase of Cr > 1.2 mg/dL or ≥ 1.25 times the upper limit of age-dependent normal, onset ≥ 3 months after HCT. Using a statistical software, dichotomous variables were tested using Chi-square or Fisher's exact test; and continuous variables using Wilcoxon rank-sum test. Univariate and multivariate analyses were used to examine the association of these variables with late renal dysfunction. RESULTS A total of 14 patients developed late renal dysfunction (11%): 6/38 patients in HDR group (14%) vs. 8/79 patients in LDR group (10%, P = 0.03). Comparison between HDR and LDR groups found no difference in age, sex, remission status, HCT comorbidity index (HCT-CI, predictive of late organ dysfunctions, factoring in baseline Cr) or baseline Cr. More patients in the HDR group were cord blood recipients taking cyclosporine/mycophenolate mofetil (37% vs. 19% in LDR, P 12), intermediate-high HCT-CI (22% vs. 6% low HCT-CI) and HDR (24% vs. 8% in LDR). On multivariate regression, late renal dysfunction remained associated with age, HCT-CI, and HDR (P = 0.01, 0.02, and < 0.01 respectively). CONCLUSION Patient's age ≤12 at HCT, intermediate-high HCT-CI, and HDR were associated with late renal dysfunction post-HCT. Since dose rate is the only modifiable factor, adoption of LDR TBI is recommended.

We present the case of a 79-year-old male, who was initially treated for mucosa-associated lymphoid tissue lymphoma (MALT lymphoma) of the right eyelid, and later for disease relapse in the stomach. During follow up, he was noted to have developed left arm nodules just medial to the proximal biceps muscle, which were found to be multiply enlarged lymph nodes on subsequent ultrasound imaging. Excisional biopsy of these nodes revealed MALT lymphoma. He was initially referred for consideration of radiation, but a restaging F-18 fluorodeoxyglucose positron emission tomography integrated with computed tomography (F-18 FDG PET/CT) further identified a focus of suspicious uptake in left calf, which was later also biopsy proven to be MALT lymphoma. His disease was upstaged as the result of this later finding, and the overall recommendation for treatment changed to favor systemic treatment with Rituximab.

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

Background. The majority of patients with localized Ewing sarcoma will remain disease-free long term, but for those who suffer recurrence, successful treatment remains a challenge. Identification of clinicopathologic factors predictive of recurrence could suggest areas for treatment optimization. We sought to describe our experience regarding predictors of recurrence and patterns of first failure in patients receiving modern systemic therapy for nonmetastatic Ewing sarcoma. Methods. The medical records of pediatric and adult patients treated for localized Ewing sarcoma between 1999 and 2019 at Johns Hopkins Hospital were retrospectively analyzed. Local control was surgery, radiotherapy, or both. Recurrence-free survival (RFS) was calculated using the Kaplan–Meier method. Univariable and multivariable Cox proportional-hazards modeling was performed to obtain hazard ratios (HR) for recurrence. Results. In 94 patients with initially localized disease, there were 21 recurrences: 4 local, 14 distant, and 3 combined. 5-year and 10-year RFS were 75.6% and 70.5%, respectively. On multivariable analysis including age at diagnosis and tumor size

PURPOSE: Numerous publications during the COVID-19 pandemic recommended the use of hypofractionated radiation therapy. This project assessed aggregate changes in the quality of the evidence supporting these schedules to establish a comprehensive evidence base for future reference and highlight aspects for future study. METHODS AND MATERIALS: Based on a systematic review of published recommendations related to dose fractionation during the COVID-19 pandemic, 20 expert panelists assigned to 14 disease groups named and graded the highest quality of evidence schedule(s) used routinely for each condition and also graded all COVID-era recommended schedules. The American Society for Radiation Oncology quality of evidence criteria were used to rank the schedules. Process-related statistics and changes in distributions of quality ratings of the highest-rated versus recommended COVID-19 era schedules were described by disease groups and for specific clinical scenarios. RESULTS: From January to May 2020 there were 54 relevant publications, including 233 recommended COVID-19-adapted dose fractionations. For site-specific curative and site-specific palliative schedules, there was a significant shift from established higher-quality evidence to lower-quality evidence and expert opinions for the recommended schedules (P = .022 and P < .001, respectively). For curative-intent schedules, the distribution of quality scores was essentially reversed (highest levels of evidence "pre-COVID" vs "in-COVID": high quality, 51.4% vs 4.8%; expert opinion, 5.6% vs 49.3%), although there was variation in the magnitude of shifts between disease sites and among specific indications. CONCLUSIONS: A large number of publications recommended hypofractionated radiation therapy schedules across numerous major disease sites during the COVID-19 pandemic, which were supported by a lower quality of evidence than the highest-quality routinely used dose fractionation schedules. This work provides an evidence-based assessment of these potentially practice-changing recommendations and informs individualized decision-making and counseling of patients. These data could also be used to support radiation therapy practices in the event of second waves or surges of the pandemic in new regions of the world.

This quality improvement study examines disparities in proton radiotherapy use in patients enrolled in Children’s Oncology Group Trials

BackgroundOutcomes for children and adults with advanced soft tissue sarcoma are poor with traditional therapy. We investigated whether the addition of pazopanib to preoperative chemoradiotherapy would improve pathological near complete response rate compared with chemoradiotherapy alone.MethodsIn this joint Children's Oncology Group and NRG Oncology multicentre, randomised, open-label, phase 2 trial, we enrolled eligible adults (aged ≥18 years) and children (aged between 2 and 16 years) performance status score of at least 70. Patients received ifosfamide (2·5 g/m2 per dose intravenously on days 1-3 with mesna) and doxorubicin (37·5 mg/m2 per dose intravenously on days 1-2) with 45 Gy preoperative radiotherapy, followed by surgical resection at week 13. Patients were randomly assigned (1:1) using a web-based system, in an unmasked manner, to receive oral pazopanib (if patients

Background: Lower-dose cone-beam computed tomography protocols for image-guided radiotherapy may permit target localization while minimizing radiation exposure. We prospectively evaluated a lower-dose cone-beam protocol for central nervous system image-guided radiotherapy across a multinational pediatrics consortium. Methods: Seven institutions prospectively employed a lower-dose cone-beam computed tomography central nervous system protocol (weighted average dose 0.7 mGy) for patients ≤21 years. Treatment table shifts between setup with surface lasers versus cone-beam computed tomography were used to approximate setup accuracy, and vector magnitudes for these shifts were calculated. Setup group mean, interpatient, interinstitution, and random error were estimated, and clinical factors were compared by mixed linear modeling. Results: Among 96 patients, with 2179 pretreatment cone-beam computed tomography acquisitions, median age was 9 years (1-20). Setup parameters were 3.13, 3.02, 1.64, and 1.48 mm for vector magnitude group mean, interpatient, interinstitution, and random error, respectively. On multivariable analysis, there were no significant differences in mean vector magnitude by age, gender, performance status, target location, extent of resection, chemotherapy, or steroid or anesthesia use. Providers rated >99% of images as adequate or better for target localization. Conclusions: A lower-dose cone-beam computed tomography protocol demonstrated table shift vector magnitude that approximate clinical target volume/planning target volume expansions used in central nervous system radiotherapy. There were no significant clinical predictors of setup accuracy identified, supporting use of this lower-dose cone-beam computed tomography protocol across a diverse pediatric population with brain tumors.

Local ablative treatment to oligometastatic patients can result in long-term disease-free survival in some cancer patients. The importance of this treatment paradigm in prostate cancer is a rapidly evolving field. Herein, we report on the safety and preliminary clinical outcomes of a modern cohort of oligometastatic prostate cancer (OPC) patients treated with consolidative stereotactic ablative radiation (SABR). Records of men with OPC who underwent consolidative SABR at our institution were reviewed. SABR was delivered in 1–5 fractions of 5–18 Gray. Kaplan–Meier estimates of local progression-free survival (LPFS), biochemical progression-free survival (bPFS; PSA nadir + 2), distant progression-free survival (DPFS), and time-to-next intervention (TTNI) were calculated. In total, 66 OPC patients were identified with consolidative SABR delivered to 134 metastases: 89 bone, 40 nodal, and 5 viscera. The majority of men (49/66) had hormone-sensitive prostate cancer (HSPC). Crude grade 1 and 2 acute toxicities were 36% and 11%, respectively, with no ≥ grade 3 toxicity. At 1 year, LPFS was 92% and bPFS and DPFS were 69%. Of the 18 men with HSPC who had deferred hormone therapy , 11 (56%) remain disease free following SABR (1-year ADT-FS was 78%). In 17 castration-resistant men, 11 had > 50% prostate-specific antigen (PSA) declines with 1-year TTNI of 30%. Consolidative SABR in OPC is feasible and well tolerated. The heterogeneity and small size of our series limit extrapolation of clinically meaningful outcomes following consolidative SABR in OPC, but our preliminary data suggest that this approach warrants continued prospective study.

Background Physicians and physicists are expected to contribute to patient safety and quality improvement (QI) in Radiation Oncology (RO), but prior studies suggest that training for this may be inadequate. RO and medical physics (MP) program directors (PDs) were surveyed to better understand the current patient safety/QI training in their residency programs. Methods PDs were surveyed via email in January 2017. Survey questions inquired about current training, curriculum elements, and barriers to development and/or improvement of safety and QI training. Results Eighty-nine RO PDs and 84 MP PDs were surveyed, and 21 RO PDs (28%) and 31 MP PDs (37%) responded. Both RO and MP PDs had favorable opinions of current safety and QI training, and used a range of resources for program development, especially safety and QI publications. Various curriculum elements were reported. Curriculum elements used by RO and MP PDs were similar, except RO were more likely than MP PDs to implement morbidity and mortality (M&M) conference (72% vs. 45%, p

Purpose Brain radiation is associated with functional deficits in children. The purpose of this study was to examine white matter integrity as measured by diffusion tensor imaging and associations with region-specific radiation dose and neuropsychological functioning in children treated with cranial irradiation. Methods and Materials A total of 20 patients and 55 age- and sex-matched controls were included in the present study. Diffusion tensor imaging and neuropsychological assessments were conducted at baseline and 6, 15, and 27 months after treatment. The neuropsychological assessment included motor dexterity, working memory, and processing speed. White matter regions were contoured, and the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) were recorded for each participant. Linear mixed effects regression models were used to prospectively compare the associations among ADC, FA, radiation dose to contoured structures, and performance on the neuropsychological assessments over time. Results The mean prescription dose was 44 Gy (range 12-54). Across visits, compared with the controls, the patients showed a significantly increased ADC across all selected regions and alterations in FA in the dorsal midbrain and corpus callosum (genu, splenium, body). An increased radiation dose to the genu and body of the corpus callosum was associated with alterations in ADC and FA and reduced neuropsychological performance, most notably motor speed and processing. Conclusions These prospective data suggest that subcortical white matter, especially the genu and body of the corpus callosum, could be regions with increased susceptibility to radiation-induced injury, with implications for cognitive function.

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 Proton therapy can allow for superior avoidance of normal tissues. A widespread consensus has been reached that proton therapy should be used for patients with curable pediatric brain tumor to avoid critical central nervous system structures. Brainstem necrosis is a potentially devastating, but rare, complication of radiation. Recent reports of brainstem necrosis after proton therapy have raised concerns over the potential biological differences among radiation modalities. We have summarized findings from the National Cancer Institute Workshop on Proton Therapy for Children convened in May 2016 to examine brainstem injury. Methods and Materials Twenty-seven physicians, physicists, and researchers from 17 institutions with expertise met to discuss this issue. The definition of brainstem injury, imaging of this entity, clinical experience with photons and photons, and potential biological differences among these radiation modalities were thoroughly discussed and reviewed. The 3 largest US pediatric proton therapy centers collectively summarized the incidence of symptomatic brainstem injury and physics details (planning, dosimetry, delivery) for 671 children with focal posterior fossa tumors treated with protons from 2006 to 2016. Results The average rate of symptomatic brainstem toxicity from the 3 largest US pediatric proton centers was 2.38%. The actuarial rate of grade ≥2 brainstem toxicity was successfully reduced from 12.7% to 0% at 1 center after adopting modified radiation guidelines. Guidelines for treatment planning and current consensus brainstem constraints for proton therapy are presented. The current knowledge regarding linear energy transfer (LET) and its relationship to relative biological effectiveness (RBE) are defined. We review the current state of LET-based planning. Conclusions Brainstem injury is a rare complication of radiation therapy for both photons and protons. Substantial dosimetric data have been collected for brainstem injury after proton therapy, and established guidelines to allow for safe delivery of proton radiation have been defined. Increased capability exists to incorporate LET optimization; however, further research is needed to fully explore the capabilities of LET- and RBE-based planning.

Purpose/Objective(s) Post-transplant lymphoproliferative disease (PTLD) is a rare disease complicating solid organ transplantation (SOT) and hematopoietic cell transplantation (HCT). Management of PTLD includes immunosuppression reduction, systemic therapy, surgery and radiation therapy (RT). Data regarding the efficacy and outcomes of radiation therapy in treatment of PTLD is limited. Here, we report our institution's experience with the treatment of PTLD including RT outcomes. Materials/Methods We retrospectively reviewed patients with biopsy proven PTLD who were treated at our institution. After obtaining Institutional Review Board approval, patient demographics, disease characteristics, treatment modalities and follow-up data were recorded. Disease response before and after RT use was assessed per response evaluation criteria in solid tumors (RECIST) 1.1 including complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan Meier method. Cox Proportional Hazards models were utilized to determine variables associated with OS. Results We identified and reviewed medical records of 48 patients with PTLD. Median follow up was 38 months. The median age was 58 (range:10-81). The majority were white (79%) and male (56%). 50% of the cohort were SOT recipients, 44% were HCT recipients and 6% underwent combined transplants. The most common site of PTLD was CNS (29%). Monomorphic PTLD was the most common histological type with EBV positivity in 75% of patients. Median time from SOT-to-PTLD was 77 months (range:5-322) and HCT-to-PTLD was 5 months (range: 2-46). Systemic therapy was the most commonly used modality in 92% of patients. The most commonly used regimen was Rituximab monotherapy. Surgery was employed in 10% of patients. RT was utilized after induction therapy in 37.5%. The most common treated site was the brain (61%). Overall response of the entire cohort was 87% (58% CR and 29% PR), 6% achieved SD and 7% had PD. Among the RT cohort, 55% achieved CR, 33% achieved PR and 12% had SD. Local control rate was 100%. Of 21 patients who did not respond completely to induction therapy, 6 patients with initial PR achieved CR, 1 patient with initial SD achieved CR, 1 patient with initial PD achieved CR, and 2 patients with initial PD achieved PR and SD, respectively, after RT receipt. The median RT dose was 3,600 cGy (range: 2400-4600). 3- and 5-year PFS were 90% and 85%, respectively, while 3- and 5-year OS were 70% and 55%, respectively. Cox hazards modeling confirmed that HCT receipt was associated with better OS on multivariate analysis (HR 0.26, 95% CI 0.008- 0.671, P = 0.007). Conclusion RT provides excellent local control and improves overall disease response of PTLD. Further optimization and standardization of combined modality paradigms are needed to improve clinical outcomes of this rare entity.

BACKGROUND Proton radiotherapy remains a limited resource despite its clear potential for reducing radiation doses to normal tissues and late effects in children in comparison with photon therapy. This study examined the impact of race and socioeconomic factors on the use of proton therapy in children with solid malignancies. METHODS This study evaluated 12,101 children (age ≤ 21 years) in the National Cancer Data Base who had been diagnosed with a solid malignancy between 2004 and 2013 and had received photon- or proton-based radiotherapy. Logistic regression analysis was used to evaluate patient, tumor, and socioeconomic variables affecting treatment with proton radiotherapy versus photon radiotherapy. RESULTS Eight percent of the patients in the entire cohort received proton radiotherapy, and this proportion increased between 2004 (1.7%) and 2013 (17.5%). Proton therapy was more frequently used in younger patients (age ≤ 10 years; odds ratio [OR], 1.9; 95% confidence interval [CI], 1.6-2.2) and in patients with bone/joint primaries and ependymoma, medulloblastoma, and rhabdomyosarcoma histologies (P < .05). Patients with metastatic disease were less likely to receive proton therapy (OR, 0.4; 95% CI, 0.3-0.6). Patients with private/managed care were more likely than patients with Medicaid or no insurance to receive proton therapy (P < .0001). A higher median household income and educational attainment were also associated with increased proton use (P < .001). Patients treated with proton therapy versus photon therapy were more likely to travel more than 200 miles (13% vs 5%; P < .0001). CONCLUSIONS Socioeconomic factors affect the use of proton radiotherapy in children. Whether this disparity is related to differences in the referral patterns, the knowledge of treatment modalities, or the ability to travel for therapy needs to be further clarified. Improving access to proton therapy in underserved pediatric populations is essential. Cancer 2017;123:4048-56. © 2017 American Cancer Society.

Objectives High-grade soft-tissue sarcoma (STS) has a poor prognosis. The goal of this study was to review treatment outcomes of patients with high-grade STS treated with interdigitated neoadjuvant chemotherapy (CT) and radiation at our institution. Materials and methods Patients with high-grade STS (1997 to 2010) were planned for treatment with 3 cycles of neoadjuvant CT, interdigitated preoperative radiation therapy (44 Gy administered in split courses with a potential 16 Gy postoperative boost), and 3 cycles of postoperative CT. Cancer control outcomes at 3 years were analyzed. Results Sixteen patients with high-grade STS were evaluated. Median age was 53 years, the median longest tumor diameter was 14.6 cm, and median follow-up was 33 months. All 16 patients received 2 or 3 cycles of neoadjuvant CT and all patients completed neoadjuvant RT. The estimated 3-year rate for local control was 100%, disease-free survival 62.5%, and overall survival 73.4%. Conclusions Patients with high-grade STS treated with interdigitated neoadjuvant CT and radiation before surgical resection had excellent rates of local control, along with disease-free survival and overall survival similar to previously published reports. This combined-modality approach continues to have a role in the treatment of patients with high-grade STS.

PURPOSE Pediatric Spinal cord ependymoma (SCE) is rare, and the management is often heterogeneous across centers. We evaluated the impact of clinical, pathologic, and treatment-related factors on outcomes in a multi-institutional, international cohort. METHODS SCE patients age RESULTS 125 patients were identified, 18 (14.4%) with metastases. Initial surgery was GTR, and STR in 44, 56% of patients respectively. Histology was grade 1, 2, and 3 in 55, 17.7 and 23.2% respectively. 55 patients with initial GTR were observed (52.7%) or irradiated (43.6%); 60 patients had STR and were observed (40%) or irradiated (60%). The 7-year event-free (EFS) and overall survival (OS) was 60% (95% CI 51.5–71.4) and 79% (95% CI 71.1–87.8) respectively. STR and metastasis increased the hazard for death [HR 1.87, 95% CI 1.02–3.57, p=0.05 (vs. GTR)] and [HR 2.28, 95% CI 1.1–5.2, p=0.048 (vs. localized)] respectively. Across 43 failures, local failure predominated (48.8%). Distant and combined failure occurred in 30.2 and 13.9% respectively. Adjuvant RT offered a 20% absolute improvement (vs. observation) in EFS at 5 years regardless of extent of resection. RPA identified thoracic (vs. non-thoracic), grade (1 & 3 vs. 2), STR (vs. GTR) and metastases as determinants of inferior EFS. CONCLUSIONS Tumor and treatment-related factors are predictive of EFS. OS is favorable despite diverse schema and frequent distant failures.

Summary Background Although severe haemoglobinopathies can be cured with allogeneic blood or bone marrow transplantation, availability of matched donors and toxic effects can be problematic. We previously found that non-myeloablative haploidentical related bone marrow transplantation with post-transplantation cyclophosphamide expanded the donor pool while limiting graft-versus-host disease (GVHD). However, graft failure—albeit with full host haemopoietic recovery—occurred in 50% of patients. In this study, we investigated whether increasing total body irradiation from 200 cGy to 400 cGy would improve engraftment while maintaining the safety profile. Methods This study was done at Johns Hopkins Hospital (Baltimore, MD, USA). Patients aged 2–70 years receiving their first bone marrow transplant were eligible for inclusion in the study. Patients received rabbit-derived intravenous anti-thymocyte globulin 0·5 mg/kg on day −9 and 2 mg/kg on days −8 and −7, intravenous fludarabine 30 mg/m2 on days −6 to −2, intravenous cyclophosphamide 14·5 mg/kg on days −6 and −5, and total body irradiation 400 cGy administered as a single fraction on day −1. We collected unmanipulated bone marrow and infused on day 0. GVHD prophylaxis comprised intravenous cyclophosphamide 50 mg/kg per day on days 3 and 4 after transplantation, oral mycophenolate mofetil 15 mg/kg per dose (maximum 1 g) every 8 h on days 5 to 35, and oral sirolimus to maintain a level of 5–15 ng/dL for at least 1 year starting on day 5. The original planned primary objectives of this phase 2 clinical trial were transplant-related mortality and progression-free survival. However, the coverage decision by the Centers for Medicare and Medicaid Services to only provide payment for allogeneic bone marrow transplantation for patients with sickle cell disease on a clinical trial that had a comparison arm with patients not receiving bone marrow transplantation prompted the closure of this trial to accrual in 2017. Therefore, as we were unable to perform our planned statistical analysis, the primary objective was modified to evaluate engraftment, assessed by chimerism. This trial is registered with ClinicalTrials.gov , number NCT00489281 . The study is closed to new participants and this is the primary analysis. Findings Between Sept 24, 2014, and Aug 1, 2017, we enrolled 17 consecutive patients: 12 (71%) with sickle cell disease and 5 (29%) with β-thalassaemia major. The median patient age was 16 years (range 6–31, IQR 7·7–27·5). One (6%) of 17 patients had primary graft failure with recovery of host haemopoiesis. 13 (76%) of 17 patients achieved full donor chimerism and three (18%) had mixed donor-host chimerism. Five (29%) of 17 patients developed grade 2–4 acute GVHD, including four (24%) with maximal grade 2 GVHD and one (6%) with grade 3 GVHD. Chronic GVHD developed in three (18%) patients. As of their last follow-up visit, GVHD had resolved in all patients and no patients were receiving systemic GVHD therapy. All patients remained alive as of Aug 4, 2018, and the median follow-up duration was 705 days (range 355–1294; IQR 398–943). Only one (6%) of the 16 engrafted patients remained transfusion dependent, and 14 (88%) discontinued immunosuppression. Interpretation Increasing total body irradiation to 400 cGy substantially reduced graft failure while maintaining the safety of haploidentical bone marrow transplantation with post-transplantation cyclophosphamide. These results suggest that engraftment after haploidentical bone marrow transplantation for haemoglobinopathies is possible, and primary graft failure—the main problem previously reported—might be addressed by this strategy. Therefore, this curative approach should no longer be restricted to patients with HLA-matched donors. Funding Maryland Stem Cell Research Fund and US National Institutes of Health.

Importance Despite progress in narrowing gender-based salary gaps, notable disparities persist in the scientific community. The significance of pay difference may be underestimated, with little data evaluating its effect on lifetime wealth after accounting for factors like time to promotion and savings. Objectives To characterize gender disparities in salary and assess the outcomes associated with a gender equity initiative (GEI). Design, Setting, and Participants Quality improvement study with simulations of salary and additional accumulated wealth (AAW) using retrospectively reviewed Johns Hopkins University School of Medicine annual salary and promotion data. All academic faculty were included in the faculty salary analysis from 2005 (n = 1481) and 2016 (n = 1885). Main Outcomes and Measures Salary and longitudinal promotion data from 2005 to 2016 were used to estimate gender-based differences in salary and time to promotion. The effect of these differences on total salary and AAW, including retirement and salary-based investments, was simulated for a representative male and female faculty member over a 30-year career in 3 scenarios: (1) pre-GEI, (2) post-GEI, and (3) in real time for GEI, beginning with and progressing through these initiatives. Results Analyses of salaries of 1481 faculty (432 women) in 2005 and 1885 faculty (742 women) in 2016 revealed that a decade after GEI implementation, the overall mean (SE) salary gap by gender decreased from −2.6% (1.2%) (95% CI, −5.6% to −0.3%) to −1.9% (1.1%) (95% CI, −4.1% to 0.3%). Simulation of pre-GEI disparities correlated with male faculty collecting an average lifetime AAW of $501 416 more than the equivalent woman, with disparities persisting past retirement. The AAW gap decreased to $210 829 in the real-time GEI simulation and to $66 104 using post-GEI conditions, reflecting success of GEI efforts. Conclusions and Relevance Even small gender-based salary gaps are associated with substantial differences in lifetime wealth, but an institutional commitment to achieving equitable promotion and compensation for women can appreciably reduce these disparities. The findings of this study support broad implementation of similar initiatives without delay, as results may take more than a decade to emerge. A modifiable version of the simulation is provided so that external users may assess the potential disparities present within their own institutions.

Importance Standard chemotherapy for first relapse of B-cell acute lymphoblastic leukemia (B-ALL) in children, adolescents, and young adults is associated with high rates of severe toxicities, subsequent relapse, and death, especially for patients with early relapse (high risk) or late relapse with residual disease after reinduction chemotherapy (intermediate risk). Blinatumomab, a bispecific CD3 to CD19 T cell-engaging antibody construct, is efficacious in relapsed/refractory B-ALL and has a favorable toxicity profile. Objective To determine whether substituting blinatumomab for intensive chemotherapy in consolidation therapy would improve survival in children, adolescents, and young adults with high- and intermediate-risk first relapse of B-ALL. Design, setting, and participants This trial was a randomized phase 3 clinical trial conducted by the Children's Oncology Group at 155 hospitals in the US, Canada, Australia, and New Zealand with enrollment from December 2014 to September 2019 and follow-up until September 30, 2020. Eligible patients included those aged 1 to 30 years with B-ALL first relapse, excluding those with Down syndrome, Philadelphia chromosome-positive ALL, prior hematopoietic stem cell transplant, or prior blinatumomab treatment (n = 669). Interventions All patients received a 4-week reinduction chemotherapy course, followed by randomized assignment to receive 2 cycles of blinatumomab (n = 105) or 2 cycles of multiagent chemotherapy (n = 103), each followed by transplant. Main outcome and measures The primary end point was disease-free survival and the secondary end point was overall survival, both from the time of randomization. The threshold for statistical significance was set at a 1-sided P Results Among 208 randomized patients (median age, 9 years; 97 [47%] females), 118 (57%) completed the randomized therapy. Randomization was terminated at the recommendation of the data and safety monitoring committee without meeting stopping rules for efficacy or futility; at that point, 80 of 131 planned events occurred. With 2.9 years of median follow-up, 2-year disease-free survival was 54.4% for the blinatumomab group vs 39.0% for the chemotherapy group (hazard ratio for disease progression or mortality, 0.70 [95% CI, 0.47-1.03]); 1-sided P = .03). Two-year overall survival was 71.3% for the blinatumomab group vs 58.4% for the chemotherapy group (hazard ratio for mortality, 0.62 [95% CI, 0.39-0.98]; 1-sided P = .02). Rates of notable serious adverse events included infection (15%), febrile neutropenia (5%), sepsis (2%), and mucositis (1%) for the blinatumomab group and infection (65%), febrile neutropenia (58%), sepsis (27%), and mucositis (28%) for the chemotherapy group. Conclusions and relevance Among children, adolescents, and young adults with high- and intermediate-risk first relapse of B-ALL, postreinduction treatment with blinatumomab compared with chemotherapy, followed by transplant, did not result in a statistically significant difference in disease-free survival. However, study interpretation is limited by early termination with possible underpowering for the primary end point. Trial registration ClinicalTrials.gov Identifier: NCT02101853.

This topic addresses the treatment of newly diagnosed patients with favorable prognosis stage I and II Hodgkin lymphoma. In most cases, combined modality therapy (chemotherapy followed by involved site radiation therapy) constitutes the current standard of care. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. By combining the most recent medical literature and expert opinion, this revised guideline can aid clinicians in the appropriate use of combined modality therapy for favorable prognosis stage I and II Hodgkin lymphoma. Increasing information about the late effects of treatment has led to attempts to decrease toxicity by using less chemotherapy (decreased duration and/or intensity or different agents) and less radiation therapy (reduced volume and/or dose) while maintaining excellent efficacy.

Patients requiring desensitization prior to renal transplantation are at risk for developing severe antibody-mediated rejection (AMR) refractory to treatment with plasmapheresis and intravenous immunoglobulin (PP/IVIg). We have previously reported success at graft salvage, long-term graft survival and protection against transplant glomerulopathy with the use of eculizumab and splenectomy in addition to PP/IVIg. Splenectomy may be an important component of this combination therapy and is itself associated with a marked reduction in donor-specific antibody (DSA) production. However, splenectomy represents a major operation, and some patients with severe AMR have comorbid conditions that substantially increase their risk of complications during and after surgery. In an effort to spare recipients the morbidity of a second operation, we used splenic irradiation in lieu of splenectomy in two incompatible live donor kidney transplant recipients with severe AMR in addition to PP/IVIg, rituximab and eculizumab. This novel approach to the treatment of severe AMR was associated with allograft salvage, excellent graft function and no short- or medium-term adverse effects of the radiation therapy. One-year surveillance biopsies did not show transplant glomerulopathy (tg) on light microscopy, but microcirculation inflammation and tg were present on electron microscopy.

BACKGROUND Cranial radiation therapy (RT) is an important component in the treatment of pediatric brain tumors. However, it can result in long-term effects on the developing brain. This prospective study assessed the effects of cranial RT on cerebral, frontal lobe, and temporal lobe volumes and their correlation with higher cognitive functioning. METHODS Ten pediatric patients with primary brain tumors treated with cranial RT and 14 age- and sex-matched healthy children serving as controls were evaluated. Quantitative magnetic resonance imaging and neuropsychological assessments (language, memory, auditory and visual processing, and vocabulary) were performed at the baseline and 6, 15, and 27 months after RT. The effects of age, the time since RT, and the cerebral RT dose on brain volumes and neuropsychological performance were analyzed with linear mixed effects model analyses. RESULTS Cerebral volume increased significantly with age in both groups (P = .01); this increase in volume was more pronounced in younger children. Vocabulary performance was found to be significantly associated with a greater cerebral volume (P = .05) and a lower RT dose (P = .003). No relation was observed between the RT dose and the cerebral volume. There was no difference in the corresponding neuropsychological tests between the 2 groups. CONCLUSIONS This prospective study found significant relations among the RT dose, cerebral volumes, and rate of vocabulary development among children receiving RT. The results of this study provide further support for clinical trials aimed at reducing cranial RT doses in the pediatric population. Cancer 2016. © 2016 American Cancer Society.

Background Retroperitoneal sarcomas are connective tissue tumors arising in the retroperitoneum. Surgical resection is the mainstay of treatment. Debate has arisen over extent of resection, changes in histological classification/grading, and interest in incorporating radiotherapy. Therefore, we reviewed our institution's experience to evaluate prognostic factors. Methods Retrospective chart review of all primary RPS patients at Johns Hopkins Hospital from 1994 to 2010. Histologic diagnosis and grading were re-evaluated with current criteria. Prognostic factors for survival, and recurrence were assessed. Results One hundred thirty-one primary RPS patients met inclusion criteria. Median survival for patients who undergo en-bloc resection to negative margins (R0/R1) is 81.7 months. Surgical margins and grade were the most important factors for survival along with age, gender, presence of metastases and resection of ≥5 organs. Five-year survival for R0/R1 resection was 60%, similar to compartmental resection. Radiotherapy significantly decreased local recurrence (P = 0.026) on multivariate analysis. Grade in leiomyosarcomas and dedifferentiation in liposarcomas dictated patterns of local versus distal recurrence. Conclusions En bloc surgical resection to R0/R1 margins remains the cornerstone of therapy and provides comparable outcomes to compartmental resections. Grade remains important for prognosis, and histology dictates recurrence patterns. Radiotherapy appears promising for local control and warrants further investigation. J. Surg. Oncol. 2016;114:56–64. © 2016 Wiley Periodicals, Inc.