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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 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.

Purpose This multi-institutional retrospective study sought to examine the hematologic effects of craniospinal irradiation (CSI) in pediatric patients with medulloblastoma using proton or photon therapy. Methods and Materials Clinical and treatment characteristics were recorded for 97 pediatric patients with medulloblastoma who received CSI without concurrent chemotherapy or with concurrent single-agent vincristine from 2000 to 2017. Groups of 60 and 37 patients underwent treatment with proton-based and photon-based therapy, respectively. Overall survival was determined by Kaplan-Meier curves with log-rank test. Comparisons of blood counts at each timepoint were conducted using multiple t tests with Bonferroni corrections. Univariate and multivariate analyses of time to grade ≥3 hematologic toxicity were performed with Cox regression analyses. Results Median age of patients receiving proton and photon CSI was 7.5 years (range, 3.5-22.7 years) and 9.9 years (range, 3.6-19.5 years), respectively. Most patients had a diagnosis of standard risk medulloblastoma, with 86.7% and 89.2% for the proton and photon cohorts, respectively. Median total dose to involved field or whole posterior fossa was 54.0 Gy/Gy relative biological effectiveness (RBE) and median CSI dose was 23.4 Gy/Gy(RBE) (range, 18-36 Gy/Gy[RBE]) for both cohorts. Counts were significantly higher in the proton cohort compared with the photon cohort in weeks 3 to 6 of radiation therapy (RT). Although white blood cell counts did not differ between the 2 cohorts, patients receiving proton RT had significantly higher lymphocyte counts throughout the RT course. Similar results were observed when excluding patients who received vertebral body sparing proton RT or limiting to those receiving 23.4 Gy. Only photon therapy was associated with decreased time to grade ≥3 hematologic toxicity on univariate and multivariable analyses. No difference in overall survival was observed, and lymphopenia did not predict survival. Conclusions Patients who receive CSI using proton therapy experience significantly decreased hematologic toxicity compared with those receiving photon therapy.

Brainstem necrosis is a rare, but dreaded complication of radiation therapy; however, data on the incidence of brainstem injury for tumors involving the posterior fossa in photon-treated patient cohorts are still needed.Clinical characteristics and dosimetric parameters were recorded for 107 pediatric patients who received photon radiation for posterior fossa tumors without brainstem involvement from 2000 to 2016. Patients were excluded if they received a prescription dose50.4 Gy, a brainstem maximum dose50.4 Gy, or had fewer than 2 magnetic resonance imaging scans within 18 months after radiation. Post-radiation therapy magnetic resonance imaging findings were recorded, and brainstem toxicity was graded using National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.The most common histologies were medulloblastoma (61.7%) and ependymoma (15.9%), and median age at diagnosis was 8.3 years (range, 0.8-20.7). Sixty-seven patients (62.6%) received craniospinal irradiation (median, 23.4 Gy; range, 18.0-39.6) as a component of their radiation therapy, and 39.3% and 40.2% of patients received an additional involved field or whole posterior fossa boost, respectively. Median prescribed dose was 55.8 Gy (range, 50.4-60.0). Median clinical and imaging follow-up were 4.7 years (range, 0.1-17.5) and 4.2 years (range, 0.1-17.3), respectively. No grade ≥2 toxicities were observed. The incidence of grade 1 brainstem necrosis was 1.9% (2 of 107). These patients were by definition asymptomatic and experienced resolution of imaging abnormality after 5.3 months and 2.1 years, respectively.Risk of brainstem necrosis was minimal in this multi-institutional study of pediatric patients treated with photon radiation therapy for tumors involving the posterior fossa with no cases of symptomatic brainstem injury, suggesting that brainstem injury risk is minimal in patients treated with photon therapy.

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.

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.

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

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.

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.

A pay gap between men and women has been identified in many medical specialties. However, radiation oncology has been excluded from most analyses. This study sought to determine whether such a disparity exists among physicians in US public academic radiation oncology departments.Radiation oncology physician faculty at US public academic medical schools were identified in states that report public university radiation oncology faculty salary. Information pertaining to sex, academic rank, experience, clinical volume, and academic productivity were collected. Simple (1 predictor) and multiple (more than 1 predictor) generalized linear mixed-effect models for compensation were used to simultaneously assess the impact of physician-level and institutional-level variables, while accounting for potential correlations within institutions. To minimize the impact of faculty members working less than a full-time equivalent, a Monte Carlo simulation-based sensitivity analysis was conducted, and faculty with reported salaries under $175,000 were excluded.A total of 247 eligible faculty (81 women, 166 men) with public salary data were identified at 22 US public academic radiation oncology departments in 14 states. Unadjusted mean salary was 12.6% ($48,974) lower for women ($341,173; 95% confidence interval [CI], $304,581-$382,162) than it was for men ($390,147; 95% CI, $353,693-$430,358; P .01). A $26,458 gap (6.4%) in mean salary between men ($411,829; 95% CI, $367,282-$461,780) and women ($385,371; 95% CI, $342,388-$433,749) persisted on multivariable analysis after accounting for other factors (P .01). The salary gap remained statistically significant on sensitivity analysis.Mean salary for women at US public academic radiation oncology departments was lower than mean salary for men, after adjusting for confounders. Our analysis was limited to public data and could not account for relevant private personal choices and departmental factors. The salary gap may differ in other practice environments. Further research is warranted to determine the cause of this disparity, whether it exists in other practice environments, and how to successfully address it.

PURPOSE For pediatric patients with large, high-grade, extremity nonrhabdomyosarcoma soft-tissue sarcomas, preoperative radiation therapy (RT) provides the opportunity for smaller radiation fields and tumor shrinkage resulting in less extensive surgery. The potential disadvantage is an increased risk of wound complications after surgery compared with rates after postoperative chemoradiation. We assessed the impact of preoperative RT technique on target coverage in relationship to dose to skin and adjacent joints to determine whether acute wound complications and late musculoskeletal injury might be influenced by treatment technique. METHODS AND MATERIALS Of 550 eligible patients

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.

Purpose Reirradiation has been proposed as an effective modality for recurrent central nervous system (CNS) malignancies in adults. We evaluated the toxicity and outcomes of CNS reirradiation in pediatric patients. Methods and Materials The data from pediatric patients Results Sixty-seven pediatric patients underwent CNS reirradiation. The primary diagnoses included medulloblastoma/primitive neuroectodermal tumor (n=20; 30%), ependymoma (n=19; 28%), germ cell tumor (n=8; 12%), high-grade glioma (n=9; 13%), low-grade glioma (n=5; 7%), and other (n=6; 9%). The median age at the first course of RT was 8.5 years (range 0.5-19.5) and was 12.3 years (range 3.3-30.2) at reirradiation. The median interval between RT courses was 2.0 years (range 0.3-16.5). The median radiation dose and fractionation in equivalent 2-Gy fractions was 63.7 Gy (range 27.6-74.8) for initial RT and 53.1 Gy (range 18.6-70.1) for repeat RT. The relapse location was infield in 52 patients (78%) and surrounding the initial RT field in 15 patients (22%). Thirty-seven patients (58%) underwent gross or subtotal resection at recurrence. The techniques used for reirradiation were intensity modulated RT (n=46), 3-dimensional conformal RT (n=9), stereotactic radiosurgery (n=4; 12-13 Gy × 1 or 5 Gy × 5), protons (n=4), combined modality (n=3), 2-dimensional RT (n=1), and brachytherapy (n=1). Radiation necrosis was detected in 2 patients after the first RT course and 1 additional patient after reirradiation. Six patients (9%) developed secondary neoplasms after initial RT (1 hematologic, 5 intracranial). One patient developed a secondary neoplasm identified shortly after repeat RT. The median overall survival after completion of repeat RT was 12.8 months for the entire cohort and 20.5 and 8.4 months for patients with recurrent ependymoma and medulloblastoma after reirradiation, respectively. Conclusions CNS reirradiation in pediatric patients could be a reasonable treatment option, with moderate survival noted after repeat RT. However, prospective data characterizing the rates of local control and toxicity are needed.

The American Association of Physicists in Medicine (AAPM) is a nonprofit professional society whose primary purposes are to advance the science, education and professional practice of medical physics. The AAPM has more than 8,000 members and is the principal organization of medical physicists in the United States. The AAPM will periodically define new practice guidelines for medical physics practice to help advance the science of medical physics and to improve the quality of service to patients throughout the United States. Existing medical physics practice guidelines will be reviewed for the purpose of revision or renewal, as appropriate, on their fifth anniversary or sooner. Each medical physics practice guideline represents a policy statement by the AAPM, has undergone a thorough consensus process in which it has been subjected to extensive review, and requires the approval of the Professional Council. The medical physics practice guidelines recognize that the safe and effective use of diagnostic and therapeutic radiology requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guidelines and technical standards by those entities not providing these services is not authorized. The following terms are used in the AAPM practice guidelines: Must and Must Not: Used to indicate that adherence to the recommendation is considered necessary to conform to this practice guideline. Should and Should Not: Used to indicate a prudent practice to which exceptions may occasionally be made in appropriate circumstances.

PURPOSE: The presented protocol for pediatric intermediate-risk Hodgkin lymphoma evaluated the use of a dose-intensive chemotherapy regimen (ABVE-PC [doxorubicin, bleomycin, vincristine, etoposide, cyclophosphamide, prednisone]) with response-based therapy augmentation (addition of DECA [dexamethasone, etoposide, cisplatin, cytarabine]) or therapy reduction (elimination of radiation). METHODS AND MATERIALS: A central review of the radiation therapy data for quality assurance was performed, and the association between radiation protocol deviation (RPD) and relapse was assessed in the pediatric group (age

Purpose To quantify the potential impact of the Integrating the Healthcare Enterprise–Radiation Oncology Quality Assurance with Plan Veto (QAPV) on patient safety of external beam radiation therapy (RT) operations. Methods and Materials An institutional database of events (errors and near-misses) was used to evaluate the ability of QAPV to prevent clinically observed events. We analyzed reported events that were related to Digital Imaging and Communications in Medicine RT plan parameter inconsistencies between the intended treatment (on the treatment planning system) and the delivered treatment (on the treatment machine). Critical Digital Imaging and Communications in Medicine RT plan parameters were identified. Each event was scored for importance using the Failure Mode and Effects Analysis methodology. Potential error occurrence (frequency) was derived according to the collected event data, along with the potential event severity, and the probability of detection with and without the theoretical implementation of the QAPV plan comparison check. Failure Mode and Effects Analysis Risk Priority Numbers (RPNs) with and without QAPV were compared to quantify the potential benefit of clinical implementation of QAPV. Results The implementation of QAPV could reduce the RPN values for 15 of 22 (71%) of evaluated parameters, with an overall average reduction in RPN of 68 (range, 0-216). For the 6 high-risk parameters (>200), the average reduction in RPN value was 163 (range, 108-216). The RPN value reduction for the intermediate-risk (200 > RPN > 100) parameters was (0-140). With QAPV, the largest RPN value for “Beam Meterset” was reduced from 324 to 108. The maximum reduction in RPN value was for Beam Meterset (216, 66.7%), whereas the maximum percentage reduction was for Cumulative Meterset Weight (80, 88.9%). Conclusion This analysis quantifies the value of the Integrating the Healthcare Enterprise–Radiation Oncology QAPV implementation in clinical workflow. We demonstrate that although QAPV does not provide a comprehensive solution for error prevention in RT, it can have a significant impact on a subset of the most severe clinically observed events.

Purpose Systems to ensure patient safety are of critical importance. The electronic incident reporting systems (IRS) of 2 large academic radiation oncology departments were evaluated for events that may be suitable for submission to a national reporting system (NRS). Methods and Materials All events recorded in the combined IRS were evaluated from 2007 through 2010. Incidents were graded for potential severity using the validated French Nuclear Safety Authority (ASN) 5-point scale. These incidents were categorized into 7 groups: ( 1 ) human error, ( 2 ) software error, ( 3 ) hardware error, ( 4 ) error in communication between 2 humans, ( 5 ) error at the human-software interface, ( 6 ) error at the software-hardware interface, and ( 7 ) error at the human-hardware interface. Results Between the 2 systems, 4407 incidents were reported. Of these events, 1507 (34%) were considered to have the potential for clinical consequences. Of these 1507 events, 149 (10%) were rated as having a potential severity of ≥2. Of these 149 events, the committee determined that 79 (53%) of these events would be submittable to a NRS of which the majority was related to human error or to the human-software interface. Conclusions A significant number of incidents were identified in this analysis. The majority of events in this study were related to human error and to the human-software interface, further supporting the need for a NRS to facilitate field-wide learning and system improvement.

To quantify the error-detection effectiveness of commonly used quality control (QC) measures.We analyzed incidents from 2007-2010 logged into a voluntary in-house, electronic incident learning systems at 2 academic radiation oncology clinics. None of the incidents resulted in patient harm. Each incident was graded for potential severity using the French Nuclear Safety Authority scoring scale; high potential severity incidents (score3) were considered, along with a subset of 30 randomly chosen low severity incidents. Each report was evaluated to identify which of 15 common QC checks could have detected it. The effectiveness was calculated, defined as the percentage of incidents that each QC measure could detect, both for individual QC checks and for combinations of checks.In total, 4407 incidents were reported, 292 of which had high-potential severity. High- and low-severity incidents were detectable by 4.0 ± 2.3 (mean ± SD) and 2.6 ± 1.4 QC checks, respectively (P.001). All individual checks were less than 50% sensitive with the exception of pretreatment plan review by a physicist (63%). An effectiveness of 97% was achieved with 7 checks used in combination and was not further improved with more checks. The combination of checks with the highest effectiveness includes physics plan review, physician plan review, Electronic Portal Imaging Device-based in vivo portal dosimetry, radiation therapist timeout, weekly physics chart check, the use of checklists, port films, and source-to-skin distance checks. Some commonly used QC checks such as pretreatment intensity modulated radiation therapy QA do not substantially add to the ability to detect errors in these data.The effectiveness of QC measures in radiation oncology depends sensitively on which checks are used and in which combinations. A small percentage of errors cannot be detected by any of the standard formal QC checks currently in broad use, suggesting that further improvements are needed. These data require confirmation with a broader incident-reporting database.

Re-Irradiation for Recurrent Pediatric CNS Malignancies : A Multi-Institutional Retrospective Review

Purpose Positron emission-tomography (PET) using 2-[ 18 F]fluoro-2-deoxyglucose (FDG-PET) increases sensitivity and specificity of disease detection in lymphoma and thus is standard in lymphoma management. This study examines the effects of coregistering FDG-PET and computed tomography (CT) (PET/CT) scans on treatment planning for lymphoma patients. Methods and Materials Twenty-nine patients (30 positive PET scans) underwent PET/CT treatment planning from July 2004 to February 2007 and were retrospectively studied. For each patient, gross tumor volume was blindly contoured on the CT-only and PET/CT studies by a radiation oncologist. Treatment plans were generated for both the CT-only and PET/CT planning target volumes (PTVs) for all patients. Normal tissue doses and PTV coverage were evaluated using dose--volume histograms for all sites. Results Thirty-two treatment sites were evaluated. Twenty-one patients had non-Hodgkin lymphoma, 5 patients had Hodgkin lymphoma, and 3 patients had plasma cell neoplasms. Previously undetected FDG-avid sites were identified in 3 patients during PET/CT simulation, resulting in one additional treatment field. Due to unexpected PET/CT simulation findings, 2 patients did not proceed with radiation treatment. The addition of PET changed the volume of 23 sites (72%). The PTV was increased in 15 sites (47%) by a median of 11% (range, 6-40%) and reduced in 8 sites (25%) by a median of 20% (range, 6%-75%). In six (19%) replanned sites, the CT-based treatment plan would not have adequately covered the PTV defined by PET/CT. Conclusions Incorporation of FDG-PET into CT-based treatment planning for lymphoma patients resulted in considerable changes in management, volume definition, and normal tissue dosimetry for a significant number of patients.

Purpose Image-guided intensity-modulated radiotherapy enables delivery of high-dose radiation to tumors close to the spinal cord. We report our experience with multifractionated regimens using image-guided intensity-modulated radiotherapy to treat gross paraspinal disease to doses beyond cord tolerance. Methods and Materials We performed a retrospective review of 27 consecutive patients with partially resected or unresectable paraspinal tumors irradiated to >5,300 cGy in standard fractionation. Results The median follow-up was 17.4 months (range, 2.1–47.3). Eighteen sarcomas, seven chordomas, and two ependymomas were treated. The median dose to the planning target volume was 6,600 cGy (range, 5,396–7,080) in 180- or 200-cGy fractions. The median planning target volume was 164 cm 3 (range, 29–1,116). Seven patients developed recurrence at the treatment site (26%), and 6 of these patients had high-grade tumors. Three patients with recurrence had metastatic disease at the time of radiotherapy. The 2-year local control rate was 65%, and the 2-year overall survival rate was 79%. Of the 5 patients who died, 4 had metastatic disease at death. Twenty-three patients (84%) reported either no pain or improved pain at the last follow-up visit. Sixteen patients discontinued narcotic use after treatment (62.5%). Twenty-three patients (89%) had a stable or improved American Spine Injury Association score at the last follow-up visit. No patient experienced radiation-induced myelopathy. Conclusions The dose to paraspinal tumors has traditionally been limited to respect cord tolerance. With image-guided intensity-modulated radiotherapy, greater doses of radiation delivered in multiple fractions can be prescribed with excellent target coverage, effective palliation, and acceptable toxicity and local control.

*Residency Program, Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York; yResidency Program, Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania; zResidency Program, Radiation Oncology, University of Chicago Medical Center, Chicago, Illinois; xRadiation Oncology Residency and Fellowship Program, M. D. Anderson Cancer Center, Houston, Texas; jjResidency Program, Department of Therapeutic Radiology, Yale University School of Medicine, New Haven, Connecticut; {Residency Program, Radiation Oncology and Molecular Radiation Sciences, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland; and Residency Program, Harvard Radiation Oncology Program, Boston, Massachusetts