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Despite women being disproportionally affected by cancer deaths at young ages, there are no global estimates of the resulting maternal orphans, who experience health and education disadvantages throughout their lives. We estimated the number of children who became maternal orphans in 2020 due to their mother dying from cancer in that year, for 185 countries worldwide and by cause of cancer-related death. Female cancer deaths—by country, cancer type and age (derived from GLOBOCAN estimates)—were multiplied by each woman’s estimated number of children under the age of 18 years at the time of her death (fertility data were derived from United Nations World Population Prospects for birth cohort), accounting for child mortality and parity-cancer risk associations. Globally, there were 1,047,000 such orphans. Over half of these were orphans due to maternal deaths from breast (258,000, 25%), cervix (210,000, 20%) and upper-gastrointestinal cancers (136,000, 13%), and most occurred in Asia (48%: India 15%, China 10%, rest of Asia 23%) and Africa (35%). Globally, there were 40 new maternal orphans due to cancer per 100,000 children, with a declining trend with a higher Human Development Index (range: 121 in Malawi to 15 in Malta). An estimated 7 million children were prevalent maternal orphans due to cancer in mid-2020. Accelerating the implementation of the World Health Organization’s cervical and breast cancer initiatives has the potential to avert not only millions of preventable female cancer deaths but also the associated, often-overlooked, intergenerational consequences of these deaths.

PURPOSE: There is a lack of level I evidence to guide radiotherapy recommendations for patients receiving neoadjuvant chemotherapy for breast cancer. We utilized four neoadjuvant chemotherapy trials to determine which patients benefit from regional nodal irradiation (RNI). MATERIALS AND METHODS: We obtained data from NSABP B-18, B-27, B-40, and B-41 clinical trials. B-40 and B-41 allowed RNI at physician’s discretion. We evaluated local-regional recurrence (LRR), distant recurrence (DR), disease-free survival (DFS), and overall survival (OS). Kaplan-Meier, Peto-Peto, Chi-squared, Fisher exact, and Wilcoxon rank-sum tests were used for survival estimates and comparison. RESULTS: Median follow-up for B-18, B-27, B-40, and B-41 was 13.7, 9.7, 4.5, and 5.1 years, respectively, including 742, 2254, 1154, and 504 patients for analysis. On multivariable analysis, factors significantly associated with RNI included tumor size, ypN status, and tumor subtype; Hispanic patients were less likely to receive RNI. Patients with ypN+HER2+ disease who received RNI had improved OS. B-40 patients with ypN+HR+ disease had improved LRR. On multivariable analysis for the B-40 and B-41 study population, RNI was not associated with significantly improved OS, DFS, DR, or LRR. CONCLUSION: RNI was associated with a clinical benefit for patients with ypN+HER2+ and ypN+HR+ disease. RNI was not significantly associated with a clinically beneficial outcome for the entire cohort. Prospective phase III clinical trials are needed to establish guidelines for patients who should receive RNI following neoadjuvant treatment, and action is necessary to eliminate the disparity in care delivery shown for Hispanic women.

Owing to adjacent critical organs, the aggressive multimodality local therapy necessary for Ewing sarcoma of the chest wall is a challenge. Our previous review of historical outcomes at our institution revealed suboptimal disease control and a high incidence of grade ≥3 toxic effects in patients treated before 2006. The purpose of this study was to evaluate changes during the past decade since the introduction of proton therapy.Thirty-nine consecutive pediatric patients with a chest wall Ewing sarcoma treated between 2006 and 2020 at the University of Florida were identified. The median maximum tumor diameter was 10 cm (range, 4-28 cm). At diagnosis, 19 patients had local disease and the others had a pleural effusion (11), pleural nodules (5), or pulmonary metastases (4). Patients were treated with chemotherapy regimens according to contemporary North American and European protocols: 7 were treated with preoperative, 18 with postoperative, and 14 with definitive radiation. Preceding primary site treatment, 15 patients required hemithorax radiation and 4 patients underwent whole-lung irradiation using photon techniques. The total median radiation dose to the primary tumor was 52.8 GyRBE [relative biological effectiveness] (range, 44.4-55.8 GyRBE).With a median follow-up of 4 years (range, 0.7-14.7 years), the 5-year local control, progression-free survival, and overall survival rates were 97.2%, 74.4%, and 81.6%, respectively, for the whole cohort. For the 19 patients with nonmetastatic disease, the 5-year local control, progression-free survival, and overall survival rates were 100%, 78.9%, and 78.9%, respectively. No patients developed grade ≥4 toxic effects. Two patients (5%) experienced grade 3 toxic effects related to multimodality treatment; both were patients who required surgery to correct scoliosis. Two patients (5%) developed grade 2 pneumonitis.Compared with our prior published institutional experience, our data suggest improvements in disease control and multimodality toxic effects since the introduction of proton therapy. This should be confirmed with a larger sample size and longer follow-up.

In 2010, we published a comprehensive review of our institutional outcomes about treating children with spinal and paraspinal Ewing sarcoma using photon therapy. Multimodality therapy was associated with fair disease control but also with serious toxicity, including a 37% rate of grade 3 or greater toxicity. We therefore sought to assess our more recent experience about treating children with more modern technology and treatment regimens.Between 2010 and 2021, 32 pediatric patients with nonmetastatic spinal and paraspinal Ewing sarcoma were treated at University of Florida and enrolled in a retrospective outcome study. Median age at diagnosis was 9.8 years (range, 2.1-21.8 years). Within the cervical, thoracic, and lumbar spine regions, 3, 22, and 7 tumors arose, respectively. Median maximum tumor diameter was 5 cm (range, 3-19 cm). At diagnosis, 28 of 32 patients had motor, bowel, or bladder deficits. Chemotherapy was delivered according to contemporary North American and European interval-compressed regimens. Before radiation therapy, 14 patients underwent gross total resection, whereas 18 underwent a biopsy or subtotal resection with cord decompression. All patients were treated with proton therapy; 6 with hardware stabilization also received a component of intensity modulated photon therapy. Median prescription dose was 50.4 gray relative biological effectiveness (GyRBE; range, 45-55.8 GyRBE). Median maximum dose to the spinal cord was 50.2 GyRBE (range, 0-54.9 GyRBE).With a median follow-up of 4.1 years (range, 0.7-9.4 years), the 5-year local control, progression-free survival, and overall survival rates were 92%, 79%, and 85%, respectively. Ten of 30 living patients have residual motor, bowel, or bladder deficits. Overall, 22% of patients experienced Common Terminology Criteria for Adverse Events grade 3 late toxicity related to multimodality treatment: kyphosis (n = 4), esophagitis (n = 2), and chronic kidney disease (n = 1). No patients developed grade 4 or greater toxicity, new neurologic deficits, or second malignancy.Modern treatment advances may offer an improved therapeutic ratio for pediatric patients with spinal and paraspinal Ewing sarcoma. With appropriate management, most patients can be cured with recovery of long-term neurologic function and modest side effects.

PURPOSE With the existing oncology disparities in Latin America, physician expertise has been cited as a possible contributor to inferior oncologic outcomes in some cancers. As two-dimensional radiotherapy rapidly evolved to intensity-modulated radiation therapy in Latin America, adequate contouring education is an actionable target to improving physician knowledge and clinical outcomes. Yet, topics of interest to Latin American radiation oncologists are underreported. We assessed Latin American interest in a virtual platform for case discussion and identified the educational topics of most interest to them. MATERIALS AND METHODS A Spanish-language online survey was designed by a team of Latin American educators. The questions assessed professional nationality, desire for an online educational platform for case presentation, career length, and topics of interest. Educational topics included head and neck (H&N), CNS, GI, lung, gynecologic, breast, and pediatric cancers, lymphoma, sarcoma, stereotactic body radiotherapy (SBRT), brachytherapy, and medical physics. RESULTS One hundred thirty-three surveys were included for analysis. Overall, 127 respondents (98%) affirmed interest in participating in a virtual platform for case discussion and treatment advances. The most popular educational themes were H&N cancers (24%), SBRT (14%), and CNS cancers (13%). Of countries with > 10 respondents, the most popular educational topic remained H&N cancers for Argentina, Chile, and Mexico, but the most popular topic among Peruvian respondents was CNS cancer (27%). CONCLUSION With international collaboration and a large sample size, we present the first survey results describing Latin American radiation oncology educational interests. Participants were overwhelmingly interested in a virtual platform, and most were specifically interested in H&N cancer education. These results can be used for focused didactic preparation in Latin America. Future efforts should expand on improving representation and outreach among Central American radiation oncologists.

We present a case of recurrent pericardial effusion presenting during proton therapy in a 24-year-old female receiving mediastinal treatment for classical Hodgkin lymphoma. Pericardial effusion is typically considered an event accompanying lymphoma diagnosis or as a subacute or late effect of radiotherapy. Rarely has it been described as occurring during radiation treatment with photon-based radiotherapy, let alone proton therapy. It is unclear what underlying cause triggered recurrent effusion in this patient. Identifying and managing pericardial effusion during treatment delivery is important to consider as it may affect radiation dosimetry, particularly with proton therapy. Doing so will help ensure patients receive optimal treatment and minimize the risks of morbidity and mortality.

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research. (c) 2021 Elsevier Inc. All rights reserved.

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 Due to the location and high dose required for disease control, pediatric chordomas are theoretically well-suited for treatment with proton therapy, but their low incidence limits the clinical outcome data available in the literature. We sought to report the efficacy and toxicity of proton therapy among a single-institution cohort. Methods and Materials Between 2008 and 2019, 29 patients with a median age of 14.8 years (range, 3.8-21.8) received passive-scattered proton therapy for nonmetastatic chordoma. No patient received prior irradiation. Twenty-four tumors arose in the clivus/cervical spine region and 5 in the lumbosacral spine. Twenty-six tumors demonstrated classic well-differentiated histology and 3 were dedifferentiated or not otherwise specified. Approximately half of the tumors underwent specialized testing: 14 were brachyury-positive and 10 retained INI-1. Three patients had locally recurrent tumors after surgery alone (n = 2) or surgery + chemotherapy (n = 1), and 17 patients had gross disease at the time of radiation. The median radiation dose was 73.8 Gy relative biological effectivness (range, 69-75.6). Results With a median follow-up of 4.3 years (range, 1.0-10.7), the 5-year estimates of local control, progression-free survival, and overall survival rates were 85%, 82%, and 86%, respectively. No disease progression was observed beyond 3 years. Excluding 3 patients with dedifferentiated/not-otherwise-specified chordoma, the 5-year local control, progression-free survival, and overall survival rates were 92%, 92%, and 91%, respectively. Serious toxicities included 3 patients with hardware failure or related infection requiring revision surgery, 2 patients with hormone deficiency, and 2 patients with Eustachian tube dysfunction causing chronic otitis media. No patient experienced brain stem injury, myelopathy, vision loss, or hearing loss after radiation. Conclusions In pediatric patients with chordoma, proton therapy is associated with a low risk of serious toxicity and high efficacy, particularly in well-differentiated tumors. Complete resection may be unnecessary for local control, and destabilizing operations requiring instrumentation may result in additional complications after therapy.

Craniopharyngioma is a rare suprasellar tumor. Approximately one-third of cases occur in pediatric patients. Depending on the size and extent of the lesion, the main treatment options include complete surgical removal of the tumor or limited surgery followed by radiotherapy. Craniopharyngiomas are not thought to be hereditary. Herein the authors present a case report of 2 brothers, ages 9 and 10, diagnosed with craniopharyngioma within weeks of each other and managed with different approaches. One sibling underwent gross total resection followed by observation while the other underwent biopsy followed by postoperative proton therapy.

To assess outcomes and toxicity after low-energy intraoperative radiotherapy (IORT) for early-stage breast cancer (ESBC).We reviewed patients with unilateral ESBC treated with breast-conserving surgery and 50-kV IORT at our institution. Patients were prescribed 20 Gy to the surface of the spherical applicator, fitted to the surgical cavity during surgery. Patients who did not meet institutional guidelines for IORT alone on final pathology were recommended adjuvant treatment, including additional surgery and/or external-beam radiation therapy (EBRT). We analyzed ipsilateral breast tumor recurrence, overall survival, recurrence-free survival and toxicity.Among 201 patients (median follow-up, 5.1 years; median age, 67 years), 88% were Her2 negative and ER positive and/or PR positive, 98% had invasive ductal carcinoma, 87% had grade 1 or 2, and 95% had clinical T1 disease. Most had pathological stage T1 (93%) N0 (95%) disease. Mean IORT applicator dose at 1-cm depth was 6.3 Gy. Post-IORT treatment included additional surgery, 10%; EBRT, 11%; adjuvant chemotherapy, 9%; and adjuvant hormonal therapy, 74%. Median total EBRT dose was 42.4 (range, 40.05-63) Gy and median dose per fraction was 2.65 Gy. At 5 years, the cumulative incidence of ipsilateral breast tumor recurrence was 2.7%, the overall survival rate was 95% with no breast cancer-related deaths, and the recurrence-free survival rate was 96%. For patients who were deemed unsuitable for postoperative IORT alone and did not receive recommended risk-adapted EBRT, the IBTR rate was 4.7% versus 1.7% (p = 0.23) for patients who were either suitable for IORT alone or unsuitable and received adjuvant EBRT. Cosmetic toxicity data was available for 83%, with 7% experiencing grade 3 breast toxicity and no grade 4-5 toxicity.IORT for select patients with ESBC results in acceptable outcomes in regard to ipsilateral breast tumor recurrence and toxicity.

To evaluate the LETd-weighted biological dose to OARs in proton therapy for breast cancer and to study the relationship of the LETd-weighted biological dose relative to the standard dose (RBE = 1.1) and thereby to provide estimations of the biological dose uncertainties with the standard dose calculations (RBE = 1.1) commonly used in clinical practice.This study included 20 patients who received IMPT treatment to the whole breast/chest wall and regional lymph nodes. The LETd distributions were calculated along with the physical dose using an open-source Monte Carlo simulation package, MCsquare. Using the McMahon linear model, the LETd-weighted biological dose was computed from the physical dose and LETd. OAR doses were compared between the Dose (RBE = 1.1) and the LETd-weighted biological dose, on brachial plexus, rib, heart, esophagus, and Ipsilateral lung.On average, the LETd-weighted biological dose compared to the Dose (RBE = 1.1) was higher by 8% for the brachial plexus D0.1 cc, 13% for the ribs D0.5 cc, 24% for mean heart dose, and 10% for the esophagus D0.1 cc, respectively. The LETd-weighted doses to the Ipsilateral lung V5, V10, and V20 were comparable to the Dose (RBE = 1.1). No statistically significant difference in biological dose enhancement to OARs was observed between the intact breast group and the CW group, with the exception of the ribs: the CW group experienced slightly greater biological dose enhancement (13% vs. 12%,Enhanced biological dose was observed compared to standard dose with assumed RBE of 1.1 for the heart, ribs, esophagus, and brachial plexus in breast/CW and regional nodal IMPT plans. Variable RBE models should be considered in the evaluation of the IMPT breast plans, especially for OARs located near the end of range of a proton beam. Clinical outcome studies are needed to validate model predictions for clinical toxicities.

Diversifying the radiation oncology workforce is an urgent and unmet need. During the American Society of Radiation Oncology (ASTRO) 2019 Annual Meeting, ASTRO's Committee on Health Equity, Diversity, and Inclusion (CHEDI) and the National Cancer Institute (NCI) collaborated on the ASTRO-NCI Diversity Symposium, entitled ''Pathways for Recruiting and Retaining Women and Underrepresented Minority Clinicians and Physician Scientists Into the Radiation Oncology Workforce.'' Herein, we summarize the presented data and personal anecdotes with the goal of raising awareness of ongoing and future initiatives to improve recruitment and retention of underrepesented groups to radiation oncology. Common themes include the pivotal role of mentorship and standardized institutional practices – such as protected time and pay parity – as critical to achieving a more diverse and inclusive workplace.

Purpose Ewing sarcoma of the pelvis is associated with inferior local control compared with those arising from other primary sites. Despite its increased use, outcome data for treatment with proton therapy remain limited. We report 3-year disease control and toxicity in pediatric patients treated with proton therapy. Methods and Materials Thirty-five patients aged ≤21 years (median, 14 years) with nonmetastatic pelvic Ewing sarcoma received proton therapy and chemotherapy between 2010 and 2018. Overall survival and tumor control rates were calculated using the Kaplan–Meier method. A log-rank test assessed significance between strata of prognostic factors. Significant toxicity was reported per the Common Terminology Criteria for Adverse Events, version 4.0. Results Most patients received definitive radiation (n = 26; median dose 55.8 Gy relative biological effectiveness [RBE]; range, 54.0-64.8), 7 received preoperative radiation (50.4 Gy RBE), and 2 received postoperative radiation (45 Gy RBE and 54 Gy RBE). The median primary tumor size was 10.5 cm. With a median follow-up of 3 years (range, 0.3-9.0 years), the 3-year overall survival, progression-free survival, and local control rates were 83% (95% confidence interval [CI], 65%-93%), 64% (95% CI, 45%-79%), and 92% (95% CI, 74%-98%), respectively. There was no association between local control, progression-free survival, or overall survival and tumor size, patient age, radiation dose, or definitive versus pre-/postoperative radiation therapy. Median time to progression was 1 year (range, 0.1-1.9 years). All patients with large tumors (≥8 cm) who underwent definitive proton therapy with a higher dose (≥59.4 Gy RBE) remained free from tumor recurrence (n = 5). Five patients experienced grade ≥2 subacute/late toxicity, all of whom were treated with combined surgery and radiation. Conclusions Definitive proton therapy offers local control comparable to photon therapy in pediatric patients with pelvic Ewing sarcoma. These data lend preliminary support to radiation dose escalation without significant toxicity, which may contribute to the favorable outcomes. Combined surgery and radiation therapy, particularly preoperative radiation, is associated with postoperative complications, but not survival, compared with radiation alone.

Background Local relapse is a predominant form of recurrence among pediatric patients with Hodgkin lymphoma (PHL). Although PHL radiotherapy doses have been approximately 20 Gy, adults with Hodgkin lymphoma receiving 30 to 36 Gy experience fewer in-field relapses. We investigated the dosimetric effect of such a dose escalation to the organs at risk (OARs). Materials and Methods Ten patients with PHL treated with proton therapy to 21 Gy involved-site radiation therapy (ISRT21Gy) were replanned to deliver 30 Gy by treating the ISRT to 30 Gy (ISRT30Gy), delivering 21 Gy to the ISRT plus a 9-Gy boost to postchemotherapy residual volume (rISRTboost), and delivering 30 Gy to the residual ISRT target only (rISRT30Gy). Radiation doses to the OARs were compared. Results The ISRT30Gy escalated the dose to the target by 42% but also to the OARs. The rISRTboost escalated the residual target dose by 42%, and the OAR dose by only 17% to 26%. The rISRT30Gy escalated the residual target dose by 42% but reduced the OAR dose by 25% to 46%. Conclusion Boosting the postchemotherapy residual target dose to 30Gy can allow for dose escalation with a slight OAR dose increase. Treating the residual disease for the full 30Gy, however, would reduce the OAR dose significantly compared with ISRT21Gy. Studies should evaluate these strategies to improve outcomes and minimize the late effects.

Purpose To study the feasibility and the effectiveness of a novel implementation of robust optimization on 2 sets of computed tomography (CT) data simultaneously for skin flashing in intensity modulated radiation therapy for breast cancer. Method and Materials Five patients who received treatment to the breast and regional lymphatics were selected for this study. For each patient, 3 plans were generated using 3 different skin-flashing methods, including (1) a manual flash plan with optimization on the nominal planning target volume (PTV) not extending beyond the skin that required manually postplanning the opening of the multi-leaf collimator and jaw to obtain flash; (2) an expanded PTV plan with optimization on an expanded PTV that included the target in the air beyond the skin; and (3) a robust-optimized (RO) plan using robust optimization that simultaneously optimizes on the nominal CT data set and a simulated geometry error CT data set. The feasibility and the effectiveness of the robust optimization approach was investigated by comparing it with the 2 other methods. The robustness of the plan against target position variations was studied by simulating 0-, 5-, 10-, and 15-mm geometry errors. Results The RO plans were the only ones able to meet acceptable criteria for all patients in both the nominal and simulated geometry error scenarios. The expanded PTV plans developed major deviation on the maximum dose to the PTV for 1 patient. For the manual flash plans, every patient developed major deviation either on 95% of the dose to the PTV or the maximum dose to the PTV in the simulated geometry error scenarios. The RO plan demonstrated the best robustness against the target position variation among the 3 methods of skin flashing. The doses to the lung and heart were comparable for all 3 planning techniques. Conclusion Using robust optimization for skin flash in breast intensity modulated radiation therapy planning is feasible. Further investigation is warranted to confirm the clinical effectiveness of this novel approach.

Purpose: In survivors of orbital embryonal rhabdomyosarcoma (ERMS), late effects include facial deformation and asymmetry. We sought to quantify orbital asymmetry in ERMS survivors and characterize the dose effect of radiation to the orbital bones. Methods and Materials: We evaluated the most recent follow-up magnetic resonance imaging (MRI) in 17 children (≤21 years old) with stage 1 group III orbital ERMS treated with proton therapy between 2007 and 2018. For all patients, the orbital socket volumes were calculated and compared with the contralateral, unirradiated orbital socket. Patient age, orbital tumor quadrant, and the radiation dose delivered to the major orbital bones (maxillary, frontal, and zygomatic bones) were recorded and correlated with the orbital socket volume difference. Results: The mean age at diagnosis was 5.4 years old (range, 1.1-9.7 years). All patients received a prescription dose of 45 GyRBE. The mean time interval between radiation and MRI was 2.9 years (range, 0.8-3.2 years). The mean age at most recent MRI was 8.4 years (range, 2.3-12.9 years). In 16 of 17 patients, the volume of the ipsilateral orbit was significantly smaller than the contralateral orbit on follow-up MRI (P ≤ .0001). In one patient with nonviable tumor in situ, the irradiated orbit was larger. The volume difference increased with follow-up time and did not correlate with age at treatment or age at MRI. A dose >40 GyRBE to all bones of the orbital rim was associated with a significant decrease in orbital volume (P < .05), but an isolated dose of >40 GyRBE to either the frontal, maxillary, or zygomatic bone was not. Conclusions: Despite the dosimetric precision of proton therapy, orbital asymmetry will develop after >40 GyRBE to multiple bones of the orbital rim. These data may be used to guide treatment planning and counsel patients on expected cosmesis.

To evaluate the relative biological effectiveness (RBE)-weighted dose to the heart and to estimate RBE uncertainties when assuming a constant RBE of 1.1, for breast cancer patients receiving intensity-modulated proton therapy (IMPT). Further, to study the impact of RBE uncertainties on the risk of an acute coronary event (ACE).We analyzed 20 patients who received IMPT to either the left breast (n = 10) or left chest wall (n = 10) and regional lymph nodes. The Monte Carlo simulation engine, MCsquare, was used to simulate the dose-averaged linear energy transfer (LETd) map. The RBE-weighted dose to the heart and its substructures was calculated using three different RBE models. The risk of ACE was estimated per its linear relationship with mean heart dose (MHD) as established by Darby et al.The median MHD increased from 1.33 GyRBE assuming an RBE of 1.1 to 1.64, 1.87, and 1.99 GyRBE when using the RBE-weighted dose models. The median values (and ranges) of the excess absolute risk of ACE were 0.4% (0.1%-0.8%) when assuming an RBE of 1.1, and 0.6% (0.2%-1.0%), 0.6% (0.2%-1.1%), and 0.7% (0.2%-1.1%) with the RBE-weighted models. For our patient cohort, the maximum excess absolute risk of ACE increased by 0.3% with the RBE-weighted doses compared to the constant RBE of 1.1, reaching an excess absolute ACE risk of 1.1%. The interpatient LETd variation was small for the relevant high-dose regions of the heart.All three RBE models predicted a higher biological dose compared to the clinical standard dose assuming a constant RBE of 1.1. An underestimation of the biological dose results in underestimation of the ACE risk. Analyzing the voxel-by-voxel biological dose and the LET map alongside clinical outcomes is warranted in the development of a more accurate normal-tissue complication probability model.

Background The United States (US) radiation oncology workforce is comparatively less diverse than the US population and US medical school graduates. Workforce diversity correlates with higher quality care and outcomes. The purpose of this study is to determine whether student members of the American Society for Radiation Oncology (ASTRO) are any more diverse than resident members-in-training, utilizing the recently established medical student membership category. Methods Self-reported sex, race and Hispanic ethnicity, medical school, and degree(s) earned for all medical students (n = 268) and members-in-training (n = 713) were collected from the ASTRO membership database. International members were excluded. The chi-square test was used to assess for differences between subgroups. Results Compared to members-in-training, student members were more likely to be female (40.0% vs. 31.5%, p = 0.032), Black or African American (10.7% vs. 4.8%, p = 0.009), candidates for or holders of a DO rather than MD degree (5.2% vs. 1.5%, p = 0.002), and from a US medical school that is not affiliated with a radiation oncology residency program (30.5% vs. 20.9%, p = 0.001). There was no significant difference in self-reported Hispanic ethnicity (7.3% vs. 5.4%, p = 0.356). There were no indigenous members in either category assessed. Conclusion Medical student members of ASTRO are more diverse in terms of Black race, female sex, and osteopathic training, though not in terms of Hispanic ethnicity or non-multiracial indigenous background, than the members-in-training. Longitudinal engagement with these students and assessment of the factors leading to specialty retention vs. attrition may increase diversity, equity, and inclusion in radiation oncology.

BACKGROUND Children with chest wall Ewing sarcoma with malignant pulmonary effusion or pleural stranding require hemithorax radiation, often with plans that exceed lung constraints. We investigated disease control and pneumonitis in children requiring hemithorax radiation. PROCEDURE Eleven children (median age 13 years) received hemithorax radiotherapy. Symptomatic radiation pneumonitis was considered National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade 1+ with respiratory symptoms. Mean lung dose (MLD), volume of lung exposed to a dose ≥5 Gy (V5), ≥20 Gy (V20), and ≥35 Gy (V35) were recorded. Adult and pediatric lung constraints were obtained from Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines and Children's Oncology Group (COG) protocols, respectively. RESULTS Median hemithorax dose was 15 Gy (1.5 Gy/fraction). Median total dose was 51 Gy (1.8 Gy/fraction). Most plans delivered both protons and photons. The ipsilateral MLD, V5, and V20 were 27.2 Gy, 100%, and 48.3%; the bilateral MLD, V20, and V35 were 14.1 Gy, 22.8%, and 14.3%, respectively. One hundred percent, 36%, and 91% of treatments exceeded recommended adult ipsilateral lung constraints of V5

Purpose To evaluate the radiobiological impact of PB algorithm versus MC algorithm in intensity-modulated proton therapy (IMPT) plans for breast cancer treatment. Methods 20 breast cancer patients who received IMPT to the breast/chest wall and regional lymphatics were included in this study. For each patient, 2 IMPT plans were generated: a PB-optimized plan and a MC-optimized plan. The radiobiological and dosimetric impact to the CTV of the dose algorithms was assessed. The Poisson Linear-Quadratic model was used to estimate the tumor control probability (TCP). The influence of the model parameter uncertainties on the TCP was tested against different sets of published model parameters. Results The PB-optimized plans significantly under-dosed the target as compared to the MC-optimized plans. The median (range) differences in CTV D95% and CTV Dmean were 1.9 (1.2–3.1) Gy and 1.2 (0.5–1.9) Gy, corresponding to 3.8% (2.4−6.2%) and 2.4% (1.0−3.8%) of the prescription dose. The TCP was lower in the PB-optimized plans than the MC-optimized plans. The median (range) of the TCP differences (ΔTCP) were 4% (2−6%), 3% (2−5%), and 2% (1−3%), respectively, when calculated using 3 different model parameter sets. The ΔTCP correlated with the CTV dose difference, and moderately correlated with the CTV volume. Conclusion Due to the inaccurate dose modeling, PB-optimized plans under-dose the target and therefore yield a lower TCP compared to MC-optimized plans in breast IMPT. The magnitude of the resulting difference in TCP reached 6% in our study.

Purpose The comprehensive identification and delineation of organs at risk (OARs) are vital to the quality of radiation therapy treatment planning and the safety of treatment delivery. This guidance aims to improve the consistency of ontouring OARs in external beam radiation therapy treatment planning by providing a single standardized resource for information regarding specific OARs to be contoured for each disease site. The guidance is organized in table format as a quality assurance tool for practices and a training resource for residents and other radiation oncology students (see supplementary materials). Methods and Materials The Task Force formulated recommendations based on clinical practice and consensus. The draft manuscript was peer reviewed by 16 reviewers, the American Society for Radiation Oncology (ASTRO) legal counsel, and ASTRO's Multidisciplinary Quality Assurance Subcommittee and revised accordingly. The recommendations were posted on the ASTRO website for public comment in June 2018 for a 6-week period. The final document was approved by the ASTRO Board of Directors in August 2018. Results Standardization improves patient safety, efficiency, and accuracy in radiation oncology treatment. This consensus guidance represents an ASTRO quality initiative to provide recommendations for the standardization of normal tissue contouring that is performed during external beam treatment planning for each anatomic treatment site. Table 1 defines 2 sets of structures for anatomic sites: Those that are recommended in all adult definitive cases and may assist with organ selection for palliative cases, and those that should be considered on a case-by-case basis depending on the specific clinical scenario. Table 2 outlines some of the resources available to define the parameters of general OAR tissue delineation. Conclusions Using this paper in conjunction with resources that define tissue parameters and published dose constraints will enable practices to develop a consistent approach to normal tissue evaluation and dose documentation.

Purpose: Despite widespread concerns of radiotherapy toxicity in children with head and neck tumors, recent Children's Oncology Group (COG) findings suggest that the use of 45 Gy results in an unacceptably high rate of local recurrences in patients with low-risk orbital rhabdomyosarcoma. We therefore evaluated outcomes in our pediatric patients who received 45 GyRBE using proton therapy. Material and methods: To assess disease control and toxicity, we reviewed the medical records of 30 children (≤21 years old) with COG stage 1, group III embryonal orbital rhabdomyosarcoma enrolled on a prospective outcome study and treated with proton therapy between 2007 and 2018. Results: Median age at the time of radiation was 4.8 years old. Twenty-one and nine patients received ifosfamide- and cyclophosphamide-based chemotherapy according to their respective cooperative group regimens. Median duration between the start of induction chemotherapy and radiation was 12 weeks. Two patients had a complete response to induction chemotherapy and two had stable disease. Twenty-six patients had a partial response to induction chemotherapy, with a median volume reduction of 66%. With a median follow-up of 4.0 years (range, 0.5-9.5 years), we observed 1 local failure 6 months following treatment in a patient who had a partial response to cyclosphophomide-based induction chemotherapy. The 5-year local control, progression-free survival, and overall survival rates were 97%, 97%, and 100%, respectively. Serious late toxicities included 18 patients with cataracts, 4 with exposure keratoconjunctivitis resulting in permanently reduced visual acuity, and 1 with chronic sinusitis. Conclusion: 45 GyRBE offers effective local control for most patients with group III orbital rhabdomyosarcoma. The delivery of proton therapy to the postinduction tumor volume plus a small margin can mitigate early- and intermediate-term toxicity, but side effects still occur and long-term data are needed to demonstrate the dosimetric advantage of proton therapy.

Purpose The International Lymphoma Radiation Oncology Group (ILROG) published consensus guidelines on the management of Hodgkin disease (HD) and nodal non-Hodgkin lymphoma (NHL), which became the most downloaded articles from International Journal of Radiation Oncology, Biology, and Physics. E-contouring workshops allow for interactive didactic sessions, allowing participants to see case-based contouring in real time. A pilot 1-hour curriculum was developed with the objective of reviewing ILROG guidelines for HD and NHL management with incorporation of e-contouring tools. This represents the first international education intervention in Spanish using e-contouring with a pre- and postintervention questionnaire. Methods A 1-hour presentation was prepared in Spanish reviewing the ILROG recommendations for HD and NHL. The review was followed by the author’s demonstration of contour creation using patients with HD and NHL prepared for the American Society for Radiation Oncology’s 2015 e-contouring lymphoma session. A five- question evaluation was prepared and administered before and after intervention. A two-tailed paired t test was performed to evaluate any significant change in test value before and after intervention. Results A total of nine quizzes were collected before and after the intervention. The average test score before the intervention was 75.6%, and the average test score after the intervention was 86.7% ( P = .051). Four students scored 100% on both the pre- and postintervention evaluations, and no student had a decrease in score from pre- to postintervention evaluation. The topic with the lowest score tested dose consideration. Conclusion A substantial but nonsignificant improvement in test evaluation was seen with this pilot curriculum. This pilot intervention identified obstacles for truly interactive didactic sessions that, when addressed, can lead to fully developed interactive didactic sessions.

Purpose Few studies report outcomes in children treated with radiation for nonmyxopapillary ependymoma of the spinal cord, and little evidence exists to inform decisions regarding target volume and prescription dose. Moreover, virtually no mature outcome data exist on proton therapy for this tumor. We describe our combined institutional experience treating pediatric classical/anaplastic ependymoma of the spinal cord with proton therapy. Methods and Materials Between 2008 and 2019, 14 pediatric patients with nonmetastatic nonmyxopapillary grade II (n = 6) and grade III (n = 8) spinal ependymoma received proton therapy. The median age at radiation was 14 years (range, 1.5-18 years). Five tumors arose within the cervical cord, 3 within the thoracic cord, and 6 within the lumbosacral cord. Before radiation therapy, 3 patients underwent subtotal resection, and 11 underwent gross-total or near total resection. Two patients received chemotherapy. For radiation, the clinical target volume received 50.4 Gy (n = 8), 52.2 (n = 1), or 54 Gy (n = 5), with the latter receiving a boost to the gross tumor volume after the initial 50.4 Gy, modified to respect spinal cord tolerance. Results With a median follow-up of 6.3 years (range, 1.5-14.8 years), no tumors progressed. Although most patients experienced neurologic sequela after surgery, only 1 developed additional neurologic deficits after radiation: An 18-year-old male who received 54 Gy after gross total resection of a lumbosacral tumor developed grade 2 erectile dysfunction. There were 2 cases of musculoskeletal toxicity attributable to surgery and radiation. At analysis, no patient had developed cardiac, pulmonary, or other visceral organ complications or a second malignancy. Conclusion Radiation to a total dose of 50 to 54 Gy can be safely delivered and plays a beneficial role in the multidisciplinary management of children with nonmyxopapillary spinal cord ependymoma. Proton therapy may reduce late radiation effects and is not associated with unexpected spinal cord toxicity.