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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 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.

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.

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.

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.

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 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.

Out-of-field neutron dissemination during double-scattered proton therapy has raised concerns of increased second malignancies, disproportionally affecting pediatric patients due to the proportion of body exposed to scatter dose and inherent radiosensitivity of developing tissue. We sought to provide empiric data on the incidence of early second tumors.Between 2006 and 2019, 1713 consecutive children underwent double-scattered proton therapy. Median age at treatment was 9.1 years; 371 were ≤3 years old. Thirty-seven patients (2.2%) had tumor predisposition syndromes. Median prescription dose was 54 Gy (range 15-75.6). Median follow-up was 3.3 years (range 0.1-12.8), including 6587 total person-years. Five hundred forty-nine patients had ≥5 years of follow-up. A second tumor was defined as any solid neoplasm throughout the body.Eleven patients developed second tumors; the 5- and 10-year cumulative incidences were 0.8% (95% CI, 0.4-1.9%) and 3.1% (95% CI, 1.5-6.2%), respectively. Using age- and gender-specific data from the Surveillance, Epidemiology, and End Results (SEER) program, the standardized incidence ratio was 13.5; the absolute excess risk was 1.5/1000 person-years. All but one patient who developed second tumors were irradiated at ≤5 years old (p .0005). There was also a statistically significant correlation between patients with tumor predisposition syndromes and second tumors (p .0001). Excluding patients with tumor predisposition syndromes, 5- and 10-year rates were 0.6% (95% CI, 0.2-1.7%) and 1.7% (95% CI, 0.7-4.0%), respectively, with all five malignant second tumors occurring in the high-dose region.Second tumors are rare within the decade following double-scattered proton therapy, particularly among children irradiated at5 years old and those without tumor predisposition syndrome.

Objectives Cost-effectiveness analyses (CEAs) may provide useful data to inform management decisions depending on the robustness of a model’s input parameters. We sought to determine the level of heterogeneity in health state utility values, transition probabilities, and cost estimates across published CEAs assessing primarily radiotherapeutic management strategies in prostate cancer. Methods We conducted a systematic review of prostate cancer CEAs indexed in MEDLINE between 2000 and 2018 comparing accepted treatment modalities across all cancer stages. Search terms included “cost effectiveness prostate,” “prostate cancer cost model,” “cost utility prostate,” and “Markov AND prostate AND (cancer OR adenocarcinoma).” Included studies were agreed upon. A Markov model was designed using the parameter estimates from the systematic review to evaluate the effect of estimate heterogeneity on strategy cost acceptability. Results Of 199 abstracts identified, 47 publications were reviewed and 37 were included; 508 model estimates were compared. Estimates varied widely across variables, including gastrointestinal toxicity risk (0%-49.5%), utility of metastatic disease (0.25-0.855), intensity-modulated radiotherapy cost ($21 193-$61 996), and recurrence after external-beam radiotherapy (1.5%-59%). Multiple studies assumed that different radiotherapy modalities delivering the same dose yielded varying cancer control rates. When using base estimates for similar parameters from included studies, the designed model resulted in 3 separate acceptability determinations. Conclusions Significant heterogeneity exists across parameter estimates used to perform CEAs evaluating treatment for prostate cancer. Heterogeneity across model inputs yields variable conclusions with respect to the favorability and cost-effectiveness of treatment options. Decision makers are cautioned to review estimates in CEAs to ensure they are up to date and relevant to setting and population.

Purpose Spinal myxopapillary ependymoma (MPE) often presents with a multifocal distribution, complicating attempts at resection. There remains no standard approach to irradiating these patients. We report disease control and toxicity in pediatric patients with multifocal spinal MPE treated with limited-volume proton therapy. Materials/methods Twelve patients (≤21 years old) with multifocal spinal MPE were treated between 2009 and 2018 with limited-volume brain-sparing proton therapy. Median age was 13.5 years (range, 7-21). Radiotherapy was given as adjuvant therapy after primary surgery in five patients (42%) and for recurrence in seven (58%). No patient received prior radiation. Eleven patients (92%) had evidence of gross disease at radiotherapy. Eleven patients received 54 GyRBE; one received 50.4 GyRBE. Treatment toxicity was graded per the CTCAEv4.0. We estimated disease control and survival using the Kaplan-Meier product-limit method. Results The median follow-up was 3.6 years (range, 1.8-10.6). The five-year actuarial rates of local control, progression-free survival, and overall survival were 100%, 92%, and 100%, respectively. One patient experienced an out-of-field recurrence in the spine superior to the irradiated region. No patients developed in-field recurrences. Following surgery and irradiation, one patient developed grade three spinal kyphosis and one patient developed grade 2 unilateral L5 neuropathy. Conclusion 54 GyRBE to a limited volume appears effective for disseminated spinal MPE in both the primary and salvage settings, sparing children the toxicity of full craniospinal irradiation. Compared with historical reports, this approach using proton therapy improves the therapeutic ratio, resulting in minimal side effects and high rates of disease control.

For curative treatment of Hodgkin lymphoma, radiation therapy benefit must be weighed against toxicity. Although more costly, proton radiation therapy reduces dose to healthy tissue, potentially improving the therapeutic ratio compared with photons. We sought to determine the cost-effectiveness of proton versus photon therapy for mediastinal Hodgkin lymphoma (MHL) based on reduced heart disease.Our model approach was 2-fold: (1) Use patient-level dosimetric information for a cost-effectiveness analysis using a Markov cohort model. (2) Use population-based data to develop guidelines for policymakers to determine thresholds of proton therapy favorability for a given photon dose. The HD14 trial informed relapse risk; coronary heart disease risk was informed by the Framingham risk calculator modified by the mean heart dose (MHD) from radiation. Sensitivity analyses assessed model robustness and identified the most influential model assumptions. A 30-year-old adult with MHL was the base case using 30.6-Gy proton therapy versus photon intensity modulated radiation therapy.Proton therapy was not cost-effective in the base case for male ($129,000/ quality-adjusted life years [QALYs]) or female patients ($196,000/QALY). A 5-Gy MHD decrease was associated with proton therapy incremental cost-effectiveness ratio$100,000/QALY in 40% of scenarios. The hazard ratio associating MHD and heart disease was the most influential clinical parameter.Proton therapy may be cost-effective a select minority of patients with MHL based on age, sex, and MHD reduction. We present guidance for clinicians using MHD to aid decision-making for radiation therapy modality.

Purpose Despite high response rates, there has been reluctance to use radiation therapy for patients with relapsed/refractory (r/r) Hodgkin (HL) or aggressive non-Hodgkin lymphoma (NHL) given concerns for subacute and late toxicities. Symptomatic pneumonitis, a subacute toxicity, has an incidence of 17% to 24% (≥grade 2) even with intensity modulated radiation therapy. Proton therapy (PT), which has no exit radiation dose, is associated with a lower dose to lung compared with other radiation techniques. As risk of radiation pneumonitis is associated with lung dose, we evaluated whether pneumonitis rates are lower with PT. Methods and Materials Within an international, multi-institutional cohort, we retrospectively evaluated the incidence and grade of radiation pneumonitis (National Cancer Institute Common Terminology Criteria for Adverse Events v4) among patients with r/r HL or NHL treated with PT. Results A total of 85 patients with r/r lymphoma (66% HL, 34% NHL; 46% primary chemorefractory) received thoracic PT from 2009 to 2017 in the consolidation (45%) or salvage (54%) setting. Median dose was 36 Gy(RBE). Before PT, patients underwent a median of 1 salvage systemic therapy (range, 0-4); 40% received PT within 4 months of transplant. With a median follow-up of 26.3 months among living patients, 11 patients developed symptomatic (grade 2) pneumonitis (12.8%). No grade 3 or higher pneumonitis was observed. Dose to lung, including mean lung dose, lung V5, and V20, significantly predicted risk of symptomatic pneumonitis, but not receipt of brentuximab, history of bleomycin toxicity, sex, or peritransplant radiation. Conclusions PT for relapsed/refractory lymphoma was associated with favorable rates of pneumonitis compared with historical controls. We confirm that among patients treated with PT, pneumonitis risk is associated with mean lung and lung V20 dose. These findings highlight how advancements in radiation delivery may improve the therapeutic ratio for patients with relapsed/refractory lymphoma. PT may be considered as a treatment modality for patients with relapsed/refractory lymphoma in the consolidation or salvage setting.

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.

Background Large-scale population studies demonstrate an association between mothers' deaths and child mortality in both lower and higher income countries. The authors estimated children's deaths in association with mothers' deaths from breast or cervical cancer, 2 common cancers in low-income and middle-income countries affecting women of reproductive age, to develop a comprehensive assessment of the death burden of these cancers. Methods A Monte Carlo simulation model was devised whereby women were at risk of dying from breast cancer, cervical cancer, or another cause. Compared with children who have living mothers, children of women who die before they reached age 10 years have an elevated risk of death from all causes. Therefore, simulations were conducted, and the impact of mothers' deaths from cervical and breast cancer on associated child mortality was quantified for Bangladesh, Burkina Faso, and Denmark (benchmark analysis), then the analyses were extended to all African countries. Results Benchmark estimates of child deaths associated with mothers' deaths from breast and cervical cancer resulted in an increment in cancer-related mortality of approximately 2% in Bangladesh, 14% in Burkina Faso, and less than 1% in Denmark. The model predicted an increment in comprehensive cancer deaths when including child death estimates by as high as 30% in certain African countries. Conclusions To the authors' knowledge, this is the first study to estimate the impact of a mother's death from cancer on child mortality. The model's estimates call for further investigation into this correlation and underscore the relevance of adequate access to prevention and treatment among women of childbearing age.

Purpose To investigate cardiac toxicity associated with breast radiation therapy (RT) at 10-year follow-up in BCIRG-001, a phase 3 trial comparing adjuvant anthracycline chemotherapy (fluorouracil, doxorubicin, and cyclophosphamide) with anthracycline–taxane chemotherapy (docetaxel, doxorubicin, and cyclophosphamide) in women with lymph node–positive early breast cancer. Methods and Materials Prospective data from all 746 patients in the control arm (fluorouracil, doxorubicin, and cyclophosphamide) of BCIRG-001 at 10-year follow-up were obtained from Project Data Sphere. Cardiac toxicities examined included myocardial infarction (MI), heart failure (HF), arrhythmias, and relative and absolute left ventricular ejection fraction decrease of >20% from baseline. Toxicities were compared between patients who received RT versus no RT, left-sided RT versus no RT, and internal mammary nodal RT versus no RT. Results Of the 746 patients, 559 (75%) received RT to a median dose of 50 Gy. Myocardial infarction occurred in 3 RT patients (0.5%) versus 6 no-RT patients (3%) ( P =.01). Heart failure was seen in 15 RT patients (2.7%) versus 3 no-RT patients (1.6%) ( P =.6). Among these, 35 RT patients (18%) had a left ventricular ejection fraction relative decrease of >20% baseline versus 7 (10%) who did not receive RT ( P =.1). Arrhythmias were more common in RT patients (3.2%) versus no-RT patients (0%) ( P =.01). On univariable and multivariable analysis HF was not significantly associated with RT, and MI was negatively associated with RT. Conclusions In this retrospective analysis of prospective toxicity outcomes, there is an increased risk of arrhythmias but no clear evidence of significantly increased risk of MI or HF at 10 years in lymph node–positive women treated with breast RT and uniform adjuvant doxorubicin-based chemotherapy. Given the low incidence of these outcomes, studies with larger numbers are needed to confirm our findings.

Purpose Despite the dosimetric advantages of proton therapy, little data exist on patients who receive proton therapy for Ewing sarcoma of the cranium and skull base. This study reports local disease control and toxicity in such patients. Materials/methods We reviewed 25 patients (≤21 years old) with nonmetastatic Ewing sarcoma of the cranium and skull base treated between 2008 and 2018. Treatment toxicity was graded per the Common Terminology Criteria for Adverse Events v4.0. The Kaplan-Meier product limit method provided estimates of disease control and survival. Results Median patient age was 5.9 years (range, 1-21.7). Tumor subsites included the skull base (48%), non-skull-base calvarial bones (28%), paranasal sinuses (20%), and nasal cavity (4%). All patients underwent multiagent alkylator- and anthracycline-based chemotherapy; 16% underwent gross total resection (GTR) before radiation. Clinical target volume (CTV) 1 received 45 GyRBE and CTV2 received 50.4 GyRBE following GTR or 54-55.8 GyRBE following biopsy or subtotal resection. Median follow-up was 3.7 years (range, 0.26-8.3); no patients were lost. The 4-year local control, disease-free survival, and overall survival rates were 96%, 86%, and 92%, respectively. Two patients experienced in-field recurrences. One patient experienced bilateral conductive hearing loss requiring aids, two patients developed intracranial vasculopathy, and 6 patients required hormone replacement therapy for neuroendocrine deficits. None developed a secondary malignancy. Conclusion Proton therapy is associated with a favorable therapeutic ratio in children with large Ewing tumors of the cranium and skull base. Despite its high conformality, we observed excellent local control and no marginal recurrences. Treatment dosimetry predicts limited long-term neurocognitive and neuroendocrine side effects.

This study aimed to report on the institutional outcomes after proton therapy for pelvic rhabdomyosarcoma (RMS).Thirty-one children (≤21 years old) with group III pelvic RMS were enrolled on a prospective outcome study and treated between 2007 and 2018. Patients with vaginal/cervical RMS were excluded. The median age was 2.6 years. Twenty-four patients had embryonal RMS. At diagnosis, the median tumor volume was 185 cmWith a median follow-up of 4.2 years, the 5-year local control, progression-free survival, and overall survival rates were 83%, 80%, and 84%, respectively. Patients3 years old had better local control (100% vs 68%; P = .02), and patients with embryonal histology had better survival (96% vs 54%; P = .02). No other factors were significantly associated with disease control or survival. Specifically, no statistically significant difference was observed in local control, progression-free survival, or overall survival when comparing patients who underwent biopsy versus gross total resection (75% vs 93%, 68% vs 93%, 75% vs 93%, respectively). Excluding patients who underwent cystectomy, urinary toxicity was limited to 2 patients with nocturnal enuresis. Exploratory surgery to address a persistent mass or thickened bladder wall after radiation was the most common source of serious toxicity.This cohort of young children with large pelvic tumors treated with proton therapy demonstrates similar local control with less toxicity than historic reports. Functional bladder preservation is possible in most patients. Exploratory biopsy in the 18 months after radiation should be approached with caution.

To determine patterns of failure, clinical outcomes, and prognostic factors among pediatric patients treated with radiation therapy for parameningeal alveolar rhabdomyosarcoma.We evaluated clinical and treatment planning records of patients aged ≤21 years with parameningeal alveolar rhabdomyosarcoma treated with definitive or adjuvant radiation therapy at our institution. The Kaplan-Meier product limit method assessed disease control and survival; the log-rank test was used to evaluate prognostic impact.We identified 24 patients with a median age of 3.5 years (range, 1-20) treated between 2009 and 2016. The median follow-up was 2.4 years for all (range, 0.3-5.6) and 3.2 years for living patients (range, 0.7-5.6). Most patients had group III (96%), node-negative (67%), positive FOX fusion status (63%) disease, and intracranial extension (54%). The paranasal sinus was the most common subsite (29%). All patients were treated with concurrent chemotherapy and proton radiation therapy with a median dose of 50.4 Gy relative biological effectiveness (range, 41.4-59.4) at a median 13 weeks after induction chemotherapy (range, 3-25). The 3-year local control, regional control, disease-free survival, and overall survival rates were 66%, 94%, 40%, and 58%, respectively. Median time to any failure was 0.5 years (range, 0.2-2.1). N1 disease and intracranial extension (ICE) portended inferior overall survival (P = .002 and .02, respectively). Female sex portended better local control (P = .05). All 7 patients with distant metastases as the first site of recurrence had central nervous system metastases. Age4 years, absence of ICE, N0 disease, and primary tumor5 cm were associated with a statistically significant improvement in freedom from distant metastases.Although regional nodal failures were rare, in-field local recurrences and leptomeiningeal progression in those with ICE suggest the need for modification of local and central nervous system therapies.

Purpose In children treated for nasopharyngeal carcinoma, proton therapy and postchemotherapy target volumes can reduce the radiation dose to developing tissue in the brain and the skull base region. We analyzed outcomes in children with nasopharyngeal carcinoma treated with induction chemotherapy followed by moderate-dose proton therapy. Methods/materials Seventeen patients with nonmetastatic nonkeratinizing undifferentiated/poorly differentiated nasopharyngeal carcinoma underwent double-scattered proton therapy between 2011 and 2017. Median age was 15.3 years (range, 7-21). The American Joint Committee on Cancer T and N stage distribution included the following: T1, one patient; T2, five patients; T3, two patients; and T4, nine patients; and N1, six patients; N2, nine patients; and N3, two patients. Median radiation dose to the primary target volume and enlarged lymph nodes was 61.2 Gy (range, 59.4-61.2). Uninvolved cervical nodes received 45 Gy (range, 45-46.8). All radiation was delivered at 1.8 Gy/fraction daily using sequential plans. In 11 patients, photon-based intensity-modulated radiotherapy was used for elective neck irradiation to optimize dose homogeneity and improve target conformity. All patients received induction chemotherapy; all but one received concurrent chemotherapy. Five received adjuvant beta-interferon therapy. Results Median follow-up was 3.0 years (range, 1.6-7.9). No patients were lost to follow-up. Overall survival, progression-free survival, and local control rates were 100%. Fifteen patients developed mucositis requiring enteral feeding (n = 14) or total parenteral nutrition (n = 1) during radiotherapy. Serious late side effects included cataract (n = 1), esophageal stenosis requiring dilation (n = 1), sensorineural hearing loss requiring aids (n = 1), and hormone deficiency (n = 5, including three with isolated hypothyroidism). Conclusion Following induction chemotherapy, moderate-dose proton therapy can potentially reduce toxicity in the brain and skull base region without compromising disease control. However, further follow-up is needed to fully characterize and evaluate any reduction in long-term complications.

Purpose To test clinical feasibility, safety, and toxicity of prone hypofractionated breast, chest wall, and nodal radiation therapy. Methods and materials Following either segmental or total mastectomy with axillary node dissection, patients were treated in an institutional review board–approved prospective trial of prone radiation therapy to the breast, chest wall, and supraclavicular and level III axillary lymph nodes. A dose of 40.5 Gy/15 fractions with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose, 48 Gy) was prescribed. In postmastectomy patients, the same treatment was prescribed, but without a tumor bed boost. The primary endpoint was incidence of >grade 2 acute skin toxicity. The secondary endpoints were feasibility of treatment using prone set-up, compliance with protocol-defined dosimetric constraints, and incidence of late toxicity. A dosimetric comparison was performed between protocol plans (prone) and nonprotocol plans (supine), targeting the same treatment volumes. Results Sixty-nine patients with stage IB-IIIA breast cancer enrolled in this trial. Surgery was segmental mastectomy (n = 45), mastectomy (n = 23), and bilateral mastectomy (n = 1), resulting in 70 cases. None experienced >grade 2 acute skin toxicity according to the Common Terminology Criteria for Adverse Events, v 3.0, meeting our primary endpoint. Ninety-six percent of patients could be treated with this technique prone. However, 17 plans (24%) exceeded protocol constraints to the brachial plexus. Maximum long-term toxicity was 1 grade 2 arm lymphedema, 1 grade 3 breast retraction, and no occurrence of brachial plexopathy. Dosimetric comparison of protocol with nonprotocol plans demonstrated significantly decreased lung and heart doses in prone plans. Conclusions Prone hypofractionated breast, chest wall, and nodal radiation therapy is safe and well tolerated in this study. Although the initial pattern of local and regional control is encouraging, longer follow-up is warranted for efficacy and late toxicity assessment, particularly to the brachial plexus.

BACKGROUND 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. METHODS AND MATERIALS: Between 2008 and 2019, 29 patients with a median age of 14.8 years (range, 3.8–21.8) received proton therapy for non-metastatic chordoma at a single institution. Twenty-four tumors arose in the clivus/cervical spine region and 5 in the lumbosacral spine. Twenty-six tumors demonstrated well-differentiated histology and 3 were dedifferentiated or not otherwise specified (NOS). Approximately half of the tumors underwent specialized testing: 14 were brachyury-positive and 10 retained INI-1. Seventeen patients had gross disease at the time of radiation. The median radiation dose was 73.8 GyRBE. 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. Excluding 3 patients with dedifferentiated/NOS 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. CONCLUSION 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 following therapy.

Purpose While Ir-192 remains the mainstay isotope for gynecologic high-dose-rate (HDR) brachytherapy in the U.S., Co-60 is used abroad. Co-60 has a longer half-life than Ir-192, which may lead to long-term cost savings; however, its higher energy requires greater shielding. This study analyzes Co-60 acceptability based on a one-time expense of additional shielding and reports the financial experience of Co-60 in Peru's National Cancer Institute, which uses both isotopes. Material and methods A nationwide survey was undertaken assessing physician knowledge of Co-60 and willingness-to-pay (WTP) for additional shielding, assuming a source more cost-effective than Ir-192 was available. With 440 respondents, 280 clinicians were decision-makers and provided WTPs, with results previously reported. After completing a shielding report, we estimated costs for shielding expansion, noting acceptability to decision makers' WTP. Using activity-based costing, we note the Peruvian fiscal experience. Results Shielding estimates ranged from $173,000 to $418,000. The percentage of respondents accepting high-density modular or lead shielding (for union and non-union settings) were 17.5%, 11.4%, 3.9%, and 3.2%, respectively. Shielding acceptance was associated with greater number of radiation oncologists in a respondent's department but not time in practice or the American Brachytherapy Society membership. Peru's experience noted cost savings with Co-60 of $52,400 annually. Conclusions By comparing the cost of additional shielding for a sample institution's HDR suite with radiation oncologists' WTP, this multi-institutional collaboration noted < 20% of clinicians would accept additional shielding. Despite low acceptability in the US, Co-60 demonstrates cost-favorability in Peru and may similarly in other locations.

BACKGROUND Proton therapy in pediatrics may improve the risk/benefit profile of radiotherapy at a greater upfront financial cost, but it may prove to be cost effective if chronic medical complications can be avoided. Tools to assist with decision making are needed to aid in selecting pediatric patients for protons, and cost-effectiveness models can provide an objective method for this. METHODS A Markov cohort-simulation model was developed to assess the expected costs and effectiveness for specific radiation doses to the hypothalamus with protons versus photons in pediatric patients. Costing data included cost of investment and the diagnosis and management of growth hormone deficiency. Longitudinal outcomes data were used to inform risk parameters for the model. With costs in 2012 US dollars and effectiveness measured in quality-adjusted life years, incremental cost-effectiveness ratios were used to measure outcomes. RESULTS Proton therapy was cost effective for some scenarios based on the difference in hypothalamic sparing. Although some scenarios were not cost effective, others were not only cost effective for proton therapy but also demonstrated that protons were cost saving compared with photons. CONCLUSIONS The current results provide the first evidence-based guide for identifying children with brain tumors who may benefit the most from proton therapy with respect to endocrine dysfunction. Proton therapy may be more cost effective for scenarios in which radiation dose to the hypothalamus can be spared, but protons may not be cost effective when tumors are involving or directly adjacent to the hypothalamus if there is a high dose to this structure. Cancer 2015;121:1694–1702. © 2015 American Cancer Society.

BACKGROUND Proton therapy has been a hotly contested issue in both scientific publications and lay media. Proponents cite the modality's ability to spare healthy tissue, but critics claim the benefit gained from its use does not validate its cost compared with photon therapy. The objective of this study was to evaluate the cost effectiveness of proton therapy versus photon therapy in the management of pediatric medulloblastoma. METHODS A cost-effective analysis was performed from the societal perspective using a Monte Carlo simulation model. A population of pediatric medulloblastoma survivors aged 18 years was studied who had received treatment at age 5 years and who were at risk of developing 10 adverse events, such as growth hormone deficiency, coronary artery disease, ototoxicity, secondary malignant neoplasm, and death. Costing data included the cost of investment and the costs of diagnosis and management of adverse health states from institutional and Medicare data. Longitudinal outcomes data and recent modeling studies informed risk parameters for the model. Incremental cost-effectiveness ratios were used to measure outcomes. RESULTS Results from the base case demonstrated that proton therapy was associated with higher quality-adjusted life years and lower costs; therefore, it dominated photon therapy. In 1-way sensitivity analyses, proton therapy remained the more attractive strategy, either dominating photon therapy or having a very low cost per quality-adjust life year gained. Probabilistic sensitivity analysis illustrated the domination of proton therapy over photon therapy in 96.4% of simulations. CONCLUSIONS By using current risk estimates and data on required capital investments, the current study indicated that proton therapy is a cost-effective strategy for the management of pediatric patients with medulloblastoma compared with standard of care photon therapy. Cancer 2013;119:4299–4307. © 2013 American Cancer Society.

Purpose Ir-192 is the predominant source for high-dose-rate (HDR) brachytherapy in United States markets. Co-60, with longer half-life and fewer source exchanges, has piloted abroad with comparable clinical dosimetry but increased shielding requirements. We sought to identify practitioner knowledge of Co-60 and establish acceptable willingness-to-pay (WTP) thresholds for additional shielding requirements for use in future cost-benefit analysis. Methods and Materials A nationwide survey of U.S. radiation oncologists was conducted from June to July 2015, assessing knowledge of HDR sources, brachytherapy unit shielding, and factors that may influence source-selection decision-making. Self-identified decision makers in radiotherapy equipment purchase and acquisition were asked their WTP on shielding should a more cost-effective source become available. Results Four hundred forty surveys were completed and included. Forty-four percent were ABS members. Twenty percent of respondents identified Co-60 as an HDR source. Respondents who identified Co-60 were significantly more likely to be ABS members, have attended a national brachytherapy conference, and be involved in brachytherapy selection. Sixty-six percent of self-identified decision makers stated that their facility would switch to a more cost-effective source than Ir-192, if available. Cost and experience were the most common reasons provided for not switching. The most common WTP value selected by respondents was Conclusions A majority of respondents were unaware of Co-60 as a commercially available HDR source. This investigation was novel in directly assessing decision makers to establish WTP for shielding costs that source change to Co-60 may require. These results will be used to establish WTP threshold for future cost-benefit analysis.

Cardiac toxicity due to conventional breast radiation therapy (RT) has been extensively reported, and it affects both the life expectancy and quality of life of affected women. Given the favorable oncologic outcomes in most women irradiated for breast cancer, it is increasingly paramount to minimize treatment side effects and improve survivorship for these patients. Proton RT offers promise in limiting heart dose, but the modality is costly and access is limited. Using cost-effectiveness analysis, we provide a decision-making tool to help determine which breast cancer patients may benefit from proton RT referral.A Markov cohort model was constructed to compare the cost-effectiveness of proton versus photon RT for breast cancer management. The model was analyzed for different strata of women based on age (40 years, 50 years, and 60 years) and the presence or lack of cardiac risk factors (CRFs). Model entrants could have 1 of 3 health states: healthy, alive with coronary heart disease (CHD), or dead. Base-case analysis assumed CHD was managed medically. No difference in tumor control was assumed between arms. Probabilistic sensitivity analysis was performed to test model robustness and the influence of including catheterization as a downstream possibility within the health state of CHD.Proton RT was not cost-effective in women without CRFs or a mean heart dose (MHD)5 Gy. Base-case analysis noted cost-effectiveness for proton RT in women with ≥1 CRF at an approximate minimum MHD of 6 Gy with a willingness-to-pay threshold of $100,000/quality-adjusted life-year. For women with ≥1 CRF, probabilistic sensitivity analysis noted the preference of proton RT for an MHD ≥5 Gy with a similar willingness-to-pay threshold.Despite the cost of treatment, scenarios do exist whereby proton therapy is cost-effective. Referral for proton therapy may be cost-effective for patients with ≥1 CRF in cases for which photon plans are unable to achieve an MHD5 Gy.

155 Background: Malnutrition incidence in cancer approaches 85%, disproportionately burdening those with lung, GI, and advanced stage cancers. Malnourished patients have impaired chemotherapy response, shorter survival, longer hospital stays, and decreased QoL. Home delivered meals are nutritional interventions that improve patient well-being, nutrition, and lower healthcare costs in the elderly but have not been studied as an intervention in cancer patients. HDMTM are nutritionist prescribed home delivered meals tailored to patient’s symptoms, co-morbidities, and health needs. Preliminary data in 211 cancer patients showed with HDMTM 87% ate more than half of meals, 91% lived more independently, 89% ate more nutritiously, and 70% had less fatigue. HDMTM may be a strategy to reduce financial toxicity and healthcare utilization and improve QoL in cancer patients, but no primary data exists evaluating its efficacy. Methods: We sought to develop the first RCT evaluating patient-centered QoL improvement from nutritional intervention with HDMTM in those with metastatic lung and non-colorectal GI cancer. We established a partnership with God’s Love We Deliver, a 501c3 non-profit specializing in HDMTM. Results: We developed a protocol for a single-institution RCT of standard of care (SoC) versus SoC and HDMTM in metastatic lung and non-colorectal GI cancer patients with primary aim comparing QoL between arms at 12 weeks using the FACT-G questionnaire. Sample size is 180. Secondary aims assess HDMTM’s impact on nutritional status, weight, mood, survival, food security, financial toxicity, healthcare utilization, and cost effectiveness. Eligible patients tolerate oral alimentation, have PS 0-3, and newly diagnosed (< 6 weeks) metastatic cancer. All patients have pre-randomization nutritional evaluation by an oncologic dietician. Conclusions: We present the first PRMC reviewed and IRB approved RCT evaluating the efficacy of HDMTM in metastatic cancer patients with primary endpoint of patient reported QoL. Investigating HDMTM expands our knowledge of nutrition as an effective arm of palliative oncology.