Outcomes following proton therapy for pediatric esthesioneuroblastoma.

BACKGROUND: Pediatric esthesioneuroblastoma (EN) can infiltrate skull base anatomy, presenting challenges due to high radiation doses and pediatric tissue sensitivity. This study reports outcomes of pediatric EN treated with proton radiotherapy (PT). PROCEDURE: Using an IRB-approved prospective outcomes registry, we evaluated patient, tumor, and treatment-related variables impacting disease control and toxicity in pediatric nonmetastatic EN treated with modern multimodality therapy, including PT. RESULTS: Fifteen consecutive patients (median age 16) comprising Kadish stage B (n = 2), C (n = 9), and D (n = 4) tumors were assessed, including six with intracranial involvement, four with cranial nerve deficits, and four with cervical lymphadenopathy. Before radiation, two had subtotal and 13 had gross total resections (endoscopic or craniofacial). Two underwent neck dissection. Eleven received chemotherapy before radiation (n = 5), concurrent with radiation (n = 4), or both (n = 2). Median total radiation dose (primary site) was 66 Gy/CGE for gross disease and 54 Gy/CGE (cobalt Gray equivalent) for microscopic disease. Median follow-up was 4.8 years. No patients were lost to follow-up. Five-year disease-free and overall survival rates were 86% (no local or regional recurrences). Two patients developed vertebral metastases and died. Two required a temporary feeding tube for oral mucositis/dysphagia. Late toxicities included symptomatic retinopathy, major reconstructive surgery, cataracts, chronic otitis media, chronic keratoconjunctivitis, hypothyroidism, and in-field basal cell skin cancer. CONCLUSIONS: A multimodality approach for pediatric EN results in excellent local control. Despite the moderate-dose PT, serious radiation toxicity was observed; further dose and target volume reductions may benefit select patients. Longer follow-up and comparative data from modern photon series are necessary to fully characterize any relative PT advantage.

Proton Therapy in the Treatment of Men with Breast Cancer.

Purpose: Male breast cancer treatment involves multimodality therapy, including radiation therapy; nevertheless, few men have received proton therapy (PT) for it. Further, heart disease is an established leading cause of death in men, and radiation therapy heart dose correlates with cardiac toxicity, highlighting the need for cardiac-sparing radiation techniques. Thus, we provide a descriptive analysis of PT in a male breast cancer cohort. Patients and Methods: Men who received PT for localized breast cancer between 2012 and 2022 were identified from a prospective database. Toxicities were prospectively recorded by using the Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Results: Five male patients were identified. All had estrogen receptor (ER)-positive, Her2neu-negative disease and received adjuvant endocrine therapy. One had genetic testing positive for BRCA2, one had a variant of unknown significance (VUS) in the APC gene, and one had a VUS in MSH2. Median age was 73 years (range, 41-80). Baseline comorbidities included obesity (n = 1), diabetes (n = 1), hypertension (n = 4), history of deep vein thrombosis (n = 1), personal history of myocardial infarction (n = 3; 1 with a pacemaker), and a history of lung cancer (n = 1). All received PT to the left chest wall and comprehensive regional lymphatics. One received passive-scattering PT, and 4 received pencil beam scanning. One patient received a boost to the mastectomy incision via electrons. Median heart dose was 1 GyRBE (range, 0-1.0), median 0.1-cm3 dose to the left anterior descending artery was 7.5 GyRBE (range, 0-14.2), and median follow-up was 2 years (range, 0.75-6.5); no patient experienced a new cardiac event, and all remain free from breast cancer recurrence and progression. Conclusion: In a small case series for a rare diagnosis, PT to the chest wall and regional lymphatics, including internal mammary nodes, resulted in low cardiac exposure, high local regional disease control rates, and minimal toxicity. Proton therapy should be considered for treating men with breast cancer to achieve cardiac sparing.

Disparities in pediatric cancer survivorship care: A systematic review.

BACKGROUND: Childhood cancer survivors (CCS) experience many long-term health problems that can be mitigated with recommended survivorship care. However, many CCS do not have access to survivorship care nor receive recommended survivorship care. We reviewed the empirical evidence of disparities in survivorship care for CCS. METHODS: This systematic review searched PubMed, CINAHL, and PsycINFO for studies on survivorship care for CCS (PROSPERO: CRD42021227965) and abstracted the reported presence or absence of disparities in care. We screened 7945 citations, and of those, we reviewed 2760 publications at full text. RESULTS: A total of 22 studies reported in 61 publications met inclusion criteria. Potential disparities by cancer treatment (N = 14), diagnosis (N = 13), sex (N = 13), and current age (N = 13) were frequently studied. There was high quality of evidence (QOE) of survivorship care disparities associated with non-White race, Hispanic ethnicity, and being uninsured. Moderate QOE demonstrated disparities among CCS who were unemployed and older. Lower QOE was found for disparities based on cancer diagnosis, cancer treatment, age at diagnosis, time since diagnosis, sex, insurance type, income, educational attainment, and geographic area. CONCLUSIONS: We found strong empirical evidence of disparities in survivorship care for CCS associated with race, ethnicity, and insurance status. Multiple other disparate groups, such as those by employment, income, insurance type, education, cancer diagnosis, age at diagnosis, time since diagnosis, cancer treatment, geographic area, sex, and self-identified gender warrant further investigation. Prospective, multilevel research is needed to examine the role of other patient characteristics as potential disparities hindering adequate survivorship care in CCS.

Palliative care utilization and racial and ethnic disparities among women with de novo metastatic breast cancer in the United States.

PURPOSE: The potential disparities in palliative care delivery for underrepresented minorities with breast cancer are not well known. We sought to determine whether race and ethnicity impact the receipt of palliative care for patients with metastatic breast cancer (MBC). METHODS: We retrospectively reviewed the National Cancer Database for female patients diagnosed with stage IV breast cancer between 2010 and 2017 who received palliative care following diagnosis of MBC to assess the proportion of patients who received palliative care, including non-curative-intent local-regional or systemic therapy. Multivariable logistic regression analysis was performed to identify variables associated with receiving palliative care. RESULTS: 60,685 patients were diagnosed with de novo MBC. Of these, only 21.4% (n = 12,963) received a palliative care service. Overall, there was a positive trend in palliative care receipt from 18.2% in 2010 to 23.0% in 2017 (P < 0.001), which persisted when stratified by race and ethnicity. Relative to non-Hispanic White women, Asian/Pacific Islander women (aOR 0.80, 95% CI 0.71-0.90, P < 0.001), Hispanic women (adjusted odds ratio [aOR] 0.69, 95% CI 0.63-0.76, P < 0.001), and non-Hispanic Black women (aOR 0.94, 95% CI 0.88-0.99, P = 0.03) were less likely to receive palliative care. CONCLUSIONS: Fewer than 25% of women with MBC received palliative care between 2010 and 2017. While palliative care has significantly increased for all racial/ethnic groups, Hispanic White, Black, and Asian/Pacific Islander women with MBC still receive significantly less palliative care than non-Hispanic White women. Further research is needed to identify the socioeconomic and cultural barriers to palliative care utilization.

Analysis of the Pediatric Radiotherapy Landscape in Mexico and a Subsequent Educational e-Contouring Intervention.

PURPOSE: Mexico and Central America have the highest childhood cancer incidence in the West. Pediatric-specific oncology knowledge contributes to the disparity. We sought to (1) determine the self-identified treatment patterns and needs of Mexican pediatric radiation oncologists and (2) pilot a workshop to improve contouring accuracy. MATERIALS AND METHODS: Partnering with local experts and the Sociedad Mexicana de Radioterapeutas (SOMERA), a 35-question survey was designed to ascertain pediatric radiotherapy capacity and distributed through the SOMERA listserv. The most challenging malignancies were selected for workshop. Participants received precontouring and postcontouring homework to assess improvement per the Dice metric. The Wilcoxon sign-rank test was used for comparative statistics. RESULTS: Ninety-four radiation oncologists attempted and 79 completed the survey. Forty-four (76%) felt comfortable treating a pediatric patient, and 36 (62%) were familiar with national protocols for pediatric treatment. Most had access to nutrition, rehabilitation, endocrinology, and anesthesia; 14% had access to fertility services and 27% to neurocognitive support; 11% noted no support, and only one respondent had child-life support. The postsurvey contouring workshop was conducted for high-grade glioma, medulloblastoma, and Hodgkin lymphoma. Significant improvements were seen in all target volumes. CONCLUSION: We present the first national survey of Mexico's pediatric radiotherapy capacity and Latin American e-contouring educational intervention with preworkshop and postworkshop Dice metrics, noting statistically significant improvement in all target volumes. Participation improved compared with prior experience through SOMERA partnership and Continuing Medical Education incentivization.

Incidence of Rib Fracture following Treatment with Proton Therapy for Breast Cancer.

Purpose: To determine the rib fracture rate in a cohort of patients with breast cancer treated with proton therapy. Patient and Methods: From a prospective database, we identified 225 patients treated with proton therapy between 2012 and 2020 (223 women; 2 men). Clinical and dosimetric data were extracted, the cumulative incidence method assessed rib fracture rate, and Fine-Gray tests assessed prognostic significance of select variables. In-field rib fracture was defined as a fracture that occurred in a rib located within the 10% isodose line. Out-of-field rib fracture was defined as a fracture occurring in a rib location outside of the 10% isodose line. Results: Of the patients, 74% had left-sided breast cancer; 5%, bilateral; and 21%, right-sided. Dual-energy x-ray absorptiometry scans showed normality in 20%, osteopenia in 34%, and osteoporosis in 6% (test not performed in 40%). Additionally, 57% received an aromatase inhibitor. Target volumes were breast ± internal mammary nodes (IMNs) (16%), breast and comprehensive regional lymphatics (32%), chest wall ± IMNs (1%), and chest wall/comprehensive regional lymphatics (51%). Passive-scattered proton therapy was used for 41% of patients, 58% underwent pencil-beam scanning (PBS), and 1% underwent a combination (passive scattering/PBS), with 85% of patients receiving a boost. Median follow-up was 3.1 years, with 97% having >12-month follow-up. The 3-year cumulative in-field rib fracture incidence was 3.7%. Eight patients developed in-field rib fractures (1 symptomatic, 7 imaging identified) for a 0.4% symptomatic rib fracture rate. Median time from radiation completion to rib fracture identification was 1.8 years (fractures were identified within 2.2 years for 7 of 8 patients). No variables were associated with rib fracture on univariate analysis. Three fractures developed outside the radiation field (0.9% cumulative incidence of out-of-field rib fracture). Conclusion: In this series of patients with breast cancer treated with proton therapy, the 3-year rib fracture rates remain low (in-field 3.7%; symptomatic 0.4%). As in photon therapy, the asymptomatic rate may be underestimated owing to a lack of routine surveillance imaging. However, patients experiencing symptomatic rib fractures after proton therapy for breast cancer are rare.

Proton Therapy for Bilateral Breast Cancer Maximizes Normal-Tissue Sparing.

Purpose: Treatment for bilateral breast cancer with radiation therapy is technically challenging. We evaluated the clinical and dosimetric outcomes of a small series of patients with synchronous bilateral breast cancer, including a photon dosimetric comparison, to identify optimal treatment planning approaches. Materials and Methods: We reviewed a registry of patients (simultaneously) diagnosed with synchronous bilateral breast cancers who underwent postoperative definitive adjuvant proton therapy at our institution between 2012 and 2021. All patients were treated with double-scattered proton or pencil-beam scanning therapies. For comparison, intensity-modulated radiation therapy photon plans optimized for organ sparing and coverage were generated after treatment. Results: Six patients were included. The median patient age was 66 years; all were female with no history of breast cancer or radiation therapy. Two (33%) patients received breast/chest wall-only treatments, 1 (17%) required breast plus level I axillary treatment to one side and breast plus regional nodal irradiation (RNI) to the other, and 3 (50%) received bilateral breast/chest plus RNI; dosimetric results are reported for each group's median. Analysis showed clinical target coverage was comparable between proton and photon techniques (V95% of 96.4% with proton, 97.8% with photon). However, protons could deliver superior organ sparing at clinically relevant dose metrics for virtually all structures: a 6.7 Gy absolute reduction in the mean heart dose (7.5 Gy with photons to 0.7 Gy with protons), a 47% to 57% relative reduction in D0.1cm3 to coronary arteries, a 54% relative reduction in lung V20 Gy, and an absolute 7.6 Gy reduction to the brachial plexus. There was also greater esophagus and spinal cord sparing. The overall survival rate was 100% at 1.5 years of median follow-up (0.5-4.9), and all patients were free of disease. For toxicity, all patients had some form of acute side effects: 66% experienced grade 2 breast/chest pain or soreness; 100% had grade 2 radiation dermatitis or skin induration; 33% had grade 2 fatigue; and 17% had grade 2 esophagitis (per the Common Terminology Criteria for Adverse Events [CTCAE] version 5.0; US National Cancer Institute, Bethesda, Maryland). Subacute toxicity (within 6 months) was observed for 17% of patients with delayed onset of grade 3 dermatitis in the setting of preexisting lupus, 17% with a delayed surgical wound complication, and 17% with grade 2 soft tissue fibrosis. No grade 4 or 5 events were observed. Conclusions: Substantial dose reductions to multiple organs at risk while maintaining target coverage make proton the preferred modality for bilateral breast cancer treatment when available.

Global and regional estimates of orphans attributed to maternal cancer mortality in 2020.

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.

Intraoperative radiation therapy for early-stage breast cancer: a single-institution experience.

Background: To assess outcomes and toxicity after low-energy intraoperative radiotherapy (IORT) for early-stage breast cancer (ESBC). Materials and methods: 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. Results: 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. Conclusions: IORT for select patients with ESBC results in acceptable outcomes in regard to ipsilateral breast tumor recurrence and toxicity.

Pericardial Effusion during Proton Therapy in a Patient with Chemorefractory Hodgkin Lymphoma.

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.

Hyperfractionated-Accelerated Reirradiation with Proton Therapy for Radiation-Associated Breast Angiosarcoma.

Purpose: Radiation-associated angiosarcoma (RAAS) is a rare complication among patients treated with radiation therapy for breast cancer. Hyperfractionated-accelerated reirradiation (HART) improves local control after surgery. Proton therapy may further improve the therapeutic ratio by mitigating potential toxicity. Materials and Methods: Six patients enrolled in a prospective registry with localized RAAS received HART with proton therapy between 2015 and 2021. HART was delivered twice or thrice daily in fraction sizes of 1.5 or 1.0 Gy, respectively. All patients received 45 Gy to a large elective volume followed by boosts to a median dose of 65 (range, 60-75) Gy. Toxicity was recorded prospectively by using the Common Terminology Criteria for Adverse Events, version 4.0. Results: The median follow-up duration was 1.5 (range, 0.25-2.9) years. The median age at RAAS diagnosis was 73 (range, 60-83) years with a median latency of 8.9 (range, 5-14) years between radiation therapy completion and RAAS diagnosis. The median mean heart dose was 2.2 (range, 0.1-4.96) Gy. HART was delivered postoperatively (n = 1), preoperatively (n = 3), preoperatively for local recurrence after initial management with mastectomy (n = 1), and as definitive treatment (n = 1). All patients had local control of disease throughout follow-up. Three of 4 patients treated preoperatively had a pathologic complete response. The patient treated definitively had a complete metabolic response on her posttreatment PET/CT (positron emission tomography-computed tomography) scan. Two patients developed distant metastatic disease despite local control and died of their disease. Acute grade 3 toxicity occurred in 3 patients: 2 patients undergoing preoperative HART experienced wound dehiscence and 1 postoperatively developed grade 3 wound infection, which resolved. Conclusion: HART with proton therapy appears effective for local control of RAAS with a high rate of pathologic complete response and no local recurrences to date. However, vigilant surveillance for distant metastasis should occur. Toxicity is comparable to that in photon/electron series. Proton therapy for RAAS may maximize normal tissue sparing in this large-volume reirradiation setting.

Evaluating Regional Nodal Irradiation Allocation and Association with Oncologic Outcomes in NSABP B-18, B-27, B-40, and B-41.

PURPOSE: There is a lack of level I evidence to guide radiation therapy recommendations for patients receiving neoadjuvant chemotherapy for breast cancer. We used 4 neoadjuvant chemotherapy trials to determine which patients benefit from regional nodal irradiation (RNI). METHODS AND MATERIALS: We obtained data from the NSABP (National Surgical Adjuvant Breast and Bowel Project) B-18, B-27, B-40, and B-41 clinical trials. B-40 and B-41 allowed RNI at physician's discretion. We evaluated locoregional recurrence (LRR), distant recurrence, disease-free survival, and overall survival (OS). Kaplan-Meier, Peto-Peto, χ2, 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, disease-free survival, distant recurrence, or LRR. CONCLUSIONS: 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 3 clinical trials are needed to establish guidelines for patients who should receive RNI after neoadjuvant treatment, and action is necessary to eliminate the disparity in care delivery shown for Hispanic women.

Comparative Effectiveness of Proton Therapy versus Photon Radiotherapy in Adolescents and Young Adults for Classical Hodgkin Lymphoma.

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%; < 30 Gy, 86%; P = .82). Likewise, there was no difference in 2-year PFS among patients who received either proton or photon radiotherapy (proton, 94%; photon, 83%; P = .07). 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.

Heterogeneity in Radiotherapeutic Parameter Assumptions in Cost-Effectiveness Analyses in Prostate Cancer: A Call for Uniformity.

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.

Simultaneous Diagnosis of Craniopharyngioma in 2 Brothers.

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.

Bicentric Treatment Outcomes After Proton Therapy for Nonmyxopapillary High-Grade Spinal Cord Ependymoma in Children.

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.

Establishing Cost-Effective Allocation of Proton Therapy for Patients With Mediastinal Hodgkin Lymphoma.

PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.