Evaluating scholastic achievement in pediatric brain tumor survivors compared to healthy controls.

BACKGROUND: Radiotherapy (RT) causes cognitive deficits in pediatric brain tumor survivors (PBTS). Traditionally, this is measured using neuropsychological testing, which lack pre-diagnosis baseline and do not necessarily trigger action. This pilot project investigated a novel patient-centered outcome of scholastic performance using state-collected educational data. METHODS: We retrospectively analyzed scholastic achievements in children residing in Florida. Eligibility in the treatment group received brain-directed RT between 2007 - 2020 at our institution. Controls were matched at a 3:1 ratio by age, grade, district, and free or reduced lunch (FRL) eligibility. The Florida Department of Education provided educational records for both groups. Generalized linear mixed-effects models were used to predict scholastic outcomes with covariates age, time (binary value of pre- or post-RT), treatment group, and the primary independent variable as the interaction term between time and treatment. Scholastic data was matched with institutional clinical data. RESULTS: Fifty PBTS and 150 matched controls were included for analysis. Median age of PBTS was 12, 12% identified as Black, and 18% as Hispanic. Fifty-two percent were FRL eligible. Forty percent received craniospinal irradiation, and 56% received chemotherapy. Post-RT PBTS had 21 times the odds of receiving accommodations (p=0.006), twice the odds of being retained (p=0.010), and 42% lower odds than controls receiving a passing mathematics score (p=0.068). CONCLUSIONS: To our knowledge, this is the first American experience to successfully link individual scholastic and clinical data. Scholastic performance serves as a meaningful patient-centered outcome complementing the existing suite of neuropsychological testing.

Long-term outcomes following proton therapy for pediatric spinal low-grade glioma.

BACKGROUND: Due to its rarity, no standard treatment guidelines exist for pediatric spinal low-grade glioma (LGG-S). Proton therapy (PT) offers an attractive modality to minimize toxicity. Herein, we present the first published series of pediatric patients who received PT for progressive LGG-S. PROCEDURES: We identified eight consecutive patients with nonmetastatic LGG-S treated with PT. Cumulative incidence method was used to estimate local control (LC), freedom from distant metastases (FFDM), and freedom from progression (FFP). The Kaplan-Meier product limit method assessed overall survival (OS). Toxicity was assessed according to the Common Terminology Criteria for Adverse Events Version 5.0. RESULTS: Median age at diagnosis was 4 years. All patients underwent attempted resection and developed recurrence/progression prior to referral for PT, with median duration between initial surgery and PT of 4.4 years. Median age at the start of PT was 8 years. Most patients (n = 5) received PT as ≥third line treatment. Seven patients were treated with PT to the primary tumor. Most patients (n = 7) received between 45-50.4 CGE. Median follow up was 7.8 years. The 10-year estimates for LC, FFDM, FFP, and OS were 85, 88, 73, and 55%, respectively. One patient experienced malignant transformation and two developed pseudoprogression following PT. No pulmonary, gastrointestinal, or musculoskeletal toxicities were observed during or after PT. CONCLUSIONS: Despite negative selection bias our experience suggests PT for pediatric LGG-S offers long-term disease control with limited toxicity. The favorable therapeutic ratio of PT suggests it should be considered among first-line therapy in children with nonmetastatic, unresectable LGG-S.

PTCOG international survey of practice patterns and trends in utilization of proton therapy for breast cancer.

Purpose/objectives: The indications, techniques, and extent to which proton beam therapy (PBT) is employed for breast cancer are unknown. We seek to determine PBT utilization for breast cancer. Materials/methods: The Particle Therapy Co-Operative Group (PTCOG) Breast Subcommittee developed an IRB-approved 29-question survey and sent it to breast cancer radiation oncologists at all active PBT centers worldwide in June 2023. Descriptive statistics were used to summarize responses, and comparisons by continent were performed using Fisher's exact tests. Results: Of 79 surveys distributed, 28 recipients submitted responses (35 % response rate) representing fifteen U.S., 8 European, and 5 Asian centers (continent response rate 50 %, 38 %, and 18 %, respectively). Overall, 93 % reported treating breast cancer patients with PBT; 13 (50 %) have treated ≥100 breast cancer patients at their center since opening. Most (89 %) have pencil beam scanning technology. Nearly half (46 %) use moderate hypofractionation (15-20 fractions) for regional nodal irradiation and 42 % conventional fractionation (25-30 fractions). More European centers prefer hypofractionation (88 %) vs. Asian (50 %) and U.S. (21 %) centers (p = 0.003). Common patient selection methods were practitioner determination/patient preference (n = 16) and comparative plan evaluation (n = 15). U.S. centers reported the most experience with breast PBT, with 71 % having treated ≥100 breast cancer patients vs. 38 % in Europe and none in Asia (p = 0.001). Of respondent centers, 39 % enrolled ≥75 % of breast PBT patients on a research study. Conclusion: Utilization, patient selection methods, and dose-fractionation approaches for breast cancer PBT vary worldwide. These survey data serve as a benchmark from which successor surveys can provide insight on practice pattern evolution.

Risk of transfusion-related iron overload varies based on oncologic diagnosis and associated treatment: Retrospective analysis from a single pediatric cancer center.

BACKGROUND: Transfusion-related iron overload (TRIO) is a widely acknowledged late effect of antineoplastic therapy in pediatric cancer survivors, but firm guidelines as to screening protocols or at-risk populations are lacking in the literature. PROCEDURE: We performed retrospective analysis of all oncology patients diagnosed at our center from 2014 to 2019, who underwent TRIO screening as part of an internal quality improvement project. Correlations of MRI-confirmed TRIO with patient-, disease-, and treatment-specific features were evaluated. RESULTS: We show that a tiered screening algorithm for TRIO, when followed as intended, led to the identification of the highest proportion of patients with TRIO. We confirm that cardiac TRIO is quite rare in the oncology patient population. However, accepted surrogate markers including red blood cell transfused volume and ferritin only modestly correlated with TRIO in our patient cohort. Instead, we found that older age, leukemia diagnosis, anthracycline exposure, and receipt of stem cell transplant were most strongly associated with risk for TRIO. CONCLUSIONS: We describe associations between TRIO and patient, disease, and treatment characteristics in a multivariate risk model that could lead to an improved risk stratification of off-therapy patients, and which should be validated in a prospective manner.

Long-term outcomes following proton therapy for non-metastatic central nervous system germinoma in children and adolescents.

BACKGROUND/PURPOSE: Radiation is a key component in the treatment of central nervous system pure germinoma (PG) in children and adolescents. Proton therapy (PT) improves normal tissue sparing and potentially reduces adverse effects (AE). The aim of this study was to present the largest single institution experience utilizing PT for the management of PG. MATERIALS METHODS: We enrolled 35 non-metastatic patients with PG that were treated with PT at our institution between July 2007 - September 2021. Most received induction chemotherapy (n = 31, 89 %) and whole ventricular irradiation with an involved field boost (n = 29, 83 %). The most common total dose was 30 CGE (n = 18, 51.4 %). We utilized the cumulative incidence method to estimate local control (LC), freedom from distant metastases (FFDM), freedom from progression (FFP), and overall survival (OS). Treatment related toxicity was assessed per CTCAE version 5. RESULTS: Median follow-up was 6.2 years (range, 0.9---15.2). The 10-year Kaplan-Meier estimates for LC, FFDM, FFP, and OS were 100 %, 100 %, 100 %, and 94 % respectively. The most common AE were hearing impairment requiring hearing aids (n = 3), transient hypersomnia requiring medication (n = 3), and new onset endocrinopathy (n = 1). Of the 23 evaluable patients ≥ 18 years old at last follow-up, 8 were high school graduates/in college, 8 college graduates, and 7 others gainfully employed. CONCLUSIONS: When utilized in modern multimodality treatment of non-metastatic PG, the precise dosimetry of PT does not compromise disease control. Although serious radiation side effects are rare, the 100% cure rate supports further investigation into selective radiation dose and volume de-escalation.

Effects on Lung Tissue After Breast Cancer Radiation: Comparing Photon and Proton Therapies.

Purpose: In breast cancer, improved treatment approaches that reduce injury to lung tissue and early diagnosis and intervention for lung toxicity are increasingly important in survivorship. The aims of this study are to (1) compare lung tissue radiographic changes in women treated with conventional photon radiation therapy and those treated with proton therapy (PT), (2) assess the volume of lung irradiated to 5 Gy (V5) and 20 Gy (V20) by treatment modality, and (3) quantify the effects of V5, V20, time, and smoking history on the severity of tissue radiographic changes. Patients and Methods: A prospective observational study of female breast cancer patients was conducted to monitor postradiation subclinical lung tissue radiographic changes. Repeated follow-up x-ray computed tomography scans were acquired through 2 years after treatment. In-house software was used to quantify an internally normalized measure of pulmonary tissue density change over time from the computed tomography scans, emphasizing the 6- and 12-month time points. Results: Compared with photon therapy, PT was associated with significantly lower lung V5 and V20. Lung V20 (but not V5) correlated significantly with increased subclinical lung tissue radiographic changes 6 months after treatment, and neither correlated with lung effects at 12 months. Significant lung tissue density changes were present in photon therapy patients at 6 and 12 months but not in PT patients. Significant lung tissue density change persisted at 12 months in ever-smokers but not in never-smokers. Conclusion: Patients treated with PT had significantly lower radiation exposure to the lungs and less statistically significant tissue density change, suggesting decreased injury and/or improved recovery compared to photon therapy. These findings motivate additional studies in larger, randomized, and more diverse cohorts to further investigate the contributions of treatment modality and smoking regarding the short- and long-term radiographic effects of radiation on lung tissue.

Axillary Surgery for Chemoresidual (ypN-Positive) Nodal Disease.

This cohort study using pooled data from 2 randomized clinical trials examines whether removing more lymph nodes with axillary lymph node dissection improved outcomes over sentinel lymph node biopsy when most patients received adjuvant radiation therapy or regional nodal irradiation.

Creating an Integrated Coaching Culture in Higher Education.

In higher education, it is a common ask to do more with less while delivering high-quality, holistic service to students. Coaching has been shown to produce significant gains in strengthening self-efficacy, improving GPA, and increasing retention through graduation (Alzen et al., 2021; Capstick et al., 2019; Catchings, 2014; Grover & Furnham, 2016; Losch et al., 2016), therefore making it a logical program to target for growth. To expand the impact of the University of Kentucky's academic coaching program, in 2020, leadership modified the Appreciative Academic Coaching framework (Bradley & Reynolds, 2021) into Integrated Success Coaching with the intent to build a coaching culture across campus. This modification created a two-pronged approach to serving students, faculty, and staff across our campus: (a) training for professionally certified International Coaching Federation (ICF) coaches across six domains, including academic life, career, finances, wellness, leadership, and identity (e.g., First Gen) to directly serve students, and (b) training in foundational coaching skills for faculty, staff, and student leaders to incorporate into their daily practice. The evolution of this coaching model has allowed for holistic support of students and immersive coaching values and practices for faculty, staff, and student leaders that have led to improved retention and better GPA outcomes for students on probation and a culture of coaching care among faculty, staff, and students.

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.

Pfizer BNT 162b2 COVID-19 vaccine-induced fulminant myopericarditis: A case study.

The use of mRNA COVID-19 vaccine can on rare occasions cause life-threatening, fulminant myopericarditis. This case report demonstrates previously reported benefit of early use of venoarterial extracorporeal membrane oxygenation mechanical assistance and supports the use of intravenous highly purified immunoglobulin pharmacotherapy to help achieve a good clinical outcome.

In-person and virtual adaptation of an interprofessional palliative care communications skills training course for pediatric oncology clinicians.

Purpose: Effective, empathic communication is crucial for pediatric oncology clinicians when discussing palliative and end-of-life (PC/EOL) care with parents of children with cancer. Unfortunately, many parents report inadequate communication at these distressing times. This study evaluates the communication skills training (CST) clinicians received to deliver a PC/EOL communication intervention as part of a multi-site randomized-controlled trial (RCT). Methods: Clinicians from eight sites formed dyads (one physician and one nurse [RN] or advanced practice provider [APP]) and were trained over 3 days (in-person or virtually). Training was adapted from VitalTalk™ and included didactic instruction, videos, visual aids, and dedicated time to practice with simulated patients. Study participants completed a confidential, post-training online evaluation survey. A self-reported quality assurance checklist was used to measure fidelity to the communication protocol when delivered to parents during the RCT. Results: Thirty clinicians completed training; 26 completed post-training surveys including twelve (46.1%) physicians, 8 (30.8%) RNs and 6 (23.1%) APPs. Most were female (65.4%); white (80.8%), not Latinx (88.5%); 40-50 years old (53.9%); and in practice over 10 years (65.4%). Nine (34.6%) trained in-person; the rest trained virtually. Ninety-two percent reported the course was valuable or very valuable for developing their PC/EOL communication skills and 96% reported learning something new. Dyads trained virtually had similar fidelity to those trained in-person (95% and 90% respectively) when delivering the PC/EOL communication intervention to parents. Conclusion: This PC/EOL CST was valuable for improving pediatric oncology clinicians' communication skills, successfully implemented in-person and virtually, and translated effectively into practice.

Liver Late Effects in Childhood Cancer Survivors Treated With Radiation Therapy: A PENTEC Comprehensive Review.

PURPOSE: A pediatric normal tissue effects in the clinic (PENTEC) comprehensive review of patients with childhood cancer who received radiation therapy (RT) to the liver was performed to develop models that may inform RT dose constraints for the liver and improve risk forecasting of toxicities. METHODS AND MATERIALS: A systematic literature search was performed to identify published data on hepatic toxicities in children. Treatment and outcome data were extracted and used to generate normal tissue complication probability (NTCP) models. Complications from both whole and partial liver irradiation were considered. For whole liver irradiation, total body irradiation and non-total body irradiation treatments were considered, but it was assumed that the entire liver received the prescribed dose. For partial liver irradiation, only Wilms tumor flank field RT could be analyzed. However, a prescribed dose assumption could not be applied, and there was a paucity of analyzable liver dosimetry data. To associate the dose-volume exposures with the partial volume complication data from flank irradiation, liver dose-volume metrics were reconstructed for Wilms tumor flank RT using age-specific computational phantoms as a function of field laterality and superior extent of the field. RESULTS: The literature search identified 2103 investigations pertaining to hepatic sinusoidal obstructive syndrome (SOS) and liver failure in pediatric patients. All abstracts were screened, and 241 articles were reviewed in full by the study team. A model was developed to calculate the risk of developing SOS after whole liver RT. RT dose (P = .006) and receipt of nonalkylating chemotherapy (P = .01) were significant. Age <20 years at time of RT was borderline significant (P = .058). The model predicted a 2% risk of SOS with zero RT dose, 6.1% following 10 Gy, and 14.5% following 20 Gy to the whole liver (modeled as the linear-quadratic equivalent dose in 2-Gy fractions [α/ß = 3 Gy]). Patients with Wilms tumor treated with right flank RT had a higher observed rate of SOS than patients receiving left flank RT, but data were insufficient to generate an NTCP model for partial liver irradiation. From the phantom-based dose reconstructions, mean liver dose was estimated to be 2.16 ± 1.15 Gy and 6.54 ± 2.50 Gy for left and right flank RT, respectively, using T10-T11 as the superior field border and a prescription dose of 10.8 Gy (based on dose reconstruction). Data were sparse regarding rates of late liver injury after RT, which suggests low rates of severe toxicity after treatment for common pediatric malignancies. CONCLUSIONS: This pediatric normal tissue effects in the clinic (PENTEC) review provides an NTCP model to estimate the risk of hepatic SOS as a function of RT dose following whole liver RT and quantifies the range of mean liver doses from typical Wilms tumor flank irradiation fields. Patients treated with right flank RT had higher rates of SOS than patients treated with left flank RT, but data were insufficient to develop a model for partial liver irradiation. Risk of SOS was estimated to be approximately ≤6% in pediatric patients receiving whole liver doses of <10 Gy.

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.

Clinical Characteristics, Treatment Considerations, and Outcomes of Infants with Rhabdomyosarcoma.

RMS most commonly presents in children and adolescents, however a subset of tumors are diagnosed in infants under one year of age. Due to the rarity of infant RMS, utilization of different treatment approaches and goals, and small sample sizes, the published studies of infants with RMS have yielded heterogeneous results. In this review, we discuss the outcomes of infants with RMS treated in various clinical trials and the strategies that various international cooperative groups have employed to reduce the morbidity and mortality related to treatment without compromising the overall survival of this population. This review discusses the unique scenarios of diagnosing and managing congenitals or neonatal RMS, spindle cell RMS and relapsed RMS. This review concludes by exploring novel approaches to diagnosis and management of infants with RMS that are currently being studied by various international cooperative groups.

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.

Facial deformation following treatment for pediatric head and neck rhabdomyosarcoma; the difference between treatment modalities. Results of a trans-Atlantic, multicenter cross-sectional cohort study.

BACKGROUND: The four different local therapy strategies used for head and neck rhabdomyosarcoma (HNRMS) include proton therapy (PT), photon therapy (RT), surgery with radiotherapy (Paris-method), and surgery with brachytherapy (AMORE). Local control and survival is comparable; however, the impact of these different treatments on facial deformation is still poorly understood. This study aims to quantify facial deformation and investigates the differences in facial deformation between treatment modalities. METHODS: Across four European and North American institutions, HNRMS survivors treated between 1990 and 2017, more than 2 years post treatment, had a 3D photograph taken. Using dense surface modeling, we computed facial signatures for each survivor to show facial deformation relative to 35 age-sex-ethnicity-matched controls. Additionally, we computed individual facial asymmetry. FINDINGS: A total of 173 HNRMS survivors were included, survivors showed significantly reduced facial growth (p < .001) compared to healthy controls. Partitioned by tumor site, there was reduced facial growth in survivors with nonparameningeal primaries (p = .002), and parameningeal primaries (p ≤.001), but not for orbital primaries (p = .080) All patients were significantly more asymmetric than healthy controls, independent of treatment modality (p ≤ .001). There was significantly more facial deformation in orbital patients when comparing RT to AMORE (p = .046). In survivors with a parameningeal tumor, there was significantly less facial deformation in PT when compared to RT (p = .009) and Paris-method (p = .007). INTERPRETATION: When selecting optimal treatment, musculoskeletal facial outcomes are an expected difference between treatment options. These anticipated differences are currently based on clinicians' bias, expertise, and experience. These data supplement clinician judgment with an objective analysis highlighting the impact of patient age and tumor site between existing treatment options.