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Background and Purpose: Regional nodal irradiation (RNI) for breast cancer delivers radiation in proximity to the shoulder and torso, and radiation exposure may contribute to long-term upper extremity and postural morbidity. To date, no studies have assessed the differential dosimetric impact of proton versus photon radiation on shoulder and torso anatomy. This study examined clinically relevant musculoskeletal (MSK) structures and assessed the dose delivered with each modality., Patients/material and Methods: Ten MSK structures were contoured on IMPT (intensity-modulated proton therapy) and VMAT (volumetric modulated arc therapy) plans for 30 patients receiving RNI. Relevant dose metrics were compared for each of the structures. Intensity-modulated proton therapy dose was calculated using the relative biological effective value of 1.1. Hypo-fractionated plans were scaled to the equivalent dose in 2 Gy fractions (EQD2) using an alpha/beta ratio of four. Wilcoxon signed rank sum tests compared doses. Select three-dimensional and optimised VMAT plans were also informally compared., Results and Interpretation: Each of the 10 structures received a statistically significantly lower dose with the use of IMPT compared with VMAT. Differences were greatest for posterior structures, including the trapezius, latissimus dorsi and glenohumeral joint. Mean absolute differences were as great as 23 Gy (supraspinatus D5cc) and up to 30-fold dose reductions were observed (deltoid D50cc). An average 3.7-fold relative dose reduction existed across all structures. Measures of low/intermediate dose (V15Gy and D50cc) showed the largest differences. Intensity-modulated proton therapy results in statistically lower radiation exposure to relevant shoulder and torso anatomy compared to photon radiation for patients requiring RNI. Prospective study is needed to correlate functional outcomes with radiation dose.

Purpose: The optimal approach for partial breast irradiation (PBI) is unknown. We investigated a novel de-intensified 3-fraction PBI regimen for photons, protons, and brachytherapy., Methods and Materials: A multicenter nonrandomized controlled trial with the primary outcome of adverse cosmesis at 3 years versus before PBI. Eligibility criteria were age ≥50 years treated with breast-conserving surgery for node-negative estrogen receptor-positive (ER+) invasive breast cancer or any ductal carcinoma in situ (DCIS) measuring ≤2.5 cm. Photon and proton PBI were prescribed 21.9 Gy (relative biological effectiveness) and brachytherapy 21 Gy in 3 fractions. Radiation therapy technique and adjuvant endocrine therapy were selected at physician and patient discretion., Results: Between June 17, 2015, and July 13, 2017, 161 eligible patients were treated with photons (56), protons (49), or brachytherapy (56). Median patient age was 66.8 years. One hundred twenty-six (78.3%) had invasive breast cancer (all ER+) and 35 (21.7%) had DCIS (88.6% ER+). Fifty-four percent of patients with invasive breast cancer and 25.8% of patients with ER+ DCIS initiated and adhered to the prescribed endocrine therapy. The proportion of patients with adverse cosmesis (by trained nurse assessment) was 14.5% at baseline and 2.3% at 3 years (difference, -12.2%; 95% CI, -100% to -6.4%). Adverse cosmesis at the last follow-up, with a median follow-up of 5 years, was 5.7% by nurse assessment, 5.6% by panel assessment of digital photographs, and 5.2% by patient self-report. There were no observed clinically meaningful changes in other patient-reported outcomes, and just 2 grade 2 or higher adverse events, both grade 2, in the brachytherapy cohort. Five-year local recurrence-free survival and progression-free survival were 98.0% and 95.5%, respectively. There were no local recurrences among 60 patients with invasive breast cancer and Ki67 ≤13.25%., Conclusions: Deintensified 3-day PBI provided favorable disease control, tolerability, and cosmetic outcomes, meeting the prespecified criteria for acceptability. This approach is an attractive option for patients with small node-negative ER+ breast cancer and DCIS., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To provide a comprehensive assessment of various fractionation schemes in radiation therapy for breast cancer, with a focus on side effects, cosmesis, quality of life, risks of recurrence, and survival outcomes., Design: Systematic review and meta-analysis., Data Sources: Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials (from inception to 23 October 2023)., Study Selection: Included studies were randomised controlled trials focusing on conventional fractionation (CF; daily fractions of 1.8-2 Gy, reaching a total dose of 50-50.4 Gy over 5-6 weeks), moderate hypofractionation (MHF; fraction sizes of 2.65-3.3 Gy for 13-16 fractions over 3-5 weeks), and/or ultra-hypofractionation (UHF; schedule of only 5 fractions)., Data Extraction: Two independent investigators screened studies and extracted data. Risk of bias and quality of evidence were assessed using the Cochrane Collaboration's tool and the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach, respectively., Data Synthesis: Pooled risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Heterogeneity was analysed using Cochran's Q test and I 2 statistic. Network meta-analysis was used to integrate all available evidence., Main Outcome Measures: The pre-specified primary outcome was grade ≥2 acute radiation dermatitis and late radiation therapy related side effects; secondary outcomes included cosmesis, quality of life, recurrence, and survival metrics., Results: From 1754 studies, 59 articles representing 35 trials (20 237 patients) were assessed; 21.6% of outcomes showed low risk of bias, whereas 78.4% had some concerns or high risk, particularly in outcome measurement (47.4%). The RR for grade ≥2 acute radiation dermatitis for MHF compared with CF was 0.54 (95% CI 0.49 to 0.61; P<0.001) and 0.68 (0.49 to 0.93; P=0.02) following breast conserving therapy and mastectomy, respectively. Hyperpigmentation and grade ≥2 breast shrinkage were less frequent after MHF than after CF, with RRs of 0.77 (0.62 to 0.95; P=0.02) and 0.92 (0.85 to 0.99; P=0.03), respectively, in the combined breast conserving therapy and mastectomy population. However, in the breast conserving therapy only trials, these differences in hyperpigmentation (RR 0.79, 0.60 to 1.03; P=0.08) and breast shrinkage (0.94, 0.83 to 1.07; P=0.35) were not statistically significant. The RR for grade ≥2 acute radiation dermatitis for UHF compared with MHF was 0.85 (0.47 to 1.55; P=0.60) for breast conserving therapy and mastectomy patients combined. MHF was associated with improved cosmesis and quality of life compared with CF, whereas data on UHF were less conclusive. Survival and recurrence outcomes were similar between UHF, MHF, and CF., Conclusions: MHF shows improved safety profile, cosmesis, and quality of life compared with CF while maintaining equivalent oncological outcomes. Fewer randomised controlled trials have compared UHF with other fractionation schedules, but its safety and oncological effectiveness seem to be similar with short term follow-up. Given the advantages of reduced treatment time, enhanced convenience for patients, and potential cost effectiveness, MHF and UHF should be considered as preferred options over CF in appropriate clinical settings, with further research needed to solidify these findings., Systematic Review Registration: PROSPERO CRD42023460249., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: no support from any organisation for the submitted work; IC has received consulting fees from Pfizer, Novartis, Eli Lilly, Seagen, Gilead, Astra Zeneca, Daiichi Sankyo, and Menarini StemLine and is a clinical board member of the European Society for Radiotherapy and Oncology (unpaid); JQC has received funding from the Canadian Institutes of Health Research and honorariums from Roche, Pfizer, Novartis, AstraZeneca, Well Doc Alberta, Merck, La Roche-Posay, Knight, Seagen, Oncology Education, and Gilead; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: The COVID-19 pandemic led to rapid expansion of telemedicine. The implications of telemedicine have not been rigorously studied in radiation oncology, a procedural specialty. This study aimed to evaluate the characteristics of in-person patients (IPPs) and virtual patients (VPs) who presented to a large cancer center before and during the pandemic and to understand variables affecting likelihood of receiving radiotherapy (yield) at our institution., Methods: A total of 17,915 patients presenting for new consultation between 2019 and 2021 were included, stratified by prepandemic and pandemic periods starting March 24, 2020. Telemedicine visits included video and telephone calls. Area deprivation indices (ADIs) were also compared., Results: The overall population was 56% male and 93% White with mean age of 63 years. During the pandemic, VPs accounted for 21% of visits, were on average younger than their in-person (IP) counterparts (63.3 years IP v 62.4 VP), and lived further away from clinic (215 miles IP v 402 VP). Among treated VPs, living closer to clinic was associated with higher yield (odds ratio [OR], 0.95; P < .001). This was also seen among IPPs who received treatment (OR, 0.96; P < .001); however, the average distance from clinic was significantly lower for IPPs than VPs (205 miles IP v 349 VP). Specialized radiotherapy (proton and brachytherapy) was used more in VPs. IPPs had higher ADI than VPs. Among VPs, those treated had higher ADI ( P < .001)., Conclusion: Patient characteristics and yield were significantly different between IPPs and VPs. Telemedicine increased reach to patients further away from clinic, including from rural or health care-deprived areas, allowing access to specialized radiation oncology care. Telemedicine has the potential to increase the reach of other technical and procedural specialties.

Objective: To determine the association between pre-operative central subfield thickness (CST) and post-radiotherapy visual acuity (VA), cystoid macular edema (CME), and intravitreal anti-vascular endothelial growth factor (VEGF) requirement., Design: Single-center retrospective study., Participants: Patients with plaque-irradiated extramacular choroidal melanoma treated between 11/11/2011 and 4/30/2021. Pre-operative CST difference between the affected and unaffected eye was used. Kaplan-Meier analysis and hazard ratios were calculated., Results: Of 85 patients, pre-operative CST was greater in the melanoma-affected eye (vs. fellow eye) by mean of 20.4 μm (median 14.0, range - 60.0-182.0). Greater CST at presentation (vs. fellow eye) was associated with larger tumor diameter (p = 0.02), greater tumor thickness (p < 0.001), and more frequent tumor-related Bruch's membrane rupture (p = 0.006). On univariate analysis of outcome data, greater CST at presentation (vs. fellow eye) was associated with higher 5-year risk (1.09 [1.02-1.17], p = 0.02) of VA 20/200 or worse and increased (1.10 [1.01-1.20], p = 0.03) likelihood for anti-VEGF injections after plaque irradiation. There was no significant association with CME. The association between CST and VA outcome remained significant on multivariate analysis accounting for impact of tumor thickness and radiation dose to optic disc, while tumor distance to fovea was the only significant factor on multivariate analysis for anti-VEGF injections., Conclusion: Greater CST at presentation (vs. fellow eye) was associated with worse VA outcome following plaque radiotherapy for choroidal melanoma. Large-sized tumors may contribute to a higher intraocular VEGF burden, potentially leading to greater preoperative CST, which correlates with poor VA outcome post-plaque radiotherapy., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Our aim was to report physician- and patient-reported outcomes of patients with localized breast cancer treated with moderate versus ultrahypofractionated whole breast irradiation (WBI) after breast-conserving surgery (BCS)., Methods and Materials: Between February 2018 and February 2020, patients with localized breast cancer (pT0-3 pN0-1 M0) were offered participation in a phase 3 randomized clinical trial assessing adjuvant moderate hypofractionation (MHF) to 40 Gy in 15 fractions versus ultrahypofractionation (UHF) to 25 Gy in 5 fractions after BCS, with an optional simultaneously integrated boost. Toxicities, cosmesis, and quality of life were assessed at baseline, end of treatment (EOT), and 3 months, 1 year, 2 years, and 3 years from irradiation using validated metric tools., Results: One hundred seven patients were randomized to MHF (n = 54) or UHF (n = 53) adjuvant WBI. The median follow-up was 42.8 months. Grade 2 radiation dermatitis was experienced by 4 patients (7.4%) in the MHF arm and 2 patients (3.7%) in the UHF arm at EOT (P = .726). No grade 3 or higher toxicities were observed. Deterioration of cosmesis by physician assessment was observed in 2 (6.7%) patients treated in the UHF arm and 1 (1.9%) patient treated in the MHF arm at EOT (P = .534), whereas at 3 months, only 1 (1.8%) patient treated in the MHF arm demonstrated deterioration of cosmesis (P = .315). At EOT, 91% and 94% of patients reported excellent/good cosmesis among those treated with MHF and UHF regimens, respectively (P = .550). At 3 months, more patients within the MHF arm reported excellent/good cosmesis compared with those in the UHF arm (100% vs 91%; P = .030). However, the difference in patient-reported cosmesis disappeared at the 1-, 2-, and 3-year time points., Conclusions: UHF WBI showed similar treatment-related late toxicities and similar provider-scored cosmesis compared with MHF radiation in patients treated adjuvantly after BCS., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To report oncologic, physician-assessed, and patient-reported outcomes (PROs) for a group of women homogeneously treated with modern, skin-sparing multifield optimized pencil-beam scanning proton (intensity modulated proton therapy [IMPT]) postmastectomy radiation therapy (PMRT)., Methods and Materials: We reviewed consecutive patients who received unilateral, curative-intent, conventionally fractionated IMPT PMRT between 2015 and 2019. Strict constraints were applied to limit the dose to the skin and other organs at risk. Five-year oncologic outcomes were analyzed. Patient-reported outcomes were evaluated as part of a prospective registry at baseline, completion of PMRT, and 3 and 12 months after PMRT., Results: A total of 127 patients were included. One hundred nine (86%) received chemotherapy, among whom 82 (65%) received neoadjuvant chemotherapy. The median follow-up was 4.1 years. Five-year locoregional control was 98.4% (95% CI, 93.6-99.6), and overall survival was 87.9% (95% CI, 78.7-96.5). Acute grade 2 and 3 dermatitis was seen in 45% and 4% of patients, respectively. Three patients (2%) experienced acute grade 3 infection, all of whom had breast reconstruction. Three late grade 3 adverse events occurred: morphea (n = 1), infection (n = 1), and seroma (n = 1). There were no cardiac or pulmonary adverse events. Among the 73 patients at risk for PMRT-associated reconstruction complications, 7 (10%) experienced reconstruction failure. Ninety-five patients (75%) enrolled in the prospective PRO registry. The only metrics to increase by >1 point were skin color (mean change: 5) and itchiness (2) at treatment completion and tightness/pulling/stretching (2) and skin color (2) at 12 months. There was no significant change in the following PROs: bleeding/leaking fluid, blistering, telangiectasia, lifting, arm extension, or bending/straightening the arm., Conclusions: With strict dose constraints to skin and organs at risk, postmastectomy IMPT was associated with excellent oncologic outcomes and PROs. Rates of skin, chest wall, and reconstruction complications compared favorably to previous proton and photon series. Postmastectomy IMPT warrants further investigation in a multi-institutional setting with careful attention to planning techniques., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

1. Background: We sought to determine acute and subacute changes in cardiac function after proton beam (PBT) and photon beam (PhT) radiotherapy (RT) using conventional and two-dimensional speckle tracking echocardiography (2D-STE) in patients with malignant breast and thoracic tumors. 2. Methods: Between March 2016 and March 2017, 70 patients with breast or thoracic cancer were prospectively enrolled and underwent transthoracic echocardiography with comprehensive strain analysis at pretreatment, mid-treatment, end of treatment, and 3 months after RT. 3. Results: PBT was used to treat 44 patients; PhT 26 patients. Mean ± SD age was 55 ± 12 years; most patients (93%) were women. The median (interquartile range) of the mean heart dose was lower in the PBT than the PhT group (47 [27-79] vs. 217 [120-596] cGy, respectively; p < 0.001). Ejection fraction did not change in either group. Only the PhT group had reduced systolic tissue Doppler velocities at 3 months. 2D-STE showed changes in endocardial and epicardial longitudinal, radial, and circumferential early diastolic strain rate (SRe) in patients undergoing PhT (global longitudinal SRe, pretreatment vs. end of treatment ( p = 0.04); global circumferential SRe, pretreatment vs. at 3-month follow-up ( p = 0.003); global radial SRe, pretreatment vs. at 3-month follow-up ( p = 0.02) for endocardial values). Epicardial strain values decreased significantly only in patients treated with PhT. Patients in the PhT group had a significant decrease in epicardial global longitudinal systolic strain rate (GLSRs) (epicardial GLSRs, at baseline vs. at end of treatment [ p = 0.009]) and in GCSRe and GRSRe (epicardial GCSRe, at baseline vs. at 3-month follow-up ( p = 0.02); epicardial GRSRe, at baseline vs. at 3-month follow-up ( p = 0.03)) during treatment and follow-up. No changes on 2D-STE were detected in the PBT group. 4. Conclusions: Patients who underwent PhT but not PBT had reduced tissue Doppler velocities and SRe values during follow-up, suggesting early myocardial relaxation abnormalities. PBT shows promise as a cardiac-sparing RT technology.

Background: Proton therapy is under investigation in breast cancer as a strategy to reduce radiation exposure to the heart and lungs. So far, studies investigating proton postmastectomy radiotherapy (PMRT) have used conventional fractionation over 25-28 days, but whether hypofractionated proton PMRT is feasible is unclear. We aimed to compare conventional fractionation and hypofractionation in patients with indications for PMRT, including those with immediate breast reconstruction., Methods: We did a randomised phase 2 trial (MC1631) at Mayo Clinic in Rochester (MN, USA) and Mayo Clinic in Arizona (Phoenix, AZ, USA) comparing conventional fractionated (50 Gy in 25 fractions of 2 Gy [relative biological effectiveness of 1·1]) and hypofractionated (40·05 Gy in 15 fractions of 2·67 Gy [relative biological effectiveness of 1·1]) proton PMRT. All patients were treated with pencil-beam scanning. Eligibility criteria included age 18 years or older, an Eastern Cooperative Oncology Group performance status of 0-2, and breast cancer resected by mastectomy with or without immediate reconstruction with indications for PMRT. Patients were randomly assigned (1:1) to either conventional fractionation or hypofractionation, with presence of immediate reconstruction (yes vs no) as a stratification factor, using a biased-coin minimisation algorithm. Any patient who received at least one fraction of protocol treatment was evaluable for the primary endpoint and safety analyses. The primary endpoint was 24-month complication rate from the date of first radiotherapy, defined as grade 3 or worse adverse events occurring from 90 days after last radiotherapy or unplanned surgical interventions in patients with immediate reconstruction. The inferiority of hypofractionation would not be ruled out if the upper bound of the one-sided 95% CI for the difference in 24-month complication rate between the two groups was greater than 10%. This trial is registered with ClinicalTrials.gov, NCT02783690, and is closed to accrual., Findings: Between June 2, 2016, and Aug 23, 2018, 88 patients were randomly assigned (44 to each group), of whom 82 received protocol treatment (41 in the conventional fractionation group and 41 in the hypofractionation group; median age of 52 years [IQR 44-64], 79 [96%] patients were White, two [2%] were Black or African American, one [1%] was Asian, and 79 [96%] were not of Hispanic ethnicity). As of data cutoff (Jan 30, 2023), the median follow-up was 39·3 months (IQR 37·5-61·2). The median mean heart dose was 0·54 Gy (IQR 0·30-0·72) for the conventional fractionation group and 0·49 Gy (0·25-0·64) for the hypofractionation group. Within 24 months of first radiotherapy, 14 protocol-defined complications occurred in six (15%) patients in the conventional fractionation group and in eight (20%) patients in the hypofractionation group (absolute difference 4·9% [one-sided 95% CI 18·5], p=0·27). The complications in the conventionally fractionated group were contracture (five [12%] of 41 patients]) and fat necrosis (one [2%] patient) requiring surgical intervention. All eight protocol-defined complications in the hypofractionation group were due to infections, three of which were acute infections that required surgical intervention, and five were late infections, four of which required surgical intervention. All 14 complications were in patients with immediate expander or implant-based reconstruction., Interpretation: After a median follow-up of 39·3 months, non-inferiority of the hypofractionation group could not be established. However, given similar tolerability, hypofractionated proton PMRT appears to be worthy of further study in patients with and without immediate reconstruction., Funding: The Department of Radiation Oncology, Mayo Clinic, Rochester, MN, the Department of Radiation Oncology, Mayo Clinic, Phoenix, AZ, USA, and the US National Cancer Institute., Competing Interests: Declaration of interests RWM reports his role as Co-Chair of the Breast Cancer Subcommittee of the Particle Therapy Cooperative Group. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Early-stage breast cancer is among the most common cancer diagnoses. Adjuvant radiotherapy is an essential component of breast-conserving therapy, and several options exist for tailoring its extent and duration. This study assesses the comparative effectiveness of partial-breast irradiation (PBI) compared with whole-breast irradiation (WBI)., Methods: A systematic review was completed to identify relevant randomized clinical trials and comparative observational studies. Independent reviewers working in pairs selected studies and extracted data. Randomized trial results were pooled using a random effects model. Prespecified main outcomes were ipsilateral breast recurrence (IBR), cosmesis, and adverse events (AEs)., Results: Fourteen randomized clinical trials and 6 comparative observational studies with 17 234 patients evaluated the comparative effectiveness of PBI. PBI was not statistically significantly different from WBI for IBR at 5 years (RR = 1.34, 95% CI = 0.83 to 2.18; high strength of evidence [SOE]) and 10 years (RR = 1.29, 95% CI = 0.87 to 1.91; high SOE). Evidence for cosmetic outcomes was insufficient. Statistically significantly fewer acute AEs were reported with PBI compared with WBI, with no statistically significant difference in late AEs. Data from subgroups according to patient, tumor, and treatment characteristics were insufficient. Intraoperative radiotherapy was associated with higher IBR at 5, 10, and over than 10 years (high SOE) compared with WBI., Conclusions: Ipsilateral breast recurrence was not statistically significantly different between PBI and WBI. Acute AEs were less frequent with PBI. This evidence supports the effectiveness of PBI among selected patients with early-stage, favorable-risk breast cancer who are similar to those represented in the included studies., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Purpose: To provide clinical guidance for centers wishing to implement photon spatially fractionated radiation therapy (SFRT) treatments using either a brass grid or volumetric modulated arc therapy (VMAT) lattice approach., Methods: We describe in detail processes which have been developed over the course of a 3-year period during which our institution treated over 240 SFRT cases. The importance of patient selection, along with aspects of simulation, treatment planning, quality assurance, and treatment delivery are discussed. Illustrative examples involving clinical cases are shown, and we discuss safety implications relevant to the heterogeneous dose distributions., Results: SFRT can be an effective modality for tumors which are otherwise challenging to manage with conventional radiation therapy techniques or for patients who have limited treatment options. However, SFRT has several aspects which differ drastically from conventional radiation therapy treatments. Therefore, the successful implementation of an SFRT treatment program requires the multidisciplinary expertise and collaboration of physicians, physicists, dosimetrists, and radiation therapists., Conclusions: We have described methods for patient selection, simulation, treatment planning, quality assurance and delivery of clinical SFRT treatments which were built upon our experience treating a large patient population with both a brass grid and VMAT lattice approach. Preclinical research and patient trials aimed at understanding the mechanism of action are needed to elucidate which patients may benefit most from SFRT, and ultimately expand its use., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Associazione Italiana di Fisica Medica e Sanitaria. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: To evaluate the long-term outcome of accelerated partial breast irradiation utilizing intraoperatively placed applicator-based brachytherapy (ABB) in early-stage breast cancer., Materials and Methods: From our prospective registry, 223 patients with pTis-T2, pN0/pN1mic breast cancer were treated with ABB. The median treatment duration including surgery and ABB was 7 days. The prescribed doses were 32 Gy/8 fx BID (n = 25), 34 Gy/10 fx BID (n = 99), and 21 Gy/3 fx QD (n = 99). Endocrine therapy (ET) adherence was defined as completion of planned ET or ≥ 80% of the follow-up (FU) period. Cumulative incidence of ipsilateral breast tumor recurrence (IBTR) was estimated and influencing factors for IBTR-free survival rate (IBTRFS) were analyzed., Results: 218/223 patients had hormone receptor-positive tumors, including 38 (17.0%) with Tis and 185 (83.0%) with invasive cancer. After a median FU of 63 months, 19 (8.5%) patients had recurrence [17 (7.6%) with an IBTR]. Rates of 5-year IBTRFS and DFS were 92.2% and 91.1%, respectively. The 5-year IBTRFS rates were significantly higher for post-menopausal women (93.6% vs. 66.4%, p  = 0.04), BMI < 30 kg/m 2 (97.4% vs. 88.1%, p  = 0.02), and ET-adherence (97.5% vs. 88.6%, p  = 0.02). IBTRFS did not differ with dose regimens., Conclusions: Postmenopausal status, BMI < 30 kg/m 2 , and ET- adherence predicted favorable IBTRFS. Our results highlight the importance of careful patient selection for ABB and encouragement of ET compliance., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

The American Academy of Pediatrics recommends premedication for all nonemergent neonatal intubations, yet there remains significant variation in this practice nationally. We aimed to standardize our unit's premedication practices for improved intubation success and reduced adverse events., Methods: The study workgroup developed educational material and protocol content. Process measures included premedication use, education, and audit form completion. Primary (success on first intubation attempt and adverse event rates) and secondary (trainee success) study outcomes are displayed using statistical process control charts and pre-post cohort comparisons., Results: Forty-seven percent (97/206) of nurses completed educational intervention before protocol release, with an additional 20% (42/206) following a staff reminder. Two hundred sixteen (216) patients were intubated per protocol with 81% (174/216) audit completion. Compared with baseline (n = 158), intubation attempts decreased from 2 (IQR, 1-2) to 1 (IQR, 1-2) ( P = 0.03), and success on the first attempt increased from 40% (63/158) to 57% (124/216) ( P < 0.01), with a notable improvement in trainee success from less than 1% (1/40) to 43% (31/72) ( P < 0.01). The rate of severe and rare adverse events remained stable; however, there was a rise in nonsevere events from 30% (48/158) to 45% (98/216). The tachycardia rate increased with atropine use. There was no change in chest wall rigidity, number of infants unable to extubate following surfactant, or decompensation awaiting medications., Conclusions: Standardizing procedural care delivery reduced intubation attempts and increased the attempt success rate. However, this was accompanied by an increase in the rate of nonsevere adverse events., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The objective of this study was to report acute changes in patient-reported quality of life (PRQOL) using the 26-item Expanded Prostate Index Composite (EPIC-26) questionnaire in a prospective study using hypofractionated intensity-modulated proton beam therapy (H-IMPT) targeting the prostate and the pelvic lymph nodes for high-risk or unfavorable intermediate-risk prostate cancer., Methods: Fifty-five patients were enrolled. H-IMPT consisted of 45 GyE to the pelvic lymph nodes and 67.5 GyE to the prostate and seminal vesicles in 25 fractions. PRQOL was assessed with the urinary incontinence (UI), urinary irritative/obstructive symptoms (UO), and bowel function (BF) domains of EPIC-26 questionnaire. Mean changes in domain scores were analyzed from pretreatment to the end of treatment and 3 months posttreatment. A clinically meaningful change (or minimum important change) was defined as a score change > 50% of the baseline standard deviation., Results: The mean scores of UO, UI, and BF at baseline were 84.6, 91.1, and 95.3, respectively. At the end of treatment, there were statistically significant and clinically meaningful declines in UO and BF scores (-13.5 and -2.3, respectively), while the decline in UI score was statistically significant but not clinically meaningful (-13.7). A clinically meaningful decline in UO, UI, and BF scores occurred in 53.5%, 22.7%, and 73.2% of the patients, respectively. At 3 months posttreatment, all three mean scores showed an improvement, with fewer patients having a clinically meaningful decline in UO, UI, and BF scores (18.4%, 20.5%, and 45.0%, respectively). There was no significant reduction in the mean UO and UI scores compared to baseline, although the mean BF score remained lower than baseline and the difference was clinically meaningful., Conclusions: UO, UI, and BF scores of PRQOL declined at the end of H-IMPT. UO and UI scores showed improvement at 3 months posttreatment and were similar to the baseline scores. However, BF score remained lower at 3 months posttreatment with a clinically meaningful decline., (© 2022 Wiley Periodicals LLC.)

Breast cancer care is often defined by preference-sensitive decisions, in which no one choice clearly dominates, and the treatment approach is ideally guided by patient values and preferences. In this context, patients are vulnerable to suboptimal decision quality due to the number and complexity of choices. Arriving at a high-quality, patient-centered decision involves both an accurate understanding of the risks and benefits of treatment options, as well as concordance with the patient's preferences and values. These 2 objectives intersect at the informed consent discussion. In radiation oncology, informed consent has an added layer of complexity related to strong desire from patients to receive the most technologically advanced treatment, often out of balance with other rational considerations. These observations highlight challenges and opportunities unique to radiation oncology in improving communication and arriving at a high-quality decision., (Copyright © 2022. Published by Elsevier Inc.)

Purpose: Inflammatory breast cancer (IBC) poses a radiotherapeutic challenge due to dermal lymphatic involvement, which often necessitates larger target volumes and chest wall boosts, making advanced planning techniques attractive to reduce exposure to nearby organs. We report our experience with intensity modulated proton therapy (IMPT) for the treatment of IBC., Methods: Between 2016 and 2020, all IBC patients treated with adjuvant IMPT at our institution were identified. Overall survival (OS) and distant metastasis-free survival (DMFS) were estimated using the Kaplan-Meier method. Adverse events (AEs) were assessed using CTCAE version 5.0., Results: Nineteen patients were identified with median 24-month follow-up. CTVs included skin, chest wall, and regional lymph nodes. Median dose was 50 Gy in 25 fractions, with fifteen receiving chest wall boost (median 56.25 Gy in 25 fractions). During treatment, plan re-optimization was required in 9 (47%). Acute grade 3 dermatitis occurred in 2 (11%). Rib facture occurred in 4 (21%). One patient with pre-existing surgical seroma experienced a grade 3 fistula. Mean heart, left anterior descending artery, and right coronary artery doses were 0.7 Gy, 2.3 Gy, and 0.1 Gy, respectively. Mean ipsilateral lung V20Gy was 14.9%. At 2 years, there were no locoregional recurrences, and OS and DMFS were 89% and 82%, respectively., Conclusion: IMPT for IBC is well-tolerated with excellent dosimetry, low rates of AEs, and favorable early locoregional control outcomes. Follow-up for long-term outcomes is ongoing. Our findings suggest that IMPT is feasible and an attractive modality worthy of further investigation in patients with IBC., Competing Interests: Conflict of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: To determine risk factors for postradiation optic atrophy (PROA) after plaque radiotherapy for uveal melanoma., Methods: A single center, retrospective cohort study of patients diagnosed with uveal melanoma involving choroid and/or ciliary body treated with plaque between January 1, 2008, and December 31, 2016. Outcomes included development of PROA with pallor alone or with concomitant neuroretinal rim thinning (NRT). Cox regression analysis was performed to identify risk factors for PROA., Results: Of 78 plaque-irradiated patients, PROA developed in 41 (53%), with concomitant NRT in 15 (19%). Risk factors for PROA of any type included presentation with worse visual acuity (odds ratio [95% confidence interval] 5.6 [2.3-14.1], P < 0.001), higher baseline intraocular pressure (IOP; 14 vs 16 mm Hg) (1.1 [1.0-1.2], P = 0.03), shorter tumor distance to optic disc (1.3 [1.2-1.5], P < 0.001) and foveola (1.2 [1.1-1.3], P < 0.001), subfoveal subretinal fluid (3.8 [2.0-7.1], P < 0.001), greater radiation prescription depth (1.3 [1.1-1.6], P = 0.002), dose to fovea (point dose) (1.01 [1.01-1.02], P < 0.001), and mean (1.02 [1.02-1.03], P < 0.001) and maximum dose to optic disc per 1 Gy increase (1.02 [1.01-1.03], P < 0.001). On multivariate modeling, dose to disc, baseline IOP, and subfoveal fluid remained significant. Subanalysis revealed risk factors for pallor with NRT of greater mean radiation dose to disc (1.03 [1.01-1.05], P = 0.003), higher maximum IOP (17 vs 20 mm Hg) (1.4 [1.2-1.7], P < 0.001), and subfoveal fluid (12 [2-63], P = 0.004)., Conclusion: PROA may result in NRT in addition to optic disc pallor. Risk factors for PROA included higher radiation dose to optic disc, higher baseline IOP, and subfoveal fluid. Higher maximum IOP contributed to concomitant NRT., Competing Interests: T. W. Olsen is a board member of the American Academy of Ophthalmology, holds an unrelated grant NIH/NEI R41EY028803 Novartis, and holds unrelated patents #08083751, #1986581, #9539082, and #10278808. The remaining authors report no conflicts of interest., (Copyright © 2021 by North American Neuro-Ophthalmology Society.)

Particle therapy has received increasing attention in the treatment of breast cancer due to its unique physical properties that may enhance patient quality of life and reduce the late effects of therapy. In this review, we will examine the rationale for the use of proton and carbon therapy in the treatment of breast cancer and highlight their potential for sparing normal tissue injury. We will discuss the early dosimetric and clinical studies that have been pursued to date in this domain before focusing on the remaining open questions limiting the widespread adoption of particle therapy.

Purpose: Synchronous bilateral breast cancer (SBBC) poses distinct challenges for radiation therapy planning. We report our proton therapy experience in treating patients with SBBC. We also provide a dosimetric comparison of intensity modulated proton therapy (IMPT) versus photon therapy., Methods and Materials: Patients with SBBC who received IMPT at our institution were retrospectively analyzed. The clinical target volume (CTV) included the breast or chest wall and comprehensive regional lymph nodes, including axilla, supraclavicular fossa, and the internal mammary chain. Intensity modulated proton therapy and volumetric modulated arc therapy (VMAT) plans were generated with the goal that 90% of the CTV would recieve at least 90% of the prescription dose (D90>=90%). Comparisons between modalities were made using the Wilcoxon signed rank test. Physician-reported acute toxic effects and photography were collected at baseline, end of treatment, and each follow-up visit., Results: Between 2015 and 2018, 11 patients with SBBC were treated with IMPT. The prescription was 50 Gy in 25 fractions. The median CTV D90 was 99.9% for IMPT and 97.6% for VMAT ( P  = .001). The mean heart dose was 0.7 Gy versus 7.2 Gy ( P  = .001), the total lung mean dose was 7.8 Gy versus 17.3 Gy ( P  = .001), and the total lung volume recieving 20 Gy was 13.0% versus 27.4% ( P  = .001). The most common acute toxic effects were dermatitis (mostly grade 1-2 with 1 case of grade 3) and grade 1 to 2 fatigue. The most common toxic effects at the last-follow up (median, 32 months) were grade 1 skin hyperpigmentation, superficial fibrosis, and extremity lymphedema. No nondermatologic or nonfatigue adverse events of grade >1 were recorded., Conclusions: Bilateral breast and/or chest wall and comprehensive nodal IMPT is technically feasible and associated with low rates of severe acute toxic effects. Treatment with IMPT offered improved target coverage and normal-tissue sparing compared with photon therapy. Long-term follow-up is ongoing to assess efficacy and toxic effects., (© 2022 The Authors.)

Background: In 2016, SSO Choosing Wisely guidelines recommended against routine sentinel lymph node (SLN) surgery in women ≥ 70 with HR+ cN0 breast cancer. Following this, we identified a group of women at low-risk of nodal positivity where SLN may be omitted (grade 1, cT1mi-T1c, or grade 2, cT1mi-T1b). This study evaluates the impact of these changes on our practice., Methods: Retrospective chart review of women aged ≥ 70 years with HR+ cN0 breast cancer at our institution from 2010 to 2020. We compared SLN use before (2010-2016)/after (2017-2020) guideline release according to clinical risk and the association with adjuvant therapy., Results: A total of 1015 breast cancers in 987 women identified. SLN surgery rate significantly decreased from 90.6% (2010-2016) to 62.8% in 2020 (p < 0.001). This was driven by breast-conserving surgery (BCS) with SLN rates of 88.2% (2010-2016) and 46.7% in 2020. During 2017-2020, SLN use varied by risk within BCS patients: 52.2% low-risk, 81.9% higher-risk, p < 0.001. In contrast, in mastectomy patients SLN was performed in ≥ 98% regardless of risk level. SLN positivity was 13.4% overall: 7.4% in low-risk and 20.8% in higher-risk, p < 0.001. After adjusting for age and clinical risk, SLN use was not associated with adjuvant radiation [odds ratio (OR) 1.61, p = 0.11] or endocrine therapy (OR 1.12, p = 0.71)., Conclusions: The Society of Surgical Oncology guideline release, followed by implementation of a clinical tool to stratify by nodal risk, was associated with decreased SLN use in women aged ≥ 70 years, in those with clinically low-risk HR+ disease surgically treated with BCS. Adjusting for confounders, omission of SLN surgery was not associated with use of subsequent adjuvant radiation or hormonal therapy., (© 2021. Society of Surgical Oncology.)

Purpose: The burnout rate among US radiation oncology residents was 33% in 2016. To our knowledge there are no published interventions addressing burnout among radiation oncology residents. We describe the implementation of a well-being curriculum, cocreated by a psychologist, a medical humanities professional, and radiation oncology attending and resident physicians., Methods and Materials: Radiation oncology residents at our institution were surveyed to determine themes that induced burnout. A curriculum was developed, with monthly small group sessions focused on 1 identified topic. Sessions alternated between psychological tool-focused approaches and humanities exercises. These were led by a psychologist or medical humanities professional. Residents were given protected time to attend sessions during business hours. Participation was optional. Participants were assigned a random identifier, and the Stanford Professional Fulfillment Index (PFI) was assessed at baseline and 3-month intervals. PFI trends were analyzed after 1 year. At the end of the year, a focus group was held to evaluate work satisfaction and self-reported interactions with patients and coworkers. This information was used to improve the curriculum., Results: All 12 residents in the radiation oncology program participated in the curriculum. There was an equal number of residents of postgraduate years 2 through 5. Six of the participants were female. Of the participants, 11 completed the PFI. At baseline, 80% of residents met criteria for burnout. This decreased to 67%, 50%, and 33% at 3, 6, and 9 months, respectively. The proportion of residents meeting criteria for very good professional fulfillment was 30%, 56%, 38%, and 22% at baseline and 3, 6, and 9 months, respectively. On average, 9 of 12 residents attended each session., Conclusions: Our experience demonstrates the feasibility of collaborating with residents in the development of a well-being curriculum to cater programming to their needs, which we believe led to excellent engagement and attendance at each session., (© 2021 The Authors.)

Background/objectives: To report clinical outcomes of modified Collaborative Ocular Melanoma Study IRIS (COMS IRIS) plaques for treatment of iris, iridociliary, and ciliary body melanoma., Subjects/methods: Retrospective, single-centre cohort study of iris melanoma treated with COMS IRIS plaque radiotherapy from July 26, 2010 to October 15, 2018. Medical records were reviewed for demographics, tumour features, treatment parameters, and clinical outcomes., Results: There were 22 cases, diagnosed at mean age of 59 years (median 65, range 21-85 years) with female sex in 14 (64%). Presenting tumour features included Snellen visual acuity (VA) ≥ 20/40 in 18 (82%) cases, mean largest tumour basal diameter 4.7 mm (median 3.9, range 2.3-13.8 mm) and thickness 1.7 mm (median 1.6 mm, range 0.8-3.9 mm), iris stromal seeding in 3 (14%) cases, angle seeding in 16 (73%), and ciliary body involvement in 13 (59%). After mean follow-up of 51 months (median 44, range 4-113 months), Snellen VA was ≥20/40 in 14 (64%) cases, with local tumour recurrence in 2 (9%), and enucleation in 2 (9%). The 3-year Kaplan-Meier estimated risk of local tumour recurrence was 7%. The most common radiation side effects were cataract in 17 (77%) patients and dry eye in 5 (23%). Systemic metastasis occurred in no cases, and 1 (5%) non-melanoma-related death due to natural causes was observed at last follow-up., Conclusions: COMS IRIS plaques are effective for treatment of iris, iridociliary, and ciliary body melanoma with modest VA outcomes and low frequency of local tumour recurrence, enucleation, radiation side effects, and systemic metastasis., (© 2020. The Author(s), under exclusive licence to The Royal College of Ophthalmologists.)

Cancer is one of the most important public health problems. However, medical education has not advanced at the same rate when it comes to cancer education. Currently, the United States Medical Licensing Examination subject examinations do not cover radiation oncology, prevention, and survivorship planning in its assessment model. Incorporating medical oncology and radiation oncology training into the undergraduate medical education curriculum can have a significant benefit in training future physicians. In this paper, we review current literature and propose some ideas that can help incorporate oncology, and specifically radiation oncology, into undergraduate medical education., (© 2021 The Authors.)

Purpose: Radiation side effects and visual outcome for uveal melanoma patients managed with plaque radiotherapy are dependent on the radiation dose administered to the tumor and nearby healthy tissues. We have developed an open-source software tool, EyeDose, to simplify and standardize tumor and critical structure dose reporting for Collaborative Ocular Melanoma Study eye plaques., Methods and Materials: EyeDose is a MATLAB-based program that calculates point dose and volume dose metrics for standard models of the tumor and critical ocular structures. It uses published three-dimensional dose distributions for eye plaques, calculated with Monte Carlo methods, which are oriented with respect to the eye using the tumor's position on a fundus diagram. A standard model for the ocular structures was created using published measurements and patient CT scans. EyeDose reports radiation statistics for the fovea, optic disc, lens, lacrimal gland, retina, and tumor. The dosimetric margin for implant placement uncertainty is also calculated., Results: EyeDose calculations were validated against previously published Monte Carlo results for eight different tumor positions, including the dose to the fovea, optic disc, lacrimal gland, lens, and along the central axis. EyeDose accepts a spreadsheet input for rapidly processing large retrospective patient data sets, with an average run time of <40 s per patient. EyeDose is published as an open-source tool for easy adaptation at different institutions., Conclusions: EyeDose calculates radiation statistics for Collaborative Ocular Melanoma Study eye plaque patients with Monte Carlo accuracy and without a treatment planning system. EyeDose streamlines data collection for large retrospective studies and can also be used prospectively to assess plaque applicability., (Copyright © 2021 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Reirradiation poses a distinct therapeutic challenge owing to risks associated with exceeding normal tissue tolerances and possibly more therapeutically resistant disease biology. We report our experience with reirradiation for locoregional recurrent or second primary breast cancer., Methods and Materials: Between 1999 and 2019, all patients with breast cancer treated with repeat breast/chest wall radiation therapy (RT) at our institution were identified. Adverse events were assessed using the Common Terminology Criteria for Adverse Events v5.0. Fisher exact, Mann-Whitney rank-sum, and unpaired t tests were used for statistical analysis. Freedom from locoregional recurrence and distant metastasis as well as overall survival were calculated using the Kaplan-Meier method., Results: Seventy-two patients underwent reirradiation. Median prior RT dose, reirradiation dose, and cumulative dose were 60 Gy (interquartile range [IQR], 50-60.4 Gy), 45 Gy (IQR, 40-50 Gy), and 103.54 Gy 2 (IQR, 95.04-109.62 Gy 2 ), respectively. Median time between RT courses was 73 months (IQR, 29-129 months). Thirty-four patients (47%) had gross residual disease at time of reirradiation. Course intent was described as curative in 44 patients (61%) and palliative in 28 (39%). Fifty-two patients (72%) were treated with photons ± electrons and 20 (28%) with protons. With a median follow-up of 22 months (IQR, 10-43 months), grade 3 adverse events were experienced by 13% of patients (10% acute skin toxicity and 3% late skin necrosis). Time between RT courses and reirradiation fields was significantly associated with the development of grade 3 toxicity at any point. Proton therapy conferred a dosimetric advantage without difference in toxicity. At 2 years, locoregional recurrence-free survival was 74.6% and overall survival was 65.5% among all patients, and 93.1% and 76.8%, respectively, among curative intent patients treated without gross disease. Distant metastasis-free survival was 59.0% among all curative intent patients., Conclusions: Reirradiation for locoregional recurrent breast cancer is feasible with acceptable rates of toxicity. Disease control and survival are promising among curative intent reirradiation patients without gross disease., (© 2020 Published by Elsevier Inc. on behalf of American Society for Radiation Oncology.)

Decreasing radiotoxicity to the heart, lungs, and contralateral breast has proven to lower the risk of secondary malignancy and improve overall outcomes when treating chest wall (CW) and regional lymph nodes in postmastectomy breast cancer patients. In this retrospective study, 11 postmastectomy patients were selected and planned with a novel hybrid treatment method and a traditional volumetric arc therapy (VMAT) approach for comparison. This hybrid technique was able to optimize tangential beams to minimize heart dose and the VMAT contribution to improve dose conformity around the planning target volume (PTV). Overall, this hybrid technique produced more homogenous target dose coverage and demonstrated a decrease of integral dose to organs at risk (OAR), while the VMAT technique demonstrated a higher affinity for maintaining dose conformity. Further observation of dose distributions also revealed that the hybrid plans were more effective in sparing low-dose spread to healthy tissue in both right- and left-sided cases. This observation was made evident by the reduction in heart V5 and D mean , decreases in all parameters regarding the contralateral lung, as well as all values other than the V20 of the ipsilateral lung. This unique hybrid planning technique could present an alternative to standard intensity-modulated radiation therapy (IMRT) planning when treating postmastectomy CW and regional lymph nodes, as it has shown the capacity to decrease cardiac, lung, and contralateral breast toxicity while maintaining quality PTV coverage., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: The relative biologic effectiveness (RBE) rises with increasing linear energy transfer toward the end of proton tracks. Presently, there is no consensus on how RBE heterogeneity should be accounted for in breast cancer proton therapy treatment planning. Our purpose was to determine the dosimetric consequences of incorporating a brachial plexus (BP) biologic dose constraint and to describe other clinical implications of biologic planning., Methods and Materials: We instituted a biologic dose constraint for the BP in the context of MC1631, a randomized trial of conventional versus hypofractionated postmastectomy intensity modulated proton therapy (IMPT). IMPT plans of 13 patients treated before the implementation of the biologic dose constraint (cohort A) were compared with IMPT plans of 38 patients treated on MC1631 after its implementation (cohort B) using (1) a commercially available Eclipse treatment planning system (RBE = 1.1); (2) an in-house graphic processor unit-based Monte Carlo physical dose simulation (RBE = 1.1); and (3) an in-house Monte Carlo biologic dose (MCBD) simulation that assumes a linear relationship between RBE and dose-averaged linear energy transfer (product of RBE and physical dose = biologic dose)., Results: Before implementation of a BP biologic dose constraint, the Eclipse mean BP D0.01 cm 3 was 107%, and the MCBD estimate was 128% (ie, 64 Gy [RBE = biologic dose] in 25 fractions for a 50-Gy [RBE = 1.1] prescription), compared with 100.0% and 116.0%, respectively, after the implementation of the constraint. Implementation of the BP biologic dose constraint did not significantly affect clinical target volume coverage. MCBD plans predicted greater internal mammary node coverage and higher heart dose than Eclipse plans., Conclusions: Institution of a BP biologic dose constraint may reduce brachial plexopathy risk without compromising target coverage. MCBD plan evaluation provides valuable information to physicians that may assist in making clinical judgments regarding relative priority of target coverage versus normal tissue sparing., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To compare dosimetric data of the organs at risk (OARs) and clinical target volumes (CTVs) between intensity-modulated proton therapy (IMPT) and volumetric-modulated arc therapy (VMAT) for patients undergoing prostate and elective, pelvic lymph node radiotherapy in the setting of unfavorable, intermediate and high-risk prostate carcinoma., Methods and Materials: A study of moderately hypofractionated proton therapy (6750 centigray [cGy] in 25 fractions) is in progress for unfavorable, intermediate and high-risk prostate cancer where treatment includes an elective pelvic nodal CTV (4500 cGy in 25 fractions). Ten consecutively accrued patients were the subjects for dose-volume histogram comparison between IMPT and VMAT. Two treatment plans (IMPT and VMAT) were prepared for each patient with predefined planning objectives for target volumes and OARs. The IMPT plans were prepared with 2 lateral beams and VMAT plans with 2 arcs., Results: The CTV coverage was adequate for both plans with 99% of CTVs receiving ≥ 100% of the prescription doses. Mean doses to the bladder, rectum, large bowel, and small bowel were lower with IMPT versus VMAT. Mean femoral head dose was greater with IMPT. The percentage of volumes of rectum receiving ≤ 47.5 Gy, large bowel receiving ≤ 27.5 Gy, small bowel receiving ≤ 30 Gy, and bladder receiving ≤ 37.5 Gy was less with IMPT versus VMAT, largely because of reduction in the low-dose "bath" associated with VMAT., Conclusions: In the setting of prostate and elective, pelvic nodal radiotherapy for prostate cancer, IMPT can significantly reduce the dose to OARs, in comparison to VMAT, and provide adequate target coverage., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to disclose., (© Copyright 2019 International Journal of Particle Therapy.)

Background and Purpose: To report dosimetry and early adverse effects, aesthetic, and patient-reported outcomes of a prospective study of 3-fraction pencil-beam scanning (PBS) proton accelerated partial irradiation (APBI)., Materials and Methods: Eligibility included women age ≥ 50 years with estrogen receptor positive (ER+), sentinel lymph node negative invasive or in-situ breast cancer measuring ≤2.5 cm. The prescription was 21.9 Gy (RBE 1.1) in 3 daily fractions to the post-operative tumor bed with a 1 cm expansion. Toxicities were collected using Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, 10-point Linear Analog Scale Assessment, Patient-Reported Outcomes Version of the CTCAE, and the Harvard Breast Cosmesis Scale., Results: Seventy-six women were treated between 2015 and 2017. The median breast volume receiving 50% of prescription or more was 28%. Median mean heart, mean ipsilateral lung, and maximum skin dose were 0 Gy, 0.1 Gy, and 20.6 Gy, respectively. With a median follow-up of 12 months, no treatment-related toxicity grade ≥ 2 has been observed. Most common grade 1 adverse events were dermatitis (68%) and skin hyperpigmentation (18%). At 12 months, the only persistent toxicities were one patient with grade 1 breast edema and one patient with a grade 1 seroma. 90% of patients reported quality of life as ≥7 out of 10 (0 indicating "as bad as it can be" and 10 indicating "as good as it can be") and 98% of patients reported excellent or good cosmesis., Conclusion: 3-fraction PBS proton APBI is well tolerated with low rates of physician and patient reported early adverse effects. Follow-up is ongoing to assess late toxicities and disease control outcomes. Further investigation of this novel adjuvant treatment strategy is warranted.

Purpose: To report reconstructive outcomes of patients treated with post-mastectomy intensity modulated proton therapy (IMPT) following immediate breast reconstruction (IBR)., Materials and Methods: Consecutive women with breast cancer who underwent implant-based IBR and post-mastectomy IMPT were included. Clinical characteristics, dosimetry, and acute toxicity were collected prospectively and reconstruction complications retrospectively., Results: Fifty-one women were treated between 2015 and 2017. Forty-two had bilateral reconstruction with unilateral IMPT. The non-irradiated contralateral breasts served as controls. Conventional fractionation (median 50 Gy/25 fractions) was administered in 37 (73%) and hypofractionation (median 40.5 Gy/15 fractions) in 14 (27%) patients. Median mean heart, ipsilateral lung V20Gy, and CTV-IMN V95% were 0.6 Gy, 13.9%, and 97.4%. Maximal acute dermatitis grade was 1 in 32 (63%), 2 in 17 (33%), and 3 in 2 (4%) patients. Surgical site infection (hazard ratio [HR] 13.19, 95% confidence interval [CI] 1.67-104.03, p = 0.0012), and unplanned surgical intervention (HR 9.86, 95% CI 1.24-78.67, p = 0.0068) were more common in irradiated breasts. Eight of 51 irradiated breasts and 2 of 42 non-irradiated breasts had reconstruction failure (HR 3.59, 95% CI 0.78-16.41, p = 0.084). Among irradiated breasts, hypofractionation was significantly associated with reconstruction failure (HR 4.99, 95% CI 1.24-20.05, p = 0.024), as was older patient age (HR 1.14, 95% CI 1.05-1.24, p = 0.002)., Conclusions: IMPT following IBR spared underlying organs and had low rates of acute toxicity. Reconstruction complications are more common in irradiated breasts, and reconstructive outcomes appear comparable with photon literature. Hypofractionation was associated with higher reconstruction failure rates. Further investigation of optimal dose-fractionation after IBR is needed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Purpose: To report early adverse events and patient-reported outcomes (PROs) of 3-fraction intracavitary catheter-based partial breast brachytherapy (ICBB)., Materials and Methods: Eligible women ≥50 years of age with ≤2.5-cm, lymph node-negative invasive or in situ breast cancer underwent breast-conserving surgery and placement of a brachytherapy applicator. ICBB was initiated on the second weekday after surgery and prescribed to 21 Gy in 3 once-daily fractions. Common Terminology Criteria for Adverse Events, version 4.0; 10-point linear analog scale assessment; the PRO version of the Common Terminology Criteria for Adverse Events; and the Harvard Breast Cosmesis Scale were used for provider and patient-reported assessments., Results: Seventy-three women were treated for invasive (79%) or in situ (21%) breast cancer. The median time to completion of surgery and radiation therapy was 6 days. After 14-months median follow-up, 2 patients (3%) had developed breast infections that resolved with oral antibiotics. There was no other treatment-associated adverse event grade ≥2. The grade 1 seroma rate at 3 months was 20%, which dropped to 8% at 12 months; no events required intervention. At 12 months, 91% of patients reported an overall quality of life score as ≥8 of 10, and patient-reported cosmesis was good or excellent in 95%. All patients are alive without relapse at the last follow-up., Conclusions: Three-fraction ICBB is associated with low rates of early provider and patient- reported adverse events and compares favorably with early outcomes of more protracted ICBB regimens, including twice-daily (3.4 Gy × 10) fractionation studied in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-39. Further investigation is warranted., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: We investigated the feasibility and accuracy of using carbon fiducials to localize the lumpectomy cavity with 2-dimensional kV imaging for early stage breast cancer radiation therapy., Methods and Materials: Carbon fiducials were placed intraoperatively in the periphery of the lumpectomy cavity. Nine patients received whole breast irradiation with a boost, and 2 patients received 3-dimensional conformal partial breast irradiation. A total of 89 fractions were assessed for setup errors relative to a predefined gold standard, cone beam computed tomography (CBCT) match to the lumpectomy cavity, using the following 4 setup methods: (1) Align skin tattoos with lasers; (2) match bone with 2-dimensional-2-dimensional (2D/2D) kV onboard imaging (OBI); (3) match the whole breast with CBCT; and (4) match carbon fiducials with 2D/2D kV OBI. The margin for the planning target volume (PTV) was calculated by 2 standard deviations of the setup errors, and compared among the 4 setup methods. Setup errors for patients treated with free breathing and patients with deep inspiration breath hold were also compared., Results: The carbon fiducials were sufficiently visible on OBI for matching and introduced minimal artifacts. Of the 4 alignment methods, 2D/2D OBI match to fiducials resulted in the smallest setup errors. The PTV margin was 12 mm for aligning skin tattoos using lasers, 9.2 mm for matching bone on OBI, 6.5 mm for matching breast on CBCT, and 3.5 mm for matching fiducials on 2D/2D OBI. Compared with free breathing, deep inspiration breath hold generally reduced the standard deviations of the setup errors, but further investigation would be needed., Conclusions: Matching to carbon fiducials increased the localization accuracy to the lumpectomy cavity. This reduces residual setup error and PTV margins, facilitating tissue sparing without diminishing treatment efficacy., (Copyright © 2018 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Purpose: Accelerated partial breast irradiation (APBI) and whole breast irradiation (WBI) are treatment options for early-stage breast cancer. The purpose of this study was to compare patient-reported-outcomes (PRO) between patients receiving multi-channel intra-cavitary brachytherapy APBI or WBI., Methods: Between 2012 and 2015, 131 patients with ductal carcinoma in situ (DCIS) or early stage invasive breast cancer were treated with adjuvant APBI (64) or WBI (67) and participated in a PRO questionnaire. The linear analog scale assessment (LASA), harvard breast cosmesis scale (HBCS), PRO-common terminology criteria for adverse events- PRO (PRO-CTCAE), and breast cancer treatment outcome scale (BCTOS) were used to assess quality of life (QoL), pain, fatigue, aesthetic and functional status, and breast cosmesis. Comparisons of PROs were performed using t-tests, Wilcoxon rank-sum, Chi square, Fisher exact test, and regression methods., Results: Median follow-up from completion of radiotherapy and questionnaire completion was 13.3 months. There was no significant difference in QoL, pain, or fatigue severity, as assessed by the LASA, between treatment groups (p > 0.05). No factors were found to be predictive of overall QoL on regression analysis. BCTOS health-related QoL scores were similar between treatment groups (p = 0.52).The majority of APBI and WBI patients reported excellent/good breast cosmesis, 88.5% versus 93.7% (p = 0.37). Skin color change (p = 0.011) and breast elevation (p = 0.01) relative to baseline were more common in the group receiving WBI., Conclusions: APBI and WBI were both associated with favorable patient-reported outcomes in early follow-up. APBI resulted in a lesser degree of patient-reported skin color change and breast elevation relative to baseline.

Patient- and provider-reported outcomes are recognized as important in evaluating quality of care, guiding health care policy, comparative effectiveness research, and decision-making in radiation oncology. Combining patient and provider outcome data with a detailed description of disease and therapy is the basis for these analyses. We report on the combination of technical solutions and clinical process changes at our institution that were used in the collection and dissemination of this data. This initiative has resulted in the collection of treatment data for 23 541 patients, 20 465 patients with provider-based adverse event records, and patient-reported outcome surveys submitted by 5622 patients. All of the data is made accessible using a self-service web-based tool.

Purpose: Increasingly, women are choosing immediate breast reconstruction (IBR) following mastectomy. Reports have indicated IBR may compromise post-mastectomy radiotherapy (PMRT). We investigated the impact of IBR on timing of PMRT, target coverage, and doses to organs at risk in a modern radiotherapy practice using advanced planning techniques., Methods: Between 2013 and 2015, PMRT was delivered to 116 patients (66 mastectomy alone, 50 IBR). PMRT was delivered with a median dose of 50 Gy in 25 fractions. Left-sided patients were treated in breath-hold under image guidance. Differences in dosimetric parameters and time to the initiation of PMRT were assessed between patients with and without reconstruction., Results: Reconstructed patients were younger and had lower clinical stage disease. Reconstruction did not significantly increase the mean time to PMRT initiation (51 days reconstructed vs. 45 days non-reconstructed, p = 0.14) or the number of patients who initiated PMRT within 12 weeks of the last therapeutic intervention (48/50 [96.0] vs. 61/66 [92.4%], p = 0.41). There was no significant difference in the percentage of patients in whom the internal mammary lymph nodes (IMNs) were targeted (72 vs. 80%, p = 0.29) or in IMN target coverage (mean IMN V40.5 Gy 92.6 vs. 94.1%, p = 0.62). Reconstruction did not significantly affect the mean ipsilateral lung V20 (25.4 vs. 26.4%, p = 0.37) or the mean heart dose (2.2 vs. 2.1 Gy, p = 0.63)., Conclusions: In a specialized breast multidisciplinary practice, immediate breast reconstruction did not significantly delay PMRT, compromise target coverage, or increase dose to organs at risk.

Purpose: The feasibility of proton postmastectomy radiation therapy in patients reconstructed with expanders has not been previously reported, limiting treatment options. We analyzed the dosimetric impact of the metallic port contained within expanders on intensity modulated proton therapy (IMPT) and report our techniques and quality control for treating patients in this setting., Methods and Materials: Twelve patients with the same expander model underwent 2-field IMPT as part of a prospective registry. All planning dosimetry was checked with an in-house graphic processing unit--based Monte Carlo simulation. Proton ranges through the expander were validated using a sample implant. Dosimetric impact of setup metallic port position uncertainty was evaluated. Pre- and posttreatment photographs were obtained and acute toxicity was graded using the Common Terminology Criteria for Adverse Events, version 4.0., Results: Nine patients had bilateral skin-sparing mastectomy with bilateral tissue expander reconstruction, and 3 patients had unilateral skin-sparing mastectomy and reconstruction. The left side was treated in 10 patients and the right side in 2. Target coverage and normal tissue dose uncertainties resulting from the expander were small and clinically acceptable. The maximum physician-assessed acute radiation dermatitis was grade 3 in 1 patient, grade 2 in 5 patients, and grade 1 in 6 patients., Conclusions: Postmastectomy IMPT in breast cancer patients with expanders is feasible and associated with favorable clinical target volume coverage and normal tissue sparing, even when taking into account treatment uncertainties; therefore, these patients should be eligible to participate in clinical trials studying the potential role of proton therapy in breast cancer. We caution, however, that institutions should carry out similar analyses of the physical properties and dosimetric impact of the particular expanders used in their practice before considering IMPT., (Copyright © 2017 American Society of Radiation Oncology. Published by Elsevier Inc. All rights reserved.)