Background: Adjuvant RT remains a standard therapy for breast cancer, reducing recurrence risk and improving survival; however, it can also induce side effects, including pain. Inflammasome-related biomarkers, such as interleukin-18 (IL-18), play a role in inflammation-mediated pain, and we hypothesize that IL-18 may serve as a potential biomarker for breast cancer RT-induced pain. Methods: The association between IL-18 and pain was assessed among breast cancer patients receiving adjuvant RT. Plasma IL-18 protein concentration was quantified before and after RT using Ella SimplePlex technology (Biotechne). Clinically relevant pain outcomes included pre-RT pain (pain score ≥ 4), post-RT pain (pain score ≥ 4), and RT-related pain (increase in pain from <4 pre-RT to ≥4 post-RT). Multivariable logistic regression assessed the association between IL-18 and pain outcomes, adjusting for demographic and treatment-related factors. The joint effect of IL-18 and obesity on pain were also explored. Results: Patients in the highest pre-RT IL-18 quartile experienced higher odds of both post-RT pain (OR = 2.36, 95% CI: 1.15-4.87) and RT-related pain (OR = 2.73, 95% CI: 1.20-6.26). IL-18 levels increased from pre-RT to post-RT with a mean change of 0.07 (SD = 0.35). In addition, patients with elevated pre-RT IL-18 levels and obesity experienced the highest odds of post-RT pain (OR = 3.97, 95% CI: 1.98-7.98) and RT-related pain (OR = 2.84, 95% CI: 1.32-6.09), suggesting a potential combined effect. Conclusions: Elevated pre-RT IL-18 levels were associated with an increased risk of pain following adjuvant RT, particularly in breast cancer patients with obesity. Thus, IL-18 may serve as a potential biomarker for identifying patients at increased risk for RT-related pain and informing treatment decision.

PURPOSE:The NRG Oncology/Radiation Therapy Oncology Group (RTOG) 9804 trial randomized patients with "good-risk" ductal carcinoma in situ (DCIS) to radiation (RT) or no RT following lumpectomy. The Eastern Cooperative Oncology Group-American College of Radiology Imaging Network E5194 trial had a comparable cohort observed without RT. Tamoxifen use was optional in both trials. This ancillary exploratory analysis combining both data sets assessed the effect of tamoxifen on ipsilateral breast recurrence (IBR) in "good-risk" DCIS treated with lumpectomy alone. METHODS AND MATERIALS:A combined database from the non-RT arm of NRG/RTOG 9804 and the "good-risk" cohort from E5194 (low- or intermediate-grade, ≤2.5 cm, excision margins ≥3 mm) was created, and distributions of patient and DCIS characteristics by tamoxifen use were compared by χ2. IBR, invasive IBR, DCIS-IBR, contralateral breast event, and overall survival were estimated, and distributions were compared between tamoxifen use groups. Univariate and multivariable Fine-Gray regression models were used to analyze factors that may be associated with endpoints. RESULTS:Eight hundred and seventy-eight patients were analyzed (317 from NRG/RTOG 9804 and 561 from E5194). The use of tamoxifen overall was 43.1% (65.6% in NRG/RTOG 9804 and 30.3% in E5194). At a median follow-up of 14.85 years, there were 117 IBRs (65 invasive and 52 DCIS). There was a significant association for reduced IBR with tamoxifen use (P = .001); estimated 15-year IBR with tamoxifen is 11.4% (95% CI, 7.9-15.5) and without is 19.0% (15.3-22.9). Tamoxifen use was significantly associated with reduced invasive IBR (P = .0048) but not DCIS-IBR (P = .089). On multivariable analysis, patients who received tamoxifen were 46% less likely to have any IBR (hazard ratio, 0.54; 95% CI, 0.35-0.83; P = .0045), and 57% less likely to have invasive IBR (hazard ratio, 0.43; 95% CI, 0.24-0.77; P = 0.0042). CONCLUSION:For patients with "good-risk" DCIS treated with lumpectomy without RT, tamoxifen use was significantly associated with a reduction in IBR overall and invasive IBR, not DCIS-IBR.

PURPOSE:Relationships between radiation therapy (RT) dose to cardiac substructures and patient-reported outcomes, as assessed by health-related quality of life (HRQOL), remain unknown. We sought to: (1) compare RT dose to cardiac substructures in patients treated with proton versus photon RT on the Radiotherapy Comparative Effectiveness (RadComp) pragmatic randomized clinical trial, which compared proton versus photon RT in breast cancer; (2) evaluate whether there were changes in HRQOL outcomes from baseline to 6 months following RT; and (3) determine the potential associations between radiation dose-volume histogram (DVH) parameters and changes in cardiac-related HRQOL. METHODS AND MATERIALS:This analysis included 1160 RadComp participants with available radiation DVH metrics for all cardiac substructures who completed baseline and ≥1 follow-up HRQOL over the 6 months post-RT. Cardiac substructures included the whole heart, left ventricle, right ventricle, left atrium, right atrium, and left anterior descending artery; exposures of interest included dose to 0.03 cm3, maximum dose, mean dose, and percent volume receiving a specified dose. HRQOL measures that we hypothesized could provide some insights into cardiac symptoms included Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue, Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) shortness of breath and chest pain, chest tightness, and angina. RESULTS:The mean dose to the whole heart was lower with protons, 0.89 Gy(relative biological effectiveness (RBE)) (Q1-Q3, 0.49-1.39), compared with photons 2.99 Gy (Q1-Q3, 1.60-4.61) (P< .001), as was the mean dose to the left ventricle, left atrium, and left anterior descending artery (P < .001). PRO-CTCAE measures were favorable at all time points with only modest changes observed, and grade ≥3 toxicity was uncommon (≤5.5%) for all measures. No DVH metrics were significantly associated with any cardiac-related HRQOL outcomes over the 6 months post-RT when evaluated by treatment arm or laterality. CONCLUSIONS:Proton RT generally conferred significantly lower doses to the heart and cardiac substructures compared with photon RT. PRO-CTCAE measures were favorable overall. No cardiac DVH parameters were associated with early HRQOL outcomes.

The COVID-19 pandemic dramatically impacted radiation oncology departments as efforts were made to maintain high-quality, timely oncologic care in the setting of multiple competing factors. By close collaborations with public health organizations, institutions, and within individual departments, innovative workflows and strategies were created to evolve the field with sustainable programs impacting all aspects of radiation oncology. This manuscript details the response of radiation oncology in a pandemic, the transformation of current radiation oncology practice and education, and the generation of preparedness for a future pandemic.

PURPOSE:EA1181 (ClinicalTrials.gov identifier: NCT04266249) is a single-arm trial evaluating neoadjuvant taxane, trastuzumab, and pertuzumab (THP) in patients with clinical stage II/IIIa human epidermal growth factor receptor 2 (HER2)-positive breast cancer. This report focuses on the secondary end points of pathologic complete response (pCR) rates and associated factors. The primary end point-3-year recurrence-free survival among patients achieving a pCR (ypT0/Tis, ypN0)-will be reported when data mature. METHODS:Patients received four cycles of trastuzumab and pertuzumab (HP) with either once per week paclitaxel (12 weeks) or docetaxel (every 3 weeks for four cycles), followed by surgery. Clinicopathologic characteristics were assessed in all patients. The HER2DX pCR score was determined using diagnostic biopsy samples in a representative subset. Logistic regression models identified factors associated with pCR. RESULTS:A total of 2,175 patients were enrolled (781 HER2+/estrogen receptor‑negative [ER-]; 1,394 HER2+/ER+). Of 2,141 patients who initiated THP, the overall pCR rate was 43.8%: 63.7% in HER2+/ER- and 32.4% in HER2+/ER+ tumors. Higher pCR rates were observed in tumors that were ER-negative or low ER expressing, progesterone receptor-negative or low expressing, HER2 immunohistochemistry (IHC) 3+, and in patients treated with once per week paclitaxel. T3 disease was associated with a lower pCR rate in HER2+/ER- tumors; otherwise, tumor (T) and nodal (N) stage did not significantly affect pCR. Among 569 patients assessed for HER2DX pCR scores, a high score was independently associated with higher pCR rates, after adjustment for clinicopathologic variables. CONCLUSION:Neoadjuvant THP achieved pCR in nearly two-thirds of patients with HER2+/ER- and one third with HER2+/ER+ breast cancer. Low hormone receptor expression, HER2 IHC 3+ status, once per week paclitaxel use, and a high HER2DX pCR score were independent predictors of pCR. These findings should help optimize risk stratification and treatment personalization for patients with HER2-positive breast cancer.

Proton therapy has emerged as an important technique for locally advanced breast cancer (LABC), driven primarily by the need to reduce cardiopulmonary dose during comprehensive nodal irradiation, particularly when the internal mammary chain is targeted. Since the first clinical proton experience in patients with LABC and unfavorable cardiac anatomy in 2010, proton radiotherapy for LABC has evolved considerably: delivery technique has progressed from passive scattering and uniform scanning to pencil beam scanning and intensity-modulated proton therapy, while breast radiation oncology overall has shifted from field-based to volumetric, contour-driven planning. X, the first large prospective randomized trial comparing proton and photon regional nodal irradiation, completed accrual in 2024 (n=1,239); its 2025 health-related quality-of-life analysis showed similarly excellent patient-reported outcomes in both arms, while the trial's primary endpoints of loco-regional control and major cardiac events remain pending. Beyond X, most published experience remains single-institutional and technically heterogeneous. This critical review examines the historical development, technical evolution, and clinical application of proton therapy for LABC, with attention to contouring philosophy, robustness evaluation, and optimization of normal tissue-related side effects. Because proton plans are more sensitive to contour accuracy, setup, and range uncertainty than photon plans, and because proton entrance-dose behavior differs fundamentally from the photon skin-sparing effect, target delineation and plan robustness assessment require deliberate, disease-specific decision-making. We provide practical guidance for radiation oncologists, physicists, and dosimetrists, particularly those at centers early in their proton breast experience, and outline priorities for standardized reporting as long-term X outcomes mature.

Importance:Radiotherapy for breast cancer exposes the heart to incidental radiation, and historical data have shown a dose-dependent increase in associated cardiac events. Although whole-heart dose metrics are commonly used for risk assessment, emerging evidence suggests that dose to the left anterior descending coronary artery (LAD) may better capture risk. Objective:To compare the ability of heart and LAD radiation dose metrics to predict cardiac risk after breast radiotherapy. Design, Setting, and Participants:This was a cross-sectional study of patients with breast cancer who were treated with either 3-dimensional conformal or intensity-modulated radiotherapy from 2008 to 2018 at a tertiary care center in Canada. The primary analysis included patients with left-sided breast cancer. Cardiac events were assessed using longitudinal follow-up data. Dosimetry was derived from computed tomography plans using automated segmentation and converted to equivalent dose in 2-Gy fractions (EQD2). Data were analyzed from September 2024 to April 2026. Main Outcomes and Measures:Adverse cardiac events defined as myocardial infarction or hospital admission or emergency department visit for unstable angina (ie, acute coronary syndrome), arrhythmia, heart failure, pericarditis, or myocarditis. The incidence of coronary angiography and coronary revascularization was also captured as coronary artery disease (CAD). Discrimination for dose metrics was performed with receiver operator characteristic curves and competing-risks regression (Fine and Gray), adjusted for cardiovascular risk factors. Results:The analysis included 4908 patients with breast cancer of whom 2223 had left-sided breast cancer. During a median (IQR) follow-up period of 10.8 (8.4-13.1) years, cumulative incidence of cardiac event or CAD was 5.0 (95% CI, 4.1-6.0) at 10 years. A data-driven cut point analysis identified 12 Gy EQD2 as the maximum LAD dose that best stratified risk. Among patients with left-sided breast cancer, maximum LAD dose (concordance [C] index, 0.58; 95% CI, 0.52-0.64) discriminated better than mean heart dose (C index, 0.53; 95% CI, 0.47-0.60). In multivariable analysis, maximum LAD of 12 Gy or greater was independently associated with higher cardiac risk (subdistribution hazard ratio = 1.81; 95% CI, 1.04-3.16; P = .04), whereas mean heart dose of 2 Gy or greater was not associated (P = .99). For clinical context, the 12-Gy EQD2 for maximum LAD dose corresponds to a physical dose of approximately 10.5 Gy for 42.5 Gy in 16 fractions and 7 Gy for 26 Gy in 5 fractions. Conclusions and Relevance:In this cross-sectional study of heart-sparing breast radiotherapy, LAD dose was associated with cardiac events, whereas whole-heart metrics was not. These findings support LAD-based planning and respiratory motion management to reduce long-term cardiovascular risk in patients with breast cancer undergoing radiotherapy.

Purpose The impact of disease site-specific peer review on radiation treatment planning recommendations is not well understood. We implemented a standardized peer review checklist to evaluate factors influencing recommendations and their implementation during disease site-specific peer review. Methods and Materials A 7-item checklist was completed prospectively during weekly or biweekly meetings in 4 disease site-specific peer review groups, including (1) radiation approach, (2) dose/fractionation, (3) prescription accuracy, (4) organ-at-risk contours, (5) target volumes, (6) plan quality evaluations, and (7) setup imaging. Review comments were divided into (A) education/discussion without change recommendation, (B) minor suggestion/optional modifications, or (C) major comment requiring plan modification. Rates of comment types and implementation of plan changes were tracked. Statistical analysis was conducted using the 2-proportion Z-test, Welch’s t-tests, and analysis of variance. Results A total of 1311 peer reviews in 914 unique patients were recorded over 6 months. The average review duration was 2 minutes 32 seconds, with significant differences across disease site groups (P < .01). There were 286 total comments: 259 (21.8%) were category A, 26 (2%) were category B, and 1 (<1%) was category C. The proportion of cases generating comments varied by disease site (10%-34%), with only a subset resulting in implemented plan changes (0%-25.8% of comments). Most implemented changes involved target volumes, organ-at-risk contours, and patient setup. Cases undergoing multiple reviews were more likely to generate comments than cases with a single review (25.0% vs 13.0%, P < .01). Furthermore, cases with multiple reviews were significantly more likely to have implemented plan changes compared with single-review cases (28.9% vs 1.2%, P < .01). Conclusions We successfully implemented a peer review checklist in the context of disease site-specific peer review meetings. There is significant variability in comments and their implementation across checklist items and disease site groups. Iterative review significantly increased the probability of treatment plan changes.

PURPOSE Radiation oncology peer review evaluates case-specific qualitative treatment planning decisions. We sought to understand interdisciplinary perspectives on peer review to identify factors affecting stakeholder engagement and implementation of recommendations. METHODS Semi-structured interviews and Likert surveys (scaled 0-10) with radiation oncology peer review participants were audio-recorded and transcribed. Two independent coders utilized a grounded theory approach to extract dominant themes. RESULTS Participants included 6 academic and 3 community radiation oncologists, 2 residents, 2 medical physicists, 2 radiation therapists, 4 dosimetrists and 1 industry representative. Thematic priorities of peer review included: Adherence to institutional guidelines, clinical background to inform decision-making, detection of rare errors and education. Key facilitators included pre-treatment peer review, clear planning guidelines and feedback on peer recommendations. Barriers to recommendation adoption included resource limitations and lack of prospective data guiding qualitative recommendations. Participant perceived benefits of peer review were assessed with Likert surveys with higher values placed on to reducing practice variation (8.0) and education (7.6), and a lower value placed on the detection of medical errors (7.4) and reduction of treatment delivery incidents (6.9). When comparing Likert scores by participant role, non-physicians rated overall importance of peer review (mean: 9.8 vs 6.5, p=0.03) and education (9.0 vs 6.7, p=0.02) significantly higher than physicians. CONCLUSION Participants in radiation oncology acknowledged the importance of peer review but there was significant variation on the perceived benefits. Higher value was placed on alignment of clinical practice and non-physician participant education. Future processes to improve communication and prospective plan review was identified as beneficial to peer review mediated plan changes.

Background: This study aims to explore metabolic biomarkers and pathways in breast cancer prognosis. Methods: We performed a global post-radiotherapy (RT) urinary metabolomic analysis of 120 breast cancer patients: 60 progression-free (PF) patients as the reference and 60 with progressive disease (PD: recurrence, second primary, metastasis, or death). UPLC-MS/MS (Metabolon Inc.) identified 1742 biochemicals (1258 known and 484 unknown structures). Following normalization to osmolality, log transformation, and imputation of missing values, a Welch’s two-sample t-test was used to identify biochemicals and metabolic pathways that differed between PF and PD groups. Data analysis and visualization were performed with MetaboAnalyst. Results: Metabolic biomarkers and pathways that significantly differed between the PD and PF groups were the following: amino acid metabolism, including phenylalanine, tyrosine, and tryptophan biosynthesis (impact value (IV) = 1.00; p = 0.0007); histidine metabolism (IV = 0.60; p < 0.0001); and arginine and proline metabolism (IV = 0.70; p = 0.0035). Metabolites of carbohydrate metabolism, including glucose (p = 0.0197), sedoheptulose (p = 0.0115), and carboxymethyl lysine (p = 0.0098), were elevated in patients with PD. Gamma-glutamyl amino acids, myo-inositol, and oxidative stress biomarkers, including 7-Hydroxyindole Sulfate and sulfate, were elevated in patients who died (p ≤ 0.05). Conclusions: Amino acid metabolism emerged as a key pathway in breast cancer progression, while carbohydrate and oxidative stress metabolites also showed potential utility as biomarkers for breast cancer progression. These findings demonstrate applications of metabolomics in identifying metabolic biomarkers and pathways as potential targets for predicting breast cancer progression.

Outcomes for patients with early breast cancer have improved in recent years as detection and treatments have improved. The goal of many recent trials has therefore been to identify patients in whom de-intensification of therapy may be appropriate, thereby maximizing the therapeutic ratio of breast cancer treatments. In each discipline within breast cancer, surgery, radiation oncology, and medical oncology, trials have explored treatment de-escalation. In surgery, studies evaluate the omission of surgery to the breast or axilla; in radiation oncology, studies evaluate reduced dose and/or number of fractions (hypofractionation), reduced target [partial breast irradiation (PBI)], and omission of RT altogether; in medical oncology, studies evaluate reduced duration, alternate forms, and omission of ET altogether. In many cases, these studies have shown that targeted omission or de-intensification does not compromise outcomes. The challenge in multidisciplinary care is how to implement these deintensification strategies for a particular patient in relation to other aspects of the overall treatment plan. In this critical review, we review the data in support of omission or de-intensification of surgical, radiation, and endocrine therapies in patients with low risk breast cancer, and consider these approaches in relation to one another.

Accurate information about locoregional breast cancer treatments following neoadjuvant systemic therapy (NST) is essential for meaningful interpretation of oncological outcomes but reporting is currently poor. We developed a core outcome set (COS) to improve the quality and consistency of locoregional outcome reporting in breast cancer NST trials. The COS was developed in three phases according to COS-STAD guidance, with the generation of a list of relevant outcome domains, prioritisation of outcomes through two rounds of an international online multi-stakeholder Delphi survey and a consensus meeting. 159 unique locoregional outcomes were classified into 101 outcome domains for inclusion in the Delphi survey, which was completed by 470 international professionals. The final 15-item COS, which included the pre-NST surgical plan, details of surgery performed following completion of treatment and details of radiation therapy, was agreed at an in-person consensus meeting. Widespread COS implementation will improve the quality and value of future NST trials.

Acute skin toxicity is a prevalent and debilitating side effect of radiotherapy (RT) for breast cancer, disproportionately impacting minority populations. Hypofractionated radiotherapy (HF-RT), which involves delivering higher doses of radiation over fewer treatment sessions, has emerged as a preferred approach during the COVID-19 pandemic due to its efficiency and convenience. This study evaluates the effectiveness of HF-RT compared to conventional fractionated RT (CF-RT) in preventing grade 2+ RT-induced skin toxicity among diverse racial and ethnic groups post-pandemic. To investigate the severity and frequency of RT-induced skin toxicity among breast cancer patients treated with HF-RT and CF-RT, as well as the associations between toxicity and patient demographics or clinical characteristics. A retrospective analysis was conducted using data from 105 breast cancer patients treated at the Sylvester Comprehensive Cancer Center. Patients were grouped based on RT type: HF-RT (42.5-50 Gy over 3-5 weeks) or CF-RT (50+ Gy over 5-7 weeks). Skin toxicity was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Patients were categorized into HF-RT (n=84), CF-RT (n=15), and partial RT (n=6) groups. Patient demographics, including age, BMI, race/ethnicity, and tumor characteristics, were analyzed for their association with toxicity grades. Statistical analyses were conducted using chi-square tests and multivariate logistic regression. 12.4% of patients experienced grade 2+ skin toxicity at follow-up, with no grade 3 or higher observed. HF-RT patients showed lower grade 2+ toxicity rates (10.7%) compared to CF-RT (26.7%), although the difference was not statistically significant (p=0.143). Age was significantly associated with skin toxicity, with patients aged ≥50 years exhibiting higher rates of grade 2+ toxicity (17.4%) compared to those <50 years (2.8%, p=0.031). Other variables, including BMI, race/ethnicity, tumor stage, and treatment location, were not significantly associated with skin toxicity. HF-RT outcomes were consistent with prior studies, demonstrating safety and feasibility across all racial/ethnic groups, including 55% Hispanic and 11% Black patients. Our findings suggest that HF-RT is feasible and safe for reducing acute skin toxicity in early-stage breast cancer patients across multi-racial/ethnic populations, with outcomes comparable to those reported in prior research conducted predominantly in Caucasian populations. These findings emphasize the importance of tailoring RT regimens to improve survivorship outcomes and address disparities in cancer care. Veronica Zhang Paley, Cristiane Takita, Isildinha M. Reis, Jean L. Wright, Jennifer J. Hu. Post-pandemic evaluation of hypofractionated radiotherapy in preventing acute skin toxicity in multiracial/ethnic breast cancer populations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4695.

e12570 Background: Accurate information about locoregional (LR) treatments following neoadjuvant systemic therapy (NST) for breast cancer is essential for interpretation of oncological outcomes, but reporting is currently poor. We aimed to develop a core outcome set (COS) to improve quality and consistency of LR outcome reporting in trials. Methods: The COS was developed in three phases according to COS-STAD guidance: 1. Generation of a long list of relevant outcome domains from a systematic literature review and stakeholder interviews. 2. Prioritisation of outcome domains using two rounds of an online Delphi survey. 3. An in-person consensus meeting to agree the final COS. Results: In total, 159 unique LR outcomes were identified from phase 1 and categorised into 101 (69 surgical/32 RT) outcomes for survey inclusion. 470 international participants (206 surgeons/144 medical oncologists/98 radiation oncologists) took part in survey Round 1, of whom 336 (71.5%) (153 surgeons/90 medical oncologists/ 77 radiation oncologists) participated in Round 2. After Round 2, 31 outcomes, combined into 15 summary outcomes, were scored as ‘consensus in’, 60 as ‘consensus out’ and 10 as ‘no consensus’. 23 professionals and 5 patient advocates attended the consensus meeting, where ‘consensus in’/’consensus out’ items were ratified, and ‘no consensus’ items discussed. A final 15 item COS for LR outcome reporting was agreed and ratified (Table). Conclusions: A COS for LR treatment reporting in NST trials has been robustly developed using an internationally collaborative approach. Widespread implemention will improve the quality and value of future breast cancer NST trials. Final COS 1 Type of breast and axillary surgery planned before starting NST 2 Proportion of patients not having surgery after NST due to disease progression, treatment toxicities or other comorbidities 3 Number/proportion of patients with a complete response to NST not having surgery to the breast and/or axilla, and how response was assessed 4 How response to NST in the breast and axilla was assessed 5 Type of initial breast and axillary surgery performed after NST 6 Proportion of patients with involved margins after initial and final surgery, and number of procedures required 7 Total number of excised and involved axillary lymph nodes, with extent of involvement 8 Further axillary treatment in patients with ypN+ disease after sentinel node biopsy/targeted axillary dissection (SLNB/TAD) 9 Proportion of patients in whom breast and/or axillary surgery was downstaged 10 Proportion of patients having radiation therapy 11 Indications for radiation therapy at trial level 12 Details of breast/chest wall and nodal targets 13 Details of dose and fractionation to breast/chest wall and nodal areas 14 Receipt of boost; indications for boost (at trial level) 15 Morbidity of locoregional treatments (short/long term as defined in protocol)

Background: Integrating a practice-based curriculum to cover essential aspects of patient safety and quality improvement (PSQI) in the outpatient setting can improve resident understanding and engagement in future projects within a radiation oncology residency program. Objectives: To develop and pilot a workshop-based PSQI curriculum to lead residents through a simulated departmental quality improvement project and enhance understanding regarding tools and metrics used within a PSQI framework. Methods: This pilot project was completed in the 2023-2024 academic year, with 13 residents in one radiation oncology program. This educational program included four two-hour interactive PSQI workshops. Residents applied PSQI tools to a simulated scenario that reflected a department priority: to improve time from computed-tomography simulation to adaptive radiation therapy. Residents completed a 5-point Likert survey and an institutionally developed PSQI in-training exam before and after receiving the program to evaluate understanding of key concepts, measurement methodologies, strategies for improvement, and attitudes towards the adoption of PSQI in clinical practice. Results: The pilot workshop was successfully implemented during resident didactics. Although all thirteen residents were able to participate, eight (62%) residents completed all questionnaires. The curriculum led to improved comfort levels in applying PSQI techniques such as fishbone diagrams (pre-post mean Likert scores: 1.7 to 3.7, p< 0.01). PSQI in-training test scores significantly increased by 13% (57% to 70%, p<0.01). Conclusions: The development and implementation of a PSQI curriculum in radiation oncology was feasible, improved baseline knowledge of PSQI techniques, and enhanced participant self-reported preparedness and skills for future PSQI projects.

Purpose: Spatial fractionation (SFRT) is a radiation therapy technique that targets bulky tumors by delivering alternating high and low doses within the tumor. Here, we report an interim analysis of a phase 1 trial examining the feasibility and safety of a novel proton SFRT approach. Methods and Materials: Ten patients with unresectable tumors of varying histopathology measuring at least 7 cm in the palliative setting were enrolled in a prospective phase 1 trial. Robust pencil-beam scanning proton SFRT plans were created using cylindrical (grid) targets within gross tumor treated to a prescription dose of 18 Gy in a single fraction. Quality assurance computed tomography imaging (qCT) was performed before treatment delivery. Results: Four patients had breast primaries, 3 patients had lung primaries, and 3 patients had pelvic primaries. Five patients had prior photon treatment to a different site. Eight patients received additional planned normofractionated radiation therapy totaling an average dose of 30 Gy. Median time from SFRT treatment to last follow-up was 25 weeks (range, 4-60 weeks). Gross tumor volume ranged from 151 cm³ to 1638 cm³. All qCTs maintained robustness, with no re-planning needed. At last follow-up, 40% showed partial response, 20% had stable disease, and 40% experienced disease progression, with half progressing in the treated area. One patient with pelvic treatment developed grade 3 small bowel obstruction, followed by late grade 2 obstructions. No other patients had grade 3 or higher acute or late toxicities attributable to the proton SFRT. Conclusions: Spatial fractionation using a novel pencil-beam scanning SFRT technique was technically feasible to deliver and reliable on robust evaluation of qCT in this small prospective cohort of patients with difficult-to-manage bulky tumors. Proton SFRT appears safe even when additional normofractionated radiation therapy is delivered. Some bulky tumors exhibited significant response to proton SFRT; thus, further work elucidating which patients most benefit from this technique is warranted.

PURPOSE:This guideline provides evidence-based recommendations on the use of postmastectomy radiation therapy (PMRT) in the treatment of breast cancer. PMRT refers to the treatment of the chest wall and ipsilateral regional nodes, including at-risk axillary, supra/infraclavicular, and internal mammary nodes. Updated recommendations detail indications for PMRT in the upfront surgical setting and after neoadjuvant systemic therapy, and provide guidance on appropriate target volumes, dosing, and treatment techniques. METHODS:The American Society for Radiation Oncology, American Society of Clinical Oncology, and the Society of Surgical Oncology convened a multidisciplinary task force to address 4 key questions focused on radiation therapy (RT) in patients with breast cancer who undergo mastectomy including (1) indications for PMRT after upfront surgery, (2) indications for PMRT after neoadjuvant systemic therapy followed by surgery, (3) appropriate PMRT treatment volumes and dose-fractionation regimens, and (4) treatment techniques. Recommendations were based on a systematic literature review and created using a predefined consensus-building methodology and system for quality of evidence grading and strength of recommendation. RESULTS:After upfront mastectomy, PMRT is indicated for most patients with node-positive breast cancer and select patients with node-negative disease. PMRT is also recommended after neoadjuvant systemic therapy, both for patients presenting with locally advanced disease and for those with residual nodal disease at the time of surgery. PMRT is conditionally recommended for patients with cT1-3N1 or cT3N0 breast cancer with pathologically negative nodes after neoadjuvant systemic therapy (ypN0). When PMRT is delivered, treatment to the ipsilateral chest wall/reconstructed breast and regional lymphatics is recommended, with moderate hypofractionation preferred, but with conventional fractionation approaches acceptable in rare cases. Computed tomography-based volumetric treatment planning with 3-dimensional conformal RT is recommended, with intensity modulated RT advised when 3-dimensional conformal RT is unable to achieve treatment goals. Deep inspiration breath hold techniques are also recommended for normal tissue sparing. For patients with skin involvement, positive superficial margins, and/or lymphovascular invasion, the use of a bolus is recommended, but the routine use of tissue-equivalent bolus is not recommended. CONCLUSIONS:These evidence-based recommendations guide clinical practice on the use of PMRT in patients with breast cancer.

PURPOSE:Guidelines for women aged ≥65 years with early-stage, hormone receptor-positive cancer allow for a range of adjuvant strategies following breast-conserving surgery. These include hormone therapy (HT) with or without radiation therapy (RT), RT alone if HT is not desired or feasible, or even no adjuvant therapy. Although these options offer flexibility, they can also create uncertainty. To address this, we implemented a simple multidisciplinary clinic (s-MDC) with same-day medical and radiation oncology consultations, alongside a previsit questionnaire assessing decision-making preferences and treatment attitudes. METHODS AND MATERIALS:We evaluated 95 patients aged ≥65 years with stage I, hormone receptor-positive breast cancer seen in the s-MDC from August 2020 to December 2023. All completed the Decision Autonomy Preference Scale, Medical Maximizing-Minimizing Scale, and e-Prognosis 10-year mortality risk estimates. We retrospectively reviewed demographics, clinical variables, and chosen treatments, examining associations using χ2 tests, t tests, and regressions. RESULTS:Among 95 patients, adjuvant treatments included no therapy (16.8%), HT alone (16.8%), RT alone (20.0%), and HT+RT (45.3%). Older age, higher mortality risk, and a preference for decision autonomy correlated with omission of all therapy or omission of HT. "Minimizers" favored HT alone, whereas "maximizers" often chose RT or HT+RT. Neither baseline patient-reported data nor most clinicopathologic factors predicted the use of RT alone. The only clinicopathologic factor associated with choice was tumor size: patients with larger (T1b/T1c) tumors more commonly received HT+RT. CONCLUSIONS:In this s-MDC setting, treatment decisions were driven largely by patient preferences, life expectancy, and treatment inclinations, rather than by baseline patient-reported measures or tumor features. These findings underscore the importance of integrating patient values into decision-making and support further research into RT-alone approaches for those forgoing HT, given the prevalence of this treatment choice.

PURPOSE:Our purpose was to evaluate the measurement properties of patient-reported outcome (PRO) measures used in the ongoing RadComp pragmatic randomized clinical trial (PRCT). METHODS AND MATERIALS:The deidentified and blinded data set included 774 English-speaking female participants who completed their 6-month posttreatment assessment. Eleven PRO measures were evaluated, including the Trial Outcome Index from the Functional Assessment of Cancer Therapy-Breast (FACT-B), Satisfaction with Breast Cosmetic Outcomes, the BREAST-Q, and selected Patient-Reported Outcomes Measurement Information System (PROMIS) measures. PROs were measured at 3 timepoints: baseline, completion of radiation therapy (RT), and 6 months post-RT. Ten variables were used as validity anchors. Pearson or Spearman correlations were calculated between PROs and convergent validity indicators. Mean PRO differences between clinically distinct categories were compared with analysis of variance methods (known-groups validity). PRO change scores were mapped to change in other variables (sensitivity to change). RESULTS:Most correlations between PROs and validity indicators were large (≥0.5). Mean score for Satisfaction with Breast Cosmetic Outcomes was higher (better) for those with a lumpectomy compared with those with a mastectomy (P < .001). Mean scores for the FACT-B Trial Outcome Index and for PROMIS Fatigue and Ability to Participate in Social Roles and Activities were better for those with good baseline performance status compared with those with poorer baseline performance status (P < .05). At completion of RT and post-RT, mean scores for Satisfaction with Breast Cosmetic Outcomes and BREAST-Q Radiation were significantly different (P < .001) across categories for all Functional Assessment of Chronic Illness Therapy -Treatment Satisfaction - General items. There were medium-sized correlations between change scores for FACT-B Trial Outcome Index, Fatigue, Anxiety, and Ability to Participate in Social Roles and change scores in the Visual Analog Scale. CONCLUSIONS:For patients with nonmetastatic breast cancer receiving radiation in the RadComp PRCT, our findings demonstrate high reliability and validity for important PRO measures, supporting their psychometric strength and usefulness to reflect the effect of RT on health-related quality of life.