PURPOSE Many patients face barriers to cancer care, leading to disparities in cancer-specific outcomes. Specifically, missing multiple radiation treatments can be associated with increased locoregional recurrence. We sought to assess the frequency and reasons for missed radiotherapy among accredited cancer programs participating in a national quality improvement (QI) collaborative addressing barriers to care. METHODS The Breaking Barriers National QI Collaborative conducted through the American College of Surgeons Cancer Programs enrolled 342 accredited cancer programs, prospectively recording patients scheduled for a 15-45-day course of radiotherapy over five separate, 60-day data collection periods (March-December 2023). Programs identified those who missed ≥three treatments, referred to as at risk of worse outcomes, and queried reasons for missed radiotherapy. Kruskal-Wallis tests assessed differences in rates of missed treatments. RESULTS In total, 332 programs (97.1%) identified at-risk patients, totaling 5,221 patients who missed ≥three treatments. The median percentage of at-risk patients per program was 9.4% (IQR, 4.5-16.5). Programs located in the Northeast (median, 11.3% [IQR, 5.4-17.3]) had the highest proportion of at-risk patients ( P = .014). Patients with rectal (13.0%) and gynecologic (11.4%) cancers were most frequently at risk ( P < .001). Overall, 91.0% of hospitals reported missed radiation treatments due to illness unrelated to treatment, 71.7% due to transportation, 54.2% due to conflicting appointments, and 53.0% due to no longer wishing to pursue treatment. CONCLUSION Barriers to completing radiotherapy are prevalent among accredited cancer programs nationwide. Future work developing interventions in response to identified barriers in this national QI collaborative may be scalable to other areas of cancer care to improve outcomes.

Background: Radiation tumor bed boost after breast-conserving surgery (BCS) and whole breast irradiation (WBI) reduces local recurrence rates in women with ductal carcinoma in situ (DCIS) and early-stage breast cancer. This prospective trial investigated the feasibility of delivering the tumor bed boost pre-operatively instead of post-operatively. The primary endpoint, the incidence of wound complication rates, was previously reported as acceptable. Additionally, we have previously shown that pre-operative boost resulted in smaller treatment volumes compared to what would have been treated with a sequential lumpectomy boost based on the post-operative seroma cavity. The pre-operative boost approach may also allow for more accurate gross tumor delineation. We hypothesize that pre-operative imaging including mammography, MRI and CT simulation used in this trial would enable the accurate delineation of gross tumor volumes (GTV) that can adequately cover the entire tumor, as demonstrated by comparison with post-lumpectomy pathological tumor (pT) size. Methods: In this prospective phase II clinical trial (NCT04871516), enrolled patients all received mammography, breast MRI and CT simulation. Target volumes and treatment planning were designed based on the baseline mammography, MRI and CT simulation acquired for each patient, generally using the surgical clip placed at the time of biopsy as the center of the tumor. The GTV was expanded by 0.5 cm to define the clinical target volume (CTV) which was then expanded an additional 0.5 cm to define the planning target volume (PTV). Patients then underwent a pre-operative boost of 13.32 Gy in 4 daily fractions, followed by BCS 1-3 weeks later, and then WBI of 36.63 Gy in 11 daily fractions 3-8 weeks post-BCS. Clinical trial and patient records were reviewed to collect patient demographics, disease characteristics, and treatment details. The largest diameter of the GTV contoured from these baseline imaging studies was compared to the largest pathologic diameter of the tumor removed during BCS using a one-tailed paired sample t-test. Results: A total of 76 patients were included in this analysis. The median age was 64 (range: 40-80). Based on initial biopsy, 64 (84.2%) patients had invasive cancer while 12 (15.8%) had DCIS. Most patients, 70 (92.1%), have ER+ disease, 63 (85.1%) have PR+ disease, and 3 (3.9%) have HER2+ disease. The median clinical tumor size was 12 mm. The median GTV diameter was 22.35 mm (range: 11.1-58.1 mm) and the median pathologic tumor (pT) size was 10 mm (range: 0-34 mm). The GTV diameter was larger than the pT size in most cases (p = <0.001). For 8 (10.5%) patients, the largest diameter of the estimated GTV did not cover the pT diameter by a median of 4.35 mm (range: 0.6-6.8 mm). However, the largest diameter of the clinical target volumes (CTV) contoured for these patients were all greater than the pT size by a median of 9.1 mm (range: 2.7-19 mm). The PTV provided another 0.5 cm margin as well. Notably, for 5 (6.6%) patients, pre-operative boost resulted in no residual disease at time of BCS. Conclusions: For most patients, pre-operative boost GTV delineation resulted in a maximum diameter greater than pT size, suggesting that the GTV covered the entire tumor volume. In the minority of cases where the GTV diameter was not greater than the pT size, the tumor was adequately covered by the CTV with an added 0.5 cm PTV margin. These findings support the feasibility of delivering a pre-operative boost for patients with DCIS and early-stage breast cancer based on mammographic CT and MRI imaging. Citation Format: Molly Chakraborty, Zohaib K. Sherwani, Lakshmi Rekha Narra, Zeinab Abou Yehia, Taoran Cui, Nisha Ohri, Firas Eladoumikdachi, Maria J. Kowzun, Shicha Kumar, Lindsay Potdevin, Deborah L. Toppmeyer, Sachin Jhawar, Bruce G. Haffty. Pre-Operative Radiation Boost Planning in a Phase II Clinical Trial Achieves Acceptable Tumor Volume Coverage [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P5-09-12.

The tumor-suppressive function of p53 is frequently disrupted by mutations in cancers. Missense mutant p53 (mutp53) protein often stabilizes and accumulates to high levels in cancers to promote tumorigenesis through the gain-of-function (GOF) mechanism. Currently, the mechanism of mutp53 accumulation and GOF is incompletely understood. Here, we identify the lipogenic enzyme FASN as an important regulator of mutp53 accumulation and GOF. FASN interacts with mutp53 to enhance mutp53 palmitoylation, which inhibits mutp53 ubiquitination to promote mutp53 accumulation and GOF. Blocking FASN genetically or by small-molecule inhibitors suppresses mutp53 palmitoylation to inhibit mutp53 accumulation, which in turn inhibits the growth of mutp53 tumors in orthotopic and subcutaneous xenograft tumor models and transgenic mice, as well as the growth of human tumor organoids carrying mutp53. Our results reveal that mutp53 palmitoylation is an important mechanism underlying mutp53 accumulation and GOF, and targeting FASN is a potential therapeutic strategy for cancers carrying mutp53.

We conducted a prospective, phase II trial in which a radiation tumor bed boost was delivered preoperatively instead of the standard postoperative approach for breast cancer patients. We hypothesized that a preoperative boost would result in a lower rate of re-excision and a shorter duration of locoregional therapy compared with a postoperative boost. Patients in this trial (NCT04871516) received a boost of 13.32 Gy in 4 fractions, followed by lumpectomy and whole-breast radiotherapy of 36.63 Gy in 11 fractions. The re-excision rate in this trial was compared with the literature-reported rate and with a cohort of contemporary patients at our institution. The time from initial diagnostic biopsy to completion of radiotherapy was compared with the same contemporary cohort and with patients treated in a previous prospective trial at our institution (NCT00909909) with the same fractionation scheme. Among 89 patients who were included, three (3.4

PURPOSE Industry payments are common among oncology researchers and can reflect professional stature and achievement; however, whether such payments differ on the basis of the sex of the recipient is unclear. METHODS To investigate potential differences in industry payments to male and female medical oncologists from 2016 through 2020, industry payment information was sourced from the Open Payments database and Centers for Medicare and Medicaid Services website. Covariate details including h-index, academic rank, institution National Institutes of Health (NIH) funding rank, sex, and practice location, were sourced from SCOPUS, Doximity, NIH RePORTER, National Plan and Provider Enumeration system, and institutional websites. Medical oncologists who received at least one industry research payment from 2016 through 2020 were included (n = 7,285). RESULTS No significant sex differences were observed in research payments; however, male medical oncologists received significantly more general payments than did female medical oncologists in several domains, including speaker fees (+194%), consulting (+204%), travel and lodging (+162%), and food and beverage (+114%). CONCLUSION Although we found no discernible sex-based differences in research funding among medical oncologists, female medical oncologists received significantly lower general payments than male medical oncologists. Efforts to improve transparency and interventions to address these discrepancies are important to ensure gender equity in oncology.

BACKGROUND AND PURPOSE:In preparation for adjuvant breast radiation therapy (RT), permanent skin tattoo marks are often placed on the patient's skin to assist patient positioning on the treatment couch. However, those marks are often undesirable, in particular, for breast cancer patients due to various cosmetic and psychological concerns and other drawbacks. With surface-guided radiation therapy (SGRT) being readily available, it becomes possible to adopt a "tattoo-free" approach for patient setup. This study evaluates the efficacy and dosimetric implications of a tattoo-free setup technique. METHODS:Thirty right-sided breast cancer patients were included in this retrospective study. All patients received an initial course of whole breast treatment of 42.56 Gy in 16 fractions using a tangential 3D conformal technique, followed by a 10 Gy boost to the lumpectomy site in four fractions. SGRT was used in daily setup to reproduce patient's positioning between the simulation and treatment. The patient's breast surface was aligned with the corresponding reference breast surface generated from the planning computed tomography (CT) images via AlignRT system. To evaluate the feasibility and accuracy of the new tattoo-free approach, at the beginning of the program and for this group of patients, daily orthogonal kV imaging pair was performed to confirm the treatment positioning by verifying the bony landmarks, and the translational couch shifts were recorded for every fraction. Those shifts were applied to the isocenter positions of the original corresponding clinical treatment plans, and dose distributions were re-computed. The dosimetric evaluation between the two setup methods, that is, the breast surface alignment versus the bony landmark alignment, were then assessed on the original clinical plan. New plan sums were obtained from the 16 fractions, where each one was recalculated based on the new isocenter positions determined with the kV imaging shifts. Boost fractions were excluded in this study, as setup was verified using surgical clips as the matching reference. RESULTS:Translational shifts for the 30 patients (N = 480) were reviewed. The mean absolute shift resulted from the orthogonal kV imaging-based setup following the SGRT setup, in lateral, vertical and longitudinal directions, were 0.20 cm (ranged from 0 to 1.98 cm with 95% confidence interval (CI) of 0.18-0.22 cm), 0.23 cm (ranged from 0-1.25 cm with 95% CI of 0.21-0.25 cm), and 0.22 cm (ranged from 0 to 1.35 cm with 95% CI of 0.19-0.24 cm), respectively. The average change in V95% coverage over the treatment course of the 30 patients was 0.99%. No significant differences in V20Gy of lung (%) and mean heart dose were observed between the original and the corresponding shifted plans. CONCLUSION:A SGRT based tattoo-free setup approach was clinically evaluated and compared to a kV orthogonal imaging-based approach for whole breast RT treatment. It was found that the tattoo-free setup approach is acceptable in treatment setup accuracy and dosimetric coverage. Caution needs to be paid to patient movement during setup and treatment to ensure the safety and efficacy of the approach.

BACKGROUND:Failure to complete cancer treatment is associated with worse oncologic outcomes. This 2-year prospective National Quality Improvement (QI) Collaborative aimed to decrease patient- and program-level rates of missed radiotherapy appointments by 20% at American College of Surgeons (ACS)-accredited cancer programs. STUDY DESIGN:One hundred ninety-four accredited cancer programs scheduled 99,057 patients for radiotherapy while voluntarily participating in the ACS Breaking Barriers National QI Collaborative from March 2023 to December 2024. Programs identified patients who missed 3 or more planned radiotherapy treatments, completed community needs assessments, engaged in educational webinars and peer learning discussions, and implemented system-level strategies to improve treatment adherence using an ACS toolkit. Chi-square tests assessed differences in rates of missed radiotherapy treatments, barriers addressed, and interventions implemented. RESULTS:Reductions of 39.8% (from 8.3% to 5.0%) and 31.7% (from 8.2% to 5.6%) were seen in no-show rates at the patient and program levels, respectively. Reductions were demonstrated for all program types, for most census regions, and for breast, gynecologic, and gastrointestinal cancers. The most frequently addressed barriers were transportation (62.3%) and patient illness unrelated to toxicity (37.1%). The most frequently implemented interventions included the development of a workflow and/or protocol related to identified barriers (68.9%) and the creation of internal resources to address these barriers (54.3%). CONCLUSIONS:Breaking Barriers is the largest prospective study to decrease rates of missed radiotherapy appointments across multiple program types, census regions, and disease sites. These findings demonstrate the strength of ACS-led National QI Collaborative as an effective large-scale approach to address modifiable barriers to high-quality cancer care delivery.

Background:Axillary surgical staging is required for patients with upgraded ductal carcinoma in situ (DCIS) (DCIS is diagnosed on core biopsy with invasive cancer found on pathology after complete surgical excision), which may lead to complications in axillary surgery. At present, there is no reliable and accurate method for predicting axillary lymph node metastasis (ALNM) in patients with upgraded DCIS; however, such a method could prevent unnecessary axillary surgical interventions from being performed. In this study, we aimed to construct a non-invasive model for predicting ALNM in DCIS patients based on clinicopathological characteristics, mammography (MG) features, and magnetic resonance imaging (MRI) features. Methods:Between February 2018 and June 2020, 326 patients with upgraded DCIS were enrolled in this retrospective analysis. These patients were randomly divided into the training cohort (80%) and validation cohort (20%). Univariate and multivariable regression analyses were conducted to identify the candidate pathological features, which then used to develop a clinicopathological model. The features of the 2-mm, 4-mm, and 6-mm intratumoral and peritumoral regions (T-PTR) were extracted to develop the MRI radiomics model, and two deep learning classification models were developed based on the medial-lateral oblique (MLO) and craniocaudal (CC) views of the MG. A fusion model was then established that combined these sub-models. The receiver operating characteristic (ROC) curve, area under the curve (AUC), and other indicators were used to evaluate the performance of these models. Results:The clinicopathological characteristics of the two cohorts were basically balanced. The AUC values of the clinicopathological model were 0.675 and 0.690 in the training and validation cohorts, respectively. The model based on the T-PTR of MRI showed promising predictive ability. Among the three MRI models, the T-PTR (4 mm) model showed the best predictivity both in the training (AUC =0.885) and validation cohorts (AUC =0.843). The AUC values for the deep learning models of the MG CC and MLO positions all exceeded 0.7, indicating reliable predictive performance. The fusion model that combined the three methods significantly improved the accuracy and robustness of ALNM prediction. In both the training (AUC =0.975) and validation (AUC =0.877) cohorts, the fusion model showed excellent performance. Conclusions:We developed a fusion model that combined clinicopathological characteristics, MRI T-PTR (4 mm) radiomics, and MG-based deep learning. Our combined model showed promising performance in predicting ALNM in patients with upgraded DCIS.

Purpose/Objective(s) Early-stage breast cancer and ductal carcinoma in situ (DCIS) are commonly treated with breast conserving surgery (BCS) followed by whole breast irradiation (WBI). Radiation tumor bed boost following BCS and WBI is also recommended depending on patient age and disease characteristics. Re-excision rates due to inadequate surgical margins are reported in the current literature to be about 17-19%. We conducted a prospective phase II clinical trial (NCT04871516) in which the boost was delivered pre-operatively instead of post-operatively. The primary endpoint is the incidence of wound complications, which was previously reported to be acceptable. Here, we report the rate of re-excision observed after pre-operative boost, which was hypothesized to be lower, and the time from initial diagnosis to end of local-regional therapy, which was hypothesized to be shorter. Materials/Methods Patients received a pre-operative boost of 13.32 Gy in 4 daily fractions, followed by BCS 1-3 weeks after boost, followed by WBI of 36.63 Gy in 11 daily fractions 3-8 weeks after surgery. Patient records were reviewed to assess disease and treatment characteristics. A 95% confidence interval of the re-excision rate was calculated using the Wilson-Score interval, and the Chi-Square goodness of fit test was used to compare the re-excision rate to the lower end of the currently reported range. The time from initial diagnostic biopsy to completion of radiation was retrospectively compared to 54 patients treated in a previous prospective trial using the same fractionation regimen but with sequential lumpectomy boost and to a contemporary cohort of 30 patients treated with the Canadian hypofractionation regimen using Welch's t-test and a two-sample t-test, respectively. Results A total of 89 patients were included with a median age of 64 (40-79). Most, 78 (87.6%) patients, had invasive cancer while 11 (12.4%) had DCIS. The median clinical tumor size was 9 mm (1.2-33) and 9 (10.1%) patients had node positive disease. Three (3.4%, 95% CI: 1.15-9.45%) patients underwent re-excision for inadequate margins following BCS, which is lower than the literature reported rate of 17-19% (p=0.0006). The median time from initial diagnosis to completion of radiation was 109 days (42-258) in this trial, 124.5 days (62-311, p=0.00006) in the previous trial, and 132.5 days (95-220, p=0.00003) in the patients treated with the Canadian hypofractionation regimen. Conclusion Delivery of pre-operative boost in this prospective phase II clinical trial resulted in low rates of re-excision compared to current data for sequential boost and resulted in a reduced amount of time from initial diagnosis to completion of radiation. This may reduce treatment cost and risk of wound complications, improve treatment experience, and allow for earlier initiation of systemic therapy.

The authors of the American Radium Society Appropriate Use Criteria for Postmastectomy Radiation Therapy (PMRT) provide a timely update to prior PMRT guidelines and discuss several important questions that clinicians are faced with in daily practice. This editorial highlights the evolving role of PMRT in breast cancer and reviews some of the major changes in the present guidelines compared with the prior 2009 American College of Radiology Appropriateness Criteria on PMRT and the 2016 American Society of Clinical Oncology (ASCO), American Society for Radiation Oncology (ASTRO), and Society of Surgical Oncology (SSO) Focused Guideline Update.

Purpose/Objective(s) The Partner and localizer of BRCA2 (PALB2) gene has crucial role in DNA double-strand break repair, upkeep of genome integrity, and suppression of cancer development. PALB2-deficient cells are known to be hypersensitive to ionizing radiation. Multigene panel testing has increasingly identified patients with PALB2 variants raising the question if those patients with heterozygous PALB2 variants have compromised outcomes or are at increased risk of radiation toxicity. We hypothesize that outcomes with radiation are acceptable with moderately hypofractionated (Hypo-RT) or conventionally fractionated (CRT) radiation after breast conserving surgery (BCS) or mastectomy in patients with heterozygous germline PALB2 pathogenic variants or variants of uncertain significance (VUS). Materials/Methods Between 2005 and 2023, breast cancer patients treated with radiation were consented for peripheral blood sequencing (PBS) on an institutionally approved IRB protocol. PALB2 variants detected by high-throughput PBS were designated benign, pathogenic, VUS, or with conflicting interpretations of pathogenicity using the ClinVar database. Variants designated benign or likely benign were excluded and those with conflicting interpretations of pathogenicity or variants of uncertain significance were classified as VUS. Toxicities were abstracted from medical records and were graded per Common Terminology Criteria for Adverse Events v5. Additional clinicopathologic information was abstracted from the medical records. Results A total of 583 patients were sequenced. After excluding benign PALB2 variants, 14 were included in this analysis: 5(36%) were pathogenic and 9(64%) were VUS. Median tumor size was 2 cm and median age at diagnosis was 51.5 years (range = 42–69). Among these patients 12(86%) had invasive disease, 10(71%) were ER+, and 9(64%) received chemotherapy; 11(79%) had BCS with 7(50%) undergoing sentinel lymph node dissection. All patients received photon based external beam radiation, 3 (21%) were treated with Hypo-RT, 11 (79%) with CRT, and 7(50%) received nodal irradiation. Median follow up was 69 months. Grade 2 acute radiation dermatitis (ARD) was noted in 8(57%) patients, and grade 3 in 2(14%) patients. For patients with grade 3 ARD, one had a pathogenic variant of PALB2, the other had a VUS. Late grade 2 fibrosis was recorded in 1(7%) patient. There were no grade 4 or 5 toxicities. Contralateral breast cancer did not occur in any patients. One patient (7%) had chest wall recurrence 4 months after finishing radiation. Conclusion This represents the first report on clinical outcomes in breast cancer patients with PALB2 undergoing radiation. We concluded that radiation therapy in individuals with heterozygous PALB2 germline pathogenic variants or variants of uncertain significance (VUS) appears to be well-tolerated with acceptable clinical outcomes.

Purpose/Objective(s) Acute radiation dermatitis (RD) is a notable side effect in breast cancer patients undergoing radiation therapy. This study aims to predict such adverse effect through an integrated machine learning model that synthesizes clinical data, mammographic radiomic features, and genetic mutations identified by single nucleotide polymorphism (SNP) testing. Materials/Methods In this retrospective study, data from 174 breast cancer patients treated with radiation following breast-conserving surgery or mastectomy between 2004 and 2016 were evaluated. Genetic profiling included 30 genes, sequenced from peripheral blood samples. Extracted genomic DNA was annotated using Illumina Variant Studio Software and verified with ClinVar database. Patients were stratified based on germline genetic status into four groups: non-carriers, carriers of benign or likely benign variants, variants of uncertain significance (VUS), and pathogenetic variants. Pre-surgery contralateral mammograms were processed to extract 94 radiomics texture features using open-source software. Clinical parameters clinical parameters such as race, age, BMI, TNM staging, total radiation dose, and hypofractionation were also recorded. RD of grade 2 or above were identified as positive cases in this work. A linear support vector machine (LSVM) model was trained with 5-fold cross-validation, to identify significant predictive features from the compiled clinical, radiomics and genomics data. Results The LSVM model with genetic data integration pinpointed 3 genetic markers (CDH1, PTEN, TGFBRAP1), 4 radiomic features, and 2 clinical features (hypofractionation and race) as significant predictors of radiation side effects, achieving an area under the ROC curve (AUC) of 0.75 (± 0.04). The inclusion of mammographic patterns offers additional insight into correlation between germline genetic status and the associated toxicities. Conclusion This study demonstrates the potential of a radiogenomic approach to predict acute radiation therapy side effects in breast cancer patients. The preliminary findings underscore the need for further investigation into the underlying mechanisms linking mammographic appearance and genomic features to side effects, facilitating personalized treatment strategies to mitigate these adverse outcomes.