TPS408 Background: Pelvic radiation therapy plays a key role in the treatment of most genitourinary (GU), gynecologic (Gyn), and gastrointestinal (GI) malignancies of the pelvis. Commonly, physicians instruct patients undergoing pelvic radiation therapy to present with a reproducibly full bladder for treatment with the hope that increasing the distance between the treatment target and normal tissues will limit toxicity. However, this is challenging for patients and often leads to uncertainties in radiation dose distribution to the adjacent pelvic organs, as the bladder volume varies during a treatment course. Retrospective data suggests that treating with an empty bladder has minimal impact on treatment-related toxicity, but prospective data is very limited. A phase III randomized trial is required to evaluate the relative merits of two bladder fill protocols in terms of safety and patient-reported outcomes. The goal of this trial is to identify the optimal bladder filling approach to minimize toxicity and maximize patient quality of life. Methods: The BEFORE trial (NCT06651697) is an investigator-initiated, multi-center, prospective, open-label, pragmatic, two-arm randomized phase III study enrolling patients undergoing pelvic radiation therapy. Patients of all genders planning to undergo pelvic radiation therapy with curative intent for a primary GU, Gyn, or GI malignancy of the pelvis are eligible. This trial aims to include 300 patients randomized to one of the two arms, empty or full bladder protocol, in a 1:1 ratio stratified by primary tumor site, treatment of lymph nodes, and prior prostatectomy. The primary endpoint is the physician-reported acute any attribution GU and/or GI grade ≥2 toxicity within 3 months post-radiation therapy. Secondary endpoints are radiation attribution acute GU and/or GI toxicity, any attribution and radiation attribution late GU and/or GI toxicity, patient-reported urinary and bowel quality of life, and percentage of treatment fractions requiring delay due to incomplete bladder filling in the full bladder arm. BEFORE has enrolled 89 of 300 planned participants. Clinical trial information: NCT06651697 .

Importance:Single-fraction preoperative ablative stereotactic partial breast irradiation (sPBI) can be safely delivered in early-stage hormone receptor-positive (HR+) breast cancer with delayed time to surgery and high pathologic complete response rates. Objectives:To examine the maximum tolerated dose (MTD) of sPBI and to evaluate clinical outcomes, including pathological complete response (pCR), time to surgery, and toxic effects, associated with dose escalation. Design, Setting, and Participants:This phase 1 nonrandomized clinical trial of dose escalation enrolled patients with HR+, ERBB2-negative, cN0 invasive breast cancer not requiring chemotherapy from a single academic center between December 2019 and April 2024. Interventions:Patients were treated with 30, 34, or 38 Gy using MR-guided linear accelerator (MR-LINAC), robotic radiosurgery, or cobalt stereotactic unit. Patients received endocrine therapy and delayed surgery (≤12 months). Main Outcomes and Measures:The MTD was evaluated using dose-limiting toxicity (DLT), defined as grade 3 or higher toxic effects within 90 days. Additionally, pCR, near pCR (npCR), the association of dose escalation with time to surgery, local control, surgical morbidity, and cosmesis were evaluated. Results:A total of 44 patients (median [range] age, 64.5 [44.0-77.0] years) were treated, with 14 (31.8%) receiving 30 Gy (median [IQR] follow-up, 52.0 [28.2-54.5] months), 15 (34.1%) receiving 34 Gy (median [IQR] follow-up, 40.0 [36.5-41.0] months), and 15 (31.4%) receiving 38 Gy (median [IQR] follow-up, 20.0 [17.0-22.0] months). MTD was not reached. pCR rates were 35.7% (5 patients), 46.7% (7 patients), and 66.7% (10 patients), while pCR with npCR rates were 64.3% (9 patients), 93.3% (14 patients), and 93.3% (14 patients), respectively. Local control was 100%, and surgical morbidity was 2.2% (1 of 44 patients). The mean (SD) Ki-67 was 11.3% (6.4%) at diagnosis, and on evaluable residual disease, it was 1.9% (2.0%) (P < .001). A time-to-surgery threshold of 277 days was the optimal cutoff for pCR (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.62-0.91). In patients with surgery more than 9 months after sPBI, pCR rates were 100% (5 of 5 patients), 66.7% (4 of 6 patients), and 64.3% (9 of 14 patients) (P = .40), and combined pCR and npCR rates were 100%, 83.3% (5 patients), and 92.9% (13 patients) (P = .69) for the 30, 34, and 38 Gy groups, respectively. For all patients who received surgery more than 9 months after sPBI, the pCR rate was 72.0% (18 of 25 patients). Longer time to surgery was associated with pCR (odds ratio, 1.02; 95% CI, 1.01-1.03; P = .005), while higher radiation dose was not. Acute toxic effects included 32 grade 1, 3 grade 2 (breast pain and dermatitis), and 1 late grade 3 (wound dehiscence in patient with uncontrolled diabetes) events. Cosmesis remained stable at 36 months. Conclusions and Relevance:In this nonrandomized clinical trial, the rate of toxic effects was low, and treatments were tolerable up to 38 Gy. Delaying surgery more than 9 months after sPBI with endocrine therapy was associated with increased pCR and npCR (>90%), while higher doses were not. These findings support further investigation of sPBI as a potential nonsurgical approach for selected patients with early-stage HR+ breast cancers. Trial Registration:ClinicalTrials.gov Identifier: NCT04040569.

Importance Single-fraction preoperative ablative stereotactic partial breast irradiation (sPBI) can be safely delivered in early-stage hormone receptor-positive (HR+) breast cancer with delayed time to surgery and high pathologic complete response rates. Objectives To examine the maximum tolerated dose (MTD) of sPBI and to evaluate clinical outcomes, including pathological complete response (pCR), time to surgery, and toxic effects, associated with dose escalation. Design, Setting, and Participants This phase 1 nonrandomized clinical trial of dose escalation enrolled patients with HR+, ERBB2-negative, cN0 invasive breast cancer not requiring chemotherapy from a single academic center between December 2019 and April 2024. Interventions Patients were treated with 30, 34, or 38 Gy using MR-guided linear accelerator (MR-LINAC), robotic radiosurgery, or cobalt stereotactic unit. Patients received endocrine therapy and delayed surgery (<= 12 months). Main Outcomes and Measures The MTD was evaluated using dose-limiting toxicity (DLT), defined as grade 3 or higher toxic effects within 90 days. Additionally, pCR, near pCR (npCR), the association of dose escalation with time to surgery, local control, surgical morbidity, and cosmesis were evaluated. Results A total of 44 patients (median [range] age, 64.5 [44.0-77.0] years) were treated, with 14 (31.8%) receiving 30 Gy (median [IQR] follow-up, 52.0 [28.2-54.5] months), 15 (34.1%) receiving 34 Gy (median [IQR] follow-up, 40.0 [36.5-41.0] months), and 15 (31.4%) receiving 38 Gy (median [IQR] follow-up, 20.0 [17.0-22.0] months). MTD was not reached. pCR rates were 35.7% (5 patients), 46.7% (7 patients), and 66.7% (10 patients), while pCR with npCR rates were 64.3% (9 patients), 93.3% (14 patients), and 93.3% (14 patients), respectively. Local control was 100%, and surgical morbidity was 2.2% (1 of 44 patients). The mean (SD) Ki-67 was 11.3% (6.4%) at diagnosis, and on evaluable residual disease, it was 1.9% (2.0%) (P < .001). A time-to-surgery threshold of 277 days was the optimal cutoff for pCR (area under the receiver operating characteristic curve, 0.77; 95% CI, 0.62-0.91). In patients with surgery more than 9 months after sPBI, pCR rates were 100% (5 of 5 patients), 66.7% (4 of 6 patients), and 64.3% (9 of 14 patients) (P = .40), and combined pCR and npCR rates were 100%, 83.3% (5 patients), and 92.9% (13 patients) (P = .69) for the 30, 34, and 38 Gy groups, respectively. For all patients who received surgery more than 9 months after sPBI, the pCR rate was 72.0% (18 of 25 patients). Longer time to surgery was associated with pCR (odds ratio, 1.02; 95% CI, 1.01-1.03; P = .005), while higher radiation dose was not. Acute toxic effects included 32 grade 1, 3 grade 2 (breast pain and dermatitis), and 1 late grade 3 (wound dehiscence in patient with uncontrolled diabetes) events. Cosmesis remained stable at 36 months. Conclusions and Relevance In this nonrandomized clinical trial, the rate of toxic effects was low, and treatments were tolerable up to 38 Gy. Delaying surgery more than 9 months after sPBI with endocrine therapy was associated with increased pCR and npCR (>90%), while higher doses were not. These findings support further investigation of sPBI as a potential nonsurgical approach for selected patients with early-stage HR+ breast cancers.

BACKGROUND:The first 3D high-dose-rate brachytherapy (3D-HDR-BT) program for gynecological cancers in Lagos, Nigeria, was launched in August 2021. A retrospective audit of the pilot program was conducted to report the institution's initial experience in treating cervical cancer within the framework of the American Brachytherapy Society (ABS) guidelines. METHODS AND MATERIALS:24 patients were audited and divided into 2 groups: Group A, which included the first twelve (who had been treated within 3 months of the program launch), and Group B, which included the next twelve (who received treatment over a subsequent period of 5 months). RESULTS:The average age was 58.04 years, with the most common stage at presentation being FIGO Stage IIB (50%). Squamous cell carcinoma was the prevalent histologic type (87.5% of cases). The predominant EBRT regimen was 1.8Gy x 25 fractions in 66.67% of patients. For brachytherapy, 62.5% received the 8Gy x 3 fractions regimen. All patients received weekly concurrent chemotherapy with external beam radiation, with the majority getting cisplatin monotherapy during external beam radiotherapy (EBRT). The mean dose to D90 of the HR-CTV was 77.48 ± 6.95Gy and 88.93 ± 4.20Gy in Group A and B patients, respectively. A comparative assessment revealed significant improvement in HRCTV D90 doses for Group B patients. CONCLUSION:We report evident improvement in HRCTV D90 doses with increasing numbers and duration of practice, indicating that team proficiency improves with an increasing number of patients treated. Future studies will focus on overall survival and local control rates among patients treated on the program.

Abstract Objective(s): To explore the impact of pre-operative single fraction stereotactic ablative partial breast irradiation (SPBI) dose escalation (30, 34, or 38Gy) on toxicity and tumor response for early-stage hormone receptor (HR)+ breast cancer in an interim analysis of an expanded cohort phase I dose escalation study (NCT04040569). Methods: Eligible patients (pts) have < 3 cm, HR+, Her2 -, cN0 invasive breast carcinomas not requiring chemotherapy. Patients are treated on either MR LINAC, robotic radiosurgery, or cobalt stereotactic breast units. Endocrine therapy is started two weeks after SPBI. Surgery is completed 2-12 months after SPBI. The primary objective is to escalate single fraction SPBI to an ablative dose without exceeding maximum tolerable dose (MTD). Secondary endpoints include pathologic complete response (pCR), local control, toxicity, cosmesis, and distant disease-free survival. Near complete response (nCR) is defined as RCB 1 and Miller-Payne 4/5. Dose limiting toxicity (DLT) is defined as grade ≥3 toxicity or any grade 4/5 toxicity attributed to SPBI. Each dose cohort enrolls 7-15 pts. Dose escalation is permitted if 0/7, 2/9, ≤3/12, or ≤4/15 patients experienced a DLT within 90 days of SPBI. MTD is exceeded if more DLTs occur in any cohort. Results: From 12/2019 to 6/2023, 11 and 15 pts were treated with 30Gy and 34Gy, respectively. Rates of pCR/nCR are 37.5% for 30Gy versus 92.8% 34 Gy (p=0.01). At 30Gy, 8/11 pts (73%) underwent surgery with a median 4.3 (range 2.8-5.9) month interval from SPBI to surgery: 0/8 (0%) had a pCR and 3/8 (37.5%) had a nCR. At dose level 34Gy, 14/15 pts (93%) underwent surgery with a median 7.3 (range 5.9-12) month interval from SPBI to surgery: 6/14 (42.8%) had a pCR while 7/14 (50%) had a nCR. Of the 8 pts with a nCR, 50% had only 1-3mm of residual disease. The mean ki67 for the entire cohort was 12.0% +/- 6.9% at diagnosis and decreased to 1.4 +/-2.3% at surgery. 13/14 (92.8%) pts with residual disease had a ki67 < 3% after surgery and SPBI. There were 33 acute grade 1; 2 acute grade 2 (breast pain and dermatitis); and 10 late grade 1 [1 grade 2 (breast pain), and 1 grade 3 (slow healing wound) in an uncontrolled diabetic] toxicities. Conclusion: First study to show pre-operative SPBI up to 34Gy in a single fraction was safe and effective for early-stage HR+ breast cancer. Escalating the dose has achieved a dramatic improvement in pCR/nCR (92.8%) suggesting this is an exciting approach for potentially eliminating tumor with radiation/endocrine therapy alone in early stage breast cancer and potentially paving a path towards non-surgical management in highly selected patients. Citation Format: Asal Rahimi, A Marilyn Leitch, Baṣak Dogan, Prasanna Alluri, Deborah Farr, Mona Arbab, Stephen Seiler, Nathan Kim, Rachel Wooldridge, Nisha Unni, Chika Nwachukwu, Ina Patel, You Zhang, David Parsons, Anvy Nguyen, Howard E Morgan, Heather McArthur, Sunati Sahoo, Robert Timmerman. Early Results of a Phase I Pre-Operative Single Fraction Ablative Trial for Early Stage Breast Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS01-09.

BACKGROUND Cervical cancer is the second most common cancer among women in Nigeria where, the gap between need for, and access to, radiation therapy including brachytherapy is significant. This report documents the implementation of the first three-dimensional high-dose-rate (3D-HDR) brachytherapy service for cervical cancer in Nigeria. PURPOSE This report details the steps taken to implement the 3D-HDR brachytherapy program, the challenges faced, and the adaptive strategies employed to overcome them. Our objective is to provide a guide for teams and centers in similar resource-restricted settings to implement 3D-HDR brachytherapy services, by leveraging our shared experience and lessons learned. METHOD AND METERIALS The implementation process required investment in infrastructure: creating a dedicated brachytherapy suite equipped with modern technology; and human capital: conducting both virtual and hands-on training for staff; and involving international experts during the initial treatment phases. Quality assurance protocols were established to ensure the accuracy and safety of treatments. Key adaptations included extensive remote training, international experts flying in for the initiation phase, and preemptively re-ordering the radioisotope to prevent delays. RESULTS The 3D-HDR brachytherapy program was successfully implemented, with five cases treated in the first 2 months despite challenges such as high equipment costs, expertise and proficiency needs, and source replacement delays. Continuous training and quality assurance measures ensured the program's sustainability and effectiveness. CONCLUSIONS Implementing a 3D-HDR brachytherapy program in a system with restricted resources is possible with thorough planning, flexible strategies, and adaptive measures. We document our experience to provide insights for other institutions aiming to establish similar programs. Collaboration and innovative financial strategies are essential for ensuring sustainable access to cancer treatment in the region. Strategies such as remote training and proactive resource management, are critical for overcoming implementation barriers.

Background3D neural network dose predictions are useful for automating brachytherapy (BT) treatment planning for cervical cancer. Cervical BT can be delivered with numerous applicators, which necessitates developing models that generalize to multiple applicator types. The variability and scarcity of data for any given applicator type poses challenges for deep learning.PurposeThe goal of this work was to compare three methods of neural network training-a single model trained on all applicator data, fine-tuning the combined model to each applicator, and individual (IDV) applicator models-to determine the optimal method for dose prediction.MethodsModels were produced for four applicator types-tandem-and-ovoid (T&O), T&O with 1-7 needles (T&ON), tandem-and-ring (T&R) and T&R with 1-4 needles (T&RN). First, the combined model was trained on 859 treatment plans from 266 cervical cancer patients treated from 2010 onwards. The train/validation/test split was 70%/16%/14%, with approximately 49%/10%/19%/22% T&O/T&ON/T&R/T&RN in each dataset. Inputs included four channels for anatomical masks (high-risk clinical target volume [HRCTV], bladder, rectum, and sigmoid), a mask indicating dwell position locations, and applicator channels for each applicator component. Applicator channels were created by mapping the 3D dose for a single dwell position to each dwell position and summing over each applicator component with uniform dwell time weighting. A 3D Cascade U-Net, which consists of two U-Nets in sequence, and mean squared error loss function were used. The combined model was then fine-tuned to produce four applicator-specific models by freezing the first U-Net and encoding layers of the second and resuming training on applicator-specific data. Finally, four IDV models were trained using only data from each applicator type. Performance of these three model types was compared using the following metrics for the test set: mean error (ME, representing model bias) and mean absolute error (MAE) over all dose voxels and ME of clinical metrics (HRCTV D90% and D2cc of bladder, rectum, and sigmoid), averaged over all patients. A positive ME indicates the clinical dose was higher than predicted. 3D global gamma analysis with the prescription dose as reference value was performed. Dice similarity coefficients (DSC) were computed for each isodose volume.ResultsFine-tuned and combined models showed better performance than IDV applicator training. Fine-tuning resulted in modest improvements in about half the metrics, compared to the combined model, while the remainder were mostly unchanged. Fine-tuned MAE = 3.98%/2.69%/5.36%/3.80% for T&O/T&R/T&ON/T&RN, and ME over all voxels = -0.08%/-0.89%/-0.59%/1.42%. ME D2cc were bladder = -0.77%/1.00%/-0.66%/-1.53%, rectum = 1.11%/-0.22%/-0.29%/-3.37%, sigmoid = -0.47%/-0.06%/-2.37%/-1.40%, and ME D90 = 2.6%/-4.4%/4.8%/0.0%. Gamma pass rates (3%/3 mm) were 86%/91%/83%/89%. Mean DSCs were 0.92%/0.92%/0.88%/0.91% for isodoses <= 150% of prescription.Conclusions3D BT dose was accurately predicted for all applicator types, as indicated by the low MAE and MEs, high gamma scores and high DSCs. Training on all treatment data overcomes challenges with data scarcity in each applicator type, resulting in superior performance than can be achieved by training on IDV applicators alone. This could presumably be explained by the fact that the larger, more diverse dataset allows the neural network to learn underlying trends and characteristics in dose that are common to all treatment applicators. Accurate, applicator-specific dose predictions could enable automated, knowledge-based planning for any cervical brachytherapy treatment.

PURPOSE: Prospectively measure change in vaginal length after definitive chemoradiation (CEBRT) with Intracavitary Brachytherapy (ICBT) for locally advanced cervix cancer (LACC) and correlate with vaginal dose (VD). MATERIALS AND METHODS: Twenty one female patients with LACC receiving C-EBRT and ICBT underwent serial vaginal length (VL) measurements. An initial measurement was made at the time of the first ICBT procedure and subsequently at 3 month intervals up to 1 year post radiation. The vagina was contoured as a 3 -dimensional structure for each brachytherapy plan. The difference in VL before and at least 6 months after the last fraction of brachytherapy was considered as an indicator of toxicity. RESULTS: The mean initial VL was 8.7 cm (6.5-12) with median value of 8.5 cm. The mean VL after 6 months was 8.6 cm (6.5-12) and VL change was not found to be statistically significant. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 129.2 Gy (99.6-252.2), 96.9 Gy (84.2-114.9), and 89.6 Gy (82.4-102.2), respectively. No significant correlation was found between vaginal length change and the dosimetric parameters calculated for all patients. CONCLUSION: Definitive C-EBRT and ICBT did not significantly impact VL in this prospective cohort probably related to acceptable doses per ICRU constraints. Estimate of vaginal stenosis and sexual function was not performed in this cohort which is a limitation of this study and which we hope to study prospectively going forward. (c) 2023 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Background and Purpose: Online cone-beam-based adaptive radiotherapy (ART) adjusts for anatomical changes during external beam radiotherapy. However, limited cone-beam image quality complicates nodal contouring. Despite this challenge, artificial-intelligence guided deformation (AID) can auto-generate nodal contours. Our study investigated the optimal use of such contours in cervical online cone-beam-based ART. Materials and Methods: From 136 adaptive fractions across 21 cervical cancer patients with nodal disease, we extracted 649 clinically-delivered and AID clinical target volume (CTV) lymph node boost structures. We assessed geometric alignment between AID and clinical CTVs via dice similarity coefficient, and 95% Hausdorff distance, and geometric coverage of clinical CTVs by AID planning target volumes by false positive dice. Coverage of clinical CTVs by AID contour-based plans was evaluated using D100, D95, V100%, and V95%. Results: Between AID and clinical CTVs, the median dice similarity coefficient was 0.66 and the median 95 % Hausdorff distance was 4.0 mm. The median false positive dice of clinical CTV coverage by AID planning target volumes was 0. The median D100 was 1.00, the median D95 was 1.01, the median V100% was 1.00, and the median V95% was 1.00. Increased nodal volume, fraction number, and daily adaptation were associated with reduced clinical CTV coverage by AID-based plans. Conclusion: In one of the first reports on pelvic nodal ART, AID-based plans could adequately cover nodal targets. However, physician review is required due to performance variation. Greater attention is needed for larger, daily-adapted nodes further into treatment.

Purpose: Online adaptive radiation therapy (ART) has emerged as a new treatment modality for cervical cancer. Daily online adapting improves target coverage and organ-at-risk (OAR) sparing compared with traditional image guided radiation therapy (IGRT); however, the required resources may not be feasible in a busy clinical setting. Less frequent adapting may still benefit cervical cancer patients due to large volume changes of the uterocervix of the treatment course. In this study, the dosimetry from different online adapt-on-demand schedules was compared. Materials and Methods: A retrospective cohort of 10 patients with cervical cancer treated with 260 fractions of definitive daily online ART was included. Plans with different adaptation schedules were simulated with adaptations weekly, every other week, once during treatment, and no adaptations (IGRT). These plans were applied to the synthetic computed tomography (CT) images and contours generated during the patient's delivered daily adaptive workflow. The dosimetry of the weekly replan, every-other-week replan, once replan, and IGRT plans were compared using a paired t test. Results: Compared with traditional IGRT plans, weekly and every-other-week ART plans had similar clinical target volume (CTV) coverage, but statistically significant improved sparing of OARs. Weekly and every-other-week ART had reduced bowel bag V40 by 1.57% and 1.41%, bladder V40 by 3.82% and 1.64%, rectum V40 by 8.49% and 7.50%, and bone marrow Dmean by 0.81% and 0.61%, respectively. Plans with a single adaptation had statistically significantly worse target coverage, and moderate improvements in OAR sparing. Of the 18-dose metrics evaluated, improvements were seen in 15 for weekly ART, 14 for every-other-week ART, and 10 for single ART plans compared with IGRT. When every-other-week ART was compared with weekly ART, both plans had similar CTV coverage and OAR sparing with only small improvements in bone marrow dosimetry with weekly ART. Conclusions: This retrospective work compares different adapt-on-demand treatment schedules using data collected from patients treated with daily online adaptive radiation therapy. Results suggest weekly or every-other-week online ART is beneficial for reduced OAR dose compared with IGRT by exploiting the gradual changes in the uterocervix target volume. (c) 2023 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Involving diverse populations in early-phase (phase I and II) cancer clinical trials is critical to informed therapeutic development. However, given the growing costs and complexities of early-phase trials, trial activation and enrollment barriers may be greatest for these studies at healthcare facilities that provide care to the most diverse patient groups, including those in historically underserved communities (e.g., safety-net healthcare systems). To promote diverse and equitable access to early-phase cancer clinical trials, we are implementing a novel program for the transfer of care to enhance access to early-phase cancer clinical trials. We will then perform a mixed-methods study to determine perceptions and impact of the program. Specifically, we will screen, recruit, and enroll diverse patients from an urban, integrated safety-net healthcare system to open and active early-phase clinical trials being conducted in a university-based cancer center. To evaluate this novel program, we will: (1) determine program impact and efficiency; and (2) determine stakeholder experience with and perceptions of the program. To achieve these goals, we will conduct preliminary cost analyses of the program. We will also conduct surveys and interviews with patients and caregivers to elucidate program impact, challenges, and areas for improvement. We hypothesize that broadening access to early-phase cancer trials conducted at experienced centers may improve equity and diversity. In turn, such efforts may enhance the efficiency and generalizability of cancer clinical research.

Rationale and Objectives: To compare rates of guideline-concordant care, imaging surveillance, recurrence and survival outcomes between a safety-net (SNH) and tertiary-care University Hospital (UH) served by the same breast cancer clinical teams. Materials and Methods: 647 women with newly diagnosed breast cancer treated in affiliated SNH and UH between 11.1.2014 and 3.31.2017 were reviewed. Patient demographics, completion of guideline-concordant adjuvant chemotherapy, radiation and hormonal therapy were recorded. Two multivariable logistic regression models were performed to investigate the effect of hospital and race on cancer stage. Kaplan-Meier log-rank and Cox-regression were used to analyze five-year recurrence-free (RFS) and overall survival (OS) between hospitals and races, (p < 0.05 significant). Results: Patients in SNH were younger (mean SNH 53.2 vs UH 57.9, p < 0.001) and had higher rates of cT3/T4 disease (SNH 19% vs UH 5.5%, p < 0.001). Patients in the UH had higher rates of bilateral mastectomy (SNH 17.6% vs UH 40.1% p < 0.001) while there was no difference in the positive surgical margin rate (SNH 5.0% vs UH 7.6%, p = 0.20), completion of adjuvant radiation (SNH 96.9% vs UH 98.7%, p = 0.2) and endocrine therapy (SNH 60.8% vs UH 66.2%, p = 0.20). SNH patients were less compliant with mammography surveillance (SNH 64.1% vs UH 75.1%, p = 0.02) and adjuvant chemotherapy (SNH 79.1% vs UH 96.3%, p < 0.01). RFS was lower in the SNH (SNH 54 months vs UH 57 months, HR 1.90, 95% CI: 1.18-3.94, p = 0.01) while OS was not significantly different (SNH 90.5% vs UH 94.2%, HR 1.78, 95% CI: 0.97-3.26, p = 0.06). Conclusion: In patients experiencing health care disparities, having access to guideline-concordant care through SNH resulted in noninferior OS to those in tertiary-care UH.

Importance The role of stereotactic ablative radiotherapy (SABR) for gynecologic malignant tumors has yet to be clearly defined despite recent clinical uptake. Objective To evaluate the outcomes of SABR in patients with oligometastatic and oligoprogressive gynecologic cancers. Design, Setting, and Participants In this retrospective pooled analysis, patients with oligometastatic and oligoprogressive gynecologic cancers receiving SABR at 5 institutions from Canada and the US were studied. Data were collected from January 2011 to December 2020, and data were analyzed from January to December 2023. Exposure Stereotactic ablative radiotherapy. Main Outcomes and Measures Cumulative incidence of local and distant recurrence, chemotherapy-free survival (CFS), and overall survival (OS) probabilities after SABR were calculated using Kaplan-Meier methods. Univariable and multivariable analysis was conducted using Cox regression methods. Results A total of 215 patients with 320 lesions meeting criteria were included in the analysis; the median (range) age at primary diagnosis was 59 (23-86) years. The median (range) follow-up from SABR was 18.5 (0.1-124.5) months. The primary site included the endometrium (n = 107), ovary (n = 64), cervix (n = 30), and vulva or vagina (n = 14). Local cumulative incidence of recurrence was 13.7% (95% CI, 9.4-18.9) and 18.5% (95% CI, 13.2-24.5) at 1 and 5 years, respectively. Distant cumulative incidence of recurrence was 48.5% (95% CI, 41.4-55.1) and 73.1% (95% CI, 66.0-79.0) at 1 and 5 years, respectively. OS was 75.7% (95% CI, 69.2-81.1) and 33.1% (95% CI, 25.3-41.1) at 1 and 5 years, respectively. The median CFS was 21.7 months (95% CI, 15.4-29.9). On multivariable analysis, local recurrence was significantly associated with nodal metastasis, lesion size, biologically effective dose, treatment indication, institution, and primary disease type. Distant progression-free survival was associated with nodal targets and lesion size. OS and CFS were significantly associated with lesion size. Conclusions and Relevance In this study, SABR appeared to have excellent local control with minimal toxic effects in this large patient group, and certain patients may achieve durable distant control and OS as well. It may be possible to delay time to chemotherapy in select patient subtypes and therefore reduce associated toxic effects. Prospective multicenter trials will be critical to establish which characteristics procure the greatest benefit from SABR use and to define the ideal time to implement SABR with other oncologic treatments.

Purpose: Inflammatory breast cancer (IBC) is the most aggressive form of breast cancer and has a high propensity for distant metastases. Our previous data suggested that aspirin (acetylsalicylic acid, ASA) use may be associated with reduced risk of distant metastases in aggressive breast cancer; however, there are no reported studies on the potential benefit of ASA use in patients with IBC. Methods: Data from patients with non-metastatic IBC treated between 2000-2017 at two institutions, were reviewed. Overall survival (OS), disease-free survival (DFS), and distant metastasis-free survival (DMFS) were performed using Kaplan-Meier analysis. Univariate and multivariable logistic regression models were used to identify significant associated factors. Results: Of 59 patients meeting the criteria for analysis and available for review, 14 ASA users were identified. ASA users demonstrated increased OS (p = 0.03) and DMFS (p = 0.02), with 5-year OS and DMFS of 92% (p = 0.01) and 85% (p = 0.01) compared to 51% and 43%, respectively, for non-ASA users. In univariate analysis, pT stage, pN stage, and ASA use were significantly correlated (p < 0.05) with OS and DFS. On multivariable analysis, ASA use (hazard ratio [HR], 0.11; 95% confidence interval [CI], 0.01-0.8) and lymph node stage (HR, 5.9; 95% CI, 1.4-25.9) remained significant for OS and DFS ASA use (HR, 0.13; 95% CI, 0.03-0.56) and lymph node stage (HR, 5.6; 95% CI, 1.9-16.4). Conclusion: ASA use during remission was associated with significantly improved OS and DMFS in patients with IBC. These results suggest that ASA may provide survival benefits to patients with IBC. Prospective clinical trials of ASA use in patients with high-risk IBC in remission should be considered.

Targeted therapies, such as endocrine therapies (ET), can exert selective pressure on cancer cells and promote adaptations that confer treatment resistance. In this study, we show that ET resistance in breast cancer drives radiation resistance through reprogramming of DNA repair pathways. We also show that pharmacological bromodomain and extraterminal domain inhibition reverses pathological DNA repair reprogramming in ET-resistant breast tumors and overcomes resistance to radiation therapy.

Purpose Prospectively measure change in vaginal length after definitive Chemoradiation (C-EBRT) with Intracavitary Brachytherapy (ICBT) for locally advanced cervix cancer (LACC) and correlate with vaginal dose (VD) Materials and Methods 21 female patients with LACC receiving C-EBRT and ICBT underwent serial vaginal length (VL) measurements. 6 of these women had Hybrid interstitial/intracavitary brachytherapy, the rest had Tandem and ovoid alone. Initial measurement was made at time of first ICBT procedure and subsequently at 3 month intervals till one year post radiation. For consistency the length was defined as distance between external cervical os and the introitus. All patients underwent radiation per ASTRO cervix cancer guidelines. Education regarding the use of vaginal dilator was given to all but compliance was less than 50%. For VD co-relation, the vagina was contoured as a 3- dimensional structure for each brachytherapy plan. All contouring was performed on CT (with MR fusion- if available) using a 0.5-cm fixed brush to outline the vagina around applicator and/or packing, expanded to include any grossly visible vagina. The surface of the cervix was specifically excluded from the contour, but the fornices were included. High-dose-rate (HDR) doses were converted to the equivalent dose in 2-Gy fractions using an α/β of 3 for late effects and added to the dose received by vagina in external beam radiotherapy. The parameters D0.1cc, D1cc, and D2cc and ICRU rectovaginal point dose were calculated for all patients. The difference in VL before and at least 6 months after the last fraction of brachytherapy was considered as an indicator of toxicity. Linear regressions were performed for the generation of Pearson correlation coefficients to explore VD with changes in VL. A Holm-Bonferroni correction was used for all correlations. Results The mean initial VL was 8.7 (6.5 - 12cm) with median value of 8.5. The mean VL after six months was 8.6 (6.5 - 12cm) and VL change was not found to be statistically significant. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 129.2 (99.6-252.2) Gy, 96.9 (84.2-114.9) Gy, and 89.6 (82.4-102.2) Gy, respectively. No significant correlation was found between vaginal length change and the dosimetric parameters calculated for all patients. The values were within normal range (ICRU 89), ICRU rectovaginal point was higher than 65Gy in 12 of patients but this did not significantly correlate with change in VL. Conclusion Definitive C-EBRT and ICBT did not significantly impact VL in this prospective cohort probably related to acceptable doses per ICRU constraints. Estimate of vaginal stenosis and sexual function was not performed in this cohort which is a limitation of this study and which we hope to study prospectively going forward. Prospectively measure change in vaginal length after definitive Chemoradiation (C-EBRT) with Intracavitary Brachytherapy (ICBT) for locally advanced cervix cancer (LACC) and correlate with vaginal dose (VD) 21 female patients with LACC receiving C-EBRT and ICBT underwent serial vaginal length (VL) measurements. 6 of these women had Hybrid interstitial/intracavitary brachytherapy, the rest had Tandem and ovoid alone. Initial measurement was made at time of first ICBT procedure and subsequently at 3 month intervals till one year post radiation. For consistency the length was defined as distance between external cervical os and the introitus. All patients underwent radiation per ASTRO cervix cancer guidelines. Education regarding the use of vaginal dilator was given to all but compliance was less than 50%. For VD co-relation, the vagina was contoured as a 3- dimensional structure for each brachytherapy plan. All contouring was performed on CT (with MR fusion- if available) using a 0.5-cm fixed brush to outline the vagina around applicator and/or packing, expanded to include any grossly visible vagina. The surface of the cervix was specifically excluded from the contour, but the fornices were included. High-dose-rate (HDR) doses were converted to the equivalent dose in 2-Gy fractions using an α/β of 3 for late effects and added to the dose received by vagina in external beam radiotherapy. The parameters D0.1cc, D1cc, and D2cc and ICRU rectovaginal point dose were calculated for all patients. The difference in VL before and at least 6 months after the last fraction of brachytherapy was considered as an indicator of toxicity. Linear regressions were performed for the generation of Pearson correlation coefficients to explore VD with changes in VL. A Holm-Bonferroni correction was used for all correlations. The mean initial VL was 8.7 (6.5 - 12cm) with median value of 8.5. The mean VL after six months was 8.6 (6.5 - 12cm) and VL change was not found to be statistically significant. The median values (interquartile ranges) for vaginal D0.1cc, D1cc, and D2cc were 129.2 (99.6-252.2) Gy, 96.9 (84.2-114.9) Gy, and 89.6 (82.4-102.2) Gy, respectively. No significant correlation was found between vaginal length change and the dosimetric parameters calculated for all patients. The values were within normal range (ICRU 89), ICRU rectovaginal point was higher than 65Gy in 12 of patients but this did not significantly correlate with change in VL. Definitive C-EBRT and ICBT did not significantly impact VL in this prospective cohort probably related to acceptable doses per ICRU constraints. Estimate of vaginal stenosis and sexual function was not performed in this cohort which is a limitation of this study and which we hope to study prospectively going forward.

1089 Background: Black women face a three- fold increase in TNBC BRCA1 gene mutations. In TNBC, there is a higher rate of recurrence and metastasis to other organs. Lower access to timely care and more advance stage at diagnosis contribute to poorer outcomes. Black women have the lowest survival rate at each stage of TNBC diagnosis compared to other demographic groups. Research Question: Over the past 10 years, what real world community interventions have been published regarding risk for and diagnosis with TNBC in Black or African American women? Methods: Using the following keywords: TNBC, diversity, health equity, young adults, Black, African American, authors conducted PUBMED and Google Scholar searches for years 2011 to 2022 to summarize publications on community-based interventions with Black or African American women at risk of or diagnosed with TNBC. Results: A validated publication assessment revealed 70 publications: 63 retrospective and 7 prospective studies. Prospective studies were categorized using the NASEM cancer continuum of care domains. The number of studies that addressed the domains included: risk=1, screening =1, diagnosis=3, treatment=2, survivorship=1 end of life=0, outcomes=1. No studies reported the following criteria: A co-creation approach with community-based participatory research principles; interventions led by patients and Black women who are at risk for TNBC; multi stakeholder interventions led by community leaders or patient organizations with long-standing trust of diverse populations; addressing and resolving social drivers of health inequities, mental health, palliative care services or implicit bias; or inclusion in clinical studies. Conclusions: It is critical to address the disproportionate impact of TNBC in partnership with Black women. To achieve equitable health outcomes, we advise public and private sector leaders to make more funding available to support community-engaged approaches in high prevalence geographic areas. 1) Provide CBPR training and opportunities for diverse investigators and patient- and community-based organizations. 2) Build capacity for social needs assessment and interventions. 3) Employ community-based implementation science focused on all care continuum domains including the gaps between domains. 4) Increase public awareness of health issues in Black women and address resistance, access and eligibility for participation in clinical research. 5) Offer RFPs to transform care through collaboration between researchers, providers, patient and community-based organizations, health departments, and payers; engaging clinical and lay navigators and community health workers; design solutions that address barriers; and development and implementation of policy with a focus on standardization, accountability, and enforceability.