Radiotherapy For Breast Cancer Research Articles

Determinants of radiation dose to immune cells during breast radiotherapy.

The immune system has been identified as an organ at risk in esophageal and lung cancers. However, the dosimetric impact of radiotherapy on immune system exposure in patients treated for breast cancer has never been studied. Amonocentric retrospective dosimetric study included 163 patients treated at the Institut Curie (Paris, France) between 2010 and 2016 with locoregional helical tomotherapy after conservative surgery or total mastectomy. The effective dose to the immune system (EDIC) was calculated based on diverse dosimetric parameters. The clinical and volumetric determinants of EDIC in adjuvant radiotherapy of breast cancer were analyzed. The median EDIC for the population was 4.23 Gy, ranging from 1.82 to 6.19Gy. Right-sided radiotherapy and regional lymph node irradiation were associated with significantly higher EDIC in univariate (4.38 Gy vs. 3.94 Gy, p < 0.01, and 4.27 Gy vs. 3.44 Gy, p < 0.01, respectively) and multivariate analyses (p < 0.01 and p < 0.01). Liver overexposure was the main contributor to EDIC increase in right-sided breast cancer patients (+0.38 Gy [95%CI: +0.30; +0.46]), while the integral total dose increase was the main contributor to EDIC increase in cases of regional node irradiation (+0.63 Gy [95%CI: +0.42; +0.85]). The EDIC score during adjuvant radiotherapy after breast cancer was statistically significantly higher in the case of right-sided radiotherapy and regional lymph node irradiation. Liver irradiation is the main contributor to immune system exposure in adjuvant irradiation of right-sided breast cancer. Populations in which an association between EDIC and survival would exist have yet to be identified but could potentially include patients treated for triple-negative breast cancer with apoor response to neoadjuvant chemoimmunotherapy.

Impact of Neoadjuvant Chemoimmunotherapy on Surgical Outcomes and Time to Radiation in Triple-Negative Breast Cancer.

We examined the association between immunotherapy-containing and standard chemotherapy regimens with treatment delays and postoperative complications in stage II-III triple-negative breast cancer. The effect of immune-related adverse events (irAEs) was compared. We compared 139 women treated with neoadjuvant pembrolizumab plus chemotherapy (KEYNOTE-522 regimen) from August 2021 to September 2022 with 287 consecutive patients who received neoadjuvant chemotherapy alone prior to July 2021 and underwent surgery. Baseline characteristics, time to treatments, and surgical complications were compared using two-sample non-parametric tests. Linear regression evaluated association of irAEs with time to surgery and radiation. Logistic regression identified factors associated with surgical complications. Age, body mass index, race, American Society of Anesthesiologists (ASA) class, and mastectomy rates were similar among cohorts. No clinically relevant difference in time from end of neoadjuvant treatment to surgery was observed [KEYNOTE-522: median 32 (IQR 27, 43) days; non-KEYNOTE-522: median 31 (IQR 26, 37) days; P = 0.048]. Time to radiation did not differ (P = 0.7). A total of 26 patients (9%; non-KEYNOTE-522) versus 11 (8%; KEYNOTE-522) experienced postoperative complications (P = 0.6). In the KEYNOTE-522 cohort, 59 (43%) of 137 patients experienced 82 irAEs; 40 (68%) required treatment. Older age (P = 0.018) and ASA class 4 (P = 0.007) were associated with delays to surgery after adjusting for clinical factors. Experiencing ≥ 1 irAE was associated with delay to radiation (P = 0.029). IrAEs were not associated with surgical complications (P = 0.4). We observed no clinically meaningful difference between times to surgery/adjuvant radiation or postoperative complications and type of preoperative chemotherapy. IrAEs were associated with delay to adjuvant radiation but not with postoperative complications or delay to surgery.

Coping with modesty during radiotherapy for breast cancer: a multicentric study.

Breast cancer is the most frequently diagnosed tumour, representing nearly 30% of all new cases in women. Radiotherapy (RT) plays a crucial role in the management of breast cancer. The objective of this study is to assess modesty in patients undergoing RT for breast cancer and take their suggestions and ideas into consideration to enhance the quality of treatment in this regard. The study enrolled 555 breast cancer patients undergoing adjuvant RT in three Italian centres. Patients completed a self-test questionnaire assessing their comfort level concerning modesty during therapy and their relationship with strangers and healthcare professionals. The impact of religious views and potential changes in sexuality were also examined. Results showed that modesty was a common concern across the overall cohort of patients, with discomfort in being undressed during RT correlating with discomfort experienced in other daily life situations. Most patients felt more at ease with same sex healthcare workers. Age was also a major factor with younger patients generally feeling more comfortable with healthcare workers of the same age group. Interestingly, the surgical technique used (mastectomy vs. quadrantectomy) did not significantly influence modesty perceptions. Patients provided valuable suggestions to improve privacy and modesty during RT. This study demonstrates that modesty is an important issue for women undergoing RT, which can be influenced by personal characteristics and hospital-related factors. A reflection about the need to address modesty concerns and to incorporate dedicated interventions for protecting patients' physical and emotional well-being is warranted. Initiatives to improve communication, involvement, and body image support should also be integrated into the care path of patients to better their overall therapeutic experience. This study paves the way for broader research and interventions in daily cancer care.

Cardiac substructure delineation in radiation therapy - A state-of-the-art review.

Delineation of cardiac substructures is crucial for a better understanding of radiation-related cardiotoxicities and to facilitate accurate and precise cardiac dose calculation for developing and applying risk models. This review examines recent advancements in cardiac substructure delineation in the radiation therapy (RT) context, aiming to provide a comprehensive overview of the current level of knowledge, challenges and future directions in this evolving field. Imaging used for RT planning presents challenges in reliably visualising cardiac anatomy. Although cardiac atlases and contouring guidelines aid in standardisation and reduction of variability, significant uncertainties remain in defining cardiac anatomy. Coupled with the inherent complexity of the heart, this necessitates auto-contouring for consistent large-scale data analysis and improved efficiency in prospective applications. Auto-contouring models, developed primarily for breast and lung cancer RT, have demonstrated performance comparable to manual contouring, marking a significant milestone in the evolution of cardiac delineation practices. Nevertheless, several key concerns require further investigation. There is an unmet need for expanding cardiac auto-contouring models to encompass a broader range of cancer sites. A shift in focus is needed from ensuring accuracy to enhancing the robustness and accessibility of auto-contouring models. Addressing these challenges is paramount for the integration of cardiac substructure delineation and associated risk models into routine clinical practice, thereby improving the safety of RT for future cancer patients.

Breast conserving surgery with intraoperative electron beam radiation therapy for low-risk breast cancer: Five-year follow-up of 306 patients.

Recent studies have reported a higher than expected risk of ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) and a single dose of electron beam intra-operative radiotherapy (IORT). This finding was the rationale to perform a retrospective single center cohort study evaluating the oncologic results of consecutive patients treated with BCS and IORT. Women were eligible if they had clinical low-risk (N0, ≤2 cm unifocal, Bloom and Richardson grade 1-2), estrogen receptor-positive and human-epidermal-growth-factor-receptor-2-negative breast cancer. Prior to BCS, pN0 status was determined by sentinel lymph node biopsy. Data on oncologic follow-up were analyzed. Between 2012 and 2019, 306 consecutive patients were treated and analyzed, with a median age of 67 (50-86) years at diagnosis. Median follow-up was 60 (8-120) months. Five-year cumulative risk of IBTR was 13.4% (95% confidence interval [CI] 9.4-17.4). True in field recurrence was present in 3.9% of the patients. In 4.6% of the patients, the IBRT was classified as a local recurrence due to seeding of tumor cells in the cutis or subcutis most likely related to percutaneous biopsy. In 2.9% of the patients, the IBRT was a new outfield primary tumor. Three patients had a regional lymph node recurrence and two had distant metastases as first event. One breast cancer-related death was observed. Estimated 5-year overall survival was 89.8% (95% CI 86.0-93.6). In conclusion, although some of IBTR cases could have been prevented by adaptations in biopsy techniques and patient selection, BCS followed by IORT was associated with a substantial risk of IBTR.

A Prospective Study on the Use of Deep Inspiration Breath-Hold Technique in External Beam Radiotherapy for Breast Cancer

Background Breast cancer is the most common cancer and the leading cause of death in women. The deep inspiration breath-hold (DIBH) technique helps reduce the dose received by the heart and lungs in breast cancers during adjuvant radiotherapy (RT). We present the dosimetry of heart and lungs with DIBH technique, reproducibility, and ease of execution. Materials and Methods This is a prospective study among breast cancer patients planned for adjuvant RT following either breast conservation or mastectomy. Patients received adjuvant RT to a dose of 42.5 Gy/16 Fr to the chest wall/whole breast followed by a boost of 10 Gy/5 Fr for breast conservation surgery patients with either three-dimensional conformal RT or volumetric modulated arc therapy technique. The dosimetric parameters such as lung mean dose, heart mean dose, and V25 Gy were compared between DIBH and free-breathing (FB) scans. Data were analyzed using SPSS software, and p-value &lt;0.05 was considered statistically significant. Results The study was conducted from September 2018 to August 2020, and 32 patients were included. The compliance to the DIBH technique was good. The dose received by ipsilateral lung V20 (17 vs. 25%) and mean dose (9 vs. 12 Gy) were significantly lower in DIBH compared with FB (p &lt; 0.001). The V5 (31 vs. 15%), V25 (9 vs. 2%), and mean dose (7 vs. 3.3 Gy) to the heart were much higher in FB compared with DIBH (p &lt; 0.001). Conclusion DIBH-based RT treatment delivery for breast cancer patients requiring adjuvant RT showed good compliance and offers a significant reduction in radiation dose to the heart and lung.

Nutritional support in the complex of medical rehabilitation at the stage of adjuvant radiation therapy of breast cancer

BACKGROUND: Currently it is known that there exists the need for complex medical rehabilitation at the stage of adjuvant radiation treatment of breast cancer. However, data on the combined use of nutritional support and physical factors at this stage of oncological treatment are not available. AIM: Evaluation of the effectiveness of specialized therapeutic and preventive nutrition in patients with malignant breast diseases and a history of polychemotherapy at the stage of adjuvant radiation therapy in complex medical rehabilitation using low-temperature plasma and general magnetic therapy. MATERIALS AND METHODS: A prospective simple randomized study was conducted, which involved 60 patients at the stage of adjuvant radiation therapy for breast cancer. The main group (n=30) received a course of medical rehabilitation with the inclusion of nutritional support using specialized therapeutic and preventive nutrition LEOVIT ONCO®, as well as exposure to low-temperature plasma and general magnetotherapy. In the comparison group (n=30), the rehabilitation course included general magnetic therapy without therapeutic and preventive nutrition. All patients underwent individual physiotherapy exercises, and sessions with a medical psychologist. The results obtained were recorded using clinical and functional, laboratory, instrumental studies. RESULTS: It has been established that the use of specialized dietary products LEOVIT ONCO and physical factors is an effective method of rehabilitation. The use of nutritional support demonstrates the maintenance of the patient’s protein status, reduces intoxication, and reduces the negative impact of oxidative stress factors in the body at the stage of adjuvant radiation treatment. The inclusion of low-temperature plasma and general magnetic therapy in the rehabilitation program has a beneficial effect on hemomicrocirculation in the area of ionizing radiation exposure. CONCLUSION: The use of nutritional support and physical factors, as a component of complex medical rehabilitation, helps to maintain the optimal nutritional status of the patient, reduces the manifestations of skin radiation reactions, improves the psycho-emotional state of patients and the quality of life of patient.

Overall survival after mastectomy versus breast-conserving surgery with adjuvant radiotherapy for early-stage breast cancer: meta-analysis.

Breast-conserving surgery with adjuvant radiotherapy and mastectomy are currently offered as equivalent surgical options for early-stage breast cancer based on RCTs from the 1970s and 1980s. However, the treatment of breast cancer has evolved and recent observational studies suggest a survival advantage for breast-conserving surgery with adjuvant radiotherapy. A systematic review and meta-analysis was undertaken to summarize the contemporary evidence regarding survival after breast-conserving surgery with adjuvant radiotherapy versus mastectomy for women with early-stage breast cancer. A systematic search of MEDLINE, the Cochrane Central Register of Controlled Trials (CENTRAL), and Embase that identified studies published between 1 January 2000 and 18 December 2023 comparing overall survival after breast-conserving surgery with adjuvant radiotherapy versus mastectomy for patients with unilateral stage 1-3 breast cancer was undertaken. The main exclusion criteria were studies evaluating neoadjuvant chemotherapy, rare breast cancer subtypes, and specific breast cancer populations. The ROBINS-I tool was used to assess risk of bias, with the overall certainty of evidence assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) tool. Studies without critical risk of bias were included in a quantitative meta-analysis. From 11 750 abstracts, 108 eligible articles were identified, with one article including two studies; 29 studies were excluded from the meta-analysis due to an overall critical risk of bias, 42 studies were excluded due to overlapping study populations, and three studies were excluded due to reporting incompatible results. A total of 35 observational studies reported survival outcomes for 909 077 patients (362 390 patients undergoing mastectomy and 546 687 patients undergoing breast-conserving surgery with adjuvant radiotherapy). The pooled HR was 0.72 (95% c.i. 0.68 to 0.75, P < 0.001), demonstrating improved overall survival for patients undergoing breast-conserving surgery with adjuvant radiotherapy. The overall certainty of the evidence was very low. This meta-analysis provides evidence suggesting a survival advantage for women undergoing breast-conserving surgery with adjuvant radiotherapy for early-stage breast cancer compared with mastectomy. Although these results should be interpreted with caution, they should be shared with patients to support informed surgical decision-making.

Immediate Breast Reconstruction With Latissimus Dorsi Myocutaneous Flap and Silicone Implant Followed by Adjuvant Radiotherapy for Breast Cancer.

About 30% to 50% of women with breast cancer undergo mastectomy, and approximately 50% of them will receive adjuvant radiotherapy (ART). This study evaluates the medium- and long-term impact of ART after immediate breast reconstruction (IBR) with latissimus dorsi myocutaneous (LDM) flap and silicone implants. Clinical, surgical, and oncological data were retrospectively collected and analyzed based on the medical records of 176 patients who had undergone IBR with LDM flap and silicone implants. The data showed that 7.4% of patients had a history of previous radiotherapy, 56.3% received ART, 31.8% developed capsular contracture with a mean follow-up of 58.1 months, and 14.2% of surgeries were categorized as procedures with a prolonged operating time, lasting above 1 SD of the observed mean. Those who experienced prolonged operating time (odds ratio, 4.72; 95% confidence interval, 1.72-12.93; P = 0.003) and those who received ART (odds ratio, 7.38; 95% confidence interval, 3.18-17.10; P < 0.001) were more likely to develop capsular contracture. Thirty-two patients (18%) underwent capsulectomy with implant replacement, and 7 patients (4%) had the implant removed. The mean time between IBR and reoperation was 29.1 months. Patients who received ART were 2.84 times more likely to experience reconstruction failure or undergo implant-related reoperation (P = 0.002). The results indicated that IBR with LDM flap and silicone implant followed by ART is a safe procedure, resulting in low rates of reconstruction failure. However, ART increased the likelihood of capsular contracture development and implant-related reoperation, having a negative effect on reconstructed breasts.

Abstract PO4-27-11: Fat grafting is oncologically safe during implant-based breast reconstruction and mastectomy after radiotherapy for breast cancer or Hodgkin Lymphoma: results of a multicentric study

Abstract Background. Fat grafting during or after mastectomy could promote the regeneration of irradiated tissues, thus improving tissue softness, increasing patient comfort and ameliorating quality of life. However, there are no conclusive data about the oncological safety of fat grafting, especially in terms of risk of tumor recurrences. The most appropriate timing of adipose tissue transplant is also debated, especially in patients with locoregional breast cancer (BC) recurrence undergoing salvage mastectomy and implant-based breast reconstruction after breast conserving surgery and radiotherapy. Methods. We conducted a prospective, multicentric Italian study to investigate the oncological safety of fat grafting between June 2007 and March 2022. One hundred sixty-three patients who had previously received radiotherapy, either as adjuvant treatment after breast conservative surgery (N=154), or as a treatment of Hodgkin Lymphoma (N=9), underwent mastectomy (simple mastectomy, NAC-sparing and skin-sparing mastectomy) and implant-based, two-stage breast reconstruction. Inclusion criteria were: age between 25 and 75 years, absence of concomitant malignancies, grade 2 or 3 of Breast post Radiotherapy Reconstruction with ExpAnder Score Test (B.R.R.E.A.S.T. score) (Tab 1). Patient BMI, hypertension, smoking history, diabetes and having received neoadjuvant chemotherapy were not considered as exclusion criteria. Contextual mastectomy and expander positioning were performed during first stage (stage I), while substitution of the expander with definitive implant occurred during second stage (stage II). Fat grafting could be performed during stage I, between stage I and II surgery, or during stage II. Results. One hundred sixty-nine mastectomy procedures (six bilateral) and first-stage implant-based reconstructions with expander were performed either as prophylactic surgery (N=23) or for the treatment of primary or recurrent BC (N=146). Thirty-four patients had ductal carcinoma in situ, whereas 112 patients had invasive disease, including: 17 patients with Luminal A BC, 67 patients with Luminal B HER2-negative BC, 3 patients with Luminal B HER-2 positive BC, 7 patients with HER-2 positive BC and 18 patients had triple-negative BC. One hundred thirty-six (80.5%) patients received at least one fat grafting. Eighty-six patients (52.8%) have received second-stage definitive implant. With a median time of observation of 25.1 months, we observed four locoregional cancer recurrences (2.4%), one of which in axillary lymph nodes. All tumor recurrences occurred in patients who had received fat grafting. Eight patients (4.9%) developed distant metastases (liver, lung, lymph nodes, and bone metastases); of these, four patients (50%) had received fat grafting. No death events occurred. Conclusion. Fat grafting after radiotherapy of the breast is associated with a low incidence of locoregional tumor recurrences and distant metastases. Although our findings need to be confirmed in larger, multicentric clinical studies, fat grafting is a safe and useful technique that can be proposed for breast reconstruction after irradiation. Table. Breast post Radiotherapy Reconstruction with ExpAnder Score Test, B.R.R.E.A.S.T score. Based on our experience, we thought to include two tissue characteristics (Pinch test ≥ 0.5 cm and presence/absence of skin teleangectasia or severe dyscromia) in a pre-operative, clinically useful, and ready-to-use score to assess soft tissue adequacy as recommended by NCCN guidelines, that we called Breast post Radiotherapy Reconstruction with ExpAnder Score Test (B.R.R.E.A.S.T. score). In our study, two-stage implant-based breast reconstruction and adipose tissue transplant with regenerative intent were performed in patients with Pinch test ≥ 0.5 cm but moderate skin teleangectasia or dyscromia (B.R.R.E.A.S.T. score 2) and in patients with Pinch test ≥ 0.5 cm and absence of skin teleangectasia or severe dyscromia (B.R.R.E.A.S.T. score 3). Patients with skin teleangectasia or dyscromia and Pinch test &amp;lt; 0.5 cm (B.R.R.E.A.S.T. score 1) were not enrolled in our study as they did not undergo alloplastic breast reconstruction but they underwent autologous reconstruction (data not shown). Citation Format: Chiara Listorti, Claudio Vernieri, Francesco Barretta, Chiara Osio, Ilaria Maugeri, Federica Pilotta, Cristina Ferraris, Massimiliano Gennaro, Gabriele Martelli, Marco Visaggio, Giulia Valeria Bianchi, Serena Di Cosimo, Gianfranco Scaperrotta, Maria Carmen De Santis, Daniela Tognali, Antonino Romeo, Matteo Mingozzi, Francesco Marongiu, Annalisa Curcio, Secondo Folli. Fat grafting is oncologically safe during implant-based breast reconstruction and mastectomy after radiotherapy for breast cancer or Hodgkin Lymphoma: results of a multicentric study [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 PO4-27-11.

Abstract ED11-03: Approaches to radiation therapy for inflammatory breast cancer

Abstract Inflammatory breasst cancer ((BC) is an uncommon and highly agressive form of breast cancer, with a predilection for both distant metastases and local regional recurrence. In this talk we will review challenges in radiation therapy planning and execution unique to IBC. These include staging studies and photographs to define the full extent of disease prior to systemic therapy, as well as current thoughts on dose and fractionation. We will also discuss pros and cons of local therapy in patients with metastatic disease, as well as ongoing research studying ways to optimize local regional control with concurrent systemic therapy and radiation. Citation Format: J. Bellon. Approaches to radiation therapy for inflammatory 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 ED11-03.

Abstract PO5-22-05: ULTRA-HYPOFRACTIONATED ADJUVANT RADIATION THERAPY FOR BREAST CANCER (UK FAST FORWARD TRIAL): A REAL LIFE SCENARIO ANALYSIS IN A DEVELOPING COUNTRY

Abstract Introduction: Selected patients showed non-inferior outcomes after conservative surgery for early breast cancer in the FAST-Forward UK (26Gy in 5 fractions) when compared to standard to date treatment. This study triggered an important change in radiation therapy routines across the world. We aimed to establish a pattern of treatment related events at a third-world country cancer center. Methods: We retrospectively analyzed all patients treated with 26Gy in 5 fractions (1 week) from January 2020 to June 2023. All data was exported and analyzed for demographics. A clinical profile was traced, dosimetric parameters and side effects assessed based on individual inquiries to each patient, per and post treatment. A strict medical record was kept in order to understand patterns of side effects and results. Results: 101 individuals were identified. Mean age was 64 years, 48 (47%) patients experienced radiation dermatitis of any grade, 33 (32%) grade 1, 9 (8%) grade 2, 6 grade 3 or 4 (5%). Patients older than 60 years showed to be a significant factor for dermatitis development (34 over a total of 48 - 70%) and 8 (53%) over 15 had grade 2 or higher dermatitis. 27 (26%) developed radiation dermatitis during sessions. 21 (20%) took 7 or less days to heal; 27 (26%) had a recovery longer than one week at an average age of 65 years - being the majority of dermatitis grade 1. Reported toxicities were sharp pain 31 (30%), burning pain 24 (23%), edema 17 (16%) and pruritus 5 (4%). At the time of this study was completed, 3 reported deaths (2%) were reported - with a 97% rate of survival. Conclusions: The fast forward trial regimen has 3 years since its publication. Our study shows that in a selected group of breast cancer patients, this novel model has shown to be a safe alternative for adjuvant radiation therapy following breast conservative surgery, results corroborating with published data. To the best of our knowledge, this is the largest single center group analyzed and published. Citation Format: Renne Bart, Daniel Przybysz, Ramon Ferrari, Leonardo Franco, Carlos Almeida, Paulo Canary. ULTRA-HYPOFRACTIONATED ADJUVANT RADIATION THERAPY FOR BREAST CANCER (UK FAST FORWARD TRIAL): A REAL LIFE SCENARIO ANALYSIS IN A DEVELOPING COUNTRY [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 PO5-22-05.

Abstract PO4-22-06: Outcomes following Stereotactic Radiotherapy in Oligometastatic Breast Cancer: a single centre retrospective review

Abstract Introduction: Stereotactic radiotherapy (SABR) is an increasingly used treatment for oligometastatic disease with evidence of survival benefit shown in the SABR-COMET trial. However, the benefit in oligometastatic breast cancer has been brought into question following initial results from the NRG-BR002 trial. Methods: A retrospective review of all patients with primary breast cancer treated with stereotactic radiotherapy for oligometastases at our institution was carried out. A total of 31 patients received treatment to 36 lesions between August 2015 and December 2022. Results: Neither median overall survival nor progression free survival were reached after median follow up time of 21.5 months. Hormone receptor status as follows: ER+, HER2- (n=25), ER+, HER2+ (n=4,), TNBC (n=2). The majority of lesions treated were bony metastases (92%, of which 17 vertebral and 11 pelvic lesions). The majority had oligometastatic disease at time of SABR (67%), with 33% treated for oligoprogression. Most patients were on systemic anti-cancer therapy (SACT) at the time of SABR, or had a planned start of SACT shortly following treatment. Breakdown of systemic therapy as follows: Endocrine therapy (ET) alone 9 patients (29%), CDK4/6 inhibitor plus ET 13 patients (42%), chemotherapy 3 patients (10%), antibody drug conjugate 2 (6%), anti-HER2 therapy + ET 2 patients (6%), none 2 patients (6%). All patients also received bone-targeted agents (zoledronic acid or denosumab). Local control was achieved in 33 lesions (92%), all of which were bony lesions. Local control was maintained in both patients who were not on SACT: one patient with ER+ HER2- disease developed distant progression after 27 months, the other with TNBC remains disease free after 13 months. Loss of local control was observed in all non-bony sites (lung, IMC node, peri-ureteric soft tissue mass) at a median interval of 10 months (range 7-43 months). 14 patients subsequently developed distant disease progression at median interval of 15 months (range 0-43 months). 12 month progression free survival was 77%. 13 patients received further SACT at median interval of 16 months. Conclusions: SABR for bony metastases from breast cancer has excellent local control rates in combination with systemic treatment but may also give patients significant time off treatment. Questions remain regarding the ideal sequencing and combination of SABR and SACT, particularly in hormone receptor positive patients where there are a number of lines of effective SACT. Citation Format: Sophie Lynch, Sugeeta Sukumar, Elinor Sawyer, Daniel Smith, Christy Goldsmith. Outcomes following Stereotactic Radiotherapy in Oligometastatic Breast Cancer: a single centre retrospective review [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 PO4-22-06.

Abstract PO3-26-07: Epigenetic approaches to deliver a targeted radiotherapy for triple negative breast cancer

Abstract The sodium iodide symporter (NIS, encoded by SLC5A5) is the sole transporter of iodide, and successfully exploited in thyroid cancer to uptake radioiodide (RAI). NIS is essentially undetected in normal mammary epithelial cells but elevated during lactation, and has a heterogeneous expression profile in breast cancer (BRCA), as evidenced by TCGA cohort and also in a ~120 sample TMA we have profiled. Furthermore, pre-clinical studies support an epigenetic mechanisms that involves Retinoic Acid Receptor alpha (RARa) to regulate SLC5A5 expression. Therefore, we have applied an orthogonal approach to both elucidate and target mechanisms that control NIS expression and function to deliver a therapeutic strategy that targets this transporter as a novel radiotherapy in BRCA. To understand the epigenetic control of expression we segregated samples in the TCGA-BRCA cohort into lower and upper quartile SLC5A5 expression and identified ~600 significant differentially expressed of genes (DEG). Interestingly, restricting analyses to either triple negative (TN) or tumors from African American (AA) patients doubled the number of DEGs. These DEGs were significantly associated with several transcription factors including LHX3, a pituitary development transcription factor regulated by thyroid signaling. The most significantly altered ~70 DEGs significantly clustered tumors by genomic ancestry and ERBB2/HER2 IHC status. The DEGs also supported a footprint of RARa signaling include PRAME, a known RARa co-repressor associated with histone deacetylase, and reflects the finding that NIS expression is highly responsive to SAHA treatment. To investigate if PRAME expression suppresses RARa regulation of SLC5A5 we have established a panel of BRCA cell lines (AU565, SKB3 SUM52 and MDA-MB-231) stably transfected with either CRISPR-VP64 (activator) and CRISPR-KRAB (repressor) to modulate PRAME and measure the epigenomic impact, the expression of SLC5A5 and the ability to transport RAI. In parallel we have applied a drug screen approach that targets non-canonical approaches to govern NIS expression, for example by targeting valosin-containing protein (VCP) that induces NIS proteolysis. In the first instance we have developed a therapeutic strategy to target NIS by inhibiting VCP. Specifically, we are screening a range of VCP inhibitors in combination with the HDAC inhibitor SAHA or the transcriptional potentiator, disulfiram metabolite Cu(DDC)2 in BRCA cell lines by testing the ability to augment RAI uptake. Remarkably, in MDA MB 231 cells, Cu(DDC)2 combined with the VCP inhibitor CB5339, resulted in a significant additive increase in RAI uptake and a prominent decrease in cell proliferation and survival. These studies combined with future murine and PDX testing of CRISPR-edited tumors and drug exposures will develop a comprehensive analyses of the mechanisms that control SLC5A5 expression across breast cancer cell types, how this can be most effectively targeted to restore NIS expression, and exploited to promote RAI as a novel targeted BRCA radiotherapy. Citation Format: Katie Brookes, Martin Read, Sajad Wani, Sissy Jhiang, Daniel Stover, Mathew Ringel, Christopher McCabe, Moray Campbell. Epigenetic approaches to deliver a targeted radiotherapy for triple negative 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 PO3-26-07.

Abstract PO1-22-04: Cosmetic results of the breast in patients treated with Five Fraction Accelerated Partial Breast Irradiation for early stage breast cancer: retrospective review comparing Daily versus Every Other Day Treatment

Abstract Introduction: Breast cosmesis results using Accelerated Partial Breast Irradiation (APBI) with IMRT external beam in 5 fractions (6Gy x 5 fractions) has been reported as good to excellent in the literature. This retrospective review compares breast cosmesis in patients treated with Daily versus Every Other Day APBI in the community practice setting. Methods: The patient electronic medical records (EMR) were used to identify APBI patients treated at the community cancer center with the 6Gy x 5 fraction regimen. Harvard breast cosmesis four point scale results (poor, fair, good, excellent results) were extracted for each treated APBI patient from clinical notes in the EMR to rate breast cosmesis. For many patients in this review, provider reporting of cosmesis in the EMR overlapped good and excellent categories and so a “good to excellent” score was assigned. Therefore, a three point scale was utilized in statistical analysis (poor-1, fair-2, good to excellent-3). Results: There were 62 patients treated with APBI at a single institution with greater than 6 months follow up (18 patients treated daily and 44 patients treated every other day). Median follow up was 12 months (range 6- 32 months). Of all patients treated there were 0 with poor cosmesis, 3 with fair (1 every other day treatment, 2 every day treatment), 59 with good to excellent cosmesis. Univariate logistical regression analysis revealed no significant difference between daily and every other day treatment (p=0.457) Conclusion: With careful patient selection, quality planning and treatment delivery, good to excellent cosmesis is achievable in the great majority of patients undergoing breast APBI (6Gy x 5 fractions) using IMRT in the community radiation oncology clinic with either daily or every other day treatment. More study is needed, but in this review cosmetic differences seem to be minimal between daily and every other day treatment schedules. Citation Format: Alex Goss, Ellaine Haroz, Anna Voltura, Jennifer McGrath, Olivia Sloan, Matthew Jackson, Savvas Morris, Bryan Goss. Cosmetic results of the breast in patients treated with Five Fraction Accelerated Partial Breast Irradiation for early stage breast cancer: retrospective review comparing Daily versus Every Other Day Treatment [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 PO1-22-04.

Abstract PO5-18-12: Can we cure de novo oligometastatic stage IV HER2+ breast cancer with multimodality therapy? (CHLOE)

Abstract Background: The current standard of care is to treat all patients with metastatic breast cancer with palliative intent, regardless of extent of disease. However, in real world practice patients with oligometastatic disease are sometimes treated with surgery and/or radiation/ablation in combination with systemic therapy to render them as having no evidence of disease. Previous randomized clinical trials have not shown a benefit to adding surgery or radiation in metastatic breast cancer, however, these trials had a small number of HER2+ patients. HER2+ patients are uniquely responsive to combination of chemotherapy and targeted HER2 therapy and therefore may have different outcomes with a multimodality approach. The goal of this project is to use a novel, user friendly, on-line clinical study platform that registers patients and enables follow-up data collection to test the hypothesis that de novo stage IV oligometastatic HER2+ patients treated with multimodality therapy may result in improved long-term distant metastasis free survival and overall survival. Trial design: This is a prospective, nationwide registry study that will enroll newly diagnosed (de novo) oligometastatic (operationally defined by local tumor boards as disease where all metastatic lesions can be ablated) HER2+ breast cancer. A secure online portal has been created by the Yale IT team in accordance with HIPPA and cybersecurity guidelines. Data will be directly entered into the online portal by participating investigators and information regarding what treatment the patient received, if they completed treatment, and survival data will be collected. All treatment decisions will be at the discretion of the treating provider. Eligibility criteria: Patients with de novo oligometastatic HER2+ breast cancer in whom local treatment of all metastatic sites by either surgery, radiation, or ablative techniques is feasible as determined by multidisciplinary discussion or local tumor board. Specific aims: Primary: To estimate the 3 year distant metastasis free survival in patients with de novo oligometastatic HER2+ breast cancer treated with a multi-modality treatment plan. Secondary: To estimate 3 year overall survival and to monitor QOL. Statistical methods: The major analysis will occur after at least 3 years following the last subject’s enrollment in a cohort, to ensure that the objective of distant metastasis free survival at 3 years will be analyzed. It will include: tabulation of all cases entered, number and location of metastases, if treatment plan was implemented, compliance rate of treatment delivery, observed results with respect to the primary endpoint. Kaplan-Meier estimates will be presented for the analysis of survival endpoints together with a summary of associated statistics (median survival time if reached, landmark survival rate estimates and estimates for every 6 months thereafter if applicable), including the corresponding two-sided 95% confidence intervals. The 95% exact Clopper Pearson confidence intervals will be presented for binary endpoints. Paired t-test or Wilcoxon signed rank test will be used to assess the difference of continuous variables measured at different time points. The secondary clinical outcome is overall survival at 3 years, defined as the percentage of patients without an event at the 3-year follow-up time point measured from the study registration date. An event is considered death from any cause. OS time will be measured from the date of randomization to the date of first OS failure or last follow-up. OS will be estimated by the Kaplan-Meier method with OS failure defined as: death from any cause. Present accrual and target accrual: 4/42 patients Contact information for people with a specific interest in the trial: Mariya.Rozenblit@yale.edu https://chloe.yalepathaws.org Citation Format: Mariya Rozenblit, Nathalie Wiesendanger, Kelly Shanahan, Christine Hodgdon, Peter Gershkovich, Mehra Golshan, Meena Moran, Maryam Lustberg, Lajos Pusztai. Can we cure de novo oligometastatic stage IV HER2+ breast cancer with multimodality therapy? (CHLOE) [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 PO5-18-12.

Abstract ED05-02: When less is more: Patient-friendly radiation courses with WBI and PBI

Abstract Over the past few decades, remarkable progress has been made in understanding the biology and pathology of breast cancer. A personalized conservative approach has been currently adopted addressing the patient's individual risk of relapse. After postoperative whole breast irradiation for early-stage breast cancer, a rate of recurrences outside the initial tumour bed lower than 4% at 5 years was observed. Thus, the highest benefits of breast irradiation seem to result from the dose delivered to the tissue neighbouring the tumour bed. Nonetheless, reducing treatment morbidity while maintaining radiation therapy's ability to decrease local recurrences is an important challenge in treating patients with radiation therapy. In this regard, strategies such as partial-breast irradiation and whole breast hypofractionation have been developed to reduce toxicity without compromising oncologic outcomes. According to the national and international published guidelines, clinical oncologists can refer to specific dose/fractionation schedules and eligible criteria. However, there are still some areas of open questions. Breast cancer represents a multidisciplinary paradigm; it should be considered a heterogeneous disease where a "one-treatment-fits-all" approach cannot be considered an appropriate option. A wide overview on the main partial and whole breast irradiation advantages, risks, timings, techniques, and available recommendations is presented, providing practical findings to support clinical decision-making, exploring future perspectives, towards a balance for optimisation of breast cancer. Citation Format: I. Meattini. When less is more: Patient-friendly radiation courses with WBI and PBI [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 ED05-02.

Abstract PO3-10-09: The allocation of US $2.6 billion in global funding for breast cancer research between 2016 – 2020: are we investing wisely for breast cancer patients?

Abstract Background: Breast cancer is a global health challenge and the highest incident cancer globally, with over 2 million new cases and 685,000 deaths in 2020, making it the highest incident cancer globally. Furthermore, it is the most prevalent cancer, resulting in the loss of more disability-adjusted life years than any other malignancy. Research is thus crucial to improving outcomes and reducing suffering for breast cancer patients worldwide. This study aimed to analyse global patterns of funding for breast cancer research. Methods: We have previously created a comprehensive database of awards for human cancer research in this period using publicly available data on research funding awards. From this database we extracted all awards relating to breast cancer research, and categorised these by cancer type, cross-cutting research theme and phase of research. Findings: We identified 7051 awards with a total investment of $2.6 billion in 2016-2020, representing 11.2% of all global public and philanthropic cancer research funding during this period. Breast cancer research funding fell year on year, from $773.4 million in 2016 to $243.8 million in 2020. The majority of the investment was in pre-clinical research ($1.9 billion, 73.9%), with clinical trials ($276 million, 10.7%) and public health ($269.2 million, 10.5%) receiving roughly equivalent amounts of funding. The USA accounted for 66.9% of all global breast cancer research investment, with China ($110.4 million, 4.3%) and the UK ($96.6 million, 3.8%) the next largest funders. By research theme, cancer biology research received most funding ($926.2 million, 37.5% of investment), with drug treatment the next best funded research area ($600.5 million, 23.4%), and diagnosis, screening and monitoring third ($396 million, 15.4%). Surgery ($65.2 million, 2.5%) and radiotherapy ($35.3 million, 1.4%) accounted for only a small proportion of research investment. There was minimal investment into breast cancer as a global health issue ($8.1 million, 0.3%). Research into metastatic disease received a greater proportion of investment in breast cancer than in the overall cancer portfolio (23.2% in breast cancer, $597.4 million, compared with 11.7% across all cancers). Conclusions: Breast cancer public and philanthropic research funding is largely invested in pre-clinical research in high-income countries, with the main areas of investment being cancer biology research and drug treatment. The direct benefit to patients from such research is likely to be low and only apparent after a substantial time lag (if at all). Despite their pivotal role in the treatment of the majority of breast cancer patients, surgery and radiotherapy research received a tiny proportion of the overall research investment. Furthermore, relatively little investment is directed towards cancer prevention and early detection, despite their acknowledged key role in cancer control globally. Finally, more equitable research funding is required to align with the global burden of breast cancer, with increased funding for low- and middle-income countries, which account for an increasing proportion of this burden. These data should be considered by funders and policymakers in the allocation of finite resources, which must be invested wisely. Citation Format: Stuart McIntosh, Ellen Copson, Ramsey Cutress, Michael Head. The allocation of US $2.6 billion in global funding for breast cancer research between 2016 – 2020: are we investing wisely for breast cancer patients? [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 PO3-10-09.

Abstract PO5-18-05: Assessment of the Potential of Photon mini-GRID Therapy for Pre-operative Partial Breast Cancer Treatment

Abstract Purpose We propose a new spatially fractionated radiation therapy (SFRT) technique, called mini-GRID therapy, to reduce normal tissue toxicities in pre-operative partial breast cancer radiotherapy. Mini-GRID therapy, an optimized implementation of GRID therapy, utilizes very narrow beams (widths ~ 1-2 mm) which significantly increase normal tissue tolerances. The concept, proposed by our team in 2017 [1], has been successfully implemented at Hospital de Santiago de Compostela (Spain) showing excellent results in terms of brain toxicity reduction [2]. Profiting from this remarkable increase in tolerance, this study aims to evaluate the feasibility and efficacy of photon mini-GRID therapy for pre-operative partial breast cancer treatment. Methods Ten unbiased clinical cases were selected for the study, comparing photon mini-GRID therapy with conventional broad beam radiotherapy. Monte Carlo simulations (TOPAS v.3.6) were performed based on the mini-GRID therapy implementation (megavoltage X-rays, Varian flattening-filter-free LINAC) realized at the University Hospital in Santiago de Compostela. A mean dose of 24 Gy was delivered in the PTV using three photon mini-GRID arrays with mini beams of approximately 1.8x1.8 mm² at the isocenter. The study aimed to achieve better tumor coverage than conventional pre-operative radiotherapy while ensuring comparable skin toxicity. Valley doses, determining tissue-sparing effects, were compared against organs-at-risk (OARs) tolerance limits. Results The mini-GRID therapy treatments ensured partial tumor coverage and met the dose tolerance limits for all the considered OARs, the most challenging of all being the skin [3]. Peak-to-valley dose ratio (PVDR) in the skin was higher than 3.5 for all the considered patients. Compared to standard radiotherapy (SRT) plans, mini-GRID therapy significantly reduced mean doses to the lungs, heart, and chest wall in the studied cases. Conclusion In this proof-of-concept study, we evaluated photon mini-GRID therapy with megavoltage X-rays as an alternative treatment approach for pre-operative partial breast cancer irradiation, demonstrating its feasibility and straightforward implementation. Because of its high skin and normal tissue-sparing capacities, photon mini-GRID therapy has great potential to improve pre-operative treatment outcomes. Complementary studies and clinical validation are needed to fully establish the optimal protocols and assess long-term effects, but the results encourage the integration of photon mini-GRID therapy as a promising modality for breast cancer therapy.

Interpretable deep learning insights: Unveiling the role of 1 Gy volume on lymphopenia after radiotherapy in breast cancer

BackgroundLymphopenia is known for its significance on poor survivals in breast cancer (BC) patients. Considering full dosimetric data, this study aimed to develop and validate predictive models for lymphopenia after radiotherapy (RT) in BC. Material and methodsBC patients treated with adjuvant RT were eligible in this multicenter study. The study endpoint was lympopenia, defined as the reduction in absolute lymphocytes and graded lymphopenia after RT. The dose-volume histogram (DVH) data of related critical structures and clinical factors were taken into account for the development of dense neural network (DNN) predictive models. The developed DNN models were validated using external patient cohorts. ResultsTotally 918 consecutive patients with invasive BC enrolled. The training, testing, and external validating datasets consisted of 589, 203, and 126 patients, respectively. Treatment volumes at nearly all dose levels of the DVH were significant predictors for lymphopenia following RT, including volumes at very low-dose 1 Gy (V1) of organs at risk (OARs) including lung, heart and body, especially ipsilateral-lung V1. A final DNN model, combining full DVH dosimetric parameters of OARs and three key clinical factors, achieved a predictive accuracy of 75 % or higher. ConclusionThis study demonstrated and externally validated the significance of full dosimetric data, particularly the volume of low dose at as low as 1 Gy of critical structures on lymphopenia after radiation in BC patients. The significance of V1 deserves special attention, as modern VMAT RT technology often has a relatively high value of this parameter. Further study warranted for RT plan optimization.