Radiotherapy For Breast Cancer Research Articles

Evaluation of the accuracy of heart dose prediction by machine learning for selecting patients not requiring deep inspiration breath‑hold radiotherapy after breast cancer surgery.

Increased heart dose during postoperative radiotherapy (RT) for left-sided breast cancer (BC) can cause cardiac injury, which can decrease patient survival. The deep inspiration breath-hold technique (DIBH) is becoming increasingly common for reducing the mean heart dose (MHD) in patients with left-sided BC. However, treatment planning and DIBH for RT are laborious, time-consuming and costly for patients and RT staff. In addition, the proportion of patients with left BC with low MHD is considerably higher among Asian women, mainly due to their smaller breast volume compared with that in Western countries. The present study aimed to determine the optimal machine learning (ML) model for predicting the MHD after RT to pre-select patients with low MHD who will not require DIBH prior to RT planning. In total, 562 patients with BC who received postoperative RT were randomly divided into the trainval (n=449) and external (n=113) test datasets for ML using Python (version 3.8). Imbalanced data were corrected using synthetic minority oversampling with Gaussian noise. Specifically, right-left, tumor site, chest wall thickness, irradiation method, body mass index and separation were the six explanatory variables used for ML, with four supervised ML algorithms used. Using the optimal value of hyperparameter tuning with root mean squared error (RMSE) as an indicator for the internal test data, the model yielding the best F2 score evaluation was selected for final validation using the external test data. The predictive ability of MHD for true MHD after RT was the highest among all algorithms for the deep neural network, with a RMSE of 77.4, F2 score of 0.80 and area under the curve-receiver operating characteristic of 0.88, for a cut-off value of 300 cGy. The present study suggested that ML can be used to pre-select female Asian patients with low MHD who do not require DIBH for the postoperative RT of BC.

Accelerated Partial Breast Irradiation for HER2-Positive Early-Stage Breast Cancer

HER2-positive (HER2+) breast cancer historically exhibited the most adverse local outcomes and, consequently, has had limited representation among trials of partial breast irradiation (PBI). We hypothesized that with contemporary HER2-targeted agents, patients may now exhibit excellent disease control outcomes after adjuvant PBI. Using a prospectively maintained institutional database, we identified patients with HER2+ breast cancer treated with breast conserving surgery (BCS) and PBI from 2000 to 2022. Salient clinicopathologic and treatment parameters were collected. All patients received external beam PBI to 40 Gy in 10 daily fractions. Cumulative incidence functions were calculated to estimate the incidence of local recurrence (LR) with the competing risk of death. We identified 1248 patients who underwent PBI at our institution, of whom the study cohort comprised 52 (4%) with HER2+ breast cancer (median age, 64 years; range, 44-87). Nearly all had T1 tumors (98%; median size, 12 mm [range, 1-21 mm]). Most had estrogen receptor positive disease (88%), and all patients had negative surgical margins. Nearly all underwent sentinel node biopsy (94%), with the remainder undergoing no surgical axillary evaluation. Forty-two (81%) received chemotherapy; 40 (77%), hormone therapy; and 42 (81%), HER2-directed therapy, most commonly trastuzumab. At 143.8 person-years of follow-up (range, 7-226 months for each patient), we observed 2 LR events at 14 and 26 months, respectively, yielding a 2-year LR rate of 3.8%. No regional or distant recurrences were observed, nor were any breast-specific mortality events. Two deaths were observed, both without evidence of disease. Among a cohort of patients with HER2+ early-stage breast cancer managed with BCS and PBI, we observed a 2-year LR rate of 3.8%, with no regional or distant recurrences and excellent overall survival. These findings require confirmation with longer follow-up among larger cohorts but appear consistent with the excellent results of contemporary randomized trials of PBI unselected for HER2 status.

Myocutaneous flap reconstruction after radiation therapy for breast cancer.

Breast cancer poses a significant physical change to the patient's body, and treatment can last months to years. This article describes the latissimus dorsi myocutaneous flap, a surgical alternative when first-line reconstructive surgical options have failed because of concurrent treatments, specifically, radiation therapy.

329P Pulmonary function and lung fibrosis up to 12 years after breast cancer radiotherapy

329P Pulmonary function and lung fibrosis up to 12 years after breast cancer radiotherapy

440P Palliative radiotherapy in metastatic breast cancer: Does molecular subtype predict patient response to radiotherapy?

440P Palliative radiotherapy in metastatic breast cancer: Does molecular subtype predict patient response to radiotherapy?

Breast Cancer: An Overview of Current Therapeutic Strategies, Challenge, and Perspectives.

Breast cancer is the most commonly diagnosed cancer and the leading cause of death among female patients, which seriously threatens the health of women in the whole world. The treatments of breast cancer require the cooperation of a multidisciplinary setting and taking tumor load and molecular makers into account. For early breast cancer, breast-conserving surgery with radiotherapy or mastectomy alone remains the standard management, and the administration of adjuvant systemic therapy is decided by the status of lymph nodes, hormone receptors, and human epidermal growth factor receptor-2. For metastatic breast cancer, the goal of treatments is to prolong survival and maintain quality of life. This review will present the current advances and controversies of surgery, chemotherapy, radiotherapy, endocrine therapy, targeted therapy, immunotherapy, gene therapy, and other innovative treatment strategies in early-stage and metastatic breast cancer.

Association Between Symptom Burden and Early Lymphatic Abnormalities After Regional Nodal Irradiation for Breast Cancer

Background: Dermal backflow visualized on near-infrared fluorescence lymphatic imaging (NIRFLI) signals preclinical lymphedema that precedes the development of volumetrically-defined lymphedema. We sought to evaluate whether dermal backflow correlates with patient-reported lymphedema outcomes (PRLO) surveys in breast cancer patients treated with regional nodal irradiation (RNI). Methods and Materials: Breast cancer patients planned for axillary dissection and RNI prospectively underwent perometry, NIRFLI, and PRLOs (the Lymphedema Symptom Intensity and Distress Survey (LSIDS) and QuickDash) at baseline, after surgery, and at 6, 12, and 18 months following radiation. Clinical lymphedema was defined as an arm volume increase ≥ 5% over baseline. Trends over time were assessed using ANOVA testing. The association between survey responses and both dermal backflow and lymphedema was assessed using a linear mixed-effects model. Results: Sixty participants completed at least two sets of measurements and surveys and were eligible for analysis. Fifty-four percent of patients had cT3-T4 disease, 53% cN3 disease, and 75% had a BMI >25. Dermal backflow and clinical lymphedema increased from 10% to 85% and from 0% to 40%, respectively, from baseline to 18mo. In the adjusted model, soft tissue sensation, neurologic sensation, and functional LSIDS subscale scores were associated with presence of dermal backflow (all p<0.05). Both dermal backflow and lymphedema were associated with Quickdash score (p<0.05). Conclusion: In this high-risk cohort, we found highly prevalent early signs of lymphedema, with increased symptom burden from baseline. Presence of dermal backflow correlated with PRLO measures, highlighting a potential NIRFLI use to identify patients for early intervention trials following RNI.

Practice Patterns and Disparities of Fractionation Schemes for Post-Mastectomy Comprehensive Nodal Irradiation

Hypofractionated (HF) radiotherapy is the established standard of care for whole breast irradiation and is being investigated for comprehensive nodal irradiation, but appropriate patient selection for the latter is currently undefined. This study aims to report national practice patterns and patient selection for HF comprehensive nodal irradiation compared to conventional fractionation (CF). The hypothesis is that the rate of HF for comprehensive nodal irradiation in breast cancer has been increasing over time and is more likely to be offered to disparate demographic populations. We queried the National Cancer Database and identified 128,693 patients who received comprehensive nodal irradiation between 2008-2016 in the United States. No patient who underwent lumpectomy received HF nodal irradiation; therefore, only post-mastectomy patients were included in this study. After the exclusion, 29,053 post-mastectomy patients with adjuvant comprehensive nodal irradiation remained. A multivariable binomial regression analysis between HF and CF patients was performed. Of the patients identified, 1,910 received HF (6.57%), and 27,143 received CF (93.43%) radiotherapy. All patients had locally advanced breast cancer treated with mastectomy, lymph node dissection, adjuvant radiation, and +/- chemotherapy. The median dose in the HF group was 4,256 cGy in 16 fractions, and in the CF group was 6,040 cGy in 33 fractions. HF rate grew from 3.56% in 2004-2007, 5.29% in 2008-2011, 7.42% in 2012-2013, and 12.05% in 2014-2016. HF was favored in older patients (median age 66 vs. 51, OR = 1.16, 95% Cl 1.11-1.22) and those who lived in suburban or rural regions compared to urban or metropolitan regions (OR = 9.48, 95% CI 1.17-76.9). However, there was no correlation when distance from treatment site was evaluated as a continuous variable. A "boost" dose was used in only 10.58% of HF patients compared to 54.6% of CF patients (OR = 0.17, 95% Cl 0.14-0.21). Chemotherapy was delivered in 36.91% of HF patients compared to 78.14% of CF patients (OR = 0.77, 95% Cl 0.59-0.99). There were no statistically significant correlates of either fractionation scheme for breast laterality, stage, grade, or receptor status. Notably, other than population density and age, demographic factors including race, Hispanic origin, insurance type, median income, and education level demonstrated no correlation with radiation fractionation scheme. HF for comprehensive nodal irradiation in breast cancer is still uncommon but growing in popularity. Currently, HF is more likely to be used in elderly patients and lower population density centers and less likely to be used in those determined to benefit from receipt of a boost or chemotherapy.

The Effect of Deep Inspiration Breath-Hold Technique on Right Coronary Artery, Heart, and Liver Doses in Right Breast Cancer Radiotherapy

The deep inspiration breath-hold (DIBH) approach has been thoroughly researched with the aim of reducing radiation exposures to normal tissues in breast cancer patients. Although heart and lung toxicity are widely addressed in many literature, radiation-associated liver toxicity and dose constraints for the right coronary artery (RCA) are not well studied in relation to breast radiotherapy. Additionally, very few studies have investigated the relationship between doses to cardiac substructures. This study aimed to determine the effect of the DIBH technique on the right coronary artery (RCA) region, cardiac substructures, and liver dose in right breast cancer irradiation. Between January 2022 and December 2022, thirty-five right breast cancer patients who previously received breast-surgery underwent computed tomography (CT) simulation with both free-breathing (FB) and DIBH techniques. Patients were contoured by a radiation oncologist on the scans using the Treatment Planning System. For cardiac substructures, reference atlas contours were used for accurate delineation and to reduce inter-observer variation. Each patient underwent two treatment plans for both the DIBH and FB datasets. The plan comprised the FB and DIBH techniques, and the doses to the cardiac substructures, ipsilateral lung, RCA region, and liver were compared using a two-tailed paired t-test. Radiotherapy was delivered with a Linac with the prescription dose of 50 Gy in 25 fractions. For both FB and DIBH irradiation groups, the mean radiation doses to the ipsilateral lung, heart, and RCA region in patients with FB and DIBH techniques were; 14.67 Gy, 2.33 Gy, 4.88 Gy and 12.05 Gy, 1.34 Gy and 3.29 Gy respectively. The mean radiation doses to the cardiac substructures; for the left ventricle, right ventricle, left atrium, and right atrium for the FB were 1.08 Gy, 1.79 Gy, 4.11 Gy, and for DIBH, 0.49 Gy, 1.49 Gy, 0.95 Gy, and 2.61 Gy, respectively. For the DIBH group, the liver maximum dose (p<0.01), right lung mean dose (p = 0.001), heart maximum dose (p = 0.009), RCA mean dose (p = 0.020), RCA maximum dose (p = 0.008), RCA V5 dose (p = 0.035), right atrium maximum dose (p = 0.009) and right ventricle mean dose (p = 0.040) were significantly lower than in patients treated in the non-gated group. DIBH resulted in considerable displacement of the liver away from the high-dose target region, such that the volume of liver in the high-dose region was reduced. Additionally, the use of the DIBH technique in right breast cancer irradiation effectively reduces the radiation doses to the cardiac substructures, such as the left ventricle, right ventricle, left atrium, right atrium, RCA region, and lungs. DIBH could lead to substantial sparing of these structures with the right breast cancer radiotherapy. Future prospective studies are required to determine whether improvements to dose-distribution will translate into improved toxicity outcomes.

Effect of Dose to the Heart and Cardiac Substructures on Cardiac Toxicity after Breast Cancer Radiation

Pre-existing cardiovascular disease, chemotherapy, and higher mean heart dose are known risk factors for cardiac toxicity after breast radiation therapy. However, the relationship between cardiac substructure radiation exposure and toxicity is not well understood. We hypothesized that mean heart dose is a surrogate for global cardiac radiation exposure but that more specific dosimetric thresholds for the heart and its substructures could be identified, which could be used to guide radiation planning for breast cancer patients in the future. In this cohort study, all breast cancer patients who received curative intent breast or chest wall radiotherapy at a single high-volume institution in 2014 and 2017 were included (n = 841). Baseline characteristics included hormone therapy, chemotherapy, menopausal status, diabetes, dyslipidemia, pre-existing cardiac toxicity, and age at diagnosis. Outcomes included any cardiac toxicity, arrhythmia, cardiomyopathy, ischemia, valvular, pericardial disease, and death. The heart and substructures, including left ventricle, right ventricle, left atrium, right atrium, aortic valve, pulmonic valve, mitral valve, tricuspid valve, and left anterior descending artery, were delineated on the simulation CT for each patient. Dosimetric variables, including mean dose, max dose, and V1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, 60, 65, and 70 Gy for the heart and substructures (in cc) were extracted. For each dosimetric variable, multivariable logistic regression was performed using baseline covariates in addition to the single dosimetric variable. Patients with missing data values were excluded. Results were combined and False Discovery Rate p-value correction was performed. Multiple cardiac substructure dosimetric variables were associated with increased risk of mortality on multivariable analysis (p < 0.05). For left atrium and right atrium, V2, 3, 4, and 5 Gy were all significant. For right ventricle, mean dose, V1, 2, 3, 4, 5, 10, 15, 20, 25, 30, and 35 Gy were significant. For mitral valve, mean dose, max dose, V3, 4, and 5 Gy were significant. For tricuspid valve, mean dose was significant. For aortic valve, max dose, mean dose, V4, and V5 Gy were significant. For the whole heart, V1, 2, 3, 4, 5, 10, 15, 20, 25, 30, and 35 Gy were significant. We have identified multiple dosimetric variables for the heart and its substructures which were associated with increased risk of mortality after breast cancer radiation. In fact, for certain structures, there were multiple exposure thresholds which showed increased risk of toxicity, highlighting the complex relationship between substructure dose and outcomes. Further study into these relationships will identify the most critical cardiac substructure constraints that could be used in radiation treatment planning.

Long Term Evaluation of Cardiac Events and Outcomes Following Breast Cancer Irradiation

Although whole heart dose has been associated with cardiac toxicity in patients receiving radiation therapy for breast cancer, data detailing the clinical significance of cardiac substructures, particularly the left anterior descending artery (LAD), are limited. We investigated whether dose to the LAD correlates with adverse cardiac events and death. We identified 190 female patients treated from 2002 to 2019 who received breast or chest wall irradiation, with or without regional nodal irradiation. Ninety-three patients were treated on their right side, 95 on their left, and two were bilateral. Medical records were queried in healthcare software to identify cardiac events after radiation therapy. Mean and maximum LAD and heart doses, as well as V15LAD, were calculated. Univariate and multivariate Cox regression analyses were performed to determine their association with cardiac toxicity as well as death. Cumulative incidence curves for death and cardiac toxicity were also calculated for the patient population. Median follow-up time was 68 months. Thirty patients experienced a cardiac event (15.7%), with three of these being grade 3 or higher. On univariate analyses, left side (hazard ratio 8, P<0.001), increased Mean LAD Dose per cGy (1.001, P = 0.01), Mean Heart Dose (1.16, P = 0.01), and anatomic stage (3.5, P = 0.003) were statistically significant predictors of death but not of adverse cardiac events. Statistically significant predictors of adverse cardiac events were the receipt of chemotherapy (2.68, p = 0.046) which remained significant even after adjusting for radiation parameters. There was no association with hormonal therapy use. Cumulative incidence curves predicted a 14.11% probability of a cardiac event 5 years after treatment and a 25.7% probability at 10 years after treatment. They also predicted a 9.43% probability of death at both 5- and 10-years post-treatment. On this long-term analysis, doses to the heart seemed to negatively impact survival, but did not have a clear association between cardiac events. In contrast, utilizing cytotoxic systemic therapy seemed have an association, even when adjusted for on multivariable models for cardiac events.

Largest Real-World Data of Regional Nodal Irradiation Using Ultra-Hypofractionated 5-Fraction Adjuvant Radiation Therapy for Breast Cancer from a Single Institute in India

Safety data for ultra-hypofractionated (UHFRT) 5-daily fractions of the supraclavicular fossa (SCF) radiation therapy (RT) have been reported only on 384 patients treated in trial setting in UK-FAST-Forward (n = 286) and HYPORT study (n = 98). Internal Mammary nodal (IMN) RT has been reported only in 6 patients from HYPORT study. We report acute and late toxicities in largest real world regional nodal irradiation (RNI) cohort of not only with 5-daily but also with 5-weekly once RT regimen. Of 1435 patients (1463 breasts) who received 5-fraction RT in an IEC approved registry and prospectively followed, we report 999 consecutive cases receiving RNI with a median age of 49 years (IQR:42-56years). During pandemic all patients were treated with 5-fr regimens only to limit hospital visits whereas prior to and subsequently only in patients with advanced age or with issues precluding daily 15-20 treatments. Of these, 431 (43.1%) had locally advanced BC, and 280 (28%) patients presented with ≥cN2 disease. Median cT and pT sizes were 4cm (IQR:3-6cm) and 2.8cm (IQR:1.5-4cm) respectively. Tumor was Her2 positive in 290(29%) and TNBC in 220(22%). Of these 999 cases, 611 received NACT, 647 had mastectomy and 351 had breast conserving surgery (BCS). Simultaneous integrated tumor bed boost (SIB) was given in 341 (97.1%) of BCS cases. The fractionation used was 26 Gy/5-daily fractions (SIB = 32 Gy) in 762 and 28.5 Gy/ 5 once weekly fractionation (SIB = 33 Gy) in 232 cases. RNI included SCF in all 999 and IMN in 168 patients. Of the 831 cases not requiring IMN RT, 573 (70.4%) had 3D conformal RT (n = 573/831,70.4%) whereas Inverse-planned intensity modulated RT was used in 152/168 (90.4%) patients requiring IMN RT. All Mono-isocentric technique was used for all RNI cases treated with 3D CRT. Nearly half of the patients treated with SIB received additional boost dose with electrons (50.5%) and the remaining with IMRT. In these 999 patients treated with UHFRT the peak RTOG grade ≥II skin and pharyngeal toxicity was 7.2% and 8.1% respectively. Among the 341 BCS cases who received SIB with UHFRT, the RTOG acute grade II and III skin toxicity was seen in 6.6% and 0.3% cases respectively. The maximum skin toxicity at 2 weeks after completion of RT of grade ≥II was significantly higher with 5-weekly compared to daily regimen (16.1 vs 4.6, p<0.01). In contrast, the maximum pharyngeal toxicity of grade ≥II was significantly higher with 5-daily compared to weekly fractionation (8.8% vs 5.2%, p = 0.04). At median follow-up of 25 months (CI:23.6-26.3 months), none of our patients had developed symptomatic radiation pneumonitis, brachial plexopathy or any major cardiac event. Five-fraction adjuvant breast cancer RT is well tolerated with low acute toxicity burden even among patients requiring regional nodal irradiation. No brachial plexopathy was observed in cases treated with mono-isocentric RNI but longer follow-up is required to inform about the late toxicities and locoregional control rates.

The Impact of Supervised, Individualized Exercise on Fatigue and Quality of Life during Adjuvant Radiotherapy for Breast Cancer

Adjuvant radiation therapy in treatment for breast cancer has been shown to improve patient outcomes and reduce mortality rates. However, many patients experience debilitating fatigue as a result. Currently, there are limited treatment options for fatigue in cancer survivors. Options include pharmaceutical agents, psychological interventions, or nutrition strategies, all of which have limited efficacy. Exercise is recommended in survivorship care plans, but it not widely implemented beyond the use of generalized statements or resource guides given to patients. Therefore, the purpose of this study was the examine the impact of an individualized exercise program on fatigue, quality of life, and physical functioning during radiation therapy for breast cancer. This multi-institutional prospective trial evaluated the effects of supervised, individualized exercise therapy in 422 patients undergoing adjuvant radiotherapy for breast cancer. Following a comprehensive fitness assessment and the completion of the Brief Fatigue Instrument (BFI) questionnaire, each participant participated in a 12-week individualized exercise program offered through Maple Tree Cancer Alliance. At its conclusion, the patients repeated the assessment and questionnaire. Individualized exercise had a positive impact on fitness parameters and severity of fatigue. Specifically, cardiovascular endurance, muscular strength, muscular endurance, and flexibility all significantly improved following the exercise intervention (p<0.05). On average, patients fatigue levels decreased by 31.1% (P<0.01). These results signify that fatigue levels are positively impacted by exercise among patients with breast cancer.

Five-Fraction Accelerated Partial Breast Irradiation [APBI] may Reduce Health Care Disparity in Patients Receiving Adjuvant Radiation Therapy for Breast Cancer by Overcoming Treatment Barriers of Distance to Treatment Center, Age, and Ethnicity

Although changing, breast irradiation is still standard of care in many patients after breast conservation therapy (lumpectomy). Distance from radiation treatment center, Age, and Ethnicity have been shown to be barriers to completing needed adjuvant radiation therapy in breast and other cancers. In this retrospective review, it was hypothesized that the Meattini five-fraction partial breast treatment (APBI) would reduce these barriers to care, and more patients would complete treatment. Data from the radiation planning system was utilized to identify all patients treated with APBI at a single community cancer center from 3/6/2020 to 10/14/2022. The Electronic Medical Record (EMR) was used to identify home addresses and then online navigation software measured patient round trip driving distance to the treatment center. Records in EMR were reviewed to see if each patient completed treatment. Patients were divided into 2 groups for three variables: 1. Distance from clinic- <40 miles round trip vs. >40 miles round trip, 2. Age- 65 and older or less than 65, 3. Ethnicity- Hispanic or Non-Hispanic. Each variable consisting of 2 groups were then evaluated statistically using two proportion Z test. Eighty-one patients were identified who underwent APBI. There were 50 patients living <40 miles round trip and 31 living >40 miles from cancer treatment center. There were 48 patients age 65 and older and 33 patients under 65. Patients self- identified their ethnicity as: Hispanic (26 patients, 32.1%), non-Hispanic (55 patients, 67.9%: European Descent-52 patients, Native American- 2 patients, Asian American- 1 patient). 80/81 APBI patients completed the planned treatment. Using the two proportion Z-test, there was no statistical difference between patients with distance to treatment center less than 40 mi round trip commute vs greater than 40 miles round trip commute (Z score 1.28, p = .20), no statistical difference by age 65 or older vs under 65 (Z score = -.83, p = 0.40), and no statistical difference between ethnicity of Hispanic vs non-Hispanic patients (Z score 0.69, p = 0.49). Shorter course radiation therapy regimens for many reasons are easier to complete than longer treatment regimens. In this single-institution retrospective review, all but one short course five-fraction APBI patient (80/81) completed treatment. APBI short course five-fraction treatment (compared to traditional longer breast radiation therapy regimens) may help increase completion of adjuvant radiotherapy and reduce healthcare disparity in breast cancer patients and may overcome barriers to treatment such as Distance to treatment center, Age, and Ethnicity.

Assessing Depression and Anxiety Levels in English and Spanish-Speaking Patients throughout a Course of Radiation Therapy

An estimated 32.2% and 41.9% of breast cancer patients experience depression and anxiety, respectively. However, distress experienced by patients with breast cancer receiving radiation therapy may vary at different time points and differ in comparison to other patients with breast cancer, potentially due to differences in the understanding of radiotherapy and variability in the severity of side effects. This study sought to describe the changes in levels of depression and anxiety experienced by English and Spanish-speaking patients throughout a course of radiation therapy for breast cancer, along with the impact of different variables on these levels of distress to better understand and quantify potential gaps. Eligibility criteria included English and Spanish-speaking females, ages 18 or older, undergoing radiation therapy treatment for breast cancer at two institutions, including a safety-net hospital. Pre- and post-treatment surveys were completed before and after delivery of radiation therapy. Sociodemographic characteristics collected included: race, ethnicity, marital status, education level, longest residency location, housing, and food security. The survey ended with the standardized PHQ-4 questionnaire, which uses a maximum total score of 12 to assess anxiety and depression. Results were analyzed using the Analysis of Covariance procedure. A total of 160 participants completed pre- and post-treatment surveys. Half of the participants were non-white (50%), primarily married (42.5%), and had a high school or associate's level education (46.9%). The total baseline distress mean (BDM) was 2.96 (Standard deviation, SD = 3.11), and the final distress mean (FDM) was 2.78 (SD = 3.78). English-speaking patients comprised 82.5% (n = 132) of the sample and had a BDM of 2.91 with an adjusted change mean (ACM) decrease of 0.45. Spanish-speaking patients comprised 17.5% (n = 28) of the sample, with a BDM of 3.21 and an ACM increase of 1.03 (P = 0.002). Housing (P = 0.021) and food insecurity (P = 0.002) also showed increasing distress with increased insecurity at baseline. Our study shows that Spanish-speaking patients present with higher levels of distress than their English-speaking counterparts and their distress increased throughout treatment as opposed to English speakers. Other factors, such as housing and food insecurity, are also significantly associated with increased distress. As the number of Spanish speakers in the US continues to increase, it will be important to continue assessing potential differences in cancer care. In addition, understanding the distress changes throughout radiation treatment could help inform future interventions that address these disparities.

Standardizing Breast Adjuvant Radiation Therapy Practices in a Diverse Health System through Development of a Delphi Consensus Supported Clinical Algorithm

Adjuvant radiation therapy (RT) for early breast cancer is a highly effective treatment option. However, the multitude of available techniques backed by strong clinical evidence can result in a lack of consistency in treatment approaches, even within a single healthcare organization. This presents challenges for both providers and patients in making informed decisions. To address this issue, our radiation department, which serves a large and diverse health system, developed a clinical algorithm for adjuvant RT for breast cancer. This algorithm was created to enhance the quality and standardization of care delivered across our network. A modified Delphi technique was used. A panel of eight experienced breast radiation oncologists from our institution was assembled. The panel first identified the common clinical scenarios encountered in treating patients with adjuvant breast RT, and then made recommendations for the primary and alternative approaches for each scenario. NCCN guidelines, ASTRO executive summaries, and published national and international randomized trials were used for reference. In case of disagreements, the final recommendation was reached through a majority vote. The draft algorithm was also shared with medical oncologists, surgeons, and patient advocates to gather their input prior to final approval by the expert panel. Consensus was reached for three broad clinical scenarios for patients who have undergone lumpectomy or mastectomy: Ductal Carcinoma in Situ (DCIS), Invasive Cancer Node Negative (ICN0), and Invasive Cancer Node Positive (ICN+). The panel agreed subdivision of the scenarios into three risk groups (low, intermediate, and high) and three age groups, based on guidelines and consensus statements. For DCIS patients, size, grade, margin status, hormone receptor status, and tumor focality were used for further stratification. For ICN0 patients, HER2 receptor status and lymphovascular space invasion were also included. For ICN+ patients, nodal status (negative versus 1-3 positive nodes versus more than 3 positive nodes) was used for stratification. Additionally, DCIS and ICN0 patients were further divided into age groups. The panel reached consensus recommendations for RT, including whole breast RT, partial breast RT, chest wall RT, regional nodal irradiation, or omission of RT for each sub-group. Clinical trial enrollment was also recommended where appropriate. A breast cancer adjuvant RT algorithm was developed with the aim of standardizing care for patients with breast cancer. Implementation is expected to standardize treatment recommendations in our health system and to streamline the shared decision-making process with patients.

Quality Assurance in a Phase III, Multicenter, Randomized Trial of POstmastectomy radioThErapy in Node posiTive Breast Cancer with or without Internal mAmmary nodaL Irradiation (POTENTIAL): A Planning Dummy Run

To report the planning dummy run results of the POstmastectomy radioThErapy in Node posiTive breast cancer with or without Internal mAmmary nodaL irradiation (POTENTIAL) trial-a multicenter, randomized, phase 3 trial-to evaluate postmastectomy radiotherapy, with or without internal mammary nodal irradiation, for patients with high-risk breast cancer. All participating institutions were provided the contours of the dummy run case, and they generated radiotherapy (RT) plans per protocol guidelines. The plans were reviewed and feedback were provided by the quality assurance team, after which the institutions resubmitted revised plans. The information on beams arrangement, skin flash, inhomogeneity corrections, and protocol compliance was assessed both in the primary and final submission. Theplans from 26 institutions were included in the analysis. A number of major deviations were found in the primary submission, such as less strict constraint on organs at risk (OARs) V5Gy, and no application of chest wall skin flash. The protocol compliance rates of the dose coverage for the planning target volume of the chest wall (PTVcw), PTV of supra/infraclavicular fossa plus axilla levels I, II, III (PTVsc+ax), and PTV of the IMN region (PTVim) were all significantly improved in the final submission compared with those in the primary submission, which were 96.2% vs. 69.2%, 100% vs. 76.9%, and 88.4% vs. 53.8, respectively. For OARs, the protocol compliance rates of heart Dmean, left anterior descending coronary artery V40Gy, ipsilateral lung V5Gy, and stomach V5Gy were significantly improved. All major deviations were corrected and protocol compliance was significantly improved and of high level in the final submission. Moreover, the variations were reduced. Therefore, a planning dummy run was essential to guarantee good RT plan quality and inter-institutional consistency for multicenter trials.

Interpretable Deep Learning Identified the Significance of 1 Gy Volume on Lymphopenia after Radiotherapy in Breast Cancer

Lymphopenia is common after radiotherapy (RT) and is known for its significance on poor survival outcomes in patients with breast cancer. Previous work has demonstrated the significance of point dosimetric factors like the volume receiving 5 Gy. Considering the full dosimetric data together, this study aimed to develop and validate predictive models for lymphopenia after RT in breast cancer. Patients with breast cancer treated with radiation therapy in adjuvant setting and with complete dosimetric data were eligible. Combining dose-volume histogram (DVH) dosimetric and clinical factors, dense neural network (DNN) models were developed to predict both the reduction in lymphocyte counts and the graded lymphopenia in breast cancer patients after adjuvant RT. A Shapley additive explanation was applied to explain each feature's directional contributions. The generalization of DNN models was validated in both internal and independent external validation cohorts. P<0.05 was considered to be significant. A total of 928 consecutive patients with invasive breast cancer were eligible for this study. Treatment volumes of nearly all irradiation dose levels of DVH were significant predictors for lymphopenia after RT, including volumes at very low-dose 1 Gy (V1) of all structures considered including the lung, heart and body. DNN models using full DVH dosimetric and clinical factors were built and a simplified model was further established and validated in both internal and external validation cohorts. This simplified DNN AI model, combining full DVH dosimetric parameters of all OARs and five key clinical factors including baseline lymphocyte counts, tumor stage, RT technique, RT fields and RT fractionation, showed a predictive accuracy of 77% and above. This study demonstrated and externally validated the significance of an AI model of combining clinical and full dosimetric data, especially the volume of low dose at as low as 1 Gy of all critical structures on lymphopenia after RT in patients with breast cancer. The significance of V1 deserves special attention, as modern arc RT technology often has relatively high value of this parameter. Further study warranted for breast cancer RT plan optimization.

A Cascaded Deep Learning-Based Cardiac Substructures Segmentation Frame and on Non-Gated Non-Enhanced Planning CT Scans in Breast Cancer Patients

To develop a deep learning-based segmentation frame for cardiac substructures especially coronary arteries (CAs) on non-gated non-enhanced planning computed tomography (CT) scans in breast cancer (BC) patients. Non-gated non-enhanced CT scans of 39 BC patients receiving adjuvant radiotherapy (RT) were collected. Cardiac substructures were manually labelled, including four chambers, left main (LM), left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA). The training, validation, and test sample is 28, 7 and 4, respectively. A cascaded network, using nnUNet as the backbone, is proposed to use chambers as prior information to constrain the segmentation of CAs. The mean Dice similarity coefficient (DSC), 95th percentile Hausdorff distance (HD95) and average symmetrical surface distance (ASSD) were used as geometric metrics. Dosimetric parameters of cardiac substructures was calculated based on the segmentation frame and manually labeled contouring, respectively. The data of cardiac examination including ultrasonography, electrocardiogram before and during the follow-up after RT were retrospectively collected. The cardiac event was any symptomatic heart disease or new-onset abnormality in the cardiac examination after RT. The mean DSC of heart, atriums and ventricles of the proposed frame was 0.93, 0.90, and 0.93, respectively. As shown in Table 1, compared with direct segmentation (as baseline), the proposed frame had a better performance in terms of HD95, ASSD, and the mean dose (Dmean) absolute error for all CAs. Compared to the dosimetric parameters of the heart collected based on the manual labelled contours, the relative errors of D5, D95, and V15Gy for LAD was 4.3±7.8%, 11.7±5.9%, and 14.6±13.0% collected based on the direct segmentation contours and 2.4±4.4%, 3.9±3.1%, 8.5±6.9% collected based on the auto-segmented contours, respectively. Multivariate analysis showed that increased V15Gy of LAD was an independent cardiac toxicity risk factor ([HR] = 1.07, 95% CI 1-1.15, p = 0.0387). We developed a cascaded network for cardiac substructures segmentation with dosimetric validation on non-enhanced CT scans in breast cancer radiotherapy. This is the first attempt to use chambers as prior information for CAs' segmentation and had a superior stable performance. Accurate segmentation will help radiation oncologists to better evaluate DVHs based on substructures and thus to estimate cardiovascular risk. An optimized cardiac substructure-based dosimetric constrain may be proposed accordingly.

Patterns and Longitudinal Changes in The Practice of Breast Cancer Radiotherapy in Korea: Korean Radiation Oncology Group 22-01

To analyze contemporary practice patterns in breast cancer radiotherapy (RT) and to assess longitudinal changes therein over 5 years in Korea. A nationwide survey was conducted among board-certified radiation oncologists in Korea by the Division for Breast Cancer of the Korean Radiation Oncology Group in March 2022. The survey consisted of 44 questions related to six domains: hypofractionated (HypoFx) whole breast RT, accelerated partial breast RT (APBI), regional nodal irradiation (RNI), RT for ductal carcinoma in situ (DCIS), postmastectomy RT (PMRT), and tumor bed boost. In total, 70 radiation oncologists from 61 of 101 (60%) institutions participated in the survey. HypoFx RT was used by 62 respondents (89%), which has significantly increased from 36% in 2017. The HypoFx RT was commonly administered at 40-42.5 Gy in 15-16 fractions. APBI was used by 12 respondents (17%), which has increased from 5% in 2017. The use of RNI did not change significantly: ≥ pN2 (6%), ≥ pN1 (33%), and ≥ pN1 with pathological risk factors (61%). However, the indications for use of internal mammary lymph node (IMN) irradiation have expanded. In particular, the rates of routine treatment of IMN (11% from 6% in 2017) and treatment in cases of ≥ pN2 (27% from 14% in 2017) have doubled; however, the rate of treatment for only IMN involvement, identified on imaging, has decreased to 31% from 47% in 2017. With regard to DCIS, the use of hypoFx RT increased to 75% from 25%, and the rate of omission on of RT after breast-conserving surgery decreased to 38% from 48% in 2017. The use of hypoFx RT for PMRT also increased to 36% from 8% in 2017. The adoption of HypoFx RT after breast-conserving surgery in invasive breast cancer and DCIS has increased significantly, whereas that for PMRT has increased moderately, compared to 2017. Further studies are required to determine the optimal use of RNI.