Machine Learning to Predict the Need for Postmastectomy Radiotherapy after Immediate Breast Reconstruction.

Background: Post mastectomy radiotherapy (PMRT) is an independent predictor of reconstructive complications. PMRT may alter the timing and type of reconstruction recommended. This study aimed to create a machine learning model to predict the probability of requiring PMRT after immediate breast reconstruction (IBR). Methods: In this retrospective study, breast cancer patients who underwent IBR from January 2017 to December 2020 were reviewed and data were collected on 81 preoperative characteristics. Primary outcome was recommendation for PMRT. Four algorithms were compared to maximize performance and clinical utility: logistic regression, elastic net (EN), logistic lasso, and random forest (RF). The cohort was split into a development dataset (75% of cohort for training-validation) and 25% used for the test set. Model performance was evaluated using area under the receiver operating characteristic curve (AUC), precision-recall curves, and calibration plots. Results: In a total of 800 patients, 325 (40.6%) patients were recommended to undergo PMRT. With the training-validation dataset (n = 600), model performance was logistic regression 0.73 AUC [95% confidence interval (CI) 0.65-0.80]; RF 0.77 AUC (95% CI, 0.74-0.81); EN 0.77 AUC (95% CI, 0.73-0.81); logistic lasso 0.76 AUC (95% CI, 0.72-0.80). Without significantly sacrificing performance, 81 predictive factors were reduced to 12 for prediction with the EN method. With the test dataset (n = 200), performance of the EN prediction model was confirmed [0.794 AUC (95% CI, 0.730-0.858)]. Conclusion: A parsimonious accurate machine learning model for predicting PMRT after IBR was developed, tested, and translated into a clinically applicable online calculator for providers and patients.

Toward a Skin Dose-Area Metric Predictive of Moist Desquamation Using In Vivo Skin Dosimetry and Skin Assessments.

Purpose: Moist desquamation (MD) is a concerning acute side effect of radiation therapy for breast cancer, often seen in skin folds for patients having large or pendulous breasts. In vivo skin dosimetry, clinical assessments, and patient-reported skin reactions were used to determine a relationship between dose-area metrics and the development of MD, to lend insight into skin tolerances and possibly guide future treatment planning dose constraints. Methods and Materials: Skin dose was measured using GafChromic film on the inner surface of an early prototype carbon-fiber accessory for breast support to remove the inframammary fold in 20 patients at high risk of developing MD undergoing adjuvant whole breast radiation therapy. Prescribed doses were 42.5 Gray (Gy) in 16 fractions or 50 Gy in 25 fractions using 6 to 15 MV x-rays. To account for fraction size differences, analysis was performed using the equivalent dose in 2 Gy fractions using α/ß = 11 (EQD211). MD was assessed out to 2 weeks post radiation therapy by trained therapists and by a patient-reported outcome questionnaire. Results: Statistically significant differences in areas receiving 30 to 48 Gy (EQD211) were observed between patients who did and did not develop MD in the inframammary area. Patients receiving EQD211 maximum dose ≤ 46 Gy and ≥ 38 Gy to ≤ 50 cm2 of their breast skin did not develop MD. Conclusions: The findings of this study offer insight into the relationship between skin toxicity and areas of skin irradiated to doses up to 50 Gy. Potential skin dose constraints to test in future studies to prevent MD are suggested.

Breast conserving surgery combined with radiation therapy offers improved survival over mastectomy in early-stage breast cancer.

INTRODUCTION: Landmark trials established equivalent survival regardless of extent of breast surgery in early-stage breast cancer. However, recent studies suggest a survival advantage for breast conserving surgery (BCS) with radiotherapy (BCT). This study assesses the impact of type of surgery on overall survival (OS), breast cancer specific survival (BCSS) and local recurrence (LR) in a modern population-based cohort. METHODS: Female patients aged ≥18, pT1-2pN0, who had surgery between 2006 and 2016 were identified from Breast Cancer Outcome Unit prospective database. Neoadjuvant chemotherapy patients were excluded. Multivariable Cox regression was used to assess the effect of surgical procedure on OS, BCSS, and LR on cohort with complete data. RESULTS: BCT was performed in 8422 patients and TM in 4034 patients. The baseline characteristics differed between the groups. Mean follow up was 8.3 years. BCT was associated with increased OS HR 1.37, p < 0.001, BCSS survival HR 1.49, p < 0.001, and similar LR HR 1.00, p > 0.90. CONCLUSION: This study supports that in early-stage breast cancer, BCT has improved BCSS compared to TM without an increased risk of LR.

Does age affect outcome with breast cancer?

Prior data about the influence of age at diagnosis of breast cancer on patient outcomes and survival has been conflicting. Using the Breast Cancer Outcomes Unit database at BC Cancer, this retrospective population-based study identified a cohort of 24,469 patients diagnosed with invasive breast cancer between 2005 and 2014. Median follow-up was 11.5 years. We analyzed clinical and pathological features at diagnosis and treatment specific variables compared across the following age cohorts: <35, 35-39, 40-49, 50-59, 60-69, 70-79, and 80 years of age and older. We assessed the impact of age on breast cancer specific survival (BCSS) and overall survival (OS) by age and subtype. There were distinct clinical-pathological and treatment pattern differences at both extremes of age at diagnosis. Patients <35 and 35-39 years old were more likely to present with higher risk features, HER2 positive or triple-negative biomarkers, and more advanced TNM stage at diagnosis. They were more likely to undergo treatment with mastectomy, axillary lymph node dissection, radiotherapy and chemotherapy. Conversely, patients ≥80 years old were generally more likely to have hormone-sensitive HER2-negative disease, and lower TNM stage at diagnosis. They were less likely to undergo surgery or be treated with radiotherapy and chemotherapy. Both younger and elderly age at breast cancer diagnosis were independent risk factors for poorer prognosis after controlling for subtype, LVI, stage, and treatment factors. This work will help clinicians to more accurately estimate patient outcomes, patterns of relapse, and provide evidence-based treatment recommendations.

Breast-Conserving Therapy is Associated with Improved Survival Without an Increased Risk of Locoregional Recurrence Compared with Mastectomy in Both Clinically Node-Positive and Node-Negative Breast Cancer Patients.

INTRODUCTION: Randomized trials demonstrated equivalent survival between breast-conserving surgery combined with radiotherapy (BCT) and mastectomy alone. Contemporary retrospective studies using pathological stage have reported improved survival with BCT. However, pathological information is unknown before surgery. To mimic real-world surgical decision-making, this study assesses oncological outcomes by using clinical nodal status. METHODS: Female patients aged 18-69 years who were treated with upfront BCT or mastectomy between 2006 and 2016 for T1-3N0-3 breast cancer were identified by using prospective, provincial database. The patients were divided into clinically node-positive (cN+) and node-negative (cN0) strata. Multivariable logistic regression was used to assess the effect of local treatment type on overall survival (OS), breast cancer-specific survival (BCSS), and locoregional recurrence (LRR). RESULTS: Of 13,914 patients, 8228 had BCT and 5686 had mastectomy. Mastectomy patients had higher-risk clinicopathological factors: pathologically positive axillary staging was 21% in BCT and 38% in mastectomy groups. Most patients received adjuvant systemic therapy. For cN0 patients, 7743 had BCT and 4794 had mastectomy. On multivariable analysis, BCT was associated with improved OS (hazard ratio [HR] 1.37, p < 0.001) and BCSS (HR 1.32, p < 0.001), whereas LRR was not different between the groups (HR 0.84, p = 0.1). For cN+ patients, 485 had BCT and 892 had mastectomy. On multivariable analysis, BCT was associated with improved OS (HR 1.46, p = 0.002) and BCSS (HR 1.44, p = 0.008), whereas LRR was not different between the groups (HR 0.89, p = 0.7). CONCLUSIONS: In the era of contemporary systemic therapy, BCT was associated with better survival than mastectomy, without an increased risk of locoregional recurrence for both cN0 and cN+ presentations.

Treatment Patterns and Outcomes of Patients with Grade 4 Glioma Treated with Radiation during the COVID-19 Pandemic.

During the first year of the COVID-19 pandemic there was a global disruption in the provision of healthcare. Grade 4 gliomas are rapidly progressive tumors, and these patients are at risk of poorer outcomes due to delays in diagnosis or treatment. We retrospectively evaluated the impact of the pandemic on treatment patterns and outcomes of patients with grade 4 gliomas in British Columbia. We identified a cohort of 85 patients treated with radiotherapy between March 2020-2021 (COVID era) and compared baseline characteristics, treatments, and outcomes with a control cohort of 79 patients treated between March 2018-2019 (pre-COVID era). There were fewer patients treated with radiotherapy over age 65 in the COVID era compared to the pre-COVID era (p = 0.037). Significantly more patients were managed with biopsy relative to partial or gross total resection during the COVID era compared to the pre-COVID era (p = 0.04), but there were no other significant differences in time to assessment, time to treatment, or administration of adjuvant therapy. There was no difference in overall survival between eras (p = 0.189). In this assessment of outcomes of grade 4 gliomas during the pandemic, we found that despite less aggressive surgical intervention during the COVID era, outcomes were similar between eras.

The Role of Imaging in the Diagnosis of Primary and Secondary Breast Angiosarcoma: Twenty-Five-Year Experience of a Provincial Cancer Institution.

BACKGROUND: Breast angiosarcoma may arise spontaneously (primary breast angiosarcoma (PBA)) or may arise secondary to a biological insult, such as radiation therapy (secondary breast angiosarcoma (SBA)). We evaluated the imaging findings of patients diagnosed with PBA and SBA within the province of British Columbia, Canada. MATERIALS AND METHODS: This was a multi-center, retrospective study of patients diagnosed with PBA and SBA over a 25-year period. Patients were identified via a provincial database which registers all cases of sarcoma. Patients diagnosed with histologically proven PBA and SBA were eligible for inclusion. Multimodal breast imaging reviewed included mammography, ultrasound, magnetic resonance imaging, and computed tomography. RESULTS: Thirteen patients were diagnosed with PBA and 22 patients were diagnosed with SBA. The median (interquartile range (IQR)) age of patients diagnosed with PBA (45.5 years (19.7 years)) was less than that of patients diagnosed with SBA (75.8 years (13.8 years), P < .001). Patients diagnosed with PBA (90.9%) were more likely to present with a parenchymal mass clinically and radiographically than those with SBA (28.6%, P < .002). Patients diagnosed with SBA (71.4%) were more likely to present with cutaneous findings than patients diagnosed with PBA (0.0%, P < .05). Without specific clinical context, the imaging findings of PBA and SBA were observed to be non-specific. CONCLUSION: This is the only study which evaluated the imaging findings of patients diagnosed with PBA and SBA within a large, defined geographical area. Given non-specific imaging findings, awareness of the disease and clear and timely communication between radiologists and clinicians is required to ensure appropriate diagnosis and management.

Intra-individual comparison of 18F-sodium fluoride PET-CT and 99mTc bone scintigraphy with SPECT in patients with prostate cancer or breast cancer at high risk for skeletal metastases (MITNEC-A1): a multicentre, phase 3 trial.

BACKGROUND: Detection of skeletal metastases in patients with prostate cancer or breast cancer remains a major clinical challenge. We aimed to compare the diagnostic performance of 99mTc-methylene diphosphonate (99mTc-MDP) single-photon emission CT (SPECT) and 18F-sodium fluoride (18F-NaF) PET-CT for the detection of osseous metastases in patients with high-risk prostate or breast cancer. METHODS: MITNEC-A1 was a prospective, multicentre, single-cohort, phase 3 trial conducted in ten hospitals across Canada. Patients aged 18 years or older with breast or prostate cancer with a WHO performance status of 0-2 and with high risk or clinical suspicion for bone metastasis, but without previously documented bone involvement, were eligible. 18F-NaF PET-CT and 99mTc-MDP SPECT were done within 14 days of each other for each participant. Two independent reviewers interpreted each modality without knowledge of other imaging findings. The primary endpoint was the overall accuracy of 99mTc-MDP SPECT and 18F-NaF PET-CT scans for the detection of bone metastases in the per-protocol population. A combination of histopathological, clinical, and imaging follow-up for up to 24 months was used as the reference standard to assess the imaging results. Safety was assessed in all enrolled participants. This study is registered with ClinicalTrials.gov, NCT01930812, and is complete. FINDINGS: Between July 11, 2014, and March 3, 2017, 290 patients were screened, 288 of whom were enrolled (64 participants with breast cancer and 224 with prostate cancer). 261 participants underwent both 18F-NaF PET-CT and 99mTc-MDP SPECT and completed the required follow-up for statistical analysis. Median follow-up was 735 days (IQR 727-750). Based on the reference methods used, 109 (42%) of 261 patients had bone metastases. In the patient-based analysis, 18F-NaF PET-CT was more accurate than 99mTc-MDP SPECT (84·3% [95% CI 79·9-88·7] vs 77·4% [72·3-82·5], difference 6·9% [95% CI 1·3-12·5]; p=0·016). No adverse events were reported for the 288 patients recruited. INTERPRETATION: 18F-NaF has the potential to displace 99mTc-MDP as the bone imaging radiopharmaceutical of choice in patients with high-risk prostate or breast cancer. FUNDING: Canadian Institutes of Health Research.

Locoregional Recurrence and Survival Outcomes in Breast Cancer Treated With Modern Neoadjuvant Chemotherapy: A Contemporary Population-based Analysis.

BACKGROUND: Data guiding radiotherapy (RT) decisions after neoadjuvant chemotherapy (NAC) is largely retrospective, based on older treatment approaches without molecular subtype information. This study evaluated outcomes in breast cancer patients treated with modern NAC by molecular subtype and locoregional treatment. MATERIALS AND METHODS: There were 949 patients diagnosed between 2005 and 2016 treated with NAC followed by surgery ± locoregional radiotherapy (LRRT). Outcomes were 7-year locoregional relapse-free survival (LRRFS), breast cancer-specific survival (BCSS), and overall survival (OS). RESULTS: Median follow-up was 6.5 years, 92% had cT2-4 and 72% cN1-3 disease. Subtypes were: 21% Luminal A, 18% Luminal B, 35% Her2+, and 21% triple-negative breast cancer (TNBC). Combined taxane and anthracycline-based NAC was used in 91.7% of cases. All patients with Her2+ disease received anti-Her2 therapy. After NAC, the majority (84.9%) underwent mastectomy, and received LRRT (86.1%). Only 11% had mastectomy without RT. Pathologic complete response (pCR) rates were 2.5% for Luminal A, 14.4% Luminal B, 27% TNBC, and 35.1% Her2+. Overall, adjuvant LRRT was associated with improved outcomes but was most significant for improved LRRFS in TNBC (92.5% vs. 68.5%, P < .001; Her2+ 95.4% vs. 93.6%, P = .81; Luminal A 97.4% vs. 100%, P = .49; Luminal B 89.7% vs. 100%, P = .17). On multivariable analysis, factors associated with reduced LRRFS were grade 3 histology (HR 4.96, P = .009) and no pCR (HR 7.0, P = .0008). Predictors of lower BCSS and OS were age >50, grade 3, cT3-4, lack of pCR, LRRT omission, and TNBC and Her2+ subtypes. CONCLUSION: In this analysis of patients treated with modern NAC, pCR rates varied by molecular subtype. Patients who did not receive LRRT, particularly those with TNBC, had lower survival compared to those treated with LRRT. These findings support the need for prospective studies to evaluate the safety of de-escalating RT after NAC.

A multi-institutional prediction model to estimate the risk of recurrence and mortality after mastectomy for T1-2N1 breast cancer.

BACKGROUND: Post-mastectomy radiation therapy (PMRT) in women with pathologic stage T1-2N1M0 breast cancer is controversial. METHODS: Data from five North American institutions including women undergoing mastectomy without neoadjuvant therapy with pT1-2N1M0 breast cancer treated from 2006 to 2015 were pooled for analysis. Competing-risks regression was performed to identify factors associated with locoregional recurrence (LRR), distant metastasis (DM), overall recurrence (OR), and breast cancer mortality (BCM). RESULTS: A total of 3532 patients were included for analysis with a median follow-up time among survivors of 6.8 years (interquartile range [IQR], 4.5-9.5 years). The 2154 (61%) patients who received PMRT had significantly more adverse risk factors than those patients not receiving PMRT: younger age, larger tumors, more positive lymph nodes, lymphovascular invasion, extracapsular extension, and positive margins (p < .05 for all). On competing risk regression analysis, receipt of PMRT was significantly associated with a decreased risk of LRR (hazard ratio [HR], 0.21; 95% confidence interval [CI], 0.14-0.31; p < .001) and OR (HR, 0.76; 95% CI, 0.62-0.94; p = .011). Model performance metrics for each end point showed good discrimination and calibration. An online prediction model to estimate predicted risks for each outcome based on individual patient and tumor characteristics was created from the model. CONCLUSIONS: In a large multi-institutional cohort of patients, PMRT for T1-2N1 breast cancer was associated with a significant reduction in locoregional and overall recurrence after accounting for known prognostic factors. An online calculator was developed to aid in personalized decision-making regarding PMRT in this population.

Validation of the BC-Brain Patient-Reported Outcome Questionnaire for Patients with Central Nervous System Tumours Treated with Radiotherapy.

The BC-brain questionnaire was developed by BC Cancer to detect health problems in patients with central nervous system (CNS) tumours in routine clinical care, treated with radiotherapy (RT), as part of the Prospective Outcomes and Support Initiative (POSI). This study aimed to present and validate the BC-brain questionnaire in patients with brain metastases (BrM) treated with RT. The BC-brain questionnaire was constructed with three subscales: mobility, thinking and CNS symptoms. Patients with BrM from five BC Cancer centres completed this questionnaire at first visit and subsequent follow-up appointments. A total of 365 patients finished the first and 105 finished the follow-up questionnaire. Summary scores of each subscale were calculated. Mobility, thinking and subtotal score showed good reliability with Cronbach's α > 0.7. Multitrait scaling analysis showed good convergent and divergent validity. The correlations between subscales ranged from 0.262 to 0.456 for baseline and from 0.378 to 0.597 for follow-up. Patients on dexamethasone had worse performance. Patients with a KPS of 70. In general, this BC-brain questionnaire has good reliability and validity, and is proper to use as an option for a patient-reported outcome (PRO) instrument to measure the quality of life in BrM patients treated with RT.

pN0(i+) and pN1mi Breast Cancer: Treatment and Outcomes in Comparison With pN0 and pN1a in the Modern Era.

PURPOSE: Locoregional recurrence risk and the role of locoregional radiation therapy (LRRT) in pN0(i+) and pN1mi breast cancer are unclear. This study compares locoregional relapse-free survival (LRRFS) in patients with pN0(i+) and pN1mi relative to pN0 and pN1a disease and evaluates LRRFS according to locoregional treatment. METHODS AND MATERIALS: We studied 10,271 patients referred between 2006 and 2011 with newly diagnosed pT1-T2, pN0, pN0(i+), pN1mi, or pN1a, M0 breast cancer. Outcomes were 10-year Kaplan-Meier LRRFS, relapse-free survival (RFS), distant relapse-free survival, and breast cancer-specific survival. Multivariable analysis of LRRFS and RFS was performed in pN0(i+) and pN1mi cohorts. RESULTS: Median follow-up was 9.3 years. In patients with pN0 (n = 7492), pN0(i+) (n = 305), pN1mi (n = 619), and pN1a (n = 1855) disease, LRRT was used in 1.1%, 24.3%, 45.7%, and 71.1%, respectively. Ten-year outcomes were LRRFS 96%, 92%, 97%, and 96% (P < .001), distant RFS 94%, 91%, 90%, and 84% (P < .001), and breast cancer-specific survival 95%, 90%, 93%, and 87% (P < .001), respectively. Ten-year LRRFS for patients treated with breast-conserving surgery alone, with breast RT, and with LRRT were 81%, 93%, and 91% for patients with pN0(i+) (P = .16) and 94%, 96%, and 100% for patients with pN1mi (P = .02), respectively. Among patients treated with mastectomy, 10-year LRRFS with surgery alone and with LRRT were 93% and 100% for patients with pN0(i+) (P = .12) and 95% and 99% for patients with pN1mi (P = .09). On multivariable analysis of patients with pN0(i+) and pN1mi, systemic therapy was associated with improved LRRFS in patients with pN0(i+) (hazard ratio [HR], 0.2; [0.06-0.6]; P = .005) and patients with pN1mi (HR, 0.1; [0.03-0.5]; P = .006). In patients with pN1mi, LRRT was associated with a trend toward increased LRRFS (HR, 0.2; [0.03-1.1]; P = .07). LRRT was not significantly associated with improved RFS in pN0(i+) or pN1mi disease. CONCLUSIONS: In the era of sentinel node staging and modern systemic therapy, patients with pN0(i+) and PN1mi treated with LRRT experienced 10-year LRR risks ≤10% after breast-conserving surgery or mastectomy and RT. LRRT was associated with a trend toward increased LRRFS in pN1mi but not pN0(i+) disease.

Survival and Recurrence Outcomes Following Adjuvant Radiotherapy for Grade 2 Intracranial Meningiomas: 13-Year Experience in a Tertiary-Care Center.

OBJECTIVE: We sought to evaluate overall survival (OS) and local recurrence (LR) in patients with grade 2 meningiomas treated with adjuvant radiotherapy compared to surgery alone at time of diagnosis. METHODS: All patients at the authors' institution between 2007 and 2020 were retrospectively reviewed. OS, LR, and treatment toxicities were assessed. Sensitivity analyses were performed for patients with initial gross total resection (GTR) and subtotal resection (STR). Kaplan-Meier analyses and log-rank test for significance were used to compare surgery alone and adjuvant radiotherapy groups. RESULTS: We included 189 patients with mean age 57.4 ± 14.6 years. Patients were 64% female, and median follow-up was 64 (interquartile range: 20-96) months. At initial treatment, 21 patients received adjuvant radiotherapy and 168 received surgery alone. There was no significant difference for OS (hazard ratio = 1.3 [95% confidence interval 0.4-4.5], P = 0.92) overall or when limited to GTR (P = 0.38) or STR (P = 0.85). There was no significant difference in LR overall (P = 0.75) or when restricted to GTR (P = 0.77) or STR (P = 0.20). No patient had radiotherapy stopped or altered because of side effects; however, 71.4% reported tolerable side effects during the treatment period and 14.3% reported chronic side effects persisting longer than 12 months post treatment. CONCLUSIONS: In a large retrospective cohort, we found no survival or local recurrence benefit to adjuvant radiotherapy in treatment of grade 2 meningiomas. Sensitivity analysis limited to initial GTR and STR also failed to demonstrate any OS or LR benefit with adjuvant radiotherapy. In our experience, there is limited utility to upfront adjuvant radiotherapy following initial surgical resection in the treatment of grade 2 meningiomas.

Impact of TAILORx on chemotherapy prescribing and 21-gene recurrence score-guided treatment costs in a population-based cohort of patients with breast cancer.

BACKGROUND: The trial assigning individualized options for treatment (Rx) (TAILORx) confirmed the predictive value of the 21-gene recurrence score (RS) assay in hormone receptor (HR)-positive, HER2-negative, node-negative breast cancer and established thresholds for chemotherapy benefit in younger and older patients. Real-world chemotherapy use and RS-guided treatment costs in British Columbia post-TAILORx were examined. METHODS: The authors assembled 3 cohorts of HR-positive, HER2-negative, node-negative patients with breast cancer defined by diagnosis: before RS funding (cohort 1 [C1]: January 2013-December 2013), after introduction of public RS funding (cohort 2 [C2]: July 2015-June 2016), and after TAILORx results (cohort 3 [C3]: July 2018-June 2019). Chemotherapy use was compared between cohorts by age and RS. Budgetary impacts of RS testing on chemotherapy costs were evaluated pre- and post-TAILORx. RESULTS: Among the 2066 patients included, chemotherapy use declined by 19% after RS funding was introduced and by an additional 23% after TAILORx publication (P = .001). Reduction in chemotherapy use was significant for RS 11-20 tumors (C3 vs C2, P = .004). There was no significant change in chemotherapy use in patients >50 years old (C2:12% vs C3:10%, P = .22). RS testing was associated with higher cost savings post-TAILORx, except in patients 70 to 80 years old, where testing led to excess costs when adjusting for the low rate of RS-concordant chemotherapy prescribed. CONCLUSIONS: TAILORx has had population-based impacts on chemotherapy prescribing in intermediate RS tumors and patients ≤50 years old. The lower clinical use of RS and increased spending in patients 70-80 years old highlights the importance of careful selection of older candidates for high-cost genomic testing. LAY SUMMARY: The 21-gene recurrence score (RS) test helps predict whether patients with hormone-positive, HER2-negative, lymph node-negative breast cancer are likely to benefit from chemotherapy. The recent trial assigning individualized options for treatment (Rx) (TAILORx) found that patients with intermediate RS tumors did not benefit from chemotherapy. The authors assessed whether TAILORx results translated to real-world changes in chemotherapy prescribing patterns. In this study, chemotherapy use decreased by 23% after TAILORx, with the greatest reductions seen among intermediate RS tumors and younger patients. In contrast, RS testing had lower clinical value and increased treatment costs in elderly patients, which requires further study to ensure optimal care for this age group.

Association Between Regional Nodal Irradiation and Breast Cancer Recurrence-Free Interval for Patients With Low-Risk, Node-Positive Breast Cancer.

PURPOSE: Randomized clinical trials have shown that regional nodal irradiation (RNI) in patients with unselected N1 breast cancer improves breast cancer-specific survival. However, the benefit of RNI in women with biologically low-risk N1 breast cancer is uncertain. We conducted a population-based study to determine whether RNI is associated with improved breast cancer recurrence-free interval (BCRFI) in this population. METHODS AND MATERIALS: Patients aged 40 to 79 years with pT1-2 pN1 (node-positive) breast cancer diagnosed between 2005 and 2014 were identified. The inclusion criteria were modeled off of the TAILOR RT study, which is a randomized noninferiority clinical trial designed to assess the value of RNI in patients with low-risk N1 disease. Eligible patients had breast-conserving surgery or mastectomy and axillary lymph node dissection with 1 to 3 positive nodes, breast-conserving surgery and sentinel lymph node biopsy with 1 to 2 positive nodes, or mastectomy and sentinel lymph node biopsy with 1 positive node. Additionally, patients had luminal A breast cancers, as approximated by estrogen receptor positive (Allred 6-8/8), progesterone receptor (PR) positive (Allred 6-8/8), human epidermal growth factor receptor 2-negative, and grade 1 to 2 immunohistochemical testing. All patients were prescribed hormonal treatment. The primary endpoint of BCRFI, the time to any breast cancer recurrence or breast cancer-related death, was analyzed using a multivariate competing risks analysis. RESULTS: The cohort included 1169 women with a median follow-up of 9.2 years. Radiation treatments were not performed in 151 women treated with mastectomy alone, were delivered to the breast only in 133 women, and were delivered locoregionally in 885 women. Patients undergoing RNI were younger (median age: 58 vs 62 years), more likely to have 2 to 3 macroscopic lymph nodes involved, and more often received chemotherapy (all P < .05). The 10-year estimate of BCRFI was 90% without RNI versus 90% with RNI (P = .5). On multivariable analysis, RNI was not a significant predictor of BCRFI (hazard ratio: 1.0; P = .9). CONCLUSIONS: In this retrospective analysis, RNI was not associated with improved BCRFI for women with biologically low-risk N1 breast cancer. We advocate accrual to the ongoing TAILOR RT study.

Breast Tangent Beam Energy, Surgical Bed-to-Skin Distance and Local Recurrence After Breast-Conserving Treatment.

PURPOSE: Higher energy (>6 MV) photons reduce dose inhomogeneity with breast tangent beams, thereby reducing late breast toxicity, but skin and superficial tissue sparing by higher energy beams raises concerns about local recurrence (LR) risk. This study aimed to determine whether beam energy and surgical bed-to-skin distance affect LR. METHODS AND MATERIALS: This population-based study included newly diagnosed invasive breast cancers without skin involvement (pT1-4a, any-N, M0) treated with breast-conserving surgery and adjuvant whole breast radiation therapy without bolus or beam spoilers. The primary endpoint was the cumulative incidence of LR (CILR). Multivariable analysis (MVA) included mean beam energy, age, T-stage, nodal status, overall stage, lymphovascular invasion (LVI), grade, margin status, extensive intraductal component (EIC), breast cancer subtype, hormone therapy, and chemotherapy. In a subgroup with contoured surgical beds, another MVA included surgical bed-to-skin distance. RESULTS: The cohort consisted of 10,083 women treated from 2002 to 2011: 327 with 4 MV, 6006 with 6 MV, 2083 with >6 to 10 MV, and 1667 with >10 MV tangents. The median follow-up time was 11.1 years. The 10-year CILR was 3.1% (95% confidence interval [CI], 1.6-5.4) with 4 MV, 2.8% (2.4-3.3) with 6 MV, 4.2% (3.4-5.3) with >6 to 10 MV, and 2.6% (1.9-3.5) with >10 MV. On MVA of the entire cohort, LR risk was increased with positive margins, LVI, EIC, and lack of hormone therapy, but was not associated with beam energy (hazard ratio [HR], 1.01; 95% CI, 0.96-1.05; P = .8). On MVA of 3359 patients with contoured surgical beds, LR risk was not associated with surgical bed-to-skin distance (HR, 1.00; 95% CI, 0.99-1.02; P = .8). CONCLUSIONS: Use of higher breast tangent beam energies is not associated with increased risk of LR, including in cases with surgical beds that are close to the skin.

A Delphi study and International Consensus Recommendations: The use of bolus in the setting of postmastectomy radiation therapy for early breast cancer.

Bolus serves as a tissue equivalent material that shifts the 95-100% isodose line towards the skin and subcutaneous tissue. The need for bolus for all breast cancer patients planned for postmastectomy radiation therapy (PMRT) has been questioned. The work was initiated by the faculty of the European SocieTy for Radiotherapy & Oncology (ESTRO) breast cancer courses and represents a multidisciplinary international breast cancer expert collaboration to optimize PMRT. Due to the lack of randomised trials evaluating the benefits of bolus, we designed a stepwise project to evaluate the existing evidence about the use of bolus in the setting of PMRT to achieve an international consensus for the indications of bolus in PMRT, based on the Delphi method.

Reduction in Doses to Organs at Risk and Normal Tissue During Breast Radiation Therapy With a Carbon-Fiber Adjustable Reusable Accessory.

PURPOSE: This pilot study (ClinicalTrials.gov NCT04543851) investigates a novel breast positioning device using a low density, high tensile carbon-fiber cradle to support the breast, remove the inframammary fold, and reduce dose to organs at risk for whole breast radiation therapy in the supine position. METHODS AND MATERIALS: Thirty patients with inframammary folds ≥1 cm or lateral ptosis in supine treatment position were planned with standard positioning and with a carbon-fiber Adjustable Reusable Accessory (CARA) breast support. Twenty patients received whole breast with or without regional nodal irradiation with 42.5 Gy in 16 fractions or 50 Gy in 25 fractions using CARA. Median body mass index was 32 in this study. RESULTS: CARA removed all inframammary folds and reduced V20Gyipsilateral lung, V105%breast, and V50% body, without compromising target coverage. Median (range) V20Gyipsilateral lung for whole breast radiation therapy was 12.3% (1.4%-28.7%) with standard of care versus 10.9% (1.2%-17.3%) with CARA (Wilcoxon P = .005). Median V105% breast was 8.0% (0.0%-29%) with standard of care versus 4.0% (0.0%-23%) with CARA (P = .006) and median V50% body was 3056 mL (1476-5285 mL) versus 2780 mL (1415-5123 mL) with CARA (P = .001). CARA was compatible with deep inspiration breath hold and achieved median V25Gyheart = 0.1% (range 0%-1.9%) for all patients with left breast cancer. Skin reactions with CARA were consistent with historical data and daily variation in treatment setup was consistent with standard supine positioning. CONCLUSIONS: CARA can reduce V105%breast, lung and normal tissue dose, and remove the inframammary fold for breast patients with large or pendulous breasts and high body mass index treated in the supine position, without compromising target coverage. CARA will undergo further study in a randomized controlled trial.