Socioeconomic Barriers to Randomized Clinical Trial Retention in Patients Treated With Adjuvant Radiation for Early-Stage Breast Cancer.

PURPOSE: Socioeconomic barriers contribute to breast cancer clinical trial enrollment disparities. We sought to identify whether socioeconomic disadvantage also is associated with decreased trial retention. METHODS AND MATERIALS: We performed a secondary analysis of 253 (of 287) patients enrolled in a randomized phase 3 trial of conventionally fractionated versus hypofractionated whole-breast irradiation. The outcome of trial retention versus dropout was defined primarily based on whether the patient completed breast cosmesis outcomes assessment at 3-year follow-up, and secondarily, at 5-year follow-up. Associations of retention with severity of socioeconomic disadvantage, quantified by patients' home neighborhood area deprivation index (ADI) rank (1 [least] to 100 [most deprivation]), were tested using the Kruskal-Wallis test and multivariate logistic regression. Associations of retention with patients' use of social resource assistance were analyzed using the χ2 test. RESULTS: In total, 21.7% (n = 55) of patients dropped out by 3 years and 36.7% (n = 92) by 5 years. Median ADI was 36.5 (interquartile range, 22-57) for retained and 46.0 (interquartile range, 29-60) for dropout patients. Dropout was associated with more severe socioeconomic deprivation (ADI ≥45 vs <45) at 3 years (odds ratio, 3.63; 95% confidence interval, 1.62-8.15; P = .002) and 5 years (odds ratio, 2.55; 95% confidence interval, 1.37-4.76; P = .003). While on study, patients who ultimately dropped out were more likely to require resource assistance for practical (transportation, housing, financial) than psychological needs (distress, grief) or advance care planning (P = .03). CONCLUSIONS: In this study, ADI was associated with disparities in clinical trial retention of patients with breast cancer receiving adjuvant radiation treatment. Results suggest that developing multidimensional interventions that extend beyond routine social determinants needs screening are needed, not only to enhance initial clinical trial access and enrollment but also to enable robust long-term retention of socioeconomically disadvantaged patients and improve the validity and generalizability of reported long-term trial clinical and patient-reported outcomes.

Consensus Quality Measures and Dose Constraints for Breast Cancer From the Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Expert Panel.

PURPOSE: Using evidence-based radiation therapy to direct care for patients with breast cancer is critical to standardize practice, improve safety, and optimize outcomes. To address this need, the Veterans Affairs (VA) National Radiation Oncology Program (NROP) established the VA Radiation Oncology Quality Surveillance Program to develop clinical quality measures (QMs). The VA NROP contracted with the American Society for Radiation Oncology to commission 5 Blue Ribbon Panels for breast, lung, prostate, rectal, and head and neck cancers. METHODS AND MATERIALS: The Breast Cancer Blue Ribbon Panel experts worked collaboratively with the NROP to develop consensus QMs for use throughout the VA system, establishing a set of QMs for patients in several areas, including consultation and work-up; simulation, treatment planning, and treatment; and follow-up care. As part of this initiative, consensus dose-volume histogram (DVH) constraints were outlined. RESULTS: In total, 36 QMs were established. Herein, we review the process used to develop QMs and final consensus QMs pertaining to all aspects of radiation patient care, as well as DVH constraints. CONCLUSIONS: The QMs and expert consensus DVH constraints are intended for ongoing quality surveillance within the VA system and centers providing community care for Veterans. They are also available for use by greater non-VA community measures of quality care for patients with breast cancer receiving radiation.

Veterans Affairs Radiation Oncology Quality Surveillance Program and American Society for Radiation Oncology Quality Measures Initiative.

PURPOSE: Ensuring high quality, evidence-based radiation therapy for patients is of the upmost importance. As a part of the largest integrated health system in America, the Department of Veterans Affairs National Radiation Oncology Program (VA-NROP) established a quality surveillance initiative to address the challenge and necessity of providing the highest quality of care for veterans treated for cancer. METHODS AND MATERIALS: As part of this initiative, the VA-NROP contracted with the American Society for Radiation Oncology to commission 5 Blue Ribbon Panels for lung, prostate, rectal, breast, and head and neck cancers experts. This group worked collaboratively with the VA-NROP to develop consensus quality measures. In addition to the site-specific measures, an additional Blue Ribbon Panel comprised of the chairs and other members of the disease sites was formed to create 18 harmonized quality measures for all 5 sites (13 quality, 4 surveillance, and 1 aspirational). CONCLUSIONS: The VA-NROP and American Society for Radiation Oncology collaboration have created quality measures spanning 5 disease sites to help improve patient outcomes. These will be used for the ongoing quality surveillance of veterans receiving radiation therapy through the VA and its community partners.

Five-Year Longitudinal Analysis of Patient-Reported Outcomes and Cosmesis in a Randomized Trial of Conventionally Fractionated Versus Hypofractionated Whole-Breast Irradiation.

PURPOSE: There are limited prospective data on predictors of patient-reported outcomes (PROs) after whole-breast irradiation (WBI) plus a boost. We sought to characterize longitudinal PROs and cosmesis in a randomized trial comparing conventionally fractionated (CF) versus hypofractionated (HF) WBI. METHODS AND MATERIALS: From 2011 to 2014, women aged ≥40 years with Tis-T2 N0-N1a M0 breast cancer who underwent a lumpectomy with negative margins were randomized to CF-WBI (50 Gray [Gy]/25 fractions plus boost) versus HF-WBI (42.56 Gy/16 fractions plus boost). At baseline (pre-radiation), at 6 months, and yearly thereafter through 5 years, PROs included the Breast Cancer Treatment Outcome Scale (BCTOS), Functional Assessment of Cancer Therapy-Breast (FACT-B), and Body Image Scale; cosmesis was reported by the treating physician using Radiation Therapy Oncology Group cosmesis values. Multivariable mixed-effects growth curve models evaluated associations of the treatment arm and patient factors with outcomes and tested for relevant interactions with the treatment arm. RESULTS: A total of 287 patients were randomized, completing a total of 14,801 PRO assessments. The median age was 60 years, 37% of patients had a bra cup size ≥D, 44% were obese, and 30% received chemotherapy. Through 5 years, there were no significant differences in PROs or cosmesis by treatment arm. A bra cup size ≥D was associated with worse BCTOS cosmesis (P < .001), BCTOS pain (P = .001), FACT-B Trial Outcome Index (P = .03), FACT-B Emotional Well-being (P = .03), and Body Image Scale (P = .003) scores. Physician-rated cosmesis was worse in patients who were overweight (P = .02) or obese (P < .001). No patient subsets experienced better PROs or cosmesis with CF-WBI. CONCLUSIONS: Both CF-WBI and HF-WBI confer similar longitudinal PROs and physician-rated cosmesis through 5 years of follow-up, with no relevant subsets that fared better with CF-WBI. This evidence supports broad adoption of hypofractionation with boost, including in patients receiving chemotherapy and in a population with a high prevalence of obesity. The associations of large breast size and obesity with adverse outcomes across multiple domains highlight the opportunity to engage at-risk patients in lifestyle intervention strategies, as well as to consider alternative radiation treatment regimens.

Organophotocatalytic Aerobic Oxygenation of Phenols in a Visible-Light Continuous-Flow Photoreactor.

A mild photocatalytic phenol oxygenation enabled by a continuous-flow photoreactor using visible light and pressurized air is described herein. Products for wide-ranging applications, including the synthesis of vitamins, were obtained in high yields by precisely controlling principal process parameters. The reactor design permits low organophotocatalyst loadings to generate singlet oxygen. It is anticipated that the efficient aerobic phenol oxygenation to benzoquinones and p-quinols contributes to sustainable synthesis.

Quantitative 3-Dimensional Photographic Assessment of Breast Cosmesis After Whole Breast Irradiation for Early Stage Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial.

PURPOSE: Our purpose was to use 3-dimensional (3D) surface photography to quantitatively measure breast cosmesis within the framework of a randomized clinical trial of conventionally fractionated (CF) and hypofractionated (HF) whole breast irradiation (WBI); to identify how 3D measurements are associated with patient- and physician-reported cosmesis; and to determine whether objective measures of breast symmetry varied by WBI treatment arm or transforming growth factor ß 1 (TGFß1) status. METHODS AND MATERIALS: From 2011 to 2014, 287 women age ≥40 with ductal carcinoma in situ or early-stage invasive breast cancer were enrolled in a multicenter trial and randomized to HF-WBI or CF-WBI with a boost. Three-dimensional surface photography was performed at 3 years posttreatment. Patient-reported cosmetic outcomes were recorded with the Breast Cancer Treatment Outcome Scale. Physician-reported cosmetic outcomes were assessed by the Radiation Therapy Oncology Group scale. Volume ratios and 6 quantitative measures of breast symmetry, termed F1-6C, were calculated using the breast contour and fiducial points assessed on 3D surface images. Associations between all metrics, patient- and physician-reported cosmesis, treatment arm, and TGFß1 genotype were performed using the Kruskal-Wallis test and multivariable logistic regression models. RESULTS: Among 77 (39 CF-WBI and 38 HF-WBI) evaluable patients, both patient- and physician-reported cosmetic outcomes were significantly associated with the F1C vertical symmetry measure (both P < .05). Higher dichotomized F1C and volumetric symmetry measures were associated with improved patient- and physician-reported cosmesis on multivariable logistic regression (both P ≤ .05). There were no statistically significant differences in vertical symmetry or volume measures between treatment arms. Increased F6C horizontal symmetry was observed in the CF-WBI arm (P = .05). Patients with the TGFß1 C-509T variant allele had lower F2C vertical symmetry measures (P = .02). CONCLUSIONS: Quantitative 3D image-derived measures revealed comparable cosmetic outcomes with HF-WBI compared with CF-WBI. Our findings suggest that 3D surface imaging may be a more sensitive method for measuring subtle cosmetic changes than global patient- or physician-reported assessments.

Association Between 21-Gene Assay Recurrence Score and Locoregional Recurrence Rates in Patients With Node-Positive Breast Cancer.

Importance: The 21-gene assay recurrence score is increasingly used to personalize treatment recommendations for systemic therapy in postmenopausal women with estrogen receptor (ER)- or progesterone receptor (PR)-positive, node-positive breast cancer; however, the relevance of the 21-gene assay to radiotherapy decisions remains uncertain. Objective: To examine the association between recurrence score and locoregional recurrence (LRR) in a postmenopausal patient population treated with adjuvant chemotherapy followed by tamoxifen or tamoxifen alone. Design, Setting, and Participants: This cohort study was a retrospective analysis of the Southwest Oncology Group S8814, a phase 3 randomized clinical trial of postmenopausal women with ER/PR-positive, node-positive breast cancer treated with tamoxifen alone, chemotherapy followed by tamoxifen, or concurrent tamoxifen and chemotherapy. Patients at North American clinical centers were enrolled from June 1989 to July 1995. Medical records from patients with recurrence score information were reviewed for LRR and radiotherapy use. Primary analysis included 316 patients and excluded 37 who received both mastectomy and radiotherapy, 9 who received breast-conserving surgery without documented radiotherapy, and 5 with unknown surgical type. All analyses were performed from January 22, 2016, to August 9, 2019. Main Outcomes and Measures: The LRR was defined as a recurrence in the breast; chest wall; or axillary, infraclavicular, supraclavicular, or internal mammary lymph nodes. Time to LRR was tested with log-rank tests and Cox proportional hazards regression for multivariate models. Results: The final cohort of this study comprised 316 women with a mean (range) age of 60.4 (44-81) years. Median (interquartile range) follow-up for those without LRR was 8.7 (7.0-10.2) years. Seven LRR events (5.8%) among 121 patients with low recurrence score and 27 LRR events (13.8%) among 195 patients with intermediate or high recurrence score occurred. The estimated 10-year cumulative incidence rates were 9.7% for those with a low recurrence score and 16.5% for the group with intermediate or high recurrence score (P = .02). Among patients who had a mastectomy without radiotherapy (n = 252), the differences in the 10-year actuarial LRR rates remained significant: 7.7 % for the low recurrence score group vs 16.8% for the intermediate or high recurrence score group (P = .03). A multivariable model controlling for randomized treatment, number of positive nodes, and surgical type showed that a higher recurrence score was prognostic for LRR (hazard ratio [HR], 2.36; 95% CI, 1.02-5.45; P = .04). In a subset analysis of patients with a mastectomy and 1 to 3 involved nodes who did not receive radiation therapy, the group with a low recurrence score had a 1.5% rate of LRR, whereas the group with an intermediate or high recurrence score had a 11.1% LRR (P = .051). Conclusions and Relevance: This study found that higher recurrence scores were associated with increased LRR after adjustment for treatment, type of surgical procedure, and number of positive nodes. This finding suggests that the recurrence score may be used, along with accepted clinical variables, to assess the risk of LRR during radiotherapy decision-making.

Excellent Locoregional Control in Inflammatory Breast Cancer With a Personalized Radiation Therapy Approach.

PURPOSE: Inflammatory breast cancer (IBC) has been characterized by high locoregional recurrence (LRR) rates even after trimodality therapy. We recently reported excellent locoregional control among patients treated since formal dedication of an IBC-specific clinic and research program in 2006. Institutionally, a standard twice-daily (BID) dose escalation regimen for all patients with IBC was de-escalated in select cases in 2006 after review demonstrated that young age, incomplete response to neoadjuvant therapy, and positive margins identified subsets with maximal benefit from dose escalation. We report local control and toxicity rates specific to BID versus once-daily (QD) radiation therapy approaches. METHODS AND MATERIALS: From a prospectively collected database, we identified 103 patients with nonmetastatic IBC who received trimodality therapy at our institution from 2007 to 2015. Descriptive statistics were used to describe the study cohort and compare retrospectively extracted rates of radiation therapy-associated toxicity. The actuarial rate of LRR-free survival was analyzed using the Kaplan-Meier method. RESULTS: The median follow-up is 3.6 years. Thirty-nine patients (37.9%) received postmastectomy radiation therapy (PMRT) to the chest wall and undissected regional lymphatics in QD fractions (median dose, 50.0 Gy in 25 fractions [fx]; median boost dose, 10.0 Gy in 5 fx) and 64 patients (62.1%) received BID PMRT (median dose, 51.0 Gy in 34 fx; median boost dose, 15.0 Gy in 10 fx). Crude rates of toxicity were not different between patients treated with QD or BID PMRT. Two BID patients (3.1%) and no QD patients (0.0%) experienced LRR (P = .53). The 3- and 5-year LRR-free survival were 95.1% and 100.0% for BID and QD patients, respectively (P = .25). CONCLUSIONS: Tailoring radiation therapy to clinical risk factors was associated with excellent locoregional control. De-escalation of PMRT from BID to QD was not clearly associated with reduced toxicity compared with BID, although retrospective data collection may limit this comparison.

Impact of Radiation on Locoregional Control in Women with Node-Positive Breast Cancer Treated with Neoadjuvant Chemotherapy and Axillary Lymph Node Dissection: Results from ACOSOG Z1071 Clinical Trial.

PURPOSE: Use of adjuvant radiation therapy (RT) after neoadjuvant chemotherapy (NAC) in node-positive breast cancer (BC) is highly variable. In ACOSOG Z1071, RT after NAC was used at the discretion of treating physicians. Herein, we report the impact of RT and pathologic response on locoregional recurrence (LRR) after NAC. METHODS AND MATERIALS: ACOSOG Z1071 enrolled women with cT0-4N1-2 BC treated with NAC from 2009 to 2011. Patients underwent sentinel node surgery and completion axillary lymph node dissection. The RT was at the discretion of the treating physicians. Patient outcomes were analyzed as a function of clinical-pathologic factors and use of RT. RESULTS: Of 701 eligible patients, mastectomy was performed in 423 (59.6%) and breast-conserving surgery in 277 (40.4%). After NAC, residual disease was observed in 506 (72.2%), and 195 (27.8%) had a pathologic complete response. Of the patients, 591 (85.3%) received adjuvant RT and 102 (14.7%) did not. Median follow-up was 5.9 years. Forty-three patients (6.1%) experienced LRR, 145 (20.7%) experienced distant metastasis, and 142 (20.4%) died. Patients with pathologic complete response had the best LRR-relapse-free survival (hazard ratio [HR], 0.32; 95% confidence interval, 0.12-0.81; P = .016), distant metastasis-free survival (HR, 0.31; 95% CI, 0.19-0.52; P < .0001), BC-specific survival (HR, 0.34; 95% CI, 0.19-0.59; P = .0001) and overall survival (HR, 0.39; 95% CI, 0.240-0.63; P = .001) compared to patients with residual disease after NAC. Patients with triple-negative BC had a higher LRR rate compared to those with hormone receptor-positive BC (HR, 5.91; 95% CI, 2.80-12.49). There was a trend toward lower LRR with the use of postmastectomy and regional nodal RT, but there was no impact on overall, disease-free, or BC-specific survival. CONCLUSION: In the ACOSOG Z1071 trial, in which the use of RT after NAC was at the discretion of the treating physicians, RT was associated with a trend toward decreased LRR. There was no association of RT with overall survival, BC-specific survival, or Disease Specific Survival. Triple-negative BC was associated with higher locoregional relapse rates.

Outcomes of Curative-Intent Treatment for Patients With Breast Cancer Presenting With Sternal or Mediastinal Involvement.

PURPOSE: Optimal treatment of patients diagnosed with de novo metastatic breast cancer limited to the mediastinum or sternum has never been delineated. Herein, we sought to determine the efficacy of multimodality treatment, including metastasis-directed radiation therapy, in curing patients with this presentation. METHODS AND MATERIALS: This is a single-institution retrospective cohort study of patients with de novo metastatic breast cancer treated from 2005 to 2014, with a 50-month median follow-up for the primary cohort. The primary patient cohort had metastasis limited to the mediastinum/sternum treated with curative intent (n = 35). We also included a cohort of patients with stage IIIC disease treated with curative intent (n = 244). Additional groups included a mediastinal/sternal palliative cohort (treatment did not include metastasis-directed radiation therapy; n = 14) and all other patients with de novo stage IV disease (palliative cohort; n = 1185). The primary study outcomes included locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), which were calculated using the Kaplan-Meier method. Cox multivariable models compared survival outcomes across treatment cohorts adjusted for molecular subtype, age, and race. RESULTS: For the mediastinal/sternal curative-intent cohort, 5-year LRRFS was 85%, RFS was 52%, and OS was 63%. After adjustment, there was no statistically significant difference in LRRFS (hazard ratio [HR], 0.39; 95% confidence interval [CI], 0.13-1.13; P = .08), RFS (HR, 0.87; 95% CI 0.50-1.49; P = .61), or OS (HR, 0.79; 95% CI 0.44-1.43; P = .44) between the stage IIIC cohort and the mediastinal/sternal curative-intent cohort (referent). In contrast, RFS was worse for the mediastinal/sternal palliative cohort (HR, 2.29; 95% CI 1.05-5.00; P = .04). OS was worst for the de novo stage IV palliative cohort (HR, 2.61; 95% CI 1.50-4.53; P < .001). CONCLUSIONS: For select patients presenting with breast cancer metastatic to the sternum and/or mediastinum, curative-intent treatment with chemotherapy, surgery, and radiation yields outcomes similar to those of stage IIIC disease and superior to de novo stage IV breast cancer treated with palliative intent.

Adjuvant Endocrine Therapy for Women With Hormone Receptor-Positive Breast Cancer: ASCO Clinical Practice Guideline Focused Update.

PURPOSE: To update the ASCO clinical practice guideline on adjuvant endocrine therapy based on emerging data about the optimal duration of aromatase inhibitor (AI) treatment. METHODS: ASCO conducted a systematic review of randomized clinical trials from 2012 to 2018. Guideline recommendations were based on the Panel's review of the evidence from six trials. RESULTS: The six included studies of AI treatment beyond 5 years of therapy demonstrated that extension of AI treatment was not associated with an overall survival advantage but was significantly associated with lower risks of breast cancer recurrence and contralateral breast cancer compared with placebo. Bone-related toxic effects were more common with extended AI treatment. RECOMMENDATIONS: The Panel recommends that women with node-positive breast cancer receive extended therapy, including an AI, for up to a total of 10 years of adjuvant endocrine treatment. Many women with node-negative breast cancer should consider extended therapy for up to a total of 10 years of adjuvant endocrine treatment based on considerations of recurrence risk using established prognostic factors. The Panel noted that the benefits in absolute risk of reduction were modest and that, for lower-risk node-negative or limited node-positive cancers, an individualized approach to treatment duration that is based on considerations of risk reduction and tolerability was appropriate. A substantial portion of the benefit for extended adjuvant AI therapy was derived from prevention of second breast cancers. Shared decision making between clinicians and patients is appropriate for decisions about extended adjuvant endocrine treatment, including discussions about the absolute benefits in the reduction of breast cancer recurrence, the prevention of second breast cancers, and the impact of adverse effects of treatment. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Accelerated partial breast irradiation: Current status with a focus on clinical practice.

Accelerated partial breast irradiation (APBI), a radiation technique in which only the tumor bed is treated, has now become an acceptable radiation modality for selected early-stage breast cancer patients. Compared to conventional whole breast irradiation (WBI), APBI has some benefits with regard to the reduced total irradiated breast volume and the shorter treatment time. The role of APBI, which can be delivered using diverse techniques, has been evaluated in several prospective randomized phase III trials. These clinical trials demonstrate diverging outcomes relating to local recurrence, while establishing comparable effect in terms of survival between APBI with WBI. The aim of this study was to review the current status of APBI with a focus on clinical practice.

Optimizing Patient Positioning to Reduce Variation in the Measurement of Breast Cancer-Related Lymphedema.

Background: Prospective lymphedema screening is recommended for breast cancer patients. We observed interoperator variation in perometer-acquired arm volume measurements (P-AVMs) due to patient instability during measurements. We hypothesized that improved positioning during perometry would reduce P-AVM variability. Methods and Results: Each arm was measured three times by each operator using a perometer. With the original configuration, P-AVM was performed by 2 operators in 30 patients and four cohorts of 5 to 6 operators in 5 volunteers. Repeatability, reproducibility, and gage precision/tolerance (P/T) ratio were calculated. A customized handlebar was installed to optimize patient positioning. P-AVMs were performed in 20 patients with both configurations. Student's t-test was used to compare variation. With the new configuration, P-AVMs were performed by three operators in five volunteers and five operators in three volunteers. Repeatability, reproducibility, and gage P/T ratio were calculated. For the original configuration, gage P/T ratio was 19.9% for two operators and 35.9% for four cohorts of five to six operators. One operator using the new handlebar decreased P-AVM variability by 28% (p = 0.02). For the new configuration, gage P/T ratio was 6.5% for three operators and 18.7% for five operators. Conclusions: Optimizing patient setup improved P-AVM accuracy. P-AVM accuracy is critical as lack of accuracy results in either overdiagnosis or underdiagnosis of lymphedema, which in turn results in either over- or undertreatment of this dreaded condition. A higher number of operators were associated with greater P-AVM variability.