Premastectomy Radiotherapy and Immediate Breast Reconstruction: A Randomized Clinical Trial.

Importance: Premastectomy radiotherapy (PreMRT) is a new treatment sequence to avoid the adverse effects of radiotherapy on the final breast reconstruction while achieving the benefits of immediate breast reconstruction (IMBR). Objective: To evaluate outcomes among patients who received PreMRT and regional nodal irradiation (RNI) followed by mastectomy and IMBR. Design, Setting, and Participants: This was a phase 2 single-center randomized clinical trial conducted between August 3, 2018, and August 2, 2022, evaluating the feasibility and safety of PreMRT and RNI (including internal mammary lymph nodes). Patients with cT0-T3, N0-N3b breast cancer and a recommendation for radiotherapy were eligible. Intervention: This trial evaluated outcomes after PreMRT followed by mastectomy and IMBR. Patients were randomized to receive either hypofractionated (40.05 Gy/15 fractions) or conventionally fractionated (50 Gy/25 fractions) RNI. Main Outcome and Measures: The primary outcome was reconstructive failure, defined as complete autologous flap loss. Demographic, treatment, and outcomes data were collected, and associations between multiple variables and outcomes were evaluated. Analysis was performed on an intent-to-treat basis. Results: Fifty patients were enrolled. Among 49 evaluable patients, the median age was 48 years (range, 31-72 years), and 46 patients (94%) received neoadjuvant systemic therapy. Twenty-five patients received 50 Gy in 25 fractions to the breast and 45 Gy in 25 fractions to regional nodes, and 24 patients received 40.05 Gy in 15 fractions to the breast and 37.5 Gy in 15 fractions to regional nodes, including internal mammary lymph nodes. Forty-eight patients underwent mastectomy with IMBR, at a median of 23 days (IQR, 20-28.5 days) after radiotherapy. Forty-one patients had microvascular autologous flap reconstruction, 5 underwent latissimus dorsi pedicled flap reconstruction, and 2 had tissue expander placement. There were no complete autologous flap losses, and 1 patient underwent tissue expander explantation. Eight of 48 patients (17%) had mastectomy skin flap necrosis of the treated breast, of whom 1 underwent reoperation. During follow-up (median, 29.7 months [range, 10.1-65.2 months]), there were no locoregional recurrences or distant metastasis. Conclusions and Relevance: This randomized clinical trial found PreMRT and RNI followed by mastectomy and microvascular autologous flap IMBR to be feasible and safe. Based on these results, a larger randomized clinical trial of hypofractionated vs conventionally fractionated PreMRT has been started (NCT05774678). Trial Registration: ClinicalTrials.gov Identifier: NCT02912312.

A phase II clinical trial of frameless, fractionated stereotactic radiation therapy for brain metastases.

Stereotactic radiation therapy yields high rates of local control for brain metastases, but patients in rural or suburban areas face geographic and socioeconomic barriers to its access. We conducted a phase II clinical trial of frameless, fractionated stereotactic radiation therapy for brain metastases in an integrated academic satellite network for patients 18 years of age or older with 4 or fewer brain metastases. Dose was based on gross tumor volume: less than 3.0 cm, 27 Gy in 3 fractions and 3.0 to 3.9 cm, 30 Gy in 5 fractions. Median follow-up was 10 months for 73 evaluable patients, with a median age of 68 years. Median intracranial progression-free survival was 7.1 months (95% confidence interval = 5.3 to not reached), and median survival was 7.2 months (95% confidence interval = 5.4 to not reached); there were no serious adverse events. Outcomes of this trial compare favorably with contemporary trials, and this treatment strategy provides opportunities to expand stereotactic radiation therapy access to underserved populations.

Optimizing Preventive Adjuvant Linac-Based (OPAL) Radiation: A Phase 2 Trial of Daily Partial Breast Irradiation.

PURPOSE: Evidence supports use of partial-breast irradiation (PBI) in the management of early breast cancer, but the optimal dose-fractionation remains unsettled. METHODS AND MATERIALS: We conducted a phase 2 clinical trial (OPAL trial) to evaluate a novel PBI dosing schedule of 35 Gy in 10 daily fractions. Patients with close (<2 mm) margins also received a boost of 9 Gy in 3 fractions. Eligible patients underwent margin-negative lumpectomy for ductal carcinoma in situ or estrogen receptor-positive invasive breast cancer, up to 3 cm, pTis-T2 N0. The primary outcome was any grade ≥2 toxic effect occurring from the start of radiation through 6 months of follow-up. Secondary outcomes included patient-reported cosmesis, breast pain, and functional status, measured using the Breast Cancer Treatment Outcomes Scale, and physician-reported cosmesis, measured using the Radiation Therapy and Oncology Group scale. The Cochran-Armitage trend test and multivariable mixed-effects longitudinal growth curve models compared outcomes for the OPAL study population with those for a control group of similar patients treated with whole-breast irradiation (WBI) plus boost. RESULTS: All 149 patients enrolled on the OPAL trial received the prescribed dose, and 17.4% received boost. The median age was 64 years; 83.2% were White, and 73.8% were overweight or obese. With median follow-up of 2.0 years, 1 patient (0.7%) experienced in-breast recurrence. Prevalence of the primary toxicity outcome was 17.4% (26 of 149 patients) in the OPAL trial compared with 72.7% (128 of 176 patients) in the control WBI-plus-boost cohort (P < .001). In longitudinal multivariable analysis, treatment on the OPAL trial was associated with improved patient-reported cosmesis (P < .001), functional status (P = .004), breast pain (P = .004), and physician-reported cosmesis (P < .001). CONCLUSIONS: Treatment with daily PBI was associated with substantial reduction in early toxicity and improved patient- and physician-reported outcomes compared with WBI plus boost. Daily external-beam partial-breast irradiation with 13 or fewer fractions merits further prospective evaluation.

Physician Perspectives on Telemedicine in Radiation Oncology.

Purpose: Telemedicine enthusiasm and uptake in radiation oncology rapidly increased during the COVID-19 pandemic, but it is unclear if and how telemedicine should be used after the COVID-19 public health emergency ends is unclear. Herein, we report on our institution's provider experience after the mature adoption of telemedicine. Methods and Materials: We distributed a survey to all radiation oncology attending physicians at our institution in October 2021 to assess satisfaction, facilitators, and barriers to telemedicine implementation. We performed quantitative and qualitative analyses to characterize satisfaction and identify influencing factors whether telemedicine is employed. We calculated the average proportion of visits that providers expected to be appropriately performed with telemedicine for each disease site and visit type. Results: A total of 60 of the 82 eligible radiation oncologists (73%) responded to the survey, of whom 78% were satisfied with telemedicine in the radiation oncology department and 83% wished to continue offering video visits after the COVID-19 public health emergency ends. Common patient factors influencing whether physicians offer telemedicine include the patient's travel burden, patient preferences, and whether a physical examination is required. Approximately 20% of new consultations and 50% of weekly management visits were estimated to be appropriate for telemedicine. The central nervous system/pediatrics and thoracic faculty considered telemedicine appropriate for the greatest proportion of new consultations, and 93% of respondents felt comfortable determining whether telemedicine was appropriate. Conclusions: Surveyed radiation oncologists were satisfied with telemedicine in their practice, and wished to continue offering video visits in the future. Our data suggest that payers should continue to support this patient-centered technology.

Contemporary Outcomes After Multimodality Therapy in Patients With Breast Cancer Presenting With Ipsilateral Supraclavicular Node Involvement.

PURPOSE: Patients with breast cancer and ipsilateral supraclavicular (SCV) node involvement at the time of diagnosis (TNM cN3c) have historically had poor outcomes. Radiation therapy (RT) has an important role because SCV nodes are not routinely surgically dissected. However, optimal locoregional management, contemporary outcomes, and prognostic factors are not well defined. METHODS AND MATERIALS: We reviewed the data of patients with cN3c breast cancer treated at our institution between 2014 and 2019 with curative intent, including neoadjuvant chemotherapy, surgery, and adjuvant RT. All patients received comprehensive regional RT, including to the SCV nodes. Institutional guidelines recommend a 10-Gy or 16-Gy boost to resolved and unresolved N3 nodes, respectively. Overall survival (OS), recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS), and supraclavicular recurrence-free survival (SCRFS) were analyzed. RESULTS: Data from 173 consecutive patients were analyzed with a median follow-up time of 2.8 years. The median age was 54 years, 76 patients (44%) were estrogen receptor positive/human epidermal growth factor receptor 2 negative, 100 patients (58%) had T3/4 disease, and 10 patients (6%) underwent a neck dissection. In addition, 156 patients (90%) received a cumulative SCV dose of ≥60 Gy. The 5-year OS, SCRFS, LRRFS, and RFS rates were 73%, 95%, 86%, and 50%, respectively. The 5-year OS rate for a cumulative SCV dose of ≥60 Gy versus <60 Gy was 75% versus 39% (P = .04). In the multivariable analysis, a cumulative SCV dose of ≥60 Gy, extranodal extension, receptor status, and Eastern Cooperative Oncology Group performance status were associated with OS. The 5-year SCRFS rates with and without neck dissection were 100% versus 95% (P = .57). Among patients with a postchemotherapy SCV node size of ≥1 cm without neck dissection, the 5-year SCRFS rate was 83%. CONCLUSIONS: In one of the largest series of patients with cN3c breast cancer, multimodality therapy using adjuvant RT with a SCV boost resulted in a 5-year LRRFS rate of 86%. There is a limited role for neck dissection as the 5-year SCRFS rate was 95% overall and 83% for residual SCV disease ≥1 cm after chemotherapy with RT alone. A cumulative SCV dose of ≥60 Gy was associated with improved OS, but not SCRFS, LRRFS, or RFS. A SCV boost should be considered in these patients as treatment was well-tolerated. Despite advances in systemic therapy, nearly half of patients developed distant metastases, highlighting the need for close observation after treatment.

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.

Implementation of a stereotactic body radiotherapy program for unresectable pancreatic cancer in an integrated community academic radiation oncology satellite network.

With increasing interest in stereotactic body radiotherapy (SBRT) for unresectable pancreatic cancer, quality improvement (QI) initiatives to develop integrated clinical workflows are crucial to ensure quality assurance (QA) when introducing this challenging technique into radiation practices. MATERIALS/METHODS: In 2017, we used the Plan, Do, Study, Act (PDSA) QI methodology to implement a new pancreas SBRT program in an integrated community radiation oncology satellite. A unified integrated information technology infrastructure was used to virtually integrate the planned workflow into the community radiation oncology satellite network (P - Plan/D - Do). This workflow included multiple prospective quality assurance (QA) measures including multidisciplinary evaluation, prospective scrutiny of radiation target delineation, prospective radiation plan evaluation, and monitoring of patient outcomes. Institutional review board approval was obtained to retrospectively study and report outcomes of patients treated in this program (S - Study). RESULTS: There were 12 consecutive patients identified who were treated in this program from 2017 to 2020 with a median follow-up of 27 months. The median survival was 13 months, median local failure free survival was 12 months and median progression free survival was 6 months from SBRT. There were no acute or late Common Terminology Criteria for Adverse Effects (CTCAE) version 5 toxicities ≥ Grade 3. CONCLUSION: We report the successful implementation of a community pancreas SBRT program involving multiple prospective QA measures, providing the groundwork to safely expand access to pancreas SBRT in our community satellite network (A - Act).

Radiation Oncology Strategies to Flatten the Curve During the Coronavirus Disease 2019 (COVID-19) Pandemic: Experience From a Large Tertiary Cancer Center.

During the coronavirus disease 2019 pandemic, minimizing exposure risk for patients with cancer and health care personnel was of utmost importance. Here, we present steps taken to date to flatten the curve at the radiation oncology division of a tertiary cancer center with the goal of mitigating risk of exposure among patients and staff, and optimizing resource utilization. Response to the coronavirus disease 2019 pandemic in this large tertiary referral center included volume reduction, personal protective equipment recommendations, flexible clinic visit interaction types dictated by need and risk reduction, and numerous social distancing strategies. We hope these outlined considerations can assist the wider radiation oncology community as we collectively face this ongoing challenge.

Mitigating the impact of COVID-19 on oncology: Clinical and operational lessons from a prospective radiation oncology cohort tested for COVID-19.

BACKGROUND AND PURPOSE: The COVID-19 pandemic warrants operational initiatives to minimize transmission, particularly among cancer patients who are thought to be at high-risk. Within our department, a multidisciplinary tracer team prospectively monitored all patients under investigation, tracking their test status, treatment delays, clinical outcomes, employee exposures, and quarantines. MATERIALS AND METHODS: Prospective cohort tested for SARS-COV-2 infection over 35 consecutive days of the early pandemic (03/19/2020-04/22/2020). RESULTS: A total of 121 Radiation Oncology patients underwent RT-PCR testing during this timeframe. Of the 7 (6%) confirmed-positive cases, 6 patients were admitted (4 warranting intensive care), and 2 died from acute respiratory distress syndrome. Radiotherapy was deferred or interrupted for 40 patients awaiting testing. As the median turnaround time for RT-PCR testing decreased from 1.5 (IQR: 1-4) to ≤1-day (P < 0.001), the median treatment delay also decreased from 3.5 (IQR: 1.75-5) to 1 business day (IQR: 1-2) [P < 0.001]. Each patient was an exposure risk to a median of 5 employees (IQR: 3-6.5) through prolonged close contact. During this timeframe, 39 care-team members were quarantined for a median of 3 days (IQR: 2-11), with a peak of 17 employees simultaneously quarantined. Following implementation of a "dual PPE policy," newly quarantined employees decreased from 2.9 to 0.5 per day. CONCLUSION: The severe adverse events noted among these confirmed-positive cases support the notion that cancer patients are vulnerable to COVID-19. Active tracking, rapid diagnosis, and aggressive source control can mitigate the adverse effects on treatment delays, workforce incapacitation, and ideally outcomes.

Evaluation and Improvement of Bottlenecking in a Multidisciplinary Oncology Clinic: An Electronic Medical Record Intervention.

PURPOSE: Clinic members reported slower patient flow in the mornings at a multidisciplinary oncology clinic. This study identified the causes of clinic bottlenecking via analysis of patient schedules and transit times, then corrected discrepancies through a quality improvement program. METHODS: Transit times were measured using tracking cards handed out at check-in, marked by each clinic member throughout the encounter, and collected upon discharge. Data were analyzed for differences between morning and afternoon patients, and a Pareto chart was formulated to assess for discrepancies in distribution. Repeat plan-do-study-act (PDSA) cycles were conducted, implementing two changes to redistribute appointments to optimize clinic workflow. RESULTS:  A total of 2951 patient appointments were analyzed: 589 at baseline, 277 following an initial intervention, and 2085 following a subsequent intervention. Analysis of patient transit times revealed no significant differences between morning and afternoon patient groups (t-test, p=.13-.99), with no transit interval markedly longer than others (t-test, p=.32-.83). However, upon evaluation of appointment times, a maldistribution was noted with 57% of patients concentrated between 9:00 am to 12:00 pm, accounting for the perception of bottlenecking. An initial intervention offering patients afternoon appointments on a voluntary basis was insufficient for rebalancing distribution (chi-square test, p=.299); however, an electronic medical record (EMR) intervention with rigid appointment templates was successful (chi-square test, p<.001). CONCLUSION: An imbalance of appointment times contributed to the perception of slow clinic throughput. This study emphasizes the importance of systematically investigating even consensus observations for validity prior to costly interventions. Furthermore, these results support the utility of information technology in optimizing clinic workflow.

Prospective Comparison of Toxicity and Cosmetic Outcome After Accelerated Partial Breast Irradiation With Conformal External Beam Radiotherapy or Single-Entry Multilumen Intracavitary Brachytherapy.

PURPOSE: This study aimed to prospectively characterize toxicity and cosmesis after accelerated partial breast irradiation (APBI) with 3-dimensional conformal radiation therapy (CRT) or single-entry, multilumen, intracavitary brachytherapy. METHODS AND MATERIALS: A total of 281 patients with pTis, pT1N0, or pT2N0 (≤3.0 cm) breast cancer treated with segmental mastectomy were prospectively enrolled from December 2008 through August 2014. APBI was delivered using 3-dimensional CRT (n = 29) or with SAVI (n = 176), Contura (n = 56), or MammoSite (n = 20) brachytherapy catheters. Patients were evaluated at protocol-specified intervals, at which time the radiation oncologist scored cosmetic outcome, toxicities, and recurrence status using a standardized template. RESULTS: The median follow-up time is 41 months. Grade 1 seroma and fibrosis were more common with brachytherapy than with 3-dimensional CRT (50.4% vs 3.4% for seroma; P < .0001 and 66.3% vs 44.8% for fibrosis; P = .02), but grade 1 edema was more common with 3-dimensional CRT than with brachytherapy (17.2% vs 5.6%; P = .04). Grade 2 to 3 pain was more common with 3-dimensional CRT (17.2% vs 5.2%; P = .03). Actuarial 5-year rates of fair or poor radiation oncologist-reported cosmetic outcome were 9% for 3-dimensional CRT and 24% for brachytherapy (P = .13). Brachytherapy was significantly associated with inferior cosmesis on mixed model analysis (P = .003). Significant predictors of reduced risk of adverse cosmetic outcome after brachytherapy were D0.1cc (skin) ≤102%, minimum skin distance >5.1 mm, dose homogeneity index >0.54, and volume of nonconformance ≤0.89 cc. The 5-year ipsilateral breast recurrence was 4.3% for brachytherapy and 4.2% for 3-dimensional CRT APBI patients (P = .95). CONCLUSIONS: Brachytherapy APBI is associated with higher rates of grade 1 fibrosis and seroma than 3-dimensional CRT but lower rates of grade 1 edema and grade 2 to 3 pain than 3-dimensional CRT. Rates of radiation oncologist-reported fair or poor cosmetic outcomes are higher with brachytherapy. We identified dosimetric parameters that predict reduced risk of adverse cosmetic outcome after brachytherapy-based APBI. Ipsilateral breast recurrence was equivalent for brachytherapy and 3-dimensional CRT.

Three-Year Outcomes With Hypofractionated Versus Conventionally Fractionated Whole-Breast Irradiation: Results of a Randomized, Noninferiority Clinical Trial.

PURPOSE: The adoption of hypofractionated whole-breast irradiation (HF-WBI) remains low, in part because of concerns regarding its safety when used with a tumor bed boost or in patients who have received chemotherapy or have large breast size. To address this, we conducted a randomized, multicenter trial to compare conventionally fractionated whole-breast irradiation (CF-WBI; 50 Gy/25 fx + 10 to 14 Gy/5 to 7 fx) with HF-WBI (42.56 Gy/16 fx + 10 to 12.5 Gy/4 to 5 fx). PATIENTS AND METHODS: From 2011 to 2014, 287 women with stage 0 to II breast cancer were randomly assigned to CF-WBI or HF-WBI, stratified by chemotherapy, margin status, cosmesis, and breast size. The trial was designed to test the hypothesis that HF-WBI is not inferior to CF-WBI with regard to the proportion of patients with adverse cosmetic outcome 3 years after radiation, assessed using the Breast Cancer Treatment Outcomes Scale. Secondary outcomes included photographically assessed cosmesis scored by a three-physician panel and local recurrence-free survival. Analyses were intention to treat. RESULTS: A total of 286 patients received the protocol-specified radiation dose, 30% received chemotherapy, and 36.9% had large breast size. Baseline characteristics were well balanced. Median follow-up was 4.1 years. Three-year adverse cosmetic outcome was 5.4% lower with HF-WBI ( Pnoninferiority = .002; absolute risks were 8.2% [n = 8] with HF-WBI v 13.6% [n = 15] with CF-WBI). For those treated with chemotherapy, adverse cosmetic outcome was higher by 4.1% (90% upper confidence limit, 15.0%) with HF-WBI than with CF-WBI; for large breast size, adverse cosmetic outcome was 18.6% lower (90% upper confidence limit, -8.0%) with HF-WBI. Poor or fair photographically assessed cosmesis was noted in 28.8% of CF-WBI patients and 35.4% of HF-WBI patients ( P = .31). Three-year local recurrence-free survival was 99% with both HF-WBI and CF-WBI ( P = .37). CONCLUSION: Three years after WBI followed by a tumor bed boost, outcomes with hypofractionation and conventional fractionation are similar. Tumor bed boost, chemotherapy, and larger breast size do not seem to be strong contraindications to HF-WBI.

Association of Transforming Growth Factor ß Polymorphism C-509T With Radiation-Induced Fibrosis Among Patients With Early-Stage Breast Cancer: A Secondary Analysis of a Randomized Clinical Trial.

Importance: Whether genetic factors can identify patients at risk for radiation-induced fibrosis remains unconfirmed. Objective: To assess the association between the C-509T variant allele in the promoter region of TGFB1 and breast fibrosis 3 years after radiotherapy. Design, Setting, and Participants: This is an a priori-specified, prospective, cohort study nested in an open-label, randomized clinical trial, which was conducted in community-based and academic cancer centers to compare hypofractionated whole-breast irradiation (WBI) (42.56 Gy in 16 fractions) with conventionally fractionated WBI (50 Gy in 25 fractions) after breast-conserving surgery. In total, 287 women 40 years or older with pathologically confirmed stage 0 to IIA breast cancer treated with breast-conserving surgery were enrolled from February 2011 to February 2014. Patients were observed for a minimum of 3 years. Outcomes were compared using the 1-sided Fisher exact test and multivariable logistic regression. Exposures: A C-to-T single-nucleotide polymorphism at position -509 relative to the first major transcription start site (C-509T) of the TGFB1 gene. Main Outcomes and Measures: The primary outcome was grade 2 or higher breast fibrosis as assessed using the Late Effects Normal Tissue/Subjective, Objective, Medical Management, Analytic scale (range, 0 to 3) three years after radiotherapy. Results: Among 287 women enrolled in the trial, TGFB1 genotype and 3-year radiotherapy-induced toxicity data were available for 174 patients, of whom 89 patients (51%) with a mean (SD) age of 60 (8) years had at least 1 copy of C-509T. Grade 2 or higher breast fibrosis was present in 12 of 87 patients with C-509T (13.8%) compared with 3 of 80 patients without the allele variant (3.8%) (absolute difference, 10.0%; 95% CI, 1.7%-18.4%; P = .02). The results of multivariable analyses indicated that only C-509T (odds ratio, 4.47; 95% CI, 1.25-15.99; P = .02) and postoperative cosmetic outcome (odds ratio, 7.09; 95% CI, 2.41-20.90; P < .001) were significantly associated with breast fibrosis risk. Conclusions and Relevance: To date, this study seems to be the first prospective validation of a genomic marker for radiation fibrosis. The C-509T allele in TGFB1 is a key determinant of breast fibrosis risk. Assessing TGFB1 genotype may facilitate a more personalized approach to locoregional treatment decisions in breast cancer. Trial Registration: ClinicalTrials.gov identifier: NCT01266642.

Lower mean heart dose with deep inspiration breath hold-whole breast irradiation compared with brachytherapy-based accelerated partial breast irradiation for women with left-sided tumors.

PURPOSE: For left-sided breast cancer, radiation to the heart is a concern. We present a comparison of mean heart and coronary artery biologically effective dose (BED) between accelerated partial breast irradiation (APBI) and whole breast irradiation with deep inspiration breath-hold technique (DIBH-WBI). METHODS AND MATERIALS: A total of 100 patients with left-sided, early-stage breast cancer were identified. Fifty underwent single-entry catheter-based APBI and 50 underwent DIBH-WBI. The heart, left anterior descending/interventricular branch, left main, and right coronary artery were delineated. BEDs were calculated from APBI treatment plans (34 Gy in 3.4 Gy twice daily fractions) and for 4 separate plans generated for each DIBH-WBI patient: 50 Gy in 25 fractions (50/25), 50/25 + 10/5 boost, 40/15, and 40/15 + 10/5 boost. RESULTS: BED to the heart and coronary vessels were statistically significantly higher with APBI than with any of the DIBH-WBI dose/fractionation schedules. CONCLUSIONS: For women with left-sided early-stage breast cancer, DIBH-WBI resulted in statistically significantly lower mean BED to the heart and coronary vessels compared with APBI. This is likely due to increased physical separation between the heart and tumor bed afforded by the DIBH-WBI technique. Long-term assessment of late effects in these tissues will be required to determine whether these differences are clinically significant.

Longitudinal analysis of patient-reported outcomes and cosmesis in a randomized trial of conventionally fractionated versus hypofractionated whole-breast irradiation.

BACKGROUND: The authors compared longitudinal patient-reported outcomes and physician-rated cosmesis with conventionally fractionated whole-breast irradiation (CF-WBI) versus hypofractionated whole-breast irradiation (HF-WBI) within the context of a randomized trial. METHODS: From 2011 to 2014, a total of 287 women with American Joint Committee on Cancer stage 0 to stage II breast cancer were randomized to receive CF-WBI (at a dose of 50 grays in 25 fractions plus a tumor bed boost) or HF-WBI (at a dose of 42.56 grays in 16 fractions plus a tumor bed boost) after breast-conserving surgery. Patient-reported outcomes were assessed using the Breast Cancer Treatment Outcome Scale (BCTOS), the Functional Assessment of Cancer Therapy-Breast, and the Body Image Scale and were recorded at baseline and 0.5, 1, 2, and 3 years after radiotherapy. Physician-rated cosmesis was assessed at the same time points. Outcomes by treatment arm were compared at each time point using a 2-sided Student t test. Multivariable mixed effects growth curve models assessed the effects of treatment arm and time on longitudinal outcomes. RESULTS: Of the 287 patients enrolled, 149 were randomized to CF-WBI and 138 were randomized to HF-WBI. At 2 years, the Functional Assessment of Cancer Therapy-Breast Trial Outcome Index score was found to be modestly better in the HF-WBI arm (mean 79.6 vs 75.9 for CF-WBI; P = .02). In multivariable mixed effects models, treatment arm was not found to be associated with longitudinal outcomes after adjusting for time and baseline outcome measures (P≥.14). The linear effect of time was significant for BCTOS measures of functional status (P = .001, improved with time) and breast pain (P = .002, improved with time). CONCLUSIONS: In this randomized trial, longitudinal outcomes did not appear to differ by treatment arm. Patient-reported functional and pain outcomes improved over time. These findings are relevant when counseling patients regarding decisions concerning radiotherapy. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2886-2894. © 2016 American Cancer Society.

Practical Implications of the Publication of Consensus Guidelines by the American Society for Radiation Oncology: Accelerated Partial Breast Irradiation and the National Cancer Data Base.

PURPOSE: To examine utilization trends of accelerated partial breast irradiation (APBI) in the American College of Surgeons' National Cancer Database and changes in APBI use after the 2009 publication of the American Society for Radiation Oncology (ASTRO) guidelines. METHODS AND MATERIALS: A total of 399,705 women were identified who were diagnosed from 2004 to 2011 with nonmetastatic invasive breast cancer or ductal carcinoma in situ who were treated with breast-conserving surgery and radiation therapy to the breast. Patients were divided by the type of treatment received (whole breast irradiation or APBI) and by suitability to receive APBI as defined by the ASTRO guidelines. Logistic regression was applied to study APBI use overall and within guideline categorization, and a multivariable model was created to determine predictors of treatment with brachytherapy-based APBI based on guideline categorization. RESULTS: For all patients, APBI use increased, from 3.8% in 2004 to 10.6% in 2011 (P<.0001). Overall rates of APBI utilization were higher among "suitable" than "cautionary"/"unsuitable" patients (14.8% vs 7.1%, P<.0001). The majority of APBI treatment was delivered using brachytherapy, for which use peaked in 2008. Starting in 2009, among "suitable" patients, utilization of APBI via brachytherapy plateaued, whereas for "cautionary"/"unsuitable" patients, treatment with brachytherapy-based APBI declined and then plateaued. CONCLUSION: Use of APBI across all patient groups increased from 2004 through 2008. After publication of the ASTRO APBI guidelines in 2009, rates of brachytherapy-based APBI treatment plateaued among "suitable" patients and declined and then plateaued among "cautionary"/"unsuitable" patients. Our study highlights how large national databases can be used to assess national trends in radiation use in response to the publication of guidelines.

Contralateral breast dose from partial breast brachytherapy.

The purpose of this study was to determine the dose to the contralateral breast during accelerated partial breast irradiation (APBI) and to compare it to external beam-published values. Thermoluminescent dosimeter (TLD) packets were used to measure the dose to the most medial aspect of the contralateral breast during APBI simulation, daily quality assurance (QA), and treatment. All patients in this study were treated with a single-entry, multicatheter device for 10 fractions to a total dose of 34 Gy. A mark was placed on the patient's skin on the medial aspect of the opposite breast. Three TLD packets were taped to this mark during the pretreatment simulation. Simulations consisted of an AP and Lateral scout and a limited axial scan encompassing the lumpectomy cavity (miniscan), if rotation was a concern. After the simulation the TLD packets were removed and the patients were moved to the high-dose-rate (HDR) vault where three new TLD packets were taped onto the patients at the skin mark. Treatment was administered with a Nucletron HDR afterloader using Iridium-192 as the treatment source. Post-treatment, TLDs were read (along with the simulation and QA TLD and a set of standards exposed to a known dose of 6 MV photons). Measurements indicate an average total dose to the contralateral breast of 70 cGy for outer quadrant implants and 181 cGy for inner quadrant implants. Compared to external beam breast tangents, these results point to less dose being delivered to the contralateral breast when using APBI.

Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial.

IMPORTANCE: The most appropriate dose fractionation for whole-breast irradiation (WBI) remains uncertain. OBJECTIVE: To assess acute and 6-month toxic effects and quality of life (QOL) with conventionally fractionated WBI (CF-WBI) vs hypofractionated WBI (HF-WBI). DESIGN, SETTING, AND PARTICIPANTS: Unblinded randomized trial of CF-WBI (n = 149; 50.00 Gy/25 fractions + boost [10.00-14.00 Gy/5-7 fractions]) vs HF-WBI (n = 138; 42.56 Gy/16 fractions + boost [10.00-12.50 Gy/4-5 fractions]) following breast-conserving surgery administered in community-based and academic cancer centers to 287 women 40 years or older with stage 0 to II breast cancer for whom WBI without addition of a third field was recommended; 76% of study participants (n = 217) were overweight or obese. Patients were enrolled from February 2011 through February 2014 and observed for a minimum of 6 months. INTERVENTIONS: Administration of CF-WBI or HF-WBI. MAIN OUTCOMES AND MEASURES: Physician-reported acute and 6-month toxic effects using National Cancer Institute Common Toxicity Criteria, and patient-reported QOL using the Functional Assessment of Cancer Therapy for Patients with Breast Cancer (FACT-B). All analyses were intention to treat, with outcomes compared using the χ2 test, Cochran-Armitage test, and ordinal logistic regression. RESULTS: Of 287 participants, 149 were randomized to CF-WBI and 138 to HF-WBI. Treatment arms were well matched for baseline characteristics, including FACT-B total score (HF-WBI, 120.1 vs CF-WBI, 118.8; P = .46) and individual QOL items such as somewhat or more lack of energy (HF-WBI, 38% vs CF-WBI, 39%; P = .86) and somewhat or more trouble meeting family needs (HF-WBI, 10% vs CF-WBI, 14%; P = .54). Maximum physician-reported acute dermatitis (36% vs 69%; P < .001), pruritus (54% vs 81%; P < .001), breast pain (55% vs 74%; P = .001), hyperpigmentation (9% vs 20%; P = .002), and fatigue (9% vs 17%; P = .02) during irradiation were lower in patients randomized to HF-WBI. The rate of overall grade 2 or higher acute toxic effects was less with HF-WBI than with CF-WBI (47% vs 78%; P < .001). Six months after irradiation, physicians reported less fatigue in patients randomized to HF-WBI (0% vs 6%; P = .01), and patients randomized to HF-WBI reported less lack of energy (23% vs 39%; P < .001) and less trouble meeting family needs (3% vs 9%; P = .01). Multivariable regression confirmed the superiority of HF-WBI in terms of patient-reported lack of energy (odds ratio [OR], 0.39; 95% CI, 0.24-0.63) and trouble meeting family needs (OR, 0.34; 95% CI, 0.16-0.75). CONCLUSIONS AND RELEVANCE: Treatment with HF-WBI appears to yield lower rates of acute toxic effects than CF-WBI as well as less fatigue and less trouble meeting family needs 6 months after completing radiation therapy. These findings should be communicated to patients as part of shared decision making. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01266642.