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There are mixed and limited data regarding radiation therapy (RT) tolerance in carriers of a germline pathogenic or likely pathogenic (P/LP) ATM variant. We investigated RT-related toxic effects in carriers of an ATM variant who received treatment for breast cancer. We identified 71 patients treated with adjuvant RT for breast cancer who were carriers of a variant in ATM: 15 were classified as P/LP and 56 classified as variants of unknown significance (VUS). We additionally identified 205 consecutively treated patients during a similar timeframe who were either confirmed ATM wild type or had no prior genetic testing. RT plans were reviewed. Acute and chronic toxic effects were evaluated using Common Terminology Criteria for Adverse Events version 4.0 criteria. Fisher's exact tests for count data were performed to compare toxic effects between the cohorts (P/LP vs VUS vs control). Wilcoxon rank-sum testing was performed to assess for differences in patient characteristics. The median toxicity follow-up was 19.4 months; median follow-up for the subcohorts was 13.3 months (P/LP), 12.6 months (VUS), and 23.3 months (control). There were no significant differences in radiation plan heterogeneity, receipt of a boost, or size of breast/chest wall planning target volume. There was greater use of hypofractionated RT in the control cohort (P =.023). After accounting for patient- and treatment-related factors that may affect toxic effects, we found no significant differences with respect to acute dermatitis, hyperpigmentation, moist desquamation, breast/chest wall pain, or breast edema. Additionally, we found no significant differences with respect to chronic breast/chest wall pain, induration, telangiectasia, or cosmetic outcome. RT as part of the management of breast cancer was well tolerated in carriers of a P/LP ATM variant, with toxic effect profiles that were similar to those seen in patients without known ATM mutations. High rates of excellent or good cosmesis were observed in carriers of a P/LP ATM variant who underwent breast conservation. [ABSTRACT FROM AUTHOR]

Adoption of hypofractionated whole breast irradiation (HWBI) for patients with early-stage, biologically high-risk breast cancer remains relatively low. We compared clinical outcomes of conventionally fractionated whole breast irradiation (CWBI) versus moderate HWBI in this patient population. We queried a prospectively maintained database for patients with early-stage (T1-2, N0, M0) breast cancer who received whole breast irradiation with either CWBI or moderate HWBI at a single institution. We included only patients with biologically high-risk tumors (defined as either estrogen receptor/progesterone receptor/human epidermal growth factor receptor 2 negative, human epidermal growth factor receptor 2 amplified, and/or patients with a high-risk multigene assay) who received systemic chemotherapy. Inverse probability of treatment weighting was used to compare treatment cohorts and to estimate 5-year time to event endpoints. Hazard ratios (HR) and 95% confidence interval (CI) were determined based on Cox proportional hazards model. We identified 300 patients, of whom 171 received CWBI and 129 received HWBI. There was a statistically significant difference in median age at diagnosis, 59 years for CWBI versus 63 years for HWBI (P =.004), and in median follow-up time, 97 months for CWBI versus 55 months for HWBI (P <.001). After accounting for differences in patient and tumor characteristics with inverse probability of treatment weighting, we found similar 5-year freedom from local recurrence (HR, 0.76; 95% CI, 0.14-4.1), freedom from regional recurrence (HR, 3.395% CI 0.15-69), freedom from distant metastasis (HR 3.9, 95% CI 0.86-17), and disease-free survival (HR 0.84; 95% CI, 0.3-2.4), between those treated with CWBI and those treated with HWBI. Results were similar among each of the 3 high-risk subtypes. Our data support the use of moderate HWBI in patients with early-stage, biologically high-risk breast cancer. [ABSTRACT FROM AUTHOR]

Purpose: Shorter courses of accelerated partial-breast irradiation delivered as single-fraction intraoperative therapy are now offered as an alternative to 4 to 6 weeks of whole-breast irradiation after lumpectomy. However, this approach has potential shortcomings in patient selection and target volume definition and in dosimetric, radiobiological, and logistical issues. We designed a prospective, phase 2, multi-institution clinical trial to study 2- or 3-day accelerated partial breast irradiation delivered with brachytherapy applicators.Methods and Materials: This trial treats select breast cancers after breast-conserving surgery with brachytherapy applicators that deliver 22.5 Gy in 3 fractions of 7.5 Gy. The planning treatment volume was 1 to 1.5 cm beyond the surgical cavity. Eligible women were aged ≥45 years with unicentric invasive or in situ tumors ≤3.0 cm with positive estrogen or progesterone receptors and no metastasis to axillary nodes that have been excised with negative margins. Strict dosimetric parameters were required to be met before acceptance into the trial.Results: A group of 200 patients was prospectively enrolled and followed for a minimum of 6 months. Two- or 3-day brachytherapy was associated with low acute or subacute toxicity, 97.25% excellent or good cosmetic outcomes, and excellent local control in select breast cancers.Conclusions: Ultrashort breast brachytherapy is dosimetrically feasible and can be delivered with excellent short-term tolerance and low toxicity. [ABSTRACT FROM AUTHOR]

Purpose Brachytherapy-based APBI (bAPBI) shortens treatment duration and limits dose to normal tissue. While studies have demonstrated similar local control when comparing bAPBI and whole breast irradiation using intensity modulated radiotherapy (WBI-IMRT), comparison of late side effects is limited. Here, we report chronic toxicity profiles associated with these two treatment modalities. Methods 1034 patients with early stage breast cancer were treated at a single institution; 489 received standard-fractionation WBI-IMRT between 2000 and 2013 and 545 received bAPBI (interstitial 40%, applicator-based 60%) between 1993 and 2013. Chronic toxicity was evaluated ≥6 months utilizing CTCAE version 3.0; cosmesis was evaluated using the Harvard scale. Results Median follow-up was 4.6 years (range 0.1–13.4) for WBI-IMRT versus 6.7 years (range 0.1–20.1) for bAPBI (p < 0.001). Compared to WBI-IMRT, bAPBI was associated with higher rates of ≥grade 2 seroma formation (14.4% vs 2.9%, p < 0.001), telangiectasia (12.3% vs 2.1%, p = 0.002) and symptomatic fat necrosis (10.2% vs 3.6%, p < 0.001). Lower rates of hyperpigmentation were observed (5.8% vs 14.5%; p = 0.001). Infection rates were similar (3.3% vs 1.3%, p = 0.07). There was no difference between rates of fair (6.1% vs. 4.1%, p = 0.30) or poor (0.2% vs. 0.5%, p = NS) cosmesis. Mastectomy rates for local recurrence (3.1% for WBI-IMRT and 1.2% for bAPBI, p = 0.06), or for other reasons (0.8% and 0.6%, p = 0.60) were similar between groups. Conclusion With 5-year follow-up, WBI-IMRT and bAPBI are associated with similar, acceptable rates of toxicity. These data further support the utilization of bAPBI as a modality to deliver adjuvant radiation in a safe and efficacious manner. [ABSTRACT FROM AUTHOR]

Purpose To develop a nomogram taking into account clinicopathologic features to predict locoregional recurrence (LRR) in patients treated with accelerated partial-breast irradiation (APBI) for early-stage breast cancer. Methods and Materials A total of 2000 breasts (1990 women) were treated with APBI at William Beaumont Hospital (n=551) or on the American Society of Breast Surgeons MammoSite Registry Trial (n=1449). Techniques included multiplanar interstitial catheters (n=98), balloon-based brachytherapy (n=1689), and 3-dimensional conformal radiation therapy (n=213). Clinicopathologic variables were gathered prospectively. A nomogram was formulated utilizing the Cox proportional hazards regression model to predict for LRR. This was validated by generating a bias-corrected index and cross-validated with a concordance index. Results Median follow-up was 5.5 years (range, 0.9-18.3 years). Of the 2000 cases, 435 were excluded because of missing data. Univariate analysis found that age <50 years, pre-/perimenopausal status, close/positive margins, estrogen receptor negativity, and high grade were associated with a higher frequency of LRR. These 5 independent covariates were used to create adjusted estimates, weighting each on a scale of 0-100. The total score is identified on a points scale to obtain the probability of an LRR over the study period. The model demonstrated good concordance for predicting LRR, with a concordance index of 0.641. Conclusions The formulation of a practical, easy-to-use nomogram for calculating the risk of LRR in patients undergoing APBI will help guide the appropriate selection of patients for off-protocol utilization of APBI. [ABSTRACT FROM AUTHOR]

Abstract: Work in the construction industry is considered inherently dangerous, despite the technological improvements regarding the safety of work conditions and equipment. To address the urgent need to identify organizational predictors of safety performance and outcomes among construction workers, the present study examined multi-level effects of two important indicators of safety climate, namely contractor error management climate and worker safety communication, on safety behavior, injury, and pain among union construction workers. Data were collected from 235 union construction workers employed by 15 contractors in Midwest and Northwest regions of the United States. Results revealed significant main effects for safety communication and error management climate on safety behaviors and pain, but not on injuries. Our findings suggest that positive safety communication and error management climate are important contributors to improving workplace safety. Specific implications of these results for organizational safety research and practice are discussed. [Copyright &y& Elsevier]

Purpose: This prospective study examines the use of three-dimensional conformal external beam radiation therapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). Four-year data on efficacy, cosmesis, and toxicity are presented. Methods: Patients with Stage O, I, or II breast cancer with lesions ≤3 cm, negative margins, and negative nodes were eligible. The 3D-CRT delivered was 38.5 Gy in 3.85 Gy/fraction. Ipsilateral breast, ipsilateral nodal, contralateral breast, and distant failure (IBF, INF, CBF, DF) were estimated using the cumulative incidence method. Disease-free, overall, and cancer-specific survival (DFS, OS, CSS) were recorded. The National Cancer Institute Common Terminology Criteria for Adverse Events (version 3) toxicity scale was used to grade acute and late toxicities. Results: Ninety-four patients are evaluable for efficacy. Median patient age was 62 years with the following characteristics: 68% tumor size <1 cm, 72% invasive ductal histology, 77% estrogen receptor (ER) (+), 88% postmenopausal; 88% no chemotherapy and 44% with no hormone therapy. Median follow-up was 4.2 years (range, 1.3–8.3). Four-year estimates of efficacy were IBF: 1.1% (one local recurrence); INF: 0%; CBF: 1.1%; DF: 3.9%; DFS: 95%; OS: 97%; and CSS: 99%. Four (4%) Grade 3 toxicities (one transient breast pain and three fibrosis) were observed. Cosmesis was rated good/excellent in 89% of patients at 4 years. Conclusions: Four-year efficacy, cosmesis, and toxicity using 3D-CRT to deliver APBI appear comparable to other experiences with similar follow-up. However, additional patients, further follow-up, and mature Phase III data are needed to evaluate thoroughly the extent of application, limitations, and complete value of this particular form of APBI. [Copyright &y& Elsevier]

Abstract: Workplace sleepiness refers to how sleepy a person feels at work, and it is thought to be associated with negative occupational safety outcomes such as injuries because sleepiness can lead to behavioral decrements at work. This study explored safety behavior as a mediator of the relationship between workplace sleepiness and occupational safety outcomes (e.g., occupational injuries). A survey was conducted on certified nursing assistants working in long term care facilities. The Stanford Sleepiness Scale was used to measure workplace sleepiness. Occupational injuries were assessed in multiple ways: injury frequency, injury severity, pain frequency, pain severity-duration, and pain severity-intensity. This study provided support for a negative relationship between workplace sleepiness and safety behavior and limited support for a positive relationship between workplace sleepiness and occupational injuries. Workplace sleepiness was significantly related to pain frequency and pain severity (as indexed by both duration and intensity); however, it was not significantly related to injury frequency or severity. The results of the study also suggest very limited support for safety behavior as a mediator of this relationship. The findings suggest that the relationship between workplace sleepiness and occupational injuries might be more complex than originally assumed. [Copyright &y& Elsevier]

To examine early and late toxicities, evaluate cosmetic results, and determine the need for reoperation or additional diagnostic procedures in patients treated with accelerated partial breast irradiation (APBI) delivered by way of an interstitial implant in breast-conserving therapy.A total of 199 patients with stage I or II breast cancer were managed with lumpectomy followed by radiation restricted to the tumor bed using an interstitial implant (APBI). Retrospective analyses were performed for early and late toxicities (infection, fat necrosis, breast pain, edema, erythema, fibrosis, pigmentation changes, and telangiectasias), need for reoperation or additional diagnostic procedures, cosmetic results, and local control. Patient selection criteria by the surgeon for referral to RT for APBI included age, tumor size, histology, nodal status, margin status, and absence of extensive intraductal component. Treatment was delivered with either a low-dose or high-dose rate implant. Median follow-up was 5.7 years, and 54% of the patients were followed-up for >7 years.Infections developed in 22 of 199 (11%) patients: 7% early (≤1 month after implant removal) and 4% late (>1 month after implant removal). Five of the 22 patients (2% of all patients) required operative intervention for the infection, either incision and drainage or debridement. There was a statistically significant difference between infection rates with open (8.5%) versus closed (2.5%) cavity placement of the interstitial needles (P = 0.005). There was no statistically significant difference between low-dose rate (inpatient) and high-dose rate (outpatient) treatment (P = 0.207). Forty-five patients (23%) had an additional diagnostic procedure to evaluate a suspicious or uncertain finding on physical examination or mammogram. Fibrosis and fat necrosis were found in 26 of the 45 patients. The incidence of fat necrosis increased with time. More patients were found to have fat necrosis after 5 years. One patient had fat necrosis diagnosed at <6 months; 8 patients (4% of total) at ≥6 months to <2 years; 10 patients (5% of total) at ≥2 years to <5 years; and 22 patients (11% of total) at ≥5 years. The majority of fat necrosis was detected on mammogram (80%) and was asymptomatic (78%). Cosmesis and toxicities were assessed at 3 defined time points: ≤6 months, 2 years, and ≥5 years of follow-up. Using Harvard criteria, good to excellent cosmetic results were observed in >90% of patients. Breast pain, edema, and erythema diminished with time. Of the 199 cases, there were only 5 ipsilateral breast failures, yielding a 5-year actuarial local recurrence rate of 1.2%. Of these 5 failures, 2 were true recurrences/marginal misses, yielding a 5-year actuarial true recurrence/marginal miss rate of 0.5%. The 5-year actuarial cause-specific survival rate was 99% for APBI patients.In selected patients with early-stage breast cancer, APBI with targeted interstitial brachytherapy offers 5-year results comparable with conventional breast-conserving therapy employing whole-breast radiation therapy. Minimal long-term toxicities were noted, most of which demonstrated continued resolution over time. Acceptable acute (7%) and delayed (4%) infection rates were observed. Fat necrosis was identified with increasing frequency with time, but the majority was asymptomatic. Cosmetic results are good to excellent (>90%). Continued follow-up by the surgeon will be required to determine the long-term efficacy of this alternative treatment approach. [Copyright &y& Elsevier]

Abstract: Although the important role of safety climate in safety outcomes has been established and many studies have been done by scholars in different disciplines and across different cultures, there are still gaps in the literature. The articles in this Special Issue explore the topics of new developments in the conceptualization of safety climate and occupational/industry-focused studies of safety climate, with the goal of identifying different challenges and findings that arise within or across various occupations or industries. We are pleased to have a closing article by Dr. Dov Zohar on “Thirty Years of Safety Climate Research: Reflections and Future Directions.” [Copyright &y& Elsevier]

Purpose: Prostate-specific antigen (PSA) bounce is a temporary elevation of the PSA level above a prior nadir. The purpose of this study was to determine whether the frequency of a PSA bounce following high-dose-rate (HDR) interstitial brachytherapy for the treatment of prostate cancer is associated with individual treatment fraction size.Methods and Materials: Between 1999 and 2014, 554 patients underwent treatment of low- or intermediate-risk prostate cancer with definitive HDR brachytherapy as monotherapy and had ≥3 subsequent PSA measurements. Four different fraction sizes were used: 950 cGy × 4 fractions, 1200 cGy × 2 fractions, 1350 cGy × 2 fractions, 1900 cGy × 1 fraction. Four definitions of PSA bounce were applied: ≥0.2, ≥0.5, ≥1.0, and ≥2.0 ng/mL above the prior nadir with a subsequent return to the nadir.Results: The median follow-up period was 3.7 years. The actuarial 3-year rate of PSA bounce for the entire cohort was 41.3%, 28.4%, 17.4%, and 6.8% for nadir +0.2, +0.5, +1.0, and +2.0 ng/mL, respectively. The 3-year rate of PSA bounce >0.2 ng/mL was 42.2%, 32.1%, 41.0%, and 59.1% for the 950-, 1200-, 1350-, and 1900-cGy/fraction levels, respectively (P=.002). The hazard ratio for bounce >0.2 ng/mL for patients receiving a single fraction of 1900 cGy compared with those receiving treatment in multiple fractions was 1.786 (P=.024). For patients treated with a single 1900-cGy fraction, the 1-, 2-, and 3-year rates of PSA bounce exceeding the Phoenix biochemical failure definition (nadir +2 ng/mL) were 4.5%, 18.7%, and 18.7%, respectively, higher than the rates for all other administered dose levels (P=.025).Conclusions: The incidence of PSA bounce increases with single-fraction HDR treatment. Knowledge of posttreatment PSA kinetics may aid in decision making regarding management of potential biochemical failures. [ABSTRACT FROM AUTHOR]

Purpose: Although global heart dose has been associated with late cardiac toxic effects in patients who received radiation therapy for breast cancer, data detailing the clinical significance of cardiac substructure dosimetry are limited. We investigated whether dose to the left anterior descending artery (LAD) correlates with adverse cardiac events.Methods and Materials: We identified 375 consecutively treated female patients from 2012 to 2018 who received left-sided breast or chest wall irradiation (with or without regional nodal irradiation). Medical records were queried to identify cardiac events after radiation therapy. Mean and maximum LAD and heart doses (LAD Dmean, LAD Dmax, heart Dmean, and heart Dmax) were calculated and converted to 2-Gy equivalent doses (EQD2). Univariate and multivariable Cox regression analyses were performed to determine association with cardiac toxic effects. Potential dose thresholds for each of the 4 dose parameters were identified by receiver operating characteristic (ROC) curve analysis, after which Kaplan-Meier analysis was performed to compare cardiac event-free survival based on these constraints.Results: Median follow-up time was 48 months. Thirty-six patients experienced a cardiac event, and 23 patients experienced a major cardiac event. On univariate and multivariable analyses, increased LAD Dmean, LAD Dmax, and heart Dmean were associated with increased risk of any cardiac event and a major cardiac event. ROC curve analysis identified a threshold LAD Dmean EQD2 of 2.8 Gy (area under the ROC curve, 0.69), above which the risk for any cardiac event was higher (P = .001). Similar results were seen when stratifying by LAD Dmax EQD2 of 6.7 Gy (P = .005) and heart Dmean EQD2 of 0.8 Gy (P = .01).Conclusions: Dose to the LAD correlated with adverse cardiac events in this cohort. Contouring and minimizing dose to the LAD should be considered for patients receiving radiation therapy for left-sided breast cancer. [ABSTRACT FROM AUTHOR]

Highlights: [•] Safety uncertainty and safety obstacles are safety specific stressors. [•] Safety specific stressors were negatively related to safety performance. [•] Supervisor support was positively related to safety performance. [•] Important to focus on specific stressors and aspects of performance. [•] General job-related communication influences safety performance. [ABSTRACT FROM AUTHOR]

Abstract: Research continues to expose ethnic disparities in safety and health outcomes, making comparative studies of work-related factors that may explain these disparities increasingly important. Such studies raise issues about the cross-ethnic validity of the measures used to assess the factors of interest, such as safety climate. The current study is the first to examine the measurement equivalence of a multidimensional safety climate scale. A multi-group confirmatory factor analytic approach was used to assess the equivalence of the measure across White English-speaking, Hispanic English-speaking, and Hispanic Spanish-speaking construction workers. Results indicated that the same pattern of factors and equivalent factor loadings adequately represented the safety climate items across groups. However, other differences in item parameters were identified, including non-equivalence of some error variances and intercepts. This study highlights the importance of establishing measurement equivalence before proceeding with mean comparisons among groups. Future research should continue to investigate why differences in safety-related perceptions across ethnicities might exist. [Copyright &y& Elsevier]

Abstract: Purpose: We present 4-year results from a Phase I/II trial using balloon-based brachytherapy to deliver accelerated partial breast irradiation in 2 days. Materials/Methods: Forty-five patients received breast-conserving surgery followed by adjuvant radiation therapy using a balloon-based brachytherapy applicator delivering 2800cGy in four fractions over 2 days. Outcomes analyzed include toxicities scored using the NCI Common Toxicity Criteria v3.0 scale, ipsilateral breast tumor recurrence, regional nodal failure, distant metastasis, disease-free survival, cause-specific survival, and overall survival. Results: Median age was 66 years (range, 48–83 years) and median tumor size was 0.6cm (range, 0.2–2.3cm). Five percent of patients were node positive (n =2), whereas 73% was estrogen receptor positive (n =33). Median followup was 3.7 years (2.4–7.0 years) with greater than 2 years of followup for all patients. Only Grades 1 and 2 chronic toxicities were noted with fat necrosis (18%) and asymptomatic seromas (42%) being the most common toxicities. Seven percent of patients developed ipsilateral rib fractures (n =3), although this was not statistically associated with maximum rib dose (p =0.31). Ninety-eight percent of patients had a good or excellent radiation-related cosmetic outcome at the time of last followup. There were no ipsilateral breast tumor recurrences or regional nodal failures; however, 2 patients developed distant metastases. Four-year actuarial disease-free survival, cause-specific survival, and overall survival were 96%, 100%, and 93%, respectively. Conclusions: Treatment of early-stage breast cancer patients with breast-conserving therapy using a 2-day radiation dose schedule resulted in acceptable chronic toxicity and similar clinical outcomes as standard 5-day fractionation. [Copyright &y& Elsevier]

Purpose: To report outcomes for ductal carcinoma in situ (DCIS) treated with breast-conserving therapy using accelerated partial breast irradiation (APBI). Methods and Materials: From March 2001 to February 2009, 53 patients with Stage 0 breast cancer were treated with breast conserving surgery and adjuvant APBI. Median age was 62 years. All patients underwent excision with margins negative by ≥1 mm before adjuvant radiotherapy (RT). A total of 39 MammoSite brachytherapy (MS) patients and 14 three-dimensional conformal external beam RT (3DCRT) patients were treated to the lumpectomy bed alone with 34 Gy and 38.5 Gy, respectively. Of the DCIS cases, 94% were mammographically detected. All patients with calcifications had either specimen radiography or postsurgical mammography confirmation of clearance. Median tumor size was 6 mm, and median margin distance was 5 mm. There were no statistically significant differences according to APBI method for race/ethnicity, tumor detection method, tumor grade, estrogen receptor (ER) status, or use of tamoxifen (p = NS). Recurrence and survival were calculated using the Kaplan–Meier method. Cosmesis was scored by the Harvard criteria. Results: With a median follow-up of 3.6 years (range, 0.4–6.3 years), the overall and cause-specific survival rates were 98% and 100%, respectively. Three-year actuarial ipsilateral breast tumor recurrence was 2%. One failure was observed at the resection bed 11 months post-RT. No other elsewhere breast failures, regional recurrences, or distant metastases were noted. Cosmesis was excellent or good in 92.4% of cases, with no statistically significant differences according to the APBI method (92.3% with MammoSite and 92.8% with 3DCRT; p = 0.649). Conclusions: APBI as part of breast-conserving therapy for pure DCIS was associated with excellent local control and survival rates, with the vast majority of patients having good to excellent cosmesis. This finding supports the recent analysis by the American Society of Breast Surgeons on a subset of DCIS patients treated efficaciously with APBI. [Copyright &y& Elsevier]

Purpose: Significant anatomic and volumetric changes occur in head and neck cancer patients during fractionated radiotherapy, and the actual dose can be considerably different from the original plan. The purposes of this study were (1) to evaluate the differences between planned and delivered dose, (2) to investigate margins required for anatomic changes, and (3) to find optimal replanning strategies. Methods and Materials: Eleven patients, each with one planning and six weekly helical CTs, were included. Intensity-modulated radiotherapy plans were generated using the simultaneous integrated boost technique. Weekly CTs were rigidly registered to planning CT before deformable registration was performed. The following replanning strategies were investigated with different margins (0, 3, 5 mm): midcourse (one replan), every other week (two replans), and every week (six replans). Doses were accumulated on the planning CT for comparison of various dose indices for target and critical structures. Results: The cumulative doses to targets were preserved even at the 0-mm margin. Doses to cord, brainstem, and mandible were unchanged. Significant increases in parotid doses were observed. Margin reduction from 5 to 0 mm led to a 22% improvement in parotid mean dose. Parotid sparing could be preserved with replanning. More frequent replanning led to better preservation; replanning more than once a week is unnecessary. Conclusion: Shrinkage does not result in significant dosimetric difference in targets and critical structures, except for the parotid gland, for which the mean dose increases by ∼10%. The benefit of replanning is improved sparing of the parotid. The combination of replanning and reduced margins can provide up to a 30% difference in parotid dose. [Copyright &y& Elsevier]

Abstract: The utility of the job demand–control-support (JDCS) model for explaining psychological and physical well-being has been documented in a variety of settings. The current study''s purpose was to assess the effectiveness of the JDCS model for predicting occupational safety well-being criteria (i.e., workplace injuries) based on two studies that employed samples of union blue-collar workers from two different regions of the United States. The JDCS model''s buffer hypotheses were evaluated using hierarchical linear modeling. Both studies showed significant interactions between situational constraints and safety control to predict workplace injuries such that safety control buffered the negative effects of situational constraints. No significant three-way interaction between situational constraints, safety control, and safety climate on workplace injuries was found for either study. The implications of the present findings for both the JDCS model and occupational safety research are discussed. [Copyright &y& Elsevier]

Purpose: A new device has been developed with the goal of making breast-conserving therapy more widely available, by making breast brachytherapy as monotherapy simpler and more accurate. This is the first published report on the dosimetric characteristics of this device.Methods and Materials: The experience of a single institution participating in a multi-institutional trial is reported. Twelve patients were enrolled, of whom 8 were treated. Computed tomography scans of all 12 patients were obtained before initiation of treatment. A commercial three-dimensional planning system was used for retrospective detailed analysis of dosimetry, including dose-volume histograms and, in selected patients, skin dose distributions. These data were compared to those of a similar group of patients, analyzed previously, that was treated with interstitial high-dose-rate brachytherapy.Results: Compared with interstitial brachytherapy, the MammoSite device resulted in a treatment dose that was less uniform, with a mean dose homogeneity index of 0.77 vs. 0.93. Coverage and reproducibility were improved, with a mean D90 (minimum dose to 90% of target volume) of 90.0% of prescribed dose (SD 0.5, range: 89.2–90.8%) vs. 69.8% (SD 7.3, range: 61.1–83.5%) for interstitial brachytherapy.Conclusions: Reproducible placement was easily achieved in this very early experience, indicating a much smaller “learning curve” than for interstitial brachytherapy. Because skin doses can be increased with the use of this device, caution is indicated, although simple maneuvers can significantly reduce skin dose. [Copyright &y& Elsevier]

Radiation therapy plays an important role in the multidisciplinary management of breast cancer. Recent years have seen improvements in breast cancer survival and a greater appreciation of potential long-term morbidity associated with the dose and volume of irradiated organs. Proton therapy reduces the dose to nontarget structures while optimizing target coverage. However, there remain additional financial costs associated with proton therapy, despite reductions over time, and studies have yet to demonstrate that protons improve upon the treatment outcomes achieved with photon radiation therapy. There remains considerable heterogeneity in proton patient selection and techniques, and the rapid technological advances in the field have the potential to affect evidence evaluation, given the long latency period for breast cancer radiation therapy recurrence and late effects. In this consensus statement, we assess the data available to the radiation oncology community of proton therapy for breast cancer, provide expert consensus recommendations on indications and technique, and highlight ongoing trials' cost-effectiveness analyses and key areas for future research. [ABSTRACT FROM AUTHOR]

Dose to the left anterior descending artery (LAD) may be significant in patients receiving left-sided irradiation for breast cancer. We investigated if prospective contouring and avoidance of the LAD during treatment planning were associated with lower LAD dose. We reviewed dosimetric plans for 323 patients who received left whole breast or chest wall irradiation with or without internal mammary node (IMLN) coverage between 1/2014 and 1/2019 at a single institution. The LAD was contoured prospectively for 155 cases, and techniques were utilized to minimize LAD dose. Dose-volume-histograms from these patients were compared to those of 168 patients for whom the LAD was contoured retrospectively after treatment completion. EQD2 was calculated to account for fractionation differences. Compared to cases where the LAD was contoured retrospectively (n = 126), prospective LAD contouring (n = 124) was associated with lower unadjusted median max and mean LAD doses for 250 patients receiving whole-breast irradiation (WBI) without IMLN coverage: 8.5 Gy vs 5.2 Gy (p < 0.0001) and 3.6 Gy vs 2.7 Gy (p < 0.0001), respectively. EQD2 median max and mean LAD doses were also lower with prospective LAD contouring: 5.2 Gy vs 3.0 Gy (p < 0.0001) and 1.9 Gy vs 1.5 Gy (p < 0.0001), respectively. Compared to cases where the LAD was contoured retrospectively (n = 42), prospective LAD contouring (n = 31) was associated with lower max LAD doses for 73 patients with IMLN coverage: 20.4 Gy vs 14.3 Gy (p = 0.042). There was a nonsignificant reduction in median mean LAD dose: 6.2 Gy vs 6.1 Gy (p = 0.33). LAD doses were reduced while maintaining IMLN coverage (mean V90% Rx >90%). Prospective contouring and avoidance of the LAD were associated with lower max and mean LAD doses in patients receiving WBI and with lower max LAD doses in patients receiving IMLN treatment. Further reduction in LAD dose may require stricter optimization weighting or compromise in IMLN coverage. [ABSTRACT FROM AUTHOR]

Purpose: We examined the distribution of pretreatment nodal metastases to the level I axilla (Ax-L1) to assess the appropriateness of current breast atlases and provide guidelines in relationship to easily identifiable anatomic landmarks for accurate delineation of this lymph node (LN) basin.Methods and Materials: Patients with newly diagnosed breast cancer and biopsy-proven metastatic Ax-L1 LNs were identified. We related the location of each LN to its most adjacent rib and its distance from the bottom of the humeral head, axillary vessels, and a line connecting the anterior aspects of the pectoralis and latissimus dorsi muscles (P-L line). LNs were mapped onto a representative planning computed tomography scan, and their distribution was used to validate the current Radiation Therapy Oncology Group, European Society for Radiotherapy and Oncology, and Radiotherapy Comparative Effectiveness breast atlases. Furthermore, we examined metastases to a subregion encompassing the superolateral Ax-L1, irradiation of which correlates highly with lymphedema.Results: We identified 106 eligible patients with 107 biopsied LNs. All LNs fell between the second and fifth ribs (mean, 3.8 ± 0.56). Mean distance from the inferior aspect of the humeral head was 4.3 ± 1.6 cm (range, 0.3-8.4). Mean distance from the inferior aspect of the axillary vessels was 2.9 ± 1.5 cm (range, -0.6 to 5.4). Mean distance from the P-L line was 0.01 ± 1.9 cm (range, -2.2 to 2.4); negative and positive values denote medial or lateral to the P-L line. A Radiation Therapy Oncology Group-compliant Ax-L1 consensus contour, created from contours by 4 attending breast radiation oncologists, partially or fully missed 45% of mapped LNs. European Society for Radiotherapy and Oncology- and Radiotherapy Comparative Effectiveness-compliant Ax-L1 similarly missed 46% and 34% of mapped LNs, respectively. LNs were most frequently missed in the lateral direction. The superolateral Ax-L1 encompassed 9.3% of the mapped LNs.Conclusions: A significant percentage of at-risk Ax-L1 tissue falls outside current contouring atlases. We propose expansion of the recommended Ax-L1 borders, most notably in the lateral direction. [ABSTRACT FROM AUTHOR]

Purpose: To construct a tumor voxel dose response matrix (DRM) and dose prescription function (DPF) for adaptive dose painting by number (DPbN) based on treatment feedback of fluoro-2-deoxyglucose (FGD) positron emission tomography (PET)/computed tomography (CT) imaging.Methods and Materials: FDG-PET/CT images obtained before and after chemoradiation therapy and at weekly chemoradiation therapy sessions for each of 18 patients with head and neck cancer, as well as the treatment outcomes, were used in the modeling. All weekly and posttreatment PET/CT images were registered voxel-to-voxel to the corresponding pretreatment baseline PET/CT image. Tumor voxel DRM was created using serial FDG-PET imaging of each patient with respect to the baseline standardized uptake value (SUV0). A tumor voxel control probability (TVCP) lookup table was created using the maximum likelihood estimation on the tumor voxel (SUV0, DRM) domain of all tumors. Tumor voxel DPF was created from the TVCP lookup table and used as the objective function for DPbN-based inverse planning optimization.Results: Large intertumoral and intratumoral variations on both tumor voxels (SUV0, DRM) were identified. Tumor voxel dose resistance did not show correlation with its baseline SUV0 value and was the major cause of the tumor local failures. Tumor voxel DPF as the function of tumor voxel (SUV0, DRM) values also showed a very large intertumoral and intratumoral heterogeneity. Most human papillomavirus-negative tumors require a treatment dose >100 Gy to certain local tumor regions. These treatment doses, which are most unlikely to be implementable in conventional radiation therapy, can be achieved using adaptive DPbN treatment. Clinical feasibility was evaluated by comparing the adaptive DPbN treatment plan with the conventional intensity modulated radiation therapy plan.Conclusions: Tumor voxel (SUV0, DRM) provides an intratumoral prognostic map to target tumor locoregional-resistant regions. The corresponding TVCP or DPF provides a quantitative objective to optimize the intratumoral dose distribution for the individuals. The adaptive DPbN with FDG-PET/CT imaging feedback is feasible to implement in clinics. [ABSTRACT FROM AUTHOR]

Purpose: Four-dimensional (4D) adaptive radiation therapy (ART) treatment planning is an alternative to the conventional margin-based treatment planning approach. In 4D ART, interfraction patient geometric variations, gathered from computed tomography (CT) or cone beam CT (CBCT) images acquired during the patient treatment course, are directly incorporated into the adaptive plan optimization using a probabilistic treatment planning method. The goal of the present planning study was to evaluate the dosimetric differences between 4D ART and conventional margin-based adaptive planning strategies for head and neck cancers. In addition, we examined whether the dose differences achieved with 4D ART would translate into clinically relevant toxicity reductions using the existing normal tissue complication probability (NTCP) models.Methods and Materials: For 18 head and neck cancer patients, the treatment plans were retrospectively generated for 4 different treatment strategies, including a solely image guided radiation therapy (IGRT) strategy (IGRT-only), 2 conventional adaptive treatment planning strategies using 3- and 0-mm planning target volume (PTV) margins, and the 4D ART strategy. In the IGRT-only strategy, a conventional 3-mm PTV margin treatment plan was applied for the entire treatment course. In the 2 conventional adaptive strategies, 2 new treatment plans were generated during the treatment course using diagnostic planning CT scans acquired after the 10th and 22nd fractions. The 4D ART followed the same adaptive schedule, except that the 4D adaptive plan was generated using 5 CBCT images acquired during the 5 most recent treatment fractions. For each strategy, the actual delivered dose for the entire treatment course was constructed by calculating the daily doses on 35 CBCT scans, deforming back to the pretreatment planning CT scan, and accumulating over all 35 fractions. The target coverage was evaluated using the percentage of target volume receiving ≥100% of the prescription dose (V100%) and the minimum dose to 99% of the target volume (D99). It was considered adequate if the V100% was ≥95% and the dose deficit in D99 was ≤2 Gy (with respect to the prescription dose). For each strategy, the dose received by the organs at risk (OARs) was also evaluated, and the corresponding NTCP values were subsequently calculated using 3 NTCP models.Results: Adequate target coverage was achieved for the primary clinical target volume (CTV1) and elective nodal CTV (CTV2) with a 3-mm PTV margin, regardless of adaptation. The 3-mm ART plan reduced the OAR mean dose by 1 to 2 Gy compared with the IGRT-only plan. The 0-mm ART plan further reduced the OAR dose by another 2 to 3 Gy at the expense of target coverage: 3 and 1 patient had V100% <95%, and 6 and 5 patients had a >2 Gy dose deficit in D99 for the CTV1 and CTV2, respectively. Use of 4D ART improved target coverage and attained OAR sparing similar to that with 0-mm ART. The number of patients with V100% <95% and >2 Gy D99 deficit decreased to 0 and 0 for CTV1 and 0 and 2 for CTV2, respectively. The NTCP calculations suggested that 4D ART could benefit a substantial portion of patients compared with IGRT-only because 17 and 12 patients had ≥5% and ≥10% NTCP reductions for parotid toxicity and 18 and 3 patients had ≥5% and ≥10% NTCP reductions for swallowing toxicity, respectively.Conclusions: Compared with margin-based adaptive planning strategies, 4D ART provides a better balance between target coverage and OAR sparing. NTCP estimation predicted for theoretical clinical benefits that warrant further clinical validation. [ABSTRACT FROM AUTHOR]

Purpose: We report the outcomes associated with 3 high-dose-rate (HDR) brachytherapy regimens used as monotherapy for favorable-risk prostate cancer.Methods and Materials: Four hundred ninety-four patients with stage ≤T2b prostate cancer, Gleason score ≤7, and prostate-specific antigen levels ≤15 ng/mL underwent HDR brachytherapy as monotherapy. Of those, 319 received 38 Gy in 4 fractions, 79 received 24 Gy in 2 fractions, and 96 received 27 Gy in 2 fractions. Acute and chronic genitourinary (GU) and gastrointestinal (GI) toxicities were defined as side effects occurring ≤6 and >6 months, respectively, after radiation therapy (RT) and were graded according to the Common Terminology Criteria for Adverse Events version 3.0. The time to toxicity was calculated from the date of RT completion. Variables were analyzed with χ(2) test. P values <.05 were considered significant.Results: The median overall follow-up time was 4 years (range, 5.5, 3.5, and 2.5 years for 38 Gy, 24 Gy, and 27 Gy, respectively, P<.001). Acute and chronic grade ≥2 GU and GI toxicity profiles were similar among groups. Acceptable rates of grade 2 GU toxicities were seen with overall acute/chronic frequency/urgency, dysuria, retention, incontinence, and hematuria rates of 14%/20%, 6%/7%, 7%/4%, 1.5%/2%, and 1.5%/7%, respectively. Minimal grade 3 and no grade 4 or 5 toxicities were seen. Grade 1, 2, and 3 chronic urethral stricture rates were 0.3%, 2%, and 1%, respectively. All GI toxicities were similar between groups, with overall rates of acute/chronic grade 2 diarrhea, rectal pain/tenesmus, rectal bleeding, and proctitis of 1%/1%, <1%/0.5%, 0%/2%, and <1%/1%, respectively. No grade 3, 4, or 5 toxicities were seen. All comparisons were similar for hormone-naïve patients. The median time to maximal GU/GI toxicity was similar between groups, ranging from 1 to 1.6 to 0.9 to 1.2 years, respectively. There were no differences in clinical outcomes between the 3 groups at 5 years.Conclusions: The acute and chronic toxicity profiles associated with these 3 HDR brachytherapy schedules were similar and were well tolerated. Acceptable grade 2, minimal grade 3, and no grade 4 or 5 toxicities were seen. This, combined with the fact that the clinical outcomes were similar, leads to the conclusion that all 3 regimens may be acceptable options for the management of low-risk to intermediate-risk prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose: Recent prospective data have shown that patients with solitary or oligometastatic disease to the brain may be treated with upfront stereotactic radiosurgery (SRS) with deferral of whole-brain radiation therapy (WBRT). This has been extrapolated to the treatment of patients with resected lesions. The aim of this study was to assess the risk of leptomeningeal disease (LMD) in patients treated with SRS to the postsurgical resection cavity for brain metastases compared with patients treated with SRS to intact metastases.Methods and Materials: Four hundred sixty-five patients treated with SRS without upfront WBRT at a single institution were identified; 330 of these with at least 3 months' follow-up were included in this analysis. One hundred twelve patients had undergone surgical resection of at least 1 lesion before SRS compared with 218 treated for intact metastases. Time to LMD and overall survival (OS) time were estimated from date of radiosurgery, and LMD was analyzed by the use of cumulative incidence method with death as a competing risk. Univariate and multivariate analyses were performed with competing risk regression to determine whether various clinical factors predicted for LMD.Results: With a median follow-up time of 9.0 months, 39 patients (12%) experienced LMD at a median of 6.0 months after SRS. At 1 year, the cumulative incidence of LMD, with death as a competing risk, was 5.2% for the patients without surgical resection versus 16.9% for those treated with surgery (Gray test, P<.01). On multivariate analysis, prior surgical resection (P<.01) and breast cancer primary (P=.03) were significant predictors of LMD development. The median OS times for patients undergoing surgery compared with SRS alone were 12.9 and 10.6 months, respectively (log-rank P=.06).Conclusions: In patients undergoing SRS with deferral of upfront WBRT for intracranial metastatic disease, prior surgical resection and breast cancer primary are associated with an increased risk for the development of LMD. [ABSTRACT FROM AUTHOR]

Purpose: To examine the prognostic significance of c-Met expression in relation to p16 and epidermal growth factor receptor (EGFR) in patients with locally advanced head and neck squamous cell carcinoma (HNSCC) treated with definitive concurrent chemoradiation. Methods and Materials: Archival tissue from 107 HNSCC patients treated with chemoradiation was retrieved, and a tissue microarray was assembled. Immunohistochemical staining of c-Met, p16, and EGFR was performed. c-Met expression was correlated with p16, EGFR, clinical characteristics, and clinical endpoints including locoregional control (LRC), distant metastasis (DM), disease-free survival (DFS), and overall survival (OS). Results: Fifty-one percent of patients were positive for p16, and 53% were positive for EGFR. Both p16-negative (P≤.001) and EGFR-positive (P=.019) status predicted for worse DFS. Ninety-three percent of patients stained positive for c-Met. Patients were divided into low (0, 1, or 2+ intensity) or high (3+ intensity) c-Met expression. On univariate analysis, high c-Met expression predicted for worse LRC (hazard ratio [HR] 2.27; 95% CI, 1.08-4.77; P=.031), DM (HR 4.41; 95% CI, 1.56-12.45; P=.005), DFS (HR 3.00; 95% CI, 1.68-5.38; P<.001), and OS (HR 4.35; 95% CI, 2.13-8.88; P<.001). On multivariate analysis, after adjustment for site, T stage, smoking history, and EGFR status, only high c-Met expression (P=.011) and negative p16 status (P=.003) predicted for worse DFS. High c-Met expression was predictive of worse DFS in both EGFR-positive (P=.032) and -negative (P=.008) patients. In the p16-negative patients, those with high c-Met expression had worse DFS (P=.036) than did those with low c-Met expression. c-Met expression was not associated with any outcome in the p16-positive patients. Conclusions: c-Met is expressed in the majority of locally advanced HNSCC cases, and high c-Met expression predicts for worse clinical outcomes. High c-Met expression predicted for worse DFS in p16-negative patients but not in p16-positive patients. c-Met predicted for worse outcome regardless of EGFR status. [Copyright &y& Elsevier]

Highlights: [•] Construction workers were surveyed to assess how leader behaviors influence safety. [•] Idealized attributes and behaviors were important predictors of safety outcomes. [•] Active management-by-exception did not uniquely contribute to any safety outcome. [•] The importance of the remaining leader behaviors varied depending on the outcome. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: We compared outcomes in intermediate-risk prostate cancer patients treated with dose-escalated adaptive image-guided radiation therapy (IGRT) or dose-escalated high-dose-rate brachytherapy boost (HDR-B). Methods and Materials: Patients with intermediate-risk prostate cancer by National Comprehensive Cancer Network criteria were treated with either CT-based off-line adaptive IGRT (n = 734) or HDR-B (n = 282). IGRT was delivered with 3D-conformal or intensity-modulated radiation therapy with a median dose of 77.4 Gy. For HDR-B, the whole pelvis received a median 46 Gy, and the prostate 2 implants of 9.5 Gy (n = 71), 10.5 Gy (n = 155), or 11.5 Gy (n = 56). Results: Median followup was 3.7 years for IGRT and 8.0 years for HDR-B (p < 0.001). Eight-year biochemical control was 86% for IGRT and 91% for HDR-B (p = 0.22), disease-free survival 67% for IGRT and 79% for HDR-B (p = 0.006), and overall survival 75% for IGRT and 86% for HDR-B (p = 0.009). Cause-specific survival (8-year, 100% vs. 99%), freedom from distant metastases (98% vs. 97%), and freedom from local recurrence (98% vs. 98%) did not differ (p > 0.50 each). A worse prognosis group was defined by percent positive prostate biopsy cores >50%, perineural invasion, or stage T2b–c, encompassing 260 (35%) IGRT and 171 (61%) HDR-B patients. These patients evidenced a 5-year biochemical control of 96% for HDR-B and 87% for IGRT (p = 0.002). Conclusions: Dose-escalated IGRT and HDR-B both yield excellent clinical outcomes for patients with intermediate-risk prostate cancer. Improved biochemical control with HDR-B for patients with worse pretreatment characteristics suggests that a subgroup of intermediate-risk prostate cancer patients may benefit from dual-modality treatment. [Copyright &y& Elsevier]

Purpose: To examine clinical outcomes of accelerated partial-breast irradiation (APBI) stratified by the number of American Society for Radiation Oncology consensus statement cautionary/unsuitable risk factors (RFs) present. Methods and Materials: A total of 692 patients were treated with APBI at a single institution between April 1993 and January 2012 using interstitial (n=195), balloon (n=292), and 3-dimensional conformal radiation therapy (n=205) techniques. Clinical outcomes were evaluated by risk group and number of RFs. Results: Median follow-up was 5.2 years (range, 0-18.3 years). Most patients were classified as suitable (n=240, 34%) or cautionary (n=343, 50%) risk, whereas 16% (n=109) were unsuitable. In patients with increasing total RFs (1 RF, 2 RF, 3+ RF), higher rates of grade 3 histology (10% vs 18% vs 32%, P<.001), estrogen receptor negativity (0 vs 12% vs 29%, P<.001), close/positive margins (0 vs 6% vs 17%, P<.001), and use of adjuvant chemotherapy (3% vs 12% vs 33%, P<.001) were noted. When pooling cautionary and unsuitable patients, increased ipsilateral breast tumor recurrence/regional recurrence was most notable for patients with 3 or more combined RFs versus 2 or fewer combined RFs (P<.001). Conclusions: Patients with 3 or more cautionary or unsuitable RFs may be at risk for higher local, regional, and distant recurrence after breast-conserving therapy using APBI. Patients with 2 or fewer total RFs have 98% locoregional control at 5 years. Inclusion of total number of RFs in future risk stratification schemes for APBI may be warranted. [Copyright &y& Elsevier]

Purpose: To determine whether the American Society for Radiation Oncology (ASTRO) Consensus Statement (CS) recommendations for accelerated partial breast irradiation (APBI) are associated with significantly different outcomes in a pooled analysis from William Beaumont Hospital (WBH) and the American Society of Breast Surgeons (ASBrS) MammoSite® Registry Trial. Methods and Materials: APBI was used to treat 2127 cases of early-stage breast cancer (WBH, n=678; ASBrS, n=1449). Three forms of APBI were used at WBH (interstitial, n=221; balloon-based, n=255; or 3-dimensional conformal radiation therapy, n=206), whereas all Registry Trial patients received balloon-based brachytherapy. Patients were divided according to the ASTRO CS into suitable (n=661, 36.5%), cautionary (n=850, 46.9%), and unsuitable (n=302, 16.7%) categories. Tumor characteristics and clinical outcomes were analyzed according to CS group. Results: The median age was 65 years (range, 32-94 years), and the median tumor size was 10.0 mm (range, 0-45 mm). The median follow-up time was 60.6 months. The WBH cohort had more node-positive disease (6.9% vs 2.6%, P<.01) and cautionary patients (49.5% vs 41.8%, P=.06). The 5-year actuarial ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), and distant metastasis (DM) for the whole cohort were 2.8%, 0.6%, 1.6%. The rate of IBTR was not statistically higher between suitable (2.5%), cautionary (3.3%), or unsuitable (4.6%) patients (P=.20). The nonsignificant increase in IBTR for the cautionary and unsuitable categories was due to increased elsewhere failures and new primaries (P=.04), not tumor bed recurrence (P=.93). Conclusions: Excellent outcomes after breast-conserving surgery and APBI were seen in our pooled analysis. The current ASTRO CS guidelines did not adequately differentiate patients at an increased risk of IBTR or tumor bed failure in this large patient cohort. [Copyright &y& Elsevier]

Abstract: The use of safety climate measures for needs assessment and interventions has become increasingly popular. However, no research to date has examined whether the meaning and level of safety climate may differ across different groups of interest. This study used multi-group confirmatory factor analyses to investigate the measurement equivalence of a multidimensional safety climate measure across ten construction trade groups (N =4725). In addition, observed mean differences in safety climate perceptions between trades were examined. Results revealed strong measurement equivalence of the safety climate measure across the construction trade groups. Further, significant mean differences were found between the ten trade groups on all four safety climate scales. [Copyright &y& Elsevier]

Purpose: We analyzed variables associated with long-term toxicity using three-dimensional conformal external beam radiation therapy (3D-CRT) to deliver accelerated partial breast irradiation. Methods and Materials: One hundred patients treated with 3D-CRT accelerated partial breast irradiation were evaluated using Common Terminology Criteria for Adverse Events version 4.0 scale. Cosmesis was scored using Harvard criteria. Multiple dosimetric and volumetric parameters were analyzed for their association with worst and last (W/L) toxicity outcomes. Results: Sixty-two patients had a minimum of 36 months of toxicity follow-up (median follow-up, 4.8 years). The W/L incidence of poor-fair cosmesis, any telangiectasia, and grade ≥2 induration, volume reduction, and pain were 16.4%/11.5%, 24.2%/14.5%, 16.1%/9.7%, 17.7%/12.9%, and 11.3%/3.2%, respectively. Only the incidence of any telangiectasia was found to be predicted by any dosimetric parameter, with the absolute breast volume receiving 5% to 50% of the prescription dose (192.5 cGy–1925 cGy) being significant. No associations with maximum dose, volumes of lumpectomy cavity, breast, modified planning target volume, and PTV, dose homogeneity index, number of fields, and photon energy used were identified with any of the aforementioned toxicities. Non-upper outer quadrant location was associated with grade ≥2 volume reduction (p = 0.02 W/p = 0.04 L). A small cavity-to-skin distance was associated with a grade ≥2 induration (p = 0.03 W/p = 0.01 L), a borderline significant association with grade ≥2 volume reduction (p = 0.06 W/p = 0.06 L) and poor-fair cosmesis (p = 0.08 W/p = 0.09 L), with threshold distances ranging from 5 to 8 mm. Conclusions: No dose--volume relationships associated with long-term toxicity were identified in this large patient cohort with extended follow-up. Cosmetic results were good-to-excellent in 88% of patients at 5 years. [ABSTRACT FROM AUTHOR]