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Purpose: The survival benefit of combined radiation therapy (RT) and androgen deprivation therapy (ADT) compared with ADT alone for clinically lymph node-positive prostate cancer remains controversial.Methods and Materials: We identified patients with clinically node-positive, nonmetastatic prostate cancer diagnosed between 2000 and 2015 and treated with ADT (n = 450) or ADT-RT (n = 198) from a national Veterans Affairs database. We compared prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) between treatment groups using multivariable competing-risks regression and Cox regression, respectively. An interaction term between ADT-RT and prostate-specific antigen (PSA) level (dichotomized about the median) was included in the multivariable models.Results: ADT-RT was associated with improved PCSM among patients with PSA levels less than the median of 26 ng/mL (sub-distribution hazard ratio, 0.50; 95% confidence interval [CI] 0.28-0.88; P = .02) but not greater than the median (hazard ratio [HR], 1.15; 95% CI 0.67-1.96; P = .62) (P = .038 for interaction). ADT-RT was also associated with improved ACM among patients with PSA levels less than the median (HR, 0.38; 95% CI 0.25-0.57; P < .001) but not greater than the median (HR, 0.91; 95% CI 0.60-1.38; P = .66) (P = .004 for interaction).Conclusions: Definitive treatment with ADT-RT is associated with improved PCSM and ACM among patients with clinically node-positive prostate cancer and lower baseline PSA levels. Patients with clinically node-positive disease appear to be a heterogeneous cohort, with a subset who may achieve long-term survival with combined RT and ADT. [ABSTRACT FROM AUTHOR]

West Africa has one of the highest incidence rates of carcinoma of the cervix in the world. The vast majority of women do not have access to screening or disease treatment, leading to presentation at advanced stages and to high mortality rates. Compounding this problem is the lack of radiation treatment facilities in Senegal and many other parts of the African continent. Senegal, a country of 13 million people, had a single 60Co teletherapy unit before our involvement and no brachytherapy capabilities. Radiating Hope, a nonprofit organization whose mission is to provide radiation therapy equipment to countries in the developing world, provided a high-dose-rate afterloading unit to the cancer center for curative cervical cancer treatment. Here we describe the implementation of high-dose-rate brachytherapy in Senegal requiring a nonstandard fractionation schedule and a novel treatment planning approach as a possible blueprint to providing this technology to other developing countries. [Copyright &y& Elsevier]

Purpose: To identify a cohort of women treated with neoadjuvant chemotherapy and mastectomy for whom postmastectomy radiation therapy (PMRT) may be omitted according to the projected risk of local-regional failure (LRF). Methods and Materials: Seven breast cancer physicians from the University of California cancer centers created 14 hypothetical clinical case scenarios, identified, reviewed, and abstracted the available literature (MEDLINE and Cochrane databases), and formulated evidence tables with endpoints of LRF, disease-free survival, and overall survival. Using the American College of Radiology appropriateness criteria methodology, appropriateness ratings for postmastectomy radiation were assigned for each scenario. Finally, an overall summary risk assessment table was developed. Results: Of 24 sources identified, 23 were retrospective studies from single institutions. Consensus on the appropriateness rating, defined as 80% agreement in a category, was achieved for 86% of the cases. Distinct LRF risk categories emerged. Clinical stage II (T1-2N0-1) patients, aged >40 years, estrogen receptor-positive subtype, with pathologic complete response or 0-3 positive nodes without lymphovascular invasion or extracapsular extension, were identified as having ≤10% risk of LRF without radiation. Limited data support stage IIIA patients with pathologic complete response as being low risk. Conclusions: In the absence of randomized trial results, existing data can be used to guide the use of PMRT in the neoadjuvant chemotherapy setting. Using available studies to inform appropriateness ratings for clinical scenarios, we found a high concordance of treatment recommendations for PMRT and were able to identify a cohort of women with a low risk of LRF without radiation. These low-risk patients will form the basis for future planned studies within the University of California Athena Breast Health Network. [ABSTRACT FROM AUTHOR]

NIBB has potential advantages over other APBI techniques by delivering highly conformal radiation with minimal collateral dose to the heart and lung compared with external beam techniques, but unlike other brachytherapy techniques NIBB is non-invasive. Previous data has shown encouraging outcomes using a 10-fraction regimen. To improve efficiency, convenience, and cost, reduction in the fraction number is desirable. Final results of a prospective phase II trial are reported. NIBB APBI was delivered using 28.5Gy in 5 fractions daily over 1 week. Patient eligibility criteria required: invasive carcinoma ≤2.0 cm or DCIS ≤3.0 cm, ER positive (if invasive), lymph node negative, LVI absent, and lumpectomy with margins negative by 2mm. The primary endpoint was grade ≥ 2 subcutaneous fibrosis/induration <30%. Secondary endpoints included any late toxicity, cosmetic outcome, and local control. 40 patients were treated with a median follow-up of 59.7 months. The mean age was 67 years (50-89 years) and tumor size was 1.0cm (0.3-2.0cm). 80% had invasive carcinoma. The mean breast separation with compression was 6.7cm (3.5-8.9cm). The 5-year actuarial local control was 96.6% and overall survival was 96.9%. Grade 2 and 3 late toxicities were 15% and 0%, respectively. The rate of grade 2 subcutaneous fibrosis/induration was 2.5% (+/-2.5%) meeting the study's primary endpoint. The most common late toxicity of any grade was skin telangiectasia; 22.5% grade 1 and 15% grade 2. Only breast separation was associated with telangiectasia risk, p=0.002. Overall cosmetic outcome was excellent, good, and fair/poor in 75%, 25%, and 0%, respectively. NIBB APBI delivered in 5 fractions results in a low rate of late toxicity and a high rate of good/excellent cosmetic outcomes. Telangiectasia risk can be minimized by keeping breast separation ≤7.0cm. The local failure rate was appropriately low. Further investigation of this technique is warranted. [ABSTRACT FROM AUTHOR]

Currently, there is a lack of patient-specific tools to guide brachytherapy planning and applicator choice for cervical cancer. The purpose of this study is to evaluate the accuracy of organ-at-risk (OAR) dose predictions using knowledge-based intracavitary models, and the use of these models and clinical data to determine the dosimetric differences of tandem-and-ring (T&R) and tandem-and-ovoids (T&O) applicators. Knowledge-based models, which predict organ D 2cc , were trained on 77/75 cases and validated on 32/38 for T&R/T&O applicators. Model performance was quantified using ΔD 2cc =D 2cc,actual –D 2cc,predicted , with standard deviation (σ(ΔD 2cc)) representing precision. Model-predicted applicator dose differences were determined by applying T&O models to T&R cases, and vice versa, and compared to clinically-achieved D 2cc differences. Applicator differences were assessed using a Student's t -test (p < 0.05 significant). Validation T&O/T&R model precision was 0.65/0.55 Gy, 0.55/0.38 Gy, and 0.43/0.60 Gy for bladder, rectum and sigmoid, respectively, and similar to training. When applying T&O/T&R models to T&R/T&O cases, bladder, rectum and sigmoid D 2cc values in EQD2 were on average 5.69/2.62 Gy, 7.31/6.15 Gy and 3.65/0.69 Gy lower for T&R, with similar HRCTV volume and coverage. Clinical data also showed lower T&R OAR doses, with mean EQD2 D 2cc deviations of 0.61 Gy, 7.96 Gy (p < 0.01) and 5.86 Gy (p < 0.01) for bladder, rectum and sigmoid. Accurate knowledge-based dose prediction models were developed for two common intracavitary applicators. These models could be beneficial for standardizing and improving the quality of brachytherapy plans. Both models and clinical data suggest that significant OAR sparing can be achieved with T&R over T&O applicators, particularly for the rectum. [ABSTRACT FROM AUTHOR]

The use of interstitial needles, combined with intracavitary applicators, enables customized dose distributions and is beneficial for complex cases, but increases procedure time. Overall, applicator selection is not standardized and depends on physician expertise and preference. The purpose of this study is to determine whether dose prediction models can guide needle supplementation decision-making for cervical cancer. Intracavitary knowledge-based models for organ-at-risk (OAR) dose estimation were trained and validated for tandem-and-ring/ovoids (T&R/T&O) implants. Models were applied to hybrid cases with 1–3 implanted needles to predict OAR dose without needles. As a reference, 70/67 hybrid T&R/T&O cases were replanned without needles, following a standardized procedure guided by dose predictions. If a replanned dose exceeded the dose objective, the case was categorized as requiring needles. Receiver operating characteristic (ROC) curves of needle classification accuracy were generated. Optimal classification thresholds were determined from the Youden Index. Needle supplementation reduced dose to OARs. However, 67%/39% of replans for T&R/T&O met all dose constraints without needles. The ROC for T&R/T&O models had an area-under-curve of 0.89/0.86, proving high classification accuracy. The optimal threshold of 99%/101% of the dose limit for T&R/T&O resulted in classification sensitivity and specificity of 78%/86% and 85%/78%. Needle supplementation reduced OAR dose for most cases but was not always required to meet standard dose objectives, particularly for T&R cases. Our knowledge-based dose prediction model accurately identified cases that could have met constraints without needle supplementation, suggesting that such models may be beneficial for applicator selection. [ABSTRACT FROM AUTHOR]

• An application for exploration and prediction of pelvic organ variability in radiotherapy. • Retrospective patient data are employed to predict anatomical changes in new incoming patients. • The prediction is linked to treatment plan evaluation, supporting the selection of the optimal treatment. • Usage scenarios and an evaluation; both conducted with eight domain experts. [Display omitted] Radiotherapy (RT) requires meticulous planning prior to treatment, where the RT plan is optimized with organ delineations on a pre-treatment Computed Tomography (CT) scan of the patient. The conventionally fractionated treatment usually lasts several weeks. Random changes (e.g., rectal and bladder filling in prostate cancer patients) and systematic changes (e.g., weight loss) occur while the patient is being treated. Therefore, the delivered dose distribution may deviate from the planned. Modern technology, in particular image guidance, allows to minimize these deviations, but risks for the patient remain. We present PREVIS : a visual analytics tool for (i) the exploration and prediction of changes in patient anatomy during the upcoming treatment, and (ii) the assessment of treatment strategies, with respect to the anticipated changes. Records of during-treatment changes from a retrospective imaging cohort with complete data are employed in PREVIS , to infer expected anatomical changes of new incoming patients with incomplete data, using a generative model. Abstracted representations of the retrospective cohort partitioning provide insight into an underlying automated clustering, showing main modes of variation for past patients. Interactive similarity representations support an informed selection of matching between new incoming patients and past patients. A Principal Component Analysis (PCA)-based generative model describes the predicted spatial probability distributions of the incoming patient's organs in the upcoming weeks of treatment, based on observations of past patients. The generative model is interactively linked to treatment plan evaluation, supporting the selection of the optimal treatment strategy. We present a usage scenario, demonstrating the applicability of PREVIS in a clinical research setting, and we evaluate our visual analytics tool with eight clinical researchers. [ABSTRACT FROM AUTHOR]

Background: Population-based studies demonstrate that Black men in the United States have an increased risk of death from prostate cancer. Determinants of racial disparities are multifactorial, including socioeconomic and biologic factors.Methods: The authors conducted a pooled analysis of patients derived from 152 centers within the Veterans Health Administration. The cohort included men who had nonmetastatic prostate diagnosed between 2001 and 2015 and received definitive radiation therapy. The primary endpoint was prostate cancer-specific mortality (PCSM). Secondary endpoints included all-cause mortality (ACM) and the time from a prostate-specific antigen level ≥4 ng/mL to biopsy and radiation therapy. A Cox regression model was performed to adjust for differences between clinical parameters.Results: Among the 31,131 patients included in the cohort, 9584 (30.8%) were Black. The 10-year cumulative incidence of death from prostate cancer was lower in Black men compared with White men (4.0% vs 4.8%; P = .004). In a competing risk model, Black race was associated with a decreased risk of PCSM (subdistribution hazard ratio, 0.79; 95% CI, 0.69-0.92; P = .002). Similarly, the 10-year cumulative incidence of death from any cause was lower in Black men (27.6% vs 31.8%; P < .001). In multivariable analysis, Black men had a 10% decreased risk of ACM (hazard ratio, 0.90; 95% CI, 0.85-0.95; P < .001).Conclusions: The current results indicate relatively lower PCSM and ACM among Black men who were included in a large Veterans Health Administration cohort and received radiation therapy as primary treatment for nonmetastatic prostate cancer. There is an ongoing need to continue to understand and mitigate the factors associated with disparities in health care outcomes. [ABSTRACT FROM AUTHOR]

While peer review is critical for quality and safety in radiotherapy, there are neither formal guidelines nor format examples for brachytherapy (BT) peer review. We report on a gynecologic BT peer-review method implemented at a high-volume academic center. We analyzed discussions at bimonthly gynecologic BT peer-review rounds between July and December 2018. Rounds consisted of 2–5 attending physicians with gynecologic BT expertise, 1–2 BT physicists, and trainees. Peer-review targets included clinical case review, contours, implant technique, dose/fractionation, and target/organ-at-risk (OAR) dosimetry. The projected/final target and OAR dosimetry were analyzed. 55 separate implants from 44 patients were reviewed. Implants were mostly reviewed after the first BT fraction (n = 16, 29%) or at another time point during BT (n = 20, 36%). One (2%) implant was presented prospectively. The applicator type and BT technique were reviewed for all implants. Dose/fractionation was evaluated for 46 implants (84%); contours were discussed for 21 (38%). Target and OAR dosimetry were reviewed for 54 (98%) and 28 implants (51%), respectively. Six cases (11%) underwent minor changes to the applicator type to improve target and/or OAR dosimetry. One case (2%) had a major change recommended to the dose/fractionation. Gynecologic BT peer review may enhance BT quality by allowing for implant optimization and formal review of challenging cases, ultimately improving medical decision-making and team communication. Peer review should be implemented in centers offering gynecologic BT. [ABSTRACT FROM AUTHOR]

• An application for cohort exploration of pelvic organ variability in radiotherapy. • Global exploration of anatomical variability in an abstracted tabular view. • Local exploration of anatomical variability with 2D/3D comparative visualizations. • Correlation of anatomical variability with radiation doses and toxicity. • Four application scenarios conducted with domain experts to showcase VAPOR. In radiation therapy (RT) for prostate cancer, changes in patient anatomy during treatment might lead to inadequate tumor coverage and higher irradiation of healthy tissues in the nearby pelvic organs. Exploring and analyzing anatomical variability throughout the course of RT can support the design of more robust treatment strategies, while identifying patients that are prone to radiation-induced toxicity. We present VAPOR , a novel application for the exploration of pelvic organ variability in a cohort of patients, across the entire treatment process. Our application addresses: (i) the global exploration and analysis of anatomical variability in an abstracted tabular view, (ii) the local exploration and analysis thereof in anatomical 2D/3D views, where comparative and ensemble visualizations are integrated, and (iii) the correlation of anatomical variability with radiation doses and potential toxicity. The workflow is based on available retrospective cohort data, which include segmentations of the bladder, the prostate, and the rectum through the entire treatment period. VAPOR is applied to four usage scenarios, which were conducted with two medical physicists. Our application provides clinical researchers with promising support in demonstrating the significance of treatment adaptation to anatomical changes. [ABSTRACT FROM AUTHOR]

The purpose of this study is to explore knowledge-based organ-at-risk dose estimation for intracavitary brachytherapy planning for cervical cancer. Using established external-beam knowledge-based dose-volume histogram (DVH) estimation methods, we sought to predict bladder, rectum, and sigmoid D 2cc for tandem and ovoid treatments. A total of 136 patients with loco-regionally advanced cervical cancer treated with 456 (356:100 training:validation ratio) CT-based tandem and ovoid brachytherapy fractions were analyzed. Single fraction prescription doses were 5.5–8 Gy with dose criteria for the high-risk clinical target volume, bladder, rectum, and sigmoid. DVH estimations were obtained by subdividing training set organs-at-risk into high-risk clinical target volume boundary distance subvolumes and computing cohort-averaged differential DVHs. Full DVH estimation was then performed on the training and validation sets. Model performance was quantified by ΔD 2cc = D 2cc (actual)-D 2cc (predicted) (mean and standard deviation). ΔD 2cc between training and validation sets were compared with a Student's t test (p < 0.01 significant). Categorical variables (physician, fraction-number, total fractions, and case complexity) that might explain model variance were examined using an analysis of variance test (Bonferroni-corrected p < 0.01 threshold). Training set deviations were bladder ΔD 2cc = −0.04 ± 0.61 Gy, rectum ΔD 2cc = 0.02 ± 0.57 Gy, and sigmoid ΔD 2cc = −0.05 ± 0.52 Gy. Model predictions on validation set did not statistically differ: bladder ΔD 2cc = −0.02 ± 0.46 Gy (p = 0.80), rectum ΔD 2cc = −0.007 ± 0.47 Gy (p = 0.53), and sigmoid ΔD 2cc = −0.07 ± 0.47 Gy (p = 0.70). The only significant categorical variable was the attending physician for bladder and rectum ΔD 2cc. A simple boundary distance-driven knowledge-based DVH estimation exhibited promising results in predicting critical brachytherapy dose metrics. Future work will examine the utility of these predictions for quality control and automated brachytherapy planning. [ABSTRACT FROM AUTHOR]

Purpose: The use of concurrent doublet chemotherapy with radiation for locoregionally advanced cervical cancer (LACC) is limited by gastrointestinal and hematologic toxicity. By reducing radiation dose to bowel and bone marrow, image guided intensity modulated radiation therapy (IG-IMRT) may improve chemotherapy tolerance. The goal of this study was to determine whether IG-IMRT could lead to improved tolerance to concurrent cisplatin and gemcitabine for LACC.Methods and Materials: We conducted an open-label, nonrandomized, prospective phase 1 dose escalation trial at a tertiary academic cancer center (ClinicalTrials.gov identifier: NCT01554410). We enrolled patients with stage IB-IVA cervical cancer, with either an intact cervix or posthysterectomy with residual/recurrent pelvic or paraortic nodal involvement, undergoing radical pelvic or extended field chemoradiation therapy. Treatment consisted of chemoradiation with IG-IMRT (45-47.6 Gy, 25-28 fractions to the pelvis ± paraortic nodes with simultaneous nodal boost to 53.2-59.4 Gy, 28 fractions) plus 5 cycles of concurrent weekly cisplatin 40 mg/m2 with escalating doses of gemcitabine (50, 75, 100, or 125 mg/m2). Cohorts were separated preregistration according to whether the patient received pelvic or extended field IG-IMRT and whether gemcitabine followed (CG) or preceded (GC) cisplatin delivery. Dose-limiting toxicity (DLT) events were monitored up to 30 days after chemoradiation therapy. The primary endpoint was maximum tolerated dose (MTD) resulting in DLT probability ≤20%.Results: Between February 2011 and June 2019, 35 patients were registered. Overall, 7 patients (20.0%) experienced DLTs. For the pelvic field cohort, the estimated MTD was 100 mg/m2 with GC sequencing, which is higher than the previously reported MTD for this regimen. The extended field cohort was closed after 2 of 3 patients experienced a DLT at the first dose level.Conclusions: IG-IMRT can permit higher doses of concurrent gemcitabine with cisplatin and pelvic radiation for LACC. However, acute toxicity remains a factor with this regimen, depending on radiation volume and chemotherapy sequencing. [ABSTRACT FROM AUTHOR]

Background: African American (AA) men in the general US population are more than twice as likely to die of prostate cancer (PC) compared with non-Hispanic white (NHW) men. The authors hypothesized that receiving care through the Veterans Affairs (VA) health system, an equal-access medical system, would attenuate this disparity.Methods: A longitudinal, centralized database of >20 million veterans was used to assemble a cohort of 60,035 men (18,201 AA men [30.3%] and 41,834 NHW men [69.7%]) who were diagnosed with PC between 2000 and 2015.Results: AA men were more likely to live in regions with a lower median income ($40,871 for AA men vs $48,125 for NHW men; P < .001) and lower high school graduation rates (83% for AA men vs 88% for NHW men; P < .001). At the time of diagnosis, AA men were younger (median age, 63.0 years vs 66.0 years; P < .001) and had a higher prostate-specific antigen level (median, 6.7 ng/mL vs 6.2 ng/mL; P < .001), but were less likely to have Gleason score 8 to 10 disease (18.8% among AA men vs 19.7% among NHW men; P < .001), a clinical T classification ≥3 (2.2% vs 2.9%; P < .001), or distant metastatic disease (2.7% vs 3.1%; P = 0.01). The 10-year PC-specific mortality rate was slightly lower for AA men (4.4% vs 5.1%; P = .005), which was confirmed in multivariable competing-risk analysis (subdistribution hazard ratio, 0.85; 95% CI, 0.78-0.93; P < .001).Conclusions: AA men diagnosed with PC in the VA health system do not appear to present with more advanced disease or experience worse outcomes compared with NHW men, in contrast to national trends, suggesting that access to care is an important determinant of racial equity. [ABSTRACT FROM AUTHOR]

Marriage has been associated with enhanced survival among cancer patients, but conflicting correlations have been suggested in cervical cancer. We assessed the impact of marital status on receipt of brachytherapy and survival in women with locally advanced cervical cancer. Three thousand, eight hundred and twelve patients with Stage IB2–IVA cervical cancer diagnosed from 2006 to 2015 treated with external beam radiotherapy were identified from the California Cancer Registry. Chi-square tests were used to compare patient characteristics by marital status and boost type. The association of marital status with brachytherapy (BT) receipt was assessed using multiple logistic regression. Fine and Gray competing risks and Cox proportional hazards regressions were used to estimate cervical cancer–specific survival (CCSS) and overall survival (OS), respectively. Most women were unmarried (58.8%). Half (50.4%) received BT, while 33.1% received no boost; most (86.3%) received chemotherapy. Unmarried women had similar odds of receiving BT as married women (OR = 1.07, 95% CI: 0.90-1.28, p = 0.4370) but were less likely to receive chemotherapy (84.3% vs. 89.1%, p < 0.0001). Singlehood was significantly associated with worse CCSS (subdistribution hazard ratio = 1.21, 95% CI: 1.03-1.42, p < 0.0174) and OS (hazard ratio = 1.18, 95% CI: 1.03-1.36, p < 0.0153). Not receiving a radiation boost was also significantly associated with worse CCSS (subdistribution hazard ratio = 1.21, 95% CI: 1.02-1.43, p = 0.0317) and OS (hazard ratio = 1.21, 95% CI: 1.05-1.40, p = 0.0100). There were no differences in BT receipt in married vs. unmarried patients. However, unmarried patients had worse CCSS and OS and were less likely to receive chemotherapy. Interventions targeting social factors are needed to improve outcomes in this vulnerable population. [ABSTRACT FROM AUTHOR]

NIBB has potential advantages over other APBI techniques by delivering highly conformal radiation with minimal collateral dose to the heart and lung compared with external beam techniques, but unlike other brachytherapy techniques NIBB is non-invasive. Previous data has shown encouraging clinical outcomes using a 10-fraction regimen. To improve efficiency, convenience, and cost, reduction in fraction number is desirable. A prospective phase II trial was initiated to evaluate NIBB APBI delivered in 5 fractions. Final results of this trial are presented. NIBB APBI was delivered using 28.5 Gy in 5 fractions daily over 1 week. Patient eligibility criteria required: invasive carcinoma ≤2.0 cm or DCIS ≤3.0 cm, ER positive (if invasive), lymph node negative, LVI absent, and lumpectomy with margins negative by 2 mm. NIBB was delivered using 2 orthogonal treatment axes for each fraction. Applicators were selected to cover the lumpectomy cavity with a 1.0 cm CTV margin and a 0-0.5 cm PTV margin. Patients were followed at 6-month intervals for 2 years then annually to 5 years. The primary endpoint was late toxicity, specifically rate of subcutaneous fibrosis/induration (grade ≥ 2) <30%. Late toxicities were evaluated and graded based on CTCAE v3.0. Cosmesis was graded based on the NRG/RTOG scale. Kaplan-Meier Method was used to calculated actuarial rate of local control and survival. Chi square and two tailed t-test were used to evaluate association of patient and treatment variables with late toxicities. 40 patients were enrolled and treated with a mean age of 67 years (range: 50-89 years). The mean tumor size was 1.0 cm (range: 0.3-2.0 cm) with 75% invasive ductal carcinoma and 20% DCIS. Mean breast separation with compression was 6.7 cm (range: 3.5-8.9 cm). Endocrine therapy was administered to 42.5% of patients and no patients received chemotherapy. At a median follow up of 59.7 months, there was 1 true local recurrence resulting in a 5-year actuarial local control rate of 96.6% (+/- 3.4%). Ipsilateral new primary, contralateral new primary, and nodal recurrence were seen in 3, 3, and 1 patient(s), respectively. Overall survival was 96.9% (+/-3.1%) at 5 years. Grade 2 and 3+ late toxicities were 15% and 0%, respectively. Grade 2 subcutaneous fibrosis or induration was seen in 2.5% (+/-2.5%) meeting the study's primary endpoint. The most common late toxicity of any grade was skin telangiectasia. Grade 1 and 2 telangiectasia was seen in 9 (22.5%) and 6 patients (15%), respectively. Evaluation revealed that only breast separation after compression was associated with increased risk of telangiectasia; ≤7 cm 17.4% and >7 cm 64.7%, p=0.002. Overall cosmetic outcome at last follow up was excellent, good, and fair/poor in 75%, 25%, and 0%, respectively. NIBB APBI delivered in 5 fractions results in a low rate of late toxicity and a high rate of good/excellent cosmetic outcomes. Telangiectasia risk can be minimized by keeping breast separation ≤7.0 cm. The local failure rate was appropriately low. Further investigation of this technique is warranted. [ABSTRACT FROM AUTHOR]

Research demonstrates that instructing patients to have a full bladder for pelvic radiotherapy results in highly variable bladder volumes at daily treatment. We aimed to determine bladder volume variation in patients with intact cervical cancer treated with intensity-modulated radiotherapy (IMRT) on an empty bladder and estimate the difference in radiation dose to the small bowel compared to treating on a full bladder. We identified 29 patients treated with IMRT from 2010 to 2013 who underwent 2 planning computed tomography (CT) scans, 1 with a full bladder followed by 1 with an empty bladder. Interfractional variation in bladder volume was measured using 782 daily cone beam computed tomography (CBCT) scans. To estimate dose to small bowel, radiation plans were created on both empty and full bladder CT scans using an automated knowledge-based planning modeling program. Mean bladder volume with empty bladder instructions was 67 ± 26 cc compared to 91 ± 43 cc for no bladder instructions and 154 ± 54 cc for full bladder instructions (p < 0.001). There was a significant reduction in the absolute bladder volume variation in patients given empty bladder instructions compared to full bladder instructions (p < 0.05) The intraclass correlation coefficient showed low reliability of bladder filling across all groups (p = 0.6). The average bowel V45 for the empty bladder plans was 188 cc, compared to 139 cc for the full bladder plans (p < 0.05). More plans created on an empty bladder exceeded Quantitative Analyses of Normal Tissue Effects in the Clinic (QUANTEC) guidelines but this was not significant (31% vs 14%, p = 0.12). Reliability of bladder volume at the time of radiation treatment is low, regardless of bladder filling instructions, although an empty bladder reduces absolute variation in bladder volume. Radiation planning on an empty bladder predicts a larger volume of small bowel receiving 45 Gy compared to a full bladder, although bowel dose on average is still within QUANTEC guidelines (V45 < 195 cc). [ABSTRACT FROM AUTHOR]

Purpose: It is unclear if additional serum testosterone suppression below the castrate threshold of 50 ng/dL improves clinical outcomes in patients with localized prostate cancer undergoing definitive therapy.Methods and Materials: We examined the association of subcastrate testosterone nadir with prostate-specific antigen (PSA) response and long-term clinical outcomes in 764 U.S. veterans with intermediate- or high-risk localized prostate cancer treated with androgen deprivation therapy and definitive radiation therapy from 2000 to 2015. Patients were categorized into testosterone nadir groups based on the minimum testosterone measurement during continuous gonadotropic-releasing hormone agonist therapy (<20 ng/dL vs 20-49 ng/dL). Outcomes included PSA response (3-month post-radiation therapy PSA and 2-year PSA nadir; multivariable linear regression) and long-term clinical outcomes (biochemical recurrence, metastasis, and prostate cancer-specific mortality; Fine-Gray competing risk regression).Results: A testosterone nadir of 20 to 49 ng/dL was associated with higher 3-month post-radiation therapy PSA compared to <20 ng/dL (ß = 0.16, 95% confidence interval [CI], 0.06-0.26, P = .001) and higher 2-year PSA nadir (ß = 0.12, 95% CI, 0.04-0.21, P = .005). Compared to the <20-ng/dL group, the 20 to 49-ng/dL group showed higher 10-year biochemical recurrence rates (28.1% vs 18.3%) and metastasis rates (12.9% vs 7.8%) persisting on multivariable analyses (biochemical recurrence: sub-distribution hazard ratio [SDHR], 1.62 for 20-49 ng/dL, 95% CI, 1.07-2.45, P = .02; metastasis: SDHR, 2.19, 95% CI, 1.21-3.94, P = .009). There was a trend toward inferior prostate cancer-specific mortality for the 20 to 49-ng/dL group (SDHR, 1.95, 95% CI, 0.90-4.22, P = .09).Conclusions: Additional serum testosterone suppression below 50 ng/dL was associated with improved PSA responses and lower rates of biochemical recurrence and metastasis in this cohort of patients with localized prostate cancer. [ABSTRACT FROM AUTHOR]

Purpose To improve efficiency, convenience, and cost, a prospective phase II trial was initiated to evaluate accelerated partial breast irradiation delivered with noninvasive image-guided breast brachytherapy (NIBB) via five once-daily fractions. Methods and Materials Women ≥50 years old with early-stage breast cancer undergoing breast conserving surgery were enrolled. Eligibility criteria included invasive carcinoma ≤2.0 cm or ductal carcinoma in situ ≤3.0 cm, ER positive (if invasive), lymph node negative, LVI absent, and margins negative by 2 mm. Patients received a total dose of 28.5 Gy in five daily fractions. NIBB was delivered using two orthogonal axes for each fraction. Applicators were selected to encompass the lumpectomy cavity with a 1.0 cm clinical target volume margin and 0 to 0.5 cm planning target volume margin. Acute and late toxicity was assessed based on CTCAE v3.0. Results Forty patients with a mean age of 67 years underwent protocol treatment. Mean tumor size was 1.0 cm (0.3–2.0 cm). Eighty percent had invasive carcinoma and the remainder had ductal carcinoma in situ. Mean tumor bed volume was 21 cc (5–79 cc) and mean breast volume was 1319 cc (499–3044 cc). Mean breast separation with compression was 6.7 cm (3.5–8.9 cm). All patients tolerated well. Median discomfort with compression was 1 (range: 0–7) on a 10-point pain scale. Acute skin reaction was Grade 0–1 in 70%, Grade 2 in 28%, and Grade 3 in 3%. Acute skin toxicity was not associated with breast size but was associated with larger breast separation with compression ( p < 0.01) and larger applicator size ( p < 0.01). No Grade 3+ late toxicity or local recurrences have been observed at a median followup of 14 months. Conclusions Accelerated partial breast irradiation delivered using NIBB over five daily fractions is a convenient treatment option that is feasible and well tolerated. [ABSTRACT FROM AUTHOR]

Background: Prostate-specific antigen (PSA) measurement after definitive radiotherapy (RT) and androgen deprivation therapy for localized prostate cancer has been proposed as an early prognostic biomarker. In the current study, the authors investigated the association between 3-month post-RT PSA level and biochemical progression-free survival (bPFS), prostate cancer-specific survival (PCSS), and overall survival (OS).Methods: A total of 5783 patients with intermediate-risk or high-risk localized prostate cancer who were diagnosed between 2000 and 2015 and treated with RT and androgen deprivation therapy were identified from Veterans Affairs data. Patients were divided into groups based on 3-month post-RT PSA values: <0.10 ng/mL, 0.10 to 0.49 ng/mL, and ≥0.50 ng/mL. The effect of the 3-month PSA group on bPFS, PCSS, and OS was evaluated in multivariable Cox models adjusting for potential confounders.Results: There were 2651 patients with intermediate-risk and 3132 with high-risk disease; approximately 11% had a 3-month PSA level of ≥0.50 ng/mL. A higher 3-month PSA level was found to be strongly associated with each outcome; compared with patients in the group with a 3-month PSA value <0.10 ng/mL, the authors noted greater hazards for the patients with a 3-month PSA value ≥0.50 ng/mL (hazard ratio for bPFS: 5.23; PCSS: 3.97; and OS: 1.50 [P<.001 for all]) and the patients with a 3-month PSA value of 0.10 to 0.49 ng/mL (hazard ratio for bPFS: 2.41 [P<.001]; PCSS: 2.29 [P<.001]; and OS: 1.21 [P = .003]). When analyzed separately, the 3-month PSA level was found to be predictive of OS in the high-risk group (P<.001) but not the intermediate-risk group (P = .21).Conclusions: The 3-month post-RT PSA level appears to be a strong prognostic biomarker for bPFS, PCSS, and OS in patients with intermediate-risk and high-risk prostate cancer, particularly those with high-risk disease. The 3-month PSA measurement may augment clinical decision making and holds promise as a potential surrogate endpoint in clinical trials. Cancer 2018;124:2939-47. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose: Despite multiple randomized trials showing the efficacy of hypofractionated radiation therapy in early-stage breast cancer, the United States has been slow to adopt this treatment. The goal of this study was to evaluate the impact of individual radiation oncologists on the early adoption of hypofractionated radiation therapy for early-stage breast cancer.Methods: We identified 22,233 Medicare beneficiaries with localized breast cancer that was diagnosed from 2004 to 2011 who underwent breast-conserving surgery with adjuvant radiation. Multilevel, multivariable logistic models clustered by radiation oncologist and geographic practice area were used to determine the impact of the provider and geographic region on the likelihood of receiving hypofractionated compared with standard fractionated radiation therapy while controlling for a patient's clinical and demographic covariates. Odds ratios (OR) describe the impact of demographic or clinical covariates, and the median OR (MOR) describes the relative impact of the individual radiation oncologist and geographic region on the likelihood of undergoing hypofractionated radiation therapy.Results: Among the entire cohort, 2333 women (10.4%) were treated with hypofractionated radiation therapy, with unadjusted rates ranging from 0.0% in the bottom quintile of radiation oncologists to 30.4% in the top quintile. Multivariable analysis found that the individual radiation oncologist (MOR 3.08) had a greater impact on the use of hypofractionation than did geographic region (MOR 2.10) or clinical and demographic variables. The impact of the provider increased from the year 2004 to 2005 (MOR 2.82) to the year 2010 to 2011 (MOR 3.16) despite the publication of long-term randomized trial results in early 2010. Male physician and radiation oncologists treating the highest volume of breast cancer patients were less likely to perform hypofractionation (P<.05).Conclusions: The individual radiation oncologist strongly influenced the likelihood of a patient's receiving hypofractionated radiation therapy, and this trend increased despite the publication of long-term data showing equivalence to standard fractionation. Future research should focus on physician-related factors that influence this decision. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate geographic heterogeneity in the delivery of hypofractionated radiation therapy (RT) for breast cancer among Medicare beneficiaries across the United States.Methods and Materials: We identified 190,193 patients from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse. The study included patients aged >65 years diagnosed with invasive breast cancer treated with breast conservation surgery followed by radiation diagnosed between 2000 and 2012. We analyzed data by hospital referral region based on patient residency ZIP code. The proportion of women who received hypofractionated RT within each region was analyzed over the study period. Multivariable logistic regression models identified predictors of hypofractionated RT.Results: Over the entire study period we found substantial geographic heterogeneity in the use of hypofractionated RT. The proportion of women receiving hypofractionated breast RT in individual hospital referral regions varied from 0% to 61%. We found no correlation between the use of hypofractionated RT and urban/rural setting or general geographic region. The proportion of hypofractionated RT increased in regions with higher density of radiation oncologists, as well as lower total Medicare reimbursements.Conclusions: This study demonstrates substantial geographic heterogeneity in the use of hypofractionated RT among elderly women with invasive breast cancer treated with lumpectomy in the United States. This heterogeneity persists despite clinical data from multiple randomized trials proving efficacy and safety compared with standard fractionation, and highlights possible inefficiency in health care delivery. [ABSTRACT FROM AUTHOR]

Purpose: Adjuvant radiation therapy, which has proven benefit against breast cancer, has historically been associated with an increased incidence of ischemic heart disease. Modern techniques have reduced this risk, but a detailed evaluation has not recently been conducted. The present study evaluated the effect of current radiation practices on ischemia-related cardiac events and procedures in a population-based study of older women with nonmetastatic breast cancer.Methods and Materials: A total of 29,102 patients diagnosed from 2000 to 2009 were identified from the Surveillance, Epidemiology, and End Results-Medicare database. Medicare claims were used to identify the radiation therapy and cardiac outcomes. Competing risk models were used to assess the effect of radiation on these outcomes.Results: Patients with left-sided breast cancer had a small increase in their risk of percutaneous coronary intervention (PCI) after radiation therapy-the 10-year cumulative incidence for these patients was 5.5% (95% confidence interval [CI] 4.9%-6.2%) and 4.5% (95% CI 4.0%-5.0%) for right-sided patients. This risk was limited to women with previous cardiac disease. For patients who underwent PCI, those with left-sided breast cancer had a significantly increased risk of cardiac mortality with a subdistribution hazard ratio of 2.02 (95% CI 1.23-3.34). No other outcome, including cardiac mortality for the entire cohort, showed a significant relationship with tumor laterality.Conclusions: For women with a history of cardiac disease, those with left-sided breast cancer who underwent radiation therapy had increased rates of PCI and a survival decrement if treated with PCI. The results of the present study could help cardiologists and radiation oncologists better stratify patients who need more aggressive cardioprotective techniques. [ABSTRACT FROM AUTHOR]