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Background Breast cancer risk models guide screening and chemoprevention decisions, but the extent and effect of variability among models, particularly at the individual level, is uncertain. Objective To quantify the accuracy and disagreement between commonly used risk models in categorizing individual women as average vs. high risk for developing invasive breast cancer. Design Comparison of three risk prediction models: Breast Cancer Risk Assessment Tool (BCRAT), Breast Cancer Surveillance Consortium (BCSC) model, and International Breast Intervention Study (IBIS) model. Subjects Women 40 to 74 years of age presenting for screening mammography at a multisite health system between 2011 and 2015, with 5-year follow-up for cancer outcome. Main Measures Comparison of model discrimination and calibration at the population level and inter-model agreement for 5-year breast cancer risk at the individual level using two cutoffs (≥ 1.67% and ≥ 3.0%). Key Results A total of 31,115 women were included. When using the ≥ 1.67% threshold, more than 21% of women were classified as high risk for developing breast cancer in the next 5 years by one model, but average risk by another model. When using the ≥ 3.0% threshold, more than 5% of women had disagreements in risk severity between models. Almost half of the women (46.6%) were classified as high risk by at least one of the three models (e.g., if all three models were applied) for the threshold of ≥ 1.67%, and 11.1% were classified as high risk for ≥ 3.0%. All three models had similar accuracy at the population level. Conclusions Breast cancer risk estimates for individual women vary substantially, depending on which risk assessment model is used. The choice of cutoff used to define high risk can lead to adverse effects for screening, preventive care, and quality of life for misidentified individuals. Clinicians need to be aware of the high false-positive and false-negative rates and variation between models when talking with patients.

ImportanceWith a shortfall in fellowship-trained breast radiologists, mammography screening programs are looking toward artificial intelligence (AI) to increase efficiency and diagnostic accuracy. External validation studies provide an initial assessment of how promising AI algorithms perform in different practice settings.ObjectiveTo externally validate an ensemble deep-learning model using data from a high-volume, distributed screening program of an academic health system with a diverse patient population.Design, Setting, and ParticipantsIn this diagnostic study, an ensemble learning method, which reweights outputs of the 11 highest-performing individual AI models from the Digital Mammography Dialogue on Reverse Engineering Assessment and Methods (DREAM) Mammography Challenge, was used to predict the cancer status of an individual using a standard set of screening mammography images. This study was conducted using retrospective patient data collected between 2010 and 2020 from women aged 40 years and older who underwent a routine breast screening examination and participated in the Athena Breast Health Network at the University of California, Los Angeles (UCLA).Main Outcomes and MeasuresPerformance of the challenge ensemble method (CEM) and the CEM combined with radiologist assessment (CEM+R) were compared with diagnosed ductal carcinoma in situ and invasive cancers within a year of the screening examination using performance metrics, such as sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC).ResultsEvaluated on 37 317 examinations from 26 817 women (mean [SD] age, 58.4 [11.5] years), individual model AUROC estimates ranged from 0.77 (95% CI, 0.75-0.79) to 0.83 (95% CI, 0.81-0.85). The CEM model achieved an AUROC of 0.85 (95% CI, 0.84-0.87) in the UCLA cohort, lower than the performance achieved in the Kaiser Permanente Washington (AUROC, 0.90) and Karolinska Institute (AUROC, 0.92) cohorts. The CEM+R model achieved a sensitivity (0.813 [95% CI, 0.781-0.843] vs 0.826 [95% CI, 0.795-0.856]; P = .20) and specificity (0.925 [95% CI, 0.916-0.934] vs 0.930 [95% CI, 0.929-0.932]; P = .18) similar to the radiologist performance. The CEM+R model had significantly lower sensitivity (0.596 [95% CI, 0.466-0.717] vs 0.850 [95% CI, 0.766-0.923]; P P P = .004).Conclusions and RelevanceThis study found that the high performance of an ensemble deep-learning model for automated screening mammography interpretation did not generalize to a more diverse screening cohort, suggesting that the model experienced underspecification. This study suggests the need for model transparency and fine-tuning of AI models for specific target populations prior to their clinical adoption.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused one of the worst pandemics in recent history. Few reports have revealed that SARS-CoV-2 was spreading in the United States as early as the end of January. In this study, we aimed to determine if SARS-CoV-2 had been circulating in the Los Angeles (LA) area at a time when access to diagnostic testing for coronavirus disease 2019 (COVID-19) was severely limited. Methods We used a pooling strategy to look for SARS-CoV-2 in remnant respiratory samples submitted for regular respiratory pathogen testing from symptomatic patients from November 2019 to early March 2020. We then performed sequencing on the positive samples. Results We detected SARS-CoV-2 in 7 specimens from 6 patients, dating back to mid-January. The earliest positive patient, with a sample collected on January 13, 2020 had no relevant travel history but did have a sibling with similar symptoms. Sequencing of these SARS-CoV-2 genomes revealed that the virus was introduced into the LA area from both domestic and international sources as early as January. Conclusions We present strong evidence of community spread of SARS-CoV-2 in the LA area well before widespread diagnostic testing was being performed in early 2020. These genomic data demonstrate that SARS-CoV-2 was being introduced into Los Angeles County from both international and domestic sources in January 2020.

Purpose To investigate the prognostic value of pre-treatment immune parameters including white blood cell count (WBC) and circulating lymphocyte count (CLC) among patients with oropharyngeal carcinoma treated by radiation therapy. Methods and Materials A total of 136 consecutive patients were treated by radiation therapy for locally advanced (stage III/IV) squamous cell carcinoma of the oropharynx with known human papillomavirus (HPV) status. Medical records were reviewed to identify patients with documented pre-treatment laboratory bloodwork. The Kaplan-Meier method and linear regression models were used to evaluate the association between pre-treatment CBC and CLC values with survival endpoints. Results One hundred and eleven patients satisfied inclusion criteria. Median age was 62 years (range, 22–91). Eighty-four patients were HPV-positive (76%) and 27 (24%) were HPV-negative. There was no difference in WBC and CLC mean values at baseline between HPV-positive and HV-negative (p > 0.05, for both). Trends were detected in the HPV-positive cohort favoring patients with higher CLC, with respect to 2-year local-regional control (93% vs. 82%, p = 0.06) and distant control (88% vs. 82%, p = 0.10) using the median CLC as cut-off. HPV-positive patients with CLC values in the lowest quartile had inferior local-regional control compared to those in the upper 3 quartiles (69% vs. 89%, p = 0.01). Conclusion Low pre-treatment CLC was correlated with local-regional recurrence and distant failure among HPV-positive patients. These associations were not observed in the HPV-negative cohort.

Background Accurately assessing the regional activity of diseases such as COVID-19 is important in guiding public health interventions. Leveraging electronic health records (EHRs) to monitor outpatient clinical encounters may lead to the identification of emerging outbreaks. Objective The aim of this study is to investigate whether excess visits where the word “cough” was present in the EHR reason for visit, and hospitalizations with acute respiratory failure were more frequent from December 2019 to February 2020 compared with the preceding 5 years. Methods A retrospective observational cohort was identified from a large US health system with 3 hospitals, over 180 clinics, and 2.5 million patient encounters annually. Data from patient encounters from July 1, 2014, to February 29, 2020, were included. Seasonal autoregressive integrated moving average (SARIMA) time-series models were used to evaluate if the observed winter 2019/2020 rates were higher than the forecast 95% prediction intervals. The estimated excess number of visits and hospitalizations in winter 2019/2020 were calculated compared to previous seasons. Results The percentage of patients presenting with an EHR reason for visit containing the word “cough” to clinics exceeded the 95% prediction interval the week of December 22, 2019, and was consistently above the 95% prediction interval all 10 weeks through the end of February 2020. Similar trends were noted for emergency department visits and hospitalizations starting December 22, 2019, where observed data exceeded the 95% prediction interval in 6 and 7 of the 10 weeks, respectively. The estimated excess over the 3-month 2019/2020 winter season, obtained by either subtracting the maximum or subtracting the average of the five previous seasons from the current season, was 1.6 or 2.0 excess visits for cough per 1000 outpatient visits, 11.0 or 19.2 excess visits for cough per 1000 emergency department visits, and 21.4 or 39.1 excess visits per 1000 hospitalizations with acute respiratory failure, respectively. The total numbers of excess cases above the 95% predicted forecast interval were 168 cases in the outpatient clinics, 56 cases for the emergency department, and 18 hospitalized with acute respiratory failure. Conclusions A significantly higher number of patients with respiratory complaints and diseases starting in late December 2019 and continuing through February 2020 suggests community spread of SARS-CoV-2 prior to established clinical awareness and testing capabilities. This provides a case example of how health system analytics combined with EHR data can provide powerful and agile tools for identifying when future trends in patient populations are outside of the expected ranges.

BACKGROUND Accurately assessing the regional activity of diseases such as COVID-19 is important in guiding public health interventions. Leveraging electronic health records (EHRs) to monitor outpatient clinical encounters may lead to the identification of emerging outbreaks. OBJECTIVE The aim of this study is to investigate whether excess visits where the word “cough” was present in the EHR reason for visit, and hospitalizations with acute respiratory failure were more frequent from December 2019 to February 2020 compared with the preceding 5 years. METHODS A retrospective observational cohort was identified from a large US health system with 3 hospitals, over 180 clinics, and 2.5 million patient encounters annually. Data from patient encounters from July 1, 2014, to February 29, 2020, were included. Seasonal autoregressive integrated moving average (SARIMA) time-series models were used to evaluate if the observed winter 2019/2020 rates were higher than the forecast 95% prediction intervals. The estimated excess number of visits and hospitalizations in winter 2019/2020 were calculated compared to previous seasons. RESULTS The percentage of patients presenting with an EHR reason for visit containing the word “cough” to clinics exceeded the 95% prediction interval the week of December 22, 2019, and was consistently above the 95% prediction interval all 10 weeks through the end of February 2020. Similar trends were noted for emergency department visits and hospitalizations starting December 22, 2019, where observed data exceeded the 95% prediction interval in 6 and 7 of the 10 weeks, respectively. The estimated excess over the 3-month 2019/2020 winter season, obtained by either subtracting the maximum or subtracting the average of the five previous seasons from the current season, was 1.6 or 2.0 excess visits for cough per 1000 outpatient visits, 11.0 or 19.2 excess visits for cough per 1000 emergency department visits, and 21.4 or 39.1 excess visits per 1000 hospitalizations with acute respiratory failure, respectively. The total numbers of excess cases above the 95% predicted forecast interval were 168 cases in the outpatient clinics, 56 cases for the emergency department, and 18 hospitalized with acute respiratory failure. CONCLUSIONS A significantly higher number of patients with respiratory complaints and diseases starting in late December 2019 and continuing through February 2020 suggests community spread of SARS-CoV-2 prior to established clinical awareness and testing capabilities. This provides a case example of how health system analytics combined with EHR data can provide powerful and agile tools for identifying when future trends in patient populations are outside of the expected ranges.

Supplemental_Appendix_1 for Pathology Trainees’ Experience and Attitudes on Use of Digital Whole Slide Images by Joann G. Elmore, Hannah Shucard, Annie C. Lee, Pin-Chieh Wang, Kathleen F. Kerr, Patricia A. Carney, Trafton Drew, Tad T. Brunyé and Donald L. Weaver in Academic Pathology

Digital whole slide images are Food and Drug Administration approved for clinical diagnostic use in pathology; however, integration is nascent. Trainees from 9 pathology training programs completed an online survey to ascertain attitudes toward and experiences with whole slide images for pathological interpretations. Respondents (n = 76) reported attending 63 unique medical schools (45 United States, 18 international). While 63% reported medical school exposure to whole slide images, most reported ≤ 5 hours. Those who began training more recently were more likely to report at least some exposure to digital whole slide image training in medical school compared to those who began training earlier: 75% of respondents beginning training in 2017 or 2018 reported exposure to whole slide images compared to 54% for trainees beginning earlier. Trainees exposed to whole slide images in medical school were more likely to agree they were comfortable using whole slide images for interpretation compared to those not exposed (29% vs 12%; P = .06). Most trainees agreed that accurate diagnoses can be made using whole slide images for primary diagnosis (92%; 95% CI: 86-98) and that whole slide images are useful for obtaining second opinions (93%; 95% CI: 88-99). Trainees reporting whole slide image experience during training, compared to those with no experience, were more likely to agree they would use whole slide images in 5 years for primary diagnosis (64% vs 50%; P = .3) and second opinions (86% vs 76%; P = .4). In conclusion, although exposure to whole slide images in medical school has increased, overall exposure is limited. Positive attitudes toward future whole slide image diagnostic use were associated with exposure to this technology during medical training. Curricular integration may promote adoption.

Myxofibrosarcoma (MFS) is reported to have a higher risk of local recurrence (LR) following definitive surgical excision relative to other soft tissue sarcomas. We reviewed our clinical experience treating MFS to investigate predictors of LR.We retrospectively reviewed treatment outcomes for MFS patients treated at our institution between 1999 and 2015. A total of 52 patients were identified. Median age was 65 years (range, 21 to 86 y). Site of disease was: upper extremity (27%), lower extremity (46%), trunk (15%), pelvic (8%), and head and neck (4%). Patients had low, intermediate, high-grade, and unknown grade in: 23%, 8%, 67%, and 2% of tumors, respectively. Tumors were categorized as ≤5 cm (35%),5 cm (56%), or unknown size (9%). In total, 71% received radiotherapy: 19% preoperative, 50% postoperative, and 2% both. All patients underwent surgery. Margins were negative in 71%, close/positive in 21%, and unknown in 8%. In total, 27% of patients received chemotherapy. Univariate Cox regression analysis was utilized to determine associations between clinical and treatment factors with LR.Median follow-up time was 2.9 years (range, 0.4 to 14.3 y). The 3-year actuarial LR, distant metastasis, and overall survival were: 31%, 15%, and 87%, respectively. Predictors of LR were patient age greater than or equal to the median of 65 years (hazard ratio, 13.46, 95% confidence interval, 1.71-106.18, P=0.013), and having close/positive tumor margins (hazard ratio, 3.4, 95% confidence interval, 1-11.53, P=0.049).In this institutional series of MFS older age and positive/close margins were significantly associated with a higher risk of LR.

Purpose To evaluate the prognostic significance of human papillomavirus (HPV) status among patients treated by salvage radiation therapy for local-regional recurrences and second primary cancers of the head and neck arising in a previously irradiated field. Methods and materials The medical records of 54 consecutive patients who underwent re-irradiation for squamous cell carcinoma of the head and neck occurring in a previously irradiated field were reviewed. Only patients with biopsy-proven evidence of recurrent disease that had previously been treated with doses of radiation therapy of at least 60 Gy were included. Determination of HPV status at the time of recurrence was performed by p16 immunohistochemistry. The median age at re-irradiation was 58.5 years (range, 27.9 to 81.5 years). Thirty patients (55.5%) were lifelong never-smokers. The Kaplan Meier method was used to calculate overall survival, progression-free survival, and local-regional control, and distant metastasis-free survival with comparisons between groups performed using the log-rank test. Results HPV status among tumors that were re-irradiated was as follows: 16 positive (29.7%); 7 negative (12.9%); 31 unknown (57.4%). The median overall survival in the entire cohort was 11.7 months (range, 8 to 27 months), with the 1-year and 2-year estimates of overall survival being 47.2% and 38.4%, respectively. A statistical trend was identified favoring patients with HPV-positive cancers with respect to the endpoints of overall survival (p = 0.06) and progression-free survival (p = 0.08) after re-irradiation when compared to the HPV-negative/unknown population. There was no significant difference in distant control between the two cohorts (p = 0.40). Conclusions The favorable prognostic significance of HPV seemingly extends to patients treated by re-irradiation suggesting that this biomarker may be useful in risk stratification in this setting.

Objectives: To investigate biochemical relapse-free survival (BRFS) in men with National Comprehensive Cancer Network-defined intermediate-risk prostate cancer (PC) treated with either stereotactic body radiotherapy (SBRT) or high-dose-rate brachytherapy (HDR-B) monotherapy. Materials and methods: A retrospective, multi-institutional analysis of 437 patients with intermediate-risk PC treated with SBRT (N=300) or HDR-B (N=137) was performed. Men who underwent SBRT were treated to 35 to 40 Gy in 4 to 5 fractions. A total of 95.6% who underwent HDR-B were treated to 42 Gy in 6 fractions. Baseline patient characteristics were compared using a T test for continuous variables and the Mantel-Haenszel χ metric or Fisher exact test for categorical variables. Kaplan-Meier curves were generated to estimate 5-year actuarial BRFS. Multivariate analysis using a Cox proportional-hazards model was used to evaluate factors associated with biochemical failure. Results: The mean age at diagnosis was 68.4 (SD±7.8) years. T-category was T1 in 63.6% and T2 in 36.4%. Mean initial prostate-specific antigen was 7.4 (SD±3.4) ng/mL. Biopsy Gleason score was ≤3+4 in 82.8% and 4+3 in 17.2%. At a median of 4.1 years of follow-up, the BRFS rate (Phoenix definition) was 96.3%, with no difference when stratifying by treatment modality or biologically equivalent dose (BED1.5). On multivariate analysis, age (hazard ratio 1.08, P=0.04) and biopsy Gleason score (hazard ratio 2.48, P=0.03) were significant predictors of BRFS. Conclusions: With a median follow-up period of 4 years, SBRT and HDR-B monotherapy provide excellent BRFS in intermediate-risk PC. Longer-term follow-up is necessary to determine the ultimate efficacy of these hypofractionated approaches, but they appear promising relative to standard fractionation outcomes.

OBJECTIVE The utility of fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to predict outcome has been well-established for patients undergoing definitive radiation in the initial management of head and neck cancer. However, the usefulness of this modality in the recurrent setting remains uncertain. We sought to evaluate the prognostic value of metabolic tumor parameters measured on FDG-PET in patients treated by reirradiation for recurrent head and neck cancer. METHODS Thirty-four tumors occurring in 29 patients were reirradiated and were evaluable. The most common disease sites were the oropharynx (n = 9), oral cavity (N = 8), and nasopharynx (n = 6). Potential correlations of FDG-PET maximum standardized uptake value (SUV) and metabolic tumor volume (MTV) with survival endpoints were explored. Multivariate analysis was performed using Cox proportional hazard. RESULTS The median MTV, SUV, and gross tumor volume, as delineated using the 50% SUVmax threshold, were 366 cc (range, 0-3,567 cc), 8.1 (range, 0-25), and 48.5 cc (range, 1-190 cc), respectively. On univariate analysis, both MTVs (as measured as a continuous variable and using the median value of 266 cc as cutoff) were predictive of decreased overall survival (P

Purpose To analyze functional outcomes for patients treated on a phase 2 trial of de-escalated chemoradiation therapy for human papillomavirus–positive oropharyngeal cancer. Methods and Materials Patient eligibility included p16-positive, stage III or IV oropharyngeal squamous cell carcinoma and a Zubrod performance status of 0 to 1. Treatment was induction chemotherapy with paclitaxel, 175 mg/m2, and carboplatin, area under the curve (AUC) of 6 mg/ml/min, for 2 cycles every 21 days, followed by concurrent paclitaxel, 30 mg/m2, every 7 days with dose-reduced radiation therapy of 54 or 60 Gy. Trends in body weight and body mass index (BMI) were analyzed with gastrostomy tube and narcotic use rates. Functional outcomes were assessed using the University of Washington Quality of Life Scale and the Functional Assessment of Cancer Therapy–Head and Neck Scale. Results Forty-five patients were registered, of whom 40 were evaluable. Only 1 patient had a BMI deemed unhealthy at the completion of treatment. For the 15 patients (38%) with a normal BMI (18-25 kg/m2) before treatment, recovery back to baseline occurred at approximately 18 months (average BMI, 23.2 kg/m2 vs 22.3 kg/m2; P=.09). In 2 patients (5%), gastrostomy tubes were placed during treatment. No patient was enteral feeding tube-dependent at 6 months after treatment. Ninety-five percent of patients tolerated a normal regular diet at last follow-up. Conclusions De-escalated chemoradiation therapy may improve functional outcomes as indicated by the relatively low incidence of gastrostomy tube placement and long-term dysphagia. In patients with a normal BMI prior to chemoradiation therapy, BMI recovered to baseline levels.

Background The current study represents a subset analysis of quality-of-life (QOL) outcomes among patients treated on a phase 2 trial of de-escalated chemoradiation for human papillomavirus (HPV)-associated oropharyngeal cancer. Methods Eligibility included newly diagnosed, (American Joint Committee on Cancer, 7th edition) stage III or IV oropharyngeal squamous cell carcinoma, p16 positivity, age ≥ 18 years, and a Zubrod performance status of 0 to 1. Treatment was induction paclitaxel at a dose of 175 mg/m2 and carboplatin at an area under the curve of 6 for 2 cycles followed by response-adapted, dose-reduced radiation of 54 Gy or 60 Gy with weekly concurrent paclitaxel at a dose of 30 mg/m2 . The University of Washington Quality of Life (UW-QOL) and the Functional Assessment of Cancer Therapy-Head and Neck questionnaires were used to assess patient-reported QOL as a secondary endpoint. Results A total of 45 patients were registered, 40 of whom completed QOL surveys and were evaluable. Nadirs for overall UW-QOL and Functional Assessment of Cancer Therapy-Head and Neck scores were reached at 4 weeks after treatment but returned to baseline at 3 months. Nearly all functional indices returned to baseline levels by 6 to 9 months. The mean overall UW-QOL score was 71.6 at baseline compared with 70.8, 73.0, 83.3, and 81.1, respectively, at 3 months, 6 months, 1 year, and 2 years after therapy. The percentage of patients rating their overall QOL as "very good" or "outstanding" at 6 months, 1 year, and 2 years using the UW-QOL was 50%, 77%, and 84%, respectively. Conclusions This de-escalation regimen achieved QOL outcomes that were favorable compared with historical controls. These results serve as powerful evidence that ongoing de-escalation efforts lead to tangible gains in function and QOL. Cancer 2018;124:521-9. © 2017 American Cancer Society.

BACKGROUND: We conducted a phase II multi-center trial of induction chemotherapy followed by response-adapted, dose-reduced radiation therapy with radiosensitizing chemotherapy for patients with locally advanced, human papillomavirus (HPV)-associated squamous cell carcinoma of the oropharynx. The aim of this study was to determine the progression-free survival for patients treated using this de-escalated approach to determine its worthiness for further investigation in a phase III setting. METHODS: Eligible patients presented with newly diagnosed, biopsy-proven stage III or IV squamous cell carcinoma of the oropharynx, p16-positivity, and Zubrod performance status 0 to 1. Smoking history was not used as a criterion for eligibility. Treatment was induction paclitaxel 175 mg/m2 and carboplatin area under the concentration-time curve (AUC) 6 for two cycles every 21 days followed by dose-reduced radiation of 54 Gy or 60 Gy for responders and non-responders, respectively, with weekly paclitaxel 30 mg/m2. Intensity-modulated radiotherapy with daily image-guidance was required. The primary endpoint was 2-year progression-free survival as determined by per protocol analysis. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195. FINDINGS: Between October 4, 2012 and March 3, 2015, forty-five patients (26 tonsil; 19 base of tongue) were registered, of which 44 were analyzable. Median age was 60 years old (IQR, 54 to 67). Sixty-nine percent of the patients were lifelong never smokers. Twenty-four patients (55%) exhibited a complete or partial response to induction chemotherapy; twenty patients (45%) had a less than partial response to induction chemotherapy. With a median follow up of 30 months (IQR, 26 to 37 months), three (7%) of 44 patients developed local-regional recurrence and another distant metastasis, yielding a 2-year progression-free survival of 92%. The most commonly observed grade 3+ toxicity was leukopenia (17 patients) with the most common grade 3+ non-hematologic toxicities being dysphagia (4 patients) and mucositis (4 patients). Seventeen (39%) of 44 patients and nine (20%) of 44 patients developed any grade 3+ and non-hematologic grade 3+ toxicity, respectively, during protocol therapy.. The proportion who were gastrostomy-tube dependent at 3- and 6-months post-therapy was 2% (1 of 44 patients) and 0%, respectively. INTERPRETATION: The rates of disease control demonstrated with this de-escalation regimen for patients with locally advanced, HPV-associated oropharyngeal carcinoma were comparable to those of historical controls treated by standard dose chemoradiotherapy regimens. Additionally, long-term side effects appeared to be reduced. By decreasing toxicity while maintaining cure rates, de-escalation of radiation dose has the potential to improve the therapeutic ratio and optimize long-term function for patients with a disease that is rapidly increasing in incidence.

BackgroundThe long natural history of prostate cancer (CaP) limits comparisons of efficacy between radical prostatectomy (RP) and external beam radiotherapy (EBRT), since patients treated years ago received treatments considered suboptimal by modern standards (particularly with regards to androgen deprivation therapy [ADT] and radiotherapy dose-escalation]. Gleason score (GS) 9-10 CaP is particularly aggressive, and clinically-relevant endpoints occur early, facilitating meaningful comparisons.ObjectiveTo compare outcomes of patients with GS 9-10 CaP following EBRT, extremely-dose escalated radiotherapy (as exemplified by EBRT+brachytherapy [EBRT+BT]), and RP.Design, setting, participantsRetrospective analysis of 487 patients with biopsy GS 9-10 CaP treated between 2000 and 2013 (230 with EBRT, 87 with EBRT+BT, and 170 with RP). Most radiotherapy patients received ADT and dose-escalated radiotherapy.Outcome measurements and statistical analysisKaplan-Meier analysis and multivariate Cox regression estimated and compared 5-yr and 10-yr rates of distant metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS).Results and limitationsThe median follow-up was 4.6 yr. Local salvage and systemic salvage were performed more frequently in RP patients (49.0% and 30.1%) when compared with either EBRT patients (0.9% and 19.7%) or EBRT+BT patients (1.2% and 16.1%, p

Breast cancer is the second most common cancer to metastasize in the brain. Little is known about how receptor subtype, including luminal A, luminal B, human epidermal growth factor receptor 2 (HER2) enriched, and triple negative (TN) affect response to radiation and distant intracranial recurrence (ICR) following radiation therapy. We conducted a single-institution retrospective analysis of 38 breast cancer brain metastasis (BCBM) patients who underwent 93 treatment courses of stereotactic radiosurgery, stereotactic radiotherapy, post-operative radiation, or whole brain radiation therapy. Endpoints included overall survival (OS), treatment response (partial/complete response, PR/CR, or progression), ICR after treatment, and time from breast cancer diagnosis to the first BCBM (time to metastasis, TTM). Subset analyses were performed for triple receptor subtype as well as estrogen receptor (ER) positive versus negative, HER2+ versus HER2-, and age ≤ 50 versus >50 years old. Median OS for the population was 22.5 months, with median follow-up after treatment of 20.5 months. TTM was shortest for HER2 enriched, TN, ER−, and younger patients. TN, HER2-, and younger patients showed the poorest OS. ICR was also greatest in TN and HER2− patients. Radiation failure at the treated BCBM was seen most prominently in HER2+ and ER− patients. Receptor subtypes that demonstrated poorer OS tended to demonstrate higher intracranial recurrence. A positive response to radiation was not associated with better OS or lower ICR. Identifying patterns based on receptor subtype may guide clinicians in management and surveillance for BCBM.

To compare patterns of prostate-specific antigen (PSA) response following stereotactic body radiation therapy (SBRT), high-dose-rate (HDR) brachytherapy, and conventionally fractionated intensity modulated radiation therapy (IMRT) in patients with low- or intermediate-risk prostate cancer (CaP).Eligible study patients included 439 patients with low- or intermediate-risk prostate cancer who were treated with radiation therapy (RT) alone between 2003 and 2013, remained free of biochemical recurrence, and had at least 2 PSA values within the first year following RT. Of these, 130 were treated with SBRT, 220 with HDR brachytherapy, and 89 with IMRT. Multivariate regression analysis was used to compare PSA nadirs (nPSA), time to nPSA, and PSA bounce parameters among the 3 modalities. Indicator variable analysis was used to develop empirical models of PSA decay using the treatment modalities as indicator variables.Significantly more patients treated with SBRT or HDR brachytherapy achieved raw nPSAs of0.5 ng/mL compared with patients treated with IMRT (76.2% and 75.9% vs 44.9%, respectively; P.0001 for SBRT or HDR brachytherapy vs IMRT). On multivariate analysis, nPSA was significantly lower with SBRT and HDR compared with IMRT (P.0001). Time to nPSA and bounce parameters was not significantly different among IMRT, SBRT, and HDR. Overall, SBRT and HDR brachytherapy caused significantly larger PSA decay rates (P.001). When truncating follow-up at 1000 days, the corresponding decay rates were larger for all 3 modalities, with no significant differences between them.Stereotactic body radiation therapy and HDR brachytherapy produce lower nPSAs than IMRT. Within 1000 days of follow-up, the modalities produce similar rates of PSA decay; subsequently, decay continues (albeit at a slower pace) after SBRT and HDR brachytherapy but plateaus with IMRT. Because nPSA is a validated predictor of long-term outcome, these data not only suggest a distinct radiobiological effect with SBRT and HDR brachytherapy, but also predict for clinical outcomes that might equal or surpass those of IMRT.

Purpose High-dose-rate (HDR) brachytherapy was originally used with external beam radiation therapy (EBRT) to increase the dose to the prostate without injuring the bladder or rectum. Numerous studies have reported HDR brachytherapy is safe and effective. We adapted it for use without EBRT for cases not requiring lymph node treatment. Patients and Methods We entered the patient demographics, disease characteristics, and treatment parameters into a prospective registry and serially added follow-up data for 448 men with low-risk (n=288) and intermediate-risk (n=160) prostate cancer treated from 1996 to 2009. Their median age was 64 years (range 42-90). The median prostate-specific antigen (PSA) level was 6.0 ng/mL (range 0.2-18.2). The Gleason score was ≤6 in 76% and 7 in 24%. The median dose was 43.5 Gy in 6 fractions. The clinical and biochemical disease control and survival rates were calculated. Adverse events were graded according to the Common Toxicity Criteria of Adverse Events. Results The median follow-up period was 6.5 years (range 0.3-15.3). The actuarial 6- and 10-year PSA progression-free survival was 98.6% (95% confidence interval [CI] 96.9%-99.4%) and 97.8% (95% CI 95.5%-98.9%). Overall survival at 10 years was 76.7% (95% CI 69.9%-82.2%). The local control, distant metastasis-free survival, and cause-specific survival were 99.7% (95% CI 97.9%-99.9%), 98.9% (95% CI 96.3%-99.7%), and 99.1% (95% CI 95.8%-99.8%). T stage, initial PSA level, Gleason score, National Comprehensive Cancer Network risk group, patient age, and androgen deprivation therapy did not significantly correlate with disease control or survival. No late grade 3 to 4 rectal toxicities developed. Late grade 3 to 4 genitourinary toxicity occurred in 4.9% (grade 3 in 4.7%). Conclusions HDR monotherapy is a safe and highly effective treatment of low- and intermediate-risk prostate cancer.

We evaluated the feasibility of planning stereotactic body radiotherapy (SBRT) for large central early-stage non-small cell lung cancer with a tri-cobalt-60 (tri-(60)Co) system equipped with real-time magnetic resonance imaging (MRI) guidance, as compared to linear accelerator (LINAC)-based SBRT. In all, 20 patients with large central early-stage non-small cell lung cancer who were treated between 2010 and 2015 with LINAC-based SBRT were replanned using a tri-(60)Co system for a prescription dose of 50Gy in 4 fractions. Doses to organs at risk were evaluated based on established MD Anderson constraints for central lung SBRT. R100 values were calculated as the total tissue volume receiving 100% of the dose (V100) divided by the planning target volume and compared to assess dose conformity. Dosimetric comparisons between LINAC-based and tri-(60)Co SBRT plans were performed using Student׳s t-test and Wilcoxon Ranks test. Blinded reviews by radiation oncologists were performed to assess the suitability of both plans for clinical delivery. The mean planning target volume was 48.3cc (range: 12.1 to 139.4cc). Of the tri-(60)Co SBRT plans, a mean 97.4% of dosimetric parameters per patient met MD Anderson dose constraints, whereas a mean 98.8% of dosimetric parameters per patient were met with LINAC-based SBRT planning (p = 0.056). R100 values were similar between both plans (1.20 vs 1.21, p = 0.79). Upon blinded review by 4 radiation oncologists, an average of 90% of the tri-(60)Co SBRT plans were considered acceptable for clinical delivery compared with 100% of the corresponding LINAC-based SBRT plans (p = 0.17). SBRT planning using the tri-(60)Co system with built-in MRI is feasible and achieves clinically acceptable plans for most central lung patients, with similar target dose conformity and organ at risk dosimetry. The added benefit of real-time MRI-guided therapy may further optimize tumor targeting while improving normal tissue sparing, which warrants further investigation in a prospective feasibility clinical trial.

Importance Many patients presently have access to their pathologic test result reports via online patient portals, yet little is known about pathologists’ perspective on this topic. Objective To examine dermatopathologists’ experience and perceptions of patient online access to pathology reports. Design, Setting, and Participants A survey of 160 dermatopathologists currently practicing in the United States who are board certified and/or fellowship trained in dermatopathology was conducted between July 15, 2018, and September 23, 2019. Those who reported interpreting skin biopsies of melanocytic lesions within the previous year and expected to continue interpreting them for the next 2 years were included. Main Outcomes and Measures Dermatopathologists’ demographic and clinical characteristics, experiences with patient online access to pathologic test result reports, potential behaviors and reactions to patient online access to those reports, and effects on patients who read their pathologic test result reports online. Results Of the 160 participating dermatopathologists from the 226 eligible for participation (71% response rate), 107 were men (67%); mean (SD) age was 49 (9.7) years (range, 34-77 years). Ninety-one participants (57%) reported that patients have contacted them directly about pathologic test reports they had written. Some participants noted that they would decrease their use of abbreviations and/or specialized terminology (57 [36%]), change the way they describe lesions suspicious for cancer (29 [18%]), and need specialized training in communicating with patients (39 [24%]) if patients were reading their reports. Most respondents perceived that patient understanding would increase (97 [61%]) and the quality of patient-physician communication would increase (98 [61%]) owing to the availability of online reports. Slightly higher proportions perceived increased patient worry (114 [71%]) and confusion (116 [73%]). However, on balance, most participants (114 [71%]) agreed that making pathologic test result reports available to patients online is a good idea. Conclusions and Relevance Dermatopathologists in this survey study perceived both positive and negative consequences of patient online access to pathologic test result reports written by the respondents. Most participants believe that making pathologic test result reports available to patients online is a good idea; however, they also report concerns about patient worry and confusion increasing as a result. Further research regarding best practices and the effect on both patients and clinicians is warranted.

Author(s): Pennington, Joseph Daniel; Eilber, Fritz C; Eilber, Frederick R; Singh, Arun S; Reed, Jarred P; Chmielowski, Bartosz; Eckardt, Jeffrey J; Bukata, Susan V; Bernthal, Nicholas M; Federman, Noah; Nelson, Scott D; Dry, Sarah M; Wang, Pin-Chieh; Luu, Michael; Selch, Michael T; Steinberg, Michael L; Kalbasi, Anusha; Kamrava, Mitchell | Abstract: OBJECTIVES:The objective of this study was to analyze outcomes for patients with soft tissue sarcoma of the extremities using neoadjuvant ifosfamide-based chemotherapy and hypofractionated reduced dose radiotherapy, followed by limb-sparing surgery. MATERIALS AND METHODS:An Institutional Review Board (IRB)-approved retrospective review of patients treated at a single institution between 1990 and 2013 was performed. In total, 116 patients were identified who received neoadjuvant ifosfamide-based chemotherapy and 28 Gy in 8 fractions of preoperative radiation (equivalent dose in 2 Gray fractions, 31.5 Gy [α/β 10] 36.4 Gy [α/β 3]) followed by limb-sparing surgery. Local recurrence (LR), distant failure (DF), and overall survival (OS) were calculated. Univariate and multivariate analysis for LR, DF, and OS were performed using Cox analysis. Statistical significance was set at a Pl0.05. RESULTS:Median follow-up was 5.9 years (range, 0.3 to 24 y). Actuarial LR at 3/6 years was 11%/17%, DF at 3/6 years was 25%/35%, and OS at 3/6 years was 82%/67%. On multivariate analysis, only a positive surgical margin was significantly correlated with worse local control (P=0.005; hazard ratio [HR], 18.33; 95% confidence interval (CI), 2.41-139.34). Age over 60 years (P=0.03; HR, 2.34; 95% CI, 1.10-4.98) and tumor size over 10 cm compared with tumor size ≤5 cm (P=0.03; HR, 3.32; 95% CI, 1.15-9.61) were associated with worse OS. CONCLUSIONS:Soft tissue extremity sarcoma patients treated using reduced dose hypofractionated preoperative radiotherapy in combination with ifosfamide-based chemotherapy shows acceptable local control and warrants further investigation.

Purpose: The practice of deliberately sparing the ipsilateral parotid gland with intensity modulated radiation therapy (IMRT) in patients with node-positive head and neck cancer is controversial. We sought to compare the clinical outcomes among consecutive cohorts of patients with head and neck cancer who were treated with differing strategies to spare the parotid gland that is ipsilateral to the involved neck using IMRT. Methods and materials: A total of 305 patients were treated with IMRT for node-positive squamous cell carcinoma of the head and neck. The first 139 patients were treated with IMRT whereby the ipsilateral parotid gland was delineated and intentionally designated as an avoidance structure during planning. The subsequent 166 patients were treated by IMRT without the deliberate sparing of the ipsilateral parotid gland. Results: The 2-year estimates of overall survival, local-regional control, and distant metastasis-free survival were 84%, 73%, and 87%, respectively. The 2-year estimates of overall survival were 77% and 86% among patients who were treated by IMRT with and without the sparing of the ipsilateral parotid gland, respectively (P = .01). The respective rates of 2-year regional control were 76% and 90% (P

Objectives We investigated the patient's perspective on SBRT for treatment of stage I NSCLC and compared the patient's perspective of SBRT to that of surgery. Materials and methods IRB approval was obtained to contact patients who had received SBRT for stage I NSCLCs. Patients were asked questions inquiring into their knowledge of SBRT and how their SBRT experience compared to their original expectations. Patients who had undergone prior surgery for a previously diagnosed stage I NSCLC were asked questions comparing their experience between SBRT and surgery. Frequencies of these reported measures were calculated and analysis was done using Fisher's exact test. Results 102 patients were contacted with 91 (89%) participating. Among all patients, prior to their radiation oncology consultation, 56% had no knowledge of SBRT and 58% believed SBRT to be as effective as resection. After consultation, 98.9% did not believe they were getting an inferior treatment with SBRT. 92.3% of patients reported less side effects, 59.3% reported SBRT to be more convenient and 87.9% reported SBRT to be less anxiety provoking than compared to their original expectations. Among patients with prior lung surgery (N = 39), compared to surgery, 100% reported an easier recovery, less treatment related anxiety and less caregiver strain with SBRT. Overall, 79.5% were more satisfied with SBRT than surgery and 89.7% would have rather had SBRT than surgery as it was performed for their prior NSCLC. Conclusion Actual experiences with SBRT are overwhelmingly superior compared to patient expectations. Patients with prior lung surgery reported significantly more satisfaction with SBRT.

In 2011, the American Board of Medical Specialties approved a pilot project submitted by the American Board of Radiology for a Focused Practice Recognition in Brachytherapy initiative. Developers had anticipated significant interest within the profession and had hoped that the project would stimulate clinical interest, research, and education in the modality. A centerpiece of the project was a National Brachytherapy Registry, which was to serve as a dynamic longitudinal database for participants and the profession. Ultimately, the project did not achieve its anticipated goals and was terminated by the American Board of Radiology in 2015. Development, implementation, problems encountered, and potential implications and solutions are discussed.

Purpose The purpose of this study was to investigate the dosimetric feasibility of liver stereotactic body radiation therapy (SBRT) using a teletherapy system equipped with 3 rotating 60 Co sources (tri- 60 Co system) and a built-in magnetic resonance imager (MRI). We hypothesized tumor size and location would be predictive of favorable dosimetry with tri- 60 Co SBRT. Methods and materials The primary study population consisted of 11 patients treated with SBRT for malignant hepatic lesions whose linear accelerator (LINAC)–based SBRT plans met all mandatory Radiation Therapy Oncology Group (RTOG) 1112 organ-at-risk (OAR) constraints. The secondary study population included 5 additional patients whose plans did not meet the mandatory constraints. Patients received 36 to 60 Gy in 3 to 5 fractions. Tri- 60 Co system SBRT plans were planned with ViewRay system software. Results All patients in the primary study population had tri- 60 Co SBRT plans that passed all RTOG constraints, with similar planning target volume coverage and OAR doses to LINAC plans. Mean liver doses and V 10Gy to the liver, although easily meeting RTOG 1112 guidelines, were significantly higher with tri- 60 Co plans. When the 5 additional patients were included in a univariate analysis, the tri- 60 Co SBRT plans were still equally able to pass RTOG constraints, although they did have inferior ability to pass more stringent liver and kidney constraints ( P 60 Co SBRT plan to meet these constraints depended on lesion location and size. Patients with smaller or more peripheral lesions (as defined by distance from the aorta, chest wall, liver dome, and relative lesion volume) were significantly more likely to have tri- 60 Co plans that spared the liver and kidney as well as LINAC plans did ( P Conclusions It is dosimetrically feasible to perform liver SBRT with a tri- 60 Co system with a built-in MRI. Patients with smaller or more peripheral lesions are more likely to have optimal liver and kidney sparing, with the added benefit of MRI guidance, when receiving tri- 60 Co–based SBRT.

Purpose Stereotactic body radiation therapy (SBRT) is a treatment option for patients with localized prostate cancer, with reported clinical and health-related quality-of-life (QOL) outcomes comparable to standard fractionation radiation therapy. The goal of this study was to evaluate correlations between short-term QOL outcomes and dosimetric parameters to guide future prostate SBRT planning. Methods and materials From 2010 to 2013, QOL data were prospectively collected from 75 patients enrolled in a prostate SBRT clinical trial. A comparison was made between Expanded Prostate Cancer Index Composite scores for patients with the top 25th percentile versus the bottom 75th percentile of the following dose-volume histogram parameters: planning target volume V100; bladder V50 and V100; and rectum V50, V80, V90, and V100. A linear mixed-effect model was used to estimate the difference between the 2 strata for each parameter. Results Median follow-up was 12 months. Patients with planning target volume V100 volumes >120 cm 3 had the worst reduction in urinary QOL. Urinary QOL was also decreased significantly in patients with bladder V100 volumes >5.5 cm 3 . Bowel QOL was decreased significantly in patients with rectal V90 and V100 volumes >4.2 and >1.5 cm 3 , respectively. Conclusions Patients with large prostate size or large volumes of rectum and bladder that receive ≥90% of the prescribed radiation dose are more susceptible to short-term QOL decrements after prostate SBRT. These volumes should be minimized to maximize recovery to baseline QOL after prostate SBRT.

Background Mastectomy rates, both therapeutic and prophylactic, are on the rise in the United States. After recent implementation of a multidisciplinary breast clinic for newly diagnosed women at our institution, we sought to examine the impact of multidisciplinary care on surgical decision making. Materials/Methods Women with newly diagnosed breast cancer at our institution are referred to a multidisciplinary breast clinic where they are seen by a team of breast specialists (MDC) or to an individual practitioner (non-MDC) for initial consultation. We retrospectively analyzed rates of breast conserving surgery (BCS) and mastectomy among women with newly diagnosed breast cancer seen in either setting. For mastectomy cases, we designated the mastectomy as clinically indicated vs not clinically indicated based on National Comprehensive Cancer Network (NCCN) guidelines for breast conservation. T-test and chi-square were used to examine the comparability between MDC and non-MDC cohorts. Logistic regression was used to evaluate the overall prevalence of BCS among MDC and non-MDC cohorts. Stratification analysis was further conducted to examine BCS rates among women in each cohort receiving neoadjuvant chemotherapy vs up front surgery. Results A total of 341 consecutive patients were analyzed, including 202 MDC and 139 non-MDC patients seen in initial consultation between June 2012 and April 2014. The MDC and non-MDC cohorts were statistically equivalent in terms of age, tumor and nodal stage, histology, biomarker status, receipt of neoadjuvant chemotherapy, and proportion with genetic mutations. In the MDC cohort, 66% underwent BCS vs 42% in the non-MDC cohort (p Conclusions Breast cancer patients seen in an MDC setting at the time of initial diagnosis are significantly more likely than women seen in a non-MDC setting to undergo breast conservation. We hypothesize that the MDC model of breast cancer care, via facilitation of more informed medical decision making, may be a viable strategy to curtail rising mastectomy rates in the United States. Citation Format: Caitlin L Gomez, Pin-Chieh Wang, Nicole A Dawson, Robyn L Dvorak, Nova Foster, Anne Hoyt, Sara A Hurvitz, Amy Kusske, Charles Y Tseng, Susan A McCloskey. Multidisciplinary breast cancer care is associated with a higher rate of breast conservation in comparison with non-multidisciplinary care [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-16-02.

Purpose To determine the ability of image-guided high-dose-rate brachytherapy (IG-HDR) to provide local control (LC) of lesions in non-traditional locations for patients with heavily pre-treated malignancies. Material and methods This retrospective series included 18 patients treated between 2012 and 2014 with IG-HDR, either in combination with external beam radiotherapy (EBRT; n = 9) or as monotherapy (n = 9). Lesions were located in the pelvis (n = 5), extremity (n = 2), abdomen/retroperitoneum (n = 9), and head/neck (n = 2). All cases were performed in conjunction between interventional radiology and radiation oncology. Toxicity was graded based on CTCAE v4.0 and local failure was determined by RECIST criteria. Kaplan-Meier analysis was performed for LC and overall survival. Results The median follow-up was 11.9 months. Two patients had localized disease at presentation; the remainder had recurrent and/or metastatic disease. Seven patients had prior EBRT, with a median equivalent dose in 2 Gy fractions (EQD2) of 47.0 Gy. The median total EQD2s were 34 Gy and 60.9 Gy for patients treated with monotherapy or combination therapy, respectively. Image-guided high-dose rate brachytherapy was delivered in one to six fractions. Six patients had local failures at a median interval of 5.27 months with a one-year LC rate of 59.3% and a one-year overall survival of 40.7%. Six patients died from their disease at a median interval of 6.85 months from the end of treatment. There were no grade ≥ 3 acute toxicities but two patients had serious long term toxicities. Conclusions We demonstrate a good one year LC rate of nearly 60%, and a favorable toxicity profile when utilizing IG-HDR to deliver high doses of radiation with high precision into targets not readily accessible by other forms of local therapy. These preliminary results suggest that further studies utilizing this approach may be considered for patients with difficult to access lesions that require LC.

The current study represents a subset analysis of quality-of-life (QOL) outcomes among patients treated on a phase 2 trial of de-escalated chemoradiation for human papillomavirus (HPV)-associated oropharyngeal cancer.Eligibility included newly diagnosed, (American Joint Committee on Cancer, 7th edition) stage III or IV oropharyngeal squamous cell carcinoma, p16 positivity, age ≥ 18 years, and a Zubrod performance status of 0 to 1. Treatment was induction paclitaxel at a dose of 175 mg/mA total of 45 patients were registered, 40 of whom completed QOL surveys and were evaluable. Nadirs for overall UW-QOL and Functional Assessment of Cancer Therapy-Head and Neck scores were reached at 4 weeks after treatment but returned to baseline at 3 months. Nearly all functional indices returned to baseline levels by 6 to 9 months. The mean overall UW-QOL score was 71.6 at baseline compared with 70.8, 73.0, 83.3, and 81.1, respectively, at 3 months, 6 months, 1 year, and 2 years after therapy. The percentage of patients rating their overall QOL as "very good" or "outstanding" at 6 months, 1 year, and 2 years using the UW-QOL was 50%, 77%, and 84%, respectively.This de-escalation regimen achieved QOL outcomes that were favorable compared with historical controls. These results serve as powerful evidence that ongoing de-escalation efforts lead to tangible gains in function and QOL. Cancer 2018;124:521-9. © 2017 American Cancer Society.

To query specialty-specific differences regarding postoperative radiotherapy (RT) for high-risk prostate cancer. Electronic mail survey of radiation oncologists (ROs) and urologists. We sought to maximize absolute response number to capture contemporary practice ethos. The outcome of interest was association between response and specialty. Training level/expertise, practice setting, percentage of consultation caseload consisting of high-risk prostate cancer, and nationality were set as effect modifiers for multivariate logistic regression. In total, 846 ROs and 407 urologists responded. ROs were more likely to prefer adjuvant radiotherapy (ART). ART or early salvage radiotherapy (SRT, with early SRT defined as that delivered at prostate-specific antigen

Radiographic changes occur in over half of patients treated with stereotactic body radiotherapy (SBRT) to the lung, correlating histopathologically with injury. We quantified radiographic density changes (ie, fibrosis) at 3, 6, and 12 months and investigated the relationship between these volumes and clinical and dosimetric parameters. The study population consisted of patients treated with SBRT to the lung for stage I primary lung cancers (n = 39) or oligometastatic lesions (n = 17). Fractionation schemes included 3 fractions of 12, 14, or 18 gray (Gy) and 4 fractions of 12 or 12.5 Gy prescribed to cover 95% of the planning target volume (PTV). Planning computed tomography (CT) scans were rigidly registered to follow-up CT scans obtained at intervals of 3, 6, and 12 months. Fibrotic volumes were contoured on the follow-up scans. Associations between the volume of fibrosis and clinical and dosimetric parameters were investigated using univariate linear regression. Scans were available for 65 and 47 lesions at 6 and 12 months, respectively. Age, years since quitting smoking, and GOLD Global Initiative for Chronic Obstructive Lung Disease score were significantly associated with increasing volume of fibrosis (P < .05). Total dose, dose per fraction, PTV, and volumetric parameters (V0-V55) were also significantly associated with increasing volumes of fibrosis (P < .01). For dosimetric parameters, the effect was largest for V55. Age, significant smoking history, and GOLD score were significantly associated with increasing volumes of fibrosis following SBRT. In a multivariate model adjusted for age and smoking history, V10 through V50 and PTV size remained significant predictors of fibrotic volume. Further, there is a strong dose-response relationship between the volume of lung exposed to a certain dose and the fibrotic volume. The predominant kinetic patterns of fibrosis demonstrate peaking fibrotic volumes at 6 and 12 months. These results provide insight for expectations of fibrosis after SBRT.

Introduction To quantify changes in gross tumour volume (GTV) between simulation and initiation of radiotherapy in patients with locally advanced malignancies of the lung and head/neck. Methods Initial cone beam computed tomography (CT) scans from 12 patients with lung cancer and 12 with head/neck cancer (head and neck squamous cell carcinoma (HNSCC)) treated with intensity-modulated radiotherapy with image guidance were rigidly registered to the simulation CT scans. The GTV was demarcated on both scans. The relationship between percent GTV change and variables including time interval between simulation and start, tumour (T) stage, and absolute weight change was assessed. Results For lung cancer patients, the GTV increased a median of 35.06% (range, −16.63% to 229.97%) over a median interval of 13 days (range, 7–43), while for HNSCC patients, the median GTV increase was 16.04% (range, −8.03% to 47.41%) over 13 days (range, 7–40). These observed changes are statistically significant. The magnitude of this change was inversely associated with the size of the tumour on the simulation scan for lung cancer patients (P 0.1). Conclusion While the observed changes in GTV were moderate from the time of simulation to start of radiotherapy, these findings underscore the importance of image guidance for target localisation and verification, particularly for smaller tumours. Minimising the delay between simulation and treatment initiation may also be beneficial.

Data from a prospective screening protocol administered for patients previously irradiated for head-and-neck cancer was analyzed to identify dosimetric predictors of brachial plexus-associated neuropathy.Three hundred fifty-two patients who had previously completed radiation therapy for squamous cell carcinoma of the head and neck were prospectively screened from August 2007 to April 2013 using a standardized self-administered instrument for symptoms of neuropathy thought to be related to brachial plexus injury. All patients were disease-free at the time of screening. The median time from radiation therapy was 40 months (range, 6-111 months). A total of 177 patients (50%) underwent neck dissection. Two hundred twenty-one patients (63%) received concurrent chemotherapy.Fifty-one patients (14%) reported brachial plexus-related neuropathic symptoms with the most common being ipsilateral pain (50%), numbness/tingling (40%), and motor weakness and/or muscle atrophy (25%). The 3- and 5-year estimates of freedom from brachial plexus-associated neuropathy were 86% and 81%, respectively. Clinical/pathological N3 disease (P.001) and maximum radiation dose to the ipsilateral brachial plexus (P=.01) were significantly associated with neuropathic symptoms. Cox regression analysis revealed significant dose-volume effects for brachial plexus-associated neuropathy. The volume of the ipsilateral brachial plexus receiving70 Gy (V70) predicted for symptoms, with the incidence increasing with V7010% (P.001). A correlation was also observed for the volume receiving74 Gy (V74) among patients treated without neck dissection, with a cutoff of 4% predictive of symptoms (P=.038).Dose-volume guidelines were developed for radiation planning that may limit brachial plexus-related neuropathies.

Background. Physical activity is associated with better physical health, possibly by changing biological markers of health such as waist circumference and inflammation, but these relationships are unclear and even less understood among older Latinos—a group with high rates of sedentary lifestyle.Methods. Participants were 120 sedentary older Latino adults from senior centers. Community-partnered research methods were used to recruit participants. Inflammatory (C-reactive protein) and metabolic markers of health (waist circumference, HDL-cholesterol, triglycerides, insulin, and glucose), physical activity (Yale physical activity survey), and physical performance (short physical performance NIA battery) were measured at baseline and 6-month followup.Results. Eighty percent of the sample was female. In final adjusted cross-sectional models, better physical activity indices were associated with faster gait speed (P<0.05). In adjusted longitudinal analyses, change in self-reported physical activity level correlated inversely with change in CRP (β=-0.05;P=0.03) and change in waist circumference (β=-0.16;P=0.02). Biological markers of health did not mediate the relationship between physical activity and physical performance.Conclusion. In this community-partnered study, higher physical activity was associated with better physical performance in cross-sectional analyses. In longitudinal analysis, increased physical activity was associated with improvements in some metabolic and inflammatory markers of health.

BACKGROUND: Taxi drivers work long hours for low wages and report hypertension, weight gain, and musculoskeletal pain associated with the sedentary nature of their job, stressful working conditions, and poor dietary habits. They also experience a high work-related fatality rate. OBJECTIVE: The objective of this study is to examine the association of taxi drivers' health status and level of job stress with work-related injury and determine if a potential interaction exists. METHODS: A survey of 309 Los Angeles taxi drivers provides basic data on health status, job stress, and work-related injuries. We further analyzed the data using a Modified Poisson regression approach with a robust error variance to estimate the relative risk (RR) and the 95% confidence intervals (CI) of work-related injuries. Focus group results supplemented and helped interpret the quantitative data. RESULTS: The joint effect of good health and low job stress was associated with a large reduction in the incidence of injuries, consistent with the hypothesis that health status and stress levels modify each other on the risk of work-related injury. CONCLUSIONS: These results suggest that the combination of stress reduction and health management programs together with changes in the stressful conditions of the job may provide targeted avenues to prevent injuries. Language: en

Purpose To evaluate the early and late health-related quality of life (QOL) outcomes among prostate cancer patients following stereotactic body radiation therapy (SBRT). Methods and Materials Patient self-reported QOL was prospectively measured among 864 patients from phase 2 clinical trials of SBRT for localized prostate cancer. Data from the Expanded Prostate Cancer Index Composite (EPIC) instrument were obtained at baseline and at regular intervals up to 6 years. SBRT delivered a median dose of 36.25 Gy in 4 or 5 fractions. A short course of androgen deprivation therapy was given to 14% of patients. Results Median follow-up was 3 years and 194 patients remained evaluable at 5 years. A transient decline in the urinary and bowel domains was observed within the first 3 months after SBRT which returned to baseline status or better within 6 months and remained so beyond 5 years. The same pattern was observed among patients with good versus poor baseline function and was independent of the degree of early toxicities. Sexual QOL decline was predominantly observed within the first 9 months, a pattern not altered by the use of androgen deprivation therapy or patient age. Conclusion Long-term outcome demonstrates that prostate SBRT is well tolerated and has little lasting impact on health-related QOL. A transient and modest decline in urinary and bowel QOL during the first few months after SBRT quickly recovers to baseline levels. With a large number of patients evaluable up to 5 years following SBRT, it is unlikely that unexpected late adverse effects will manifest themselves.

To characterize the magnitude and kinetics of prostate-specific antigen (PSA) bounces after high-dose-rate (HDR) monotherapy and determine relationships between certain clinical factors and PSA bounce.Longitudinal PSA data and various clinical parameters were examined in 157 consecutive patients treated with HDR monotherapy between 1996 and 2005. We used the following definition for PSA bounce: rise in PSA ≥threshold, after which it returns to the prior level or lower. Prostate-specific antigen failure was defined per the Phoenix definition (nadir +2 ng/mL).A PSA bounce was noted in 67 patients (43%). The number of bounces per patient was 1 in 45 cases (67%), 2 in 19 (28%), 3 in 2 (3%), 4 in 0, and 5 in 1 (1%). The median time to maximum PSA bounce was 1.3 years, its median magnitude was 0.7, and its median duration was 0.75 years. Three patients (2%) were noted to have PSA failure. None of the 3 patients who experienced biochemical failure exhibited PSA bounce. In the fully adjusted model for predicting each bounce, patients aged55 years had a statistically significant higher likelihood of experiencing a bounce (odds ratio 2.22, 95% confidence interval 1.38-3.57, P=.001). There was also a statistically significant higher probability of experiencing a bounce for every unit decrease in Gleason score (odds ratio 1.52, 95% confidence interval 1.01-2.04, P=.045).A PSA bounce occurs in a significant percentage of patients treated with HDR monotherapy, with magnitudes varying from1 in 28% of cases to ≥1 in 15%. The median duration of bounce is1 year. More bounces were identified in patients with lower Gleason score and age55 years. Further investigation using a model to correlate magnitude and frequency of bounces with clinical variables are under way.

Background Musculoskeletal disorders (MSDs) persist among clerical workers despite ergonomic advances. Methods A cross-sectional survey among2,310 clerical workers investigated MSD cases, defined as musculoskeletal discomfort and seeking treatment for that discomfort in the past 12 months. A modified Poisson regression model was adopted to assess the association between work and individual factors and the risk of MSDs. Results Over half of respondents reported musculoskeletal discomfort. The prevalence of MSD cases was: 37.2% neck/shoulders, 21.7% upper extremities, 18% lower extremities, and 34.3% back region. Elevated risk of MSDs was associated with less workstation adjustability; work schedule, gender, age, and BMI were also significant. Positive trends wereobservedbetweencomputeruseandMSDsfortheneck/shoulderregionandtheeffect was amplified among those reporting insufficient workstation adjustability and lacking computer ergonomics training. Conclusions Results demonstrate the need to limit continuous computer use and to improve the human–machine interface through adjustable workstations and worker training to enhance use of adjustable features. Am. J. Ind. Med. 56:1072–1081, 2013. 2013 Wiley Periodicals, Inc.

Purpose We performed a dosimetry analysis to determine how well the goals for clinical target volume coverage, dose homogeneity, and normal tissue dose constraints were achieved with high-dose-rate (HDR) prostate brachytherapy. Methods and Materials Cumulative dose-volume histograms for 208 consecutively treated HDR prostate brachytherapy implants were analyzed. Planning was based on ultrasound-guided catheter insertion and postoperative CT imaging; the contoured clinical target volume (CTV) was the prostate, a small margin, and the proximal seminal vesicles. Dosimetric parameters analyzed for the CTV were D90, V90, V100, V150, and V200. Dose to the urethra, bladder, bladder balloon, and rectum were evaluated by the dose to 0.1 cm 3 , 1 cm 3 , and 2 cm 3 of each organ, expressed as a percentage of the prescribed dose. Analysis was stratified according to prostate size. Results The mean prostate ultrasound volume was 38.7 ± 13.4 cm 3 (range: 11.7-108.6 cm 3 ). The mean CTV was 75.1 ± 20.6 cm 3 (range: 33.4-156.5 cm 3 ). The mean D90 was 109.2% ± 2.6% (range: 102.3%-118.4%). Ninety-three percent of observed D90 values were between 105 and 115%. The mean V90, V100, V150, and V200 were 99.9% ± 0.05%, 99.5% ± 0.8%, 25.4% ± 4.2%, and 7.8% ± 1.4%. The mean dose to 0.1 cm 3 , 1 cm 3 , and 2 cm 3 for organs at risk were: Urethra: 107.3% ± 3.0%, 101.1% ± 14.6%, and 47.9% ± 34.8%; bladder wall: 79.5% ± 5.1%, 69.8% ± 4.9%, and 64.3% ± 5.0%; bladder balloon: 70.3% ± 6.8%, 59.1% ± 6.6%, and 52.3% ± 6.2%; rectum: 76.3% ± 2.5%, 70.2% ± 3.3%, and 66.3% ± 3.8%. There was no significant difference between D90 and V100 when stratified by prostate size. Conclusions HDR brachytherapy allows the physician to consistently achieve complete prostate target coverage and maintain normal tissue dose constraints for organs at risk over a wide range of target volumes.

BACKGROUND: In focused radiotherapy for prostate cancer (PC), a full dose of radiation is delivered to the index lesion while reduced dose is delivered to the remaining prostate to reduce morbidity. As PC is commonly multifocal, we investigated whether baseline clinical characteristics or multiparametric magnetic resonance imaging (mpMRI) may be useful to predict the actual pathologic distribution of PC in men with intermediate- or high-risk PC, which may better inform how to deliver focused radiotherapy. METHODS: A retrospective single-institutional study was performed on 71 consecutive men with clinically localized, intermediate-or high-risk PC who underwent mpMRI followed by radical prostatectomy (RP) from January 2012 to December 2012. Logistic regression analysis was performed to evaluate preoperative predictors for satellite lesions. Performance characteristics of mpMRI to detect satellite lesions and the extent of prostate disease (one hemi-gland vs both) were also evaluated. RESULTS: In all, 50.7% had satellite lesions on mpMRI. On RP specimen analysis, 66.2% had satellite lesions and 55.3% of these satellite lesions had pathologic Gleason score (pGS) ⩾ 3+4. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy for mpMRI detecting a satellite lesion being present in the RP specimen were 59.6%, 66.7%, 77.8%, 45.7% and 62.0%, respectively. The presence of MRI satellite lesions was the only preoperative predictor significantly associated with finding satellite lesions on final pathology (hazard ratio (HR), 2.95, P= 0.040). There was agreement in 76.1% of the entire cohort for unilateral vs bilateral disease when incorporating both biopsy and mpMRI information and comparing with the RP specimen. CONCLUSIONS: In intermediate risk or greater PC, only the presence of mpMRI satellite lesions could predict for pathologic satellite lesions. While combining biopsy and mpMRI information may improve preoperative disease localization, the relatively high incidence of bilateral hemi-gland involvement with pGS ⩾ 7 satellite lesions makes it challenging to appropriately select men eligible for hemi-gland therapy.

To evaluate a single-institutional experience with the use of re-irradiation for recurrent and new primary cancers of the head and neck.The medical charts of 80 consecutive patients who underwent re-irradiation for local-regionally recurrent or second primary head and neck cancer between November 1998 and December 2015 were analyzed. Multivariate analysis was performed using Cox proportional hazard and logistic regression to determine predictors of clinical outcomes.Seventy-six of the 80 patients were evaluable. The median age was 57.5 (range 26.6-84.9); Intensity-modulated radiotherapy (IMRT) was used in 71 (93.4%) patients with a median dose of 60Gy. Thirty-one patients (40.8%) underwent salvage surgery before re-irradiation and 47 (61.8%) received concurrent systemic therapy. The median time interval between radiation courses was 25.3months (range 2-322months). The 2-year estimates of overall survival, progression free survival, locoregional control, and distant control were 51.0%, 31.3%, 36.8% and 68.3%, respectively. Patients who underwent salvage surgery prior to re-irradiation had significantly improved locoregional control, progression free survival, and overall survival (p0.05, for all). On multivariate analysis, gross tumor volume (GTV) at re-irradiation and interval between radiation courses were associated with improved overall survival. Severe (grade⩾3) late complications were observed in 25 patients (32.8%).Re-irradiation for recurrent or second primary head and neck cancer is feasible and effective in select patients with head and neck cancer. The high observed rate of treatment-related morbidity highlights the continue challenges that accompany this approach.