Association of Baseline Magnetic Resonance Imaging Prostate Imaging Reporting and Data System Score With Prostate Cancer Active Surveillance Early Biopsy Reclassification: Data From the Michigan Urological Surgery Improvement Collaborative (MUSIC).

PURPOSE: The purpose of our study was to evaluate the association of baseline MRI Prostate Imaging Reporting and Data System (PI-RADS) score with biopsy reclassification in a multicenter active surveillance (AS) cohort. MATERIALS AND METHODS: We identified men in the Michigan Urological Surgery Improvement Collaborative registry (46 hospital-based/academic/private practice urology groups) with National Comprehensive Cancer Network (NCCN) low-risk and favorable intermediate-risk prostate cancer who underwent MRI within 6 months before or after initial biopsy and enrolled in AS from June 2016 to January 2021. The primary objective was to determine the association of baseline MRI PI-RADS score (≥4 lesion) with reclassification to high-grade prostate cancer (≥grade group 3) on surveillance biopsy. Multivariable Cox proportional hazards regression models were constructed and adjusted for pathologic, MRI, and clinical/biopsy factors, with landmark time of 6 months from diagnostic biopsy. We included an interaction term between PI-RADS score and NCCN group in the Cox model. RESULTS: A total of 1491 men were included with median age 64 years (IQR: 59-69) with median follow-up 11.0 months (IQR: 6.0-23.0) after landmark. Baseline PI-RADS ≥ 4 lesion was associated with an increased hazard of biopsy reclassification (HR: 2.3 [95% CI: 1.6-3.2], P < .001), along with grade group 2 vs 1 (HR: 2.5 [95% CI: 1.7-3.7], P < .001), and increasing age (per 10 years; HR: 1.8 [95% CI: 1.4-2.4], P < .001). The interaction between NCCN risk group with MRI findings was not significant (P = .7). CONCLUSIONS: In this multicenter cohort study of real-world data, baseline MRI PI-RADS score was significantly associated with early biopsy reclassification in men undergoing AS with NCCN low- or favorable intermediate-risk prostate cancer.

21 Gy single fraction prostate HDR brachytherapy: 5-year results of a single institution prospective pilot study.

PURPOSE: To present the outcome and toxicity results of a prospective trial of 21 Gy single fraction high-dose-rate (HDR) brachytherapy for men with low- or intermediate-risk prostate cancer. METHODS AND MATERIALS: Patients were treated according to an IRB-approved prospective study of single fraction HDR brachytherapy. Eligible patients had low- or intermediate-risk prostate cancer with tumor stage ≤ T2b, PSA ≤ 15, and Gleason score ≤ 7. Patients underwent trans-rectal ultrasound-guided trans-perineal implant of the prostate followed by single fraction HDR brachytherapy to a dose of 21 Gy. The primary endpoint was grade ≥ 2 urinary/GI toxicity rates. RESULTS: Twenty-six patients were enrolled with a median follow up of 5.1 years and median age of 64 years. 88.5% of patients had T1 disease, 15.4% had Gleason score 6 (84.6% Gleason 7), and median pre-treatment PSA was 5.0 ng/mL. Acute and chronic grade ≥ 2 urinary toxicity rates were 38.5% and 38.5%, respectively. There were no grade ≥ 2 acute or chronic GI toxicities. Six (23.1%) patients experienced biochemical failure, six (23.1%) patients experienced radiographic local failure, and five (19.2%) patients had biopsy-proven local failure. No patients developed regional lymph node recurrence or distant metastasis. 5-year overall survival and cause-specific survival were 96.2% and 100%, respectively. CONCLUSIONS: 21 Gy single fraction HDR brachytherapy was associated with modestly higher-than-anticipated chronic urinary toxicity, as well as high biochemical and local failure rates. The results from this prospective pilot study do not support the use of this regimen in standard clinical practice.

Prostatic Urethral Length on MRI Potentially Predicts Late Genitourinary Toxicity After Prostate Cancer Radiation.

RATIONALE AND OBJECTIVES: The purpose of our study was to evaluate pretreatment prostate quantitative magnetic resonance imaging (MRI) measurements and clinical characteristics in predicting genitourinary (GU) toxicity after radiotherapy (RT) for prostate cancer. MATERIALS AND METHODS: In this single-institution retrospective cohort study, we evaluated patients with prostate adenocarcinoma who underwent MRI within 6 months before completing definitive RT and follow-up information in our GU toxicity database from June 2016 to February 2023. MRI measurements included quantitative urethra, prostate, and bladder measurements. GU toxicity was physician-scored using the Common Terminology Criteria for Adverse Events (CTCAE v4.0) with acute toxicity defined as ≤180 days and late defined as >180 days. Multivariable logistic regression model was constructed for grade ≥2 acute toxicity and Cox proportional hazards regression for late toxicity, adjusted for clinical factors and RT method. RESULTS: A total of 361 men (median age 68 years, interquartile range [IQR] 62-73) were included; 14.4% (50/347) men experienced grade ≥2 acute toxicity. Brachytherapy (odds ratio [OR]: 2.9, 95% confidence interval [CI]: 1.5-5.8), P < 0.01) was associated with increased odds of acute GU toxicity, and longer MUL (OR: 0.41 [95%CI: 0.18-0.92], P = 0.03) with decreased odds. Median follow-up for late toxicity was 15.0 months (IQR: 9.0-28.0) with approximately 88.7% and 72.0% patients free of toxicity at 1 and 3 years, respectively. Only longer prostatic urethral length (hazard ratio [HR]: 1.6, 95%CI: 1.2-2.1, P < 0.01) was associated with increased risk of late GU toxicity, notably urinary frequency/urgency symptoms (HR: 1.7 [95%CI: 1.3-2.3], P < 0.01). CONCLUSION: Longer prostatic urethral length measured on prostate MRI is independently associated with higher risk of developing late grade ≥2 GU toxicity after radiation therapy for prostate cancer. This pretreatment metric may be potentially valuable in risk-stratification models for quality of life following prostate RT.

High-dose-rate brachytherapy as monotherapy versus as boost in unfavorable intermediate-risk localized prostate cancer: A matched-pair analysis.

PURPOSE: High-dose-rate brachytherapy as monotherapy (HDR-M), or as a boost combined with external beam radiotherapy (HDR-B), are both suitable treatments for intermediate-risk prostate cancer. However, data directly comparing these two approaches for men with unfavorable intermediate-risk (UIR) patients are lacking. METHODS AND MATERIALS: Patients with NCCN-defined UIR prostate cancer treated from 1997 to 2020 were identified in a prospectively maintained, single institution database. HDR-M and HDR-B patients were matched using three factors: age ±3 years; Gleason score (major and minor); and clinical T stage. Biochemical failure was defined as PSA nadir (nPSA) + 2. Available acute and chronic toxicities are additionally reported. RESULTS: A total of 247 patients were identified (170 receiving HDR-B, 77 receiving HDR-M), ultimately yielding 70 matched pairs (140 patients) for inclusion. The median followup time was 5.2 years for HDR-M compared with 9.3 years for HDR-B (p < 0.001). The two cohorts had similar calculated prostate EQD2 (HDR-B 118 Gy vs. HDR-M 115 Gy, p = 0.977). No significant differences in OS, CSS, DM, LRR, or FFBF were identified. HDR-B had an increased rate of any acute grade 2+ gastrointestinal toxicity and worse acute dysuria and diarrhea. Chronic gastrointestinal and genitourinary toxicity was similar. CONCLUSIONS: These data suggest that HDR brachytherapy as monotherapy is an effective treatment option for selected patients with unfavorable intermediate-risk prostate cancer and provides a more favorable gastrointestinal toxicity profile than HDR-B. Prospective trials should be conducted to refine the selection process for this heterogeneous cohort of patients.

Impact of the bladder detrusor muscular ring on lower urinary tract symptoms due to benign prostatic hyperplasia: A quantitative MRI analysis.

BACKGROUND: The etiology of lower urinary tract symptoms secondary to benign prostatic hyperplasia (LUTS/BPH) remains uncertain. OBJECTIVE: The purpose of our study was to quantitatively analyze anatomic characteristics on magnetic resonance imaging (MRI) to assess novel independent factors for symptoms. METHODS: This retrospective single-institution study evaluated treatment-naïve men who underwent prostate MRI within 3 months of international prostate symptom score (IPSS) scoring from June 2021 to February 2022. Factors measured on MRI included: size of the detrusor muscular ring (DMR) surrounding the bladder outlet, central gland (CG) mean apparent diffusion coefficient (ADC), levator hiatus (LH) volume, intrapelvic volume, intravesicular prostate protrusion (IPP) volume, CG volume, peripheral zone (PZ) volume, prostate urethra angle (PUA), and PZ background ordinal score. Multivariable logistic regression and receiver operating characteristic analysis were used to analyze factors for moderate/severe (IPSS ≥ 8) and severe LUTS/BPH (IPSS ≥ 20). RESULTS: A total of 303 men (mean age: 66.1 [SD: 8.1]) were included: 154 demonstrated moderate or severe symptoms with 28 severe and 149 with asymptomatic/mild symptoms. Increasing age [p = 0.02; odds ratio (OR): 1.05 (1.01-1.08)], PUA [p = 0.02; OR: 1.05 (1.01-1.09)], LH volume [p = 0.04; OR: 1.02 (1.00-1.05)], and DMR size measured as diameter [p < 0.001; OR: 5.0 (3.01-8.38)] or area [p < 0.001; OR: 1.92 (1.47-2.49)] were significantly independently associated with moderate/severe symptoms, with BMI [p = 0.02; OR: 0.93 (0.88-0.99)] inversely related. For every one cm increase in DMR diameter, patients had approximately five times the odds for moderate/severe symptoms. Increasing DMR size [diameter p < 0.001; OR: 2.74 (1.76-4.27) or area p < 0.001; OR: 1.37 (1.18-1.58)] was independently associated with severe symptoms. Optimal criterion cutoff of DMR diameter for moderate/severe symptoms was 1.2 cm [sensitivity: 77.3; specificity: 71.8; AUC: 0.80 (0.75-0.84)]. Inter-reader reliability was excellent for DMR diameter [ICC = 0.92 (0.90-0.94)]. CONCLUSION: Expansion of the DMR surrounding the bladder outlet is a novel anatomic factor independently associated with moderate and severe LUTS/BPH, taking into account prostate volumes, including quantified IPP volume, which were unrelated. Detrusor ring diameter, easily and reliably measured on routine prostate MRI, may relate to detrusor dysfunction from chronic stretching of this histologically distinct smooth muscle around the bladder neck.

Toxicity and Efficacy After Adjuvant Vaginal Brachytherapy Using 30 Gy in 6 Fractions for Stages I and II Endometrial Cancer.

PURPOSE: This study aimed to evaluate outcomes and toxicity in patients with endometrial cancer per our institutional adjuvant vaginal cuff brachytherapy (VBT) fractionation scheme. METHODS AND MATERIALS: We identified women with International Federation of Gynecology and Oncology stages I and II endometrial cancer who underwent surgical staging and adjuvant high-dose-rate VBT without external beam radiation. All patients received 30 Gy in 6 fractions to the upper one-third of the vagina, prescribed to a depth of 5 mm and delivered twice weekly. Toxicities were prospectively elicited at each follow up, and rates of recurrence and survival were retrospectively assessed. RESULTS: We identified 247 eligible patients treated between 1992 and 2018 with a median follow up of 5.8 years (range, 0.1-24.7 years). Most patients had stage I disease (52% stage IA; 37% stage IB), and 11% of patients were stage II. Deep myometrial invasion was predictive of local recurrence (P = .002). The 5-year rates of local recurrence, regional recurrence, and distant metastases were 5%, 5%, and 7%, respectively. Five-year overall and disease-free survival were 91% and 83%, respectively. The most common grade 1 toxicities were acute fatigue (11% crude rate), urinary frequency (11%), chronic (>6 months) urinary frequency (13%), urinary incontinence (13%), and vaginal stenosis (21%). There were few grade 2 toxicities (all <5%) and no grade 3 to 5 toxicities. CONCLUSIONS: The adjuvant VBT fractionation scheme of 30 Gy in 6 fractions results in low rates of toxicity, with no grade ≥3 adverse events, and local control rates comparable with those from other published series using different fractionation schemes.

Which measurement method should be used for prostate volume for PI-RADS? A comparison of ellipsoid and segmentation methods.

PURPOSE: Prostate volume and PSA density (PSAd) are important in the risk stratification of suspected prostate cancer (Pca). PI-RADS v2.1 allows for determining volume via segmentation or ellipsoid calculation. The purpose of our study was to compare ellipsoid and segmentation volume calculation methods and evaluate if PSAd diagnostic performance is altered. METHODS: We retrospectively assessed 397 patients (mean age/standard deviation: 63.7/7.4 years) who underwent MRI and prostate biopsy or prostatectomy, with Pca classified by Gleason ≥3 + 4 and ≥4 + 4 disease. Prostate total volumes were determined with ellipsoid calculations (TVe) and with semi-automated segmentation (TVs), along with inter-rater reliability with intraclass correlation coefficient (ICC). PSAd was calculated for TVe and TVs and ROC curves were created to compare performance for Gleason ≥3 + 4 and ≥4 + 4 disease. RESULTS: TVe was significantly higher than TVs (p < 0.0001), with mean TVe = 55.4 mL and TVs = 51.0 mL. ROC area under the curve for PSAd derived with TVe (0.63, 95%CI:0.59-0.68) and TVs (0.64, 95%CI:0.59-0.68) showed no significant difference for Gleason ≥3 + 4 disease (p = 0.45), but PSAd derived with TVs (0.63, 95%CI: 0.58-0.68) significantly outperformed TVe (0.61, 95%CI: 0.57-0.67) for Gleason ≥4 + 4 disease (p = 0.02). Both methods demonstrated excellent inter-rater reliability with TVe with ICC of 0.93(95%CI: 0.92-0.94) and TVs with ICC of 0.98(95%CI: 0.98-0.99). CONCLUSION: Traditional ellipsoid measurements tend to overestimate total prostate volume compared to segmentation, but both methods demonstrate similar diagnostic performance of derived PSA density for PI-RADS clinically significant disease. For higher grade disease, PSAd derived from segmentation volumes demonstrates statistically significant superior performance. Both methods are viable, but segmentation volume is potentially better.

Evaluation of VMAT Planning Strategies for Prostate Patients with Bilateral Hip Prosthesis.

Purpose: In this study, we investigate linac volumetric-modulated arc therapy (VMAT) planning strategies for bilateral hip prostheses prostate patients with respect to plan quality and deliverability, while limiting entrance dose to the prostheses. Methods: Three VMAT plans were retrospectively created for 20 patients: (1) partial arcs (PA), (2) 2 full arcs optimized with 500 cGy max prostheses dose (MD), and (3) 2 full arcs optimized with max dose-volume histogram (DVH) constraint of 500 cGy to 10% prostheses volume (MDVH). PA techniques contained 6 PA with beam angles that avoid entering each prosthesis. For each patient, other than prostheses constraints, the same Pinnacle VMAT optimization objectives were used. Plans were normalized with PTV D95% = 79.2 Gy prescription dose. Organ-at-risk DVH metrics, monitor units (MUs), conformality, gradient, and homogeneity indices were evaluated for each plan. Mean entrance prosthesis dose was determined in Pinnacle by converting each arc into static beams and utilizing only control points traversing each prosthesis. Plan deliverability was evaluated with SunNuclear ArcCheck measurements (gamma criteria 3%/2 mm) on an Elekta machine. Results: MD and MDVH had similar dosimetric quality, both improved DVH metrics for rectum and bladder compared to PA. Plan complexities among all plans were similar (average MUs: 441-518). Conformality, homogeneity, and gradient indices were significantly improved in MD and MDVH versus PA (P < .001). Gamma pass rates for MD (99.0 ± 1.2%) and MDVH (99.2 ± 0.99%) were comparable. A significant difference over PA was observed (96.8 ± 1.6%, P < .001). Field-by-field analysis demonstrated 12/20 PA plans resulted in fields with pass rates <95% versus 1/20 plans for MD and none for MDVH. Cumulative mean entrance doses to each prosthesis were 62.9 ± 17.7 cGy for MD plans and 83.4 ± 27.5 cGy for MDVH plans. Conclusion: MD and MDVH plans had improved dosimetric quality and deliverability over PA plans with minimal entrance doses (∼1% of prescription) to each prosthesis and are an improved alternative for bilateral prostheses prostate patients.

Adjuvant radiotherapy improves overall survival when added to surgery and chemotherapy for uterine carcinosarcoma: a surveillance, epidemiology, and end results analysis.

BACKGROUND: Uterine carcinosarcoma (UCS) confers a high recurrence risk following surgery, and adjuvant chemotherapy (CHT) is typically administered in all stages. The benefit of radiation therapy (RT) in UCS, when added to adjuvant CHT, is unknown. We sought to analyze the Surveillance, Epidemiology, and End Results (SEER) database to ascertain whether RT improves overall survival (OS) when added to surgery and CHT for UCS. METHODS: SEER 18 Custom Data registries (Nov 2018 submission) were queried for uterine (ICD10 C54.1-9, C55.9) carcinosarcoma (ICD-0-3 8980-3). Patients with stage I-III UCS who underwent surgery and CHT ± RT were analyzed with univariate analysis (UVA) and multivariable analysis (MVA) using Kaplan-Meier and Cox proportional hazards regression modeling. Propensity-score matched analysis with inverse probability of treatment weighting (IPTW) was performed to account for indication bias. Furthermore, conditional landmark analysis (minimum three-month follow-up) was performed to minimize immortal time bias. RESULTS: All 1541 patients (1988-2016) underwent surgery and CHT and 54% received RT. On UVA, RT improved median and 5-year OS from 41 to 87 months and 43-55%, respectively (HR 0.65, 95% CI 0.56-0.77) (p < 0.001). After IPTW adjustment, RT improved median and 5-year OS from 46 to 65 months and 46-53%, respectively (HR 0.74, 95% CI 0.63-0.87) (p < 0.001). The benefit of RT remained on unadjusted and adjusted MVA and conditional landmark analysis. CONCLUSION: In stage I-III UCS treated with surgery and CHT, receipt of RT is associated with OS benefit. Further prospective data are needed to investigate the RT's benefit in UCS.

Benign prostate hyperplasia as a potential protective factor against prostate cancer: Insights from a magnetic resonance imaging study of compositional characteristics.

PURPOSE: The structural relationship between benign prostate hyperplasia (BPH) and prostate cancer (Pca) is controversial. The purpose of our study was to examine the association between quantitative prostate compositional metrics by magnetic resonance imaging (MRI) and Pca. METHODS: We identified 405 patients who underwent prostate MRI and biopsy and/or prostatectomy from January 2019 to January 2021 at our institution. Segmentation volumetric methods were used to assess central gland (CG) and peripheral zone (PZ) volume. PZ mean thickness and mean apparent diffusion coefficient (ADC), marker of underlying histologic components, were measured. Multivariable logistic regression was performed with outcomes of ≥Grade Group (GG) 2 Pca and for multifocal disease. RESULTS: On multivariable analysis, higher CG volumes were at lower odds of ≥GG2 disease (n = 227) (OR: 0.97, 95% CI 0.96-0.98, p < 0.0001), taking into account PZ volume (p = 0.18) and thickness (p = 0.70). For every one cc increase in CG volume, there was an approximately 3% decrease in odds of ≥GG2 disease. Similar findings were noted for multifocal disease (n = 180) (OR: 0.97, 95% CI 0.96-0.98, p < 0.0001). Notably, ADC of the normal PZ was not significantly associated with CG volume (p = 0.21) nor a predictor of disease (p = 0.49). CONCLUSIONS: Increasing central gland volume, driven by BPH, is associated with lower odds of significant Pca, including multifocal disease, while PZ anatomic and histologic surrogate changes were noncontributory. Findings support BPH impediment of global tumor growth predicted by theoretical mechanobiological model. This potential stabilizing factor should be further studied for risk stratification and in consideration for BPH therapy.

Combined Adjuvant Chemotherapy and Radiation Therapy Improves Disease-Free Survival for Uterine Serous Cancer.

PURPOSE: Uterine serous carcinoma (USC) is a rare but aggressive endometrial cancer histology. We reviewed outcomes for patients with USC to identify the best adjuvant treatment strategy. METHODS AND MATERIALS: We retrospectively identified 162 patients with The International Federation of Gynecology and Obstetrics (FIGO) stage I-IVA USC treated at our institution. Baseline characteristics, treatment details, clinical outcomes, and toxicity data were recorded. RESULTS: Median follow-up was 3.4 years (0.3-26 years). A variety of adjuvant therapy strategies were employed: 14% no adjuvant therapy, 28% radiation alone, 15% chemotherapy alone, and 43% combined chemotherapy and radiation. Distant metastasis was the most common type of recurrence (37% at 5 years). For patients with stage I-IVA disease, there were no significant differences in outcomes by treatment type. For patients with stage I-II disease (70% of the cohort), disease-free survival was significantly higher after chemotherapy (alone or with radiation therapy, P = .005) and after combined chemotherapy and radiation compared with all other treatments (P = .025). Toxicity outcomes were favorable, with minimal grade 3 and no grade 4 or 5 events. CONCLUSIONS: Patients with USC experience high rates of recurrence and mortality. Distant metastasis is the most common pattern of failure for all stages. For patients with early-stage disease, combined chemotherapy and radiation improves 5-year disease-free survival compared with either single adjuvant treatment alone or no adjuvant treatment. The relatively large group of patients with USC included in this study may account for our ability to detect this improvement whereas clinical trials have failed to do so, possibly owing to the relatively small percentages of patients with USC enrolled.

Outcomes After Salvage Radiation Therapy for Recurrent Endometrial Cancer in Patients With No Prior Adjuvant Therapy: An Institutional Review.

PURPOSE: After definitive surgery, women with early-stage, low-risk endometrial cancer are observed. However, some will require salvage radiation therapy for recurrence. The purpose of this study was to evaluate our experience using salvage radiation for recurrent endometrial cancer in patients who did not receive upfront adjuvant therapy. METHODS AND MATERIALS: Twenty-eight women with endometrial cancer who had undergone initial definitive hysterectomy without adjuvant therapy developed isolated local or regional recurrence and were treated with salvage radiation in our department from 2004 to 2018. Salvage radiation included whole pelvic radiation, vaginal brachytherapy, or both. Patient and tumor characteristics, treatment details, and toxicities were recorded and analyzed. RESULTS: The median time to first recurrence was 1.7 years. First recurrences consisted of local recurrence in 23 patients, regional recurrence in 4, and both in 1. The median times from hysterectomy to first recurrence, local and regional, were 1.2 and 4.0 years, respectively. All patients underwent salvage radiation for management of their first recurrence. The median total equivalent dose in 2 Gy fractions for this treatment was 67.6 Gy (37.5-81.8 Gy). Two second recurrences occurred following salvage treatment, both local recurrence, at 6.5 and 13.5 months after radiation. The 2-year rates of local control, disease-free survival, and overall survival were 93%, 80%, and 88%, respectively. Treatment was well-tolerated, with low rates of gastrointestinal and genitourinary toxicity. CONCLUSIONS: In this group of patients, salvage radiation therapy for local or regional recurrence of endometrial cancer resulted in excellent control with low rates of acute and chronic toxicities.

Sequencing of Adjuvant Chemoradiation for Advanced Stage Endometrial Cancer: Outcomes and Toxicity Profiles.

OBJECTIVES: Radiation is frequently added to chemotherapy for adjuvant treatment of advanced stage endometrial cancer. Multiple adjuvant therapy sequencing options exist, and little data is available to compare these. We compared outcomes and toxicities after "sandwich" chemoradiation (chemotherapy, then radiation, then chemotherapy) and nonsandwich sequences (chemotherapy then radiation, radiation then chemotherapy, or concurrent chemoradiation). MATERIALS AND METHODS: We recorded baseline characteristics, adjuvant treatment details, clinical outcomes, and toxicities for stage III to IVA patients who underwent surgical staging followed by both adjuvant chemotherapy and radiation therapy at our institution. Effects of adjuvant treatment order (sandwich or nonsandwich) on these outcomes were analyzed. Toxicities were graded according to CTCAE v4.0. RESULTS: We identified 107 patients with a median follow-up of 3.2 years. Five-year local, regional, and distant recurrence were 7%, 15%, and 33%; disease-free and overall survival were 61% and 68%, respectively. Outcomes did not differ by sequence group. The overall rate of acute toxicity did not differ by sequence group. The overall rate of chronic toxicity was significantly lower for sandwich patients (P<0.001), as were overall rates of chronic genitourinary (P=0.048) and gynecologic (P<0.001) toxicities. There were no grade 4 or 5 acute or chronic toxicities. CONCLUSIONS: Advanced stage endometrial cancer is an aggressive disease and adjuvant chemotherapy and radiation therapy are indicated. Clinical outcomes were similar amongst the different sequences; however, sandwich therapy led to less chronic toxicity, offering an opportunity for improved quality of life in survivorship.

Trends in Medicare Reimbursement and Work Relative Value Unit Production in Radiation Oncology.

PURPOSE: Medicare payments to individual physicians are released annually by the CMS. The purpose of this study is to analyze trends in Medicare reimbursement and work relative value unit (wRVU) production to radiation oncologists. MATERIALS AND METHODS: The Medicare Physician Supplier and Other Provider Public Use File and the CMS Physician Fee Schedule Relative Value Files (to calculate wRVUs) for the calendar years 2012 to 2015 were used in this analysis. Medicare reimbursement was aggregated for each calendar year. Using the CMS Physician Fee Schedule Relative Value Files, the number of Medicare wRVUs was calculated for each radiation oncologist. RESULTS: In 2015, 4,323 radiation oncologists produced 12,895,298 wRVUs compared with 11,352,286 wRVUs produced in 2012. These datasets include only Medicare reimbursements and do not include wRVUs from private insurance or other payers. In 2015, radiation oncologists produced a median of 2,486 wRVUs from Medicare (range 3 to 24,349). Billing to Healthcare Common Procedure Coding System Code 77427 (radiation treatment management, five treatments), a proxy for total radiation treatments, fell from 1,111,670 in 2012 to 1,039,403 in 2015, a decline of 7%. CONCLUSION: The total number of wRVUs produced by radiation oncologists has risen by 14% from 2012 to 2015. However, the number of external beam radiation fractions has declined by approximately 7% over this same period, likely due to a trend toward hypofractionated courses of treatment and use of special treatment modalities such as proton beam therapy or stereotactic body radiation therapy.

A novel panel of biomarkers predicts radioresistance in patients with squamous cell carcinoma of the head and neck.

PURPOSE: Global gene expression analysis was performed on pre-treatment biopsies from patients with squamous cell carcinoma of the head and neck (SCCHN) to discover biomarkers that can predict outcome of radiation based therapy. METHODS: We initially evaluated RNA expression using cDNA microarray analysis of 38 patients that received radiotherapy (RT). The five strongest candidates (VEGF, BCL-2, CLAUDIN-4, YAP-1 and c-MET) were then analysed in pre-treatment biopsies in a second group of 86 patients who received radiation based treatment using immunohistochemical staining (IHC), prepared by tissue microarray. RESULTS: In the first population, 13 of 38 (34%) had no (NR) or partial response (PR) to RT. cDNA microarrays revealed 60 genes that were linked to response to therapy. In the second series, 12 of 86 patients (14%) experienced NR or PR to CRT. Cause specific survival (CSS) and recurrence free survival (RFS) at 2 years was 85% and 90% and at 3 years 81% and 84%, respectively. Biomarkers predictive for NR/PR were increased expression of vascular endothelial growth factor (VEGF) (p=0.02), Yes-associated protein (YAP-1) (p<0.01), CLAUDIN-4 (p<0.01), c-MET (p<0.01) and BCL-2 (p=0.02). Biomarkers predictive of poor RFS were YAP-1 (p=0.01) and BCL-2 (p<0.01). Biomarkers predictive of poor CSS were YAP-1 (p=0.04), VEGF (p=0.03) and CLAUDIN-4 (p=0.03). Furthermore, when YAP-1 and c-MET expression levels were combined the prediction of radio-resistance was increased. CONCLUSION: All five biomarkers were predictive of poor response to radiation based therapy. In particular, YAP-1 and c-MET have synergistic power and could be used to make treatment decisions.

Rates of second malignancies after definitive local treatment for ductal carcinoma in situ of the breast.

PURPOSE: We analyzed the risk of second malignancies developing in patients with ductal carcinoma in situ (DCIS) undergoing surgery and radiotherapy (S+RT) vs. surgery alone. METHODS AND MATERIALS: The S+RT cohort consisted of 256 women treated with breast-conserving therapy at William Beaumont Hospital. The surgery alone cohort consisted of 2,788 women with DCIS in the regional Surveillance, Epidemiology, and End Results database treated during the same time period. A matched-pair analysis was performed in which each S+RT patient was randomly matched with 8 surgery alone patients (total of 2,048 patients). Matching criteria included age±2 years. The rates of second malignancies were analyzed overall and as contralateral breast vs. non-breast cancers and by organ system. RESULTS: Median follow-up was 13.7 years for the S+RT cohort and 13.3 years for the surgery alone cohort. The overall 10-/15-year rates of second malignancies among the S+RT and surgery alone cohorts were 14.2%/24.2% and 16.4%/22.6%, respectively (p=0.668). The 15-year second contralateral breast cancer rate was 14.2% in the S+RT cohort and 10.3% in the surgery alone cohort (p=0.439). The 15-year risk of a second non-breast malignancy was 14.2% for the S+RT cohort and 13.4% for the surgery alone cohort (p=0.660). When analyzed by organ system, the 10- and 15-year rates of second malignancies did not differ between the S+RT and surgery alone cohorts for pulmonary, gastrointestinal, central nervous system, gynecologic, genitourinary, lymphoid, sarcomatoid, head and neck, or unknown primary tumors. CONCLUSIONS: Compared with surgery alone, S+RT is not associated with an overall increased risk of second malignancies in women with DCIS.

Possible biliary disease: diagnostic performance of high-spatial-resolution isotropic 3D T2-weighted MRCP.

PURPOSE: To retrospectively assess the diagnostic performance of magnetic resonance cholangiopancreatography (MRCP) performed by using a high-spatial-resolution isotropic three-dimensional (3D) fast-recovery fast spin-echo (FSE) sequence with parallel imaging for the evaluation of possible biliary disease. MATERIALS AND METHODS: This HIPAA-compliant study was approved by the institutional review board; informed consent was waived. Ninety-five patients (58 female, 37 male; mean age, 51 years; range, 15-91 years) underwent MRCP by using the respiratory-triggered isotropic 3D fast-recovery FSE sequence and endoscopic or percutaneous direct visualization between March 2003 and June 2007. Two independent readers evaluated the MRCP images for strictures, dilatation, and intraductal filling defects. Sensitivity, specificity, and interobserver agreement (kappa statistics) were determined. RESULTS: The respective sensitivity and specificity for strictures, dilatation, and intraductal filling defects (all choledocholithiasis) were 86% (40 of 47) and 94% (45 of 48), 98% (57 of 58) and 100% (37 of 37), and 68% (19 of 28) and 97% (65 of 67) for reader 1 and 88% (41 of 47) and 94% (45 of 48), 96% (56 of 58) and 100% (37 of 37), and 75% (21 of 28) and 99% (66 of 67) for reader 2. The sensitivity for stones larger than 3 mm was 94% (15 of 16) for reader 1 and 100% (16 of 16) for reader 2, whereas the sensitivity for stones 3 mm or smaller was 33% (four of 12) for reader 1 and 42% (five of 12) for reader 2. Agreement between readers was good to excellent, with kappa values of 0.76, 0.85, and 0.98 for strictures, dilatation, and choledocholithiasis, respectively. CONCLUSION: MRCP by using the respiratory-triggered isotropic 3D fast-recovery FSE sequence with parallel imaging demonstrates excellent diagnostic capabilities for possible biliary disease, although it is limited for stones 3 mm or smaller in size.

Diagnostic performance of positron emission tomography in the detection of coronary artery disease: a meta-analysis.

RATIONALE AND OBJECTIVES: Although myocardial perfusion positron emission tomography (PET), using either cyclotron-produced ammonia or generator-produced rubidium 82, has reported excellent diagnostic capabilities in the detection of coronary artery disease (CAD) in individual studies, the technique is not widely used in practice. This may be driven by cost and availability or by unawareness of performance. The purpose of our study was to conduct an evidence-based evaluation of PET in the diagnosis of CAD. MATERIALS AND METHODS: We examined studies from January 1977 to July 2007 using MEDLINE and EMBASE. A study was included if it (1) used PET as a diagnostic test for CAD and (2) used catheter x-ray angiography as the reference standard (> or =50% diameter stenosis). Analysis was performed on a subject and coronary territory level. RESULTS: Nineteen studies (1442 patients) met the inclusion criteria. On a patient level, PET demonstrated a sensitivity of 0.92 (95% confidence interval [CI]: 0.90-0.94) and specificity of 0.85 (CI: 0.79-0.90), with a positive likelihood ratio (LR+) of 6.2 (CI: 3.3-11.8) and negative likelihood ratio (LR-) of 0.11 (CI: 0.08-0.14). On a coronary territory level (n = 1130), PET showed a sensitivity of 0.81 (CI: 0.77-0.84) and specificity of 0.87 (CI: 0.84-0.90), with an LR+ of 5.9 (CI: 4.5-7.9) and an LR- of 0.19 (CI: 0.09-0.38). CONCLUSION: PET demonstrates excellent diagnostic properties in the diagnosis of CAD, especially at the patient level. The capabilities appear superior to those reported in meta-analyses for perfusion imaging with Tl-201 and sestamibi, or anatomical imaging with coronary MDCT angiography or MRA. Given that previous studies have found PET to be cost-effective and the current findings of excellent sensitivity and specificity, the modality should be more widely considered as an initial test in the diagnosis of CAD.