Predicted Inferior Outcomes for Lung SBRT With Treatment Planning Systems That Fail Independent Phantom-Based Audits.

PURPOSE: More than 15% of radiation therapy clinics fail external audits with anthropomorphic phantoms conducted by Imaging and Radiation Oncology Core-Houston (IROC-H) while passing other industry-standard quality assurance (QA) tests. We seek to evaluate the predicted effect of such failed plans on outcomes for patients treated with stereotactic body radiation therapy (SBRT) for lung tumors. METHODS AND MATERIALS: We conducted a retrospective study of 55 patients treated with SBRT for lung tumors with a prescription biologically equivalent dose (BED)10 ≥100 Gy using a treatment planning system (TPS) that passed IROC-H phantom audits. Sample linear accelerator beam models with introduced errors were commissioned by varying the multileaf collimator leaf-tip offset parameter (ie, dosimetric leaf gap) over the range ±1.0 mm relative to the validated model. These models mimic TPS that pass internal QA measures but fail IROC-H tests. Patient plans were recalculated on sample beam models. The predicted tumor control probability (TCP) and normal tissue complication probability (NTCP) were calculated based on published dose-response models. RESULTS: A leaf-tip offset value of -1.0 mm decreased the fraction of plans receiving a planning treatment volume of BED10 ≥100 Gy from 95% to 27%. This translated to a significant decrease in 2-year TCP of 4.8% (95% CI: 2.0%-5.5%) with a decrease in TCP up to 21%. Conversely, a leaf-tip offset of +1.0 mm resulted in 36% of patients exceeding previously met organs at risk (OAR) constraints, including 2 instances of spinal cord and brachial plexus overdoses and a small increase in chest wall NTCP of 0.7%, (95% CI: 0.5%-0.8%). CONCLUSIONS: Simulated treatment plans with modest MLC leaf offsets result in lung SBRT plans that significantly underdose tumor or exceed OAR constraints. These dosimetric endpoints translate to significant detriments in TCP. These simulated plans mimic planning systems that pass internal QA measures but fail independent phantom-based tests, underscoring the need for enhanced quality assurance including external audits of TPS.

Disparities in Access to Radiation Therapy by Race and Ethnicity in the United States With Focus on American Indian/Alaska Native People.

OBJECTIVES: Striking disparities in access to radiation therapy (RT) exist, especially among racial and ethnic-minority patients. We analyzed census block group data to evaluate differences in travel distance to RT as a function of race and ethnicity, socioeconomic status, and rurality. METHODS: The Directory of Radiotherapy Centers provided the addresses of facilities containing linear accelerators for RT. We classified block groups as majority (≥ 50%) American Indian/Alaska Native (AI/AN), black, white, Asian, no single racial majority, or Hispanic regardless of race. We used the Area Deprivation Index to classify deprivation and Rural-Urban Commuting Area codes to classify rurality. Generalized linear mixed models tested associations between these factors and distance to nearest RT facility. RESULTS: Median distance to nearest RT facility was 72 miles in AI/AN-majority block groups, but 4 to 7 miles in block groups with non-AI/AN majorities. Multivariable models estimated that travel distances in AI/AN-majority block groups were 39 to 41 miles longer than in areas with non-AI/AN majorities. Travel distance was 1.3 miles longer in the more deprived areas versus less deprived areas and 16 to 32 miles longer in micropolitan, small town, and rural areas versus metropolitan areas. CONCLUSIONS: Cancer patients in block groups with AI/AN-majority populations, nonmetropolitan location, and low socioeconomic status experience substantial travel disparities in access to RT. Future research with more granular community- and individual-level data should explore the many other known barriers to access to cancer care and their relationship to the barriers posed by distance to RT care.

A Prospective Study of a Resorbable Intravesical Fiducial Marker for Bladder Cancer Radiation Therapy.

Purpose: We conducted a prospective pilot study to evaluate safety and feasibility of TraceIT, a resorbable radiopaque hydrogel, to improve image guidance for bladder cancer radiation therapy (RT). Methods and Materials: Patients with muscle invasive bladder cancer receiving definitive RT were eligible. TraceIT was injected intravesically around the tumor bed during maximal transurethral resection of bladder tumor. The primary endpoint was the difference between radiation treatment planning margin on daily cone beam computed tomography based on alignment to TraceIT versus standard-of-care pelvic bone anatomy. The Van Herk margin formula was used to determine the optimal planning target volume margin. TraceIT visibility, recurrence rates, and survival were estimated by Kaplan-Meier method. Toxicity was measured by Common Terminology Criteria for Adverse Events version 4.03. Results: The trial was fully accrued and 15 patients were analyzed. TraceIT was injected in 4 sites/patient (range, 4-6). Overall, 94% (95% confidence interval [CI], 90%-98%) of injection sites were radiographically visible at RT initiation versus 71% (95% CI, 62%-81%) at RT completion. The median duration of radiographic visibility for injection sites was 106 days (95% CI, 104-113). Most patients were treated with a standard split-course approach with initial pelvic radiation fields, then midcourse repeat transurethral resection of bladder tumor followed by bladder tumor bed boost fields, and 14/15 received concurrent chemotherapy. Alignment to fiducials could allow for reduced planning target volume margins (0.67 vs 1.56 cm) for the initial phase of RT, but not for the boost (1.01 vs 0.96 cm). This allowed for improved target coverage (D95% 80%-83% to 91%-94%) for 2 patients retrospectively planned with both volumetric-modulated arc therapy and 3-dimensional conformal RT. At median follow-up of 22 months, no acute or late complications attributable to TraceIT placement occurred. No patients required salvage cystectomy. Conclusions: TraceIT intravesical fiducial placement is safe and feasible and may facilitate tumor bed delineation and targeting in patients undergoing RT for localized muscle invasive bladder cancer. Improved image guided treatment may facilitate strategies to improve local control and minimize toxicity.

Disparities in Access to Radiation Therapy Facilities Among American Indians/Alaska Natives and Hispanics in Washington State.

PURPOSE: Racial and ethnic minorities in the state of Washington experience higher cancer mortality relative to whites. We sought to characterize differences in travel distance to radiation therapy (RT) facilities in Washington by race and ethnicity with a special focus on non-Hispanic American Indians and Alaska Natives as a contributor to limited access and cancer disparities. METHODS AND MATERIALS: Geocoded mortality data from Washington Department of Health (2011-2018) were used to identify decedents with mortality related to all-causes, all cancers, and cancers likely requiring access to RT. This was determined from optimal RT usage estimates by diagnosis. RT facility locations were ascertained from the Directory of Radiation Therapy Centers and confirmed. Distance from decedents' address listed on death certificates to nearest RT facility was calculated. Generalized mixed models were used for statistical analysis. RESULTS: We identified 418,754 deaths; 109,134 were cancer-related, 60,973 likely required RT. Among decedents with cancers likely requiring RT, non-Hispanic American Indians and Alaska Natives decedents would have had to travel 1.16 times (95% confidence interval [CI], 1.09-1.24) farther from their residences to reach the nearest treatment facility compared with non-Hispanic whites. This association existed in metro counties but was more pronounced in nonmetro counties (1.39 times farther; 95% CI, 1.22-1.58). In addition, Hispanics would have had to travel 1.11 times farther (95% CI, 1.06-1.16) to reach the nearest facility compared with non-Hispanic whites, primarily due to differences in urban counties. Decedents in nonmetro counties lived on average 35 miles (SD = 29) from RT centers and non-Hispanic American Indians and Alaska Natives in nonmetro counties 53 miles (SD = 38). Compared with non-Hispanic white decedents, those who were non-Hispanic black, non-Hispanic Asian, and non-Hispanic Native Hawaiian decedents lived closer to RT facilities. CONCLUSIONS: We observed significant disparities in access to RT facilities in Washington, specifically for non-Hispanic American Indians and Alaska Natives and rural decedents. The findings call for initiatives to improve access to critical cancer treatment services for these underserved populations with known disparities in cancer deaths.

Comparisons of 3-Dimensional Conformal and Intensity-Modulated Neutron Therapy for Head and Neck Cancers.

PURPOSE: Neutron therapy is a high linear energy transfer modality that is useful for the treatment of radioresistant head and neck (H&N) cancers. It has been limited to 3-dimensioanal conformal-based fast-neutron therapy (3DCNT), but recent technical advances have enabled the clinical implementation of intensity-modulated neutron therapy (IMNT). This study evaluated the comparative dosimetry of IMNT and 3DCNT plans for the treatment of H&N cancers. MATERIALS AND METHODS: Seven H&N IMNT plans were retrospectively created for patients previously treated with 3DCNT at the University of Washington (Seattle). A custom RayStation model with neutron-specific scattering kernels was used for inverse planning. Organ-at-risk (OAR) objectives from the original 3DCNT plan were initially used and were then systematically reduced to investigate the feasibility of improving a therapeutic ratio, defined as the ratio of the mean tumor to OAR dose. The IMNT and 3DCNT plan quality was evaluated using the therapeutic ratio, isodose contours, and dose volume histograms. RESULTS: When compared with the 3DCNT plans, IMNT reduces the OAR dose for the equivalent tumor coverage. Moreover, IMNT is most advantageous for OARs in close spatial proximity to the target. For the 7 patients with H&N cancers examined, the therapeutic ratio for IMNT increased by an average of 56% when compared with the 3DCNT. The maximum OAR dose was reduced by an average of 20.5% and 20.7% for the spinal cord and temporal lobe, respectively. The mean dose to the larynx decreased by an average of 80%. CONCLUSION: The IMNT significantly decreases the OAR doses compared with 3DCNT and provides comparable tumor coverage. Improvements in the therapeutic ratio with IMNT are especially significant for dose-limiting OARs near tumor targets. Moreover, IMNT provides superior sparing of healthy tissues and creates significant new opportunities to improve the care of patients with H&N cancers treated with neutron therapy.

Interreader Variability of Prostate Imaging Reporting and Data System Version 2 in Detecting and Assessing Prostate Cancer Lesions at Prostate MRI.

OBJECTIVE. The purpose of this study was to evaluate agreement among radiologists in detecting and assessing prostate cancer at multiparametric MRI using Prostate Imaging Reporting and Data System version 2 (PI-RADSv2). MATERIALS AND METHODS. Treatment-naïve patients underwent 3-T multipara-metric MRI between April 2012 and June 2015. Among the 163 patients evaluated, 110 underwent prostatectomy after MRI and 53 had normal MRI findings and transrectal ultrasound-guided biopsy results. Nine radiologists participated (three each with high, intermediate, and low levels of experience). Readers interpreted images of 58 patients on average (range, 56-60) using PI-RADSv2. Prostatectomy specimens registered to MRI were ground truth. Interob-server agreement was evaluated with the index of specific agreement for lesion detection and kappa and proportion of agreement for PI-RADS category assignment. RESULTS. The radiologists detected 336 lesions. Sensitivity for index lesions was 80.9% (95% CI, 75.1-85.9%), comparable across reader experience (p = 0.392). Patient-level specificity was experience dependent; highly experienced readers had 84.0% specificity versus 55.2% for all others (p < 0.001). Interobserver agreement was excellent for detecting index lesions (index of specific agreement, 0.871; 95% CI, 0.798-0.923). Agreement on PI-RADSv2 category assignment of index lesions was moderate (κ = 0.419; 95% CI, 0.238-0.595). For individual category assignments, proportion of agreement was slight for PI-RADS category 3 (0.208; 95% CI, 0.086-0.284) but substantial for PI-RADS category 4 (0.674; 95% CI, 0.540-0.776). However, proportion of agreement for T2-weighted PI-RADS 4 in the transition zone was 0.250 (95% CI, 0.108-0.372). Proportion of agreement for category assignment of index lesions on dynamic contrast-enhanced MR images was 0.822 (95% CI, 0.728-0.903), on T2-weighted MR images was 0.515 (95% CI, 0.430-0623), and on DW images was 0.586 (95% CI, 0.495-0.682). Proportion of agreement for dominant lesion was excellent (0.828; 95% CI, 0.742-0.913). CONCLUSION. Radiologists across experience levels had excellent agreement for detecting index lesions and moderate agreement for category assignment of lesions using PI-RADS. Future iterations of PI-RADS should clarify PI-RADS 3 and PI-RADS 4 in the transition zone.

Can Apparent Diffusion Coefficient Values Assist PI-RADS Version 2 DWI Scoring? A Correlation Study Using the PI-RADSv2 and International Society of Urological Pathology Systems.

OBJECTIVE: The purposes of this study were to assess correlation of apparent diffusion coefficient (ADC) and normalized ADC (ratio of tumor to nontumor tissue) with the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) and updated International Society of Urological Pathology (ISUP) categories and to determine how to optimally use ADC metrics for objective assistance in categorizing lesions within PI-RADSv2 guidelines. MATERIALS AND METHODS: In this retrospective study, 100 patients (median age, 62 years; range, 44-75 years; prostate-specific antigen level, 7.18 ng/mL; range, 1.70-84.56 ng/mL) underwent 3-T multiparametric MRI of the prostate with an endorectal coil. Mean ADC was extracted from ROIs based on subsequent prostatectomy specimens. Histopathologic analysis revealed 172 lesions (113 peripheral, 59 transition zone). Two radiologists blinded to histopathologic outcome assigned PI-RADSv2 categories. Kendall tau was used to correlate ADC metrics with PI-RADSv2 and ISUP categories. ROC curves were used to assess the utility of ADC metrics in differentiating each reader's PI-RADSv2 DWI category 4 or 5 assessment in the whole prostate and by zone. RESULTS: ADC metrics negatively correlated with ISUP category in the whole prostate (ADC, τ = -0.21, p = 0.0002; normalized ADC, τ = -0.21, p = 0.0001). Moderate negative correlation was found in expert PI-RADSv2 DWI categories (ADC, τ = -0.34; normalized ADC, τ = -0.31; each p < 0.0001) maintained across zones. In the whole prostate, AUCs of ADC and normalized ADC were 87% and 82% for predicting expert PI-RADSv2 DWI category 4 or 5. A derived optimal cutoff ADC less than 1061 and normalized ADC less than 0.65 achieved positive predictive values of 83% and 84% for correct classification of PI-RADSv2 DWI category 4 or 5 by an expert reader. Consistent relations and predictive values were found by an independent novice reader. CONCLUSION: ADC and normalized ADC inversely correlate with PI-RADSv2 and ISUP categories and can serve as quantitative metrics to assist with assigning PI-RADSv2 DWI category 4 or 5.

Computer-aided diagnosis prior to conventional interpretation of prostate mpMRI: an international multi-reader study.

OBJECTIVES: To evaluate if computer-aided diagnosis (CAD) prior to prostate multi-parametric MRI (mpMRI) can improve sensitivity and agreement between radiologists. METHODS: Nine radiologists (three each high, intermediate, low experience) from eight institutions participated. A total of 163 patients with 3-T mpMRI from 4/2012 to 6/2015 were included: 110 cancer patients with prostatectomy after mpMRI, 53 patients with no lesions on mpMRI and negative TRUS-guided biopsy. Readers were blinded to all outcomes and detected lesions per PI-RADSv2 on mpMRI. After 5 weeks, readers re-evaluated patients using CAD to detect lesions. Prostatectomy specimens registered to MRI were ground truth with index lesions defined on pathology. Sensitivity, specificity and agreement were calculated per patient, lesion level and zone-peripheral (PZ) and transition (TZ). RESULTS: Index lesion sensitivity was 78.2% for mpMRI alone and 86.3% for CAD-assisted mpMRI (p = 0.013). Sensitivity was comparable for TZ lesions (78.7% vs 78.1%; p = 0.929); CAD improved PZ lesion sensitivity (84% vs 94%; p = 0.003). Improved sensitivity came from lesions scored PI-RADS < 3 as index lesion sensitivity was comparable at PI-RADS ≥ 3 (77.6% vs 78.1%; p = 0.859). Per patient specificity was 57.1% for CAD and 70.4% for mpMRI (p = 0.003). CAD improved agreement between all readers (56.9% vs 71.8%; p < 0.001). CONCLUSIONS: CAD-assisted mpMRI improved sensitivity and agreement, but decreased specificity, between radiologists of varying experience. KEY POINTS: • Computer-aided diagnosis (CAD) assists clinicians in detecting prostate cancer on MRI. • CAD assistance improves agreement between radiologists in detecting prostate cancer lesions. • However, this CAD system induces more false positives, particularly for less-experienced clinicians and in the transition zone. • CAD assists radiologists in detecting cancer missed on MRI, suggesting a path for improved diagnostic confidence.

The Problems with the Kappa Statistic as a Metric of Interobserver Agreement on Lesion Detection Using a Third-reader Approach When Locations Are Not Prespecified.

RATIONALE AND OBJECTIVES: To point out the problems with Cohen kappa statistic and to explore alternative metrics to determine interobserver agreement on lesion detection when locations are not prespecified. MATERIALS AND METHODS: Use of kappa and two alternative methods, namely index of specific agreement (ISA) and modified kappa, for measuring interobserver agreement on the location of detected lesions are presented. These indices of agreement are illustrated by application to a retrospective multireader study in which nine readers detected and scored prostate cancer lesions in 163 consecutive patients (n = 110 cases, n = 53 controls) using the guideline of Prostate Imaging Reporting and Data System version 2 on multiparametric magnetic resonance imaging. RESULTS: The proposed modified kappa, which properly corrects for the amount of agreement by chance, is shown to be approximately equivalent to the ISA. In the prostate cancer data, average kappa, modified kappa, and ISA equaled 30%, 55%, and 57%, respectively, for all lesions and 20%, 87%, and 87%, respectively, for index lesions. CONCLUSIONS: The application of kappa could result in a substantial downward bias in reader agreement on lesion detection when locations are not prespecified. ISA is recommended for assessment of reader agreement on lesion detection.

Multiparametric MRI for the detection of local recurrence of prostate cancer in the setting of biochemical recurrence after low dose rate brachytherapy.

PURPOSE: Prostate multiparametric magnetic resonance imaging (mpMRI) has utility in detecting post-radiotherapy local recurrence. We conducted a multireader study to evaluate the diagnostic performance of mpMRI for local recurrence after low dose rate (LDR) brachytherapy. METHODS: A total of 19 patients with biochemical recurrence after LDR brachytherapy underwent 3T endorectal coil mpMRI with T2-weighted imaging, dynamic contrast-enhanced imaging (DCE) and diffusion-weighted imaging (DWI) with pathologic confirmation. Prospective reads by an experienced prostate radiologist were compared with reads from 4 radiologists of varying experience. Readers identified suspicious lesions and rated each MRI detection parameter. MRI-detected lesions were considered true-positive with ipsilateral pathologic confirmation. Inferences for sensitivity, specificity, positive predictive value (PPV), kappa, and index of specific agreement were made with the use of bootstrap resampling. RESULTS: Pathologically confirmed recurrence was found in 15 of 19 patients. True positive recurrences identified by mpMRI were frequently located in the transition zone (46.7%) and seminal vesicles (30%). On patient-based analysis, average sensitivity of mpMRI was 88% (standard error [SE], 3.5%). For highly suspicious lesions, specificity of mpMRI was 75% (SE, 16.5%). On lesion-based analysis, the average PPV was 62% (SE, 6.7%) for all lesions and 78.7% (SE, 10.3%) for highly suspicious lesions. The average PPV for lesions invading the seminal vesicles was 88.8% (n=13). The average PPV was 66.6% (SE, 5.8%) for lesions identified with T2-weighted imaging, 64.9% (SE, 7.3%) for DCE, and 70% (SE, 7.3%) for DWI. CONCLUSION: This series provides evidence that mpMRI after LDR brachytherapy is feasible with a high patient-based cancer detection rate. Radiologists of varying experience demonstrated moderate agreement in detecting recurrence.

All over the map: An interobserver agreement study of tumor location based on the PI-RADSv2 sector map.

BACKGROUND: Prostate imaging reporting and data system version 2 (PI-RADSv2) recommends a sector map for reporting findings of prostate cancer mulitparametric MRI (mpMRI). Anecdotally, radiologists may demonstrate inconsistent reproducibility with this map. PURPOSE: To evaluate interobserver agreement in defining prostate tumor location on mpMRI using the PI-RADSv2 sector map. STUDY TYPE: Retrospective. POPULATION: Thirty consecutive patients who underwent mpMRI between October, 2013 and March, 2015 and who subsequently underwent prostatectomy with whole-mount processing. FIELD STRENGTH: 3T mpMRI with T2 W, diffusion-weighted imaging (DWI) (apparent diffusion coefficient [ADC] and b-2000), dynamic contrast-enhanced (DCE). ASSESSMENT: Six radiologists (two high, two intermediate, and two low experience) from six institutions participated. Readers were blinded to lesion location and detected up to four lesions as per PI-RADSv2 guidelines. Readers marked the long-axis of lesions, saved screen-shots of each lesion, and then marked the lesion location on the PI-RADSv2 sector map. Whole-mount prostatectomy specimens registered to the MRI served as ground truth. Index lesions were defined as the highest grade lesion or largest lesion if grades were equivalent. STATISTICAL TEST: Agreement was calculated for the exact, overlap, and proportion of agreement. RESULTS: Readers detected an average of 1.9 lesions per patient (range 1.6-2.3). 96.3% (335/348) of all lesions for all readers were scored PI-RADS ≥3. Readers defined a median of 2 (range 1-18) sectors per lesion. Agreement for detecting index lesions by screen shots was 83.7% (76.1%-89.9%) vs. 71.0% (63.1-78.3%) overlap agreement on the PI-RADS sector map (P < 0.001). Exact agreement for defining sectors of detected index lesions was only 21.2% (95% confidence interval [CI]: 14.4-27.7%) and rose to 49.0% (42.4-55.3%) when overlap was considered. Agreement on defining the same level of disease (ie, apex, mid, base) was 61.4% (95% CI 50.2-71.8%). DATA CONCLUSION: Readers are highly likely to detect the same index lesion on mpMRI, but exhibit poor reproducibility when attempting to define tumor location on the PI-RADSv2 sector map. The poor agreement of the PI-RADSv2 sector map raises concerns its utility in clinical practice. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2018;48:482-490.

What Are We Missing? False-Negative Cancers at Multiparametric MR Imaging of the Prostate.

Purpose To characterize clinically important prostate cancers missed at multiparametric (MP) magnetic resonance (MR) imaging. Materials and Methods The local institutional review board approved this HIPAA-compliant retrospective single-center study, which included 100 consecutive patients who had undergone MP MR imaging and subsequent radical prostatectomy. A genitourinary pathologist blinded to MP MR findings outlined prostate cancers on whole-mount pathology slices. Two readers correlated mapped lesions with reports of prospectively read MP MR images. Readers were blinded to histopathology results during prospective reading. At histopathologic examination, 80 clinically unimportant lesions (<5 mm; Gleason score, 3+3) were excluded. The same two readers, who were not blinded to histopathologic findings, retrospectively reviewed cancers missed at MP MR imaging and assigned a Prostate Imaging Reporting and Data System (PI-RADS) version 2 score to better understand false-negative lesion characteristics. Descriptive statistics were used to define patient characteristics, including age, prostate-specific antigen (PSA) level, PSA density, race, digital rectal examination results, and biopsy results before MR imaging. Student t test was used to determine any demographic differences between patients with false-negative MP MR imaging findings and those with correct prospective identification of all lesions. Results Of the 162 lesions, 136 (84%) were correctly identified with MP MR imaging. Size of eight lesions was underestimated. Among the 26 (16%) lesions missed at MP MR imaging, Gleason score was 3+4 in 17 (65%), 4+3 in one (4%), 4+4 in seven (27%), and 4+5 in one (4%). Retrospective PI-RADS version 2 scores were assigned (PI-RADS 1, n = 8; PI-RADS 2, n = 7; PI-RADS 3, n = 6; and PI-RADS 4, n = 5). On a per-patient basis, MP MR imaging depicted clinically important prostate cancer in 99 of 100 patients. At least one clinically important tumor was missed in 26 (26%) patients, and lesion size was underestimated in eight (8%). Conclusion Clinically important lesions can be missed or their size can be underestimated at MP MR imaging. Of missed lesions, 58% were not seen or were characterized as benign findings at second-look analysis. Recognition of the limitations of MP MR imaging is important, and new approaches to reduce this false-negative rate are needed. © RSNA, 2017 Online supplemental material is available for this article.

Validation of the Disease-Specific GPA for Patients With 1 to 3 Synchronous Brain Metastases in Newly Diagnosed NSCLC.

BACKGROUND: The disease-specific graded prognostic assessment (DS-GPA) for brain metastases is a powerful prognostic tool but has not been validated for patients with synchronous brain metastases (SBM) in newly diagnosed non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: We identified patients with newly diagnosed NSCLC with 1 to 3 SBM treated with stereotactic radiosurgery (SRS) between 1997 and 2012. We included patients whose brain metastases were treated with SRS alone or combined SRS and whole-brain radiotherapy (WBRT). Patients were stratified according to NSCLC DS-GPA to evaluate the accuracy of survival estimates. RESULTS: One hundred sixty-four patients were treated with either SRS alone (n = 85; 52%) or SRS and WBRT (n = 79; 48%). Median overall survival (OS) stratified according to DS-GPA of 0 to 1, 1.5 to 2, 2.5 to 3, and 3.5 to 4 were 2.8, 6.7, 9.8, and 13.2 months, respectively, consistent with OS reported for brain metastases in NSCLC DS-GPA (3.0, 6.5, 11.3, and 14.8 months, respectively). No difference in median progression-free survival or OS was noted with combined use of SRS and WBRT: 6.0 versus 6.1 months (P = .81) and 8.5 versus 9.1 months (P = .093), respectively. In multivariable analysis, Karnofsky performance status (hazard ratio [HR], 0.98; P = .008), extracranial metastases (HR, 0.498; P = .0003), squamous histology (HR, 1.81; P = .02), and number of brain metastases (2 vs. 1; HR, 1.504; P = .04, and 3 vs. 1; HR, 1.66; P = .05) were significant predictors of OS. CONCLUSION: The DS-GPA accurately estimates the prognosis of patients with SBM in newly diagnosed NSCLC. Patients with synchronous brain metastasis in newly diagnosed NSCLC should be carefully stratified for consideration of aggressive therapy.

Validation of the Dominant Sequence Paradigm and Role of Dynamic Contrast-enhanced Imaging in PI-RADS Version 2.

Purpose To validate the dominant pulse sequence paradigm and limited role of dynamic contrast material-enhanced magnetic resonance (MR) imaging in the Prostate Imaging Reporting and Data System (PI-RADS) version 2 for prostate multiparametric MR imaging by using data from a multireader study. Materials and Methods This HIPAA-compliant retrospective interpretation of prospectively acquired data was approved by the local ethics committee. Patients were treatment-naïve with endorectal coil 3-T multiparametric MR imaging. A total of 163 patients were evaluated, 110 with prostatectomy after multiparametric MR imaging and 53 with negative multiparametric MR imaging and systematic biopsy findings. Nine radiologists participated in this study and interpreted images in 58 patients, on average (range, 56-60 patients). Lesions were detected with PI-RADS version 2 and were compared with whole-mount prostatectomy findings. Probability of cancer detection for overall, T2-weighted, and diffusion-weighted (DW) imaging PI-RADS scores was calculated in the peripheral zone (PZ) and transition zone (TZ) by using generalized estimating equations. To determine dominant pulse sequence and benefit of dynamic contrast-enhanced (DCE) imaging, odds ratios (ORs) were calculated as the ratio of odds of cancer of two consecutive scores by logistic regression. Results A total of 654 lesions (420 in the PZ) were detected. The probability of cancer detection for PI-RADS category 2, 3, 4, and 5 lesions was 15.7%, 33.1%, 70.5%, and 90.7%, respectively. DW imaging outperformed T2-weighted imaging in the PZ (OR, 3.49 vs 2.45; P = .008). T2-weighted imaging performed better but did not clearly outperform DW imaging in the TZ (OR, 4.79 vs 3.77; P = .494). Lesions classified as PI-RADS category 3 at DW MR imaging and as positive at DCE imaging in the PZ showed a higher probability of cancer detection than did DCE-negative PI-RADS category 3 lesions (67.8% vs 40.0%, P = .02). The addition of DCE imaging to DW imaging in the PZ was beneficial (OR, 2.0; P = .027), with an increase in the probability of cancer detection of 15.7%, 16.0%, and 9.2% for PI-RADS category 2, 3, and 4 lesions, respectively. Conclusion DW imaging outperforms T2-weighted imaging in the PZ; T2-weighted imaging did not show a significant difference when compared with DW imaging in the TZ by PI-RADS version 2 criteria. The addition of DCE imaging to DW imaging scores in the PZ yields meaningful improvements in probability of cancer detection. © RSNA, 2017 An earlier incorrect version of this article appeared online. This article was corrected on July 27, 2017. Online supplemental material is available for this article.

Detection of prostate cancer in multiparametric MRI using random forest with instance weighting.

A prostate computer-aided diagnosis (CAD) based on random forest to detect prostate cancer using a combination of spatial, intensity, and texture features extracted from three sequences, T2W, ADC, and B2000 images, is proposed. The random forest training considers instance-level weighting for equal treatment of small and large cancerous lesions as well as small and large prostate backgrounds. Two other approaches, based on an AutoContext pipeline intended to make better use of sequence-specific patterns, were considered. One pipeline uses random forest on individual sequences while the other uses an image filter described to produce probability map-like images. These were compared to a previously published CAD approach based on support vector machine (SVM) evaluated on the same data. The random forest, features, sampling strategy, and instance-level weighting improve prostate cancer detection performance [area under the curve (AUC) 0.93] in comparison to SVM (AUC 0.86) on the same test data. Using a simple image filtering technique as a first-stage detector to highlight likely regions of prostate cancer helps with learning stability over using a learning-based approach owing to visibility and ambiguity of annotations in each sequence.

PI-RADSv2: How we do it.

Much criticism has been leveled at screening for prostate cancer using prostate-specific antigen (PSA) testing, yet there is no suitable replacement to improve the detection of clinically significant cancer (CSC). Prostate multiparametric magnetic resonance imaging (mpMRI) combined with mpMRI-guided biopsies is one possible solution, as it reduces detection of low-grade disease and increases detection of CSC. However, mpMRI is critically limited by lack of standardization across institutions and low interobserver agreement. The Prostate Imaging Reporting and Diagnostic System version 2 (PI-RADSv2) aims to address these concerns. We discuss the clinical and technical considerations for implementing PI-RADSv2, how we have adapted to PI-RADSv2, and review current research. While PI-RADSv2 represents a major step forward for standardizing prostate mpMRI, it does not provide a level of standardization that is routine with clinical blood tests and reader reproducibility remains an issue. Future research should seek to further improve quality assurance of mpMRI building on the important contributions of PI-RADSv2. LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 2 J. MAGN. RESON. IMAGING 2017;46:11-23.

Accuracy and agreement of PIRADSv2 for prostate cancer mpMRI: A multireader study.

PURPOSE: Multiparametric MRI (mpMRI) improves the detection of clinically significant prostate cancer, but is limited by interobserver variation. The second version of theProstate Imaging Reporting and Data System (PIRADSv2) was recently proposed as a standard for interpreting mpMRI. To assess the performance and interobserver agreement of PIRADSv2 we performed a multi-reader study with five radiologists of varying experience. MATERIALS AND METHODS: Five radiologists (n = 2 prostate dedicated, n = 3 general body) blinded to clinicopathologic results detected and scored lesions on prostate mpMRI using PIRADSv2. The endorectal coil 3 Tesla MRI included T2W, diffusion-weighted imaging (apparent diffusion coefficient, b2000), and dynamic contrast enhancement. Thirty-four consecutive patients were included. Results were correlated with radical prostatectomy whole-mount histopathology produced with patient-specific three-dimensional molds. An index lesion was defined on pathology as the lesion with highest Gleason score or largest volume if equivalent grades. Average sensitivity and positive predictive values (PPVs) for all lesions and index lesions were determined using generalized estimating equations. Interobserver agreement was evaluated using index of specific agreement. RESULTS: Average sensitivity was 91% for detecting index lesions and 63% for all lesions across all readers. PPV was 85% for PIRADS ≥ 3 and 90% for PIRADS ≥ 4. Specialists performed better only for PIRADS ≥ 4 with sensitivity 90% versus 79% (P = 0.01) for index lesions. Index of specific agreement among readers was 93% for the detection of index lesions, 74% for the detection of all lesions, and 85% for scoring index lesions, and 58% for scoring all lesions. CONCLUSION: By using PIRADSv2, general body radiologists and prostate specialists can detect high-grade index prostate cancer lesions with high sensitivity and agreement. LEVEL OF EVIDENCE: 1 J. Magn. Reson. Imaging 2017;45:579-585.

Multiparametric Magnetic Resonance Imaging of Recurrent Prostate Cancer.

There is growing consensus that multiparametric magnetic resonance imaging (mpMRI) is an effective modality in the detection of locally recurrent prostate cancer after prostatectomy and radiation therapy. The emergence of magnetic resonance (MR)-guided focal therapies, such as cryoablation, high-intensity focused ultrasound, and laser ablation, have made the use of mpMRI even more important, as the normal anatomy is inevitably altered and the detection of recurrence is made more difficult. The aim of this article is to review the utility of mpMRI in detecting recurrent prostate cancer in patients following radical prostatectomy, radiation therapy, and focal therapy and to discuss expected post-treatment mpMRI findings, the varied appearance of recurrent tumors, and their mimics.

Prospective Evaluation of the Prostate Imaging Reporting and Data System Version 2 for Prostate Cancer Detection.

PURPOSE: Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) was developed to standardize the interpretation and reporting of multiparametric prostate magnetic resonance imaging and provide guidelines for biopsy of multiparametric magnetic resonance imaging findings. We prospectively evaluated the cancer detection rate at each overall PI-RADSv2 score. MATERIALS AND METHODS: This prospective study included 62 consecutive patients with 116 lesions who underwent multiparametric prostate magnetic resonance imaging at 3T with PI-RADSv2 evaluation and subsequent targeted magnetic resonance imaging/transrectal ultrasound fusion guided biopsy and concurrent 12-core systematic prostate biopsy between May and September 2015. Median patient age and prostate specific antigen values were 65.5 years (range 50.3 to 76.6) and 7.10 ng/ml (range 0.47 to 863.0), respectively. Mean lesion size was 12.7 mm overall. Lesion based cancer detection rates for all tumors and for Gleason 3+4 or greater tumors at each PI-RADSv2 score were calculated. Univariate analysis was performed to assess differences in the cancer detection rate among PI-RADSv2 scores. RESULTS: A total of 116 lesions in 62 patients were evaluated prospectively (0 PI-RADS 1, 18 PI-RADS 2, 19 PI-RADS 3, 47 PI-RADS 4, 32 PI-RADS 5), and the patients underwent magnetic resonance/transrectal ultrasound fusion guided biopsy and systematic biopsy. Histopathology revealed 55 of 116 (47.4%) cancers (17 Gleason 3+3, 16 Gleason 3+4, 6 Gleason 4+3, 12 Gleason 4+4, 3 Gleason 4+5 and 1 Gleason 5+4). Based on targeted biopsy on a per lesion basis, the overall cancer detection rates of PI-RADS 2, 3, 4 and 5 scores for all tumors was 22.2%, 15.8%, 29.8% and 78.1%, respectively. The cancer detection rate of PI-RADS 2, 3, 4 and 5 scores for Gleason 3+4 or greater tumors was 5.6%, 0%, 21.3% and 75%, respectively. Differences in the cancer detection rate between overall PI-RADS 4 and 5 scores were significant (p <0.001 for Gleason greater than 3+3 and Gleason 3+4 or greater cancers). CONCLUSIONS: A PI-RADS score of 5 had the highest prospective cancer detection rate (78%). A PI-RADS score of 4 had only a 30% cancer detection rate, which is lower than expected. Surprisingly, no or few significant cancers were detected at a PI-RADS score of 3 (16%). These early prospective data suggest that current criteria result in a high false-positive rate that lowers the cancer detection rate. Therefore, stricter criteria may be needed in the future to decrease false-positives and increase the cancer detection rate for PI-RADS scores of 3, 4 and 5.

Carotid blowout in a patient with nasopharyngeal carcinoma treated with SBRT re-irradiation for local recurrence using twice weekly treatment.

We present the case of a patient undergoing reirradiation for a T4 nasopharyngeal tumor 1 year after his initial radiation, treated with SBRT to a moderate dose with twice weekly fractionation. Despite the measures of caution employed, the patient had a fatal carotid blowout at 7 months following SBRT. This suggests that spacing apart fractions of SBRT alone may not be sufficient to obviate the risk of carotid blowout syndrome and other risk factors and interventions should be considered.