A pilot study treatment of malignant tumors using low-dose 18F-fluorodeoxyglucose (18F-FDG).

Photons, electrons and protons have therapeutic use however positrons have only been used for diagnostic imaging purposes. The energies of positrons (ß+) from F-18 (0.633 MeV) and electrons (ß-) from I-131 (0.606 MeV) are very close and have similar equilibrium dose constants. Since [18F]-fluorodeoxyglucose (18F-FDG) clears rapidly from circulation, administration of 37-74 GBq (1-2 Ci) of 18F-FDG is relatively safe from an internal radiation dosimetry point of view. We initiated a phase I dose escalation study to assess the safety, toxicity, and potential therapeutic utility of administering 100-200 mCi/m2 18F-FDG delivered over a 1 to 5 day period in patients with advanced lymphomas and solid tumors refractory to standard of care treatment (SCT). Here we report the results of the first four patients treated. Four patients with advanced cancers received a single dose of 3.7-7.4 GBq/m2 (100-200 mCi/m2) 18F-FDG. We monitored the patients for adverse effects and for response. No treatment-related toxicities were observed. There was no increased radiation exposure to personnel. Two patients showed decrease in the index lesions' SUVs by 17-33% (Day 1) and 25-31% (Day 30) post treatment. The two other patients showed stable disease on 18F-PET-CT. Interestingly, responses were seen at low radiotherapy doses (below 1 Gy). This exploratory study demonstrated the safety of therapeutic administration of up to 14.2 GBq (385 mCi) 18F-FDG. In patients with 18F-FDG-avid cancers, targeted radionuclide 18F-FDG therapy appears safe and may offer clinical benefit.

Implementation of multiparametric magnetic resonance imaging technology for evaluation of patients with suspicion for prostate cancer in the clinical practice setting.

OBJECTIVES: To investigate the impact of implementing magnetic resonance imaging (MRI) and ultrasonography fusion technology on biopsy and prostate cancer (PCa) detection rates in men presenting with clinical suspicion for PCa in the clinical practice setting. PATIENTS AND METHODS: We performed a review of 1 808 consecutive men referred for elevated prostate-specific antigen (PSA) level between 2011 and 2014. The study population was divided into two groups based on whether MRI was used as a risk stratification tool. Univariable and multivariable analyses of biopsy rates and overall and clinically significant PCa detection rates between groups were performed. RESULTS: The MRI and PSA-only groups consisted of 1 020 and 788 patients, respectively. A total of 465 patients (45.6%) in the MRI group and 442 (56.1%) in the PSA-only group underwent biopsy, corresponding to an 18.7% decrease in the proportion of patients receiving biopsy in the MRI group (P < 0.001). Overall PCa (56.8% vs 40.7%; P < 0.001) and clinically significant PCa detection (47.3% vs 31.0%; P < 0.001) was significantly higher in the MRI vs the PSA-only group. In logistic regression analyses, the odds of overall PCa detection (odds ratio [OR] 1.74, 95% confidence interval [CI] 1.29-2.35; P < 0.001) and clinically significant PCa detection (OR 2.04, 95% CI 1.48-2.80; P < 0.001) were higher in the MRI than in the PSA-only group after adjusting for clinically relevant PCa variables. CONCLUSION: Among men presenting with clinical suspicion for PCa, addition of MRI increases detection of clinically significant cancers while reducing prostate biopsy rates when implemented in a clinical practice setting.

Ultralow Dose Dynamic Expiratory Computed Tomography for Evaluation of Tracheomalacia.

OBJECTIVE: The aim of this study was to determine the average effective radiation dose and feasibility of ultralow dose dynamic expiratory computed tomography (CT) for evaluation of tracheomalacia (ULD) and to evaluate factors that impact image quality. METHODS: This is a retrospective study of 64 consecutive patients from September to October 2016 for the evaluation of tracheomalacia. All studies were performed with routine inspiration chest CT followed by ULD z(kilovoltage peak (kVp) 80, 100, or 120 and fixed milliamperage 10) or typical dose CT (TD) (kVp 100 or 120 with automated milliamperage) dynamic expiration CT. Image quality was considered diagnostic if the trachea area could be accurately measured for tracheomalacia assessment, and diagnostic studies were graded fair, good, or excellent. Scan length, image quality, and effective radiation dose were compared for ULD versus TD and ULD at 100 kVp versus ULD at 80 kVp. For ULD studies, patient factors were compared across image quality. RESULTS: The ULD had a mean effective radiation dose of 0.08 mSv, with all studies of diagnostic image quality. The ULD showed 95% reduction in effective radiation dose (P < 0.001), 14% significant reduction in scan length (P = 0.029), and qualitatively decreased image quality compared w2 ith TD (P < 0.001). The ULD at 100 kVp had significantly better image quality compared with ULD at 80 kVp (P = 0.041) with higher effective radiation dose (0.09 vs 0.05 mSv) (P < 0.001). Body mass index significantly impacted image quality for all ULD studies but not for ULD at 80 or 100 kVp. CONCLUSION: For evaluation of tracheomalacia, ULD showed low effective radiation dose less than 0.1 mSv and maintained diagnostic image quality.

Multi-parametric MRI of the prostate: Factors predicting extracapsular extension at the time of radical prostatectomy.

OBJECTIVE: Extracapsular extension (ECE) of prostate cancer is a poor prognostic factor associated with progression, recurrence after treatment, and increased prostate cancer-related mortality. Accurate staging prior to radical prostatectomy is crucial in avoidance of positive margins and when planning nerve-sparing procedures. Multi-parametric magnetic resonance imaging (mpMRI) of the prostate has shown promise in this regard, but is hampered by poor sensitivity. We sought to identify additional clinical variables associated with pathologic ECE and determine our institutional accuracy in the detection of ECE amongst patients who went on to radical prostatectomy. METHODS: mpMRI studies performed between the years 2012 and 2014 were cross-referenced with radical prostatectomy specimens. Predictive properties of ECE as well as additional clinical and biochemical variables to identify pathology-proven prostate cancer ECE were analyzed. RESULTS: The prevalence of ECE was 32.4%, and the overall accuracy of mpMRI for ECE was 84.1%. Overall mpMRI sensitivity, specificity, positive predictive value, and negative predictive value for detection of ECE were 58.3%, 97.8%, 93.3%, and 81.5%, respectively. Specific mpMRI characteristics predictive of pathologic ECE included primary lesion size ((20.73 ± 9.09) mm, mean ± SD, p < 0.001), T2 PIRADS score (p = 0.009), overall primary lesion score (p < 0.001), overall study suspicion score (p = 0.003), and MRI evidence of seminal vesicle invasion (SVI) (p = 0.001). CONCLUSION: While mpMRI is an accurate preoperative assessment tool for the detection of ECE, its overall sensitivity is poor, likely related to the low detection rate of standard protocol MRI for microscopic extraprostatic disease. The additional mpMRI findings described may also be considered in surgical margin planning prior to radical prostatectomy.

Role of multi-parametric MRI of the prostate for screening and staging: Experience with over 1500 cases.

OBJECTIVE: Contemporary prostate cancer (PCa) screening modalities such as prostate specific antigen (PSA) and digital rectal examination (DRE) are limited in their ability to predict the detection of clinically significant disease. Multi-parametric magnetic resonance imaging (mpMRI) of the prostate has been explored as a staging modality for PCa. Less is known regarding its utility as a primary screening modality. We examined our experience with mpMRI as both a screening and staging instrument. METHODS: mpMRI studies performed between 2012 and 2014 in patients without PCa were cross-referenced with transrectal ultrasonography (TRUS) biopsy findings. Statistical analyses were performed to determine association of mpMRI findings with overall cancer diagnoses and clinically significant (Gleason score ≥7) disease. Subgroup analyses were then performed on patients with a history of prior negative biopsy and those without a history of TRUS biopsy. mpMRI studies were also cross-referenced with RP specimens. Statistical analyses determined predictive ability of extracapsular extension (ECE), seminal vesicle involvement (SVI), and pathologic evidence of clinically significant disease (Gleason score ≥7). RESULTS: Four hundred biopsy naïve or prior negative biopsy patients had positive mpMRI studies. Overall sensitivity, specificity, positive and negative predictive values were 94%, 37%, 58%, and 87%, respectively and 95%, 31%, 42%, and 93%, respectively for overall cancer detection and Gleason score ≥7 disease. In patients with no prior biopsy history, mpMRI sensitivity, specificity, positive and negative predictive values were 94%, 36%, 65%, and 82%, for all cancers, and 95%, 30%, 50%, and 89% for Gleason score≥7 lesions, respectively. In those with prior negative biopsy sensitivity, specificity, positive and negative predictive values were 94%, 37%, 52%, and 90% for all cancers, and 96%, 32%, 36%, and 96% for Gleason score ≥7 lesions, respectively. Seventy-four patients underwent radical prostatectomy (RP) after mpMRI. Lesion size on mpMRI correlated with the presence of Gleason score ≥7 cancers (p = 0.005). mpMRI sensitivity, specificity, positive and negative predictive values were 84%, 39%, 81%, and 44% respectively, for Gleason ≥7 cancer. For ECE and SVI, sensitivity and specificity were 58% and 98% and 44% and 97%, respectively. CONCLUSION: mpMRI is an accurate predictor of TRUS biopsy and RP outcomes. mpMRI has significant potential to change PCa management, particularly in the screening population, in whom a significant proportion may avoid TRUS biopsy. Further studies are necessary to determine how mpMRI should be incorporated into the current PCa screening and staging paradigms.

Risk stratification of prostate cancer utilizing apparent diffusion coefficient value and lesion volume on multiparametric MRI.

PURPOSE: To evaluate the performance of apparent diffusion coefficient (ADC) and lesion volume in potentially risk-stratifying patients with prostate cancer (PCa). MATERIALS AND METHODS: Men with elevated prostate-specific antigen or abnormal digital rectal exam underwent a 3T multiparametric magnetic resonance imaging (mpMRI) with endorectal coil. ADC maps were calculated using b values of 0, 500, 1000, and 1500; additional images were obtained with b value of 2000. We prospectively enrolled 312 men with lesions suspicious for cancer (suspicion score 2-5) on mpMRI. MRI/ultrasound fusion-guided prostate biopsies were performed. Mean ADC of suspicious lesions were correlated against lesion volume, Gleason and D'Amico risk. RESULTS: The cancer detection rate of fusion biopsy per lesion was 45.6% (206/452). Cancerous lesions were larger (median volume: 0.40 vs. 0.30 cm3 ; P = 0.016). The median ADC (×10-6 mm2 /sec) for lesions negative and positive for PCa were 984.5 and 666.5, respectively (P < 0.0001). The AUC of ADC in predicting PCa was 0.79. Larger lesions were associated with higher risk PCa (Gleason and D'Amico) and lower ADC (all P < 0.0001). CONCLUSION: The mean ADC of suspicious lesions on mpMRI was inversely correlated, while lesion volume had a direct correlation with PCa detection. Future follow-up studies are needed to assess longitudinal cancer risks of suspicious mpMRI lesions. LEVEL OF EVIDENCE: 2 J. Magn. Reson. Imaging 2017;45:610-616.

Reproducibility of Multiparametric Magnetic Resonance Imaging and Fusion Guided Prostate Biopsy: Multi-Institutional External Validation by a Propensity Score Matched Cohort.

PURPOSE: As the adoption of magnetic resonance imaging/ultrasound fusion guided biopsy expands, the reproducibility of outcomes at expert centers becomes essential. We sought to validate the comprehensive NCI (National Cancer Institute) experience with multiparametric magnetic resonance imaging and fusion guided biopsy in an external, independent, matched cohort of patients. MATERIALS AND METHODS: We compared 620 patients enrolled in a prospective trial comparing systematic biopsy to fusion guided biopsy at NCI to 310 who underwent a similar procedure at Long Island Jewish Medical Center. The propensity score, defined as the probability of being treated outside NCI, was calculated using the estimated logistic regression model. Patients from the hospital were matched 1:1 for age, prostate specific antigen, magnetic resonance imaging suspicion score and prior negative biopsies. Clinically significant disease was defined as Gleason 3 + 4 or greater. RESULTS: Before matching we found differences between the cohorts in age, magnetic resonance imaging suspicion score (each p <0.001), the number of patients with prior negative biopsies (p = 0.01), and the overall cancer detection rate and the cancer detection rate by fusion guided biopsy (each p <0.001). No difference was found in the rates of upgrading by fusion guided biopsy (p = 0.28) or upgrading to clinically significant disease (p = 0.95). A statistically significant difference remained in the overall cancer detection rate and the rate by fusion guided biopsy after matching. On subgroup analysis we found a difference in the overall cancer detection rate and the rate by fusion guided biopsy (p <0.001 and 0.003) in patients with prior negative systematic biopsy but no difference in the 2 rates (p = 0.39 and 0.51, respectively) in biopsy naïve patients. CONCLUSIONS: Improved detection of clinically significant cancer by magnetic resonance imaging and fusion guided biopsy is reproducible by an experienced multidisciplinary team consisting of dedicated radiologists and urologists.

Comparison of Multiparametric MRI Scoring Systems and the Impact on Cancer Detection in Patients Undergoing MR US Fusion Guided Prostate Biopsies.

INTRODUCTION: Multiple scoring systems have been proposed for prostate MRI reporting. We sought to review the clinical impact of the new Prostate Imaging Reporting and Data System v2 (PI-RADS) and compare those results to our proposed Simplified Qualitative System (SQS) score with respect to detection of prostate cancers and clinically significant prostate cancers. METHODS: All patients who underwent multiparametric prostate MRI (mpMRI) had their images interpreted using PI-RADS v1 and SQS score. PI-RADS v2 was calculated from prospectively collected data points. Patients with positive mpMRIs were then referred by their urologists for enrollment in an IRB-approved prospective phase III trial of mpMRI-Ultrasound (MR/TRUS) fusion biopsy of suspicious lesions. Standard 12-core biopsy was performed at the same setting. Clinical data were collected prospectively. RESULTS: 1060 patients were imaged using mpMRI at our institution during the study period. 341 participants were then referred to the trial. 312 participants underwent MR/TRUS fusion biopsy of 452 lesions and were included in the analysis. 202 participants had biopsy-proven cancer (64.7%) and 206 (45.6%) lesions were positive for cancer. Distribution of cancer detected at each score produced a Gaussian distribution for SQS while PI-RADS demonstrates a negatively skewed curve with 82.1% of cases being scored as a 4 or 5. Patient-level data demonstrated AUC of 0.702 (95% CI 0.65 to 0.73) for PI-RADS and 0.762 (95% CI 0.72 to 0.81) for SQS (p< 0.0001) with respect to the detection of prostate cancer. The analysis for clinically significant prostate cancer at a per lesion level resulted in an AUC of 0.725 (95% CI 0.69 to 0.76) and 0.829 (95% CI 0.79 to 0.87) for the PI-RADS and SQS score, respectively (p< 0.0001). CONCLUSIONS: mpMRI is a useful tool in the workup of patients at risk for prostate cancer, and serves as a platform to guide further evaluation with MR/TRUS fusion biopsy. SQS score provided a more normal distribution of scores and yielded a higher AUC than PI-RADS v2. However until our findings are validated, we recommend reporting of detailed sequence-specific findings. This will allow for prospectively collected data to be utilized in determining the impact of ongoing changes to these scoring systems as our understanding of mpMRI interpretation evolves.

In patients with a previous negative prostate biopsy and a suspicious lesion on magnetic resonance imaging, is a 12-core biopsy still necessary in addition to a targeted biopsy?

OBJECTIVES: To evaluate the performance of multiparametric magnetic resonance imaging (mpMRI) in predicting prostate cancer on repeat biopsy; and to compare the cancer detection rates (CDRs) of MRI/transrectal ultrasonography (TRUS) fusion-guided biopsy with standard 12-core biopsy in men with at least one previous negative biopsy. PATIENTS AND METHODS: We prospectively enrolled men with elevated or rising PSA levels and/or abnormal digital rectal examination into our MRI/TRUS fusion-guided prostate biopsy trial. Participants underwent a 3 T mpMRI with an endorectal coil. Three radiologists graded all suspicious lesions on a 5-point Likert scale. MRI/TRUS fusion-guided biopsies of suspicious prostate lesions and standard TRUS-guided 12-core biopsies were performed. Analysis of 140 eligible men with at least one previous negative biopsy was performed. We calculated CDRs and estimated area under the receiver operating characteristic curves (AUCs) of mpMRI in predicting any cancer and clinically significant prostate cancer. RESULTS: The overall CDR was 65.0% (91/140). Higher level of suspicion on mpMRI was significantly associated with prostate cancer detection (P < 0.001) with an AUC of 0.744 compared with 0.653 and 0.680 for PSA level and PSA density, respectively. The CDRs of MRI/TRUS fusion-guided and standard 12-core biopsy were 52.1% (73/140) and 48.6% (68/140), respectively (P = 0.435). However, fusion biopsy was more likely to detect clinically significant prostate cancer when compared with the 12-core biopsy (47.9% vs 30.7%; P < 0.001). Of the cancers missed by 12-core biopsy, 20.9% (19/91) were clinically significant. Most cancers missed by 12-core biopsy (69.6%) were located in the anterior fibromuscular stroma and transition zone. Using a fusion-biopsy-only approach in men with an MRI suspicion score of ≥4 would have missed only 3.5% of clinically significant prostate cancers. CONCLUSIONS: Using mpMRI and subsequent MRI/TRUS fusion-guided biopsy platform may improve detection of clinically significant prostate cancer in men with previous negative biopsies. Addition of a 12-core biopsy may be needed to avoid missing some clinically significant prostate cancers.

Multiparametric magnetic resonance imaging outperforms the Prostate Cancer Prevention Trial risk calculator in predicting clinically significant prostate cancer.

BACKGROUND: The Prostate Cancer Prevention Trial risk calculator for high-grade (PCPTHG) prostate cancer (CaP) was developed to improve the detection of clinically significant CaP. In this study, the authors compared the performance of the PCPTHG against multiparametric magnetic resonance imaging (MP-MRI) in predicting men at risk of CaP. METHODS: Men with an abnormal prostate-specific antigen (PSA) level or digital rectal examination (DRE) and a suspicious lesion on a 3-Tesla MP-MRI were enrolled prospectively. Three radiologists reviewed and graded all lesions on a 5-point Likert scale. Biopsy of suspicious lesion(s) was performed using a proprietary MRI/transrectal ultrasound fusion-guided prostate biopsy system, after which 12-core biopsy was performed. A genitourinary pathologist reviewed all pathology slides. The performance of PCPTHG was compared with that of MP-MRI in predicting clinically significant CaP. RESULTS: Of 175 men who were eligible for analysis, 64.6% (113 of 175 men) were diagnosed with CaP, including 93 of 113 men (82.3%) who had clinically significant disease. Age, abnormal DRE, PSA, PSA density, prostate size, extraprostatic extension on MRI, apparent diffusion coefficient value, and MRI lesion size were identified as significant predictors of high-grade CaP (all P < .05). The area under the receiver operating characteristic curve of PCPTHG for predicting high-grade CaP was 0.676 (95% confidence interval [CI], 0.592-0.751). By using a risk cutoff of ≥15% for biopsy as, proposed previously for high-grade CaP, sensitivity was 96.4%, specificity was 7.6%, and the false-positive rate was 51.1%. In contrast, the area under the receiver operating characteristic curve of MP-MRI for high-grade CaP was 0.769 (95% CI, 0.703-0.834), and it was 0.812 (95% CI, 0.754-0.869) for clinically significant CaP. CONCLUSIONS: MP-MRI outperforms PCPTHG in predicting clinically significant CaP, and its application may help select patients who will benefit from CaP diagnosis and treatment.

Improving detection of clinically significant prostate cancer: magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy.

PURPOSE: Given the limitations of prostate specific antigen and standard biopsies for detecting prostate cancer, we evaluated the cancer detection rate and external validity of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system used at the National Institutes of Health. MATERIALS AND METHODS: We performed a phase III trial of a magnetic resonance imaging/transrectal ultrasound fusion guided prostate biopsy system with participants enrolled between 2012 and 2013. A total of 153 men consented to the study and underwent 3 Tesla multiparametric magnetic resonance imaging with an endorectal coil for clinical suspicion of prostate cancer. Lesions were classified as low or moderate/high risk for prostate cancer. Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy and standard 12-core prostate biopsy were performed and 105 men were eligible for analysis. RESULTS: Mean patient age was 65.8 years and mean prostate specific antigen was 9.5 ng/ml. The overall cancer detection rate was 62.9% (66 of 105 patients). The cancer detection rate in those with moderate/high risk on imaging was 72.3% (47 of 65) vs 47.5% (19 of 40) in those classified as low risk for prostate cancer (p<0.05). Mean tumor core length was 4.6 and 3.7 mm for fusion biopsy and standard 12-core biopsy, respectively (p<0.05). Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy detected prostate cancer that was missed by standard 12-core biopsy in 14.3% of cases (15 of 105), of which 86.7% (13 of 15) were clinically significant. This biopsy upgraded 23.5% of cancers (4 of 17) deemed clinically insignificant on 12-core biopsy to clinically significant prostate cancer necessitating treatment. CONCLUSIONS: Magnetic resonance imaging/transrectal ultrasound fusion guided biopsy can improve prostate cancer detection. The results of this trial support the external validity of this platform and may be the next step in the evolution of prostate cancer management.