Mapping expanded prostate cancer index composite to EQ5D utilities to inform economic evaluations in prostate cancer: Secondary analysis of NRG/RTOG 0415.

PURPOSE: The Expanded Prostate Cancer Index Composite (EPIC) is the most commonly used patient reported outcome (PRO) tool in prostate cancer (PC) clinical trials, but health utilities associated with the different health states assessed with this tool are unknown, limiting our ability to perform cost-utility analyses. This study aimed to map EPIC tool to EuroQoL-5D-3L (EQ5D) to generate EQ5D health utilities. METHODS AND MATERIALS: This is a secondary analysis of a prospective, randomized non-inferiority clinical trial, conducted between 04/2006 and 12/2009 at cancer centers across the United States, Canada, and Switzerland. Eligible patients included men >18 years with a known diagnosis of low-risk PC. Patient HRQoL data were collected using EPIC and health utilities were obtained using EQ5D. Data were divided into an estimation sample (n = 765, 70%) and a validation sample (n = 327, 30%). The mapping algorithms that capture the relationship between the instruments were estimated using ordinary least squares (OLS), Tobit, and two-part models. Five-fold cross-validation (in-sample) was used to compare the predictive performance of the estimated models. Final models were selected based on root mean square error (RMSE). RESULTS: A total of 565 patients in the estimation sample had complete information on both EPIC and EQ5D questionnaires at baseline. Mean observed EQ5D utility was 0.90±0.13 (range: 0.28-1) with 55% of patients in full health. OLS models outperformed their counterpart Tobit and two-part models for all pre-determined model specifications. The best model fit was: "EQ5D utility = 0.248541 + 0.000748*(Urinary Function) + 0.001134*(Urinary Bother) + 0.000968*(Hormonal Function) + 0.004404*(Hormonal Bother)- 0.376487*(Zubrod) + 0.003562*(Urinary Function*Zubrod)"; RMSE was 0.10462. CONCLUSIONS: This is the first study to identify a comprehensive set of mapping algorithms to generate EQ5D utilities from EPIC domain/ sub-domain scores. The study results will help estimate quality-adjusted life-years in PC economic evaluations.

Report dose-to-medium in clinical trials where available; a consensus from the Global Harmonisation Group to maximize consistency.

PURPOSE: To promote consistency in clinical trials by recommending a uniform framework as it relates to radiation transport and dose calculation in water versus in medium. METHODS: The Global Quality Assurance of Radiation Therapy Clinical Trials Harmonisation Group (GHG; www.rtqaharmonization.org) compared the differences between dose to water in water (Dw,w), dose to water in medium (Dw,m), and dose to medium in medium (Dm,m). This was done based on a review of historical frameworks, existing literature and standards, clinical issues in the context of clinical trials, and the trajectory of radiation dose calculations. Based on these factors, recommendations were developed. RESULTS: No framework was found to be ideal or perfect given the history, complexity, and current status of radiation therapy. Nevertheless, based on the evidence available, the GHG established a recommendation preferring dose to medium in medium (Dm,m). CONCLUSIONS: Dose to medium in medium (Dm,m) is the preferred dose calculation and reporting framework. If an institution's planning system can only calculate dose to water in water (Dw,w), this is acceptable.

Adherence of US Insurance Payer Policies to the American Society of Radiation Oncology Stereotactic Radiosurgery Model Policy.

PURPOSE: The medical necessity of stereotactic radiosurgery (SRS) is nonuniform across insurance policies. The American Society for Radiation Oncology (ASTRO) created a model policy based on the consensus of the radiation oncology community to communicate medically necessary indications for SRS. We compared the current insurance policies for SRS with those of the ASTRO model policy. METHODS AND MATERIALS: We identified 58 insurance payers and 3 national benefits managers with SRS policies. Among these, 7 insurance payers were excluded for policies that were not reviewed after 2015 and for not detailing individual medically necessary indications. For each of the indications listed in ASTRO's model policy, we determined the proportion of payers that considered SRS medically necessary. We compared these proportions for national versus regional payers and policies updated in the last 12 months versus those updated less often using Fisher exact and χ2 tests. RESULTS: All insurance policies reviewed considered SRS as medically necessary for brain metastases, medically refractory trigeminal neuralgia, and arteriovenous malformations. Compared with national payers, regional payers were less likely to deem other schwannomas, and a boost for large cranial or spinal lesions medically necessary (P < .05). The indication with the lowest coverage was medically refractory movement disorders (44.4%), followed by medically refractory epilepsy (33.3%). However, policies that were updated within the last year were more likely to deem medical necessity for epilepsy, movement disorders, hemangioblastoma, pineal gland tumors, and other schwannomas. CONCLUSIONS: Significant discrepancy remains among insurance policies for several indications in ASTRO's model policy for SRS; however, national payers and those with recent policy updates have a greater concordance with the ASTRO model policy.

Effectiveness of postoperative radiotherapy after radical cystectomy for locally advanced bladder cancer.

BACKGROUND: Local-regional failure (LF) for locally advanced bladder cancer (LABC) after radical cystectomy (RC) is common even with chemotherapy and is associated with high morbidity/mortality. Postoperative radiotherapy (PORT) can reduce LF and may enhance overall survival (OS) but has no defined role. We hypothesized that the addition of PORT would improve OS in LABC in a large nationwide oncology database. METHODS: We identified ≥ pT3pN0-3M0 LABC patients in the National Cancer Database diagnosed 2004-2014 who underwent RC ± PORT. OS was calculated using Kaplan-Meier and Cox proportional hazards regression modeling was used to identify predictors of OS. Propensity matching was performed to match RC patients who received PORT vs those who did not. RESULTS: 15,124 RC patients were identified with 512 (3.3%) receiving PORT. Median OS was 20.0 months (95% CI, 18.2-21.8) for PORT vs 20.8 months (95% CI, 20.3-21.3) for no PORT (P = 0.178). In multivariable analysis, PORT was independently associated with improved OS: hazard ratio 0.87 (95% CI, 0.78-0.97); P = 0.008. A one-to-three propensity match yielded 1,858 patients (24.9% receiving PORT and 75.1% without). In the propensity-matched cohort, median OS was 19.8 months (95% CI, 18.0-21.6) for PORT vs 16.9 months (95% CI, 15.6-18.1) for no PORT (P = 0.030). In the propensity-matched cohort of urothelial carcinoma patients (N = 1,460), PORT was associated with improved OS for pT4, pN+, and positive margins (P < 0.01 all). CONCLUSION: In this observational cohort, PORT was associated with improved OS in LABC. While the data should be interpreted cautiously, these results lend support to the use of PORT in selected patients with LABC, regardless of histology. Prospective trials of PORT are warranted.

NCTN Assessment on Current Applications of Radiomics in Oncology.

Radiomics is a fast-growing research area based on converting standard-of-care imaging into quantitative minable data and building subsequent predictive models to personalize treatment. Radiomics has been proposed as a study objective in clinical trial concepts and a potential biomarker for stratifying patients across interventional treatment arms. In recognizing the growing importance of radiomics in oncology, a group of medical physicists and clinicians from NRG Oncology reviewed the current status of the field and identified critical issues, providing a general assessment and early recommendations for incorporation in oncology studies.

Relief of Urinary Symptom Burden after Primary Prostate Cancer Treatment.

PURPOSE: Harms of prostate cancer treatment on urinary health related quality of life have been thoroughly studied. In this study we evaluated not only the harms but also the potential benefits of prostate cancer treatment in relieving the pretreatment urinary symptom burden. MATERIALS AND METHODS: In American (1,021) and Spanish (539) multicenter prospective cohorts of men with localized prostate cancer we evaluated the effects of radical prostatectomy, external radiotherapy or brachytherapy in relieving pretreatment urinary symptoms and in inducing urinary symptoms de novo, measured by changes in urinary medication use and patient reported urinary bother. RESULTS: Urinary symptom burden improved in 23% and worsened in 28% of subjects after prostate cancer treatment in the American cohort. Urinary medication use rates before treatment and 2 years after treatment were 15% and 6% with radical prostatectomy, 22% and 26% with external radiotherapy, and 19% and 46% with brachytherapy, respectively. Pretreatment urinary medication use (OR 1.4, 95% CI 1.0-2.0, p = 0.04) and pretreatment moderate lower urinary tract symptoms (OR 2.8, 95% CI 2.2-3.6) predicted prostate cancer treatment associated relief of baseline urinary symptom burden. Subjects with pretreatment lower urinary tract symptoms who underwent radical prostatectomy experienced the greatest relief of pretreatment symptoms (OR 4.3, 95% CI 3.0-6.1), despite the development of deleterious de novo urinary incontinence in some men. The magnitude of pretreatment urinary symptom burden and beneficial effect of cancer treatment on those symptoms were verified in the Spanish cohort. CONCLUSIONS: Men with pretreatment lower urinary tract symptoms may experience benefit rather than harm in overall urinary outcome from primary prostate cancer treatment. Practitioners should consider the full spectrum of urinary symptom burden evident before prostate cancer treatment in treatment decisions.

Multinational Prospective Study of Patient-Reported Outcomes After Prostate Radiation Therapy: Detailed Assessment of Rectal Bleeding.

PURPOSE: The new short Expanded Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) patient-reported health-related quality of life (HRQOL) tool has removed the rectal bleeding question from the previous much longer version, EPIC-26. Herein, we assess the impact of losing the dedicated rectal bleeding question in 2 independent prospective multicenter cohorts. METHODS AND MATERIALS: In a prospective multicenter test cohort (n=865), EPIC-26 patient-reported HRQOL data were collected for 2 years after treatment from patients treated with prostate radiation therapy from 2003 to 2011. A second prospective multicenter cohort (n=442) was used for independent validation. A repeated-effects model was used to predict the change from baseline in bowel summary scores from longer EPIC instruments using the change in EPIC-CP bowel summary scores with and without rectal bleeding scores. RESULTS: Two years after radiation therapy, 91% of patients were free of bleeding, and only 2.6% reported bothersome bleeding problems. Correlations between EPIC-26 and EPIC-CP bowel scores were very high (r2=0.90-0.96) and were statistically improved with the addition of rectal bleeding information (r2=0.94-0.98). Considering all patients, only 0.2% of patients in the test cohort and 0.7% in the validation cohort reported bothersome bleeding and had clinically relevant HRQOL changes missed with EPIC-CP. However, of the 2.6% (n=17) of men with bothersome rectal bleeding in the test cohort, EPIC-CP failed to capture 1 patient (6%) as experiencing meaningful declines in bowel HRQOL. CONCLUSIONS: Modern prostate radiation therapy results in exceptionally low rates of bothersome rectal bleeding, and <1% of patients experience bothersome bleeding and are not captured by EPIC-CP as having meaningful HRQOL declines after radiation therapy. However, in the small subset of patients with bothersome rectal bleeding, the longer EPIC-26 should strongly be considered, given its superior performance in this patient subset.

Online Magnetic Resonance Image Guided Adaptive Radiation Therapy: First Clinical Applications.

PURPOSE: To demonstrate the feasibility of online adaptive magnetic resonance (MR) image guided radiation therapy (MR-IGRT) through reporting of our initial clinical experience and workflow considerations. METHODS AND MATERIALS: The first clinically deployed online adaptive MR-IGRT system consisted of a split 0.35T MR scanner straddling a ring gantry with 3 multileaf collimator-equipped (60)Co heads. The unit is supported by a Monte Carlo-based treatment planning system that allows real-time adaptive planning with the patient on the table. All patients undergo computed tomography and MR imaging (MRI) simulation for initial treatment planning. A volumetric MRI scan is acquired for each patient at the daily treatment setup. Deformable registration is performed using the planning computed tomography data set, which allows for the transfer of the initial contours and the electron density map to the daily MRI scan. The deformed electron density map is then used to recalculate the original plan on the daily MRI scan for physician evaluation. Recontouring and plan reoptimization are performed when required, and patient-specific quality assurance (QA) is performed using an independent in-house software system. RESULTS: The first online adaptive MR-IGRT treatments consisted of 5 patients with abdominopelvic malignancies. The clinical setting included neoadjuvant colorectal (n=3), unresectable gastric (n=1), and unresectable pheochromocytoma (n=1). Recontouring and reoptimization were deemed necessary for 3 of 5 patients, and the initial plan was deemed sufficient for 2 of the 5 patients. The reasons for plan adaptation included tumor progression or regression and a change in small bowel anatomy. In a subsequently expanded cohort of 170 fractions (20 patients), 52 fractions (30.6%) were reoptimized online, and 92 fractions (54.1%) were treated with an online-adapted or previously adapted plan. The median time for recontouring, reoptimization, and QA was 26 minutes. CONCLUSION: Online adaptive MR-IGRT has been successfully implemented with planning and QA workflow suitable for routine clinical application. Clinical trials are in development to formally evaluate adaptive treatments for a variety of disease sites.

Quality of Intensity Modulated Radiation Therapy Treatment Plans Using a 6°Co Magnetic Resonance Image Guidance Radiation Therapy System.

PURPOSE: This work describes a commercial treatment planning system, its technical features, and its capabilities for creating (60)Co intensity modulated radiation therapy (IMRT) treatment plans for a magnetic resonance image guidance radiation therapy (MR-IGRT) system. METHODS AND MATERIALS: The ViewRay treatment planning system (Oakwood Village, OH) was used to create (60)Co IMRT treatment plans for 33 cancer patients with disease in the abdominal, pelvic, thorax, and head and neck regions using physician-specified patient-specific target coverage and organ at risk (OAR) objectives. Backup plans using a third-party linear accelerator (linac)-based planning system were also created. Plans were evaluated by attending physicians and approved for treatment. The (60)Co and linac plans were compared by evaluating conformity numbers (CN) with 100% and 95% of prescription reference doses and heterogeneity indices (HI) for planning target volumes (PTVs) and maximum, mean, and dose-volume histogram (DVH) values for OARs. RESULTS: All (60)Co IMRT plans achieved PTV coverage and OAR sparing that were similar to linac plans. PTV conformity for (60)Co was within <1% and 3% of linac plans for 100% and 95% prescription reference isodoses, respectively, and heterogeneity was on average 4% greater. Comparisons of OAR mean dose showed generally better sparing with linac plans in the low-dose range <20 Gy, but comparable sparing for organs with mean doses >20 Gy. The mean doses for all (60)Co plan OARs were within clinical tolerances. CONCLUSIONS: A commercial (60)Co MR-IGRT device can produce highly conformal IMRT treatment plans similar in quality to linac IMRT for a variety of disease sites. Additional work is in progress to evaluate the clinical benefit of other novel features of this MR-IGRT system.

Preliminary patient-reported outcomes analysis of 3-dimensional radiation therapy versus intensity-modulated radiation therapy on the high-dose arm of the Radiation Therapy Oncology Group (RTOG) 0126 prostate cancer trial.

BACKGROUND: The authors analyzed a preliminary report of patient-reported outcomes (PROs) among men who received high-dose radiation therapy (RT) on Radiation Therapy Oncology Group study 0126 (a phase 3 dose-escalation trial) with either 3-dimensional conformal RT (3D-CRT) or intensity-modulated RT (IMRT). METHODS: Patients in the 3D-CRT group received 55.8 gray (Gy) to the prostate and proximal seminal vesicles and were allowed an optional field reduction; then, they received 23.4 Gy to the prostate only. Patients in the IMRT group received 79.2 Gy to the prostate and proximal seminal vesicles. PROs were assessed at 0 months (baseline), 3 months, 6 months, 12 months, and 24 months and included bladder and bowel function assessed with the Functional Alterations due to Changes in Elimination (FACE) instrument and erectile function assessed with the International Index of Erectile Function (IIEF). Analyses included the patients who completed all data at baseline and for at least 1 follow-up assessment, and the results were compared with an imputed data set. RESULTS: Of 763 patients who were randomized to the 79.2-Gy arm, 551 patients and 595 patients who responded to the FACE instrument and 505 patients and 577 patients who responded to the IIEF were included in the completed and imputed analyses, respectively. There were no significant differences between modalities for any of the FACE or IIEF subscale scores or total scores at any time point for either the completed data set or the imputed data set. CONCLUSIONS: Despite significant reductions in dose and volume to normal structures using IMRT, this robust analysis of 3D-CRT and IMRT demonstrated no difference in patient-reported bowel, bladder, or sexual functions for similar doses delivered to the prostate and proximal seminal vesicles with IMRT compared with 3D-CRT delivered either to the prostate and proximal seminal vesicles or to the prostate alone.

Cost effectiveness of proton versus photon radiation therapy with respect to the risk of growth hormone deficiency in children.

BACKGROUND: Proton therapy in pediatrics may improve the risk/benefit profile of radiotherapy at a greater upfront financial cost, but it may prove to be cost effective if chronic medical complications can be avoided. Tools to assist with decision making are needed to aid in selecting pediatric patients for protons, and cost-effectiveness models can provide an objective method for this. METHODS: A Markov cohort-simulation model was developed to assess the expected costs and effectiveness for specific radiation doses to the hypothalamus with protons versus photons in pediatric patients. Costing data included cost of investment and the diagnosis and management of growth hormone deficiency. Longitudinal outcomes data were used to inform risk parameters for the model. With costs in 2012 US dollars and effectiveness measured in quality-adjusted life years, incremental cost-effectiveness ratios were used to measure outcomes. RESULTS: Proton therapy was cost effective for some scenarios based on the difference in hypothalamic sparing. Although some scenarios were not cost effective, others were not only cost effective for proton therapy but also demonstrated that protons were cost saving compared with photons. CONCLUSIONS: The current results provide the first evidence-based guide for identifying children with brain tumors who may benefit the most from proton therapy with respect to endocrine dysfunction. Proton therapy may be more cost effective for scenarios in which radiation dose to the hypothalamus can be spared, but protons may not be cost effective when tumors are involving or directly adjacent to the hypothalamus if there is a high dose to this structure.

Cost effectiveness of proton therapy compared with photon therapy in the management of pediatric medulloblastoma.

BACKGROUND: Proton therapy has been a hotly contested issue in both scientific publications and lay media. Proponents cite the modality's ability to spare healthy tissue, but critics claim the benefit gained from its use does not validate its cost compared with photon therapy. The objective of this study was to evaluate the cost effectiveness of proton therapy versus photon therapy in the management of pediatric medulloblastoma. METHODS: A cost-effective analysis was performed from the societal perspective using a Monte Carlo simulation model. A population of pediatric medulloblastoma survivors aged 18 years was studied who had received treatment at age 5 years and who were at risk of developing 10 adverse events, such as growth hormone deficiency, coronary artery disease, ototoxicity, secondary malignant neoplasm, and death. Costing data included the cost of investment and the costs of diagnosis and management of adverse health states from institutional and Medicare data. Longitudinal outcomes data and recent modeling studies informed risk parameters for the model. Incremental cost-effectiveness ratios were used to measure outcomes. RESULTS: Results from the base case demonstrated that proton therapy was associated with higher quality-adjusted life years and lower costs; therefore, it dominated photon therapy. In 1-way sensitivity analyses, proton therapy remained the more attractive strategy, either dominating photon therapy or having a very low cost per quality-adjust life year gained. Probabilistic sensitivity analysis illustrated the domination of proton therapy over photon therapy in 96.4% of simulations. CONCLUSIONS: By using current risk estimates and data on required capital investments, the current study indicated that proton therapy is a cost-effective strategy for the management of pediatric patients with medulloblastoma compared with standard of care photon therapy.

An evaluation of departmental radiation oncology incident reports: anticipating a national reporting system.

PURPOSE: Systems to ensure patient safety are of critical importance. The electronic incident reporting systems (IRS) of 2 large academic radiation oncology departments were evaluated for events that may be suitable for submission to a national reporting system (NRS). METHODS AND MATERIALS: All events recorded in the combined IRS were evaluated from 2007 through 2010. Incidents were graded for potential severity using the validated French Nuclear Safety Authority (ASN) 5-point scale. These incidents were categorized into 7 groups: (1) human error, (2) software error, (3) hardware error, (4) error in communication between 2 humans, (5) error at the human-software interface, (6) error at the software-hardware interface, and (7) error at the human-hardware interface. RESULTS: Between the 2 systems, 4407 incidents were reported. Of these events, 1507 (34%) were considered to have the potential for clinical consequences. Of these 1507 events, 149 (10%) were rated as having a potential severity of ≥2. Of these 149 events, the committee determined that 79 (53%) of these events would be submittable to a NRS of which the majority was related to human error or to the human-software interface. CONCLUSIONS: A significant number of incidents were identified in this analysis. The majority of events in this study were related to human error and to the human-software interface, further supporting the need for a NRS to facilitate field-wide learning and system improvement.

A research agenda for radiation oncology: results of the radiation oncology institute's comprehensive research needs assessment.

PURPOSE: To promote the rational use of scarce research funding, scholars have developed methods for the systematic identification and prioritization of health research needs. The Radiation Oncology Institute commissioned an independent, comprehensive assessment of research needs for the advancement of radiation oncology care. METHODS AND MATERIALS: The research needs assessment used a mixed-method, qualitative and quantitative social scientific approach, including structured interviews with diverse stakeholders, focus groups, surveys of American Society for Radiation Oncology (ASTRO) members, and a prioritization exercise using a modified Delphi technique. RESULTS: Six co-equal priorities were identified: (1) Identify and develop communication strategies to help patients and others better understand radiation therapy; (2) Establish a set of quality indicators for major radiation oncology procedures and evaluate their use in radiation oncology delivery; (3) Identify best practices for the management of radiation toxicity and issues in cancer survivorship; (4) Conduct comparative effectiveness studies related to radiation therapy that consider clinical benefit, toxicity (including quality of life), and other outcomes; (5) Assess the value of radiation therapy; and (6) Develop a radiation oncology registry. CONCLUSIONS: To our knowledge, this prioritization exercise is the only comprehensive and methodologically rigorous assessment of research needs in the field of radiation oncology. Broad dissemination of these findings is critical to maximally leverage the impact of this work, particularly because grant funding decisions are often made by committees on which highly specialized disciplines such as radiation oncology are not well represented.

Dosimetric evaluation of heterogeneity corrections for RTOG 0236: stereotactic body radiotherapy of inoperable stage I-II non-small-cell lung cancer.

PURPOSE: Using a retrospective analysis of treatment plans submitted from multiple institutions accruing patients to the Radiation Therapy Oncology Group (RTOG) 0236 non-small-cell stereotactic body radiotherapy protocol, the present study determined the dose prescription and critical structure constraints for future stereotactic body radiotherapy lung protocols that mandate density-corrected dose calculations. METHOD AND MATERIALS: A subset of 20 patients from four institutions participating in the RTOG 0236 protocol and using superposition/convolution algorithms were compared. The RTOG 0236 protocol required a prescription dose of 60 Gy delivered in three fractions to cover 95% of the planning target volume. Additional requirements were specified for target dose heterogeneity and the dose to normal tissue/structures. The protocol required each site to plan the patient's treatment using unit density, and another plan with the same monitor units and applying density corrections was also submitted. These plans were compared to determine the dose differences. Two-sided, paired Student's t tests were used to evaluate these differences. RESULTS: With heterogeneity corrections applied, the planning target volume receiving >/=60 Gy decreased, on average, 10.1% (standard error, 2.7%) from 95% (p = .001). The maximal dose to any point >/=2 cm away from the planning target volume increased from 35.2 Gy (standard error, 1.7) to 38.5 Gy (standard error, 2.2). CONCLUSION: Statistically significant dose differences were found with the heterogeneity corrections. The information provided in the present study is being used to design future heterogeneity-corrected RTOG stereotactic body radiotherapy lung protocols to match the true dose delivered for RTOG 0236.

Clinical assessment of outcome of prostate cancer (TCP, NTCP).

In the recent past there have been major advances in the management of patients with prostate cancer. New imaging procedures as 3-D CRT and IMRT have played a major role in the tretament of patients with localized prostate cancer. 3-D CRT allows higher doses to be delivered more precisely to the target volume with acceptable organs at risk morbidity. Improved tumor control results in lower incidence of distant metastases and better survival with an enhanced quality of life. This outcome yields a lower cost per treatment of patients over their life time.

Positron tomographic assessment of androgen receptors in prostatic carcinoma.

PURPOSE: The purpose of this study was to evaluate the feasibility of androgen receptor (AR) imaging with 16beta-[18F]fluoro-5alpha-dihydrotestosterone (FDHT) by positron emission tomography (PET) and to assess the binding selectivity of FDHT to AR in patients with prostate cancer. METHODS: Twenty men (age range 56-87 years) with advanced prostate cancer were studied. All except one had metastatic disease confirmed by biopsy and/or radiological studies. One patient who had radiological findings suggesting a single hepatic metastasis was found to have focal fatty infiltration on biopsy obtained after FDHT-PET and was excluded from further data analysis. FDHT uptake was assessed semiquantitatively by determination of the standardized uptake value (SUV) and tumor-to-muscle ratio (T/M). Additionally, to assess the AR binding selectivity of FDHT, patients with one or more foci of abnormally increased FDHT accumulation were studied after administration of an AR antagonist (flutamide). RESULTS: Conventional imaging demonstrated innumerable lesions in two patients and 43 lesions in the remaining 17 patients with advanced prostate cancer. FDHT-PET was positive in 12 of 19 patients (sensitivity of 63%), including the two patients with innumerable lesions. FDHT-PET detected 24 of 28 known lesions (86%) in the remaining ten patients. In addition, FDHT-PET detected 17 unsuspected lesions in five of these ten patients. All 12 patients with positive FDHT-PET underwent a repeat PET study after receiving flutamide for 1 day (250 mg t.i.d.). In all of these patients, there was a decrease in tumor FDHT uptake after flutamide; the mean (+/- standard deviation) SUV and T/M decreased from 7.0+/-4.7 and 6.9+/-3.9, respectively, to 3.0+/-1.5 and 3.0+/-1.6, respectively (p=0.002). The mean PSA in patients with positive FDHT-PET was significantly higher than that in patients with negative FDHT-PET (p=0.006). CONCLUSION: Our results document the feasibility of PET imaging of prostate cancer with FDHT and suggest that tumor uptake of FDHT is a receptor-mediated process. Positive PET studies were associated with higher PSA levels and thus, presumably, with greater tumor burden.