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Background Although immunotherapy (IO) in combination with chemotherapy has improved progression free and overall survival in patients with PD-L1+ metastatic triple negative breast cancer (mTNBC), prognosis remains poor. A potential therapeutic strategy to restore sensitivity to IO in patients with progressive disease is to introduce agents that re-sensitize the immune system to IO leading to a more tumor-specific and less toxic treatment in the second-line setting or beyond. Both talazoparib, a PARP inhibitor, and radiation (XRT) independently increase PD-L1 expression on the tumor cell surface resulting in heightened sensitivity to IO agents like atezolizumab, a PD-L1 inhibitor. Although a local treatment, XRT has the ability to produce an abscopal effect resulting in systemic shrinkage of non-irradiated tumors outside/distant to the XRT field, a phenomenon observed in patients receiving concurrent IO. While talazoparib is standard treatment in patients with gBRCA1 and 2 mutations, it is also a potent radiosensitizing agent that suppresses homologous recombination and PARP-1-dependent nonhomologous end joining (NHEJ) repair while promoting error-prone alt-NHEJ. When combined with IO, talazoparib can amplify immune responses by generating immunogenic neo-antigens independent of gBRCA1/2 status. We, therefore, hypothesize that the combination of talazoparib, XRT, and atezolizumab will re-sensitize mTNBC tumors to IO and promote a durable tumor-specific response that spares patients from toxicities associated with traditional chemotherapy regimens. Methods This is a Phase II multi-institutional study designed to assess efficacy and safety of talazoparib, high dose XRT, and atezolizumab given in the second-, third-, or fourth-line settings to patients with mTNBC that is PD-L1 positive. A total of 23 patients with mTNBC who do not carry gBRCA pathogenic variants will be enrolled. All patients will be treated with induction talazoparib of 1mg PO daily starting Day 1 of a 28-day cycle. Patients will then receive 8 Gy x 3 fractions to 1-4 metastatic lesions QOD beginning Day 12, 13, or 14. Atezolizumab will be given intravenously (840 mg)) on Day 15 of the 1st cycle and then on Day 1 and Day 15 of the subsequent cycles. Talazoparib and atezolizumab treatment will continue until progression or severe toxicity. The primary endpoint is objective response rate (ORR) in non-irradiated lesions 8 weeks after the first dose of atezolizumab. Key inclusion criteria include biopsy proven mTNBC (ER< 10%, PR< 10%, Her2-) with at least 2 extracranial metastatic lesions. Patients must have at least 1 extracranial metastatic lesion amenable to high dose radiotherapy and at least one additional extracranial lesion of measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST v1.1) that will not receive radiotherapy. Tumors must be PD-L1 positive as defined as >1% on IHC using the SP142 Ventana Assay. Key exclusion criteria include patients with germline BRCA pathogenic variants, more than three previous lines of chemotherapy treatment in the advanced setting with or without IO, and breast cancer progression within the first 3 months of previous IO treatment for non-metastatic or metastatic breast cancer. Sample size was determined using Simon’s 2-stage Minimax design to detect a 20% increase in ORR. The null hypothesis that the true response rate among gBRCA1/2 negative patients of 10% will be tested against a one-sided alternative. Inflammatory cytokines, circulating B cells, and ctDNA will be collected for correlative analysis. Enrollment began in April 2021. The study is managed by the Hoosier Cancer Research Network and is open to accrual at Emory University and University of Alabama at Birmingham. Clinical trial information: NCT04690855 Citation Format: Mylin A. Torres, Kevin Kalinsky, Erica Stringer-Reasor, Ahmed Elkhanany, Jolinta Lin, David M. Schuster, Sarah Friend, Jeffrey Switchenko, Manali Bhave. HCRN BRE 19-433: A Multi-institutional Phase II Study to Evaluate Efficacy and Safety of TAlazoparib, Radiotherapy and Atezolizumab in gBRCA 1/2 negative Patients with PD-L1+ Metastatic Triple Negative Breast Cancer (TARA) [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr OT2-10-03.

Background There is an increasing body of evidence indicating Y90 dose thresholds for tumor response and treatment-related toxicity. These thresholds are poorly studied in resin Y90, particularly in hepatocellular carcinoma (HCC). Purpose To evaluate the efficacy of prospective voxel-based dosimetry for predicting treatment response and adverse events (AEs) in patients with HCC undergoing resin-based Y90 radioembolization. Materials and methods This correlative study was based on a prospective single-arm clinical trial (NCT04172714), which evaluated the efficacy of low/scout (555 MBq) activity of resin-based Y90 for treatment planning. Partition model was used with goal of tumor dose (TD) > 200 Gy and non-tumoral liver dose (NTLD) Results N = 30 patients were treated with 33 tumors (19 segmental and 14 non-segmental). One patient died before the first imaging, and clinical follow-up was excluded from this analysis. Overall, 26 (81%) of the tumors had an OR and 23 (72%) had a CR. A mean TD of 253 Gy predicted an OR with 92% sensitivity and 83% specificity (area under the curve (AUC = 0.929, p p Conclusion In patients with HCC undergoing resin-based Y90, there are dose response and dose toxicity thresholds directly affecting outcomes. Clinical trial number: NCT04172714.

18F-Fluciclovine PET is approved for the evaluation of patients with suspected prostate cancer recurrence. 18F-Fluciclovine PET is highly specific for the localization of extraprostatic disease even with negative conventional images and low prostate-specific antigen and has been reported to influence patients' management and improve outcome. With the recent Food and Drug Administration approval of prostate-specific membrane antigen (PSMA) PET, 18F-Fluciclovine is likely to be used as an adjunct modality in patients with suspected occult local recurrence and/or negative PSMA findings.

The staging and surveillance of testicular cancer is a complex topic, which integrates clinical, biochemical, and imaging components. The use of imaging for staging and surveillance of testicular cancer is individually tailored to each patient by considering tumor histology and prognosis. This document discusses the rationale for use of imaging by imaging modality during the initial staging of testicular seminoma and nonseminoma tumors and during the planned surveillance of stage IA and IB testicular cancer by histological subtype integrating clinical suspicion for disease recurrence in surveillance protocols. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, [68Ga]Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of [68Ga]Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: [68Ga]Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those, 2/17 had NePC. A semiquantitative analysis with standardized uptake values (SUV) (e.g., SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. [68Ga]Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastatic lesion with identifiable [68Ga]Ga-DOTATATE uptake. Marked [68Ga]Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. Three patients had mild [68Ga]Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after [68Ga]Ga-DOTATATE imaging. Conclusions: [68Ga]Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with [68Ga]Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC.

Objectives: Prostate cancer is well known to express high levels of somatostatin receptors and preliminary data suggests that PET imaging with the somatostatin analog, 68Ga-DOTATATE, may allow for whole body staging of patients with metastatic castration resistant prostate cancer (mCRPC) and neuroendocrine prostate cancer (NePC). This study explores the utility of 68Ga-DOTATATE PET-CT to identify metastatic deposits in men with mCRPC and NePC and prognosticate disease progression. Methods: 68Ga-DOTATATE PET-CT was performed in 17 patients with mCRPC and of those 2/17 had NePC. Semiquantitative analysis with standardized uptake values (SUV) (e.g. SUVmax, SUVmean) was performed for each metastatic lesion and reference background tissues. 68Ga-DOTATATE uptake in metastatic deposits was further classified as: mild (less than liver), moderate (up to liver average), or marked (greater than liver). Serial prostate-specific antigen measurements and patient survival were followed up to 3 years after PET imaging to assess response to standard of care treatment. Results: All patients had at least one metastic lesion with identifiable 68Ga-DOTATATE uptake. Marked 68Ga-DOTATATE uptake was found in 7/17 patients, including both NePC patients, and all were non-responders to systemic therapy and died within the follow up period, with a mean time to death of 8.1 months. 3 patients had mild 68Ga-DOTATATE uptake, and all were responders to systemic therapy and were alive 36 months after 68Ga-DOTATATE imaging. Conclusions: 68Ga-DOTATATE is able to identify mCRPC and NePC metastatic deposits, and lesions with 68Ga-DOTATATE uptake > liver may portend poor outcomes in patients with mCRPC.

Incidental concomitant second primary malignancy may be detected on PET/CT imaging. We present an 18F-fluciclovine PET/CT of a patient undergoing evaluation of biochemically recurrent prostate cancer with incidental radiotracer uptake within lytic osseous lesions confirmed to be multiple myeloma. We present the 18F-fluciclovine PET/CT images of an 83-year-old man with prostate cancer treated in 2005 who presented with back pain and a CT scan revealing multiple lytic osseous lesions concerning for metastases versus a plasma cell neoplasm. Prostate-specific antigen at the time of evaluation was 0.1 ng/mL.

PURPOSE: To compare the accuracy and safety of 0.56 GBq resin yttrium-90 ((90)Y) (scout(90)Y) microspheres with those of technetium-99m macroaggregated albumin (MAA) in predicting the therapeutic (90)Y (Rx(90)Y) dose for patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This prospective single-arm clinical trial (Clinicaltrials.gov: NCT04172714) recruited patients with HCC. Patients underwent same-day mapping with MAA and scout(90)Y. Rx(90)Y activity was administered 3 days after mapping. Using paired t test and Pearson correlation, the tumor-to-normal ratio (TNR), lung shunt fraction (LSF), predicted mean tumor dose (TD), and nontumoral liver dose (NTLD) by MAA and scout(90)Y were compared with those by Rx(90)Y. Bland-Altman plots compared the level of agreement between the TNR and LSF of scout(90)Y and MAA with that of Rx(90)Y. The safety of scout(90)Y was evaluated by examining the discrepancy in extrahepatic activity between MAA and scout(90)Y. RESULTS: Thirty patients were treated using 19 segmental and 14 nonsegmental (ie, 2 contiguous segments or nonsegmental) therapies. MAA had weak LSF, moderate TNR, and moderate TD linear correlation with Rx(90)Y. Scout(90)Y had a moderate LSF, strong TNR, strong TD, and very strong NTLD in correlation with those of Rx(90)Y. Furthermore, the TNR and LSF of scout(90)Y had a stronger agreement with those of Rx(90)Y than with those of MAA. In the nonsegmental subgroup, MAA had no significant correlation with the TD and NTLD of Rx(90)Y, whereas scout(90)Y had a very strong correlation with both of these factors. In the segmental subgroup, both MAA and scout(90)Y had a strong linear correlation with the TD and NTLD of Rx(90)Y. CONCLUSIONS: Compared with MAA, scout(90)Y is a more accurate surrogate for Rx(90)Y biodistribution for nonsegmental therapies.

The EMPIRE-1 (Emory Molecular Prostate Imaging for Radiotherapy Enhancement-1) trial reported a survival advantage in recurrent prostate cancer salvage radiotherapy (SRT) guided by

Summary Background Molecular imaging is increasingly used to guide treatment decisions and planning in prostate cancer. We aimed to evaluate the role of 18F-fluciclovine-PET/CT in improving cancer control compared with conventional imaging (bone scan and either CT or MRI) alone for salvage postprostatectomy radiotherapy. Methods In EMPIRE-1, a single-centre, open-label, phase 2/3 randomised controlled trial, patients with prostate cancer with detectable PSA after prostatectomy and negative conventional imaging (no extrapelvic or bone findings) were randomly assigned in a 1:1 ratio to radiotherapy directed by conventional imaging alone or to conventional imaging plus 18F-fluciclovine-PET/CT. Computer-generated randomisation was stratified by PSA concentration, adverse pathology indicators, and androgen deprivation therapy intent. In the 18F-fluciclovine-PET/CT group, radiotherapy decisions were rigidly determined by PET findings, which were also used for target delineation. The primary endpoint was 3 year event-free survival, with events defined as biochemical or clinical recurrence or progression, or initiation of systemic therapy, using univariate and multivariable analyses in patients who received radiotherapy. This trial is registered with ClinicalTrials.gov , NCT01666808 and is closed to new participants. Findings From Sept 18, 2012, to March 4, 2019, 165 patients were randomly assigned, with median follow-up of 3·52 years (95% CI 2·98–3·95). PET findings resulted in four patients in the 18F-fluciclovine-PET/CT group having radiotherapy aborted; these patients were excluded from survival analyses. Median survival was not reached (95% CI 35·2–not reached; 33% of 81 patients had events) in the conventional imaging group compared with not reached (95% CI not reached–not reached; 20% of 76 patients) in the 18F-fluciclovine-PET/CT group, and 3 year event-free survival was 63·0% (95% CI 49·2–74·0) in the conventional imaging group versus 75·5% (95% CI 62·5–84·6) for 18F-fluciclovine-PET/CT (difference 12·5; 95% CI 4·3–20·8; p=0·0028). In adjusted analyses, study group (hazard ratio 2·04 [95% CI 1·06–3·93], p=0·0327) was significantly associated with event-free survival. Toxicity was similar in both study groups, with the most common adverse events being late urinary frequency or urgency (37 [46%] of 81 patients in the conventional imaging group and 31 [41%] of 76 in the PET group), and acute diarrhoea (11 [14%] in the conventional imaging group and 16 [21%] in the PET group). Interpretation Inclusion of 18F-fluciclovine-PET into postprostatectomy radiotherapy decision making and planning significantly improved survival free from biochemical recurrence or persistence. Integration of novel PET radiotracers into radiotherapy decisions and planning for prostate cancer patients warrants further study. Funding National Institutes of Health/National Cancer Institute, Blue Earth Diagnostics, and Winship Cancer Institute of Emory University.

Background A systematic literature review of the performance of 18Fluorine-fluciclovine PET/CT for imaging of men with recurrent prostate cancer was performed. Methods Scientific literature databases (MEDLINE, ScienceDirect and Cochrane Libraries) were searched systematically during Oct 2020 using PRISMA criteria. No limit was put on the date of publication. Prospective studies reporting a patient-level 18F-fluciclovine detection rate (DR) from ≥25 patients with recurrent prostate cancer were sought. Proceedings of relevant meetings held from 2018 through Oct 2020 were searched for abstracts meeting criteria. Results Searches identified 321 unique articles. In total, nine articles (six papers and three conference abstracts), comprising a total of 850 patients met inclusion criteria. Most studies (n = 6) relied on ASTRO-Phoenix Criteria, EAU-ESTRO-SIOG, and/or ASTRO-AUA guidelines to identify patients with biochemical recurrence. Patients’ PSA levels ranged from 0.02–301.7 ng/mL (median level per study, 0.34–4.10 ng/mL [n = 8]). Approximately 64% of patients had undergone prostatectomy, but three studies focused solely on post-prostatectomy patients. Adherence to imaging protocol guidelines was heterogeneous, with variance seen in administered activity, uptake and scan times. Overall patient-level DR varied between studies from 26% to 83%, with 78% of studies reporting a DR > 50%. DR was proportional to PSA, but even at PSA n = 7) ranged from 18% to 78% and extra-prostatic rates (n = 6) from 8% to 72%. Pelvic node and bone lesion DR ranged from 8% to 47% and 0% to 26%, respectively (n = 5). 18F-Fluciclovine PET/CT was shown to impact patient management and outcomes. Two studies reported 59–63% of patients to have a management change post-scan. A further study showed significant increase in failure-free survival following 18F-fluciclovine-guided compared with conventional imaging-guided radiotherapy planning. Conclusions 18F-Fluciclovine PET/CT shows good performance in patients with recurrent prostate cancer leading to measurable clinical benefits. Careful adherence to recommended imaging protocols may help optimize DR.

PURPOSE To quantify the relationship of the tumor-to-normal ratio (TNR) attained from the technetium-99m macroaggregated albumin (MAA) and posttreatment yttrium-90 bremsstrahlung (Y90-Brem) single-photon emission computerized tomography (SPECT)/computer tomography (CT) studies in patients with hepatocellular carcinoma (HCC) treated with glass microspheres. MATERIALS AND METHODS Retrospectively, a total of 190 consecutive patients with HCC who underwent 204 MAA and Y90-Brem SPECT/CT for glass microsphere Y90 radiation segmentectomy (Y90-RS) or lobar treatment (Y90-RLT) between 2013 and 2018 were included. Semi-automated regions-of-interests were drawn around the targeted tumor and nontumoral liver tissue on the SPECT/CT studies. TNR values from MAA and Y90-Brem SPECT/CT were compared using paired t-tests, Pearson correlation, and median with interquartile ranges (IQR). RESULTS The mean TNR for MAA and Y90-Brem SPECT/CT was 2.96 ± 1.86 (median, 2.64; IQR, 2.50) and 2.29 ± 1.10 (median, 2.06; IQR, 1.05), respectively (P < .0001). The mean Y90-RLT TNR was 2.88 ± 1.67 (median, 2.59; IQR, 0.83) and 2.17 ± 0.89 (median, 1.98; IQR, 0.81) for MAA and Y90-Brem SPECT/CT, respectively (P < .0001). The mean Y90-RS TNR was 3.02 ± 2.01 (median, 2.87; IQR, 3.01) and 2.39 ± 1.25 (median, 2.11; IQR, 1.28) for MAA and Y90-Brem SPECT/CT, respectively (P = .0003). TNR attained from MAA and Y90 SPECT/CT studies showed a moderate correlation in a positive linear fashion for the overall (r = 0.54; P < .001), Y90-RLT (r = 0.66, P < .001), and Y90-RS cohorts (r = 0.48, P < .001). CONCLUSIONS The TNR attained from Y90-Brem SPECT/CT is often underestimated, positively correlated, and less variable than that attained from MAA SPECT/CT.

PSMA is a transmembrane protein that is markedly overexpressed in prostate cancer, making it an excellent target for imaging and treating patients with prostate cancer. Several small molecule inhibitors and antibodies of PSMA have been radiolabeled for use as therapeutic agents and are currently under clinical investigation. PSMA-based radionuclide therapy is a promising therapeutic option for men with metastatic prostate cancer. The phase II TheraP study demonstrated superior efficacy, lower side effects, and improved patient-reported outcomes compared with cabazitaxel. The phase III VISION study demonstrated that radionuclide therapy with β-emitter 177Lu-PSMA-617 can prolong survival and improve quality of life when offered in addition to standard-of-care therapy in men with PSMA-positive metastatic castration-resistant prostate cancer whose disease had progressed with conventional treatments. Nevertheless, up to 30% of patients have inherent resistance to PSMA-based radionuclide therapy, and acquired resistance is inevitable. Hence, strategies to increase the efficacy of PSMA-based radionuclide therapy have been under clinical investigation. These include better patient selection; increased radiation damage delivery via dosimetry-based administered dose or use of α-emitters instead of β-emitters; or using combinatorial approaches to overcome radioresistance mechanisms (innate or acquired), such as with novel hormonal agents, PARP inhibitors, or immunotherapy.

Background: Prostate cancer (PCa) is a highly heterogeneous disease, and mortality is mainly due to metastases. However, the molecular underpinnings that lead to the initial steps of metastasis have not been well characterized. We have performed integrative whole exome sequencing and transcriptome analysis of primary prostate tumor foci and corresponding lymph node metastases (LNM). Design: Primary tumor foci (PTF) and LNM from 40 patients with high-risk PCa were analyzed by RNAseq. Two or more PTF and all available LNM greater than 0.4cm were subjected to sequencing. Of these 40 patients, 17 (42.5%) had LNM and 23 (57.5%) had benign LNs. A total of 155 tissue samples (97 PTF, 39 benign LNs, and 19 LNM) were sequenced and mapped to the human transcriptome with STAR mapper after QC trimming and removal of adapter sequences using TrimGalore. Differentially expressed genes between PTF, LNM, and benign LNs were identified using DESeq2, and gene set enrichment analysis was performed using WebGestalt. WES data was analyzed using GATK pipelines including Mutect2. Results: A median of 57 million paired-end reads were obtained per sample, with a median of 10 million total readcounts per sample across the transcriptome, and 39,021 transcripts were detected in at least 5% of samples. Comparing PTF to LNM, 6203 transcripts were differentially expressed (p-adj < 0.01). PTF were enriched relative to LNM in gene sets associated with Wnt signaling, hormone signaling, Hippo signaling, KRAS signaling, and the epithelial to mesenchymal transition. Comparing PTF from metastatic patients to non-metastatic patients, 1265 transcripts were differentially expressed (p-adj < 0.01). PTF from metastatic patients were enriched in gene sets associated with cell cycle progression, oxidative phosphorylation, ER stress, fatty acid metabolism, and DNA repair. LNM gene sets were enriched in endoplasmic reticulum (ER) stress and oxidative phosphorylation. The top 500 upregulated genes in malignant tissues were significantly enriched in genes related to androgen and estrogen signaling as expected. We also identified a set of 193 genes whose expression was significantly increased in primary tumor over benign LNs and in LNM over primary tumors. This gene set was significantly enriched in genes related to oxidative phosphorylation and included oncogenes such as PIK3CB, NCOA2, and SCHLAP1. Integrative RNAseq analyses with WES will be discussed. Conclusions: Signaling pathways associated with ER stress, oxidative phosphorylation, metabolism, and cell cycle progression are prominent in LNM of aggressive PCa. PIK3CB, NCOA2, and SCHLAP1 expression are significantly increased in LNM. Citation Format: Carlos S. Moreno, Cynthia L. Winham, Emma R. Klein, Yijian Huang, David M. Schuster, Martin G. Sanda, Adeboye O. Osunkoya. Integrative genomic analysis of primary prostate tumors and corresponding lymph node metastases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6081.

LBA602 Background: The increasing detection of renal masses presents a significant patient management challenge. Diagnostic options include cross-sectional imaging, which cannot reliably differentiate benign and malignant renal masses, and biopsy, which is invasive and subject to sampling errors. These limitations highlight the unmet need for accurate noninvasive techniques to guide patient management. Girentuximab is a monoclonal antibody that targets carbonic anhydrase IX (CAIX), an enzyme highly expressed in clear cell renal carcinoma (ccRCC). Radiolabeled 89Zr-DFO-girentuximab (TLX250-CDx) is highly specific for CAIX and can aid differentiation between ccRCCs and other renal lesions. The ZIRCON study evaluated the performance of TLX250-CDx PET/CT for detection of ccRCC in adult patients with indeterminate renal masses (IDRM). Methods: ZIRCON was an open-label, multicenter clinical trial. Patients with an IDRM (≤ 7 cm; tumor stage cT1) who were scheduled for partial nephrectomy within 90 days from planned TLX250-CDx administration were eligible. Enrolled patients received a single dose of TLX250-CDx IV (37 MBq ± 10%; 10 mg girentuximab) on Day 0 and underwent PET/CT imaging on Day 5 (± 2 days) prior to surgery. Blinded central histology review determined ccRCC status. The coprimary objectives were to evaluate both the sensitivity and specificity of TLX250-CDx PET/CT imaging in detecting ccRCC in patients with IDRM, using histology as the standard of truth. Key secondary objectives included sensitivity and specificity of TLX250-CDx PET/CT imaging in the subgroup of patients with IDRM ≤ 4 cm (cT1a). Other secondary objectives included positive and negative predictive values, safety, and tolerability. The Wilson 95% confidence intervals (CI) lower bound for sensitivity and specificity had to be > 70% and 68% respectively for ≥ 2 independent readers to declare the study successful. Results: 300 patients received TLX250-CDx; mean age was 62 ± 12 y; 71% were males. Of 288 patients with central histopathology of surgical samples, 193 (67%) had ccRCC, and 179 (62%) had CT1a; Of 284 evaluable patients included in primary analysis, the average across all 3 readers for sensitivity and specificity was 86% [80%, 90%] and 87% [79%, 92%] respectively for coprimary endpoints; and 85% [77%, 91%] and 90% [79%, 95%] respectively for key secondary endpoints. For all readers, the lower boundaries of 95% CI for coprimary and key secondary endpoints were > 75%. For all evaluable patients, positive and negative predictive values were ≥ 91.7% and ≥ 73.7%, respectively. Of 263 treatment-emergent adverse events (TEAEs), 2 TEAEs were treatment related. Conclusions: This study confirms that TLX250-CDx PET/CT is well tolerated and can accurately and noninvasively identify ccRCC, with promising utility for designing best management approaches for patients with IDRM. Clinical trial information: NCT03849118 .

This study evaluated the impact of 18F-fluciclovine positron emission tomography/computed tomography (PET/CT) on salvage radiotherapy management decisions in patients with recurrent prostate cancer (PCa) post-prostatectomy. Methods: Patients with detectable prostate-specific antigen (PSA) post-prostatectomy were randomized to undergo either conventional imaging (CI) only (Arm A) or CI plus 18F-fluciclovine PET/CT (Arm B) prior to radiotherapy. In Arm B, positivity rates on CI and 18F-fluciclovine PET/CT for detection of recurrent PCa were determined. Final radiotherapy decisions, a) to offer radiotherapy or not and b) extent of radiotherapy field - prostate bed only or to include pelvis, were based on 18F-fluciclovine PET/CT findings. Radiotherapy decisions before and after 18F-fluciclovine PET/CT were compared. Statistical significance of decision changes was determined using Clopper-Pearson (exact) binomial method. Prognostic factors were compared between patients with and without decision changes. Results: All 165 patients enrolled in the study had standard-of-care CI and were initially planned for radiotherapy. Sixty-three of 79 (79.7%) patients (median PSA 0.33 ng/mL) who underwent 18F-fluciclovine PET/CT (Arm B) had positive findings. 18F-Fluciclovine PET/CT had significantly higher positivity rate than CI for whole body (79.7% vs 13.9%; P

Purpose The aim of the study was to evaluate the effects of tumour dose on tumour response and overall survival (OS) in patients with chemo-refractory metastatic breast cancer (MBC) to the liver undergoing yttrium-90 radioembolisation (Y90 RE). Materials and methods In 20 consecutive patients with chemo-refractory MBC to the liver undergoing 33 total Y90 RE resin treatments, volumes of interest were drawn around the five largest tumours of the targeted liver lobe on post-Y90 RE Bremsstrahlung single-photon emission computed tomography/computed tomography using MIM software v.6.9 (MIM Software, Cleveland, Ohio, USA) and dose-volume histograms were calculated. Response Evaluation Criteria in Solid Tumours (RECIST) was used to determine tumour response at 3 months. Receiver operating characteristics (ROC) curves were used to determine thresholds for various dosimetry parameters. Kaplan-Meier estimation was used to determine OS. Results Overall, 11 of 33 (33%) Y90 RE treatments resulted in complete or partial response according to RECIST criteria with a median OS of 20.97 months compared to 11.73 months for nonresponders (P = 0.003). Mean tumour dose, defined as the aggregate tumour dose of up to the five largest tumours in the targeted lobe, was the most predictive of tumour response with the highest area under the ROC curve of 0.967. Mean tumour dose >70 Gy had 91% sensitivity and 100% specificity for predicting tumour response. Patients with mean tumour dose >70 Gy experienced a median OS of 16.1 months vs. 12.8 months for those who did not (P = 0.008). Conclusion For patients with chemo-refractory breast cancer with liver metastases, achieving a mean tumour dose >70 Gy is a significant predictor of tumour response and prolonged OS.

BACKGROUND: Accurate identification and discrimination of post treatment changes from recurrent disease remains a challenge for patients with intracranial malignancies despite advances in molecular and magnetic resonance imaging. We have explored the ability of readily available Rubidium-82 chloride ((82)RbCl) positron emission tomography (PET) to identify and distinguish progressive intracranial disease from radiation necrosis in patients previously treated with radiation therapy. METHODS: Six patients with a total of 9 lesions of either primary (N.=3) or metastatic (N.=6) intracranial malignancies previously treated with stereotactic radiation surgery (SRS) and persistent contrast enhancement on MRI underwent brain (82)RbCl PET imaging. Two patients with arteriovenous malformations previously treated with SRS, also had brain (82)RbCl PET imaging for a total of 11 lesions studied. Histological confirmation via stereotactic biopsy/excisional resection was obtained for 9 lesions with the remaining 2 classified as either recurrent tumor or radiation necrosis based on subsequent MRI examinations. (82)RbCl PET time activity curve analysis was performed which comprised lesion SUV(max), contralateral normal brain SUV(max), and tumor to background ratios (TB(max)). RESULTS: (82)RbCl demonstrates uptake greater than normal brain parenchyma in all lesions studied. Time activity curves demonstrated progressive uptake of (82)RbCl in all lesions without evidence of washout. While recurrent disease demonstrated a greater mean SUV(max) compared to radiation necrosis, no statistically significant difference between lesion SUV(max) nor TB(max) was found (P>0.05). CONCLUSIONS: (82)RbCl PET produces high-contrast uptake of both recurrent disease and radiation necrosis compared to normal brain. However, no statistically significant difference was found between recurrent tumor and radiation necrosis.

Dose escalation to dominant intraprostatic lesions (DILs) is a novel treatment strategy to improve the treatment outcome of prostate radiation therapy. Treatment planning requires accurate and fast delineation of the prostate and DILs. In this study, a 3D cascaded scoring convolutional neural network is proposed to automatically segment the prostate and DILs from MRI.The proposed cascaded scoring convolutional neural network performs end-to-end segmentation by locating a region-of-interest (ROI), identifying the object within the ROI, and defining the target. A scoring strategy, which is learned to judge the segmentation quality of DIL, is integrated into cascaded convolutional neural network to solve the challenge of segmenting the irregular shapes of the DIL. To evaluate the proposed method, 77 patients who underwent MRI and PET/CT were retrospectively investigated. The prostate and DIL ground truth contours were delineated by experienced radiologists. The proposed method was evaluated with fivefold cross-validation and holdout testing.The average centroid distance, volume difference, and Dice similarity coefficient (DSC) value for prostate/DIL are 4.3 ± 7.5/3.73 ± 3.78 mm, 4.5 ± 7.9/0.41 ± 0.59 cc, and 89.6 ± 8.9/84.3 ± 11.9%, respectively. Comparable results were obtained in the holdout test. Similar or superior segmentation outcomes were seen when compared the results of the proposed method to those of competing segmentation approaches.The proposed automatic segmentation method can accurately and simultaneously segment both the prostate and DILs. The intended future use for this algorithm is focal boost prostate radiation therapy.

Purpose:Accurate preoperative staging of prostate cancer is essential for treatment planning. Conventional imaging is limited in detection of metastases. Our primary aim was to determine if [18F]fl...

Purpose Conventional imaging rarely localizes the site(s) of prostate cancer recurrence in patients undergoing evaluation for salvage radiation therapy (sRT) after radical prostatectomy (RP). LOCATE (NCT02680041) was a prospective, multicenter study investigating the impact of 18F-fluciclovine positron emission tomography and computed tomography (PET/CT) on the management of patients with biochemical recurrence of prostate cancer after curative-intent radiation or RP and negative or equivocal conventional imaging. Our objective was to determine the impact of 18F-fluciclovine PET/CT on treatment decisions for men planning to undergo sRT for biochemical recurrence post-RP. Methods and Materials We conducted a subgroup analysis of post-RP patients enrolled in LOCATE who were planning to undergo sRT with or without hormonal therapy based on prescan documentation. 18F-Fluciclovine PET/CT was performed according to standardized procedures. The treatment plan postscan was compared with the prescan plan, and Fisher exact test was used to determine the impact of prescan prostate-specific antigen (PSA) and Gleason sum (GS) on positivity and anatomic patterns of uptake. Results A total of 114 patients (median prescan PSA 0.42 [interquartile range, 0.3-1.1] ng/mL) met selection criteria (54% of patients in LOCATE). Forty-eight (42%) had 18F-fluciclovine-avid lesions. Twelve patients (11%) had positive findings only in the prostate bed, 24 (21%) had positivity only in the pelvis (prostate bed or pelvic nodes), and 24 (21%) had extrapelvic findings. PSA >0.5 ng/mL and GS ≥8 were associated with a higher risk of extrapelvic positivity (P Postscan, 55 (48%) patients had a management change; 37 (32%) had a change in overall treatment approach (ie, omission of sRT); and 18 (16%) had sRT target modification. Conclusions 18F-Fluciclovine PET/CT is positive in nearly half of patients planning to undergo post-RP sRT with negative/equivocal conventional imaging, with findings frequently leading to changes in management. PSA >0.5 ng/mL and GS ≥8 are associated with a higher risk of extrapelvic positive findings.

Incidental PET radiotracer uptake is not infrequently encountered in PET/CT imaging. We present the 18F-fluciclovine PET/CT of a 60-year-old man undergoing evaluation of biochemically recurrent prostate cancer with incidental radiotracer uptake in the thoracic spinal canal, which was proven to be a World Health Organization grade I spinal meningioma on surgical pathology. 18F-fluciclovine and 18F-FDG PET/CT images of a 60-year-old man with biochemically recurrent prostate cancer prostate cancer with a prostate-specific antigen of 14.4 ng/mL, 7 years after primary external beam radiation followed by a prostate-specific antigen nadir of 1.6 ng/mL, are presented.

The aim of this guideline is to provide standards for the recommendation, performance, interpretation, and reporting of [18F]Fluciclovine PET/CT for prostate cancer imaging. These recommendations will help to improve accuracy, precision, and repeatability of [18F]Fluciclovine PET/CT for prostate cancer essentially needed for implementation of this modality in science and routine clinical practice.

Lower urinary tract symptoms due to benign prostatic enlargement have a high prevalence in men over 50 years of age. Diagnosis is made with a combination of focused history and physician examination and validated symptom questionnaires. Urodynamic studies can help to differentiate storage from voiding abnormalities. Pelvic ultrasound may be indicated to assess bladder volume and wall thickness. Other imaging modalities, including prostate MRI, are usually not indicated in the initial workup and evaluation of uncomplicated lower urinary tract symptoms from an enlarged prostate. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

The role of PET imaging with 11C-choline and 18F-fluciclovine in evaluating patients with prostate cancer (PCa) has become more important over the years and has been incorporated into the NCCN guidelines. A new generation of PET radiotracers targeting the prostate-specific membrane antigen (PSMA) is widely used outside the United States to evaluate patients with primary PCa and PCa recurrence. PET imaging influences treatment planning and demonstrates a significantly higher disease detection rate than conventional imaging such as computed tomography and MR imaging. Early data indicate that using PET radiotracers such as 18F-fluciclovine and PSMA improves patient outcomes. 68-Ga-PSMA-11 and 18F-DCFPyL-PET/CT were recently approved by the US Food & Drug Administration (FDA) for clinical use. Other PSMA radiotracers, including fluorinated variants, will likely gain FDA approval in the not-too-distant future.

The purpose of this study was to evaluate (18)F-fluciclovine PET/CT detection rates in the evaluation of biochemical recurrence in prostate cancer patients with very low (≤0.3 ng/mL) serum prostate-specific antigen (PSA) levels following definitive treatment. Prostate cancer patients with biochemical recurrence and very low serum PSA (≤0.3 ng/mL) who underwent clinical (18)F-fluciclovine PET/CT were included in this single-institution retrospective study. PET/CT clinical reports at the time of interpretation were reviewed and categorized as positive or negative. In patients who had further evaluation with imaging and/or biopsy, the results were recorded to determine the true detection rate. Of the 64 eligible patients with very low serum PSA (median serum PSA of 0.17 ng/mL), 57.8% (37/64) scans were categorized as positive. Stratified by PSA levels, positivity rates were 43.8% (7/16), 60.0% (15/25) and 65.2% (15/23) for PSA

Purpose: F-18-fluciclovine PET is approved for prostate cancer recurrence imaging. According to the radiopharmaceutical package insert only 3% of the tracer is expected to be excreted in the urine over the first four hours. Yet, in clinical practice we noticed a higher percentage of bladder excretion. We sought to evaluate and quantify early fluciclovine bladder radioactivity and determine if refraining from voiding before fluciclovine injection would mitigate it. Materials and Methods: 159 patients underwent fluciclovine PET/CT imaging as part of their clinical workup. The first 36 patients were instructed to void just before fluciclovine injection, the subsequent 123 patients were not requested to void. The SUVmax and SUVmean of the bladder, aorta, marrow, liver, and bladder volumes were collected. Comparing SUVmean of bladder to background, we characterized bladder radioactivity as: "Insignificant" (bladder aorta, marrow, liver). Differences between the protocols were investigated. Results: Overall, 22% (35/159) of patients had moderate, and 8.8% (14/159) had intense bladder activity. A negative association was found between bladder volumes and SUVmean. A significant difference was found between voiding and non-voiding protocol groups, with 38.9% (14/36) vs. 17.1% (21/123) of patients having moderate, and 22.2% (8/36) vs. 4.9% (6/123) of patients having intense bladder activity, respectively. Conclusion: Refraining from voiding prior to F-18-fluciclovine injection results in significantly lower urinary bladder radioactivity compared to purposeful voiding pre-injection. We have modified our practice accordingly, particularly as moderate and intense bladder activity may mask/mimic local prostate cancer recurrence. Mechanisms underlying this phenomenon should be further investigated.