Salivary toxicity from PSMA-targeted radiopharmaceuticals: What we have learned and where we are going.

Clinical trials of prostate-specific membrane antigen (PSMA) targeted radiopharmaceuticals have shown encouraging results. Some agents, like lutetium-177 [177Lu]Lu-PSMA-617 ([177Lu]Lu-PSMA-617), are already approved for late line treatment of metastatic castration-resistant prostate cancer (mCRPC). Projections are for continued growth of this treatment modality; [177Lu]Lu-PSMA-617 is being studied both in earlier stages of disease and in combination with other anti-cancer therapies. Further, the drug development pipeline is deep with variations of PSMA-targeting radionuclides, including higher energy alpha particles conjugated to PSMA-honing vectors. It is safe to assume that an increasing number of patients will be exposed to PSMA-targeted radiopharmaceuticals during the course of their cancer treatment. In this setting, it is important to better understand and mitigate the most commonly encountered toxicities. One particularly vexing side effect is xerostomia. In this review, we discuss the scope of the problem, inventories to better characterize and monitor this troublesome side effect, and approaches to preserve salivary function and effectively palliate symptoms. This article aims to serve as a useful reference for prescribers of PSMA-targeted radiopharmaceuticals, while also commenting on areas of missing data and opportunities for future research.

Critical updates in neuroendocrine tumors: Version 9 American Joint Committee on Cancer staging system for gastroenteropancreatic neuroendocrine tumors.

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.

Targeted Alpha-Particle Therapy: A Review of Current Trials.

Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as catalysts. Targeted alpha emitters are in current development for several potential oncologic indications. Herein, we review the three most prevalently studied conjugated/chelated alpha emitters (225actinium, 212lead, and 211astatine) and focus on contemporary clinical trials in an effort to more fully appreciate the breadth of the current evaluation. Phase I trials targeting multiple diseases are now underway, and at least one phase III trial (in selected neuroendocrine cancers) is currently in the initial stages of recruitment. Combination trials are now also emerging as alpha emitters are integrated with other therapies in an effort to create solutions for those with advanced cancers. Despite the promise of targeted alpha therapies, many challenges remain. These challenges include the development of reliable supply chains, the need for a better understanding of the relationships between administered dose and absorbed dose in both tissue and tumor and how that predicts outcomes, and the incomplete understanding of potential long-term deleterious effects of the alpha emitters. Progress on multiple fronts is necessary to bring the potential of targeted alpha therapies into the clinic.

Health-related quality of life and pain outcomes with [177Lu]Lu-PSMA-617 plus standard of care versus standard of care in patients with metastatic castration-resistant prostate cancer (VISION): a multicentre, open-label, randomised, phase 3 trial.

BACKGROUND: In VISION, the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy lutetium-177 [177Lu]Lu-PSMA-617 (vipivotide tetraxetan) improved radiographic progression-free survival and overall survival when added to protocol-permitted standard of care in patients with metastatic castration-resistant prostate cancer. Here, we report additional health-related quality of life (HRQOL), pain, and symptomatic skeletal event results. METHODS: This multicentre, open-label, randomised, phase 3 trial was conducted at 84 cancer centres in nine countries in North America and Europe. Eligible patients were aged 18 years or older; had progressive PSMA-positive metastatic castration-resistant prostate cancer; an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; and had previously received of at least one androgen receptor pathway inhibitor and one or two taxane-containing regimens. Patients were randomly assigned (2:1) to receive either [177Lu]Lu-PSMA-617 plus protocol-permitted standard of care ([177Lu]Lu-PSMA-617 group) or standard of care alone (control group) using permuted blocks. Randomisation was stratified by baseline lactate dehydrogenase concentration, liver metastases, ECOG performance status, and androgen receptor pathway inhibitor inclusion in standard of care. Patients in the [177Lu]Lu-PSMA-617 group received intravenous infusions of 7·4 gigabecquerel (GBq; 200 millicurie [mCi]) [177Lu]Lu-PSMA-617 every 6 weeks for four cycles plus two optional additional cycles. Standard of care included approved hormonal treatments, bisphosphonates, and radiotherapy. The alternate primary endpoints were radiographic progression-free survival and overall survival, which have been reported. Here we report the key secondary endpoint of time to first symptomatic skeletal event, and other secondary endpoints of HRQOL assessed with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-5L, and pain assessed with the Brief Pain Inventory-Short Form (BPI-SF). Patient-reported outcomes and symptomatic skeletal events were analysed in all patients who were randomly assigned after implementation of measures designed to reduce the dropout rate in the control group (on or after March 5, 2019), and safety was analysed according to treatment received in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, NCT03511664, and is active but not recruiting. FINDINGS: Between June 4, 2018, and Oct 23, 2019, 831 patients were enrolled, of whom 581 were randomly assigned to the [177Lu]Lu-PSMA-617 group (n=385) or control group (n=196) on or after March 5, 2019, and were included in analyses of HRQOL, pain, and time to first symptomatic skeletal event. The median age of patients was 71 years (IQR 65-75) in the [177Lu]Lu-PSMA-617 group and 72·0 years (66-76) in the control group. Median time to first symptomatic skeletal event or death was 11·5 months (95% CI 10·3-13·2) in the [177Lu]Lu-PSMA-617 group and 6·8 months (5·2-8·5) in the control group (hazard ratio [HR] 0·50, 95% CI 0·40-0·62). Time to worsening was delayed in the [177Lu]Lu-PSMA-617 group versus the control group for FACT-P score (HR 0·54, 0·45-0·66) and subdomains, BPI-SF pain intensity score (0·52, 0·42-0·63), and EQ-5D-5L utility score (0·65, 0·54-0·78). Grade 3 or 4 haematological adverse events included decreased haemoglobin (80 [15%] of 529 assessable patients who received [177Lu]Lu-PSMA-617 plus standard of care vs 13 [6%] of 205 who received standard of care only), lymphocyte concentrations (269 [51%] vs 39 [19%]), and platelet counts (49 [9%] vs five [2%]). Treatment-related adverse events leading to death occurred in five (1%) patients who received [177Lu]Lu-PSMA-617 plus standard of care (pancytopenia [n=2], bone marrow failure [n=1], subdural haematoma [n=1], and intracranial haemorrhage [n=1]) and no patients who received standard of care only. INTERPRETATION: [177Lu]Lu-PSMA-617 plus standard of care delayed time to worsening in HRQOL and time to skeletal events compared with standard of care alone. These findings support the use of [177Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer who received previous androgen receptor pathway inhibitor and taxane treatment. FUNDING: Advanced Accelerator Applications (Novartis).

A VISION Substudy of Reader Agreement on 68Ga-PSMA-11 PET/CT Scan Interpretation to Determine Patient Eligibility for 177Lu-PSMA-617 Radioligand Therapy.

[ 68Ga]Ga-PSMA-11 ( 68Ga-PSMA-11) is used to identify prostate-specific membrane antigen (PSMA)-positive tumors on PET scans. In the VISION study, 68Ga-PSMA-11 was used to determine the eligibility of patients with metastatic castration-resistant prostate cancer for treatment with [177Lu]Lu-PSMA-617 (177Lu-PSMA-617), based on predefined read criteria. This substudy aimed to investigate the interreader variability and intrareader reproducibility of visual assessments of 68Ga-PSMA-11 PET/CT scans using the VISION read criteria and evaluate the agreement between read results for this and the VISION study. Methods: In VISION, 68Ga-PSMA-11 PET/CT scans were centrally read as inclusion cases if they had at least 1 PSMA-positive lesion and no PSMA-negative lesions that fulfilled the exclusion criteria. In this substudy, 125 PET/CT scans (75 inclusion and 50 exclusion cases) were randomly selected from VISION and retrospectively assessed by 3 independent central readers. A random subset of 20 cases (12 inclusion and 8 exclusion cases) was recoded for assessment of intrareader reproducibility. Classification of cases as inclusion or exclusion cases was based on the VISION read criteria. Overall interreader variability was assessed by Fleiss κ-statistics, and pairwise variability and intrareader reproducibility were assessed by Cohen κ-statistics. Results: For interreader variability, the readers agreed on 77% of cases (overall average agreement rate, 0.85; Fleiss κ, 0.60 [95% CI, 0.50-0.70]). The pairwise agreement rate was 0.82, 0.88, and 0.84, and the corresponding Cohen κ was 0.54 (95% CI, 0.38-0.71), 0.67 (95% CI, 0.52-0.83), and 0.59 (95% CI, 0.43-0.75), respectively. For intrareader reproducibility, the agreement rate was 0.90, 0.90, and 0.95, and the corresponding Cohen κ was 0.78 (95% CI, 0.49-0.99), 0.76 (95% CI, 0.46-0.99), and 0.89 (95% CI, 0.67-0.99), respectively. The number of actual VISION inclusion cases out of the total number of cases scored as inclusion in this substudy was 71 of 93 (agreement rate, 0.76; 95% CI, 0.66-0.85) for reader 1, 70 of 88 (0.80; 0.70-0.87) for reader 2, and 73 of 96 (0.76; 0.66-0.84) for reader 3. All readers agreed on 66 of 75 VISION inclusion cases. Conclusion: Moderate-to-substantial interreader agreement and substantial-to-almost perfect intrareader reproducibility for 68Ga-PSMA-11 PET/CT scan assessment using the VISION read criteria were observed. The read rules applied in VISION can be readily learned and demonstrate good reproducibility.

Clinical utility of somatostatin receptor positron emission tomography imaging biomarkers for characterization of meningioma among incidental central nervous system lesions.

OBJECTIVES: Somatostatin receptor (SSTR) PET imaging is utilized with increasing frequency in the clinical management of neuroendocrine tumors. Incidental PET-avid CNS lesions are commonly noted and presumed to be meningiomas. However, SSTR PET lacks specificity for meningioma identification. This study aimed to clarify the role of SSTR-based imaging in the classification of incidental CNS lesions based on current clinical practice. METHODS: Patients who underwent both Ga-68-DOTATATE PET and brain MRI and had an incidental CNS lesion identified with a radiographic prediction of meningioma via one (discordant prediction) or both (concordant prediction) imaging modalities were retrospectively analyzed. Imaging indication, semiquantitative measures, and clinical history were recorded. RESULTS: Among 48 patients with a CNS lesion identified on both imaging modalities, most scans were performed for a history of neuroendocrine tumor (64.6%). Cases with concordant lesion-type prediction of meningioma between imaging modalities ( N = 24) displayed a significantly higher SUV max (median 7.9 vs. 4.0; P = 0.008) and Krenning score (median 3.0 vs. 2.0; P = 0.005) on Ga-68-DOTATATE PET compared with cases with a discordant prediction of meningioma ( N = 24). In cases with lower SUV max values, Ga-68-DOTATATE was more likely to discordantly predict meningioma without agreement by the corresponding MRI. Prior cranial radiation or use of somatostatin mimetics did not affect quantitative radiographic measures, and MRI-based tumor size was similar across groups. CONCLUSION: Lesions with increased avidity may be more confidently predicted as meningioma in Ga-68-DOTATATE PET scans, whereas there is more discrepancy in prediction among low SUV cases.

Status of PSMA-targeted radioligand therapy in prostate cancer: current data and future trials.

Metastatic prostate cancer continues to be an incurable disease. Despite all the novel therapies approved in the past two decades, overall patient outcomes remain relatively poor, and these patients die on a regular basis. Clearly, improvements in current therapies are needed. Prostate-specific membrane antigen (PSMA) is a target for prostate cancer given its increased expression on the surface of the prostate cancer cells. PSMA small molecule binders include PSMA-617 and PSMA-I&T and monoclonal antibodies such as J591. These agents have been linked to different radionuclides including beta-emitters such as lutetium-177 and alpha-emitters such as actinium-225. The only regulatory-approved PSMA-targeted radioligand therapy (PSMA-RLT) to date is lutetium-177-PSMA-617 in the setting of PSMA-positive metastatic castration-resistant prostate cancer that has failed androgen receptor pathway inhibitors and taxane chemotherapy. This approval was based on the phase III VISION trial. Many other clinical trials are evaluating PSMA-RLT in various settings. Both monotherapy and combination studies are underway. This article summarizes pertinent data from recent studies and provides an overview of human clinical trials in progress. The field of PSMA-RLT is rapidly evolving, and this therapeutic approach will likely play an increasingly important role in the years to come.

Incorporating radioligand therapy in clinical practice in the United States for patients with prostate cancer.

Prostate cancer (PC) is the second most commonly diagnosed cancer in the United States. Advanced PC evolves to metastatic castration-resistant PC (mCRPC). Theranostics combining prostate-specific membrane antigen-targeted positron emission tomography imaging and radioligand therapy (RLT) represents a precision medicine approach to PC treatment. With the recent approval of lutetium Lu 177 (177Lu) vipivotide tetraxetan for men with mCRPC, the utilization of RLT will increase. In this review, we suggest a framework for incorporating RLT for PC into clinical practice. A search of PubMed and Google Scholar was performed using keywords related to PC, RLT, prostate-specific membrane antigen, and novel RLT centers. The authors also provided opinions based on their clinical experience. The setup and operation of an RLT center requires the diligence and cooperation of a well-trained multidisciplinary team committed to patient safety and clinical efficacy. Administrative systems should ensure that treatment scheduling, reimbursement, and patient monitoring are efficient. For optimal outcomes, the clinical care team must have an organizational plan that delineates the full range of required tasks. Establishing new RLT centers for treatment of PC is possible with appropriate multidisciplinary planning. We provide an overview of the key elements to consider when establishing a safe, efficient, and high-quality RLT center.

Radiographic paradoxical response in metastatic castrate-resistant prostate cancer (mCRPC) managed with new generation anti-androgens: a retrospective analysis.

BACKGROUND: Prostatic specific antigen (PSA) has well-recognized limitations as a marker for treatment response and disease progression. Post hoc analysis of the PREVAIL trial reported 24.5% of chemotherapy naïve metastatic castration-resistant prostate cancer (mCRPC) patients on enzalutamide had radiographic progression on conventional imaging with nonrising PSA. In this study, we sought to study the discordance of imaging with PSA kinetics in mCRPC patients on second generation anti-androgens (SGA) post-chemotherapy using combined conventional imaging, and new generation imaging in the form of C-11 choline positron emission tomography/computed tomography (C[11] choline PET/CT) scan. METHODS: We retrospectively reviewed the medical records of 123 patients with mCRPC treated with SGA (Abiraterone or Enzalutamide) after docetaxel between 2016 and 2019. Patients underwent PSA testing, and C[11] choline PET/CT scan at baseline level before starting treatment with SGA, then every 3-6 months as part of their follow up evaluation. Loss of response to SGA was defined by increase in corrected maximum standardized uptake value (SUVmax) of pretreatment lesions on C-11 Choline PET/CT, and/or development of new lesions. Suspicious new lesions were confirmed by biopsy and/or conventional imaging. RESULTS: We identified 123 mCRPC patients who received SGA (Abiraterone, n = 106; Enzalutamide, n = 17) after docetaxel. Median duration of therapy was 13.9 months (interquartile range: 8.75-21.14). Approximately 43% (n = 53) of subjects in this study exhibited an increase in choline avidity while on SGA. Of this group, 60.4% of patients experienced a parallel rise in PSA (Group-A), whereas 39.6% displayed a paradoxical response (PR) (Group-B), defined as increased choline avidity combined with stable or down-trending PSA. Median PSA at time of increase in choline avidity was 3.1 ng/ml for Group-A, and 1.3 ng/ml for Group-B (p = 0.0176). Median SUVmax was similar in both groups (4.9 for Group-A, 4.6 for Group-B; p = 0.6072). The median time for increase in choline avidity was 9.5 versus 3.9 months for Group-A versus Group-B, respectively (Log-Rank = 0.0063). CONCLUSION: Nearly 40% of mCRPC patients placed on SGA post docetaxel chemotherapy will exhibit paradoxical responses to therapy, therefore, warranting close follow up with imaging. C-11 choline PET/CT imaging is a useful tool that can help in early predication of disease progression or treatment failure.

The impact of genetic aberrations on response to radium-223 treatment for castration-resistant prostate cancer with bone metastases.

BACKGROUND: Radium (Ra)-223 is an established treatment option for patients with metastatic castrate-resistant prostate cancer (mCRPC) who have symptomatic bone metastases without soft tissue disease. Studies have indicated genetic aberrations that regulate DNA damage response (DDR) in prostate cancer can increase susceptibility to treatments such as poly ADP-ribose polymerase inhibitors and platinum-based therapies. This study aims to evaluate mCRPC response to Ra-223 stratified by tumor genomics. METHODS: This is a retrospective study of mCRPC patients who received Ra-223 and genetic testing within the Mayo Clinic database (Arizona, Florida, and Minnesota) and Tulane Cancer Center. Patient demographics, genetic aberrations, treatment responses in terms of alkaline phosphatase (ALP) and prostate-specific antigen (PSA), and survival were assessed. Primary end points were ALP and PSA response. Secondary end points were progression-free survival (PFS) and overall survival (OS) from time of first radium treatment. RESULTS: One hundred and twenty-seven mCRPC patients treated with Ra-223 had germline and/or somatic genetic sequencing. The median age at time of diagnosis and Ra-223 treatment was 61.0 and 68.6 years, respectively. Seventy-nine (62.2%) had Gleason score ≥ 8 at time of diagnosis. 50.4% received prior docetaxel, and 12.6% received prior cabazitaxel. Notable alterations include TP53 (51.7%), BRCA 1/2 (15.0%), PTEN (13.4%), ATM (11.7%), TMPRSS2-ERG (8.2%), RB deletion (3.4%), and CDK12 (1.9%). There was no significant difference in ALP or PSA response among the different genetic aberrations. Patients with a TMPRSS2-ERG mutation exhibited a trend toward lower OS 15.4 months (95% confidence interval [CI] 10.0-NR) versus 26.8 months (95% CI 20.9-35.1). Patients with an RB deletion had a lower PFS 6.0 months (95% CI 1.28-NR) versus 9.0 months (95% CI 7.3-11.1) and a lower OS 13.9 months (95% CI 5.2-NR) versus 26.5 months (95% CI 19.8-33.8). CONCLUSIONS: Among mCRPC patients treated with Ra-223 at Mayo Clinic and Tulane Cancer Center, we did not find any clear negative predictors of biochemical response or survival to treatment. TMPRSS2-ERG and RB mutations were associated with a worse OS. Prospective studies and larger sample sizes are needed to determine the impact of genetic aberrations in response to Ra-223.

Rituximab for the Treatment of Refractory Cardiac Sarcoidosis: A Single-Center Experience.

BACKGROUND: We sought to examine the effect of anti-B-cell therapy (rituximab) on cardiac inflammation and function in corticosteroid-refractory cardiac sarcoidosis. Cardiac sarcoidosis (CS) is a rare cause of cardiomyopathy characterized by granulomatous inflammation involving the myocardium. Although typically responsive to corticosteroid treatment, there is a critical need for identifying effective steroid-sparing agents for disease control. Despite increasing evidence on the role of B cells in the pathogenesis of sarcoidosis, there is limited data on the efficacy of anti-B-cell therapy, specifically rituximab, for controlling CS. METHODS AND RESULTS: We reviewed the clinical experience at a tertiary care referral center of all patients with CS who received rituximab after failing to improve with initial immunosuppression therapy, which included corticosteroids. Fluorodeoxyglucose positron emission tomography (FDG PET/CT) images before and after rituximab treatment were evaluated. All images were interpreted by 2 experienced nuclear medicine trained physicians. We identified 7 patients (5 men, 2 women; mean age at diagnosis, 49.0 ± 7.9 years) with active CS who were treated with rituximab. The median length of follow-up was 5.1 years. All individuals, but 1, had received prior steroid-sparing agents in addition to corticosteroids. Rituximab was administered either as 1000 mg intravenously ×1 or ×2 doses, separated by 2 weeks. Repeat dosing, if appropriate, was considered after 6 months. All tolerated the infusions well. Inflammation as assessed by maximum standardized uptake value on cardiac FDG PET/CT uptake significantly decreased in 6 of 7 patients (median 6.0-4.5, Wilcoxon signed rank z -1.8593, W 3), whereas the left ventricular ejection fraction improved or stabilized in 4 patients but decreased in 3. The mean left ventricular ejection fraction was 40.1% and 43.3% before and after treatment, respectively (P = .28). Three patients reported improved physical capacity, and 5 patients showed improved arrhythmic burden on Holter monitoring or implantable cardioverter-defibrillator interrogation. One patient subsequently developed a fungal catheter-associated infection and sepsis requiring discontinuation. CONCLUSIONS: Rituximab was well-tolerated and seemed to decrease inflammation, as assessed by cardiac FDG PET/CT in all but 1 patient with active CS. These data suggest that rituximab may be a promising therapeutic option for CS, which deserves merits further study.

Prognostic role of 11C-choline PET/CT scan in patients with metastatic castrate resistant prostate cancer undergoing primary docetaxel chemotherapy.

BACKGROUND: We sought to assess the prognostic utility of 11C-choline positron emission tomography/computed tomography (PET/CT) in patients with metastatic castrate resistant prostate cancer (mCRPC) undergoing primary docetaxel chemotherapy. METHODS: We performed a single institution retrospective analysis of 77 mCRPC patients who were treated with 6 cycles of docetaxel chemotherapy, and who also underwent 11C-choline PET/CT scans at baseline (before chemotherapy), mid-course (after 3 cycles), and posttherapy (after 6 cycles). We evaluated treatment response based on percent change in blood pool-corrected maximum standardized uptake value (SUVmax) of the target lesion on PET/CT, as well as percent change in serum prostate specific antigen (PSA). Logistic regression analysis was used to identify factors associated with complete treatment response. Progression free survival (PFS) analysis was performed using log-rank test and shown on Kaplan-Meier plot. RESULTS: Percent change in blood pool-corrected SUVmax on mid-course scan was a significant predictor of complete response (odds ratio [OR]: 0.98, 95% confidence interval [CI]: 0.96-0.99, p = .0003), whereas percent change in PSA was not (OR: 0.99, 95% CI: 0.99-1.01, p = .6025). 57 of 77 patients (74%) achieved ≥20% reduction in blood pool-corrected SUVmax on mid-course; these patients were 3.6 times more likely to achieve complete response after full 6 cycles of docetaxel chemotherapy, compared to patients with <20% reduction in blood pool-corrected SUVmax (OR: 3.56, 95% CI: 1.04-16.52, p = .0420). Median PFS in the complete response group was 35.1 months (95% CI: 26.0-52.7 months), compared to 9.4 months (95% CI: 6.9-13.0 months) in the incomplete response group (p = .0005). CONCLUSIONS: Our study showed that mid-course and posttherapy 11C-choline PET/CT evaluation for mCRPC patients undergoing primary docetaxel chemotherapy can predict full course treatment response and PFS, respectively. 11C-choline PET/CT imaging may provide valuable prognostic information to guide treatment choices for patients with mCRPC.

18F-FDG PET/CT of hepatocellular adenoma subtypes and review of literature.

INTRODUCTION: This study evaluates 18F-FDG PET/CT imaging characteristics of pathologically proven hepatocellular adenoma (HCA) subtypes. METHODS: This is a retrospective review of an institutional database (2011-2017) for subjects with a pathologic diagnosis of hepatic adenomas established within 6 months of a pre-treatment 18F-FDG PET/CT exam. An expert pathological review by a hepatopathologist was performed to confirm diagnosis and subtype HCA. A review of the 18F-FDG PET/CT exams was performed by two board-certified nuclear radiologists in consensus. Corresponding demographic and clinical data were obtained by electronic chart review. RESULTS: Nine subjects were identified. An HCA subtype was established in seven subjects (4 HNF1A-mutated and 3 Inflammatory). The mean HCA lesion size was 2.8 cm (range 0.6-6.2, SD 2.0) with a mean SUVmax of 5.9 (range 2.1-18.9, SD 5.1). The SUV values of HNF1A-mutated HCA were significantly higher than inflammatory HCA: lesion SUVmax (5.3 ± 1.48 vs. 2.8 ± 0.59, p < 0.033), lesion-to-liver SUVmax ratio (1.4 ± 0.22 vs. 0.8 ± 0.21, p = 0.031), lesion SUVmean (3.6 ± 0.37 vs. 2.0 ± 0.46, p = 0.0086). CONCLUSION: HNF1A-mutated HCA may have greater SUV values than inflammatory HCA on 18F-FDG PET/CT exams. However, there are contradictory data in the literature and further investigation is warranted.

Prognostic value of radiographically defined extranodal extension in human papillomavirus-associated locally advanced oropharyngeal carcinoma.

BACKGROUND: Pathologic extranodal extension (ENE) has traditionally guided the management of head and neck cancers. The prognostic value of radiographic ENE (rENE) in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV + OPX) is uncertain. METHODS: Patients with HPV + OPX with adequate pretreatment radiographic nodal evaluation from a single institution were analyzed. rENE status was determined by neuroradiologists' at time of diagnosis. Distant metastasis-free survival (DMFS), overall survival (OS), and locoregional recurrence-free survival (LRFS) were estimated using Kaplan-Meier methods. Cox proportional hazards models were fit to assess the impact of rENE on survival endpoints. RESULTS: Hundred sixty-eight patients with OPX + squamous cell carcinomas diagnosed between April 2008 and December 2014 were included for analysis with median follow-up of 3.3 years. Eighty-eight percent of patients received concurrent chemoradiotherapy. rENE was not prognostic; its presence in patients with HPV + OPX did not significantly impact OS, LRFS, or DMFS. CONCLUSIONS: In patients with HPV + OPX, rENE was not significantly associated with OS, LRFS, or DMFS.

Skeletal Metastasis Evaluation: Value and Impact of PET/Computed Tomography on Diagnosis, Management and Prognosis.

A number of PET agents are useful for evaluation of skeletal metastatic disease, and have significant advantages over 99mTc-MDP scintigraphy, including superior diagnostic accuracy, higher spatial resolution, and shorter imaging times- often with the ability to depict soft tissue local recurrence and metastasis in the same examination. While these agents have excellent diagnostic utility, they are not 100% specific for skeletal metastasis, and so normal patterns of biodistribution, benign osseous lesions that may demonstrate radiotracer uptake, and the significance of morphologic changes on CT such as osteolysis or osteosclerosis must be kept in mind to ensure accurate interpretation.

Bone Scan in Evaluation of Bone Viability in Severe Frostbite of the Hand.

A 39-year-old male presented to the emergency department (ED) with frostbite to the fingers of both hands. In the ED, he received warm baths, acetylsalicylic acid, clopidogrel, and heparin. A three-phase bone scintigraphy with technetium-99m-methylene diphosphonate revealed absent radiotracer uptake in distal phalanges of both hands. The patient received acetylsalicylic acid, clopidogrel and wound care for the next 5 days and made an excellent recovery with satisfactory wound healing in both hands. Early rapid rewarming and reperfusion can improve the prognosis significantly and therefore bone scan done within first 1-2 days may give spurious results.

Nested Stromal-epithelial Tumor of Liver with Recurrent Extrahepatic Metastasis: Role of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

Nested stromal-epithelial tumor (NSET) is a very rare nonhepatocytic and nonbiliary primary tumor of the liver. An 8-year-old boy was incidentally detected with hepatic lesions, involving both lobes of the liver for which he later underwent orthotopic liver transplant. The hepatic lesions were confirmed to be NSET following histopathological examination of explant liver specimen. He later developed recurrence with multiple metastatic lesions, including multi-station nodal and right talar bone involvement. We here present the case highlighting the importance of 18F-fludeoxyglucose positron emission tomography/computed tomography in the management of this rare tumor, in particular for monitoring disease progression and/or recurrence.

PET/CT in an 8-Year-Old Girl With Epstein-Barr Virus-Associated Smooth Muscle Tumor.

Epstein-Barr virus-associated smooth muscle tumor is a rare indolent neoplasm, which can occur in unusual locations. It has been reported in immunosuppressed individuals in only 3 settings: posttransplant, human immunodeficiency virus infection, and primary immunodeficiency. Here, we present CT, MRI, and F-FDG PET/CT findings of Epstein-Barr virus-associated smooth muscle tumor in an 8-year-old girl with primary immunodeficiency and metachronous adrenal involvement.

Standardized Added Metabolic Activity Predicts Survival After Intra-arterial Resin-Based 90Y Radioembolization Therapy in Unresectable Chemorefractory Metastatic Colorectal Cancer to the Liver.

PURPOSE: Standardized added metabolic (SAM) activity is a functional objective measurement of the total tumoral metabolic activity that avoids partial volume effect and thresholding, which limit conventional PET parameters. The purpose of this study is to investigate the role of SAM in predicting survival in unresectable, chemorefractory colorectal hepatic metastatic disease treated with resin-based Y radioembolization. MATERIALS AND METHODS: This is a prospective correlative study of patients with unresectable, chemorefractory colorectal liver metastasis who underwent F-FDG PET/CT and CT/MRI before and after Y. Target RECIST, PERCIST, change in total glycolytic activity (ΔTGA), and ΔSAM treatment response were assessed. Percentage changes in diameter, SUVpeak, TGA, and SAM were calculated pre- and post-Y therapy and objective response was defined as >30% change (responders). Survival analysis by Kaplan-Meier, log-rank, and Cox proportional hazard models were performed and significance was set at <0.05. RESULTS: Sixteen patients (mean age of 61.6) were enrolled and performed a total of 20 Y therapies. After Y, target ΔSAM showed an objective response rate of 40% vs. 35%, 30%, and 22.2% based on target ΔTGA, PERCIST, and RECIST criteria, respectively. Median overall survival (OS) of the cohort after Y was 9.2 months (CI 95% 2.2-16.2). Patients demonstrating objective response based on ΔSAM had a median OS of 22.7 months (CI 95% 12.4-33.0) vs. 6.7 (CI 95% 4.2-9.2) in non-responders (P = 0.007). On multivariate analysis, hazard ratios for the objective response group based on target ΔSAM were 0.01 (P = 0.03) vs. 0.05 (P = 0.08), 0.20 (P = 0.29), and 0.91 (P = 0.98) based on target ΔTGA, PERCIST, and RECIST criteria, respectively. CONCLUSIONS: In unresectable colorectal liver metastatic disease refractory to standard chemotherapy, ΔSAM predicted OS for assessment of response following Y radioembolization therapy, whereas RECIST, PERCIST, and ΔTGA did not.