Deciphering Tumor Response: The Role of Fluoro-18-d-Glucose Uptake in Evaluating Targeted Therapies with Tyrosine Kinase Inhibitors.

Background/Objectives: The inhibitory effects of tyrosine kinase inhibitors (TKIs) on glucose uptake through their binding to human glucose transporter-1 (GLUT-1) have been well documented. Thus, our research aimed to explore the potential impact of various TKIs of GLUT-1 on the standard [18F]FDG-PET monitoring of tumor response in patients. Methods: To achieve this, we conducted an analysis on three patients who were undergoing treatment with different TKIs and harbored actionable alterations. Alongside the assessment of FDG data (including SUVmax, total lesion glycolysis (TLG), and metabolic tumor volume (MTV)), we also examined the changes in tumor sizes through follow-up [18F]FDG-PET/CT imaging. Notably, our patients harbored alterations in BRAFV600, RET, and c-KIT and exhibited positive responses to the targeted treatment. Results: Our analysis revealed that FDG data derived from SUVmax, TLG, and MTV offered quantifiable outcomes that were consistent with the measurements of tumor size. Conclusions: These findings lend support to the notion that the inhibition of GLUT-1, as a consequence of treatment efficacy, could be indirectly gauged through [18F] FDG-PET/CT imaging in cancer patients undergoing TKI therapy.

Safety, efficacy and determinants of response of allogeneic CD19-specific CAR-NK cells in CD19+ B cell tumors: a phase 1/2 trial.

There is a pressing need for allogeneic chimeric antigen receptor (CAR)-immune cell therapies that are safe, effective and affordable. We conducted a phase 1/2 trial of cord blood-derived natural killer (NK) cells expressing anti-CD19 chimeric antigen receptor and interleukin-15 (CAR19/IL-15) in 37 patients with CD19+ B cell malignancies. The primary objectives were safety and efficacy, defined as day 30 overall response (OR). Secondary objectives included day 100 response, progression-free survival, overall survival and CAR19/IL-15 NK cell persistence. No notable toxicities such as cytokine release syndrome, neurotoxicity or graft-versus-host disease were observed. The day 30 and day 100 OR rates were 48.6% for both. The 1-year overall survival and progression-free survival were 68% and 32%, respectively. Patients who achieved OR had higher levels and longer persistence of CAR-NK cells. Receiving CAR-NK cells from a cord blood unit (CBU) with nucleated red blood cells ≤ 8 × 107 and a collection-to-cryopreservation time ≤ 24 h was the most significant predictor for superior outcome. NK cells from these optimal CBUs were highly functional and enriched in effector-related genes. In contrast, NK cells from suboptimal CBUs had upregulation of inflammation, hypoxia and cellular stress programs. Finally, using multiple mouse models, we confirmed the superior antitumor activity of CAR/IL-15 NK cells from optimal CBUs in vivo. These findings uncover new features of CAR-NK cell biology and underscore the importance of donor selection for allogeneic cell therapies. ClinicalTrials.gov identifier: NCT03056339 .

Positron emission tomography derived metrics in relapsed or refractory large B-cell lymphoma with residual disease before autologous stem cell transplant.

Salvage chemotherapy followed by high-dose chemotherapy and autologous stem cell transplantation (ASCT) is a potentially curative treatment for patients with relapsed or refractory large B-cell lymphoma (rrLBCL) with chemosensitive disease. A18 F-fluorodeoxyglucose positron emission tomography (PET) scan after salvage chemotherapy is used to assess response and eligibility for ASCT, but metrics for chemosensitivity in patients with residual disease are not well defined. We performed a single-centre retrospective analysis of 92 patients with a partial response or stable disease after salvage chemotherapy for rrLBCL who received ASCT to investigate PET-derived parameters and their prognostic utility. The Deauville 5-point Scale (D-5PS) score, maximum standardised uptake value (SUVmax ), total metabolic tumour volume (TMTV), and total lesion glycolysis (TLG) were calculated from the post-salvage/pre-ASCT PET scan. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 40% and 54% respectively. A D-5PS score of 5 (p = 0.0082, hazard ratio [HR] 2.09), high SUVmax (p = 0.0015, HR 2.48), TMTV (p = 0.035, HR 1.83) and TLG (p = 0.0036, HR 2.27) were associated with inferior PFS. A D-5PS score of 5 (p = 0.030, HR 1.98) and high SUVmax (p = 0.0025, HR 2.55) were associated with inferior OS. PET-derived parameters may help prognosticate outcomes after ASCT in patients with rrLBCL with residual disease after salvage chemotherapy.

A Retrospective Comparative Study of Sodium Fluoride Na18F-PET/CT and 68Ga-PSMA-11 PET/CT in the Bone Metastases of Prostate Cancer Using a Volumetric 3-D Radiomic Analysis.

Bone is the most common metastatic site in prostate cancer (PCa). 68Ga-PSMA-11 (or gozetotide) and sodium fluoride-18 (Na18F) are rather new radiopharmaceuticals for assessing PCa-associated bone metastases. Gozetotide uptake reflects cell membrane enzyme activity and the sodium fluoride uptake measures bone mineralization in advanced PCa. Here, we aim to characterize this difference and possibly provide a new method for patient selection in targeted therapies. Methods: The study consisted of 14 patients with advanced PCa (M group > 5 lesions), who had had routine PET/CT both with PSMA and NaF over consecutive days, and 12 PCa patients with no skeletal metastases (N). The bone regions in CT were used to coregister the two PET/CT scans. The whole skeleton volume(s) of interest (VOIs) were defined using the CT component of PET (HU > 150); similarly, the sclerotic/dense bone was defined as HU > 600. Additional VOIs were defined for PET, with pathological threshold values for PSMA (SUV > 3.0) and NaF (SUV > 10). Besides the pathological bone volumes measured with each technique (CT, NaF, and PSMA-PET) and their contemporaneous combinations, overlapping VOIs with the CT-based skeletal and sclerotic volumes were also recorded. Additionally, thresholds of 4.0, 6.0, and 10.0 were tested for SUVPSMA. Results: In group M, the skeletal VOI volumes were 8.77 ± 1.80 L, and the sclerotic bone volumes were 1.32 ± 0.50 L; in contrast, in group N, they were 8.73 ± 1.43 L (skeletal) and 1.23 ± 0.28 L (sclerosis). The total enzyme activity for PSMA was 2.21 ± 5.15 in the M group and 0.078 ± 0.053 in the N group (p < 0.0002). The total bone demineralization activity for NaF varied from 4.31 ± 6.17 in the M group and 0.24 ± 0.56 in group N (p < 0.0002). The pathological PSMA volume represented 0.44−132% of the sclerotic bone volume in group M and 0.55−2.3% in group N. The pathological NaF volume in those patients with multiple metastases represented 0.27−68% of the sclerotic bone volume, and in the control group, only 0.00−6.5% of the sclerotic bone volume (p < 0.0003). Conclusions: These results confirm our earlier findings that CT alone does not suit the evaluation of the extent of active skeletal metastases in PCa. PSMA and NaF images give complementary information about the extent of the active skeletal disease, which has a clinical impact and may change its management. The PSMA and NaF absolute volumes could be used for planning targeted therapies. A cut-off value 3.0 for SUVPSMA given here is the best correlation in the presentation of active metastatic skeletal disease.

18F-Fluciclovine versus PSMA PET Imaging in Primary Tumor Detection during Initial Staging of High-Risk Prostate Cancer: A Systematic Review and Meta-Analysis.

Purpose Fluorine 18 (18F)-fluciclovine and prostate-specific membrane antigen (PSMA) tracers are commonly used for localizing biochemical recurrence of prostate cancer, but their accuracy in primary tumor detection in the initial staging of high-risk prostate cancer has not been established. Materials and Methods A systematic review was performed of the electronic databases for original studies published between 2012 and 2020. Included studies were those in which 18F-fluciclovine or PSMA PET was used for initial staging of patients with high-risk prostate cancer. The diagnostic performance data were collected for primary tumor with histopathologic results as reference standard. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used for quality appraisal. A random-effects model was used to summarize the effect sizes and to evaluate the difference between two groups. Results Overall, 28 studies met the eligibility criteria, and 17 were included in the meta-analysis (18F-fluciclovine = 4, PSMA = 13). Of these 17 studies, 12 (70%) were judged to have high risk of bias in one of the evaluated domains, and nine studies were deemed to have applicability concerns. The pooled sensitivity, specificity, and diagnostic odds ratio for 18F-fluciclovine versus PSMA were 85% (95% CI: 73%, 92%) versus 84% (95% CI: 77%, 89%) (P = .78), 77% (95% CI: 60%, 88%) versus 83% (95% CI: 76%, 89%) (P = .40), and 18.88 (95% CI: 5.01, 71.20) versus 29.37 (95% CI: 13.35, 64.60) (P = .57), respectively, with no significant difference in diagnostic test accuracy. Conclusion 18F-fluciclovine and PSMA PET demonstrated no statistically significant difference in diagnostic accuracy in primary tumor detection during initial staging of high-risk prostate cancer. Keywords: PET, Prostate, Molecular Imaging-Cancer, Staging Supplemental material is available for this article. © RSNA, 2022.

Lesion-Based Radiomics Signature in Pretherapy 18F-FDG PET Predicts Treatment Response to Ibrutinib in Lymphoma.

PURPOSE: The aim of this study was to develop a pretherapy PET/CT-based prediction model for treatment response to ibrutinib in lymphoma patients. PATIENTS AND METHODS: One hundred sixty-nine lymphoma patients with 2441 lesions were studied retrospectively. All eligible lymphomas on pretherapy 18F-FDG PET images were contoured and segmented for radiomic analysis. Lesion- and patient-based responsiveness to ibrutinib was determined retrospectively using the Lugano classification. PET radiomic features were extracted. A radiomic model was built to predict ibrutinib response. The prognostic significance of the radiomic model was evaluated independently in a test cohort and compared with conventional PET metrics: SUVmax, metabolic tumor volume, and total lesion glycolysis. RESULTS: The radiomic model had an area under the receiver operating characteristic curve (ROC AUC) of 0.860 (sensitivity, 92.9%, specificity, 81.4%; P < 0.001) for predicting response to ibrutinib, outperforming the SUVmax (ROC AUC, 0.519; P = 0.823), metabolic tumor volume (ROC AUC, 0.579; P = 0.412), total lesion glycolysis (ROC AUC, 0.576; P = 0.199), and a composite model built using all 3 (ROC AUC, 0.562; P = 0.046). The radiomic model increased the probability of accurately predicting ibrutinib-responsive lesions from 84.8% (pretest) to 96.5% (posttest). At the patient level, the model's performance (ROC AUC = 0.811; P = 0.007) was superior to that of conventional PET metrics. Furthermore, the radiomic model showed robustness when validated in treatment subgroups: first (ROC AUC, 0.916; P < 0.001) versus second or greater (ROC AUC, 0.842; P < 0.001) line of defense and single treatment (ROC AUC, 0.931; P < 0.001) versus multiple treatments (ROC AUC, 0.824; P < 0.001). CONCLUSIONS: We developed and validated a pretherapy PET-based radiomic model to predict response to treatment with ibrutinib in a diverse cohort of lymphoma patients.

A prospective study on early PET/CT scans during the first cycle of salvage chemotherapy for relapsed or refractory diffuse large B-cell lymphoma.

Many patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) will not respond to platinum-containing salvage chemotherapy. Predicting treatment failure earlier could help clinicians minimize chemotherapy toxicities for non-responders in favor of other treatments. We conducted a pilot study where 2 early PET/CTs were obtained on days 4 (D4) and 21 (D21) of cycle 1 (C1) of salvage therapy for DLBCL. Twenty-five patients were enrolled and have evaluable data. Ten (40%) had an unplanned therapy change after C1 and before end-of-treatment (EOT) evaluation due to treatment failure on early PET/CT as interpreted by the treating physician. Early PET/CT response at D4 or D21 was not associated with EOT response in evaluable patients. Disease specific survival was longer for patients with a persistent response on both D4 and D21 (p = 0.042). Early PET/CT may predict salvage chemotherapy failure and could inform future clinical trials investigating early therapy change to non-chemotherapy treatments.

A Prospective Comparative Study of Using Ultrasonography, 4D-CT and Parathyroid Dual-Phase Scintigraphy with SPECT in Patients with Primary Hyperparathyroidism.

Thirty-one consecutive patients were included in this study who were planned for parathyroidectomy due to primary hyperparathyroidism. They were studied with US, 4D-CT and dual-phase scintigraphy including SPECT/CT, and possible adenomas were identified in each imaging modality. Imaging data were quantified with US, CT and SPECT. Parathyroidectomies were performed as minimally invasive according to preoperative imaging findings. A total of 16 adenomas were found in 15 patients, and the surgery was negative in four patients. The imaging results were compared with each other and correlated to histology findings and blood biochemistry (S-Ca and P-PTH). Quantitative SPECT found a strong correlation between the quantification methods-Conjugate Gradient with Attenuation and Scatter Correction with a zone map (CGZAS) and Conjugate Gradient with Attenuation and Scatter Correction (CGAS)-measured as SUVmax and kBq/mL. However, a statistically significant correlation between the quantitative parameters (CGZAS and CGAS) and serum biomarkers (S-PTH and S-Ca) was not observed. The sensitivities of the imaging methods were calculated using histopathology as a gold standard. SPECT/CT demonstrated 93% sensitivity, 4D-CT 93% sensitivity and ultrasonography 73% sensitivity. The imaging methods were compared with each other using parathyroid regions because findings and locations varied between the modalities. Our prospective study supports that quantitative SPECT/CT is useful for presurgical assessment of primary hyperparathyroidism.

18F-sodium fluoride positron emission tomography (NaF-18-PET/CT) radiomic signatures to evaluate responses to alpha-particle Radium-223 dichloride therapy in osteosarcoma metastases.

Patients with osteoblastic metastases from high risk osteosarcoma continue to have a poor prognosis after progression from standard-of-care multi-agent chemotherapy. In a first-in-human dose escalation trial of bone targeted Radium 223 dichloride alpha-particle therapy in 18 patients with advanced osteosarcoma only 1 patient responded based on conventional Response Evaluation Criteria in Solid Tumors (RECIST). Na18F PET response Criteria in Solid Tumors(NAFCIST), based on Sodium fluoride-18 (Na18F) positron emission tomography (PET)-CT was developed to better evaluate bone specific response. To further appreciate the spatial and temporal heterogeneity of the partial or mixed responses, a radiomics method was developed. Analyses were performed with 18F-sodium fluoride positron emission tomography imaging studies before and after alpha-particle therapy. Radioactive 18F- -atom concentrations were measured in soft-tissues, in approximately 1000 concentration data points for 18F- per 1 cm3 metastatic tumor. Data was analyzed from the SUV intensity values, the histogram of intensities and entropy values. Radiomics may inform intra-tumoral and inter-tumoral heterogeneity in response of bone forming osteosarcoma to alpha particle therapy. Each patient (and each tumor) represents an "N of 1" case and warrants in depth analysis individually.

Monoclonal antibody based radiopharmaceuticals for imaging and therapy.

The concept of personalized medicine has been steadily growing for the past decades. Monoclonal antibodies (mAbs) are undoubtedly playing an important role in the transition away from conventional medical practice to a more tailored approach to deliver the best therapy with the highest safety margin to a specific patient. In certain instances, mAbs and antibody drug conjugates (ADCs) may represent the preferred therapeutic option for several types of cancers due to their high specificity and affinity to the antigen. Monoclonal antibodies can be labeled with specific radionuclides well-suited for PET (Positron Emission Tomography) or gamma camera scintigraphy. The use of radiolabeled mAbs allows the interrogation of specific biomarkers and assessment of tumor heterogeneity in vivo by a single diagnostic imaging scan that includes the whole-body in the field-of-view. Moreover, the same mAb can then be radiolabeled with an analogous radionuclide for the delivery of beta-minus radiation or alpha-particles as part of a radioimmunotherapy (RIT) approach. However, the path to develop, validate, and implement mAb-based radiopharmaceuticals from bench-to-bedside is complex due to the extensive pre-clinical experiments and toxicological studies required, and the necessity of labor-intensive clinical trials that often require multi-time-point imaging and blood draws for internal radiation dosimetry and pharmacokinetics. As more mAb-based radiopharmaceuticals have been developed and evaluated, the opportunities and limitations offered by mAbs have become better defined. Our aim with this manuscript is therefore to provide an overview of the recent advances in the development of mAb-based radiopharmaceuticals and their clinical applications in Oncology.

Computer-aided detection of mantle cell lymphoma on 18F-FDG PET/CT using a deep learning convolutional neural network.

18F-FDG PET/CT can provide quantitative characterization with prognostic value for mantle cell lymphoma (MCL). However, detection of MCL is performed manually, which is labor intensive and not a part of the routine clinical practice. This study investigates a deep learning convolutional neural network (DLCNN) for computer-aided detection of MCL on 18F-FDG PET/CT. We retrospectively analyzed 142 baseline 18F-FDG PET/CT scans of biopsy-confirmed MCL acquired between May 2007 and October 2018. Of the 142 scans, 110 were from our institution and 32 were from outside institutions. An Xception-based U-Net was constructed to classify each pixel of the PET/CT images as MCL or not. The network was first trained and tested on the within-institution scans by applying five-fold cross-validation. Sensitivity and false positives (FPs) per patient were calculated for network evaluation. The network was then tested on the outside-institution scans, which were excluded from network training. For the 110 within-institution patients (85 male; median age, 58 [range: 39-84] years), the network achieved an overall median sensitivity of 88% (interquartile range [IQR]: 25%) with 15 (IQR: 12) FPs/patient. Sensitivity was dependent on lesion size and SUVmax but not on lesion location. For the 32 outside-institution patients (24 male; median age, 59 [range: 40-67] years), the network achieved a median sensitivity of 84% (IQR: 24%) with 14 (IQR: 10) FPs/patient. No significant performance difference was found between the within and outside institution scans. Therefore, DLCNN can potentially help with MCL detection on 18F-FDG PET/CT with high sensitivity and limited FPs.

Diagnostic performance of 18F-fluciclovine PET/CT in prostate cancer patients with rising PSA level ≤ 0.5 ng/ml after multiple treatment failures.

This retrospective study is to assess the performance of 18F-Fluciclovine PET/CT in prostate cancer (PC) patients with multiple treatment failures and prostate-specific antigen (PSA) ≤ 0.5 ng/mL. PC patients with multiple treatment failures who had PSA level within 2-week interval of 18F-Fluciclovine PET/CT (PSAPET) ≤ 0.5 ng/mL were identified in retrospective review of our institution's database (n=28). Patient, tumor, treatment, PSA and castration characteristics as well as findings on 18F-Fluciclovine PET/CT were collected and compared between positive and negative 18F-Fluciclovine PET/CT subgroups by using Fisher's exact test. The overall detection rate of 18F-Fluciclovine PET/CT was 7 of 28 studies (25%). PSAPET > 0.2 ng/mL was associated with higher detection rates in all (33.3 vs 10%, P=0.172), castration-resistant (CR) (50 vs 20%, P=0.343) and castration-sensitive (CS) (28.6 vs 0%, P=0.179) patients. Sites of recurrence were local 42.9% (3/7), nodal 42.9% (3/7) and bone metastases 14.3% (1/7). Higher Gleason score (GS 8-10) (33.3 vs 14.5%, P=0.396), advanced tumor stage (T3-T4) (35.7 vs 20%, P=0.653), second-line androgen deprivation therapy (ADT) uses (66.7 vs 20%, P=0.145), chemotherapy uses (50 vs 23.1%, P=0.444) and CRPC (33.3 vs 21.1%, P=0.483) related to positivity of 18F-Fluciclovine PET/CT but none reached statistical significance. Performance of 18F-Fluciclovine PET/CT in prostate cancer patients with multiple treatment failures and PSAPET ≤ 0.5 ng/mL was acceptable particularly in patients with PSAPET ≥ 0.3 ng/mL, CRPC, initial GS ≥ 8 or T3-T4.

What Is the Optimal Method on Myocardial Suppression in FDG PET/CT Evaluation of Cardiac Sarcoidosis?

ABSTRACT: Based on the recent publications, including large cohort retrospective study and prospective clinical trial data, we are commenting on the optimal methods on myocardial suppression in FDG PET/CT evaluation of patients with suspected cardiac sarcoidosis.

18F-Fluorothymidine PET is an early and superior predictor of progression-free survival following chemoimmunotherapy of diffuse large B cell lymphoma: a multicenter study.

PURPOSE: To determine whether interim 3'-deoxy-3'-[18F]fluorothymidine (iFLT) PET/CT is a superior predictor of progression-free survival (PFS) compared with interim 18F-fluorodeoxyglucose (iFDG) PET/CT in patients with diffuse large B cell lymphoma (DLBCL) treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or rituximab, etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (R-EPOCH). METHODS: Ninety-two prospectively enrolled patients with DLBCL underwent both FLT-PET/CT and FDG-PET/CT 18-24 days after two cycles of R-CHOP/R-EPOCH. Deauville-criteria, PERCIST1.0, standardized uptake value (SUV), total lesion glycolysis (TLG), and metabolic tumor volume were used to interpret iFDG-PET/CT while dichotomous visual interpretation was used to interpret iFLT-PET/CT and the results were compared with the 3- and 5-year PFS. RESULTS: iFLT-PET/CT was negative in 67 (73%) and positive in 25 (27%) patients. iFDG-PET/CT by Deauville criteria was negative (Deauville scores [DS] of 1-3) in 53 (58%) and positive (DS = 4-5) in 39 (42%) patients. Of the 67 iFLT-PET/CT-negative patients, 7 (10.4%) progressed at a median of 14.1 months whereas 14/25 (56.0%) iFLT-PET/CT-positive patients progressed at a median of 7.8 months (P < .0001). Of the 53 Deauville-negative patients, 9 (17.0%) progressed at a median of 14.1 months whereas 12/39 (30.8%) Deauville-positive patients progressed at a median of 5.6 months (P = .11). In multivariate analysis, including iFLT-PET/CT, PERCIST, interim TLG, and interim SUVmax, only iFLT-PET/CT was an independent predictor for 3- and 5-year PFS (P < .0001 and P = .001, respectively). CONCLUSIONS: In patients with DLBCL given R-CHOP/R-EPOCH, iFLT-PET/CT is a superior independent predictor of outcome compared with iFDG-PET/CT.

Rate of incidental central nervous system meningioma detected in patients undergoing 18F-fluciclovine PET/CT imaging for evaluation of prostate cancer.

OBJECTIVE: To evaluate the rate of incidental detection of central nervous system (CNS) meningioma in patients undergoing 18F-fluciclovine PET/computed tomography (CT) imaging for the evaluation of prostate cancer. METHODS: The reports of 850 18F-fluciclovine PET/CT scans in 566 patients with pathologically proven prostate cancer performed from April 2017 to July 2019, were retrospectively reviewed for the presence of CNS meningioma. RESULTS: A total of 14 patients (2.8%) (age range: 54-82 years old) had abnormal focal intracranial 18F-fluciclovine uptake, all extra-axial in location (SUVmax range: 3.2-19.3). Two cases out of 14 (0.35%) were diagnosed as metastatic lesions. Twelve out of the 14 patients, had 18F-fluciclovine PET/CT imaging findings suspicious for CNS meningioma, 2 of them received another diagnosis on further imaging, and only 10 cases (2%) had the diagnosis of meningioma according to follow-up MRI and 18F-fluciclovine PET/CT. CONCLUSION: Focal 18F-fluciclovine avid intracranial lesions incidentally detected in patients undergoing PET/CT imaging for prostate cancer are most often CNS meningiomas.

Disease control and failure patterns of unresectable hepatocellular carcinoma following transarterial radioembolization with yttrium-90 microspheres and with/without sorafenib.

BACKGROUND: Impressive survival outcome of our previous study in unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass microspheres transarterial radioembolization (TARE) with/without sorafenib according to individuals' disease burden, i.e., intrahepatic tumor load (IHT) and adverse disease features (ADFs) might partly be confounded by other treatments and underlying hepatic function. Therefore, a dedicated study focusing on treatment response and assessment of failure patterns might be a way to improve treatment outcome in addition to patient selection based on the disease burden. AIM: To assess the tumor response, disease control and patterns of disease progression following TARE with/without sorafenib in unresectable HCC patients. METHODS: This retrospective study was conducted in successful TARE procedures with available pre- and post-treatment imaging studies (n = 169). Three treatment subgroups were (1) TARE only (TARE_alone) for IHT ≤ 50% without ADFs, i.e., macrovascular invasion, extrahepatic disease (EHD) and infiltrative/ill-defined HCC (n = 63); (2) TARE with sorafenib (TARE_sorafenib) for IHT > 50% and/or presence of ADFs (n = 81); and (3) TARE only for patients who could not receive sorafenib due to contraindication or intolerance (TARE_no_sorafenib) (n = 25). Objective response rate (ORR; consisted of complete response (CR) and partial response (PR)), disease control rate (DCR; consisted of CR, PR and stable disease) and failure patterns of treated, intrahepatic and extrahepatic sites were assessed using the modified response evaluation criteria in solid tumors. Time to progression (TTP) was calculated from TARE to the first radiologic progression at any site using Kaplan-Meier method. Identification of prognostic factors for TTP using the univariate Kaplan-Meier method and multivariate Cox proportional hazard model were performed in major population subgroups, TARE_alone and TARE_sorafenib. RESULTS: The median radiologic follow-up time was 4.4 mo (range 0.5-48.8). In treated area, ORR was highest in TARE_sorafenib (53.1%), followed by TARE_alone (41.3%) and TARE_no_sorafenib (16%). In intrahepatic area, DCR remained highest in TARE_sorafenib (84%), followed by TARE_alone (79.4%) and TARE_no_sorafenib (44%). The overall DCR was highest in TARE_alone (79.4%), followed by TARE_sorafenib (71.6%) and TARE_no_sorafenib (40%). Dominant failure patterns were intrahepatic for both TARE_alone (44.5%) and TARE_sorafenib (38.4%). Extrahepatic progression was more common in TARE_sorafenib (32%) and TARE_no_sorafenib (40%) than in TARE_alone (12.7%). TTP was longest in TARE_alone (8.6 mo; 95%CI: 3.4-13.8), followed by TARE_sorafenib (5.1 mo; 95%CI: 4.0-6.2) and TARE_no_sorafenib (2.7 mo; 95%CI: 2.2-3.1). Pre-existing EHD (HR: 0.37, 95%CI: 0.24-0.56, P < 0.001) was a sole prognostic factor for TTP in TARE_sorafenib with no prognostic factor for TTP in TARE_alone. CONCLUSION: TARE with/without sorafenib according to individuals' disease burden provided DCR approximately 70% with intrahepatic progression as dominant failure pattern. Extrahepatic progression was more common in procedures with initially high disease burden.

A Retrospective Comparative Study of Sodium Fluoride (NaF-18)-PET/CT and Fluorocholine (F-18-CH) PET/CT in the Evaluation of Skeletal Metastases in Metastatic Prostate Cancer Using a Volumetric 3-D Radiomics Analysis.

Bone metastases are common in prostate cancer (PCa). Fluorocholine-18 (FCH) and sodium fluoride-18 (NaF) have been used to assess PCa associated skeletal disease in thousands of patients by demonstrating different mechanism of uptake-cell membrane (lipid) synthesis and bone mineralization. Here, this difference is characterized quantitatively in detail. Our study cohort consisted of 12 patients with advanced disease (> 5 lesions) (M) and of five PCa patients with no skeletal disease (N). They had routine PET/CT with FCH and NaF on consecutive days. Skeletal regions in CT were used to co-register the two PET/CT scans. Bone 3-D volume of interest (VOI) was defined on the CT of PET with a threshold of HU > 150, and sclerotic/dense bone as HU > 600, respectively. Additional VOIs were defined on PET uptake with the threshold values on both FCH (SUV > 3.5) and NaF (SUV > 10). The pathologic skeletal volumes for each technique (CT, HU > 600), NaF (SUV > 10) and FCH (SUV > 3.5) were developed and analyzed. The skeletal VOIs varied from 5.03 L to 7.31 L, whereas sclerotic bone VOIs were from 0.88 L to 2.99 L. Total choline kinase (cell membrane synthesis) activity for FCH (TCA) varied from 0.008 to 4.85 [kg] in M group and from 0.0006 to 0.085 [kg] in N group. Total accelerated osteoblastic (bone demineralization) activity for NaF (TBA varied from 0.25 to 13.6 [kg] in M group and varied from 0.000 to 1.09 [kg] in N group. The sclerotic bone volume represented only 1.86 ± 1.71% of the pathologic FCH volume and 4.07 ± 3.21% of the pathologic NaF volume in M group, and only 0.08 ± 0.09% and 0.18 ± 0.19% in N group, respectively. Our results suggest that CT alone cannot be used for the assessment of the extent of active metastatic skeletal disease in PCa. NaF and FCH give complementary information about the activity of the skeletal disease, improving diagnosis and disease staging.

Survival Outcomes for Yttrium-90 Transarterial Radioembolization With and Without Sorafenib for Unresectable Hepatocellular Carcinoma Patients.

PURPOSE: To assess the overall survival (OS) and progression-free survival (PFS) of unresectable hepatocellular carcinoma (HCC) patients undergoing yttrium-90 glass-microsphere transarterial radioembolization (TARE) with and without concurrent sorafenib. METHODS: OS and PFS were analyzed in 55 patients with an intrahepatic tumor (IHT) ≤50% without advanced or aggressive disease features (ADFs), which was referred to presence of infiltrative/ill-defined HCC, macrovascular invasion, or extrahepatic disease treated with only TARE (TARE_alone) and in 74 patients with IHT ≤50% with ADFs or IHT >50% treated with TARE and sorafenib (TARE_sorafenib). Prognostic factors for OS and PFS were identified using univariate and multivariate analyses. RESULTS: Median OS and PFS of TARE_alone patients were 21.6 (95% CI 6.1-37.1) and 9.1(95% CI 5.2-13.0) months, respectively, and for TARE_sorafenib patients 12.4 (95% CI 9.1-15.6) and 5.1 (95% CI 2.6-7.5) months, respectively. Better OS was associated with serum AFP <400 (HR 0.27, p=0.02) in TARE_alone, and IHT ≤50% (HR 0.39, p=0.004) and AFP <400 (HR 0.5, p=0.027) in TARE_sorafenib. Unilobar involvement (HR 0.43, p=0.029) and AFP <400 ng/mL (HR 0.52, p=0.015) correlated with better PFS in TARE_alone and TARE_sorafenib, respectively. Adverse events (AEs) were more frequent in TARE_sorafenib than TARE_alone (92.4 vs 80.3%), but only 9.3% were grade 3 or higher AEs. CONCLUSION: TARE_alone provided the most prominent survival benefit in IHT ≤50%-without ADF patients who had unilobar HCC and serum AFP <400 ng/mL. TARE and sorafenib yielded the best outcomes in patients with IHT ≤50% and serum AFP <400 ng/mL, with some additional grade 1-2 AEs compared to TARE only.

Phase I Study of P-cadherin-targeted Radioimmunotherapy with 90Y-FF-21101 Monoclonal Antibody in Solid Tumors.

PURPOSE: 90Y-FF-21101 is an Yttrium-90-conjugated, chimeric mAb that is highly specific for binding to human placental (P)-cadherin, a cell-to-cell adhesion molecule overexpressed and associated with cancer invasion and metastatic dissemination in many cancer types. We report the clinical activity of 90Y-FF-21101 in a first-in-human phase I study in patients with advanced solid tumors. PATIENTS AND METHODS: The safety and efficacy of 90Y-FF-21101 were evaluated in a phase I 3+3 dose-escalation study in patients with advanced solid tumors (n = 15) over a dose range of 5-25 mCi/m2. Dosimetry using 111In-FF-21101 was performed 1 week prior to assess radiation doses to critical organs. Patients who demonstrated clinical benefit received repeated 90Y-FF-21101 administration every 4 months. RESULTS: 111In-FF-21101 uptake was observed primarily in the spleen, kidneys, testes, lungs, and liver, with tumor uptake observed in the majority of patients. Organ dose estimates for all patients were below applicable limits. P-cadherin expression H-scores ranged from 0 to 242 with 40% of samples exhibiting scores ≥100. FF-21101 protein pharmacokinetics were linear with increasing antibody dose, and the mean half-life was 69.7 (±12.1) hours. Radioactivity clearance paralleled antibody clearance. A complete clinical response was observed in a patient with clear cell ovarian carcinoma, correlating with a high tumor P-cadherin expression. Stable disease was observed in a variety of other tumor types, without dose-limiting toxicity. CONCLUSIONS: The favorable safety profile and initial antitumor activity observed for 90Y-FF-21101 warrant further evaluation of this radioimmunotherapeutic (RIT) approach and provide initial clinical data supporting P-cadherin as a potential target for cancer treatment.

Diagnostic performance of F-18 fluciclovine PET/CT in post-radical prostatectomy prostate cancer patients with rising prostate-specific antigen level ≤0.5 ng/mL.

PURPOSE: The aim of the study was to assess the diagnostic performance of fluciclovine positron emission tomography (PET)/computerized tomography (CT) in post-radical prostatectomy prostate cancer patients with rising prostate-specific antigen (PSA) ≤0.5 ng/mL, and identify the associated predictive factors of positive studies. PATIENTS AND METHODS: From 30 June 2017 to 9 August 2019, patients with post-radical prostatectomy prostate cancer who underwent F-18 fluciclovine PET/CT and had PSA level within 2-week interval (PSAPET) ≤0.5 ng/mL were enrolled into this single-institution retrospective study. Data on tumor characteristics, including Gleason scores, extra-prostatic extension, seminal vesicle invasion, surgical margin and nodal metastasis, PSA after radical prostatectomy, previous hormonal therapy, PSA doubling time (PSADT), scanner type, PSAPET and site of recurrence were collected. Comparison of these factors between groups of positive and negative fluciclovine PET/CT was done by using Mann-Whitney U-test and Fisher's exact test. RESULTS: Of 94 eligible patients with post-radical prostatectomy prostate cancer, 10 patients had positive studies (10.6%). Detection rate at PSAPET 0.1, 0.2, 0.3, 0.4 and 0.5 ng/mL were 0% (0/11), 0% (0/15), 20% (6/30), 4% (1/25) and 23.1% (3/13), respectively. Upon multivariate analysis of clinical factors, only a PSADT <3 months (P = 0.023) was shown to have a statistically significant correlation with a positive study. CONCLUSION: In post-radical prostatectomy prostate cancer patients with rising PSA 0.1-0.5 ng/mL, the sensitivity of F-18 fluciclovine PET/CT for identifying tumor recurrence/metastases is poor with an overall detection rate of 10.6%. Larger prospective studies are required to validate these findings.