CT-based assessment of body composition following neoadjuvant chemohormonal therapy in patients with castration-naïve oligometastatic prostate cancer.

BACKGROUND: The purpose of this study is to assess the body composition changes in men with recently diagnosed oligometastatic prostate cancer following neoadjuvant chemohormonal therapy. Further, we evaluated whether CT-based body composition parameters are associated with biochemical recurrence or imaging progression. MATERIAL AND METHODS: Recently diagnosed castration-naïve oligometastatic prostate cancer patients who received neoadjuvant docetaxel chemotherapy and androgen deprivation treatment (ADT) before prostatectomy and consolidation of local and oligometastatic disease (total eradication therapy), as part of a phase-II prospective clinical trial were included. Body composition parameters including cross-sectional areas of the psoas muscle, total, visceral, and subcutaneous adipose tissue were measured on serial CT scans obtained before and following completion of neoadjuvant treatment. RESULTS: A total of 22 prostate cancer patients were included (median age 58 years, median Gleason score 8). The median time intervals between commencement of neoadjuvant chemohormonal therapy and first and second follow-up CTs were 3 and 12 months, respectively. Compared to the baseline scan, there were significant declines in psoas muscle cross-sectional areas with estimated percentage declines of -13.9% (IQR: 7.6%-16.5%, p < .001) and -13.2% (IQR: 6%-11.2%, p < .001) on first and second follow-up CTs. There were significant increases in subcutaneous adipose tissue following neoadjuvant chemohormonal therapy with percentage increases of +8.9% (IQR: 5.1%-21.5%, p = .002) and +18.9% (IQR: 6.1%-33.8%, p < .001), respectively. The median follow-up was 34.5 months. The estimated 2-year prostate-specific antigen progression-free and radiologic progression-free survival were 95.5%. No significant association between baseline or percentage change in body composition parameters and disease progression were identified. CONCLUSIONS: Our findings showed a significant reduction in muscle mass and an increase in subcutaneous adiposity in men treated with neoadjuvant docetaxel and ADT, more pronounced on the first follow-up scan after completion of neoadjuvant treatment. Body composition parameters were not found to be significant predictors of disease progression in our cohort.

The combination of size-based separation and selection-free technology provides higher circulating tumour cells detection sensitivity than either method alone in patients with metastatic prostate cancer.

OBJECTIVE: To investigate the circulating tumour cells (CTCs) capture abilities of two technologies that are not dependent on cell-surface marker expression: a selection-free platform [AccuCyte® -CyteFinder® system (Rarecyte)] and a size-based platform [fluid-assisted separation technology (FAST)]. In addition, the combination of the two systems to more completely assess CTCs was investigated. PATIENTS AND METHODS: In all, 28 patients with metastatic prostate cancer were included. Two 6 mL peripheral blood samples were taken from each patient at the same time-point. The samples were then subjected to the two different technology platforms in parallel. An additional group of samples was acquired by applying the waste chamber material from the FAST-group tests (flow-through that goes through the FAST filter membrane) to the Rarecyte system for the detection any CTCs that were not captured by FAST. RESULTS: The three groups had significantly different putative CTC-positive tests, with positive rates of 29% for Rarecyte, 57% for FAST, and 79% for the combination. We also assessed CTC phenotype: 56.6% of the CTCs were cytokeratin (CK)+/epithelial cell adhesion molecule (EpCAM)-, 3.1% were CK-/EpCAM+, and 40.3% were CK+/EPCAM+. The captured CTCs diameter ranged from 5.2 to 16.9 µm. The mean CTC size from the FAST waste chamber was significantly smaller. The diameters for each of the phenotypic groups were significantly different. CONCLUSIONS: These data highlight disparities in the positive rates and enumerated CTC numbers detected by the two techniques. Notably, the combination of the two technologies resulted in the highest CTC-capture rates. Smaller CTCs were more likely to be missed by the FAST as they passed through the filter system. Sizes of CTCs varied with different cell surface marker phenotypes.

Stereotactic ablative radiation therapy for oligometastatic prostate cancer delays time-to-next systemic treatment.

PURPOSE: Local ablative treatment to oligometastatic patients can result in long-term disease-free survival in some cancer patients. The importance of this treatment paradigm in prostate cancer is a rapidly evolving field. Herein, we report on the safety and preliminary clinical outcomes of a modern cohort of oligometastatic prostate cancer (OPC) patients treated with consolidative stereotactic ablative radiation (SABR). METHODS: Records of men with OPC who underwent consolidative SABR at our institution were reviewed. SABR was delivered in 1-5 fractions of 5-18 Gray. Kaplan-Meier estimates of local progression-free survival (LPFS), biochemical progression-free survival (bPFS; PSA nadir + 2), distant progression-free survival (DPFS), and time-to-next intervention (TTNI) were calculated. RESULTS: In total, 66 OPC patients were identified with consolidative SABR delivered to 134 metastases: 89 bone, 40 nodal, and 5 viscera. The majority of men (49/66) had hormone-sensitive prostate cancer (HSPC). Crude grade 1 and 2 acute toxicities were 36% and 11%, respectively, with no ≥ grade 3 toxicity. At 1 year, LPFS was 92% and bPFS and DPFS were 69%. Of the 18 men with HSPC who had deferred hormone therapy , 11 (56%) remain disease free following SABR (1-year ADT-FS was 78%). In 17 castration-resistant men, 11 had > 50% prostate-specific antigen (PSA) declines with 1-year TTNI of 30%. CONCLUSIONS: Consolidative SABR in OPC is feasible and well tolerated. The heterogeneity and small size of our series limit extrapolation of clinically meaningful outcomes following consolidative SABR in OPC, but our preliminary data suggest that this approach warrants continued prospective study.

Open-Label Single-Arm Phase II Trial of Sorafenib Therapy with Drug-eluting Bead Transarterial Chemoembolization in Patients with Unresectable Hepatocellular Carcinoma: Clinical Results.

PURPOSE: To determine the efficacy of combined continuous sorafenib therapy and drug-eluting bead (DEB) transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This study was conducted in accordance with the principles of the Declaration of Helsinki, and all patients provided written informed consent prior to enrollment. Inclusion criteria included unresectable HCC, a treatment naïve status, an Eastern Cooperative Oncology Group score of 0-1, and a Child-Pugh score of A-B7. Continuous sorafenib therapy (400 mg twice daily) was started 1 week before the first round of DEB TACE, which was performed in 6-week cycles. Up to four rounds of DEB TACE therapy were allowed on demand within 6 months. The primary end point was safety. Secondary end points were time to progression (TTP), response rate, and overall survival (OS) and were stratified by the Barcelona Clinic Liver Cancer (BCLC) stage and the duration of sorafenib therapy. OS was assessed with Kaplan-Meier estimates, and the Mantel-Cox log-rank test was used to determine differences in survival. A two-sided P value of less than .05 was considered to indicate a significant difference. The study was approved by the Johns Hopkins institutional review board and remained open from March 2009 to January 2012. RESULTS: Fifty patients--of whom 76% were male, 92% had a Child-Pugh score of A, and 62% had BCLC stage C disease--underwent a median of three cycles of therapy. The 6-month disease control rate (defined as complete response plus partial response plus stable disease) was 94% according to the response evaluation criteria in solid tumors. Median TTP and OS were 13.9 and 20.4 months, respectively, and 81% of toxicities were grades 1-2. There was one death that was possibly treatment related. CONCLUSION: Combined continuous sorafenib therapy and on-demand DEB TACE provided excellent local disease control and did not lead to multiplicative toxicities. Long-term administration of sorafenib therapy in combination with DEB TACE may have a survival benefit in patients with advanced HCC.

Volumetric assessment of tumour response using functional MR imaging in patients with hepatocellular carcinoma treated with a combination of doxorubicin-eluting beads and sorafenib.

OBJECTIVE: To prospectively assess treatment response using volumetric functional magnetic resonance imaging (MRI) metrics in patients with hepatocellular carcinoma (HCC) treated with the combination of doxorubicin-eluting bead-transarterial chemoembolization (DEB TACE) and sorafenib. METHODS: A single center study enrolled 41 patients treated with systemic sorafenib, 400 mg twice a day, combined with DEB TACE. All patients had a pre-treatment and 3-4 week post-treatment MRI. Anatomic response criteria (RECIST, mRECIST and EASL) and volumetric functional response (ADC, enhancement) were assessed. Statistical analyses included paired Student's t-test, Kaplan-Meier curves, Cohen's Kappa, and multivariate cox proportional hazard model. RESULTS: Median tumour size by RECIST remained unchanged post-treatment (8.3 ± 4.1 cm vs. 8.1 ± 4.3 cm, p = 0.44). There was no significant survival difference for early response by RECIST (p = 0.93). EASL and mRECIST could not be analyzed in 12 patients. Volumetric ADC increased significantly (1.32 × 10(-3) mm(2)/sec to 1.60 × 10(-3) mm(2)/sec, p < 0.001), and volumetric enhancement decreased significantly in HAP (38.2% to 17.6%, p < 0.001) and PVP (76.6% to 41.2%, p < 0.005). Patients who demonstrated ≥ 65% decrease PVP enhancement had significantly improved overall survival compared to non-responders (p < 0.005). CONCLUSION: Volumetric PVP enhancement was demonstrated to be significantly correlated with survival in the combination of DEB TACE and sorafenib for patients with HCC, enabling precise stratification of responders and non-responders. KEY POINTS: • PVP enhancement is significantly correlated with survival in responders (p < 0.005). • There was no significant survival difference for early response using RECIST (p = 0.93). • mRECIST or EASL could not assess tumour response in 29% of patients.

Response stratification and survival analysis of hepatocellular carcinoma patients treated with intra-arterial therapy using MR imaging-based arterial enhancement fraction.

PURPOSE: To investigate the feasibility that arterial enhancement fraction (AEF) is associated with response of hepatocellular carcinoma (HCC) following intra-arterial therapy (IAT) and to compare AEF response with currently used tumor response metrics. MATERIALS AND METHODS: The AEF, Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) of the largest treated index lesion and AEF of the tumor-free hepatic parenchyma was measured on representative axial images in 131 patients (108 male; mean age, 61.9 years). Clinical measures and patient survival were assessed. Statistical analysis included Wilcoxon signed-rank test and the COX proportional hazards model. RESULTS: After IAT, the mean AEF of the tumor decreased by 22% (66.7-44.8%, P < 0.0001), while the mean AEF of the tumor-free parenchyma remained unchanged (27.2-26.5%, P = 0.50). Median survival of all 131 patients with liver cancer was 17 months. Patients were stratified into AEF-responders if they had an AEF-decrease ≥35% (AEF-responders: n = 67; AEF-nonresponders: n = 64). AEF-responders survived longer than nonresponders (34.8 months versus 10.8 months, hazard ratio = 0.39; P < 0.0001). Responders according to RECIST, mRECIST, or EASL did not survive significantly longer compared with nonresponders. CONCLUSION: Evaluating the AEF values based on tri-phasic MRI is associated with tumor response in patients with unresectable HCC treated with IAT.

Phase 2 trial of concurrent bevacizumab and transhepatic arterial chemoembolization in patients with unresectable hepatocellular carcinoma.

BACKGROUND: Vascular endothelial growth factor is up-regulated in hepatocellular carcinoma (HCC) and is further up-regulated after transhepatic arterial chemoembolization. The authors of this report conducted a phase 2 trial to evaluate the safety and efficacy of bevacizumab combined with chemoembolization in patients with unresectable HCC. METHODS: Patients who had an Eastern Cooperative Oncology Group performance of status 0 to 2, a Child-Pugh score of A or B, and Barcelona Clinic Liver Cancer stage B or C HCC were eligible. Treatment consisted of bevacizumab every 2 weeks and chemoembolization during the third week of a 6-week cycle for up to 3 cycles over 6 months. The primary endpoints were safety and efficacy. RESULTS: Twenty-five patients received chemoembolization and bevacizumab. The most common grade 3 and 4 events after the first treatment cycle were leukocytopenia (12%), fatigue (12%), and hyponatremia (12%). Serious toxicities that had a known association with bevacizumab were observed in 4 patients. Thirty-day mortality was 0%. The median time to tumor progression for the targeted lesions was not reached, and overall survival was 10.8 months. The objective response rate was 60% using enhancement response evaluation criteria, and the disease control rate was 100%. CONCLUSIONS: Concurrent treatment with bevacizumab and chemoembolization was safe in carefully selected patients and demonstrated antitumor activity in patients with unresectable HCC. These results support the further development of bevacizumab combined with chemoembolization as a treatment for unresectable HCC.

Neuroendocrine liver metastasis treated by using intraarterial therapy: volumetric functional imaging biomarkers of early tumor response and survival.

PURPOSE: To determine if volumetric changes of diffusion-weighted and contrast material-enhanced magnetic resonance (MR) imaging can help assess early tumor response to intraarterial therapy (IAT) in neuroendocrine liver metastasis (NELM). MATERIALS AND METHODS: This retrospective single-center comprehensive imaging analysis was performed in compliance with HIPAA and was institutional review board approved. Informed patient consent was waived. Seventy-one patients (39 men; mean age, 62.3 years) with NELM treated with IAT were analyzed retrospectively. MR studies were performed before and 3-4 weeks after therapy. The index lesion was segmented to provide volumetric functional analysis of apparent diffusion coefficient (ADC) and contrast-enhanced MR imaging in the hepatic arterial phase (HAP) and portal venous phase (PVP). Tumor response was defined as increase in volumetric ADC of 15% or greater and decrease in volumetric enhancement of 25% or greater during the HAP or of 50% or greater during the PVP. Patient overall survival was the primary end point after therapy initiation. Univariate analysis included Kaplan-Meier survival curves. The Cox proportional hazards regression model was used to detect interactions between volumetric ADC and contrast-enhanced MR imaging and to calculate the hazard ratio. RESULTS: There was significant increase in mean volumetric ADC (27%, P < .0001) and significant decrease in mean volumetric enhancement during the HAP (-25.3%, P < .0001) and the PVP (-22.4%, P < .0001) in all patients. Patients who had 15% or greater volumetric ADC increase (n = 49) after therapy had better prognosis than those who had less than 15% increase in volumetric ADC (n = 22) (log-rank test, P < .002). Patients who had 25% or greater decrease in volumetric arterial enhancement (n = 40) or 50% or greater decrease in venous enhancement (n = 18) had better prognosis than those who had less than 25% decrease in volumetric arterial enhancement (n = 31) or less than 50% decrease in venous enhancement (n = 53) (log-rank test, P < .02). CONCLUSION: Volumetric functional MR imaging criteria may act as biomarkers of early response, indicating that these criteria may be important to incorporate in future NELM clinical trials.

Unresectable hepatocellular carcinoma: MR imaging after intraarterial therapy. Part I. Identification and validation of volumetric functional response criteria.

PURPOSE: To identify and validate the optimal thresholds for volumetric functional MR imaging response criteria to predict overall survival after intraarterial treatment (IAT) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Institutional review board approval and waiver of informed consent were obtained. A total of 143 patients who had undergone MR imaging before and 3-4 weeks after the first cycle of IAT were included. MR imaging analysis of one representative HCC index lesion was performed with proprietary software after initial treatment. Subjects were randomly divided into training (n = 114 [79.7%]) and validation (n = 29 [20.3%]) data sets. Uni- and multivariate Cox models were used to determine the best cutoffs, as well as survival differences, between response groups in the validation data set. RESULTS: Optimal cutoffs in the training data set were 23% increase in apparent diffusion coefficient (ADC) and 65% decrease in volumetric enhancement in the portal venous phase (VE). Subsequently, 25% increase in ADC and 65% decrease in VE were used to stratify patients in the validation data set. Comparison of ADC responders (n = 12 [58.6%]) with nonresponders (n = 17 [34.5%]) showed significant differences in survival (25th percentile survival, 11.2 vs 4.9 months, respectively; P = .008), as did VE responders (n = 9 [31.0%]) compared with nonresponders (n = 20 [69.0%]; 25th percentile survival, 11.5 vs 5.1 months, respectively; P = .01). Stratification of patients with a combination of the criteria resulted in significant differences in survival between patients with lesions that fulfilled both criteria (n = 6 [20.7%]; too few cases to determine 25th percentile), one criterion (n = 9 [31.0%]; 25th percentile survival, 6.0 months), and neither criterion (n = 14 [48.3%]; 25th percentile survival, 5.1 months; P = .01). The association between the two criteria and overall survival remained significant in a multivariate analysis that included age, sex, Barcelona Clinic for Liver Cancer stage, and number of follow-up treatments. CONCLUSION: After IAT for unresectable HCC, patients can be stratified into significantly different survival categories based on responder versus nonresponder status according to MR imaging ADC and VE cutoffs.

Unresectable hepatocellular carcinoma: MR imaging after intraarterial therapy. Part II. Response stratification using volumetric functional criteria after intraarterial therapy.

PURPOSE: To assess whether volumetric functional magnetic resonance (MR) results 3-4 weeks after initial intraarterial therapy can aid accurate distinction between responders and nonresponders, to determine whether overall survival (OS) is improved, and to compare volumetric functional MR response with anatomic response criteria (Response Evaluation Criteria in Solid Tumors [RECIST], modified RECIST [mRECIST], European Association for the Study of the Liver [EASL]), as well as α1-fetoprotein [AFP] level. MATERIALS AND METHODS: In this single-institution HIPAA-compliant retrospective, institutional review board-approved study, informed consent was waived; 143 patients with hepatocellular carcinoma underwent intraarterial therapy between October 2005 and February 2011. Volumetric functional MR response (25% or more increase in apparent diffusion coefficient, 65% or more decrease in enhancement) was stratified as follows: Dual-parameter responders fulfilled both criteria, single-parameter responders fulfilled one criterion, and those with stable disease (SD) fulfilled neither. RECIST, mRECIST, EASL, and AFP response criteria were determined. Kaplan-Meier technique, log-rank tests, and the Cox proportional hazards model were used to test whether OS was different per response. RESULTS: OS differed significantly between single-parameter responders and dual-parameter responders (P = .01) and between single-parameter responders and those with SD (P = .001). Dual-parameter responders' response improved OS compared with single-parameter responders; risk of death decreased (hazard ratio [HR] = 0.28, P = .01). In those with SD compared with single-parameter responders, risk of death increased (HR = 2.09, P = .001). RECIST, mRECIST, and EASL stratification was short of significant; most lesions were classified as SD. Baseline AFP level increased in 55 patients; AFP responders versus AFP nonresponders had decreased risk of death (HR = 0.36, P = .002). Agreement between anatomic response criteria and volumetric functional MR findings (κ = 0.06-0.12) and between AFP response and imaging criteria (κ = -0.04 to 0.14) was low. CONCLUSION: Volumetric functional MR response 3-4 weeks after initial intraarterial therapy showed improved OS. Volumetric functional MR was superior to current imaging (RECIST, mRECIST, and EASL) and biochemical (AFP level) response criteria.

Multi-timepoint imaging with PSMA-targeted [18F]F-Florastamin PET/CT: lesion detection and comparison to conventional imaging.

OBJECTIVE: The aims of this study were to investigate the utility of [18F]F-Florastamin, a novel prostate-specific membrane antigen (PSMA)-targeted PET radiotracer with facile radiochemistry, relative to the conventional imaging for the detection of sties of disease and evaluate the effect of multi-timepoint imaging with [18F]F-Florastamin PET on lesion detectability. METHODS: Eight prostate cancer patients with known or suspected recurrence who underwent [18F]F-Florastamin PET/CT at 1-h and 2-h imaging time-points were included in this prospective pilot study. [18F]F-Florastamin PET images were interpreted visually and quantitatively at both time points and compared with CIM. RESULTS: [18F]F-Florastamin PET was superior to CT in the detection of active osseous metastases and small-sized metastatic lymph nodes that do not fall under the anatomic imaging size criteria for metastasis. Multi-timepoint imaging showed a significant reduction in the blood pool, bone marrow and muscular uptake, and increase in liver uptake over time. There is a significant improvement in tumor-to-background ratio (TBR) at the 2-h imaging time-point (P = 0.04). The mean percentage change in TBR at 2-h was 21% (SD = 0.31). CONCLUSIONS: [18F]F-Florastamin is a promising new radioligand for PSMA-targeted PET with suitable lesion detectability and high TBR at both time points.

Intrahepatic cholangiocarcinoma treated with local-regional therapy: quantitative volumetric apparent diffusion coefficient maps for assessment of tumor response.

PURPOSE: To evaluate volumetric changes in apparent diffusion coefficient (ADC) and contrast material enhancement on contrast-enhanced (CE) magnetic resonance (MR) images in hepatic arterial and portal venous phases for assessing early response in cholangiocarcinoma treated with transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: Twenty-nine patients with unresectable cholangiocarcinoma, including 11 men (mean age, 60 years; standard deviation, 16.8) and 18 women (mean age, 63 years; standard deviation, 11.5) were included in this retrospective institutional review board-approved, HIPAA-compliant study; informed consent was waived. Sixty-nine TACE procedures were performed during the observational time (range, one to five TACE sessions). No patients received another form of therapy after treatment with TACE. MR Imaging was performed before and 3-4 weeks after TACE, and images were analyzed with a semiautomatic volumetric software package. Patients were stratified as responders and nonresponders on the basis of overall survival (OS) as the primary end point. Differences between responders and nonresponders were analyzed with paired t tests, and OS was calculated with the Kaplan-Meier method. Significant differences were analyzed with the log-rank test. RESULTS: Mean volumetric ADC increased from 1.54×10(-3) mm2/sec to 1.92×10(-3) mm2/sec (P<.0001), with no significant decrease in mean volumetric enhancement in hepatic arterial (40.6% vs 37.5%, P=.546) and portal venous (79.0% vs 70.0%, P=.105) phases. Patients who demonstrated improved survival of 10 months or more had a significant increase in mean volumetric ADC and volumetric ADC above the threshold level of 1.60×10(-3) mm2/sec (P<.002). Patients with 45% or greater (n=21; log-rank test, P<.02) and 60% or greater (n=12; log-rank test, P<.009) ADC changes for the whole tumor volume demonstrated better OS compared with patients in whom these ADC changes were not achieved. CONCLUSION: Patients with percentage tumor volume increase in ADC of 45% or greater and 60% or greater above the threshold level of 1.60×10(-3) mm2/sec had favorable response to therapy and improved survival.

Islet cell liver metastases: assessment of volumetric early response with functional MR imaging after transarterial chemoembolization.

PURPOSE: To assess early response to transarterial chemoembolization by using volumetric functional magnetic resonance (MR) imaging in patients with islet cell liver metastases (ICLMs). MATERIALS AND METHODS: This retrospective institutional review board-approved HIPAA-compliant study included 215 ICLMs in 26 patients (15 men, 11 women; mean age, 59.7 years; age range, 37-79 years). Volumetric measurements were performed by an experienced radiologist on diffusion-weighted and contrast material-enhanced MR images at baseline and 1-month follow-up. Measurements included mean change (three-dimensional [3D] mean apparent diffusion coefficient [ADC], 3D mean enhancement) and percentage of tumor with change above a predetermined threshold (3D threshold ADC, 3D threshold enhancement). Response by volumetric measurements at 1-month follow-up was compared with Response Evaluation Criteria in Solid Tumors (RECIST) at 6-month follow-up. Lesions that had complete or partial response were considered responders, while those with stable or progressive disease were considered nonresponders. Statistical analysis included the t test, receiver operating characteristic (ROC) curve analysis, and logistic regression analysis. RESULTS: RECIST criteria at 6-month follow-up indicated 78 (36.3%) lesions responded, while 137 (63.7%) did not. The increase in 3D mean ADC was significantly higher in responders than in nonresponders (median, 26.2% vs 10.9%; P<.001). The 3D threshold ADC was 71.1% in responders and 47.6% in nonresponders (P<.001). Decrease in 3D mean arterial enhancement (AE) was significantly higher in responders than in nonresponders (median, 40.5% vs 18.0%; P<.001). Decrease in 3D mean venous enhancement (VE) was significantly higher in responders than in nonresponders (median, 28.0% vs 10.0%; P<.001). The 3D threshold VE and 3D threshold AE did not differ between responders and nonresponders. In unadjusted logistic regression analyses, 3D mean ADC and 3D threshold ADC had the highest odds ratio (1.02 and 1.03, respectively) and the largest area under the ROC curve (0.698 and 0.695, respectively). CONCLUSION: Volumetric functional MR imaging could be used to predict early response of hepatic ICLMs to therapy and to distinguish between responders and nonresponders.

Quantitative and volumetric European Association for the Study of the Liver and Response Evaluation Criteria in Solid Tumors measurements: feasibility of a semiautomated software method to assess tumor response after transcatheter arterial chemoembolization.

PURPOSE: To show that hepatic tumor volume and enhancement pattern measurements can be obtained in a time-efficient and reproducible manner on a voxel-by-voxel basis to provide a true three-dimensional (3D) volumetric assessment. MATERIALS AND METHODS: Magnetic resonance (MR) imaging data obtained from 20 patients recruited for a single-institution prospective study were retrospectively evaluated. All patients had a diagnosis of hepatocellular carcinoma (HCC) and underwent drug-eluting beads (DEB) transcatheter arterial chemoembolization for the first time. All patients had undergone contrast-enhanced MR imaging before and after DEB transcatheter arterial chemoembolization; poor image quality excluded 3 patients, resulting in a final count of 17 patients. Volumetric RECIST (vRECIST) and quantitative EASL (qEASL) were measured, and segmentation and processing times were recorded. RESULTS: There were 34 scans analyzed. The time for semiautomatic segmentation was 65 seconds±33 (range, 40-200 seconds). vRECIST and qEASL of each tumor were computed<1 minute for each. CONCLUSIONS: Semiautomatic quantitative tumor enhancement (qEASL) and volume (vRECIST) assessment is feasible in a workflow-efficient time frame. Clinical correlation is necessary, but vRECIST and qEASL could become part of the assessment of intraarterial therapy for interventional radiologists.

RNA profiling of circulating tumor cells systemically captured from diagnostic leukapheresis products in prostate cancer patients.

The application of circulating tumor cells (CTCs) in both clinical practice and research has been continuously limited by the rare number of targets that can be found in a tube of peripheral blood. Diagnostic leukapheresis (DLA) was used to increase the sampling volume. AdnaTest was used to process the whole leukopak, and the RNAs of captured CTCs was then profiled by NanoString nCounter platform. Spike-in experiments and leukopaks from patients with metastatic prostate cancer were used to validate this new strategy. The whole leukopak was further concentrated five times to reduce the total volume from 150 â€‹mL to 30 â€‹mL, which enabled it to be processed by 3 separate AdnaTest kits. The spike-in experiment demonstrated a reliable capture when there were more than 100 cancer cells/10 â€‹mL of concentrated leukopak. In 1 out of 5 real patient samples, CTCs were only detected in the leukopak, but not in peripheral blood. The RNA profiling of DLA CTCs indicated a more aggressive phenotype of CTCs occurred when the patient was experiencing a disease relapse, even when the serum prostate specific antigen (PSA) level was still relatively low and CTCs in peripheral blood were not detectable. We established a new protocol, integrating DLA, AdnaTest and NanoString nCounter technology, to profile RNAs from CTCs captured from a large blood screening volume. The new protocol can process the whole leukopak with sensitive CTC capture. The RNA profiling of CTCs can provide valuable information for disease monitoring.

Interim analysis of companion, prospective, phase II, clinical trials assessing the efficacy and safety of multi-modal total eradication therapy in men with synchronous oligometastatic prostate cancer.

Multimodal therapies were combined to eradicate the primary site, metastatic, and micrometastatic disease in men with newly diagnosed, synchronous, oligometastatic prostate cancer. The investigation included companion, phase II studies: total eradication therapy-1 (TET-1) for those treatment-naïve and total eradication therapy-2 (TET-2) for those post-prostatectomy. The treatment-naive protocol included androgen deprivation and docetaxel (with concurrent abiraterone added in a protocol amendment), followed by a prostatectomy, adjuvant radiation (if positive margins, T3/4, or detectable PSA), and metastasis-directed therapy. The post-prostatectomy protocol assigned the same therapies (omitting the prostatectomy). The primary endpoint was an undetectable PSA with recovered testosterone. The safety boundaries were ≤ 50% for grade 3/4 neutropenic and ≤ 20% for grade 3/4 surgical- and radiation-related toxicities. Enrollment was planned for 60 patients per protocol, to detect a PSA progression-free survival ≥ 32%, as compared to 15% in a historic control. Enrollment closed early. An interim analysis was conducted once > 50% of patients were evaluable for the primary endpoint. The primary endpoint duration was assessed by median progression-free survival. 52 patients were enrolled (n = 26 per protocol). Medium follow-up was 30.3 months. 80% (24/30) of evaluable patients achieved the primary endpoint; the duration was not reached. Of those not evaluable, 77% (17/22) had not reached the endpoint and 23% (5/22) had exited. There were 8% (4/52) grade 3/4 neutropenic and 2% (1/48) grade 3/4 surgical or radiation-induced toxicities. Interim findings suggest the trials' endpoints were met, advancing the concept of total eradication therapy in men with oligometastatic prostate cancer.

Complications of loco-regional therapy in the liver-spectrum of imaging findings by CT and MRI.

The aim of this study was to discuss the appearance of common complications from loco-regional therapy of primary and secondary malignant liver neoplasms on cross-sectional imaging. Knowledge of common complications is important for the safe performance of loco-regional therapy (LRT) and for the interpretation of post-LRT follow-up imaging. With careful patient selection, LRT represents an effective and safe treatment of primary and secondary hepatic malignancies; however, complications related to LRT methods infrequently lead to additional morbidity.

Peripheral androgen blockade in men with castrate-sensitive biochemical recurrent prostate cancer.

The aim of the study was to evaluate the feasibility of utilizing peripheral androgen blockade in men with biochemical recurrent castrate-sensitive prostate cancer. A registration study to track outcomes of men with biochemical recurrent castrate-sensitive prostate cancer treated with peripheral androgen blockade utilizing concomitant administration of finasteride and bicalutamide. Men were on intermittent peripheral blockade for a median 20.2 months, continuous peripheral blockade for a median 6.8 months, intermittent triple dose peripheral androgen blockade for a median 10.7 months, and continuous triple dose peripheral androgen blockade for 4.4 months before failing therapy. Six men (21%) had additional therapies during treatment that included metastasis-directed therapy (5/37, 14%), systemic Lu-177 (2/37, 5%), and salvage RT (1/37, 3%). The median time to progression, which includes time from initiation through all therapies to the initiation of ADT, was 37.6 months (IQR 20-74.7). From the start of PAB, median time to castrate resistance was 49.8 months (IQR 40.9-NR). After starting ADT, median time to castrate resistance was 8.8 months (IQR 4.6-17.7). Our data support the exploration of PAB as a treatment option in carefully selected patients who present with biochemical recurrence after failure of definitive local therapy for prostate cancer.

Prospective Comparison of PET Imaging with PSMA-Targeted 18F-DCFPyL Versus Na18F for Bone Lesion Detection in Patients with Metastatic Prostate Cancer.

Bone metastases in prostate cancer (PCa) have important prognostic significance, and imaging modalities used for PCa staging should have high sensitivity for detecting such lesions. Prostate-specific membrane antigen (PSMA)-targeted PET radiotracers are promising new agents for imaging PCa. We undertook a head-to-head comparison of PSMA-targeted 2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) PET to Na18F PET to determine which modality was more sensitive for the detection of lesions suggestive of bone metastases in a group of patients with metastatic PCa. Methods: Patients with progressive, metastatic PCa were prospectively imaged with both 18F-DCFPyL and Na18F PET/CT, with both scans occurring within 24 h of each other. A consensus 2-reader central review was performed to identify all bone lesions suggestive of sites of PCa involvement on both scans, and maximized SUVs corrected for body weight (SUVmax) and lean body mass (SULmax) were recorded. Soft-tissue lesions were also noted on both scans, and SUVmax, SULmax, and PSMA reporting and data system (RADS) version 1.0 scores were recorded. Data from the 2 scans were compared using a generalized estimating equation. Results: In total, 16 patients meeting all inclusion criteria were enrolled in this study, and 15 of the 16 (93.8%) were imaged with both PET radiotracers. In total, 405 bone lesions suggestive of sites of PCa were identified on at least 1 scan. On 18F-DCFPyL PET/CT, 391 (96.5%) were definitively positive, 4 (1.0%) were equivocally positive, and 10 (2.5%) were negative. On Na18F PET/CT, the corresponding values were 388 (95.8%), 4 (1.0%), and 13 (3.2%). Of the definitively negative lesions on 18F-DCFPyL PET, 8 of 10 (80.0%) were sclerotic and 2 of 10 (20.0%) were infiltrative or marrow-based. Additionally, 12 of 13 (92.3%) of the definitively negative lesions on Na18F PET were infiltrative or marrow-based and 1 of 13 (7.7%) was lytic. Also identified were 78 PSMA-RADS-4, 17 PSMA-RADS-5, and 1 PSMA-RADS-3C soft-tissue lesions. Conclusion: PET/CT imaging using 18F-DCFPyL and Na18F PET had nearly identical sensitivities for the detection of bone lesions in patients with metastatic PCa. As would be expected, PSMA-targeted PET provides more information on soft-tissue disease. There may be little additional value to imaging PCa patients with Na18F after a PSMA-targeted PET scan has already been performed.

Unresectable hepatocellular carcinoma: serial early vascular and cellular changes after transarterial chemoembolization as detected with MR imaging.

PURPOSE: To prospectively assess serial changes in contrast material-enhanced and diffusion-weighted (DW) magnetic resonance (MR) imaging values within 1 month after transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Institutional review board approval was obtained for this prospective HIPAA-compliant study. MR imaging was performed before and within 24 hours after TACE in 24 patients with HCC (21 male, three female; mean age, 59 years and 62 years, respectively). Serial MR imaging was subsequently performed 1, 2, 3, and 4 weeks after therapy. The imaging protocol included fast spin-echo T2-weighted MR imaging, breath-hold DW echo-planar MR imaging, and breath-hold unenhanced and contrast-enhanced T1-weighted three-dimensional fat-suppressed gradient-recalled-echo MR imaging in the arterial and portal venous phases. Tumor size, enhancement, and apparent diffusion coefficient (ADC) values were recorded before and sequentially after treatment. Regression models for the correlated data were used to assess changes in these parameters over time after TACE. RESULTS: Mean tumor size was 7.5 cm and was unchanged up to 4 weeks after therapy. Reduction in tumor enhancement in the arterial phase occurred immediately after TACE, with a consistent reduction occurring 1-3 weeks after therapy (P = .001). Reduction in tumor enhancement in the portal venous phase also occurred immediately after TACE, with a consistent reduction occurring 1-3 weeks after therapy (P = .0003). The increase in tumor ADC value was significant 1-2 weeks after therapy (P = .004), borderline significant 3 weeks after therapy, and insignificant 24 hours and 4 weeks after therapy. CONCLUSION: Significant reduction in tumor enhancement occurred within 24 hours after TACE and persisted up to 4 weeks after TACE. Lesser changes in the ADC value appeared 1 week after TACE, persisted through 2 weeks after TACE, and became less apparent 3 and 4 weeks after TACE. No change in tumor size was recorded during the follow-up period.