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Adrenocortical carcinoma (ACC) is a rare malignancy with an overall unfavorable prognosis. Clinicians treating patients with ACC have noted accelerated growth in metastatic liver lesions that requires rapid intervention compared to other metastatic locations. This study measured and compared the growth rates of metastatic ACC lesions in the lungs, liver, and lymph nodes using volumetric segmentation. A total of 12 patients with metastatic ACC (six male; six female) were selected based on their medical history. Computer tomography (CT) exams were retrospectively reviewed and a sampling of ≤5 metastatic lesions per organ were selected for evaluation. Lesions in the liver, lung, and lymph nodes were measured and evaluated by volumetric segmentation. Statistical analyses were performed to compare the volumetric growth rates of the lesions in each organ system. In this cohort, 5/12 had liver lesions, 7/12 had lung lesions, and 5/12 had lymph node lesions. A total of 92 lesions were evaluated and segmented for lesion volumetry. The volume doubling time per organ system was 27 days in the liver, 90 days in the lungs, and 95 days in the lymph nodes. In this series of 12 patients with metastatic ACC, liver lesions showed a faster growth rate than lung or lymph node lesions.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) may occur in 30% to 90% of patients with multiple endocrine neoplasia type 1 (MEN1). However, only 1% of GEP-NETs are grade 3 (G3). Given the rarity of these aggressive tumors, treatment of advanced G3 GEP-NETs in MEN1 is based on the treatment guidelines for sporadic GEP-NETs. We report a 43-year-old male with germline MEN1 followed at our institution, with clinical features including hyperparathyroidism, a nonfunctional pancreatic NET, and Zollinger–Ellison syndrome. On routine surveillance imaging at age 40, computed tomography/positron emission tomography imaging showed 2 arterially enhancing intraluminal masses on the medial aspect of the gastric wall. Anatomical imaging confirmed 2 enhancing masses within the pancreas and a rounded mass-like thickening along the lesser curvature of the stomach. The gastric mass was resected, and pathology reported a well-differentiated G3 NET with a Ki-67 >20%. The patient continued active surveillance. Eighteen months later cross-sectional imaging studies showed findings consistent with metastatic disease within the right hepatic lobe and bland embolization was done. On follow-up scans, including 68Ga-DOTATATE (68Ga-DOTA(0)-Tyr(3)-octreotate) imaging, interval increase in number and avidity of metastatic lesions were compatible with disease progression. Given a paucity of treatment recommendations for G3 tumors in MEN1, the patient was counseled based on standard NET treatment guidelines and recommended 177Lu-DOTATATE treatment. PRRT (peptide receptor radionuclide therapy) with 177Lu-DOTATATE (177Lu-tetraazacyclododecanetetraacetic acid-octreotide) is an important therapeutic modality for patients with somatostatin receptor–positive NETs. However, prospective studies are needed to understand the role of PRRT in G3 NETs.

Background To evaluate outcomes and survival rates in patients with metastatic adrenocortical carcinoma (ACC) who were treated with image‐guided locoregional treatments (IGLTs). Purpose To evaluate the overall survival (OS) and clinical impact of IGLT in the management of patients with advanced metastatic ACC. Methods Retrospective review of 39 patients treated with IGLT between 1999 and 2018 was performed. Short‐ and long‐term efficacy of treatments were defined based upon imaging and clinical data. Subgroup survival analysis was performed on patients with metastatic disease at diagnosis (N = 17) and compared with the same stage group from the most recent National Cancer Database (NCDB) report. Statistical analysis was performed using Cox proportional hazards model. Results Treatments were performed at different anatomic sites including liver (N = 46), lung (N = 14), retroperitoneum (N = 5), bone (N = 4), subcutaneous (N = 2), and intracaval (N = 1). Radiofrequency, microwave, cryoablation, or a combination of two modalities (45, 18, 3, 3, respectively) were used in 69 ablation sessions. Intra‐arterial procedures were performed in 12 patients in 18 treatment cycles (range 1–3 per patient). As of a 2019 analysis, 11 patients were alive with a mean follow‐up of 169 months (range 63–292 months) from diagnosis. Two‐ and 5‐year OS rates for all patients were 84.5% and 51%, respectively, and 76.5% and 59% for patients with metastatic disease at diagnosis (N = 17). This compares favorably with an NCDB report of 35% 5‐year survival rate for patients with metastatic disease. Female gender and longer time from diagnosis to first IGLT were found to be predictors of prolonged survival with hazard ratios of 0.23 (p, Treatment of patients with advanced adrenocortical carcinoma with image‐guided locoregional therapies may be associated with prolonged survival, especially in females. Challenging clinical decisions for this rare disease with few effective treatment options may be informed by our two‐decade experience with locoregional therapies. Such a combined approach with surgery, ablation, and/or embolization may be associated with better than previously reported long‐term patient survivals.

Background Prostate cancer recurrence is found in up to 40% of men with prior definitive (total prostatectomy or whole-prostate radiation) treatment. Prostate-specific membrane antigen PET agents such as 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) may improve detection of recurrence compared with multiparametric MRI; however, histopathologic validation is lacking. Purpose To determine the sensitivity, specificity, and positive predictive value (PPV) of 18F-DCFPyL PET/CT based on histologic analysis and to compare with pelvic multiparametric MRI in men with biochemically recurrent prostate cancer. Materials and Methods Men were prospectively recruited after prostatectomy and/or radiation therapy with rising prostate-specific antigen level (median, 2.27 ng/mL; range, 0.2-27.45 ng/mL) and a negative result at conventional imaging (bone scan and/or CT). Participants underwent 18F-DCFPyL PET/CT imaging and 3.0-T pelvic multiparametric MRI. Statistical analysis included Wald and modified χ2 tests. Results A total of 323 lesions were visualized in 77 men by using 18F-DCFPyL or multiparametric MRI, with imaging detection concordance of 25% (82 of 323) when including all lesions in the MRI field of view and 53% (52 of 99) when only assessing prostate bed lesions. 18F-DCFPyL depicted more pelvic lymph nodes than did MRI (128 vs 23 nodes). Histologic validation was obtained in 80 locations with sensitivity, specificity, and PPV of 69% (25 of 36; 95% confidence interval [CI]: 51%, 88%), 91% (40 of 44; 95% CI: 74%, 98%), and 86% (25 of 29; 95% CI: 73%, 97%) for 18F-DCFPyL and 69% (24 of 35; 95% CI: 50%, 86%), 74% (31 of 42; 95% CI: 42%, 89%), and 69% (24 of 35; 95% CI: 50%, 88%) for multiparametric MRI (P = .95, P = .14, and P = .07, respectively). In the prostate bed, sensitivity, specificity, and PPV were 57% (13 of 23; 95% CI: 32%, 81%), 86% (18 of 21; 95% CI: 73%, 100%), and 81% (13 of 16; 95% CI: 59%, 100%) for 18F-DCFPyL and 83% (19 of 23; 95% CI: 59%, 100%), 52% (11 of 21; 95% CI: 29%, 74%), and 66% (19 of 29; 95% CI: 44%, 86%) for multiparametric MRI (P = .19, P = .02, and P = .17, respectively). The addition of 18F-DCFPyL to multiparametric MRI improved PPV by 38% overall (P = .02) and by 30% (P = .09) in the prostate bed. Conclusion Findings with 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (18F-DCFPyL) were histologically validated and demonstrated high specificity and positive predictive value. In the pelvis, 18F-DCFPyL depicted more lymph nodes and improved positive predictive value and specificity when added to multiparametric MRI. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Zukotynski and Rowe in this issue.

Background To evaluate the therapeutic efficacy, safety and overall clinical outcome of multiprobe stereotactic RF ablation (SRFA) as first-line treatment of HCC recurrence after hepatic resection (HR). Study design In this retrospective single-center study, 34 consecutive patients with previous HR were treated by SRFA between 2006 and 2018 for 140 HCCs in 60 ablation sessions. Results The median treated tumor size was 3.0 cm (range 0.5–10 cm). SRFA was primarily successful for 133/140 (95%) tumors. Four tumors were successfully retreated, resulting in a secondary technical efficacy rate of 97.9%. Local tumor recurrence developed in 4 of 140 tumors (2.9%). The major complication rate was 4.8% (3 of 60 ablations). No periprocedural deaths occurred. The overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 94.0%, 70.2%, and 53.3%, respectively, with a median OS of 69.1 months (95% CI 18.8–119.3). The disease-free survival (DFS) was 52.6%, 19.7% and 15.8%, at 1-, 3- and 5- years, respectively, with a median DFS of 12.8 months (95% CI 9.0–28.9). Conclusion Stereotactic RFA is a safe, feasible and useful option in the management of recurrent HCC following HR with low morbidity paired with good clinical outcome.

PURPOSE National Cancer Institute (NCI)–sponsored clinical trial network studies frequently require biopsy specimens for pharmacodynamic and molecular biomarker analyses, including paired pre- and post-treatment samples. The purpose of this meeting of NCI-sponsored investigators was to identify local institutional standard procedures found to ensure quantitative and qualitative specimen adequacy. METHODS NCI convened a conference on best biopsy practices, focusing on the clinical research community. Topics discussed were (1) criteria for specimen adequacy in the personalized medicine era, (2) team-based approaches to ensure specimen adequacy and quality control, and (3) risk considerations relevant to academic and community practitioners and their patients. RESULTS AND RECOMMENDATIONS Key recommendations from the convened consensus panel included (1) establishment of infrastructure for multidisciplinary biopsy teams with a formalized information capture process, (2) maintenance of standard operating procedures with regular team review, (3) optimization of tissue collection and yield methodology, (4) incorporation of needle aspiration and other newer techniques, and (5) commitment of stakeholders to use of guideline documents to increase awareness of best biopsy practices, with the goal of universally improving tumor biopsy practices.

Achievement of adequate treatment margins may be challenging when the target is either difficult to visualize, awkward to access, or situated adjacent to vulnerable structures. Treatment of tumors located close to the diaphragm in the hepatic dome is challenging for percutaneous radiofrequency (RF) ablation for these reasons. The purpose was to assess the feasibility, safety, and clinical outcome of multi-probe stereotactic RF ablation (SRFA) of liver tumors in the subdiaphragmatic area. Between 2006 and 2018, 177 patients (82 HCCs, 6 ICCs, and 89 metastatic tumors) underwent SRFA of 238 tumors abutting the diaphragm in the hepatic dome. For comparison, 177 patients were randomly selected from our database by the R package “MatchIt” for propensity score matching to compare treatment safety and efficacy in this retrospective, single-center study. Median treated tumor size was 2.2 cm (range 0.5 to 10 cm). SRFA was primarily successful for 232/238 (97.5%) tumors. Five tumors were successfully retreated, resulting in a secondary technical efficacy rate of 99.6%. Local tumor recurrence developed in 21 of 238 tumors (8.8%). The major ablation complication rate was 10.7% (22 of 204). Twelve (55%) of 22 major complications could be successfully treated by the interventional radiologist in the same anesthesia session. There was no significant difference in adverse events or disease control rates between the subdiaphragmatic tumors and matched controls. SRFA is a safe and feasible option in the management of difficult-to-treat tumors abutting the diaphragm in the hepatic dome, with similar safety profile compared with matched controls. • RFA was primarily successful for 232/238 (97.5%) subdiaphragmatic dome tumors. Local tumor recurrence developed in 21 of 238 tumors (8.8%). • The major complication rate directly related to ablation of the hepatic dome tumors was 10.7% (22 of 204). 12/22 (55%) of major complications could be successfully treated in the same anesthesia session. • There was no significant difference in adverse events or disease control rates between the subdiaphragmatic tumors and matched controls.

According to Barcelona Clinic Liver Cancer (BCLC) guidelines, interventional radiology procedures are valuable treatment options for many hepatocellular carcinomas (HCCs) that are not amenable to resection or transplantation. Accurate assessment of the efficacy of therapies at earlier stages enables completion of treatment, optimal follow-up and to prevent potentially unnecessary treatments, side effects and costly failure. The goal of this review is to summarize and describe the radiological strategies that have been proposed to predict survival and to stratify HCC responses after interventional radiology therapies. New techniques currently in development are also described.

Differences in drug metabolism associated with UGT1A1 polymorphism could result in individualized local response to hepatic chemoembolization with irinotecan-eluting beads (DEBIRI) or predictable toxicities. Five patients with inoperable hepatic metastases from colorectal or anal malignancies treated with DEBIRI were assessed for UGT1A1 mutations. No difference in area under the curve (AUC) for SN38 in normal liver and tumor tissue samples was noted with variant or wild-type UBT1A1 (P = .16 and P = .05, respectively). Plasma SN-38 AUC was significantly lower in wild-type compared to variant patients (P < .0001). UGT1A1 genotype may not be predictive of hematologic toxicity after DEBIRI.

OATP1B3 is expressed de novo in primary prostate cancer tissue and to a greater degree in prostate cancer metastases. Gadoxetate disodium is a substrate of OATP1B3, and its uptake has been shown to correlate with OATP1B3 expression in other cancers. We aimed to evaluate use of gadoxetate disodium to image prostate cancer and to track its utility as a biomarker. A single center open-label non-randomized pilot study recruited men with (1) localized, and (2) metastatic castration resistant prostate cancer (mCRPC). Gadoxetate disodium-enhanced MRI was performed at four timepoints post-injection. The Wilcoxon signed rank test was used to compare MRI contrast enhancement ratio (CER) pre-injection and post-injection. OATP1B3 expression was evaluated via immunohistochemistry (IHC) and a pharmacogenomic analysis of OATP1B3, NCTP and OATP1B1 was conducted. The mCRPC subgroup (n = 9) demonstrated significant enhancement compared to pre-contrast images at 20-, 40- and 60-min timepoints (p n = 11) demonstrated earlier enhancement compared to the mCRPC group, but no retention over time (p > 0.05). OATP1B3 expression on IHC trended higher contrast enhancement between 20–40 min (p ≤ 0.064) and was associated with contrast enhancement at 60 min (p = 0.0422). OATP1B1 haplotype, with N130D and V174A substitutions, impacted enhancement at 40–60 min (p ≤ 0.038). mCRPC lesions demonstrate enhancement after injection of gadoxetate disodium on MRI and retention over 60 min. As inter-individual variability in OATP1B3 expression and function has both predictive and prognostic significance, gadoxetate disodium has potential as a biomarker in prostate cancer.

The purpose of this study was to evaluate the health-related quality of life (HRQoL) after stereotactic radiofrequency ablation (SRFA) of liver tumors and identify variables associated with decreased HRQoL and to compare it to other treatments in case of concurrency. From 2011 to 2017 577 patients underwent SRFA for liver tumors in 892 ablation sessions. 303 (52.5%) patients completed a HRQoL questionnaire once after the ablation. HRQoL was assessed by the Short Form (SF)-12 health survey with mental and physical component scales and by a general questionnaire to assess disease and treatment-specific items as well as to compare tolerability of SRFA to transarterial chemoembolization (TACE), hepatic resection (HR) and chemotherapy (CTX). The median SF-12 PCS was 46.6 and MCS was 53.2. Patients experiencing pain or complications and patients refusing repeat SRFA showed significantly lower PCS (43.2 vs 48.6, p = 0.0003; 32.8 vs 46.9, p = 0.005 and 40.6 vs 46.9, p = 0.009). 355 (97.8%) patients indicated willingness to undergo repeat SRFA with little to no fear in 292 (80.7%) patients. Among patients with multiple therapies, SRFA was rated by 40 (90.9%) as preferred re-treatment, HR by 1 (2.3%) and CTX by 3 (6.8%). In conclusion, we have shown that SRFA has good HRQoL-outcomes and reported low morbidity rates. Consequently the vast majority of study patients would accept a repeated SRFA if necessary (97.8%), without fear (80.7%). SRFA was preferred among patients who experienced concurrent treatments, such as HR or CTX.

Background Prostate cancer recurrence is found in up to 40% of men with prior definitive (total prostatectomy or whole-prostate radiation) treatment. Prostate-specific membrane antigen PET agents such as 2-(3-{1-carboxy-5-[(6-[18F]fluoro-pyridine 3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid (

Our objective was to investigate the lesion detection rate of (18)F-DCFPyL PET/CT, a prostate-specific membrane antigen (PSMA)–targeted PET agent, in patients with biochemically relapsed prostate cancer after primary local therapy. Methods: This was a prospective institutional review board–approved study of 90 patients with documented biochemical recurrence (median prostate-specific antigen [PSA], 2.5 ng/mL; range, 0.21–35.5 ng/mL) and negative results on conventional imaging after primary local therapies, including radical prostatectomy (n = 38), radiation (n = 27), or a combination of the two (n = 25). Patients on androgen deprivation therapy were excluded. Patients underwent whole-body (18)F-DCFPyL PET/CT (299.9 ± 15.5 MBq) at 2 h after injection. The PSMA PET lesion detection rate was correlated with PSA, PSA kinetics, and original primary tumor grade. Results: Seventy patients (77.8%) showed positive PSMA PET results, with a total of 287 lesions identified: 37 prostate bed foci, 208 lesions in lymph nodes, and 42 in distant sites in bones or organs, Eleven patients had negative results, and 9 patients showed indeterminate lesions, which were considered negative in this study. The detection rates were 47.6% (n = 10/21), 50% (n = 5/10), 88.9% (n = 8/9), and 94% (n = 47/50) for PSA levels of >0.2 to

PURPOSE: Topotecan is a camptothecin analogue with potential advantages over irinotecan for transarterial chemoembolization (TACE) of hepatic colorectal metastases including greater anti-neoplastic activity without enzymatic activation. The purpose of this study was to assess safety and tolerability of topotecan-loaded radiopaque microspheres (ROMTOP) administered by TACE in a rabbit model, and to compare the in vitro elution of topotecan from microspheres to irinotecan. MATERIALS AND METHODS: Topotecan was loaded into radiopaque microspheres (70–150 μm, DC Bead LUMI™, Biocompatibles UK Ltd – Boston Scientific Corporation) to the maximum capacity of 80 mg/mL of microspheres. Six healthy New Zealand White rabbits underwent hepatic TACE with ROMTOP under fluoroscopic guidance until angiographic stasis. Assessment of toxicities included regular liver function tests and complete blood counts until euthanasia 28 days post TACE. In vitro topotecan elution from the microspheres was assessed using an open-loop flow-through system and compared to irinotecan. RESULTS: The mean bead volume and topotecan dose delivered were 0.086 mL (0.076–0.105 mL) and 1.99 mg/kg (1.51–2.55 mg/kg), respectively. Aspartate aminotransferase and alanine aminotransferase were elevated post-embolization but resolved within two weeks. One rabbit died two days after TACE with pyloric duodenal perforation observed at necropsy, potentially due to non-target embolization. In vitro elution of topotecan from ROMTOP was complete in 10 h compared to 3 h for irinotecan-loaded microspheres. CONCLUSION: Selective embolization with ROMTOP was tolerated at a dose of 2 mg/kg (24 mg/m(2)) in rabbits. In vitro topotecan elution from microspheres was more prolonged compared to irinotecan.

Purpose: Preclinical studies suggest PARP inhibition (PARPi) induces immunostimulatory micromilieu in ovarian cancer thus complementing activity of immune checkpoint blockade. We conducted a phase II trial of PARPi olaparib and anti–PD-L1 durvalumab and collected paired fresh core biopsies and blood samples to test this hypothesis. Patients and Methods: In a single-center, proof-of-concept phase II study, we enrolled women aged ≥18 with recurrent ovarian cancer. All patients were immune checkpoint inhibitor–naïve and had measurable disease per RECISTv1.1, ECOG performance status 0–2, and adequate organ and marrow function. Patients received olaparib 300 mg twice daily and durvalumab 1,500 mg intravenously every 4 weeks until disease progression, unacceptable toxicity, or withdrawal of consent. Primary endpoint was overall response rate (ORR). Secondary objectives were safety and progression-free survival (PFS). Translational objectives included biomarker evaluation for relationships with clinical response and immunomodulatory effects by treatment. Results: Thirty-five patients with ovarian cancer [median, four prior therapies (IQR, 2–5.5), predominantly platinum-resistant (86%), BRCA wild-type (77%)] received at least one full cycle of treatment. ORR was 14% [5/35; 95% confidence interval (CI), 4.8%–30.3%]. Disease control rate (PR+SD) was 71% (25/35; 95% CI, 53.7%–85.4%). Treatment enhanced IFNγ and CXCL9/CXCL10 expression, systemic IFNγ/TNFα production, and tumor-infiltrating lymphocytes, indicating an immunostimulatory environment. Increased IFNγ production was associated with improved PFS [HR, 0.37 (95% CI, 0.16–0.87), P = 0.023], while elevated VEGFR3 levels were associated with worse PFS (HR, 3.22 (95% CI, 1.23–8.40), P = 0.017]. Conclusions: The PARPi and anti–PD-L1 combination showed modest clinical activity in recurrent ovarian cancer. Our correlative study results suggest immunomodulatory effects by olaparib/durvalumab in patients and indicate that VEGF/VEGFR pathway blockade would be necessary for improved efficacy of the combination.

Purpose To correlate bead location and attenuation on CT images with the quantity and distribution of drug delivered to the liver following transarterial chemoembolization (TACE) with radiopaque drug-eluting beads (DEB) in a rabbit tumor model. Materials and Methods All procedures were performed with a protocol approved by the Institutional Animal Care and Use Committee. TACE was performed in rabbits (n = 4) bearing VX2 liver tumors by using radiopaque DEB (70-150 µm) loaded with doxorubicin (DOX). Livers were resected 1 hour after embolization, immediately frozen, and cut by using liver-specific three-dimensional-printed molds for colocalization of liver specimens and CT imaging. DOX penetration into tissue surrounding beads was evaluated with fluorescence microscopy. DOX levels in liver specimens were predicted by using statistical models correlating DOX content measured in tissue with bead volume and attenuation measured on CT images. Model predictions were then compared with actual measured DOX concentrations to assess the models' predictive power. Results Eluted DOX remained in close proximity (

This review describes the historical development of an imageable spherical embolic agent and focuses on work performed in collaboration between Biocompatibles UK Ltd (a BTG International group company) and the NIH to demonstrate radiopaque bead utility and bring a commercial offering to market that meets a clinical need. Various chemistries have been investigated and multiple prototypes evaluated in search of an optimized product with the right balance of handling and imaging properties. Herein, we describe the steps taken in the development of DC Bead LUMI™, the first commercially available radiopaque drug-eluting bead, ultimately leading to the first human experience of this novel embolic agent in the treatment of liver tumors.

Noncirrhotic portal hypertension (NCPH) is a rare disease that may lead to serious clinical consequences. Currently, noninvasive tools for the assessment of NCPH are absent. We investigated the utility of spleen and liver volumetrics as a marker of the presence and severity of portal hypertension in this population. A cohort of NCPH patients evaluated between 2003 and 2015 was retrospectively studied. The association of spleen and liver volumes with the hepatic venous pressure gradient (HVPG) level was evaluated using locally weighted scatterplot smoothing curves. A cohort of patients with viral hepatitis-related liver disease was used as controls. Of the 86 patients with NCPH evaluated during the study period, 75 (mean age, 35 ± 17; 73% males) were included in the final analysis. Patients with portal hypertension had significantly higher spleen and liver to body mass index (BMI) ratios compared to patients with HVPG

Purpose To evaluate outcomes in patients with liver metastases from breast cancer treated with stereotactic radiofrequency (RF) ablation. Materials and Methods A retrospective analysis of 29 stereotactic RF ablation treatment sessions in 26 consecutive patients with 64 biopsy-proven breast cancer liver metastases (BCLMs) was conducted. Patients were included only if systemic treatment failed and all visible BCLMs were treatable. Results Primary and secondary technical success rates were 96.9% (62 of 64) and 100%, respectively. There were no perioperative mortalities. Local recurrence was identified in 5 tumors (7.8%), with no significant differences among tumor sizes ( P = .662): 5 cm (8.3%). Median estimated overall survival (OS) from first stereotactic ablation treatment was 29.3 months ± 8.9 (95% confidence interval [CI], 11.9–46.8 mo; mean, 28.7 mo) after a median follow-up of 23.1 months (mean, 31.3 mo; range, 0.1–100.8 mo). No significant differences in OS ( P = .223) were observed among tumor volumes 3 (median, 84.9 mo ± 53.1; mean, 58.4 mo), 50–100 cm 3 (median, 37.8 mo ± 5.7; mean, 36.3 mo), and > 100 cm 3 (median, 17.1 mo ± 3.5; mean, 21.8 mo). Numbers of metastases did not affect estimated OS, with a median OS of 32.7 months ± 10.4 (mean, 35.8 mo) for single lesions vs 17.7 months ± 3.2 (mean, 25.9 mo) for 2/3 lesions and a mean of 68.4 months ± 17.23 for > 3 lesions ( P = .113). Conclusions Multiple-electrode stereotactic RF ablation proved to be a safe minimally invasive alternative to surgical liver resection in selected patients with BCLMs.

Introduction:18F-DCFPyL, 18F-NaF and 18F-FDG PET/CT were compared in a prospective cohort of men with metastatic prostate cancer (PCa). Materials and Methods: 67 men (Group 1) with documented metastatic PCa underwent 18F-DCFPyL and 18F-NaF PET/CT and a subgroup of 30 men (Group 2) underwent additional imaging with 18F-FDG PET/CT. The tracers were compared for their detection rates, imaging concordance, associations with Prostate Specific Antigen (PSA), treatment at the time of imaging and castration status. Results: Overall, 61 men had metastatic disease detected on one or more scans, while 6 men were negative. In Group 1, 18F-NaF detected significantly more metastatic lesions than 18F-DCFPyL (median of 3 lesions versus 2, P = 0.001) even after eliminating benign causes of 18F-NaF uptake. This difference was particularly clear for men receiving treatment (P = 0.005) or who were castrate resistant (P = 0.014). The median percentage of bone lesions that were concordant on 18F-DCFPyL and 18F-NaF was 50%. In Group 2, 18F-DCFPyL detected more lesions than 18F-FDG (median of 5 lesions versus 2, P = 0.0003), regardless of PSA level, castration status or treatment. The median percentage of lesions that were concordant on 18F-DCFPyL and 18F-FDG was 22.2%. This percentage was slightly higher for castrate-resistant than castrate-sensitive men (P = 0.048). Conclusion:18F-DCFPyL PET/CT is the most versatile of the three PET agents for metastatic PCa however, 18F-NaF detects more bone metastases. Imaging reveals substantial tumor heterogeneity with only 50% concordance between 18F-DCFPyL and 18F-NaF and 22% concordance for 18F-DCFPyL and 18F-FDG. This indicates considerable phenotypic differences among metastatic lesions.

Tumor-induced osteomalacia (TIO) is a debilitating paraneoplastic condition caused by small phosphaturic mesenchymal tumors (PMTs) that secrete large amounts of the phosphate-regulating and vitamin D-regulating hormone, FGF23. Tumor removal results in cure. However, because of high perioperative comorbidity, either from tumor location or host factors, surgery is sometimes not an option. Tumor destruction via cryoablation may be an effective option for inoperable PMTs. Three subjects with a confirmed diagnosis of TIO were studied. All three underwent cryoablation of suspected PMTs rather than surgery due to significant medical comorbidities or challenging anatomical location. Subject 3 had tumor embolization 24 hours prior to cryoablation because of the size and hypervascularity of the tumor. The success of the tumor cryoablation was defined by normalization of serum phosphate and FGF23. Cryoablation resulted in a rapid decrease in plasma intact FGF23 by 24 hours postprocedure in all three subjects (0, 2, and 9 pg/mL, respectively) with normalization of blood phosphate by postprocedure day 3. Three-day renal tubular reabsorption of phosphate increased to 76%, 94%, and 95.2%, respectively; 1, 25(OH)2 vitamin D increased to 84, 138, and 196 pg/ml, respectively. All three had dramatic clinical improvement in pain and weakness. Two subjects tolerated the procedure well with no complications; one had significant prolonged procedure-related localized pain. Although surgery remains the treatment of choice, cryoablation may be an effective, less invasive, and safe treatment for patients with difficult to remove tumors or who are poor surgical candidates. © 2017 American Society for Bone and Mineral Research.

Background & Aims Tremelimumab is a fully human monoclonal antibody that binds to cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) on the surface of activated T lymphocytes. Ablative therapies induce a peripheral immune response which may enhance the effect of anti-CTLA4 treatment in patients with advanced hepatocellular carcinoma (HCC). This study aimed to demonstrate whether tremelimumab could be combined safely and feasibly with ablation. Methods Thirty-two patients with HCC were enrolled: male:female: 28:4; median age: 62 (range 36–76). Patients were given tremelimumab at two dose levels (3.5 and 10mg/kg i.v.) every 4weeks for 6 doses, followed by 3-monthly infusions until off-treatment criteria were met. On day 36, patients underwent subtotal radiofrequency ablation or chemoablation. Staging was performed by contrast-enhanced CT or MRI scan every 8weeks. Results No dose-limiting toxicities were encountered. The most common toxicity was pruritus. Of the 19 evaluable patients, five (26.3%; 95% CI: 9.1–51.2%) achieved a confirmed partial response. Twelve of 14 patients with quantifiable HCV experienced a marked reduction in viral load. Six-week tumor biopsies showed a clear increase in CD8 + T cells in patients showing a clinical benefit only. Six and 12-month probabilities of tumor progression free survival for this refractory HCC population were 57.1% and 33.1% respectively, with median time to tumor progression of 7.4months (95% CI 4.7 to 19.4months). Median overall survival was 12.3months (95% CI 9.3 to 15.4months). Conclusions Tremelimumab in combination with tumor ablation is a potential new treatment for patients with advanced HCC, and leads to the accumulation of intratumoral CD8 + T cells. Positive clinical activity was seen, with a possible surrogate reduction in HCV viral load. Lay summary Studies have shown that the killing of tumors by direct methods (known as ablation) can result in the immune system being activated or switched on. The immune system could potentially also recognize and kill the cancer that is left behind. There are new drugs available known as immune checkpoint inhibitors which could enhance this effect. Here, we test one of these drugs (tremelimumab) together with ablation. Clinical trial number ClinicalTrials.gov: NCT01853618.

Background The prognosis of metastatic colorectal cancer (mCRC) is poor. We assessed the feasibility, safety, and efficacy of the anti-programmed cell death 1 fusion protein AMP-224 in combination with low-dose cyclophosphamide and stereotactic body radiation (SBRT) treatment in patients with mCRC refractory to standard chemotherapy. Patients and Methods Fifteen patients were enrolled. Six received SBRT 8 Gy on day 0 (dose level 1), whereas 9 received 8 Gy on days −2 to day 0. All received cyclophosphamide 200 mg/m2 intravenously (I.V.) on day 0. On day 1, both groups received AMP-224 10 mg/kg I.V., repeated every 2 weeks for a total of 6 doses. Primary end points were feasibility and safety. Results Ten (67%) patients completed 6 doses of AMP-224; 5 patients (33%) discontinued treatment because of disease progression. No dose-limiting toxicity was observed; 9 patients (60%) experienced treatment-related adverse events, all Grade 1 or 2. No objective response was noted; 3 patients (20%) had stable disease. Median progression-free survival and overall survival were 2.8 months (95% confidence interval [CI], 1.2-2.8 months) and 6.0 months (95% CI, 2.8-9.6 months), respectively. M2 macrophage polarization was present in the pretreatment tumor biopsy samples, but not post-treatment samples. Conclusion AMP-224 in combination with SBRT and low-dose cyclophosphamide was well tolerated, however, no significant clinical benefit was observed in patients with mCRC.

INTRODUCTION AND OBJECTIVES:Delayed bleeding is an infrequent complication after partial nephrectomy, with reported rates of 2-3%. Patients with hereditary kidney cancer are often managed with rese...

Purpose Despite high tumor mutationburden, immune checkpoint blockade has limited efficacy in SCLC. We hypothesized that poly (ADP-ribose) polymerase inhibition could render SCLC more susceptible to immune checkpoint blockade. Methods A single-arm, phase II trial (NCT02484404) enrolled patients with relapsed SCLC who received durvalumab, 1500 mg every 4 weeks, and olaparib, 300 mg twice a day. The primary outcome was objective response rate. Correlative studies included mandatory collection of pretreatment and during-treatment biopsy specimens, which were assessed to define SCLC immunephenotypes: desert (CD8-positive T-cell prevalence low), excluded (CD8-positive T cells in stroma immediately adjacent/within tumor), and inflamed (CD8-positive T cells in direct contact with tumor). Results A total of 20 patients were enrolled. Their median age was 64 years, and most patients (60%) had platinum-resistant/refractory disease. Of 19 evaluable patients, two were observed to have partial or complete responses (10.5%), including a patient with EGFR-transformed SCLC. Clinical benefit was observed in four patients (21.1% [95% confidence interval: 6.1%–45.6%]) with confirmed responses or prolonged stable disease (≥8 months). The most common treatment-related adverse events were anemia (80%), lymphopenia (60%), and leukopenia (50%). Nine of 14 tumors (64%) exhibited an excluded phenotype; 21% and 14% of tumors exhibited the inflamed and desert phenotypes, respectively. Tumor responses were observed in all instances in which pretreatment tumors showed an inflamed phenotype. Of the five tumors without an inflamed phenotype at baseline, no during-treatment increase in T-cell infiltration or programmed death ligand 1 expression on tumor-infiltrating immune cells was observed. Conclusions The study combination did not meet the preset bar for efficacy. Pretreatment and during-treatment biopsy specimens suggested that tumor immune phenotypes may be relevant for SCLC responses to immune checkpoint blockade combinations. The predictive value of preexisting CD8-positive T-cell infiltrates observed in this study needs to be confirmed in larger cohorts.

Background Chronic liver injury can result in fibrosis that may progress over years to end-stage liver disease. The most effective anti-fibrotic therapy is treatment of the underlying disease, however when not possible, interventions to reverse or slow fibrosis progression are needed. Aim The aim of this study was to study the safety and tolerability of simtuzumab, a monoclonal antibody directed against lysyl oxidase-like 2 (LOXL2) enzyme, in subjects with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or HCV-HIV co-infection and advanced liver disease. Methods Eighteen subjects with advanced liver fibrosis received simtuzumab 700 mg intravenously every 2 weeks for 22 weeks. Transjugular liver biopsies were performed during screening and at the end of treatment to measure hepatic venous pressure gradient (HVPG) and to stage fibrosis. Results Treatment was well-tolerated with no discontinuations due to adverse events. No significant changes were seen in HVPG or liver biopsy fibrosis score after treatment. Exploratory transcriptional and protein profiling using paired pre- and post-treatment liver biopsy and serum samples suggested up-regulation of TGF-β3 and IL-10 pathways with treatment. Conclusion In this open-label, pilot clinical trial, simtuzumab treatment was well-tolerated in HCV- and HIV-infected subjects with advanced liver disease. Putative modulation of TGF-β3 and IL-10 pathways during simtuzumab treatment merits investigation in future trials.

e17114 Background: Adrenocortical carcinoma (ACC) is a rare cancer with an incidence of 0.7 – 2 cases per million persons per year, and generally has a poor prognosis with a 5-year survival rate of 20-25%. In a previous review of 330 patients with ACC, the median overall survival time of patients with Stage IV ACC was 0.9 years. Currently, complete surgical resection is the only curative treatment for ACC. Cases of recurrent or metastatic ACC are infrequently curable by surgery alone and systemic therapies have limited benefit. A previous study has suggested that local interventions to resect liver metastases improve survival. We hypothesize that local therapies increase survival of patients with metastatic ACC and here we describe the characteristics of various types of regional therapies. Methods: We conducted a retrospective chart review of 26 patients with ACC who were seen at the National Institutes of Health (NIH) between 2002 and 2019 and who are currently alive. These patients had multiple interventions that were performed including surgeries, radiofrequency ablations/embolizations/cryoablations and systemic therapies. Results: The group of patients we studied were 92% female and 8% male. The ages ranged from 23 to 77, with an average age of 57. Out of the 26 patients, 11 (42%) patients had liver metastases, 17 (65%) patients had lung metastases, 4 (15%) patients had retroperitoneal recurrence, and 5 (19%) patients had lymph node involvement. All patients with lung, retroperitoneum, liver, and lymph node metastases underwent surgical intervention. In patients with liver metastases, 73% underwent liver-directed therapies and 91% received systemic therapy. In patients with lung metastases, 59% underwent radiofrequency ablation or cryoablation and 94% had systemic therapy. Among the systemic therapies, 15% of patients received zero lines of treatment, 50% of patients received one line, 12% of patients received two lines, 19% of patients received three lines, and 4% of patients received more than three lines of treatment. Conclusions: The analysis of this cohort indicates that multiple local therapies could increase patient survival. ACC metastases are most common in the liver, followed by the lungs. Patients with recurrent/metastatic ACC should be considered for regional therapies such as metastasectomy/ablation in experienced hands which can increase long-term survival in selected patients.

Treatment options for patients with advanced biliary tract cancer are limited. Dysregulation of the immune system plays an important role in the pathogenesis of biliary tract cancer (BTC). This study aimed to investigate whether tremelimumab, an anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) inhibitor, could be combined safely with microwave ablation to enhance the effect of anti-CTLA4 treatment in patients with advanced BTC. Patients were enrolled to receive monthly tremelimumab (10 mg/kg, intravenously) for six doses, followed by infusions every 3 months until off-treatment criteria were met. Thirty-six days after the first tremelimumab dose, patients underwent subtotal microwave ablation. Interval imaging studies were performed every 8 weeks. Adverse events (AEs) were noted and managed. Tumor and peripheral blood samples were collected to perform immune monitoring and whole-exome sequencing (WES). Twenty patients with refractory BTC were enrolled (median age, 56.5 years). No dose-limiting toxicities were encountered. The common treatment-related AEs included lymphopenia, diarrhea, and elevated transaminases. Among 16 patients evaluable for efficacy analysis, 2 (12.5%) patients achieved a confirmed partial response (lasting for 8.0 and 18.1 months, respectively) and 5 patients (31.3%) achieved stable disease. Median progression free survival (PFS) and overall survival (OS) were 3.4 months (95% confidence interval [CI], 2.5-5.2) and 6.0 months (95% CI, 3.8-8.8), respectively. Peripheral blood immune cell subset profiling showed increased circulating activated human leukocyte antigen, DR isotype ([HLA-DR] positive) CD8+ T cells. T-cell receptor (TCR)β screening showed tremelimumab expanded TCR repertoire, but not reaching statistical significance (P = 0.057). Conclusion: Tremelimumab in combination with tumor ablation is a potential treatment strategy for patients with advanced BTC. Increased circulating activated CD8+ T cells and TCR repertoire expansion induced by tremelimumab may contribute to treatment benefit.

PURPOSE: To evaluate the effect of embolic diameter on the achievement of hypoxia following embolization in a preclinical model of liver tumors. MATERIALS AND METHODS: Inoculation of Vx2 tumors in the left liver lobe was performed successfully in 12 new Zealand white rabbits weighing 3.7 kg ± 0.5kg (mean + SD). Tumors were deemed eligible for oxygen measurements when the maximum transverse diameter measured 15mm or more by ultrasound examination. Direct monitoring of oxygenation of implanted rabbit hepatic Vx2 tumors was performed with a fiberoptic electrode during and following transarterial embolization of the proper hepatic artery to angiographic flow stasis with microspheres measuring 70–150, 100–300, or 300–500 microns in diameter. RESULTS: Failure to achieve tumor hypoxia as defined despite angiographic flow stasis was observed in ten of eleven total animals. Embolization microsphere size effect failed to demonstrate a significant trend on hypoxia outcome among the diameters tested, and pair-wise comparisons of different embolic diameter treatment groups showed no difference in hypoxia outcome. All microsphere diameters tested resulted in similar absolute reduction (24.3 ± 18.3, 29.1 ± 1.8, and 19.9 ± 9.3 mm Hg, p=0.66) and percentage drop in oxygen (56.0 ± 23.9, 56.0 ±6.4, and 35.8 ± 20.6 mm Hg, p=0.65) Pairwise comparisons for percent tumor area occupied by embolics showed a significantly reduced fraction for 300–500 μm compared to 70–150 μm diameters (p < 0.05). CONCLUSION: In the rabbit Vx2 liver tumor model, three tested microsphere diameters failed to cause tumor hypoxia measured by a fiberoptic probe sensor according to the adopted hypoxia definitions, although an influence of embolic diameter upon achieved post-embolization hypoxia severity was determined.