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1.
Cancers (Basel) ; 16(1)2024 Jan 01.
Article in English | MEDLINE | ID: mdl-38201633

ABSTRACT

BACKGROUND: While multiple cyst features are evaluated for stratifying pancreatic intraductal papillary mucinous neoplasms (IPMN), cyst size is an important factor that can influence treatment strategies. When magnetic resonance imaging (MRI) is used to evaluate IPMNs, no universally accepted sequence provides optimal size measurements. T2-weighted coronal/axial have been suggested as primary measurement sequences; however, it remains unknown how well these and maximum all-sequence diameter measurements correlate with pathology size. This study aims to compare agreement and bias between IPMN long-axis measurements on seven commonly obtained MRI sequences with pathologic size measurements. METHODS: This retrospective cohort included surgically resected IPMN cases with preoperative MRI exams. Long-axis diameter tumor measurements and the presence of worrisome features and/orhigh-risk stigmata were noted on all seven MRI sequences. MRI size and pathology agreement and MRI inter-observer agreement involved concordance correlation coefficient (CCC) and intraclass correlation coefficient (ICC), respectively. The presence of worrisome features and high-risk stigmata were compared to the tumor grade using kappa analysis. The Bland-Altman analysis assessed the systematic bias between MRI-size and pathology. RESULTS: In 52 patients (age 68 ± 13 years, 22 males), MRI sequences produced mean long-axis tumor measurements from 2.45-2.65 cm. The maximum MRI lesion size had a strong agreement with pathology (CCC = 0.82 (95% CI: 0.71-0.89)). The maximum IPMN size was typically observed on the axial T1 arterial post-contrast and MRCP coronal series and overestimated size versus pathology with bias +0.34 cm. The radiologist interobserver agreement reached ICCs 0.74 to 0.91 on the MRI sequences. CONCLUSION: The maximum MRI IPMN size strongly correlated with but tended to overestimate the length compared to the pathology, potentially related to formalin tissue shrinkage during tissue processing.

2.
Oncotarget ; 13: 1314-1321, 2022 12 06.
Article in English | MEDLINE | ID: mdl-36473155

ABSTRACT

INTRODUCTION: Hepatocellular carcinoma (HCC) has limited systemic therapy options when discovered at an advanced stage. Thus, there is a need for accessible and minimally invasive biomarkers of response to guide the selection of patients for treatment. This study investigated the biomarker value of plasma growth hormone (GH) level as a potential biomarker to predict outcome in unresectable HCC patients treated with current standard therapy, atezolizumab plus bevacizumab (Atezo/Bev). MATERIALS AND METHODS: Study included unresectable HCC patients scheduled to receive Atezo/Bev. Patients were followed to determine progression-free survival (PFS) and overall survival (OS). Plasma GH levels were measured by ELISA and used to stratify the HCC patients into GH-high and GH-low groups (the cutoff normal GH levels in women and men are ≤3.7 µg/L and ≤0.9 µg/L, respectively). Kaplan-Meier method was used to calculate median OS and PFS and Log rank test was used to compare survival outcomes between GH-high and -low groups. RESULTS: Thirty-seven patients were included in this analysis, of whom 31 were males and 6 females, with a median age of 67 years (range: 37-80). At the time of the analysis, the one-year survival rate was 70% (95% CI: 0.51, 0.96) among GH low patients and 33% (95% CI: 0.16, 0.67) among GH high patients. OS was significantly superior in GH-low compared to GH-high patients (median OS: 18.9 vs. 9.3 months; p = 0.014). PFS showed a non-significant trend in favor of GH-low patients compared to the GH-high group (median PFS: 6.6 vs. 2.9 months; p = 0.053). DISCUSSION AND CONCLUSIONS: Plasma GH is a biomarker candidate for predicting treatment outcomes in advanced HCC patients treated with Atezo/Bev. This finding should be further validated in larger randomized clinical trials in advanced HCC patients.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Bevacizumab/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Growth Hormone , Liver Neoplasms/drug therapy
3.
Lancet Gastroenterol Hepatol ; 7(3): 208-218, 2022 03.
Article in English | MEDLINE | ID: mdl-35065057

ABSTRACT

BACKGROUND: Hepatocellular carcinoma has high recurrence rates after surgery; however, there are no approved standard-of-care neoadjuvant or adjuvant therapies. Immunotherapy has been shown to improve survival in advanced hepatocellular carcinoma; we therefore aimed to evaluate the safety and tolerability of perioperative immunotherapy in resectable hepatocellular carcinoma. METHODS: In this single-centre, randomised, open-label, phase 2 trial, patients with resectable hepatocellular carcinoma were randomly assigned (1:1) to receive 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery at 6 weeks) followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for 2 years, or 240 mg of nivolumab intravenously every 2 weeks (for up to three doses before surgery) plus one dose of 1 mg/kg of ipilimumab intravenously concurrently with the first preoperative dose of nivolumab, followed in the adjuvant phase by 480 mg of nivolumab intravenously every 4 weeks for up to 2 years plus 1 mg/kg of ipilimumab intravenously every 6 weeks for up to four cycles. Patients were randomly assigned to the treatment groups by use of block randomisation with a random block size. The primary endpoint was the safety and tolerability of nivolumab with or without ipilimumab. Secondary endpoints were the proportion of patients with an overall response, time to progression, and progression-free survival. This trial is registered with ClinicalTrials.gov (NCT03222076) and is completed. FINDINGS: Between Oct 30, 2017, and Dec 3, 2019, 30 patients were enrolled and 27 were randomly assigned: 13 to nivolumab and 14 to nivolumab plus ipilimumab. Grade 3-4 adverse events were higher with nivolumab plus ipilimumab (six [43%] of 14 patients) than with nivolumab alone (three [23%] of 13). The most common treatment-related adverse events of any grade were increased alanine aminotransferase (three [23%] of 13 patients on nivolumab vs seven [50%] of 14 patients on nivolumab plus ipilimumab) and increased aspartate aminotransferase (three [23%] vs seven [50%]). No patients in either group had their surgery delayed due to grade 3 or worse adverse events. Seven of 27 patients had surgical cancellations, but none was due to treatment-related adverse events. Estimated median progression-free survival was 9·4 months (95% CI 1·47-not estimable [NE]) with nivolumab and 19·53 months (2·33-NE) with nivolumab plus ipilimumab (hazard ratio [HR] 0·99, 95% CI 0·31-2·54); median time to progression was 9·4 months (95% CI 1·47-NE) in the nivolumab group and 19·53 months (2·33-NE) in the nivolumab plus ipilimumab group (HR 0·89, 95% CI 0·31-2·54). In an exploratory analysis, three (23%) of 13 patients had an overall response with nivolumab monotherapy, versus none with nivolumab plus ipilimumab. Three (33%) of nine patients had a major pathological response (ie, ≥70% necrosis in the resected tumour area) with nivolumab monotherapy compared with three (27%) of 11 with nivolumab plus ipilimumab. INTERPRETATION: Perioperative nivolumab alone and nivolumab plus ipilimumab appears to be safe and feasible in patients with resectable hepatocellular carcinoma. Our findings support further studies of immunotherapy in the perioperative setting in hepatocellular carcinoma. FUNDING: Bristol Myers Squibb and the US National Institutes of Health.


Subject(s)
Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Ipilimumab/administration & dosage , Liver Neoplasms/drug therapy , Nivolumab/administration & dosage , Aged , Alanine Transaminase/blood , Antineoplastic Agents, Immunological/adverse effects , Aspartate Aminotransferases/blood , Carcinoma, Hepatocellular/surgery , Female , Humans , Ipilimumab/adverse effects , Liver Neoplasms/surgery , Male , Middle Aged , Nivolumab/adverse effects , Perioperative Care , Progression-Free Survival
4.
Nanomedicine ; 39: 102465, 2022 01.
Article in English | MEDLINE | ID: mdl-34571240

ABSTRACT

Embolic agents used in transarterial embolization for intermediate stage hepatocellular carcinoma reduce blood flow into tumors and can deliver anticancer drugs. Tumor blood supply can be interrupted using doxorubicin-eluting beads (DEB-TACE) or non-loaded beads (TAE) of different calibers. In this preclinical study, we characterized the extent of remaining stressed tumor cells after treatment, hypoxia within the surviving tumor regions, and inflammatory immune cell infiltrates after embolization with 40-60 or 70-150 µm with non-loaded or doxorubicin-loaded beads at 3 and 7 days after treatment. TAE-treated tumors had more stressed and surviving tumor cells after 3 days, irrespective of bead size, compared with DEB-TACE-treated tumors. Hypoxic stress of residual cells increased after treatment with 70-150 µm beads without or with doxorubicin. Treatment with DEB-TACE of 70-150 µm resulted in increased inflammation and proliferation in the adjacent parenchyma. Inflammatory cell infiltrates were reduced at the periphery of tumors treated with 40-60 µm DEB-TACE.


Subject(s)
Carcinoma, Hepatocellular , Chemoembolization, Therapeutic , Liver Neoplasms , Animals , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Chemoembolization, Therapeutic/methods , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Rats , Treatment Outcome
5.
Oncotarget ; 12(8): 756-766, 2021 Apr 13.
Article in English | MEDLINE | ID: mdl-33889299

ABSTRACT

BACKGROUND: Sorafenib was the first systemic therapy approved for the treatment of Child-Turcotte-Pugh (CTP) class A patients with advanced hepatocellular carcinoma (HCC). However, there are no biomarkers to predict survival and treatment outcomes and guide HCC systemic therapy. Type 1 insulin-like growth factor (IGF-1)/CTP composite score has emerged as a potential hepatic reserve assessment tool. Our study investigated the association of the IGF/CTP score with overall survival (OS) and progression-free survival (PFS) of HCC patients treated with sorafenib. MATERIALS AND METHODS: In this prospective study, patients with HCC were treated with sorafenib and followed up until progression/death. We calculated the IGF/CTP score and used the Kaplan-Meier method and log-rank test to estimate and compare the time-to-event outcomes between patient subgroups. RESULTS: 171 patients were included, 116 of whom were CTP class A. Median PFS for IGF/CTP score AA and AB patients were 6.88 and 4.28 months, respectively (p = 0.1359). Median OS for IGF/CTP score AA and AB patients were 14.54 and 7.60 months, respectively (p = 0.1378). The PFS and OS was superior in AA patients, but the difference was not significant, likely due to the sample size. However, there was a significant difference in early OS and PFS curves between AA and AB (p = 0.0383 and p = 0.0099), respectively. CONCLUSIONS: In CTP class A patients, IGF/CTP score B was associated with shorter PFS and OS, however, study was underpowered to reach statistical significance. If validated in larger cohorts, IGF/CTP score may serve as stratification tool in clinical trials, a hepatic reserve assessment tool for HCC outcomes prediction and to assist in therapy decisions.

6.
Abdom Radiol (NY) ; 46(7): 3378-3386, 2021 07.
Article in English | MEDLINE | ID: mdl-33580348

ABSTRACT

INTRODUCTION: Magnetic resonance imaging (MRI) has played an increasingly major role in the evaluation of patients with prostate cancer, although prostate MRI presents several technical challenges. Newer techniques, such as deep learning (DL), have been applied to medical imaging, leading to improvements in image quality. Our goal is to evaluate the performance of a new deep learning-based reconstruction method, "DLR" in improving image quality and mitigating artifacts, which is now commercially available as AIRTM Recon DL (GE Healthcare, Waukesha, WI). We hypothesize that applying DLR to the T2WI images of the prostate provides improved image quality and reduced artifacts. METHODS: This study included 31 patients with a history of prostate cancer that had a multiparametric MRI of the prostate with an endorectal coil (ERC) at 1.5 T or 3.0 T. Four series of T2-weighted images were generated in total: one set with the ERC signal turned on (ERC) and another set with the ERC signal turned off (Non-ERC). Each of these sets then reconstructed using two different reconstruction methods: conventional reconstruction (Conv) and DL Recon (DLR): ERCDLR, ERCConv, Non-ERCDLR, and Non-ERCConv. Three radiologists independently reviewed and scored the four sets of images for (i) image quality, (ii) artifacts, and (iii) visualization of anatomical landmarks and tumor. RESULTS: The Non-ERCDLR scored as the best series for (i) overall image quality (p < 0.001), (ii) reduced artifacts (p < 0.001), and (iii) visualization of anatomical landmarks and tumor. CONCLUSION: Prostate imaging without the use of an endorectal coil could benefit from deep learning reconstruction as demonstrated with T2-weighted imaging MRI evaluations of the prostate.


Subject(s)
Deep Learning , Multiparametric Magnetic Resonance Imaging , Prostatic Neoplasms , Humans , Magnetic Resonance Imaging , Male , Prostatic Neoplasms/diagnostic imaging
7.
Abdom Radiol (NY) ; 46(3): 1008-1015, 2021 03.
Article in English | MEDLINE | ID: mdl-32974761

ABSTRACT

PURPOSE: Sarcopenia is an independent prognostic indicator for hepatocellular carcinoma (HCC). Our objective was to determine the effect of sarcopenia on response to systemic targeted therapy in patients with advanced HCC. MATERIALS AND METHODS: This was a retrospective, Institutional Review Board approved study of 36 patients on systemic targeted therapy with immune checkpoint blockade (n = 25) or tyrosine kinase inhibitor (n = 11) for biopsy-proven advanced HCC. Skeletal muscle index (SMI) was calculated from erector spinae muscle area (SMA) at the level of T12 on pretreatment CT: [SMI = SMA (cm2)/height (m2)]. SMI was compared to treatment response defined as overall survival ≥ 1 year (nonsurgical patients) or > 50% HCC necrosis (surgical patients). Receiver operating characteristic curve and area under the curve was used for analysis with p < 0.05 for statistical significance. RESULTS: Median age of men and women was 66.5 years (range 32-83) and 70 years (range 54-78), respectively. Liver disease etiology was nonalcoholic steatohepatitis (n = 9), hepatitis C (n = 10), hepatitis B (n = 5), alcohol (n = 3) and unknown (n = 9). Mean (± SD) height and SMI for men were 1.7 m (± 0.1) and 11.4 (± 3.6); values for women were 1.7 m (± 0.1) and 8.2 (± 1.9). Treatment was withdrawn in five patients due to treatment intolerance. Response occurred in 10/31 (32.3%) patients (23 men, 8 women). T12SMI correlated with treatment response using a threshold of 7.21-8.23 for women (AUC = 1; p = 0.037), and 11.47 for men (AUC = 0.83; p = 0.015); correlation was increased for men ≥ 60 years, (AUC = 0.87; p = 0.023). CONCLUSION: Sarcopenia was associated with reduced survival and HCC necrosis in patients treated with systemic targeted therapy. CLINICAL RELEVANCE: Sarcopenia may help in predicting outcomes to targeted therapy in advanced HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Sarcopenia , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/drug therapy , Female , Humans , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Male , Middle Aged , Prognosis , Retrospective Studies , Sarcopenia/diagnostic imaging
8.
J Hepatocell Carcinoma ; 7: 143-153, 2020.
Article in English | MEDLINE | ID: mdl-32984091

ABSTRACT

BACKGROUND: The Child-Turcotte-Pugh score (CTP) is the most commonly used tool to assess hepatic reserve and predict survival in hepatocellular cancer (HCC). The CTP stratification accuracy has been questioned and attempts have been made to improve the objectivity of the system. Serum insulin-like growth factor-1 (IGF-1)-CTP has been proposed to improve CTP prognostic accuracy. We aimed to validate the IGF-CTP score in our patient population. PATIENTS AND METHODS: A total of 84 diagnosed HCC patients were enrolled prospectively. IGF-CTP scores in addition to CTP scores were calculated. C-index was used to compare the prognostic significance of the two scoring systems and overall survival (OS). RESULTS: Cirrhosis was present in 48 (57.1%) patients, 35 (41.7%) patients were non-cirrhotic, 36 (42.8%) patients were hepatitis B (HBV) positive, and 8 (9.5%) patients were hepatitis C (HCV) positive. Serum IGF-1 levels were significantly lower in cirrhotic compared with non-cirrhotic patients (p=0.04). There was a significant difference in OS rates of patients with serum IGF-1 level <50 ng/mL and patients with serum IGF-1 levels ≥50 ng/mL (p=0.02); the OS rates were 6.5 and 14.8 months, respectively (p=0.02). The median OS of all patients was 7.38 months (95% CI: 5.89-13.79). The estimated C-index for CTP and IGF-CTP scores was 0.605 (95% CI: 0.538, 0.672) and 0.599 (95% CI: 0.543, 0.655), respectively. The U statistics indicated that the C-indices between two scoring systems are not statistically different (P= 0.91). CONCLUSION: This study evaluated IGF-1 levels and the IGF-CTP classification in a predominantly HBV (+) cohort of HCC patients with 41.7% non-cirrhotic. Although the prognostic value was similar, among patients with CTP-A, class those reclassified as IGF-CTP B had shorter OS than those with IGF-CTP score A. Thus, further validations of IGF-CTP score in similar populations may add additional value as a stratification tool to predict HCC outcome.

9.
Front Oncol ; 10: 572, 2020.
Article in English | MEDLINE | ID: mdl-32457831

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is the most common liver malignancy and the leading cause of death in patients with cirrhosis. Various treatments for HCC are available, including transarterial chemoembolization (TACE), which is the commonest intervention performed in HCC. Radiologic tumor response following TACE is an important prognostic factor for patients with HCC. We hypothesized that, for large HCC tumors, assessment of treatment response made with automated volumetric response evaluation criteria in solid tumors (RECIST) might correlate with the assessment made with the more time- and labor-intensive unidimensional modified RECIST (mRECIST) and manual volumetric RECIST (M-vRECIST) criteria. Accordingly, we undertook this retrospective study to compare automated volumetric RECIST (A-vRECIST) with M-vRECIST and mRESIST for the assessment of large HCC tumors' responses to TACE. Methods:We selected 42 pairs of contrast-enhanced computed tomography (CT) images of large HCCs. Images were taken before and after TACE, and in each of the images, the HCC was segmented using both a manual contouring tool and a convolutional neural network. Three experienced radiologists assessed tumor response to TACE using mRECIST criteria. The intra-class correlation coefficient was used to assess inter-reader reliability in the mRECIST measurements, while the Pearson correlation coefficient was used to assess correlation between the volumetric and mRECIST measurements. Results:Volumetric tumor assessment using automated and manual segmentation tools showed good correlation with mRECIST measurements. For A-vRECIST and M-vRECIST, respectively, r = 0.597 vs. 0.622 in the baseline studies; 0.648 vs. 0.748 in the follow-up studies; and 0.774 vs. 0.766 in the response assessment (P < 0.001 for all). The A-vRECIST evaluation showed high correlation with the M-vRECIST evaluation (r = 0.967, 0.937, and 0.826 in baseline studies, follow-up studies, and response assessment, respectively, P < 0.001 for all). Conclusion:Volumetric RECIST measurements are likely to provide an early marker for TACE monitoring, and automated measurements made with a convolutional neural network may be good substitutes for manual volumetric measurements.

10.
Cardiovasc Intervent Radiol ; 43(2): 311-321, 2020 Feb.
Article in English | MEDLINE | ID: mdl-31591689

ABSTRACT

PURPOSE: To determine the tumor immune cell landscape after transcatheter arterial bland embolization (TAE) in a clinically relevant rat hepatocellular carcinoma (HCC) model. MATERIALS AND METHODS: Buffalo rats (n = 21) bearing syngeneic McArdle RH-7777 rat hepatoma cells implanted into the left hepatic lobe underwent TAE using 70-150 µm beads (n = 9) or hepatic artery saline infusion (n = 12). HCC nodules, peritumoral margin, adjacent non-cancerous liver, and splenic parenchyma were collected and disaggregated to generate single-cell suspensions for immunological characterization 14 d after treatment. Changes in tumor-infiltrating immune subsets including CD4 T cells (Th17 and Treg), CD8 cytotoxic T cells (IFNγ), and neutrophils were evaluated by multiparameter flow cytometry. Migration and colony formation assays were performed to examine the effect of IL-17, a signature cytokine of Th17 cells, on McArdle RH-7777 hepatoma cells under conditions simulating post-embolization environment (i.e., hypoxia and nutrient privation). Statistical significance was determined by the Student unpaired t test or one-way ANOVA. RESULTS: TAE induces increased infiltration of Th17 cells in liver tumors when compared with controls 14 d after treatment (0.29 ± 0.01 vs. 0.19 ± 0.02; p = 0.02). A similar pattern was observed in the spleen (1.41 ± 0.13 vs. 0.57 ± 0.08; p < 0.001), indicating both local and systemic effect. No significant differences in the percentage of FoxP3 + Tregs, IFNγ-producing CD4 T cells, and CD8 T cells were observed between groups (p > 0.05). In vitro post-embolization assays demonstrated that IL-17 reduces McA-RH7777 cell migration at 24-48 h (p = 0.003 and p = 0.002, respectively). CONCLUSION: Transcatheter hepatic arterial bland embolization induces local and systemic increased infiltration of Th17 cells and expression of their signature cytokine IL-17. In a simulated post-embolization environment, IL-17 significantly reduced McA-RH7777 cell migration.


Subject(s)
Carcinoma, Hepatocellular/therapy , Embolization, Therapeutic/methods , Liver Neoplasms/therapy , Th17 Cells/metabolism , Animals , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/immunology , Disease Models, Animal , Humans , Liver/diagnostic imaging , Liver/immunology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/immunology , Magnetic Resonance Imaging/methods , Male , Radiology, Interventional/methods , Rats , Rats, Inbred BUF , Th17 Cells/immunology
11.
J Immunother Cancer ; 7(1): 329, 2019 11 28.
Article in English | MEDLINE | ID: mdl-31779702

ABSTRACT

BACKGROUND: Currently, there are no imaging predictors of immunotherapy outcome in hepatocellular carcinoma (HCC). The study aim was to determine if stiffness changes measured by magnetic resonance elastography (MRE) can be a predictor of immunotherapy response in patients with advanced HCC. MATERIALS AND METHODS: This was a prospective study of 15 patients with biopsy proven-advanced HCC treated with Pembrolizumab. All patients had liver MRE and liver biopsy at baseline and at 6 weeks of therapy. Change in HCC stiffness on MRE was compared with overall survival (OS), time to disease progression (TTP), and number of intratumoral CD3+ T lymphocytes. Analysis was performed using descriptive statistics and Spearman correlation (R); p-value < 0.05 was considered statistically significant. RESULTS: Nine patients were evaluable. Median age was 71 years (range, 54-78). Etiology of liver disease was HCV (n = 4), HBV (n = 1) and NASH (n = 4). Median OS and TTP were 44 weeks and 13 weeks, respectively. Average baseline HCC stiffness and change in HCC stiffness were 5.0 kPa and 0.12 kPa, respectively. In contrast, average non-tumor liver stiffness was 3.2 kPa, and did not significantly change at 6 weeks (p = 0.42). Average size of measured tumor and change in size were 4 cm and - 0.32 cm, respectively. Change in HCC stiffness at 6 weeks correlated significantly with OS (R = 0.81), and TTP (R = 0.88,p < 0.01). Abundance of intratumoral T lymphocytes on tumor biopsy correlated significantly with HCC stiffness (R = 0.79,p = 0.007). CONCLUSION: Our pilot MRE data suggests early change in tumor stiffness may be an indicator of immunotherapy response in patients with advanced HCC.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Elasticity Imaging Techniques , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Aged , Biomarkers , Biopsy , Carcinoma, Hepatocellular/therapy , Female , Humans , Immunotherapy , Liver Neoplasms/therapy , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/metabolism , Lymphocytes, Tumor-Infiltrating/pathology , Male , Middle Aged , Prognosis , Severity of Illness Index , Treatment Outcome , Tumor Microenvironment
12.
J Comput Assist Tomogr ; 43(3): 499-506, 2019.
Article in English | MEDLINE | ID: mdl-31082956

ABSTRACT

PURPOSE: This pilot study evaluates the feasibility of automated volumetric quantification of hepatocellular carcinoma (HCC) as an imaging biomarker to assess treatment response for sorafenib. METHODS: In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study, a training database of manually labeled background liver, enhancing and nonenhancing tumor tissue was established using pretherapy and first posttherapy multiphasic computed tomography images from a registry of 13 HCC patients. For each patient, Hounsfield density and geometry-based feature images were generated from registered multiphasic computed tomography data sets and used as the input for a random forest-based classifier of enhancing and nonenhancing tumor tissue. Leave-one-out cross-validation of the dice similarity measure was applied to quantify the classifier accuracy. A Cox regression model was used to confirm volume changes as predictors of time to progression (TTP) of target lesions for both manual and automatic methods. RESULTS: When compared with manual labels, an overall classification accuracy of dice similarity coefficient of 0.71 for pretherapy and 0.66 posttherapy enhancing tumor labels and 0.45 for pretherapy and 0.59 for posttherapy nonenhancing tumor labels was observed. Automated methods for quantifying volumetric changes in the enhancing lesion agreed with manual methods and were observed as a significant predictor of TTP. CONCLUSIONS: Automated volumetric analysis was determined to be feasible for monitoring HCC response to treatment. The information extracted using automated volumetrics is likely to reproduce labor-intensive manual data and provide a good predictor for TTP. Further work will extend these studies to additional treatment modalities and larger patient populations.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Cone-Beam Computed Tomography/methods , Liver Neoplasms/diagnostic imaging , Sorafenib/administration & dosage , Aged , Carcinoma, Hepatocellular/drug therapy , Female , Humans , Liver Neoplasms/drug therapy , Male , Middle Aged , Pilot Projects , Regression Analysis , Retrospective Studies , Sorafenib/therapeutic use , Treatment Outcome
13.
Abdom Radiol (NY) ; 43(11): 3101-3108, 2018 11.
Article in English | MEDLINE | ID: mdl-29671009

ABSTRACT

PURPOSE: Large adrenal masses pose a diagnostic dilemma. The purpose of this study was twofold: first, to assess the degree of interobserver agreement in evaluating the morphology of pathologically proven adrenal adenomas and adrenocortical carcinomas larger than 4 cm in diameter; and second, to identify morphologic characteristics that correlated with the pathologic diagnosis. MATERIALS AND METHODS: For this blinded, retrospective study, we collected cases of 25 adrenal adenomas and 33 adrenocortical carcinomas measuring larger than 4 cm. Two radiologists evaluated morphologic characteristics of the lesions on CT. Interobserver agreement was evaluated using kappa statistics, and the correlation of imaging characteristics with the diagnosis was evaluated using a logistic regression model. RESULTS: We found the highest interobserver agreement in the assessment of precontrast attenuation (Κ = 0.81) as well as substantial agreement in determining the shape and the presence of calcifications (Κ = 0.69 and 0.74, respectively). Readers agreed less often regarding the presence of fat (Κ = 0.48), as well as regarding the presence of necrosis, heterogeneity, and the overall impression (Κ = 0.15, 0.24, and 0.26, respectively). CT characteristics correlated with benignity included round shape (p = 0.02), an overall radiologic impression of a benign lesion (p < 0.0001), the presence of fat (p = 0.01), and a precontrast attenuation of less than 10 Hounsfield units (p < 0.0001). The latter two of these characteristics were highly specific for benign pathology (93% and 100%, respectively). CONCLUSION: Our study suggests that CT has the ability to consistently identify characteristics significantly correlated with benign vs. malignant adrenal tumors.


Subject(s)
Adrenal Gland Neoplasms/diagnostic imaging , Adrenocortical Adenoma/diagnostic imaging , Adrenocortical Carcinoma/diagnostic imaging , Tomography, X-Ray Computed/methods , Adrenal Gland Neoplasms/pathology , Adrenocortical Adenoma/pathology , Adrenocortical Carcinoma/pathology , Aged , Contrast Media , Female , Humans , Male , Middle Aged , Observer Variation , Retrospective Studies
14.
J Clin Med ; 7(4)2018 Apr 14.
Article in English | MEDLINE | ID: mdl-29661994

ABSTRACT

Predicting outcomes in patients with hepatocellular carcinoma (HCC) who undergo locoregional therapies remains a substantial clinical challenge. The purpose of this study was to investigate pre-procedure diffusion weighted magnetic resonance imaging (DW-MRI) as an imaging biomarker for tumoral response to therapy for patients with HCC undergoing drug eluting embolic (DEE) chemoembolization and radioembolization. A retrospective review of HCC patients who underwent DEE chemoembolization or radioembolization was performed. Of the 58 patients who comprised the study population, 32 underwent DEE chemoembolization and 26 underwent radioembolization. There was no significant difference in median apparent diffusion coefficient (ADC) values across the two treatment groups (1.01 × 10-3 mm²/s, P = 0.25). The immediate objective response (OR) rate was 71% (40/56). Tumors with high ADC values were found to have a higher probability of OR within 90 days (odds ratio 4.4, P = 0.03). Moreover, index lesion specific progression free survival (PFS) was greater for high ADC tumors, independent of conventional predictors of treatment response (hazard ratio 0.44, P = 0.01). Low ADC was associated with poorer PFS (P = 0.02). Pre-procedure ADC < 1.01 × 10-3 mm²/s is an independent predictor of poorer immediate OR and index lesion specific PFS in patients with HCC undergoing DEE chemoembolization or radioembolization.

15.
J Am Coll Radiol ; 14(11S): S391-S405, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29101980

ABSTRACT

Because liver fibrosis can be treated, it is important to diagnose liver fibrosis noninvasively and monitor response to treatment. Although ultrasound (grayscale and Doppler) can diagnose cirrhosis, it does so unreliably using morphologic and sonographic features and cannot diagnose the earlier, treatable stages of hepatic fibrosis. Transient elastography, ultrasound elastography with acoustic radiation force impulse, and MR elastography are modalities that can assess for hepatic fibrosis. Although all international organizations recommend ultrasound for screening for hepatocellular carcinoma, ultrasound is particularly limited for identifying hepatocellular carcinoma in patients with obesity, nonalcoholic fatty liver disease, and nodular cirrhotic livers. In these patient groups as well as patients who are on the liver transplant wait list, ultrasound is so limited that consideration can be made for screening for hepatocellular carcinoma with either MRI or multiphase CT. Additionally, patients who have been previously diagnosed with and treated for hepatocellular carcinoma require continued surveillance for recurrent hepatocellular carcinoma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Diagnostic Imaging/methods , Fatty Liver/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Chronic Disease , Evidence-Based Medicine , Humans , Societies, Medical , United States
16.
J Am Coll Radiol ; 14(11S): S560-S569, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29101993

ABSTRACT

Pancreatic adenocarcinoma is associated with poor overall prognosis. Complete surgical resection is the only possible option for cure. As such, increasingly complex surgical techniques including sophisticated vascular reconstruction are being used. Continued advances in surgical techniques, in conjunction with use of combination systemic therapies, and radiation therapy have been suggested to improve outcomes. A key aspect to surgical success is reporting of pivotal findings beyond absence of distant metastases, such as tumor size, location, and degree of tumor involvement of specific vessels associated with potential perineural tumor spread. Multiphase contrast-enhanced multidetector CT and MRI are the imaging modalities of choice for pretreatment staging and presurgical determination of resectability. Imaging modalities such as endoscopic ultrasound and fluorine-18-2-fluoro-2-deoxy-D-glucose imaging with PET/CT are indicated for specific scenarios such as biopsy guidance and confirmation of distant metastases, respectively. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Subject(s)
Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathology , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/pathology , Diagnostic Imaging/methods , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/pathology , Adenocarcinoma/surgery , Carcinoma, Pancreatic Ductal/surgery , Evidence-Based Medicine , Humans , Neoplasm Staging , Pancreatic Neoplasms/surgery , Prognosis , Societies, Medical , United States
17.
J Am Coll Radiol ; 14(5S): S103-S117, 2017 May.
Article in English | MEDLINE | ID: mdl-28473066

ABSTRACT

Because liver fibrosis can be treated, it is important to diagnose liver fibrosis noninvasively and monitor response to treatment. Although ultrasound (grayscale and Doppler) can diagnose cirrhosis, it does so unreliably using morphologic and sonographic features and cannot diagnose the earlier, treatable stages of hepatic fibrosis. Transient elastography, ultrasound elastography with acoustic radiation force impulse, and MR elastography are modalities that can assess for hepatic fibrosis. Although all international organizations recommend ultrasound for screening for hepatocellular carcinoma, ultrasound is particularly limited for identifying hepatocellular carcinoma in patients with obesity, nonalcoholic fatty liver disease, and nodular cirrhotic livers. In these patients, as well as patients who are on the liver transplant wait list, ultrasound is so limited that consideration can be made for screening for hepatocellular carcinoma with either MRI or multiphase CT. Additionally, patients who have been previously diagnosed with and treated for hepatocellular carcinoma require continued surveillance for recurrent hepatocellular carcinoma. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Subject(s)
Carcinoma, Hepatocellular/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Liver Neoplasms/diagnostic imaging , Chronic Disease , Diagnostic Imaging/methods , Humans , Liver Diseases/diagnostic imaging , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Radiology , Societies, Medical , United States
18.
J Am Coll Radiol ; 14(5S): S314-S325, 2017 May.
Article in English | MEDLINE | ID: mdl-28473088

ABSTRACT

Liver metastases are the most common malignant liver tumors. The accurate and early detection and characterization of liver lesions is the key to successful treatment strategies. Increasingly, surgical resection in combination with chemotherapy is effective in significantly improving survival if all metastases are successfully resected. MRI and multiphase CT are the primary imaging modalities in the assessment of liver metastasis, with the relative preference toward multiphase CT or MRI depending upon the clinical setting (ie, surveillance or presurgical planning). The optimization of imaging parameters is a vital factor in the success of either modality. PET/CT, intraoperative ultrasound are used to supplement CT and MRI. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer-reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.


Subject(s)
Liver Neoplasms/diagnostic imaging , Liver Neoplasms/secondary , Evidence-Based Medicine , Humans , Liver Neoplasms/therapy , Magnetic Resonance Imaging , Multidetector Computed Tomography , Positron Emission Tomography Computed Tomography , Radiology , Societies, Medical , United States
19.
Radiology ; 283(2): 314-340, 2017 05.
Article in English | MEDLINE | ID: mdl-28418819

ABSTRACT

The field of cancer genomics is rapidly evolving and has led to the development of new therapies. Knowledge of commonly involved cellular pathways and genetic mutations is now essential for radiologists reading oncology cases. Radiogenomics is an emerging area of research that seeks to correlate imaging features with cancer genotypes. Such knowledge may extend the utility of multiparametric imaging to yield information regarding cancer prognosis and likelihood of therapeutic response. To date, only a handful of radiogenomics studies have been performed to evaluate solid tumors of the body, and there is much to explore. Before doing so, however, it behooves us to have adequate background knowledge of clinical cancer genomics to design meaningful radiogenomics projects and explore imaging phenotypes. Herein, an up-to-date, detailed overview is provided of well-known and common mutations of solid body tumors (such as human epithelial growth factor receptor 2, breast cancer susceptibility protein), newer genomic alterations with potential for clinical relevance, and a discussion of known related imaging findings, including existing radiogenomics data and other radiologic patterns of disease. © RSNA, 2017 Online supplemental material is available for this article.


Subject(s)
Biomarkers, Tumor/genetics , Genes, Neoplasm/genetics , Neoplasm Proteins/genetics , Neoplasms/diagnostic imaging , Neoplasms/genetics , Polymorphism, Single Nucleotide/genetics , DNA Mutational Analysis/methods , Diagnostic Imaging/methods , Genetic Predisposition to Disease/genetics , Humans , Mutation/genetics
20.
J Comput Assist Tomogr ; 41(1): 67-74, 2017 Jan.
Article in English | MEDLINE | ID: mdl-27529683

ABSTRACT

PURPOSE: To qualitatively and quantitatively compare abdominal computed tomography (CT) images reconstructed with a new version of model-based iterative reconstruction (Veo 3.0; GE Healthcare) to those created with Veo 2.0. MATERIALS AND METHODS: This retrospective study was approved by our institutional review board and was Health Insurance Portability and Accountability Act compliant. The raw data from 29 consecutive patients who had undergone CT abdomen scanning was used to reconstruct 4 sets of 3.75-mm axial images: Veo 2.0, Veo 3.0 standard, Veo 3.0 5% resolution preference (RP), and Veo 3.0 20% RP. A slice thickness optimization of 3.75 mm and texture feature was selected for Veo 3.0 reconstructions.The images were reviewed by 3 independent readers in a blinded, randomized fashion using a 5-point Likert scale and 5-point comparative scale.Multiple 2-dimensional circular regions of interest were defined for noise and contrast-to-noise ratio measurements. Line profiles were drawn across the 7 lp/cm bar pattern of the CatPhan 600 phantom for spatial resolution evaluation. RESULTS: The Veo 3.0 standard image set was scored better than Veo 2.0 in terms of artifacts (mean difference, 0.43; 95% confidence interval [95% CI], 0.25-0.6; P < 0.0001), overall image quality (mean difference, 0.87; 95% CI, 0.62-1.13; P < 0.0001) and qualitative resolution (mean difference, 0.9; 95% CI, 0.69-1.1; P < 0.0001). Although the Veo 3.0 standard and RP05 presets were preferred across most categories, the Veo 3.0 RP20 series ranked best for bone detail. Image noise and spatial resolution increased along a spectrum with Veo 2.0 the lowest and RP20 the highest. CONCLUSION: Veo 3.0 enhances imaging evaluation relative to Veo 2.0; readers preferred Veo 3.0 image appearance despite the associated mild increases in image noise. These results provide suggested parameters to be used clinically and as a basis for future evaluations, such as focal lesion detection, in the oncology setting.


Subject(s)
Abdominal Neoplasms/diagnostic imaging , Algorithms , Radiographic Image Interpretation, Computer-Assisted/methods , Radiography, Abdominal/methods , Software , Tomography, X-Ray Computed/methods , Adult , Female , Humans , Male , Radiographic Image Enhancement/methods , Random Allocation , Reproducibility of Results , Sensitivity and Specificity , Signal-To-Noise Ratio , Young Adult
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