Comparative assessment of standard and immune response criteria for evaluation of response to PD-1 monotherapy in unresectable HCC.

PURPOSE: To assess response to programmed death-1 (PD-1) monotherapy (nivolumab) in hepatocellular carcinoma (HCC) patients using RECIST1.1, modified RECIST (mRECIST), and immune RECIST (iRECIST). A secondary objective was to identify clinicolaboratory and imaging variables predictive of progressive disease (PD) and overall survival (OS). METHODS: Patients with HCC treated with nivolumab at a single institution from 5/2016 to 12/2019 with MRI or CT performed ≥ 4 weeks post treatment were retrospectively assessed. Patients who received concurrent locoregional, radiation, or other systemic therapies were excluded. Response was assessed by 2 observers in consensus using RECIST1.1, mRECIST, and iRECIST at 3/6/9/12-month time points. Time to progression (TTP) and OS were recorded. Clinicolaboratory and imaging variables were evaluated as predictors of PD and OS using uni-/multivariable and Cox regression analyses. RESULTS: Fifty-eight patients (42M/16F) were included. 118 target lesions (TL) were identified before treatment. Baseline mean TL size was 49.1 ± 43.5 mm (range 10-189 mm) for RECIST1.1/iRECIST and 46.3 ± 42.3 mm (range 10-189 mm) for mRECIST. Objective response rate (ORR) was 21% for mRECIST/iRECIST/RECIST1.1, with no cases of pseudoprogression. Median OS and median TTP were 717 days and 127 days for RECIST1.1/mRECIST/iRECIST-iUPD (unconfirmed PD). Older age, MELD/Child-Pugh scores, AFP, prior transarterial radioembolization (TARE), and larger TL size were predictive of PD and/or poor OS using mRECIST/iRECIST. The strongest predictor of PD (HR = 2.49, 95% CI 1.29-4.81, p = 0.007) was TARE. The strongest predictor of poor OS was PD by mRECIST/iRECIST at 3 months (HR = 2.26, 95% CI 1.00-5.10, p = 0.05) with borderline significance. CONCLUSION: Our results show ORR of 21%, equivalent for mRECIST, iRECIST, and RECIST1.1 in patients with advanced HCC clinically treated with nivolumab.

4D flow MRI for the assessment of renal transplant dysfunction: initial results.

OBJECTIVES: (1) Determine inter-observer reproducibility and test-retest repeatability of 4D flow parameters in renal allograft vessels; (2) determine if 4D flow measurements in the renal artery (RA) and renal vein (RV) can distinguish between functional and dysfunctional allografts; (3) correlate haemodynamic parameters with estimated glomerular filtration rate (eGFR), perfusion measured with dynamic contrast-enhanced MRI (DCE-MRI) and histopathology. METHODS: Twenty-five prospectively recruited renal transplant patients (stable function/chronic renal allograft dysfunction, 12/13) underwent 4D flow MRI at 1.5 T. 4D flow coronal oblique acquisitions were performed in the transplant renal artery (RA) (velocity encoding parameter, VENC = 120 cm/s) and renal vein (RV) (VENC = 45 cm/s). Test-retest repeatability (n = 3) and inter-observer reproducibility (n = 10) were assessed by Cohen's kappa, coefficient of variation (CoV) and Bland-Altman statistics. Haemodynamic parameters were compared between patients and correlated to the estimated glomerular filtration rate, DCE-MRI parameters (n = 10) and histopathology from allograft biopsies (n = 15). RESULTS: For inter-observer reproducibility, kappa was > 0.99 and 0.62 and CoV of flow was 12.6% and 7.8% for RA and RV, respectively. For test-retest repeatability, kappa was > 0.99 and 0.5 and CoV of flow was 27.3% and 59.4%, for RA and RV, respectively. RA (p = 0.039) and RV (p = 0.019) flow were both significantly reduced in dysfunctional allografts. Both identified chronic allograft dysfunction with good diagnostic performance (RA: AUC = 0.76, p = 0.036; RV: AUC = 0.8, p = 0.018). RA flow correlated negatively with histopathologic interstitial fibrosis score ci (ρ = - 0.6, p = 0.03). CONCLUSIONS: 4D flow parameters had better repeatability in the RA than in the RV. RA and RV flow can identify chronic renal allograft dysfunction, with RA flow correlating with histopathologic interstitial fibrosis score. KEY POINTS: • Inter-observer reproducibility of 4D flow measurements was acceptable in both the transplant renal artery and vein, but test-retest repeatability was better in the renal artery than in the renal vein. • Blood flow measurements obtained with 4D flow MRI in the renal artery and renal vein are significantly reduced in dysfunctional renal transplants. • Renal transplant artery flow correlated negatively with histopathologic interstitial fibrosis score.

Does quantitative assessment of arterial phase hyperenhancement and washout improve LI-RADS v2018-based classification of liver lesions?

OBJECTIVES: To compare interreader agreement and diagnostic accuracy of LI-RADS v2018 categorization using quantitative versus qualitative MRI assessment of arterial phase hyperenhancement (APHE) and washout (WO) of focal liver lesions. METHODS: Sixty patients (19 female; mean age, 56 years) at risk for HCC with 71 liver lesions (28 HCCs, 43 benign) who underwent contrast-enhanced MRI were included in this retrospective study. Four blinded radiologists independently assigned a qualitative LI-RADS score per lesion. Two other radiologists placed ROIs within the lesion, adjacent liver parenchyma, and paraspinal musculature on pre- and post-contrast MR images. The percentage of arterial enhancement and the liver-to-lesion contrast ratio were calculated for quantification of APHE and WO. Using these quantitative parameters, a quantitative LI-RADS score was assigned. Interreader agreement and AUCs were calculated. RESULTS: Interreader agreement was similar for qualitative and quantitative LI-RADS (κ = 0.38 vs. 0.40-0.47) with a tendency towards improved agreement for quantitatively assessed APHE (κ = 0.65 vs. 0.81) and WO (κ = 0.53 vs. 0.78). Qualitative LI-RADS showed an AUC of 0.86, 0.94, 0.94, and 0.91 for readers 1, 2, 3, and 4, respectively. The quantitative LI-RADS score where APHE/WO/or both were replaced showed an AUC of 0.89/0.84/0.89, 0.95/0.92/0.92, 0.93/0.91/0.89, and 0.91/0.86/0.88 for readers 1, 2, 3, and 4, respectively. Sensitivity of LR-4/5 slightly increased, while specificity slightly decreased using quantitative APHE. CONCLUSION: Qualitative and quantitative LI-RADS showed similar performance. Quantitatively assessed APHE showed the potential to increase interreader agreement and sensitivity of HCC diagnosis, whereas quantitatively assessed WO had the opposite effect and needs to be redefined. KEY POINTS: • Quantitative assessment of arterial phase hyperenhancement shows the potential to increase interreader agreement and sensitivity to diagnose hepatocellular carcinoma. • Adding quantitative measurements of major LI-RADS features does not improve accuracy over qualitative assessment alone according to the LI-RADS v2018 algorithm.

Volumetric assessment of solid pulmonary nodules on ultralow-dose CT: a phantom study.

BACKGROUND: To reduce the radiation exposure from chest computed tomography (CT), ultralow-dose CT (ULDCT) protocols performed at sub-millisievert levels were previously tested for the evaluation of pulmonary nodules (PNs). The purpose of our study was to investigate the effect of ULDCT and iterative image reconstruction on volumetric measurements of solid PNs. METHODS: CT datasets of an anthropomorphic chest phantom containing solid microspheres were obtained with a third-generation dual-source CT at standard dose, 1/8th, 1/20th and 1/70th of standard dose [CT volume dose index (CTDIvol): 0.03-2.03 mGy]. Semi-automated volumetric measurements were performed on CT datasets reconstructed with filtered back projection (FBP) and advanced modelled iterative reconstruction (ADMIRE), at strength level 3 and 5. Absolute percentage error (APE) evaluated measurement accuracy related to the effective volume. Scan repetition differences were evaluated using Bland-Altman analysis. Two-way analysis of variance (ANOVA) assessed influence of different scan parameters on APE. Proportional differences (PDs) tested the effect of dose settings and reconstruction algorithms on volumetric measurements, as compared to the standard protocol (standard dose-FBP). RESULTS: Bland-Altman analysis revealed small mean interscan differences of APE with narrow limits of agreement (-0.1%±4.3% to -0.3%±3.8%). Dose settings (P<0.001), reconstruction algorithms (P<0.001), nodule diameters (P<0.001) and nodule density (P=0.011) had statistically significant influence on APE. Post-hoc Bonferroni tests showed slightly higher APE when scanning with 1/70th of standard dose [mean difference: 3.4%, 95% confidence interval (CI): 2.5-4.3%; P<0.001], and for image reconstruction with ADMIRE5 (mean difference: 1.8%, 95% CI: 1.0-2.5%; P<0.001). No significant differences for scanning with 1/20th of standard dose (P=0.42), and image reconstruction with ADMIRE3 (P=0.19) were found. Scanning with 1/70th of standard dose and image reconstruction with FBP showed the widest range of PDs (-16.8% to 23.4%) compared to standard dose-FBP. CONCLUSIONS: Our phantom study showed no significant difference between nodule volume measurements on standard dose CT (CTDIvol: 2 mGy) and ULDCT with 1/20th of standard dose (CTDIvol: 0.10 mGy).