Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area: What's new 12 months later?

INTRODUCTION AND OBJECTIVES: The lockdown policy introduced in 2020 to minimize the spread of the COVID-19 pandemic, significantly affected the management and care of patients affected by hepatocellular carcinoma (HCC). The aim of this follow-up study was to determine the 12 months impact of the COVID-19 pandemic on the cohort of patients affected by HCC during the lockdown, within six French academic referral centers in the metropolitan area of Paris. MATERIALS AND METHODS: We performed a 12 months follow-up of the cross-sectional study cohort included in 2020 on the management of patients affected by HCC during the first six weeks of the COVID-19 pandemic (exposed), compared to the same period in 2019 (unexposed). Overall survival were compared between the groups. Predictors of mortality were analysed with Cox regression. RESULTS: From the initial cohort, 575 patients were included (n = 263 Exposed_COVID, n = 312 Unexposed_COVID). Overall and disease free survival at 12 months were 59.9 ± 3.2% vs 74.3 ± 2.5% (p<0.001) and 40.2 ± 3.5% vs 63.5 ± 3.1% (p<0.001) according to the period of exposure (Exposed_COVID vs Unexposed_COVID, respectively). Adjusted Cox regression revealed that the period of exposure (Exposed_COVID HR: 1.79, 95%CI (1.36, 2.35) p<0.001) and BCLC stage B, C and D (BCLC B HR: 1.82, 95%CI (1.07, 3.08) p = 0.027 - BCLC C HR: 1.96, 95%CI (1.14, 3.38) p = 0.015 - BCLC D HR: 3.21, 95%CI (1.76, 5.85) p<0.001) were predictors of death. CONCLUSIONS: Disruption of routine healthcare services because of the pandemic translated to reduced 1 year overall and disease-free survival among patients affected by HCC, in the metropolitan area of Paris, France.

Impact of Extended Use of Ablation Techniques in Cirrhotic Patients with Hepatocellular Carcinoma: A Cost-Effectiveness Analysis.

BACKGROUND: To evaluate the cost-effectiveness of the extended use of ablation for the treatment of hepatocellular carcinoma (HCC) with cirrhosis in an expert ablation center when compared to the non-extended use of ablation in equivalent tertiary care centers. METHODS: Consecutive cirrhotic patients with non-metastatic HCC, no prior treatment, and referred to three tertiary care centers between 2012 and 2016 were retrospectively identified. The Bondy group, including all of the patients treated at Jean Verdier Hospital, where the extended use of ablation is routinely performed, was compared to the standard of care (SOC) group, including all of the patients treated at the Beaujon and Mondor Hospitals, using propensity score matching. A cost-effectiveness analysis was carried out from the perspective of French health insurance using a Markov model on a lifetime horizon. RESULTS: 532 patients were matched. The Bondy group led to incremental discounted lifetime effects of 0.8 life-years gained (LYG) (95% confidence interval: 0.4, 1.3) and a decrease in lifetime costs of EUR 7288 (USD 8016) (95% confidence interval: EUR 5730 [USD 6303], EUR 10,620 [USD 11,682]) per patient, compared with the SOC group, resulting in a dominant mean incremental cost-effectiveness ratio (ICER). A compliance with the Barcelona Clinic Liver Classification (BCLC) guidelines for earlier stage contributed to the greater part of the ICER. CONCLUSION: The extended use of ablation in cirrhotic patients with HCC was more effective and less expensive than the non-extended use of the ablation strategy.

Impact of COVID-19 on the management of hepatocellular carcinoma in a high-prevalence area.

BACKGROUND & AIMS: Patients affected by hepatocellular carcinoma (HCC) represent a vulnerable population during the COVID-19 pandemic and may suffer from altered allocation of healthcare resources. The aim of this study was to determine the impact of the COVID-19 pandemic on the management of patients with HCC within 6 referral centres in the metropolitan area of Paris, France. METHODS: We performed a multicentre, retrospective, cross-sectional study on the management of patients with HCC during the first 6 weeks of the COVID-19 pandemic (exposed group), compared with the same period in 2019 (unexposed group). We included all patients discussed in multidisciplinary tumour board (MTB) meetings and/or patients undergoing a radiological or surgical programmed procedure during the study period, with curative or palliative intent. Endpoints were the number of patients with a modification in the treatment strategy, or a delay in decision-to-treat. RESULTS: After screening, n = 670 patients were included (n = 293 exposed to COVID, n = 377 unexposed to COVID). Fewer patients with HCC presented to the MTB in 2020 (p = 0.034) and fewer had a first diagnosis of HCC (n = 104 exposed to COVID, n = 143 unexposed to COVID, p = 0.083). Treatment strategy was modified in 13.1% of patients, with no differences between the 2 periods. Nevertheless, 21.5% vs. 9.5% of patients experienced a treatment delay longer than 1 month in 2020 compared with 2019 (p <0.001). In 2020, 7.1% (21/293) of patients had a diagnosis of an active COVID-19 infection: 11 (52.4%) patients were hospitalised and 4 (19.1%) patients died. CONCLUSIONS: In a metropolitan area highly impacted by the COVID-19 pandemic, we observed fewer patients with HCC, and similar rates of treatment modification, but with a significantly longer treatment delay in 2020 vs. 2019. LAY SUMMARY: During the coronavirus disease 2019 (COVID-19) pandemic era, fewer patients with hepatocellular carcinoma (HCC) presented to the multidisciplinary tumour board, especially with a first diagnosis of HCC. Patients with HCC had a treatment delay that was longer in the COVID-19 period than in 2019.

B1 artifact reduction in abdominal DCE-MRI using kT -points: First clinical assessment of dynamic RF shimming at 3T.

BACKGROUND: The excitation inhomogeneity artifact occurring at 3T in the abdomen can lead to dramatic loss of signal and contrast, thereby hampering diagnosis. PURPOSE: To assess excitation homogeneity and image quality achieved by nonselective prototypical kT -points pulses, compared to tailored static RF shimming, in clinical routine on a commercial dual-transmit scanner. STUDY TYPE: Retrospective study with Institutional Review Board approval; informed consent was waived. POPULATION: Fifty consecutive patients referred for liver MRI at a single hospital. FIELD STRENGTH/SEQUENCE: 3D breath-hold dynamic contrast-enhanced (DCE) MRI at 3T. ASSESSMENT: Flip angle homogeneity was estimated via numerical simulation based on measured static and RF field maps. In all, 20 of the 50 patients underwent DCE-MRI while a pulse designer was present. The effect of RF shimming and kT -point pulses could be compared by repeating the acquisition with each transmit scheme before injection and in the late phase. Signal homogeneity, T1 contrast, enhancement quality, structure details, and global image quality were assessed on a 4-level scale (0 to 3) by two radiologists. STATISTICAL TESTS: Means were compared using Wilcoxon signed-rank tests. RESULTS: Normalized root mean square flip angle error was significantly reduced with kT -points compared to static RF shimming (8.5% ± 1.5% [mean ± standard deviation, SD] vs. 20.4% ± 9.8%; P < 0.0001). The worst case (heavy ascites) led to 13.0% (kT -points) vs. 54.9% (RF shimming). Global image quality was significantly higher for kT -points (2.3 ± 0.5 vs. 1.9 ± 0.6; P = 0.008). One subject's examination was judged unusable with RF shimming by one reader, none with kT -points. 85% of kT -points acquisitions were graded at least 2/3, and only 55% for static RF shimming. DATA CONCLUSION: KT -points reduce excitation inhomogeneity quantitatively and qualitatively, especially in patients with ascites and prone to B1 shading. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:1562-1571.

Hepatectomy for hepatocellular carcinoma larger than 10 cm: preoperative risk stratification to prevent futile surgery.

OBJECTIVES: Appropriate patient selection is important to achieving good outcomes and obviating futile surgery in patients with huge (≥10 cm) hepatocellular carcinoma (HCC). The aim of this study was to identify independent predictors of futile outcomes, defined as death within 3 months of surgery or within 1 year from early recurrence following hepatectomy for huge HCC. METHODS: The outcomes of 149 patients with huge HCCs who underwent resection during 1995-2012 were analysed. Multivariate logistic regression analysis was performed to identify preoperative independent predictors of futility. RESULTS: Independent predictors of 3-month mortality (18.1%) were: total bilirubin level >34 µmol/l [P = 0.0443; odds ratio (OR) 16.470]; platelet count of <150 000 cells/ml (P = 0.0098; OR 5.039), and the presence of portal vein tumour thrombosis (P = 0.0041; OR 5.138). The last of these was the sole independent predictor of 1-year recurrence-related mortality (17.2%). Rates of recurrence-related mortality at 3 months and 1 year were, respectively, 6.3% and 7.1% in patients with Barcelona Clinic Liver Cancer (BCLC) stage A disease, 12.5% and 14% in patients with BCLC stage B disease, and 37.8% (P = 0.0002) and 75% (P = 0.0002) in patients with BCLC stage C disease. CONCLUSIONS: According to the present data, among patients submitted to hepatectomy for huge HCC, those with a high bilirubin level, low platelet count and portal vein thrombosis are at higher risk for futile surgery. The presence of portal vein tumour thrombosis should be regarded as a relative contraindication to surgery.

Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

OBJECTIVES: Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. MATERIALS AND METHODS: This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. RESULTS: A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate. CONCLUSIONS: Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it should be considered in the routine evaluation of solid tumors treated with antiangiogenic therapy.

Is multidetector computed tomography a suitable alternative to MR imaging for the assessment of myocardial necrosis after alcohol septal ablation?

BACKGROUND: To compare magnetic resonance (MR) imaging and multidetector computed tomography (MDCT) for the assessment of myocardial infarction (MI) after alcohol septal ablation (ASA). METHODS: Ten patients (mean age, 60 years ± 16) were examined with both MDCT and 1.5-T MR imaging performed 10 minutes after injection, within 3 days after ASA. Half of them had a temporary pacemaker (PM) during MDCT examination. Global image quality (IQ) and localization of MI were noticed on both MDCT and MR images. Volumes of MI, contrast-to-noise ratios (CNR) and signal-to-noise ratios (SNR) were also calculated. ASA effectiveness was evaluated by echocardiography immediately and 3 months after procedure. RESULTS: Global IQ was considered adequate for both procedures. In 8 patients, MI reached the basal part of the septum on both MDCT and MR images. The 2 remaining patients exhibited sparing of the basal septum on MDCT and MR images. Volumes of MI were within the same range with the 2 techniques (MDCT: 22.1 ± 8.8 mL; MR imaging: 23.8 ± 9.4 mL) and correlated well each other (R(2)=0.85, p<0.002). The 2 patients with sparing of the basal interventricular septum had persistent gradient on echocardiography 3 months after ASA, suggesting failure of the procedure. The volumes of MI didn't correlate with the reduction of pressure gradient on echocardiography 3 months after ASA (R(2)=0.02, p<0.05). CONCLUSIONS: Evaluation of post ASA MI is feasible with MDCT by comparison with MR imaging. MDCT might serve as an alternative imaging method in case of PM implantation.

Whole-body diffusion magnetic resonance imaging in the assessment of lymphoma.

The current evidence regarding the usefulness of whole-body diffusion-weighted magnetic resonance imaging (diffusion MRI) in the assessment of lymphoma is reviewed. Diffusion MRI combining both anatomical and bio-physiological information is currently under investigation as a valuable tool in the oncology field including lymphoma, not only for staging but also for the assessment of response. Representative images for each purpose are shown. Diffusion MRI requires no administration of contrast medium and does not use ionizing radiation, which could be particularly advantageous for repeat follow-up surveillance in lymphoma patients. Diffusion MRI may prove to be a useful biomarker in clinical decision making for patients with lymphoma. Large-scale prospective studies are warranted to further establish its complementary value to the current standard of care, [(18)F]fluorodeoxyglucose positron emission tomography/computed tomography.

Whole-body diffusion-weighted imaging with apparent diffusion coefficient mapping for treatment response assessment in patients with diffuse large B-cell lymphoma: pilot study.

OBJECTIVES: The aim of this pilot study was to assess post-treatment apparent diffusion coefficient (ADC) changes of diffuse large B-cell lymphoma lesions on respiratory-gated whole-body diffusion-weighted imaging (DWI), with integrated (18)F-fluoro-2-deoxyglucose positron emission tomography/computed tomography (PET/CT) as the reference standard. MATERIALS AND METHODS: A total of 15 patients underwent both whole-body DWI (b = 50, 400, 800 s/mm(2)) and PET/CT before initiation and after 4 cycles of chemotherapy. ADC of residual masses (lymph node and organ lesions) was assessed both visually and quantitatively, including measurement of mean ADC (ADC).(Figure is included in full-text article.) RESULTS: After chemotherapy, among 85 examined lymph node regions, residual nodes were present in 62 (73%) regions on DWI. Of these 62 regions, 26 had persistent lymph nodes with longest transverse diameter >10 mm, ie, positive based on DWI size criteria. The mean ADC of these 26 regions increased from 0.658 × 10(-3) ± 0.153 mm(2)/s (standard deviation) at baseline to 1.501 × 10(-3) ± 0.307 mm(2)/s (paired t test, P < 0.0001). Only 6 of these 26 regions were considered positive on PET/CT. Combining visual ADC analysis to size criteria reduced the number of false-positive results of DWI from 20 to 2 regions. For organ involvement, ADC values also increased compared with baseline (1.558 × 10(-3) ± 0.424 mm(2)/s vs. 0.675 × 10(-3) ± 0.135 mm(2)/s, respectively; P = 0.0009). CONCLUSIONS: Whole-body DWI with ADC mapping can show a significant increase in ADC values of residual masses persisting after treatment and may help to assess the treatment response in patients with diffuse large B-cell lymphoma.

Multiple myeloma treatment response assessment with whole-body dynamic contrast-enhanced MR imaging.

PURPOSE: To compare posttreatment bone marrow changes at whole-body dynamic contrast material-enhanced magnetic resonance (MR) imaging with clinical response in patients with multiple myeloma (MM) and to determine if this technique can be used to assess treatment response in patients with MM. MATERIALS AND METHODS: This study was approved by an institutional review board; all patients gave informed written consent. Thirty patients (21 men, nine women; mean age, 58 years +/- 10 [standard deviation]) underwent whole-body dynamic contrast-enhanced MR imaging before treatment, after induction chemotherapy (n = 30), and after autologous stem cell transplantation (ASCT) (n = 20). Maximal percentages of bone marrow (BME(max)) and focal lesion (FLE(max)) enhancement were assessed at each MR imaging examination. Clinical responses were determined on the basis of international uniform response criteria. Posttreatment changes in BME(max)and FLE(max)were compared with clinical response to therapy by using the Mann-Whitney U test. Receiver operating characteristic (ROC) analysis of posttreatment BME(max)was used to identify poor responders. RESULTS: Eleven of 30 patients were good responders to induction chemotherapy; 16 of 20 patients were good responders to ASCT. After induction chemotherapy, mean BME(max)differed between good and poor responders (94.3% vs 138.4%, respectively; P = .02). With the exclusion of results from six examinations with focal lesions in which a poor clinical response was classified but BME(max)had normalized, a posttreatment BME(max)of more than 96.8% had 100% sensitivity for the identification of poor responders (specificity, 76.9%; area under the ROC curve, 0.90; P = .0001). Mean FLE(max)after induction chemotherapy did not differ between good and poor responders. Mean timing (ie, the number of postcontrast dynamic acquisitions where FLE(max)was observed) was significantly delayed in good responders compared with poor responders (4.7 vs 2.9, P < .0001). Post-ASCT MR imaging results correctly depicted all four clinically good responders whose disease subsequently progressed. CONCLUSION: With quantitative analysis of BME(max)and the timing of FLE(max), whole-body dynamic contrast-enhanced MR imaging can be used to assess treatment response in patients with MM.

Early 18F-FDG PET for prediction of prognosis in patients with diffuse large B-cell lymphoma: SUV-based assessment versus visual analysis.

UNLABELLED: The purpose of this study was to assess the prognostic value of early (18)F-FDG PET using standardized uptake value (SUV) compared with visual analysis in patients with diffuse large B-cell lymphoma (DLBCL). METHODS: Ninety-two patients with newly diagnosed DLBCL underwent (18)F-FDG PET prospectively before and after 2 cycles of chemotherapy (at midtherapy). Maximum SUV (SUVmax) and mean SUV (SUVmean) normalized to body weight and body surface area, as well as tumor-to-normal ratios, were computed on the most intense uptake areas. The SUVs, tumor-to-normal ratios, and their changes over time were compared with visual analysis for predicting event-free survival (EFS) and overall survival, using receiver-operating-characteristic (ROC) analysis. Survival curves were estimated with Kaplan-Meier analysis and compared using the log-rank test. RESULTS: With visual analysis, the accuracy of early PET to predict EFS was 65.2%. The 2-y estimate for EFS was 51% (95% confidence interval [CI], 34%-68%) in the PET-positive group compared with 79% (95% CI, 68%-90%) in the PET-negative group (P = 0.009). An optimal cutoff value of 65.7% SUVmax reduction from baseline to midtherapy obtained from ROC analysis yielded an accuracy of 76.1% to predict EFS. The 2-y estimate for EFS was 21% (95% CI, 0%-42%) in patients with SUVmax reduction 65.7% (P < 0.0001). Fourteen patients considered as positive on visual analysis could have been reclassified as good responders. CONCLUSION: SUV-based assessment of therapeutic response during first-line chemotherapy improves the prognostic value of early (18)F-FDG PET compared with visual analysis in DLBCL.

Assessment of critical limb ischemia in patients with diabetes: comparison of MR angiography and digital subtraction angiography.

OBJECTIVE: The purpose of our study was to evaluate the diagnostic accuracy of hybrid MR angiography by comparison with digital subtraction angiography (DSA) in diabetic patients with critical limb ischemia. SUBJECTS AND METHODS: Thirty-one patients prospectively underwent both hybrid MR angiography and DSA. The hybrid MR angiography study consisted of high-resolution MR angiography of a single calf and foot using a contrast-enhanced 3D gradient-echo volumetric interpolated breath-hold examination with surface coils, followed by three-station bolus chase MR angiography with a dedicated peripheral vascular coil. Two blinded reviewers separately analyzed maximum-intensity-projection hybrid MR angiograms and DSA images. The peripheral vessels were divided into 10 anatomic segments for review. The status of each segment was graded as normal, stenosis less than 50% in diameter, stenosis greater than 50%, or occluded. The sensitivity and specificity of hybrid MR angiography were determined using DSA as the gold standard. Treatment options were considered separately from the results of each examination. RESULTS: Among 310 analyzed segments, the sensitivities of hybrid MR angiography for stenosis and occlusion were, respectively, 95% and 95% for reviewer 1 and 96% and 90% for reviewer 2. The specificities of hybrid MR angiography for stenosis and occlusion were, respectively, 98% and 98% for reviewer 1 and 98% and 99% for reviewer 2. In 25 patients (81%), the quality of bolus chase MR angiography images was insufficient to assess runoff arteries. All treatments proposed on the basis of DSA findings were endorsed by hybrid MR angiography findings. Eleven more treatments were formulated on the basis of hybrid MR angiography findings. Of these, four were due to overestimation of stenosis on MR angiography and seven were due to the detection of patent infrageniculate arteries on hybrid MR angiography that were not detected on DSA. CONCLUSION: Hybrid MR angiography depicts runoff arteries not seen on DSA. Hybrid MR angiography may be useful for treatment planning in selected diabetic patients with critical limb ischemia.