Prognostic factors influencing outcomes in hepatocellular carcinoma patients undergoing selective internal radiation therapy.

Selective internal radiation therapy (SIRT) has emerged as a viable endovascular treatment strategy for hepatocellular carcinoma (HCC). According to the Barcelona Clinic Liver Cancer (BCLC) classification, SIRT is currently recommended for early- and intermediate-stage HCC that is unsuitable for alternative locoregional therapies. Additionally, SIRT remains a recommended treatment for patients with advanced-stage HCC and portal vein thrombosis (PVT) without extrahepatic metastasis. Several studies have shown that SIRT is a versatile and promising treatment with a wide range of applications. Consequently, given its favourable characteristics in various scenarios, SIRT could be an encouraging treatment option for patients with HCC across different BCLC stages. Over the past decade, an increasing number of studies have focused on better understanding the prognostic factors associated with SIRT to identify patients who derive the most benefit from this treatment or to refine the optimal technical procedures of SIRT. Several variables can influence treatment decisions, with a growing emphasis on a personalised approach. This review, based on the literature, will focus on the prognostic factors associated with the effectiveness of radioembolization and related complications. By comprehensively analysing these factors, we aimed to provide a clearer understanding of how to optimise the use of SIRT in managing HCC patients, thereby enhancing outcomes across various clinical scenarios.

Interest of Integrated Whole-Body PET/MR Imaging in Gastroenteropancreatic Neuroendocrine Neoplasms: A Retro-Prospective Study.

INTRODUCTION AND AIM: Simultaneous positron emission tomography/magnetic resonance imaging (PET-MRI) combines the high sensitivity of PET with the high specificity of MRI and is a tool for the assessment of gastroenteropancreatic neuroendocrine neoplasms (G-NENs). However, it remains poorly evaluated with no clear recommendations in current guidelines. Thus, we evaluated the prognostic impact of PET-MRI in G-NEN patients. METHODS: From June 2017 to December 2021, 71 G-NEN patients underwent whole-body PET-MRI for staging and/or follow-up purposes. A whole-body emission scan with 18F-6-fluoro-L-dihydroxyphenylalanine (18FDOPA, n = 30), 18F-fluoro-2-deoxy-D-glucose (18FDG, n = 21), or 68Ga-(DOTA(0)-Phe(1)-Tyr(3))-octreotide (68Ga-DOTATOC, n = 20) with the simultaneous acquisition of a T1-Dixon sequence and diffusion-weighed imaging (DWI), followed by a dedicated step of MRI sequences with a Gadolinium contrast was performed. The patients underwent PET-MRI every 6-12 months during the follow-up period until death. Over this period, 50 patients with two or more PET-MRI were evaluated. RESULTS: The mean age was 61 [extremes, 31-92] years. At the baseline, PET-MRI provided new information in 12 cases (17%) as compared to conventional imaging: there were more metastases in eight, an undescribed location (myocardia) in two, and an unknown primary location in two cases. G grading at the baseline influenced overall survival. During the follow-up (7-381 months, mean 194), clinical and therapy managements were influenced by PET-MRI in three (6%) patients due to new metastases findings when neither overall, nor disease-free survivals in these two subgroups (n = 12 vs. n = 59), were different. CONCLUSION: Our study suggests that using PET/MRI with the appropriate radiotracer improves the diagnostic performance with no benefit on survival. Further studies are warranted to evaluate the cost-effectiveness of this procedure.

Selective internal radiation therapy for unresectable HCC: The SIRT downstaging study.

BACKGROUND: Selective internal radiation therapy (SIRT) is recommended as a downstaging (DS) strategy for solitary unresectable HCC <8 cm. The aim of this study was to report the results of acquired experience in a tertiary center for all unresectable HCCs. METHODS: We conducted a retrospective, observational study using data collected from consecutive patients undergoing SIRT between October 2013 and June 2020. DS was considered achieved when a curative treatment could be proposed 6 months after SIRT. RESULTS: One hundred twenty-seven patients were included (male = 90%, 64 ± 11 y), of whom 112 (n = 88%) had cirrhosis. HCC was classified as BCLC stage C in 64 patients (50%), with a median diameter of 61 mm, an infiltrative pattern in 51 patients (40%), and portal vein invasion in 62 (49%) patients. Fifty patients (39%) achieved DS 6 months following SIRT, with 29 of them (23%) undergoing curative treatment in a median time of 4.3 months: 17 (13%) were transplanted, 11 (85%) had liver resection, and 1 patient had a radiofrequency ablation. The median overall survival of patients with or without DS was 51 versus 10 months, respectively (p < 0.001). In patients who achieved DS, progression-free survival was higher in patients who underwent surgery: 47 versus 11 months (p < 0.001). Four variables were independently associated with DS: age (OR: 0.96, 95% CI: [0.92, 0.99]; p = 0.032), baseline α-fetoprotein (OR: 1.00, 95% CI: [1.00, 1.00]; p = 0.034), HCC distribution (OR: 0.3, 95% CI: [0.11, 0.75]; p = 0.012), and ALBI grade (OR: 0.34. 95% CI: [0.14, 0.80]; p = 0.014). CONCLUSIONS: These results suggest that SIRT in patients with unresectable HCC could be an effective treatment: DS was achieved for around 39% of the patients and more than half of these then underwent curative treatment.

Long-Term Overall Survival After Selective Internal Radiation Therapy for Locally Advanced Hepatocellular Carcinomas: Updated Analysis of DOSISPHERE-01 Trial.

Interim analysis of the DOSISPHERE-01 study demonstrated a strong improvement in response and overall survival (OS) on using 90Y-loaded glass microspheres with personalized dosimetry compared with standard dosimetry in patients with nonoperable locally advanced hepatocellular carcinoma. This report sought to provide a long-term analysis of OS. Methods: In this phase II study (ClinicalTrials.gov identifier NCT02582034), treatment was randomly assigned (1:1) with the goal to deliver either at least 205 Gy (if possible >250-300 Gy) to the index lesion in the personalized dosimetry approach (PDA) or 120 ± 20 Gy to the treated volume in the standard dosimetry approach (SDA). The 3-mo response of the index lesion was the primary endpoint, with OS being one of the secondary endpoints. This report is a post hoc long-term analysis of OS. Results: Overall, 60 hepatocellular carcinoma patients with at least 1 lesion larger than 7 cm and more than 30% of hepatic reserve were randomized (intent-to-treat population: PDA, n = 31; SDA, n = 29), with 56 actually treated (modified intent-to-treat population: n = 28 in each arm). The median follow-up for long-term analysis was 65.8 mo (range, 2.1-73.1 mo). Median OS was 24.8 mo and 10.7 mo (hazard ratio [HR], 0.51; 95% CI, 0.29-0.9; P = 0.02) for PDA and SDA, respectively, in the modified intent-to-treat population. Median OS was 22.9 mo for patients with a tumor dose of at least 205 Gy, versus 10.3 mo for those with a tumor dose of less than 205 Gy (HR, 0.42; 95% CI, 0.22-0.81; P = 0.0095), and was 22.9 mo for patients with a perfused liver dose of 150 Gy or higher, versus 10.3 mo for those with a perfused liver dose of less than 150 Gy (HR, 0.42; 95% CI, 0.23-0.75; P = 0.0033). Lastly, median OS was not reached in patients who were secondarily resected (n = 11, 10 in the PDA group and 1 in the SDA group), versus 10.8 mo in those without secondary resection (n = 45) (HR, 0.17; 95% CI, 0.065-0.43; P = 0.0002). Only resected patients displayed favorable long-term OS rates, meaning an OS of more than 50% at 5 y. Conclusion: After longer follow-up, personalized dosimetry sustained a meaningful improvement in OS, which was dramatically improved for patients who were accurately downstaged toward resection, including most portal vein thrombosis patients.

Accuracy and reproducibility of a cone beam CT-based virtual parenchymal perfusion algorithm in the prediction of SPECT/CT anatomical and volumetric results during the planification of radioembolization for HCC.

OBJECTIVES: To evaluate anatomical and volumetric predictability of a cone beam computed tomography (CBCT)-based virtual parenchymal perfusion (VPP) software for the single-photon-emission computed tomography (SPECT)/CT imaging results during the work-up for transarterial radioembolization (TARE) procedure in patients with hepatocellular carcinoma (HCC). METHODS: VPP was evaluated retrospectively on CBCT data of patients treated by TARE for HCC. 99mTc macroaggregated albumin particles (99mTc-MAA) uptake territories on work-up SPECT/CT was used as ground truth for the evaluation. Semi-quantitative evaluation consisted of the ranking of visual consistency of the parenchymal enhancement and portal vein tumoral involvement on VPP and 99mTc-MAA SPECT/CT, using a three-rank scale and two-rank scale, respectively. Inter-reader agreement was evaluated using a kappa coefficient. Quantitative evaluation included absolute volume error calculation and Pearson correlation between volumes enhanced territories on VPP and 99mTc-MAA SPECT/CT. RESULTS: Fifty-two CBCTs were performed in 33 included patients. Semi-quantitative evaluation showed a good concordance between actual 99mTc-MAA uptake and the virtual enhanced territories in 73% and 75% of cases; a mild concordance in 12% and 10% and a poor concordance in 15%, for the two readers. Kappa coefficient was 0.86. Portal vein involvement evaluation showed a good concordance in 58.3% and 66.7% for the two readers, respectively, with a kappa coefficient of 0.82. Quantitative evaluation showed a volume error of 0.46 ± 0.78 mL [0.01-3.55], and Pearson R2 factor at 0.75 with a p value < 0.01. CONCLUSION: CBCT-based VPP software is accurate and reliable to predict 99mTc-MAA SPECT/CT anatomical and volumetric results in HCC patients during TARE. KEY POINTS: • Virtual parenchymal perfusion (VPP) software is accurate and reliable in the prediction of 99mTc-MAA SPECT volumetric and targeting results in HCC patients during transarterial radioembolization (TARE). • VPP software may be used per-operatively to optimize the microcatheter position for 90Y infusion allowing precise tumor targeting while preserving non-tumoral parenchyma. • Post-operatively, VPP software may allow an accurate estimation of the perfused volume by each arterial branch and, thus, a precise 90Y dosimetry for TARE procedures.

Utility of Early Posttreatment PET/CT Evaluation Using FDG or 18F-FCH to Predict Response to 90Y Radioembolization in Patients With Hepatocellular Carcinoma.

BACKGROUND. Assessment of hepatocellular carcinoma (HCC) treatment response after transarterial radioembolization (TARE) is challenging, because response by conventional imaging criteria may not become apparent until 6 months after treatment. Though HCC exhibits variable avidity for FDG, some cases of HCC without avidity for FDG show avidity for 18F-fluorocholine (18F-FCH). OBJECTIVE. The purpose of this study was to evaluate the utility of early posttreatment evaluation by PET/CT using FDG or 18F-FCH to predict 6-month treatment response and survival after TARE in patients with HCC. METHODS. This retrospective study included 37 patients (mean age, 67 years; 34 men, three women) with documented HCC treated by TARE who underwent both pre-treatment FDG PET/CT and 18F-FCH PET/CT and early FDG PET/CT and/or 18F-FCH PET/CT 4-8 weeks after treatment; FDG PET/CT and 18F-FCH PET/CT examinations were performed on separate dates. Only one of 73 initially identified potentially eligible patients was excluded because of lack of HCC avidity for both FDG and 18F-FCH. Response assessment by modified RECIST (mRECIST) on multiphase CT or MRI was performed at 1 month and 6 months in 23 patients. Early responses seen on PET/CT and 1-month mRECIST response were assessed as predictors of 6-month mRECIST response. Univariable and multivariable predictors of overall survival (OS) were identified. RESULTS. On pretreatment PET/CT, 28 (76%) patients were FDG-positive (showed visual uptake on FDG PET/CT and tumor-to-normal liver ratio > 1.15), 15 (41%) were FCH-positive (showed visual uptake on 18F-FCH PET/CT), and six (16%) were both FDG-positive and FCH-positive. Twelve of 28 FDG-positive HCCs exhibited early response by FDG PET/CT; seven of 15 FCH-positive HCCs exhibited early response by 18F-FCH PET/CT. Twelve (52%) patients exhibited 6-month mRECIST response. Response seen on early posttreatment PET/CT exhibited 100% (12/12) sensitivity and 100% (11/11) specificity for 6-month mRECIST response, whereas 1-month mRECIST response exhibited 67% (8/12) sensitivity and 100% (11/11) specificity for 6-month mRECIST response. Response seen on early posttreatment PET/CT was a significant independent predictor of OS on univariable (hazard ratio [HR], 0.4; 95% CI, 0.2-0.9; p = .03) and multivariable (HR, 0.2; 95% CI, 0.1-0.8; p = .01) analyses. CONCLUSION. Early evaluation after TARE by PET/CT using FDG or 18F-FCH may pre dict 6-month response and OS in patients with HCC. CLINICAL IMPACT. Early posttreatment evaluation with PET/CT could help more reliably identify true nonresponders after TARE, which in turn could prompt early response-adapted therapeutic management.

Non-invasive diagnosis and follow-up of primary malignant liver tumours.

Among a wide range of malignant liver tumours, hepatocellular carcinoma (HCC) developed on a background of cirrhosis represents the most frequent clinical situation. In this setting, HCC is one of the rare solid tumours for which histological confirmation is not mandatory. The convergence of multiple arguments obtained by non-invasive parameters using radiological findings allows to avoid liver biopsy in a large proportion of patients when a diagnosis of underlying cirrhosis is ascertained. Conversely, in case of atypical presentation or in order to exclude other rare malignant tumours mostly developed in the absence of cirrhosis, liver biopsy will then be essential. Based on typical radiological patterns described by contrast-enhanced imaging, numerous clinical guidelines have endorsed non-invasive diagnosis, staging and monitoring of HCC patients under treatment since 20 years. These algorithms have evolved over the years, taking into account progress in radiological technology and advances in curative or palliative procedures. Large cohort studies have also helped to refine diagnostic criteria and prognostication in the setting of complex therapeutic strategy. Unsupervised multi-analysis approaches both at the biological and radiological levels will in the future enrich the panel of non-invasive markers useful in clinical practice to manage HCC and other malignant tumours.

Chest PET/MRI in Solid Cancers: Comparing the Diagnostic Performance of a Free-Breathing 3D-T1-GRE Stack-of-Stars Volume Interpolated Breath-Hold Examination (StarVIBE) Acquisition With That of a 3D-T1-GRE Volume Interpolated Breath-Hold Examination (VIBE) for Chest Staging During Whole-Body PET/MRI.

BACKGROUND: Whole-body positron emission tomography/magnetic resonance imaging (WB-PET/MRI) is increasingly used in oncology. However, chest staging remains challenging. PURPOSE: To compare the diagnostic performance of a free-breathing 3D-T1-GRE stack-of-stars volume interpolated breath-hold examination (StarVIBE) with that of a 3D-T1-GRE volume interpolated breath-hold examination (VIBE) during WB-PET/MRI for chest staging. STUDY TYPE: Retrospective, cohort study. POPULATION: One hundred and twenty-three patients were referred for initial staging of solid cancer, 46 of whom had pulmonary nodules and 14 had pulmonary metastasis. FIELD STRENGTH/SEQUENCE: Free-breathing 3D-T1-GRE stack-of-stars (StarVIBE) and Cartesian 3D-T1-GRE VIBE at 3.0 T. ASSESSMENT: Image quality was assessed using a 4-point scale and using the signal-to-noise ratio (SNR) of lung parenchyma and contrast-to-noise ratio (CNR) of pulmonary nodules. Diagnostic performances of both sequences were determined by three independent radiologists for detection of pulmonary nodules, lymph node involvement, and bone metastases using chest CT, pathology, and follow-up as reference standards. STATISTICAL TESTS: Paired Student's t-test; chi-squared; Fisher's exact test. A P value <0.05 was considered statistically significant. RESULTS: StarVIBE quality was judged as better in 34% of cases and at least equivalent to VIBE in 89% of cases, with significantly higher quality scores (4 [4-4] vs. 3 [3-4], respectively). SNR and CNR values were significantly higher with StarVIBE (8 ± 1.3 and 9.7 ± 4.6, respectively) than with VIBE (1.8 ± 0.2 and 5.5 ± 3.3, respectively). Compared to VIBE, StarVIBE showed significantly higher sensitivity (73% [95% CI 62-82] vs. 44% [95% CI 33-55], respectively) and specificity (95% [95% CI 88-99] vs. 67% [95% CI 56-77]) for pulmonary nodules detection and significantly higher sensitivity (100% [95% CI 89-100] vs. 67% [95% CI 48-82], respectively) for detection of lymph node involvement. Sensitivities for bone metastases detection were not significantly different (100% [95% CI 88-100] vs. 82% [95% CI 63-94], P = 0.054). DATA CONCLUSION: Owing to improved SNR and CNR and spatial resolution, a free-breathing 3D stack-of-stars T1-GRE sequence improves chest staging in comparison with standard 3D-T1-GRE VIBE and may be integrated in WB-PET/MRI acquisitions for initial staging of solid cancer. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Impact of the 18F-FDG-PET/MRI on Metastatic Staging in Patients with Hepatocellular Carcinoma: Initial Results from 104 Patients.

Optimal HCC therapeutic management relies on accurate tumor staging. Our aim was to assess the impact of 18F-FDG-WB-PET/MRI on HCC metastatic staging, compared with the standard of care CT-CAP/liver MRI combination, in patients with HCC referred on a curative intent or before transarterial radioembolization. One hundred and four consecutive patients followed for HCC were retrospectively included. The WB-PET/MRI was compared with the standard of care CT-CAP/liver MRI combination for HCC metastatic staging, with pathology, followup, and multidisciplinary board assessment as a reference standard. Thirty metastases were identified within 14 metastatic sites in 11 patients. The sensitivity of WB-PET/MRI for metastatic sites and metastatic patients was significantly higher than that of the CT-CAP/liver MRI combination (respectively 100% vs. 43%, p = 0.002; and 100% vs. 45%, p = 0.01). Metastatic sites missed by CT-CAP were bone (n = 5) and distant lymph node (n = 3) in BCLC C patients. For the remaining 93 nonmetastatic patients, three BCLC A patients identified as potentially metastatic on the CT-CAP/liver MRI combination were correctly ruled out with the WB-PET/MRI without significant increase in specificity (100% vs. 97%; p = 0.25). The WB-PET/MRI may improve HCC metastatic staging and could be performed as a "one-stop-shop" examination for HCC staging with a significant impact on therapeutic management in about 10% of patients especially in locally advanced HCC.

Personalised versus standard dosimetry approach of selective internal radiation therapy in patients with locally advanced hepatocellular carcinoma (DOSISPHERE-01): a randomised, multicentre, open-label phase 2 trial.

BACKGROUND: All randomised phase 3 studies of selective internal radiation therapy for advanced hepatocellular carcinoma published to date have reported negative results. However, these studies did not use personalised dosimetry. We aimed to compare the efficacy of a personalised versus standard dosimetry approach of selective internal radiation therapy with yttrium-90-loaded glass microspheres in patients with hepatocellular carcinoma. METHODS: DOSISPHERE-01 was a randomised, multicentre, open-label phase 2 trial done at four health-care centres in France. Patients were eligible if they were aged 18 years or older and had unresectable locally advanced hepatocellular carcinoma, at least one measurable lesion 7 cm or more in size, a hepatic reserve of at least 30% after selective internal radiation therapy, no extrahepatic spread (other than to the lymph nodes of the hilum, with a lesion <2 cm in size), and no contraindications to selective internal radiation therapy, as assessed by use of a technetium-99m macro-aggregated albumin scan. Patients were randomly assigned (1:1) by use of a permutated block method, with block sizes of four and without stratification, to receive either standard dosimetry (120 ±â€ˆ20 Gy) targeted to the perfused lobe; standard dosimetry group) or personalised dosimetry (≥205 Gy targeted to the index lesion; personalised dosimetry group). Investigators, patients, and study staff were not masked to treatment. The primary endpoint was the investigator-assessed objective response rate in the index lesion, according to European Association for the Study of the Liver criteria, at 3 months after selective internal radiation therapy in the modified intention-to-treat population. Safety was assessed in all patients who received at least one selective internal radiation therapy injection, and analysed on the basis of the treatment actually received (defined by central dosimetry assessment). The trial is registered with ClinicalTrials.gov, NCT02582034, and has been completed. FINDINGS: Between Dec 5, 2015, and Jan 4, 2018, 93 patients were assessed for eligibility. Of these patients, 60 were randomly assigned: 31 to the personalised dosimetry group and 29 to the standard dosimetry group (intention-to-treat population). 56 (93%) patients (28 in each group) were treated (modified intention-to-treat population). In the modified intention-to-treat population, 20 (71% [95% CI 51-87]) of 28 patients in the personalised dosimetry group and ten (36% [19-56]) of 28 patients in the standard dosimetry group had an objective response (p=0·0074). In the safety analysis population, a least one serious adverse event was reported in seven (20%) of the 35 patients who received personalised dosimetry, and in seven (33%) of the 21 patients who received standard dosimetry. The most frequent (ie, occurring in >5% of patients) grade 3 or higher adverse events were ascites (one [3%] patient who received personalised dosimetry vs two [10%] patients who received standard dosimetry), hepatic failure (two [6%] vs none), lymphopenia (12 [34%] vs nine [43%]), increased aspartate aminotransferase concentrations (three [9%] vs two [10%]), increased alanine aminotransferase concentrations (three [9%] vs none), anaemia (two [6%] vs one [5%]), gastrointestinal haemorrhage (none vs two [10%]), and icterus (none vs two [10%]). One treatment-related death occurred in each group. INTERPRETATION: Compared with standard dosimetry, personalised dosimetry significantly improved the objective response rate in patients with locally advanced hepatocellular carcinoma. The results of this study suggest that personalised dosimetry is likely to improve outcomes in clinical practice and should be used in future trials of selective internal radiation therapy. FUNDING: Biocompatibles UK, a Boston Scientific Group company.