Watch-and-wait strategy vs. resection in patients with radiologic complete response after conversion therapy for initially unresectable hepatocellular carcinoma: a propensity score-matching comparative study.

BACKGROUND: The optimal subsequent management for patients with initially unresectable hepatocellular carcinoma (uHCC) who have achieved complete response (CR) following conversion therapy remains unclear. This study aims to evaluate the feasibility and outcomes of the watch-and-wait (W-W) strategy versus surgical resection (SR) for these patients. MATERIALS AND METHODS: This retrospective study reviewed patients with initially uHCC who underwent conversion therapy employing transarterial therapies combined with or without systemic therapies. Radiologic CR (rCR), clinical CR (cCR), and pathologic CR (pCR) were evaluated. Overall survival (OS) and progression-free survival (PFS) were compared between the W-W and SR groups. RESULTS: Among 1880 patients with uHCC who underwent conversion therapy, 207 (11.0%) achieved rCR. Finally, we enrolled 149 patients meeting the inclusion criteria, including 74 receiving W-W strategy and 75 undergoing SR. Among the 149 patients with rCR, the W-W group demonstrated comparable 3-year OS rates to the SR group (80.9 vs 83.1%, P =0.77), but demonstrated inferior PFS rates (14.4 vs 46.5%, P =0.002). These results remained consistent after propensity score matching. For the 57 patients who achieved cCR, the W-W group exhibited comparable 3-year OS (88.1 vs 87.9%, P =0.89) and PFS rates (27.8 vs 40.8%, P =0.34) compared to SR group. Among the 75 patients in the SR group, 31 (41.3%) achieved pCR and 44 (58.7%) reached non-pCR. When compared with patients with pCR, those who achieved rCR in the W-W group showed comparable OS but inferior PFS rates. Moreover, patients who achieved rCR in the W-W group displayed both comparable OS and PFS rates to those with non-pCR. CONCLUSION: The W-W strategy offered comparable survival outcomes to SR in patients with initially uHCC who achieved rCR or cCR after conversion therapy. For these patients, the W-W strategy could be offered as an alternative treatment option.

Prognostic value of metastatic cervical lymph node stiffness in nasopharyngeal carcinoma: A prospective cohort study.

OBJECTIVES: Extracellular matrix stiffness plays an important role in tumorigenesis. In this study, we assessed the prognostic value of metastatic cervical lymph node (CLN) stiffness measured using ultrasound shear wave elastography (SWE) in patients with nasopharyngeal carcinoma (NPC). METHODS: A total of 325 consecutive patients with NPC and CLN metastases were prospectively enrolled in this study. The association between the CLN stiffness and patient characteristics was also evaluated. Survival analysis was performed for 307 patients with stage M0 disease. Distant metastasis-free survival (DMFS) was the primary endpoint. Log-rank test and multivariate analysis were used to explore the prognostic value of CLN stiffness. RESULTS: Eighteen patients developed distant metastases before treatment (stage M1) and had significantly higher CLN stiffness (Pt-test < 0.001) than the other patients (stage M0). For stage M0 patients, those in the high-stiffness group had lower 3-year DMFS (83.3% vs. 91.7%, P = 0.013) and 3-year progression-free survival (PFS) (78.2% vs. 87.9%, P = 0.015) than those in the low-stiffness group. Multivariate analysis identified CLN stiffness and pretreatment Epstein-Barr virus (EBV) DNA as independent prognostic factors for DMFS and PFS. We further established stiffness-EBV risk stratification based on these two factors. The concordance index, receiver operating characteristic curve, and decision curve analyses showed that our risk stratification outperformed the TNM classification for predicting metastasis. CONCLUSION: The stiffness of metastatic CLN is closely associated with the prognosis of patients with NPC. SWE can be used as a pretreatment examination for CLN-positive patients. A multicenter study is required to verify our results.

Repeat hepatectomy versus percutaneous ablation for recurrent hepatocellular carcinoma: emphasis on the impact of early or late recurrence.

PURPOSE: Recurrent hepatocellular carcinoma (rHCC) patients with early recurrence usually suffer a poorer prognosis than those with late recurrence. We aimed to compare the treatment efficacy of repeat hepatectomy (RH) and percutaneous ablation (PA) in early-stage rHCC patients with early or late recurrence. METHODS: This retrospective study enrolled 268 patients diagnosed with early-stage rHCC who received RH and PA. Overall survival (OS) and repeat recurrence-free survival (rRFS) were compared using log-rank analysis. Propensity score matching (PSM) was used to reduce the confounding bias. RESULTS: Among the 268 patients with early-stage rHCC, 79 underwent RH and 189 underwent PA. Early (n = 174) and late (n = 94) recurrence was defined as recurrence within and after 2 years following initial hepatectomy, respectively. For patients with early recurrence, RH and PA provided similar 5-year OS (71.5% versus 74.4%, P = 0.87) and rRFS rates (24.7% versus 24.9%, P = 0.73). For patients with late recurrence, RH resulted in comparable 5-year OS (73.1% versus 86.1%, P = 0.62) and rRFS rates (36.6% versus 27.8%, P = 0.34) as PA. After PSM, RH continued to share similar 5-year OS and rRFS rates with PA in patients with early recurrence, and comparable efficacy of RH and PA was also observed in patients with late recurrence. CONCLUSION: RH can offer comparable OS and rRFS rates as PA for early-stage rHCC patients, regardless of whether they experience early or late recurrence. Therefore, both RH and PA are feasible treatment options for early-stage rHCC patients.

Contrast-enhanced US with Sulfur Hexafluoride and Perfluorobutane: LI-RADS for Diagnosing Hepatocellular Carcinoma.

Background Liver Imaging Reporting and Data System (LI-RADS) was designed for contrast-enhanced US (CEUS) with pure blood pool agents to diagnose hepatocellularfcarcinoma (HCC), such as sulfur hexafluoride (SHF), but Kupffer-cell agents, such as perfluorobutane (PFB), allow additional lesion characterization in the Kupffer phase yet remain unaddressed. Purpose To compare the diagnostic performance of three algorithms for HCC diagnosis: two algorithms based on CEUS LI-RADS version 2017 for both SHF and PFB and a modified algorithm incorporating Kupffer-phase findings for PFB. Materials and Methods This multicenter prospective study enrolled high-risk patients for HCC from June 2021 to December 2021. Each participant underwent same-day SHF-enhanced US followed by PFB-enhanced US. Each liver observation was assigned three LI-RADS categories according to each algorithm: LI-RADS SHF, LI-RADS PFB, and modified PFB. For modified PFB, observations at least 10 mm with nonrim arterial phase hyperenhancement were upgraded LR-4 to LR-5 if there was no washout with a Kupffer defect and were reassigned LR-M to LR-5 if there was early washout with mild Kupffer defect. The reference standard was pathologic confirmation or composite (typical CT or MRI features, or 1-year size stability and/or reduction). Diagnostic metrics of LR-5 for HCC using the three algorithms were calculated and compared using the McNemar test. Results Overall, 375 patients (mean age, 56 years ± 11 [SD]; 318 male patients, 57 female patients) with 424 observations (345 HCCs, 40 non-HCC malignancies, 39 benign lesions) were enrolled. PFB and SHF both using LI-RADS showed no significant difference in sensitivity (60% vs 58%; P = .41) and specificity (96% vs 95%; P > .99). The modified algorithm with PFB had increased sensitivity (80% vs 58%; P < .001) and a nonsignificant decrease in specificity (92% vs 95%; P = .73) compared with LI-RADS SHF. Conclusion Based on CEUS LI-RADS version 2017, both SHF and PFB achieved high specificity and relatively low sensitivity for HCC diagnosis. When incorporating Kupffer-phase findings, PFB had higher sensitivity without loss of specificity. Chinese Clinical Trial Registry no. ChiCTR2100047035 © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Kim in this issue.

Head and neck MRI-based T stage and [18F]FDG PET/CT-based N/M stage improved prognostic stratification in primary nasopharyngeal carcinoma.

OBJECTIVES: To evaluate whether MRI-based T stage (TMRI), [18F]FDG PET/CT-based N (NPET/CT), and M stage (MPET/CT) are superior in NPC patients' prognostic stratification based on long-term survival evidences, and whether TNM staging method involving TMRI + NPET/CT + MPET/CT could improve NPC patients' prognostic stratification. METHODS: From April 2007 to December 2013, 1013 consecutive untreated NPC patients with complete imaging data were enrolled. All patients' initial stages were repeated based on (1) the NCCN guideline recommended "TMRI + NMRI + MPET/CT" ("MMP") staging method; (2) the traditional "TMRI + NMRI + Mconventional work-up (CWU)" ("MMC") staging method; (3) the single-step "TPET/CT + NPET/CT + MPET/CT" ("PPP") staging method; or (4) the "TMRI + NPET/CT + MPET/CT" ("MPP") staging method recommended in present research. Survival curve, ROC curve, and net reclassification improvement (NRI) analysis were used to evaluate the prognosis predicting ability of different staging methods. RESULTS: [18F]FDG PET/CT performed worse on T stage (NRI = - 0.174, p < 0.001) but better on N (NRI = 0.135, p = 0.004) and M stage (NRI = 0.126, p = 0.001). The patients whose N stage upgraded by [18F]FDG PET/CT had worse survival (p = 0.011). The "TMRI + NPET/CT + MPET/CT" ("MPP") method performed better on survival prediction when compared with "MMP" (NRI = 0.079, p = 0.007), "MMC" (NRI = 0.190, p < 0.001), or "PPP" method (NRI = 0.107, p < 0.001). The "TMRI + NPET/CT + MPET/CT" ("MPP") method could reclassify patients' TNM stage to a more appropriate stage. The improvement is significant in patients with more than 2.5-years follow-up according to the time-dependent NRI values. CONCLUSIONS: The MRI is superior to [18F]FDG PET/CT in T stage, and [18F]FDG PET/CT is superior to CWU in N/M stage. The "TMRI + NPET/CT + MPET/CT" ("MPP") staging method could significantly improve NPC patients' long-term prognostic stratification. CLINICAL RELEVANCE STATEMENT: The present research provided long-term follow-up evidence for benefits of MRI and [18F]FDG PET/CT in TNM staging for nasopharyngeal carcinoma, and proposes a new imaging procedure for TNM staging incorporating MRI-based T stage and [18F]FDG PET/CT-based N and M stage, which significantly improves long-term prognostic stratification for patients with NPC. KEY POINTS: • The long-term follow-up evidence of a large-scale cohort was provided to evaluate the advantages of MRI, [18F]FDG PET/CT, and CWU in the TNM staging of nasopharyngeal carcinoma. • A new imaging procedure for TNM stage of nasopharyngeal carcinoma was proposed.

Evolutionary route of nasopharyngeal carcinoma metastasis and its clinical significance.

It is critical to understand factors associated with nasopharyngeal carcinoma (NPC) metastasis. To track the evolutionary route of metastasis, here we perform an integrative genomic analysis of 163 matched blood and primary, regional lymph node metastasis and distant metastasis tumour samples, combined with single-cell RNA-seq on 11 samples from two patients. The mutation burden, gene mutation frequency, mutation signature, and copy number frequency are similar between metastatic tumours and primary and regional lymph node tumours. There are two distinct evolutionary routes of metastasis, including metastases evolved from regional lymph nodes (lymphatic route, 61.5%, 8/13) and from primary tumours (hematogenous route, 38.5%, 5/13). The hematogenous route is characterised by higher IFN-γ response gene expression and a higher fraction of exhausted CD8+ T cells. Based on a radiomics model, we find that the hematogenous group has significantly better progression-free survival and PD-1 immunotherapy response, while the lymphatic group has a better response to locoregional radiotherapy.

Nomogram to differentiate benign and malignant thyroid nodules in the American College of Radiology Thyroid Imaging Reporting and Data System level 5.

OBJECTIVES: To develop and validate a nomogram for differentiating benign and malignant thyroid nodules of American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (TI-RADS) level 5 (TR5) and improving the performance of the guideline. METHODS: From May 2018 to December 2019, 640 patients with TR5 nodules were retrospectively included in the primary cohort. Univariate and multivariable analyses were performed to determine the risk factors for thyroid cancer. A nomogram was established on the basis of multivariable analyses; the performance of the nomogram was evaluated with respect to discrimination, calibration, and clinical usefulness. The nomogram model was also compared to the ACR score model. External validation was performed and the independent validation cohort contained 201 patients from April 2021 to January 2022. RESULTS: Multivariable analyses showed that age, tumour location, multifocality, concomitant Hashimoto's disease, neck lymph node status reported by ultrasound (US) and ACR score were the independent risk factors for thyroid cancer (all p < .05). The nomogram showed good discrimination, with an area under the curve (AUC) of 0.786 (95% confidence interval [CI]: 0.742-0.830) and 0.712 (95% CI: 0.615-0.809) in the primary cohort and external validation cohort, respectively. Decision curve analysis demonstrated the clinical usefulness of the model. Compared to the ACR score model, the nomogram showed higher AUC (0.786 vs. 0.626, p < .001) and specificity (0.783 vs. 0.391). CONCLUSIONS: The presented nomogram model, based on age, tumour features and ACR score, can differentiate benign and malignant thyroid nodules in TR5 and had a high specificity.

Neoantigen landscape in metastatic nasopharyngeal carcinoma.

Background: Reportedly, nasopharyngeal carcinoma (NPC) patients with MHC I Class aberration are prone to poor survival outcomes, which indicates that the deficiency of tumor neoantigens might represent a mechanism of immune surveillance escape in NPC. Methods: To clearly delineate the landscape of neoantigens in NPC, we performed DNA and RNA sequencing on paired primary tumor, regional lymph node metastasis and distant metastasis samples from 26 patients. Neoantigens were predicted using pVACseq pipeline. Subtype prediction model was built using random forest algorithm. Results: Portraying the landscape of neoantigens in NPC for the first time, we found that the neoantigen load of NPC was above average compared to that of other cancers in The Cancer Genome Atlas program. While the quantity and quality of neoantigens were similar among primary tumor, regional lymph node metastasis and distant metastasis samples, neoantigen depletion was more severe in metastatic sites than in primary tumors. Upon tracking the clonality change of neoantigens, we found that neoantigen reduction occurred during metastasis. Building a subtype prediction model based on reported data, we observed that subtype I lacked T cells and suffered from severe neoantigen depletion, subtype II highly expressed immune checkpoint molecules and suffered from the least neoantigen depletion, and subtype III was heterogenous. Conclusions: These results indicate that neoantigens are conducive to the guidance of clinical treatment, and personalized therapeutic vaccines for NPC deserve deeper basic and clinical investigations to make them feasible in the future.

Long-term outcome for colorectal liver metastases: combining hepatectomy with intraoperative ultrasound guided open microwave ablation versus hepatectomy alone.

OBJECTIVE: To compare the long-term outcome of combining hepatectomy with intraoperative ultrasound (IOUS)-guided open microwave ablation (MWA) versus hepatectomy alone in patients with colorectal cancer liver metastases (CRLM). METHOD: A retrospective analysis of patients with CRLM who underwent hepatectomy alone (HT group; 380 patients) or hepatectomy combined with IOUS-guided open MWA (HT + MWA group; 57 patients) from April 2002 to September 2018 was conducted at our center. A propensity score-matched (PSM) analysis was used to reduce data bias between the two groups. RESULTS: The overall survival (OS) and disease-free survival (DFS) were not significantly different between the two groups after matching. Although intrahepatic recurrence was more frequent in the HT + MWA group in both the whole and matched cohort, the two groups exhibited similar rates of extrahepatic recurrence as well as concomitant intra- and extrahepatic recurrence. A higher number of CRLM (>3), larger maximum-size and absence of response to induction chemotherapy were independent risk factors for OS. CONCLUSION: The oncological outcomes of hepatectomy combined with intraoperative open ablation was not significantly different to hepatectomy alone and should be considered as a safe and fair option for patients with difficultly resectable CRLM.

Thyroid nodule recognition using a joint convolutional neural network with information fusion of ultrasound images and radiofrequency data.

OBJECTIVE: To develop a deep learning-based method with information fusion of US images and RF signals for better classification of thyroid nodules (TNs). METHODS: One hundred sixty-three pairs of US images and RF signals of TNs from a cohort of adult patients were used for analysis. We developed an information fusion-based joint convolutional neural network (IF-JCNN) for the differential diagnosis of malignant and benign TNs. The IF-JCNN contains two branched CNNs for deep feature extraction: one for US images and the other one for RF signals. The extracted features are fused at the backend of IF-JCNN for TN classification. RESULTS: Across 5-fold cross-validation, the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUROC) obtained by using the IF-JCNN with both US images and RF signals as inputs for TN classification were respectively 0.896 (95% CI 0.838-0.938), 0.885 (95% CI 0.804-0.941), 0.910 (95% CI 0.815-0.966), and 0.956 (95% CI 0.926-0.987), which were better than those obtained by using only US images: 0.822 (0.755-0.878; p = 0.0044), 0.792 (0.679-0.868, p = 0.0091), 0.866 (0.760-0.937, p = 0.197), and 0.901 (0.855-0.948, p = .0398), or RF signals: 0.767 (0.694-0.829, p < 0.001), 0.781 (0.685-0.859, p = 0.0037), 0.746 (0.625-0.845, p < 0.001), 0.845 (0.786-0.903, p < 0.001). CONCLUSIONS: The proposed IF-JCNN model filled the gap of just using US images in CNNs to characterize TNs, and it may serve as a promising tool for assisting the diagnosis of thyroid cancer. KEY POINTS: • Raw radiofrequency signals before ultrasound imaging of thyroid nodules provide useful information that is not carried by ultrasound images. • The information carried by raw radiofrequency signals and ultrasound images for thyroid nodules is complementary. • The performance of deep convolutional neural network for diagnosing thyroid nodules can be significantly improved by fusing US images and RF signals in the model as compared with just using US images.

Conversion to Resectability Using Transarterial Chemoembolization Combined With Hepatic Arterial Infusion Chemotherapy for Initially Unresectable Hepatocellular Carcinoma.

Objective: To evaluate whether this conversion rate to resectability could be increased when patients are treated with transarterial chemoembolization and hepatic arterial infusion chemotherapy (TACE-HAIC) using oxaliplatin plus fluorouracil/leucovorin. Background: Conventional TACE (c-TACE) is a common regimen for initially unresectable hepatocellular carcinoma (HCC), which converts to curative-intent resection in about 10% of those patients. It is urgent need to investigated better regimen for those patients. Methods: The data of 83 initially unresectable HCC patients were examined, including 41 patients in the TACE-HAIC group and 42 patients in the c-TACE group. Their response rate, conversion rate to resection, survival outcome, and adverse events were compared. Results: The conversion rate was significantly better in the TACE-HAIC group than in the c-TACE group (48.8% vs 9.5%; P < 0.001). The TACE-HAIC had marginal superiority in overall response rate as compared to c-TACE (14.6% vs 2.4%; P = 0.107 [RECIST]; 65.9% vs 16.7%; P < 0.001 [mRECIST], respectively). The median progression-free survival was not available and 9.2 months for the TACE-HAIC and cTACE groups, respectively (hazard rate [HR]: 0.38; 95% confidence interval [CI], 0.20-0.70; P = 0.003). The median overall survival was not available and 13.5 months for the TACE-HAIC and c-TACE groups, respectively (HR, 0.63; 95% CI, 0.34-1.17; P = 0.132). The 2 groups had similar rates of grade 3/4 adverse events (all P > 0.05). Conclusions: TACE-HAIC demonstrated a higher conversion rate and progression-free survival benefit than c-TACE and could be considered as a more effective regimen for patients with initially unresectable HCC. Future prospective randomized trials are needed to confirm it.

Transcatheter arterial chemoembolization alone or combined with ablation for recurrent intermediate-stage hepatocellular carcinoma: a propensity score matching study.

PURPOSE: The recurrence after curative hepatectomy is common. Limited data have investigated the effect of transcatheter arterial chemoembolization (TACE) combined with ablation in treating recurrent intermediate-stage hepatocellular carcinoma (HCC) after hepatectomy. We aim to compare the efficacy of TACE combined with ablation versus TACE alone in treating recurrent intermediate-stage HCC after hepatectomy. METHODS: A total of 183 patients with recurrent intermediate-stage HCC after hepatectomy were enrolled at Sun Yat-sen University Cancer Centre, including 111 patients who underwent TACE alone and 72 patients who underwent TACE combined with ablation (TACE-Ablation). Overall survival (OS) and progression-free survival (PFS) were compared by the log-rank test. Propensity score matching (PSM) was used to reduce the confounding bias. RESULTS: Before PSM, the 5-year OS rates were 43.3% vs. 27.9% (P = 0.001), and the 5-year PFS rates were 21.7% vs. 13.0% (P < 0.001) for TACE-Ablation and TACE-alone groups, respectively. After PSM, TACE-Ablation still resulted in better 5-year OS (41.6% vs. 30.2%, P = 0.028) and 5-year PFS rate (21.3% vs. 15.8%, P = 0.024) than that of TACE alone. Patients in TACE-Ablation group exhibited similar major complication rates to TACE-alone group but higher minor complication rates both before and after PSM. Cox regression analysis identified TACE-alone modality as an independently unfavourable predictor for OS and PFS (both P < 0.05). CONCLUSION: TACE combined with ablation is safe and superior to TACE alone in tumour control and prolonging overall survival in recurrent intermediate-stage HCC after hepatectomy.

Lymph-node Epstein-Barr virus concentration in diagnosing cervical lymph-node metastasis in nasopharyngeal carcinoma.

PURPOSE: Cervical lymph-node (CLN) metastasis commonly occurs in patients with nasopharyngeal carcinoma (NPC) metastasis. The presence of Epstein-Barr virus (EBV) genomes in neck lymph nodes may diagnose CLN. This research was designed to appraise the diagnostic value of EBV concentration for cervical lymph nodes in NPC. METHODS: Two hundred and fifty-three NPC patients with 276 CLNs were enrolled. MRI was performed to detect CLN metastasis, and plasma EBV concentration was measured by quantitative PCR before treatment. Ultrasonography (US) and US-FNA were subsequently performed in the suspicious lymph nodes. Fifteen patients (22 lymph nodes) underwent fine-needle aspiration cytology (FNAC), and the remaining 242 patients (254 lymph nodes) underwent core needle biopsy (CNB) for CLNs at the clinician's demand. The aspiration needle was rinsed with 1 ml of normal saline for EBV detection. The method of lymph-node EBV measurement was consistent with that for plasma. The MRI results and EBV concentrations in plasma and lymph nodes were recorded and analyzed. Plasma EBV concentrations ≥ 4000 copies/ml were regarded as positive. RESULTS: CLN-EBV concentrations ≥ 787.5 copies/ml were regarded as positive according to receiver-operating characteristic curve analysis. The AUC of the EBV (0.925) concentration in CLN metastasis was significantly larger than the AUC of MRI (0.714) (P < 0.001). The sensitivity and specificity were 94.09% and 48.72% for MRI in lymph-node metastasis and 95.36% (P > 0.05) and 84.62% (P < 0.01) for EBV DNA in CLN metastasis, respectively. The sensitivity and specificity of EBV in plasma were 77.2% and 71.8%, respectively. The diagnostic specificity and AUC of EBV in CLNs were higher than those of MRI and plasma EBV (P < 0.005). CONCLUSIONS: Ultrasound-guided CLN FNA to obtain EBV concentrations may provide a new method to diagnose CLN metastasis with high sensitivity and specificity.

Comparison of the prognostic value of inflammation-based scores in early recurrent hepatocellular carcinoma after hepatectomy.

BACKGROUND & AIMS: Inflammation-based prognostic scores, such as the Glasgow Prognostic Score (GPS), modified Glasgow Prognostic Score (mGPS), Prognostic Index (PI), Prognostic Nutritional Index (PNI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), lymphocyte to monocyte ratio (LMR) and systemic immune-inflammation index (SII), are correlated with the survival of hepatocellular carcinoma (HCC) patients, while remain unclear for recurrent HCC. This study aimed to compare the prognostic value of inflammation-based prognostic scores for post-recurrence survival (PRS) in patients with early recurrent HCC (ErHCC, within 2 years after hepatectomy). METHODS: A total of 580 patients with ErHCC were enrolled retrospectively. The association between the independent baseline and the time-dependent variables and PRS was evaluated by cox regression. The prediction accuracy of the inflammation-based prognostic scores was assessed by time-dependent receiver operating characteristic (ROC) and Harrell's concordance index (C-index) analyses. RESULTS: The GPS, mGPS, PI, PNI, NLR, PLR, LMR and SII were all related to the PRS of ErHCC patients, while only the SII (P < .001) remained an independent predictor for PRS in multivariate analysis (hazard ratio: 1.92, 95% confidence interval: 1.33-2.79). Both the C-index of the SII (0.65) and the areas under the ROC curves showed that the SII score was superior to the other inflammation-based prognostic scores for predicting the PRS of ErHCC patients. CONCLUSIONS: The SII is a useful prognostic indicator for PRS in patients with ErHCC after hepatectomy and is superior to the other inflammation-based prognostic scores in terms of prognostic ability.

Microwave ablation versus resection for hepatocellular carcinoma within the Milan criteria: a propensity-score analysis.

BACKGROUND: Whether the efficient heat-generating mechanism of microwave ablation (MWA) is comparable with resection (RES) in treating hepatocellular carcinoma (HCC) remains unclear. METHODS: This retrospective cohort study comprised 126 and 1183 patients with HCC meeting the Milan criteria who received MWA or RES between 2002 and 2017. We compared 5-year overall survival (OS) and recurrence-free survival (RFS) using both propensity-score matching (PSM) and inverse-probability-of-treatment-weighting (IPW) analysis and investigated the prognostic factors with multivariate Cox analysis. RESULTS: After PSM (1:2), although MWA (n = 116) offered decreased 5-year RFS (30.6% versus 57.5%, p < 0.001) compared with RES (n = 212), both treatments provided similar 5-year OS (82.2% versus 80.5%, p = 0.360) because most patients with intrahepatic recurrence remained eligible for repeat treatments; similar results were found in the IPW analysis. Additionally, the comparable efficacy of MWA and RES was consistent across all subgroups: those with solitary HCC ⩽ 3.0 cm or >3.0 cm, or multifocal HCCs within the Milan criteria, patients with liver function of albumin-bilirubin grade 1 or 2, and older (⩾60 years) or younger (<60 years) patients. Multivariate Cox analysis confirmed that no difference was seen between MWA and RES in OS (hazard ratio = 0.85; p = 0.581) in the overall population; similar results were obtained in the propensity-score-matched and IPW cohorts. CONCLUSIONS: Compared with RES, MWA offered worse RFS for HCC within the Milan criteria; however, both treatments provided equivalent long-term OS because most patients with intrahepatic recurrence remained eligible for repeat treatments.

Resection vs Ablation for Multifocal Hepatocellular Carcinomas meeting the Barcelona-Clinic Liver Cancer A Classification: A Propensity Score Matching Study.

With development of surgical technology, we aimed to investigate whether resection could challenge the standard treatment, ablation, in treating multifocal hepatocellular carcinomas meeting the Barcelona-Clinic Liver Cancer A stage. From January 2005 to January 2017, the oncological outcomes of patients undergoing resection (n = 72) or ablation (n = 63) were retrospectively analysed using propensity score matching. At baseline, patients in the ablation group had more tri-focal lesions (30.2% vs. 6.9%, P = 0.001) and smaller tumours (2.00 cm vs. 2.50 cm, P = 0.002) than resection group. After matching, the baseline was well-balanced between treatments (n = 46 pairs); resection provided comparable 5-year overall survival (77.0% vs. 83.6, P = 0.790) and superior 5-year recurrence-free survival (40.4% vs. 16.9%, P = 0.022) to ablation. The multivariate Cox model confirmed that ablation was not associated with worse overall survival (HR = 0.89; 95% CI, 0.33 - 2.42, P = 0.819), but identified ablation as an unfavourable predictor of recurrence-free survival (HR = 2.13; 95% CI, 1.27 - 3.57, P <0.001). For subgroup patients with multifocal tumours located in different segments, both treatments offered similar 5-year overall survival (74.3% vs. 95.5%, P = 0.190) and 5-year recurrence-free survival (42.9 vs. 25.9%, P = 0.170). Additionally, ablation resulted in less major complications than resection (3.2% vs 13.9%, P = 0.035). Compared with ablation, resection achieved comparable overall survival and even superior recurrence-free survival for patients with multifocal hepatocellular carcinomas meeting the BCLC A stage.

Predictive factors for the benefit of triple-drug transarterial chemoembolization for patients with unresectable hepatocellular carcinoma.

BACKGROUND: Compared with single-drug TACE, our previous phase III study demonstrated that triple-drug transarterial chemoembolization (TACE) prolonged overall survival (OS) in patients with unresectable hepatocellular carcinoma (HCC). The aim of this study was to find which patients can benefit from the triple drugs TACE compared with single-drug TACE. METHODS: Patients in the triple-drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin, 50 mg lobaplatin, 6 mg mitomycin C, and lipiodol, while patients in the single-drug TACE arm received sponge embolization and emulsions composed of 50 mg epirubicin and lipiodol. From July 2007 to November 2009, 244 patients (224 men and 20 women; age ranged from 21 to 75 years) from our phase III study formed the initial cohort. From January 2010 to June 2015, external validation cohort was composed of 449 patients (411 men and 38 women; age ranged from 18 to 75 years) from another institution. The validation cohort after propensity score matching (PSM) (n = 374) was analyzed. Cox proportional hazard model was used to evaluate the interaction term between treatments for each subgroup. This retrospective study was approved by the institutional review board at each center. RESULTS: No difference was observed in the baseline characteristic of three cohorts. This exploratory analysis showed that triple-drug TACE brought a survival benefit in the initial cohort, validation cohort (before PSM), and validation cohort (after PSM) compared with single-drug TACE. The outcomes of three cohorts all showed that a significantly greater OS triple-drug chemotherapy benefit versus single-drug chemotherapy was seen in patients with large tumors (larger than 10 cm) while no survival difference was seen in patients with small tumors (10 cm or smaller). CONCLUSIONS: Triple-drug TACE seems to benefit patients with HCC larger than 10 cm in particular compared with single-drug TACE.

Sorafenib Plus Hepatic Arterial Infusion of Oxaliplatin, Fluorouracil, and Leucovorin vs Sorafenib Alone for Hepatocellular Carcinoma With Portal Vein Invasion: A Randomized Clinical Trial.

Importance: Sorafenib is the first-line treatment for hepatocellular carcinoma with portal vein invasion; however, it has shown unsatisfactory survival benefit. Sorafenib plus hepatic arterial infusion chemotherapy (HAIC) of oxaliplatin, fluorouracil, and leucovorin (FOLFOX) has shown promising results for these patients in a previous phase 2 study. Objective: To investigate the efficacy and safety of sorafenib plus HAIC compared with sorafenib for hepatocellular carcinoma with portal vein invasion. Design, Setting, and Participants: This randomized, open-label clinical trial enrolled 818 screened patients. Of the 818 participants, 247 with hepatocellular carcinoma and portal vein invasion were randomly assigned (1:1) via a computer-generated sequence to receive sorafenib plus HAIC or sorafenib. This trial was conducted at 5 hospitals in China and enrolled patients from April 1, 2016, to October 10, 2017, with a follow-up period of 10 months. Interventions: Randomization to receive 400 mg sorafenib twice daily (sorafenib group) or 400 mg sorafenib twice daily plus HAIC (SoraHAIC group) (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, fluorouracil bolus 400 mg/m2 on day 1, and fluorouracil infusion 2400 mg/m2 for 46 hours, every 3 weeks). Main Outcomes and Measures: The primary endpoint was overall survival by intention-to-treat analysis. Safety was assessed in patients who received at least 1 dose of study treatment. Results: For 247 patients (median age, 49 years; range, 18-75 years; 223 men and 24 women), median overall survival was 13.37 months (95% CI, 10.27-16.46) in the SoraHAIC group vs 7.13 months (95% CI, 6.28-7.98) in the sorafenib group (hazard ratio [HR], 0.35; 95% CI, 0.26-0.48; P < .001). The SoraHAIC group showed a higher response rate than the sorafenib group (51 [40.8%] vs 3 [2.46%]; P < .001), and a longer median progression-free survival (7.03 [95% CI, 6.05-8.02] vs 2.6 [95% CI, 2.15-3.05] months; P < .001). Grade 3/4 adverse events that were more frequent in the SoraHAIC group than in the sorafenib group included neutropenia (12 [9.68%] vs 3 [2.48%]), thrombocytopenia (16 [12.9%] vs 6 [4.96%]), and vomiting (8 [6.45%] vs 1 [0.83%]). Conclusions and Relevance: Sorafenib plus HAIC of FOLFOX improved overall survival and had acceptable toxic effects compared with sorafenib in patients with hepatocellular carcinoma and portal vein invasion. Trial Registration: ClinicalTrials.gov identifier: NCT02774187.

Lipiodol deposition in portal vein tumour thrombus predicts treatment outcome in HCC patients after transarterial chemoembolisation.

OBJECTIVE: To study lipiodol deposition in portal vein tumour thrombus (PVTT) in predicting the treatment outcome of hepatocellular carcinoma (HCC) patients after transarterial chemoembolisation (TACE). METHODS: We retrospectively reviewed data from 379 HCC patients with PVTT who underwent TACE as the initial treatment at Sun Yat-Sen University Cancer Center from January 2008 to December 2015. Patients were grouped by positive and negative lipiodol deposition based on the extent of lipiodol deposition in PVTT. The overall survival (OS) and progression-free survival (PFS) were compared between negative and positive lipiodol deposition groups; furthermore, the value of the combinatorial evaluation of tumour responses and lipiodol deposition in PVTT in predicting prognosis was analysed in subgroup patients with stable disease (SD) after TACE. RESULTS: Of the 379 patients, 264 (69.7%) had negative and 115 (30.3%) had positive lipiodol deposition in PVTT after TACE. Multivariate analysis identified positive lipiodol deposition in PVTT as an independent prognostic factor for favourable OS (p = 0.001). The median OS and PFS of negative and positive lipiodol deposition groups were 4.70 vs. 8.97 months (p = 0.001) and 3.1 months vs. 5.8 months (p < 0.001). In subgroup patients, the median OS and PFS of negative and positive lipiodol deposition groups were 4.7 months vs. 10.5 months (p < 0.001) and 3.5 months vs. 7.0 months (p < 0.001), respectively. CONCLUSIONS: The patients with positive lipiodol deposition in PVTT had a longer OS than those with negative lipiodol deposition. Furthermore, the positive lipiodol deposition in PVTT can further differentiate HCC patients with favourable prognosis from SD patients. KEY POINTS: • Lipiodol deposition in PVTT is a prognostic indicator for HCC patients after TACE treatment. • Positive lipiodol deposition in PVTT is associated with a better prognosis.