Quantitative SPECT/CT Metrics in Early Prediction of [177Lu]Lu-DOTATATE Treatment Response in Gastroenteropancreatic Neuroendocrine Tumor Patients.

Our objective is to explore quantitative imaging markers for early prediction of treatment response in patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) undergoing [177Lu]Lu-DOTATATE therapy. By doing so, we aim to enable timely switching to more effective therapies in order to prevent time-resource waste and minimize toxicities. Methods: Patients diagnosed with unresectable or metastatic, progressive, well-differentiated, receptor-positive GEP-NETs who received 4 sessions of [177Lu]Lu-DOTATATE were retrospectively selected. Using SPECT/CT images taken at the end of treatment sessions, we counted all visible tumors and measured their largest diameters to calculate the tumor burden score (TBS). Up to 4 target lesions were selected and semiautomatically segmented. Target lesion peak counts and spleen peak counts were measured, and normalized peak counts were calculated. Changes in TBS (ΔTBS) and changes in normalized peak count (ΔnPC) throughout treatment sessions in relation to the first treatment session were calculated. Treatment responses were evaluated using third-month CT and were binarized as progressive disease (PD) or non-PD. Results: Twenty-seven patients were included (7 PD, 20 non-PD). Significant differences were observed in ΔTBSsecond-first, ΔTBSthird-first, and ΔTBSfourth-first (where second-first, third-first, and fourth-first denote scan number between the second and first, third and first, and fourth and first [177Lu]Lu-DOTATATE treatment cycles), respectively) between the PD and non-PD groups (median, 0.043 vs. -0.049, 0.08 vs. -0.116, and 0.109 vs. -0.123 [P = 0.023, P = 0.002, and P < 0.001], respectively). ΔnPCsecond-first showed significant group differences (mean, -0.107 vs. -0.282; P = 0.033); ΔnPCthird-first and ΔnPCfourth-first did not reach statistical significance (mean, -0.122 vs. -0.312 and -0.183 vs. -0.405 [P = 0.117 and 0.067], respectively). At the optimal threshold, ΔTBSfourth-first exhibited an area under the curve (AUC) of 0.957, achieving 100% sensitivity and 80% specificity. ΔTBSsecond-first and ΔTBSthird-first reached AUCs of 0.793 and 0.893, sensitivities of 71.4%, and specificities of 85% and 95%, respectively. ΔnPCsecond-first, ΔnPCthird-first, and ΔnPCfourth-first showed AUCs of 0.764, 0.693, and 0.679; sensitivities of 71.4%, 71.4%, and 100%; and specificities of 75%, 70%, and 35%, respectively. Conclusion: ΔTBS and ΔnPC can predict [177Lu]Lu-DOTATATE response by the second treatment session.

Tumor burden score is superior to primary liver cancer stages in predicting prognosis for patients with combined hepatocellular-cholangiocarcinoma after surgery: A multi-center study.

BACKGROUND: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is poorly understood, while the predictive value of the staging in which it is included is controversial. METHODS: Patients with cHCC-CCA underwent radical hepatectomy in two medical centers in China were enrolled and staged based on optimal cut-off values of tumor burden score (TBS), determined using the X-Tile. The association between TBS and prognosis was evaluated by Cox proportional hazard models and Kaplan-Meier curves with Log-rank test. TBS model and primary liver cancer (PLC) stages were compared by discrimination, consistency, and clinical utility, which were further validated by a 5-folds cross-validation. RESULTS: A total of 192 patients were stratified into low, medium, and high TBS, comprising 92, 51 and 49 patients, respectively. Prognoses worsened with elevated TBS in both the training and validation cohorts. TBS was not only an independent prognostic indicator in univariate and multivariate cox regression, but also a stable risk factor in subgroup analysis according to baseline variables. TBS exhibited best discrimination within these predictive models, as evidenced by the highest c-index and area under curve values of time-dependent receiver operating curves within 5 years post-surgery. TBS calibration plots revealed favorable consistency between prediction and observation. Decision curve analysis suggested higher net benefits for TBS. A 5-folds cross-validation revealed consistent results. CONCLUSIONS: TBS could be applied to stratify cHCC-CCA patients after surgery into groups with statistically different prognoses. Moreover, TBS exhibited optimal prognostic value over all available PLC stages and may inform clinical decisions.

A CT-based radiomics tumor quality and quantity model to predict early recurrence after radical surgery for colorectal liver metastases.

PURPOSE: This study aimed to develop a tumor radiomics quality and quantity model (RQQM) based on preoperative enhanced CT to predict early recurrence after radical surgery for colorectal liver metastases (CRLM). METHODS: A retrospective analysis was conducted on 282 cases from 3 centers. Clinical risk factors were examined using univariate and multivariate logistic regression (LR) to construct the clinical model. Radiomics features were extracted using the least absolute shrinkage and selection operator (LASSO) for dimensionality reduction. The LR learning algorithm was employed to construct the radiomics model, RQQM (radiomics-TBS), combined model (radiomics-clinical), clinical risk score (CRS) model and tumor burden score (TBS) model. Inter-model comparisons were made using area under the curve (AUC), decision curve analysis (DCA) and calibration curve. Log-rank tests assessed differences in disease-free survival (DFS) and overall survival (OS). RESULTS: Clinical features screening identified CRS, KRAS/NRAS/BRAF and liver lobe distribution as risk factors. Radiomics model, RQQM, combined model demonstrated higher AUC values compared to CRS and TBS model in training, internal and external validation cohorts (Delong-test P < 0.05). RQQM outperformed the radiomics model, but was slightly inferior to the combined model. Survival curves revealed statistically significant differences in 1-year DFS and 3-year OS for the RQQM (P < 0.001). CONCLUSIONS: RQQM integrates both "quality" (radiomics) and "quantity" (TBS). The radiomics model is superior to the TBS model and has a greater impact on patient prognosis. In the absence of clinical data, RQQM, relying solely on imaging data, shows an advantage in predicting early recurrence after radical surgery for CRLM.

A preoperative model to predict overall survival in patients with hepatoma undergoing resection.

BACKGROUND: We aimed to develop a preoperative model to predict overall survival (OS) in patients with hepatoma undergoing liver resection (LR). METHODS: Patients who underwent LR for Barcelona Clinic Liver Cancer (BCLC) stage 0, A, or B hepatoma were enrolled. Tumor burden score (TBS) scores were determined using the following equation: TBS (Pinna et al., 2018) 2 = (largest tumor size [in cm])(Pinna et al., 2018) 2 â€‹+ â€‹(tumor number) (Pinna et al., 2018) 22. The cutoff values for radiographic TBS were based on our recently published paper: low, <2.6; medium, 2.6-7.9; high, >7.9. RESULTS: Multivariate analysis showed that radiographic TBS (low: referent; medium: HR â€‹= â€‹2.89; 95 â€‹% CI: 1.60-5.21; p â€‹< â€‹0.001; high, HR â€‹= â€‹7.60; 95 â€‹% CI: 3.80-15.2; p â€‹< â€‹0.001), AFP (<400 â€‹ng/mL: referent; ≧400 â€‹ng/mL: HR â€‹= â€‹1.67, 95 â€‹% CI: 1.11-2.52, p â€‹= â€‹0.014), and cirrhosis (absence: referent; presence: HR â€‹= â€‹1.88, 95 â€‹% CI: 1.30-2.72, p â€‹< â€‹0.001) were associated with OS. A simplified risk score was superior to BCLC system in concordance index (0.688 vs. 0.623). CONCLUSIONS: We have developed a preoperative model that performs better in predicting OS than the BCLC system.

Prognostic Indicators of Overall Survival in Hepatocellular Carcinoma Patients Undergoing Liver Resection.

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and the third contributor to malignancy-related deaths worldwide. The hepatic venous pressure gradient (HVPG), transient elastography-liver stiffness measurement (TE-LSM), and the association between TBS (tumor burden score), alpha-fetoprotein levels, and the Child-Pugh classification (TAC score) can serve as valuable prognostic indicators for these patients. Therefore, the main objective of our research was to analyze the prognostic value of the HVPG, TE-LSM, TBS, and TAC scores. An observational and survival study was conducted on 144 subjects. Our findings indicated that HVPG greater than 10 mmHg, AFP surpassing 400 ng/mL, an advanced C-P class, and low TAC score are independent predictors of overall survival. During the multivariate analysis, AFP serum levels and C-P class proved statistically significant. The present study revealed significant differences in overall survival between the two groups divided upon HVPG values and settled by the cutoff of 10 mmHg (p = 0.02). Moreover, by dividing the cohort into three groups based on the TAC score (very low, low, and moderate), statistically significant differences in overall survival were observed across the groups (p = 0.004).

Construction of a prognostic model for hepatocellular carcinoma patients receiving transarterial chemoembolization treatment based on the Tumor Burden Score.

BACKGROUND: Patients with hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) may have varied outcomes based on their liver function and tumor burden diversity. This study aims to assess the prognostic significance of the tumor burden score (TBS) in these patients and develop a prognostic model for their overall survival. METHODS: The study involved a retrospective analysis of 644 newly diagnosed HCC patients undergoing TACE treatment. The individuals were assigned randomly to a training cohort (n = 452) and a validation cohort (n = 192). We utilized a multivariate Cox proportional risk model to identify independent preoperative predictive factors. We then evaluated model performance using the area under the curve (AUC), consistency index (c-index), calibration curve, and decision curve analysis (DCA) methods. RESULTS: The multivariate analysis revealed four prognostic factors associated with overall survival: Tumor Burden Score, Tumor Extent, Types of portal vein invasion (PVI), and Child-Pugh score. The total score was calculated based on these factors. The model demonstrated strong discriminative ability with high AUC values and c-index, providing high net clinical benefits for patients. Based on the model's scoring results, patients were categorized into high, medium, and low-risk groups. These results were validated in the validation cohort. CONCLUSIONS: The tumor burden score shows promise as a viable alternative prognostic indicator for assessing tumor burden in cases of HCC. The new prognostic model can place patients in one of three groups, which will estimate their individual outcomes. For high-risk patients, it is suggested to consider alternative treatment options or provide the best supportive care, as they may not benefit significantly from TACE treatment.

Tumor burden score and carcinoembryonic antigen predict outcomes in patients with intrahepatic cholangiocarcinoma following liver resection: a multi­institutional analysis.

BACKGROUND: The prognostic significance of tumor burden score (TBS) in relation to carcinoembryonic antigen (CEA) has not been investigated among patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). This study aimed to develop and validate a simplified model, a combination of TBS and CEA (CTC grade), for predicting the long-term outcomes of postoperative ICC patients. METHODS: Patients who underwent curative - intent resection of ICC between 2011 and 2019 were identified from a large multi - institutional database. The impact of TBS, CEA, and the CTC grade on overall survival (OS) and recurrence - free survival (RFS) was evaluated in both the derivation and validation cohorts. The receiver operating characteristic curve was utilized for assessing the predictive accuracy of the model. Subgroup analyses were performed across 8th TNM stage system stratified by CTC grade to assess the discriminatory capacity within the same TNM stage. RESULTS: A total of 812 patients were included in the derivation cohort and 266 patients in the validation cohort. Survival varied based on CEA (low: 36.7% vs. high: 9.0%) and TBS (low: 40.3% vs. high: 17.6%) in relation to 5 - year survival (both p < 0.001). As expected, patients with low CTC grade (i.e., low TBS/low CEA) were associated with the best OS as well as RFS, while high CTC grade (i.e., high TBS/high CEA) correlated to the worst outcomes. The model exhibited well performance in both the derivation cohort (area under the curve of 0.694) and the validation cohort (0.664). The predictive efficacy of the CTC grade system remains consistently stable across TNM stages I and III/IV. CONCLUSION: The CTC grade, a composite parameter derived from the combination of TBS and CEA levels, served as an easy - to - use tool and performed well in stratifying patients with ICC relative to OS and RFS.

The tumor burden score may be a discriminator in microwave ablation versus liver resection for hepatocellular carcinoma within the Milan criteria: a propensity score matching and inverse probability of treatment weighting study.

Purpose: This study aims to compare the prognostic outcome of resection (RES) and microwave ablation (MWA) in different tumor burden score (TBS) cohorts. Patients and Methods: We retrospectively analyzed 479 patients with primary hepatocellular carcinoma (HCC) who underwent RES (n = 329) or MWA (n = 150) with curative intent at our institution. We assessed their overall survival (OS) and progression-free survival (PFS) using the Kaplan-Meier curve. Propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) were performed to minimize selection and confounding biases. Multivariate Cox regression was used to define the association between surgical modalities and outcomes. Results: Following PSM, in the TBS ≤3 cohort, the cumulative 1-, 3-, 5- year OS in the RES and MWA groups were 92.5% vs. 98.8%, 82.7% vs. 90.0%, and 82.7% vs. 83.2% (P = 0.366), respectively. The corresponding PFS rates in the RES and MWA groups were 82.7% vs. 88.0%, 63.6% vs. 68.3% and 55.2% vs. 56.3, respectively (P = 0.218). In the TBS >3 cohort, the cumulative 1-, 3-, 5- year OS between the RES and MWA groups were 92.5% vs. 95.0%, 82.8% vs. 73.2% and 76.3% vs. 55.1%, (P = 0.034), respectively. The corresponding PFS rates in the RES and MWA groups were 78.0% vs. 67.5%, 63.6% vs. 37.5% and 55.2% vs. 37.1%, respectively (P = 0.044). The IPTW analysis showed similar results as shown in PSM analysis. The multivariate Cox regression indicated that the type of surgical modality was not associated with a poorer prognostic outcome in the TBS ≤3 cohort, unlike in the TBS >3 cohort. Conclusion: TBS, as a discriminator, might help guide treatment decision-making for HCC within the Milan criteria.

Neoadjuvant chemotherapy weakens the prognostic value of the pathological tumor burden score for colorectal cancer liver metastases.

BACKGROUND: The pathological tumor burden score (TBS) has been proven to be a better risk stratification tool for liver metastasis of colorectal cancer than the traditional clinical risk score (CRS). The aim of this study was to evaluate the prognostic value of the pathological tumor burden score in patients with or without neoadjuvant chemotherapy (NAC). METHODS: A total of 348 patients with colorectal liver metastases (CRLM) who underwent curative hepatic resection were retrospectively enrolled from September 1999 to December 2016. Univariable and multivariable Cox regression analyses were conducted to identify the independent predictors of prognosis. Kaplan-Meier curves and log-rank tests were used to determine whether TBS has enough discriminatory ability under certain grouping. RESULTS: Patients who received NAC had a higher median TBS than patients who did not receive NAC (4.07 vs. 2.69, P < 0.001). Among patients who did not receive NAC, those with TBS > 3 showed a significantly worse 3-year RFS (41.1% vs. 63.6%, P < 0.001) and 3-year OS rate (73.3% vs. 84.1%, P = 0.003) than those with TBS ≤ 3. Among the patients who received NAC, those with TBS ≤ 3 or TBS > 3 showed comparable 3-year RFS (33.3% vs. 26.4%, P = 0.400) and 3-year OS rates (76.5% vs. 58.2%, P = 0.064) to those who did not. Regardless of the regimen and response to NAC, there was no significant difference about 3-year RFS and 3-year OS rates between the TBS ≤ 3 and TBS > 3 groups. CONCLUSION: Pathological TBS can be applied to predict the RFS and OS of patients suffering from CRLM who did not receive NAC. However, pathological TBS might not be regard as prognosis in patients who did receive NAC.

Tumor burden score-AFP-albumin-bilirubin grade score predicts the survival of patients with hepatocellular carcinoma after liver resection.

PURPOSE: There is little information regarding the overall survival (OS) predictive ability of the combination of tumor burden score (TBS), α-fetoprotein (AFP), and albumin-bilirubin (ALBI) grade for patients with hepatocellular carcinoma (HCC). Here, we aimed to develop a model including TBS, AFP, and ALBI grade to predict HCC patient OS following liver resection. METHODS: Patients (N = 1556) from six centers were randomly divided 1:1 into training and validation sets. The X-Tile software was used to determine the optimal cutoff values. The time-dependent area under the receiver operating characteristic curve (AUROC) was calculated to assess the prognostic ability of the different models. RESULTS: In the training set, tumor differentiation, TBS, AFP, ALBI grade, and Barcelona Clinic Liver Cancer (BCLC) stage were independently related to OS. According to the coefficient values of TBS, AFP, and ALBI grade, we developed the TBS-AFP-ALBI (TAA) score using a simplified point system (0, 2 for low/high TBS, 0, 1 for low/high AFP and 0,1 for ALBI grade 1/2). Patients were further divided into low TAA (TAA ≤ 1), medium TAA (TAA = 2-3), and high TAA (TAA= 4) groups. TAA scores (low: referent; medium, HR = 1.994, 95% CI = 1.492-2.666; high, HR = 2.413, 95% CI = 1.630-3.573) were independently associated with patient survival in the validation set. The TAA scores showed higher AUROCs than BCLC stage for the prediction of 1-, 3-, and 5-year OS in both the training and validation sets. CONCLUSION: TAA is a simple score that has better OS prediction performance than the BCLC stage in predicting OS for HCC patients after liver resection.

Radiographic tumor burden score is useful for stratifying the overall survival of hepatocellular carcinoma patients undergoing resection at different Barcelona Clinic Liver Cancer stages.

PURPOSE: The Barcelona Clinic Liver Cancer (BCLC) staging system has been recommended for prognostic prediction. However, prognosis is variable at different BCLC stages. We aimed to evaluate whether the radiographic tumor burden score (TBS) could be used to stratify prognosis in different BCLC stages. METHODS: Hepatocellular carcinoma (HCC) patients undergoing liver resection (LR) at BCLC-0, -A, or -B stage in our institution in 2007-2018 were divided into derivation and validation cohorts. Overall survival (OS) was analyzed according to the TBS and BCLC stage. TBS cutoff values for OS were determined with X-tile. RESULTS: Of the 749 patients in the derivation cohort, 138 (18.4%) had BCLC-0, 542 (72.3%) BCLC-A, and 69 (9.2%) BCLC-B HCC; 76 (10.1%) had a high TBS (> 7.9), 477 (63.7%) a medium TBS (2.6-7.9), and 196 (26.2%) a low TBS (< 2.6). OS worsened progressively with increasing TBS in the cohort (p < 0.001) and in BCLC-A (p = 0.04) and BCLC-B (p = 0.002) stages. Multivariate analysis showed that the TBS was associated with OS of patients with BCLC-A (medium vs. low TBS: hazard ratio [HR] = 2.390, 95% CI = 1.024-5.581, p = 0.04; high vs. low TBS: HR = 3.885, 95% CI = 1.443-10.456, p = 0.007) and BCLC-B (high vs. medium TBS: HR = 2.542, 95% CI = 1.077-6.002, p = 0.033) HCC. The TBS could also be used to stratify the OS of patients in the validation cohort (p < 0.001). CONCLUSION: The TBS could be used to stratify the OS of the entire cohort and BCLC stages A and B of HCC patients undergoing LR.

Comparison of survival rates as predicted by total tumor volume or tumor burden score in patients with hepatocellular carcinoma concurrent with fatty liver disease and hepatitis B virus.

OBJECTIVES: To analyze prognostic value of total tumor volume (TTV) and tumor burden score (TBS) in surgically treated patients with hepatocellular carcinoma and concurrent fatty liver disease and hepatitis B virus (FLD-HCC). METHODS: FLD-HCC patients who treated with hepatectomy from 2010 to 2018 were analyzed. Prognostic performance of TTV and TBS was determined by ROC analysis. Patients were stratified into low and high tumor burden by optimal cutoff value of 113.4 cm3 for TTV or 6.3 points for TBS. Survival rates were compared between subgroups and independent risk factors were identified by Cox regression. Correlation between TTV and TBS was evaluated. RESULTS: This study enrolled 342 FLD-HCC patients. Survival was significantly higher among patients with low tumor burden than among those with high tumor burden (p < 0.001). High TTV and TBS were independent risk factors for poor survival of FLD-HCC (HR: 3.27 (2.17-4.93) and 3.48 (2.31-5.26), respectively, all p < 0.001). ROC analyses revealed that TTV and TBS had comparable discriminative ability in stratifying overall and recurrence-free survival of FLD-HCC. Correlation analysis revealed a strong correlation between TTV and TBS. CONCLUSIONS: Both TTV and TBS have comparable prognostic value and high TTV/TBS predicts poor survival of patients with FLD-HCC.

Alpha-Fetoprotein Combined with Radiographic Tumor Burden Score to Predict Overall Survival after Liver Resection in Hepatocellular Carcinoma.

We evaluated whether combining the radiographic tumor burden score (TBS) and alpha-fetoprotein (AFP) level could be used to stratify overall survival (OS) among hepatocellular carcinoma (HCC) patients after liver resection (LR). Patients who underwent LR for Barcelona Clinic Liver Cancer stage 0, A, or B HCC between 2011 and 2018 were enrolled. TBS scores were calculated using the following equation: TBS2 = (largest tumor size (in cm))2 + (tumor number)2. Among 743 patients, 193 (26.0%) patients had a low TBS (<2.6), 474 (63.8%) had a moderate TBS (2.6-7.9), and 75 (10.1%) had a high TBS (>7.9). Those with a TBS ≤ 7.9 and AFP < 400 ng/mL had a significantly better OS than those with a TBS > 7.9 and an AFP < 400 ng/mL (p = 0.003) or ≥ 400 ng/mL (p < 0.001). A multivariate analysis using TBS ≤ 7.9 and AFP < 400 ng/mL as the reference values showed that a TBS > 7.9 and an AFP < 400 ng/mL (hazard ratio (HR): 2.063; 95% confidence interval [CI]: 1.175-3.623; p = 0.012) or ≥ 400 ng/mL (HR: 6.570; 95% CI: 3.684-11.719; p < 0.001) were independent predictors of OS. In conclusion, combining radiographic TBSs and AFP levels could stratify OS among HCC patients undergoing LR.

TAC score better predicts survival than the BCLC following resection of hepatocellular carcinoma.

BACKGROUND: Heterogeneity in hepatocellular carcinoma (HCC) still exists within the Barcelona clinic liver cancer (BCLC) subcategories. We developed a simple model to better discriminate and predict prognosis following resection. METHODS: Patients who underwent curative-intent resection for HCC were identified from a multi-institutional database. Predictive factors of survival were identified to develop TAC (tumor burden score [TBS], alpha-fetoprotein [AFP], Child-Pugh CP]) score. RESULTS: Among 1435 patients, median TBS was 5.1 (interquartile range [IQR]: 3.2-8.1), median AFP was 18.3 ng/ml (IQR 4.0-362.5), and 1391 (96.9%) patients were classified as CP-A. Factors associated with overall survival (OS) included TBS (low: referent; medium: HR 2.26, 95% CI: 1.73-2.96; high: HR = 3.35, 95% CI: 2.22-5.07), AFP (<400 ng/ml: referent; >400 ng/ml: HR = 1.56, 95% CI: 1.27-1.92), and CP (A: referent; B: HR = 1.81, 95% CI: 1.12-2.92) (all p < 0.05). A simplified risk score demonstrated superior concordance index, Akaike information criteria, homogeneity, and area under the curve versus BCLC (0.620 vs. 0.541; 5484.655 vs. 5536.454; 60.099 vs. 16.194; 0.62 vs. 0.55, respectively), and further stratified patients within BCLC groups relative to OS (BCLC 0, very low: 86.8%, low: 47.8%) (BCLC A, very low: 79.7%, low: 68.1%, medium: 52.5%, high: 35.6%) (BCLC B, low: 59.8%, medium: 43.7%, high: N/A). CONCLUSION: TAC is a simple, holistic score that consistently outperformed BCLC relative to discrimination power and prognostication following resection of HCC.

Impacts of primary tumor location on outcomes in patients undergoing hepatectomy for colorectal liver metastasis vary according to tumor burden.

Purpose: The purpose of this study was to verify whether the prognostic value of primary tumor location (PTL) for patients undergoing resection for colorectal liver metastasis (CRLM) is affected by tumor burden. Methods: Patients who underwent a first curative-intent surgery for CRLM from 2006 to 2017 were enrolled. The imaging tumor burden score (TBS) was calculated as TBS2 = (maximum tumor diameter in cm)2 + (number of lesions)2. Then, the prognostic role of PTL was assessed in different TBS zones. Results: The patient population consisted of 524 left-sided (LS) and 118 right-sided (RS) primary tumors. The distribution of TBS in the patient cohort was: Zone1: TBS <3 [n = 161 (25.1%)], zone 2: TBS ≥3 to <7 [n = 343 (53.4%)], and zone 3: TBS ≥7 [n = 138 (21.5%)]. In the whole cohort, the 5-year overall survival (OS) in the RS group was worse than that in the LS group (35.6% vs. 45.4%). However, after adjustment for known prognostic confounders, the RS group was not independently associated with a poorer OS (HR 1.18, p = 0.247). Among patients with TBS <7, OS in the RS group was significantly shorter than that in the LS group in both univariate and multivariate analyses. The prognostic role of PTL remained significant after propensity score matching or excluding patients who received anti-EGFR agents. Conversely, the association between PTL and OS was no longer evident in patients with TBS ≥7. Conclusion: The current study demonstrates that the prognostic value of PTL varies by TBS, and RS tumors are only associated with shorter survival in patients with low or medium TBS.

Simple systemic index associated with oxaliplatin-induced liver damage can be a novel biomarker to predict prognosis after resection of colorectal liver metastasis.

Aim: Oxaliplatin, an anticancer drug for advanced colorectal cancer, causes liver sinusoidal damage, sometimes with portal hypertension. We conducted a retrospective comparative study of the relationship of liver sinusoidal disorders and liver function with the prognosis in patients who underwent hepatectomy for colorectal liver metastasis (CRLM). Methods: In total, 158 patients who underwent hepatectomy for CRLM were included in the study, and the effect of chemotherapy-associated liver damage on the prognosis was examined. Results: Preoperative oxaliplatin was used in 75 of 158 patients; of these 75 patients, 26 had intraoperative blue liver (BL). In a comparison of the BL group (n = 26) and non-BL group (n = 132), patients in the BL group had a significantly lower serum albumin concentration and a significantly higher indocyanine green test result, aspartate aminotransferase-to-platelet ratio index (APRI), and FIB-4 score. Operative morbidities were not significantly different between the two groups. The overall survival rate after hepatectomy was significantly worse in the BL group than in the non-BL group. In the univariate analysis, the serum albumin concentration, indocyanine green test, a high tumor burden score (TBS), and the APRI were statistically significant poor prognostic factors. In the multivariate analysis, the APRI and a high TBS were independent poor prognostic factors. Conclusion: The APRI and TBS in patients with CRLM are prognostic predictors after hepatectomy for metastatic liver cancer. This study indicated that liver damage in patients treated with preoperative oxaliplatin has an effect on the prognosis.

Radiofrequency Ablation versus Transarterial Chemoembolization for Hepatocellular Carcinoma within Milan Criteria: Prognostic Role of Tumor Burden Score.

Tumor burden score (TBS), estimated by the diameter and number of tumor nodules, was recently proposed to assess the tumor burden in hepatocellular carcinoma (HCC). We aimed to evaluate the prognostic impact of TBS on HCC patients within the Milan criteria undergoing radiofrequency ablation (RFA) or transarterial chemoembolization (TACE). A total of 883 patients undergoing RFA and TACE were included. The multivariate Cox proportional hazards model was used to determine independent prognostic predictors in different patient cohorts. The TACE group had significantly higher TBS compared with the RFA group. The RFA group had better long-term survival than the TACE group in patients within the Milan criteria in univariate survival analysis. In the Cox model, serum α-fetoprotein (AFP) > 20 ng/mL, performance status 1−2, medium and high TBS, albumin−bilirubin (ALBI) grade 2 and grade 3 were independent predictors linked with mortality (all p < 0.001). Overall, TACE was not an independent predictor; among patients with low TBS, TACE was independently associated with decreased survival compared with RFA (p = 0.034). Conclusions: TBS is a feasible prognostic marker for HCC patients within the Milan criteria. TACE may be an effective treatment alternative for these patients. Among patients with low TBS, RFA should be considered the priority treatment modality.

Tumor Burden Score and Serum Alpha-fetoprotein Subclassify Intermediate-Stage Hepatocellular Carcinoma.

BACKGROUND: Resection of Barcelona Clinic Liver Cancer (BCLC) intermediate-stage hepatocellular carcinoma (HCC) remains controversial. While not recommended by the BCLC algorithm, some patients may indeed benefit from hepatectomy. We sought to identify that subset of patients who might derive long-term survival benefit from resection. METHODS: Intermediate-stage HCC patients who underwent curative-intent resection were identified from an international multi-institutional database. Factors associated with long-term prognosis were identified using multivariate analysis and a risk score was developed and assessed. RESULTS: Among 194 patients, most individuals had two tumors (n = 123, 63.4%) with a median size of 6.0 cm (IQR, 4.0-8.4) for a median tumor burden score (TBS) of 6.5 (IQR, 5.0-9.1); median alpha-fetoprotein (AFP) was 23.9 ng/mL (IQR, 5.0-503.2), and median overall survival (OS) was 69 months (IAR, 60.7-77.3). Factors associated with OS included AFP (referent ≤ 20 ng/mL, > 20 ng/mL: HR 1.78 95%CI, 1.09-2.89) and TBS (referent TBS ≤ 8.0, TBS > 8.0: HR 1.72 95%CI, 1.07-2.75). While 71 (36.6%) patients had neither risk factor, 79 (40.7%) and 44 (22.7%) had 1 or 2, respectively. A simplified score stratified patients relative to recurrence-free survival (RFS) (0: 33.6% vs. 1: 18.0% vs. 2: 14.7%) (AUC 0.60) and recurrence time (i.e., < 6 months after surgery) (0: 21.3% vs. 1: 43.1% vs. 2: 68.6%) (AUC 0.69) (both p < 0.001). Of note, a higher score was also associated with incrementally worse 5-year OS (0: 68.1% vs. 1: 61.0% vs. 2: 29.9%) (AUC 0.62) (p < 0.001). CONCLUSION: Long-term OS and RFS outcomes varied considerably. Using a simple risk score, patients with low AFP and low TBS were identified as the subset of individuals most likely to benefit from resection.