Development and validation of the OSASH score to predict overall survival of hepatocellular carcinoma after surgical resection: a dual-institutional study

Objective To develop and validate a risk score based on preoperative clinical-radiological parameters for predicting overall survival (OS) in patients undergoing surgical resection for hepatocellular carcinoma (HCC). Methods From July 2010 to December 2021, consecutive patients with surgically-proven HCC who underwent preoperative contrast-enhanced MRI were retrospectively enrolled. A preoperative OS risk score was constructed in the training cohort using a Cox regression model and validated in a propensity score-matched internal validation cohort and an external validation cohort. Results A total of 520 patients were enrolled, among whom 210, 210, and 100 patients were from the training, internal validation, and external validation cohorts, respectively. Independent predictors for OS included incomplete tumor “capsule,” mosaic architecture, tumor multiplicity, and serum alpha-fetoprotein, which were incorporated into the “OSASH score.” The C-index the OSASH score was 0.85, 0.81, and 0.62 in the training, internal, and external validation cohorts, respectively. Using 32 as the cutoff point, the OSASH score stratified patients into prognostically distinct low- and high-risk groups among all study cohorts and six subgroups (all p < 0.05). Furthermore, patients with BCLC stage B-C HCC and OSASH-low risk achieved comparable OS to that of patients with BCLC stage 0-A HCC and OSASH-high risk in the internal validation cohort (5-year OS rates, 74.7 vs. 77.8%; p = 0.964). Conclusion The OSASH score may help predict OS in HCC patients undergoing hepatectomy and identify potential surgical candidates among those with BCLC stage B-C HCC. Clinical relevance statement By incorporating three preoperative MRI features and serum AFP, the OSASH score may help predict postsurgical overall survival in patients with hepatocellular carcinoma and identify potential surgical candidates among those with BCLC stage B and C HCC. Key Points • The OSASH score incorporating three MRI features and serum AFP can be used to predict OS in HCC patients who received curative-intent hepatectomy. • The score stratified patients into prognostically distinct low- and high-risk strata in all study cohorts and six subgroups. • Among patients with BCLC stage B and C HCC, the score identified a subgroup of low-risk patients who achieved favorable outcomes after surgery. Supplementary Information The online version contains supplementary material available at 10.1007/s00330-023-09725-7.


MRI technique
At institution 1, gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) was performed with four 3.0-T systems (GE SIGNA™ Architect; GE SIGNA™ Premier; GE Discovery MR 750; Siemens MAGNETOM Skyra) and a 1.5-T system (uMR588), and extracellular contrast agent-enhanced MRI was performed with five 3.0-T systems (Siemens MAGNETOM Skyra; Siemens TrioTim; GE SIGNA™ Architect; GE Discovery MR 750; Philips Ingenia Elition X) and two 1.5-T systems (Siemens Avanto; uMR588).At institution 2, EOB-MRI was performed with a 3.0-T system (GE Discovery MR 750).Liver MRI protocols involved T2-weighted imaging, diffusion-weighted imaging (b values: 0-1200 s/mm 2 at institution 1; 0-3000 s/mm 2 at institution 2) with apparent diffusion coefficient (ADC) maps, T1-weighted in-and opposed-phase imaging, and dynamic T1-weighted imaging before and after injection of contrast agent in the late arterial phase, portal venous phase (60 s), delayed phase (ECA-MRI; 180s) or transitional phase (EOB-MRI; 180 s), and hepatobiliary phase (EOB-MRI; 20 minutes).At both institution 1 and 2, the arterial phase images were obtained either by the acquisition triggered 7 s after arrival of the contrast bolus in the celiac trunk or a multiple arterial phase (MAP) imaging technique.In specific, the MAP images were acquired with an 18 s breath hold 20 s after the contrast media injection, and further reconstructed with a temporal resolution of 3 s.For EOB-MRI, gadoxetate disodium (Primovist®; Bayer Schering Pharma AG) was administered intravenously at 1.0-2.0ml/s (0.025 mmol/kg of body weight), with an immediately followed 20-30 ml saline flush.For ECA-MRI, gadopentetate dimeglumine (Magnevist®; Bayer Schering Pharma AG) or gadoterate meglumine (Dotarem®; Guerbet) or gadobenate dimeglumine (MultiHance®; Bracco) was administered intravenously at 2.5 ml/s (0.1 mmol/kg of body weight).MRI sequences and parameters are detailed in Table S1.Unless indicated otherwise, data are the number of patients, with percentages in parentheses.SMD was defined as follows: <0.1, very small differences; 0.1-0.3,small differences; 0.3-0.5, moderate differences; and >0.5, large differences.Group comparison was performed with the Student's t test for continuous variable and Chi-square test or Fisher's exact test for categorical variables, as appropriate.†Data are means ± standard deviations.§Data are presented as the absolute value of SMD.
BCLC, Barcelona Clinic Liver Cancer; ECA-MRI, extracellular contrast agent-enhanced magnetic resonance imaging; PSM, propensity score matching; SMD, standardized mean difference.The patient was alive throughout the follow-up period of 51.1 months.AFP, alpha-fetoprotein; BCLC, Barcelona Clinic Liver Cancer; HCC, hepatocellular carcinoma; MRI, magnetic resonance imaging.

Figure S2
Figure S2 Kaplan-Meier curves demonstrating differences in OS between the OSASH-low and OSASH-high risk patients with HCC in six subgroups in

Figure S3
Figure S3Kaplan-Meier curves demonstrating differences in OS between the OSASH-low and OSASH-high risk patients with HCC in six subgroups in

Figure S4
Figure S4 An OSASH-low risk patient with BCLC stage C HCC in the internal validation cohort.Pathologically confirmed HCC in a 64-year-

Table S1
MRI sequences and parameters

Table S2
Characteristics of study patients before PSM and SMDs before and after PSM

Table S4
Median OS, 3-and 5-year OS rates, and hazard ratios for BCLC stage subgroups and OSASH score risk subclasses in patients with BCLC stage 0-A and B-C HCC in the training and internal validation cohorts