Supplementary Material for: Nutritional Index as Prognostic Indicator in Patients Receiving Lenvatinib Treatment for Unresectable Hepatocellular Carcinoma

<b><i>Background/Aim:</i></b> Few studies have examined the details of nutritional status in patients with unresectable hepatocellular carcinoma (u-HCC) undergoing systemic chemotherapy with lenvatinib. We evaluated the prognostic/predictive value of nutritional status using Onodera’s prognostic nutritional index (O-PNI) for overall survival among patients with u-HCC treated with lenvatinib. <b><i>Methods:</i></b> Three-hundred and seventy-five u-HCC patients treated with lenvatinib were enrolled (median age 72 years; Child-Pugh class A/B/C: <i>n</i> = 312/60/3; BCLC stage A/B/C/D: <i>n</i> = 2/159/212/2). We examined median survival time (MST) and time to progression (TTP) in all patients (<i>n</i> = 375), prognosis according to the O-PNI (high/low: &gt;40/≤40) in 298 patients with lymphocyte findings, and the prognostic/predictive values of Child-Pugh stage, albumin-bilirubin (ALBI)/modified ALBI (mALBI) grade, and O-PNI for Chemotherapy grade (OPNIC grade 1/2/3: O-PNI &gt;40/≤40 to &gt;36/≤36). <b><i>Results:</i></b> The MST and TTP were 16.6 and 8.0 months, respectively. The MST and TTP according to the O-PNI (&gt;40/≤40) were “not reached” (NR)/12.4 months (<i>p</i> &lt; 0.001) and 10.0/6.1 months (<i>p</i> = 0.012), respectively. There was a good correlation noted between ALBI score and O-PNI (<i>r</i> = −0.939, <i>p</i> &lt; 0.001). The predictive value of the O-PNI for mALBI grade 2a was 36.0 (specificity/sensitivity = 0.894/0.942; area under the curve [AUC] = 0.978), while that for mALBI grade 1 was 39 (specificity/sensitivity = 0.920/0.929; AUC = 0.972), which was very similar to a high O-PNI. The MST analyzed with the OPNIC in the 298 patients was NR/16.2/10.4 months for OPNIC grade 1/2/3 (<i>p</i> &lt; 0.001), respectively, and the c-index was 0.632, the same as that for mALBI grade (0.632), while that for Child-Pugh class was 0.571. <b><i>Conclusions:</i></b> OPNIC grading might have a potential for easy substitution of mALBI grading. A good nutritional status (OPNIC grade 1) or mALBI grade 1 is the best indication for lenvatinib use, while with an OPNIC grade 3, lenvatinib might be not suitable.