The University of Texas MD Anderson Cancer Center, Houston, TX
Michael Brian LaPelusa , Shadi Chamseddine , Lianchun Xiao , Elshad Hasanov , Priya Bhosale , Yehia I. Abugabal , Betul Gok Yavuz , Shalini S. Yadav , Hop Sanderson Tran Cao , Li Xu , Zishuo Ian Hu , Sunyoung S. Lee , Divya Sakamuri , Michael A. Curran , Sonali Jindal , Gabriel Dan Duda , Padmanee Sharma , Aliya Qayyum , Ahmed Omar Kaseb
Background: Neoadjuvant immunotherapy can induce a major pathologic response (MPR) in patients with resectable hepatocellular carcinoma (HCC), which may be associated with prolonged recurrence-free survival. This study aimed to understand which variables correlate with achieving an MPR. Methods: Patients with resectable HCC who received either neoadjuvant nivolumab plus ipilimumab or nivolumab alone and underwent surgery were included. 18 patients had baseline and post-treatment computed tomography, alpha-fetoprotein (AFP), and elastography. 17 of these patients had baseline and post-treatment tissue available for immunohistochemistry. Patients were classified into two groups: MPR, defined as necrosis of >70%, and no MPR. Data was summarized using descriptive statistics and compared using Wilcoxon rank sum test. P value <0.05 was considered statistically significant. Results: Statistically significant differences in objective response (OR) and changes in CD8, Granzyme B, and PD-1 expression were identified upon comparison of patients with an MPR to those without an MPR (Table 1). Additionally, numerical differences in baseline tumor size, change in AFP, and both non-tumor and tumor liver fibrosis (at baseline, after treatment, and interim change) were identified upon comparison of patients with an MPR to those without an MPR. Conclusions: Our data show that large baseline tumor size, greater OR, reduction in AFP, increase in liver and tumor fibrosis, and increase in CD8, Granzyme B, and PD-1 expression after receipt of neoadjuvant immunotherapy are associated with achieving an MPR in patients with resectable HCC.
Pathologic Response(# of patients) | Mean +/- SD | Median (range) | p-value | |
---|---|---|---|---|
Baseline tumor size (cm) | MPR (6) | 9.52 +/- 4.08 | 9.4 (2.30, 13.60) | 0.0501 |
No MPR (12) | 4.99 +/- 3.69 | 4.65 (1.20, 14.00) | ||
Objective response (%) | MPR (6) | -0.15 +/- 0.35 | -0.27 (-0.35, 0.56) | 0.0417 |
No MPR (12) | 0.09 +/- 0.16 | 0.05 (-0.08, 0.41) | ||
Change in AFP (%) | MPR (6) | -24.20 +/- 148.02 | -93.23 (-99.58, 273.65) | 0.0853 |
No MPR (12) | -14.00 +/- 31.02 | -5.00 (-98.40, 16.00) | ||
Baseline fibrosis (kPa) | MPR (6) | 2.87 +/- 0.70 | 2.90 (1.80, 3.70) | 0.1768 |
No MPR (12) | 2.33 +/- 0.58 | 2.15 (1.70, 3.40) | ||
Post-treatment fibrosis (kPa) | MPR (6) | 3.12 +/- 0.73 | 3.20 (2.20, 3.90) | 0.1008 |
No MPR (12) | 2.40 +/- 0.92 | 2.20 (1.20, 4.60) | ||
Change in fibrosis (%) | MPR (6) | 11.13 +/- 23.52 | 10.52 (-20.59, 48) | 0.3858 |
No MPR (12) | 2.15 +/- 24.65 | 0 (-29.41, 52.94) | ||
Change in CD8 expression (% cells/mm2) | MPR (6) | 26.92 +/- 19.88 | 24.19 (-3.00, 51.50) | 0.0255 |
No MPR (11) | -0.04 +/- 7.93 | 0.18 (-15.53, 17.20) | ||
Change in Granzyme B expression (% cells/mm2) | MPR (6) | 15.56 +/- 10.31 | 17.21 (-1.13, 30.72) | 0.0112 |
No MPR (11) | -2.24 +/- 4.14 | -2.26 (-9.33, 6.45) | ||
Change in PD-1 expression (% cells/mm2) | MPR (6) | 20.17 +/- 13.70 | 25.49 (-1.06, 38.48) | 0.0480 |
No MPR (11) | 0.40 +/- 3.49 | 0.86 (-5.70, 5.63) |
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