Local and abscopal responses in advanced intrahepatic cholangiocarcinoma with low TMB, MSS, pMMR and negative PD-L1 expression following combined therapy of SBRT with PD-1 blockade
Abstract
Late-stage or recurrent intrahepatic cholangiocarcinoma (ICC) patients exhibit poor prognosis due to limited sensitivity to chemotherapy or radiotherapy and coexistence of multiple lesions. Programmed cell death protein 1 (PD-1) blockade provides a therapeutic opportunity for patients with high tumor mutation burden (TMB), high microsatellite instability (MSI-H), deficient mismatch repair (dMMR) and/or positive programmed cell death ligand 1 (PD-L1) expression. However, it is currently believed that patients with low TMB, microsatellite stable (MSS), proficient mismatch repair (pMMR) or negative PD-L1 expression are less likely to benefit from PD-1 blockade. Here we provide the first report on the therapeutic responses of ICC patients treated with combined PD-1 blockade with stereotactic body radiotherapy (SBRT) (Cyberknife) in the background of low TMB, MSS, pMMR and negative PD-L1 expression. One stage IVA ICC patients and two postsurgical recurrent ICC patients were involved in this study and the responses of both locally irradiated tumor(s) and the abscopal tumors or metastasis to the combined therapy were assessed by magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT). The stage I...Continue Reading
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