Background Immune checkpoint inhibitors (ICI), such as atezolizumab (anti-programmed death-ligand 1; PD-L1), have been proven to be an effective strategy in solid cancers. However, the overall response rate to ICI is currently limited to an intrinsically responsive tumor immune microenvironment (TIME) or depended on an appropriate foregone immune stimulus, such as radiotherapy. The concept of combining radiotherapy with ICI is currently investigated in a variety of solid cancers. However, little data is known on the expression dynamics of immune checkpoint ligands, such as PD-L1, during neoadjuvant chemoradiotherapy (CRT) or short-course preoperative radiotherapy (SCPRT) in human solid malignancies.
Materials and Methods This is a prospective non-randomized open-label single-center investigator-initiated pilot study (NCT no. NCT04564482). Patients with either rectal cancer (RC), oesophageal adenocarcinoma (EAC), gastroesophageal junction (GEJ) cancer or oesophageal squamous cell carcinoma (ESCC), whom are assigned by the routine multidisciplinary tumor board (MDT) to receive a standard neoadjuvant CRT/SCPRT, will be enrolled. Standard neoadjuvant regimens include CRT (50 Gy in 2 Gy fractions over 25 working days + capecitabine 1650 mg/m2/d PO) or SCPRT (25 Gy in 5 Gy fractions over 5 working days) for RC patients and CRT according to the CROSS protocol (41.4 Gy in 1.8 Gy fractions over 23 working days + carboplatin AUC of 2 mg/ml/min + paclitaxel 50 mg/m2 IV Q1W) for patients with EAC, ESCC or GEJ cancer. Patients will receive a PD-L1 (89Zr-atezolizumab) positron emission tomography (PET) CT (for EAC, ESCC or GEJ cancers) or MRI (for RC) bevor (day 0) and during neoadjuvant treatment (day 10-14).
Results The primary endpoint of this pilot study is the none-invasive assessment of PD-L1 expression dynamics during neoadjuvant CRT/SCPRT by a PD-L1 PET imaging approach. Secondary objectives are the correlation between PD-L1 PET expression dynamics and radiographic as well as pathological therapy response.
Conclusions This is the first in human study, which assesses PD-L1 expression dynamics during different neoadjuvant radiotherapeutic regimens. A detailed understanding of the impact of radiotherapy on PD-L1 expression, monitored by an none-invasive PET imaging approach, allows the application of radiotherapy as part of a novel immunotherapeutic concept.
Disclosure Information J. Laengle: None. D. Tamandl: None. R. Schmid: None. J. Widder: None. M. Bergmann: None. A. Haug: None.
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