TY  - JOUR
A1  - Müller-von der Grün, Jens
A1  - Winkelmann, Anne Ria
A1  - Burck, Iris
A1  - Martin, Daniel, 
A1  - Rödel, Franz
A1  - Wild, Peter Johannes
A1  - Bankov, Katrin
A1  - Weigert, Andreas
A1  - Kur, Ivan
A1  - Brandts, Christian Hubertus
A1  - Filmann, Sonja Natalie
A1  - Issing, Christian
A1  - Thönissen, Philipp Nikolaus
A1  - Tanneberger, Anna Maria
A1  - Rödel, Claus
A1  - Ghanaati, Shahram Michael
A1  - Balermpas, Panagiotis
T1  - Neoadjuvant chemoradiotherapy for oral cavity cancer: predictive factors for response and interim analysis of the prospective INVERT-Trial
T2  - Frontiers in oncology
N2  - Background: To study neoadjuvant chemoradiotherapy (nCRT) and potential predictive factors for response in locally advanced oral cavity cancer (LA-OCC).

Methods: The INVERT trial is an ongoing single-center, prospective phase 2, proof-of-principle trial. Operable patients with stage III-IVA squamous cell carcinomas of the oral cavity were eligible and received nCRT consisting of 60 Gy with concomitant cisplatin and 5-fluorouracil. Surgery was scheduled 6-8 weeks after completion of nCRT. Explorative, multiplex immunohistochemistry (IHC) was performed on pretreatment tumor specimen, and diffusion-weighted magnetic resonance imaging (DW-MRI) was conducted prior to, during nCRT (day 15), and before surgery to identify potential predictive biomarkers and imaging features. Primary endpoint was the pathological complete response (pCR) rate.

Results: Seventeen patients with stage IVA OCC were included in this interim analysis. All patients completed nCRT. One patient died from pneumonia 10 weeks after nCRT before surgery. Complete tumor resection (R0) was achieved in 16/17 patients, of whom 7 (41%, 95% CI: 18-67%) showed pCR. According to the Clavien-Dindo classification, grade 3a and 3b complications were found in 4 (25%) and 5 (31%) patients, respectively; grade 4-5 complications did not occur. Increased changes in the apparent diffusion coefficient signal intensities between MRI at day 15 of nCRT and before surgery were associated with better response (p=0.022). Higher abundances of programmed cell death protein 1 (PD1) positive cytotoxic T-cells (p=0.012), PD1+ macrophages (p=0.046), and cancer-associated fibroblasts (CAFs, p=0.036) were associated with incomplete response to nCRT.

Conclusion: nCRT for LA-OCC followed by radical surgery is feasible and shows high response rates. Larger patient cohorts from randomized trials are needed to further investigate nCRT and predictive biomarkers such as changes in DW-MRI signal intensities, tumor infiltrating immune cells, and CAFs.
KW  - neoadjuvant chemoradiotherapy
KW  - oral cavity cancer
KW  - multiplexed immunofluorescence
KW  - diffusion-weighted magnetic resonance imaging
KW  - predictive biomarker
Y1  - 2022
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/73973
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-739733
SN  - 2234-943X
N1  - This work was supported by grants from the Mildred-Scheel-Nachwuchszentrum (MSNZ) of the German Cancer Aid to JG.
N1  - The study was partially funded by a research grant received by Panagiotis Balermpas for the INVERT trial by the Clinical Trial Center Network of the University Cancer Center Frankfurt, 2012.
N1  - The data presented in this study are available on request from the corresponding author. Requests to access the datasets should be directed to Jens von der Grün, jens.vondergruen@kgu.de.
VL  - 24
IS  - art. 817692
SP  - 1
EP  - 13
PB  - Frontiers Media
CY  - Lausanne
ER  -