Jens Müller-von der Grün, Anne Ria Winkelmann, Iris Burck, Martin, Daniel, Franz Rödel, Peter Johannes Wild, Katrin Bankov, Andreas Weigert, Ivan Kur, Christian Hubertus Brandts, Sonja Natalie Filmann, Christian Issing, Philipp Nikolaus Thönissen, Anna Maria Tanneberger, Claus Rödel, Shahram Michael Ghanaati, Panagiotis Balermpas
- 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.
MetadatenAuthor: | Jens Müller-von der GrünORCiDGND, Anne Ria WinkelmannGND, Iris BurckORCiDGND, Martin, DanielGND, Franz RödelORCiDGND, Peter Johannes WildORCiDGND, Katrin BankovORCiDGND, Andreas WeigertORCiDGND, Ivan KurORCiDGND, Christian Hubertus BrandtsORCiDGND, Sonja Natalie FilmannORCiDGND, Christian IssingORCiDGND, Philipp Nikolaus ThönissenGND, Anna Maria TannebergerGND, Claus RödelORCiDGND, Shahram Michael GhanaatiORCiDGND, Panagiotis BalermpasORCiDGND |
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URN: | urn:nbn:de:hebis:30:3-739733 |
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DOI: | https://doi.org/10.3389/fonc.2022.817692 |
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ISSN: | 2234-943X |
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Parent Title (English): | Frontiers in oncology |
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Publisher: | Frontiers Media |
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Place of publication: | Lausanne |
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Document Type: | Article |
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Language: | English |
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Date of Publication (online): | 2022/03/24 |
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Date of first Publication: | 2022/03/24 |
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Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
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Release Date: | 2023/06/02 |
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Tag: | diffusion-weighted magnetic resonance imaging; multiplexed immunofluorescence; neoadjuvant chemoradiotherapy; oral cavity cancer; predictive biomarker |
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Volume: | 24 |
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Issue: | art. 817692 |
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Article Number: | 817692 |
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Page Number: | 13 |
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First Page: | 1 |
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Last Page: | 13 |
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Note: | This work was supported by grants from the Mildred-Scheel-Nachwuchszentrum (MSNZ) of the German Cancer Aid to JG. |
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Note: | 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. |
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Note: | 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. |
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Institutes: | Medizin |
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Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Sammlungen: | Universitätspublikationen |
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Licence (German): | Creative Commons - CC BY - Namensnennung 4.0 International |
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