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© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Simple Summary

The treatment outcomes in patients with head and neck cancer vary greatly, and serious side effects are often observed. Being able to predict therapy effects is therefore crucial for choosing the best treatment option for each patient. In this study, we developed an assay to evaluate how head and neck tumor cells respond to radiation and chemotherapy. Treatment of thin patient-derived cancer tissue slices in the laboratory (in vitro) resulted in large differences in individual tumor’s reactions to treatment. In the sensitive tumors, cancer cells repaired the DNA damage inflicted by therapy only partially, stopped multiplying, and showed increased levels of cell death. On the other hand, resistant tumors were able to recover from the damage caused by the treatment. The next crucial step is to investigate whether the differences we observed in vitro can indeed predict the treatment outcomes; this is currently being tested in an ongoing clinical trial.

Abstract

Background: Head and neck squamous cell carcinoma (HNSCC) displays a large heterogeneity in treatment response, and consequently in patient prognosis. Despite extensive efforts, no clinically validated model is available to predict tumor response. Here we describe a functional test for predicting tumor response to radiation and chemotherapy on the level of the individual patient. Methods: Resection material of 17 primary HNSCC patients was cultured ex vivo, irradiated or cisplatin-treated, after which the effect on tumor cell vitality was analyzed several days after treatment. Results: Ionizing radiation (IR) affected tumor cell growth and viability with a clear dose-response relationship, and marked heterogeneity between tumors was observed. After a single dose of 5Gy, proliferation in IR-sensitive tumors dropped below 30% of the untreated level, while IR-resistant tumors maintained at least 60% of proliferation. IR-sensitive tumors showed on average a twofold increase in apoptosis, as well as an increased number and size of DNA damage foci after treatment. No differences in the homologous recombination (HR) proficiency between IR-sensitive and –resistant tumors were detected. Cisplatin caused a decrease in proliferation, as well as induction of apoptosis, again with marked variation between the samples. Conclusions: Our functional ex vivo assay discriminated between IR-sensitive and IR-resistant HNSCC tumors, and may also be suitable for predicting response to cisplatin. Its predictive value is currently under investigation in a prospective clinical study.

Details

Title
Ex Vivo Functional Assay for Evaluating Treatment Response in Tumor Tissue of Head and Neck Squamous Cell Carcinoma
Author
Capala, Marta E 1 ; Pachler, Katrin S 2 ; Lauwers, Iris 1 ; de Korte, Maarten A 1 ; Verkaik, Nicole S 2 ; Mast, Hetty 3 ; Jonker, Brend P 3 ; Sewnaik, Aniel 4 ; Hardillo, Jose A 4   VIAFID ORCID Logo  ; Keereweer, Stijn 4   VIAFID ORCID Logo  ; Monserez, Dominiek 4   VIAFID ORCID Logo  ; Koljenovic, Senada 5 ; Mostert, Bianca 6 ; Verduijn, Gerda M 1   VIAFID ORCID Logo  ; Petit, Steven 1 ; van Gent, Dik C 2   VIAFID ORCID Logo 

 Department of Radiotherapy, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 Rotterdam, The Netherlands 
 Department of Molecular Genetics, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 Rotterdam, The Netherlands 
 Department of Oral and Maxillofacial Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 Rotterdam, The Netherlands 
 Department of Otorhinolaryngology and Head and Neck Surgery, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 Rotterdam, The Netherlands 
 Department of Pathology, Antwerp University Hospital, 2650 Edegem, Belgium 
 Department of Medical Oncology, Erasmus MC Cancer Institute, University Medical Center Rotterdam, 3015 Rotterdam, The Netherlands 
First page
478
Publication year
2023
Publication date
2023
Publisher
MDPI AG
e-ISSN
20726694
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2767191159
Copyright
© 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.