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Copenhagen, Denmark
Onsite/Online

ESTRO 2022

Session Item

Saturday
May 07
10:30 - 11:30
Mini-Oral Theatre 1
03: Radiobiology
Kim Kampen, The Netherlands;
Paul Span, The Netherlands
Mini-Oral
Radiobiology
PORT-C improves LRC in a subset of patients with intermediate-risk HNSCC: A matched pair analysis
Shivaprasad Patil, Germany
MO-0139

Abstract

PORT-C improves LRC in a subset of patients with intermediate-risk HNSCC: A matched pair analysis
Authors:

Shivaprasad Patil1,2, Annett Linge1,2,3,4, Hannah Hiepe1,2,3, Marianne Grosser5, Fabian Lohaus1,2,3,4, Volker Gudziol4,6, Alexander Nowak4,7, Inge Tinhofer8,9, Volker Budach8,9, Maja Guberina10,11, Martin Stuschke10,11, Panagiotis Balermpas12,13, Claus Rödel12,13, Henning Schäfer14,15, Anca-Ligia Grosu14,15, Amir Abdollahi16,17,18,19,20, Jürgen Debus16,17,18,19,21, Claus Belka22,23,24, Steffi Pigorsch22,25, Stephanie E. Combs22,25,26, Simon Boeke27,28, Daniel Zips27,28, Michael Baumann1,2,3, Mechthild Krause1,2,3,4, Steffen Löck1,2,3,4

1German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Dresden, Dresden, Germany; 2OncoRay – National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Helmholtz-Zentrum Dresden - Rossendorf, Dresden, Germany; 3Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 4National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany, and Helmholtz Association / Helmholtz-Zentrum Dresden - Rossendorf (HZDR), Dresden, Germany; 5Institute of Pathology, Faculty of Medicine and University Hospital Carl Gustav Carus,Technische Universität Dresden, Dresden, Germany; 6Department of Otorhinolaryngology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 7Department of Oral and Maxillofacial Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany; 8German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Berlin, Berlin, Germany; 9Charité University Medicine Berlin, Department of Radiooncology and Radiotherapy, Berlin, Germany; 10German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Essen, Essen, Germany; 11Department of Radiation Therapy, University Hospital, Medical Faculty, University of Duisburg-Essen, Essen, Germany; 12German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Frankfurt, Frankfurt, Germany; 13Department of Radiotherapy and Oncology, Goethe-University Frankfurt, Frankfurt, Germany; 14German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Freiburg, Freiburg, Germany; 15Department of Radiation Oncology, Medical Center, Medical Faculty, University of Freiburg, Freiburg, Germany; 16German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Heidelberg, Heidelberg, Germany; 17Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Heidelberg, Germany; 18Heidelberg Ion Therapy Center (HIT), Department of Radiation Oncology, University of Heidelberg Medical School, Heidelberg, Germany; 19National Center for Tumor Diseases (NCT), University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Heidelberg, Germany; 20Translational Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Heidelberg, Germany; 21Clinical Cooperation Unit Radiation Oncology, University of Heidelberg Medical School and German Cancer Research Center (DKFZ), Heidelberg, Germany; 22German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Munich, Munich, Germany; 23Department of Radiotherapy and Radiation Oncology, University Hospital, Ludwig-Maximilians-Universität, Munich, Germany; 24Clinical Cooperation Group Personalized Radiotherapy in Head and Neck Cancer, Helmholtz Zentrum Munich, Neuherberg, Munich, Germany; 25Department of RadioOncology, Technische Universität München, Munich, Germany; 26Department of Radiation Sciences (DRS), Institut für Innovative Radiotherapie (iRT), Helmholtz Zentrum Munich, Neuherberg, Munich, Germany; 27German Cancer Research Center (DKFZ), Heidelberg, Germany, German Cancer Consortium (DKTK), partner site Tübingen, Tübingen, Germany; 28Department of Radiation Oncology, Faculty of Medicine and University Hospital Tübingen, Eberhard Karls Universität Tübingen, Tübingen, Germany

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Purpose or Objective

The aim of this matched-pair study including patients with locally advanced head and neck squamous cell carcinoma (HNSCC) was to develop a novel gene signature in order to identify patients amongst those who are at intermediate risk according to clinical risk factors but biologically at high risk for the development of loco-regional recurrences after surgery and postoperative radiotherapy (PORT).

Material and Methods

Gene expression analysis was performed using GeneChip Human Transcriptome Array 2.0 on a multicentre retrospective cohort of 221 patients that were treated with postoperative radiochemotherapy (PORT-C) and 283 patients that were treated with PORT alone within the German Cancer Consortium Radiation Oncology Group (DKTK-ROG). Propensity score matching (PSM) analysis was performed to identify matched patient pairs from the PORT and PORT-C cohorts using the matchIt R package. The nearest method was used on the logit of the propensity score using a caliper of width equal to 0.2 times the standard deviation. The clinical parameters T-stage, tumour localization (oral cavity vs others), N-stage and tumour grade were used for matching as they were expected to differ between the cohorts. Differential gene expression (DGE) analysis was performed between the resulting matched cohorts. The genes with a fold-change (FC) of ≥1.5 and an FDR adjusted p-value of ≤ 0.05 in Cox regression analysis on the PORT cohort were selected to develop a gene signature.

Results

124 patient pairs treated with PORT-C or PORT were generated with low standardized mean differences in the matched clinical parameters. We identified a 2-gene signature consisting of MIR548A1 and MIR3186, that was used to stratify patients into risk groups for loco-regional recurrence in the PORT cohort (p<0.001) but not in the PORT-C cohort (p=0.32). High risk was related to down-regulation of the two genes. The comparison of the high-risk patients between the two types of treatment showed better LRC after treatment with PORT-C (p=0.011). While 94% of patients were recurrence-free after two years in the high-risk group of the PORT-C cohort, this was true for only 63% in the corresponding group of the PORT cohort. A multivariable Cox model including the 2-gene signature, treatment type and their interaction showed a significant interaction term (p=0.039), i.e. the 2-gene signature was indicative for the type of treatment.

Conclusion

We have identified a novel 2-gene signature for LRC that may be used to identify high-risk HNSCC patients amongst those who are clinically at intermediate risk and thus often treated with PORT, who can benefit from additional concurrent chemotherapy. Independent prospective validation of this retrospective result is required before potential application in a clinical trial.