Journal Article

DKFZ-2024-01774

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Early circulating tumor DNA changes predict outcomes in head and neck cancer patients under re-radiotherapy.

Janke, F. (First author)DKFZ* ; Stritzke, F. (First author)DKFZ* ; Dvornikovich, K. ; Franke, H. ; Angeles, A. K.DKFZ* ; Riediger, A. L.DKFZ* ; Ogrodnik, S.DKFZ* ; Gerhardt, S.DKFZ* ; Regnery, S. ; Schröter, P. ; Bauer, L. ; Weusthof, K. ; Görtz, M.DKFZ* ; Harrabi, S.DKFZ* ; Herfarth, K.DKFZ* ; Neelsen, C.DKFZ* ; Paech, D.DKFZ* ; Schlemmer, H.-P.DKFZ* ; Abdollahi, A.DKFZ* ; Adeberg, S.DKFZ* ; Debus, J.DKFZ* ; Sültmann, H. (Last author)DKFZ* ; Held, T. (Last author)DKFZ*

2025
Wiley-Liss Bognor Regis

This record in other databases:  

Please use a persistent id in citations: doi:10.1002/ijc.35152

Abstract: Local recurrence after radiotherapy is common in locally advanced head and neck cancer (HNC) patients. Re-irradiation can improve local disease control, but disease progression remains frequent. Hence, predictive biomarkers are needed to adapt treatment intensity to the patient's individual risk. We quantified circulating tumor DNA (ctDNA) in sequential plasma samples and correlated ctDNA levels with disease outcome. Ninety four longitudinal plasma samples from 16 locally advanced HNC patients and 57 healthy donors were collected at re-radiotherapy baseline, after 5 and 10 radiation fractions, at irradiation end, and at routine follow-up visits. Plasma DNA was subjected to low coverage whole genome sequencing for copy number variation (CNV) profiling to quantify ctDNA burden. CNV-based ctDNA burden was detected in 8/16 patients and 25/94 plasma samples. Ten additional ctDNA-positive samples were identified by tracking patient-specific CNVs found in earlier sequential plasma samples. ctDNA-positivity after 5 and 10 radiation fractions (both: log-rank, p = .050) as well as at the end of irradiation correlated with short progression-free survival (log-rank, p = .006). Moreover, a pronounced decrease of ctDNA toward re-radiotherapy termination was associated with worse treatment outcome (log-rank, p = .005). Dynamic ctDNA tracking in serial plasma beyond re-radiotherapy reflected treatment response and imminent disease progression. In five patients, molecular progression was detected prior to tumor progression based on clinical imaging. Our findings emphasize that quantifying ctDNA during re-radiotherapy may contribute to disease monitoring and personalization of adjuvant treatment, follow-up intervals, and dose prescription.

Keyword(s): circulating tumor DNA ; copy number variations ; head and neck cancer ; predictive biomarker ; re‐radiotherapy

Note: #EA:B063#EA:E050#LA:B063#LA:E050# / 2025 Feb 15;156(4):853-864

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Contributing Institute(s):

1. B063 Krebsgenomforschung (B063)
2. NWG KKE Multiparametrische Methoden zur Früherkennung des Prostatakarzinoms (E250)
3. E050 KKE Strahlentherapie (E050)
4. E210 KKE Translationale Radioonkologie (E210)
5. DKTK HD zentral (HD01)
6. E010 Radiologie (E010)

Research Program(s):

1. 315 - Bildgebung und Radioonkologie (POF4-315) (POF4-315)

Appears in the scientific report 2024

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DEAL Wiley ; Essential Science Indicators ; IF >= 5 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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