TY  - JOUR
AU  - Janke, Florian
AU  - Stritzke, Florian
AU  - Dvornikovich, Katharina
AU  - Franke, Henrik
AU  - Angeles, Arlou Kristina
AU  - Riediger, Anja Lisa
AU  - Ogrodnik, Simon
AU  - Gerhardt, Sabrina
AU  - Regnery, Sebastian
AU  - Schröter, Philipp
AU  - Bauer, Lukas
AU  - Weusthof, Katharina
AU  - Görtz, Magdalena
AU  - Harrabi, Semi
AU  - Herfarth, Klaus
AU  - Neelsen, Christian
AU  - Paech, Daniel
AU  - Schlemmer, Heinz-Peter
AU  - Abdollahi, Amir
AU  - Adeberg, Sebastian
AU  - Debus, Jürgen
AU  - Sültmann, Holger
AU  - Held, Thomas
TI  - Early circulating tumor DNA changes predict outcomes in head and neck cancer patients under re-radiotherapy.
JO  - International journal of cancer
VL  - 156
IS  - 4
SN  - 0020-7136
CY  - Bognor Regis
PB  - Wiley-Liss
M1  - DKFZ-2024-01774
SP  - 853-864
PY  - 2025
N1  - #EA:B063#EA:E050#LA:B063#LA:E050# / 2025 Feb 15;156(4):853-864
AB  - 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.
KW  - circulating tumor DNA (Other)
KW  - copy number variations (Other)
KW  - head and neck cancer (Other)
KW  - predictive biomarker (Other)
KW  - re‐radiotherapy (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:39212345
DO  - DOI:10.1002/ijc.35152
UR  - https://inrepo02.dkfz.de/record/292528
ER  -