Präzisionstherapie von Kopf-Hals-Tumorpatienten durch Tumorgewebeschnitte: Korrelation präklinischer Daten mit klinischen Ergebnissen

Introduction: Precision oncology describes how individual patient"s tumor characteristics dictate effective individualized therapy concepts. Functional precision testing describes a strategy in which patient derived tumor cell treatment at the bench provide immediately translatable, personalized information to guide patient"s therapy at bedside. Tumor slice radiosensitivity assays, in particular, hold potential for refining radiotherapy approaches, although their clinical reliability remains to be established.

Methods: Thin slices of patient-derived tumor cells were cultivated, irradiated, and fixed following established protocols (PMID: 35093407). DNA double-strand breaks (DSBs) were quantified by assessing 53BP1 foci, which reflect individual DNA damage repair capacity. The assay"s results were correlated with clinical radiation response data.

Results: Residual DNA damage after irradiation was measured ex vivo in 65 patients. Residual foci counts across various HNC subtypes aligned with clinically expected radioresponsiveness, with EBV-positive nasopharyngeal carcinoma and HPV-positive oropharyngeal carcinoma (OPC) showing higher residual DNA damage compared to HPV-negative OPC and laryngeal cancer. Patients with higher residual foci counts demonstrated longer progression-free survival compared to those with lower DNA damage measured ex vivo (median follow-up: 42 months).

Conclusions: This assay has a promising potential for individualizing radiotherapy, for example in the context of stratified de-escalation radiotherapy for HPV-positive OPC. Further validation is warranted through translational co-clinical trials with cross-validation of preclinical results and clinical outcome.

Referentenhonorare: BMS, MSD, Merck, Sanofi, Regeneron