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Selected Publication:
John, N.
Clinical relevance of immunological biomarkers in NSCLC
Doktoratsstudium der Medizinischen Wissenschaft; Humanmedizin; [ Dissertation ] Medizinische Universität Graz; 2025. pp. 103
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- Authors Med Uni Graz:
- Advisor:
- Douschan Philipp
- Fuchsjäger Michael
- Stradner Martin Helmut
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- Abstract:
- Recommendation of immune checkpoint inhibitors (ICIs) for the treatment of non-small cell lung cancer (NSCLC) depends on PD-L1 expression on tumor cells. Although PD-L1 expression levels correlate with response to ICI treatment, PD-L1 alone often fails to predict treatment response. In our retrospective cohort of early-stage NSCLC patients, we compared PD-L1 expression in patients with available initial biopsy samples, samples from primary curative surgical and rebiopsy samples in case of subsequent recurrence. In all cases Ventana PD-L1 (SP263) assay was used. We scored PD-L1 expression into clinically relevant groups defined as 0%, 1-49% and ≥50%. Our main interest was the change of PD-L1 score-group between the different matched tumor samples in NSCLC patients. In total 395 patients with stage I-III NSCLC were identified forming our main cohort. 136 (34%) out of 395 patients relapsed. For 87 patients of these patients at least two specimens for PD-L1 expression comparison, namely initial biopsy and rebiopsy were available. In 72 cases PD-L1 expression could be compared between all-time points. Between initial preoperative biopsy and matched surgical specimens, a clinically relevant conversion of PD-L1 expression group was found in 25 patients (34.7%). We could not identify a statistically significant influence of neoadjuvant treatment on PD-L1 alteration (p=0.39). When we compared PD-L1 expression from preoperative samples with rebiopsy samples a clinically relevant change in PD-L1 expression was found in 32 (36.8%) out of 87 patients. Similar to the neoadjuvant therapy, adjuvant treatment was also not associated with a change in the PD-L1 expression group (p=0.16). Overall, 39 patients (54.2%) showed at least one change into a different PD-L1 score group. In fourteen patients (19.4%) PD-L1 expression score group changed twice and in five patients (6.9%) PD-L1 score group was different in every analysed sample. We conclude, that there is clinically relevant PD-L1 expression change in NSCLC patients during the course of disease. We hypothesize that there is an unmet need for guidelines to define PD-L1 testing strategy including indication for re-assessment, biopsy number and appraisal of surgical specimens.