non-small cell lung cancer, neoadjuvant, immunotherapy, complete pathological response
Conditions
Interventions
Blood will be drawn for ctDNA analysis at baseline, after two cycles neoadjuvant chemoimmunotherapy, at the time of the pre-operative [18F]FDG-PET scan and appoximately one and six months post-surgery
Optionally, patients can undergo a 31P-MRI scan 
before and after chemoimmunotherapy.
Sponsors
Antoni van Leeuwenhoek (AVL)
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Pathologically proven NSCLC stage IIA – IIIB according to the 9th edition of the American Joint Commission on Cancer (AJCC) staging deemed resectable by the MDT.(baseline) histological tumor specimen with tumor cell percentage (TCP) =20% OR =20 ng dsDNA tumor genomic DNA isolated from FFPE (see subsection 5.2 of the protocol) Patient deemed operable by the multidisciplinary team meeting.Indication for neoadjuvant chemoimmunotherapy.
Exclusion criteria
Exclusion criteria: No baseline (within 6 weeks of inclusion) [18F]FDG-PET scan with EARL reconstruction. Only cytological baseline tumor material availableAny condition that, in the opinion of the investigator, would interfere with evaluation of metabolic response evaluation or ctDNA analysis (i.e. second active malignancy)
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Discriminatory accuracy of a diagnostic model combining [18F]FDG-PET, ctDNA and PD-L1 TPS to distinguish between pCR and non-pCR. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary study endpoints:Cross-validation of the diagnostic model.Discriminatory accuracy of [18F]FDG-PET and ctDNA to distinguish between pCR and non-pCR.Discriminatory accuracy of [18F]FDG-PET, ctDNA and PD-L1 TPS to distinguish between MPR and non-MPR.Correlation between metabolic response EORTC criteria and RECIST 1.1 criteria.Proportion of cancelled resections due to progressive metabolic disease (PMD) not detected by RECIST 1.1. Proportion of patients with PMD without pathologic progression (i.e. pseudoprogression/nodal immune flare).Concordance between objective response rate (ORR) and metabolic response rate.Correlation between metabolic response, ctDNA and depth of pathological response.EFS and OS in ITT population and biomarker-selected subgroups.Exploratory study endpoints:Integration of PET/CT radiomics/AI-assisted volume measurements in diagnostic modeling.The change in metabolic ratio of the phospholipids PC, PE, PGE, GPC, Pi, PCr, and ATP from the area under the curve (AUC) of the corresponding spectral peaks between the measurements at baseline after treatment. Correlation of metabolic MRI-features with pathological response and with metabolic response on [18F]FDG-PET. | — |
Countries
Netherlands
Contacts
Public ContactJ. F. De Vries
Antoni van Leeuwenhoek (AVL)
Outcome results
None listed