Response monitoring during neoadjuvant targeted treatment in early stage non‐small cell lung cancer

In the current era of new treatments, early and rapid response monitoring is increasingly relevant.
This thesis focuses on whether erlotinib (EGFR-TKI) could make an extra contribution to the curative treatment of early stage non-small cell lung cancer (NSCLC). Currently there is no agreement on the optimal modality for assessment of response. The aim of this thesis was to investigate various aspects of these challenges and the potential of early response assessment. This thesis provides a review of literature reporting on FDG-PET/CT response evaluation in patients with NSCLC, treated with EGFR-TKI. Although different criteria are used, FDG-PET/CT response is associated with response and with survival. Early decision making as to the effect of experimental treatment is essential. This thesis shows that FDG-PET/CT is superior to CT for identification of histopathologic response to neoadjuvant erlotinib and that metabolic activity within 1 week after initiation of erlotinib is informative for a histopathologic response after 3 weeks. Skin rash in response to EGFR-TKI therapy may be an expression of the therapeutic effect on tumors. However, this thesis showes that skin rash did not adequately predict response in a neoadjuvant setting. Accurate FDG measurements could suffer from competitive inhibition of FDG uptake by blood glucose. Although, correction of SUVmax according to patient’s blood glucose level was predictive for survival it did not show a substantially improved predictive ability compared to SUVmax alone. Finally, this thesis shows the potential of metabolic response monitoring as a surrogate marker for survival in patients treated with neoadjuvant erlotinib.