Prognostic value of 1H NMR spectroscopy in the treatment of non-small cell lung cancer

Abstract

Introduction: Lung cancer is the leading cause of cancer mortality worldwide. Despite progress in treatment of lung cancer we experience unacceptable toxicities without a significant increase in overall survival (OS) and progression free survival (PFS). Clinical trials do not answer the question of who will benefit the most of therapy and who may be harmed. The goal of this study is to find an answer on this question by metabolic profiling of plasma of untreated lung cancer patients. Objective: Differentiating responder and non-responder NSCLC patients based on differences in their metabolic profiles. Methods:This project investigates subjects with the diagnosis of NSCLC independent of stage and who are candidate to receive chemotherapy. All patients have a newly diagnosed NSCLC. Participants are asked to give one fasted sample of blood. Samples are collected before the start of the treatment and analysed by 1H-NMR spectroscopy using a 400 MHz spectrometer.Slightly T2-weighted spectra were acquired using a CPMG pulse sequence and are referred to TSP resonance at 0.015 ppm. The integration values of 110 spectral regions are analyzed by a Mann-Whitney test to identify those which differ significantly between responders and non-responders, followed by an orthogonal partial least squares discriminant analysis to investigate whether a discriminating classifier can be constructed. In this way we aim to distinguish a metabolic profile that differs between responders and non-responders.The patient is followed-up by CT scan after every 2 cycles of chemotherapy and every 3 months after completion of the first line treatment or earlier if clinical arguments for relapse appear. Disease progression and response to therapy are defined following the RECIST criteria of 2009. Responders are defined as patients with a PFS of at least 1 year during a minimal follow-up of 1 year. Non responders are patients with progression within 1 year of follow-up. Results: No significant difference between the metabolic profile of responders (n =18) and non-responders (n =29) of chemotherapy. This might be the result of a non-homogeneous small group and interference of medications for co-morbidities. Conclusion: In this small patient cohort, responding and non-responding NSCLC patients could not be differentiated based on the metabolic profiles obtained by 1H-NMR spectroscopy. This probably due to the heterogeneous composition of the subgroups.