Evaluation of Platinum-based Therapy Response in Non-Small Cell Lung Cancer

Abstract

Aim: To evaluate the clinical value of PET imaging for an early prediction of tumor response to platinum-based therapy in patients with non-small cell lung cancer (NSCLC). In order to avoid unnecessary toxicity of ineffective chemotherapy treatment, an early identification of NSCLC patients who benefit from this therapy is mandatory. Materials and methods: Seventeen patients are enrolled prospectively: 18F-FDG-PET examinations are carried out before treatment and after the first course. The lesions with the highest uptake in each patient are evaluated according to EORTC, PERCIST and RECIST classifications to discriminate between patients who respond (complete and partial response) from those who do not respond (stable and progressive disease) to treatment. Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) are also used to evaluate therapeutic response. MTV indicates the volume of metabolically active tumors; TLG is the product between SUV mean and MTV. In literature, there are no cut-off points for therapy evaluation based on TLG or MTV variations (Δ) in sequential scans. In order to estimate cut-off values for these parameters, receiver operating characteristic (ROC) curves are used. RECIST classification is used as the outcome for the ROC analysis. Kaplan-Meier test is used to calculate Overall Survival (OS) time. OS is compared between responders and non-responders using a log-rank test. The level of statistical significance is defined as a p-value (p) of less than 0.05. Results: The ROC analysis indicates a cut-off point of -36% for ΔTLG, and -8% for ΔMTV. The Kaplan-Meier analysis shows that RECIST, ∆TLG, and ∆MTV prove to be a significant prognostic factor for predicting OS. For RECIST responder patients median OS is 595 days whereas for non-responder patients median OS is 238 days. ΔTLG shows a median OS of 492 days for responders and 238 days for non-responders. ΔMTV shows a median of 423 days for responders versus 188 days for non-responders. Conversely, EORTC and PERCIST classifications are inadequate to discriminate between responder and non-responder patients (p>0.13). For this reason, we use ROC analysis to propose an alternative PERCIST threshold of 17% for an early therapy monitoring. Conclusion: PET examinations provide an early identification of patients who benefit from platinum-based treatment. Results confirm that TLG proves a strong early prognostic factor in patients with NSCLC and could play a significant role in the field of personalized medicine, avoiding the unnecessary administration of non-curative and toxic drugs to preserve the patient’s quality of life.