¹⁸F-FDG PET as a Surrogate Biomarker in Non–Small Cell Lung Cancer Treated with Erlotinib: Newly Identified Lesions Are More Informative Than Standardized Uptake Value

Abstract

This study assesses the predictive value of 18 F-FDG PET for overall survival in lung cancer patients treated with a targeted drug. Methods: 18 F-FDG PET was performed in 125 second-or thirdline non-small cell lung cancer (NSCLC) patients with a baseline Eastern Cooperative Oncology Group performance status less than 3 before treatment with erlotinib (150 mg daily) and 2 wk into treatment. The predictive value of 18 F-FDG PET, clinical parameters, and epithelial growth factor receptor (EGFR) mutation status for survival duration was evaluated by fitting accelerated failure time models. Results: New lesions on PET at 2 wk, EGFR mutation status, performance status, and baseline tumor burden were independent and significant predictors of overall survival. Reduction of maximum standardized uptake value by at least 35% was predictive of survival only when EGFR mutation status was not accounted for. Conclusion: 18 F-FDG PET in second-or third-line NSCLC patients at 2 wk after starting treatment with erlotinib carries information about overall survival. Parametric survival modeling enables a quantitative assessment of the predictive value of 18 F-FDG PET in the context of clinical and laboratory information. New-lesion status by 18 F-FDG PET at 2 wk is a potential surrogate biomarker for survival in NSCLC.

TLG-S criteria are superior to both EORTC and PERCIST for predicting outcomes in patients with metastatic lung adenocarcinoma treated with erlotinib

“…Because several papers addressing these issues have been published [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19], we also performed a retrospective review of our cohort data. The first goal of the retrospective analysis was to investigate whether early FDG-PET assessment of treatment response using TLG-S would be superior to either local assessment with EORTC criteria or hottest-single-lesion assessment with PERCIST criteria for predicting 2-year survival outcomes.…”

“…Although patients carrying mutations of the EGFR gene generally respond better to tyrosine kinase inhibitors (TKIs) [1], erlotinib may improve survival even in subjects with EGFR wild-type tumors [2]. Several studies have shown that FDG-PET is a useful imaging modality for predicting response to erlotinib in patients with non-small cell lung cancer (NSCLC) [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. However, most of these studies used only the primary tumor as the target lesion for sequential imaging [3][4][5][6][7][8][9][10][11][12], and treatment response was largely assessed using the European Organization for Research and Treatment of Cancer (EORTC) criteria [3][4][5][6][7][8][9]20].…”

Update on F-18-fluoro-deoxy-glucose-PET/computed tomography in nonsmall cell lung cancer

“…Another study by O'Brien et al [70] showed in 38 patients (stage IIIB-IV) that a decrease in SUV at least 25% after 6 weeks showing significantly longer survival in patients treated with EGFR-TKI. A study by Bengtsson et al [71] showed that after 2 weeks EGFR-TKI treatment, new lesions on PET were independent and significant predictors of OS. Although FDG is a widely used radiotracer, other tracers for early response prediction for EGFR-TKIs are promising, such as F-18-fluoro-thymidine (FLT), which reflects cellular proliferation.…”

“…Several studies investigated FDG-PET/CT to address metabolic response [69][70][71] in NSCLC patients treated with epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKI). Takahashi et al [69] showed that in 19 patients (stage IIIA, IIIB, IV) after 2 days of treatment, at least 20% decrease in maximum SUV (optimal cut-off) was associated with a significantly longer PFS.…”

Qualification of National Cancer Institute–Designated Cancer Centers for Quantitative PET/CT Imaging in Clinical Trials

“…Incr easingly, 18 F-FDG and other radiopharmaceuticals are being used as PET/CT quantitative imaging biomarkers in oncology to assess treatment efficacy (1)(2)(3)(4)(5)(6)(7)(8). Although many factors, both physiologic and instrumental (9)(10)(11)(12), influence quantitative accuracy, the ability to determine treatment efficacy on the basis of PET is predicated on the ability of PET scanners to provide stable measurements of radiotracer concentrations-thus allowing the treatment response to be tracked over months or years.…”