Predictive value of interim 18F-FDG-PET in patients with non-small cell lung cancer treated with definitive radiation therapy

PLOS ONE RESEARCH ARTICLE Predictive value of interim 18F-FDG-PET in patients with non-small cell lung cancer treated with definitive radiation therapy Nalee Kim1,2, Jin Sung Kim ID1, Chang Geol Lee ID1* 1 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea, 2 Department of Radiation Oncology, Samsung Medical Center, Seoul, Republic of Korea * a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 Abstract Purpose We evaluated that early metabolic response determined by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) during radiotherapy (RT), predicts outcomes in non-small cell lung cancer. Material and methods OPEN ACCESS Citation: Kim N, Kim JS, Geol Lee C (2020) Predictive value of interim 18F-FDG-PET in patients with non-small cell lung cancer treated with definitive radiation therapy. PLoS ONE 15(7): e0236350. https://doi.org/10.1371/journal. pone.0236350 Editor: Domenico Albano, Spedali Civili of Brescia, University of Brescia, ITALY Received: April 1, 2020 Accepted: July 4, 2020 Published: July 20, 2020 Copyright: © 2020 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: The author(s) received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Twenty-eight patients evaluated using pretreatment 18F-FDG-PET/CT (PETpre) and interim 18 F-FDG-PET/CT (PETinterim) after 11 fractions of RT were retrospectively reviewed. Maximum standardized uptake value (SUVmax) was calculated for primary lesion. Predictive value of gross tumor volume (ΔGTV) and SUVmax (ΔSUVmax) changes was evaluated for locoregional control (LRC), distant failure (DF), and overall survival (OS). Metabolic responders were patients with ΔSUVmax >40%. Results Metabolic responders showed better trends in 1-year LRC (90.9%) than non-responders (47.1%) (p = 0.086). Patients with large GTVpre (�120 cc) demonstrated poor LRC (hazard ratio 4.14, p = 0.022), while metabolic non-responders with small GTVpre (<120 cc) and metabolic responders with large GTVpre both had 1-year LRC rates of 75.0%. Reduction of 25% in GTV was not associated with LRC; however, metabolic responders without a GTV response showed better 1-year LRC (83.3%) than metabolic non-responders with a reduction in GTV (42.9%). Metabolic responders showed lower 1-year DF (16.7%) than nonresponders (50.0%) (p = 0.025). An ΔSUVmax threshold of 40% yielded accuracy of 64% for predicting LRC, 75% for DF, and 54% for OS. However, ΔGTV > 25% demonstrated inferior diagnostic values than metabolic response. Conclusions Changes in tumor metabolism diagnosed using PETinterim during RT better predicted treatment responses, recurrences, and prognosis than other factors historically used. PLOS ONE | https://doi.org/10.1371/journal.pone.0236350 July 20, 2020 1 / 13 PLOS ONE Predictive value of interim 18F-FDG-PET in NSCLC Background Fluoro-2-deoxy-D-glucose-positron emission tomography (FDG-PET) imaging has become an important and popular tool for determining the disease stage in patients with non-smallcell lung cancer (NSCLC). The National Comprehensive Cancer Network recommends the use of 18F-FDG-PET/computed tomography (CT) for the appropriate staging of lung cancer [1]. There are several roles of FDG-PET/CT in NSCLC, such as diagnosis, prognosis, and radiotherapy (RT) planning. Recent investigations have shown that FDG-PET/CT has more than 90% accuracy in diagnosis of malignant nodules, with a low false-positive rate [2]. FDG-PET also plays a significant role in nodal staging (accuracy 90%, sensitivity 79–85%, and specificity 87–92%) [3, 4] and distant metastasis detection, with previously unsuspected diagnosis of extrathoracic lesions in up to 10% of patients, beyond CT alone [5]. FDG-PET offers a benefit over conventional CT after treatment where, for example, although tumor shrinkage may be observed, inflammation and fibrosis after neoadjuvant chemotherapy or RT make assessment difficult [1]. In addition, FDG-PET plays an important role in target volume delineation of the gross tumor volume (GTV), for both the primary tumor and lymph nodes [6]. Its superior contrast between tumor and non-tumor tissue means that FDG-PET can also decrease inter-physician contouring variability, compared to delineation with CT alone [7]. It also greatly assists physicians in distinguishing the tumor tissue from atelectasis [8]. Therefore, a consensus report has been endorsed for target volume delineation using PET imaging [9]. Currently, chemoradiotherapy (sequential or concurrent) is considered as a standard treatment for locally advanced NSCLC. Despite the emergence of immunotherapy, targeted therapy, and new RT techniques, the prognosis of those patients remains poor. Therefore, the ability to identify non-responders during treatment, in order to change ineffective treatment early on, is very desirable [10]. Several studies have demonstrated interim PET (PETinterim) metrics as a prognostic factor, but most of these included conventional three-dimensional conformal RT and various chemotherapy regimens, with varied timing of PETinterim. Therefore, in this study, we focused on metabolic and volumetric parameters, which are easily accessible during RT, in patients treated with modern RT and certain chemotherapy regimens. Materials and methods Study population Patients diagnosed with NSCLC who had undergone RT with PETinterim between March 2015 and January 2018 were enrolled. Patients were excluded if they underwent RT with preoperative aim (n = 7), if pre-RT FDG-PET/CT (PETpre) was not available or was performed at another institution (n = 6), if they did not complete RT (n = 2), and if follow-up details were missing (n = 4). Ultimately, we retrospectively reviewed medical records and tumor characteristics of 28 patients, as well as their clinical outcomes. This study was approved by the Health Institutional Review Board of Yonsei University Hospital (No. 4-2019-0608). The study was conducted in accordance with the provisions of the 1975 Declaration of Helsinki. The requirement for informed consent was waived owing to the retrospective nature of this study. All data between March 2015 and May 2019 were fully anonymized before authors accessed them. Treatment All patients, except three patients who were medically ineligible due to poor performance and comorbidity, received chemotherapy using a platinum- and taxane-based regimen. Twenty- PLOS ONE | https://doi.org/10.1371/journal.pone.0236350 July 20, 2020 2 / 13 PLOS ONE Predictive value of interim 18F-FDG-PET in NSCLC five pa (...truncated)