AUTHOR=Simoni Nicola , Rossi Gabriella , Benetti Giulio , Zuffante Michele , Micera Renato , Pavarana Michele , Guariglia Stefania , Zivelonghi Emanuele , Mengardo Valentina , Weindelmayer Jacopo , Giacopuzzi Simone , de Manzoni Giovanni , Cavedon Carlo , Mazzarotto Renzo 

TITLE=18F-FDG PET/CT Metrics Are Correlated to the Pathological Response in Esophageal Cancer Patients Treated With Induction Chemotherapy Followed by Neoadjuvant Chemo-Radiotherapy

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.599907

DOI=10.3389/fonc.2020.599907

ISSN=2234-943X

ABSTRACT=Background and Objective: The aim of this study was to assess the ability of Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography (18F-FDG PET/CT) to provide functional information useful in predicting pathological response to an intensive neoadjuvant chemo-radiotherapy (nCRT) protocol for both esophageal squamous cell carcinoma (SCC) and adenocarcinoma (ADC) patients.
Material and Methods: Esophageal carcinoma (EC) patients, treated in our Center between 2014 and 2018, were retrospectively reviewed. The nCRT protocol schedule consisted of an induction phase of weekly administered docetaxel, cisplatin, and 5-fluorouracil (TCF) for 3 weeks, followed by a concomitant phase of weekly TCF for 5 weeks with concurrent radiotherapy (50-50.4 Gy in 25-28 fractions). Three 18F-FDG PET/CT scans were performed: before (PET1) and after (PET2) induction chemotherapy (IC), and prior to surgery (PET3). Correlation between PET parameters [maximum and mean standardized uptake value (SUVmax and SUVmean), metabolic tumor volume (MTV), and total lesion glycolysis (TLG)], radiomic features and tumor regression grade (TGR) was investigated. 
Results: Fifty-four patients (35 ADC, 19 SCC; 48 cT3/4; 52 cN+) were eligible for the analysis. Pathological response to nCRT was classified as major (TRG1-2, 41/54, 75.9%) or non-response (TRG3-4, 13/54, 24.1%). A major response was statistically correlated with SCC subtype (p = 0.02) and smaller tumor length (p = 0.03). MTV and TLG measured prior to IC (PET1) were correlated to TRG1-2 response (p = 0.02 and p = 0.02, respectively). After IC (PET2), SUVmean and TLG correlated with major response (p = 0.03 and p = 0.04, respectively). No significance was detected when relative changes of metabolic parameters between PET1 and PET2 were evaluated. At textural quantitative analysis, three independent radiomic features extracted from PET1 images [JointEnergy and InverseDifferenceNormalized of GLCM and LowGrayLevelZoneEmphasis of GLSZM] were statistically correlated with major response (p < 0.0002).
Conclusions: 18F-FDG PET/CT traditional metrics and textural features seem to predict pathologic response (TRG) in EC patients treated with induction chemotherapy followed by neoadjuvant chemo-radiotherapy. Further investigations are necessary in order to obtain a reliable predictive model to be used in the clinical practice.