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

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

doi:10.3389/fonc.2020.599907

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

Front Oncol. 2020 Nov 27:10:599907. doi: 10.3389/fonc.2020.599907. eCollection 2020.

Affiliations

¹ Department of Radiation Oncology, University of Verona Hospital Trust, Verona, Italy.
² Department of Medical Physics, University of Verona Hospital Trust, Verona, Italy.
³ Department of Nuclear Medicine, University of Verona Hospital Trust, Verona, Italy.
⁴ Department of Oncology, University of Verona Hospital Trust, Verona, Italy.
⁵ Department of General and Upper G.I. Surgery, University of Verona Hospital Trust, Verona, Italy.

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 (SUV_max and SUV_mean), 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), SUV_mean 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.

Keywords: chemo-radiation; esophageal cancer; induction chemotherapy; neoadjuvant therapy; pathological response; positron emission tomography metrics; radiomic features.