Reliability of Quantitative 18F-FDG PET/CT Imaging Biomarkers for Classifying Early Response to Chemoradiotherapy in Patients With Locally Advanced Non-Small Cell Lung Cancer

Abstract

Purpose of the report: We evaluated the reliability of 18F-FDG PET imaging biomarkers to classify early response status across observers, scanners, and reconstruction algorithms in support of biologically adaptive radiation therapy for locally advanced non-small cell lung cancer.

Patients and methods: Thirty-one patients with unresectable locally advanced non-small cell lung cancer were prospectively enrolled on a phase 2 trial (NCT02773238) and underwent 18F-FDG PET on GE Discovery STE (DSTE) or GE Discovery MI (DMI) PET/CT systems at baseline and during the third week external beam radiation therapy regimens. All PET scans were reconstructed using OSEM; GE-DMI scans were also reconstructed with BSREM-TOF (block sequential regularized expectation maximization reconstruction algorithm incorporating time of flight). Primary tumors were contoured by 3 observers using semiautomatic gradient-based segmentation. SUVmax, SUVmean, SUVpeak, MTV (metabolic tumor volume), and total lesion glycolysis were correlated with midtherapy multidisciplinary clinical response assessment. Dice similarity of contours and response classification areas under the curve were evaluated across observers, scanners, and reconstruction algorithms. LASSO logistic regression models were trained on DSTE PET patient data and independently tested on DMI PET patient data.

Results: Interobserver variability of PET contours was low for both OSEM and BSREM-TOF reconstructions; intraobserver variability between reconstructions was slightly higher. ΔSUVpeak was the most robust response predictor across observers and image reconstructions. LASSO models consistently selected ΔSUVpeak and ΔMTV as response predictors. Response classification models achieved high cross-validated performance on the DSTE cohort and more variable testing performance on the DMI cohort.

Conclusions: The variability FDG PET lesion contours and imaging biomarkers was relatively low across observers, scanners, and reconstructions. Objective midtreatment PET response assessment may lead to improved precision of biologically adaptive radiation therapy.

Conflict of interest statement

Conflicts of interest and sources of funding: This investigation was funded by NIH/NCI R01CA204301. J.Z. and R.R. serve as consultants to AstraZeneca. P.E.K. declares support from GE Healthcare and is cofounder of PET/X, LLC. R.S.M. declares support from Philips Healthcare. R.S.M. and H.J.V. serve as consultants for MIM Software. The other authors have nothing to disclose.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

Figures

FIGURE 1:

Flow chart indicating the study workflow from data acquisition through analysis.

FIGURE 2:. Example images from DMI OSEM and BSREM-TOF reconstructions.

Single transaxial, sagittal, and coronal slices from PETpre OSEM (A) and BSREM-TOF (B) reconstructions acquired on the DMI for patient FLARE 025. These images provide a visual comparison between the two reconstruction algorithms. Intensity-scale bars on the right indicate absolute activity in SUVs with an upper limit saturation threshold of 10.

FIGURE 3:. Examples of a response and a non-response to therapy as defined by the multidisciplinary clinical mid-treatment response assessment.

Single transaxial, sagittal, and coronal slices of OSEM reconstructions acquired on the DSTE. A, B: A clinically classified responder (FLARE 008) demonstrates a ΔSUVpeak decrease of 60% and a ΔMTV decrease of 56% between PETpre (A) and PETmid (B). C, D: A clinically classified non-responder (FLARE 010) demonstrates a ΔSUVpeak decrease of 23% and a ΔMTV decrease of 20% between PETpre (C) and PETmid (D). Intensity-scale bars on the right indicate absolute activity in SUVs with an upper limit saturation threshold of 10.

FIGURE 4:. Examples of lower and higher inter-observer and intra-observer variability in lesion contouring.

Single transaxial, sagittal, and coronal slices of OSEM and BSREM-TOF PETpre reconstructions acquired on the DMI. A, B: A patient (FLARE 034) with inter-observer dice indices of 0.97 on the OSEM (A) and 0.98 on BSREM-TOF (B) reconstructions. Inter-reconstruction/intra-observer dice indices are 0.95 for observer 1 (yellow), 0.96 for observer 2 (red), and 0.95 for observer 3 (blue). C, D: A patient (FLARE 025) with inter-observer dice indices of 0.74 on the OSEM (c) and 0.88 on BSREM-TOF (D) reconstructions. Inter-reconstruction/intra-observer dice indices are 0.85 for observer 1 (yellow), 0.85 for observer 2 (red), and 0.88 for observer 3 (blue). Intensity-scale bars on the right indicate absolute activity in SUVs with an upper limit saturation threshold of 10.