Prediction of Response to Immune Checkpoint Inhibitor Therapy Using Early-Time-Point 18F-FDG PET/CT Imaging in Patients with Advanced Melanoma

Steve Y Cho; Evan J Lipson; Hyung-Jun Im; Steven P Rowe; Esther Mena Gonzalez; Amanda Blackford; Alin Chirindel; Drew M Pardoll; Suzanne L Topalian; Richard L Wahl

doi:10.2967/jnumed.116.188839

Prediction of Response to Immune Checkpoint Inhibitor Therapy Using Early-Time-Point ¹⁸F-FDG PET/CT Imaging in Patients with Advanced Melanoma

J Nucl Med. 2017 Sep;58(9):1421-1428. doi: 10.2967/jnumed.116.188839. Epub 2017 Mar 30.

Authors

Steve Y Cho^{1

2}, Evan J Lipson³, Hyung-Jun Im^{2

4}, Steven P Rowe³, Esther Mena Gonzalez³, Amanda Blackford³, Alin Chirindel³, Drew M Pardoll³, Suzanne L Topalian³, Richard L Wahl^{3

5}

Affiliations

¹ Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland scho@uwhealth.org.
² University of Wisconsin School of Medicine and Public Health and Carbone Comprehensive Cancer Center, Madison, Wisconsin.
³ Johns Hopkins University School of Medicine and Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
⁴ Department of Transdisciplinary Studies, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea; and.
⁵ Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, Missouri.

Abstract

The purpose of this study was to evaluate ¹⁸F-FDG PET/CT scanning as an early predictor of response to immune checkpoint inhibitors (ICIs) in patients with advanced melanoma. Methods: Twenty patients with advanced melanoma receiving ICI prospectively underwent ¹⁸F-FDG PET/CT at 3 scan intervals: before treatment initiation (SCAN-1), at days 21-28 (SCAN-2), and at 4 mo (SCAN-3). This study was approved by the institutional review board, and informed consent was received from all patients who were enrolled between April 2012 and December 2013. Tumor response at each posttreatment time point was assessed according to RECIST 1.1, immune-related response criteria, PERCIST (PERCIST 1.0), and European Organization for Research and Treatment of Cancer (EORTC) criteria. Performance characteristics of each metric to predict best overall response (BOR) at ≥ 4 mo were assessed. Results: Twenty evaluable patients were treated with ipilimumab (n = 16), BMS-936559 (n = 3), or nivolumab (n = 1). BOR at ≥ 4 mo included complete response (n = 2), partial response (n = 2), stable disease (n = 1), and progressive disease (n = 15). Response evaluations at SCAN-2 using RECIST 1.1, immune-related response criteria, PERCIST, and EORTC criteria demonstrated accuracies of 75%, 70%, 70%, and 65%, respectively, to predict BOR at ≥ 4 mo. Interestingly, the optimal PERCIST and EORTC threshold values at SCAN-2 to predict BOR were >15.5% and >14.7%, respectively. By combining anatomic and functional imaging data collected at SCAN-2, we developed criteria to predict eventual response to ICI with 100% sensitivity, 93% specificity, and 95% accuracy. Conclusion: Combining functional and anatomic imaging parameters from ¹⁸F-FDG PET/CT scans performed early in ICI appears predictive for eventual response in patients with advanced melanoma. These findings require validation in larger cohorts.

Trial registration: ClinicalTrials.gov NCT01666353.

Keywords: FDG; PET/CT; immune checkpoint inhibitor; melanoma; response assessment.

Publication types

Clinical Trial
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Adult
Aged
Female
Fluorodeoxyglucose F18*
Humans
Male
Melanoma / diagnostic imaging*
Melanoma / immunology
Melanoma / pathology
Melanoma / therapy*
Middle Aged
Positron Emission Tomography Computed Tomography*
Signal Transduction / drug effects*
Signal Transduction / immunology*
Treatment Outcome

Substances

Fluorodeoxyglucose F18

Associated data

ClinicalTrials.gov/NCT01666353