Immunotherapy Monitoring with Immune Checkpoint Inhibitors Based on [18F]FDG PET/CT in Metastatic Melanomas and Lung Cancer

Abstract

Immunotherapy with checkpoint inhibitors has prompted a major change not only in cancer treatment but also in medical imaging. In parallel with the implementation of new drugs modulating the immune system, new response criteria have been developed, aiming to overcome clinical drawbacks related to the new, unusual, patterns of response characterizing both solid tumors and lymphoma during the course of immunotherapy. The acknowledgement of pseudo-progression, hyper-progression, immune-dissociated response and so forth, has become mandatory for all imagers dealing with this clinical scenario. A long list of acronyms, i.e., irRC, iRECIST, irRECIST, imRECIST, PECRIT, PERCIMT, imPERCIST, iPERCIST, depicts the enormous effort made by radiology and nuclear medicine physicians in the last decade to optimize imaging parameters for better prediction of clinical benefit in immunotherapy regimens. Quite frequently, a combination of clinical-laboratory data with imaging findings has been tested, proving the ability to stratify patients into various risk groups. The next steps necessarily require a large scale validation of the most robust criteria, as well as the clinical implementation of immune-targeting tracers for immuno-PET or the exploitation of radiomics and artificial intelligence as complementary tools during the course of immunotherapy administration. For the present review article, a summary of PET/CT role for immunotherapy monitoring will be provided. By scrolling into various cancer types and applied response criteria, the reader will obtain necessary information for better understanding the potentials and limitations of the modality in the clinical setting.

Keywords: [18F]FDG PET/CT; checkpoint inhibitors; immuno-PET; immunotherapy; metabolic response; tumor response.

Figure 1

Spectrum of irAEs associated with immunomodulatory antibodies (available via license: Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported, as published by Liu J, et al. Clin. Transl. Immunol. 2014, 3, e22) [35].

Figure 2

Example of a 78-year old female with advanced NSCLC treated with nivolumab and imaged with [¹⁸F]FDG PET/CT at baseline (A,C) and after 4 cycles of therapy (B,D). The patient resulted in overall stable on morphological imaging performed prior to PET/CT, which on the contrary documented a progressive metabolic disease. In fact, the tumor had an increase in metabolism (SUVmax and MTV), and showed the appearance of new lesions in the liver ((B); white hollowed arrows), only partially detectable on baseline imaging.

Figure 3

Herein, the imaging findings of a 66-year old male with metastatic NSCLC investigated before (A–C) and after 3 cycles of pembrolizumab (D–F). An overall response to treatment is easily visible on MIP (maximal intensity projection) images (C,F), including a complete metabolic remission of all bony lesions ((C); white hollowed arrow). On the contrary, morphological imaging proved the appearance of a new bone lesion in the first lumbar vertebra ((A,D); white arrows), which in fact corresponded to a healed metastasis on PET/CT (B,E). Note also the appearance of diffuse thyroid uptake ((F); red arrow), consistent with thyroiditis, one of the irAEs that typically predicts treatment response and good patient’s outcome.

Figure 4

Comparison of [¹⁸F]FDG PET/CT with anti-PD-L1 (18F-BMS-986192) and anti-PD-1 (89Zr-labeled Nivolumab) immuno-PET images in the same patient with NSCLC. Along the high glucose metabolism of the tumor in both lungs and mediastinal lymph nodes, a heterogeneous tracer uptake for 18F-BMS-986192 PET/CT and 89Zr-labeled Nivolumab PET/CT within and between tumors is demonstrated. Modified from Niemeijer AN et al. Whole body PD-1 and PD-L1 positron emission tomography in patients with non-small-cell lung cancer. Nat Commun 2018;9:4664. [106]; Licensed under a Creative Commons license: http://creativecommons.org/licenses/by/4.0/) Last access date: 2 November 2021.