Assessing immune organs on 18F-FDG PET/CT imaging for therapy monitoring of immune checkpoint inhibitors: ….

[D.ap]

Assessing immune organs on 18F-FDG PET/CT imaging for therapy monitoring of immune checkpoint inhibitors: inter-observer variability, prognostic value and evolution during the treatment course of melanoma patients

Abstract

Background
Immune checkpoint inhibitors (ICIs) have significantly improved survival in advanced melanoma. There is a need for robust biomarkers to identify patients who do not respond. We analysed 14 baseline 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metrics and their evolution to assess their correlation with patient outcome, compared with 7 established biological markers and 7 clinical variables.

Methods
We conducted a retrospective monocentric observational study of 29 patients with advanced melanoma who underwent baseline 18F-FDG PET/CT, followed by an early monitoring PET/CT (iPET) scan after 1 month of treatment and follow-up studies at 3rd (M3PET) and 6th month (M6PET). 18F-FDG uptake in immune organs (spleen, bone marrow, ileocecal valve) and derived spleen-to-liver (SLR) and bone-to-liver (BLR) ratios were reviewed by two PET readers for reproducibility analysis purposes including 14 PET variables. The most reproducible indexes were used for evaluation as predictors of overall survival (OS) in comparison with PET response using imPERCIST5, whole-body metabolic active tumour volume (WB-MATV) and biological parameters (lactate dehydrogenases (LDH), reactive protein c (CRP), white blood count (WBC), absolute lymphocyte count (ALC), neutrophil to lymphocyte ratio (NLR) and derived neutrophils to lymphocyte ratio).

Results
Strong reproducibility’s (intraclass coefficients of correlation (ICC) > 0.90) were observed for spleen anterior SUVpeak, spleen MV, spleen TLG, spleen length and BLRmean. ICC for SLRmean and ileocecal SUVmean were 0.86 and 0.65, respectively. In the 1-year OS 1 group, SLRmean tended to increase at each time point to reach a significant difference at M6-PET (p = 0.019). The same trends were observed with spleen SUVpeak anterior and spleen length. In the 1-year OS 0 group, a significative increase of spleen length was found at iPET, as compared with baseline PET (p = 0.014) and M3-PET (p = 0.0239). Univariable Kaplan-Meier survival analysis found that i%var spleen length, M3%var SLRmean, baseline LDH, i%var NLR and response at M6PET were all predictors of 1-year OS.

Conclusions
SLRmean is recommended as a prognosticator in melanoma patients under immunotherapy: its increase greater than 25% at 3 months, compared with baseline, was associated with poor outcome after ICIs.

https://link.springer.com/article/10.10 ... 20-05103-3

FDG-positive lesions often mean cancer, but not always. A variety of lesions have increased FDG radiotracer including infection, inflammation, autoimmune processes, sarcoidosis, and benign tumors. If such conditions are not identified accurately and in a timely manner, misdiagnosis can lead to inadequate therapies.May 5, 2015
https://link.springer.com › article
PET scan findings can be false positive |

[D.ap]

Hello Olga

Could you explain what your understanding is of how an assement of alveolar soft part sarcoma differs on a Pet scan say compared to a higher metabolic type sarcoma/ cancer, when looking at SUV values ?
Thanks in advance.

[Olga]

Deb if you question re. 18F-FDG uptake in ASPS tumors is related to the subject of the article, I think it is not relevant here.
This article talks about the 18F-FDG uptake in immune organs (spleen, bone marrow, ileocecal valve) not affected by the melanoma primary tumors or metastases. I.e. normal organs. There should be no difference for ASPS patients in how their normal immune organs would respond to immune therapy.
They see that these immune organs 18F-FDG uptake changed during the immunotherapy due to increased immune cells activity and different processes that take place there. Spleen is a major immune organ where immune cells are produced and differentiated, but this processes can go wrong with the splenic accumulation of monocytes and neutrophils and after prolonged accumulation of these cells, they can eventually acquire suppressor functions and chronically inhibit tumor-specific T cell immunity. But it is a super complicated subject for me to discuss in any meaningful way. It seems that this accumulation can manifest as the longitudinal increase in size and the increased inflammatory activity can be detected as an increased 18F-FDG uptake.
the article is super interesting though.
more reading on immune processes happening in spleen
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3912742/

[D.ap]

Morning Olga,

Thanks for the response.
I was looking for an article that was applicable to lower metabolic cancer’s like ASPS, so I guess my question is in looking at a PET scan , how is ASPS read as the possible metastasis verses infection and or for that matter benign mass ?

I understand that it would be speculative as only a biopsy would be the definitive tool to rule whether it would be ASPS or other possible issues such as infection etc.

I’ve noticed in Europe that the PET seems to be the scan of choice to look for responses to ICIs and I was wondering if the PETS were being based on true understandings of what is known of ASPSs indolent tendencies of SUV uptake values ?
All other labs of blood work can be attributed to the ICI , right ?
Obviously we now have ratios of white blood cells etc to follow , as a possible liquid biopsy gage circulating metastatic
cells , but that’s another discussion.

I placed this article here because I felt ICI discussions and the use of PET scans , should be clarified in some manner. As pertaining to ASPS.
There was discussion as far back as 2007 On the forum of the uselessness of the PET below 5mm? But maybe with the added CT machine to the PET, it is now a viable tool for ASPS?

When Josh started Opdivo in 2016, I had a brief talk with our oncologist about using PET to see how systemically it was reaching his tumors . At that time it was explained that it wouldn’t be a good tool to use as multiple areas would “ light” up and be hard to discern from active Mets and say infection etc ?

If you’d like , I could move this to the medical
post.