FDG-PET in the evaluation of response to nivolumab in recurrent non-small-cell lung cancer

Higuchi, Mitsunori; Owada, Yohei; Inoue, Takuya; Watanabe, Yuzuru; Yamaura, Takumi; Fukuhara, Mitsuro; Hasegawa, T.; Suzuki, Hiroyuki

doi:10.1186/s12957-016-0998-y

Cited by 25 publications

(15 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, it is necessary to determine the effect of anti-PD-1 treatment on the uptake of [ 18 F]FDG, a marker of glucose uptake in cells (e.g., effector immune cells and cancer cells). Clinical studies reported that immune checkpoint inhibitors increased [ 18 F]FDG uptake; however, other studies showed the opposite effect [22][23][24][25]. In this study, Fig.…”

Section: Discussionmentioning

confidence: 43%

See 1 more Smart Citation

Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor

et al. 2020

View full text Add to dashboard Cite

Background: Anti-programmed cell death 1 (PD-1) antibody is an immune checkpoint inhibitor, and anti-PD-1 therapy improves the anti-tumor functions of T cells and affects tumor microenvironment. We previously reported that anti-PD-1 treatment affected tumor glycolysis by using 2-deoxy-2-[ 18 F]fluoro-D-glucose ([ 18 F]FDG) positron emission tomography (PET). That study showed that anti-PD-1 therapy in a mouse B16F10 melanoma model increased glucose metabolism in cancer cells at the point where anti-PD-1 therapy did not cause a significant inhibition of tumor growth. However, the B16F10 melanoma model is poorly immunogenic, so it is not clear how anti-PD-1 treatment affects glucose metabolism in highly immunogenic cancer models. In this study, we used a cyclic dinucleotide GMP-AMP (cGAMP)-injected B16F10 melanoma model to investigate the effect of anti-PD-1 therapy on [ 18 F]FDG uptake in a highly immune activated tumor in mice. Results: To compare the cGAMP-injected B16F10 model with the B16F10 model, experiments were performed as described in our previous manuscript. [ 18 F]FDG-PET was measured before treatment and 7 days after the start of treatment. In this study, [ 18 F]FDG uptake in tumors in the cGAMP/anti-PD-1 combination group was lower than that in the anti-PD-1 treatment group tumors on day 7, as shown by PET and ex vivo validation. Flow-cytometry was performed to assess immune cell populations and glucose metabolism. Anti-PD-1 and/or cGAMP treatment increased the infiltration level of immune cells into tumors. The cGAMP/anti-PD-1 combination group had significantly lower levels of GLUT1 high cells/hexokinase II high cells in CD45 − cancer cells compared with tumors in the anti-PD-1 treated group. These results suggested that if immune responses in tumors are higher than a certain level, glucose uptake in cancer cells is reduced depending on that level. Such a change of glucose uptake might be caused by the difference in infiltration or activation level of immune cells between the anti-PD-1 treated group and the cGAMP/anti-PD-1 combination group. Conclusions: [ 18 F]FDG uptake in cancer cells after anti-PD-1 treatment might be affected by the tumor immune microenvironment including immune cell infiltration, composition, and activation status.

show abstract

Section: Discussionmentioning

confidence: 43%

“…a Illustration of in vivo and ex vivo study timelines. b Tumor growth curves after anti-PD-1 or cGAMP treatment (n =[14][15][16][17][18][19][20][21][22][23][24][25][26][27]. Data of the non-treatment group and anti-PD-1 treated group were quoted from[11].…”

mentioning

confidence: 99%

Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Although little is known about PERCIST criteria with respect to response to immunotherapy of NSCLC, there are a few studies or case reports describing its role in evaluating response to immune checkpoint inhibitors [15,25,[28][29][30]. In a recent study, 24 patients treated with PD-1 blockade (nivolumab) were investigated at baseline and 1 month after the start of treatment [15].…”

Section: Discussionmentioning

confidence: 99%

The efficiency of 18F-FDG PET-CT for predicting the major pathologic response to the neoadjuvant PD-1 blockade in resectable non-small cell lung cancer

Tao

et al. 2020

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

Purpose Investigate whether 18 F-FDG PET-CT has the potential to predict the major pathologic response (MPR) to neoadjuvant sintilimab in resectable NSCLC patients, and the potential of sifting patients who probably benefit from immunotherapy. Methods Treatment-naive patients with resectable NSCLC (stage IA-IIIB) received two cycles of sintilimab (200 mg, intravenously, day 1 and 22). Surgery was performed between day 29 and 43. PET-CT was obtained at baseline and prior to surgery. The following lean body mass-corrected metabolic parameters were calculated by PET VCAR: SUL max , SUL peak , MTV, TLG, ΔSUL max %, ΔSUL peak %, ΔMTV%, ΔTLG%. PET responses were classified using PERCIST. The above metabolic information on FDG-PET was correlated with the surgical pathology. (Registration Number: ChiCTR-OIC-17013726).Results Thirty-six patients received 2 doses of sintilimab, all of whom underwent PET-CT twice and had radical resection (35) or biopsy (1). MPR occurred in 13 of 36 resected tumors (36.1%, 13/36). The degree of pathological regression was positively correlated with SUL max (p = 0.036) of scan-1, and was negatively correlated with all metabolic parameters of scan-2, and the percentage changes of the metabolic parameters after neoadjuvant therapy (p < 0.05). According to PERCIST, 13 patients (36.1%, 13/36) showed partial metabolic response (PMR), 21 (58.3%, 21/36) had stable metabolic disease, and 2 (5.6%, 2/36) had progressive metabolic disease (PMD). There was a significant correlation between the pathological response and the PET responses which were classified using PERCIST. All (100.0%) the PMR (ΔSUL peak % < − 30.0%) tumors showed MPR. Conclusions 18 F-FDG PET-CT can predict MPR to neoadjuvant sintilimab in resectable non-small cell lung cancer.

show abstract

“…Because PD-1 inhibition increases glucose metabolism of immune cells and reduces cancer cell metabolism (23,29), 18 F-FDG uptake could be used for early treatment response evaluation. Recently, several studies showed the feasibility of applying 18 F-FDG PET in lung cancer patients as a tool for early response monitoring of immunotherapy (32,33). A recent finding of increased 18 F-FDG uptake in lymphoid tissue associated with immunotherapy response could also support the feasibility of 18 F-FDG PET as a valuable biomarker for response monitoring based on the mechanism of competitive 18 F-FDG uptake between immune cells and cancer cells (34).…”

Section: Discussionmentioning

confidence: 99%

Tumor Metabolic Features Identified by ¹⁸F-FDG PET Correlate with Gene Networks of Immune Cell Microenvironment in Head and Neck Cancer

Choi²

2017

J Nucl Med

View full text Add to dashboard Cite

The importance of F-FDG PET in imaging head and neck squamous cell carcinoma (HNSCC) has grown in recent decades. Because PET has prognostic values, and provides functional and molecular information in HNSCC, the genetic and biologic backgrounds associated with PET parameters are of great interest. Here, as a systems biology approach, we aimed to investigate gene networks associated with tumor metabolism and their biologic function using RNA sequence andF-FDG PET data. Using RNA sequence data of HNSCC downloaded from The Cancer Genome Atlas data portal, we constructed a gene coexpression network. PET parameters including lesion-to-blood-pool ratio, metabolic tumor volume, and tumor lesion glycolysis were calculated. The Pearson correlation test was performed between module eigengene-the first principal component of modules' expression profile-and the PET parameters. The significantly correlated module was functionally annotated with gene ontology terms, and its hub genes were identified. Survival analysis of the significantly correlated module was performed. We identified 9 coexpression network modules from the preprocessed RNA sequence data. A network module was significantly correlated with total lesion glycolysis as well as maximum and mean F-FDG uptake. The expression profiles of hub genes of the network were inversely correlated withF-FDG uptake. The significantly annotated gene ontology terms of the module were associated with immune cell activation and aggregation. The module demonstrated significant association with overall survival, and the group with higher module eigengene showed better survival than the other groups with statistical significance ( = 0.022). We showed that a gene network that accounts for immune cell microenvironment was associated withF-FDG uptake as well as prognosis in HNSCC. Our result supports the idea that competition for glucose between cancer cell and immune cell plays an important role in cancer progression associated with hypermetabolic features. In the future, PET parameters could be used as a surrogate marker of HNSCC for estimating molecular status of immune cell microenvironment.

show abstract

FDG-PET in the evaluation of response to nivolumab in recurrent non-small-cell lung cancer

Cited by 25 publications

References 23 publications

Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor

Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor

The efficiency of 18F-FDG PET-CT for predicting the major pathologic response to the neoadjuvant PD-1 blockade in resectable non-small cell lung cancer

Tumor Metabolic Features Identified by ¹⁸F-FDG PET Correlate with Gene Networks of Immune Cell Microenvironment in Head and Neck Cancer

Contact Info

Product

Resources

About

FDG-PET in the evaluation of response to nivolumab in recurrent non-small-cell lung cancer

Cited by 25 publications

References 23 publications

Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor

Influence on [18F]FDG uptake by cancer cells after anti-PD-1 therapy in an enforced-immune activated mouse tumor

The efficiency of 18F-FDG PET-CT for predicting the major pathologic response to the neoadjuvant PD-1 blockade in resectable non-small cell lung cancer

Tumor Metabolic Features Identified by 18F-FDG PET Correlate with Gene Networks of Immune Cell Microenvironment in Head and Neck Cancer

Contact Info

Product

Resources

About

Tumor Metabolic Features Identified by ¹⁸F-FDG PET Correlate with Gene Networks of Immune Cell Microenvironment in Head and Neck Cancer