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Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery

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Abstract

Purpose

Eliciting antitumor T-cell response by targeting the PD-1/PD-L1 axis with checkpoint inhibitors has emerged as a novel therapeutic strategy in non-small cell lung cancer (NSCLC). The identification of predictors for sensitivity or resistance to these agents is, therefore, needed. Herein, we investigate the correlation of metabolic information on FDG-PET with tissue expression of immune-checkpoints and other markers of tumor-related immunity in resected NSCLC patients.

Materials and methods

All patients referred to our institution for upfront surgical resection of NSCLC, who were investigated with FDG-PET prior to surgery, were consecutively included in the study. From January 2010 to May 2014, 55 patients (stage IA-IIIB; M:F = 42:13; mean age 68.9 years) were investigated. Sampled surgical tumor specimens were analyzed by immunohistochemistry (IHC) for CD68-TAMs (tumor-associated macrophages), CD8-TILs (tumor infiltrating lymphocytes), PD-1-TILs, and PD-L1 tumor expression. Immunoreactivity was evaluated, and scores were compared with imaging findings. FDG-PET images were analyzed to define semi-quantitative parameters: SUVmax and SUVmean. Metabolic information on FDG-PET was correlated with tissue markers expression and disease-free survival (DFS) considering a median follow-up of 16.2 months.

Results

Thirty-six adenocarcinomas (ADC), 18 squamous cell carcinomas (SCC), and one sarcomatoid carcinoma were analyzed. All tumors resulted positive at FDG-PET: median SUVmax 11.3 (range: 2.3–32.5) and SUVmean 6.4 (range: 1.5–13) both resulted significantly higher in SCC compared to other NSCLC histotypes (p = 0.007 and 0.048, respectively). IHC demonstrated a median immunoreactive surface covered by CD68-TAMs of 5.41 % (range: 0.84–14.01 %), CD8-TILs of 2.9 % (range: 0.11–11.92 %), PD-1 of 0.65 % (range: 0.02–5.87 %), and PD-L1 of 0.7 % (range: 0.03–10.29 %). We found a statistically significant correlation between SUVmax and SUVmean with the expression of CD8 TILs (rho = 0.31; p = 0.027) and PD-1 (rho = 0.33; p = 0.017 and rho = 0.36; p = 0.009, respectively). The other tissue markers correlated as follows: CD8 TILs and PD-1 (rho = 0.45; p = 0.001), CD8 TILs and PD-L1 (rho = 0.41; p = 0.003), CD68-TAMs and PD-L1 (rho = 0.30; p = 0.027), PD-1 and PD-L1 (rho = 0.26; p = 0.059). With respect to patients’ outcome, SUVmax, SUVmean, and disease stage showed a statistically significant correlation with DFS (p = 0.002, 0.004, and <0.001, respectively).

Conclusions

The present study shows a direct association between metabolic parameters on FDG-PET and the expression of tumor-related immunity markers, suggesting a potential role for FDG-PET to characterize the tumor microenvironment and select NSCLC patients candidate to checkpoint inhibitors.

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Author notes

    Authors and Affiliations

    1. Nuclear Medicine Department, Humanitas Clinical and Research Hospital, Via Manzoni 56, 20089, Rozzano, MI, Italy

      Egesta Lopci, Laura Olivari & Arturo Chiti

    2. Oncology, Humanitas Clinical and Research Hospital, 20089, Rozzano, Milan, Italy

      Luca Toschi, Silvia Marchetti, Daniela Pistillo & Armando Santoro

    3. Department of Immunology and Inflammation, Humanitas Clinical and Research Hospital, 20089, Rozzano, Milan, Italy

      Fabio Grizzi, Giovanni Francesco Castino, Nina Cortese, Dorina Qehajaj & Federica Marchesi

    4. Department of Pathology, Humanitas Clinical and Research Hospital, 20089, Rozzano, Milan, Italy

      Daoud Rahal & Massimo Roncalli

    5. Thoracic Surgery, Humanitas Clinical and Research Hospital, 20089, Rozzano, Milan, Italy

      Marco Alloisio

    6. Humanitas University, Rozzano, Milan, Italy

      Massimo Roncalli, Paola Allavena, Armando Santoro & Arturo Chiti

    7. Department of Medical Biotechnologies and Translational Medicine, University of Milan, 20122, Milan, Italy

      Federica Marchesi

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    1. Egesta Lopci
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    Correspondence to Egesta Lopci.

    Ethics declarations

    The study herein presented was approved by the local review board and performed in accordance with the principles of good clinical practice, with the Declaration of Helsinki, and with the national regulations regarding clinical trials. Informed consent was obtained for all patients or their legal guardians, and patient assent was obtained whenever appropriate.

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    The authors have declared no conflicts of interest.

    Additional information

    Egesta Lopci and Luca Toschi contributed equally to this work.

    Arturo Chiti and Federica Marchesi can be considered as co-last authors.

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    Lopci, E., Toschi, L., Grizzi, F. et al. Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery. Eur J Nucl Med Mol Imaging 43, 1954–1961 (2016). https://doi.org/10.1007/s00259-016-3425-2

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    • DOI: https://doi.org/10.1007/s00259-016-3425-2

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