Keywords:
Tissue characterisation, Cancer, Segmentation, Decision analysis, Computer Applications-Detection, diagnosis, Image manipulation / Reconstruction, CT-Quantitative, CT, Thorax, Oncology, Computer applications
Authors:
G. Ficarra1, E. Barabino1, C. Genova1, S. Mennella1, M. Verda2, G. Pittaluga1, F. Grossi1, G. Cittadini1; 1Genova/IT, 2Imperia/IT
Conclusion
As the use of immune checkpoint blockade agents increases,
so does the challenge of assessing their efficacy.
CT scans might demonstrate unconventional or delayed patterns of response,
so morphologic imaging evaluation of tumor response is challenging; although repeated tumor biopsies during treatment might provide useful information about the viability of tumor cells and the activity of the immune response within a lesion,
biopsy is not always achievable because tumors may be inaccessible or multiple.
Additionally,
biopsy of a single lesion may not accurately capture patients experiencing a mixed response.
Lung cancer is the fourth most frequently diagnosed malignancy in Europe22 and the leading cause of cancer-related mortality; thus,
the research for a non-invasive predictor of tumor response to immunotherapy is mandatory.
In our cohort of patients CTTA derived parameter acted as prognostic predictors in patients receiving immune checkpoint inhibitors for advanced NSCLC.
In particular,
absolute variations in those features reflecting an increased tissue heterogeneity (Entropy associated parameters) strongly correlated with a higher overall survival.
Traditionally heterogeneity has been interpreted as intratumoral variation in cellularity,
distribution of tumor vessels,
extracellular matrix,
hemorrhage and necrosis.
Programmed cell death-1 (PD-1) is an inhibitory receptor expressed on activated T and B cells,
which normally function to dampen the immune response,
and is engaged by ligands (PD-L1 and PD-L2) which are expressed by tumor cells.
Inhibition of the interaction between PD-1 and PD-1 ligands can enhance anti-tumor responses,
delay tumor growth,
and facilitate tumor rejection.
Anti-PD-1 antibodies (nivolumab) block PD-1 interactions with both PD-L1 and PD-L2,
and stimulates memory response to tumor antigen-specific T cell proliferation,
thus triggering the immune system’s response to NSCLC.
Based upon our hypothesis,
an absolute increase in tissue heterogeneity between baseline and first follow up CT after introduction of immune checkpoint inhibitors based therapy may reflect the appearance of a lymphocitic infiltrate in the tumor,
thus representing an early biomarker for response to treatment in our study population.
Texture analysis has the potential to strongly impact on patient clinical management and healthcare systems,
if its capability to characterize lesions in vivo and to provide predictive information will be demonstrated in larger prospective studies.