Computerized features of spatial arrangement of tumor-infiltrating lymphocytes from H&E images predicts survival and response to checkpoint inhibitors in gynecologic cancers.

Authors

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Sepideh Azarianpour Esfahani

Case Western Reserve University, Cleveland Heights, OH

Sepideh Azarianpour Esfahani , Germán Corredor , Kaustav Bera , PingFu Fu , Amy Joehlin-Price , Haider Mahdi , Anant Madabhushi

Organizations

Case Western Reserve University, Cleveland Heights, OH, Case Western Reserve University, Cleveland, OH, Case Comprehensive Cancer Center, Cleveland, OH, Cleveland Clinic, Cleveland, OH, Case Western Reserve University, Louis Stokes Cleveland Veterans Administration Medical Center, Cleveland, OH

Research Funding

U.S. National Institutes of Health
U.S. National Institutes of Health

Background: Immune checkpoint inhibitors (ICI) have demonstrated success in solid tumors. In gynecologic cancers (GC), the response rate is still low (~10-15%) except in MSI-H endometrial cancer (~ 50%). Current biomarkers (e.g. PDL1 expression) have limited utility in identifying benefit from ICI in GC. In this work we evaluated the ability of computational measurements of spatial arrangement of tumor infiltrating lymphocytes (TIL) from H&E slide images in predicting overall survival (OS) and response to ICI in ovarian, cervical and endometrial cancers. Methods: The study included 151 patients, including 102 ovarian carcinomas treated with surgery and chemotherapy (D1) and another set (D2) of n=49 patients (n=14 ovarian, n=27 endometrial and n=8 cervical), treated with different ICI agents (Pembrolizumab, Nivolumab, Ipilimumab, Avelumab) in the second line setting. Progressors and non-progressors in D2 were classified according to clinical improvement and radiologic assessment by RECIST. A machine learning approach was employed to identify tumor regions on the diagnostic slides from D1 and D2 and then used to automatically identify TILs within the tumor regions. Subsequently machine learning was used to define TIL clusters based on TIL proximity, and graph network theory was used to capture measurements relating to spatial arrangement of TIL clusters. The multivariable Cox regression model (MCRM) was trained on n=51 patients from D1 to predict OS and then independently evaluated in predicting (1) OS on the hold-out n=51 patients in D1 and (2) response and progression-free survival (PFS) in D2. Results: Statistical analysis identified 7 prognostic features relating to interaction of TIL clusters with cancer nuclei. MCRM was prognostic of OS on the n=51 hold out patients in D1 (hazard ratio (HR)=2.06, 95% confidence interval [1.04- 4.07], p=0.008) and predictive of PFS in D2 (HR=2.24, CI=[1.13-4.44], p=0.03). The AUC for MCRM in predicting progression in D2 was 82%. Conclusions: Computerized features of spatial arrangement of TILs on H&E images were prognostic of OS and PFS and predicted response to ICI in three gynecological cancers. These findings need to be validated in larger, multi-site validation sets.

Multivariable analysis
HRp
SpaTIL2.24 [1.13-4.44]0.03
Age (>65 vs. <65)0.97 [0.48-1.96]0.93
BMI (>30 vs. <30)1.09 [0.52-2.28]0.82
Grade (1,2 vs. 3)1.20 [0.50-2.85]0.68
Stage at initial diagnosis (1, 2 vs. others)0.96 [0.43-2.11]0.91

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Session

Session Title

Gynecologic Cancer

Track

Gynecologic Cancer

Sub Track

Ovarian Cancer

Citation

J Clin Oncol 38: 2020 (suppl; abstr 6074)

DOI

10.1200/JCO.2020.38.15_suppl.6074

Abstract #

6074

Poster Bd #

245

Abstract Disclosures