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. 2024 May 1;30(9):1811-1821.
doi: 10.1158/1078-0432.CCR-23-3211.

Improved Risk-Stratification Scheme for Mismatch-Repair Proficient Stage II Colorectal Cancers Using the Digital Pathology Biomarker QuantCRC

Christina Wu #  1 , Reetesh K Pai #  2 , Heidi Kosiorek  3 , Imon Banerjee  4 , Ashlyn Pfeiffer  5 , Catherine E Hagen  6 , Christopher P Hartley  6 , Rondell P Graham  6 , Mohamad B Sonbol  1 , Tanios Bekaii-Saab  1 , Hao Xie  7 , Frank A Sinicrope  7   8 , Bhavik Patel  4 , Thomas Westerling-Bui  9 , Sameer Shivji  10 , James Conner  10 , Carol Swallow  11   12   13   14 , Paul Savage  11   13 , David P Cyr  11   12   13   14 , Richard Kirsch  10 , Rish K Pai  5
Affiliations

Improved Risk-Stratification Scheme for Mismatch-Repair Proficient Stage II Colorectal Cancers Using the Digital Pathology Biomarker QuantCRC

Christina Wu et al. Clin Cancer Res. .

Abstract

Purpose: There is a need to improve current risk stratification of stage II colorectal cancer to better inform risk of recurrence and guide adjuvant chemotherapy. We sought to examine whether integration of QuantCRC, a digital pathology biomarker utilizing hematoxylin and eosin-stained slides, provides improved risk stratification over current American Society of Clinical Oncology (ASCO) guidelines.

Experimental design: ASCO and QuantCRC-integrated schemes were applied to a cohort of 398 mismatch-repair proficient (MMRP) stage II colorectal cancers from three large academic medical centers. The ASCO stage II scheme was taken from recent guidelines. The QuantCRC-integrated scheme utilized pT3 versus pT4 and a QuantCRC-derived risk classification. Evaluation of recurrence-free survival (RFS) according to these risk schemes was compared using the log-rank test and HR.

Results: Integration of QuantCRC provides improved risk stratification compared with the ASCO scheme for stage II MMRP colorectal cancers. The QuantCRC-integrated scheme placed more stage II tumors in the low-risk group compared with the ASCO scheme (62.5% vs. 42.2%) without compromising excellent 3-year RFS. The QuantCRC-integrated scheme provided larger HR for both intermediate-risk (2.27; 95% CI, 1.32-3.91; P = 0.003) and high-risk (3.27; 95% CI, 1.42-7.55; P = 0.006) groups compared with ASCO intermediate-risk (1.58; 95% CI, 0.87-2.87; P = 0.1) and high-risk (2.24; 95% CI, 1.09-4.62; P = 0.03) groups. The QuantCRC-integrated risk groups remained prognostic in the subgroup of patients that did not receive any adjuvant chemotherapy.

Conclusions: Incorporation of QuantCRC into risk stratification provides a powerful predictor of RFS that has potential to guide subsequent treatment and surveillance for stage II MMRP colorectal cancers.

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Conflict of interest statement

CW has received research funding (as a clinical trial investigator) from Vaccinex, Boston Biomedical, Lycera, Seattle Genetics, Symphogen, RAPT Therapeutics, and INHBRX. She has also received honoraria from Array Biopharma, Signatera, PrecisCA, and the Oncology Learning Network and served as a consultant to Nova Research Company

RKP1, RK report consulting income from Alimentiv Inc.

RKP2 reports consulting income from Alimentiv Inc., Allergan, and Verily

MBS has received consulting income from Novartis

TBS has received consulting income from Boehringer Ingelheim, TreosBio, Sobi, Ipsen, Array Biopharma, Seattle Genetics, Bayer, Genentech, Incyte, Merck, Boston Biomedical, Bayer, Amgen, Merck, Celgene, Lilly, Ipsen, Clovis, Seattle Genetics, Array Biopharma, Genentech, Abgenomics, Incyte

FS is a consultant for Guardant Health and has received research funding from Ventana Medical Systems

TW-B is an employee of Aiforia Inc.

All other authors report no financial relationships

Figures

Figure 1.
Figure 1.
Recurrence free survival in stage II MMRP colorectal carcinomas according pathologic and QuantCRC features using Kaplan-Meier analysis. A. pT-stage. B. Pathologist tumor budding grade. C. VELIPI. D. QuantCRC %TB/PDC. E. QuantCRC %Immature stroma (tumor bed). F. QuantCRC tumor:stroma ratio. Abbreviations: Bd, tumor budding grade; TB/PDC, tumor budding/poorly differentiated clusters; VELIPI, venous/lymphatic/perineural invasion.
Figure 2.
Figure 2.
ASCO and QuantCRC-integrated risk schemes used in this study (blue = low-risk, green = intermediate-risk, red = high-risk). A. Flow chart of the stage II QuantCRC-integrated risk scheme (blue = low-risk, green = intermediate-risk, red = high-risk). B. Flowchart of the stage II ASCO risk scheme (blue = low-risk, green = intermediate-risk, red = high-risk). C. Recurrence free survival in stage II MMRP colorectal carcinomas regardless of ACT according to the QuantCRC scheme. D. Recurrence free survival in stage II MMRP colorectal carcinomas regardless of ACT according to the ASCO scheme. E. Recurrence free survival in stage II MMRP colorectal carcinomas in those receiving no ACT according to the QuantCRC scheme. F. Recurrence free survival in stage II MMRP colorectal carcinomas in those receiving no ACT according to the ASCO scheme. Abbreviations: ASCO, American Society of Clinical Oncology; HR, high-risk; IR, intermediate-risk; LN, lymph node; LR, low-risk.
Figure 3.
Figure 3.
QuantCRC features according to ASCO and QuantCRC-integrated risk schemes. A. QuantCRC was applied to the stage II MMRP cohort which segments the image in a stepwise manner. First the image is segmented into carcinoma (green), stroma (light blue), mucin (dark blue), TB/PDC (red), necrosis (brown), smooth muscle (purple), and fat (yellow). Next the stroma is segmented into immature (teal), mature (green), and inflammatory (gray). The carcinoma is segmented into low-grade (purple), high-grade (orange), and signet ring cell (light green). Finally, TILs are recognized as objects (blue dots) within the tumor epithelium. After this segmentation, fifteen features are calculated from each image as shown. Two tumors with different classifications in the ASCO and QuantCRC-integrated scheme are shown. B. Scatter plot of %TB/PDC according to ASCO and QuantCRC-integrated risk shemes. C. Scatter plot of tumor:stroma ratio according to ASCO and QuantCRC-integrated risk shemes. D. Scatter plot of %immature stroma (tumor bed) according to ASCO and QuantCRC-integrated risk shemes. E. Scatter plot of %inflammatory stroma (stromal area) according to ASCO and QuantCRC-integrated risk sheme. Shown are the P-values for comparisons between LR, IR, and HR groups within the QuantCRC-integrated and ASCO risk schemes. Abbreviations: ASCO, American Society of Clinical Oncology; B, tumor bed; ; HR, high-risk; IR, intermediate-risk; LR, low-risk, SRCC, signet ring cell carcinoma; ST, stromal region; TB/PDC, tumor budding/poorly differentiated clusters; TIL, tumor infiltrating lymphocytes.
See this image and copyright information in PMC

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