A retrospective analysis using deep-learning models for prediction of survival outcome and benefit of adjuvant chemotherapy in stage II/III colorectal cancer

Most early-stage colorectal cancer (CRC) patients can be cured by surgery alone, and only certain high-risk early-stage CRC patients benefit from adjuvant chemotherapies. However, very few validated biomarkers are available to accurately predict survival benefit from postoperative chemotherapy. We developed a novel deep-learning algorithm (CRCNet) using whole-slide images from Molecular and Cellular Oncology (MCO) to predict survival benefit of adjuvant chemotherapy in stage II/III CRC. We validated CRCNet both internally through cross-validation and externally using an independent cohort from The Cancer Genome Atlas (TCGA). We showed that CRCNet can accurately predict not only survival prognosis but also the treatment effect of adjuvant chemotherapy. The CRCNet identified high-risk subgroup benefits from adjuvant chemotherapy most and significant longer survival is observed among chemo-treated patients. Conversely, minimal chemotherapy benefit is observed in the CRCNet low- and medium-risk subgroups. Therefore, CRCNet can potentially be of great use in guiding treatments for Stage II/III CRC.

[1]  F. D. De Braud,et al.  Capecitabine Plus Oxaliplatin Compared With Fluorouracil/Folinic Acid As Adjuvant Therapy for Stage III Colon Cancer: Final Results of the NO16968 Randomized Controlled Phase III Trial. , 2015, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[2]  D. Kerr,et al.  Validation study of a quantitative multigene reverse transcriptase-polymerase chain reaction assay for assessment of recurrence risk in patients with stage II colon cancer. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  F. Marincola,et al.  Multicenter International Society for Immunotherapy of Cancer Study of the Consensus Immunoscore for the Prediction of Survival and Response to Chemotherapy in Stage III Colon Cancer. , 2020, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[4]  S. Shchegrova,et al.  Analysis of Plasma Cell-Free DNA by Ultradeep Sequencing in Patients With Stages I to III Colorectal Cancer , 2019, JAMA oncology.

[5]  Peter Regitnig,et al.  Interpretable survival prediction for colorectal cancer using deep learning , 2021, npj Digital Medicine.

[6]  A. Madabhushi,et al.  Artificial intelligence in digital pathology — new tools for diagnosis and precision oncology , 2019, Nature Reviews Clinical Oncology.

[7]  N. Dubrawsky Cancer statistics , 1989, CA: a cancer journal for clinicians.

[8]  F. Marincola,et al.  Towards the introduction of the ‘Immunoscore’ in the classification of malignant tumours , 2013, The Journal of pathology.

[9]  Steven J. M. Jones,et al.  Comprehensive molecular characterization of human colon and rectal cancer , 2012, Nature.

[10]  J. Hecht,et al.  Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. , 2012, The Lancet. Oncology.

[11]  R. Labianca,et al.  ESMO Consensus Guidelines for management of patients with colon and rectal cancer. a personalized approach to clinical decision making. , 2012, Annals of oncology : official journal of the European Society for Medical Oncology.

[12]  Constantino Carlos Reyes-Aldasoro,et al.  Predicting survival from colorectal cancer histology slides using deep learning: A retrospective multicenter study , 2019, PLoS medicine.

[13]  Jitendra Jonnagaddala,et al.  Whole slide images based cancer survival prediction using attention guided deep multiple instance learning networks , 2020, Medical Image Anal..

[14]  I Tomlinson,et al.  Prognostic markers for colorectal cancer: estimating ploidy and stroma , 2017, Annals of oncology : official journal of the European Society for Medical Oncology.

[15]  J. Ptak,et al.  Circulating Tumor DNA Analyses as Markers of Recurrence Risk and Benefit of Adjuvant Therapy for Stage III Colon Cancer. , 2019, JAMA oncology.

[16]  N. Petrelli,et al.  Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. , 2011, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[17]  Lin Wang,et al.  Prognostic value of nucleotyping, DNA ploidy and stroma in high-risk stage II colon cancer , 2020, British Journal of Cancer.

[18]  S. Paik,et al.  Relationship between tumor gene expression and recurrence in four independent studies of patients with stage II/III colon cancer treated with surgery alone or surgery plus adjuvant fluorouracil plus leucovorin. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[19]  C. Compton,et al.  The Staging of Colorectal Cancer: 2004 and Beyond , 2004, CA: a cancer journal for clinicians.

[20]  C. Begg,et al.  Adjuvant chemotherapy use for Medicare beneficiaries with stage II colon cancer. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[21]  Margarita Lopatin,et al.  Validation of the 12-gene colon cancer recurrence score in NSABP C-07 as a predictor of recurrence in patients with stage II and III colon cancer treated with fluorouracil and leucovorin (FU/LV) and FU/LV plus oxaliplatin. , 2013, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[22]  Marco Novelli,et al.  Deep learning for prediction of colorectal cancer outcome: a discovery and validation study , 2020, The Lancet.

[23]  T. Hickish,et al.  Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. , 2009, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[24]  Jeffrey S. Morris,et al.  The Consensus Molecular Subtypes of Colorectal Cancer , 2015, Nature Medicine.

[25]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[26]  Ahmed Kamel,et al.  Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology. , 2017, Journal of the National Comprehensive Cancer Network : JNCCN.

[27]  Robyn Ward,et al.  Integration and Analysis of Heterogeneous Colorectal Cancer Data for Translational Research , 2016, Nursing Informatics.