Nomograms for overall survival (OS) and progression-free survival (PFS) in metastatic colorectal cancer (mCRC): Construction from 19,678 ARCAD patients.

Authors

Katrin Sjoquist

Katrin Marie Sjoquist

NHMRC Clinical Trials Centre, University of Sydney and Cancer Care Centre, St. George Hospital, Sydney, Australia

Katrin Marie Sjoquist , Lindsay A. Renfro , John Simes , Niall C. Tebbutt , Stephen John Clarke , Jeffrey P. Meyers , Wilson I. Gonsalves , Richard Adams , Matthew T. Seymour , Leonard Saltz , Hans Schmoll , Daniel J. Sargent , Aimery De Gramont , John Raymond Zalcberg

Organizations

NHMRC Clinical Trials Centre, University of Sydney and Cancer Care Centre, St. George Hospital, Sydney, Australia, Mayo Clinic, Rochester, MN, Rochester, MN, NHMRC Clinical Trials Centre, Sydney, Australia, Austin Health, Melbourne, Australia, Royal North Shore Hospital, St Leonards, Australia, Cardiff University and Velindre Cancer Centre, Cardiff, United Kingdom, Cancer Research UK Clinical Centre, Leeds, United Kingdom, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, Martin Luther University, Halle, Germany, Hospital Saint Antoine, Paris, France, School of Public Health, Monash University, Melbourne, Australia

Research Funding

No funding sources reported

Background: Prospective survival prediction of patients with metastatic colorectal cancer is difficult. Prognosis estimation based on readily available clinicopathologic factors has the potential to inform clinical practice and improve risk stratification for clinical trials. We constructed prognostic nomograms for OS and PFS in mCRC using the multi-trial ARCAD database. Methods: Data from 19,678 mCRC pts accrued to 24 first line randomized phase III clinical trials since 1997 were used to construct and validate Cox models for PFS and OS, stratified by treatment arm within each study. Candidate variables included age, gender, BMI, performance status, colon vs. rectal cancer, prior chemotherapy, number of metastatic sites, sites of metastases (liver, lung, lymph nodes), and baseline bilirubin, albumin, white blood cell count, hemoglobin, platelets, absolute neutrophil count, and derived neutrophil:lymphocyte ratio (dNLR). Missing data (<11%) were imputed, continuous variables modeled with splines, and clinically relevant pairwise interactions considered if p<0.001. Final models were internally validated via bootstrapping to obtain optimism-corrected calibration and discrimination C-indices, and externally validated using a 10% holdout sample from each trial. Results: Nomograms for OS and PFS including remaining variables were well calibrated with C-indices of 0.66 and 0.60, respectively. Evaluation of external validity revealed good concordance; 71% and 67% respectively between predicted (> vs. <50% probability) and actual (yes/no) 1-year OS and 6-month PFS, and median 1-year OS and 6-month PFS predictions fell within the actual 95% Kaplan-Meier intervals. Gender, liver and lung metastases, and dNLR were not prognostic for OS; prior chemo, colon vs. rectum, dNLR, liver and lymph node metastases, and gender did not predict for PFS. No clinically relevant pairwise interactions were identified. Conclusions: The proposed nomograms are well calibrated and internally and externally valid. These tools have the potential to aid prognostication and patient/physician communication, and balance risk in randomized trials in mCRC.

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Abstract Details

Meeting

2015 Gastrointestinal Cancers Symposium

Session Type

Poster Session

Session Title

General Poster Session C: Cancers of the Colon, Rectum, and Anus

Track

Cancers of the Colon, Rectum, and Anus

Sub Track

Multidisciplinary Treatment

Citation

J Clin Oncol 33, 2015 (suppl 3; abstr 659)

DOI

10.1200/jco.2015.33.3_suppl.659

Abstract #

659

Poster Bd #

D1

Abstract Disclosures