Development and validation of a prognostic nomogram for recurrence-free survival after complete surgical resection of localised primary gastrointestinal stromal tumour: a retrospective analysis

Abstract

Background: Adjuvant imatinib mesylate prolongs recurrence-free survival (RFS) after resection of localised primary gastrointestinal stromal tumours (GIST). We aimed to develop a nomogram to predict RFS after surgery in the absence of adjuvant therapy to help guide patient selection for adjuvant imatinib therapy.

Methods: A nomogram to predict RFS based on tumour size (cm), location (stomach, small intestine, colon/rectum, or other), and mitotic index (<5 or > or =5 mitoses per 50 high-power fields) was developed from 127 patients treated at Memorial Sloan-Kettering Cancer Center (MSKCC), New York, NY, USA. The nomogram was tested in patients from the Spanish Group for Research on Sarcomas (GEIS; n=212) and the Mayo Clinic, Rochester, MN, USA (Mayo; n=148). The nomogram was assessed by calculating concordance probabilities and testing calibration of predicted RFS with observed RFS. Concordance probabilities were also compared with those of three commonly used staging systems.

Findings: The nomogram had a concordance probability of 0.78 (SE 0.02) in the MSKCC dataset, and 0.76 (0.03) and 0.80 (0.02) in the validation cohorts. Nomogram predictions were well calibrated. Inclusion of tyrosine kinase mutation status in the nomogram did not improve its discriminatory ability. Concordance probabilities of the nomogram were better than those of the two NIH staging systems (0.76 [0.03] vs 0.70 [0.04, p=0.04] and 0.66 [0.04, p=0.01] in the GEIS validation cohort; 0.80 [0.02] vs 0.74 [0.02, p=0.04] and 0.78 [0.02, p=0.05] in the Mayo cohort) and similar to those of the AFIP-Miettinen staging system (0.76 [0.03] vs 0.73 [0.004, p=0.28] in the GEIS cohort; 0.80 [0.02] vs 0.76 [0.003, p=0.09] in the Mayo cohort). Nomogram predictions of RFS seemed better calibrated than predictions made with the AFIP-Miettinen system.

Interpretation: The nomogram accurately predicts RFS after resection of localised primary GIST and could be used to select patients for adjuvant imatinib therapy.

Conflict of interest statement

AUTHORS’ DISCLOSRES OF POTENTIAL CONFLICTS OF INTEREST.

Drs. Gönen, Martín Broto, García-del-Muro, Maki and DeMatteo report receiving honoraria and consulting fees from Novartis Pharmaceuticals.

Figures

Figure 1. Recurrence-free survival for the 3 patient populations

Kaplan Meier estimates of recurrence-free survival of localized, primary gastrointestinal stromal tumors after complete surgical resection based on patient series from 2 North American institutions and a Spanish sarcoma registry are shown.

Figure 2. Nomogram to predict the probabilities of 2- and 5-year recurrence-free survival

Points are assigned for size, mitotic index, and site of origin by drawing a line upward from the corresponding values to the “Points” line. The sum of these 3 points plotted on the “Total Points” line corresponds to predictions of 2- and 5-year RFS.

Figure 3. Performance of the nomogram

Calibration of nomogram-predicted recurrence-free survival (RFS) with observed RFS is shown at (A) 2 years and (B) 5 years for the Memorial Sloan-Kettering Cancer Center series.

Figure 4. Nomogram scores compared to commonly used risk groupings

Nomogram predictions of recurrence-free survival (RFS) for individual patients in all 3 datasets are shown by 10 percentile intervals for each (A) NIH-Fletcher, (B) NIH-Miettinen, and (C) AFIP-Miettinen stage.