Chee Khoon Lee1, David Goldstein2, Emma Gibbs1, Heikki Joensuu3, John Zalcberg4, Jaap Verweij5, Paolo G Casali6, Robert G Maki7, Angela Cioffi7, Grant Mcarthur8, Sarah J Lord9, Desmond Yip10, Yada Kanjanapan11, Piotr Rutkowski12. 1. National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia. 2. Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, Australia. 3. Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland. 4. Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia. 5. Faculty of Medicine, Erasmus University, Rotterdam, The Netherlands. 6. Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. 7. Department of Medicine, Mount Sinai School of Medicine, NY, USA. 8. Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, Melbourne, Australia. 9. National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia; School of Medicine, The University of Norte Dame, Sydney, Australia. 10. Department of Medical Oncology, The Canberra Hospital, Canberra, Australia; ANU Medical School, Australian National University, Canberra, Australia. 11. Department of Medical Oncology, The Canberra Hospital, Canberra, Australia. 12. Department of Soft Tissue/Bone Sarcoma and Melanoma, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. Electronic address: rutkowskip@coi.waw.pl.
Abstract
PURPOSE:Metastatic gastrointestinal stromal tumour (GIST) is generally an incurable disease with variable response to imatinib. We aimed to develop prognostic nomograms to predict overall survival (OS) and progression-free survival (PFS) for patients treated with imatinib. METHODS: Nomograms were developed in a training cohort (n=330) of patients treated in a randomised trial (EORTC-ISG-AGITG 62005 phase III study) using Cox regression models, and validated in patients (n=236) treated in routine clinical care from six referral centres. Nomogram performance was assessed by calculating the c statistic. A classification based on the nomograms' scores was generated to group patients according to risk. RESULTS: Nomogram risk factors for OS and PFS were size of the largest metastasis, tumour genotype, primary tumour mitotic count, haemoglobin and blood neutrophil count at commencement of imatinib. The nomograms predicted survival with a c statistic of 0.75 (training) and 0.62 (validation) for OS, and 0.69 (training) and 0.62 (validation) for PFS. When tested in the validation cohort, the nomograms discriminated well the high and intermediate risk from low risk patients (hazard ratio [HR] for OS 3.83, 95% confidence interval [CI] 1.71-8.56; and 2.48, 95% CI 1.12-5.50; for PFS 2.84, 95% CI 1.66-4.87; and 1.45, 95% CI 0.87-2.41, respectively). CONCLUSION: The nomograms predicted the risk of GIST progression and death with good discrimination of risk groups, and may be of value for patient counselling and risk stratification.
RCT Entities:
PURPOSE:Metastatic gastrointestinal stromal tumour (GIST) is generally an incurable disease with variable response to imatinib. We aimed to develop prognostic nomograms to predict overall survival (OS) and progression-free survival (PFS) for patients treated with imatinib. METHODS: Nomograms were developed in a training cohort (n=330) of patients treated in a randomised trial (EORTC-ISG-AGITG 62005 phase III study) using Cox regression models, and validated in patients (n=236) treated in routine clinical care from six referral centres. Nomogram performance was assessed by calculating the c statistic. A classification based on the nomograms' scores was generated to group patients according to risk. RESULTS: Nomogram risk factors for OS and PFS were size of the largest metastasis, tumour genotype, primary tumour mitotic count, haemoglobin and blood neutrophil count at commencement of imatinib. The nomograms predicted survival with a c statistic of 0.75 (training) and 0.62 (validation) for OS, and 0.69 (training) and 0.62 (validation) for PFS. When tested in the validation cohort, the nomograms discriminated well the high and intermediate risk from low risk patients (hazard ratio [HR] for OS 3.83, 95% confidence interval [CI] 1.71-8.56; and 2.48, 95% CI 1.12-5.50; for PFS 2.84, 95% CI 1.66-4.87; and 1.45, 95% CI 0.87-2.41, respectively). CONCLUSION: The nomograms predicted the risk of GIST progression and death with good discrimination of risk groups, and may be of value for patient counselling and risk stratification.