title: Development and validation of prognostic nomograms for metastatic gastrointestinal stromal tumour treated with imatinib.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors: National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia.
authors: Chee Khoon
authors: CK
authors: Lee
authors: Department of Medical Oncology, Prince of Wales Hospital, Sydney, Australia; Prince of Wales Clinical School, University of New South Wales, Sydney, Australia.
authors: David
authors: D
authors: Goldstein
authors: National Health and Medical Research Council Clinical Trials Centre, The University of Sydney, Sydney, Australia.
authors: Emma
authors: E
authors: Gibbs
authors: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland.
authors: Heikki
authors: H
authors: Joensuu
authors: Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia.
authors: John
authors: J
authors: Zalcberg
authors: Faculty of Medicine, Erasmus University, Rotterdam, The Netherlands.
authors: Jaap
authors: J
authors: Verweij
authors: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors: Paolo G
authors: PG
authors: Casali
authors: Department of Medicine, Mount Sinai School of Medicine, NY, USA.
authors: Robert G
authors: RG
authors: Maki
authors: Department of Medicine, Mount Sinai School of Medicine, NY, USA.
authors: Angela
authors: A
authors: Cioffi
authors: Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, Melbourne, Australia.
authors: Grant
authors: G
authors: Mcarthur
authors: 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.
authors: Sarah J
authors: SJ
authors: Lord
authors: Department of Medical Oncology, The Canberra Hospital, Canberra, Australia; ANU Medical School, Australian National University, Canberra, Australia.
authors: Desmond
authors: D
authors: Yip
authors: Department of Medical Oncology, The Canberra Hospital, Canberra, Australia.
authors: Yada
authors: Y
authors: Kanjanapan
authors: 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.
authors: Piotr
authors: P
authors: Rutkowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides / Q000627:therapeutic use*; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D046152:Gastrointestinal Stromal Tumors / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D049451:Nomograms; D010879:Piperazines / Q000627:therapeutic use*; D011379:Prognosis; D011743:Pyrimidines / Q000627:therapeutic use*; D016019:Survival Analysis; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate
keywords: Gastrointestinal stromal tumour; Imatinib; Nomogram; Prognosis