Validation of prognostic scoring and assessment of clinical benefit for patients with bone sarcomas enrolled in phase I clinical trials

// J. Andrew Livingston 1 , Kenneth R. Hess 2 , Aung Naing 3 , David S. Hong 3 , Shreyaskumar Patel 4 , Robert S. Benjamin 4 , Joseph A. Ludwig 4 , Anthony Conley 4 , Cynthia E. Herzog 5 , Pete Anderson 6 Funda Meric-Bernstam 3 , Razelle Kurzrock 7 and Vivek Subbiah 3 1 Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2 Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 3 Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 4 Department of Sarcoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 5 Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 6 Pediatric Hematology Oncology, The Cleveland Clinic, Cleveland, Ohio, USA 7 Experimental Therapeutics Program, University of California – San Diego, San Diego, California, USA Correspondence to: Vivek Subbiah, email: // Keywords : bone sarcoma; phase 1 trials; prognosis scores; Ewing sarcoma; osteosarcoma Received : June 13, 2016 Accepted : June 26, 2016 Published : July 28, 2016 Abstract Background: We sought to validate the Royal Marsden Hospital (RMH) and MD Anderson Cancer Center (MDACC) prognostic scoring systems for the selection of bone sarcoma patients for phase I clinical trials and to identify additional risk factors related to survival. Patients and Methods: We retrospectively reviewed the baseline characteristics and outcomes of 92 bone sarcoma patients who were referred to MDACC’s Phase I Clinical Trials Program. Results: Ninety-two patients with Ewing sarcoma ( N = 47), osteosarcoma ( N = 22), chondrosarcoma ( N = 16), and other tumors ( N = 7) were evaluated; 78 were enrolled in at least 1 of 43 different phase I trials. The median overall survival (OS) was 8.8 months (95% confidence interval [CI] = 6.8–13.7 months). Independent factors that predicted shorter survival were male sex, >2 metastatic sites, >3 previous therapies, hemoglobin level <10.5 g/dL, platelet count >200 x10 3 /L, creatinine level ≥1.3 mg/dL, and lactate dehydrogenase level >ULN. Patients with good RMH scores (0-1) had longer OS than patients with poor RMH scores (2-3) (HR = 5.8, 95% CI = 2.9–11.0; P < 0.0001), as did patients with low MDACC scores (0-1) as compared to patients with higher MDACC scores (2–4) (HR = 3.2, 95% CI = 1.9–5.6; P < 0.0001). Conclusion: The RMH prognostic score can be used to predict the OS of bone cancer patients referred for phase I trials. The MDACC score added no value to the RMH score and therefore does not have a role in assessment of patients with bone tumors. Patients with advanced bone sarcomas should be considered for phase I trials.