Reham Abdel-Wahab1,2, Manal M Hassan1, Bhawana George3, Roberto Carmagnani Pestana1,4, Lianchun Xiao5, Sahin Lacin1,6, Suayib Yalcin6, Ahmed S Shalaby1, Humaid O Al-Shamsi7,8,9, Kanwal Raghav1, Robert A Wolff1, James C Yao1, Lauren Girard1, Abedul Haque3, Dan G Duda10, Simona Dima11, Irinel Popescu11, Hesham A Elghazaly12, Jean-Nicolas Vauthey13, Thomas A Aloia13, Ching-Wei Tzeng13, Yun Shin Chun13, Asif Rashid14, Jeffrey S Morris5, Hesham M Amin3,15, Ahmed O Kaseb16. 1. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 2. Department of Clinical Oncology, Assiut University, Assiut, Egypt. 3. Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 4. Department of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 5. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 6. Hacettepe University Institute of Cancer, Ankara, Turkey. 7. Medical Oncology Department, Alzahra Hospital Dubai, Dubai, United Arab Emirates. 8. College of Medicine, University of Sharjah, Sharjah, United Arab Emirates. 9. Emirates Oncology Society, Dubai, United Arab Emirates. 10. Steele Laboratories, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. 11. Dan Setlacec Center of General Surgery and Liver Transplantation, Fundeni Clinical Institute, Bucharest, Romania. 12. Department of Clinical Oncology, Ain Shams University, Cairo, Egypt. 13. Department of Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 14. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. 15. The University of Texas MD Anderson Cancer Center UT Health Graduate School of Biomedical Sciences, Houston, Texas, USA. 16. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA, akaseb@mdanderson.org.
Abstract
BACKGROUND: Liver reserve affects survival in hepatocellular carcinoma (HCC). Model for End-Stage Liver Disease (MELD) score is used to predict overall survival (OS) and to prioritize HCC patients on the transplantation waiting list, but more accurate models are needed. We hypothesized that integrating insulin-like growth factor 1 (IGF-1) levels into MELD score (MELD-IGF-1) improves OS prediction as compared to MELD. METHODS: We measured plasma IGF-1 levels in training (n = 310) and validation (n = 155) HCC cohorts and created MELD-IGF-1 score. Cox models were used to determine the association of MELD and MELD-IGF-1 with OS. Harrell's c-index was used to compare the predictive capacity. RESULTS: IGF-1 was significantly associated with OS in both cohorts. Patients with an IGF-1 level of ≤26 ng/mL in the training cohort and in the validation cohorts had significantly higher hazard ratios than patients with the same MELD but IGF-1 >26 ng/mL. In both cohorts, MELD-IGF-1 scores had higher c-indices (0.60 and 0.66) than MELD scores (0.58 and 0.60) (p < 0.001 in both cohorts). Overall, 26% of training and 52.9% of validation cohort patients were reclassified into different risk groups by MELD-IGF-1 (p < 0.001). CONCLUSIONS: After independent validation, the MELD-IGF-1 could be used to risk-stratify patients in clinical trials and for priority assignment for patients on liver transplantation waiting list.
BACKGROUND: Liver reserve affects survival in hepatocellular carcinoma (HCC). Model for End-Stage Liver Disease (MELD) score is used to predict overall survival (OS) and to prioritize HCCpatients on the transplantation waiting list, but more accurate models are needed. We hypothesized that integrating insulin-like growth factor 1 (IGF-1) levels into MELD score (MELD-IGF-1) improves OS prediction as compared to MELD. METHODS: We measured plasma IGF-1 levels in training (n = 310) and validation (n = 155) HCC cohorts and created MELD-IGF-1 score. Cox models were used to determine the association of MELD and MELD-IGF-1 with OS. Harrell's c-index was used to compare the predictive capacity. RESULTS:IGF-1 was significantly associated with OS in both cohorts. Patients with an IGF-1 level of ≤26 ng/mL in the training cohort and in the validation cohorts had significantly higher hazard ratios than patients with the same MELD but IGF-1 >26 ng/mL. In both cohorts, MELD-IGF-1 scores had higher c-indices (0.60 and 0.66) than MELD scores (0.58 and 0.60) (p < 0.001 in both cohorts). Overall, 26% of training and 52.9% of validation cohort patients were reclassified into different risk groups by MELD-IGF-1 (p < 0.001). CONCLUSIONS: After independent validation, the MELD-IGF-1 could be used to risk-stratify patients in clinical trials and for priority assignment for patients on liver transplantation waiting list.
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