An Inflammation Based Score Can Optimize the Selection of Patients with Advanced Cancer Considered for Early Phase Clinical Trials |
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Authors: | David J. Pinato Chara Stavraka Michael J. Flynn Martin D. Forster Séan M. O'Cathail Michael J. Seckl Rebecca S. Kristeleit David Olmos Samantha J. Turnbull Sarah P. Blagden |
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Affiliation: | 1. Wellcome Trust McMichael Clinical Research Facility, Imperial College London, Hammersmith Hospital, London, United Kingdom.; 2. University College London Clinical Research Facility, University College London Hospital, London, United Kingdom.; 3. Department of Oncology, Imperial College London. Hammersmith Campus, London, United Kingdom.; 4. Royal Marsden Hospital and Institute of Cancer Research, Sutton, United Kingdom.; University of Verona, Italy, |
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Abstract: | BackgroundAdequate organ function and good performance status (PS) are common eligibility criteria for phase I trials. As inflammation is pathogenic and prognostic in cancer we investigated the prognostic performance of inflammation-based indices including the neutrophil (NLR) and platelet to lymphocyte ratio (PLR).MethodsWe studied inflammatory scores in 118 unselected referrals. NLR normalization was recalculated at disease reassessment. Each variable was assessed for progression-free (PFS) and overall survival (OS) on uni- and multivariate analyses and tested for 90 days survival (90DS) prediction using receiving operator curves (ROC).ResultsWe included 118 patients with median OS 4.4 months, 23% PS>1. LDH≥450 and NLR≥5 were multivariate predictors of OS (p<0.001). NLR normalization predicted for longer OS (p<0.001) and PFS (p<0.05). PS and NLR ranked as most accurate predictors of both 90DS with area under ROC values of 0.66 and 0.64, and OS with c-score of 0.69 and 0.60. The combination of NLR+PS increased prognostic accuracy to 0.72. The NLR was externally validated in a cohort of 126 subjects.ConclusionsWe identified the NLR as a validated and objective index to improve patient selection for experimental therapies, with its normalization following treatment predicting for a survival benefit of 7 months. Prospective validation of the NLR is warranted. |
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