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.
Highlights
The safety of individuals participating into phase I oncology studies is of paramount importance, where potentially high-risk investigational medicinal products (IMP) are administered for the first time in patients who may have limited life expectancy [1].Stringent eligibility criteria are pre-defined to avoid the exposure of frail patients to potentially harmful or ineffective experimental treatments, as well as to protect trial results from possible inconsistencies in the assessment of the safety and tolerability of the IMP.Despite this, the eligibility assessment of phase I candidates varies significantly as a function of the study protocol and relies mostly on subjective clinical parameters such as performance status (PS) and predicted life expectancy [2]
Demographics One hundred and twenty six patients were identified as new consecutive referrals to the WTMCRF at Imperial College London
Baseline bloods were available for all patients, albumin was missing in 58 (49%) patients and lactate dehydrogenase (LDH) in 41 (34%) patients
Summary
The safety of individuals participating into phase I oncology studies is of paramount importance, where potentially high-risk investigational medicinal products (IMP) are administered for the first time in patients who may have limited life expectancy [1].Stringent eligibility criteria are pre-defined to avoid the exposure of frail patients to potentially harmful or ineffective experimental treatments, as well as to protect trial results from possible inconsistencies in the assessment of the safety and tolerability of the IMP.Despite this, the eligibility assessment of phase I candidates varies significantly as a function of the study protocol and relies mostly on subjective clinical parameters such as performance status (PS) and predicted life expectancy [2]. The safety of individuals participating into phase I oncology studies is of paramount importance, where potentially high-risk investigational medicinal products (IMP) are administered for the first time in patients who may have limited life expectancy [1]. Scoring PS = 2) can be safely offered the option of experimental treatments For these reasons, increasing research efforts have been made to qualify novel and more objective prognostic determinants in the phase I oncology patient population. A number of prognostic models have been proposed to improve the eligibility assessment and better predict their survival [4] These models variously encompass predictors of worse outcome such as hypoalbuminemia, high tumour burden, elevated serum lactate dehydrogenase (LDH), lymphopenia as well as advanced PS [5,6,7,8,9]. 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)
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