Discussion
cancers, cancer, tumour, deaths, Cancer
CANCER, CANCERS, TUMOUR, CANCER
Similar to other studies, we found the 90-day mortality rate in Phase I studies in our patient population to be ~17%, but treatment-related deaths were very rare [Compared to the original RMH score validation cohort [Our study is one of the first studies aiming to validate the RMH score in the Asian population participating in Phase 1 studies. Minami et al. [Although other groups have shown the prognostic ability of NLR [The NCIS score holds its place amongst prognostic scores. The inclusion of variables such as ECOG PS and tumour type does improve the predictive ability of the score. This was confirmed and applied in the MD Anderson Cancer Centre (MDACC) score which also incorporates ECOG PS and tumour type [A key strength of this study is the analysis of the prognostic scores’ predictive strengths over time, based on iAUC and AUC(As previously mentioned, another strength of the paper is that this is the first paper to validate the RMH score in a population of Asian Phase I patients, and one of the largest validation studies of Phase I patients in general. The NCIS prognostic score is also developed in patients on more contemporary treatments such as immunotherapy and vaccine therapy. While additional variables may be more challenging to apply in clinical practice, such information is routinely obtained and unlikely to be a hindrance. It would also be very possible to incorporate automated calculation onto electronic clinical records platforms to facilitate decision making, thus meaningful to validate this score prospectively.There are however limitations to this study. As a retrospective analysis, it is subject to selection bias. We attempted to minimise bias by having clear inclusion criteria and including all patients who met the inclusion criteria within the time frame of analysis. This resulted in a broad sample of various cancer types and histologies. We also recognise the varying prognosis of different cancers from the point of diagnosis, with the rapid progression of cancer therapy. Thus including all cancer types might appear to result in a highly heterogeneous population. The target population of our study however are cancer patients being considered for Phase I clinical trials, who are usually heavily pre-treated and have exhausted standard therapy. The outcome measure is survival from point of first visit, which is more homogeneous amongst different cancer types than overall survival from the point of diagnosis. Furthermore, a prediction of 90-day mortality from the time of study enrolment is a standard inclusion criterion for Phase I trials. Phase 1 studies consist of the basket and non-basket trials. Thus having a simple score that applies to all tumour types and different Phase 1 trial designs allow for easier and hence broader uptake at the point of the first visit. This is also a single-centre study with a modest sample size, and would require additional studies before clear conclusions can be made of the Asian oncology population at large. The limited sample size also resulted in inadequate power to establish statistical significance in the comparison of AUC(