The Hammersmith Score Optimises Patient Selection and Predicts for Overall Survival in Early-Phase Cancer Trial Participants Independent of Tumour Burden.

INTRODUCTION: As tumour response rates are increasingly demonstrated in early-phase cancer trials (EPCT), optimal patient selection and accurate prognostication are paramount. Hammersmith Score (HS), a simple prognostic index derived on routine biochemical measures (albumin <35 g/L, lactate dehydrogenase >450 IU/L, sodium <135 mmol/L), is a validated predictor of response and survival in EPCT participants. HS has not been validated in the cancer immunotherapy era. METHODS: We retrospectively analysed characteristics and outcomes of unselected referrals to our early-phase unit (12/2019-12/2022). Independent predictors for overall survival (OS) were identified from univariable and multivariable models. HS was calculated for 66 eligible trial participants and compared with the Royal Marsden Score (RMS) to predict OS. Multivariable logistic regression and C-index was used to compare predictive ability of prognostic models. RESULTS: Of 212 referrals, 147 patients were screened and 82 patients treated in EPCT. Prognostic stratification by HS identifies significant difference in median OS, and HS was confirmed as a multivariable predictor for OS (HR: HS 1 vs. 0 2.51, 95% CI: 1.01-6.24, p = 0.049; HS 2/3 vs. 0: 10.32, 95% CI: 2.15-49.62, p = 0.004; C-index 0.771) with superior multivariable predictive ability than RMS (HR: RMS 2 vs. 0/1 5.46, 95% CI: 1.12-26.57, p = 0.036; RMS 3 vs. 0/1 6.83, 95% CI: 1.15-40.53, p < 0.001; C-index 0.743). CONCLUSIONS: HS is a validated prognostic index for patients with advanced cancer treated in the context of modern EPCTs, independent of tumour burden. HS is a simple, inexpensive prognostic tool to optimise referral for EPCT.

The level of endogenous DNA damage in lymphocytes isolated from blood is associated with the fluctuation of 17beta-estradiol concentration in the follicular phase of healthy young women.

The aim of this study was to evaluate whether the differences in plasma 17beta-estradiol concentration in early and late follicular phases of the menstrual cycle can affect the level of endogenous DNA damage in lymphocytes assessed by comet assay, and whether the extent of this damage in the follicular phase is associated with the genotype of catechol-O-methyltransferase (COMT). The level of DNA damage was positively correlated with 17beta-estradiol concentration only in the late follicular phase. Subjects with the COMT L/L homozygous mutated variant revealed more DNA damage as compared to individuals with the COMT wild-type and heterozygous (H/L+HH) genotype.