Cost-effectiveness of trifluridine/tipiracil for previously treated metastatic colorectal cancer in England and Wales

Background Treatment options at third-line and beyond for patients with late-line metastatic colorectal cancer (mCRC) are limited, and outcomes are poor with best supportive care (BSC). This study investigated the cost-effectiveness of trifluridine/tipiracil and regorafenib relative to BSC alone in patients with mCRC who have been previously treated with, or are not considered candidates for, standard chemotherapies. Materials and Methods A partitioned survival model was constructed to assess the lifetime costs and benefits accrued by patients. Clinical data were derived from the pivotal phase III (Randomized, Double-Blind, Phase 3 Study of TAS-102 plus Best Supportive Care [BSC] versus Placebo plus BSC in Patients with Metastatic Colorectal Cancer Refractory to Standard Chemotherapies [RECOURSE]) and supporting phase II (J003-10040030) randomized controlled trial of trifluridine/tipiracil + BSC versus placebo + BSC, as well as the phase III Colorectal Cancer Treated With Regorafenib or Placebo After Failure of Standard Therapy (CORRECT) randomized controlled trial of regorafenib, and were extrapolated to estimate lifetime outcomes. Costs were taken from published sources, and health effects sourced from previous mCRC studies. Results Trifluridine/tipiracil was associated with a 0.27 incremental life year versus BSC alone, which corresponds to a 0.17 quality-adjusted life year gain. The incremental cost of treatment with trifluridine/tipiracil was £8,479, resulting in an incremental cost-effectiveness ratio of £51,194 per quality-adjusted life year gained. Trifluridine/tipiracil was shown to dominate regorafenib (improve outcomes with reduced costs). Sensitivity analyses showed principal areas of uncertainty were survival estimates and patient utility. Conclusions The results show that trifluridine/tipiracil is more clinically and cost-effective than regorafenib, with clinical outcomes greatly exceeding those for patients treated with BSC alone. Based on the results of the analysis, trifluridine/tipiracil offers an important new treatment option for patients with mCRC maintaining good performance status at the end of life

Status of the Stardust ISPE and the Origin of Four Interstellar Dust Candidates

Some bulk properties of interstellar dust are known through infrared and X-ray observations of the interstellar medium. However, the properties of individual interstellar dust particles are largely unconstrained, so it is not known whether individual interstellar dust particles can be definitively distinguished from interplanetary dust particles in the Stardust Interstellar Dust Collector (SIDC) based only on chemical, mineralogical or isotopic analyses. It was therefore understood from the beginning of the Stardust Interstellar Preliminary Examination (ISPE) that identification of interstellar dust candidates would rest on three criteria - broad consistency with known extraterrestrial materials, inconsistency with an origin as secondary ejecta from impacts on the spacecraft, and consistency, in a statistical sense, of observed dynamical properties - that is, trajectory and capture speed - with an origin in the interstellar dust stream. Here we quantitatively test four interstellar dust candidates, reported previously [1], against these criteria

Four Interstellar Dust Candidates from the Stardust Interstellar Dust Collector

In January 2006, the Stardust sample return capsule returned to Earth bearing the first solid samples from a primitive solar system body, Comet 81P/Wild2, and a collector dedicated to the capture and return of contemporary interstellar dust. Both collectors were approx. 0.1 sq m in area and were composed of aerogel tiles (85% of the collecting area) and aluminum foils. The Stardust Interstellar Dust Collector (SIDC) was exposed to the interstellar dust stream for a total exposure factor of 20 sq m/day. The Stardust Interstellar Preliminary Examination (ISPE) is a consortium-based project to characterize the collection using nondestructive techniques. The goals and restrictions of the ISPE are described . A summary of analytical techniques is described

Constraining the Origin of Impact Craters on Al Foils from the Stardust Interstellar Dust Collector

Preliminary examination (PE) of the aerogel tiles and Al foils from the Stardust Interstellar Dust Collector has revealed multiple impact features. Some are most likely due to primary impacts of interstellar dust (ISD) grains, and others are associated with secondary impacts of spacecraft debris, and possibly primary impacts of interplanetary dust particles (IDPs) [1, 2]. The current focus of the PE effort is on constraining the origin of the individual impact features so that definitive results from the first direct laboratory analysis of contemporary ISD can be reported. Because crater morphology depends on impacting particle shape and composition, in addition to the angle and direction of impact, unique particle trajectories are not easily determined. However, elemental analysis of the crater residues can distinguish real cosmic dust from the spacecraft debris, due to the low cosmic abundance of many of the elements in the spacecraft materials. We present here results from the elemental analysis of 24 craters and discuss the possible origins of 4 that are identified as candidate ISD impact

Microanalysis of Hypervelocity Impact Residues of Possible Interstellar Origin

The NASA Stardust spacecraft deployed two collector trays, one dedicated to the collection of dust from Comet Wild 2, and the other for the capture of interstellar dust (ISD). The samples were returned successfully to Earth in 2006, and now provide an unprecedented opportunity for laboratory-based microanalysis of materials from the outer solar system and beyond. Results from the cometary sample studies have demonstrated that Wild 2 contains much more refractory condensate material and much less pristine extra-solar material than expected, which further indicates that there was significant transport of inner solar system materials to the Kuiper Belt in the early solar system [1]. The analysis of the interstellar samples is still in the preliminary examination (PE) phase, due to the level of difficulty in the definitive identification of the ISD features, the overall low abundance, and its irreplaceable nature, which necessitates minimally invasive measurements [2]. We present here coordinated microanalysis of the impact features on the Al foils, which have led to the identification of four impacts that are possibly attributable to interstellar dust. Results from the study of four ISD candidates captured in aerogel are presented elsewhere [2]

Neuroblastoma chemotherapy can be augmented by immunotargeting O-acetyl-GD2 tumor-associated ganglioside

International audienc

Regulation of hepatokine gene expression in response to fasting and feeding: Influence of PPAR-α and insulin-dependent signalling in hepatocytes

International audienc