A Pilot Basket Study to Evaluate Multi-Analyte Liquid Biopsies for Personalized Treatments in Advanced Refractory Cancers

Prior attempts at personalizing anticancer treatments based on univariate tumor profiling (single gene variant) for selection of monotherapy with targeted agents (single drug) have generally yielded poor response rates. We report findings from the LIQUID IMPACT pilot trial where Multi-analyte Liquid Biopsy (MLB) profiling of circulating tumor analytes in peripheral blood was used to inform selection of personalized combination regimens in advanced refractory cancers. Among the 43 patients evaluable as per study protocol, 34 had targetable pathway activations. Partial Response (PR) was observed in 14 (41.1%) of the 34 patients with signaling pathway activation, including 5 (50%) of 10 cases with mTOR activation, 8 (44.4%) of 18 cases with activation of angiogenesis and 4 (50.0%) of 8 cases with EGFR / ERBB2 activation. PR was not reported among the 9 cases with no detectable pathway activation. Toxicities were manageable and there were no treatment related deaths. The study findings suggest that MLB may be able to inform safe and efficacious combination regimens in patients with advanced refractory cancers.

Cavitation upon low-speed solid–liquid impact

When a solid object impacts on the surface of a liquid, extremely high pressure develops at the site of contact. Von Karman’s study of this classical physics problem showed that the pressure on the bottom surface of the impacting body approaches infinity for flat impacts. Yet, in contrast to the high pressures found from experience and in previous studies, we show that a flat-bottomed cylinder impacting a pool of liquid can decrease the local pressure sufficiently to cavitate the liquid. Cavitation occurs because the liquid is slightly compressible and impact creates large pressure waves that reflect from the free surface to form negative pressure regions. We find that an impact velocity as low as ~3 m/s suffices to cavitate the liquid and propose a new cavitation number to predict cavitation onset in low-speed solid-liquid impact-scenarios. These findings imply that localized cavitation could occur in impacts such as boat slamming, cliff jumping, and ocean landing of spacecraft.

Study on Forming Characteristics of Natural Bulging Area of Metal Thin-walled Tube Under Liquid Impact Forming

Liquid Impact Forming (LIF) is a new composite forming technology based on Tube Hydroforming (THF) technology, which changes the volume of mould cavity through impact load and rapidly generates internal pressure to realize tube forming. It does not need external pressure supply source, and it is low cost and high efficiency. In order to study the forming characteristics of the natural bulging area of thin-walled metal tubes under different model side lengths and different model closing velocities, the change of the cavity volume of thin-walled metal tubes under impact hydraulic bulging was firstly analyzed theoretically, and a mathematical model of internal pressure was established. Then the effects of different loading parameters on the internal pressure, bulging height and wall thickness distribution in the natural bulging area of thin-walled metal tube were studied. Finally, through the comparison of finite element simulation analysis and experiment, it was found that the deviation between the experimental results and the numerical simulation was within 5%, which verified the accuracy and reliability of LIF. It also provides a certain theoretical research and application basis for the development of LIF of metal thin-walled tube.

Multi-Analyte Liquid Biopsies for Treatment Guidance in Advanced Refractory Cancers: Findings of the LIQUID IMPACT Trial

Background LIQUID IMPACT (CTRI/2019/02/017548) is a single arm, open label, phase II/III study to evaluate the feasibility of providing therapeutic guidance in cancers based on non-invasive interrogation of circulating tumor analytes in peripheral blood (Encyclopedic Liquid Biopsy: eLB). The study enrolled patients with solid organ cancers where the disease had progressed following systemic therapy failure, where no (further) viable standard of care (SoC) therapy options were available, and where invasive biopsies to obtain tumor tissue (for molecular profiling) were contraindicated. Methods Encyclopedic Liquid Biopsy (eLB) interrogated gene alterations in cell-free tumor DNA (ctDNA), and differentially expressed genes in exosomal mRNA. eLB also evaluated Circulating Tumor Associated Cells for expression of therapeutically relevant cell-surface signaling receptors as well as the chemoresistance profile towards systemic anticancer agents. Patients who received personalized combination therapy regimens based on eLB findings were evaluated radiologically to determine response to treatment, Objective Response Rate (ORR) and Quality of Life (QoL). Results At the time of submission of this manuscript, Partial Response (PR) was observed in 14 of 43 patients evaluable per protocol (ORR = 32.6%). Majority of patients reported stable to improved QoL. Conclusion The present study demonstrated that refractory cancers have latent vulnerabilities which can be identified via non-invasive eLB to design personalized label- and organ-agnostic treatment regimens to yield meaningful treatment benefit. Trial registration Clinical Trial Registry – India, CTRI/2019/02/017548 [Registered on: 02/08/2019] - http://ctri.nic.in/Clinicaltrials/pdf_generate.php?trialid=31265&EncHid=&modid=&compid=%27,%2731265det%27; Trial Registered Prospectively.

Frictional characteristics of thin-walled tubes in liquid impact forming

Purpose This paper aims to study frictional characteristics of thin-walled tubes in the liquid impact forming (LIF) process. Design/methodology/approach LIF experiments under various impacting velocities were performed on SUS304 stainless steel tubes with various guiding lengths on a custom-designed measurement system to investigate the effects of impacting velocity and guiding length on the coefficient of friction (COF) in the guiding zone. Findings The results indicate that the COF changes dynamically in the guiding zone and decreases with the deformation process. The reduction range of the COF is wider in LIF than in both the conventional and pulsating hydroforming (THF), which may be contributed to the impacting velocities in a short time. Moreover, the COF decreases faster in the first half of the LIF process than in the second half. Under different impacting velocities and guiding lengths, the decreasing rate of the COF in the first half is more sensitive and obvious than that in the second half. Originality/value A method for determining the COF in the guiding zone in LIF is proposed and the frictional characteristics in LIF are studied. Comparing the COF of tubes in conventional THF, pulsating THF and the LIF process is valuable for improving and predicting the tubular formability in various hydraulic environments for industrial production. Peer review The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-07-2019-0269