No abstract

Pretreatment detection of peripheral blood malignant circulating plasma cells (CPCs) has been shown to be of negative prognostic value in multiple myeloma (MM). We hypothesized that the assessment of CPC kinetics in response to one therapy cycle using six-color flow cytometry could be helpful in the early detection of MM refractoriness to treatment. Forty-two patients with refractory or relapsed (RR) MM were enrolled. Median time to tumor progression (TTP) of 51 days and median overall survival (OS) of 308 days was shortest in patients whose CPCs with aberrant phentoype (aCPCs) did not decrease after one therapy cycle compared to patients with decreasing (median TTP 258 days and OS 856 days) or undetectable (median TTP 581 days and OS 1006 days) aCPCs (p < 0.001 and p = 0.007 for TTP and OS, respectively). Non-reduction of aCPCs in patients with RR MM after the first cycle of therapy may be useful in early identification of patients resistant to a given therapy.

Background The high prevalence of cardiovascular diseases cannot be explained completely by conventional risk factors such as older age, smoking, diabetes mellitus, hypertension, obesity, and dyslipidemia. Results of recent studies indicate that chronic stress may be an independent risk factor for cardiovascular morbidity and mortality. Thus, the aim of our study was to investigate the associations between the hair cortisol concentration (HCC), which is considered as a potential biomarker of long-term psychosocial stress, and traditional cardiovascular risk factors, including smoking, dyslipidemia, hypertension, and obesity. Material/Methods Fasting blood samples and anthropometric and lifestyle data were collected from 163 apparently healthy men. HCC was determined using high-performance liquid chromatography. Allostatic load (AL) index, defined as an integrated score of multiple interacting systems involved in the adaptation to adverse physical or psychosocial situations, was also calculated. Results We found that many prevalent cardiovascular risk factors, including hypertension, smoking, higher than recommended waist circumference (WC), and low-density lipoprotein cholesterol (LDL-C) median values, are associated with higher HCC. Hair cortisol level was also positively associated with the manifestation of individual cardiovascular risk factors such as higher-than-recommended total cholesterol, LDL-C, non-high-density lipoprotein cholesterol, body mass index, and WC median values. Moreover, a significant positive relationship between HCC and AL index was observed. Conclusions The results of this study suggest that increased prevalence of traditional cardiovascular risk factors is associated with higher HCC. Also, both HCC and AL index might be appropriate markers for the evaluation of chronic stress level.

No abstract

optimization of adjuvant chemotherapy, and early detection of recurrence. We present here the study design of an ongoing trial.Trial design: GALAXY (UMIN000039205) is a prospective observational study to monitor the ctDNA status and to establish the registry data in patients with resectable CRC who underwent radical surgery. The study utilizes a personalized, tumor-informed ctDNA assay that is designed to track 16 patient-specific somatic variants (SignateraÔ bespoke multiplex-PCR NGS assay) based on whole-exome sequencing of tumor tissue sample. Blood samples will be collected at the following time points: at pre-surgery and 1, 3, 6, 9, 12, 18, and 24 months post-surgery, and at the same time the computed tomography (CT) image will be performed. Mutations in RAS, BRAF and microsatellite instability tests by validated PCR methods will be assessed centrally. Key eligibility criteria include histologically confirmed colorectal adenocarcinoma and clinical stage IIeIV or relapsed disease amenable to radical surgical resection. The primary endpoint is disease-free survival. Key secondary endpoints are overall survival, ctDNA status at each time point, association between clinical characteristics and gene alterations, and association between ctDNA detection and relapse detection by the CT image (that is, whether ctDNA monitoring could replace the CT image). There is no pre-planned statistical hypothesis due to the nature of observational study. Target sample size is 2,500 patients. Based on ctDNA results in the GALAXY trial, patients can be enrolled in investigator-initiated phase 3 trials, either the VEGA (deescalation) or the ALTAIL trial (escalation). The VEGA trial assesses the non-inferiority of observation vs. adjuvant CAPOX in GALAXY participants with an absence of ctDNA 1 month post-surgery. The ALTAIR trial evaluates the superiority of FTD/TPI over placebo in GALAXY participants with ctDNA status that remains positive after standard therapy. Moreover, additional tumor tissue and blood samples will be banked for further translational research.