Depth of response may predict clinical outcome in patients with recurrent/metastatic head and neck cancer treated with pembrolizumab-containing regimens

BackgroundPembrolizumab-containing regimens are standards of care for recurrent and metastatic head and neck squamous cell carcinoma (R/M HNSCC). The depth of response (DpR) predicts the survival of patients with several types of solid cancers; however, its association with the survival outcomes of patients with R/M HNSCC treated with pembrolizumab-containing regimens remains unclear.MethodsThis study included 66 patients with R/M HNSCC who received a pemblolizumab-containing regimen as a first-line therapy at Tohoku University Hospital, Sendai, Japan. The patients’ characteristics, combined positive score, baseline tumor size, tumor response, DpR, overall survival (OS), progression-free survival (PFS), PFS2, and adverse events were reviewed. The associations between DpR and survival outcomes were analyzed.ResultsThe 1 year-OS and 1 year-PFS rates of pembrolizumab-containing regimens were 69.4% and 24.4%, respectively. The response rate was 28.8%. The mean and median values of tumor change from baseline were 5.1% and −9.0%. In the correlation analysis, a significant negative correlation was observed between tumor change rate from baseline and survival outcomes (OS: r= −0.41, p=0.0017; PFS: r=−0.49, p<0.001). In the multivariate analysis, DpR with tumor change of ≤−45 was associated with better OS and PFS.ConclusionDpR induced by pembrolizumab-containing regimens may be a predictive factor for OS and PFS in patients with R/M HNSCC

Phase II study of trifluridine/tipiracil (TAS‑102) therapy in elderly patients with colorectal cancer (T‑CORE1401): geriatric assessment tools and plasma drug concentrations as possible predictive biomarkers

Purpose The current study aimed to determine the efficacy of trifluridine/tipiracil for elderly patients with advanced colorectal cancer. Methods This single-arm, open-label, multicenter, phase II study included elderly patients aged 65 years or more who had fluoropyrimidine-refractory advanced colorectal cancer and received trifluridine/tipiracil (70 mg/m2, days 1–5 and 8–12, every 4 weeks). The primary endpoint was progression-free survival (PFS), while secondary endpoints included overall survival (OS), overall response rate (ORR), toxicities, association between efficacy and geriatric assessment scores, and association between toxicity and plasma drug concentrations. Results A total of 30 patients with a mean age of 73 years were enrolled. Median PFS was 2.3 months (95% confidence interval, 1.9–4.3 months), while median OS was 5.7 months (95% confidence interval, 3.7–8.9 months). Patients had an ORR of 0%, with 57% having stable disease. Grade 4 neutropenia was observed in 13% of the patients. Patients with a higher G8 score (15 or more) showed longer PFS than those with a lower G8 score (median 4.6 vs. 2.0 months; p = 0.047). Moreover, patients with grade 3 or 4 neutropenia showed higher maximum trifluridine concentrations than those with grade 1 or 2 neutropenia (mean 2945 vs. 2107 ng/mL; p = 0.036). Discussion The current phase II trial demonstrated that trifluridine/tipiracil was an effective and well-tolerated option for elderly patients with advanced colorectal cancer. Moreover, geriatric assessment tools and/or plasma drug concentration monitoring might be helpful in predicting the efficacy and toxicities in elderly patients receiving this drug. Trial registration number UMIN000017589, 15/May/2015 (The University Hospital Medical Information Network

Therapeutic Potential of HDL in Cardioprotection and Tissue Repair

Epidemiological studies support a strong association between high-density lipoprotein (HDL) cholesterol levels and heart failure incidence. Experimental evidence from different angles supports the view that low HDL is unlikely an innocent bystander in the development of heart failure. HDL exerts direct cardioprotective effects, which are mediated via its interactions with the myocardium and more specifically with cardiomyocytes. HDL may improve cardiac function in several ways. Firstly, HDL may protect the heart against ischaemia/reperfusion injury resulting in a reduction of infarct size and thus in myocardial salvage. Secondly, HDL can improve cardiac function in the absence of ischaemic heart disease as illustrated by beneficial effects conferred by these lipoproteins in diabetic cardiomyopathy. Thirdly, HDL may improve cardiac function by reducing infarct expansion and by attenuating ventricular remodelling post-myocardial infarction. These different mechanisms are substantiated by in vitro, ex vivo, and in vivo intervention studies that applied treatment with native HDL, treatment with reconstituted HDL, or human apo A-I gene transfer. The effect of human apo A-I gene transfer on infarct expansion and ventricular remodelling post-myocardial infarction illustrates the beneficial effects of HDL on tissue repair. The role of HDL in tissue repair is further underpinned by the potent effects of these lipoproteins on endothelial progenitor cell number, function, and incorporation, which may in particular be relevant under conditions of high endothelial cell turnover. Furthermore, topical HDL therapy enhances cutaneous wound healing in different models. In conclusion, the development of HDL-targeted interventions in these strategically chosen therapeutic areas is supported by a strong clinical rationale and significant preclinical data.status: publishe

Production of various ion species by gas pulsing technique for multi ion irradiation at NIRS-HEC ion source

High-energy carbon-ion radiotherapy is being carried out at Heavy Ion Medical Accelerator in Chiba (HIMAC). Over 11000 cancer patients have been treated with carbon beams having energies of between 56-430 MeV/u since 1994. At present, multi ion irradiation method by various ion species is being studied for optimization of LET and dose distribution. An ion source has to produce the helium, carbon, oxygen and neon at pulse by pulse for this method. Requirement currents for He2+, C2+, O3+ and Ne4+ are 500, 150, 230 and 300 euA, respectively. We obtained beam current of 482, 151, and 270 euA for He2+, C2+ and O3+ with mixed helium and CO2 gases under the extraction voltage of 27 kV. Beam current of 27 and 15 euA for C5+ and O7+ ions were also obtained in this time. He2+ beam include full striped ion such as C6+, N7+ and O8+. We have to increase the purity of He2+ beam. The gas feed system was modified for making pulsed gas by using a solenoid valve for switching different gas. Some experimental results of various ion productions will be described.23rd International workshop on ECR ion sources (ECRIS2018)

Antibiotics Improve the Treatment Efficacy of Oxaliplatin-Based but Not Irinotecan-Based Therapy in Advanced Colorectal Cancer Patients

Background. Oxaliplatin and irinotecan are generally used to treat advanced colorectal cancer (CRC) patients. Antibiotics improve the cytotoxicity of oxaliplatin but not irinotecan in a colon cancer cell line in vitro. This study retrospectively assessed whether antibiotics improve the treatment efficacy of oxaliplatin- but not irinotecan-based therapy in advanced CRC patients. Patients and Methods. The medical records of 220 advanced CRC patients who underwent oxaliplatin- or irinotecan-based therapy were retrospectively reviewed. The oxaliplatin and irinotecan groups were further divided into antibiotic-treated (group 1) and antibiotic-untreated (group 2) subgroups. Results. In oxaliplatin groups 1 and 2, the response rate (RR) was 58.2% and 30.2%, while the disease control rate (DCR) was 92.5% and 64.2%, respectively; the median progression-free survival (PFS) was 10.5 months (95% confidence interval (CI) = 7.5–12.2) and 7.0 months (95% CI = 17.0–26.0), respectively, and the median overall survival (OS) was 23.8 months (95% CI = 5.1–9.1) and 17.4 months (95% CI = 13.1–24.9), respectively. In irinotecan groups 1 and 2, the RR was 17.8% and 20.0%, while the DCR was 75.6% and 69.1%, respectively; the median PFS was 8.2 months (95% CI = 6.2–12.7) and 7.9 months (95% CI = 12.0–23.0), respectively, and the median OS was 16.8 months (95% CI = 5.9–10.6) and 13.1 months (95% CI = 10.4–23.7), respectively. Conclusion. To improve the treatment efficacy of oxaliplatin-based therapy in advanced CRC patients, adding antibiotics is a potential therapeutic option

Additional file 2: Figure S1. of microRNA-193a-3p is specifically down-regulated and acts as a tumor suppressor in BRAF-mutated colorectal cancer

Correlations between the microarray results and the qPCR results in a screening set (n = 30). The signal intensities obtained by microarray analysis were well correlated with the expression results determined by qPCR for a miR-193a-3p and b miR-16. Pearson’s correlation coefficient was presented. (PPTX 42 kb

Concept design of new compact electron cyclotron resonance ion source with permanent magnets for multi-ion radiotherapy.

The multi-ion radiotherapy with dose distribution and Liner Energy Transfer optimization is being studied at QST. Helium, carbon, oxygen and neon ions are considered as ion species for multi-ion therapy. A basic experiment using these ion beams has been carried out at the HIMAC. For heavy-ion radiotherapy facility, it is desirable to operate with only one ECR ion source. We considered the operating method with only one ion source for multi-ion radiotherapy. Ionization gases were helium, methane, oxygen, and neon to produce He2+, C4+, O6+ and Ne7+ ions. Requirement values of beam current were 940 µA correspond to He2+, 290 µA to C4+, 330 µA to O6+, and 245 µA to Ne7+, respectively. This value was obtained from the number of particles required for the cancer treatment and the transmission efficiency of the accelerator in the HIMAC. We performed some beam tests for design of a new compact ion source with the existing 18 GHz ECR ion source (NIRS-HEC). From the results of the beam tests, we estimate the mirror magnetic field ofNIRS-HEC by using POISSON/SUPERFISH code. Then, the structure of the permanent magnets for new ECR ion source is determined so that they reproduce the values of the upstream mirror peak (Binj), B minimum (Bmin) and the downstream mirror peak (Bext) at the NIRS-HEC. The magnetic field of Binj, Bmin and Bext at NIRS-HEC were 1.14 T, 0.475 T and 0.9 T, respectively.We will describe about the beam tests with the NIRS-HEC and design of the new compact ECR ion source