The majority of published studies in recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) are single-arm trials. Reliable modelling of progression-free survival (PFS) and overall survival (OS) ...outcomes, therefore, is difficult. This study aim to analyse existent literature to estimate the relative efficacy of available systemic regimens in RM-NPC, as well as provide estimates of aggregate OS and PFS.
We conducted a systematic search of MEDLINE, EMBASE and the Cochrane Library to March 2015. Clinical trials (in English only) investigating cytotoxic and molecularly targeted agents in adult patients with RM-NPC were included. All relevant studies were assessed for quality using Downs and Blacks (DB) checklist (maximum quality score of 27). Aggregate data analysis and Student's t-test were performed for all identified studies (model A). For studies that published analysable Kaplan-Meier curves, survival data were extracted and marginal proportional hazards models were constructed (model B).
A total of 56 studies were identified and included in model A, 26 of which had analysable Kaplan-Meier curves and were included in model B. The 26 studies in model B had significantly higher mean DB scores than the remaining 30 (17.3 vs 13.7, P=0.002). For patients receiving first line chemotherapy, the estimated median OS was 15.7 months by model A (95% CI, 12.3-19.1), and 19.3 months by model B (95% CI, 17.6-21.1). For patients undergoing second line or higher therapies (2nd+), the estimated median OS was 11.5 months by model A (95% CI 10.1-12.9), and 12.5 months by model B (95% CI 11.9-13.4). PFS estimates for patients undergoing first-line chemotherapy by model A was 7.6 months (95% CI, 6.2-9.0), and 8.0 months by model B (95% CI, 7.6-8.8). For patients undergoing therapy in the 2nd+ setting, the estimated PFS by model A was 5.4 months (95% CI, 3.8-7.0), and 5.2 months by model B (95% CI, 4.7-5.6).
We present the first aggregate estimates of OS and PFS for RM-NPC patients receiving first and second-line or higher treatment settings, which could inform the design of future clinical trials in this disease setting.
Following initial characterization of the reference human genome, initiatives have evolved worldwide to identify genomic aberrations in cancer with the aim of deriving diagnostic, prognostic and ...predictive information. However, the functional and clinical relevance of many somatic variants in cancer are presently unknown and there is no consensus definition of ‘actionability’ for genomic aberrancies. Therefore, while robust detection of a variety of genetic aberrations in clinical specimens remains a technical hurdle, the greater challenge lies in the interpretation of these alterations. Critical evaluation of genomic variation in cancer requires the integration of available clinical and preclinical evidence related to their frequencies, functions and roles as therapeutic targets. Many publicly accessible data resources have compiled such evidence to facilitate the understanding of genomic results and ultimately translating results to clinical action. Information for these data resources is derived from various sources including large population genomic datasets, curation of published literature, and data sharing by the scientific community. Currently, there is no widely accepted guidance to definitively assess and integrate the diagnostic, prognostic and predictive information of somatic variants using these knowledge databases. This review will describe data resources pertinent to the identification and interpretation of actionable genomic aberrations by clinicians, and highlight relevant issues in the clinical application of tumor molecular profiling results.
Deregulation of the PI3K signalling pathway is frequent in squamous cell carcinoma of the head and neck (SCCHN) and may be implicated in radioresistance. We report on the results from a phase I 3 + 3 ...dose escalation study of alpelisib, a class I α-specific PI3K inhibitor in combination with concurrent cisplatin-based chemoradiation (CRT) in patients with locoregionally advanced SCCHN (LA-SCCHN).
Eligible patients had previously untreated LA-SCCHN and were candidates for CRT. The primary objective was to evaluate safety and determine the recommended phase II dose (RP2D). Alpelisib was given orally once daily at two dose levels: 200 mg and 250 mg. CRT consisted of cisplatin 100 mg/m2 IV every three weeks and standard fractionation radiotherapy (IMRT) 70 Gy in 35 fractions.
Nine patients were enrolled (six alpelisib 200 mg, three 250 mg). Oropharynx was the primary site in all patients (seven p16-positive; five T1-2N2M0, four T3-4N2-3M0 AJCC 7th edition). All patients completed CRT within seven weeks. Grade 3 alpelisib-related toxicities occurred in four patients. No dose-limiting toxicity (DLT) was observed at 200 mg among three DLT-evaluable patients. Two of two DLT-evaluable patients treated at 250 mg experienced DLTs (inability to complete ≥75% alpelisib secondary to radiation dermatitis and febrile neutropenia). Thus, RP2D was declared at 200 mg. After median follow-up of 39.7 months, two patients developed pulmonary metastases despite locoregional control. Three-year overall survival was 77.8% (95% CI 36.5%–93.9%).
Alpelisib at 200 mg has a manageable safety profile in combination with cisplatin-based CRT in LA-SCCHN.
Abstract
Human activity causes water pollution in Situ Cikaret and Situ Cilodong, in Bogor and Depok, West Java, respectively. The pollutant and toxicant altered the behaviour, anatomy, and ...physiology of fish in those habitats. This study aimed to analyze the histopathological features of fish gills in Situ Cikaret and Situ Cilodong. The physical and chemical parameters, including pH, temperature, and dissolved oxygen (DO), were measured. Four fish species, Spotted barb fish (
Barbodes binotatus
), Amazon sailfin catfish (
Pterygoplichthys pardalis
), Yellow rasbora fish (
Rasbora lateristriata
), and Louhan fish (
Amphilopus citrinellus
) were collected. The gills were processed with paraffin, cut into 5 μm, and stained with hematoxylin-eosin. The histological features of Amazon sailfin catfish showed a normal feature, whilst the others showed an abnormality, including hyperplasia, leucocyte proliferation, secondary lamella fusion, vasodilatation, oedema, necrosis, and hypertropia mucus cells, and chloride cells. Although the temperatures, pH, and DO in this study were within the normal values, the abnormality of histological features indicated that Situ Cikaret and Situ Cilodong were polluted.
Next-generation sequencing (NGS) diagnostics have shown clinical utility in predicting survival benefits in patients with certain cancer types who are undergoing targeted drug therapies. Currently, ...there are no guidelines or recommendations for the use of NGS in patients with metastatic cancer from an Asian perspective. In this article, we present the Asia-Pacific Oncology Drug Development Consortium (APODDC) recommendations for the clinical use of NGS in metastatic cancers.
The APODDC set up a group of experts in the field of clinical cancer genomics to (i) understand the current NGS landscape for metastatic cancers in the Asia-Pacific (APAC) region; (ii) discuss key challenges in the adoption of NGS testing in clinical practice; and (iii) adapt/modify the European Society for Medical Oncology guidelines for local use. Nine cancer types breast cancer (BC), gastric cancer (GC), nasopharyngeal cancer (NPC), ovarian cancer (OC), prostate cancer, lung cancer, and colorectal cancer (CRC) as well as cholangiocarcinoma and hepatocellular carcinoma (HCC) were identified, and the applicability of NGS was evaluated in daily practice and/or clinical research. Asian ethnicity, accessibility of NGS testing, reimbursement, and socioeconomic and local practice characteristics were taken into consideration.
The APODDC recommends NGS testing in metastatic non-small-cell lung cancer (NSCLC). Routine NGS testing is not recommended in metastatic BC, GC, and NPC as well as cholangiocarcinoma and HCC. The group suggested that patients with epithelial OC may be offered germline and/or somatic genetic testing for BReast CAncer gene 1 (BRCA1), BRCA2, and other OC susceptibility genes. Access to poly (ADP-ribose) polymerase inhibitors is required for NGS to be of clinical utility in prostate cancer. Allele-specific PCR or a small-panel multiplex-gene NGS was suggested to identify key alterations in CRC.
This document offers practical guidance on the clinical utility of NGS in specific cancer indications from an Asian perspective.
•Clinical adoption of NGS is heterogeneous in the APAC region due to diversity in access, practice guidelines, and funding.•The APODDC group recommends routine NGS testing for daily practice in patients presenting with advanced NSCLC.•Routine multigene NGS testing is not recommended in metastatic GC, cholangiocarcinoma, NPC, BC, and HCC.•In research centres with molecular screening programs, NGS can enhance understanding of promising targets in OC.•Allele-specific PCRs or a small-panel, multiplex-gene NGS testing was suggested to identify key alterations in CRC.
Background: PTC596 is a first-in-class, oral investigational new drug that reduces levels of BMI1, a protein required for CSC survival. PTC596 reduced the number of CSCs in preclinical models and ...slowed growth rates of several tumor xenografts. The primary objectives of this first-inhuman trial of PTC596 are to determine safety, dose-limiting toxicities (DLTs), maximum tolerated dose (MTD), and pharmacokinetics (PK). Secondary objectives include initial assessment of biological efficacy, pharmacodynamic changes and anti-tumor activity. Methods: A 2-stage. Phase I multi-center study is being conducted in patients with advanced solid tumors. PTC596 is administered in 4 week cycles using bodyweight-adjusted twice-per-week (biw) oral dosing. Stage 1 involves dose escalation using a modified 3+3 design. Anti-tumor activity is assessed by RECIST 1.1. Additional cohorts are being enrolled to obtain pre- and post-treatment (C2D1) tumor biopsies for markers of target engagement. In stage 2, up to 40 patients with a limited number of tumor types will be enrolled at the recommended Phase 2 dose (RP2D). Patients who derive benefit may remain on PTC596. Results: To date, 18 patients have been enrolled at doses of 0.65 (N = 3), 1.3 (N = 3). 2.6 (N = 3), 5.2 (N = 6) and 10 mg/kg (N = 3). No DLTs or drug related grade 2 toxicities were observed in the first 3 cohorts. Grade 1 nausea and vomiting were seen at these lower doses. Grade 2 diarrhea was seen in 2 patients dosed at 5.2 mg/kg. Though a protocol defined MTD was not reached, the dose of 10mg/kg was deemed intolerable due to Grade 2 nausea, vomiting, and diarrhea in 2 of 3 patients. One Grade 4 DLT of neutropenia and thrombocytopenia was observed in a patient receiving 10.0 mg/kg. An intermediate dosing cohort at 7.0 mg/kg has been initiated. Over the dosing range, plasma concentrations of PTC596 increased in an approximately dose-proportional manner. Though no objective responses have been observed to date, at doses of ^2.6 mg/kg biw, plasma concentrations of PTC596 exceed those demonstrated to be efficacious in mouse xenograft models. Conclusion: PTC596 lowers levels of BMI1 in preclinical tumor models and is generally well tolerated as a monotherapy at doses that result in preclinical target plasma concentrations.
This study aims to determine and analyze the effect of social shopping, adventure shopping, value shopping, relaxation shopping, and idea shopping in influencing impulsive online buying behavior ...moderated by scarcity and serendipity information. The research method used is the quantitative research paradigm using surveys as a medium to obtain primary data. The paper examines the theoretical research model and tested fifteen hypotheses. The questionnaire was developed based on indicators from previous research. A non-probability sampling framework is used in this study. The data collection method uses electronic and online questionnaires to collect primary data with a total sample of 330 taken with the criteria of having made transactions in e-commerce Shopee in the last three months. Data analysis tools using Structural Equation Modelling (SEM) approach. The results showed that 8 out of 15 hypotheses were accepted and supported. The results show that there is a relationship between the value of hedonic shopping, scarcity, and serendipity information on impulsive online buying behavior. Therefore, analyzing the needs of customers, optimizing customer satisfaction, service excellence, website quality, and the ease of use of e-shopping itself especially in the e-commerce industry should be taken seriously nowadays. KCI Citation Count: 0
Krueng Raya waters in Aceh Besar and Lhok Kruet waters in Aceh Jaya are quiet potential for lift net fishing. Lift net fishermen in both areas have different operational technique and characteristic. ...This research aimed to describe how lift net operates and to analyze fishing catch of lift net in Krueng Raya and Lhok Kruet waters. This research had been done from October until November 2017 in Lhok Kruet and January 2018 in Krueng Raya. The fishing process was analyzed through onboard observation during fishing operation and interviewing to the lift net's fishermen. Operational technique and fishing catch composition are the data that would be analyzed in this research. The research result showed differences both of operational technique specifically in the setting process and fishing catch composition of lift nets in Krueng Raya and Lhok Kruet. Lift net setting in Krueng Raya started with lowering the net from abaft while in Lhok Kruet the net will be lowering from the bottom of the chart. The total number of catch in Krueng Raya is 22.890 kg, and Lhok Kruet is 2.400 kg. However, lift net in Krueng Raya only catched squid meanwhile in Lhok Kruet had grouper seed and snapper as their fishing catch.
This paper propose a preprocessing techniques in lung segmentation scheme using Anisotropic Diffusion filters. The aim is to improve the accuracy, sensitivity and specificity results of segmentation. ...This method was chosen because it has the ability to detect the edge, namely in doing smoothing, this method can obscure noise, while maintaining the edges of objects in the image. Characteristics such as this is needed to process medical image filter, where the boundary between the organ and the background is not so clear. The segmentation process is done by K-means Clustering and Active Contour to segment the lungs. Segmentation results were validated using the Receiver Operating Characteristic (ROC) showed an increased accuracy, sensitivity and specificity, when compared with the results of segmentation in the previous paper, in which the preprocessing method used is Gaussian Lowpass filter.
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