ABSTRACT
Although comprehensive biomarker testing is recommended for all patients with advanced/metastatic non-small cell lung cancer (NSCLC) before initiation of first-line treatment, tissue availability can limit testing. Genomic testing in liquid biopsies can be utilized to overcome the inherent limitations of tissue sampling and identify the most appropriate biomarker-informed treatment option for patients. The Blood First Assay Screening Trial is a global, open-label, multicohort trial that evaluates the efficacy and safety of multiple therapies in patients with advanced/metastatic NSCLC and targetable alterations identified by liquid biopsy. We present data from Cohort D (ROS1-positive). Patients ≥18 years of age with stage IIIB/IV, ROS1-positive NSCLC detected by liquid biopsies received entrectinib 600 mg daily. At data cutoff (November 2021), 55 patients were enrolled and 54 had measurable disease. Cohort D met its primary endpoint: the confirmed objective response rate (ORR) by investigator was 81.5%, which was consistent with the ORR from the integrated analysis of entrectinib (investigator-assessed ORR, 73.4%; data cutoff May 2019, ≥12 months of follow-up). The safety profile of entrectinib was consistent with previous reports. These results demonstrate consistency with those from the integrated analysis of entrectinib in patients with ROS1-positive NSCLC identified by tissue-based testing, and support the clinical value of liquid biopsies to inform clinical decision-making. The integration of liquid biopsies into clinical practice provides patients with a less invasive diagnostic method than tissue-based testing and has faster turnaround times that may expedite the reaching of clinical decisions in the advanced/metastatic NSCLC setting. ClinicalTrials.gov registration: NCT03178552 .
Subject(s)
Benzamides , Carcinoma, Non-Small-Cell Lung , Indazoles , Lung Neoplasms , Protein-Tyrosine Kinases , Proto-Oncogene Proteins , Humans , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Carcinoma, Non-Small-Cell Lung/pathology , Indazoles/therapeutic use , Indazoles/adverse effects , Benzamides/therapeutic use , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Female , Male , Middle Aged , Aged , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins/metabolism , Protein-Tyrosine Kinases/antagonists & inhibitors , Protein-Tyrosine Kinases/genetics , Adult , Aged, 80 and over , Liquid Biopsy , Biomarkers, Tumor/genetics , Biomarkers, Tumor/metabolism , Protein Kinase Inhibitors/therapeutic use , Protein Kinase Inhibitors/adverse effectsABSTRACT
Poly(3-hexylthiophene) (P3HT) is a polymer used in organic solar cells as a light absorber and an electron donor. Photogenerated excitons diffuse and dissociate into free charge carriers provided they reach the absorber boundaries. The device efficiency is therefore dependent on the exciton diffusion. Although measurements can be performed for example by time-resolved photoluminescence, a quantitative modeling is highly desirable to get an insight into the relationship between the atomic structure at finite temperature and the diffusion coefficient of the exciton. This is the objective of the present work, achieved by resorting to first-principles molecular dynamics in combination with the restricted open-shell approach to model the singlet excited state. The maximally localized Wannier functions and their centers are used to monitor and localize the electron and the hole along the dynamics. The resulting diffusion coefficient is in close agreement with available measurements.
ABSTRACT
The human papillomavirus (HPV) is a major public health concern affecting both females and males. HPV is associated with cervical, anal, head and neck cancers. About 99% of all cervical cancers are related to HPV. HPV vaccines, Gardasil, Cervarix, and Gardasil 9 are used in the primary prevention of HPV related cancers. Gardasil and Gardasil 9 are available for use in both females and males ages 9 to 26, while Cervarix is available for females ages 9 to 25. Gardasil 9 was approved by the FDA for prevention against additional HPV types. Despite the availability of this preventative measure against cervical cancer, the rate of HPV vaccination in the United States remains lower than that of other industrialized nations. The purpose of this study is to elucidate mechanisms to help increase the HPV vaccination rate by using education as a tool; by simplifying the president report so that lay person can understand the information presented in the report. Through the quantitative examination of the data from the states with the lowest and highest vaccination rates, using SPSS statistical analysis; we analyzed several factors involved with the low uptake of the vaccines. The results collected show that socioeconomic status, misconceptions about HPV, and misconceptions about the safety of the vaccines were identified as possible obstacles to the effective uptake of HPV vaccinations. The proposals made by the President's Cancer Panel to accelerate the uptake of vaccines include, increasing coverage of the vaccines through government-sponsored programs, and the Affordable Care Act; increasing accessibility to vaccines through pharmacies, schools, and clinics; and disseminating more information on HPV to healthcare providers, parents, caregivers, and patients. Allowing greater accessibility to the vaccines for all populations regardless of income, education, and eliminating misconceptions of the vaccines would play a significant role in eliminating cancer.