Real-world treatment patterns and outcomes among individuals receiving first-line pembrolizumab therapy for recurrent/metastatic head and neck squamous cell carcinoma

BackgroundPembrolizumab, a PD-1 immune checkpoint inhibitor, is approved as first-line (1L) treatment for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) as monotherapy or in combination with platinum and 5-fluorouracil chemotherapy. Limited data exist on the use of these regimens in real-world settings.ObjectiveOur primary objectives were to describe baseline characteristics and real-world overall survival (rwOS), time on treatment (rwToT), and time to next treatment (rwTTNT) among individuals with R/M HNSCC receiving approved 1L pembrolizumab therapies. We also aimed to identify baseline factors associated with choice of 1L pembrolizumab therapy and with rwOS.MethodsThis was a retrospective cohort study of adults with R/M HNSCC receiving 1L pembrolizumab monotherapy or pembrolizumab plus chemotherapy. We used Kaplan-Meier analyses to assess real-world outcomes, logistic regression modeling to identify factors associated with choice of 1L pembrolizumab therapy, and Cox proportional hazards models to identify factors associated with rwOS.ResultsThe study population included 431 individuals receiving 1L pembrolizumab monotherapy and 215 receiving 1L pembrolizumab plus chemotherapy. The use of 1L pembrolizumab monotherapy was associated with higher baseline combined positive score for PD-L1 expression, older age, higher Eastern Cooperative Oncology Group performance status (ECOG PS), laryngeal tumor site, and human papillomavirus (HPV)-positive tumor status. The pembrolizumab monotherapy group had a median (95% CI) rwOS of 12.1 (9.2–15.1) months, rwToT of 4.2 (3.5–4.6) months, and rwTTNT of 6.5 (5.4–7.4) months. Among this group, HPV-positive tumor status and lower ECOG PS were associated with longer rwOS, and oral cavity tumor site with shorter rwOS. The pembrolizumab plus chemotherapy cohort had a median (95% CI) rwOS of 11.9 (9.0–16.0) months, rwToT of 4.9 (3.8–5.6) months, and rwTTNT of 6.6 (5.8–8.3) months. In this group, HPV-positive tumor status was associated with longer rwOS.ConclusionsThis study adds to clinical trial data by summarizing real-world treatment outcomes with 1L pembrolizumab-containing therapies in a more heterogeneous population. Overall survival outcomes in both treatment groups were similar to those observed in the registration clinical trial. These findings support the use of pembrolizumab as standard of care for R/M HNSCC

Pengembangan Media Pembelajaran Matematika Berbantu Wondershare dengan Pendekatan Rme pada Materi SMP

Pemilihan media pembelajaran yang kurang tepat dapat membuat siswa kurang antusias terhadap mata pelajaran matematika. Sehingga banyak siswa yang mendapat nilai dibawah KKM. Solusinya dibutuhkan media pembelajaran yang menarik serta dapat menumbuhkan antusias siswa dalam belajar.Penelitian ini bertujuan untuk mengembangkan media pembelajaran berbantu wondershare dengan pendekatan RME sehingga menghasilkan media yang layak dan efektif digunakan selama pembelajaran. Jenis penelitian ini adalah penelitian Research and Development dengan menggunakan model pengembangan ADDIE, terdiri dari 5 tahapan yaitu analisis, design, developmen, implementasi, evaluasi.Sebelum diimplementasikan, media pembelajaran terlebih dahulu dilakukan uji validasi oleh ahli media, ahli materi serta angket tanggapan siswa. Hasil validasi ahli tersebut berkriteria sangat baik sehingga media pembelajaran layak untuk digunakan.Pembelajaran dengan media pembelajaran berbantu wondershare dengan pendekatan RME efektif digunakan oleh peserta didik. Hal ini di buktikan dari rata rata kelas eksperimen dan kontrol yaitu 82,03 dan 60,54. Ketuntasan belajar individu kelas ekperimen terdapat 31 siswa tuntas dari 36 siswa, dan kelas kontrol terdapat 8 siswa tuntas dari 27 siswa. Dilihat dari ketuntasan belajar klasikal siswa untuk kelas kontrol dan eksperimen sebesar 22,86% dan 86,11%. Dengan analisis menggunakan uji t pihak kanan diperoleh nilaiyaitu 9,607>1,667 maka H0 ditolak, jadi pembelajaran dengan menggunakan media pembelajaran berbantuan wondershare dengan pendekatan RME lebih baik dibandingkan dengan pembelajaran konvensional pada materi SMP

Quantification of nanoscale density fluctuations by electron microscopy: probing cellular alterations in early carcinogenesis *

Abstract Most cancers are curable if they are diagnosed and treated at an early stage. Recent studies suggest that nanoarchitectural changes occur within cells during early carcinogenesis and that such changes precede microscopically evident tissue alterations. It follows that the ability to comprehensively interrogate cell nanoarchitecture (e.g., macromolecular complexes, DNA, RNA, proteins and lipid membranes) could be critical to the diagnosis of early carcinogenesis. We present a study of the nanoscale mass-density fluctuations of biological tissues by quantifying their degree of disorder at the nanoscale. Transmission electron microscopy images of human tissues are used to construct corresponding effective disordered optical lattices. The properties of nanoscale disorder are then studied by statistical analysis of the inverse participation ratio (IPR) of the spatially localized eigenfunctions of these optical lattices at the nanoscale. Our results show an increase in the disorder of human colonic epithelial cells in subjects harboring early stages of colon neoplasia. Furthermore, our findings strongly suggest that increased nanoscale disorder correlates with the degree of tumorigenicity. Therefore, the IPR technique provides a practicable tool for the detection of nanoarchitectural alterations in the earliest stages of carcinogenesis. Potential applications of the technique for early cancer screening and detection are also discussed

Light scattering spectroscopy identifies the malignant potential of pancreatic cysts during endoscopy

Pancreatic cancers are usually detected at an advanced stage and have poor prognosis. About one fifth of these arise from pancreatic cystic lesions. Yet not all lesions are precancerous, and imaging tools lack adequate accuracy for distinguishing precancerous from benign cysts. Therefore, decisions on surgical resection usually rely on endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). Unfortunately, cyst fluid often contains few cells, and fluid chemical analysis lacks accuracy, resulting in dire consequences, including unnecessary pancreatic surgery for benign cysts and the development of cancer. Here, we report an optical spectroscopic technique, based on a spatial gating fibre-optic probe, that predicts the malignant potential of pancreatic cystic lesions during routine diagnostic EUS-FNA procedures. In a double-blind prospective study in 25 patients, with 14 cysts measured in vivo and 13 postoperatively, the technique achieved an overall accuracy of 95%, with a 95%confidence interval of 78–99%, in cysts with definitive diagnosis

Measurement of optical scattering properties with low-coherence enhanced backscattering spectroscopy

Low-coherence enhanced backscattering (LEBS) is a depth selective technique that allows noninvasive characterization of turbid media such as biological tissue. LEBS provides a spectral measurement of the tissue reflectance distribution as a function of distance between incident and reflected ray pairs through the use of partial spatial coherence broadband illumination. We present LEBS as a new depth-selective technique to measure optical properties of tissue in situ. Because LEBS enables measurements of reflectance due to initial scattering events, LEBS is sensitive to the shape of the phase function in addition to the reduced scattering coefficient (\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}\mu _s^{\bf *}\end{equation*} \end{document}μs*). We introduce a simulation of LEBS that implements a two parameter phase function based on the Whittle–Matérn refractive index correlation function model. We show that the LEBS enhancement factor (E) primarily depends on \documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{upgreek} \usepackage{mathrsfs} \setlength{\oddsidemargin}{-69pt} \begin{document} \begin{equation*}\mu _s^{\bf *}\end{equation*} \end{document}μs*, the normalized spectral dependence of E (Sn) depends on one of the two parameters of the phase function that also defines the functional type of the refractive index correlation function (m), and the LEBS peak width depends on both the anisotropy factor (g) and m. Three inverse models for calculating these optical properties are described and the calculations are validated with an experimental measurement from a tissue phantom