Medicine and Health Sciences Commons^™

Predicting Malignant Nodules From Screening Ct Scans, Samuel Hawkins, Hua Wang, Ying Liu, Alberto Garcia, Olya Stringfield, Henry Krewer, Qiang Li, Dmitry Cherezov, Matthew Schabath, Lawrence O. Hall, Robert J. Gillies

Computer Science and Engineering Faculty Publications

Objectives

The aim of this study was to determine whether quantitative analyses (“radiomics”) of low-dose computed tomography lung cancer screening images at baseline can predict subsequent emergence of cancer.

Methods

Public data from the National Lung Screening Trial (ACRIN 6684) were assembled into two cohorts of 104 and 92 patients with screen-detected lung cancer and then matched with cohorts of 208 and 196 screening subjects with benign pulmonary nodules. Image features were extracted from each nodule and used to predict the subsequent emergence of cancer.

Results

The best models used 23 stable features in a random forests classifier and could …

Increasing Tumor Volume Is Predictive Of Poor Overall And Progression-Free Survival: Secondary Analysis Of The Radiation Therapy Oncology Group 93-11 Phase I-Ii Radiation Dose-Escalation Study In Patients With Inoperable Non-Small-Cell Lung Cancer, Maria Werner-Wasik, R. Suzanne Swann, Phd, Jeffrey Bradley, Md, Mary Graham, Md, Bahman Emani, Md, James Purdy, Phd, William Sause, Md

Bodine Journal

Purpose

Patients with non–small-cell lung cancer (NSCLC) in the Radiation Therapy Oncology Group (RTOG) 93-11 trial received radiation doses of 70.9, 77.4, 83.8, or 90.3 Gy. The locoregional control and survival rates were similar among the various dose levels.We investigated the effect of the gross tumor volume (GTV) on the outcome.

Methods and Materials

The GTV was defined as the sum of the volumes of the primary tumor and involved lymph nodes. The tumor response, median survival time (MST), and progression-free survival (PFS) were analyzed separately for smaller (≤45 cm3) vs. larger (>45 cm3) tumors.

Results

The distribution of …

Management Of Co-Existing Lung Cancer And Endobronchal Hamartomas, Mark H. Cooper, Md

Mark Hayden Cooper, MD, PhD

Abstract: The coexistence of lung cancer with an endobronchial hamartoma is infrequent, and requires accurate oncologic evaluation of the endobronchial lesion prior to potential surgical treatment of the lung cancer. We describe a patient who presented with an undiagnosed endobronchial mass and and a biopsy-proven lung cancer which were successfully managed by a staged approach using initial bronchoscopic resection of the endobronchial lesion and subsequent lobectomy for squamous cell lung cancer.

Selective Anticancer Activity Of Hydroxyapatite/Chitosan-Poly(D,L)-Lactide-Co-Glycolide Particles Loaded With An Androstane-Based Cancer Inhibitor, Nenad Ignjatović, Katarina M. Penov-Gaši, Victoria M. Wu, Jovana J. Ajduković, Vesna V. Kojić, Dana Vasiljević-Radović, Maja Kuzmanović, Vuk Uskoković, Dragab Uskoković

Pharmacy Faculty Articles and Research

In an earlier study we demonstrated that hydroxyapatite nanoparticles coated with chitosan-poly(d,l)-lactide-co-glycolide (HAp/Ch-PLGA) target lungs following their intravenous injection into mice. In this study we utilize an emulsification process and freeze drying to load the composite HAp/Ch-PLGA particles with 17β-hydroxy-17α-picolyl-androst-5-en-3β-yl-acetate (A), a chemotherapeutic derivative of androstane and a novel compound with a selective anticancer activity against lung cancer cells. ¹H NMR and ¹³C NMR techniques confirmed the intact structure of the derivative A following its entrapment within HAp/Ch-PLGA particles. The thermogravimetric and differential thermal analyses coupled with mass spectrometry were used to assess the …

Investigating The Role Of The Retinoblastoma Protein In The Expression Of Immunosuppressive Factors, Felipe Pérez Deliz, Pedro Santiago-Cardona, Phd, J. González, Phd, Jaileene Pérez-Morales, Meng

Journal of Health Disparities Research and Practice

Lung cancer remains one of the deadliest types of cancer, causing approximately 160,000 deaths per year in the US alone. Because of its poor detection techniques and highly invasive abilities, conventional treatments -such as radiation and chemotherapy- fail to improve long-term survival of patients. At the moment, the 5-year survival rate for all stages of lung cancer is only 16%. Recent breakthroughs in cancer research establish immunotherapy, which involves the stimulation of the immune system to target and attack cancer cells, as a highly promising alternative treatment against this deadly disease. However, the efficiency of this treatment varies on each …

The Causal Relevance Of Body Mass Index In Different Histological Types Of Lung Cancer: A Mendelian Randomization Study, Robert Carreras-Torres, Philip C. Haycock, Caroline L. Relton, Richard M. Martin, George Davey Smith, Peter Kraft, Chi Gao, Shelley Tworoger, Loic Le Marchand, Lynne R. Wilkens, Sungshim L. Park, Christopher Haiman, John K. Field, Michael Davies, Mihcael Marcus, Geoffrey Liu, Neil E. Caporaso, David C. Christiani, Yongyue Wei, Chu Chen, Jennifer A. Doherty, Gianluca Severi, Gary E. Goodman, Rayjean J. Hung, Christopher I. I. Amos, James Mckay, Mattias Johansson, Paul Brennan

Dartmouth Scholarship

Body mass index (BMI) is inversely associated with lung cancer risk in observational studies, even though it increases the risk of several other cancers, which could indicate confounding by tobacco smoking or reverse causality. We used the two-sample Mendelian randomization (MR) approach to circumvent these limitations of observational epidemiology by constructing a genetic instrument for BMI, based on results from the GIANT consortium, which was evaluated in relation to lung cancer risk using GWAS results on 16,572 lung cancer cases and 21,480 controls. Results were stratified by histological subtype, smoking status and sex. An increase of one standard deviation (SD) …

Aptamer-Hybrid Nanoparticle Bioconjugate Efficiently Delivers Mirna-29b To Non-Small-Cell Lung Cancer Cells And Inhibits Growth By Downregulating Essential Oncoproteins., Maryna Perepelyuk, Christina Maher, Ashakumary Lakshmikuttyamma, Sunday A. Shoyele

College of Pharmacy Faculty Papers

MicroRNAs (miRNAs) are potentially attractive candidates for cancer therapy. However, their therapeutic application is limited by lack of availability of an efficient delivery system to stably deliver these potent molecules intracellularly to cancer cells while avoiding healthy cells. We developed a novel aptamer-hybrid nanoparticle bioconjugate delivery system to selectively deliver miRNA-29b to MUC1-expressing cancer cells. Significant downregulation of oncoproteins DNMT3b and MCL1 was demonstrated by these MUC1 aptamer-functionalized hybrid nanoparticles in A549 cells. Furthermore, downregulation of these oncoproteins led to antiproliferative effect and induction of apoptosis in a superior version when compared with Lipofectamine 2000. This novel aptamer-hybrid nanoparticle bioconjugate …

Optimizing Respiratory Gated Intensity Modulated Radiation Therapy Planning And Delivery Of Early-Stage Non-Small Cell Lung Cancer, Ilma Xhaferllari

Electronic Thesis and Dissertation Repository

Stereotactic ablative body radiotherapy (SABR) is the standard of care for inoperable early-stage non-small cell lung cancer (NSCLC) patients. However, thoracic tumours are susceptible to respiratory motion and, if unaccounted for, can potentially lead to dosimetric uncertainties. Respiratory gating is one method that limits treatment delivery to portions of the respiratory cycle, but when combined with intensity-modulated radiotherapy (IMRT), requires rigorous verification. The goal of this thesis is to optimize respiratory gated IMRT treatment planning and develop image-guided strategies to verify the dose delivery for future early-stage NSCLC patients.

Retrospective treatment plans were generated for various IMRT delivery techniques, including …

Delaying Chemotherapy In The Treatment Of Stage Iv Non-Small Cell Lung Cancer Does Not Adversely Affect Survival Outcome, Mohammad Mozayen Md, Mohamed Alsharedi, Inderjit Mehmi, Todd W. Gress Md, Maria Tria Tirona Md

Maria Tirona

Background: Whether a delay in the initiation of chemotherapy for advanced non-small cell lung cancer (NSCLC) can affect overall survival is not well studied. We aim to evaluate the effect of the time interval between diagnosis and initiation of chemotherapy on overall survival in patients with stage IV NSCLC. Methods: A retrospective review of newly diagnosed stage IV NSCLC patients who received chemotherapy between 1995 and 2012 was conducted. Demographics, histology and site(s) of metastases of patients were reviewed. Time interval between the date of diagnosis and the date of starting chemotherapy was calculated in days. Patients were divided in …

Esophageal Diagnosis Of A Malignant Aspergilloma, Muneer Al Zoby, Nancy Munn,, Yousef Shweihat

Internal Medicine

A 59-year-old male patient developed a new 4 cm × 6 cm cavitary left upper lung lesion over a 2 months period. The patient had a prior history of a surgically resected Stage IA non-small cell lung cancer in the right upper lobe 3 years prior. He was treated for possible infection with radiographic improvement on subsequent imaging. Further imaging after 3 months revealed an oval soft tissue density within the cavity with air crescent sign. Bronchoscopy with transbronchial biopsies showed an acute and chronic granulomatous inflammation. Aspergillus fumigatus was noted on culture and voriconazole was initiated. Subsequent imaging showed …

Management Of Co-Existing Lung Cancer And Endobronchal Hamartomas, Mark H. Cooper, Md

Marshall Journal of Medicine

Abstract:

The coexistence of lung cancer with an endobronchial hamartoma is infrequent, and requires accurate oncologic evaluation of the endobronchial lesion prior to potential surgical treatment of the lung cancer. We describe a patient who presented with an undiagnosed endobronchial mass and and a biopsy-proven lung cancer which were successfully managed by a staged approach using initial bronchoscopic resection of the endobronchial lesion and subsequent lobectomy for squamous cell lung cancer.

Alternative Regulation Of Myc In Lung Cancer, Patrick N. Backman

Open Access Theses

Lung cancer is the leading cause of cancer deaths in the United States, accounting for 27% of all cancer induced deaths1. In an attempt to create a effective targeted therapy for the treatment of lung cancer, a strategy used to treat an activated KrasG12D/+;p53 R172H/+ transgenic lung cancer mouse model was to deliver a known tumor suppressive microRNA (miRNA) to stop tumor growth. The tumor suppressive miRNA let-7 was lentivirally delivered in the form of its primary transcript, pri-let-7a-1, and resulted in increased lung size and inflammation compared to lungs exposed to a control lentivirus. It was identified …

Biodistribution And Pharmacokinetics Study Of Sirna-Loaded Anti-Ntsr1-Mab-Functionalized Novel Hybrid Nanoparticles In A Metastatic Orthotopic Murine Lung Cancer Model., Maryna Perepelyuk, Chellappagounder Thangavel, Yi Liu, Robert B. Den, Bo Lu, Adam E. Snook, Sunday A. Shoyele

Department of Radiation Oncology Faculty Papers

Small interfering RNA (siRNA) is effective in silencing critical molecular pathways in cancer. The use of this tool as a treatment modality is limited by lack of an intelligent carrier system to enhance the preferential delivery of this molecule to specific targets in vivo. In the present study, the in vivo behavior of novel anti-NTSR1-mAb-functionalized antimutant K-ras siRNA-loaded hybrid nanoparticles, delivered by i.p. injection to non-small-cell lung cancer in mice models, was investigated and compared to that of a naked siRNA formulation. The siRNA in anti-NTSR1-mAb-functionalized hybrid nanoparticles was preferentially accumulated in tumor-bearing lungs and metastasized tumor for at least …

The Associations Of Selected Lifestyle Patterns And Lung Cancer Risk: An Evidence-Based Update, Joanna Kruk, Basil H. Aboul-Enein

Health & Wellness Department Faculty Publications and Research

Diagnosis of lung cancer (LC) has been fraught with difficulty and by the time of definitive diagnosis, most patients are in later stages of the disease. Epidemiological studies have demonstrated that lifestyle behaviors play an etiological role in LC risk; however data in the literature on this topic often appears inconclusive or require further study. Understanding of the mechanisms operating between lifestyle patterns and their impact on LC is important for the disease’s prevention and treatment. The purpose of this study was to review the current evidence on the role of diet, body mass index (BMI), physical activity, smoking, alcohol …

Delaying Chemotherapy In The Treatment Of Stage Iv Non-Small Cell Lung Cancer Does Not Adversely Affect Survival Outcome, Mohammad Mozayen Md, Mohamed Alsharedi, Inderjit Mehmi, Todd W. Gress Md, Maria Tria Tirona Md

Biochemistry and Microbiology

Background: Whether a delay in the initiation of chemotherapy for advanced non-small cell lung cancer (NSCLC) can affect overall survival is not well studied. We aim to evaluate the effect of the time interval between diagnosis and initiation of chemotherapy on overall survival in patients with stage IV NSCLC.

Methods: A retrospective review of newly diagnosed stage IV NSCLC patients who received chemotherapy between 1995 and 2012 was conducted. Demographics, histology and site(s) of metastases of patients were reviewed. Time interval between the date of diagnosis and the date of starting chemotherapy was calculated in days. Patients were divided in …

Lung Cancer Metastasis Presenting As A Solitary Skull Mass, Ryan C. Turner, Brandon P. Lucke-Wold, Roy Hwang, Bill D. Underwood

Faculty & Staff Scholarship

Lung cancer has been well documented to spread to bone and the axial skeleton after metastasis to adjacent organs. Bony metastasis is not, however, the typical presenting manifestation. The differential diagnosis for a tissue mass on the skull should warrant a workup for metastatic disease. Bony metastasis plays an important role in treatment and disease management. We report an exceptionally rare case of stage IV lung adenocarcinoma that presented with a solitary skull metastasis and a significant soft-tissue component. The lesion was treated by excision via craniotomy and subsequent medical management of the adenocarcinoma. This case illustrates a very rare …

Comparing African- And U.S.-Born Blacks At Stage Of Diagnosis And Treatment For Nonsmall Cell Lung Cancer, Relindis K. Fofung

Walden Dissertations and Doctoral Studies

Lung cancer is a disease with a high mortality rate for the U.S. Black population. There had been considerable research done on different population demographics, necessary to achieve the Healthy People 2020 overarching goals to eliminate health disparities, gain health equity and maintain quality health. Yet, the African-born Black (AFBB) population has been understudied for nonsmall cell lung cancer (NSCLC). This study sought to determine whether within race differences in stage at diagnosis and treatment of NSCLC exists between AFBB and American-born Blacks (AMBB) populations in the United States. The study data is secondary data collected as part of the …

Documentation Of Smoking History And Adherence To The Uspstf Recommendation For Lung Cancer Screening: A Retrospective Chart Review, Laura A. Golden

DNP Projects

Purpose: The purpose of this project was to evaluate provider compliance with documentation of smoking history and, if criteria met, referral for lung cancer screening as recommended by the United States Preventive Services Task Force in 2013.

Methods: A retrospective chart review was conducted using an electronic medical record (EMR) at a large, rural community family practice clinic. Patients meeting inclusion criteria of having a smoking history (current or past) of 30 pack years, aged 55 to 80 years, and no history of lung cancer diagnosis were included for randomization. One hundred patients were selected from 300 randomized charts; five …

Altering Metabolism In The Tumor Microenvironment To Enhance Anti-Tumor Immunity For Lung Cancer, Cara Schafer

All ETDs from UAB

Overcoming cancer cell immune escape represents a fundamental obstacle in the treatment of cancer. Indoleamine 2,3-dioxygenase (IDO)-expressing myeloid-derived suppressor cells (MDSCs) are known to induce oxidative stress and alter amino acid metabolism within the tumor microenvironment (TME). The tryptophan (Trp)-catabolizing action of IDO not only promotes T cell tolerance and evasion but is also associated with impaired quality of life in cancer patients. We have previously demonstrated that a novel combination therapy, consisting of MDSC-depleting gemcitabine and a superoxide dismutase mimetic, prolonged survival of tumor-bearing mice by enhancing CD8+ memory T cell metabolism. We identify that combination therapy inhibits IDO …

Synthesis, Characterization, And In Vitro Anti-Tumor Studies Of Bis Imidazolium Salts With Alkyl Chain Linkers And Naphthylmethyl Substituents, Steven R. Crabtree

Williams Honors College, Honors Research Projects

Bis imidazolium salts, with alkyl chain linkers ranging from methylene to dodecyl, were synthesized with naphthylmethyl substituents at the N¹ and N^1’ positions for a structure-activity relationship (SAR) study. All compounds were characterized by ¹H and ¹³C NMR spectroscopy. The cationic portion of 2 as the PF₆ salt, 3, 4, and 5 were also characterized by single-crystal X-ray crystallography. Compounds 1-8, 10, and 12 were tested for their in vitro anti-cancer activity against four NSCLC cell lines via the MTT assay (NCI–H460, NCI–H1975, HCC827, and A549). Compounds 10 and 12 which …

New Immunohistochemical Markers In The Differential Diagnosisof Nonsmall Cell Lung Carcinoma, Ferda Bi̇r, Duygu Çeli̇ker, Bi̇nnaz Fatma Evyapan, Arzu Yaren, Tamer Edi̇rne

Turkish Journal of Medical Sciences

Background/aim: The aim of this study was to investigate Napsin-A, NTRK-1, NTRK-2, Desmoglein-3, and Desmocollin-3 in the differential diagnosis and prognosis of nonsmall cell lung cancer. Materials and methods: The expression of Napsin-A, NTRK-1, NTRK-2, and Desmoglein-3 was examined by immunohistochemistry in 50 squamous cell carcinomas and 50 adenocarcinomas. Desmocollin-3 was investigated in 29 squamous cell carcinoma and 29 adenocarcinoma cases. Associations between expression profiles of Napsin-A, NTRK-1, NTRK-2, Desmoglein-3, and Desmocollin-3 in lung cancers and clinicopathological variables were analyzed. Results: Napsin-A staining was statistically significant in detecting adenocarcinomas versus squamous cell carcinomas. The sensitivity of Napsin-A for adenocarcinomas was …

Exploration Of The Srx-Prx Axis As A Small-Molecule Target, Murli Mishra

Theses and Dissertations--Toxicology and Cancer Biology

Lung cancer is a leading cause of cancer-related mortality irrespective of gender. The Sulfiredoxin (Srx) and Peroxiredoxin (Prx) are a group of thiol-based antioxidant proteins that plays an essential role in non-small cell lung cancer. Understanding the molecular characteristics of the Srx-Prx interaction may help design the strategies for future development of therapeutic tools. Based on existing literature and preliminary data from our lab, we hypothesized that the Srx plays a critical role in lung carcinogenesis and targeting the Srx-Prx axis or Srx alone may facilitate future development of targeted therapeutics for prevention and treatment of lung cancer. First, …

Cost-Effectiveness Analysis Of Pemetrexed And Gemcitabine Treatment For Advanced Nonsmall Cell Lung Cancer In Turkey, Pinar Yalçin Balçik, Bayram Şahi̇n

Turkish Journal of Medical Sciences

Background/aim: The purpose of the study is to determine the cost-effectiveness of the chemotherapy medications that contain gemcitabine and pemetrexed, which are used in the treatment of advanced nonsmall cell lung cancer (NSCLC). Materials and methods: The study evaluated the effectiveness and cost of platinum-based pemetrexed and gemcitabine treatments as the first-line treatment of advanced NSCLC with the use of the Markov model, and from the perspective of the Social Security Institution. NSCLC costs calculated on the basis of experts' opinions and the effectiveness values calculated by administering the EQ-5D questionnaire to the patients were analyzed. All direct medical costs …

The Link Between Smoking, Lung Cancer And Socioeconomic Factors In Kentucky, Shreya Berlia

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

Background and Purpose

Lung cancer is the leading cause of cancer death and the second most diagnosed cancer in both men and women in the United States. An estimated 158,080 deaths from lung cancer are expected to occur in 2016, which will account for approximately 1 in 4 of all cancer deaths. The 1- and 5-year relative survival rates for lung cancer are 44% and 17%, respectively. The incidence rate for lung cancer has been declining since the mid-1980s in men, but only since the mid-2000s in women. Tobacco smoke is the leading cause of preventable disease and death in …

Development Of Multiple Primary Cancers In Lung Cancer Patients: Appalachian Vs. Non-Appalachian Populations Of Kentucky, Vira Pravosud

Theses and Dissertations--Public Health (M.P.H. & Dr.P.H.)

OBJECTIVE: This study examined whether there were differences in the development of multiple primary cancers in lung cancer patients residing in the Appalachian versus Non-Appalachian regions of Kentucky. The study also identified other factors associated with the development of another primary cancer in lung cancer patients.

HYPOTHESIS: Lung cancer patients residing in Appalachian Kentucky are more likely to develop multiple primary cancers compared to patients residing in Non-Appalachian Kentucky.

METHODS: This was a retrospective, population-based cohort study of Kentucky patients (N=26456) aged 20 years and older, diagnosed with primary lung cancer between January 1, 2000 and December 31, 2013. The …