Oncology Commons^™

Impact Of Select Actionable Genomic Alterations On Efficacy Of Neoadjuvant Immunotherapy In Resectable Non-Small Cell Lung Cancer, Nicolas Zhou, Cheuk H Leung, William N William, Annikka Weissferdt, Apar Pataer, Myrna C B Godoy, Brett W Carter, Frank V Fossella, Anne S Tsao, George R Blumenschein, Xiuning Le, Jianjun Zhang, Ferdinandos Skoulidis, Jonathan M Kurie, Mehmet Altan, Charles Lu, Bonnie S Glisson, Lauren A Byers, Yasir Y Elamin, Reza J Mehran, David C Rice, Garrett L Walsh, Wayne L Hofstetter, Jack A Roth, Hai T Tran, Jia Wu, Luisa M Solis Soto, Humam Kadara, Stephen G Swisher, Ara A Vaporciyan, Don L Gibbons, Heather Y Lin, J Jack Lee, John V Heymach, Marcelo V Negrao, Boris Sepesi, Tina Cascone

Faculty, Staff and Student Publications

Background: Neoadjuvant immune checkpoint inhibitors (ICIs) have improved survival outcomes compared with chemotherapy in resectable non-small cell lung cancer (NSCLC). However, the impact of actionable genomic alterations (AGAs) on the efficacy of neoadjuvant ICIs remains unclear. We report the influence of AGAs on treatment failure (TF) in patients with resectable NSCLC treated with neoadjuvant ICIs.

Methods: Tumor molecular profiles were obtained from patients with stage I-IIIA resectable NSCLC (American Joint Committee on Cancer seventh edition) treated with either neoadjuvant nivolumab (N, n=23) or nivolumab+ipilimumab (NI, n=21) followed by surgery in a previously reported phase-2 randomized study (NCT03158129). TF …

Flash Radiation Ultra-High Dose Rate Radiation With Potential For Sensitization By Platinum, Abigail A. Jaczkowski, Stephen Brown Ph.D.

Medical Student Research Symposium

External beam radiation therapy, a cornerstone in cancer treatment for 50% of patients, poses challenges due to its toxicity to both cancer and healthy cells. Seeking to mitigate side effects, the emerging FLASH radiation technology employs ultra-high dose rates, promising quicker treatments with reduced impact on surrounding normal tissue. Platinum, recognized as a radiation sensitizer, enhances the effectiveness of radiation therapy by increasing sensitization at higher energy levels through pair-production.

This study explores the hypothesis that Cisplatin, a platinum-based chemotherapy agent, will exhibit a synergistic effect when combined with FLASH radiation. Using A549 cells from non-small cell lung cancer, the …

Using Machine Learning Models To Address Challenges In Lung Cancer Care, Salma Dammak

Electronic Thesis and Dissertation Repository

Lung cancer is characterized by its aggressiveness, heterogeneity, and wide array of treatments. Choosing the best treatment requires extensive patient information, which may sometimes be incomplete, presenting several clinical challenges. This thesis addresses two such challenges and introduces three machine-learning-based models to address them.

The first challenge focuses on identifying lung squamous cell carcinoma (SqCC) patients who could benefit from immunotherapy based on their tumour mutational burden (TMB). TMB is a promising but often unavailable biomarker in routine clinical practice. To address this, we developed a model capable of predicting TMB from standard-of-care tumour excision slides. Using 50 slides from …

Characterizing Pulmonary Function Test Changes For Patients With Lung Cancer Treated On A 2-Institution, 4-Dimensional Computed Tomography-Ventilation Functional Avoidance Prospective Clinical Trial, Ryan C. Miller, Richard Castillo, Edward Castillo, Bernard L Jones, Moyed Miften, Brian Kavanagh, Bo Lu, Maria Werner-Wasik, Nader Ghassemi, Joseph Lombardo, Julie Barta, Inga Grills, Chad G Rusthoven, Thomas Guerrero, Yevgeniy Vinogradskiy

Department of Radiation Oncology Faculty Papers

Purpose: Four-dimensional computed tomography (4DCT)-ventilation-based functional avoidance uses 4DCT images to generate plans that avoid functional regions of the lung with the goal of reducing pulmonary toxic effects. A phase 2, multicenter, prospective study was completed to evaluate 4DCT-ventilation functional avoidance radiation therapy. The purpose of this study was to report the results for pretreatment to posttreatment pulmonary function test (PFT) changes for patients treated with functional avoidance radiation therapy.

Methods and materials: Patients with locally advanced lung cancer receiving chemoradiation were accrued. Functional avoidance plans based on 4DCT-ventilation images were generated. PFTs were obtained at baseline and 3 months …

Targeting Bcl-2 Family Proteins In Therapy Induced Senescent Cancer Cell Models, Wade Cook

Theses and Dissertations

Non-small Cell Lung Cancer (NSCLC) originates from numerous different cell types in the lungs and is among the deadliest of cancers. Head and Neck Squamous Cell Carcinomas (HNSCC) are derived from the mucosal membranes of the oral cavity, pharynx, and larynx. Both NSCLC and HNSCC are predominately caused by tobacco smoke inhalation and as such mutations in the tumor suppressor gene TP53 are common. Since similarities exist in the root cause of NSCLC and HNSCC, they may also share similarities in treatment methods. Cisplatin is a platinum-based DNA damaging agent that has been used as a cancer chemotherapy for decades. …

An Examination Of Lung Cancer Treatment Characteristics On Lung Cancer Patients With Co-Existing Heart Disease, Elias Rhanime

Honors Undergraduate Theses

With the rising rates of heart disease incidents in the United States and the increase in lung cancer deaths as well, many individuals suffer and get their treatments compromised due to these diseases. Especially considering that many lung cancer and heart disease patients are over 70 years of age, treatment options and success rates drop significantly. Due to this, a great concern is raised for patients with co-existing heart disease and lung cancer. This was a case-control study that assessed lung cancer treatment options and success rates for patients with co-existing heart disease. We used research papers that discussed lung …

Barriers To Lung Cancer Screening Among African American Males Aged 50-70 In The United States, Edward Marines

Rowan-Virtua Research Day

Objectives:

• Identify the different barriers to lung cancer screening among African American males
• Examine potential methods of increasing access and participation within this population

The Maine Lung Cancer Coalition: A Statewide, Multi-Sector Partnership To Improve Evidence-Based Lung Cancer Prevention & Screening, Leo B Waterston, Liz Scharnetzki, Susan Leeds, Jaclyn A. Janis, Lee Lucas, Deborah Deatrick, Rebecca Boulos, Neil Korsen, Paul K.J. Han

Costas T. Lambrew Research Retreat 2021

MLCC has two primary goals:

1. Engage and educate about evidence based lung cancer prevention and screening practices

2. Develop, implement, and evaluate innovative programs to increase access to prevention, screening, and treatment services for all Mainers

Residential Radon Exposure, Its Contribution To Lung Cancer, And Social Determinants Of Radon Testing, Stacy Stanifer

Theses and Dissertations--Nursing

Lung cancer is a highly preventable form of cancer. Cigarette smoking is the leading cause of lung cancer followed by radon gas exposure and exposure to secondhand smoke. Kentucky leads the nation in both incidence and mortality from lung cancer. Tobacco use in Kentucky continues to be a major public health concern as nearly one-quarter of adults report current tobacco use and just over one-third of Kentucky homes with children lack rules which prohibit smoking in the home. Radon, a colorless, odorless radioactive gas, occurs naturally from the decay of uranium found in rocks and soil and is harmful when …

A Cytotoxic Evaluation Of A Chalcone Derivative Library On A549 Cells, Mary Elaine Kuo

Undergraduate Theses

Chalcones, a precursor to flavonoids, are chemical compounds found naturally in plants. The chalcones’ structure consists of a ketone bridge attached to two aromatic rings. Varying substituents on the aromatic rings allow for different affects, including anti-cancer properties. As a Michael acceptor, chalcones interact with pathways that cause inhibition of the initiation, promotion, and progression of cancer tumors. We have screened 32 compounds for growth inhibition in lung cells that vary the flexibility and confirmation of the 3 carbon bridge between the two aromatic rings as well as the effects of electronic modifications to the aromatic ring. We have found …

Clinicians’ Perspectives On Adopting A Lung Cancer Palliative Care Intervention, Shaunna Siler

Loma Linda University Electronic Theses, Dissertations & Projects

Despite the significant progress in implementing palliative care interventions for cancer patients, few intervention studies seek healthcare clinicians’ input prior to implementation. The purpose of this research was then to explore palliative care and oncology clinicians’ (e.g., physicians, nurses, social workers, and chaplains) perspectives on current challenges and useful practices in meeting the quality of life needs of lung cancer patients and family caregivers, and to increase the likelihood of the adoption of a palliative care intervention based on understanding current trends in palliative care delivery at three outpatient oncology sites. The conceptual framework used for this study was the …

Is Necitumumab An Effective Addition To Traditional Chemotherapeutic Regiments When Treating Stage Iv Lung And Colon Cancer?, J. Ross Hosford

PCOM Physician Assistant Studies Student Scholarship

Objective: The objective of this selective EBM review is to determine whether or not Necitumumab is an effective add on treatment to traditional chemotherapy regimes when treating stage IV lung or colon cancer.

Study Designs: Review of two open label, randomized, controlled phase III trials and one single arm multicenter phase II study.

Outcomes Measured: Objective tumor response rate was measured for patients with colon cancer. Overall survival rate and length of survival were measured for patients with lung cancer. This was measured in Kapler Meier Methodology.

Results: For two trials the addition of Necitumumab improved …

The Roles Of Malt1 In Nf-Κb Activation And Solid Tumor Progression, Deng Pan

Dissertations & Theses (Open Access)

The transcription factor NF-κB plays a central role in many aspects of biological processes and diseases, such as inflammation and cancer. Although it has been suggested thatNF-κB is critical in tumorigenesis and tumor progression, the molecular mechanism by which NF-κB is activated in solid tumor remains largely unknown. In the current work, we focus on growth factor receptor-induced NF-κB activation and tumor progression, including epidermal growth factor receptor (EGFR)-induced NF-κB in lung cancer and heregulin receptor (HER2)-induced NF-κB in breast cancer. We found that Mucosa-associated lymphoma translocation protein 1 (MALT1), also known as paracaspase, is required for EGFR-induced NF-κB activation …

Lung Cancer Epidemiology – A Global View, Patricia Tai, Edward Yu, Rashmi Koul, Arbind Dubey

Edward Yu

Smoking, air pollution and radon exposure are causally related to lung cancer. This review analyzes trends of smoking habits by age, sex and ethnicity and their correlation with incidence and mortality of lung cancer. Unfortunately the use of tobacco by adolescents is on the rise. Most developed countries are still showing the rising trend of mortality in female smokers. In Asia, cigarette smoking has become a major health risk with one in three of all cigarettes in the world today are smoked in China. Estimated one hundred million young ( < 29 years old) Chinese smokers will eventually die from lung …

Lung Cancer Brachytherapy: Robotics-Assisted Minimally Invasive Approach, Edward Yu, Craig Lewis, Ana Trejos, Rajni Patel, Richard Malthaner

Edward Yu

New technological concepts have been evolving to manage the relative poor prognosis of lung cancer. Brachytherapy is becoming an option for both unresectable and early resectable lung cancer. Three-dimensional ultrasound (US) of lung tumours and image-guided minimally invasive robotics-assisted brachytherapy are feasible for dosimetry planning and management of lung tumours. The present article reviews the current knowledge of lung brachytherapy and discusses its potential in future management of lung cancer.

Hedgehog Signaling: A Potential Therapeutic Target For Non-Small Cell Lung Cancer, Ma'in Yehya Maitah

Wayne State University Dissertations

The American Cancer Society estimated that 222,520 Americans were diagnosed with lung cancer and 157,300 died of lung cancer in 2010 (Jemal et al. 2009, 225-249;Jemal et al. 2011, 69-90). The clinical outcome of patients diagnosed with non-small cell lung cancer (NSCLC), the major lung cancer sub-types, is very poor, which calls for innovative research for finding novel therapeutic targets and agents for better treatment outcome.

Emerging evidences have suggested that a phenomenon called Epithelial-to-Mesenchymal Transition (EMT), which shares similar molecular characteristics with cancer stem-like cells, contributes to lung cancer treatment failure. In view of the fact that EMT process …

Pathologic Correlation Of Pet-Ct Based Auto Contouring For Radiation Planning In Lung Cancer, S. E. Fogh, A. Farach, C. Intenzo, R. Axelrod, P. Mccue, A. Harper, A. Nelson, M Werner-Wasik

Bodine Journal

Purpose/Objective(s): Radiation therapy in lung cancer relies on CT and functional imaging (FDG-PET) to delineate tumor volumes. Semi-automatic contouring tools have been developed for PET to improve on the inter-observer bias of manual contouring and intrinsic differences in imaging equipment. A common method involves using a threshold at a given percentage of the max activity, which may be less accurate with smaller tumors and tumors with low source to background ratio. To overcome this deficiency, a gradient algorithm, which detects changes in image counts at the border of the tumor, has been developed. Few studies have correlated these methods to …

Chemosensitization Of Cancer Cells By Sirna Using Targeted Nanogel Delivery, Erin B. Dickerson, William H. Blackburn, Michael H. Smith, Laura B. Kapa, L. Andrew Lyon, John F. Mcdonald

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Background: Chemoresistance is a major obstacle in cancer treatment. Targeted therapies that enhance cancer cell sensitivity to chemotherapeutic agents have the potential to increase drug efficacy while reducing toxic effects on untargeted cells. Targeted cancer therapy by RNA interference (RNAi) is a relatively new approach that can be used to reversibly silence genes in vivo by selectively targeting genes such as the epidermal growth factor receptor (EGFR), which has been shown to increase the sensitivity of cancer cells to taxane chemotherapy. However, delivery represents the main hurdle for the broad development of RNAi therapeutics.

Methods: We report here …

Initial Tumor Metabolic Parameters (Maximum Suv And Metabolic Volume) Predict Death From Lung Cancer And Rapid Suv Decline Is Associated With Local Control, Maria Werner-Wasik, Edward Pequignot, Terry Hyslop, Brian Shulli, Ying Xiao, Mitchell Machtay, Amy Taylor, Walter Curran, Rita Axelrod

Department of Radiation Oncology Faculty Papers

Factors associated with local failure and death from lung cancer were evaluated based on post-treatment FDG-PET imaging in patients (pts) with non-small cell lung cancer (NSCLC).

PET-CT scans were obtained 6-8 weeks after thoracic RT and approximately every 3 months thereafter.

Mira V: An Integrated System For Minimally Invasive Robot-Assisted Lung Brachytherapy, A. Trejos, A. Lin, S. Mohan, H. Bassan, C. Edirisinghe, R. Patel, C. Lewis, E. Yu, A. Fenster, R. Malthaner

Edward Yu

An integrated system for minimally invasive robot-assisted image-guided lung brachytherapy has been developed. The system incorporates an experimental setup for accurate radioactive seed placement with commercially available dosimetry planning software. The end result is a complete system that allows planning and executing a brachytherapy procedure with increased accuracy. The results of the in vitro seed placement evaluation show that seed misplacement has a significant effect on the volume receiving more than 200% of the dose (V200), and the minimum dosage received by 90% of the volume (D90).

Dosimetric Evaluation Of Helical Tomotherapy Treatment Planning For Non-Small Cell Lung Cancer, Karen Chu, George Rodrigues, Slav Yartsev, A. Rashid Dar, Edward Yu, Robert Ash, Brian Yaremko, Marc Mackenzie, Harvey Quon, Glenn Bauman, Wilson Roa

Edward Yu

Helical tomotherapy (HT) is a novel technique to deliver intensity modulated radiation therapy guided by 3D megavoltage CT imaging. The purpose of our study is to assess the dosimetric parameters related to HT and 3DCRT in advanced non-small cell lung cancer (NSCLC). Eleven patients from the London Regional Cancer Centre and the Cross Cancer Institute with NSCLC underwent individualized treatment planning on both HT and 3DCRT. Corresponding HT and 3DCRT plans for each patient were analyzed using dose-volume histograms for GTV, PTV (median dose 60Gy/30 fractions), and critical structures (lung V5-30, esophageal V50-60, and spinal cord D1). Observed differences in …

The Association Of Lung Cancer Mortality With Income And Education In Kentucky Counties, David A. Gross

Center of Excellence in Rural Health Presentations

Lung cancer, the primary cause of cancer death in the United States, is particularly problematic in Kentucky, which has the nation’s highest rate of adult smokers. In fact, each Kentucky county exceeds the national rate for per capita lung cancer deaths. This project analyzes the relationships between lung cancer deaths, high school graduation rates, per capita personal income and adult smoking – and whether statistically significant differences exist among the variables between Kentucky’s Appalachian and non-Appalachian counties.

Lung Cancer Trends. Part 2: Beyond North America, P. Tai, E. Yu

Edward Yu

No abstract provided.