Small cell lung cancer (SCLC) is characterized by prompt response to chemotherapy and radiotherapy but relapsing with drug resistance and distant metastasis, leading to poor overall prognosis. New anticancer agents and regimens are drastically needed for SCLC treatment. Arsenic trioxide (ATO), a traditional Chinese medicine used as a poison for thousands of years, has been tested in many hematological and solid cancers both in vitro and in vivo, with promising effects. In order to establish the scientific ground for future clinical application of ATO in SCLC, this study aimed to investigate the anticancer effect and mechanism of ATO in SCLC using in vitro and in vivo models, either as a single agent or in combination with standard chemotherapy. In addition, an ATO-acquired resistant cell line (H841-AR) derived from SCLC cell line H841 was used to explore potential mechanisms of ATO resistance and cross-resistance to other chemotherapeutic drugs. In the first part of this study, ATO was shown to exert cytotoxic effect in all of the chosen SCLC cell lines. Various cellular mechanisms were triggered upon ATO exposure: redox status disturbances (hydrogen peroxide (H2O2) generation, glutathione (GSH) depletion and thioredoxin 1 (Trx1) down-regulation), mitochondrial membrane depolarization (MMD), DNA damage, apoptosis and necroptosis. In concert with this, Bcl-2 was down-regulated accompanied by MMD, release of AIF and SMAC, DNA degradation, XIAP inhibition and caspases activation. Adoption of N-acetyl-L-cysteine (NAC) and buthionine sulfoximine (BSO) demonstrated GSH depletion and reactive oxygen species (ROS) generation played the pivotal role to mediate cytotoxic effect of ATO in SCLC. In the second part of this study, when combined with chemotherapeutic agents, ATO displayed synergistic and antagonistic interaction with cisplatin and etoposide respectively in SCLC cell line models. The beneficial combination of ATO and cisplatin was also substantiated by tumor xenograft models. Augmented GSH depletion and suppressed drug efflux mechanism were found to explain the synergistic effects. In the last part of this study, H841-AR was generated as an acquired multi-drug resistant (ATO, cisplatin and etoposide) cell line to investigate the potential resistance mechanisms and possible future drug combinations. Comparing H841-AR cells with parental H841 cells using cDNA microarray, a long list of genes was altered in ATO-resistant cells. At least 20 up-regulated and 45 down-regulated genes were short-listed as candidates with a cut-off at 5-fold change. Interestingly, qPCR data has shown that 5 selected up-regulated genes in H841-AR cells were also highly expressed in DMS79 cells with intrinsic ATO resistance compared to the relatively sensitive cell lines, indicating that these genes might be associated with ATO resistance in SCLC. In summary, ATO was shown to be an active anticancer agent in SCLC, either alone or in combination with cisplatin. The major mechanisms of action of ATO and its synergism with cisplatin in SCLC were elucidated. Genetic data derived from an acquired resistant (to ATO, cisplatin and etoposide) SCLC cell line may help to uncover the mechanisms of resistance to ATO, allowing possible future drug combinations. / published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

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 cancer treatment success in patients with heart disease to gather data on the subject. Furthermore, we used the 2020 NHIS to gather demographic data on the interviewed adults who answered the questions regarding lung cancer and heart disease. At the start, we hypothesized that there wasn’t going to be a high success rate for lung cancer treatment in patients with heart disease due to the invasive nature of the treatment available. We found that most patients with pre-existing heart disease that sought lung cancer treatment had their condition worsened due to severe invasive treatments such as chemotherapy and radiotherapy. In most surgical lung cancer treatment options, patients with pre-existing heart disease were more likely to die after the operation than patients without pre-existing heart disease. Currently and in future times, it’s more likely to find individuals with both diseases due to the rising culture which endorses poor habits in eating, alcohol consumption, smoking, and the utilization of drugs. Understanding the difficulty and dangers that are found in current treatment options for heart disease patients suffering from lung cancer will allow for innovation and improvement in treating such patients.

published_or_final_version / abstract / Surgery / Doctoral / Doctor of Philosophy

An improved method is introduced for prediction of local tumor control following lung stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC) patients using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET). A normalized background-corrected tumor maximum Standard Uptake Value (SUVcmax) is introduced using the mean uptake of adjacent aorta (SUVref), instead of the maximum uptake of lung tumor (SUVmax). This method minimizes the variations associated with SUVmax and objectively demonstrates a strong correlation between the low SUVcmax (< 2.5-3.0) and local control of post lung SBRT. The false positive rates of both SUVmax and SUVcmax increase with inclusion of early (<6 months) PET scans, therefore such inclusion is not recommended for assessing local tumor control of post lung SBRT. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2013.

Evaluation of dose optimization using the Pencil Beam (PB) and Monte Carlo (MC) algorithms may allow physicists to apply dosimetric offsets to account for inaccuracies of the PB algorithm for lung cancer treatment with Stereotactic Body Radiotherapy (SBRT). 20 cases of Non-Small Cell Lung Cancer (NSCLC) were selected. Treatment plans were created with Brainlab iPlanDose® 4.1.2. The D97 of the Planning Target Volume (PTV) was normalized to 50 Gy on the Average Intensity Projection (AIP) using the fast PB and compared with MC. This exact plan with the same beam Monitor Units (MUs) was recalculated over each respiratory phase. The results show that the PB algorithm has a 2.3-2.4% less overestimation at the maximum exhalation phase than the maximum inhalation phase when compared to MC. Significantly smaller dose difference between PB and MC is also shown in plans for peripheral lesions (7.7 ± 0.7%) versus central lesions (12.7±0.8%)(p< 0.01). / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

Empirical methods of beam angle optimization (BAO) are tested against the BAO that is currently employed in Eclipse treatment planning software. Creating an improved BAO can decrease the amount of time a dosimetrist spends on making a treatment plan, improve the treatment quality and enhance the tools an inexperienced dosimetrist can use to develop planning techniques. Using empirical data created by experienced dosimetrists from 69 patients treated for lung cancer, the most frequently used gantry angles were applied to four different regions in each lung to gather an optimal set of fields that could be used to treat future lung cancer patients. This method, given the moniker FAU BAO, is compared in 7 plans created with the Eclipse BAO choosing 5 fields and 9 fields. The results show that the conformality index improved by 30% or 3% when using the 5 and 9 fields. The conformation number was better by 12% from the 5 fields and 9% from the 9 fields. The organs at risk (OAR) were overall more protected to produce fewer nonstochastic effects from the radiation treatment with the FAU BAO. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

The purpose of this research is to determine the feasibility of introducing the Monte Carlo (MC) dose calculation algorithm into the clinical practice. Unlike the Ray Tracing (RT) algorithm, the MC algorithm is not affected by the tissue inhomogeneities, which are significant inside the chest cavity. A retrospective study was completed for 102 plans calculated using both the RT and MC algorithms. The D95 of the PTV was 26% lower for the MC calculation. The first parameter of conformality, as defined as the ratio of the Prescription Isodose Volume to the PTV Volume was on average 1.27 for RT and 0.67 for MC. The results confirm that the RT algorithm significantly overestimates the dosages delivered confirming previous analyses. Correlations indicate that these overestimates are largest for small PTV and/or when the ratio of the volume of lung tissue to the PTV approaches 1. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2014. / FAU Electronic Theses and Dissertations Collection

Monte Carlo (MC) and Pencil Beam (PB) calculations are compared to their measured planar dose distributions using a 2-D diode array for lung Stereotactic Body Radiation Therapy (SBRT). The planar dose distributions were studied for two different phantom types: an in-house heterogeneous phantom and a homogeneous phantom. The motivation is to mimic the human anatomy during a lung SBRT treatment and incorporate heterogeneities into the pre-treatment Quality Assurance process, where measured and calculated planar dose distributions are compared before the radiation treatment. Individual and combined field dosimetry has been performed for both fixed gantry angle (anterior to posterior) and planned gantry angle delivery. A gamma analysis has been performed for all beam arrangements. The measurements were obtained using the 2-D diode array MapCHECK 2™. / Includes bibliography. / Thesis (M.S.)--Florida Atlantic University, 2015. / FAU Electronic Theses and Dissertations Collection

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 National Cancer Institute's Surveillance Epidemiologic and End Result (SEER) Program from 2004-2011. Athough no significant difference was found between AFBB (n = 119) and AMBB (n = 238) relative to NSCLC stage at diagnosis, differences in treatments were found. The proportion of AFBB patients with early stage (I and II) NSCLC who underwent surgery differed significantly from that of AMBB (p < 0.05); AFBB patients were more likely to receive surgical therapy. The proportion of AFBB patients with stages I-IV of the disease who received radiation treatment also differed significantly from that of AMBB patients (p < 0.05); the latter were more likely to receive radiation therapy. Results from logistic regression analysis indicate that AFBB patients were more likely to receive surgical treatment while AMBB patients were more likely to receive radiation treatment. This study outcome can inform other NSCLC research to provide better insights to the cause of the treatment differences within the race from differing birth places, and efficient planning, evaluation of control programs and management of the disease.