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Lung cancer remains the leading cause of cancer deaths in the United States despite public health campaigns aimed at reducing its rate of mortality. Kentucky is the state with the highest lung cancer incidence and mortality. This study aims to assess the impact of misclassification of cause of death from Lung Cancer in Kentucky for the period 1979 to 2002. We will examine the potential competing classification of death for two other smoking-related diseases, Chronic Obstructive Pulmonary Disease (COPD) and Emphysema. Age-adjusted mortality rates for these diseases for white males were obtained from the National Center for Health Statistics. There was little evidence that any misclassification between COPD or Emphysema mortality rates was in agreement with the rising lung cancer rates in Kentucky. The long-term increase in lung cancer mortality in Kentucky is likely because of a combination of risk effects between smoking and other risk-factors for this disease.

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Introduction: Lung cancer is the leading cause of cancer death worldwide. In Canada, in 2021 alone, an estimated 21,000 patients have died from this disease. Non-small cell lung cancer (NSCLC) constitutes 85% of all lung cancer cases diagnosed. Over the past 30 years, treatment of unresected locally advanced (LA)-NSCLC evolved from treatment with chest radiotherapy (RT) alone to the current standard of care (SOC) of concurrent chemo-radiation (cCRT), followed by consolidative immunotherapy. Modern RT has influenced the survival of LA-NSCLC patients. In this work we analyzed data from provincial and local institutional databases to evaluate whether, i) the use of modern imaging with 18F-deoxyglucose (FDG)-positron emission tomography (PET), ii) dose of chest RT to tumors and iii) unintentional irradiation of normal tissues during treatment for lung cancer, influence outcomes of patients managed with RT. Methodology: Ontario provincial databases were searched through the Institute of Clinical Evaluative Sciences (IC/ES) for stage III NSCLC patients diagnosed between 2007 and 2017. Surgical patients were excluded, and all patients that received RT with or without chemotherapy were selected. Patients were divided into groups of different RT doses (<40Gy, 40-55.9Gy, and ≥56Gy) and whether they underwent diagnostic FDG-PET. For the next study phase (the institutional level), we retrospectively identified and reviewed LA-NSCLC patients treated at local health integration network area 4 (LHIN4) cancer centres (Juravinski and Walker Family Cancer Centres) from 2009 to 2019. We selected patients treated in that period with chest RT > 40Gy with or without chemotherapy. Patients’ data were reviewed individually for disease characteristics, staging investigations, RT treatment parameters and survival outcomes. Dosimetric analysis was performed on both groups of patients (RT alone group and cCRT group). Results: The provincial analysis included 5,577 stage III patients who had received chest RT without surgery between January 2007 and March 2017. Within this group, 39.8% (2,225) received RT alone, 47.4% (2,645) received concurrent chemo-radiotherapy (cCRT), and 12.6% (707) received sequential chemo-radiotherapy (sCRT). Median overall survival (OS) with RT alone in three dose groups <40Gy, 40-55.9Gy, ≥ 56Gy was 7.2, 8.5 and 13.3 months compared to 16.5, 15.8 and 22 months for cCRT patients. Higher RT dose and PET utilization were independently associated with improved survival in multivariate analysis. At the institutional analysis, 84 patients were treated with RT alone, 184 with cCRT and patients with sequential CRT were excluded. In the RT alone group, the median, 1- and 3-year overall survival were 18.1 months, 64.4% and 24.3%, respectively. In comparison, the median, 1- and 3-year survival outcomes in the cCRT group were 36.3 months, 82.5%, and 50.4%, respectively. Additionally, 79.8% of patients in the radiation alone group and 95.1% in cCRT group had PET staging. In univariate analysis, the RT dose prescribed to the tumor and RT dose delivered to the heart were significantly associated with survival, while multivariate analysis only showed the significant association between RT dose to heart and overall survival. Conclusions: Our population-based analysis confirmed that radiation monotherapy remains a widely used treatment modality in LA-NSCLC. Higher RT doses and utilization of FDG-PET imaging are associated with improved survival in patients with unresected LA-NSCLC managed with RT. The institutional analysis suggests that in well-staged patients with LA-NSCLC, chest RT of ≥40Gy is associated with improved survival outcomes that compare favorably with historical results of definitive RT alone treatment. Further, survival of patients staged well with FDG-PET and treated with SOC cCRT was higher than historical reports. Importantly, in this study we found that RT dose delivered to the heart associates negatively with patient survival. These findings can help improve clinical decision-making in the management of unresected LA-NSCLC and can serve as basis for future clinical trials. / Thesis / Master of Science (MSc) / Lung cancer is the leading cause of cancer death in Canada and worldwide. These tumors are present as two main histological types, small cell and non-small cell lung cancer, the latter of which consists the majority of the cases diagnosed. Although treatments with surgery or radiotherapy provide reasonable outcomes in lung cancer cases detected early, a high proportion of patients present with localized but advanced disease that is inoperable. Over the last three decades, treatment of locally advanced non-small cell lung cancer has evolved from radiation alone to chemoradiation and immunotherapy. These developments have increased the survival of these patients. In this thesis, we tried to dissect the elements that play roles in the survival of locally advanced non-small cell lung cancer patients. To do this, we evaluated such patients at two levels. First, at the provincial level, we evaluated the type of treatments, and we explored the association of metabolic imaging with positron emission tomography (PET) and the use of high-dose chest radiotherapy with patient survival. Second, at the institutional level, we assessed patients’ outcomes with a more detailed approach. We analyzed the type of treatment along with a detailed dosimetric analysis. The results of our analysis suggest that the use of PET scans and curative radiotherapy is associated with improved survival. On the other hand, the unintentional treatment of the heart with increasing doses of radiotherapy, taking place during chest radiation for lung cancer, is associated with poor outcomes. These results provide a basis for further investigation to improve outcomes of radiotherapy in this disease.

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Lung cancer is one the most dangerous types of all cancer. Several studies have explored the use of machine learning methods to predict and diagnose this cancer. This study explored the potential of decision tree (DT) and random forest (RF) classification models, in the context of a small transcriptome dataset for outcome prediction of different subtypes on lung cancer. In the study we compared the three subtypes; adenocarcinomas (AC), small cell lung cancer (SCLC) and squamous cell carcinomas (SCC) with normal lung tissue by applying the two machine learning methods from caret R package. The DT and RF model and their validation showed different results for each subtype of the lung cancer data. The DT found more features and validated them with better metrics. Analysis of the biological relevance was focused on the identified features for each of the subtypes AC, SCLC and SCC. The DT presented a detailed insight into the biological data which was essential by classifying it as a biomarker. The identified features from this research may serve as potential candidate genes which could be explored further to confirm their role in corresponding lung cancer types and contribute to targeted diagnostics of different subtypes.

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The stage at diagnosis is the single most important predictor of lung cancer outcome. Therefore, detecting lung cancer early is of utmost importance. Low-dose computed tomography (LDCT) has proven beneficial in the early detection and mortality reduction of lung cancer. Despite this, very few of the high-risk population get annual LDCT done. Patients' attitudes towards tobacco usage and preventive care can be a factor in getting LDCT. We analyzed the relationship between the willingness to undergo LDCT and a person's readiness to try tobacco cessation medication or get the pneumococcal vaccine. We also analyzed the relationship between patients who had tobacco cessation counseling and their willingness to get LDCT and pneumococcal vaccine. Medical records of high-risk patients seen in the East Tennessee State University (ETSU) clinics between January 1, 2016, and November 30, 2020, were analyzed retrospectively. In the data obtained, a total of 2,834 patients were current smokers and were included in the research. The study subjects were assessed in two ways, which from here on will be referred to as method one and method two. In the first method, patients who underwent LDCT were assessed, and the outcome investigated was tobacco cessation counseling, tobacco cessation medication prescription, and pneumococcal vaccination. In the second method, patients who had tobacco cessation counseling were assessed, and the outcome evaluated was LDCT, tobacco cessation medication prescription, and pneumococcal vaccination. In the first method, out of 2,834 total population, 570 had undergone at least one LDCT screening during the study period. Of the 570 patients who underwent LDCT, 22.8% tried one of the tobacco cessation medications at least once during the study period (vs. 9.8% in patients who did not get the LDCT). Also, 71.5% of patients who had LDCT received at least one dose of pneumonia vaccine (vs. 35.5% in patients who did not get the LDCT). In the second method, 1,673 out of 2,834 patients received at least one tobacco cessation counseling, and out of those, 27.5% had LDCT screening (vs. 9.5% among those who never received counseling). Also, 54.9% received a pneumococcal vaccine (vs. 45.1% among those who did not receive counseling). The study demonstrates a relationship between getting LDCT and getting a pneumococcal vaccine or tobacco cessation medications. It also reveals that tobacco cessation counseling increases the odds of getting LDCT, tobacco cessation medications, and pneumococcal vaccine.

Cardiac arrest due to air embolism is an infrequent complication. Air embolism can be associated with procedures like endoscopic retrograde cholangiopancreatography, endoscopic variceal ligation, operative hysteroscopy, laparoscopic surgery, pacemaker placement, cardiac ablation, fiberoptic bronchoscopy, and decompression sickness. In rare cases, air embolus can be a catastrophic complication of computed tomography (CT) guided lung biopsy, which can lead to cardiac arrest. We present a case of a 67-year-old male chronic smoker with a left lower lobe pulmonary nodule who had a cardiac arrest due to air embolism as a consequence of CT guided biopsy of the pulmonary nodule found on a CT scan of the chest. He was successfully resuscitated and intubated for mechanical ventilation. He was managed conservatively and discharged home in a stable condition.