{"id":{"repo_id":"buffalo","oai_identifier":"oai:ubir.buffalo.edu:10477/86474"},"canonical_url":"https://search.dev.ndltd.org/etd/buffalo/oai:ubir.buffalo.edu:10477/86474","repository":{"repo_id":"buffalo","name":"Buffalo","base_url":"https://ubir.buffalo.edu/oai/request"},"display":{"title":"Survival and Biomarker Trends for Non-Small Cell Lung Cancer with the Implementation of Cuban Developed Therapies","abstract":"Ph.D.","abstract_html":"Ph.D.","abstract_has_math":false,"creators":["Evans, Rachel; 0000-0001-8817-5128"],"institution":"State University of New York at Buffalo","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Reid, Mary","Roswell Park"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-02-21T17:22:47Z","date_published":"2025-02-21T17:22:47Z","updated_at":"2026-07-27T19:05:32Z","subjects":["epidemiology"],"languages":["eng"],"rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10477/86474","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Reid, Mary","Roswell Park"]},{"key":"dc:creator","label":"Author","values":["Evans, Rachel; 0000-0001-8817-5128"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-02-21T17:22:47Z","2020"]},{"key":"dc:publisher","label":"Institution","values":["State University of New York at Buffalo"]},{"key":"dc:type","label":"Dc Type","values":["Text","Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["epidemiology"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/10477/86474"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Ph.D.","Background: Lung cancer remains one of the most diagnosed cancers worldwide and accounts for the majority of cancer-related deaths. Mortality rates are now on the decline over the past few years due to declining smoking rates and improvements in treatment. Curative treatments are currently only an option for early-stage lung cancer but unfortunately, the majority of lung cancer is diagnosed in advanced stages. Lung cancer screening offers an opportunity for lung cancer to be detected at an earlier stage, leading to a reduction in disease-specific mortality, and potentially all-cause mortality as well. In addition to diagnosing lung cancer earlier through screening, more research is needed to identify biomarkers of lung cancer risk and treatment efficacy. An international collaboration with Havana, Cuba has afforded a new opportunity to evaluate therapies developed in Cuba for the treatment of advanced staged non-small cell lung carcinoma (NSCLC). In the context of early phase clinical trials and new biomarkers, using minimally invasive collection strategies are being evaluated to study the safety and efficacy of CIMAvax-EGF in combination with an FDA-approved therapy. Methods: To better understand the impact of lung cancer screening guidelines, it is important to look at the change in incidence rates when comparing diagnosis data from before and after the release of such guidelines. In Chapter 2, public data available through the Surveillance, Epidemiology, and End Results (SEER) database was utilized to evaluate the change in incidence and hazard ratios of NSCLC before and after the implementation of the lung cancer screening guidelines in 2011 to understand the effects of lung cancer screening and to address issues of screening implementation. Phase 1 trials are primarily conducted to evaluate the safety and tolerability of new therapies or combinations of therapies. Chapter 3 presents the results of a phase 1 clinical trial conducted to evaluate the safety of CIMAvax-EGF in combination with FDA-approved anti-PD1 inhibitor Nivolumab using the “3+3” trial design. Biomarkers from blood and nasal brush samples were analyzed at different timepoints throughout treatment to establish a profile of which markers may be associated with treatment response. Flow cytometry and Luminex assays were used to analyze the blood samples. Multiple cox regression method was used to evaluate association of immunophenotype samples with survival outcomes. Mann Whitney test was also used to evaluate the association with response. To evaluate less invasive methods for biomarker development, bulk RNA sequencing was used to analyze the nasal epithelium samples in Chapter 4. Results: Incidence rates of NSCLC did not differ greatly after the release of the lung cancer screening guidelines when compared to pre-guideline rates. Survival rates have improved after the release of these guidelines but further research is warranted as there is limited follow-up data due to the more recent diagnosis of cases after the release of the guidelines. When treating advanced staged NSCLC cases, CIMAvax-EGF and nivolumab can be administered at each single-agent dose schedule safely together based on the phase I trial data. The objective response rate was 31% (95% CI 9% to 61%) according to irRECIST. Based on a generalized linear model, there was a significant inverse correlation between induction of anti-EGF antibody titers and depleting serum EGF levels. Within the nasal epithelium, a total of 127 genes were differentially expressed between baseline (pre-treatment) and end of loading dose (post-treatment) samples, p<0.005. The EGF analyte signature seen in the nasal brushings suggested a trend that was associated with the response status of the patients. Initial analysis using pathway enrichment, down-regulated genes were suggestive of EGFR signaling within cancer, the Pi3K pathway, and the TP53 pathway. Conclusions: Broad-based implementation of the lung cancer screening guidelines remains an issue in clinical practice even after definitive research has shown that screening significantly decreases the mortality rates of lung cancer. Further policies need to address how clinical practices can increase the implementation of these guidelines so lung cancer can be caught earlier to further decrease the mortality rate from this cancer. While the Cuban developed therapy of CIMAvax-EGF for lung cancer has shown that it can be administered safety with checkpoint inhibitors, further research is needed to understand how these therapies affect the tumor microenvironment and which biomarkers identify the subgroup of patients most likely to benefit from this drug combination. A phase II clinical trial is currently ongoing that will evaluate overall survival, progression free survival and objective response rates of patients receiving CIMAvax-EGF in combination with immune checkpoint inhibitors. Biomarkers from the nasal epithelium may provide additional information on the effect of CIMAvax-EGF on the lung injury field. Further research is needed to tease out the gene expression changes associated with the individual therapies when administered alone.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Survival and Biomarker Trends for Non-Small Cell Lung Cancer with the Implementation of Cuban Developed Therapies"]}]}],"canonical_facts":{"dc:contributor":["Reid, Mary","Roswell Park"],"dc:creator":["Evans, Rachel; 0000-0001-8817-5128"],"dc:date":["2025-02-21T17:22:47Z","2020"],"dc:description":["Ph.D.","Background: Lung cancer remains one of the most diagnosed cancers worldwide and accounts for the majority of cancer-related deaths. Mortality rates are now on the decline over the past few years due to declining smoking rates and improvements in treatment. Curative treatments are currently only an option for early-stage lung cancer but unfortunately, the majority of lung cancer is diagnosed in advanced stages. Lung cancer screening offers an opportunity for lung cancer to be detected at an earlier stage, leading to a reduction in disease-specific mortality, and potentially all-cause mortality as well. In addition to diagnosing lung cancer earlier through screening, more research is needed to identify biomarkers of lung cancer risk and treatment efficacy. An international collaboration with Havana, Cuba has afforded a new opportunity to evaluate therapies developed in Cuba for the treatment of advanced staged non-small cell lung carcinoma (NSCLC). In the context of early phase clinical trials and new biomarkers, using minimally invasive collection strategies are being evaluated to study the safety and efficacy of CIMAvax-EGF in combination with an FDA-approved therapy. Methods: To better understand the impact of lung cancer screening guidelines, it is important to look at the change in incidence rates when comparing diagnosis data from before and after the release of such guidelines. In Chapter 2, public data available through the Surveillance, Epidemiology, and End Results (SEER) database was utilized to evaluate the change in incidence and hazard ratios of NSCLC before and after the implementation of the lung cancer screening guidelines in 2011 to understand the effects of lung cancer screening and to address issues of screening implementation. Phase 1 trials are primarily conducted to evaluate the safety and tolerability of new therapies or combinations of therapies. Chapter 3 presents the results of a phase 1 clinical trial conducted to evaluate the safety of CIMAvax-EGF in combination with FDA-approved anti-PD1 inhibitor Nivolumab using the “3+3” trial design. Biomarkers from blood and nasal brush samples were analyzed at different timepoints throughout treatment to establish a profile of which markers may be associated with treatment response. Flow cytometry and Luminex assays were used to analyze the blood samples. Multiple cox regression method was used to evaluate association of immunophenotype samples with survival outcomes. Mann Whitney test was also used to evaluate the association with response. To evaluate less invasive methods for biomarker development, bulk RNA sequencing was used to analyze the nasal epithelium samples in Chapter 4. Results: Incidence rates of NSCLC did not differ greatly after the release of the lung cancer screening guidelines when compared to pre-guideline rates. Survival rates have improved after the release of these guidelines but further research is warranted as there is limited follow-up data due to the more recent diagnosis of cases after the release of the guidelines. When treating advanced staged NSCLC cases, CIMAvax-EGF and nivolumab can be administered at each single-agent dose schedule safely together based on the phase I trial data. The objective response rate was 31% (95% CI 9% to 61%) according to irRECIST. Based on a generalized linear model, there was a significant inverse correlation between induction of anti-EGF antibody titers and depleting serum EGF levels. Within the nasal epithelium, a total of 127 genes were differentially expressed between baseline (pre-treatment) and end of loading dose (post-treatment) samples, p<0.005. The EGF analyte signature seen in the nasal brushings suggested a trend that was associated with the response status of the patients. Initial analysis using pathway enrichment, down-regulated genes were suggestive of EGFR signaling within cancer, the Pi3K pathway, and the TP53 pathway. Conclusions: Broad-based implementation of the lung cancer screening guidelines remains an issue in clinical practice even after definitive research has shown that screening significantly decreases the mortality rates of lung cancer. Further policies need to address how clinical practices can increase the implementation of these guidelines so lung cancer can be caught earlier to further decrease the mortality rate from this cancer. While the Cuban developed therapy of CIMAvax-EGF for lung cancer has shown that it can be administered safety with checkpoint inhibitors, further research is needed to understand how these therapies affect the tumor microenvironment and which biomarkers identify the subgroup of patients most likely to benefit from this drug combination. A phase II clinical trial is currently ongoing that will evaluate overall survival, progression free survival and objective response rates of patients receiving CIMAvax-EGF in combination with immune checkpoint inhibitors. Biomarkers from the nasal epithelium may provide additional information on the effect of CIMAvax-EGF on the lung injury field. Further research is needed to tease out the gene expression changes associated with the individual therapies when administered alone.","**To request an accessible version of the file(s) associated with this item, contact library@buffalo.edu. Please include the item's persistent URL [http://hdl.handle.net/. . .] in your request.**"],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/10477/86474"],"dc:language":["eng"],"dc:publisher":["State University of New York at Buffalo"],"dc:rights":["Users of works found in University at Buffalo Institutional Repository (UBIR) are responsible for identifying and contacting the copyright owner for permission to reuse. University at Buffalo Libraries do not manage rights for copyright-protected works and cannot assist with permissions.","Copyright retained by author."],"dc:subject":["epidemiology"],"dc:title":["Survival and Biomarker Trends for Non-Small Cell Lung Cancer with the Implementation of Cuban Developed Therapies"],"dc:type":["Text","Dissertation"]},"updated_at":"2026-07-27T19:05:32Z"}