Graduation Date

Summer 8-14-2020

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Programs

Medical Sciences Interdepartmental Area

First Advisor

Jane Meza

Second Advisor

Chi Lin

Third Advisor

Ward Chambers

Fourth Advisor

Michael Baine

Abstract

Pancreatic adenocarcinoma (PDAC) represents 7.2% of all cancer deaths, and by 2030, it will become the second leading cause of death due to cancer. The median overall survival (OS) is 17-23 months in resectable and 4-6 months in metastatic PC [8-9]. The 5-year survival of resectable PC is 22%, and unresectable PC is 8%. A majority of patients treated with standard treatments such as surgery, chemotherapy, and radiation therapy eventually succumb to the disease due to widespread micrometastases at the time of diagnosis. Due to the minimal effect of the current treatments, novel treatment strategies such as immunotherapeutics have been proposed. Immunotherapy has shown excellent efficacy in many other malignancies, but its role in the survival of PC patients is unclear.

The objectives of this dissertation were to investigate the impact of immunotherapy, including the sequence of treatments on the OS of PC patients stratified by definitive surgery of the pancreatic tumor. Data from the National Cancer Database was used to address these objectives. In this study, immunotherapy was associated with improved OS compared to no immunotherapy in both patients who received definitive surgery of the pancreatic tumor and patients who did not undergo surgery. In the surgery group, patients who received chemotherapy plus immunotherapy or chemoradiation plus immunotherapy had better OS compared to their counterparts without immunotherapy. In the no surgery group, patients who received chemoradiation plus immunotherapy had better OS compared to patients who received chemoradiation without immunotherapy. There was no significant difference in the OS of patients who started immunotherapy 31-90 days before chemotherapy, patients who started immunotherapy 91-180 days before chemotherapy, and patients who started chemotherapy and immunotherapy within 30 days of each other. There was also no significant difference in the OS of patients who started RT> 30 days before the start of immunotherapy, patients who started immunotherapy > 30 days before RT, and patients who started RT and immunotherapy within 30 days of each other. There was no significant difference in the OS of patients who received neoadjuvant immunotherapy and patients who received adjuvant immunotherapy. The study also highlighted the need for improving access to novel treatments as patients with older age, Black race, living in the rural areas, living in the areas with low education level, and diagnosis before 2011 were less likely to receive immunotherapy compared to their counterparts. The findings of the current study warrant future clinical trials of immunotherapy in PDAC patients.

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