Effectiveness of Immune Checkpoint Inhibitor Therapy on Bone Metastases in Non-Small-Cell Lung Cancer

Abbott, Annalise Georgia

Effectiveness of Immune Checkpoint Inhibitor Therapy on Bone Metastases in Non-Small-Cell Lung Cancer

dc.contributor.advisor	Monument, Michael
dc.contributor.author	Abbott, Annalise Georgia
dc.contributor.committeemember	Puloski, Shannon
dc.contributor.committeemember	Cheung, Winson
dc.contributor.committeemember	Morris, Don
dc.date	2023-11
dc.date.accessioned	2023-08-23T19:42:31Z
dc.date.available	2023-08-23T19:42:31Z
dc.date.issued	2023-07
dc.description.abstract	Background: Bone metastases (BoMs) are prevalent in patients with metastatic non-small- cell lung cancer (NSCLC) and frequently result in intractable pain, pathologic fracture, and immobility. Patients who respond to immune checkpoint inhibitors (ICIs) demonstrate meaningful survival improvements, however, there are limited data detailing how BoMs respond. The primary aim of this study was to compare the response of BoMs against visceral lesions in patients treated with ICIs. The secondary aim was to evaluate the effect of BoMs on survival. Methods: A retrospective, multicenter cohort study was conducted in patients with NSCLC treated with ICI in Alberta, Canada from 2015 to 2020. The primary endpoint was the time to progression of bone versus visceral lesions measured with serial imaging studies. Visceral lesions were categorized as adrenal, brain, liver, lung, lymph node, or other intra- abdominal lesions. The secondary outcome was overall survival (OS) amongst patients with and without BoMs. Sub-group analysis was performed in patients with high PD-L1 expression (≥50%). Results: A total of 573 patients were included with a median age of 69.9 years (IQR: 60.6- 73.4) and 268 (46.8%) had high PD-L1 expression. All patients had visceral metastases and 243 patients (42.4%) had BoMs. Median OS for the entire cohort was 8.1 months (95%CI: 6.9-9.1) and median progression free survival (PFS) was 3.8 months (95%CI: 3.1-4.4). No difference was found between the time to progression of bone, liver, and intra-abdominal lesions (p=0.20, p=0.76), but BoMs demonstrated faster progression than the other sites of disease. Subgroup analysis of patients with high PD-L1 expression (≥50%) demonstrated no significant difference in the time to progression between extra-thoracic sites of disease, including BoMs. The presence of BoMs was found to be an independent prognostic factor for OS (HR 1.26, 95%CI: 1.05-1.53, p=0.01) but this was not significant in the high PD-L1 expression subgroup (HR: 1.24, 95%CI: 0.92-1.68, p=0.16). Conclusion: Bone, liver, and intra-abdominal lesions demonstrated a significantly shorter time to progression than other visceral lesions, and patients with BoMs had inferior clinical outcomes. PD-L1 status was identified as an important biomarker predicting response, as patients with high PD-L1 expression demonstrated equivalent responses to ICI amongst extra-thoracic sites of disease.
dc.identifier.citation	Abbott, A. G. (2023). Effectiveness of immune checkpoint inhibitor therapy on bone metastases in non-small-cell lung cancer (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.
dc.identifier.uri	https://hdl.handle.net/1880/116879
dc.identifier.uri	https://dx.doi.org/10.11575/PRISM/41721
dc.language.iso	en
dc.publisher.faculty	Graduate Studies
dc.publisher.institution	University of Calgary
dc.rights	University of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.
dc.subject	Immunotherapy
dc.subject	Lung Cancer
dc.subject	Metastatic Bone Disease
dc.subject.classification	Medicine and Surgery
dc.title	Effectiveness of Immune Checkpoint Inhibitor Therapy on Bone Metastases in Non-Small-Cell Lung Cancer
dc.type	master thesis
thesis.degree.discipline	Medicine – Medical Sciences
thesis.degree.grantor	University of Calgary
thesis.degree.name	Master of Science (MSc)
ucalgary.thesis.accesssetbystudent	I require a thesis withhold – I need to delay the release of my thesis due to a patent application, and other reasons outlined in the link above. I have/will need to submit a thesis withhold application.