Author ORCID Identifier
Date of Award
2026
Document Type
Thesis (Ph.D.)
Department or Program
Engineering Sciences
First Advisor
Linton T. Evans
Second Advisor
David Gladstone
Third Advisor
P. Jack Hoopes
Abstract
Most tumors affecting the brain and spine are managed through a combination of surgical resection, radiation, and chemotherapy; however, operative morbidity from invasive surgery, the narrow therapeutic window of conventional radiotherapy, and poor blood-brain barrier penetration of systemic agents are critical barriers that hinder long term tumor control. This thesis presents three complementary strategies to advance brain and spine tumor therapy. First, we investigate laser interstitial thermal therapy (LITT) in the treatment of spinal tumors with metastatic epidural spinal cord compression, replacing “separation surgery” with a minimally invasive, image-guided approach that maximizes tumor ablation while preserving neurologic function. Second, we characterize the normal-tissue sparing of ultra-high dose-rate (UHDR) radiation in preclinical models, shedding light on key in-vivo parameters that optimize the therapeutic index. Third, we evaluate LITT-facilitated targeting of chemotherapy to tumor tissue within the central nervous system (CNS), leveraging heat-released chemotherapy and transient blood-brain barrier disruption to spatially target drug release and minimize systemic toxicity. Data demonstrates (1) successful LITT ablation & thermography motion compensation in the first large animal model of metastatic epidural spinal cord compression, (2) UHDR reduction in radiation-induced normal tissue toxicity modulated by tissue oxygenation, and (3) targeted local drug accumulation with LITT-mediated chemotherapy delivery without added neurotoxicity. By integrating minimally invasive surgery, advanced radiotherapy, and spatially targeted chemotherapy, this work lays a cohesive roadmap toward durable, less-morbid control of tumors involving the CNS and spine. The resulting mechanistic insights and optimized treatment parameters will inform early-phase clinical trials and ultimately improve outcomes for patients facing these devastating diagnoses.
Recommended Citation
Tavakkoli, Armin David, "Advancing CNS Tumor Management: Novel Modalities in Surgery, Radiation, and Chemotherapy" (2026). Dartmouth College Ph.D Dissertations. 478.
https://digitalcommons.dartmouth.edu/dissertations/478
Included in
Biomedical Engineering and Bioengineering Commons, Neurosurgery Commons, Oncology Commons
