Accelerated Neuromodulation to Alleviate Cognitive Deficits Due to Cancer Therapy

Repetitive Intermittent Accelerated Theta-burst Transcranial Stimulation(iTBS) as a Potential Intervention for Chemotherapy Induced Cognitive Deficits (CICD)- a Pilot Clinical Trial to Explore Feasibility and Efficacy

This project is aimed at the discovery of neuro-modulation techniques that may alleviate chemotherapy induced cognitive deficits (CICD), especially in executive (higher-order) cognitive function (EF).

The specific aim for this study is to use magnetic resonance spectroscopy (MRS), self-report, and neuropsychological testing to identify changes in brain metabolite concentrations/ratios and changes in EF deficits associated with chemotherapy, before and after accelerated theta-burst transcranial stimulation (iTBS). The secondary aim is to assess for any association of changes in executive function with brain metabolite concentrations.

Inclusion Criteria:

• Women or men with a history of non-metastatic cancer who have completed definitive curative cancer therapy
• Received cytotoxic chemotherapy as a part of their therapy for cancer and at least one month has passed since the final cytotoxic chemotherapy treatment
• ≥ 18 years of age at time of cancer diagnosis and receipt of chemotherapy
• Patients must report subjective symptoms of "chemo-brain" (memory loss, difficulty with concentration, word-finding difficulties) with a FACT-Cog perceived cognitive impairment score < 60
• Ability to sign informed consent and comply with study procedures

Exclusion Criteria:

• Patients with a recurrence of cancer or those with current metastatic disease
• Patients with a history or current diagnosis of brain metastasis
• Patients with a history or current diagnosis of a primary brain tumor
• Patients with a history of brain surgery or brain radiation
• Patients receiving maintenance systemic therapy for cancer, other than endocrine therapy
• Patients who cannot produce or request adequate medical record documentation to ensure they meet inclusion and exclusion criteria
• Women who are currently pregnant
• History of childhood cancer or receipt of chemotherapy in childhood (<age 18). Developmental insult to the PFC, can be associated with long-term, durable and sometime debilitating cognitive deficits. Hence, we avoid any cognitive confounds that maybe related to this issue.
• Patients with a weight over 250 lbs., as these patients would not fit in the MRI scanner used in the protocol
• Patients who require benzodiazepines for MRI due to claustrophobic anxiety
• Patients with chest wall tissue expanders or other retained 7 Tesla MRI-incompatible metal. Any other specific contraindication to TMS or MRI not already listed above, including:
• (a) any implanted device in the head, neck or upper body (e.g. cochlear implant, cranial or other electrodes, pacemaker or defibrillator, medication pump, stent, aneurysm clip, etc.)
• (b) personal history of seizures or epilepsy, personal history of multiple concussions or unexplained loss of consciousness. This will be determined by physician judgement
• History of adverse reaction to previous TMS or MRI exposure
• Active substance use disorder in the past 6 months, excluding tobacco use disorder, as diagnosed by study physicians