1. Background
TRD, left breast cancer, treatment-resistant depression, cognitive impairment, memory difficulties, cancer, neurotoxicity, depressive disorder, psychiatric, visuo-spatial skills, migraine, depression
CANCER, AIDS, SENTINEL LYMPH NODE, SECONDARY, MIGRAINE, DISEASES, CORTEX
This pilot feasibility study aimed to evaluate the effects of transcranial magnetic stimulation (TMS) on chemotherapy-related cognitive impairment (CRCI), and we report here on the first patient. Background: Deleterious cognitive changes due to chemotherapy or CRCI are commonly referred to as “chemo brain”. With the increasing survival of cancer patients, this poorly understood and inadequately treated condition will likewise have an increasing toll on individuals and society. Since there is no approved treatment for chemo brain, we have initiated a therapeutic trial using transcranial magnetic stimulation (TMS), a non-invasive brain stimulation technique approved in many countries for the treatment of neurologic and psychiatric conditions like migraine and depression. Case presentation: A 58-year-old woman, diagnosed 7 years prior with left breast cancer, underwent partial mastectomy with sentinel lymph node biopsy. She then received four cycles of adjuvant chemotherapy followed by radiation therapy. Afterwards, she was on tamoxifen for 4 years and then switched to aromatase inhibitors. The patient’s CRCI started during chemotherapy and severely impaired her quality of life for an additional two years. In the third year after chemotherapy, the CRCI partially cleared to stabilize to the level at the time of presentation for this trial. The patient continues to have memory difficulties and decreased concentration, which makes multi-tasking very difficult to impossible. She is reliant on memory aids at work and at home. The participant underwent 10 consecutive sessions of TMS during weekdays for 2 weeks. Stimulation was directed to the left dorsolateral prefrontal cortex. After TMS, the participant significantly improved in memory function on neuropsychological testing. While she reported no subjective differences in concentration or memory, she did report an improvement in her sleep. Functional magnetic resonance imaging of the brain before and after TMS showed increased resting-state functional connectivity between the stimulation site and several brain regions. Remarkably, after 6 years of chemo brain and remaining in the same position at work due to her inability to concentrate and multi-task, she applied for and received a promotion 5–6 months after her TMS treatments. Conclusions: This first patient in the phase 1 clinical trial testing of TMS for the treatment of “chemo brain” provided important lessons for feasibility and insights into mechanisms of potential benefit.Chemo brain goes by many names, like chemotherapy-related cognitive impairment (CRCI), and is defined as cognitive changes that occur during and/or after chemotherapy. These changes may include the impairment of memory, learning, concentration, executive function, and visuo-spatial skills [There is still no clear understanding regarding the mechanisms involved in CRCI. Some theories suggest that cytotoxic antitumoral drugs inhibit enzymes that allow DNA replication or interfere with DNA synthesis and its components, leading to antiproliferative effects that can also negatively impact neurons throughout the body, resulting in neurotoxicity or reduced neurogenesis [The intricate situation draws parallels with treatment-resistant depression (TRD), where transcranial magnetic stimulation (TMS) has been FDA-approved to efficaciously alleviate symptoms of TRD. TMS is a non-invasive and safe magnetic brain stimulation technique which does not involve any form of general anesthesia or sedation. Since its introduction by Barker et al. in 1985 [In 2018, the USFDA approved an intermittent theta burst stimulation (iTBS) treatment, a form of shorter rTMS that facilitates cortical excitability, as a protocol stimulating the left dorsolateral prefrontal cortex (DLPFC) for the treatment of major depressive disorder. Cumulative evidence has indicated the effectiveness of excitatory iTBS over the left DLPFC in improving cognitive performance in psychiatric/neurological diseases or healthy volunteers [The primary aim is to determine the feasibility of iTBS for the treatment of CRCI. A secondary aim is to examine potential efficacy measured by standard neuropsychological testing and functional MRI. Our hypothesis is that excitatory iTBS exerts its effect by improving brain activity at the stimulation locus, thereby potentially eliciting neuroplasticity. This method distinctly focuses on the PFC, specifically DLPFC, the region most susceptible to CRCI, with the aim of counteracting the disruption of LTP and neural circuits. This strategic intervention holds the promise of enhancing intricate cerebral functions, consequently offering a prospective avenue for the amelioration of CRCI. 