title: Feasibility of Non-invasive Brain Modulation for Management of Pain Related to Chemoradiotherapy in Patients with Advanced Head and Neck Cancer.
abstract: Patients with head and neck cancer often experience a significant decrease in their quality of life during chemoradiotherapy (CRT) due to treatment-related pain, which is frequently classified as severe. Transcranial direct current stimulation (tDCS) is a method of non-invasive brain stimulation that has been frequently used in experimental and clinical pain studies. In this pilot study, we investigated the clinical impact and central mechanisms of twenty primary motor cortex (M1) stimulation sessions with tDCS during 7 weeks of CRT for head and neck cancer. From 48 patients screened, seven met the inclusion criteria and were enrolled. Electroencephalography (EEG) data were recorded before and after tDCS stimulation as well as across the trial to monitor short and long-term impact on brain function. The compliance rate during the long trial was extremely high (98.4%), and patients mostly reported mild side effects in line with the literature (e.g., tingling). Compared to a large standard of care study from our institution, our initial results indicate that M1-tDCS stimulation has a pain relief effect during the CRT that resulted in a significant attenuation of weight reduction and dysphagia normally observed in these patients. These results translated to our patient cohort not needing feeding tubes or IV fluids. Power spectra analysis of EEG data indicated significant changes in α, β, and γ bands immediately after tDCS stimulation and, in addition, α, δ, and θ bands over the long term in the seventh stimulation week (p< 0.05). The independent component EEG clustering analysis showed estimated functional brain regions including precuneus and superior frontal gyrus (SFG) in the seventh week of tDCS stimulation. These areas colocalize with our previous positron emission tomography (PET) study where there was activation in the endogenous μ-opioid system during M1-tDCS. This study provides preliminary evidence demonstrating the feasibility and safety of M1-tDCS as a potential adjuvant neuromechanism-driven analgesic therapy for head and neck cancer patients receiving CRT, inducing immediate and long-term changes in the cortical activity and clinical measures, with minimal side-effects.
authors.affiliation: Headache and Orofacial Pain Effort Lab, School of Dentistry, Department of Biologic and Materials Sciences, University of MichiganAnn Arbor, MI, USA; Center for Human Growth and Development, University of MichiganAnn Arbor, MI, USA.
authors.forename: Xiao-Su
authors.initials: XS
authors.lastname: Hu
authors.affiliation: Headache and Orofacial Pain Effort Lab, School of Dentistry, Department of Biologic and Materials Sciences, University of MichiganAnn Arbor, MI, USA; Division of Oral Pathology, Department of Periodontics and Oral Medicine, University of MichiganAnn Arbor, MI, USA.
authors.forename: Clayton A
authors.initials: CA
authors.lastname: Fisher
authors.affiliation: Department of Oral and Maxillofacial Surgery/Hospital Dentistry, University of Michigan Ann Arbor, MI, USA.
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Munz
authors.affiliation: Headache and Orofacial Pain Effort Lab, School of Dentistry, Department of Biologic and Materials Sciences, University of Michigan Ann Arbor, MI, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Toback
authors.affiliation: Headache and Orofacial Pain Effort Lab, School of Dentistry, Department of Biologic and Materials Sciences, University of Michigan Ann Arbor, MI, USA.
authors.forename: Thiago D
authors.initials: TD
authors.lastname: Nascimento
authors.affiliation: Headache and Orofacial Pain Effort Lab, School of Dentistry, Department of Biologic and Materials Sciences, University of MichiganAnn Arbor, MI, USA; Biostatistics Department, University of MichiganAnn Arbor, MI, USA.
authors.forename: Emily L
authors.initials: EL
authors.lastname: Bellile
authors.affiliation: Biostatistics Department, University of Michigan Ann Arbor, MI, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Rozek
authors.affiliation: Department of Radiation Oncology, University of Michigan Ann Arbor, MI, USA.
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
authors.affiliation: Department of Internal Medicine Oncology, University of Michigan Ann Arbor, MI, USA.
authors.forename: Francis P
authors.initials: FP
authors.lastname: Worden
authors.affiliation: Division of Oral Pathology, Department of Periodontics and Oral Medicine, University of Michigan Ann Arbor, MI, USA.
authors.forename: Theodora E
authors.initials: TE
authors.lastname: Danciu
authors.affiliation: Headache and Orofacial Pain Effort Lab, School of Dentistry, Department of Biologic and Materials Sciences, University of MichiganAnn Arbor, MI, USA; Center for Human Growth and Development, University of MichiganAnn Arbor, MI, USA.
authors.forename: Alexandre F
authors.initials: AF
authors.lastname: DaSilva
keywords: EEG; adjuvant; chemotherapy; head and neck cancer; pain management; tDCS