scholarly journals Human caudate nucleus subdivisions in tinnitus modulation

2020 ◽  
Vol 132 (3) ◽  
pp. 705-711 ◽  
Author(s):  
Philip L. Perez ◽  
Sarah S. Wang ◽  
Susan Heath ◽  
Jennifer Henderson-Sabes ◽  
Danielle Mizuiri ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Electrical Stimulation ◽  
Functional Connectivity ◽  
Auditory Cortex ◽  
Phase I ◽  
Caudate Nucleus ◽  
The Body ◽  
Electrode Placement ◽  
Caudate Head ◽  
Acute Tinnitus

OBJECTIVEThe object of this study was to define caudate nucleus locations responsive to intraoperative direct electrical stimulation for tinnitus loudness modulation and relate those locations to functional connectivity maps between caudate nucleus subdivisions and auditory cortex.METHODSSix awake study participants who underwent bilateral deep brain stimulation (DBS) electrode placement in the caudate nucleus as part of a phase I clinical trial were analyzed for tinnitus modulation in response to acute stimulation at 20 locations. Resting-state 3-T functional MRI (fMRI) was used to compare connectivity strength between centroids of tinnitus loudness-reducing or loudness-nonreducing caudate locations and the auditory cortex in the 6 DBS phase I trial participants and 14 other neuroimaging participants with a Tinnitus Functional Index > 50.RESULTSAcute tinnitus loudness reduction was observed at 5 caudate locations, 4 positioned at the body and 1 at the head of the caudate nucleus in normalized Montreal Neurological Institute space. The remaining 15 electrical stimulation interrogations of the caudate head failed to reduce tinnitus loudness. Compared to the caudate head, the body subdivision had stronger functional connectivity to the auditory cortex on fMRI (p < 0.05).CONCLUSIONSAcute tinnitus loudness reduction was more readily achieved by electrical stimulation of the caudate nucleus body. Compared to the caudate head, the caudate body has stronger functional connectivity to the auditory cortex. These first-in-human findings provide insight into the functional anatomy of caudate nucleus subdivisions and may inform future target selection in a basal ganglia–centric neuromodulation approach to treat medically refractory tinnitus.Clinical trial registration no.: NCT01988688 (clinicaltrials.gov)

Can polymetastatic disease be arrested using SABR? A dosimetric analysis to inform development of a phase I trial.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21567-e21567
Author(s):  
Mark Thomas Corkum ◽  
Hatim Fakir ◽  
David A. Palma ◽  
Timothy K. Nguyen ◽  
Glenn Bauman
Keyword(s):  
Clinical Trial ◽  
Phase I ◽  
Dose Level ◽  
Phase I Trial ◽  
The Body ◽  
Phase Iii ◽  
Whole Body ◽  
Stereotactic Ablative Radiotherapy ◽  
Test Cases ◽  
Dose Escalation Study

e21567 Background: Phase II randomized trials suggest that stereotactic ablative radiotherapy (SABR) improves progression-free and overall survival in patients with oligometastatic cancer, with phase III trials currently testing SABR in up to 10 metastases. Whether SABR could provide similar benefits in polymetastatic disease ( > 10 metastases) is unknown. A critical first step is to determine the feasibility of planning SABR for a large number of metastases throughout the body while maintaining acceptable organ at risk (OAR) doses. Therefore, we sought to evaluate the dosimetric feasibility of using SABR in polymetastatic disease ( > 10 sites) while adhering to OAR constraints to be used in a phase I trial (ARREST). Methods: Five craniospinal CT simulations were utilized to retrospectively contour 24 (n = 2), 30 (n = 2) and 50 (n = 1) tumour targets not present on the initial scan. Standard PTV margins were added based on institutional immobilization practices. OAR constraints from published clinical trial protocols were used. Radiotherapy plans for the highest dose level in our planned phase I trial (30Gy in 5 fractions) were created utilizing a minimum number of isocentres. Plans were created using Raystation (RaySearch Laboratories, Stockholm, Sweden) for delivery on linear accelerators using volumetric modulated arc therapy. Results: The gross tumour volumes (GTVs) ranged from 134.8– 184.2cm3 in our five test cases. The first two cases with 24 GTVs have been planned and were deemed to be clinically acceptable. PTV volumes were 483.0cm3 and 417.4cm3, utilizing five and six isocentres for treatment respectively. Median PTV D95 was 29.7Gy and 29.0Gy, whole body V10 was 21.2% and 17.4%, and V5 was 41.8% and 44.8%. All OAR goals were met, though low-dose conformality was less than traditional SABR treatment plans (R100 of 1.04 and 0.93; R50 of 9.90 and 6.98, respectively). The remainder of the test cases will be presented. Conclusions: In our test cases, planning SABR in polymetastatic disease appears dosimetrically feasible. Our phase I clinical trial (ARREST) is under development, which will evaluate the feasibility and toxicity of delivering SABR in polymetastatic disease in a 3+3 dose escalation study. The starting dose level will be 12Gy in 2 weekly fractions, escalating the dose by adding 6Gy weekly until our target dose of 30Gy in 5 weekly fractions. Our study population will include > 10 sites of disease, all tumour types, and patients must have exhausted standard lines of systemic therapy.

A first in human study using photodynamic therapy with Redaporfin in advanced head and neck cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e14056-e14056 ◽  
Author(s):  
Julio Oliveira ◽  
Eurico Monteiro ◽  
Juliana Santos ◽  
Jose Dinis Silva ◽  
Luis Almeida ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Head And Neck Cancer ◽  
Photodynamic Therapy ◽  
Phase I ◽  
Head And Neck ◽  
Effective Dose ◽  
Neck Cancer ◽  
Tumor Necrosis ◽  
Human Study ◽  
The Body

e14056 Background: Photodynamic therapy (PDT) may be an appealing approach when head and neck cancer (HNC) patients (pts) develop locoregional standard treatment failure. Currently available systemic photosensitizers (PST) present several limitations, such as longstanding photosensitivity. Redaporfin is a new PST specifically designed to achieve improved efficacy and safety over existing options. Methods: This phase I/IIa clinical trial had the objective to determined Redaporfin tolerability, anti-tumor effect and pharmacokinetics (PK). “Dose-finding phase”: each patient was submitted to a single-ascending dose of Redaporfin, administered by iv infusion, lasting 10-20 minutes, in ≥ 21 days interval; drug was titrated up to a dose that, in combination with a laser light of 50 J/cm2 at 749±3 nm, was safe and caused tumor necrosis (“effective dose”) in a spot of 1.0 cm of diameter of tumor surface. “Final PDT session”: all accessible tumor was treated with the individual effective dose. Results: Thirteen pts (10 men, 3 women; median age 62 yrs; range 35-80) with advanced HNC in symptomatic treatment were submitted to Redaporfin doses: 0.05 mg/kg (n = 6), 0.1 mg/kg (n = 4), 0.25 mg/kg (n = 2), 0.5 mg/kg (n = 4), 0.75 mg/kg (n = 6) and 1.0 mg (n = 1). Treatment-related adverse events (TRAE): 2 pts had grade (G) 3 photosensitivity reaction (PR) after accidental exposure to intense sun-light (0.75 mg/Kg dose); G≤2 TRAEs in 7 pts (G2 infusion-related reactions in 2 pts and PR in 2 pts). Photodynamic effect was observed in all subjects at doses ≥ 0.5 mg/kg and was dose-dependent; 0.75 mg/kg dose caused necrosis in 1 cm diameter target spot deeper than 5 mm. The patient submitted to final PDT session achieved complete tumor necrosis of treated area. PK showed to be linear; drug was eliminated from the body in a relatively fast manner (half-life of 19 hrs following Redaporfin 0.75mg/Kg). Reported data allowed to conclude phase I part of the trial; next steps of clinical development were authorized. Conclusions: Redaporfin effective dose was established at 0.75 mg/Kg. PDT with Redaporfin revealed anti-tumor effect and was safe in patients with advanced HNC. Further research with this promising compound is ongoing. Clinical trial information: NCT02070432.

Role of convalescent plasma therapy in new Coronavirus disease (nCOVID-19): A review

2020 ◽  
Vol 11 (SPL1) ◽  
pp. 546-549
Author(s):  
Shweta Dadarao Parwe ◽  
Milind Abhimanyu Nisargandha ◽  
Rishikesh Thakre
Keyword(s):  
Clinical Trial ◽  
Immune Responses ◽  
Indian Population ◽  
Preventive Treatment ◽  
The Body ◽  
Therapeutic Antibodies ◽  
Plasma Therapy ◽  
Host Immune Responses ◽  
Transparent Liquid

Hitherto, there is no proper line of treatment for the new (nCOVID19). The development of unique antiviral drugs has taken precedence. Therapeutic antibodies () will be a significantly beneficial agent against nCOVID-19. Here the host immune responses to new discussed in this review provide strategy and further treatment and understanding of clinical interventions against nCOVID-19. Plasma therapy uses the antibodies found in the blood of people recovering (or convalesced) from an infection to treat infected patients. When an infection occurs, the body begins producing proteins specially made to kill the germ, called antibodies. Those antibodies coat specifically plasma in the blood of survivors, the yellow transparent liquid blood portion for months or even years. research assesses plasma use from Convalescent patients of infected with nCOVID-19 as a possible preventive treatment. But it is not yet recommended as a line of treatment, and it is used as a clinical trial in the new in Indian population.

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