Jordan H. Garst

Reduced-dose radiotherapy for human papillomavirus-associated squamous-cell carcinoma of the oropharynx: a single-arm, phase 2 study

BACKGROUND Head and neck cancers positive for human papillomavirus (HPV) are exquisitely radiosensitive. We investigated whether chemoradiotherapy with reduced-dose radiation would maintain survival outcomes while improving tolerability for patients with HPV-positive oropharyngeal carcinoma. METHODS We did a single-arm, phase 2 trial at two academic hospitals in the USA, enrolling patients with newly diagnosed, biopsy-proven stage III or IV squamous-cell carcinoma of the oropharynx, positive for HPV by p16 testing, and with Zubrod performance status scores of 0 or 1. Patients received two cycles of induction chemotherapy with 175 mg/m2 paclitaxel and carboplatin (target area under the curve of 6) given 21 days apart, followed by intensity-modulated radiotherapy with daily image guidance plus 30 mg/m2 paclitaxel per week concomitantly. Complete or partial responders to induction chemotherapy received 54 Gy in 27 fractions, and those with less than partial or no responses received 60 Gy in 30 fractions. The primary endpoint was progression-free survival at 2 years, assessed in all eligible patients who completed protocol treatment. This study is registered with ClinicalTrials.gov, numbers NCT02048020 and NCT01716195. FINDINGS Between Oct 4, 2012, and March 3, 2015, 45 patients were enrolled with a median age of 60 years (IQR 54-67). One patient did not receive treatment and 44 were included in the analysis. 24 (55%) patients with complete or partial responses to induction chemotherapy received 54 Gy radiation, and 20 (45%) with less than partial responses received 60 Gy. Median follow-up was 30 months (IQR 26-37). Three (7%) patients had locoregional recurrence and one (2%) had distant metastasis; 2-year progression-free survival was 92% (95% CI 77-97). 26 (39%) of 44 patients had grade 3 adverse events, but no grade 4 events were reported. The most common grade 3 events during induction chemotherapy were leucopenia (17 [39%]) and neutropenia (five [11%]), and during chemoradiotherapy were dysphagia (four [9%]) and mucositis (four [9%]). One (2%) of 44 patients was dependent on a gastrostomy tube at 3 months and none was dependent 6 months after treatment. INTERPRETATION Chemoradiotherapy with radiation doses reduced by 15-20% was associated with high progression-free survival and an improved toxicity profile compared with historical regimens using standard doses. Radiotherapy de-escalation has the potential to improve the therapeutic ratio and long-term function for these patients. FUNDING University of California.

Use of multivariate linear regression and support vector regression to predict functional outcome after surgery for cervical spondylotic myelopathy

This study introduces the use of multivariate linear regression (MLR) and support vector regression (SVR) models to predict postoperative outcomes in a cohort of patients who underwent surgery for cervical spondylotic myelopathy (CSM). Currently, predicting outcomes after surgery for CSM remains a challenge. We recruited patients who had a diagnosis of CSM and required decompressive surgery with or without fusion. Fine motor function was tested preoperatively and postoperatively with a handgrip-based tracking device that has been previously validated, yielding mean absolute accuracy (MAA) results for two tracking tasks (sinusoidal and step). All patients completed Oswestry disability index (ODI) and modified Japanese Orthopaedic Association questionnaires preoperatively and postoperatively. Preoperative data was utilized in MLR and SVR models to predict postoperative ODI. Predictions were compared to the actual ODI scores with the coefficient of determination (R(2)) and mean absolute difference (MAD). From this, 20 patients met the inclusion criteria and completed follow-up at least 3 months after surgery. With the MLR model, a combination of the preoperative ODI score, preoperative MAA (step function), and symptom duration yielded the best prediction of postoperative ODI (R(2)=0.452; MAD=0.0887; p=1.17 × 10(-3)). With the SVR model, a combination of preoperative ODI score, preoperative MAA (sinusoidal function), and symptom duration yielded the best prediction of postoperative ODI (R(2)=0.932; MAD=0.0283; p=5.73 × 10(-12)). The SVR model was more accurate than the MLR model. The SVR can be used preoperatively in risk/benefit analysis and the decision to operate.

Utilization of a novel digital measurement tool for quantitative assessment of upper extremity motor dexterity: a controlled pilot study

BackgroundThe current methods of assessing motor function rely primarily on the clinician’s judgment of the patient’s physical examination and the patient’s self-administered surveys. Recently, computerized handgrip tools have been designed as an objective method to quantify upper-extremity motor function. This pilot study explores the use of the MediSens handgrip as a potential clinical tool for objectively assessing the motor function of the hand.MethodsEleven patients with cervical spondylotic myelopathy (CSM) were followed for three months. Eighteen age-matched healthy participants were followed for two months. The neuromotor function and the patient-perceived motor function of these patients were assessed with the MediSens device and the Oswestry Disability Index respectively. The MediSens device utilized a target tracking test to investigate the neuromotor capacity of the participants. The mean absolute error (MAE) between the target curve and the curve tracing achieved by the participants was used as the assessment metric. The patients’ adjusted MediSens MAE scores were then compared to the controls. The CSM patients were further classified as either “functional” or “nonfunctional” in order to validate the system’s responsiveness. Finally, the correlation between the MediSens MAE score and the ODI score was investigated.ResultsThe control participants had lower MediSens MAE scores of 8.09%±1.60%, while the cervical spinal disorder patients had greater MediSens MAE scores of 11.24%±6.29%. Following surgery, the functional CSM patients had an average MediSens MAE score of 7.13%±1.60%, while the nonfunctional CSM patients had an average score of 12.41%±6.32%. The MediSens MAE and the ODI scores showed a statistically significant correlation (r=-0.341, p<1.14×10-5). A Bland-Altman plot was then used to validate the agreement between the two scores. Furthermore, the percentage improvement of the the two scores after receiving the surgical intervention showed a significant correlation (r=-0.723, p<0.04).ConclusionsThe MediSens handgrip device is capable of identifying patients with impaired motor function of the hand. The MediSens handgrip scores correlate with the ODI scores and may serve as an objective alternative for assessing motor function of the hand.

Unobtrusive and Continuous Monitoring of Alcohol-impaired Gait Using Smart Shoes

BACKGROUND Alcohol ingestion influences sensory-motor function and the overall well-being of individuals. Detecting alcohol-induced impairments in gait in daily life necessitates a continuous and unobtrusive gait monitoring system. OBJECTIVES This paper introduces the development and use of a non-intrusive monitoring system to detect changes in gait induced by alcohol intoxication. METHODS The proposed system employed a pair of sensorized smart shoes that are equipped with pressure sensors on the insole. Gait features were extracted and adjusted based on individuals gait profile. The adjusted gait features were used to train a machine learning classifier to discriminate alcohol-impaired gait from normal walking. In experiment of pilot study, twenty participants completed walking trials on a 12 meter walkway to measure their sober walking and alcohol-impaired walking using smart shoes. RESULTS The proposed system can detect alcohol-impaired gait with an accuracy of 86.2 % when pressure value analysis and person-dependent model for the classifier are applied, while statistical analysis revealed that no single feature was discriminative for the detection of gait impairment. CONCLUSIONS Alcohol-induced gait disturbances can be detected with smart shoe technology for an automated monitoring in ubiquitous environment. We demonstrated that personal monitoring and machine learning-based prediction could be customized to detect individual variation rather than applying uniform boundary parameters of gait.

Identifying predictors for postoperative clinical outcome in lumbar spinal stenosis patients using smart-shoe technology

BackgroundApproximately 33% of the patients with lumbar spinal stenosis (LSS) who undergo surgery are not satisfied with their postoperative clinical outcomes. Therefore, identifying predictors for postoperative outcome and groups of patients who will benefit from the surgical intervention is of significant clinical benefit. However, many of the studied predictors to date suffer from subjective recall bias, lack fine digital measures, and yield poor correlation to outcomes.MethodsThis study utilized smart-shoes to capture gait parameters extracted preoperatively during a 10 m self-paced walking test, which was hypothesized to provide objective, digital measurements regarding the level of gait impairment caused by LSS symptoms, with the goal of predicting postoperative outcomes in a cohort of LSS patients who received lumbar decompression and/or fusion surgery. The Oswestry Disability Index (ODI) and predominant pain level measured via the Visual Analogue Scale (VAS) were used as the postoperative clinical outcome variables.ResultsThe gait parameters extracted from the smart-shoes made statistically significant predictions of the postoperative improvement in ODI (RMSE =0.13, r=0.93, and p<3.92×10−7) and predominant pain level (RMSE =0.19, r=0.83, and p<1.28×10−4). Additionally, the gait parameters produced greater prediction accuracy compared to the clinical variables that had been previously investigated.ConclusionsThe reported results herein support the hypothesis that the measurement of gait characteristics by our smart-shoe system can provide accurate predictions of the surgical outcomes, assisting clinicians in identifying which LSS patient population can benefit from the surgical intervention and optimize treatment strategies.

A Prediction Model for Functional Outcomes in Spinal Cord Disorder Patients Using Gaussian Process Regression

Predicting the functional outcomes of spinal cord disorder patients after medical treatments, such as a surgical operation, has always been of great interest. Accurate posttreatment prediction is especially beneficial for clinicians, patients, care givers, and therapists. This paper introduces a prediction method for postoperative functional outcomes by a novel use of Gaussian process regression. The proposed method specifically considers the restricted value range of the target variables by modeling the Gaussian process based on a truncated Normal distribution, which significantly improves the prediction results. The prediction has been made in assistance with target tracking examinations using a highly portable and inexpensive handgrip device, which greatly contributes to the prediction performance. The proposed method has been validated through a dataset collected from a clinical cohort pilot involving 15 patients with cervical spinal cord disorder. The results show that the proposed method can accurately predict postoperative functional outcomes, Oswestry disability index and target tracking scores, based on the patients preoperative information with a mean absolute error of 0.079 and 0.014 (out of 1.0), respectively.

Objective assessment of overexcited hand movements using a lightweight sensory device

Hyperexcitability in hand is a disorder characterized by exaggerated muscle movement, and is a common symptom associated with neuro-degenerative diseases and spinal cord injuries. Current assessment methods for hyperexcitability rely on subjective examination, or on methods that evaluate the overall hand grip performance without particularization in the excitation. This paper introduces a system that utilizes an inexpensive body sensor device combined with a series of signal processing units that extract information specifically related to physiological phenomena generated by hyperexcitability. A clinical cohort study has been conducted on nine patients with cervical spinal cord injuries (mean age 58.2 ± 13.5). The experimental results show that the proposed signal processing mechanism accurately detects and analyzes the body signal. The medical significance of the experimental results is also investigated. This opens up a new opportunity for patients and clinical professionals to obtain accurate feedback of patients motor function in an economical and ubiquitous manner.

Effect of psychosocial distress on outcome for head and neck cancer patients undergoing radiation

To determine the impact of pretreatment psychosocial distress on compliance to radiation therapy (RT) and clinical outcomes for patients with head and neck cancer

Patient-reported quality-of-life outcomes after de-escalated chemoradiation for human papillomavirus-positive oropharyngeal carcinoma: Findings from a phase 2 trial: HPV-Positive Oropharyngeal Carcinoma

The current study represents a subset analysis of quality‐of‐life (QOL) outcomes among patients treated on a phase 2 trial of de‐escalated chemoradiation for human papillomavirus (HPV)‐associated oropharyngeal cancer.

Quantitative assessment of hand motor function in cervical spinal disorder patients using target tracking tests

Cervical spondylotic myelopathy (CSM) is a chronic spinal disorder in the neck region. Its prevalence is growing rapidly in developed nations, creating a need for an objective assessment tool. This article introduces a system for quantifying hand motor function using a handgrip device and target tracking test. In those with CSM, hand motor impairment often interferes with essential daily activities. The analytic method applied machine learning techniques to investigate the efficacy of the system in (1) detecting the presence of impairments in hand motor function, (2) estimating the perceived motor deficits of CSM patients using the Oswestry Disability Index (ODI), and (3) detecting changes in physical condition after surgery, all of which were performed while ensuring test-retest reliability. The results based on a pilot data set collected from 30 patients with CSM and 30 nondisabled control subjects produced a c-statistic of 0.89 for the detection of impairments, Pearson r of 0.76 with p < 0.001 for the estimation of ODI, and a c-statistic of 0.82 for responsiveness. These results validate the use of the presented system as a means to provide objective and accurate assessment of the level of impairment and surgical outcomes.