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With the advent of platinum and taxane compounds used as single agents or in combination regimens, survival rates for some of the most common cancers have improved substantially. However, information on differences in the chemotherapy-induced peripheral neuropathy (CIPN) phenotype among single and combination regimens is limited. Study's purposes were to evaluate for differences in demographic and clinical characteristics; subjective and objective measures of CIPN; as well as the severity of common symptoms and quality of life among survivors who received platinum- (n = 95), taxane- (n = 200), or platinum and taxane-containing (n = 131) regimens. Patients completed self-report questionnaires (ie, duration of CIPN, pain intensity, pain qualities, pain interference) and underwent a physical examination that evaluated light touch, pain, and cold sensations and balance. For most of the subjective and objective measures of CIPN, as well as symptom severity and quality of life scores, no differences were found among the 3 chemotherapy groups. In all 3 chemotherapy treatment groups, CIPN was a painful, small fiber, and length dependent neuropathy. These findings support the hypothesis that CIPN induced by different classes of chemotherapy, as single agents or in combination, produce a similar CIPN phenotype which raises the possibility that CIPN induced by diverse chemotherapy protocols has the same underlying mechanism. PERSPECTIVE: In this study, that compared patients who received only platinum, only taxane, or both platinum and taxane containing regimens, no differences were found among the 3 groups in the CIPN phenotype. Findings raise the possibility that CIPN induced by diverse chemotherapy protocols has the same underlying mechanism.

Alzheimer’s disease (AD) is the most common form of dementia, progressively impairing memory and cognition. While neuroimaging studies have revealed functional abnormalities in AD, how these relate to aberrant neuronal circuit mechanisms remains unclear. We employed a spectral graph-theory model (SGM) to identify abnormal biophysical markers of neuronal activity in AD. SGM is an analytic model that describes how long-range fiber projections in the brain mediate excitatory and inhibitory activity of local neuronal subpopulations. We estimated SGM parameters that captured the regional power spectra obtained from magnetoencephalography imaging of a well-characterized population of patients with AD and controls. The long-range excitatory time constant was the most important feature for the accurate classification of AD and controls and was associated with global cognitive deficits in AD. These results indicate that a global impairment in the long-range excitatory neurons might be a sufficient factor underlying spatiotemporal alterations of neuronal activity in AD.

Laryngeal dystonia is a debilitating disorder of voicing in which the laryngeal muscles are intermittently in spasm resulting in involuntary interruptions during speech. The central pathophysiology of laryngeal dystonia, underlying computational impairments in vocal motor control, remains poorly understood. Although prior imaging studies have found aberrant activity in the CNS during phonation in patients with laryngeal dystonia, it is not known at what timepoints during phonation these abnormalities emerge and what function may be impaired. To investigate this question, we recruited 22 adductor laryngeal dystonia patients (15 female, age range = 28.83–72.46 years) and 18 controls (eight female, age range = 27.40–71.34 years). We leveraged the fine temporal resolution of magnetoencephalography to monitor neural activity around glottal movement onset, subsequent voice onset and after the onset of pitch feedback perturbations. We examined event-related beta-band (12–30 Hz) and high-gamma-band (65–150 Hz) neural oscillations. Prior to glottal movement onset, we observed abnormal frontoparietal motor preparatory activity. After glottal movement onset, we observed abnormal activity in the somatosensory cortex persisting through voice onset. Prior to voice onset and continuing after, we also observed abnormal activity in the auditory cortex and the cerebellum. After pitch feedback perturbation onset, we observed no differences between controls and patients in their behavioural responses to the perturbation. But in patients, we did find abnormal activity in brain regions thought to be involved in the auditory feedback control of vocal pitch (premotor, motor, somatosensory and auditory cortices). Our study results confirm the abnormal processing of somatosensory feedback that has been seen in other studies. However, there were several remarkable findings in our study. First, patients have impaired vocal motor activity even before glottal movement onset, suggesting abnormal movement preparation. These results are significant because (i) they occur before movement onset, abnormalities in patients cannot be ascribed to deficits in vocal performance and (ii) they show that neural abnormalities in laryngeal dystonia are more than just abnormal responses to sensory feedback during phonation as has been hypothesized in some previous studies. Second, abnormal auditory cortical activity in patients begins even before voice onset, suggesting abnormalities in setting up auditory predictions before the arrival of auditory feedback at voice onset. Generally, activation abnormalities identified in key brain regions within the speech motor network around various phonation events not only provide temporal specificity to neuroimaging phenotypes in laryngeal dystonia but also may serve as potential therapeutic targets for neuromodulation.

ObjectivesLittle is known about hearing loss and tinnitus associated with neurotoxic chemotherapy. Study evaluated for differences in occurrence rates and effects of hearing loss and tinnitus in survivors who received a platinum alone, a taxane alone or a platinum and taxane containing regimen.MethodsTotal of 273 survivors with breast, gastrointestinal, gynaecological or lung cancer completed self-report measures of hearing loss and tinnitus and had an audiometric assessment that obtained pure tone air conduction thresholds bilaterally at frequencies of between 0.25 kHz to 16.0 kHz. To adjust for age-related and gender-related changes in hearing, each survivor’s audiogram was evaluated using the National Health and Nutrition Examination Survey-modified Occupational Safety and Health Administration standards. Survivor was classified as having hearing loss if at any frequency they scored poorer than the 50th percentile for their age and gender. Survivors were categorised as having tinnitus if they reported that for >10% of their time awake, they were consciously aware of their tinnitus. Differences among the chemotherapy groups were evaluated using parametric and non-parametric tests.ResultsFor most of the demographic and clinical characteristics, no differences were found among the three chemotherapy groups. Occurrence rates for audiogram-confirmed hearing loss ranged from 52.3% to 71.4%. Occurrence rates for tinnitus ranged from 37.1% to 40.0%. No differences were found among the three chemotherapy groups in the occurrence rates or effects of hearing loss and tinnitus.ConclusionThese findings suggest that regardless of the chemotherapy regimen common mechanistic pathway(s) may underlie these two neurotoxicities.

The aim of this study was to determine the sorption location of full-length recombinant human proteoglycan 4 (rhPRG4) tagged with fluorescein isothiocyanate (FITC) to four silicone hydrogel contact lenses [balafilcon A (PureVision, Bausch + Lomb), senofilcon A (Acuvue Oasys, JohnsonJohnson), comfilcon A (Biofinity, CooperVision), lotrafilcon B (Air Optix, Alcon)] and one conventional hydrogel lens [etafilcon A (Acuvue 2, JohnsonJohnson)], using confocal laser scanning microscopy (CLSM). Lenses (

Introduction: To investigate the inter-observer and inter-modality variabilities of two imaging guided equipments—cone-beam computed tomography (CBCT) and ultrasound (US) in kidney stereotactic body radiotherapy. Methods: A renal metastasis case implanted with three gold anchor fiducial markers was firstly scanned by US to acquire a 3-dimension US image and followed by 4-dimension CBCT in every fraction. Seven observers retrospectively registered the pre-treatment images with the corresponding reference images based on the gold markers. Registration uncertainty of the observers between two imaging modalities was evaluated. Results: The uncertainties over whole treatment course in CBCT were 0.88 mm, 1.94 mm and 0.86 mm in lateral, longitudinal and vertical directions respectively; while 0.8 mm, 0.97 mm and 1.36 mm were found in US. Conclusion: The greatest uncertainty was found in longitudinal direction in CBCT due to the fact that the respiration motion is the most rigorous in cranial-caudal direction. In US, since the probe was hold almost in upright position, the strong echo in vertical direction was attributed to the greatest uncertainty for such direction.

Objective: To evaluate the effectiveness of a patient-specific immobilization and positioning device in prostate radiotherapy. Methods: Eighty patients were immobilized and positioned by a patient-specific device. Prostate translations and rotations were estimated from daily cone beam computed tomography scans using a contour-based approach assisted by auto-registration and quantified by the group mean GM, systematic Σ and random σ' errors. Dosimetric impacts of residual prostate rotations where the translation errors were corrected were evaluated by robustness plan analysis. Results: Using the patient-specific immobilization alone without online image-guidance, the GM, Σ and σ' of the prostate translations were 0.8, 1.7, and 1.5 mm (left-right; LR), 0.8, 2.1, and 1.9 mm (superior-inferior; SI), and 0.5, 1.7 and 1.5 mm (anterior-posterior; AP), while for the prostate rotations they were 0.0°, 0.6°, and 0.7° (pitch), 0.2°, 0.5°, and 0.6° (roll), and 0.2°, 0.5°, and 0.6° (yaw). The resulting van Herk’s margin was 5.8 (LR), 7.3 (SI) and 5.8 (AP) mm. With adaptive online image-guidance based on estimates from the first 5 fractions, Σ were reduced by 0.7 - 1.2 mm for the prostate translations, resulting in a margin reduction by 2 - 3.5 mm. Changes of Σ and σ' in the prostate rotations were insignificant regardless of translation corrections. Dosimetric impacts of residual rotation errors were negligible if a 2 mm margin was applied. Conclusions: Our patient-specific immobilization system can effectively limit the prostate translations and rotations, which is important without 6D treatment couches or using ultrasound image-guidance without rotational corrections.

Purpose To provide a pilot dosimetric study of computed tomography (CT)-guided high-dose-rate (HDR) brachytherapy (BRT) and stereotactic body radiotherapy (SBRT) for primary and metastatic lung lesions. Material and methods For nine lung primary and metastasis patients, 3D image-based BRT plan using a single virtual catheter was planned for 34 Gy in single fraction to the gross tumor volume (GTV) + 3 mm margin to account for tumor deformation. These plans were compared to margin-based (MB-) and robustness optimized (RO-) SBRT, assuming the same tumor deformation under real-time tumor tracking. Consistent dose calculation was ensured for both BRT and SBRT plans using the same class of collapsed cone convolution superposition algorithm. Plan quality metrics were compared by Friedman tests and Wilcoxon t-tests. Results and Conclusions Brachytherapy plans showed significant higher GTV mean dose compared to MB- and RO-SBRT (122.2 Gy vs. 50.4 and 44.7 Gy, p < 0.05), and better dose gradient index (R50) = 2.9 vs. 4.3 and 8.4 for MB- and RO-SBRT, respectively. Dose constraints per the RTOG 0915 protocol were achieved for all critical organs except chest wall in BRT. All other dose-volume histograms (DVH) metrics are comparable between BRT and SBRT. Treatment delivery time of BRT and SBRT plans significantly increased and decreased with increasing GTV size, respectively. SBRT using advanced MLC tracking technique and non-coplanar VMAT can achieve comparable dosimetric quality to HDR BRT. Whether or not, the significantly higher GTV dose can increase killing of radioresistant tumor cells and offset the effect of tumor reoxygenation in single fraction BRT, requires further clinical investigation.

Background To derive and exploit the optimal prescription isodose level (PIL) in inverse optimization of volumetric modulated arc radiotherapy (VMAT) as a potential approach to dose de–escalation in stereotactic body radiotherapy for non–small cell lung carcinomas (NSCLC). Methods For ten patients, inverse Monte Carlo dose optimization was performed to cover 95% PTV by varying prescription isodose lines (PIL) at 60 to 80% and reference 85%. Subsequently, these were re–normalized to the median gross tumor volume dose (GTV–based prescription) to assess the impacts of PTV and normal tissue dose reduction. Results With PTV–based prescription, GTV mean dose was much higher with the optimized PIL at 60% with significant reduction of normal lung receiving 30 to 10 Gy (V 30–10Gy ), and observable but insignificant dose reduction to spinal cord, esophagus, ribs, and others compared with 85% PIL. Mean doses to the normal lung between PTV and GTV was higher with 60–70% PIL than 85%. The dose gradient index was 5.0 ± 1.1 and 6.1 ± 1.4 for 60 and 85% PIL (p

Background Aim of this study was to comparatively evaluate the accuracy of respiration–correlated (4D) and uncorrelated (3D) cone beam computed tomography (CBCT) in localizing lipiodolized hepatocellular carcinomas during stereotactic body radiotherapy (SBRT). Methods 4D–CBCT scans of eighteen HCCs were acquired during free–breathing SBRT following trans–arterial chemo–embolization (TACE) with lipiodol. Approximately 1320 x–ray projections per 4D–CBCT were collected and phase–sorted into ten bins. A 4D registration workflow was followed to register the reconstructed time–weighted average CBCT with the planning mid–ventilation (MidV) CT by an initial bone registration of the vertebrae and then tissue registration of the lipiodol. For comparison, projections of each 4D–CBCT were combined to synthesize 3D–CBCT without phase–sorting. Using the lipiodolized tumor, uncertainties of the treatment setup estimated from the absolute and relative lipiodol position to bone were analyzed separately for 4D– and 3D–CBCT. Results Qualitatively, 3D–CBCT showed better lipiodol contrast than 4D–CBCT primarily because of a tenfold increase of projections used for reconstruction. Motion artifact was observed to subside in 4D–CBCT compared to 3D–CBCT. Group mean, systematic and random errors estimated from 4D– and 3D–CBCT agreed to within 1 mm in the cranio–caudal (CC) and 0.5 mm in the anterior–posterior (AP) and left–right (LR) directions. Systematic and random errors are largest in the CC direction, amounting to 4.7 mm and 3.7 mm from 3D–CBCT and 5.6 mm and 3.8 mm from 4D–CBCT, respectively. Safety margin calculated from 3D–CBCT and 4D–CBCT differed by 2.1, 0.1 and 0.0 mm in the CC, AP, and LR directions. Conclusions 3D–CBCT is an adequate alternative to 4D–CBCT when lipoid is used for localizing HCC during free–breathing SBRT. Similar margins are anticipated with 3D– and 4D–CBCT.

The purpose of this study was to use atomic force microscopy to compare and characterize the cleaning abilities of a hydrogen peroxide-based system (HPS) and a polyhexamethylene biguanide-containing multipurpose solution (MPS) at removing in vitro deposited tear film constituents, as well as to determine deposition patterns on various silicone hydrogel contact lenses.Silicone hydrogel materials-balafilcon A (BA), lotrafilcon B (LB), and senofilcon A (SA)-were incubated for 1 week in an artificial tear solution (ATS) containing representative lipids, proteins, and salts from the tear film. Atomic force microscopy was used to resolve each lens before and after being cleaned overnight in HPS or MPS. Atomic force microscopy was used again to resolve HPS/MPS-cleaned lenses, which were reincubated in fresh ATS for 1 week, before and after an overnight clean in their respective cleaning solution.Atomic force microscopy imaging was able to characterize lens deposits with high resolution. Lenses incubated in ATS revealed distinct differences in their deposition pattern across lens materials. The surface of BA contained about 20-nm-high deposits, whereas deposit heights up to 150 nm completely occluded the surface of SA. Lotrafilcon B lenses revealed clusters of deposits up to 90 nm. The use of either lens solution left trace amounts of tear film constituents, although components from the MPS were seen adsorbed onto the surface after cleaning. Surface roughness (Ra) measurements revealed a significant difference between ATS-incubated and HPS/MPS-cleaned SA and LB lenses (p0.05). Ra between first incubated and HPS/MPS-cleaned reincubated SA and LB was also significant (p0.05).Unique variations in ATS deposition patterns were seen between lenses with atomic force microscopy. The application of both HPS and MPS removed most visible surface deposits.