Quantifying the impact of optical surface guidance in the treatment of cancers of the head and neck.

Surface guided radiation therapy (SGRT) is increasingly being adopted for use in radiation treatment delivery for Head and Neck (H&N) cancer patients. This study investigated the improvement of patient setup accuracy and reduction of setup time for SGRT compared to a conventional setup. A total of 60 H&N cancer patients were retrospectively included. Patients were categorized into three groups: oral cavity, oropharynx and nasopharynx/sinonasal sites with 20 patients in each group. They were further separated into two (2) subgroups, depending on whether they were set up with the aid of SGRT. The Align-RT™ system was used for SGRT in this work. Positioning was confirmed by daily kV-kV imaging in conjunction with weekly CBCT scans. Translational and rotational couch shifts along with patient setup times were recorded. Imaging setup time, which was defined as the elapsed time from the acquisition of the first image set to the end of the last image set, was recorded. Average translational shifts were larger in the non-SGRT group. Vertical shifts showed the most significant reduction in the SGRT group for both oropharynx and oral cavity groups. Pitch corrections were significantly higher in the SGRT group for oropharynx patients and higher pitch corrections were also observed in the SGRT groups of oral cavity and nasopharynx/sinonasal patients. The average setup time when SGRT guidance was employed was shorter for all three treatment sites although this did not reach statistical significance. The largest time reduction between the SGRT and non-SGRT groups was seen in the nasopharynx/sinonasal group. This study suggests that the use of SGRT decreases the magnitude of translational couch shifts during patient setup. However, the rotational corrections needed were generally higher with SGRT group. When SGRT was employed, a definite reduction in patient setup time was observed for nasopharynx/sinonasal and hypopharynx cancer patients.

Evaluating different routes of extracellular vesicle administration for cranial therapies.

AIM: Human stem cell-derived extracellular vesicles (EV) provide many advantages over cell-based therapies for the treatment of functionally compromised tissue beds and organ sites. Here we aimed to highlight multiple administration routes for the potential treatment of various forms of brain injury. METHODS: Human neural stem cell-derived EV were isolated from conditioned media and administered via three distinct routes: intrahippocampal transplantation, retro-orbital vein injection, and intranasal. EV were administered after which brains were evaluated to determine the capability of EV to translocate into normal tissue. RESULTS: Data showed no significant differences in the amount of EV able to translocate across the brain, indicating the functional equivalence of each administration route to effectively deliver EV to the brain parenchyma. CONCLUSION: Findings show that both systemic administration routes (retro-orbital vein or intranasal delivery) afforded effective penetrance and perfusion of EV throughout the brain in a minimally invasive manner, and point to a translationally tractable option for treating certain neurological disorders including those resulting from cranial irradiation procedures.

Radiation oncology resident education in palliative care.

Palliative and supportive care education for radiation oncologists in training is essential to deliver comprehensive care to patients. Surveys on palliative care education among radiation oncology program directors and residents demonstrate a disparity in formal teaching and didactics. Integration of formal didactics, communications skills programs, and teaching modules are being piloted at academic centers. A dedicated palliative radiation oncology service has been implemented and the experience evaluated. Future directions to improve resident education in palliative care include improving access and time dedicated to formal didactics, online and interactive modules, rotation in a palliative care service, emphasis on board examinations, and consideration of an advanced palliative care fellowship for radiation oncologists. This is the first review of the available literature reviewing formal palliative education in radiation oncology training programs in the United States.

Histology, Tumor Volume, and Radiation Dose Predict Outcomes in NSCLC Patients After Stereotactic Ablative Radiotherapy.

INTRODUCTION: It remains unclear if histology should be independently considered when choosing stereotactic ablative body radiotherapy dose prescriptions for NSCLC. METHODS: The study population included 508 patients with 561 lesions between 2000 and 2016, of which 442 patients with 482 lesions had complete dosimetric information. Eligible patients had histologically or clinically diagnosed early-stage NSCLC and were treated with 3 to 5 fractions. The primary endpoint was in-field tumor control censored by either death or progression. Involved lobe control was also assessed. RESULTS: At 6.7 years median follow-up, 3-year in-field control, involved lobe control, overall survival, and progression-free survival rates were 88.1%, 80.0%, 49.4%, and 37.2%, respectively. Gross tumor volume (GTV) (hazard ratio [HR] = 1.01 per mL, p = 0.0044) and histology (p = 0.0225) were independently associated with involved lobe failure. GTV (HR = 1.013, p = 0.001) and GTV dose (cutoff of 110 Gy, biologically effective dose with α/ß = 10 [BED10], HR = 2.380, p = 0.0084) were independently associated with in-field failure. For squamous cell carcinomas, lower prescription doses were associated with worse in-field control (12 Gy × 4 or 10 Gy × 5 versus 18 Gy or 20 Gy × 3: HR = 3.530, p = 0.0447, confirmed by propensity score matching) and was independent of GTV (HR = 1.014 per mL, 95% confidence interval: 1.005-1.022, p = 0.0012). For adenocarcinomas, there were no differences in in-field control observed using the above dose groupings (p = 0.12 and p = 0.31, respectively). CONCLUSIONS: In the absence of level I data, GTV and histology should be considered to personalize radiation dose for stereotactic ablative body radiotherapy. We suggest lower prescription doses (i.e., 12 Gy × 4 or 10 G × 5) should be avoided for squamous cell carcinomas if normal tissue tolerances are met.

Fear extinction deficits following acute stress associate with increased spine density and dendritic retraction in basolateral amygdala neurons.

Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retraction in the medial prefrontal cortex. Here, we examined extinction learning and basolateral amygdala pyramidal neuron morphology in adult male rats following a single elevated platform stress. Acute stress impaired extinction acquisition and memory, and produced dendritic retraction and increased mushroom spine density in basolateral amygdala neurons in the right hemisphere. Unexpectedly, irrespective of stress, rats that underwent fear and extinction testing showed basolateral amygdala dendritic retraction and altered spine density relative to non-conditioned rats, particularly in the left hemisphere. Thus, extinction deficits produced by acute stress are associated with increased spine density and dendritic retraction in basolateral amygdala pyramidal neurons. Furthermore, the finding that conditioning and extinction as such was sufficient to alter basolateral amygdala morphology and spine density illustrates the sensitivity of basolateral amygdala morphology to behavioral manipulation. These findings may have implications for elucidating the role of the amygdala in the pathophysiology of stress-related disorders.