Dual-Target Radiosurgery for Concomitant Continuous Pain Presentation of Trigeminal Neuralgia: Radiomodulation Effect and Dose.

OBJECTIVES: Patients with trigeminal neuralgia (TN) experience concomitant continuous pain (CCP) that can be difficult to treat. A dual-target approach delivering a high dose of radiation to the nerve and the contralateral thalamus can develop a fast radiomodulation effect on lowering pain. We sought to determine if this effect was dose dependent. METHODS: We retrospectively reviewed 21 patients treated with radiosurgery in CCP and severe TN pain, with a visual analog scale (VAS) score of nine out of 10 at the time of treatment. Ten patients were treated with a high dose (>120 Gy) in the thalamus 90 Gy to the nerve, and the rest with a low dose (<120 Gy) to the thalamus and >90 Gy to the nerve. RESULTS: Of those who received the high dose to the thalamus, six patients (60%) received 140 Gy, and four (40%) received 120 Gy, with a median dose to the trigeminal nerve of 90 and 85 Gy, respectively. The high thalamus dose showed a radiomodulation effect from day 1. The low thalamus dose did not produce radiomodulation on any of the first four days. The percentage of VAS score reduction one month after treatment was higher in the high-thalamus dose group than in the low-thalamus dose group. At three months, VAS score was 2 in the high-dose group and 4 in the low-dose group. CONCLUSIONS: The radiomodulation effect in pain and dual-target radiosurgery is dose dependent in CCP in TN; a high dose can provide a more consistent clinical result than a lower dose.

Garzapelta muelleri gen. et sp. nov., a new aetosaur (Archosauria: Pseudosuchia) from the Late Triassic (middle Norian) middle Cooper Canyon Formation, Dockum Group, Texas, USA, and its implications on our understanding of the morphological disparity of the aetosaurian dorsal carapace.

The Late Triassic Dockum Group in northwestern Texas preserves a rich diversity of pseudosuchian taxa, particularly of aetosaurs. In this contribution, we present Garzapelta muelleri gen. et sp. nov., a new aetosaur from the Late Triassic middle Cooper Canyon Formation (latest Adamanian-earliest Revueltian teilzones) in Garza County, Texas, based on an associated specimen that preserves a significant portion of its dorsal carapace. The carapace of G. muelleri exhibits a striking degree of similarity between that of the paratypothoracin Rioarribasuchus chamaensis and desmatosuchins. We quantitatively assessed the relationships of G. muelleri using several iterations of the matrix. Scoring the paramedian and lateral osteoderms of G. muelleri independently results in conflicting topologies. Thus, it is evident that our current matrix is limited in its ability to discern the convergence within this new taxon and that our current character lists are not fully accounting for the morphological disparity of the aetosaurian carapace. Qualitative comparisons suggest that G. muelleri is a Rioarribasuchus-like paratypothoracin with lateral osteoderms that are convergent with those of desmatosuchins. Although the shape of the dorsal eminence, and the presence of a dorsal flange that is rectangular and proportionately longer than the lateral flange are desmatosuchin-like features of G. muelleri, the taxon does not exhibit the articulation style between the paramedian and lateral osteoderms which diagnose the Desmatosuchini (i.e., a rigid interlocking contact, and an anteromedial edge of the lateral osteoderm that overlaps the adjacent paramedian osteoderm).

Incongruent ontogenetic maturity indicators in a Late Triassic archosaur (Aetosauria: Typothorax coccinarum).

Maximum individual body size in pseudosuchian archosaurs is not well constrained in the fossil record, but it may be influenced by a variety of factors including basal metabolic rate, evolutionary relationships, and environmental conditions. Body size varies among the Aetosauria in which estimated total length ranges between 1 m (e.g., Coahomasuchus kahleorum) and 5 m (e.g., Desmatosuchus spurensis). A new, very large specimen of the aetosaurian Typothorax coccinarum from Petrified Forest National Park in northeastern Arizona is nearly twice the size of all other known specimens of Typothorax and is the largest aetosaur specimen currently known worldwide. The specimen lacks co-ossified neurocentral sutures in the trunk vertebrae which may suggest that the individual had not yet reached skeletal maturity, yet smaller specimens of T. coccinarum exhibit partially or fully co-ossified neurocentral sutures in the same region. If body size correlates with skeletal maturity in aetosaurs, this discrepancy warns that timing of neurocentral suture co-ossification in aetosaurs may not be a reliable indicator of ontogenetic stage. Osteohistological observations of a trunk rib demonstrate that although PEFO 42506 shows a large body size, the specimen did not deposit an external fundamental system despite depositing as many as 19 growth lines, further indicating that it had not yet reached skeletal maturity. Thus, at least within Aetosauria, neurocentral suture co-ossification and skeletal maturity may correlate, whereas body size can be incongruent in comparison. Furthermore, this specimen indicates that non-desmatosuchin aetosaurs could exhibit large body sizes and suggests that some aetosaurs may have experienced indeterminate growth.

Two-Session Radiosurgery for Large Primary Tumors Affecting the Brain.

Introduction Surgery is an option for patients with large, symptomatic primary tumors affecting the brain. However, surgery might not be suitable for all tumors, especially those located in sensitive areas such as the pineal region and the hypothalamus. Single-session stereotactic radiosurgery (SRS) might not provide an adequate dose for long-term local control due to the initial tumor volume and the involvement of radiation sensitive organs at risk (OARs). Two-session radiosurgery has been described as a feasible strategy for dose escalation in large secondary brain tumors. This report describes a series of patients treated upfront with two-session radiosurgery for primary tumors affecting the brain. Materials and methods From May 2017 to January 2020, eight patients with primary tumors affecting the brain were treated with two-session radiosurgery due to either an initial large tumor volume or tumor localization and the involvement of OARs. The response was assessed by imaging and clinical evaluations. Results A total of eight patients were treated, nine tumors were treated with two-session radiosurgery, four patients had tumors in the pineal region (50%), and the rest were in the hypothalamic region (25%) or elsewhere. The mean tumor volume for the first SRS session was 15 mL (range 5.2 to 51.6 mL), the mean prescription dose was 13 Gy, and the timespan between both sessions was 30 days (range, 30 to 42 days). During the second session, tumor volume was reduced to 73.6% (range, -20% to 98.7%) of the original dimension, mean tumor volume was 5 mL (range, 0.1 to 17.8 ml), mean prescription dose for the second session was 16.2 Gy estimated by time, dose, and fractionation and by bioequivalent dose under alpha-beta values often to be equivalent to a single dose of 15.8 Gy. Doses to the OARs for the optic pathway were equivalent to a single maximum dose of 9.75 Gy (range, 7.12 to 10.92), and to the brainstem, the equivalent was a maximum dose of 12.3 Gy (range, 5.6 to 15.07). At last follow-up, at a mean of 336.5 days (range, 65 to 962 days), seven patients were alive, five tumors had a partial response (PR), and three had stable disease in accordance to Response Evaluation Criteria in Solid Tumors (RECIST) criteria. One patient died 435 days after treatment, the Karnofsky Performance Status (KPS) was 90 at the first session, 90 at the second session, and was maintained at last follow-up. No adverse radiation effects were reported. Conclusions Two-stage SRS proved to be a safe method to escalate dose in proportionately large volume primary brain tumors whose histology is expected to have a quick biological response to radiation. Longer follow-up is needed to determine the long-term effectiveness by tumor subtypes of two-stage SRS in the same manner as it has been proven in single session SRS series in smaller tumor volumes.

Stereotactic Gamma Ray Radiosurgery to the Centromedian and Parafascicular Complex of the Thalamus for Trigeminal Neuralgia and Other Complex Pain Syndromes.

Introduction We report our initial series of patients treated with radiosurgery to the Centromedian (CM) and Parafascicular (Pfc) Complex (CM-Pf) of the contralateral thalamus mainly for trigeminal neuralgia that had failed most known forms of conventional treatments. The coordinates were co-registered to a three-dimensional atlas of the thalamus in order to have a better comprehension of isodose curves distribution. Methods A fully automated rotating gamma ray unit was used to deliver a high dose of radiation (140 Gy) using a 4-mm collimator to the CM-Pf of the contralateral thalamus in 14 patients suffering from refractory trigeminal pain and other complex pain syndromes. The best stereotactic coordinates were plotted in a thalamic three-dimensional atlas space along with isodose curves corresponding to 50% of the dose prescription and the dose gradient. Results From November 2016 to July 2019, 14 patients experiencing severe forms of different pain syndromes were treated, and 10 were eligible for follow-up evaluation. Pain deriving from trigeminal neuralgia was present in the majority (80%) of patients and from other complex pain syndromes in the rest (20%). Median follow-up was 384 days (range: 30-994). The Visual Analogue Scale (VAS) score before treatment was 9 (range: 7-10) and standardized to 10. Before treatment, all the patients had a Barrow Neurological Institute Pain Scale (BNI) of 5 (V). The median years suffering from pain was 4.5 years (range: 1-15), the number of procedures including radiosurgery to the trigeminal nerve before thalamotomy was four (range: 1-10). Most patients (90%) reported some form of relief, the average VAS at the time of response was 3.5 (range: 0-9), and the average time to response was 67.3 days (range: 2-210). The neuromodulation effect of radiation was seen in 60% of patients. The average BNI score at response was 2.7 (range: 1-5). The final VAS score at last follow-up was 5.5 (range: 0-10) in six patients. In four patients (40%), the procedure had failed with a final BNI of IV, and V, three patients (30%) had excellent response (BNI of I), and three patients (30%) had worthwhile results with BNI of IIIa and IIIb. The total success rate (BNI of I to IIIb) was 60%, and the number of patients experiencing more than 50% of pain reduction at final follow-up was five (50%). Excluding both patients that were treated for pain outside of trigeminal neuralgia, 75% of the patients responded. The best coordinates on average were X: 5.5 mm from the thalamic border, Y: 3.7 mm anterior to the posterior commissure, and Z: 3.7 mm from the intercomissural line. There were no complications to report. Conclusion Radiosurgery to the CM-Pf of the thalamus was demonstrated to be a safe and relatively effective alternative to treat refractory trigeminal neuralgia. Further studies are needed to optimize target dimensions based on the three-dimensional studies of isodose curves as well as coordinates. Longer follow-up is necessary to evaluate recurrence rates that could not be reached.

Two-session Radiosurgery as Initial Treatment for Newly Diagnosed Large, Symptomatic Brain Metastases from Breast and Lung Histology.

Introduction Surgery is considered the treatment of choice for patients with large, symptomatic brain metastases. This report describes a series of patients treated with upfront two-session radiosurgery rather than surgery for large brain metastases from breast and lung histology. Methods From October 2016 to January 2019, 10 consecutive patients with neurologic symptoms from large brain metastases producing mass effects underwent two sessions of radiosurgical treatments 30 days apart. The response was assessed by imaging and clinical evaluations.  Results Ten patients had a total of 36 tumors; of these, 22 lesions with a mean volume of 12.3 ml (range, 7-78.4 ml) underwent two-session radiosurgery. The mean prescription dose for the first treatment was 13 Gy (range, 9-18 Gy) to the 50% isodose line, and the intratumoral mean dose was 17.9 Gy (12-22.9). All 10 patients had neurological symptoms, with a mean Karnofsky physical score (KPS) of 60 (range, 50-70) on the day of treatment. None of these patients required neurosurgical or emergency consultation related to worsening of neurological symptoms between the first and second treatments. At 30 days, the mean KPS was 80 and maintained at 80 at the last follow-up (range, 60-100; P=0.002), and mean lesion volume was 4.1 ml (range, 1.3-70 ml). The mean prescription dose for the second treatment was 12 Gy (range, 9-18 Gy) to the 50% isodose line, and the intratumoral mean dose was 17.9 Gy (11-22.4). The mean overall survival was 24 months (range, 3-32 months). At last follow-up, three patients (30%) had died, two of systemic progression and one of tumor progression, and at one year, local tumor control was 91% and 19 (86%) lesions showed documented local control at last follow up. In those tumors that progressed, the mean time to progression was eight months (range, 5-20 months), and the mean time to surgery was nine months (range, 5-32 months). Conclusion Two-session radiosurgery proved to be a safe treatment for patients with large, symptomatic metastases in this series. Neurological worsening after radiosurgery for large lesions of breast and lung histology may be an infrequent event. This strategy in radiosurgery may have neurological benefits for these patients providing adequate local tumor control while reducing the need of upfront surgery at diagnosis.

Automated Stereotactic Gamma Ray Radiosurgery to the Pituitary Gland in Terminally Ill Cancer Patients with Opioid Refractory Pain.

Introduction We report our initial series of terminally ill cancer patients treated with radiosurgery to the pituitary gland to alleviate pain. Methods A fully automated rotating gamma ray unit was used to deliver a high dose of radiation (150Gy) using an 8 mm collimator to the neurohypophysis in 11 patients suffering from opioid-refractory pain deriving from cancer. Results From November 2016 to November 2018, 11 patients were treated, and 10 were eligible for follow-up evaluation. Pain from bone metastases was present in 70%; others suffered from neuropathic and visceral pain. The median survival was 119.7 days (range: 32 to 370). The visual analogue scale (VAS) was nine (7-10) and standardized to 10; eight patients (80%) responded. The average VAS at the time of response was three (range: 1-6), and the average time to response was 2.8 days (range: 2-5). In the first week, 40% of the patients categorized the result as 'excellent', 30% deemed the result 'good', and 20% reported the result as 'poor'. One patient (10%) referred to the result as 'regular'. Those who responded were able to reduce their medications by at least 25%. The one-month average VAS score was five (range: 1-6), 60% reported a 'good' effect, 20% reported 'excellent' results, and 20% had no response. Of the study participants, 60% maintained their level of medicine consumption at lower than baseline. At the end of life, five patients (50%) presented substantial pain, two (20%) never had a therapeutic effect, and three (30%) died without substantial pain. There were no clinical complications that could be attributed directly to the treatment.  Conclusion Radiosurgery to the pituitary gland is effective and safe and warrants further investigation to understand its potential role in palliative care in cancer patients.

Dosimetry and Treatment Descriptions Using the First Completely Automated Stereotactic Intracranial Radiosurgery Rotating Gamma Ray Unit in America.

Introduction The objective is to report the dosimetry and safety profiles of the first fully automatized rotating gamma ray unit for intracranial radiosurgery in America. Methods Dosimetry tests were conducted by our institution using the standard of examination and calibration and the Intelligent γ Radiometer of the China Research Institute of Measurement. The phantom and dosimetry tests were performed by the Outreach Physics Section of MD Anderson Cancer Center and the Anchorage Radiation Therapy Center using the Radiation Therapy Oncology Group (RTOG) radiosurgery quality assurance guidelines. Clinically, 233 patients were treated. Results Mechanical precision was 0.16 mm and the offset registered at the phantom on all axes was 0.0. The ratio of the dose to the center was 0.97 (0.95-1.05), the ratio of the treated volume was 0.95 (0.75-1.25), the ratio of the measured treated volume to the volume of the target was 1.29 (1.00-2.00), the ratio of the minimal dose to the dose prescribed was 1.05 (>0.90), with a treated volume of 0.95 (0.75-1.25) and a minimum dose to target of 1.05 (>0.90). The dose rate at loading was 3.89 Gy per minute. None of the patients treated experienced severe complications. Conclusions The dosimetry studies are compliant with quality assurance standards for intracranial radiosurgery.