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.

Radiomodulation in Mixed, Complex Cancer Pain by Triple Target Irradiation in the Brain: A Preliminary Experience.

Introduction Up to 30% of terminally ill cancer patients experiencing intense pain might be refractory to opioid treatment. Complex cancer pain can be a mixture of somatic, visceral, and neuropathic pain with few or no effective alternatives to ameliorate pain. Radiosurgery to treat refractory pain in cancer has been reported with different degrees of success. Radiomodulation in pain could be defined as a fast (<72 h), substantial (>50%) pain relief by focal irradiation to a peripheric, and/or central mediated pain circuitry. Based on our previous experience, mixed, refractory cancer pain is usually unresponsive to single target irradiation of the hypophysis. We treated three patients using a multi-target approach. Methods Three terminally ill oncological patients experiencing refractory, complex, mixed pain from bone, abdomen, thorax, and brachial plexus were treated with triple target irradiation which consisted of irradiating with a maximum dose (Dmax) of 90 Gy to the hypophysis using either an 8 mm collimator with gamma ray (Infini) (Shenzhen, China: Masep Medical Company) or a 7.5 circular collimator with Cyberknife (Sunnyvale, CA: Accuray Inc.), the other two targets were the mesial structures of the thalamus bilaterally using a 4 mm collimator with Infini and the 5 mm circular collimator with CK delivering 90 Gy Dmax to each region. Patients had a VAS of 10 despite the best medical treatment. A correlation was made between the 45 Gy and 20 Gy isodose curves of the two different technologies to the Morel stereotactic atlas of the thalamus and basal ganglia for further understanding of dose distribution reconstructions in accordance with the São Paulo-Würzburg atlas of the Human Brain Project were performed. Lastly, a scoping review of the literature regarding radiosurgery for oncological pain was performed. Results Radiomodulation effect was achieved in all patients; case 1 had a VAS of five at 72 h, three at 15 days, and three at the time of death (21 days after treatment). Case 2 had a VAS of six at 72 h, five at 15 days, and four at the time of death (29 days after treatment). Case 3 had a VAS of five at 72 h, six at 15 days, and six at the time of death (30 days). Morphine rescues for cases 1 and 2 were reduced to 84%, and 70% for case 3. Overall, there were no adverse effects to treatment although excessive sleepiness was reported by one patient. After reading the title and abstract, only 14 studies remained eligible for full-text evaluation, and only nine studies met inclusion criteria after full-text reading. For most reports (seven), the target was the hypophysis and in two reports, the target was the thalamus either with single or bilateral irradiation. Conclusions In complex, for refractory oncological pain of mixed nature (nociceptive, neuropathic, and visceral), very few, if any, treatment alternatives are currently available. We provide a small proof of concept that multitarget intracranial radiosurgery might be effective in ameliorating pain in this population. The doses administered per target are the lowest that have shown effectiveness thus far, a different strategy might be needed as opposed to single target "large" dose approach that has been tried in the past for complex mixed refractory oncological pain. By no means, in our experience, these treatments traduce in elimination of pain, clinical results might make pain to be more bearable and respond better to pain medication.

Visual Symptoms Outcomes in Cavernous Sinus Radiosurgery and a Systematic Review.

Introduction The complex anatomy of the cavernous sinus confers a true challenge when it comes to safe tumor resection. Due to its non-invasive nature, stereotactic radiosurgery (SRS) is expected to have lower mortality and morbidity rates than microsurgery. The purpose of this study was to evaluate clinical results regarding visual symptoms after SRS for benign tumors invading the cavernous sinus. We also conducted a systematic literature review to provide a robust analysis regarding visual outcomes. Methods The study included 58 patients (43 women and 15 men; mean age: 52 years) with benign tumors invading the cavernous sinus (27 pituitary adenomas and 31 meningiomas) who underwent SRS with different platforms between August 2011 and December 2021. Of these, 26 patients underwent surgery before SRS, and the remaining 32 had SRS as first-line therapy. We identified symptoms involving cranial nerves (CN) II, III, IV, and VI in 38 patients at the time of SRS. We conducted a systematic review to identify all original studies assessing visual outcomes. We searched PubMed, the Latin American and Caribbean Health Sciences Literature index, and Google Scholar using the Medical Subject Heading search terms "radiosurgery" and "cavernous sinus" for valid studies published until January 31, 2022. Results Regarding pituitary adenomas, median tumor volume was 2.05 cc, 3.12 cc, and 2.39 cc for Gamma Knife (GK), CyberKnife (CK), and tomotherapy (Tomo), respectively. Median doses were 14 Gy for GK, 17 Gy for CK, and 15 Gy for Tomo. For meningiomas, median tumor volume was 10.2 cc, 2.62 cc, and 16.3 cc for GK, CK, and Tomo, respectively. The median dose was 14 Gy for GK, 14 Gy for CK, and 14.5 Gy for Tomo. The overall tumor control rate was 100% with a median follow-up of 33 months (range: 6-128 months). A reduction of >30% in total tumor size per the Response Evaluation Criteria in Solid Tumors (RECIST) classification was documented in seven patients (RECIST II; 12.1%), 51 patients (87.9%) had stable disease (RECIST III), and no increase in tumor volume was documented in any patient. Visual symptoms improved in 51.7% of patients. In the systematic review, the mean visual improvement was 36% (range: 25.8-42.5%). Conclusion SRS is an effective treatment for benign tumors invading the cavernous sinus. In this series, patients who underwent SRS as a primary treatment showed improvement in pre-existing cranial neuropathy and visual symptoms. Given the natural history of these tumors, which tend to grow and cause visual alternations, treating asymptomatic patients is a feasible approach worth considering for the appropriate patients.

Radioneuromodulation by Dual-Target Irradiation in Pain Crisis From Trigeminal Neuralgia.

Background Radioneuromodulation (RNM) can explain the immediate pain relief experienced by a subgroup of patients after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). In this study, our main objective was to demonstrate that a minimum of a 50% reduction in TN pain can be achieved consistently in under 72 hours by targeting the affected nerve, the contralateral centromedian nucleus, and parafascicular complex in patients experimenting a prolonged refractory pain crisis. Methodology We treated eight patients experiencing severe TN pain crisis in whom percutaneous procedures had failed or were unwanted with SRS with an intention to procure pain relief in under 72 hours. The affected trigeminal nerve was targeted using a 4-mm collimator with an 80 to 90-Gy dose; an additional target was defined in the mesial portions of the thalamus and irradiated using the 4-mm collimator with a 120 to 140-Gy dose. Results The median duration of TN was 60 months, the median duration of pain crisis was 10.7 weeks despite the best medical treatment, and the mean presenting visual analogue score (VAS) was 10 at the time of treatment. The median follow-up was 135 days (range, 65-210). Twenty-four hours after treatment, two (25%) patients had no pain (VAS 0), three (37.5%) had mild pain (VAS 1 to 3), and three (37.5%) had moderate pain (VAS 4 to 7). Forty-eight hours after treatment, all patients reported pain relief, seven (87.5%) reported >50%, and one (12.5%) patients reported 30% relief. The three-month median VAS score was 3 (range, 0 to 5). At the last follow-up, there were no adverse events to report. Conclusions Dual irradiation to the affected trigeminal nerve and contralateral mesial structures of the thalamus may provide fast pain relief for patients experiencing a prolonged pain crisis from TN, which veers away from the concept that the SRS pain relief effect is generally delayed and holds no place in the management of such patients. Although this is a small series with a limited follow-up duration, no adverse effects were noted. RNM can be defined as the capacity to alter neuronal activity through targeted delivery of a stimulus of radiation at a duration too brief to be explained by the development of a focal lesion. The immediate pain relief and its habitual oscillatory nature of lesser pain recurrence in most patients until enough time elapses for pain stabilization clinically demonstrates that the pain circuitry is altered and remains functional, thus accomplishing a neuromodulation effect even at the face of an apparent doses suspected to be ablative. Further research is needed to understand if this clinical effect is achieved with a suspected sub-ablative dose.

Stereotactic Radiosurgery for Recurrent Glioblastoma Multiforme: A Retrospective Multi-Institutional Experience.

Introduction Glioblastoma multiforme (GBM) is the most common and lethal primary malignancy of the central nervous system. Despite standard therapy protocols, such as aggressive surgical resection, radiotherapy, and chemotherapy, GBM's aggressive nature produces low survival rates. Tumor recurrence and progression are nearly universal. Stereotactic radiosurgery (SRS) has been studied as an alternative treatment for recurrent GBM as a minimally invasive option that might prolong survival. The objective of this retrospective study was to evaluate the efficacy of SRS as a treatment modality considering overall survival (OS) in patients with GBM who had tumor recurrence and were treated with SRS in three different institutions. Materials and methods We retrospectively reviewed patients who received SRS for recurrent GBM between 1992 and 2020. A total of 46 patients were included in this study. We recorded age at diagnosis, the extent of surgical resection, radiation treatment, chemotherapy regimen, Karnofsky Performance Status at the time of SRS and at last follow-up, use of adjuvant chemotherapy after SRS, and response evaluation criteria in solid tumors. Primary endpoints were OS after initial diagnosis and OS from the date of the SRS procedure. Results Patients received SRS at a median of 10 months (range, 1 to 94 months) after their initial diagnoses. Median follow-up was seven months from the time of SRS and 22.8 months since diagnosis. The estimated median OS for all patients was nine months (range, 1 to 42 months) after SRS and 23.8 months (range, 4 to 102 months) after diagnosis. Median OS after SRS was seven months for patients treated from 1992 to 2011 and nine months for those treated from 2012 to 2020 (p = 0.008; X2 = 7.008). Median OS for younger patients (i.e., those aged <50 years) was 37.1 months compared to 18.6 months for older patients (i.e., those aged >50 years; p = 0.04; X2 = 3.870). Patients who received SRS after 10 months since diagnosis had a median OS of 36.2 months versus those who received SRS sooner than 10 months, who had an OS of 15 months (p = 0.004; X2 = 8.145). Radiosurgery doses larger than 15 Gy correlated with a median survival of nine months versus seven months in those treated with doses <15 Gy (p = 0.01; X2 = 6.756). Lastly, patients who received adjuvant bevacizumab (BEV) and or chemotherapy after SRS had a median survival of 12 months versus seven months for patients who did not receive any additional therapy after SRS (p = 0.04; X2 = 4.196). Conclusion SRS focal recurrent GBM in selected patients may improve OS, especially when combined with adjuvant therapy such as BEV and chemotherapy. Other prognostic variables proved relevant such as patients' age, the dose delivered, and surgery-to-SRS time that translates to the time of recurrence. Our results were consistent with the published literature and added to the accumulating evidence regarding SRS in recurrent GBM; however, extensive, multi-center studies are required to make definitive recommendations on this treatment approach.

Gamma Ray Radiosurgery for Trigeminal Neuralgia: Targeting Proximal or Distal to the Dorsal Root Entry Zone.

Introduction Stereotactic radiosurgery for trigeminal neuralgia (TN) has gained interest among patients who are not suitable for surgical procedures. Although two target zones are more recognized - dorsal root entry zone (DREZ) and retrogasserian zone (RGZ) - the optimal targeting technique remains controversial in terms of clinical outcomes and rates of complications. Therefore, various modifications to the radiosurgical technique for TN have been made. Objective This study aimed to determine the differences in shoot location (i.e., RGZ vs. DREZ) regarding effectiveness and adverse effects in patients with medically refractory TN. Additionally, we evaluated the effect of the integral dose (ID) on treatment outcomes and complications. Methods We present a retrospective cohort study of 49 patients with primary, drug-resistant TN treated with gamma knife radiosurgery targeting the distal and proximal parts of the nerve regarding the DREZ with a prescription dose of 90 Gy (80 to 96 Gy). A subset of these patients (n=38) where the ID could be measured to the nerve was correlated to treatment outcomes and complications. Results The median follow-up time was 36 months for RGZ and 51 months for DREZ targets. Neurovascular conflict was identified in 87.5% of the RGZ group and 88.2% of the DREZ group. Using the Barrow Neurological Institute (BNI) pain score, 26 (81.3%) RGZ and 12 (70.6%) DREZ patients were successfully treated (BNI I-IIIb; p=0.02). Seven (21.9%) RGZ and eight (47.1%) DREZ patients reported complete pain relief without medication (BNI I). Time response was 22.3 days for RGZ and 34.1 days for DREZ (p=0.277). There were 10 (31.3%) patients in the RGZ group with associated complications versus six (35.3%) patients in the DREZ group (χ2=0.0826, degree of freedom=1, p=0.773). Treatment outcomes using higher ID were better in the RGZ than DREZ (81.8% vs. 57.1, respectively), and a significant association was found between a higher ID delivered to the nerve and the development of complications (p=0.02). Conclusion Based on the obtained results, the RGZ was a more effective targeting area with better treatment outcomes without significant differences in complication rates than DREZ. A higher ID at the RGZ than DREZ had a greater therapeutical effect. Further investigation regarding the optimal target area along the ID delivered and clinical outcomes are required.

Multiplatform Radiosurgery for Intracranial Meningiomas and Dose to the Dural Tail.

Introduction Meningiomas are extra-axial central nervous system tumors. Complete resection is often curative with macroscopically complete removal of the tumor, excision of its dural attachment, and any abnormal bone. Radiosurgery is also an option for high-risk patients or in patients with surgically residual disease. Dural tail is a typical radiological sign on contrast-enhanced MRI; it can contain tumor cells or be a reaction due to vascular congestion and edema. Radiosurgical planning treatment varies regarding the identification and coverage of the dural tail. This study aimed to retrospectively analyze a series of 143 patients with WHO Grade I meningiomas treated with different radiosurgical platforms, and dosing parameters focused on planning and dose delivery to the dural tail. Methods From February 2011 to July 2020, 143 patients with histologically confirmed or radiologically assumed WHO Grade I meningiomas were treated using rotating gamma-ray Infini™ (Gamma [MASEP Medical Science Technology Development Co., Shenzhen, China]), TomoTherapy® (Tomo [Accuray Inc., Sunnyvale, CA]), and CyberKnife® (CK [Accuray Inc.]). All plans were retrospectively reviewed to establish the maximum distance (MaxDis) from the prescription dose to the end of the dural tail and the minimum dose at the dural tail (MinDoseT) at this point. We also established the midpoint distance (MPDis) from the prescription dose to MaxDis and the dose at this point (MPDose). Plans were further distinguished when the physician intended to cover the dural tail versus when not. Patients and tumor response were assessed by imaging and clinical and phone call evaluations. Results Of the 143 patients, 81 were treated using Gamma, 34 using Tomo, and 28 using CK. Eighty patients were eligible for follow-up, of whom 58 (72.5%) had an unmistakable dural tail sign. Median follow-up was 1,118 days (range 189-3,496), mean age was 54.5 (range 19-90), and 61 were women, and 19 were men. Overall tumor volume was 6.5 cc (range 0.2-59); mean tumor volumes by different platforms were 2.4, 9.45, and 8 cc; dose prescribed and mean tumor coverage were 14 Gy and 92%, 14.5 Gy and 95%, and 14 Gy and 95.75% with Gamma, Tomo, and CK, respectively. The dural tail was drawn and planned with an attempt to treat in 18 patients (31%); the mean MaxDis, MinDoseT, MPDis, and MPDose were 9.0 mm, 2 Gy, 4.5 mm, and 10.6 Gy, respectively. At last follow-up, tumor control was achieved in 96% of patients for the whole series, and there were no statistical variations regarding tumor volume, dose, conformality, or control when stereotactic radiosurgery was used to cover the dural tail versus when it was not (p=0.105). One patient experienced a Grade 4 Radiation Therapy Oncology Group toxicity as an adverse radiation effect that required surgery, and 11 (7.6%) experienced a Grade 1 toxicity. Conclusions This is our preliminary report regarding the efficacy of radiosurgery for meningiomas using diverse platforms at three years of follow-up; the results regarding tumor control are in accordance with the published literature as of this writing. A conscious pursuit of the dural tail with the prescription dose has not proven to provide better tumor control than not doing so - even small areas of the tumor uncovered by the prescription dose did not alter tumor control at current follow-up. The doses delivered to these uncovered areas are quite significant; further follow-up is necessary to validate these findings.

Comparación dosimétrica en radiocirugía intracraneal entre Cyberknife y un bisturí de rayos gamma y su puesta en marcha Centroamérica / Dosimetric comparison in intracranial radiosurgery between Cyberknife and a gamma knife and its implementation Central America

Introducción: La dupla Cyberknife y bisturí de rayos gamma (Infini) que se describe es la primera en Latinoamérica. Ambas máquinas han mostrado ser los mejores equipos para radiocirugía intracraneal. Se describe la experiencia inicial de Cyberknife en Centroamérica y su incorporación a un programa existente de bisturí de rayos gamma por vía de análisis comparativos dosimétricos. Material y método: En el año 2019 se realizaron planes comparativos y se trataron 180 pacientes con radiocirugía intracraneal con ambos sistemas tanto en patología tumoral, como vascular y funcional. Resultados: En el análisis dosimétrico comparativo en el gradiente de dosis de Infini mostró ser superior a Cyberknife en todos los casos. Para una esfera utilizando el colimador de 4 mm en Infini y de 5 mm en Cyberknife utilizando un plan isocéntrico con el -Trigeminal Path- el gradiente de dosis para Infini fue de 1.5 y para Cyberknife de 1.66. Para los casos de patología el gradiente de dosis media para Infini fue de 3 mm y para Cyberknife de 3.8 mm. Dando un puntaje de gradiente de dosis (Gradient Score Index) si Infini fuese de 100, Cyberknife obtuvo 87.3. Cyberknife mostró mejor conformalidad y cobertura (97% versus 96%) para todos los targets. Entre enero 2019 y enero 2020 se realizaron 180 radiocirugías, 60 con Cyberknife y 120 con Infini, 60 pacientes recibieron 146 sesiones con Cyberknife, radiocirugía fraccionada 39 (65%) y 21 (35%) en sesión única. Las dosis medias en tumores en dosis única fue 15 Gy (12.5 a 25 Gy) y en radiocirugía fraccionada 21 Gy (18 y 35). Ningún paciente ha experimentado toxicidad mayor a grado dos. Conclusiones: El bisturí de rayos gamma rotatorio reveló superioridad en gradiente de dosis con relación al Cyberknife. En su primer año Cyberknife ha mostrado ser una herramienta segura en el tratamiento de patología intracraneal. Más seguimiento clínico y radiológico es necesario para verificar su efectividad comparativa

Introduction: The match between Cyberknife and Infini here described in this article is the first in Latinamerica. Both machines have proven to be the best for intracranial radiosurgery, we describe our initial experience with Cyberknife in Central America and how it was incorporated in an existing gamma ray program by ways of dosimetry comparisons. Methods: During 2019 comparative plans were made and a total of 180 patients received intracranial radiosurgery with both technologies, patients were treated for tumors, vascular anomalies, and functional pathology. Results: Basic dosimetry analysis regarding dose gradient the Infini proved superior to Cyberknife in all plans. For a sphere using the 4 mm collimator in Infini and the 5 mm in Cyberknife along with an isocentric plan using the -Trigeminal Path- dose gradient was 1.5 for Infini and 1.66 for Cyberknife. For the pathology cases Infini was 3 mm and for Cyberknife 3.8 mm on mean. Giving a Gradient Score Index (GSI) if Infini would be 100, Cyberknife would be 87.3. Cyberknife showed better conformality and coverage for all pathology targets (97% versus 96%). From January 2019 to January 2020, 180 intracranial radiosurgeries were done, 60 with Cyberknife and 120 with Infini, 60 patients received 146 sessions with Cyberknife, fractionated scheme 39 (65%) and 21 (35%) single dose. The median dose for tumors was 15 Gy (12.5 a 25 Gy) for single session and 21 Gy (18 y 35) for fractionated scheme. No patient experienced a higher toxicity tan grade two. Conclusions: In its first year Cyberknife has shown to be safe in treating intracranial pathology. Infini had a better dose gradient than Cyberknife. Longer clinical and radiological follow-up is needed to verify its comparative effectiveness.

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.

Toxicity outcome in patients treated with modulated arc radiotherapy for localized prostate cancer.

AIM: This study evaluates the acute toxicity outcome in patients treated with RapidArc for localized prostate cancer. BACKGROUND: Modern technologies allow the delivery of high doses to the prostate while lowering the dose to the neighbouring organs at risk. Whether this dosimetric advantage translates into clinical benefit is not well known. MATERIALS AND METHODS: Between December 2009 and May 2012, 45 patients with primary prostate adenocarcinoma were treated using RapidArc. All patients received 1.8 Gy per fraction, the median dose to the prostate gland, seminal vesicles, pelvic lymph nodes and surgical bed was 80 Gy (range, 77.4-81 Gy), 50.4 Gy, 50.4 Gy and 77.4 Gy (range, 75.6-79.2 Gy), respectively. RESULTS: The time between the last session and the last treatment follow up was a median of 10 months (range, 3-24 months). The incidence of grade 3 acute gastrointestinal (GI) and genitourinary (GU) toxicity was 2.2% and 15.5%, respectively. Grade 2 acute GI and GU toxicity occurred in 30% and 27% of patients, respectively. No grade 4 acute GI and GU toxicity were observed. Older patients (>median) or patients with V60 higher than 35% had significantly higher rates of grade ≥2 acute GI toxicity compared with the younger ones. CONCLUSIONS: RapidArc in the treatment of localized prostate cancer is tolerated well with no Grade >3 GI and GU toxicities. Older patients or patients with higher V60 had significantly higher rates of grade ≥2 acute GI toxicity. Further research is necessary to assess definitive late toxicity and tumour control outcome.