Stereotactic Techniques Research Articles

A review of stereotactic body radiotherapy for the spine.

Radiation therapy of the spine, as recourse for spinal tumours, is an effective method of achieving pain reduction and local control. Hypofractionated techniques like stereotactic body radiation therapy and especially stereotactic radiosurgery are quickly becoming more popular as studies are published demonstrating their superior outcomes. This review concerns aspects of spinal radiotherapy of interest to the clinical medical physicist, with a focus on stereotactic techniques. The literature surveyed is mostly from the last two decades, concentrating particularly on studies from the last few years. Clinical aspects of spinal disease are covered to give context to the development of different radiotherapy techniques and thus the changing suitability criteria of patients. The latest studies concerning the treatment pathway are reviewed and summarised-from simulation and prescription to contouring, treatment planning and treatment delivery. This then leads into a discussion of the accuracy and uncertainties surrounding different methods of immobilisation and image guidance. Treatment planning algorithms and approaches are also reviewed. Finally, we survey the most recent outcomes and statistics concerning failures, toxicity, survivability and control rates. With careful consideration of the latest literature, patients suffering from spinal disease have a good chance of positive outcomes following radiotherapy.

Peroxisome proliferator-activated receptor-γ mediates the antihypertensive effects of acupuncture in spontaneously hypertensive rats.

We investigated a central antihypertensive effect of acupuncture in rostral ventrolateral medulla (RVLM) in spontaneously hypertensive rats (SHRs). In total, 56 rats were randomly divided into seven groups as follows: the SHR group, SHR+acupuncture (SHR+Acu) group, SHR+nonacupuncture (SHR+Non-acu) group, GW9662+acupuncture (GW9662+Acu) group, GW9662+GW1929 group, GW9662 group, and 2% DMSO group (n = 8 per group). The whole eight Wistar-Kyoto rats were assigned to the WKY group. The acupuncture treatment lasting for 14 days was performed at the Taichong acupoint (LR3) or at a nonacupoint (non-acu) once daily. The peroxisome proliferator-activated receptor (PPAR)-γ agonist GW1929 and the PPAR-γ inhibitor GW9662 were microinjected by the brain stereotactic technique. Blood pressure was measured by the tail-cuff method. Sympathetic vasomotor activity was determined by implanting in a telemetry electrocardiogram radio transmitter. The expression of PPARs in the RVLM of the rats was detected using Western blot. We demonstrated that acupuncture attenuated blood pressure, heart rate, and sympathetic vasomotor activity in SHRs. The protein expression of PPAR-γ was significantly increased in SHRs treated with acupuncture. The antihypertensive effects of acupuncture in SHRs were abrogated by microinjection bilaterally into RVLM of GW9662. Microinjection of GW1929 mimicked the antihypertensive effect of acupuncture. PPAR-γ expression was negatively correlated with blood pressure and sympathetic vasomotor activity in SHRs treated with acupuncture. These results suggested that acupuncture promoted a central antihypertensive effect by increasing the expression of PPAR-γ in RVLM of SHRs.

Intraoperative Squash Cytology in CNS Lesions - How Fine is the Resolution?

Introduction: With the advent of minimally invasive/ stereotactic neurosurgical techniques accurate localization of tumor and differentiation from surrounding normal brain parenchyma has become imperative to give maximal benefit of surgery and reducing collateral neurodeficit. Despite the advancement of non-invasive radiological tools, direct evidence from the microscope during the operation guides the surgeon and gives the patient optimal benefit of the surgery. The aim of this study is to correlate intraoperative squash cytology and final histopathological diagnosis and find out efficacy and reliability of squash as a diagnostic tool. Method/study design: A cross sectional observational study conducted in the Department of Neuropathology from August 2018 to June 2019. All neurosurgical cases received for both intra-operative diagnosis and histopathology sample were included. Results: Total ninety four cases of squash smear and corresponding histopathology with immunohistochemistry was studied and overall sensitivity of squash was calculated to be 91.3%. Individual sensitivity, specificity and positive predictive value for major lesions were also calculated. Conclusion: The role of intraoperative diagnosis in CNS tumors need not be overemphasized. It can achieve targeting of lesion and provide guidance to the neurosurgeon in modifying and monitoring the surgical approach.

Novel treatment strategies for early-stage lung cancer: the oncologist's perspective.

Management of early-stage non-small cell lung cancer (NSCLC) consists in multimodal treatment, including surgery, radiotherapy and chemotherapy. The mainstay of treatment is radical surgery. Definitive radiotherapy using stereotactic techniques can provide adequate local disease control, and is the treatment of choice in medically inoperable patients. Most early-stage patients are at significant risk of disease relapse after local treatment. Adjuvant platinum-based chemotherapy has demonstrated to provide an absolute survival benefit of 5% compared to observation. However, unlike advanced/metastatic disease, little progress has been made in the treatment of early-stage NSCLC over the past decade. In recent years, plenty of research has focused on the optimization of adjuvant and neoadjuvant treatment. Several trials with novel drugs, such as targeted agents and immune-checkpoint inhibitors are currently underway, with preliminary positive results. Customization of treatment on patients’ characteristics before, and major pathological response after therapy, will further improve survival outcomes in this subset of patients.

Long-Term Outcomes of Sporadic Vestibular Schwannomas Treated with Recent Stereotactic Radiosurgery Techniques

Vestibular schwannomas (VSs) are benign; thus, understanding long-term tumor control and late adverse radiation effects of stereotactic radiosurgery (SRS) through current radiosurgical techniques is important to inform treatment decisions. Our aim was to clarify long-term tumor control rates and incidence of late adverse radiation effects in patients with VSs followed for 5 years or longer after SRS. Altogether, 615 patients with VSs (excluding neurofibromatosis type 2 and partially treated tumors) followed for 5 years or longer after SRS using recent radiosurgical techniques were evaluated. All patients were treated at a margin dose of less than 14 Gy. All tumors were classified into 4 categories: type A (intracanalicular tumor, 87 patients [14%]), type B (cerebellopontine angle [CPA] tumor, 325 patients [53%]), type C (CPA tumor compressing the brain stem, 138 patients [22%]), and type D (CPA tumor compressing the brain stem with a deviation of the fourth ventricle, 65 patients [11%]). Median tumor volume was 2.0 cm3 and median marginal dose was 12 Gy. Median follow-up period was 158 months. Actuarial 5-, 10-, and 15-year or longer local control (LC) rates were 93%, 91%, and 89%, respectively. Tumor type (P < .001, hazard ratio 2.389) and number of prior surgeries (P = .007, hazard ratio 1.698) were significant for LC. Depending on the tumor type, the actuarial 10-year LC rates were 100%, 93%, 88%, and 70% in type A, B, C, and D tumors, respectively. No patient developed persistent facial palsy. Twenty patients (3.3%) developed delayed cysts. One patient developed malignant transformation (0.2%). SRS is a safe and effective treatment for VSs in the long term, excluding VSs compressing the brain stem witha deviation of the fourth ventricle. Delayed cysts such as cyst formation, enlarged preexisting cysts or extratumoral cysts, and malignant transformation should be considered possible causes of long-term treatment failures.

Metformin loaded phosphatidylserine nanoliposomes improve memory deficit and reduce neuroinflammation in streptozotocin-induced Alzheimer's disease model

Alzheimer's disease (AD) is closely associated with neuroinflammation development in the brain. Co-delivery of metformin (MET) with phosphatidylserine liposomes neuroprotectant may be beneficial in ameliorating AD-related symptoms like memory impairment and inflammation. Therefore, we aimed to prepare metformin containing phosphatidylserine nanoliposomes formulation (MET-PSL) and to evaluate its effect on rats subjected to AD. Alzheimer's disease model was induced by bilateral intracerebroventricular injection of streptozotocin (3 mg/kg) into rat brains using the stereotactic technique. MET-PSL, MET, and PSL alone were administered intraperitoneally to AD-induced animals and factors including learning and memory storage in addition to cytokine and tissue inflammatory changes were evaluated after a 22-day experiment period. The learning and memory parameters significantly (P < 0.05) improved in AD-rats treated with MET-PSL. Moreover, MET-PSL administration significantly (P < 0.05) decreased cytokine levels of IL1-β, TNF-α, and TGF-β in hippocampal tissues of rats with AD. Histological results indicated a considerable reduction in inflammatory and necrotic neural cells along with significantly (P < 0.05) increased neurogenesis in MET-PSL treated rats. Furthermore, our results showed that MET-PSL formulation could potentially act better than the free form of MET and PSL alone in the recovery process of rats with AD. In general, our data suggest that combination therapy of metformin loaded phosphatidylserine liposomes may enhance the therapeutic performance in AD patients of a clinical study.

Frame-Based Stereotactic Endoscopic Third Ventriculostomy—Toward Improved Precision and Minimizing Morbidities

Endoscopic third ventriculostomy (ETV) is a widely accepted treatment for obstructive hydrocephalus. For most practitioners, this procedure will be performed without navigation guidance. Without such guidance, the complications associated with the procedure have ranged from 1% to 8%. We hypothesized that the discrepancy between the surface bony anatomy and internal cranial anatomy contributes to the morbidities associated with ETV. We tested this hypothesis by comparing the position of the entry point defined by the classic Kocher's point relative to the ideal entry point that would result in no manipulation of the endoscope defined by frame-based stereotaxis. The cranial computed tomography scan of 58patients who had undergone frame-based stereotactic ETV was reformatted into 3-dimensional renderings. The location of this entry point was compared with the Kocher point, as determined by the external bony anatomy. Overall, >70% of the burr holes that provided an ideal trajectory to the third ventricle were ≥0.5 cm from the Kocher point in both the sagittal and the coronal planes. Median deviations of 0.74 and 0.81 cm in the coronal (P < 0.01) and sagittal (P < 0.0001) planes were observed. The use of stereotactic endoscopic techniques increase the safety of third ventriculostomy by adding precision and reducing otherwise unnecessary surgical maneuvering.

Quality of teaching radiation oncology in Germany\u2014where do we stand?

PurposeMedical students’ knowledge of radiation oncology (RO) is of increasing importance with a rising prevalence of malignancies. However, RO teaching in medical schools is heterogeneous and has not been analyzed at a federal level yet. Therefore, the following survey aims to provide a national overview of RO teaching in Germany.MethodsA questionnaire containing multiple-choice and free-text questions covering the extent and topics of RO teaching was sent to RO departments of all university hospitals in Germany and was answered by the heads of department/main lecturers.Results24/35 (68.6%) RO departments returned completed forms. Most faculties employ lectures (91.7%), seminars (87.5%), and practical/bedside training (75.0%), whereas training in radiation biology and medical physics are rare (25% and 33.3%, respectively). Main topics covered are general RO (100%), radiation biology (91.7%), and side effects (87.5%). Regarding RO techniques and concepts, image-guided and intensity-modulated radiotherapy are taught at all faculties, followed by palliative and stereotactic techniques (87.5% each). Notably, all departments offered at least a partial rotation in RO in conjunction with radiology and/or nuclear medicine departments in the last year of medical school, while only 70.8% provided a complete rotation in RO. In addition, 57.1% of the departments have taken measures concerning the upcoming National Competence-Based Learning Objectives Catalogue (NKLM) for medical education.ConclusionRO plays an integral but underrepresented role in clinical medical education in Germany, but faces new challenges in the development of practical and competence-based education, which will require further innovative and interdisciplinary concepts.

On the complexity of helical tomotherapy treatment plans

PurposeMultiple metrics are proposed to characterize and compare the complexity of helical tomotherapy (HT) plans created for different treatment sites.MethodsA cohort composed of 208 HT plans from head and neck (105), prostate (51) and brain (52) tumor sites was considered. For each plan, 14 complexity metrics were calculated. Those metrics evaluate the percentage of leaves with small opening times or approaching the projection duration, the percentage of closed leaves, the amount of tongue‐and‐groove effect, and the overall modulation of the planned sinogram. To enable data visualization, an approach based on principal component analysis was followed to reduce the dataset dimensionality. This allowed the calculation of a global plan complexity score. The correlation between plan complexity and pretreatment verification results using the Spearman’s rank correlation coefficients was investigated.ResultsAccording to the global score, the most complex plans were the head and neck tumor cases, followed by the prostate and brain lesions irradiated with stereotactic technique. For almost all individual metrics, head and neck plans confirmed to be the plans with the highest complexity. Nevertheless, prostate cases had the highest percentage of leaves with an opening time approaching the projection duration, whereas the stereotactic brain plans had the highest percentage of closed leaves per projection. Significant correlations between some of the metrics and the pretreatment verification results were identified for the stereotactic brain group.ConclusionsThe proposed metrics and the global score demonstrated to be useful to characterize and quantify the complexity of HT plans of different treatment sites. The reported differences inter‐ and intra‐group may be valuable to guide the planning process aiming at reducing uncertainties and harmonize planning strategies.

Spine stereotactic radiosurgery for metastases from hepatobiliary malignancies: patient selection using PRISM scoring.

Dose escalation via stereotactic radiation therapy techniques has been necessary for hepatobiliary malignancies in the primary and oligometastatic setting, but such dose escalation is challenging for spine metastases due to spinal cord proximity. Here, we investigate the role of spine stereotactic radiosurgery (SSRS) in the management of such metastases. We retrospectively reviewed patients treated with SSRS to spinal metastases from hepatobiliary malignancies between 2004 and 2017 at our Institution. We used the Kaplan-Meier method to calculate overall survival (OS) and local control (LC) and Cox regression analysis to identify factors associated with disease-related outcomes. We identified 28 patients treated to 43 spinal metastases with SSRS for either HCC or cholangiocarcinoma. The 1-year LC and OS were 85% and 23%, respectively. The median time to death was 6.2months, while median time to local failure was not reached. Tumor volume > 60cc (SHR 6.65, p = 0.03) and Bilsky ≥ 1c (SHR 4.73, p = 0.05) predicted for poorer LC, while BED10 > 81Gy trended towards better local control (SHR 4.35, p = 0.08). Child-Pugh Class (HR 3.02, p = 0.003), higher PRISM Group (HR 3.49, p = 0.001), and systemic disease progression (HR 3.65, p = 0.001) were associated with worse mortality based on univariate modeling in patients treated with SSRS; on multivariate analysis, PRISM Group (HR 2.28, p = 0.03) and systemic disease progression (HR 2.67, p = 0.03) remained significant. Four patients (10%) developed compression deformity and one patient (2%) developed radiation neuritis. SSRS provides durable local control in patients with metastatic hepatobiliary malignancies, with higher BED necessary to ensure excellent LC. PRISM scoring is a promising prognostic tool to aid SSRS patient selection.

Thermal ablation—an option in curative treatment of HCC

SummaryMinimally invasive thermal ablation techniques are an integral part of international treatment guidelines in hepatocellular carcinoma (HCC). Due to highly effective local tumor control in nonresectable liver tumors with a relatively low rate of morbidity and mortality, thermal ablation even challenges the surgical approach as the first-line treatment in selected patients. Ablation outcome is largely dependent on the size and location of the HCC as well as on the applied ablation technique and image guidance. The creation of a sufficient ablation margin (A0 ablation in analogy to R0 resection) is prerequisite to assure low recurrence rates. In large tumors, tumor-free margins can be achieved only by overlapping ablation zones, which can be accomplished using stereotactic multiprobe ablation techniques (stereotactic radiofrequency ablation [SRFA], stereotactic microwave ablation [SMWA], stereotactic irreversible electroporation [SIRE]) in combination with 3D trajectory planning and image fusion for intraoperative evaluation of treatment results.

Different strategies in the management of thalamic space-occupying lesions

IntroductionThalamic space-occupying lesions (SOL) are considered challenging for microsurgical removal. Unfortunately, the pathological features of lesions occurring in the thalamic region are different with a wide variation in clinical behavior and outcome. Although microsurgery is still the gold standard in the management of these lesions through different approaches, questions remain whether surgery is feasible and safe in these patients and what are the alternatives? It is well known that stereotactic techniques may be favorable especially in cystic, small, multiple lesions and in combination with adjuvant therapy. Transventricular endoscopic approach is also an alternative technique to combine tumor biopsy and treatment of hydrocephalus.Aim of the studyThe identification of the different procedures for the management of thalamic SOL in respect to the age of the patient, the clinical condition, and the site of the lesion as well as its extent and pathology.Patients and methodsThis prospective study included 35 patients having thalamic lesions with a mean age of 27 years old who were treated with different approaches including microsurgical, stereotactic, and endoscopic approaches. The clinical outcome was assessed as the same, improved, deteriorated, or died in comparison to the initial clinical status, while the radiological control was measured as no gross residual, residual < 10% and residual > 10%. Chi-square test was used to test the association between two categorical variables.ResultsThirty-five patients were included in this study, 20 were males and 15 were females. Eight cases were children, and 27 cases were adults. The most common clinical presentation was contralateral hemiparesis. The most common pathology was pilocytic astrocytoma. Radiological studies showed that the total thalamic type was the most common topographic variant and that 10 cases had hydrocephalus treated with CSF diversion procedures. For the definitive lesion, 2 cases underwent endoscopic biopsy and cystoventriculostomy and 18 cases had stereotactic technique in the form of biopsy, aspiration, and ommaya reservoir application, while 15 cases had microsurgery through different approaches with stereotactic technique preceding surgery in 2 of them.ConclusionThe main factors involved in choosing the appropriate approach included nature of the lesion (solid or cystic, multiplicity), suspected pathological type, and diffusion tensor imaging. Abscesses are best treated with stereotaxy, while non-neoplastic cystic lesions (other than abscesses) related to the ventricles are best treated with endoscopy. For the remaining pathologies, maximum surgical removal is the best management. Best lesion control was provided by microsurgery.Trial registrationISRCTN 1380 registered 6/11/2018

Outcomes and the Role of Primary Histology Following LINAC-based Stereotactic Radiation for Sarcoma Brain Metastases.

The brain is a rare site for sarcoma metastases. Sarcoma's radioresistance also makes standard whole-brain radiotherapy less appealing. We hypothesize that stereotactic radiation techniques (stereotactic radiosurgery [SRS]/stereotactic fractionated radiotherapy [FSRT]) may provide effective local control. This single-institution retrospective analysis evaluated our experience with linear acceleator-based SRS/FSRT for sarcoma brain metastases. Time to event analysis was estimated via Kaplan-Meier. Univariable/multivariable Cox regression analyses followed to assess the impact of patient and disease characteristics on outcomes. Between 2003 and 2018, 24 patients were treated with 34 courses of SRS/FSRT to 58 discrete lesions. The median age at first treatment was 57 years (range: 25 to 87 y). Majority of patients had concurrent lung metastases (n=21; 88%), diagnosed spindle cell sarcoma (n=15; 25%) or leiomyosarcoma (n=12; 21%) histology, and were treated with either SRS (n=43; median dose=19 Gy, range: 15 to 24 Gy) or FSRT (n=17; 3/5 fractions, median dose=25 Gy, range: 25 to 35 Gy). With a median follow-up after brain metastasis of 7.3 months, the 6 month/12 month local control, distant brain control, and overall survival of 89%/89%, 59%/34%, and 50%/38%, respectively. All local failures were of primary spindle cell histology (P<0.001), which was associated with poorer distant control (hazard ratio=25.8, 95% confidence interval: 3.1-536.4; P=0.003) on univariable analysis, and OS (hazard ratio=7.1, 95% confidence interval: 2.0-26.1; P=0.003) on multivariable analysis. This is the largest patient cohort with sarcoma brain metastases treated with SRS/FSRT, it provides durable local control, despite a reputation for radioresistance. Further prospective evidence is required to determine the impact of primary histology on control and survival following brain metastasis diagnosis.

Slim electrodes for improved targeting in deep brain stimulation

Objective. The efficacy of deep brain stimulation can be limited by factors including poor selectivity of stimulation, targeting error, and complications related to implant reliability and stability. We aimed to improve surgical outcomes by evaluating electrode leads with smaller diameter electrode and microelectrodes incorporated which can be used for assisting targeting. Approach. Electrode arrays were constructed with two different diameters of 0.65 mm and the standard 1.3 mm. Micro-electrodes were incorporated into the slim electrode arrays for recording spiking neural activity. Arrays were bilaterally implanted into the medial geniculate body (MGB) in nine anaesthetised cats for 24–40 h using stereotactic techniques. Recordings of auditory evoked field potentials and multi-unit activity were obtained at 1 mm intervals along the electrode insertion track. Insertion trauma was evaluated histologically. Main results. Evoked auditory field potentials were recorded from ring and micro-electrodes in the vicinity of the medial geniculate body. Spiking activity was recorded from 81% of the microelectrodes approaching the MGB. Histological examination showed localized surgical trauma along the implant. The extent of haemorrhage surrounding the track was measured and found to be significantly reduced with the slim electrodes (541 ± 455 µm vs. 827 ± 647 µm; P < 0.001). Scoring of the trauma, focusing on tissue disruption, haemorrhage, oedema of glial parenchyma and pyknosis, revealed a significantly lower trauma score for the slim electrodes (P < 0.0001). Significance. The slim electrodes reduced the extent of acute trauma, while still providing adequate electrode impedance for both stimulating and recording, and providing the option to target stimulate smaller volumes of tissue. The incorporation of microelectrodes into the electrode array may allow for a simplified, single-step surgical approach where confirmatory micro-targeting is done with the same lead used for permanent implantation.

Low-Cost Stereotactic Brain Biopsy Simulation Model

Simulation training improves technical skills in a safe environment. Stereotactic techniques are widely used in neurosurgery for different kinds of procedures. The objective of the study was to describe a combined cadaveric and synthetic low-cost stereotactic simulation model and its validation by neurosurgeons. The brain was made using self-supporting gel with solid and cystic lesions. We used imaging scans to calculate x, y, and z target coordinates. A standard frame needle biopsy was performed. We calculated the number of mistakes and time needed to accomplish the task, and we evaluated the frame assembly and biopsy performance. Wilcoxon signed rank was used to analyzed the data; we considered a P value <0.05 as statistically significant. The median initial number of mistakes was 32(interquartile range [IQR]: 27.5-37) and after repeated training and feedback the final median number was 3.5 (IQR: 2-6) (P < 0.001). The median time needed to finish the exercises before training was 1020.5 seconds (IQR: 908-1125.5) and after using the model the final median time was 479 seconds (IQR: 423-503) (P < 0.0001). We presented a stereotactic simulation model with immediate haptic feedback. The model can be easily handmade in any neurosurgical laboratory. This model allows neurosurgeons in training to acquire and improve stereotactic techniques, reducing the number of surgical mistakes and time needed to finish the task.

A Novel Approach for Treatment of Uterine Fibroids: Stereotactic Radiosurgery as a Proposed Treatment Modality

Minimally invasive therapeutic interventions and the field of stereotactic radiosurgery have advanced enormously in recent years. We briefly review the field of stereotactic radiosurgery and propose its use as a novel treatment modality for benign gynecologic conditions such as uterine fibroids. Computerized searches of Medline and PubMed were conducted using the key words “stereotactic radiosurgery,” “CyberKnife®,” “uterine fibroids,” and “radiation therapy.” References from identified sources were manually searched to allow for a thorough review. Data from relevant sources was compiled to create this review article. Stereotactic techniques have not only significantly reshaped the field of neurosurgery from open to noninvasive treatment, but also has impacted the field of radiation oncology by improving precision and reducing radiation exposure of normal tissues. Stereotactic radiation has proven to be a safe and effective method for the treatment of both benign and malignant conditions. Over the past two decades, new technologies have expanded the application of stereotactic radiosurgery to include spinal, renal, cardiac, lung, liver, prostate, and gynecologic cancers, and very recently even for the treatment of some non-neoplastic conditions such as cardiac arrhythmias. With success in so many disciplines, it is proposed that stereotactic radiosurgery may be a promising tool for the treatment of benign gynecologic conditions. Additional clinical experience is needed to further define the safety and efficacy of this proposed new treatment paradigm.

Radioterapia chorych na czerniaka

The role of radiotherapy (RT) in the treatment of melanoma is constantly evolving. Although melanoma is considered a radioresistant tumour with great potential for repairing sub-lethal damage, RT is an important component of treatment. Indications for sole or adjuvant radiotherapy of the primary lesion are limited and include desmoplastic melanoma, the presence of satellite lesions and/or in-transit metastases, the presence of melanoma cells in blood or lymphatic vessels, infiltration of nerve trunks, recurrence after previous surgery, and locally advanced melanomas of the head and neck region, especially inoperable. In the past, the most common indication for radiotherapy in melanoma was adjuvant treatment after lymphadenectomy in patients with risk factors for nodal recurrence (large metastasis diameter, multiple nodes involved, extracapsular extension). Adjuvant radiotherapy after lymphadenectomy has been shown to almost double the local control of the disease, but it does not affect patient survival and may also lead to significant toxicity. Nevertheless, currently the recommended approach is systemic adjuvant treatment (anti-PD-1 immunotherapy with pembrolizumab or nivolumab and, in the presence of BRAF mutation, BRAF/MEK inhibitors), and RT should be reserved for situations in which there are contraindications to other adjuvant treatment. Stereotactic techniques, including radiosurgery of brain metastases, are becoming more widely used. RT could be a definitive treatment for a limited number of metastases or in cases of limited progression on systemic treatment. The effectiveness of RT can be increased by combining with hyperthermia. An increasing number of reports suggest great benefit from the combination of RT with immunotherapy. At present, there is no convincing evidence supporting the combination of RT with molecularly targeted treatment, and according to emerging data on the toxicity of such a combination it should be used with caution.

Frameless Stereotactic Targeting of the Cerebellar Dentate Nucleus in Nonhuman Primates: Translatable Model for the Surgical Delivery of Gene Therapy

Background: Stereotactic targeting techniques in nonhuman primate (NHP) models are often utilized in the preclinical investigation of new drug therapies with the goal of demonstrating accurate and reliable delivery of a therapy to the target tissue. However, targeting certain neuroanatomical structures can be challenging. The deep cerebellar nuclei, specifically the dentate nucleus, are potential stereotactic targets for the treatment of certain ataxias. Currently, there are no detailed techniques describing frameless targeting of these structures in a NHP model. A well-defined, accurate, and reliable stereotactic surgical approach to the dentate in these animal models is critical to prove the feasibility and safety of drug delivery in order to develop clinical protocols. Methods: Frameless stereotactic neuronavigation was employed to target the bilateral dentate nuclei of the cerebellum in four healthy juvenile Cynomolgus monkeys via a suboccipital, transcerebellar approach. The precision and accuracy of the targeting were evaluated radiologically and histologically. Results: Using the described surgical methodology, we were successful in hitting the target deep cerebellar nuclei seven out of eight times. Conclusion: Frameless stereotactic targeting of the cerebellar dentate nuclei in NHPs for future investigational drug delivery is feasible, safe, and accurate as described by this report. Potential areas for improving the technique are discussed.

Computer-assisted planning for minimally invasive anterior two-thirds laser corpus callosotomy: A feasibility study with probabilistic tractography validation.

Anterior two-thirds corpus callosotomy is an effective palliative neurosurgical procedure for drug-refractory epilepsy that is most commonly used to treat drop-attacks. Laser interstitial thermal therapy is a novel stereotactic ablative technique that has been utilised as a minimally invasive alternative to resective and disconnective open neurosurgery. Case series have reported success in performing laser anterior two-thirds corpus callosotomy. Computer-assisted planning algorithms may help to automate and optimise multi-trajectory planning for this procedure. To undertake a simulation-based feasibility study of computer-assisted corpus callostomy planning in comparison with expert manual plans in the same patients. Ten patients were selected from a prospectively maintained database. Patients had previously undergone diffusion-weighted imaging and digital subtraction angiography as part of routine SEEG care. Computer-assisted planning was performed using the EpiNav™ platform and compared to manually planned trajectories from two independent blinded experts. Estimated ablation cavities were used in conjunction with probabilistic tractography to simulate the expected extent of interhemispheric disconnection. Computer-assisted planning resulted in significantly improved trajectory safety metrics (risk score and minimum distance to vasculature) compared to blinded external expert manual plans. Probabilistic tractography revealed residual interhemispheric connectivity in 1/10 cases following computer-assisted planning compared to 4/10 and 2/10 cases with manual planning. Computer-assisted planning successfully generates multi-trajectory plans capable of LITT anterior two-thirds corpus callosotomy. Computer-assisted planning may provide a means of standardising trajectory planning and serves as a potential new tool for optimising trajectories. A prospective validation study is now required to determine if this translates into improved patient outcomes.

Metachronous NSCLC in previously irradiated patients: is re-irradiation with SBRT a good option as definitive treatment?

AbstractAim:Treatment of metachronous second primary non-small cell lung cancer (NSCLC) in patients already treated with definitive radiotherapy is a matter of debate, since most patients are excluded from surgical treatment, which remains a therapeutic standard for patients with isolated lung masses. Salvage chemotherapy or immunotherapy alone offers a low probability of disease control. The option of re-irradiation often remains the only viable, but the risks of severe acute or late toxicities affecting the surrounding normal tissues make this a real clinical challenge.Materials and methods:From January 2015 to April 2018, five patients (male/female: 4/1; age 54–81 years, median 68) with previously irradiated NSCLC presented with a second primary lung tumour.Results:A partial response was seen in four patients, one complete responses in the fifth. The toxicity was low: two patients experienced a grade 2 asymptomatic radiation pneumonitis after 6 and 12 months from the end of stereotactic body radiation therapy, resolved with cortisone therapy. No acute or late oesophageal or cardiac toxicity was found.Findings:In this work, we present our initial experience about the use of stereotactic radiotherapy technique in already irradiated patients. We reported a local disease control in all cases with an acceptable toxicity.