Somatotopy of the sensory thalamus: inputs from directional deep brain stimulation in pain patients.

OBJECTIVE: The sensory ventroposterior (VP) thalamic nuclei display a mediolateral somatotopic organization (respectively head, arm, and leg). We studied this somatotopy using directional VP deep brain stimulation (DBS) in patients treated for chronic neuropathic pain. METHODS: Six patients with central (four) or peripheral (two) neuropathic pain were treated by VP DBS using directional leads in a prospective study (clinicaltrials.gov NCT03399942). Lead-DBS toolbox was used for leads localization, visualization, and modeling of the volume of tissue activated (VTA). Stimulation was delivered in each direction, 1 month after surgery and correlated to the location of stimulation-induced paresthesias. The somatotopy was modeled by correlating the respective locations of paresthesias and VTAs. We recorded 48 distinct paresthesia maps corresponding to 48 VTAs (including 36 related to directional stimulation). RESULTS: We observed that, in each patient, respective body representations of the trunk, upper limb, lower limb, and head were closely located around the lead. These representations differed across patients, did not follow a common organization and were not concordant with the previously described somatotopic organization of the sensory thalamus. INTERPRETATION: Thalamic reorganization has been reported in chronic pain patients compared to non-pain patients operated for movement disorders in previous studies using intraoperative recordings and micro-stimulation. Using a different methodology, namely 3D representation of the VTA by the directional postoperative stimulation through a stationary electrode, our study brings additional arguments in favor of a reorganization of the VP thalamic somatotopy in patients suffering from chronic neuropathic pain of central or peripheral origin.

Surgical management of large lower cranial nerves schwannomas: long term results of a less aggressive resection strategy.

In an effort to reduce the high morbidity and life-threatening complications after radical resection in large schwannoma surgery, alternative strategies of nontotal resections have emerged. To evaluate the long term clinical and oncological outcome after lower cranial nerves (LCN) schwannoma surgery operated on with a cranial nerve-sparing technique. Single center retrospective cohort study of 8 consecutive patients harboring LCN schwannomas operated on between March 2005 and October 2021. The mean LCN schwannoma diameter was 33 mm (range 26-51). Seven patients (87,5%) underwent a modified retrosigmoid approach. Three patients underwent gross total resection (37,5%), 3 had received neartotal resection (mean tumor residue 0,25 cc) and subtotal resection in 2 patients who presented with an extracranial extension of the tumor (mean tumor residue 2,44 cc). Both patients had received upfront additional GKRS. The three patients who presented with preoperative CN IX & X injuries recovered within 6 months after surgery. All of the five patients freed from any preoperative CNs IX & X symptoms experienced transient (80%) or definitive (one patient) disturbances after surgery. They all improved within 6 months but one who required long term gastrostomy feeding tube. This patient harbored a schwannoma originating from the glossopharyngeal nerve, which could not be anatomically preserved during surgery. Tumor control was achieved in 100% of cases with a mean follow-up of 91 months. LCN schwannomas could be surgically removed through a less aggressive non-radical resection strategy with acceptable functional results and excellent tumor control.

Management of sporadic intracanalicular vestibular schwannomas: A critical review and International Stereotactic Radiosurgery Society (ISRS) practice guidelines.

BACKGROUND: The choice of an appropriate strategy for intracanalicular vestibular schwannoma (ICVS) is still debated. We conducted a systematic review and meta-analysis with the aim to compare treatment outcomes amongst management strategies (conservative surveillance (CS), microsurgical resection (MR), or stereotactic radiosurgery (SRS)) aiming to inform guideline recommendations on behalf of the International Stereotactic Radiosurgery Society (ISRS). METHODS: Using PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2021 referenced in PubMed or Embase. Inclusion criteria were peer-reviewed clinical studies or case series reporting a cohort of ICVS managed with CS, MR, or SRS. Primary outcome measures included tumor control, the need for additional treatment, hearing outcomes, and posttreatment neurological deficits. These were pooled using meta-analytical techniques and compared using meta-regression with random effect. RESULTS: Forty studies were included (2371 patients). The weighted pooled estimates for tumor control were 96% and 65% in SRS and CS series, respectively (P < .001). Need for further treatment was reported in 1%, 2%, and 25% for SRS, MR, and CS, respectively (P = .001). Hearing preservation was reported in 67%, 68%, and 55% for SRS, MR, and CS, respectively (P = .21). Persistent facial nerve deficit was reported in 0.1% and 10% for SRS and MR series, respectively (P = .01). CONCLUSIONS: SRS is a noninvasive treatment with at least equivalent rates of tumor control and hearing preservation as compared to MR, with the caveat of better facial nerve preservation. As compared to CS, upfront SRS is an effective treatment in achieving tumor control with similar rates of hearing preservation.

Assessing Tumor Volume for Sporadic Vestibular Schwannomas: A Comparison of Methods of Volumetry.

INTRODUCTION: The size of vestibular schwannomas (VS) is a major factor guiding the initial decision of treatment and the definition of tumor control or failure. Accurate measurement and standardized definition are mandatory; yet no standard exist. Various approximation methods using linear measures or segmental volumetry have been reported. We reviewed different methods of volumetry and evaluated their correlation and agreement using our own historical cohort. METHODS: We selected patients treated for sporadic VS by Gammaknife radiosurgery (GKRS) in our department. Using the stereotactic 3D T1 enhancing MRI on the day of GKRS, 4 methods of volumetry using linear measurements (5-axis, 3-axis, 3-axis-averaged, and 1-axis) and segmental volumetry were compared to each other. The degree of correlation was evaluated using an intraclass correlation test (ICC 3,1). The agreement between the different methods was evaluated using Bland-Altman diagrams. RESULTS: A total of 2,188 patients were included. We observed an excellent ICC between 5-axis volumetry (0.98), 3-axis volumetry (0.96), and 3-axis-averaged volumetry (0.96) and segmental volumetry, respectively, irrespective of the Koos grade or Ohata classification. The ICC for 1-axis volumetry was lower (0.72) and varied depending on the Koos and Ohata subgroups. None of these methods were substitutable. CONCLUSION: Although segmental volumetry is deemed the most accurate method, it takes more effort and requires sophisticated computation systems compared to methods of volumetry using linear measurements. 5-axis volumetry affords the best adequacy with segmental volumetry among all methods under assessment, irrespective of the shape of the tumor. 1-axis volumetry should not be used.

Long-Term Hearing Outcome After Radiosurgery for Vestibular Schwannoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Stereotactic radiosurgery (SRS) is one of the main treatment options in the management of small to medium size vestibular schwannomas (VSs), because of high tumor control rate and low cranial nerves morbidity. Series reporting long-term hearing outcome (>3 years) are scarce. OBJECTIVE: To perform a systematic review of the literature and meta-analysis, with the aim of focusing on long-term hearing preservation after SRS. METHODS: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we reviewed articles published between January 1990 and October 2020 and referenced in PubMed or Embase. Inclusion criteria were peer-reviewed clinical study or case series of VSs treated with SRS (single dose), reporting hearing outcome after SRS with a median or mean audiometric follow-up of at least 5 years. Hearing preservation, cranial nerves outcomes, and tumor control were evaluated. RESULTS: Twenty-three studies were included. Hearing preservation was found in 59.4% of cases (median follow-up 6.7 years, 1409 patients). Main favorable prognostic factors were young age, good hearing status, early treatment after diagnosis, small tumor volume, low marginal irradiation dose, and maximal dose to the cochlea. Tumor control was achieved in 96.1%. Facial nerve deficit and trigeminal neuropathy were found in 1.3% and 3.2% of patients, respectively, both significantly higher in Linear Accelerator series than Gamma Knife series ( P < .05). CONCLUSION: Long-term hearing preservation remains one of the main issues after SRS, with a major impact on health-related quality of life. Our meta-analysis suggests that hearing preservation can be achieved in almost 60% of patients after a median follow-up of 6.7 years, irrespective of the technique.

Occipital Nerve Stimulation for Recurrent Trigeminal Neuralgia Without Occipital Pain.

OBJECTIVES: Trigeminal neuralgia (TN) is a severe, debilitating pain condition causing physical and emotional distress. Although the management of TN is well codified with medical and then surgical treatments, 15% to 30% of patients will experience intractable pain. Neuromodulation techniques have been scarcely used for refractory TN, with only small case series and short-term follow-up. MATERIALS AND METHODS: We conducted a retrospective study of patients treated with occipital nerve stimulation (ONS) for medically and surgically resistant TN without painful trigeminal neuropathy. The effectiveness of the ONS was evaluated using the Barrow Neurological Institute (BNI) pain score and the pain relief (0%-100%) at best and at last follow-up. RESULTS: Seven patients who have refractory TN were included. The mean age at ONS was 49 years. The mean pain duration was 8.6 years. The mean number of medical and surgical treatments before ONS was six and five, respectively. A percutaneous trial was performed in five of seven patients; all responded (pain relief > 40%), and four of five patients experienced pain recurrence after explantation. Eventually, six patients had a permanent ONS implantation. The average BNI pain score before implantation was V. The mean follow-up after implantation was 59 months. All patients reported an improvement after implantation. The average BNI score and mean pain relief at best were IIIa and 86.7%, respectively. At last follow-up, the average BNI score and mean pain relief were IIIa and 58.0%, respectively, with three patients experiencing pain recurrence. Adverse events were reported for four patients who required surgical revision for lead breakage (1), erosion (1), migration (1), or hardware-related discomfort (1). One patient finally underwent explantation because of infection. CONCLUSIONS: Although ONS is not validated in this indication, these results suggest that it can induce an improvement in TN recurring after several surgical treatments, and the benefit of the stimulation can be sustained in the long term. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT01842763.

Surgical management of large cerebellopontine angle meningiomas: long-term results of a less aggressive resection strategy.

OBJECTIVE: Cerebellopontine angle (CPA) meningiomas present many surgical challenges depending on their volume, site of dural attachment, and connection to surrounding neurovascular structures. Assuming that systematic radical resection of large CPA meningiomas carries a high risk of permanent morbidity, the authors adopted an alternative strategy of optimal resection followed by radiosurgery or careful observation of the residual tumor and assessed the efficiency and safety of this approach to meningioma treatment management. METHODS: This single-center retrospective cohort study included 50 consecutive patients who underwent surgery for meningioma between January 2003 and February 2020. RESULTS: The most common main dural attachments of the meningiomas were posterior (42%) and superior (26%) to the internal auditory meatus. The suboccipital retrosigmoid route was the most routinely used (92%). At the last follow-up examination, 93% of the patients with normal preoperative facial nerve (FN) function retained good House-Brackmann (HB) grades of I and II, whereas 3 patients (7%) displayed intermediate HB grade III FN function. Hearing preservation was achieved in 86% of the patients who presented with preoperative serviceable hearing, and recovery after surgery was achieved in 19% of the patients experiencing preoperative hearing loss. In order to preserve all cranial nerve function, gross-total resection was obtained in 26% of patients. Of the 35 patients who had undergone subtotal resection, 20 (57%) had been allocated into a wait-and-rescan treatment approach and 15 (43%) underwent upfront Gamma Knife surgery (GKS). The mean postoperative tumor volume was 1.20 cm3 in the upfront GKS group and 0.73 cm3 in the wait-and-rescan group (p = 0.08). Tumor control was achieved in 87% and 55% of cases (p < 0.001), with a mean follow-up of 85 and 69 months in the GKS and wait-and-rescan groups, respectively. The 1-, 5-, and 7-year tumor progression-free survival rates were 100%, 100%, and 89% in the GKS group and 95%, 59%, and 47% in the wait-and-rescan group, respectively (p < 0.001). CONCLUSIONS: Optimal nonradical resection of large CPA meningiomas provides favorable long-term tumor control and functional preservation. Adjuvant GKS does not carry additional morbidity and appears to be an efficient adjuvant treatment.

Stereotactic radiosurgery for post operative brain metastasic surgical cavities: a single institution experience.

BACKGROUND: The standard therapy for brain metastasis was surgery combined with whole brain radiotherapy (WBRT). The latter is however, associated with important neurocognitive toxicity. To reduce this toxicity, postoperative stereotactic radiosurgery (SRS) is a promising technique. We assessed the efficacy and the tolerance to postoperative Gamma Knife radiosurgery (GK) on the tumor bed after resection of brain metastases. METHODS: Between February 2011 and December 2016, following macroscopic complete surgical resection, 64 patients and 65 surgical cavities were treated by GK in our institution. The indication for adjuvant radiosurgery was a multidisciplinary decision. The main assessment criteria considered in this study were local control, intracranial metastasis-free survival (ICMFS), overall survival and toxicity. RESULTS: Median follow-up: 11.1 months. Median time between surgery and radiosurgery: 35 days. Median dose was 20 Gy prescribed to the 50% isodose line, for a median treated volume of 5.6 cc. Four patients (7%) suffered from local recurrence. Local recurrence-free, intracranial recurrence-free and overall survival at 1 year were 97.5%, 57.6% and 62.4% respectively. In total, 23 patients (41%) suffered from intracranial recurrence outside the tumor bed. In univariate analysis: concomitant GK treatment of multiple lesions and the tumor bed was associated with a decrease in ICMFS (HR = 1.16 [1.005-1.34] p = 0.04). In multivariate analysis: a non-lung primary tumor was significantly associated with a decrease in ICMFS (HR = 8.04 [1.82-35.4] p = 0.006). An increase in performance status (PS) and in the initial number of cerebral metastases significantly reduced overall survival (HR = 5.4 [1.11-26.3] p = 0.037, HR = 2.7 [1.004-7.36] p = 0.049, respectively) and One radiation necrosis histologically proven. CONCLUSION: Our study confirmed that postoperative GK after resection of cerebral metastases is an efficient and well-tolerated technique, to treat volumes of all sizes (0.8 to 40 cc). Iterative SRS or salvage WBRT can be performed in cases of intracranial relapse, postponing WBRT with its potential side effects.

Is salvage surgery for large vestibular schwannomas after failed gamma knife radiosurgery more challenging?

In order to verify whether a previous gamma knife surgery (GKS) treatment could influence the oncological and functional outcome in large vestibular schwannoma (VS) surgery, we have compared group of patients operated on for large VS after failed GKS to a group of genuine VS that underwent the same functional nerve-sparing resection technique regimen in the same period. Single center retrospective cohort study of 23 consecutive GKS failure and 170 genuine VS patients operated on between April 2003 and March 2019. After resection, patients were allocated to a Wait-&-rescan or an upfront GKS policy. At last follow-up examination, the facial nerve function was good (House-Brackmann grades I or II) in 95% of the GKS failure and 84% of the genuine VS patients (p = .25). The median volume of tumor residue was .56 cc in the GKS failure group and .62 cc in the genuine VS group (p = .70). Tumor control was achieved in 91% and 83% of cases with a mean follow-up of 74 and 63 months in the GKS failure and the genuine VS populations, respectively. The 1-, 5-, and 7-year progression-free survival were 100%, 95%, and 85% respectively in the GKS failure group and 97%, 80%, and 81% in the genuine VS group (p = .27). Despite significant modifications of the microsurgical environment associated to salvage surgery after GKS failure, a functional nerve-sparing resection is an effective strategy to optimize the results on facial nerve function, with similar long-term tumor control to those observed in the genuine VS population.

Is Real-Time Inverse Planning Optimizing Dose to the Normal Brain? A Prospective Comparative Trial in a Series of Brain Metastases Treated by Stereotactic Radiosurgery.

BACKGROUND: Radiosurgery has demonstrated good safety and efficacy in the treatment of multiple brain metastases (BMs). However, multi-target dose planning can be challenging and time-consuming. A recently developed real-time inverse treatment planning (IP) by convex optimization has been demonstrated to produce high-quality treatment plans with good conformity and selectivity in single-target plans. We intended to test the capacity of this IP to rapidly generate efficient plans while optimizing the preservation of normal tissue in multiple BM. METHODS: Seventy-nine patients (mean age 62.4, age range 22-85) with a total of 272 BMs were treated by Gamma Knife Radiosurgery. All subjects were treated using a forward planning (FP) technique by an expert neurosurgeon. The new Intuitive Plan was applied and able to automatically generate an alternative plan for each patient. All planning variables were collected from the IP to be compared with the corresponding measurements obtained from the FP. A paired sample t test was applied to compare the 2 plans for the following variables: brain volumes receiving 10 Gy (V10) (primary endpoint), and 12 Gy (V12), planning indices (selectivity, coverage, gradient, and Paddick Conformity Index [PCI]), beam-on time (BOT), and integral doses. Additionally, the noninferiority margin for each item was calculated, and the 2 plans were compared for noninferiority using a paired t test. RESULTS: The mean age of patients was 62.4 years old (age range 22-85), with a sex ratio of 1.02. The average number of lesions per patient was 3.4 (range 1-12). The mean prescription dose was 21.46 Gy (range 14-24 Gy). Noninferiority of the IP was concluded for V10, V12, prescription isodose volume, BOT, PCI, and selectivity. The V10 (and V12) was significantly lower with the IP (p < 0.001). These volumes were 8.69 cm3 ± 11.39 and 5.47 cm3 ± 7.03, respectively, for the FP and 7.57 cm3 ± 9.44 and 4.78 cm3 ± 5.86 for the IP. Only the coverage was significantly lower with the IP (-2.3%, p < 0.001), but both selectivity (+17%) and PCI (+15%) were significantly higher with the IP than FP (p < 0.001). CONCLUSION: This IP demonstrated its capacity to generate multi-target plans rapidly, with a dose to the brain (V10) and BOT noninferior to the one of a human expert planner. These results would benefit from confirmation in a larger prospective series.

Mask-Based versus Frame-Based Gamma Knife ICON Radiosurgery in Brain Metastases: A Prospective Randomized Trial.

BACKGROUND: Radiosurgery is performed with a diversity of instruments relying usually either on a stereotactic frame or a mask for patient head fixation. Comfort and safety efficacy of the 2 systems have never been rigorously evaluated and compared. MATERIAL AND METHOD: Between February 2016 and January 2017, 58 patients presenting with nonsmall cell lung cancer brain metastases have been treated by Gamma Knife radiosurgery (GKS) with random use of a frame or a mask for fixation were included patients older than 18, with <5 brain metastases (at the exclusion of brainstem and optic pathway's locations) and no earlier history of radiotherapy. The primary outcome measure was the pain scale assessment (PSA) at the beginning of the GKS procedure. RESULTS: The PSA at the beginning of the GKS procedure was not different between the 2 groups. The PSA at the day before GKS, before magnetic resonance imaging, just after frame application, and the day after radiosurgery (departure) has shown no difference between the 2 groups. At the end of the radiosurgery itself (just after frame or mask removal) and 1 h after, the mean pain scale was higher in patients treated with the frame (p < 0.05 and p < 0.001, respectively) but 2 patients were not able to tolerate the mask discomfort and had to be treated with frame. Tumor control and morbidity probability were demonstrated to be no difference between the 2 groups in this population of patients with BM not in highly functional area. The median of the extra dose to the body due to the cone-beam computed tomography was 7.5 mGy with a maximum of 35 mGy in patients treated with a mask fixation (null in the others treated with frame). Mask fixation was associated to longer treatment time although the beam on time was not different between the 2 groups. CONCLUSION: In selected patients, with brain oligo-metastases out of critical location, single-dose mask-based GKS can be done with a comfort and a safety efficacy comparable to frame-based GKS. There seems to be no clear patient data that confirm the value of the mask system with regards to comfort.

Gamma Knife surgery for recurrent or persistent Cushing disease: long-term results and evaluation of biological effective dose in a series of 26 patients.

INTRODUCTION: Here we report long-term results after stereotactic radiosurgery (SRS) with Gamma Knife (GKRS) for Cushing disease. We further evaluated the potential role of the biological effective dose (BED) in the cure of this disease. METHODS: A retrospective review of a prospectively collected database (n = 26) was undertaken at Lille University Hospital, France. The mean follow-up period was 66 months (median 80, range 19–108). The mean marginal prescribed dose was 28.5 Gy (median 27.5, range 24–35) and the mean BED was 208.5 Gy2.47 (median 228.1, range 160–248). We divided patients with endocrine remission into a high BED group (160–228 Gy2.47, n = 6) and a low BED group (228–248 Gy2.47, n = 12). RESULTS: Eighteen (69.2%) patients had endocrine remission in the absence of any pharmacological therapy after a mean of 36 months (median 24, range 6–98). The actuarial probability of endocrine remission was 59% at 3 years and 77.6% at 7 years, which remained stable up to 10 years. There was a tendency to a higher overall probability of biological remission associated with higher BED values (77% versus 66% at last follow-up), although this did not reach statistical significance. Of note, the numbers of patients reflecting this actuarial probability at 12, 24, 36, 51 and 96 months were 21, 15, 11, 7 and 3, respectively. Tumour control was achieved in all cases (mean decrease in size for patients experiencing one was 29.4%, range 0–100%). Seven patients developed new pituitary insufficiency after GKRS. CONCLUSONS: Gamma Knife radiosurgery offers high rates of tumour control and endocrine remission on a long-term basis for ACTH-secreting pituitary adenomas. In this small series, higher BED values appeared to be associated with better endocrine remission rates. Owing to the limited sample size, such results should be validated in a larger cohort.

Repeat stereotactic radiosurgery for progressive vestibular schwannomas after previous radiosurgery: a systematic review and meta-analysis.

Vestibular schwannomas (VS) are slow-growing intracranial extraaxial benign tumors, developing from the vestibular part of the eight cranial nerves. Stereotactic radiosurgery (SRS) has now a long-term scientific track record as first intention treatment for small- to medium-sized VS. Though its success rate is very high, SRS for VS might fail to control tumor growth in some cases. However, the literature on repeat SRS after previously failed SRS remains scarce and reported in a low number of series with a limited number of cases. Here, we aimed at performing a systematic review and meta-analysis of the literature on repeat SRS for VS. Using PRISMA guidelines, we reviewed manuscripts published between January 1990 and October 2020 and referenced in PubMed. Tumor control and cranial nerve outcomes were evaluated with separate meta-analyses. Eight studies comprising 194 patients were included. The overall rate of patients treated in repeat SRS series as per overall series with first SRS was 2.2% (range 1.2-3.2%, p < 0.001). The mean time between first and second SRS was 50.7 months (median 51, range 44-64). The median marginal dose prescribed at first SRS was 12 Gy (range 8-24) and at second SRS was 12 Gy (range 9.8-19). After repeat SRS, tumor stability was reported in 61/194 patients, i.e., a rate of 29.6% (range 20.2-39%, I2 = 49.1%, p < 0.001). Tumor decrease was reported in 83/194 patients, i.e., a rate of 54.4% (range 33.7-75.1%, I2 = 89.1%, p < 0.001). Tumor progression was reported in 50/188 patients, i.e., a rate of 16.1% (range 2.5-29.7%, I2 = 87.1%, p = 0.02), rarely managed surgically. New trigeminal numbness was reported in 27/170 patients, i.e., a rate of 9.9% (range 1.4-18.3%, p < 0.02). New facial nerve palsy of worsened of previous was reported in 8/183 patients, i.e., a rate of 4.3% (range 1.4-7.2%, p = 0.004). Hearing loss was reported in 12/22 patients, i.e., a rate of 54.3% (range 24.8-83.8%, I2 = 70.7%, p < 0.001). Repeat SRS after previously failed SRS for VS is associated with high tumor control rates. Cranial nerve outcomes remain favorable, particularly for facial nerve. The rate of hearing loss appears similar to the one related to first SRS.

Clinical evaluation of a real-time inverse planning for Gamma Knife radiosurgery by convex optimization: a prospective comparative trial in a series of vestibular schwannoma patients.

BACKGROUND: Gamma Knife radiosurgery (GKRS) inverse dose planning is currently far from competing effectively with the quality of dose planning developed by experienced experts. A new inverse planning (IP) method based on « efficient convex optimization algorithms ¼ is proposed, providing high-quality dose plans in real time. MATERIALS AND METHODS: Eighty-six patients treated by GKRS for vestibular schwannomas (VS) were recruited. The treatment plans created by the first author, who has 27 years of experience and has developed and delivered more than 15,000 dose plans, served as reference. A first set of basic constraints determined by default led the IP for an initial real-time dose plan. Additional constraints were interactively proposed by the planner to take other parameters into account. A second optimized plan was then calculated by the IP. The primary endpoint was the Paddick Conformity Index (PCI). The statistical analysis was planned on a non-inferiority trial design. Coverage, selectivity, and gradient indexes, dose at the organ(s) at risk, and 12 Gy isodose line volume were compared. RESULTS: After a single run of the IP, the PCI was shown to be non-inferior to that of the "expert." For the expert and the IP, respectively, the median coverage index was 0.99 and 0.98, the median selectivity index 0.92 and 0.90, the median gradient index 2.95 and 2.84, the median dose at the modiolus of the cochlea 2.83 Gy and 2.86 Gy, the median number of shots 14.31 and 24.13, and the median beam-on time 46.20 min and 26.77 min. In a few specific cases, advanced tools of the IP were used to generate a second run by adding new constraints either globally (for higher selectivity) or locally, in order to increase or decrease these constraints focally. CONCLUSION: These preliminary results showed that this new IP method based on « efficient convex optimization algorithms ¼, called IntuitivePlan®, provided high-quality dose plans in real time with excellent coverage, selectivity, and gradient indexes with optimized beam-on time. If the new IP evaluated here is able to compete in real time with the quality of the treatment plans of an expert with extensive radiosurgical experience, this could allow new planners/radiosurgeons with limited or no experience to immediately provide patients with high-quality GKRS for benign and malignant lesions.

Gamma Knife radiosurgery for acromegaly: Evaluating the role of the biological effective dose associated with endocrine remission in a series of 42 consecutive cases.

INTRODUCTION: Stereotactic radiosurgery (SRS) is a valuable treatment option for persistent and/or recurrent acromegaly secondary to growth hormone (GH) secreting pituitary adenoma (PA). Here, we assess the role of biological effective dose (BED) received by PA treated with SRS in relation with endocrine remission. METHODS: Forty-two patients (minimum 6 months follow-up) were included. Mean marginal dose was 27.7 (median 28, 20-35), and mean BED received by tumour was 193.1 Gy2.47 (median 199.7, 64.1-237.1). Based on the median values, we divided the patients in high tumour BED group (H-BEDtm, 199.7-237.1 Gy2.47, n = 12) and low BED one (L- BEDtm, 64.1-199.7 Gy2.47 , n = 10). The two groups did not differ by pretherapeutic IGF-1 levels (p = .1) or by the prescribed dose (p = .6). RESULTS: Mean follow-up period was 62.5 months (median 60.5, 9-127). Probability of IGF-1 normalization was 65% at 3 years and 72.4% at 4 years, remaining stable until last follow-up. Twenty-two (52.4%) patients had complete endocrine remission in absence of any Somatostatin analogues. Actuarial rates were 33% at 3 years and 57.4% at 7 years, further remaining stable during follow-up course. In univariate analysis, only statistically significant parameter was pretherapeutic serum IGF-1 and IGF-1 index (p = .01). Five patients (5/26, 19.3%) without previous hypopituitarism developed new pituitary insufficiency. H-BEDtm was associated with higher rates of endocrine remission compared with L-BEDtm, with actuarial probability of 70.2% versus 48.2% at 9 years, although this did not reach statistical significance (p > .05). CONCLUSION: Our study confirms that SRS by Gamma Knife is safe and effective for GH-secreting PA. Pretherapeutic serum levels of IGF-1 were only statistically significant parameter for endocrine remission.

Stereotactic radiosurgery combined with anti-PD1 for the management of melanoma brain metastases: A retrospective study of safety and efficacy.

BACKGROUND: Brain metastases can be effectively treated with stereotactic radiosurgery (SRS). Immune checkpoint inhibitors are now pivotal in metastatic melanoma care, but some concerns have emerged regarding the safety of their combination with radiation therapy. METHODS: We present a retrospective analysis of a cohort of patients treated by anti-PD1 and SRS as a sole modality of radiation therapy (no whole brain radiation therapy at any time) in a single institution. We included patients on anti-PD1 at the time of SRS or patients who started anti-PD1 within a maximum period of 3 months following SRS and were treated at least one year before the analysis. Clinical and serial imaging data were reviewed to determine the efficacy and the rate of adverse radiation effectss of the combination. RESULTS: A total of 50 patients were included. SRS targeted 1, 2 to 3 and >3 brain metastases in 17, 16 and 17 patients, respectively. Two patients died before the first evaluation. Nine patients presented with an increase in peritumoral oedema, three with intracranial haemorrhage and one patient with both oedema and haemorrhage. Median follow-up was 38.89 months (interquartile range 24.43; 45.28). Median overall survival from SRS was 16.62 months with 1-, 2- and 3-year rates of 60%, 40% and 35%, respectively. Median brain-Progression Free Survival was 13.2 months with 1, 2 and 3-year rates of 62.1%, 49.7% and 49.7%, respectively. CONCLUSIONS: This real-world cohort of patients treated with a homogeneous strategy combining upfront stereotactic radiosurgery and anti-PD1 shows remarkable survival rates and does not reveal unexpected toxicity.

Cortical stimulation in aphasia following ischemic stroke: toward model-guided electrical neuromodulation.

The aim of this paper is to integrate different bodies of research including brain traveling waves, brain neuromodulation, neural field modeling and post-stroke language disorders in order to explore the opportunity of implementing model-guided, cortical neuromodulation for the treatment of post-stroke aphasia. Worldwide according to WHO, strokes are the second leading cause of death and the third leading cause of disability. In ischemic stroke, there is not enough blood supply to provide enough oxygen and nutrients to parts of the brain, while in hemorrhagic stroke, there is bleeding within the enclosed cranial cavity. The present paper focuses on ischemic stroke. We first review accumulating observations of traveling waves occurring spontaneously or triggered by external stimuli in healthy subjects as well as in patients with brain disorders. We examine the putative functions of these waves and focus on post-stroke aphasia observed when brain language networks become fragmented and/or partly silent, thus perturbing the progression of traveling waves across perilesional areas. Secondly, we focus on a simplified model based on the current literature in the field and describe cortical traveling wave dynamics and their modulation. This model uses a biophysically realistic integro-differential equation describing spatially distributed and synaptically coupled neural networks producing traveling wave solutions. The model is used to calculate wave parameters (speed, amplitude and/or frequency) and to guide the reconstruction of the perturbed wave. A stimulation term is included in the model to restore wave propagation to a reasonably good level. Thirdly, we examine various issues related to the implementation model-guided neuromodulation in the treatment of post-stroke aphasia given that closed-loop invasive brain stimulation studies have recently produced encouraging results. Finally, we suggest that modulating traveling waves by acting selectively and dynamically across space and time to facilitate wave propagation is a promising therapeutic strategy especially at a time when a new generation of closed-loop cortical stimulation systems is about to arrive on the market.

Does NF2 status impact the results of combined surgery and adjunctive Gamma Knife surgery for large vestibular schwannomas?

In order to verify whether neurofibromatosis type 2 (NF2) could influence the oncological and functional outcome in large vestibular schwannoma (VS) surgery, we compared a group of NF2 patients operated with a facial nerve-sparing technique to a group of sporadic VSs of similar volume that underwent the same treatment regimen in the same period. Single-center retrospective cohort study about 12 consecutive NF2 and 69 non-NF2 patients operated on for large VS between September 2006 and November 2016. After resection, patients were allocated to an upfront Gamma Knife surgery policy of the tumor residue. At last follow-up examination, the facial nerve function was good (House-Brackmann grades I or II) in 92% of the NF2 and 83% of the non-NF2 patients (p = .90). The median volume of tumor residue was .92 cc in the NF2 group and .54 cc in the non-NF2 group (p = .14). Tumor control was achieved in 83% and 81% of cases in the NF2 and the non-NF2 populations, respectively, with a mean follow-up of 73 months in both groups. The 1-, 5-, and 7-year progression-free survival were 92%, 83%, and 83% respectively in the NF2 group, and 99%, 83%, and 80% in the non-NF2 group (p = .96). Our analysis of 12 NF2 and 69 non-NF2 patients operated on by the same surgical team with the same treatment regimen did not show any functional or tumor control difference between those groups.