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Abstract Background Single session radiosurgery represents a widely accepted treatment for intracranial meningiomas. However, this approach could involve a high risk of treatment-related complications when applied to large volume lesions. In these cases and for those not suitable for surgical resection, radiosurgery in multisession setting could represents a viable option. The literature results are reassuring in terms of correlated adverse events as well as in terms of tumor control. However, no prospective long-term results are available. In this scenario, we design a prospective monocentric phase II study, in order to verify the safety of a multisession radiosurgery schedule delivering 25 Gy in 5 daily fractions. Methods Patients diagnosed with large and/or near to critical structures, intracranial meningiomas have been treated by means of multisession radiosurgery in both exclusive and postoperative settings. The primary study aim is safety that has been being prospectively scored based on international scales, including NCI Common Toxicity criteria, version 4.03, Barrow Neurological Institute pain intensity score, Barrow Neurological Institute facial numbness score and House-Brackmann Facial Nerve Grading System for qualitative analysis. Secondary aim is treatment efficacy in terms of local control that has been being assessed on volumetric analysis. Discussion This is the first prospective phase II trial on multisession radiosurgery for large and/or near to critical structures intracranial meningiomas. If positive results will be found, this study could represent the starting point for a phase III trial exploring the role of multisession radiosurgery in the exclusive and postoperative radiation therapy treatment of intracranial meningiomas. Trial registration Trial registration: clinicaltrials.gov platform (Multisession Radiosurgery in Large Meningiomas –MuRaLM- identifier NCT02974127). Registered: November 28, 2016. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02974127?term=radiosurgery&cond=Intracranial+Meningioma&draw=2&rank=1

Purpose: to predict vestibular schwannoma (VS) response to radiosurgery by applying machine learning (ML) algorithms on radiomic features extracted from pre-treatment magnetic resonance (MR) images., Methods: patients with VS treated with radiosurgery in two Centers from 2004 to 2016 were retrospectively evaluated. Brain T1-weighted contrast-enhanced MR images were acquired before and at 24 and 36 months after treatment. Clinical and treatment data were collected contextually. Treatment responses were assessed considering the VS volume variation based on pre- and post-radiosurgery MR images at both time points. Tumors were semi-automatically segmented and radiomic features were extracted. Four ML algorithms (Random Forest, Support Vector Machine, Neural Network, and extreme Gradient Boosting) were trained and tested for treatment response (i.e., increased or non-increased tumor volume) using nested cross-validation. For training, feature selection was performed using the Least Absolute Shrinkage and Selection Operator, and the selected features were used as input to separately build the four ML classification algorithms. To overcome class imbalance during training, Synthetic Minority Oversampling Technique was used. Finally, trained models were tested on the corresponding held out set of patients to evaluate balanced accuracy, sensitivity, and specificity., Results: 108 patients treated with Cyberknife ® were retrieved; an increased tumor volume was observed at 24 months in 12 patients, and at 36 months in another group of 12 patients. The Neural Network was the best predictive algorithm for response at 24 (balanced accuracy 73% ± 18%, specificity 85% ± 12%, sensitivity 60% ± 42%) and 36 months (balanced accuracy 65% ± 12%, specificity 83% ± 9%, sensitivity 47% ± 27%)., Conclusions: radiomics may predict VS response to radiosurgery avoiding long-term follow-up as well as unnecessary treatment.

The aim of this study was to evaluate the clinical outcomes of a large series of brain metastatic renal cell carcinoma (BMRCC) patients treated in three Italian centers., Methods: A total of 120 BMRCC patients with a total of 176 lesions treated were evaluated. Patients received surgery plus postoperative HSRS, single-fraction SRS, or hypofractionated SRS (HSRS). Local control (LC), brain distant failure (BDF), overall survival (OS), toxicities, and prognostic factors were assessed., Results: The median follow-up time was 77 months (range 16-235 months). Surgery plus HSRS was performed in 23 (19.2%) cases, along with SRS in 82 (68.3%) and HSRS in 15 (12.5%). Seventy-seven (64.2%) patients received systemic therapy. The main total dose and fractionation used were 20-24 Gy in single fraction or 32-30 Gy in 4-5 daily fractions. Median LC time and 6 month and 1, 2 and 3 year LC rates were nr, 100%, 95.7% ± 1.8%, 93.4% ± 2.4%, and 93.4% ± 2.4%. Median BDF time and 6 month and 1, 2 and 3 year BDF rates were n.r., 11.9% ± 3.1%, 25.1% ± 4.5%, 38.7% ± 5.5%, and 44.4% ± 6.3%, respectively. Median OS time and 6 month and 1, 2 and 3 year OS rates were 16 months (95% CI: 12-22), 80% ± 3.6%, 58.3% ± 4.5%, 30.9% ± 4.3%, and 16.9% ± 3.6, respectively. No severe neurological toxicities occurred. Patients with a favorable/intermediate IMDC score, a higher RCC-GPA score, an early occurrence of BMs from primary diagnosis, absence of EC metastases, and a combined local treatment (surgery plus adjuvant HSRS) had a better outcome., Conclusions: SRS/HSRS is proven to be an effective local treatment for BMRCC. A careful evaluation of prognostic factors is a valid step to manage the optimal therapeutic strategy for BMRCC patients.

Background: To define efficacy and toxicity of Immunotherapy (IT) with stereotactic radiotherapy (SRT) including radiosurgery (RS) or hypofractionated SRT (HFSRT) for brain metastases (BM) from non-small cell lung cancer (NSCLC) in a multicentric retrospective study from AIRO (Italian Association of Radiotherapy and Clinical Oncology)., Methods: NSCLC patients with BM receiving SRT + IT and treated in 19 Italian centers were analyzed and compared with a control group of patients treated with exclusive SRT., Results: One hundred patients treated with SRT + IT and 50 patients treated with SRT-alone were included. Patients receiving SRT + IT had a longer intracranial Local Progression-Free Survival (iLPFS) (propensity score-adjusted P = .007). Among patients who, at the diagnosis of BM, received IT and had also extracranial progression (n = 24), IT administration after SRT was shown to be related to a better overall survival (OS) (P = .037). A multivariate analysis, non-adenocarcinoma histology, KPS = 70 and use of HFSRT were associated with a significantly worse survival (P = .019, P = .017 and P = .007 respectively). Time interval between SRT and IT ≤7 days (n = 90) was shown to be related to a longer OS if compared to SRT-IT interval >7 days (n = 10) (propensity score-adjusted P = .008). The combined treatment was well tolerated. No significant difference in terms of radionecrosis between SRT + IT patients and SRT-alone patients was observed. The time interval between SRT and IT had no impact on the toxicity rate., Conclusions: Combined SRT + IT was a safe approach, associated with a better iLPFS if compared to exclusive SRT., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: This systematic review reports on outcomes and toxicities following stereotactic radiosurgery (SRS) for non-functioning pituitary adenomas (NFAs) and presents consensus opinions regarding appropriate patient management., Methods: Using the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, a systematic review was performed from articles of ≥10 patients with NFAs published prior to May 2018 from the Medline database using the key words "radiosurgery" and "pituitary" and/or "adenoma." Weighted random effects models were used to calculate pooled outcome estimates., Results: Of the 678 abstracts reviewed, 35 full-text articles were included describing the outcomes of 2671 patients treated between 1971 and 2017 with either single fraction SRS or hypofractionated stereotactic radiotherapy (HSRT). All studies were retrospective (level IV evidence). SRS was used in 27 studies (median dose: 15 Gy, range: 5-35 Gy) and HSRT in 8 studies (median total dose: 21 Gy, range: 12-25 Gy, delivered in 3-5 fractions). The 5-year random effects local control estimate after SRS was 94% (95% CI: 93.0-96.0%) and 97.0% (95% CI: 93.0-98.0%) after HSRT. The 10-year local control random effects estimate after SRS was 83.0% (95% CI: 77.0-88.0%). Post-SRS hypopituitarism was the most common treatment-related toxicity observed, with a random effects estimate of 21.0% (95% CI: 15.0-27.0%), whereas visual dysfunction or other cranial nerve injuries were uncommon (range: 0-7%)., Conclusions: SRS is an effective and safe treatment for patients with NFAs. Encouraging short-term data support HSRT for select patients, and mature outcomes are needed before definitive recommendations can be made. Clinical practice opinions were developed on behalf of the International Stereotactic Radiosurgery Society (ISRS)., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.)

Background: Single session radiosurgery represents a widely accepted treatment for intracranial meningiomas. However, this approach could involve a high risk of treatment-related complications when applied to large volume lesions. In these cases and for those not suitable for surgical resection, radiosurgery in multisession setting could represents a viable option. The literature results are reassuring in terms of correlated adverse events as well as in terms of tumor control. However, no prospective long-term results are available. In this scenario, we design a prospective monocentric phase II study, in order to verify the safety of a multisession radiosurgery schedule delivering 25 Gy in 5 daily fractions., Methods: Patients diagnosed with large and/or near to critical structures, intracranial meningiomas have been treated by means of multisession radiosurgery in both exclusive and postoperative settings. The primary study aim is safety that has been being prospectively scored based on international scales, including NCI Common Toxicity criteria, version 4.03, Barrow Neurological Institute pain intensity score, Barrow Neurological Institute facial numbness score and House-Brackmann Facial Nerve Grading System for qualitative analysis. Secondary aim is treatment efficacy in terms of local control that has been being assessed on volumetric analysis., Discussion: This is the first prospective phase II trial on multisession radiosurgery for large and/or near to critical structures intracranial meningiomas. If positive results will be found, this study could represent the starting point for a phase III trial exploring the role of multisession radiosurgery in the exclusive and postoperative radiation therapy treatment of intracranial meningiomas., Trial Registration: Trial registration: clinicaltrials.gov platform (Multisession Radiosurgery in Large Meningiomas -MuRaLM- identifier NCT02974127). Registered: November 28, 2016. Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02974127?term=radiosurgery&cond=Intracranial+Meningioma&draw=2&rank=1.

The level of evidence to provide treatment recommendations for vestibular schwannoma is low compared with other intracranial neoplasms. Therefore, the vestibular schwannoma task force of the European Association of Neuro-Oncology assessed the data available in the literature and composed a set of recommendations for health care professionals. The radiological diagnosis of vestibular schwannoma is made by magnetic resonance imaging. Histological verification of the diagnosis is not always required. Current treatment options include observation, surgical resection, fractionated radiotherapy, and radiosurgery. The choice of treatment depends on clinical presentation, tumor size, and expertise of the treating center. In small tumors, observation has to be weighed against radiosurgery, in large tumors surgical decompression is mandatory, potentially followed by fractionated radiotherapy or radiosurgery. Except for bevacizumab in neurofibromatosis type 2, there is no role for pharmacotherapy., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Radiotherapy is a pivotal treatment for treating breast cancer. However, its role in the management of elderly patients is still under debate. Some authors suggest be avoided after surgery for early stage, some others advocate its adoption. For breast cancer treatment different schedules are used both for whole and partial breast irradiation, in adjuvant as well as definitive setting. Which one is better for elderly patients is a controversial topic. Numerous studies focused on both moderate or extreme hypofractionated irradiation have been published. However, only few addressed the topic on elderly patient population. The data on hypofractionated radiotherapy showed that for whole breast, locoregional and post-mastectomy treatment, this approach is a valid option reporting similar efficacy and toxicity to the standard fractionation. Also accelerated partial breast irradiation for patients with favourable early stage disease represents a viable option allowing for de-escalation by targeting radiation dose to the part of breast tissue at highest recurrence risk. Undoubtedly, for frail and elderly patients a short course of radiotherapy could increase their adherence and the quality of life. In the same manner, the preoperative approach has been applied for both whole and partial breast irradiation, allowing for more precise target delineation compared to the post-surgical one, eventually leading to a smaller treatment volume, to less geographical missing and possibly to a lower radiation-induced toxicity. Some more long-term results could make us more confident in prescribing adjuvant or preoperative partial breast irradiation. These approaches could be the most appropriate treatment for elderly patients, potentially preserving quality of life and increasing the tolerability to the irradiation., (2020 Translational Cancer Research. All rights reserved.)

Treatment options for intracranial meningiomas are surgical resection alone, surgery followed by adjuvant radiation therapy (RT), or exclusive RT. Parasagittal and parafalcine meningiomas are a subgroup of meningeal disease located close to the vascular structures. Considering the frequent venous invasion, a complete resection is not possible in the majority of cases, and even if a Simpson Grade I resection can be performed, the risk of recurrence is relevant. To date, few studies are focused on parasagittal and parafalcine meningiomas. Because of their specific related issues, particular considerations on decision-making process, outcome, and toxicity follow-up are mandatory. In fact, parasagittal and parafalcine meningiomas require a clear-cut radiological assessment, as well as a tailored toxicity risk evaluation. Moreover, similarly to other meningioma sites, also for parasagittal and parafalcine ones, a standardization of local control, toxicity, and quality of life evaluation is needed in order to lead to a pooled analysis of the results. In this context, our aim was to review the literature data regarding the role of both single-session and multisession radiosurgery (RS), and stereotactic radiotherapy (SRT) for parasagittal and parafalcine meningioma management, summarizing available data on safety and efficacy. It was also discussed how RS and SRT can be performed in a setting of evolving views concerning the treatment paradigm of the parasagittal and parafalcine meningiomas., Competing Interests: M Marchetti reports grants and personal fees from accuracy europe and from AB Medica, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2019 Pinzi et al.)

Background: Local recurrences after breast conserving treatment are mainly close to the original tumor site, and as such shorter fractionation strategies focused on and nearest mammary gland, i.e. accelerated partial breast irradiation (APBI), have been developed. Stereotactic APBI has been attempted, although there is little experience using CyberKnife (CK) for early breast cancer., Methods: This pilot study was designed to assess the feasibility of CK-APBI on 20 evaluable patients of 29 eligible, followed for 2 years. The primary endpoint was acute/sub-acute toxicity; secondary endpoints were late toxicity and the cosmetic result., Results: Mean pathological tumor size was 10.5 mm (±4.3, range 3-18), 8 of these patients were classified as LumA-like, 11 as LumB-like, and 1 as LumB-HER2-enriched. Using CK-APBI with Iris, the treatment time was approximately 60 min (range~ 35 to ~ 120). All patients received 30 Gy in five fractions delivered to the PTV. The median number of beams was 180 (IQR 107-213; range:56-325) with a median PTV isodose prescription of 86.0% (IQR 85.0-88.5; range:82-94). The median PTV was 88.1 cm3 (IQR 63.8-108.6; range:32.3-238.8). The median breast V100 and V50 was 0.6 (IQR 0.1-1.5; range:0-13) and 18.6 (IQR 13.1-21.7; range:7.5-37), respectively. The median PTV minimum dose was 26.2 Gy (IQR 24.7-27.6; range 22.3-29.3). Mild side effects were recorded during the period of observation. Cosmetic evaluations were performed by three observers from the start of radiotherapy up to 2 years. Patients' evaluation progressively increase from 60% to 85% of excellent rating; this trend was similar to that of external observer., Conclusions: These preliminary results showed the safe feasibility of CK-APBI in early breast cancer, with mild acute and late toxicity and very good cosmetic results., Trial Registration: The present study is registered at Clinicaltrial.gov ( NCT02896322 ). Retrospectively egistered August 4, 2016.

In a two-stage phase II study, 24 patients with first diagnosis of glioblastoma (GBM) were treated with dendritic cell (DC) immunotherapy associated to standard radiochemotherapy with temozolomide (TMZ) followed by adjuvant TMZ. Three intradermal injections of mature DC loaded with autologous GBM lysate were administered before adjuvant TMZ, while 4 injections were performed during adjuvant TMZ. According to a two-stage Simon design, to proceed to the second stage progression-free survival (PFS) 12 months after surgery was expected in at least 8 cases enrolled in the first stage. Evidence of immune response and interaction with chemotherapy were investigated. After a median follow up of 17.4 months, 9 patients reached PFS12. In these patients (responders, 37.5%), DC vaccination induced a significant, persistent activation of NK cells, whose increased response was significantly associated with prolonged survival. CD8 + T cells underwent rapid expansion and priming but, after the first administration of adjuvant TMZ, failed to generate a memory status. Resistance to TMZ was associated with robust expression of the multidrug resistance protein ABCC3 in NK but not CD8 + T cells. The negative effect of TMZ on the formation of T cell-associated antitumor memory deserves consideration in future clinical trials including immunotherapy.

Background: Radiosurgery(RS), both in single and multiple sessions, have been performed for intracranial meningiomas. Different aspects are still controversial on this field. The aim of this systematic review is to summarize the current literature on long-term efficacy and safety of RS for meningiomas., Methods: Online databases were searched for studies published until April 2015. The primary outcomes were disease control and progression-free-survival(PFS). The secondary outcomes were symptom control and radiation-induced toxicity., Results: The estimate of disease control rate ranged from 87.0% to 100.0% at 5 years and from 67.0% to 100.0% at 10 years. The PFS rate ranged 78.0%-98.9% and 53.1%-97.2% at 5 and 10 years, respectively. The overall symptom control was 92.3%, the overall toxicity was 8.1%., Conclusions: RS can be considered a safe and effective treatment. Efforts are needed in standardizing the definition of local and symptom control and toxicity in order to properly compare different treatment schedules., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Gafchromic EBT3 film dosimetry in radiosurgery (RS) and hypofractionated radiotherapy (HRT) is complicated by the limited film accuracy at high fractional doses. The aim of this study is to develop and evaluate sum signal (SS) film dosimetry to increase dose resolution at high fractional doses, thus allowing for use of EBT3 for dose distribution verification of RS/HRT treatments. To characterize EBT3 dose-response, a calibration was performed in the dose range 0.44-26.43 Gy. Red (RC) and green (GC) channel net optical densities were linearly added to produce the SS. Dose resolution and overall accuracy of the dosimetric protocol were estimated and compared for SS,RC, and GC. A homemade Matlab software was developed to compare, in terms of gamma analysis, dose distributions delivered by a Cyberknife on EBT3 films to dose distributions calculated by the treatment planning system. The new SS and conventional single channel (SC) methods were compared, using 3%/1 and 4%/1 mm acceptance criteria, for 20 patient plans. Our analysis shows that the SS dose-response curve is characterized by a steeper trend in comparison with SC, with SS providing a higher dose resolution in the whole dose range investigated. Gamma analysis confirms that the percentage of points satisfying the agreement criteria is significantly higher for SS compared to SC: 95.03% vs. 88.41% (P = 0.014) for 3%/1 mm acceptance criteria and 97.24% vs. 93.58% (P = 0.048) for 4%/1 mm acceptance criteria. This study demonstrates that the SS approach is a new and effective method to improve dosimetric accuracy in the framework of the RS-HRT patient-specific quality assurance protocol., (© 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.)

Background: A new transcranial focused ultrasound device has been developed that can induce hyperthermia in a large tissue volume. The purpose of this work is to investigate theoretically how glioblastoma multiforme (GBM) can be effectively treated by combining the fast hyperthermia generated by this focused ultrasound device with external beam radiotherapy., Methods/design: To investigate the effect of tumor growth, we have developed a mathematical description of GBM proliferation and diffusion in the context of reaction-diffusion theory. In addition, we have formulated equations describing the impact of radiotherapy and heat on GBM in the reaction-diffusion equation, including tumor regrowth by stem cells. This formulation has been used to predict the effectiveness of the combination treatment for a realistic focused ultrasound heating scenario. Our results show that patient survival could be significantly improved by this combined treatment modality., Discussion: High priority should be given to experiments to validate the therapeutic benefit predicted by our model.

Despite the advances in techniques and technologies, the management of cavernous sinus (CS) meningiomas still remains a challenge for both neurosurgeons and radiation oncologists. On the other hand, the improvement of the anatomical knowledge and the microsurgical techniques together with diffusion of radiosurgery are currently changing the treatment strategy, opening new perspectives to the patients which are suffering from such lesions. The authors reviewed here the literature data. A multidisciplinary treatment algorithm is also proposed.

Background: A multidisciplinary and multi-institutional working group applied the Failure Mode and Effects Analysis (FMEA) approach to assess the risks for patients undergoing Stereotactic Body Radiation Therapy (SBRT) treatments for lesions located in spine and liver in two CyberKnife® Centres., Methods: The various sub-processes characterizing the SBRT treatment were identified to generate the process trees of both the treatment planning and delivery phases. This analysis drove to the identification and subsequent scoring of the potential failure modes, together with their causes and effects, using the risk probability number (RPN) scoring system. Novel solutions aimed to increase patient safety were accordingly considered., Results: The process-tree characterising the SBRT treatment planning stage was composed with a total of 48 sub-processes. Similarly, 42 sub-processes were identified in the stage of delivery to liver tumours and 30 in the stage of delivery to spine lesions. All the sub-processes were judged to be potentially prone to one or more failure modes. Nineteen failures (i.e. 5 in treatment planning stage, 5 in the delivery to liver lesions and 9 in the delivery to spine lesions) were considered of high concern in view of the high RPN and/or severity index value., Conclusions: The analysis of the potential failures, their causes and effects allowed to improve the safety strategies already adopted in the clinical practice with additional measures for optimizing quality management workflow and increasing patient safety.

Background: Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010., Methods: Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004-2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997-2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively., Results: Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II)., Conclusions: We found a significant increase in overall survival, PFS, and survival after recurrence after 2004, likely due to improvements in surgical techniques, introduction of the Stupp protocol as a first-line treatment, and new standard protocols for second-line chemotherapy and radiosurgery after tumor recurrence. In both cohorts, reoperation after tumor recurrence did not improve survival.

Although the evidence for the benefit of adding temozolomide (TMZ) to radiotherapy (RT) is limited to glioblastoma patients, there is currently a trend toward treating anaplastic astrocytomas (AAs) with combined RT + TMZ. The aim of the present study was to describe the patterns of care of patients affected by AA and, particularly, to compare the outcome of patients treated exclusively with RT with those treated with RT + TMZ. Data of 295 newly diagnosed AAs treated with postoperative RT ± TMZ in the period from 2002 to 2007 were reviewed. More than 75% of patients underwent a surgical removal. All the patients had postoperative RT; 86.1% of them were treated with 3D-conformal RT (3D-CRT). Sixty-seven percent of the entire group received postoperative chemotherapy with TMZ (n = 198). One-hundred sixty-six patients received both concomitant and sequential TMZ. Prescription of postoperative TMZ increased in the most recent period (2005-2007). One- and 4-year survival rates were 70.2% and 28.6%, respectively. No statistically significant improvement in survival was observed with the addition of TMZ to RT (P = .59). Multivariate analysis showed the statistical significance of age, presence of seizures, Recursive Partitioning Analysis classes I-III, extent of surgical removal, and 3D-CRT. Changes in the care of AA over the past years are documented. Currently there is not evidence to justify the addition of TMZ to postoperative RT for patients with newly diagnosed AA outside a clinical trial. Results of prospective and randomized trials are needed.

A human glioblastoma multiforme cell line (U87) and its derived-spheroids were irradiated either using a conventional irradiation (CIR) or a CK-like irradiation (IIR) in which the 8 Gy was delivered intermittently over a period of 40 minutes. The ability of glioma cells to migrate into a matrigel matrix was evaluated on days 1-8 from irradiation. Irradiation with CK-driven IIR significantly increased the invasion potential of U87 cells in a matrigel-based assay. In contrast to CIR, IIR was associated with increased levels of TGF-β at four days (Real time PCR), β1-integrin at 4-5 days (real-time PCR and western blot) and no elevation in phosphorylated AKT at days 4 and 5 (western blot). Our data suggests that glioma cell invasion as well as elevations of TGF-β and β1-integrin are associated with IIR and not CIR.

Background/aims: We present the preliminary results of a cost-effectiveness analysis of cyberknife radiosurgery (CKR) versus microvascular decompression (MVD) for patients with medically unresponsive trigeminal neuralgia., Methods: Direct healthcare costs from hospital's perspective attributable to CKR and MVD were collected. Pain level caused by trigeminal neuralgia was measured through the Barrow Neurological Institute pain intensity scoring criteria, at admission and after an average of 6 months follow-up., Results: 20 patients for both arms were enrolled, for a total of 40 patients. The two procedures resulted equally effective at 6 month follow-up, with different resources consumption: CKR reducing hospital costs by an average of 34% per patient. The robustness of these results was confirmed in appropriate sensitivity analyses., Conclusion: CKR resulted to be a cost-saving alternative compared with the surgical intervention.

Reliable data on large cohorts of patients with glioblastoma are needed because such studies differ importantly from trials that have a strong bias toward the recruitment of younger patients with a higher performance status. We analyzed the outcome of 676 patients with histologically confirmed newly diagnosed glioblastoma who were treated consecutively at a single institution over a 7-year period (1997-2003) with follow-up to April 30, 2006. Survival probabilities were 57% at 1 year, 16% at 2 years, and 7% at 3 years. Progression-free survival was 15% at 1 year. Prolongation of survival was significantly associated with surgery in patients with a good performance status, whatever the patient's age, with an adjusted hazard ratio of 0.55 (p < 0.001) or a 45% relative decrease in the risk of death. Radiotherapy and chemotherapy improved survival, with adjusted hazard ratios of 0.61 (p = 0.001) and 0.89 (p = 0.04), respectively, regardless of age, performance status, or residual tumor volume. Recurrence occurred in 99% of patients throughout the follow-up. Reoperation was performed in one-fourth of these patients but was not effective, whether performed within 9 months (hazard ratio, 0.86; p = 0.256) or after 9 months (hazard ratio, 0.98; p = 0.860) of initial surgery, whereas second-line chemotherapy with procarbazine, lomustine, and vincristine (PCV) or with temozolomide improved survival (hazard ratio, 0.77; p = 0.008). Surgery followed by radiotherapy and chemotherapy should be considered in all patients with glioblastoma, and these treatments should not be withheld because of increasing age alone. The benefit of second surgery at recurrence is uncertain, and new trials are needed to assess its effectiveness. Chemotherapy with PCV or temozolomide seems to be a reasonable option at tumor recurrence.