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Background The COVID-19 pandemic has inferred on patients (PTS) with cancer regarding disease evolution as well as the emotional and social functioning. The assessment of the needs and perceptions of PTS and their caregivers, is a priority to ensure an adequate standard in taking care and to promote the compliance to the treatments. The aim of this study is to understand how COVID-19 affects the emotional state and medical relationship in neuro-oncology. Material and Methods From Apr 2020 to Dec 2021 a prospective study was conducted on neuro-oncological PTS and their caregivers, including a 41-question and 16-question survey respectively. Results 162 PTS and 66 caregivers completed the questionnaire. 57.5% of PTS perceived grater risk , 37.5% the same risk and 5% lower risk of contracting the COVID-19 disease compared to the general population. 9.6% of PTS got SARS-CoV2 infection.Using a scale 0-10 for the assessment of anxiety, PTS experienced 5.8 (standard deviation, sd 2.6) as anxiety level related to tumor and 4.6 (sd 2.5) level about COVID-19 risk. For the most part there was no change in the treatment of cancer (81.5%). Due to the COVID-19 pandemic, 9.2% of PTS decided to delay anti-tumoral therapeutic schedule and 27.9% referred to be worried about going to hospital for consultation. Overall, 93.5% of PTS was satisfied with the treatments received. 52.6% of PTS felt different perception of the future during COVID-19, mostly referred like more uncertain. Caregivers experienced 7.7 (sd 2.1) anxiety level about tumor and 5.5 (sd 2.4) about COVID-19 risk. In 67.7% of caregivers the perception of the future has been changed, mostly towards greater insecurity. 75.0% of PTS described at least good Quality of Life (QoL), 65.4% of PTS declared to have sufficient resources to deal with the situation. There was a correlation between QoL and resources (P = 0.000). 77.3% of caregivers defined their care burden increased during the pandemic and 73.4% defined their QoL at least as good. We found a correlation between COVID-19 anxiety and anxiety for tumor diagnosis (ρ=0.53%, P = 0.000) as well as with future perception (Mann Whitney U test between PTS with different versus unchanged future perception, P = 0.001) in the PTS population. Conclusion The WHO definition of health refers to the biopsychosocial model. This model attributes the outcome of disease, as well as health, to the intricate and variable interaction of biological, psychological factors and social factors. In line with this model, it is essential to guarantee and improve the standard of care, also based to the real needs perceived by PTS and caregivers and to historical and social context. This is especially important in a pandemic period like COVID-19 is in which the good QoL can be compromised. An appropriate health-system organization and a special attention to patient doctor communication can make the different on QoL and the future perception.

Background Meningioma are the second most common brain tumors in adults and can cause significant morbidity and mortality. The scarcity of in vitro and in vivo models represents the major obstacle to understand the molecular basis of meningioma tumorigenesis. The main aim of this study was to assess a method for radiobiology of meningioma cells colture by means of well-known meningioma lines. New method We carried out a protocol of cells culture for irradiation of meningioma cells. We used the immortalized cell lines IOMM-Lee and CH-157 to study their radiation-reponse by means of clonogenic assays and to evaluate their proliferation and apoptosis. We irradiated the cells with different total doses using two different linear accelerators. Results We observed a more radiation resistance of the IOMM-Lee than the CH-157. Indeed, the cellular death of CH-157 was obtained at a very low dose irradiation. Moreover, we showed a dose-response effect due to the early and late apoptosis, in fact the rate of apoptotic cells is greater than that of the necrotic cells at any dose of irradiation and at any time of analysis. Comparison with existing methods There is not a standardized method for radiobiology of meningioma experiments. Conclusions Our method of cells culture appears suitable for radiosensitivity studies on meningioma. We can confirm that the response to radiotherapy depends not only on irradiation features, but also on tumor radiosensitivity.

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

Additional file 1: Appendix I. Karnofsky Performance Status Scale

BACKGROUND Glioblastoma is associated with a poor prognosis in the elderly. Survival has been shown to increase among patients 70 years of age or younger when temozolomide chemotherapy is added to standard radiotherapy (60 Gy over a period of 6 weeks). In elderly patients, more convenient shorter courses of radiotherapy are commonly used, but the benefit of adding temozolomide to a shorter course of radiotherapy is unknown.METHODS We conducted a trial involving patients 65 years of age or older with newly diagnosed glioblastoma. Patients were randomly assigned to receive either radiotherapy alone (40 Gy in 15 fractions) or radiotherapy with concomitant and adjuvant temozolomide.RESULTS A total of 562 patients underwent randomization, 281 to each group. The median age was 73 years (range, 65 to 90). The median overall survival was longer with radiotherapy plus temozolomide than with radiotherapy alone (9.3 months vs. 7.6 months; hazard ratio for death, 0.67; 95% confidence interval [CI], 0.56 to 0.80; PCONCLUSIONS In elderly patients with glioblastoma, the addition of temozolomide to short-course radiotherapy resulted in longer survival than short-course radiotherapy alone. Funded by the Canadian Cancer Society Research Institute and others; ClinicalTrials. gov number, NCT00482677.)

BACKGROUND Primary Central nervous system (CNS) lymphomas (PCNSL) are extranodal, malignant non- Hodgkin lymphomas of the diff use large B-cell type, confined to CNS. It accounts for up to 1% of all lymphomas and about 3% of all CNS tumours. The incidence continues to rise in immuno- competent elderly patients.Although the prognosis of PCNSL remains poor, it has improved in the past two decades as a result of better treatment strategies. However, treatment recommendations still result mainly from retrospective series or single-arm phase 2 studies and a few three completed randomised trials. We described a series of patients with newly diagnosis of PCNSL treated with modified-schedula published by Omuro MATERIAL AND METHODS Patients was treated with HD-MTX, procarbazine, vincristine, received four 28-day cycles of chemotherapy, on schedule: HD-MTX (3·5 g/m²) days 1 and 15; Procarbazine (100 mg/m²) on days 1–7. Vincristine (1·4 mg/m²) on days 1 and 15. Toxicity was assessed with Common Terminology Criteria for Adverse Events version 4. The International PCNSL Collaborative Group Response Criteria were used for response assessment. Endpoints include overall survival (OS) and adverse events (AE). RESULTS 21 immunocompetent patients (12 females and 9 males) were retrospectively studied, among 2014 to 2019. Median age at diagnosis 61 years (range 41–76). Median KPS at diagnosis was 70 (range 40–100). Clinical and radiological data and treatment related toxicity were described CONCLUSION Present combination regimen is effective; however, AE incidence is high, and often induces schedule modification

Introduction: Extra cranial metastasis of glioblastoma (GBM) are fairly rare event: they occur in only 1% of all GBM patients. The most frequent sites of colonization are generally cervical lymph nodes, lungs, liver, bones and the spine. The most common way of metastasis spread is hematogenous but also through lymph nodes, especially in patients undergoing surgical resection. METHODS: We report the case of a 38 year old male that in 2012 underwent to surgical resection of GBM (methylated MGMT, negative IDH1, MIB1 20%), followed by radiotherapy (RT) (60 Gy) and subsequently treated with concomitant and adjuvant Temozolomide (TMZ) up to 6 cycles. The patient remained stable over the year when he was re-operated due to recurrence. Because of the extremely good response to prior TMZ schedule, it was decided to try a rechallenge with adjuvant TMZ for 6 months. The sudden onset of of paresthesia and hypoesthesia on the right upper limb, induced physicians to performed an MRI that showed an increase of the lesion with nodular component parasagittal. After surgery, the patient was treated with anti-angiogenic treatment achieving a good radiological response and stabilization of disease. In February 2016, due to a neck pain associated with weakness of upper right limb, MRI found significant reduction of the lesion but revealed the presence of pathological enhancement at C4- C7. In suspicion of dissemination of the disease, chest-abdomen CT scan was performed showing 3 suspected pulmonary nodules metastasize. Results: Biopsy confirmed the presence of compatible tissue with GBM metastases and PET TC total body highlighted a mass effect in highly hypermetabolic character that stretched from C4 to C6-C7. Also it showed accumulations in the lymph nodes, lungs, and in the right iliac crest, and multiple thoracic vertebrae. The patient was radiated on bone localization and promptly started a new chemotherapy treatment with etoposide and oncocarbide but he died on 09.04.2016. CONCLUSION: Despite the peculiar tendency of GBM to remain confined within the central nervous system, a low percentage of them may metastasize. The biological-genetic mechanisms involved in the pathogenesis remain unclear but risk factors seems to include long survival, surgery procedures and vascular involvement. Therapeutic experience is limited making the management of GBM an even greater challenge.

Extra-cranial metastases of glioblastoma (GBM) represent a rare event, and the biological-genetic mechanisms involved in the pathogenesis have not yet been determined. We report the case of a young patient with multiple visceral and osseous metastases occurred after 4 years after first diagnosis of GBM. The strangeness as well as the rarity of this event does not allow to identify an effective treatment for GBM metastases, making the management of this ominous tumor an even greater challenge.

Purpose This phase III trial compared adjuvant whole-brain radiotherapy (WBRT) with observation after either surgery or radiosurgery of a limited number of brain metastases in patients with stable solid tumors. Here, we report the health-related quality-of-life (HRQOL) results. Patients and Methods HRQOL was a secondary end point in the trial. HRQOL was assessed at baseline, at 8 weeks, and then every 3 months for 3 years with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 and Brain Cancer Module. The following six primary HRQOL scales were considered: global health status; physical, cognitive, role, and emotional functioning; and fatigue. Statistical significance required P ≤ .05, and clinical relevance required a ≥ 10-point difference. Results Compliance was 88.3% at baseline and dropped to 45.0% at 1 year; thus, only the first year was analyzed. Overall, patients in the observation only arm reported better HRQOL scores than did patients who received WBRT. The differences were statistically significant and clinically relevant mostly during the early follow-up period (for global health status at 9 months, physical functioning at 8 weeks, cognitive functioning at 12 months, and fatigue at 8 weeks). Exploratory analysis of all other HRQOL scales suggested worse scores for the WBRT group, but none was clinically relevant. Conclusion This study shows that adjuvant WBRT after surgery or radiosurgery of a limited number of brain metastases from solid tumors may negatively impact some aspects of HRQOL, even if these effects are transitory. Consequently, observation with close monitoring with magnetic resonance imaging (as done in the EORTC trial) is not detrimental for HRQOL.

In 1991, a prospective phase II trial was initiated to evaluate the efficacy of treatment for adults with medulloblastoma (MB). After surgery, patients were staged with a neuroradiologic examination of the brain and neuroaxis and by cerebrospinal fluid cytology. All patients received three cycles of upfront cisplatinum (cisplatinum) and etoposide (VP16) chemotherapy followed by cranio-spinal radiation therapy. The current article reports on the long-term results from that trial. After a median follow-up of 14.9 years, among a total of 28 adults with MB, the overall progression-free survival and overall survival (OS) rates at 5 years were 57.6 and 80%, respectively. The median OS for the whole group of patients was 11.3 years. The observed toxicity was mainly hematological, with leukopenia and thrombocytopenia (16% of grades 3 and 4). In summary, in our small series of patients, the role of combination administration of CDDP + VP16 started before the initiation of radiotherapy in reducing recurrences, particularly distant recurrences, remains unclear. To know whether adding chemotherapy to craniospinal radiation in adult therapy increases relapse-free and overall survival, we must await the results of a larger randomized controlled clinical trial.

Purpose This European Organisation for Research and Treatment of Cancer phase III trial assesses whether adjuvant whole-brain radiotherapy (WBRT) increases the duration of functional independence after surgery or radiosurgery of brain metastases. Patients and Methods Patients with one to three brain metastases of solid tumors (small-cell lung cancer excluded) with stable systemic disease or asymptomatic primary tumors and WHO performance status (PS) of 0 to 2 were treated with complete surgery or radiosurgery and randomly assigned to adjuvant WBRT (30 Gy in 10 fractions) or observation (OBS). The primary end point was time to WHO PS deterioration to more than 2. Results Of 359 patients, 199 underwent radiosurgery, and 160 underwent surgery. In the radiosurgery group, 100 patients were allocated to OBS, and 99 were allocated to WBRT. After surgery, 79 patients were allocated to OBS, and 81 were allocated to adjuvant WBRT. The median time to WHO PS more than 2 was 10.0 months (95% CI, 8.1 to 11.7 months) after OBS and 9.5 months (95% CI, 7.8 to 11.9 months) after WBRT (P = .71). Overall survival was similar in the WBRT and OBS arms (median, 10.9 v 10.7 months, respectively; P = .89). WBRT reduced the 2-year relapse rate both at initial sites (surgery: 59% to 27%, P < .001; radiosurgery: 31% to 19%, P = .040) and at new sites (surgery: 42% to 23%, P = .008; radiosurgery: 48% to 33%, P = .023). Salvage therapies were used more frequently after OBS than after WBRT. Intracranial progression caused death in 78 (44%) of 179 patients in the OBS arm and in 50 (28%) of 180 patients in the WBRT arm. Conclusion After radiosurgery or surgery of a limited number of brain metastases, adjuvant WBRT reduces intracranial relapses and neurologic deaths but fails to improve the duration of functional independence and overall survival.

BACKGROUND: A subset of meningiomas recur after surgery and radiation therapy, no proven effective medical therapy for this sub group of meningioma patients exists. Both recurrent or progressive cases, may exhibit tumor growth involving critical neurovascular structures or diffuse growth, resulting in limited efficacy and higher risk of treatments. MATERIAL AND METHODS: We retrospectively analysed the efficacy and tolerability of systemic chemotherapy with Hydroxyurea (HU) or more complex VAC (Vincristine, Adriamycin and Cyclophosphamide) in a group of recurrent meningioma patients treated at Fondazione IRCCSS Istituto Neurologico Carlo Besta between 2015 and 2017. RESULTS: Twelve patients with high-grade meningioma (8 atypical and 4 anaplastic) were treated with VAC (7) chemotherapy or HU (5). All, patients were heavily pre-treated (median number of 4 recurrences, range 2–7). Responses were assessed using modified Macdonald criteria. The Kaplan-Meier technique was used to estimate PFS and OS. The 95% confidence intervals (CIs) were calculated for all point estimates. The majority of patients came off treatment because of progressive disease. PFS6 rate was 42%. Median PFS was 5.3 months (95% CI: 2.1–9.3 mo), and median overall survival was 19 months (95% CI: 16.5–38.4 mo). No treatment related death occurred. Main treatment-related toxicities were observe in the patients treated by VAC CONCLUSION: HU and VAC chemotherapies are feasible but these treatments have limited activity in recurrent meningiomas. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified due to the small number of prospective clinical trials available

Meningiomas are known to be induced by low and high-dose radiotherapy and several studies suggest an inverse relationship between dose administered and time of tumor development. Radiation-induced meningiomas have been usually reported to be histologically atypical, multiple, associated with a poor clinical outcome. We report a case of a young woman operated upon in 1990 at the age of 18 years old for ependymoma in the 4th ventricle. Three years later a local recurrence was detected, and a chemotherapy was began. During follow-up, MRI revealed a meningeal dissemination and the patient was treated with whole brain radiotherapy and intrathecal chemotherapy. She was radiologically stable for 10 years, then she presented another new mass, an acoustic neurinoma, treated with radiosurgery. In August 2010 the patient complained headache which gradually increases over the preceding weeks. A new MRI revealed the presence of multiple meningeal nodules, rapidly growing in a couple of months. The largest one (30 mm diameter) grew from the falx, in right parieto-occipital lobe; this mass was isointense in T1-weighted images, with a definite uptake of contrast enhancement. Histopathological examination showed a transitional meningioma with dural infiltration consistent with radiation-induced meningiomas. Lesions remained unchanged for several months, and, despite of number of nodules, the patient was almost asymptomatic. In our case report, many evidences, such as the younger age, the radiotherapy treatment and the latency interval between radiotherapy and lesions finding, suggest that the multiple meningeal nodules were radiation-induced meningiomas. The lack of information about the clinical and biological features of radiation-induced meningiomas does not actually allow to understand the clinical behavior of these lesions. Considering the increasing number of patients treated with radiotherapy, we believe it is essential to understand which patient features are linked to the development of radiation-induced meningiomas, in order to identify a subset of patients with higher risk.

INTRODUCTION. The concern about radiation induced optic neuropathy (RION) strongly characterized the recent past. This has probably been the main limit to a wider diffusion of radiotherapy and radiosurgery as treatment of meningiomas involving the anterior optic pathways. In spite of this consideration, during the last few years the radiotherapy activity for such lesions is continuously increasing. The aim of the present study is to define the risk of RION on a medium to long term follow-up period in a large series of patients treated by radiosurgery. The efficacy of the treatment is also investigated. MATERIALS AND METHODS: The visual outcome of 97 patients which underwent radiosurgery due to a meningioma involving the anterior optic pathways has been retrospectively evaluated. Patients with a minimum follow-up period longer than 12 months were included. Sixteen patients had a single session radiosurgery (sSRS) with a mean dose of 12 Gy (range 8-13 Gy; median 13 Gy). In these cases the mean tumour volume was 4,9 cc (range 0,3-10,5 cc; median 3.6 cc) Eighty-one patients underwent a multi-session radiosurgery (mSRS). The mean prescription dose was 24 Gy (range 15-30Gy; median 25Gy), the mean tumour volume was 9,5 cc (range 0,5-65 cc; median 6,5 cc) The visual outcome was evaluated in all cases. All the included patients had at least a pre-treatment and a last follow-up visual function assessment. Furthermore local control has been analyzed. RESULTS: The mean follow-up is 43 months (range 12-96 months; 56 patients f-up ≥ 36 monts; 23 patients f-up ≥ 60 months) Compared to the baseline the visual function improved in 24 patients (24 %) and was unchanged in 65 (68 %). Seven patients worsened 8 (8 %). Three out of these experienced a tumour progression. Only two patients with no progression disease developed a “de novo” visual deficit. At the analysis time, the overall local control was 94 %. Eighteen lesions (18%) showed a partial shrinkage, seventy-three (72%) were stable and 6 patients (6%) experienced a progression of the disease. When observed, the tumour progression always occurred later than 36 months post-treatment. CONCLUSIONS: The study confirms the low risk of radiation induced optic neuropathy both in case of sSRS and mSRS. Multisession radiosurgery makes also the larger lesions manageable. The high local control rate and the low toxicity suggest that radiosurgery could be proposed also as a primary treatment.

We report a patient with POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, Skin changes) treated with high dose chemotherapy and auto-Peripheral Blood Stem Cell Transplantation (auto-PBSCT) who had a very good response with complete clinical remission. Seven years later, she relapsed and a new sclerotic bone lesion was found. To our knowledge, this is the first POEMS syndrome relapse after successful auto-PBSCT.

In malignant gliomas, the management of symptoms and minimization of side effects assume major importance. Corticosteroids provide transient relief from neurological symptoms. However, treatment with steroids is also commonly associated with considerable side-effects including: hyperglycemia, osteoporosis, myopathy, lymphopenia and others. Sometimes, antiepileptic drugs may contribute to clinical decline of neuro-oncological patients in stable disease not only by neuropsychological impairment but also by metabolic interations. Several studies have demonstrated a high frequency of hyponatremia among patients treated with carbamazepine and particularly with oxacarbamazepine. Venous thromboembolism is a common complication in patients with cancer and it is particularly high in malignant gliomas, occurring in approximately 20–30% of such patients. Prophylactic treatment in patients with glioblastoma is a key topic. The role of prophylaxis has not yet been established with certainty. Overall the data show a clear reduction of venous thromboembolic events in patients treated with intermittent pneumatic compression (IPC). The addition of enoxaparin dose of 6.000 UI, starting in the perioperative period, induces an increase of major bleeding events. In the absence of availability of IPC, the use of enoxaparin 4.000 UI in addition to graduated compression stockings, reduces thromboembolic events without major bleeding events.

Analysis of the results of the various methods for treatment of typical trigeminal neuralgia (TN) based on the literature and personal experience. The personal experience includes 847 cases: total thyzotomy in the posterior fossa 17 cases; rhyzotomy in the posterior fossa sparing the intermediate fibers 16 cases; microvascular decompression (MVD) 141 cases; controlled thermorhizotomy (PTR) 54 cases; Fogarty Balloon compression (FBC) 223 cases; glycerol ganglyolis (PGG) 12 cases; miscellaneous 48 case; medical treatment only 310 cases; cyberknife radiosurgery (CKR) 46 cases. The follow-up in this series is 1-32 years. MVD of the Vth cranial nerve in posterior fossa gives the best results in term of long-term pain relief without collateral effects in drug-resistant TN. Percutaneous techniques (PTR, PGG, FBC) are indicated in patients either without neurovascular conflict or with excessive surgical risk. Stereotactic radiosurgery (SRS) and CKR might be considered an improvement of percutaneous and surgical techniques, but contrary to the expectations, the rate of complete pain relief at long term is lower. SRS and CKR are less effective than MVD which, in spite of the risks it entails, remains the choice treatment for typical trigeminal neuralgia.

Ninety-nine patients bearing recurrent malignant glioma sequentially selected according to strict eligibility criteria (72 GBL and 27 AA) entered the study. All patients were previously managed with radiotherapy 60 Gy total dose and chemotherapy with nitrosoureas and platinum compounds. At recurrence they were subdivided in homogeneous groups, all treated with the same systemic chemotherapy protocol: 27 GBL (group A) only systemically treated, 20 GBL (group B) treated also locally by delivering 4mg of mitoxantrone every 20 days through the Ommaya reservoire, and 25 GBL (group C) treated with a second surgery and locally as group B. Of the AA group, 13/27 were treated locally trough the Ommaya reservoir after repeat surgery. A trend to different demographic features among subgroups (with locoregionally treated patients and patients undergoing repeat surgery being younger than the others) was seen in this non-randomized study, but this was not statistically significant. Median overall survival was 27, 26 and 15.5 months respectively for groups c, b and a (log-rank = 0.1). After tumor recurrence median survival was 16.8, 12 and 6.6 months respectively for groups c, b and a (log-rank = 0.001) For the 29 AA, overall survival was 48.5 and 100 months (log-rank = 0.03) if treated locally with second tumor debulking. Our results stress the opinion that a second operation could be indicated only if it is a part of a therapeutic protocol to allow a locoregional treatment. Moreover we can finally assume that local delivery of chemotherapy after tumor recurrence, possibly extends patients survival but certainly improves the number of long-survivors.

PURPOSE: Numerous treatment options are available for recurrent high-grade gliomas (rHGG), including re-irradiation. Both fractionated stereotactic radiotherapy (FSRT) and radiosurgery (SRS) represent an optimal method to deliver high-dose radiotherapy to the small volume. Re-irradiation is often limited due to the dose-prescription and target volume. The primary end point of this retrospective study is to evaluate the efficacy of salvage SRS and FSRT in terms of overall survival; toxicity was analyzed as well. PATIENTS AND METHODS: Between 2004 and 2011, 128 patients (158 lesions) with recurrent high-grade gliomas (69% glioblastoma multiforme, WHO grade IV; 31% WHO grade III) were treated with CyberKnife stereotactic re-irradiation. FSRT was performed in 96 lesions with 3-5 fractions; SRS in 62 lesions. The median time from first irradiation and SRS re-irradiation was 12 months (range 6-171 months). RESULTS: A median survival time from the date of diagnosis was 32 months (95% CI, 25-43). Median survival time from the re-irradiation treatment was 11.5 months (95% CI, 10-12). Multivariate analysis confirmed that younger age and salvage surgery after SRS were associated with a significant improvement in survival. There have been 19 patients (15%) of G1-G2 acute toxicity (with headache, nausea, fatigue and alopecia) and 7 pts. (6%) of G3-G4 late toxicity (radiation-induced necrosis and neurological deterioration). CONCLUSIONS: Salvage re-irradiation with CyberKnife stereotactic radiotherapy for recurrent high-grade gliomas is safe and well tolerated. This strategy can be considered an effective treatment for recurrent HGG.

We investigated the efficacy of 3 different systemic chemotherapy regimes in 122 patients with histologically confirmed glioblastoma, KPS60, age65. Locoregional chemotherapy was delivered to 22 patients from all three systemic chemotherapy groups. Chemotherapy was given before and during radiotherapy, which was the same for all patients consisting of unconventional fractionation with a break between courses. Survival (Kaplan-Meier) was significantly longer in the subgroup receiving cisplatinum plus BCNU compared to those receiving cisplatinum plus etoposide or carboplatinum plus BCNU with median survival time 21.5 months, 15 months and 15 months respectively (log rank test p = 0.01). Survival was also significantly longer in patients who received locoregional therapy compared to those who received only systemic chemotherapy (21 vs 15 months, p = 0.01). Univariate analysis showed that age, postoperative Karnofsky status and extent of resection were not predictive of survival in the series, although there were trends to better outcome in younger patients and those undergoing total/subtotal resection. Age, systemic chemotherapy type and interstitial treatment were included in a multivariate analysis, and both locoregional treatment and chemotherapy with cisplatinum plus BCNU were significantly predictive of survival [P = 0.01]. These encouraging preliminary results suggest that further trials with locoregional and systemic therapy prior to radiotherapy are worth pursuing.

We devised a treatment protocol for anaplastic gliomas consisting of:(a) chemotherapy prior to radiotherapy (b) a second chemotherapy regimen at tumor recurrence (c) repeated surgery whenever possible. 41 Anaplastic Astrocytoma (AA), 16 Anaplastic oligoastrocytoma (AOA) and 14 anaplastic oligodendroglioma (AOD) patients were treated. After surgery all patients received 5-6 cycles of carmustine+Cisplatinum chemotherapy. Radiotherapy was started during the last 2-3 cycles of chemotherapy. 17 patients (30.5%) were reoperated on at recurrence. All recurring patients underwent PVC chemotherapy. At this moment disease recurred in 56 patients. Median TTP was 24.5, 38.7 and 58.2 months for AA, AOA and AOD respectively. Median ST was 38.8, 71.8 and 73 months. In conclusion our sandwich protocol of prior chemotherapy, overlapping irradiation with second chemotherapy and, in favourable cases, a second surgical intervention, is of benefit in patients with anaplastic gliomas.

9036 Background: This study aimed to evaluate the effects of adjuvant whole brain radiotherapy (WBR) compared to no further radiotherapy after local treatment of a limited number of brain metastases in patients with stable solid tumor. We present the Health Related Quality of Life (HRQOL) results. Methods: HRQOL (EORTC QOL-C30 and BN-20) was a secondary endpoint in the trial. Out of 359, 317 patients (88.3% compliance) had baseline HRQOL assessments. Compliance was a challenge in this population: at month 6 some 51% of patients completed a HRQOL measure and at year one 45.1%. Therefore the analysis focuses on only the first year post baseline. The primary HRQOL endpoint was global QoL; secondary HRQOL endpoints were Cognitive, Physical, Emotional, Role Functioning and Fatigue. Sensitivity analyses were planned and undertaken for all scales. Statistical significance required p≤0.05 and clinical relevance ≥10 pt difference. Results: Over the year studied, there were no significant differences in the primary...

Thirty-five adult recurrent GBM patients, divided randomly in two groups of 19 and 16 cases, had been treated with two regimens of chemotherapy: a) 'eight-drugs-in-one-day'; b) procarbazine + CCNU + vincristine (PCV) respectively. Chemotherapy was planned at the tumour relapse and delivered as long as tolerated without irreversible sequelae or until the CT scan showed tumor progression. Multiple agents are used simultaneously in the therapeutic approach using 'eight-in-one' to kill as many heterogeneous cells of malignant glial tumor as possible and minimize the emergence of cellular resistance to chemotherapy. Rate response to chemotherapy and the median adjunctive survival time (6.5 and 6 months, respectively) are not significantly different in the two arms of this study. Our experience with such an aggressive multi-drugs combination 'eight-in-one-day' was disappointing if compared with less toxic, better tolerated and easy delivered (PCV) regimen.

2008 Background: The EORTC Radiotherapy and Brain Tumor Groups conducted a phase III trial to define the role of adjuvant whole brain irradiation (WBRT) after local treatment (surgery or radiosurgery) for brain metastases. It was hypothetized that WBRT would increase the duration of functional independence by reducing the number of intracranial relapses. Methods: Pts eligible for radiosurgery (RS) had 1–3 metastases of solid tumors (SCLC excluded) ≤ 3.0 cm in diameter (≤ 2.5 cm for 2–3 lesions). In case of surgery (S), a complete resection was mandatory. Only pts with no or stable systemic disease or with asymptomatic synchronous primary tumors, and with WHO PS 0–2 were allowed. Pts were randomized for adjuvant WBRT or observation (OBS). Primary endpoint was survival with functional independence measured by the time to WHO PS deterioration to > 3. Analysis is by intent-to-treat (Logrank, two-sided α = 0.05). Results: From 1996–2007, 359 pts were recruited. 160 surgical pts had resection of one (96%) or two (4%) metastases, and 185 (of 199 scheduled pts) had RS (marginal dose 20Gy, target dose 25Gy) of one (67%), two (23%), or three (10%) lesions. Adjuvant whole brain irradiation (30Gy/10 fractions) was given to 166/180 pts. (92%) randomized for WBRT and to 4/179 pts (2%) in the OBS arm. Median time to WHO PS > 3 was 9.8 months (95% CI 8.0 - 11.7) in the OBS arm and 9.8 months (95% CI 7.8 - 12.6) in the WBRT arm (p > 0.5). It was only significantly influenced by initial WHO PS and initial systemic disease status (p < 0.01). Overall survival was 10.9 months (95% CI 9.2 - 14.6) in both arms (p > 0.5). Cumulative incidence of intracranial progression at 6 and 24 months was 39.7% (95% CI 32.5 - 46.8) and 54.0% (95% CI 46.7 - 61.3) of the OBS pts, but only 15.2% (95% CI 9.9 - 20.5) and 31.4% (95% CI 24.5 - 38.2) of the WBRT pts (p < 0.0001). Intracranial progression was a cause of the death in 77/179 pts (43%) of the OBS group and in only 45/180 pts (25%) of the WBRT group. Conclusions: After radiosurgery or surgery of 1–3 brain metastases, adjuvant WBRT reduces the frequency of intracranial relapses and neurologic deaths but fails to prolong the time period of functional independence and overall survial time. Updated results will be presented at the Meeting. No significant financial relationships to disclose.