Radiolabeled Somatostatin Receptor Antagonist Versus Agonist for Peptide Receptor Radionuclide Therapy in Patients with Therapy-Resistant Meningioma: PROMENADE Phase 0 Study.

Our primary aim was to compare the therapeutic index (tumor-to-bone marrow and tumor-to-kidney absorbed-dose ratios) of the new radiolabeled somatostatin receptor antagonist [177Lu]Lu-DOTA-JR11 with the established radiolabeled somatostatin receptor agonist [177Lu]Lu-DOTATOC in the same patients with progressive, standard therapy-refractory meningioma. Methods: In this prospective, single-center, open-label phase 0 study (NCT04997317), 6 consecutive patients were included: 3 men and 3 women (mean age, 63.5 y). Patients received 6.9-7.3 GBq (standard injected radioactivity) of [177Lu]Lu-DOTATOC followed by 3.3-4.9 GBq (2 GBq/m2 × body surface area) of [177Lu]Lu-DOTA-JR11 at an interval of 10 ± 1 wk. In total, 1 [177Lu]Lu-DOTATOC and 2-3 [177Lu]Lu-DOTA-JR11 treatment cycles were performed. Quantitative SPECT/CT was done at approximately 24, 48, and 168 h after injection of both radiopharmaceuticals to calculate meningioma and organ absorbed doses as well as tumor-to-organ absorbed-dose ratios (3-dimensional segmentation approach for meningioma, kidneys, liver, bone marrow, and spleen). Results: The median of the meningioma absorbed dose of 1 treatment cycle was 3.4 Gy (range, 0.8-10.2 Gy) for [177Lu]Lu-DOTATOC and 11.5 Gy (range, 4.7-22.7 Gy) for [177Lu]Lu-DOTA-JR11. The median bone marrow and kidney absorbed doses after 1 treatment cycle were 0.11 Gy (range, 0.05-0.17 Gy) and 2.7 Gy (range, 1.3-5.3 Gy) for [177Lu]Lu-DOTATOC and 0.29 Gy (range, 0.16-0.39 Gy) and 3.3 Gy (range, 1.6-5.9 Gy) for [177Lu]Lu-DOTA-JR11, resulting in a 1.4 (range, 0.9-1.9) times higher median tumor-to-bone marrow absorbed-dose ratio and a 2.9 (range, 2.0-4.8) times higher median tumor-to-kidney absorbed-dose ratio with [177Lu]Lu-DOTA-JR11. According to the Common Terminology Criteria for Adverse Events version 5.0, 2 patients developed reversible grade 2 lymphopenia after 1 cycle of [177Lu]Lu-DOTATOC. Afterward, 2 patients developed reversible grade 3 lymphopenia and 1 patient developed reversible grade 3 lymphopenia and neutropenia after 2-3 cycles of [177Lu]Lu-DOTA-JR11. No grade 4 or 5 adverse events were observed at 15 mo or more after the start of therapy. The disease control rate was 83% (95% CI, 53%-100%) at 12 mo or more after inclusion. Conclusion: Treatment with 1 cycle of [177Lu]Lu-DOTA-JR11 showed 2.2-5.7 times higher meningioma absorbed doses and a favorable therapeutic index compared with [177Lu]Lu-DOTATOC after injection of 1.4-2.1 times lower activities. The first efficacy results demonstrated a high disease control rate with an acceptable safety profile in the standard therapy for refractory meningioma patients. Therefore, larger studies with [177Lu]Lu-DOTA-JR11 are warranted in meningioma patients.

Long-Term Tumor Control Following Targeted Alpha Therapy (TAT) of Low-Grade Gliomas (LGGs): A New Treatment Paradigm?

The median survival time has been reported to vary between 5 and 8 years in low-grade (WHO grade 2) astrocytoma, and between 10 and 15 years for grade 2 oligodendroglioma. Targeted alpha therapy (TAT), using the modified peptide vector [213Bi]Bi/[225Ac]Ac-DOTA-substance P, has been developed to treat glioblastoma (GBM), a prevalent malignant brain tumor. In order to assess the risk of late neurotoxicity, assuming that reduced tumor cell proliferation and invasion should directly translate into good responses in low-grade gliomas (LGGs), a limited number of patients with diffuse invasive astrocytoma (n = 8) and oligodendroglioma (n = 3) were offered TAT. In two oligodendroglioma patients, TAT was applied as a second-line treatment for tumor progression, 10 years after targeted beta therapy using [90Y]Y-DOTA-substance P. The radiopharmaceutical was locally injected directly into the tumor via a stereotactic insertion of a capsule-catheter system. The activity used for radiolabeling was 2-2.5 GBq of Bismuth-213 and 17 to 35 MBq of Actinium-225, mostly applied in a single fraction. The recurrence-free survival times were in the range of 2 to 16 years (median 11 years) in low-grade astrocytoma (n = 8), in which TAT was administered following a biopsy or tumor debulking. Regarding oligodendroglioma, the recurrence-free survival time was 24 years in the first case treated, and 4 and 5 years in the two second-line cases. In conclusion, TAT leads to long-term tumor control in the majority of patients with LGG, and recurrence has so far not manifested in patients with low-grade (grade 2) astrocytomas who received TAT as a first-line therapy. We conclude that targeted alpha therapy has the potential to become a new treatment paradigm in LGG.

Does Functional Imaging Play a Role in Pre-Operative Diagnosis of Brain Tumours?

Although there is a large variability in the neural organization of language function between individuals, there is an ongoing debate about functional imaging as a standard procedure in the preoperative setting of brain tumors. Brain mapping of the language centers differs from individual to individual in multilingual patients and changes in its architecture may occur as a result of neuroplasticity induced by a mass lesion. This article discusses the role of functional imaging in the preoperative setting.

Effects of two types of exercise training on psychological well-being, sleep and physical fitness in patients with high-grade glioma (WHO III and IV).

BACKGROUND: There is evidence that regular exercise training has the potential to improve psychological well-being among cancer survivors. However, limited findings are available for individuals with high-grade glioma (HGG; WHO grade III and IV) after neurosurgery and undergoing radiochemotherapy. Given this, endurance and strengths training were employed to investigate their impact on symptoms of depression, feelings of stress and anxiety, fatigue, insomnia, and physical fitness, compared to an active control condition. METHODS: A total of 29 patients (M = 52.07, SD = 12.45, 55.2% women) participated in this randomized controlled trial (RCT). After neurosurgical treatment and during adjuvant radiotherapy and chemotherapy or combined radiochemotherapy, patients were randomly assigned to the following conditions: Endurance training (n = 10); strengths training (n = 11); active control condition (n = 8). At baseline, three weeks and six weeks later at the end of the study physical fitness was objectively measured with a 6-min walk test (6MWT) and a handgrip test. Participants completed a series of questionnaires covering sociodemographic information, symptoms of depression, stress, anxiety, fatigue, and insomnia. Further, experts rated participants' severity of symptoms of depression. RESULTS: Over time and compared to the strengths and active control condition, self-rated symptoms of depression, state and trait anxiety, stress and insomnia decreased in the endurance condition. Over time and compared to the endurance and active control condition, no changes on symptoms of depression, anxiety, stress, or insomnia were observed in the strengths condition. Over time and compared to the endurance and strengths condition, symptoms of depression (self-ratings), stress, insomnia and fatigue decreased in the active control condition. Fatigue increased in both exercising conditions. Over time and irrespective from the study condition, physical fitness did neither improve nor decrease. CONCLUSIONS: The pattern of results suggests that endurance training and an active control condition improved dimensions of depression, stress, and anxiety, while mere strengths training appeared to neither improve, nor decrease dimensions of psychological functioning. Further, exercise interventions did not change physical fitness, but increased fatigue. Overall, endurance training and an active control condition appeared to favorably impact on psychological well-being among patients with high-grade glioma after neurosurgery and undergoing radiochemotherapy.

The Role of Endonasal Endoscopic Skull Base Repair in Posttraumatic Tension Pneumocephalus.

OBJECTIVES: Information about the endonasal endoscopic approach (EEA) for the management of posttraumatic tension pneumocephalus (PTTP) remains scarce. Concomitant rhinoliquorrhea and posttraumatic hydrocephalus (PTH) can complicate the clinical course. METHODS: The authors systematically reviewed pertinent articles published between 1961 and December 2020 and identified 6 patients with PTTP treated by EEA in 5 reports. Additionally, the authors share their institutional experience including a seventh patient, where an EEA resolved a recurrent PTTP without rhinoliquorrhea. RESULTS: Seven PTTP cases in which EEA was used as part of the treatment regime were included in this review. All cases presented with a defect in the anterior skull base, and 3 of them had concomitant rhinoliquorrhea. A transcranial approach was performed in 6/7 cases before EEA was considered to treat PTTP. In 4/7 cases, the PTTP resolved after the first intent; in 2/ 7 cases a second repair was necessary because of recurrent PTTP, 1 with and 1 without rhinoliquorrhea, and 1/7 case because of recurrent rhinoliquorrhea only. Overall, PTTP treated by EEA resolved with a mean radiological resolution time of 69 days (range 23-150 days), with no late recurrences. Only 1 patient developed a cerebrospinal fluid diversion infection probably related to a first incomplete EEA skull base defects repair. A permanent cerebrospinal fluid diversion was necessary in 3/7 cases. CONCLUSIONS: Endonasal endoscopic approach repair of air conduits is a safe and efficacious second-line approach after failed transcranial approaches for symptomatic PTTP. However, the strength of recommendation for EEA remains low until further evidence is presented.

Fitness-to-drive for glioblastoma patients: Guidance from the Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM).

OBJECTIVE: The management of brain tumour patients who would like to resume driving is complex, and needs multidisciplinary input and a consensus among treating physicians. The Swiss Neuro-Oncology Society (SwissNOS) and the Swiss Society for Legal Medicine (SGRM) aim to provide guidance on how to assess "fitness-to-drive" of glioblastoma patients and to harmonise the relevant procedures in Switzerland. METHODS: At several meetings, Swiss neuro-oncologists discussed common practices on how to advise patients with a stable, i.e., non-progressive, glioblastoma, who wish to resume driving after the initial standard tumour treatment. All participants of the SwissNOS meetings were invited twice to return a questionnaire (modified Delphi process) on specific tools/procedures they commonly use to assess "fitness-to-drive" of their patients. Answers were analysed to formulate a tentative consensus for a structured and reasonable approach. RESULTS: Consensus on minimum requirements for a "fitness-to-drive" programme for glioblastoma patients could be reached among Swiss neuro-oncologists. The recommendations were based on existing guidelines and expert opinions regarding patients with seizures, visual disturbances, cognitive impairment or focal deficits for safe driving. At this point in time, the Swiss neuro-oncologists agreed on the following requirements for glioblastoma patients after the initial standard therapy and without a seizure for at least 12 months: (1) stable cranial magnetic resonance imaging (MRI) according to Response Assessment in Neuro-Oncology (RANO) criteria, to be repeated every 3 months; (2) thorough medical history, including current or new medication, a comprehensive neurological examination at baseline (T0) and every 3 months thereafter, optionally an electrocencephalogram (EEG) at baseline; (3) ophthalmological examination including visual acuity and intact visual fields; and (4) optional neuropsychological assessment with a focus on safe driving. Test results have to be compatible with safe driving at any time-point. Patients should be informed about test results and optionally sign a document. CONCLUSIONS: We propose regular thorough clinical neurological examination and brain MRI, optional EEG, neuropsychological and visual assessments to confirm "fitness-to-drive" for glioblastoma patients after initial tumour-directed therapy. The proposed "fitness-to-drive" assessments for glioblastoma patients serves as the basis for a prospective Swiss Pilot Project GLIODRIVE (BASEC ProjectID 2020-00365) to test feasibility, adherence and safety in a structured manner for patients who wish to resume driving. Research will focus on confirming the usefulness of the proposed tools in predicting "fitness-to-drive" and match results with events obtained from the road traffic registry (Strassenverkehrsamt).

Association between IL-8 (-251T/A) and IL-6 (-174G/C) Polymorphisms and Oral Cancer Susceptibility: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVE: Inflammation and cell-mediated immunity can have significant roles in different stages of carcinogenesis. The present meta-analysis aimed to evaluate the association between the polymorphisms of IL-8 (-251T/A) and IL-6 (-174G/C) and the risk of oral cancer (OC). METHODS: PubMed/MEDLINE, Web of Science, Cochrane Library, and Scopus databases were searched until December 18, 2020 without any restrictions. RevMan 5.3 software was used to calculate the results of forest plots (odds ratios (ORs) and 95% confidence intervals (CIs)); CMA 2.0 software was used to calculate funnel plots (Begg's and Egger's tests), and SPSS 22.0 was used for the meta-regression analysis. Moreover, trial sequential analysis was conducted to estimate the robustness of the results. RESULTS: Eleven articles including twelve studies were selected for the meta-analysis. The pooled ORs for the association between IL-8 (-251T/A) polymorphism and the risk of OC in the models of A vs. T, AA vs. TT, TA vs. TT, AA + TA vs. TT, and AA vs. TT + TA were 0.97 (p = 0.78), 0.86 (p = 0.55), 0.78 (p = 0.37), 0.83 (p = 0.45), and 1.10 (p = 0.34), respectively. The pooled ORs IL-6 (-174G/C) polymorphism and the risk of OC in the models of C vs. G, CC vs. GG, GC vs. GG, CC + GC vs. GG, and CC vs. GG + GC were 1.07 (p = 0.87), 1.17 (p = 0.82), 1.44 (p = 0.38), 1.28 (p = 0.61), and 0.96 (p = 0.93), respectively. There was no association between IL-8 (-251T/A) polymorphism and OC susceptibility, but the C allele and GC and CC genotypes of IL-6 (-174G/C) polymorphism were associated with the risk of OC based on subgroup analyses, that is to say, the source of control and the genotyping method might bias the pattern of association. CONCLUSIONS: The meta-analysis confirmed that there was no association between the polymorphisms of IL-6 (-174G/C) and IL-8 (-251T/A) and the susceptibility of OC. However, the source of control and the genotyping method could unfavorably impact on the association between the polymorphisms of IL-6 (-174G/C) and the risk OC.

High Precision Bone Cutting by Er: YAG Lasers Might Minimize the Invasiveness of Navigated Brain Biopsies.

Biopsies of brain tissue are sampled and examined to establish a diagnosis and to plan further treatment, e.g. for brain tumors. The neurosurgical procedure of sampling brain tissue for histologic examination is still a relatively invasive procedure that carries several disadvantages. The "proof of concept"-objective of this study is to answer the question if laser technology might be a potential tool to make brain biopsies less invasive, faster and safer. Laser technology might carry the opportunity to miniaturize the necessary burr hole and also to angulate the burr hole much more tangential in relation to the bone surface in order to take biopsies from brain regions that are usually only difficult and hazardous to access. We examined if it is possible to miniaturize the hole in the skull bone to such a high extent that potentially the laser-created canal itself may guide the biopsy needle with sufficient accuracy. The 2-dimensional, i.e. radial tolerance of the tip of biopsy needles inserted in these canals was measured under defined lateral loads which mimic mechanical forces applied by a surgeon. The canals through the skull bones were planned in angles of 90° (perpendicular) and 45° relative to the bone surface. We created a total of 33 holes with an Er : YAG laser in human skull bones. We could demonstrate that the achievable radial tolerance concerning the guidance of a biopsy needle by a laser created bone canal is within the range of the actual accuracy of a usual navigated device if the canal is at least 4 mm in length. Lateral mechanical loads applied to the biopsy needle had only minor impact on the measurable radial tolerance. Furthermore, in contrast to mechanical drilling systems, laser technology enables the creation of bone canals in pointed angles to the skull bone surface. The latter opens the perspective to sample biopsies in brain areas that are usually not or only hazardous to access.

Differentiation of rare brain tumors through unsupervised machine learning: Clinical significance of in-depth methylation and copy number profiling illustrated through an unusual case of IDH wildtype glioblastoma.

Methylation profiling has become a mainstay in brain tumor diagnostics since the introduction of the first publicly available classification tool by the German Cancer Research Center in 2017. We demonstrate the capability of this system through an example of a rare case of IDH wildtype glioblastoma diagnosed in a patient previously treated for T-cell acute lymphoblastic leukemia. Our novel in-house diagnostic tool EpiDiP provided hints arguing against a radiation-induced tumor, identified a novel recurrent genetic aberration, and thus informed about a potential therapeutic target.

Among Persons With Multiple Sclerosis (MS), Objective Sleep, Psychological Functioning, and Higher Physical Activity Scores Remained Stable Over 2 Years-Results From a Small Study Under Naturalistic Conditions.

Background: Persons with multiple sclerosis (PwMS) are at increased risk to report poor sleep patterns and lower physical activity indices. To date, data on longitudinal objectively sleep assessment is missing. In the present study, we investigated the pattern of objective sleep and subjective physical activity indices over a period of 13.5 months, under naturalistic conditions. Method: 13.5 months after their first assessment, a total of 16 PwMS (mean age = 49.13 median EDSS score: 5; 11 females) were reassessed on their objective sleep via portable sleep-electroencephalogram (EEG-) devices, along with their subjective sleep patterns (symptoms of insomnia, restless legs syndrome (RLS), and sleep-disordered breathing), physical activity indices, psychological functioning (symptoms of depression, fatigue, daytime sleepiness), and MS-related information (fatigue, EDSS; disease-modifying treatments). While the baseline assessment was performed in a rehabilitation center, the follow-up assessment took place at participants' naturalistic and familiar setting. Results: Statistically, symptoms of depression and fatigue, subjective sleep, and physical activity levels did neither increase, nor decrease over time, although descriptively, both moderate and vigorous physical activity levels decreased, and fatigue and subjective insomnia increased. Time awake after sleep onset statistically significantly decreased, while light sleep duration increased by trend. Conclusions: Among a smaller sample of PwMS, objective sleep in their naturalistic setting remained fairly stable over a mean time lapse of 13.5 months after clinic discharge. Physical activity levels descriptively decreased. The present results are of clinical and practical importance for treatment counseling: PwMS can be reassured that their sleep quality does not deteriorate, once they have left a rehabilitation center. Further, they should be encouraged to keeping their physical activity levels as stable as possible.

An Unusual Bump on the Head: Intracranial and Extracranial Cytokeratin-Positive Interstitial Reticular Cell Tumor.

BACKGROUND: We describe a cytokeratin positive interstitial reticulum cell tumor (CPIRCT) as the cause of a large and defacing scalp tumor. Clinically these tumors manifest as progressive, painless swelling. Treatment usually consists of surgery with or without irradiation; chemotherapy is applied in metastatic disease. CASE DESCRIPTION: A patient was referred after attempted removal of a large bump on the head. The tumor was initially noted about 12 months earlier. Assuming a benign lipoma, resection without prior imaging was attempted. During surgery, the underlying bone was found to be profoundly destroyed. Cranial magnetic resonance imaging revealed a large mass with an extracranial and intracranial component. Subsequent extensive resection finally led to the diagnosis of CPIRCT. CONCLUSIONS: Most CPIRCTs manifest as progressive palpable or visible masses. Radical excision is usually the mainstay of treatment, although there is no generally accepted treatment strategy. A needle biopsy might not be diagnostic and can complicate future curative surgery. Especially in fast-growing lesions, imaging studies should be considered before surgery. Their potential recurrence and metastatic spread render CPIRCTs an interdisciplinary challenge and highlight the need for long-term follow-up.

The cerebellar peduncle as localization of a recurrent atypical plexus papilloma: A case report.

BACKGROUND: Choroid plexus papillomas (CPPs) are infrequently encountered brain tumors with the majority originating in the ventricular system. Rarely, CPP occurs outside of the ventricles. CASE DESCRIPTION: We report the case of a recurrent CPP that initially originated within the fourth ventricle, though years later it recurred in the left middle cerebellar peduncle. CONCLUSION: Patients with cerebellar plexus papilloma need long-term follow-up comprising regular magnetic resonance imagings since, in patients with a history of CPP, any new mild symptomatology, even years after the initial presentation, may be an early sign of tumor recurrence.

Effects of two types of exercise training on psychological well-being, sleep, quality of life and physical fitness in patients with high-grade glioma (WHO III and IV): study protocol for a randomized controlled trial.

BACKGROUND: There is existing evidence on whether and to what degree regular exercise training improves the quality of life (QoL) among cancer survivors. However, in regards to patients with high-grade glioma (HGG; WHO grade III and IV), no conclusive study has been performed so far. The present trial aims to fill this gap by examining whether psychological well-being, sleep, QoL and physical fitness might be improved with two different types of exercise, as compared to an active control condition. Active control condition represent individuals participating at regular meetings to talk about their current life situation, though, the meetings were not intended as that of the psychotherapy group. Regular meetings are of the same frequency, duration, and intensity as the exercise interventions. METHODS: A total of 45 patients with HGG after undergoing neurosurgery and adjuvant radiotherapy, chemotherapy, or chemoradiotherapy will be consecutively and randomly assigned to (a) an endurance training, (b) a resistance training or (c) to an active control condition. The intervention will last for 6 consecutive weeks, consisting of 2 weekly sessions (30-45 min per session). Measurements would take place at three time points, namely at the beginning of the study (baseline), 3 weeks after the beginning of the study, and 6 weeks after the beginning of the study. The last measurement also represents the end of the study. Aerobic exercise performance will be assessed objectively with a 6-min walking test, and a handgrip test will be used to assess the upper body strength. Further, participants will complete a battery of questionnaires covering sociodemographic information, QoL, sleep quality and sleep patterns, coping with stress, state- and trait-anxiety, depression, and fatigue. In parallel, experts will use the Hamilton Depression Rating Scale to determine and rate participants' symptoms of depression. SIGNIFICANCE: The present study will be the first to investigate and compare the impact of two different exercise modalities, namely endurance and resistance training, on physical fitness and dimensions of well-being, and sleep among patients with HGG who underwent neurosurgery followed by adjuvant radiotherapy, chemotherapy, or chemoradiotherapy. Importantly, unlike the majority of previous studies, the control condition consists of an active set-up to detect possible factual beneficial effects of exercise training, irrespective of social interactions. Trial registration https://register.clinicaltrials.gov ; identifier: NCT03775369.

Long-Term Results of Targeted Low-Grade Glioma Treatment with 213Bi-DOTA-[Thi8,Met(O2)11]-Substance P.

The aim was to evaluate long-term effectiveness, functional outcome, and side effects of targeted α radiotherapy as an alternative treatment for low-grade gliomas (LGGs) in eloquent brain areas. Five patients with gliomas World Health Organization (WHO) II-IV were treated with tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-213Bi substance P. In this study, the LGG patients' (WHO II) clinical and radiological long-term outcome was examined. Ten years after treatment with DOTA-213Bi substance P, both LGG patients are still alive without evidence for tumor recurrence and without new functional deficits. Targeted α radiotherapy of LGG might have the potential of long-term tumor control, due to the short tissue range of α particles especially for eloquently located LGG.

Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.

OBJECTIVE: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. METHODS: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. RESULTS: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. CONCLUSION: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET. IMPORTANCE OF THE STUDY: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Targeted Radiolabeled Compounds in Glioma Therapy.

Malignant gliomas of World Health Organization (WHO) grades II-IV represent the largest entity within the group of intrinsic brain tumors and are graded according to their pathophysiological features with survival times between more than 10 years (WHO II) and only several months (WHO IV). Gliomas arise from astrocytic or oligodendrocytic precursor cells and exhibit an infiltrative growth pattern lacking a clearly identifiable tumor border. The development of effective treatment strategies of the invasive tumor cell front represents the main challenge in glioma therapy. The therapeutic standard consists of surgical resection and, depending on the extent of resection and WHO grade, adjuvant external beam radiotherapy or systemic chemotherapy. Within the last decades, there has been no major improvement of the prognosis of patients with glioma. The consistent overexpression of neurokinin type 1 receptors in gliomas WHO grades II-IV has been used to develop a therapeutic substance P-based targeting system. A substance P-analogue conjugated to the DOTA or DOTAGA chelator has been labeled with different alpha-particle or beta-particle emitting radionuclides for targeted glioma therapy. The radiopharmaceutical has been locally injected into the tumors or the resection cavity. In several clinical studies, the methodology has been examined in adjuvant and neoadjuvant clinical settings. Although no large controlled series have so far been generated, the results of radiolabeled substance P-based targeted glioma therapy compare favorably with standard therapy. Recently, labeling with the alpha particle emitting Bi-213 has been found to be promising due to the high linear energy transfer and the very short tissue range of 0.08 mm. Further development needs to focus on the improvement of the stability of the compound and the application by dedicated catheter systems to improve the intratumoral distribution of the radiopharmaceutical within the prognostically critical infiltrative growing zone of the glioma.

90Y-DOTATOC as a Therapeutic Option for Complex Recurrent or Progressive Meningiomas.

UNLABELLED: The standard treatment of meningiomas is surgery or radiotherapy. Complex, especially recurrent or progressive cases, may exhibit tumor growth involving critical neurovascular structures or diffuse growth, resulting in limited efficacy and higher risk of standard treatment. We evaluated whether somatostatin receptor-targeted radionuclide therapy with (90)Y-DOTATOC may be a therapeutic option. METHODS: Fifteen patients with recurrent or progressive meningiomas after multimodal pretreatment or unfavorable medical risk profile were treated with systemic (90)Y-DOTATOC. Endpoints were progression-free survival and toxicity. RESULTS: Usually applied doses were 7,400 MBq/m(2) of (90)Y-DOTATOC in 2 fractions. Mean observation time was 49.7 mo (range, 12-137 mo). Overall median progression-free survival was at least 24 mo. Toxicity was moderate, mostly hematologic (n = 8) and transient. CONCLUSION: (90)Y-DOTATOC therapy is feasible and may represent a promising second- or third-line option for complex meningiomas, which are progressive or otherwise not treatable with a reasonable risk-benefit ratio.