In 2020, the German Federal Constitutional Court declared the criminal prohibition of assisted suicide as unconstitutional, thereby abolishing previous restrictions. Since then, requests and cases have increased steadily. To ensure transparency and traceability of national assisted suicide practices, systematic and reliable data are required. However, no comprehensive registry currently exists to document and analyze assisted suicide cases in Germany, resulting in a significant data gap for epidemiology, health reporting, and healthcare development. The development, implementation, and evaluation of such a registry is essential to better understand current practices, identify challenges, and improve prevention and support strategies. Iterative, mixed-methods, design-based implementation study with five work packages: 1. conceptual, ethical, and legal development of registry content through a scoping review and a group Delphi process; 2. establishment of the legal, ethical, and technical framework of the registry using an iterative, design-based approach; 3. evaluating and refining the registry through a formative mixed-methods design combining quantitative user surveys and web analytics with qualitative think-aloud and retrospective interviews; 4. exploring barriers to the adoption, continuation, and use of the registry through quantitative surveys and in-depth qualitative interviews with potential users; 5. strategic development, dissemination, and integration of the registry within existing healthcare and suicide prevention structures. The study involves expert consultations and stakeholder engagement and is conducted by a multidisciplinary consortium of palliative care and suicide prevention experts in Germany. The establishment of a permanent registry for assisted suicide could substantially improve transparency and empirical knowledge in a highly sensitive and ethically complex field. Systematic documentation may help identify needs, vulnerabilities, and structural challenges faced by individuals considering assisted suicide. In the long term, the findings derived from the registry are expected to contribute to the development of targeted support services in Germany. The study results may also provide valuable insights for other countries facing comparable ethical, legal, and regulatory challenges. Registered on 25 October 2025 in the BQS (Institute for Quality and Patient Safety) registry, No. 2020467 and on 29 April 2026 in the German Clinical Trials Register (DRKS), No. DRKS00040174.

Abstract Background Multiple sclerosis is associated with complex individual disease trajectories with a high symptom burden affecting physical, psychological and social life, accompanied by fractured biographies and increased suicide rates. In this complex situation coordinating and providing necessary health and social services and treatments by themselves is often perceived as unmanageable. Care and case management (CCM) aims to ensure optimal care in all dimensions of life. The aim of this sub-study of the COCOS-MS (Communication, coordination and security for people with severe Multiple Sclerosis) trial was to evaluate the CCM intervention at the individual and overall level. Methods The analysis of the long-term cross-sectoral CCM intervention included: descriptive statistical analysis of the individually defined goals and actions taken together with the CCM and the statistical evaluation of the evolution of unmet needs of people with severe MS (PwsMS) and caregivers considering physical health, mental health, self-sufficiency, social situation and participation utilizing the sign test (α < 0.05) and cross tables. The data were analyzed in accordance with the modified intention-to-treat principle. Results Compliant to protocol, a total of 40 PwsMS were randomized to the intervention group; 18 caregivers of these PwsMS also participated. In 80% the individually set goals were realized during the CCM intervention. They were mostly related to healthcare, organizational issues or general aspects like: receiving information). The participants benefited from the CCM in all assessed dimensions, which was especially reflected in a significant reduction of unmet needs in relation to: MS related physical health (p = 0.039), medical, nursing and therapeutic care (p = 0.008), and increased autonomy regarding the pursuit of hobbies and interests (p = 0.002). Across 30 sub-domains, on average 6.3 improvements and 1.6 deteriorations per sub-domains were recorded on PwsMSs’ side. Conclusions The CCM is a worthwhile approach to the comprehensive networking of health and social structures. It helps PwsMS to manage their disease and its associated problems more effectively and broadly. Thereby, they gain resources for their life outside their illness. Improved self-sufficiency and social participation lead to a consolidated identity. This could increase feelings of dignity and counteract life-denying thoughts. Trial registration German Register for Clinical Studies (DRKS) (DRKS00022771, 11th January 2021).

Background Although palliative and hospice care are essential for individuals with life-limiting illnesses, academic inpatient hospices, which combine care with research and education, remain rare. This study explores the experiences, perceptions, and expectations of patients and their relatives regarding palliative and hospice care with the aim of informing the development of an academic inpatient hospice. Methods Semi-structured individual and dyadic interviews were conducted with patients and relatives who had experience with palliative and hospice care services in an academic setting in Germany. The data were analyzed using qualitative content analysis. Results A total of 14 interviews were conducted with 17 participants (10 patients, 7 relatives). Participants reported initial uncertainty and skepticism regarding palliative and hospice care; however, direct experiences led to more positive attitudes. Key aspects valued included psychosocial support, effective symptom management, and a non-clinical atmosphere. The preservation of autonomy and dignity, meaningful personal interactions, and the active involvement of relatives were considered essential. The transition from a hospital-based palliative care unit to an inpatient hospice was often perceived as abrupt and emotionally challenging, creating a risk of losing established familiarity. Participants responded positively to the idea of an academic inpatient hospice. They highlighted the potential benefits of integrating palliative and hospice services within a unified and familiar environment, including smoother transitions and continuity of care. Conclusions An academic inpatient hospice offers opportunities to address end-of-life care needs by strengthening existing structures and ensuring continuity and comprehensiveness of care. It can support patient-centered care, provide a platform for education and research, and promote greater public awareness and understanding of palliative and hospice care.

BACKGROUND:People with severe multiple sclerosis (PsMS) have multidimensional, complex needs. COCOS-MS is an exploratory study of the effect of cross-sectoral care and case management (CCM) on these patients' quality of life, palliative care needs, and psychological distress, as well as caregivers' burden. METHODS:We conducted a randomized, controlled, phase II trial (DRKS00022771) with two parallel treatment arms: standard care versus CCM in addition to standard care over a 12-month period. A trial-specific CCM manual was used. The target variables were recorded in standardized fashion at baseline (T0) and every three months thereafter (T1 until the end of the intervention at T4, then T5 three months after the end of the intervention to determine sustainability). The primary endpoint was the change in the patients' quality of life (HALEMS) from baseline to month 12 in a group comparison. A modified intention-to-treat (mITT) was performed based on a mixed linear model with repeated measures over time (ARH1-structured covariance matrix). Values of p less than 0.05 were considered significant. RESULTS:80 PsMS were randomly assigned 1:1 to one of the two treatment arms (male: female 1:2, median age 55 years [IQR 49-62], EDSS 6.5 [6-7.5], dropout rate 10%). There was no significant improvement in HALEMS after one year (T4) in the group comparison (-0.08 [-0.31, 0.15], p = 0.503; NNT = 22). Secondary endpoints such as subjective health status, psychological distress, and palliative care needs showed a clear response at the end of the intervention. After the intervention ended, the values approached the baseline level. CONCLUSION:The primary endpoint did not reach significance in this health services research feasibility study. For further development of the study design, the focus will be on the psychological and palliative factors in which PsMS-a reference group for long-term neurological conditions-were found to benefit from the CCM.

OBJECTIVES:Standardized measures to evaluate neurological patients in palliative care are missing. The Integrated Palliative Outcome Scale, a self-report tailored for neurological patients (IPOS Neuro-S8) helps identify symptom burden but lacks validation in German. This study aimed to validate the IPOS Neuro-S8 in severely affected multiple sclerosis (MS) patients. METHODS:This validation study is a secondary analysis of data from a clinical phase II intervention study with severely affected MS patients. The original study enrolled German-speaking patients aged 18 with severe MS who receive an escalating immunotherapeutic agent and/or exhibit a high level of disability were recruited from the administrative district Cologne (#DRKS00021783). In this validation study, we evaluated construct, discriminant, and convergent validity, internal consistency, test-retest reliability, and sensitivity to change of the IPOS Neuro-S8, using the "Hamburger Lebensqualitätsmessinstrument" (HALEMS), and the Hospice and Palliative Care Evaluation supplemented by neurological symptoms (HOPE+) as comparison measures. RESULTS:Data from 80 MS patients (mean age 56, SD = 11) were analyzed. Exploratory and confirmatory factor analyses revealed a 3-factor structure (r = 0.34-0.63), reflecting distinct clinical patterns, i.e., breath-mouth connection, pain-sleep cycle, and nausea-vomiting link. Significant convergent validity to hypothesized total score of the HOPE+ (rs(78) = 0.71, p < 0.001) and good discriminant validity using the HALEMS total score (rs(78) = 0.48, p < 0.001) were observed. Correlation with physical symptoms of the HALEMS was stronger than with nonphysical aspects. Internal consistency (Cronbach's α = 0.67) and test-retest reliability (intraclass coefficient = 0.75) were acceptable. SIGNIFICANCE OF RESULTS:IPOS Neuro-S8 displays promising psychometric properties for assessing palliative care symptoms in severe MS, a model for other severe neurological diseases due to MS's broad central nervous involvement, allowing findings to be transferable to other neurological diseases. A criterion for minimal clinically important difference was established to evaluate the sensitivity to change. Additional validation across different neurological conditions and disease severities is warranted to enhance generalizability and clinical utility.

Purpose Especially in Europe, amino acid PET is increasingly integrated into multidisciplinary neuro-oncological tumor boards (MNTBs) to overcome diagnostic uncertainties such as treatment-related changes. We evaluated the accuracy of MNTB decisions that included the O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET information compared with FET PET results alone to differentiate tumor relapse from treatment-related changes. Patients and Methods In a single academic center, we retrospectively evaluated 180 MNTB decisions of 151 patients with CNS WHO grade 3 or 4 gliomas (n = 122) or brain metastases (n = 29) presenting equivocal MRI findings following anticancer treatment. All patients underwent FET PET imaging besides MRI before MNTB discussion. Additionally, the patient’s clinical status and pretreatment were considered for decision-making. The diagnostic performance was calculated for FET PET findings alone and MNTB decisions that included FET PET results using 2 × 2 contingency tables. MNTB decisions were validated using the neuropathological result in 43% (n = 78) or clinicoradiologically in 57% (n = 102). Results FET PET results alone yielded an accuracy of 87% (sensitivity, 90%; specificity, 65%; positive predictive value, 95%). When integrating FET PET results for decision-making in the MNTB setting, the accuracy increased to 95% (sensitivity, 99%; specificity, 70%; positive predictive value, 96%; P = 0.002). In MNTB decisions concerning glioblastoma patients, the median survival was 2.4 times longer when FET PET suggested treatment-related changes (15.6 vs 6.4 months; P = 0.009). Conclusions Our results suggest that MNTB discussion further enhances the FET PET value for identifying brain tumor relapse. A prospective evaluation of FET PET results with and without integration in an MNTB is warranted.

Background: People with severe multiple sclerosis (PsMS) have multidimensional, complex needs. COCOS-MS is an exploratory study of the effect of cross-sectoral care and case management (CCM) on these patients' quality of life, palliative care needs, and psychological distress, as well as caregivers' burden. Methods: We conducted a randomized, controlled, phase II trial (DRKS00022771) with two parallel treatment arms: standard care versus CCM in addition to standard care over a 12-month period. A trial-specific CCM manual was used. The target variables were recorded in standardized fashion at baseline (T0) and every three months thereafter (T1 until the end of the intervention at T4, then T5 three months after the end of the intervention to determine sustainability). The primary endpoint was the change in the patients' quality of life (HALEMS) from baseline to month 12 in a group comparison. A modified intention-to-treat (mITT) was performed based on a mixed linear model with repeated measures over time (ARH1-structured covariance matrix). Values of p less than 0.05 were considered significant. Results: 80 PsMS were randomly assigned 1:1 to one of the two treatment arms (male: female 1:2, median age 55 years [IQR 49-62], EDSS 6.5 [6-7.5], dropout rate 10%). There was no significant improvement in HALEMS after one year (T4) in the group com parison (-0.08 [-0.31, 0.15], p = 0.503; NNT = 22). Secondary endpoints such as subjective health status, psychological distress, and palliative care needs showed a clear response at the end of the intervention. After the intervention ended, the values approached the baseline level. Conclusion: The primary endpoint did not reach significance in this health services research feasibility study. For further development of the study design, the focus will be on the psychological and palliative factors in which PsMS-a reference group for long-term neurological conditions-were found to benefit from the CCM.

Background Persons with severe Multiple Sclerosis (PwsMS) face complex needs and daily limitations that make it challenging to receive optimal care. The implementation and coordination of health care, social services, and support in financial affairs can be particularly time consuming and burdensome for both PwsMS and caregivers. Care and case management (CCM) helps ensure optimal individual care as well as care at a higher-level. The goal of the current qualitative study was to determine the experiences of PwsMS, caregivers and health care specialists (HCSs) with the CCM.Methods In the current qualitative sub study, as part of a larger trial, in-depth semi-structured interviews with PwsMS, caregivers and HCSs who had been in contact with the CCM were conducted between 02/2022 and 01/2023. Data was transcribed, pseudonymized, tested for saturation and analyzed using structuring content analysis according to Kuckartz. Sociodemographic and interview characteristics were analyzed descriptively.Results Thirteen PwsMS, 12 caregivers and 10 HCSs completed interviews. Main categories of CCM functions were derived deductively: (1) gatekeeper function, (2) broker function, (3) advocacy function, (4) outlook on CCM in standard care. Subcategories were then derived inductively from the interview material. 852 segments were coded. Participants appreciated the CCM as a continuous and objective contact person, a person of trust (92 codes), a competent source of information and advice (on MS) (68 codes) and comprehensive cross-insurance support (128 codes), relieving and supporting PwsMS, their caregivers and HCSs (67 codes).Conclusions Through the cross-sectoral continuous support in health-related, social, financial and everyday bureaucratic matters, the CCM provides comprehensive and overriding support and relief for PwsMS, caregivers and HCSs. This intervention bears the potential to be fine-tuned and applied to similar complex patient groups.Trial registration The study was approved by the Ethics Committee of the University of Cologne (#20-1436), registered at the German Register for Clinical Studies (DRKS00022771) and in accordance with the Declaration of Helsinki.

Persons with MS (PwMS) ≥ 55 years are underrepresented in therapy studies leading to a lack of evidence. To study the subgroup of PwMS ≥ 55 years in the German MS registry in comparison with PwMS < 55 years. Endpoints of interest were the grade of disability, leading symptoms, clinical and magnetic resonance imaging activity, and use of disease modifying therapy. At the time of analysis, data from 40,428 PwMS were available for analysis. In PwMS aged ≥ 65 and PwMS aged ≥ 55 to 64 years, compared with PwMS aged < 55 years, the mean Expanded Disability Status Scale Scores were higher (5.3, 4.2 and 2.7, respectively), while the proportion of individuals with current use of disease modifying therapy was lower (42.6

OBJECTIVES:Standardized measures for assessing neurological patients needing palliative care remain scarce. The Integrated Palliative care Outcome Scale for neurological patients in its short form (IPOS Neuro-S8) helps assess and identify patients' symptom burden and needs early but has not yet been validated in German. The aim was to culturally adapt and translate the IPOS Neuro-S8 into the German health-care context and evaluate its face and content validity. METHODS:Cultural adaptation study following the first 6 out of 8 phases of the Palliative care Outcome Scale measures manual: (1) conceptual definition, (2) forward translation to German, (3) backward translation to English, (4) expert review, (5) cognitive debriefing, (6) proofreading. Neurological patients needing palliative care and clinical staff of the Department of Palliative Medicine or Neurology of the University Hospital of Cologne were included. Data were analyzed using thematic content analysis and descriptive statistics. RESULTS:A total of 13 patients and 16 clinical staff participated in this study. The expert review panel (phase 4) consisted of 11 additional members. While patients (n = 9) and clinical staff (n = 11) confirmed that the IPOS Neuro-S8 is an intelligible tool that is well accepted (phase 5), some linguistic and cultural differences were found between the original English and German versions. These mainly concerned the items mouth problems and spasms. SIGNIFICANCE OF RESULTS:The German version of the IPOS Neuro-S8 has demonstrated face and content validity and captures relevant symptoms of neurological patients needing palliative care. Its psychometric properties, including construct and criterion validity, will be investigated next.

IntroductionPatients with multiple sclerosis (MS) have complex needs that range from organising one’s everyday life to measures of disease-specific therapy monitoring to palliative care. Patients with MS are likely to depend on multiple healthcare providers and various authorities, which are often difficult to coordinate. Thus, they will probably benefit from comprehensive cross-sectoral coordination of services provided by care and case management (CCM). Though studies have shown that case management improves quality of life (QoL), functional status and reduces service use, such benefits have not yet been investigated in severely affected patients with MS. In this explorative phase ll clinical trial, we evaluated a CCM with long-term, cross-sectoral and outreaching services and, in addition, considered the unit of care (patients and caregivers).Methods and analysisEighty patients with MS and their caregivers will be randomly assigned to either the control (standard care) or the intervention group (standard care plus CCM (for 12 months)). Regular data assessments will be done at baseline and then at 3-month intervals. As primary outcome, we will evaluate patients’ QoL. Secondary outcomes are patients’ treatment-related risk perception, palliative care needs, anxiety/depression, use of healthcare services, caregivers’ burden and QoL, meeting patients’ and caregivers’ needs, and evaluating the CCM intervention. We will also evaluate CCM through individual interviews and focus groups. The sample size calculation is based on a standardised effect of 0.5, and one baseline and four follow-up assessments (with correlation 0.5). Linear mixed models for repeated measures will be applied to analyse changes in quantitative outcomes over time. Multiple imputation approaches are taken to assess the robustness of the results. The explorative approach (phase ll clinical trial) with embedded qualitative research will allow for the development of a final design for a confirmative phase lll trial.Ethics and disseminationThe trial will be conducted under the Declaration of Helsinki and has been approved by the Ethics Commission of Cologne University’s Faculty of Medicine. Trial results will be published in an open-access scientific journal and presented at conferences.Trial registration numberGerman Register for Clinical Studies (DRKS) (DRKS00022771).

Visual Abstract In light of increasing health-care costs, higher medical expenses should be justified socioeconomically. Therefore, we calculated the effectiveness and cost effectiveness of PET using the radiolabeled amino acid O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) compared with conventional MRI for early identification of responders to adjuvant temozolomide chemotherapy. A recently published study in isocitrate dehydrogenase wild-type glioma patients suggested that 18F-FET PET parameter changes predicted a significantly longer survival already after 2 cycles whereas MRI changes were not significant. Methods: To determine the effectiveness and cost effectiveness of serial 18F-FET PET imaging, we analyzed published clinical data and calculated the associated costs from the perspective of the German Statutory Health Insurance system. Based on a decision-tree model, the effectiveness of 18F-FET PET and MRI was calculated—that is, the probability to correctly identify a responder as defined by an overall survival of at least 15 mo. To determine the cost effectiveness, the incremental cost effectiveness ratio (ICER) was calculated—that is, the cost for each additionally identified responder by 18F-FET PET who would have remained undetected by MRI. The robustness of the results was tested by deterministic and probabilistic Monte Carlo sensitivity analyses. Results: Compared with MRI, 18F-FET PET increased the rate of correctly identified responders to chemotherapy by 26%; thus, 4 patients needed to be examined by 18F-FET PET to identify 1 additional responder. Considering the respective costs for serial 18F-FET PET and MRI, the ICER resulted in €4,396.83 for each additional correctly identified responder by 18F-FET PET. Sensitivity analyses confirmed the robustness of the results. Conclusion: In contrast to conventional MRI, the model suggests that 18F-FET PET is cost-effective in terms of ICER values. Considering the high cost of temozolomide, the integration of 18F-FET PET has the potential to avoid premature chemotherapy discontinuation at reasonable cost.

Purpose/Objectives: Care and case management (CCM) aims to provide optimal care for patients and their caregivers on an individual and superordinate level of health care providers and authorities. To facilitate a clear and systematic CCM process as part of a clinical study intervention, a semistructured manual is the prerequisite. Primary Practice Setting(s): The ongoing COCOS-MS (Communication, Coordination and Security for People with Multiple Sclerosis) study is a randomized controlled Phase II clinical intervention study. The CCM manual is being tested on the intervention group consisting of severely affected individuals with multiple sclerosis (MS; Expanded Disability Status Scale [EDSS] >5) and their caregivers receiving CCM for 12 months in addition to standard care. The intervention comprises monthly personal visits and weekly telephone calls during which the CCM manual is applied. Findings/Conclusions: The CCM manual has been developed on the basis of previous literature and well-established questionnaires following theoretical aspects and prior scientific work covering individual domains of life of people with MS. Within the COCOS-MS study, its feasibility is being tested meticulously. It allows for a standardized assessment while being tailored to the individual. At the end of the intervention period, it will be analyzed statistically and qualitatively. Consequently, conclusions can be drawn as to whether the CCM manual is feasible or has to be adapted for use in standard care after analyzation. Implications for Case Management Practice: The CCM manual serves as a tool for the continuous, long-term, cross-sectoral care for patients suffering from severe MS and their caregivers. The manual provides guidance in adequately addressing patients' complex symptoms, problems, and needs, as well as assessing existing resources both at the individual patient level and at a superordinate level.

O-(2-[18F]fluoroethyl)-L-tyrosine (FET) is a widely used amino acid tracer for positron emission tomography (PET) imaging of brain tumours. This retrospective study and survey aimed to analyse our extensive database regarding the development of FET PET investigations, indications, and the referring physicians’ rating concerning the role of FET PET in the clinical decision-making process. Between 2006 and 2019, we performed 6534 FET PET scans on 3928 different patients against a backdrop of growing demand for FET PET. In 2019, indications for the use of FET PET were as follows: suspected recurrent glioma (46%), unclear brain lesions (20%), treatment monitoring (19%), and suspected recurrent brain metastasis (13%). The referring physicians were neurosurgeons (60%), neurologists (19%), radiation oncologists (11%), general oncologists (3%), and other physicians (7%). Most patients travelled 50 to 75 km, but 9% travelled more than 200 km. The role of FET PET in decision-making in clinical practice was evaluated by a questionnaire consisting of 30 questions, which was filled out by 23 referring physicians with long experience in FET PET. Fifty to seventy per cent rated FET PET as being important for different aspects of the assessment of newly diagnosed gliomas, including differential diagnosis, delineation of tumour extent for biopsy guidance, and treatment planning such as surgery or radiotherapy, 95% for the diagnosis of recurrent glioma, and 68% for the diagnosis of recurrent brain metastases. Approximately 50% of the referring physicians rated FET PET as necessary for treatment monitoring in patients with glioma or brain metastases. All referring physicians stated that the availability of FET PET is essential and that it should be approved for routine use. Although the present analysis is limited by the fact that only physicians who frequently referred patients for FET PET participated in the survey, the results confirm the high relevance of FET PET in the clinical diagnosis of brain tumours and support the need for its approval for routine use.

Background: The goal of this study was to compare the value of contrast-enhanced MRI and O-(2-[F-18]fluoroethyl)-L-tyrosine (F-18-FET) PET for response assessment in gliomapatients after adjuvant temozolomide chemotherapy (TMZ). Methods: After biopsy or resection and completion of radiotherapywith concomitant TMZ, 41 newly diagnosed andhistomolecularlycharacterizedgliomapatients (glioblastoma, 90%; age range, 20-79 y) were subsequently treated with adjuvant TMZ. MR and F-18-FETPET imagingwereperformedatbaseline andafter the second cycle of adjuvant TMZ. We obtained F-18-FETmetabolic tumor volumes (MTVs) as well as mean and maximum tumor-to-brain ratios (TBRmean and TBRmax, respectively). Threshold values of F-18-FET PET parameters to predict outcome were established by receiver-operating-characteristic analyses using a median progression-free survival (PFS) of >= 9 mo and overall survival (OS) of >= 15 mo as reference. MRI response assessment was based on the Response Assessment in Neuro-Oncology (RANO) working group criteria. The predictive value of changes of F-18-FET PET andMRI parameters on survival was evaluated subsequently using univariate andmultivariate survival estimates. Results: After 2 cycles of adjuvant TMZ chemotherapy, a treatmentinduced reduction of MTV and TBRmax predicted a significantly longer PFS and OS (both P <= 0.03; univariate survival analyses) whereas RANO criteria were not significant (P = 0.05). Multivariate survival analysis revealed that TBRmax changes predicted a prolonged PFS (P > 0.012) and changes of MTV a prolonged OS (P > 0.005) independent of O-6-methylguanine-DNA-methyltransferase promoter methylation and other strong prognostic factors. Conclusion: Changes of F-18-FET PET parameters appear to be helpful for identifying responders to adjuvant TMZ early after treatment initiation.

The goal of this prospective study was to compare the value of conventional MRI and O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET for response assessment in patients with malignant glioma treated with first-line adjuvant temozolomide chemotherapy (TMZ). After biopsy/resection and completion of radiotherapy with concomitant temozolomide, 34 malignant glioma patients (glioblastoma, n=31; IDH-wildtype anaplastic astrocytoma, n=2; H3K27-mutated midline glioma, n=1) (age range, 20–66 years) were subsequently treated with adjuvant TMZ (5/28). FET-PET scans were performed at baseline and after 10–12 weeks. The first follow-up MRI after radiotherapy (9 ± 3 weeks) was compared with the early postoperative MRI. We obtained FET metabolic tumor volumes (MTV) and tumor/brain ratios (TBR). Threshold values of FET-PET parameters for treatment response were established by ROC analyses using the progression-free survival (PFS) ≤/>9 months as reference. MRI response assessment was based on RANO criteria. The predictive ability of FET-PET thresholds and MRI changes on early response assessment was evaluated subsequently concerning PFS using univariate survival estimates. Relative TBR changes were not predictive for a PFS>9 months (P>0.05), whereas the absolute MTV at follow-up significantly predicted a PFS>9 months (P=0.016; threshold, 14.5 ml). The relative MTV change enabled the most significant PFS prediction. Responders defined by relative MTV changes (threshold, ≤0%) had a significantly 2-fold longer PFS than non-responders (16 vs. 8 months, P=0.003). RANO criteria at the first follow-up MRI after radiotherapy were not predictive for a PFS>9 months (P=0.260). CONCLUSIONS: FET-PET appears to be useful for identifying responders to adjuvant TMZ early after treatment initiation.

Novel therapeutic targets in malignant glioma patients are urgently needed. Point mutations of the v-Raf murine sarcoma viral oncogene homolog B (BRAF) gene occur predominantly in melanoma patients, but may also occur in gliomas. Thus, this is a target of great interest for this group of patients. In a nine-year-old male patient, an anaplastic astrocytoma in the left temporoparietal region was diagnosed histologically. After first-and second-line treatment, a malignant progression to a secondary glioblastoma was observed ten years after the initial diagnosis. Within the following seven years, all other conventional treatment options were exhausted. At this time point, recurrent tumor histology revealed an epithelioid glioblastoma, without a mutation in the isocitrate dehydrogenase gene (IDH wild-type). In order to identify a potential target for an experimental salvage therapy, mutational tumor analysis showed a BRAF V600E mutation. Consecutively, dabrafenib treatment was initiated. The patient remained clinically stable, and follow-up magnetic resonance images (MRI) were consistent with "Stable Disease" according to the Response Assessment in Neuro-Oncology Working Group (RANO) criteria for the following ten months until tumor progression was detected. The patient died 16 months after dabrafenib treatment initiation. Particularly in younger glioma patients as well as in patients with an epithelioid glioblastoma, screening for a V600E BRAF mutation is promising since, in these cases, targeted therapy with BRAF inhibitors seems to be a useful salvage treatment option.

The goal of this prospective study was to compare the value of both conventional MRI and O-(2-18F-fluoroethyl)-L-tyrosine (FET) PET for response evaluation in glioblastoma patients treated with bevacizumab plus lomustine (BEV/LOM) at first progression.