Palliative care for in-patient malignant glioma patients in Germany.

OBJECTIVE: Malignant gliomas impose a significant symptomatic burden on patients and their families. Current guidelines recommend palliative care for patients with advanced tumors within eight weeks of diagnosis, emphasizing early integration for malignant glioma cases. However, the utilization rate of palliative care for these patients in Germany remains unquantified. This study investigates the proportion of malignant glioma patients who either died in a hospital or were transferred to hospice care from 2019 to 2022, and the prevalence of in-patient specialized palliative care interventions. METHODS: In this cross-sectional, retrospective study, we analyzed data from the Institute for the Hospital Remuneration System (InEK GmbH, Siegburg, Germany), covering 2019 to 2022. We included patients with a primary or secondary diagnosis of C71 (malignant glioma) in our analysis. To refine our dataset, we identified cases with dual-coded primary and secondary diagnoses and excluded these to avoid duplication in our final tally. The data extraction process involved detailed scrutiny of hospital records to ascertain the frequency of hospital deaths, hospice transfers, and the provision of complex or specialized palliative care for patients with C71-coded diagnoses. Descriptive statistics and inferential analyses were employed to evaluate the trends and significance of the findings. RESULTS: From 2019 to 2022, of the 101,192 hospital cases involving malignant glioma patients, 6,129 (6% of all cases) resulted in in-hospital mortality, while 2,798 (2.8%) led to hospice transfers. Among these, 10,592 cases (10.5% of total) involved the administration of complex or specialized palliative medical care. This provision rate remained unchanged throughout the COVID-19 pandemic. Notably, significantly lower frequencies of complex or specialized palliative care implementation were observed in patients below 65 years (p < 0.0001) and in male patients (padjusted = 0.016). In cases of in-hospital mortality due to malignant gliomas, 2,479 out of 6,129 cases (40.4%) received specialized palliative care. CONCLUSION: Despite the poor prognosis and complex symptomatology associated with malignant gliomas, only a small proportion of affected patients received advanced palliative care. Specifically, only about 10% of hospitalized patients with malignant gliomas, and approximately 40% of those who succumb to the disease in hospital settings, were afforded complex or specialized palliative care. This discrepancy underscores an urgent need to expand palliative care access for this patient demographic. Additionally, it highlights the importance of further research to identify and address the barriers preventing wider implementation of palliative care in this context.

Development and implementation of a student tumor board as a teaching format for medical students.

PURPOSE: Tumor boards serve as established platforms for interdisciplinary expert discussions and therapeutic recommendations tailored to individual patient characteristics. Despite their significance, medical students often lack exposure to such interdisciplinary discussions as tumor boards are currently not integrated into medical curricula. To address this, we aimed to enhance future physicians' interdisciplinary communication skills and subject-specific knowledge by introducing an interactive series of five linked tumor board seminars within the domain of neuro-oncology. METHODS: We developed a neuro-oncological student tumor board using a flipped-classroom format. The primary objectives of this case-centered approach included fostering an understanding of the tumor board process, active participation in multidisciplinary case discussions, honing appropriate communication strategies, and creating personalized therapy plans that consider inputs from all relevant disciplines, individual patient factors, and ethical considerations. To gauge the effectiveness of the seminar series, we administered structured pre- and post-course questionnaires. RESULTS: Fourteen medical students in third to fifth year participated in the pilot series. Despite its organizational complexity, the interdisciplinary seminars were feasible. Students demonstrated significant growth in competence, aligned with predefined learning objectives. Notably, they appreciated the supportive learning environment and interactive teaching format, which kindled their interest in interdisciplinary oncology. CONCLUSION: Active participation in a student tumor board can empower students to tackle the diverse challenges of caring for cancer patients within an interdisciplinary team during the early stages of their careers. The student tumor board represents an innovative, learner-centered approach to teach interdisciplinary cancer treatment, communication strategies, and ethical aspects of medical practice.

Frequency of social burden and underage children in neuro-oncological patients.

OBJECTIVE: Brain tumours can cause significant burden for patients and their families, including physical, psychological, and social challenges. This burden can be particularly difficult for patients with malignant brain tumours and those with underage children. However, the frequency of social burden among neuro-oncological patients and the proportion of patients with underaged children is currently unknown. The aim of this retrospective study is to determine the frequency of social and family dysfunction among neuro-oncological patients, the percentage of such patients who have underage children, and to assess their associated burden. METHODS: During a 22-month period, all brain tumour patients were asked to complete a short questionnaire that included epidemiological data, the EORTC-qlq-C30 and -BN20 questionnaire, and the distress thermometer. Data were collected and analysed using Prism 9 for macOS (version 9, GraphPad Prism). RESULTS: Our analysis included 881 brain tumour patients, of which 540 were female. Median age was 61 years (ranging from 16 to 88 years). Of all patients, 228 suffered from malignant intracranial tumours. More than half of all patients and more than 65% of patients with malignant tumours reported that their illness or medical treatment interfered with their social activities and family life. Almost 30% of patients reported moderate or severe complaints. About 27% of all patients (and 31% of patients with malignancies) expressed moderate or major concerns that their family life could be disrupted. Among the patients with malignancies, 83.5% of patients had a total of 318 children at the time of tumour diagnosis, with a mean age of 33 ± 0.9. Of these patients with malignancies, 38 (17.9%) had a total of 56 underage children at the time of tumour diagnosis, and currently have 53 underage children. Patients with minor children had more financial worries but less interference of their disease with social activities, less psycho-oncological distress, and a more positive outlook into the future (each, p < 0.0001). They evaluated their general health status and quality of life in the week prior to their current appointment significantly better (each p < 0.0001). CONCLUSION: Our study found that 17.9% of patients with malignant brain tumours have underage children. However, having underage children may actually be a positive resource for these patients, as they show lower distress values and better quality of life.

Would they do it again? Final treatment decisions in malignant brain tumour patients-a caregiver's perspective.

PURPOSE: Overall survival of malignant brain tumour patients has significantly been increased over the last years. However, therapy remains palliative, and side effects should be balanced. Once terminal phase is entered, both patients and caregivers may find it hard to accept, and further therapies are demanded. But little is known about this highly sensitive period. Therefore, we analysed the last therapy decisions from the family caregiver's perspective. Would they support their beloved ones in the same way or would they now recommend a different therapy decision? METHODS: Caregivers of deceased malignant brain tumour patients, treated at our neurooncological centre between 2011 and 2017, were included. We designed a questionnaire to analyse the impact of the last therapy decision (resection, chemotherapy, radiotherapy), focusing on probable repeat of the choice taken and general therapy satisfaction. Independent variables, for example "satisfaction with therapy", were analysed using linear regression analysis, the coefficient of determination R2 and the standardized regression coefficient ß. The binary logistic regression analyses were taken to illustrate relationships with the dichotomously scaled outcome parameter "re-choice of therapy". Odds ratio analyses were used to determine the strength of a relationship between two characteristics. RESULTS: Data from 102 caregivers (life partners (70.6%)) were analysed retrospectively. Each 40% of patients died in a hospice or at home (20% in a hospital). In 67.6% the last therapy was chemotherapy followed by radiotherapy (16.7%) and surgery (15.7%). A positive evaluation of the last therapy was significantly correlated to re-choosing of respective therapy (chemo-/radiotherapy: p = 0.000) and satisfaction with informed consent (p = 0.000). Satisfaction regarding interpersonal contact was significantly correlated to satisfaction with resection (p = 0.000) and chemotherapy (p = 0.000 27 caregivers (28.7%) felt overburdened with this situation). CONCLUSION: This analysis demonstrates a significant correlation between a positive relation of patient/caregiver/physician and the subjective perception of the latest therapy. It underlines the central role of caregivers, who should be involved in therapy discussions. Neurooncologists should be specially trained in communication and psycho-oncology.

Psychooncological distress in low-grade glioma patients-a monocentric study.

BACKGROUND: Patients diagnosed with low-grade glioma (LGG) must live with constant knowledge of an upcoming malignant tumor transformation which may lead to increased anxiety and reduced quality of life. Here, we (1) analyzed the prevalence and risk factors for distress in LGG patients using (2) different screening tools to subsequently (3) evaluate their need for psychological support. METHOD: Patients with LGG-suspicious findings in MRI studies as well as patients with histopathological confirmed LGG were screened using three established self-assessment instruments (Hospital Anxiety and Depression Scale, Distress Thermometer, EORTC-QLQ-C30-BN20). Screening results were correlated with sociodemographic factors. RESULTS: One hundred forty-nine patients (74 men and 75 women) were prospectively included. Patients were further divided into different subgroups regarding the time of screening and diagnosis. An increased level of distress was observed in 20.8% (mean score 1.21, 95% CI 1.15-1.28) of all patients screened by HADS. Significant associated factors were pre-existing psychiatric disorders (p = 0.003) and psychotropic medication (p = 0.029). HRQoL (p = 0.022) and global health item (p = 0.015), as well as future uncertainty (p = 0.047), assessed by the EORTC-QLQ-C30-BN20 were significantly higher in those patients without histopathological diagnosis. Increased distress was significantly correlated with results in chosen sub-items of the HRQoL questionnaire (p < 0.001). CONCLUSIONS: Our results demonstrate the need for frequent distress screening. If specific tools are not available, HRQoL questionnaires can also be used. Patients with pre-existing psychological stress should be offered additional psychooncological support, irrespectively of the time of screening or tumor diagnosis. CLINICAL TRIAL REGISTRATION NUMBER: 4087.

Proposed definition of competencies for surgical neuro-oncology training.

OBJECTIVE: The aim of this work is to define competencies and entrustable professional activities (EPAs) to be imparted within the framework of surgical neuro-oncological residency and fellowship training as well as the education of medical students. Improved and specific training in surgical neuro-oncology promotes neuro-oncological expertise, quality of surgical neuro-oncological treatment and may also contribute to further development of neuro-oncological techniques and treatment protocols. Specific curricula for a surgical neuro-oncologic education have not yet been established. METHODS: We used a consensus-building approach to propose skills, competencies and EPAs to be imparted within the framework of surgical neuro-oncological training. We developed competencies and EPAs suitable for training in surgical neuro-oncology. RESULT: In total, 70 competencies and 8 EPAs for training in surgical neuro-oncology were proposed. EPAs were defined for the management of the deteriorating patient, the management of patients with the diagnosis of a brain tumour, tumour-based resections, function-based surgical resections of brain tumours, the postoperative management of patients, the collaboration as a member of an interdisciplinary and/or -professional team and finally for the care of palliative and dying patients and their families. CONCLUSIONS AND RELEVANCE: The present work should subsequently initiate a discussion about the proposed competencies and EPAs and, together with the following discussion, contribute to the creation of new training concepts in surgical neuro-oncology.

Sudden death in epilepsy: There is room for intracranial pressure.

INTRODUCTION: Sudden unexpected death in patients with epilepsy (SUDEP) remains a poorly understood entity, and it is unclear whether the same pathomechanisms underlie all sudden deaths occurring in patients with epilepsy. One aspect not included in current models of SUDEP is the role of increased intracranial pressure (ICP) which can be observed immediately upon seizure activity in neurosurgical practice. METHODS: We conducted a systematic review of the occurrence of edema in patients with epilepsy reported to have died of sudden death who underwent brain autopsy or postmortem brain imaging and discuss how increased ICP may contribute to clinical features of SUDEP. RESULTS: 19 eligible studies comprising a total of 623 patients were identified. Edema-mostly mild or moderate-was reported in 17% of cases and 74% of studies. 1% (n = 6) of the overall cases were clearly identified as having Dravet syndrome or an SCN1A mutation. In these patients, edema was found in 4 (67%) of cases. CONCLUSION: Edema is regularly found in patients with epilepsy classified to have died from SUDEP. We argue that seizures preceding SUDEP may in certain cases elicit acute edema which may represent an additional contributing factor in the cascade of events leading to sudden death of patients with epilepsy. Furthermore, we hypothesize that mild edema may especially progress to severe edema in patients with sodium channel mutations which may represent an important mechanism to investigate in the context of understanding the significantly elevated risk of SUDEP in patients with SCN1A mutations.

Quantification of PpIX-fluorescence of cerebral metastases: a pilot study.

5-ALA fluorescence-guided surgery (FGS) is a major advance in neuro-oncological surgery. So far, Protoporphyrin IX (PpIX)-fluorescence has been observed in about half of cerebral metastases resected with routinely equipped microscopes during 5-ALA FGS. The aim of the present pilot study was to quantify PpIX-induced fluorescence of cerebral metastases with a spectrometer. We hypothesize that non-fluorescing metastases under the operating microscope may have spectrometrically measurable levels of fluorescence. A second aim was to analyze correlations between quantified 5-ALA fluorescence and histology or primary tumor type, respectively. Standard FGS was performed in all patients. The fluorescence intensity of the metastasis was semi-quantitatively determined in vivo by a senior surgeon using a special surgical microscope equipped for FGS. A systematic spectrometric ex vivo evaluation of tumor specimens and PpIX-induced fluorescence was performed using a spectrometer connected by optic fibers to a handheld probe. Quantification of 5-ALA-derived fluorescence was measured in a standardized manner with direct contact between mini-spectrometer and metastasis. The difference between the maximum PpIX-fluorescence at 635 nm and the baseline fluorescence was defined as the PpIX fluorescence intensity of the metastasis and given in arbitrary units (AU). Diagnosis of a cerebral metastasis was confirmed by histopathological analysis. A total of 29 patients with cerebral metastases were included. According to neuropathological analysis, 11 patients suffered from non-small cell lung cancer, 10 patients from breast cancer, 6 patients from cancer originating in the gastro-intestinal tract, 1 patient suffered from a malignant melanoma and one patient from renal cancer. The mean age was 63 years (37-81 years). 15 patients were female, 14 patients male. 13 cerebral metastases were considered as ALA-positive by the surgeon. In nine metastases, 5-ALA fluorescence was not visible to the naked eye and could only be detected using the spectrometer. The threshold for an ALA signal rated as "positive" by the surgeon was PpIX fluorescence above 1.1 × 106 AU. The mean PpIX fluorescence of all analyzed cerebral metastases was 1.29 × 106 ± 0.23 × 106 AU. After quantification, we observed a significant difference between the mean 5-ALA-derived fluorescence in NSCLC and breast cancer metastases (Mean Diff: - 1.2 × 106; 95% CI of difference: - 2.2 × 106 to - 0.15 × 106; Sidák-adjusted p = 0.026). In our present pilot series, about half of cerebral metastases showed a 5-ALA fluorescence invisible to the naked eye. Over 50% of these non-fluorescent metastases show a residual 5-ALA fluorescence which can be detected and quantified using a spectrometer. Moreover, the quantified 5-ALA signal significantly differed with respect to the primary tumor of the corresponding cerebral metastasis. Further studies should evaluate the predictive value of the 5-ALA signal and if a quantified 5-ALA signal enables a reliable intraoperative differentiation between residual tumor tissue and edematous brain-in particular in metastases with a residual fluorescence signal invisible to the naked eye.

Risk factors for in-brain local progression in elderly patients after resection of cerebral metastases.

Intracranial metastases are the most frequent brain tumor with recurrence rates after treatment of around 40-60%. Age is still considered a determinant of treatment and prognosis in this pathology. Recent studies analyzing the impact of metastasectomy in elderly patients focused on reporting perioperative mortality and morbidity rates but not on the evaluation of oncological outcome parameters. Aim of this study is to determine risk factors for in-brain local recurrence after brain surgery in this sub-population. From October 2009 until September 2016 all patients aged 65 years and above with histopathologically confirmed metastasis after surgical resection were retrospectively studied. Clinical, radiological and perioperative information was collected and statistically analysed. Follow-up consisted of clinical and radiological assessment every 3-months following surgery. 78 patients were included, of these 50% were female (39 patients). Median age was 71 years (66-83). Early postoperative-MRI verified a complete surgical resection in 41 patients (52.6%) and showed a tumor-remnant in 15 patients (19.2%). In 22 patients the MRI result was inconclusive (28.2%). None of the patients experienced severe complications due to surgery. The median postoperative NIHSS was adequate 1 ± 1.4 (0-6), nonetheless, insignificantly improved in comparison to the preoperative NIHSS (p = 0.16). A total of 20 patients (25.6%) presented local recurrence. The only statistically significant factor for development of local in-brain recurrence after resection of cerebral metastases in patients above 65 years of age was a tumor-remnant in the early postoperative MRI (p = 0.00005). Median overall survival was 13 months. Local in-brain recurrence after surgical resection of a cerebral metastasis in patients above 65 years of age was 25.6%. In our analysis, tumor-remnant in early postoperative MRI is the only risk factor for local in-brain recurrence. Oncological parameters in the present cohort do not seem to differ from recent phase III studies with non-geriatric patients. Nevertheless, controlled studies on the impact of metastasectomy in elderly patients delivering high quality reliable data are required.

Is 5-ALA fluorescence of cerebral metastases a prognostic factor for local recurrence and overall survival?

BACKGROUND: 5-Aminolevulinic acid (5-ALA) fluorescence-guided resection technique was first introduced for malignant glioma. However, the impact of the 5-ALA fluorescence behaviour of cerebral metastases is still unclear. Aim of this study was to determine the impact of PpIX-fluorescence on the local progression-free and overall survival. MATERIALS AND METHODS: A secondary analysis was performed and included an updated follow-up of 136 patients comprised in two previous studies. Additionally, 82 new patients were included. All patients underwent surgical resection of cerebral metastasis and intraoperative estimation of 5-ALA-induced fluorescence. The 5-ALA fluorescence behaviour of cerebral metastases was correlated with the rate of local recurrences, the local progression-free and overall survival. RESULTS: 218 patients suffering from cerebral metastatic spread fulfilled the inclusion criteria and were analysed: complete surgical resection could be achieved in 123/218 patients (56.4%). Dichotomised degree of surgical resection (complete vs. incomplete or questionable complete resection) was not related to dichotomized 5-ALA fluorescence of cerebral metastases (p = 0.66). 51 patients (23.4%) developed a local in-brain progression within or at the border of the resection cavity. Of these, 8 patients showed a PpIX-fluorescent metastasis. There was a trend towards a correlation between a higher local in-brain progression in PpIX-non-fluorescent metastases (p = 0.03). Median time to local in-brain progression was 4 ± 11 months. PpIX-fluorescent and PpIX-non-fluorescent metastases showed a significantly different progression-free survival (p = 0.01). PpIX-positive and -negative metastases showed a significantly different overall survival (20 and 14 months respectively; p = 0.006). CONCLUSION: The 5-ALA fluorescence behaviour was related to the local progression-free and the overall survival in the present retrospective series and might be considered a prognostic marker. Further studies are required to appreciate the oncological impact of the 5-ALA induced fluorescence behaviour of cerebral metastases.