Association of Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination With Extension of Survival Among Patients With Newly Diagnosed and Recurrent Glioblastoma: A Phase 3 Prospective Externally Controlled Cohort Trial.

Importance: Glioblastoma is the most lethal primary brain cancer. Clinical outcomes for glioblastoma remain poor, and new treatments are needed. Objective: To investigate whether adding autologous tumor lysate-loaded dendritic cell vaccine (DCVax-L) to standard of care (SOC) extends survival among patients with glioblastoma. Design, Setting, and Participants: This phase 3, prospective, externally controlled nonrandomized trial compared overall survival (OS) in patients with newly diagnosed glioblastoma (nGBM) and recurrent glioblastoma (rGBM) treated with DCVax-L plus SOC vs contemporaneous matched external control patients treated with SOC. This international, multicenter trial was conducted at 94 sites in 4 countries from August 2007 to November 2015. Data analysis was conducted from October 2020 to September 2021. Interventions: The active treatment was DCVax-L plus SOC temozolomide. The nGBM external control patients received SOC temozolomide and placebo; the rGBM external controls received approved rGBM therapies. Main Outcomes and Measures: The primary and secondary end points compared overall survival (OS) in nGBM and rGBM, respectively, with contemporaneous matched external control populations from the control groups of other formal randomized clinical trials. Results: A total of 331 patients were enrolled in the trial, with 232 randomized to the DCVax-L group and 99 to the placebo group. Median OS (mOS) for the 232 patients with nGBM receiving DCVax-L was 19.3 (95% CI, 17.5-21.3) months from randomization (22.4 months from surgery) vs 16.5 (95% CI, 16.0-17.5) months from randomization in control patients (HR = 0.80; 98% CI, 0.00-0.94; P = .002). Survival at 48 months from randomization was 15.7% vs 9.9%, and at 60 months, it was 13.0% vs 5.7%. For 64 patients with rGBM receiving DCVax-L, mOS was 13.2 (95% CI, 9.7-16.8) months from relapse vs 7.8 (95% CI, 7.2-8.2) months among control patients (HR, 0.58; 98% CI, 0.00-0.76; P < .001). Survival at 24 and 30 months after recurrence was 20.7% vs 9.6% and 11.1% vs 5.1%, respectively. Survival was improved in patients with nGBM with methylated MGMT receiving DCVax-L compared with external control patients (HR, 0.74; 98% CI, 0.55-1.00; P = .03). Conclusions and Relevance: In this study, adding DCVax-L to SOC resulted in clinically meaningful and statistically significant extension of survival for patients with both nGBM and rGBM compared with contemporaneous, matched external controls who received SOC alone. Trial Registration: ClinicalTrials.gov Identifier: NCT00045968.

Resilience in Lower Grade Glioma Patients.

Current data show that resilience is an important factor in cancer patients' well-being. We aim to explore the resilience of patients with lower grade glioma (LGG) and the potentially influencing factors. We performed a cross-sectional assessment of adult patients with LGG who were enrolled in the LoG-Glio registry. By phone interview, we administered the following measures: Resilience Scale (RS-13), distress thermometer, Montreal Cognitive Assessment Test for visually impaired patients (MoCA-Blind), internalized stigmatization by brain tumor (ISBI), Eastern Cooperative Oncological Group performance status (ECOG), patients' perspective questionnaire (PPQ) and typical clinical parameters. We calculated correlations and multivariate regression models. Of 74 patients who were assessed, 38% of those showed a low level of resilience. Our results revealed significant correlations of resilience with distress (p < 0.001, −0.49), MOCA (p = 0.003, 0.342), ECOG (p < 0.001, −0.602), stigmatization (p < 0.001, −0.558), pain (p < 0.001, −0.524), and occupation (p = 0.007, 0.329). In multivariate analyses, resilience was negatively associated with elevated ECOG (p = 0.020, ß = −0.383) and stigmatization levels (p = 0.008, ß = −0.350). Occupation showed a tendency towards a significant association with resilience (p = 0.088, ß = −0.254). Overall, low resilience affected more than one third of our cohort. Low functional status is a specific risk factor for low resilience. The relevant influence of stigmatization on resilience is a novel finding for patients suffering from a glioma and should be routinely identified and targeted in clinical routine.

Eloquent Lower Grade Gliomas, a Highly Vulnerable Cohort: Assessment of Patients' Functional Outcome After Surgery Based on the LoG-Glio Registry.

Majority of lower grade glioma (LGG) are located eloquently rendering surgical resection challenging. Aim of our study was to assess rate of permanent deficits and its predisposing risk factors. We retrieved 83 patients harboring an eloquently located LGGs from the prospective LoG-Glio Database. Patients without surgery or incomplete postoperative data were excluded. Sign rank test, explorative correlations by Spearman ρ and multivariable regression for new postoperative deficits were calculated. Eloquent region involved predominantly motor (45%) and language (40%). At first follow up after 3 months permanent neuro-logical deficits (NDs) were noted in 39%. Mild deficits remained in 29% and severe deficits in 10%. Complete tumor removal (CTR) was successfully in 62% of intended cases. Postoperative and 3-month follow up National Institute of Health Stroke Score (NIHSS) showed significantly lower values than preoperatively (p<0.001). 38% cases showed a decreased NIHSS at 3-month, while occurrence was only 14% at 9-12-month follow up. 6/7 patients with mild aphasia recovered after 9-12 months, while motor deficits present at 3-month follow up were persistent in majority of patients. Eastern oncology group functional status (ECOG) significantly decreased by surgery (p < 0.001) in 31% of cases. Between 3-month and 9-12-months follow up no significant improvement was seen. In the multivariable model CTR (p=0.019, OR 31.9), and ECOG>0 (p=0.021, OR 8.5) were independent predictors for permanent postoperative deficit according to NIHSS at 3-month according to multivariable regression model. Patients harboring eloquently located LGG are highly vulnerable for permanent deficits. Almost one third of patients have a permanent reduction of their functional status based on ECOG. Risk of an extended resection has to be balanced with the respective oncological benefit. Especially, patients with impaired pre-operative status are at risk for new permanent deficits. There is a relevant improvement of neurological symptoms in the first year after surgery, especially for patients with slight aphasia.

Glioma patients in outpatient care-optimization of psychosocial care in neuro-oncological patients (GLIOPT): Protocol for a cluster randomized controlled trial.

BACKGROUND: Patients with high-grade gliomas (HGG) often suffer from high distress and require psychosocial support. However, due to neurological and neurocognitive deficits, adequate assessment of distress and support needs remains challenging in clinical practice. The objective of the present study is to investigate whether a systematic implementation of signaling questions into the routine outpatient consultation will be helpful to bridge this gap. METHODS/DESIGN: This is a multicenter cluster randomized study with two arms. Randomization is done on a cluster level with 13 hospitals providing regular neuro-oncological outpatient services conducted by neurologists and/or neurosurgeons. The intervention will include an assessment of psychosocial distress of patients in doctor-patient conversation compared to assessment of psychosocial distress via questionnaire (control, standard of care). In total, 616 HGG patients will be enrolled. The outcome will be the number of HGG patients with increased psychosocial distress who receive professional support from psychosocial services. Secondary endpoints are inter alia number of patients reporting psychosocial distress and unmet needs detected correctly by the respective method; quality of life; psychological well-being and burden of the patients before and after doctor-patient consultation; as well as the length of the doctor-patient consultation. DISCUSSION: Patients with HGG are confronted with an oncological diagnosis and at the same time with high symptom burden. This often leads to distress, which is not always adequately recognized and treated. So far, only a limited number of adequate instruments are available to assess HGG patient's distress. Yet, an adequate care and support network might facilitate the course of the disease and tumor therapies for patients. Our hypothesis is that an assessment conducted directly by attending doctors and in which the doctors talk to patients with HGG will be more effective than an assessment via a questionnaire, leading to better identifying patients in need of support. This may lead to an improvement of health care in these patients. Further, this method might be implemented also in other brain tumor patients (e.g., patients with brain metastases). TRIAL REGISTRATION: German Clinical Trials Register, DRKS00018079. Registered on 3rd September 2019.

Neurocognitive functioning and health-related quality of life in adult medulloblastoma patients: long-term outcomes of the NOA-07 study.

BACKGROUND: Combined radiochemotherapy followed by maintenance chemotherapy with cisplatin, lomustine and vincristine within the NOA-07 study resulted in considerable short-term toxicity in adult medulloblastoma patients. Here we investigated the long-term impact of this treatment, focusing on neurocognitive functioning and health-related quality of life (HRQoL). METHODS: Neurocognitive functioning and HRQoL scores over time were determined, and differences between the post-treatment and follow-up assessments were calculated up to 18 months for neurocognition and 60 months for HRQoL. RESULTS: 28/30 patients were analyzed. The three preselected HRQoL scales (role, social and cognitive functioning) showed improved scores, to a clinically relevant extent (≥ 10 points), compared to post-treatment levels up to 30 months, but decreased afterwards. Z-scores for verbal working memory were worse during follow-up compared to post-treatment scores and remained impaired during 18 months follow-up (i.e. z-score below - 1 standard deviation). Attention was impaired post-treatment, and remained impaired to a clinically relevant extent during follow-up. Coordination/processing speed and lexical verbal fluency improved compared to post-treatment scores, and remained within the normal range thereafter. Other tests of verbal fluency were stable over time, with z-scores within the normal range. CONCLUSIONS: This long-term follow-up study showed that the NOA-07 treatment regimen was not associated with a deterioration in HRQoL in the post-treatment period. Verbal working memory deteriorated, while other neurocognitive domains did not seem to be impacted negatively by the treatment.

Health-related quality of life and distress in elderly vs. younger patients with high-grade glioma-results of a multicenter study.

OBJECTIVE: Half of all newly diagnosed patients with glioblastoma are > 65 years still with a poor prognosis. Preserving quality of life is of high importance. However, patient reported outcome (PRO) data in this patient group is rare. The aim was to compare health-related quality of life (HRQoL) and distress between elderly and younger patients with high-grade glioma (HGG). METHODS: We used baseline data of a prospective study where HGG patients were enrolled from 4 hospitals. Distress was measured using the distress thermometer (DT), HRQoL using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) plus brain module (BN20). We compared distress and HRQoL by age (≥ 65 vs. < 65 years), gender, performance score, and time since diagnosis using multivariate linear and logistic regressions. RESULTS: A total of n = 93 (30%) out of n = 309 patients were ≥ 65 years (mean 70 years, range 65-86 years). Mean DT score of elderly patients (5.2, SD 2.6) was comparable with younger patients (4.9, SD 2.6). Elderly patients reported significantly lower global health (GHS, mean elderly vs. younger; 50.8 vs. 60.5, p = 0.003), worse physical (56.8 vs. 73.3, p < 0.001) and lower cognitive functioning (51.1 vs. 63.2, p = 0.002), worse fatigue (52.5 vs. 43.5, p = 0.042), and worse motor dysfunction (34.9 vs. 23.6, p = 0.030). KPS and not age was consistently associated with HRQoL. CONCLUSION: Physical functioning was significantly reduced in the elderly compared with younger HGG patients, and at the same time, emotional functioning and DT scores were comparable. KPS shows a greater association with HRQoL than with calendric age in HGG patients reflecting the particular importance for adequate assessment of HRQoL and general condition in elderly patients.

Multicentric Registry Study on Epidemiological and Biological Disease Profile as Well as Clinical Outcome in Patients with Low-Grade Gliomas: The LoG-Glio Project.

BACKGROUND: World Health Organization (WHO) grade II low-grade gliomas (LGGs) in adults are rare, and patients' mean overall survival (OS) is relatively long. Epidemiological data on factors influencing tumor genesis and progression are scarce, and prospective data on surgical management are still lacking. Because of the molecular heterogeneity of LGG, a comprehensive molecular characterization is required for any clinical and epidemiological research. Further, a detailed radiologic assessment is needed as the only established objective criterion for progressive disease. Both radiologic and molecular assessments have to be standardized to produce comparable data. The aim of the registry is to improve the evidence for surgical management of LGG patients by establishing a multicenter registry with a strong surgical and clinical focus including mandatory biobanking. METHODS: The LoG-Glio project is a prospective national observational multicenter registry that began on November 1, 2015. Inclusion criteria encompass all patients > 18 years of age with a radiologic suspicion of LGG. Patients with severe neurologic or psychiatric disorders that may interfere with their informed consent or if there is no possibility for further follow-up are excluded. Diagnosis of glioblastoma WHO grade IV isocitrate dehydrogenase (IDH) wild type leads to a secondary exclusion of patients. In addition to demographic data, results of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, add-on for patients with brain tumors, and National Health Institute Stroke Scale before and after surgery and during regular follow-ups are collected. At each time point a detailed recording of surgical and adjuvant treatment is performed. Radiologic assessment involves three-dimensional (3D) acquisition of T1, fluid-attenuated inversion recovery, and T2 sequences. For the final evaluation, a central detailed neuropathologic and molecular assessment of tumor samples and a radiologic evaluation of imaging sets are part of the study protocol. RESULTS: We report the first 100 consecutively registered patients for LoG-Glio. Three patients dropped out due to loss of follow-up. Of the remaining recruited patients, 8 were classified as wait and scan; 89 had surgery. Using the inclusion criteria described previously, 70 patients had an IDH-mutated glioma, 10 had miscellaneous rare LGGs, and 8 patients had an IDH wild-type WHO grade II or III glioma. CONCLUSION: The LoG-Glio registry has been successfully implemented. Applied selection criteria result in an appropriately balanced patient cohort. Short-term outcome data on epidemiology as well as the influence of current surgical techniques and adjuvant treatment on patient outcomes are expected. In the long run, the aim of the registry is to validate the new molecular-based WHO classification and the influence of the extent of resection on progression-free survival and OS. The registry provides an open platform for future research projects benefiting patients with LGG. TRIAL REGISTRATION: NCT02686229 Clinical trials.

Evaluation of the psychological burden during the early disease trajectory in patients with intracranial tumors by the ultra-brief Patient Health Questionnaire for Depression and Anxiety (PHQ-4).

PURPOSE: Depressive symptoms of patients with intracranial tumors need to be assessed adequately. The Patient Health Questionnaire for Depression and Anxiety (PHQ-4) is an ultra-short screening tool consisting of four items, a cutoff of six indicates depressive symptoms. The aim was to assess patients' psychological burden by the PHQ-4 compared with the results of well-established screening instruments. METHODS: Patients were screened three times after primary diagnosis postoperatively (t1), after 3 (t2) and 6 (t3) months using the PHQ-4, the Hornheide Screening Instrument (HSI), the NCCN Distress Thermometer (DT), and the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire with its brain module (EORTC QLQ-C30 + BN20). Demographic, tumor-related data, and Karnofsky Performance Scale (KPS) were analyzed. A cutoff value for PHQ-4 indicating a need for support or increased distress was determined by applying receiver operating characteristic (ROC). RESULTS: The proportion of patients reaching a total score ≥ 6 was n = 32 out of 139 (23%) at t1; at t2, n = 12 out of 117 (10%) scored ≥ 6. At t3, n = 8 out of 96 (8%) scored ≥ 6. At t1, PHQ-4 scores did not differ significantly between gender, age groups, and tumor laterality. A cutoff value of 2.5 was identified to moderately discriminate between patients in or not in distress (sensitivity 76.8%) and between patients wishing further, specific support or not (sensitivity 82.5%). CONCLUSION: The PHQ4 can be applied in this patient cohort to detect those with relevant psychological comorbidities. The cutoff value should be re-evaluated in a larger cohort as we observed that a cutoff of 6, as recommended previously, may be too high in order to detect affected patients adequately.

Screening for distress in patients with intracranial tumors during the first 6 months after diagnosis using self-reporting instruments and an expert rating scale (the basic documentation for psycho-oncology short form - PO-Bado SF).

OBJECTIVE: Psychosocial screening in brain tumor patients is of high importance. We applied The Basic Documentation for Psycho-Oncology Short Form (PO-Bado SF) in primary brain tumor patients and patients with metastasis. The aim was to evaluating consistency between physicians' perception and the results of the patients' self-assessment. MATERIALS AND METHODS: 140 patients with first diagnosis of a brain tumor were screened during their hospital stay (t1) using Distress Thermometer (DT) and Hornheide Screening Instrument (HSI), health-related quality of life was assessed by EORTC QLQ-C30 + BN20. After 3 (t2) and 6 months (t3), patients were re-evaluated. Attending neuro-oncologists completed the PO-Bado SF at all three time points (cut-off for being in need for support >8). RESULTS: At t1, the mean of the PO-Bado SF total score was 7.71 (SD = 4.08), at t2 8.22 (SD = 5.40) and at t3 7.62 (SD = 5.72).The proportion of patients reaching a total score >8 was at t1: 43%, at t2: 41% and at t3: 47% (t1-3). Discrimination of PO-Bado SF total score, between patients in (DT ≥6) and those not in distress was more sensitive (cut-off 8.5, AUC 0.772, sens. 71.3%, spec. 67.6%) than discrimination compared to the HIS (cut-off 9.5, AUC 0.779, sens. 65.1%, spec. 77.7%). Higher PO-Bado-SF total score correlated with higher DT scores (r = 0.6, p < 0.0001) and lower EORTC GHS scores (r = -0.55, p < 0.0001). CONCLUSION: Physicians' perception according to PO-Bado SF provides a different measure for psychosocial burden in patients with brain tumors, however does not completely reflect patients' wishes.

Suppression of antitumor T cell immunity by the oncometabolite (R)-2-hydroxyglutarate.

The oncometabolite (R)-2-hydroxyglutarate (R-2-HG) produced by isocitrate dehydrogenase (IDH) mutations promotes gliomagenesis via DNA and histone methylation. Here, we identify an additional activity of R-2-HG: tumor cell-derived R-2-HG is taken up by T cells where it induces a perturbation of nuclear factor of activated T cells transcriptional activity and polyamine biosynthesis, resulting in suppression of T cell activity. IDH1-mutant gliomas display reduced T cell abundance and altered calcium signaling. Antitumor immunity to experimental syngeneic IDH1-mutant tumors induced by IDH1-specific vaccine or checkpoint inhibition is improved by inhibition of the neomorphic enzymatic function of mutant IDH1. These data attribute a novel, non-tumor cell-autonomous role to an oncometabolite in shaping the tumor immune microenvironment.

Compliance with patient-reported outcome assessment in glioma patients: predictors for drop out.

BACKGROUND: Patient-reported outcomes are of high importance in clinical neuro-oncology. However, assessment is still suboptimal. We aimed at exploring factors associated with the probability for a) drop out of study and b) death during follow-up. METHODS: Patients were assessed twice during follow-up visits scheduled within 3 to 5 months of each other by using 3 validated patient-reported outcome measures (t1: first assessment, t2: second assessment). As "death" was seen as a competing risk for drop out, univariate competing risk Cox regression models were applied to explore factors associated with dropping out (age, gender, WHO grade, living situation, recurrent surgery, Karnofsky Performance Status, time since diagnosis, and patient-reported outcomes assessed by Distress Thermometer, EORTC-QLQ-C30, EORTC-QLQ-BN20, and SCNS-SF-34G). RESULTS: Two hundred forty-six patients were eligible, 173 (70%) participated. Patients declining participation were diagnosed with glioblastomas more often than with other gliomas (56% vs 39%). At t2, 32 (18%) patients dropped out, n = 14 death-related, n = 18 for other reasons. Motor dysfunction (EORTC-QLQ-BN20) was associated with higher risk for non-death-related drop out (HR: 1.02; 95% CI, 1.00-1.03; P = .03). Death-related drop out was associated with age (HR: 1.09; 95% CI, 1.03-1.14; P = .002), Karnofsky Performance Status (HR: 0.92; 95% CI, 0.88-0.96; P < .001), lower physical functioning (EORTC-QLQ-C30; HR: 0.98; 95% CI, 0.96-1.00; P = .04) and lower motor functioning (EORTC-QLQ-BN20; HR: 1.020; 95% CI, 1.00-1.04; P = .02). CONCLUSION: Patients with motor dysfunction and poorer clinical condition seem to be more likely to drop out of studies applying patient-reported outcome measures. This should be taken into account when planning studies assessing glioma patients and for interpretation of results of patient-reported outcome assessments in clinical routine.

The patients' view: impact of the extent of resection, intraoperative imaging, and awake surgery on health-related quality of life in high-grade glioma patients-results of a multicenter cross-sectional study.

The objective of the present study is to assess the influence of extent of resection (EoR), use of intraoperative imaging, and awake surgery on health-related quality of life (HRQoL) in high-grade glioma (HGG) patients in a prospective multicenter study. We analyzed 170 surgeries of patients suffering from a HGG. During the first year after resection, HRQoL was evaluated using the European Organization of Research and Treatment of Cancer Core Questionnaire C30 and Brain Neoplasm 20 questionnaires. We assessed the influence of EoR; awake surgery; and use of 5-aminolevulinic acid (5-ALA), intraoperative MRI (iMRI), and their combination on sum scores for function and symptoms as well as several neurological single items. In mixed-model analyses, adjustments for age, Karnofsky performance status (KPS), and eloquent location were performed. In the mixed model, EoR generally did not significantly influence HRQoL (p = 0.10). Yet, patients receiving subtotal resection (STR) vs. patients with biopsy showed significantly better QoL and role and cognitive functions (p = 0.04, p = 0.02, and p < 0.01, respectively). The combination of iMRI and 5-ALA reached the highest EoR (95%) followed by iMRI alone (94%), 5-ALA alone (74%), and no imaging (73%). Thereby, neurological symptoms were lowest and functioning score highest after combined use of iMRI and 5-ALA, without reaching significance (p = 0.59). Despite lower scores in emotional function (59 vs. 46, p = 0.24), no significant impact of awake surgery on HRQoL was found (p = 0.70). In HGG patients, STR compared to biopsy was significantly associated with better HRQoL and fewer neurological symptoms in this series. An escalated use of intraoperative imaging increased EoR with stable or slightly better HRQoL and fewer neurological symptoms. Based on HRQoL, awake surgery was a well-tolerated and safe method in our series.

Factors associated with supportive care needs in glioma patients in the neuro-oncological outpatient setting.

Objective of this study aimed at assessing glioma patients' supportive care needs in a neurosurgical outpatient setting and identifying factors that are associated with needs for support. In three neuro-oncological outpatient departments, glioma patients were assessed for their psychosocial needs using the Supportive Care Needs Survey short-form (SCNS-SF34-G). Associations between clinical, sociodemographic, treatment related factors as well as distress (measured with the distress thermometer) and supportive care needs were explored using multivariable general linear models. One-hundred and seventy three of 244 eligible glioma patients participated, most of them with primary diagnoses of a high-grade glioma (81%). Highest need for support was observed in 'psychological needs' (median 17.5, range 5-45) followed by 'physical and daily living needs' (median 12.5, range 0-25) and 'health system and information needs' (median 11.3, range 0-36). Needs in the psychological area were associated with distress (R2 = 0.36) but not with age, sex, Karnofsky performance status (KPS), extend of resection, currently undergoing chemotherapy and whether guidance during assessment was offered. Regarding 'health system and information needs', we observed associations with distress, age, currently undergoing chemotherapy and guidance (R2 = 0.31). In the domain 'physical and daily living needs' we found associations with KPS, residual tumor, as well as with distress (R2 = 0.37). Glioma patients in neuro-oncological departments report unmet supportive care needs, especially in the psychological domain. Distress is the factor most consistently associated with unmet needs requiring support and could serve as indicator for clinical neuro-oncologists to initiate support.

Therapy for Recurrent High-Grade Gliomas: Results of a Prospective Multicenter Study on Health-Related Quality of Life.

OBJECTIVE: To assess the impact of therapy on patients' health-related quality of life (HRQoL) in recurrent high-grade glioma (HGG) in an unselected cohort. METHODS: In this prospective multicenter study, we analyzed European Organization for Research and Treatment of Cancer Quality of Life core questionnaire and European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Brain Neoplasm module questionnaires of 92 patients within 1 year after diagnosis of tumor recurrence of a HGG and respective treatment. We evaluated the influence of re-radiation, second- and third-line chemotherapies, and number of recurrent surgeries on summary scores for functioning, symptoms, and total score as well as on subscores for functioning and neurologic symptoms using multivariate mixed models and descriptive statistics. RESULTS: After we adjusted for Karnofsky Performance Score and age, different recurrent therapies did not significantly impact HRQoL. Neither re-radiation nor recurrent surgery significantly influenced HRQoL (total score, P = 0.66; P = 0.64). Patients receiving second-line chemotherapy showed moderately better physical and role functioning as well as less motor dysfunction than patients receiving third-line chemotherapy. When we compared HRQoL after second-line chemotherapies, patients receiving intensified temozolomide dosages demonstrated a moderately better outcome for cognitive functioning and less communication deficits (P = 0.055) than patients treated with bevacizumab. Regarding number of recurrent surgeries, we found stable HRQoL scores until second recurrent surgery, whereas after third recurrent surgery HRQoL decreased. CONCLUSIONS: Our results from an unselected cohort of recurrent HGGs show that the currently available treatment options have no negative impact on HRQoL. Thus, treatment decisions can be made individually, without fear of jeopardizing HRQoL for better survival. Only, the third recurrent surgery remains a very individual decision even in younger patients with high Karnofsky Performance Score.

Evaluating patients for psychosocial distress and supportive care needs based on health-related quality of life in primary brain tumors: a prospective multicenter analysis of patients with gliomas in an outpatient setting.

The association between health-related quality of life (HRQoL), psychosocial distress, and supportive care is in the focus of patient-centered neuro-oncology. We investigated the relationship between the aforementioned in glioma-patients to evaluate the association of these instruments and determine cut-off values for suitable HRQoL scales indicating a potential need for intervention. In an observational multi-center study, outpatients completed the Distress Thermometer (DT), EORTC Quality of Life Questionnaire (EORTC-QLQ-C30/BN20, HRQoL), and Supportive-Care-Needs-Survey-SF34-G (SCNS). Based on nine EORTC-function and selected -symptom scales items of the questionnaires were matched. Convergent validity of related single items and scores across the instruments was estimated. EORTC cut-off values were calculated. Data of 167 patients were analyzed. The strongest correlation of EORTC-QLQ-C30 and DT was found for cognitive function (cogf), global health status (GHS), emotional (emof), role function (rolef), future uncertainty (FU), fatigue, and between EORTC-QLQ-C30 and SCNS for FU, emof, rolef (r = |0.4-0.7|; p < 0.01). EORTC cut-off values of <54.2 (GHS/QoL) and <62.5 (emof) predicted a DT ≥ 6 (AUC 0.79, 0.85, p < 0.01). EORTC cut-off values of <70.8 (emof) and <52.8 (FU) predicted the need for supportive care (AUC 0.78, 0.85; p < 0.01). Worse EORTC-C30 scores correlate with higher DT and SCNS scores. With this exploratory assessment, cut-off values for EORTC-C30 subscores to predict distress and pathological SCNS-scores could be determined, which could influence patients' referral to further treatment. However, further prospective clinical trials are needed to confirm the clinical relevance of these cut-off values.

Suicidal ideation, depression, and health-related quality of life in patients with benign and malignant brain tumors: a prospective observational study in 83 patients.

OBJECTIVE: Health-related quality of life (HRQoL) and psychosocial burden are of relevance in patients with intracranial tumors. We investigated the prevalence of suicidal ideation (SI), depression, and their association with HRQoL in patients with intra- (IA) and extraaxial (EA) tumors during the first 9 months after diagnosis. METHODS: Patients were recruited immediately following surgery, and re-evaluated after 3, 6, and 9 months (EORTC QLQ-C30/BN20, Beck Depression Inventory (BDI) and Appendix). Patients with a personal history of psychological comorbidity were excluded. Sociodemographic and clinical data were evaluated. RESULTS: IA patients had lower functioning scores and experienced more symptoms. Global Health Status was significantly lower at baseline (p = 0.038), but improved over time (p < 0.001). Seventeen patients (21.5 %) admitted to having had SI at least once during the study period (IA: n = 10/EA: n = 7). The highest rates were observed after 6 (IA: 18.8 %) and 9 months (EA: 10.0 %). Patients reporting SI had significantly higher BDI scores [p = 0.22 (baseline), p = 0.031 (3 months), p < 0.001 (6 months)]. After 6 months, HRQoL differed greatest between patients with and without SI. Most patients experienced good familial support (76 %). CONCLUSIONS: Patients with intracranial tumors suffer from decreased HRQoL and SI regardless of histopathology. SI is associated with higher BDI scores, but not evident depression (BDI ≥ 18). Thus, patients should be screened specifically and regularly. Lower HRQoL and greatest prevalence of SI at 6 months may help clinicians to find the right time for careful monitoring of patients at risk.

Feasibility of fluorescence-guided resection of recurrent gliomas using five-aminolevulinic acid: retrospective analysis of surgical and neurological outcome in 58 patients.

Five-aminolevulinic-acid (5-ALA) is known for its benefits in surgery of primary gliomas, but has only been cautiously used in recurrent gliomas dreading over-resection, insufficient or false-positive fluorescence in adjuvantly treated tumors. We evaluated intraoperative fluorescence based on tumor pathology, pretreatment as well as surgical and neurological outcome in patients with recurrent gliomas. Patients who underwent fluorescence-guided surgery for recurrent gliomas between 6/2010 and 2/2014 at our institution were retrospectively selected. Degree of surgical resection, neurological status, pathology results, intraoperative fluorescence and follow up status were analyzed. Patients who underwent repeat surgery without 5-ALA were selected as controls. 58 patients with high grade gliomas (°III and °IV) were included. 10 of 63 tumors (15.9 %) failed to fluoresce intraoperatively of which nine (90 %) had been adjuvantly treated prior to recurrence, as were 46 of the 53 fluorescing tumors (86.8 %). Non-fluorescing tumors were IDH mutated significantly more often (p = 0.005). 30 tumors (47.6 %) were located eloquently. 51 (80.9 %) patients showed no new neurologic deficits postoperatively. 13 patients (20.6 %) showed no signs of recurrence at their latest follow up. Eight patients were lost to follow up. Overall survival was significantly longer in the 5-ALA group (p = 0.025). Fluorescence-guided surgery in recurrent gliomas is safe and allows for a good surgical and neurological outcome in a difficult surgical environment, especially when used in combination with neuronavigation and intraoperative ultrasound to prevent over-resection. Adjuvant therapy did not significantly influence fluorescing properties.

Navigated versus non-navigated intraoperative ultrasound: is there any impact on the extent of resection of high-grade gliomas? A retrospective clinical analysis.

INTRODUCTION: The extent of tumor resection is a significant predictor of survival in high-grade gliomas. In recent years, several authors showed the benefit of intraoperative ultrasound partially matched with magnetic resonance imaging (MRI). The aim of this study was to find out if intraoperative neuronavigation in combination with intraoperative ultrasound has any impact on the complete resection of gliomas. A comparison between the ultrasound-controlled resection of brain tumors and operations controlled by navigated ultrasound was performed. MATERIALS AND METHODS: A total of 92 patients (54 men and 39 women) with a mean age of 53.2 years underwent 93 operations over a period of 4 years (2007-2010). They harbored a tumor with suspicion of glioma; 32 of them had undergone previous surgery, and additional chemotherapy, and 29 of them had undergone irradiation. Overall, 49 operations were performed with navigated ultrasound (group A) and 44 with non-navigated ultrasound (group B). A standardized early postoperative MRI was performed . Complete or gross total resection (GTR) was defined by a resection of ≥ 95% of the tumor. Skin incision and craniotomy were planned after registration of the neuronavigation system. The ultrasound system was used systematically before and after opening the dura, and during and at the end of resection. RESULTS: GTR could be achieved in 28 of 49 cases in group A and in 23 of 44 cases in group B. In group A, sensitivity and specificity of tumor remnants detected by ultrasound were higher than in group B. Concerning recurrent gliomas, the sensitivity of ultrasound visualizing tumor remnants was lower than in primary tumors. In case of preoperatively planned GTR, in both groups (navigated and non-navigated ultrasound) similar tumor remnant sizes were postoperatively detected by MRI. In nine cases the removal was incomplete because of eloquently located tumors. There was no significant difference between navigated and not-navigated ultrasound concerning GTR (p > 0.05). CONCLUSION: Navigated ultrasound is an important technical tool that helps in intraoperative orientation. Further prospective investigation is needed to assess the impact on GTR.