Objective: The implantation of biodegradable carmustine (BCNU) wafers is a treatment option for recurrent high-grade glioma (HGG), but its efficacy is debated. We evaluated its impact on overall survival (OS) and survival after recurrence (SAR) considering recurrence timing after first-line treatment. Methods: In this single-center retrospective study, we analyzed patients who underwent surgery for glioblastoma (GBM) recurrence following initial diagnosis (pre- and post-WHO classification 2016) between 2007 and 2022. All patients received standard first-line therapy, including maximal safe resection, radiotherapy with concomitant temozolomide, and adjuvant temozolomide. Recurrent GBM treatment involves resection, with or without adjuvant chemo- and/or radiotherapy. Patients who received carmustine wafer implantation (CWI) during resection were compared to those without wafer placement. Recurrences were classified by timing relative to first-line therapy: (1) post-radiochemotherapy, pre-adjuvant temozolomide; (2) during adjuvant temozolomide; (3) during prolonged temozolomide; (4) >1 month after completion of all therapy. Primary endpoints were OS and SAR, with prognostic factors analyzed. Results: A total of 176 patients were enrolled, with 59.7% (105/176) receiving CWI. Recurrence treatment included surgery without adjuvant therapy in 23.3% (41/176) of cases (26.7% of CWI+ and 18.3% of CWI-), adjuvant chemotherapy in 39.8% (70/176) (41% of CWI+ and 38% of CWI-), radiotherapy in 7.4% (13/176) (7.6% of CWI+ and 7% of CWI-), and combined radiochemotherapy in 29.5% (52/176) (24.8% of CWI+ and 36.6% of CWI-). No significant differences were found between groups in age (p = 0.684), residual tumor volume after initial (p = 0.988) or recurrence surgery (p = 0.356), MGMT status (p = 0.766) and KPS post 1st-line-therapy (p = 0.833). Median OS was 20 months [range 18-24] for CWI+ and 22 months [range 20-27] for CWI- (p = 0.487). The median SAR was 10 months [range 8-12] for CWI+ and 12 months [range 10-13] for CWI- (p = 0.252). Later recurrence (type 4) significantly correlated with prolonged OS (HR 0.16, 95% CI: 0.04-0.66, p = 0.011). Age (p < 0.001), MGMT methylation (p = 0.017), and smaller residual tumor volume post-recurrence surgery (p = 0.008) were also associated with longer survival. Conclusions: CWI did not significantly improve OS or SAR in recurrent GBM patients. However, younger age, MGMT methylation, smaller residual tumor volume, and later recurrence were linked to better survival outcomes, underscoring their prognostic importance.

Importance:Randomized trials established the safety of omitting axillary lymph node dissection (ALND) among patients with clinically node-negative breast cancer and less than 3 positive sentinel lymph nodes (+SLNs) having upfront surgery and adjuvant radiation. Patients with palpable mobile level I/II axillary adenopathy (cN1) were not eligible for these studies. Presently, more than 80% of patients with HR+/HER2- cN1 disease undergo ALND either at upfront surgery or after neoadjuvant therapy, despite evidence that 50% to 60% will have only 1 or 2 positive nodes. Objective:To determine upfront sentinel lymph node biopsy (SLNB) feasibility and evaluate ALND rate among patients with HR+/HER2- cN1 breast cancer selected with axillary ultrasound (AUS). Design, Setting, and Participants:This nonrandomized clinical trial involved patients with cTx/cT1-2 cN1 HR+/HER2- breast cancer with 3 or fewer morphologically abnormal nodes on AUS at 4 centers. The trial began on April 20, 2021, and the database for this report was frozen on September 26, 2024. Interventions:Patients underwent upfront lumpectomy/mastectomy and SLNB, with single/dual-tracer mapping. ALND was indicated for 3 or more positive SLNs. Main Outcomes and Measures:The primary outcome was ALND rate. Secondary outcomes were frequency of palpable nodes being radioactive/blue and locoregional recurrence. Results:Among 78 enrolled patients, the median (IQR) age was 58 (49.0-66.5) years. Most tumors were cT1 (37 [47%]) or cT2 (40 [51%]), 56 patients (72%) had ductal histology, and 59 tumors (76%) were moderately differentiated. On AUS, 39 patients (50%) had 1 abnormal-appearing node, 33 (42%) had 2, and 6 (8%) had 3. Median (IQR) pathologic tumor size was 2.3 (1.6-3.3) cm, 50 patients (64%) had lymphovascular invasion, and 54 (69%) had extracapsular extension. SLNB was performed with dual tracer in 68 (87%), and 3 or more SLNs were retrieved in 75 (96%). The palpable diseased nodes were blue and/or radioactive in 107 of 161 instances (66.5%). Overall, 24 patients (31%) had 1 +SLN, 30 patients (38%) had 2 +SLNs, and 24 patients (31%) had 3 or more +SLNs. SLNB alone was performed in 59 patients (76%), while 19 (24%) had ALND; indicated ALND was deferred in 5 cases. Among those with 12 months or more follow-up (n = 68; median, 25 months), there have been no isolated axillary or locoregional recurrences. Conclusions and Relevance:This study found that SLNB is feasible among patients with cN1 HR+/HER2- disease and that resection of palpable nodes is necessary to minimize false-negative rates. This approach affords the opportunity to omit ALND and minimize morbidity among patients with cN1 cancer and limited nodal burden. Trial Registration:ClinicalTrials.gov Identifier: NCT04854005.

This nonrandomized clinical trial analyzes data for patients who underwent upfront surgery to determine the feasibility of upfront sentinel lymph node biopsy and evaluate the rate of axillary lymph node dissection. QuestionWhat is the feasibility of upfront sentinel lymph node biopsy (SLNB) and the rate of axillary lymph node dissection (ALND) among patients with HR+/HER2- cN1 breast cancer selected with axillary ultrasound?FindingsIn this nonrandomized clinical trial including 78 consecutive patients with cTx/cT1-2 cN1 HR+/HER2- breast cancer with palpable, biopsy-proven nodal metastases, SLNB was feasible among patients with cN1 HR+/HER2- disease, with 3 or more SLNs retrieved in 96% of cases, and nearly 70% of patients meeting criteria for SLNB alone and able to avoid ALND.MeaningThis approach affords the opportunity to omit ALND and minimize morbidity among cN1 patients with limited nodal disease burden. ImportanceRandomized trials established the safety of omitting axillary lymph node dissection (ALND) among patients with clinically node-negative breast cancer and less than 3 positive sentinel lymph nodes (+SLNs) having upfront surgery and adjuvant radiation. Patients with palpable mobile level I/II axillary adenopathy (cN1) were not eligible for these studies. Presently, more than 80% of patients with HR+/HER2- cN1 disease undergo ALND either at upfront surgery or after neoadjuvant therapy, despite evidence that 50% to 60% will have only 1 or 2 positive nodes.ObjectiveTo determine upfront sentinel lymph node biopsy (SLNB) feasibility and evaluate ALND rate among patients with HR+/HER2- cN1 breast cancer selected with axillary ultrasound (AUS).Design, Setting, and ParticipantsThis nonrandomized clinical trial involved patients with cTx/cT1-2 cN1 HR+/HER2- breast cancer with 3 or fewer morphologically abnormal nodes on AUS at 4 centers. The trial began on April 20, 2021, and the database for this report was frozen on September 26, 2024.InterventionsPatients underwent upfront lumpectomy/mastectomy and SLNB, with single/dual-tracer mapping. ALND was indicated for 3 or more positive SLNs.Main Outcomes and MeasuresThe primary outcome was ALND rate. Secondary outcomes were frequency of palpable nodes being radioactive/blue and locoregional recurrence.ResultsAmong 78 enrolled patients, the median (IQR) age was 58 (49.0-66.5) years. Most tumors were cT1 (37 [47%]) or cT2 (40 [51%]), 56 patients (72%) had ductal histology, and 59 tumors (76%) were moderately differentiated. On AUS, 39 patients (50%) had 1 abnormal-appearing node, 33 (42%) had 2, and 6 (8%) had 3. Median (IQR) pathologic tumor size was 2.3 (1.6-3.3) cm, 50 patients (64%) had lymphovascular invasion, and 54 (69%) had extracapsular extension. SLNB was performed with dual tracer in 68 (87%), and 3 or more SLNs were retrieved in 75 (96%). The palpable diseased nodes were blue and/or radioactive in 107 of 161 instances (66.5%). Overall, 24 patients (31%) had 1 +SLN, 30 patients (38%) had 2 +SLNs, and 24 patients (31%) had 3 or more +SLNs. SLNB alone was performed in 59 patients (76%), while 19 (24%) had ALND; indicated ALND was deferred in 5 cases. Among those with 12 months or more follow-up (n = 68; median, 25 months), there have been no isolated axillary or locoregional recurrences.Conclusions and RelevanceThis study found that SLNB is feasible among patients with cN1 HR+/HER2- disease and that resection of palpable nodes is necessary to minimize false-negative rates. This approach affords the opportunity to omit ALND and minimize morbidity among patients with cN1 cancer and limited nodal burden.Trial RegistrationClinicalTrials.gov Identifier: NCT04854005

Patients with glioblastoma represent a highly vulnerable cohort as they often experience rapid health deterioration with severe symptom burden including neurological, (neuro)psychological, and psychiatric symptoms. The aim of this sub-analysis of the “Early Palliative Care for Patients with Glioblastoma” (EPCOG) trial was to investigate the specific challenges of conducting a multicenter, randomized, controlled, clinical trial in glioblastoma patients testing a specialized palliative care (PC) intervention. We analyzed screening protocols and protocol deviations with respect to number and reasons for non-participation, skipped/delayed visits and attrition using descriptive statistics and content analysis of free-text comments. In total, 41.5

BACKGROUND:Positive effects of early integration of palliative care (EIPC) have been shown for systemic solid malignant tumors. We tested the hypothesis that EIPC improves quality of life (QoL), palliative care (PC) problems and mood in glioblastoma patients and reduces caregiver burden. METHODS:This randomized, rater-blinded, controlled trial conducted in six German university medical centers included glioblastoma patients within four weeks after diagnosis (first/recurrent) and their caregivers. Patients received standard care (control) or standard care and EIPC (intervention) for 12 months. Primary outcome was change in QoL after six months measured by the trial outcome index of the FACT-Br. Data were assessed 3-monthly for up to 24 months. RESULTS:Between 05/2019 and 04/2021 patients were enrolled and randomized to the intervention (n = 109) or control group (n = 108). QoL at month six was in favor of the intervention, however not statistically significant (mean difference 4.1 with 95% CI, -4.4 to 12.6, P = .34; intervention: n = 98 (m = 54/f = 44); control: n = 89 (m = 50/f = 39)). In an analysis adjusted for time of death, performed because of a significant survival difference (control superior to intervention, P = .018), QoL was better in the intervention group (P = .041). Secondary outcomes showed that patients significantly benefited from EIPC regarding PC problems and mood especially after intervention ended, while caregivers did not seem to benefit. CONCLUSIONS:Provided that the survival difference is included in the analysis, EIPC improves QoL in glioblastoma patients. This, in addition to improved mood and PC problems, demonstrates that EIPC sustainably improves 'how to live' but not 'length of life'.

INTRODUCTION:Significant studies have substantiated the evidence for complete resection of intrinsic brain tumours in recent years. However, achieving this through a single surgery is not always possible due to tumour localisation in eloquent areas. Therefore, the present analysis aimed to evaluate surgical outcomes in a cohort of patients undergoing planned two-stage glioma surgery. METHODS:Patients who underwent surgery for diffusely infiltrating brain tumours between 2013 and 2023 at the Department of Neurosurgery at Düsseldorf University Hospital were screened for undergoing two-stage surgery, defined by a priori-considered surgical re-intervention up to 6 weeks after the initial surgery. RESULTS:Of 1558 patients with glioma, 447 underwent multiple surgeries, of whom 36 underwent planned two-stage surgery during the course of their disease. Two-stage surgery was performed mostly as glioma surgery at first diagnosis (75%). The mean time between the first and second surgery was 11.67 days (±7.59). Two-stage surgery was performed due to various reasons, mostly in localisations that required multifocal approaches (47.2%), due to non-compliance during initial awake surgery (30.6%), or cases with primary debulking for subsequent awake-surgery approaches (22.2%). Tumours were mainly located in the left hemisphere (50%) (right hemisphere 25%, or bilateral 25%) and motor- or speech-eloquent in 61.11%. Tumours were 72.2% IDH-wildtype. An intended complete resection result was achieved in 58.88% after the second surgery, changing from 93.94% submaximal resection to 58.88% supramaximal and maximal resection after the second surgery. Second surgery significantly reduced residual tumour volume of both T1-CE (Wilcoxon signed-rank test, Z = -4.62, p < 0.001) and T2-nCE (Z = -4.62, p < 0.001). In contrast, functional (KPS: Z = -0.93, p = 0.350) and neurological status (NIHSS: Z = -0.89, p = 0.372) did not significantly change. Perioperative complications of the second surgery occurred in nine (25%) cases, requiring surgical intervention under general anaesthesia or ICU treatment (Clavien-Dindo grade IIIb/IV) in six (16.67%) cases. CONCLUSION:Planned two-stage surgery was mostly performed as a surgical strategy in eloquent locations to achieve supramaximal or maximal resection. A two-staged surgery significantly extended resection results without neurological and functional deterioration. Despite relevant complication rates, primary debulking followed by staged resection as well as two-staged multifocal approaches may yield a favourable risk-benefit profile.

Objective:Recent data underscore the impact of supramarginal resection of gliomas on prolonging survival. The state-of-the-art approach, aimed at preventing permanent postoperative neurological deficits, involves intraoperative functional mapping and monitoring of eloquent regions. Awake surgery has thus become the gold standard method to assess language function. However, at present, no test battery is sensitive enough to reliably detect and map complex language functions intraoperatively-functions that are crucial for patients' communicative abilities and strongly impact their quality of life. Except for the dated (60 years old) sentence-level Token Test, patients' language is typically examined at the word level (e.g., picture naming and identification). We have developed and administered six highly sensitive sentence-level tests that reflect a broad range of supra-lexical language functionalities. To assess test sensitivity, we compared the results of our 6 new tests to those of a battery of 11 standard tests. Patients and methods:In this retrospective, monocentric analysis, 48 patients with eloquently located tumors and electively planned awake surgery were analyzed pre- and postoperatively using standard language assessment and our app-based high-resolution test battery. Results:A novel set of supra-lexical simple and complex sentence-level tests is at the heart of this work. Most patients performed equally well on simple sentence-level and standard tests. Performance on linguistically complex sentence-level tests was significantly lower and showed high between-patient variability, as was demonstrated by a variety of statistical analyses. Conclusion:Our results underscore the value of tests that feature complex sentence-level stimuli used in everyday communication. The more complex tests exhibit significantly higher sensitivity compared to standard language assessment. Our results thus demonstrate the utility of such tests in preserving patients' postoperative quality of life and call for their widespread use in awake surgery.

Abstract Background The CeTeG/NOA-09 trial showed improved survival with lomustine (CCNU) plus temozolomide (TMZ) over TMZ alone in O6-methylguanine-DNA-methyltransferase (MGMT) promoter-methylated glioblastoma patients aged 18-70 years. Data on feasibility, tolerability, and outcomes in patients over 70 receiving this regimen are lacking and were evaluated in this study. Methods We conducted a retrospective multicenter cohort study including patients aged >70 years with newly diagnosed, histologically confirmed, MGMT promoter-methylated glioblastoma treated with first-line radiotherapy and CCNU/TMZ. Progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Toxicity was evaluated according to the Common Terminology Criteria for Adverse Events v5.0. Results Eighteen patients (median age of 72 years, range 71-78) were included. Most patients had a good clinical status (median Karnofsky Performance Status of 90%, interquartile range [IQR] 80-90). Patients received a median of 5.5 (IQR 3.5-6) TMZ and 5 (IQR 3-6) CCNU cycles. Hematotoxicity occurred in 50% of patients, with grade ≥3 hematotoxicity in 33%. Hepatotoxicity was observed in two cases (11%), both grade 3. Toxicity-related treatment discontinuation occurred in 11%, with no treatment-related deaths. Median follow-up was 15.8 months (range: 4-82.5), median PFS was 11.5 months (95% CI, 8.9-21.1), and median OS was 19.1 months (95% CI, 13.3-46.4). Conclusions In this highly selected multicenter cohort of patients with MGMT promoter-methylated glioblastoma, first-line CCNU/TMZ combined with radiotherapy was feasible and tolerable. Survival outcomes were encouraging but descriptive, warranting prospective studies that include geriatric assessment before broader implementation in elderly patients.

Complete resection (CR) of contrast-enhancing (CE) and non-contrast-enhancing (nCE) tumour compartments is a key prognostic factor in diffuse gliomas. However, despite an intraoperative impression of CR, early postoperative MRI may reveal residual tumour. This study evaluated outcomes of patients undergoing early second-look surgery for unplanned residual tumour volume. Patients undergoing surgery for diffuse gliomas between 2013 and 2023 were screened for surgical re-intervention within six weeks after initial resection. Patients undergoing early second-look surgery due to unplanned residual tumour on postoperative MRI were included. Volumetric MRI analyses, RANO resection classification, functional neurological outcomes, perioperative complications, and survival were assessed. Among 1.558 glioma patients (CNS WHO grade 2–4), 447 underwent multiple surgeries, of whom 46 received second-look surgery for residual tumour. Resection status shifted from 80.4

Purpose Whether adjuvant cavity radiotherapy remains beneficial after complete resection of brain metastases confirmed on early postoperative magnetic resonance imaging (MRI) is uncertain. We compared fractionated stereotactic radiotherapy (fSRT) with observation. Methods In this single-center, randomized, phase 2 trial, adults with 1 to 3 resected brain metastases from a solid tumor other than small-cell carcinoma, including melanoma, with complete resection confirmed on MRI within 72 hours were randomized 1:1 to cavity fSRT, 30 Gy in 10 fractions, or observation. The primary endpoint was local recurrence-free interval at the cavity; secondary endpoints included overall survival, neurocognition, quality of life, and adverse events. Results Of 61 patients randomized, 8 withdrew consent, leaving 53 (28 fSRT, 25 observation). At a median follow-up of 61.3 months, local recurrence-free interval was longer with fSRT by intention-to-treat (hazard ratio 0.33; 95% CI 0.12–0.94; P = 0.029) and in the prespecified as-treated analysis (hazard ratio 0.13; 95% CI 0.03–0.57; P = 0.001); 17 local recurrences occurred (5 fSRT, 12 observation). Overall survival did not differ (hazard ratio 0.88; 95% CI 0.46–1.68; P = 0.70). Neurocognitive and quality-of-life measures showed no between-group differences except the headache subscale, favoring fSRT. Radiotherapy-attributable grade 3 events occurred in 2 patients (7%); none were grade 4 or 5. Conclusion Adjuvant fSRT prolonged local recurrence-free interval after early-MRI-confirmed complete resection, without measurable detriment to survival, cognition, or quality of life. An early postoperative MRI showing no residual tumor is insufficient to safely omit cavity radiotherapy. Trial registration This trial was not registered in a public trial registry. It was approved by the institutional ethics committee (study number 5029R) and conducted under the Coordinating Center for Clinical Trials (KKS) Düsseldorf, reference 2015043469.

One of the most common clinical indications for amino acid PET using the tracer O-(2-[18F]-fluoroethyl)-l-tyrosine (18F-FET) is the differentiation of tumor relapse from treatment-related changes in patients with gliomas. A subset of patients may present with an uptake of 18F-FET close to recommended threshold values. The goal of this study was to investigate the frequency of borderline cases and the role of quantitative 18F-FET PET parameters in this situation. Methods: We retrospectively identified 439 patients with pretreated gliomas who underwent 18F-FET PET for suspected tumor relapse and in whom the final diagnoses were confirmed by histopathology (n = 175) or clinical course (n = 264). Two experienced nuclear medicine physicians, masked to the final diagnoses, evaluated visually the PET scans by consensus. The findings were classified into 3 categories: clearly positive findings, borderline findings, or clearly negative findings. The diagnostic performance of established 18F-FET PET parameters (i.e., tumor-to-brain ratio [TBR], time-to-peak ratio, slope, intercept) was evaluated separately for these 3 groups using receiver operating characteristics analyses. Results: In the visual analysis, 18F-FET uptake was classified as clearly negative in 67 patients (15%), clearly positive in 234 patients (53%), and borderline in 136 patients (31%), with averaged mean TBR values of 1.5, 2.3, and 1.9, respectively. Receiver operating characteristics analysis showed a high accuracy for TBR values in patients rated as clearly positive or negative in visual rating (area under curve [AUC], 0.84-0.86), whereas the diagnostic performance of TBR values in borderline cases according to visual analysis was significantly lower (AUC, <0.60). Using TBR values ± 10% above or below the cutoff values increased the AUC by approximately 10% (AUC, 0.82-0.84). Conclusion: A considerable number of patients may present with borderline findings in 18F-FET PET. In these patients, quantitative parameters should be used with caution for decision-making. The use of TBR values above or below the range of the cutoff values ±10% may increase the reliability of quantitative parameters to differentiate between tumor relapse and treatment-related changes.

Background Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating adverse effect of neurotoxic chemotherapy characterized by symptoms such as numbness, tingling, and weakness. Effective monitoring and detection of CIPN are crucial for avoiding progression to irreversible symptoms. Due to the inconvenience of clinic-based objective assessment, CIPN detection relies primarily on patients’ reporting of subjective symptoms, and patient-reported outcomes are used to facilitate CIPN detection. Our previous study found evidence that objective functional assessments completed within a smartphone app may differentiate patients with and those without CIPN after treatment. Objective This prospective, longitudinal observational cohort study aimed to determine the feasibility and accuracy of app-based remote monitoring of CIPN in patients with cancer undergoing neurotoxic chemotherapeutic treatment and to conduct exploratory comparisons of app-based functional CIPN monitoring versus patient-reported outcome–only monitoring. Methods The NeuroDetect app (Medable Inc) includes subjective EORTC (European Organization for Research and Treatment of Cancer) Quality of Life Questionnaire (QLQ)–20-item scale (CIPN20) and 6 objective functional assessments that use smartphone sensors to mimic neurological examinations, such as walking, standing, and manual dexterity tests. The functional assessment data were collected from patients with cancer undergoing neurotoxic chemotherapy, and a neurological examination was conducted at the end of treatment to diagnose CIPN in the feet (CIPN-f) or CIPN in the hands (CIPN-h). Various classification models including NeuroDetect features only (NeuroDetect Model) CIPN20-only (CIPN20 Model) or a combination of both (Combined Model) were trained and evaluated for accuracy in predicting CIPN probability. Results Of the 45 patients who completed functional assessments and neurological examinations, 24 had CIPN-f, and 29 had CIPN-h. The NeuroDetect Model could discriminate between patients with and those without CIPN-f (area under the curve=83.8%, comparison with no information rate P=.02) but not CIPN-h (area under the curve=67.9%, P=.18). The rolling rotation features from the eyes-closed phase of the Romberg Stance assessment showed the greatest contribution to CIPN-f (40% of total variable importance) and the Finger Tapping assessment showed the greatest contribution to CIPN-h (85% of total variable importance). The NeuroDetect Model had numerically, and at some time points statistically, superior performance to the CIPN20 Model in both CIPN-f and CIPN-h, particularly before and early in treatment. The Combined Model numerically, though not statistically, outperformed either assessment strategy individually, indicating that the combination of functional and patient-reported assessment within a smartphone may be optimal to CIPN detection. Conclusions Our findings demonstrate the feasibility of integrating subjective and objective CIPN assessment into a smartphone app for remote, longitudinal CIPN monitoring. Studies of larger patient cohorts are needed to refine the app-based CIPN detection models and determine whether their use in practice improves CIPN detection.

Although the number of female medical school students is increasing, there is an imbalance regarding women in neurosurgery. In addition, a huge gender gap concerning leading positions as well as scientific careers exists. We performed a questionnaire-based data assessment of former and current neurosurgical residents, medical school students in their final and medical school students in their first year. The questionnaire assessed reasons for resigning from the residency program as well as possible discrimination or gender-specific disadvantages which prevent medical school students from choosing a surgical speciality. We found that significantly more (p = 0.05) female residents left neurosurgical training and indicated gender-based inequalities during the program (p < 0.001). Significantly fewer final-year students would choose a surgical career compared to first-year medical students (p < 0.001). The main reasons against neurosurgical training were poor work-life balance, psychological stress and difficulties in family/child care. Women must continue to be supported to pursue surgical and scientific careers.

OBJECTIVE:Until recently, a prerequisite for fluorescence-guided surgery (FGS) was the use of a specialized microscope. With the availability of a system that combines surgical loupes with an FGS-enabled headlamp, the standard approach to FGS of gliomas is challenged. We therefore investigated the potential change in practice of FGS for gliomas, if the surgeon had the choice between both systems. METHODS:Patients with a lesion indicating FGS were included. Surgery was performed by 3 specialized neurooncological neurosurgeons, who were provided with a headlamp-loupe system (HLLS) (5-aminolevulinic acid headlamp and surgeon-adapted loupes, 3.5X, customized fitted). We recorded surgeons' choice between HLLS and microscope and semi-quantified the statements. Additionally, in one case, specificity and sensitivity of various protoporphyrin IX (PpIX) fluorescence (PpIX-f) were histopathologically evaluated. RESULTS:We report 206 procedures in 198 patients. Surgeons opted in 194 (94%) of the cases for HLLS and did not switch from HLLS to microscope in any case. Three biopsies taken from areas with negative, faint, and highly positive PpIX-f, as revealed by the HLLS but not by the microscope, corresponded to normal brain tissue (negative PpIX-f), infiltration zone (faint PpIX-f), and highly cellular tumor tissue with microvascular proliferation (strong PpIX-f). CONCLUSIONS:Our center changed the practice of FGS by switching from microscopes to loupes. The reported experience might have an important impact on the general use and availability of FGS, as the HLLS and the in-house preparation of 5-aminolevulinic acid come at a fraction of the costs of the commonly practiced approach.

Background:Amino acid PET using the tracer O-(2-[18F]fluoroethyl)-l-tyrosine (FET) is one of the most reliable imaging methods for detecting glioma recurrence. Here, we hypothesized that functional MR connectivity between the metabolic active recurrent tumor region and resting-state networks of the brain could serve as a prognostic imaging biomarker for overall survival (OS). Methods:The study included 82 patients (26-81 years; median Eastern Cooperative Oncology Group performance score, 0) with recurrent gliomas following therapy (WHO-CNS 2021 grade 4 glioblastoma, n = 57; grade 3 or 4 astrocytoma, n = 12; grade 2 or 3 oligodendroglioma, n = 13) diagnosed by FET PET simultaneously acquired with functional resting-state MR. Functional connectivity (FC) was assessed between tumor regions and 7 canonical resting-state networks. Results:WHO tumor grade and IDH mutation status were strong predictors of OS after recurrence (P < .001). Overall FC between tumor regions and networks was highest in oligodendrogliomas and was inversely related to tumor grade (P = .031). FC between the tumor region and the dorsal attention network was associated with longer OS (HR, 0.88; 95%CI, 0.80-0.97; P = .007), and showed an independent association with OS (HR, 0.90; 95%CI, 0.81-0.99; P = .033) in a model including clinical factors, tumor volume and MGMT. In the glioblastoma subgroup, tumor volume and FC between the tumor and the visual network (HR, 0.90; 95%CI, 0.82-0.99, P = .031) were independent predictors of survival. Conclusions:Recurrent gliomas exhibit significant FC to resting-state networks of the brain. Besides tumor type and grade, high FC between the tumor and distinct networks could serve as independent prognostic factors for improved OS in these patients.

Background: Glioblastoma (GBM) patients exhibit a median overall survival of 12-18 months post-diagnosis, with disease recurrence typically emerging within 6-9 months. Due to the absence of standardized therapeutic protocols at recurrence, management is highly individualized. This study comprehensively evaluates overall survival (OS) time to subsequent progression, and clinical status evolution following diverse interventions for first GBM recurrence. Methods: Data from 350 patients were retrospectively analyzed. The entire cohort was divided into the following four groups: (A) patients with no further therapy at recurrence, (B) combined re-radiation and chemotherapy with temozolomide with or without lomustine or other individual medication, (C) surgery without re-adjuvant treatment, and (D) surgery and at least one cycle of chemotherapy or re-radiation or a combination. Statistical analyses were performed using non-parametric tests. Additionally, various regression analyses were performed. Results: Patients receiving invasive therapeutic regimens with or without adjuvant re-therapy (groups C and D) demonstrated significantly prolonged OS (p < 0.001) alongside superior Karnofsky performance status (KPS) at both 3-month (p = 0.016) and 6-month (p < 0.001) intervals post-intervention. Multivariate analysis confirmed surgical resection, temozolomide (TMZ) chemotherapy, and radiotherapy as independent positive predictors of OS (respective p-values: <0.001, <0.001, and 0.048). Notably, surgical resection significantly improved clinical status (p < 0.001), whereas radiotherapy had a significant negative effect on clinical status (p = 0.016). Conclusions: Contrary to the prevailing hypothesis that survival extension through extensive therapy at recurrence necessitates compromised clinical status, our findings demonstrate that contemporary recurrence therapies-particularly multimodal approaches-simultaneously enhance both OS and functional outcomes in GBM patients. This paradigm challenges conventional expectations of therapeutic trade-offs at disease recurrence.

Introduction: Knowledge of fiber tract organization is vital for understanding brain connectivity and function. Integrating traditional anatomical dissection with advanced imaging methods like diffusion tensor imaging (DTI) and 3D-photographic surface scanning (photogrammetry) provides detailed visualization of white matter (WM) pathways. However, both modalities are typically presented as separate 3D-models. This study presents photorealistic 3D photogrammetric models of lateral-to-medial dissections of clinically relevant fiber tracts combined with 3D DTI fiber tract data. Research question: Can the integration of photorealistic 3D photogrammetric models and DTI data enhance the understanding of WM fiber tract anatomy and improve its educational and neurosurgical applications? Material and methods: One brain fixed using Klingler's method was dissected. Stepwise identification of the arcuate, superior longitudinal, inferior fronto-occipital fasciculi, uncinate fascicle, anterior commissure, Mayer's loop, and the internal capsule was documented with detailed 3D-photogrammetric models generated at each dissection step. Relevant fiber tracts were also generated from population-averaged DTI data using open-access databases and software. Results: Seven photorealistic models and five integrated DTI-photogrammetry fusion 3D models were produced. Data fusion in 3D software enabled integrated models showing spatial relationships and boundaries between fiber tracts, adjustable by viewing angle and opacity changes. Combining photogrammetry with DTI-segmentation added educational value for understanding 3D-localization and fiber tract trajectories. Discussion and conclusion: The photogrammetric models and DTI data presented enhance the comprehension of critical WM fiber tracts, benefiting education and surgical planning. Customizable views allow straightforward comparisons between Klingler dissection models and fully explorable DTI models, providing a comprehensive understanding of WM anatomy.

OBJECTIVE:Malignant brain tumors place significant physical, cognitive, and emotional strain on patients and caregivers. Psychosocial distress screening is part of standard care for patients, while caregiver screening remains challenging. This study examined the association of patient psychosocial distress at diagnosis with caregiver anxiety and depression over time. METHODS:This secondary analysis used data from a prospective, single-center, observational study of malignant brain tumor dyads. To assess the association of patient psychosocial distress at diagnosis (T0) with caregiver anxiety and depression at T0 and at 3 (T1) and 6 (T2) months post-diagnosis, the Actor-Partner Interdependence Model (APIM) was used. RESULTS:Complete data from 58 dyads were included at T0, 43 at T1, and 41 at T2. Patient distress at T0 predicted caregiver depression at T1 (β = 0.310, p = 0.007) and T2 (β = 0.322, p = 0.005), and caregiver anxiety at T2 (β = 0.303, p = 0.020). Caregiver distress at T0 did not predict patient anxiety and depression at any time point. For both patients and caregivers, distress at T0 predicted their own anxiety and depression at T0 and their anxiety at T1. For caregivers, distress at diagnosis also predicted anxiety at T2. CONCLUSIONS:Psychosocial distress experienced by patients with malignant brain tumors at diagnosis significantly predicts their caregivers' anxiety and depression over time. Caregivers at risk of increased anxiety and depression could therefore be identified by screening for patient distress. These findings also highlight the critical need for early psychosocial support for both patients and caregivers. TRIAL REGISTRATION:Retrospectively registered in the German Clinical Trial Register (10 July 2024; DRKS00034637).

The gold standard to diagnose leptomeningeal metastasis (LM) is to identify malignant cells in the cerebrospinal fluid (CSF) or in a leptomeningeal biopsy. Using conventional cytology its sensitivity remains low with approximately 50% and 85% for the first and the second lumbar puncture, respectively. While rare cell capture technologies like the CellSearch system reach higher sensitivity than conventional cytology, they have limitations, including capturing only cells with sufficient EpCAM antigen expression, limited antibody customization, and high costs. Once diagnosed with LMs, to date most patients are still treated with untargeted therapies with limited effectiveness and significant side effects. To address this, we developed a workflow using Sievewell 370 K microwell chips. Each chip contains 370,000 hexagonal microwells (20 μm in diameter, 25 μm deep) with two 2 μm pores at the bottom. On the chip, individual cells are separated, identified with cytokeratin antibodies, and isolated as single cells via micromanipulation for molecular analysis. 15 CSF samples from 9 LM-patients were analyzed on the microwell chips and by conventional cytology in parallel. The isolated cells’ DNA was amplified by whole genome amplification and sequenced by low pass whole genome sequencing and panel sequencing on single cell level and compared to extracranial tissue biopsies. On-chip immunostaining achieved less than 5% cell loss and over 95% single cell isolation for the MCF7 breast cancer cell line. For 10 of the 15 CSF samples, concordant results were obtained by analysis on the microwell chips and conventional cytology: 1 sample was tumor cell-negative, 9 samples were tumor cell-positive. In the other 5 samples, tumor cells were detected by analysis on the microwell chip with either inconclusive (3 samples) or negative (2 samples) results obtained by cytological analysis. With the microwell chips, 5 to 10,000 (mean 1,218; median 116) CSF-CTCs were found per mL CSF. The detection of chromosomal aberrations confirmed the malignant origin of detected tumor cells, including those from samples that were tumor cell-negative in conventional cytology. A high level of clonality was observed among the tumor cells in the CSF of each patient, yet these CSF tumor cells often exhibited an aberration pattern with distinct differences compared to the corresponding extracranial metastases or primary tumors. In addition to mutations shared by corresponding tissue biopsies, panel sequencing revealed private mutations of CSF-CTCs in resistance related genes and tumor driver genes. In conclusion, the microwell-based CSF-CTC detection appears superior to conventional cytology. The high level of clonality indicates a very close evolutionary relationship within the CSF-CTCs and a monoclonal origin of LMs. Private mutations in resistance related genes and tumor driver genes could impact drug susceptibility and therapy resistance. Therefore, the CSF-based liquid biopsy should be considered for genetic profiling of LMs, potentially improving diagnosis, treatment monitoring, and targeted therapy selection. Citation Format: André Franken, Martin Schramm, Barbara Alberter, Jens Warfsmann, Bernhard Polzer, Franziska Meier-Stiegen, Natalia Krawczyk, Michael Sabel, Marion Rapp, Eugen Ruckhäberle, Tanja Fehm, Hans Neubauer. Detection, isolation, and genetic characterization of circulating tumor cells from the cerebrospinal fluid of breast cancer patients with leptomeningeal metastasis [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P4-01-27.