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Background: The expression level of the programmed cell death ligand 1 (PD-L1) appears to be a predictor for response to immunotherapy using checkpoint inhibitors in patients with non-small cell lung cancer (NSCLC). As differences in terms of PD-L1 expression levels in the extracranial primary tumor and the brain metastases may occur, a reliable method for the non-invasive assessment of the intracranial PD-L1 expression is, therefore of clinical value. Here, we evaluated the potential of radiomics for a non-invasive prediction of PD-L1 expression in patients with brain metastases secondary to NSCLC., Patients and Methods: Fifty-three NSCLC patients with brain metastases from two academic neuro-oncological centers (group 1, n = 36 patients; group 2, n = 17 patients) underwent tumor resection with a subsequent immunohistochemical evaluation of the PD-L1 expression. Brain metastases were manually segmented on preoperative T1-weighted contrast-enhanced MRI. Group 1 was used for model training and validation, group 2 for model testing. After image pre-processing and radiomics feature extraction, a test-retest analysis was performed to identify robust features prior to feature selection. The radiomics model was trained and validated using random stratified cross-validation. Finally, the best-performing radiomics model was applied to the test data. Diagnostic performance was evaluated using receiver operating characteristic (ROC) analyses., Results: An intracranial PD-L1 expression (i.e., staining of at least 1% or more of tumor cells) was present in 18 of 36 patients (50%) in group 1, and 7 of 17 patients (41%) in group 2. Univariate analysis identified the contrast-enhancing tumor volume as a significant predictor for PD-L1 expression (area under the ROC curve (AUC), 0.77). A random forest classifier using a four-parameter radiomics signature, including tumor volume, yielded an AUC of 0.83 ± 0.18 in the training data (group 1), and an AUC of 0.84 in the external test data (group 2)., Conclusion: The developed radiomics classifiers allows for a non-invasive assessment of the intracranial PD-L1 expression in patients with brain metastases secondary to NSCLC with high accuracy., (© 2023. The Author(s).)

Purpose: In glioma patients, tumor development and multimodality therapy are associated with changes in health-related quality of life (HRQoL). It is largely unknown how different types and locations of tumor- and treatment-related brain lesions, as well as their relationship to white matter tracts and functional brain networks, affect HRQoL., Methods: In 121 patients with pretreated gliomas of WHO CNS grades 3 or 4, structural MRI, O-(2-[ 18 F]fluoroethyl)-L-tyrosine (FET) PET, resting-state functional MRI (rs-fMRI) and self-reported HRQoL questionnaires (EORTC QLQ-C30/BN20) were obtained. Resection cavities, T1-enhancing lesions, T2/FLAIR hyperintensities, and lesions with pathologically increased FET uptake were delineated. Effects of tumor lateralization, involvement of white matter tracts or resting-state network nodes by different types of lesions and within-network rs-fMRI connectivity were analyzed in terms of their interaction with HRQoL scores., Results: Right hemisphere gliomas were associated with significantly less favorable outcomes in physical, role, emotional and social functioning, compared with left-sided tumors. Most functional HRQoL scores correlated significantly with right-sided white-matter tracts involvement by T2/FLAIR hyperintensities and with loss of within-network functional connectivity of right-sided nodes. Tumors of the left hemisphere caused significantly more communication deficits., Conclusion: In pretreated high-grade gliomas, right hemisphere lesions are associated with reduced HRQoL scores in most functional domains except communication ability, compared to tumors of the left hemisphere. These relationships are mainly observed for T2/FLAIR lesions involving structural and functional networks in the right hemisphere. The data suggest that sparing the right hemisphere from treatment-related tissue damage may improve HRQoL in glioma patients., (© 2023. The Author(s).)

Purpose: To provide detailed long-term data after initial observation for patients after histological confirmation of low grade (WHO II) gliomas according to molecular stratification., Methods: A series of 110 patients with watchful waiting strategy after initial surgery for LGG and re-surgery at tumor progression were analyzed. Progression-free survival, time to malignant transformation, post-recurrence survival, and overall survival were estimated with the Kaplan-Meier method. Prognostic factors were identified by the Log Rank test and Cox multivariate proportional hazards model., Results: The cohort comprised 18 IDH wild type (IDH wt ) and 53 IDH mutated (IDH mut ) astrocytomas, and 39 IDH mutated and 1p 19q co-deleted (IDH mut/codel ) patients. The median follow-up was 126 (95% CI 109-143) months. Surgery was gross total resection in 58, subtotal resection in 28, and biopsy in 24 patients. Progression-free survival rates at 5, 10 and 15 years was 38% 18% and 1%. The corresponding malignant transformation rates were 17%, 39% and 71%. The initial extent of resection influenced progression-free survival, time to malignant transformation and overall survival. Molecular subtype IDH mut/codel was the strongest prognostic factor for overall survival and for time to malignant transformation., Conclusion: The strongest determinant of the patients' course after initial watchful waiting was the molecular tumor status. Extensive resection may increase time to progression and malignant transformation. Observation may be justified in selected patients.

The implementation of self-reported outcome measurements into clinical routine was tested to help facilitate early access to palliative care (PC) for glioblastoma (GBM)-patients. Measures detail PC symptoms and concerns and caregiver burden. Between January 2014 and December 2016, a total of 337 GBM-patients were discussed during meetings of the neuro-oncology tumor board to examine further treatment options. Each patient, along with their caregivers, was requested to participate in self-assessment using the palliative outcome scale (POS) and the Zarit Burden Interview (ZBI). Analyses encompassed summary statistics, non-parametric tests, visual graphic analysis, content analysis and assessing the utilization of the specialized PC consulting service (SPCCS). Ninety-five (28%) GBM-patients and 71 (21%) caregivers completed the self-assessment. Of these, 20 patients and 12 caregivers repeated the assessment at least once more during follow-up. POS total scores were similar in the group of patients with initial diagnosis [10 (0-31)] and those with later disease stages like recurrent diagnosis [9 (0-25)], but ZBI total scores differed [14 (0-51) vs. 24 (2-62)]. Single item analysis demonstrated that anxiety and worries about the future predominated. Caregivers were torn between high engagement in caring and feeling overburdened. Still, requests for the SPCCS showed no increase. Actual implementation of measures like POS and ZBI for detecting PC concerns and caregiver burden with GBM-patients in the field remains challenging as indicated by the limited response rate and lack of increased requests for the SPCCS. Modified clinical routines including strengthening awareness of PC, and allowing proxy-assessment might help to overcome barriers.

To evaluate risk profile, diagnostic yield and impact on treatment decision of stereotactic biopsy (SB) in elderly patients with unclear cerebral lesions. In this single center retrospective analysis we identified all patients aged ≥70 years receiving SB between January 2005 and December 2015. Demographic data, Karnofsky Performance Status (KPS), histology, comorbidity (by CHA2DS2-VASc Score) and use of anticoagulation were retrieved. We scrutinized diagnostic yield, procedural complications (mortality, transient and permanent morbidity), hospitalization time and therapeutic consequence. For correlation analysis Chi-Square, Mann-Whitney rank sum test and binary regression were used. Two hundred and thirty patients were included. In 229 patients SB was technically successful. Median age was 74 (70-87) years, 56.1% of patients were male and median preoperative KPS was 80% (30-100). Median CHA2DS2-VASc Score was 4 (1-9), with 29.6% receiving anticoagulation. Median hospital stay was 8 (2-29) days. Pathological diagnosis was conclusive in 97% revealing neoplastic lesions in 91.7% (high-grade glioma 62.6%, lymphoma 18.3%, metastasis 4.8%, low-grade glioma 3.0% and other tumors 3.0%) and non-neoplastic lesions in 5.3% of cases. Procedure-related mortality was 0.4%, transient and permanent morbidity occurred in 19 patients (8.3%) and eight patients (3.5%). Complication rate was not associated with any of the above-mentioned parameters. Adjuvant therapy was initiated in 171 (74.3%) patients. Decision against disease-specific therapy was only influenced by preoperative KPS (p < 0.001). SB in elderly patients is characterized by a favorable risk profile and high diagnostic yield, allowing tissue based therapeutic consequences even in patients with high comorbidity and anticoagulant medication.

The current study analyzed the outcome after stereotactic brachytherapy (SBT) using iodine-125 seeds in anaplastic astrocytoma, oligoastrocytoma or oligodendroglioma not suitable for resection. Out of 223 patients harbouring a malignant glioma treated according to a prospective protocol, 172 patients were selected who received SBT to treat a WHO grade III de-novo/residual tumor (n = 99) or a tumor recurrence after multimodal treatment (n = 73). We assessed progression free survival (PFS), overall survival (OS), radiological and clinical outcome and determined prognostic factors using univariate and multivariate regression analyses. The median follow-up time was 38 months. Median OS and median PFS was 28.9 and 21.4 months in the de-novo group vs. 49.4 and 32.6 months in the recurrence group. Recurrent tumors had more frequently (p = 0.01) an oligodendroglial-component compared to de novo tumors. According to cohort-specific univariate analyses KPS at SBT had a significant (p = 0.008) impact on OS in the de-novo group. In the recurrence group, (Cox regression analysis) OS was significantly associated with histology subtype (oligoastro-/oligodendroglioma vs. astrocytoma, p = 0.043). Transient and permanent morbidity (~1 %) was low. For patients unable to undergo surgery due to eloquent tumour location or reduced general condition SBT is an effective treatment option, which does not foreclose additional therapeutic interventions.

Treatment options for inoperable glioblastoma are limited. Low-dose-rate stereotactic iodine-125 brachytherapy (SBT) has been reported as an effective and low-risk treatment option for circumscribed low-grade gliomas and brain metastases. The present study evaluates this treatment approach for patients with inoperable glioblastoma. Between 1990 and 2012, 201 patients with histologically proven glioblastoma were treated with SBT (iodine-125 seeds; median cumulative surface dose, 60 Gy; median dose-rate, 6 cGy/h; median gross-tumor-volume, 17 ml) either as primary treatment (n = 103) or at recurrence (n = 98). In addition to SBT, 90.3 % of patients in the primary treatment group received external boost radiotherapy (median dose, 25.2 Gy). Adjuvant chemotherapy was added for 30.8 % of patients following SBT and consisted of temozolomide for the majority of cases (88.7 %). Procedure-related complications, clinical outcome, progression-free and overall survival (PFS, OS) were evaluated. Median follow-up was 9.8 months. The procedure-related mortality was zero. During follow-up, transient and permanent procedure-related morbidity was observed in 7.5 and 2.0 %, respectively. Calculated from the time of SBT, median OS and PFS rates were 10.5 and 6.2 months, with no significant differences among primary and recurrent tumors (11.1 vs.10.4 months for OS and 6.2 vs. 5.9 months for PFS). For OS, multivariate analysis revealed Karnofsky performance score, age, and adjuvant chemotherapy as independent prognostic factors (all p < 0.01). Low-dose-rate SBT is a relatively safe and potentially effective local treatment option for patients with circumscribed inoperable glioblastoma initially or at recurrence. It deserves prospective validation since it may improve the outcome for a subset of patients with inoperable GBM.

Microsurgical resection is the most frequently suggested treatment option for accessible focal brainstem gliomas (F-BSG) of World Health Organization (WHO) grades I and II. Because of their location in the highly eloquent brain, however, resection is associated with permanent postoperative morbidity, ranging from 12 to 33 %. Only a few reports have suggested stereotactic brachytherapy (SBT) with implantation of iodine-125 seeds as a local treatment alternative. Between 1993 and 2010, 47 patients were treated with SBT (iodine-125 seeds; cumulative surface dose 50-65 Gy) for inoperable F-BSG, WHO grades I and II, in one of the largest reported patient series. We evaluated procedure-related complications, clinical outcome, and progression-free and overall survival (PFS, OS). Median follow-up was 81.6 months. Procedure-related mortality was zero. Within 30 days of seed implantation six patients (12.8 %) had transient neurological deficits. Two patients (4.3 %) deteriorated permanently. Space-occupying cysts occurred in six patients (12.8 %) after a median of 28.5 months, and required surgical intervention. Nine patients (19.1 %) presented with tumor relapse after a median of 56.6 months (range 7.9-118.0 months). For the remaining 38 patients complete response was observed for 23.4 %, partial response for 29.8 %, and stable disease for 27.7 %. Actuarial PFS was 97.7 ± 2.2, 92.8 ± 4.0, 81.2 ± 6.5, and 62.0 ± 10.4 % after 1, 2, 5, and 10 years, respectively. Corresponding OS was 100 ± 0.0 % (1 and 2 years), 97.4 ± 2.6 % (5 years), and 87.6 ± 7.0 % (10 years). SBT is a comparatively safe, minimally invasive, and highly effective local treatment option for patients with inoperable F-BSG WHO grades I and II; it merits further evaluation in prospective randomized trials.

This paper reports on stereotactic biopsy combined with stereotactic (125)iodine brachytherapy (SBT) for locally recurrent, previously irradiated cerebral metastases, focusing on feasibility, complications, cerebral disease control, and survival. All patients with suspected locally recurrent metastases detected by MRI were selected for this combined procedure. After stereotactic biopsy, all patients with a verified vital tumor underwent SBT (50 Gy surface dose applied for 42 days) during the same surgical procedure. Histological results of biopsy, complications, treatment response, local and distant disease control, and survival were evaluated. Thirty patients underwent stereotactic biopsy, and 27 were treated with SBT for histologically proved tumor recurrence. There was no treatment-related mortality, and morbidity was transient and low (6.6%). Median survival was 14.8 months. After one year the actuarial incidence of local and distant relapse was 6.7 and 45.5%, respectively. There was no grade 3 or 4 CNS toxicity, even among the 18.5% of patients with tumors >30 mm. For these patients stereotactic biopsy seems to be a safe and valuable means of differentiating between radiation-induced tissue changes and tumor recurrence/progression. SBT is a safe, minimally invasive, and highly effective treatment option for cerebral disease control and survival. Furthermore, it can be performed during the same stereotactic operation.

The present prospective study intends to evaluate health-related quality of life (HRQL) and cognitive functioning in adult patients with supratentorial World Health Organization (WHO) grade II glioma (LGG) prior to observation/therapy and to determine possible influences of tumor-related factors on these measures. Adult patients with biopsy-proven supratentorial LGG were considered eligible (study period 18 months). Besides detailed documentation of patient clinical status we evaluated HRQL using the Short Form-36 (SF-36) Health Survey and applied the Beck Depression Inventory. Furthermore, attention and verbal memory functions were tested. Data from matched healthy control populations served as reference, and T-values were compared using Mann-Whitney U tests. For correlation of scores the Pearson test was utilized. Thirty-three patients with median Karnofsky Performance Status (KPS) of 80 were evaluated. Selective and divided attention showed significant impairment (P < 0.005), while verbal memory functions were unaffected. HRQL evaluated by SF-36 Health Survey was significantly reduced predominantly in the psychological domains (P < 0.025 to P < 0.0005). Nine patients displayed mild to moderate depression. Duration of symptoms >20 weeks and presence of seizures negatively affected aspects of HRQL, while cognitive functions were not influenced. KPS <80 correlated significant only with reduced physical functioning (P < 0.002) and role functioning (P < 0.01) on the SF-36 Health Survey. While displaying good clinical status, patients with LGG showed significant impairment in aspects of attention and affections of HRQL already at time of diagnosis. These results suggest that these impairments originate from the tumor and/or potentially from confrontation with the diagnosis itself.