Role of microsurgical tumor burden reduction in patients with breast cancer brain metastases considering molecular subtypes: a two-center volumetric survival analysis.

BACKGROUND: Advancements in metastatic breast cancer (BC) treatment have enhanced overall survival (OS), leading to increased rates of brain metastases (BM). This study analyzes the association between microsurgical tumor reduction and OS in patients with BCBM, considering tumor molecular subtypes and perioperative treatment approaches. METHODS: Retrospective analysis of surgically treated patients with BCBM from two tertiary brain tumor Swiss centers. The association of extent of resection (EOR), gross-total resection (GTR) achievement, and postoperative residual tumor volume (RV) with OS and intracranial progression-free survival (IC-PFS) was evaluated using Cox proportional hazard model. RESULTS: 101 patients were included in the final analysis, most patients (38%) exhibited HER2-/HR + BC molecular subtype, followed by HER2 + /HR + (25%), HER2-/HR- (21%), and HER2 + /HR- subtypes (13%). The majority received postoperative systemic treatment (75%) and radiotherapy (84%). Median OS and intracranial PFS were 22 and 8 months, respectively. The mean pre-surgery intracranial tumor volume was 26 cm3, reduced to 3 cm3 post-surgery. EOR, GTR achievement and RV were not significantly associated with OS or IC-PFS, but higher EOR and lower RV correlated with extended OS in patients without extracranial metastases. HER2-positive tumor status was associated with longer OS, extracranial metastases at BM diagnosis and symptomatic lesions with shorter OS and IC-PFS. CONCLUSIONS: Our study found that BC molecular subtypes, extracranial disease status, and BM-related symptoms were associated with OS in surgically treated patients with BCBM. Additionally, while extensive resection to minimize residual tumor volume did not significantly affect OS across the entire cohort, it appeared beneficial for patients without extracranial metastases.

A T-cell antigen atlas for meningioma: novel options for immunotherapy.

Meningiomas are the most common primary intracranial tumors. Although most symptomatic cases can be managed by surgery and/or radiotherapy, a relevant number of patients experience an unfavorable clinical course and additional treatment options are needed. As meningiomas are often perfused by dural branches of the external carotid artery, which is located outside the blood-brain barrier, they might be an accessible target for immunotherapy. However, the landscape of naturally presented tumor antigens in meningioma is unknown. We here provide a T-cell antigen atlas for meningioma by in-depth profiling of the naturally presented immunopeptidome using LC-MS/MS. Candidate target antigens were selected based on a comparative approach using an extensive immunopeptidome data set of normal tissues. Meningioma-exclusive antigens for HLA class I and II are described here for the first time. Top-ranking targets were further functionally characterized by showing their immunogenicity through in vitro T-cell priming assays. Thus, we provide an atlas of meningioma T-cell antigens which will be publicly available for further research. In addition, we have identified novel actionable targets that warrant further investigation as an immunotherapy option for meningioma.

Symptom Burden in Glioblastoma: A Prospective Pilot Study from Diagnosis to First Progression.

INTRODUCTION: The evaluation of symptom burden, performance status, and neurological function is still challenging in glioblastoma (GBM) patients. Patients may suffer from a wide spectrum of neurological symptoms like cognitive deficits, aphasia, or hemiparesis, which interfere to report to comprehensive questionnaires. However, an integrated and reliable neuro-oncological assessment is the key in the clinical management and in the evaluation of treatment benefits for GBM patients. METHODS: We implemented an easy-to-use clinical toolkit for the prospective assessment and follow-up evaluation of GBM patients using the Karnofsky performance status (KPS), the National Institute of Health Stroke Scale (NIH-SS), and simple scores for the evaluation of key symptoms like fatigue, depression, and headache. RESULTS: We prospectively followed 50 patients. The composite score (headache, depression, and fatigue), fatigue alone, the NIHSS, and the KPS were suitable biomarkers to evaluate symptom burden in GBM patients and indicate clinical disease progression. DISCUSSION/CONCLUSION: The proposed clinical toolkit seems feasible in routine clinical practice and reflects changes in symptom burden in different stages of the postsurgical course of GBM patients in this monocentric clinical pilot trial.

Longitudinal smartphone-based self-assessment of objective functional impairment in patients undergoing surgery for lumbar degenerative disc disease: initial experience.

BACKGROUND: The worldwide spread of smartphone usage enables new possibilities for longitudinal monitoring of objective functional impairment (OFI) in patients undergoing surgery for lumbar degenerative disc disease (DDD). METHODS: Three patients, undergoing elective surgery for lumbar DDD, self-assessed OFI using a recently validated 6-min walking test (6WT) smartphone application. Results are presented as raw 6-min walking distance (6WD) as well as in reference to age- and sex-specific healthy population reference values using standardized z-scores (number of standard deviations). In parallel, patient-reported outcome measures (PROMs), including numeric rating scale (NRS) leg-pain and Core Outcome Measures Index (COMI) were obtained before (pre) and 6 weeks (6 W) as well as 3 months (3 M) after surgery. Descriptive analyses were used to compare PROMs with repeated 6WT measurements over time. The feasibility and benefits of the longitudinal OFI measurements using the 6WT app are discussed. RESULTS: One patient presented a favorable outcome, reflected by a clinically meaningful improvement in PROMs. Correspondingly, the 6WT distance gradually improved above the normal population values ((pre 399 m (z-score - 1.96) vs. 6 W 494 m (- 0.85) vs. 3 M 557 m (- 0.1)). One patient experienced initial improvement at 6 W, followed by a decline in 6WD at 3 M which promoted further interventions with subsequent recovery ((358 m (z-score - 3.29) vs 440 m (- 2.2) vs 431 m (- 2.32) vs 471 m (- 1.78)). The last patient showed a lack of improvement in PROMs as well as in OFI (360 m (z-score 0.0) vs 401 m (0.30) vs 345 m (- 0.11)) resulting in secondary surgery. CONCLUSION: The longitudinal assessment of OFI using the 6WT app was feasible and provided the physician with a detailed history of patients' postoperative walking capacity complementing commonly used PROMs.

Association of pre- and postoperative αKlotho levels with long-term remission after pituitary surgery for acromegaly.

Soluble αKlotho (sKl) is a disease-specific biomarker that is elevated in patients with acromegaly and declines after surgery for pituitary adenoma. Approximately 25% of patients do not achieve remission after surgery, therefore a risk stratification for patients early in the course of their disease may allow for the identification of patients requiring adjuvant treatment. Growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have been assessed as biomarker for disease activity, however the value of sKl as a predictive biomarker of surgical success has not been evaluated yet. In this study, we measured serum biomarkers before and after transsphenoidal pituitary surgery in 55 treatment-naïve patients. Based on biochemical findings at follow-up (7-16 years), we divided patients into three groups: (A) long-term cure (defined by normal IGF-1 and random low GH (< 1 µg/l) or a suppressed GH nadir (< 0.4/µg/l) on oral glucose testing); (B) initial remission with later disease activity; (C) persistent clinical and/or biochemical disease activity. sKl levels positively related to GH, IGF-1 levels and tumor volume. Interestingly, there was a statistically significant difference in pre- and postoperative levels of sKl between the long-term cure group and the group with persistent disease activity. This study provides first evidence that sKl may serve as an additional marker for surgical success, decreasing substantially in all patients with initial clinical remission while remaining high after surgery in patients with persistent disease activity.

Assessment of neurological function using the National Institute of Health Stroke Scale in patients with gliomas.

BACKGROUND: The evaluation of treatment response in patients with gliomas is performed using the Response Assessment in Neuro-Oncology (RANO) criteria. These criteria are based on cerebral magnetic resonance imaging (MRI), steroid use, and neurological function. However, a standardized tool for evaluating neurological function was lacking. We compared changes in the National Institute of Health Stroke Scale (NIHSS) to changes in the RANO categories to determine the relationship between clinical and neuroradiological findings. METHODS: We reviewed data on all adult patients with supratentorial gliomas WHO grade II-IV who were treated at the Cantonal Hospital St. Gallen from 2008 to 2015. The NIHSS was performed prospectively at baseline and at 3-month intervals simultaneously to MRI. Associations between changes in the NIHSS and RANO categories were assessed using the Stuart-Maxwell test. RESULTS: Our cohort consisted of 61 patients from which 471 observations were analyzed. The most common histological diagnosis was glioblastoma (49.2%). In total, 74% of RANO categories and 81% of the NIHSS scores remained stable on follow-up. Statistically, contemporaneous changes in the RANO category did not correlate with changes in the NIHSS (P < .0001). CONCLUSION: The application of the NIHSS is easy and feasible in the heterogeneous population of glioma patients. In our cohort, the RANO categories did not reflect contemporaneous changes in the NIHSS. A validated clinical outcome measure with a well-defined minimal clinically important difference is warranted in neuro-oncological research and clinical practice.

Patients undergoing surgery for lumbar degenerative spinal disorders favor smartphone-based objective self-assessment over paper-based patient-reported outcome measures.

BACKGROUND CONTEXT: Smartphone-based applications enable new prospects to monitor symptoms and assess functional outcome in patients with lumbar degenerative spinal disorders. However, little is known regarding patient acceptance and preference towards new modes of digital objective outcome assessment. PURPOSE: To assess patient preference of an objective smartphone-based outcome measure compared to conventional paper-based subjective methods of outcome assessment. STUDY DESIGN: Prospective observational cohort study. PATIENT SAMPLE: Fourty-nine consecutive patients undergoing surgery for lumbar degenerative spinal disorder. OUTCOME MEASURES: Patients completed a preference survey to assess different methods of outcome assessment. A 5-level Likert scale ranged from strong disagreement (2 points) over neutral (6 points) to strong agreement (10 points) was used. METHODS: Patients self-determined their objective functional impairment using the 6-minute Walking Test application (6WT-app) and completed a set of paper-based patient-reported outcome measures (PROMs) before and 6 weeks after surgery. Patients were then asked to rate the methods of outcome assessment in terms of suitability, convenience, and responsiveness to their symptoms. RESULTS: The majority of patients considered the 6WT-app a suitable instrument (median 8.0, interquartile range [IQR] 4.0). Patients found the 6WT more convenient (median 10.0, IQR 2.0) than the Zurich Claudication Questionnaire (ZCQ; median 8.0, IQR 4.0, p=.019) and Core Outcome Measure Index (COMI; median 8.0, IQR 4.0, p=.007). There was good agreement that the 6WT-app detects change in physical performance (8.0, IQR 4.0). 78 % of patients considered the 6WT superior in detecting differences in symptoms (vs. 22% for PROMs). Seventy-six percent of patients would select the 6WT over the other, 18% the ZCQ and 6% the COMI. Eighty-two percent of patients indicated their preference to use a smartphone app for the assessment and monitoring of their spine-related symptoms in the future. CONCLUSIONS: Patients included in this study favored the smartphone-based evaluation of objective functional impairment over paper-based PROMs. Involving patients more actively by means of digital technology may increase patient compliance and satisfaction as well as diagnostic accuracy.

Smartphone-Based Self-Assessment of Objective Functional Impairment (6-Minute Walking Test) in Patients Undergoing Epidural Steroid Injection.

Epidural steroid injection (ESI) represents a popular treatment option in patients with lumbar degenerative disc disease (DDD). The main objective of the article was to determine whether the 6-minute walking test (6WT) could assist in the discrimination between ESI responders and nonresponders. We used a validated 6WT smartphone application to assess self-measured objective functional impairment (OFI) in 3 patients with DDD undergoing ESI. Patient-reported outcome measures (PROMs), including the Core Outcome Measures Index and the Oswestry Disability Index, were obtained at baseline and at the 3-, 7-, and 28-day follow-up. Descriptive analyses were used to compare PROMs with OFI over time. Two patients responded well to the ESI, illustrated by clinically meaningful improvements in PROMs. This improvement was accompanied by a substantial increase in the 6WT distance (case I: 358 m vs. 517 m and case II: 296 m vs. 625 m). One patient reported only moderate improvement in leg pain and conflicting results in the other PROMs. The 6WT demonstrated a persistent OFI (487 m vs. 488 m). This patient was considered a nonresponder and underwent surgical treatment. This case series illustrates the feasibility of the smartphone-based 6WT as a tool to assess OFI in patients undergoing ESI for lumbar DDD.