App-based assessment of patient-reported outcomes in the Molecular Tumor Board in the Center for Personalized Medicine-(TRACE).

Background: Biomarker-based therapies are increasingly used in cancer patients outside clinical trials. Systematic assessment of patient-reported outcomes (PRO) is warranted to take patients' perspectives during biomarker-based therapies into consideration. We assessed the feasibility of an electronic PRO assessment via a smartphone application. Methods: An interdisciplinary expert panel developed a smartphone application based on symptom burden and health-related quality of life (HRQoL) metrics reported in a retrospective analysis of 292 neuro-oncological patients. The app included validated assessments of health-related quality of life (HRQoL), the burden of symptoms, and psychological stress. Feasibility and usability were tested in a pilot study. Semi-structured interviews with patients and health care professionals (HCP) were conducted, transcribed, and analyzed according to Mayring´s qualitative content analysis. Furthermore, we assessed compliance and descriptive data of ePROs. Results: A total of 14 patients have been enrolled, (9 female, 5 male). A total of 4 HCPs, 9 patients, and 1 caregiver were interviewed regarding usability/feasibility. The main advantages were the possibility to complete questionnaires at home and comfortable implementation in daily life. Compliance was high, for example, 82% of the weekly distributed NCCN distress thermometer questionnaires were answered on time, however, with interindividual variability. We observed a median distress score of 5 (range 0-10, 197 results, n = 12, weekly assessed) and a median Global health score of 58.3 according to the EORTC QLQ-C30 instrument (range 16.7-100, 77 results, n = 12, monthly assessed). Conclusions: This pilot study proved the feasibility and acceptance of the app. We will therefore expand its application during biomarker-guided therapies to enable systematic PRO assessments.

Preoperative growth dynamics of untreated glioblastoma: Description of an exponential growth type, correlating factors, and association with postoperative survival.

Background: Little is known about the growth dynamics of untreated glioblastoma and its possible influence on postoperative survival. Our aim was to analyze a possible association of preoperative growth dynamics with postoperative survival. Methods: We performed a retrospective analysis of all adult patients surgically treated for newly diagnosed glioblastoma at our center between 2010 and 2020. By volumetric analysis of data of patients with availability of ≥3 preoperative sequential MRI, a growth pattern was aimed to be identified. Main inclusion criterion for further analysis was the availability of two preoperative MRI scans with a slice thickness of 1 mm, at least 7 days apart. Individual growth rates were calculated. Association with overall survival (OS) was examined by multivariable. Results: Out of 749 patients screened, 13 had ≥3 preoperative MRI, 70 had 2 MRI and met the inclusion criteria. A curve estimation regression model showed the best fit for exponential tumor growth. Median tumor volume doubling time (VDT) was 31 days, median specific growth rate (SGR) was 2.2% growth per day. SGR showed negative correlation with tumor size (rho = -0.59, P < .001). Growth rates were dichotomized according to the median SGR.OS was significantly longer in the group with slow growth (log-rank: P = .010). Slower preoperative growth was independently associated with longer overall survival in a multivariable Cox regression model for patients after tumor resection. Conclusions: Especially small lesions suggestive of glioblastoma showed exponential tumor growth with variable growth rates and a median VDT of 31 days. SGR was significantly associated with OS in patients with tumor resection in our sample.

Clinical outcome of biomarker-guided therapies in adult patients with tumors of the nervous system.

Background: The clinical utility of molecular profiling and targeted therapies for neuro-oncology patients outside of clinical trials is not established. We aimed at investigating feasibility and clinical utility of molecular profiling and targeted therapy in adult patients with advanced tumors in the nervous system within a prospective observational study. Methods: molecular tumor board (MTB)@ZPM (NCT03503149) is a prospective observational precision medicine study for patients with advanced tumors. After inclusion of patients, we performed comprehensive molecular profiling, formulated ranked biomarker-guided therapy recommendations based on consensus by the MTB, and collected prospective clinical outcome data. Results: Here, we present initial data of 661 adult patients with tumors of the nervous system enrolled by December 31, 2021. Of these, 408 patients were presented at the MTB. Molecular-instructed therapy recommendations could be made in 380/408 (93.1%) cases and were prioritized by evidence levels. Therapies were initiated in 86/380 (22.6%) cases until data cutoff. We observed a progression-free survival ratio >1.3 in 31.3% of patients. Conclusions: Our study supports the clinical utility of biomarker-guided therapies for neuro-oncology patients and indicates clinical benefit in a subset of patients. Our data might inform future clinical trials, translational studies, and even clinical care.

Arm swing asymmetry in overground walking.

Treadmill experiments suggest that left-dominant arm swing is common in healthy walking adults and is modulated by cognitive dual-tasking. Little is known about arm swing asymmetry in overground walking. We report directional (dASI) and non-directional arm swing symmetry indices (ndASI) from 334 adults (mean age 68.6 ± 5.9 y) walking overground at comfortable (NW) and fast (FW) speeds and while completing a serial subtraction task (DT). dASI and ndASI were calculated from sagittal shoulder range of motion data generated by inertial measurement units affixed to the wrist. Most (91%) participants were right-handed. Group mean arm swing amplitude was significantly larger on the left in all walking conditions. During NW, ndASI was 39.5 ± 21.8, with a dASI of 21.9 ± 39.5. Distribution of dASI was bimodal with an approximately 2:1 ratio of left:right-dominant arm swing. There were no differences in ndASI between conditions but dASI was smaller during DT compared to FW (15.2 vs 24.6; p = 0.009). Handedness was unrelated to ndASI, dASI or the change in ASI metrics under DT. Left-dominant arm swing is the norm in healthy human walking irrespective of walking condition or handedness. As disease markers, ndASI and dASI may have different and complementary roles.