Search

Simple Summary: This research investigates the identification of tumor-specific serological biomarkers for the early diagnosis of glioblastoma multiforme (GBM) recurrence using peripheral whole blood samples in a minimally invasive approach known as "liquid biopsy". Our results indicate that gene expression analysis can detect changes in transcriptional (mRNAs) and post-transcriptional (small RNAs) levels after surgery and upon tumor recurrence. This prospective study aims to develop a diagnostic tool complementary to MRI modalities in the clinical follow-up, helping to track tumor progression/recurrence and to make clinical decisions. GBM WHO CNS Grade 4 represents a major challenge for oncology due to its aggressive behavior. Conventional imaging has restrictions in detecting tumor recurrence. This prospective study aims to identify gene-based biomarkers in whole blood instead of isolating exosomes for the early detection of tumor recurrence. Blood samples (n = 33) were collected from seven GBM patients at time points before and after surgery as well as upon tumor recurrence. Four tumor tissue samples were assessed in parallel. Next-generation sequencing (NGS), including mRNA-seq and small RNA-seq, was used to analyze gene expression profiles in blood samples and tumor tissues. A novel filtering pipeline was invented to narrow down potential candidate genes. In total, between 6–93 mRNA and 1–19 small RNA candidates could be identified among the seven patients. The overlap of genes between the patients was minimal, indicating significant inter-individual variance among GBM patients. In summary, this prospective study supports the applicability of gene expression measurements in whole blood for the detection of tumor recurrence. It might provide an alternative to the challenging workflow of liquid biopsy after laborious exosome isolation from whole blood. [ABSTRACT FROM AUTHOR]

Simple Summary: Management of brain metastases adjacent to the motor cortex and pyramidal tract bears an elevated risk for treatment-related morbidity and, hence, a reduced quality of life. For safe resection, navigated transcranial magnetic stimulation (nTMS) motor mapping combined with diffusion tensor imaging (DTI)-based fiber tracking (DTI-FTmot.TMS) is used to guide the neurosurgeon to preserve motor function. So far, during radiotherapy motor structures are not respected as organs at risk. In this study, the practicability of DTI-FTmot.TMS in adjuvant radiotherapy planning of brain metastases was investigated, demonstrating a potentially significant dose reduction to cortical and subcortical motor structures. Background: Resection of brain metastases (BM) close to motor structures is challenging for treatment. Navigated transcranial magnetic stimulation (nTMS) motor mapping, combined with diffusion tensor imaging (DTI)-based fiber tracking (DTI-FTmot.TMS), is a valuable tool in neurosurgery to preserve motor function. This study aimed to assess the practicability of DTI-FTmot.TMS for local adjuvant radiotherapy (RT) planning of BM. Methods: Presurgically generated DTI-FTmot.TMS-based corticospinal tract (CST) reconstructions (FTmot.TMS) of 24 patients with 25 BM resected during later surgery were incorporated into the RT planning system. Completed fractionated stereotactic intensity-modulated RT (IMRT) plans were retrospectively analyzed and adapted to preserve FTmot.TMS. Results: In regular plans, mean dose (Dmean) of complete FTmot.TMS was 5.2 ± 2.4 Gy. Regarding planning risk volume (PRV-FTTMS) portions outside of the planning target volume (PTV) within the 17.5 Gy (50%) isodose line, the DTI-FTmot.TMS Dmean was significantly reduced by 33.0% (range, 5.9–57.6%) from 23.4 ± 3.3 Gy to 15.9 ± 4.7 Gy (p < 0.001). There was no significant decline in the effective treatment dose, with PTV Dmean 35.6 ± 0.9 Gy vs. 36.0 ± 1.2 Gy (p = 0.063) after adaption. Conclusions: The DTI-FTmot.TMS-based CST reconstructions could be implemented in adjuvant IMRT planning of BM. A significant dose reduction regarding motor structures within critical dose levels seems possible. [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in systemic cancer management have improved survival for numerous types of solid cancer; therefore, the number of patients harboring BM is increasing. According to established guidelines, resection should be carried out in patients with single brain metastases and controlled primary disease or when histopathologic diagnosis is crucial for decision-making in cancer management. Post-surgery rates of local recurrence are high; hence, adjuvant local radiation therapy (RT) is indicated to improve outcomes. So far, there is no standard of care regarding dose and fractionation; furthermore, delineation of the cavity can be challenging. Lately, low-energy X-ray intraoperative radiation therapy (IORT) applied to the resection bed has emerged in clinical practice, offering local ablative treatment with steep dose gradients towards the surrounding healthy brain. We here retrospectively describe 18 patients with resected brain metastases, which had undergone IORT, demonstrating the effectiveness and safety of this technique in accordance with previous studies. Background: Resection followed by local radiation therapy (RT) is the standard of care for symptomatic brain metastases. However, the optimal technique, fractionation scheme and dose are still being debated. Lately, low-energy X-ray intraoperative RT (lex-IORT) has been of increasing interest. Method: Eighteen consecutive patients undergoing BM resection followed by immediate lex-IORT with 16–30 Gy applied to the spherical applicator were retrospectively analyzed. Demographic, RT-specific, radiographic and clinical data were reviewed to evaluate the effectiveness and safety of IORT for BM. Descriptive statistics and Kaplan–Meyer analysis were applied. Results: The mean follow-up time was 10.8 months (range, 0–39 months). The estimated local control (LC), distant brain control (DBC) and overall survival (OS) at 12 months post IORT were 92.9% (95%-CI 79.3–100%), 71.4% (95%-CI 50.2–92.6%) and 58.0% (95%-CI 34.1–81.9%), respectively. Two patients developed radiation necrosis (11.1%) and wound infection (CTCAE grade III); both had additional adjuvant treatment after IORT. For five patients (27.8%), the time to the start or continuation of systemic treatment was ≤15 days and hence shorter than wound healing and adjuvant RT would have required. Conclusion: In accordance with previous series, this study demonstrates the effectiveness and safety of IORT in the management of brain metastases despite the small cohort and the retrospective characteristic of this analysis. [ABSTRACT FROM AUTHOR]