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.

Recent studies suggested that postoperative hypoxia might trigger invasive tumor growth, resulting in diffuse/multifocal recurrence patterns. Aim of this study was to analyze distinct recurrence patterns and their association to postoperative infarct volume and outcome. 526 consecutive glioblastoma patients were analyzed, of which 129 met our inclusion criteria: initial tumor diagnosis, surgery, postoperative diffusion-weighted imaging and tumor recurrence during follow-up. Distinct patterns of contrast-enhancement at initial diagnosis and at first tumor recurrence (multifocal growth/progression, contact to dura/ventricle, ependymal spread, local/distant recurrence) were recorded by two blinded neuroradiologists. The association of radiological patterns to survival and postoperative infarct volume was analyzed by uni-/multivariate survival analyses and binary logistic regression analysis. With increasing postoperative infarct volume, patients were significantly more likely to develop multifocal recurrence, recurrence with contact to ventricle and contact to dura. Patients with multifocal recurrence (Hazard Ratio (HR) 1.99, P = 0.010) had significantly shorter OS, patients with recurrent tumor with contact to ventricle (HR 1.85, P = 0.036), ependymal spread (HR 2.97, P = 0.004) and distant recurrence (HR 1.75, P = 0.019) significantly shorter post-progression survival in multivariate analyses including well-established prognostic factors like age, Karnofsky Performance Score (KPS), therapy, extent of resection and patterns of primary tumors. Postoperative infarct volume might initiate hypoxia-mediated aggressive tumor growth resulting in multifocal and diffuse recurrence patterns and impaired survival.

Gliomas are primary brain tumors that present the majority of malignant adult brain tumors. Gliomas are subdivided into low- and high-grade tumors. Despite extensive research in recent years, the prognosis of malignant glioma patients remains poor. This is caused by naturally highly infiltrative capacities as well as high levels of radio- and chemoresistance. Additionally, it was shown that low linear energy transfer (LET) irradiation enhances migration and invasion of several glioma entities which might counteract today’s treatment concepts. However, this finding is discussed controversially. In the era of personalized medicine, this controversial data might be attributed to the patient-specific heterogeneity that ultimately could be used for treatment. Thus, current developments in glioma therapy should be seen in the context of intrinsic and radiation-enhanced migration and invasion. Due to the natural heterogeneity of glioma cells and different radiation responses, a personalized radiation treatment concept is suggested and alternative radiation concepts are discussed.

Despite rapid progress in the treatment of many cancers, glioblastoma remains a devastating disease with dismal prognosis. The aim of this study was to identify chaperone- and immune-related biomarkers to improve prediction of outcome in glioblastoma. Depending on its intra- or extracellular localization the major stress-inducible heat shock protein 70 (Hsp70) fulfills different tasks. In the cytosol Hsp70 interferes with pro-apoptotic signaling pathways and thereby protects tumor cells from programmed cell death. Extracellular Hsp70 together with pro-inflammatory cytokines are reported to stimulate the expression of activatory NK cell receptors, recognizing highly aggressive human tumor cells that present Hsp70 on their cell surface. Therefore, intra-, extracellular and membrane-bound Hsp70 levels were assessed in gliomas together with activatory NK cell receptors. All gliomas were found to be membrane Hsp70-positive and high grade gliomas more frequently show an overexpression of Hsp70 in the nucleus and cytosol. Significantly elevated extracellular Hsp70 levels are detected in glioblastomas with large necrotic areas. Overall survival (OS) is more favorable in patients with low Hsp70 serum levels indicating that a high Hsp70 expression is associated with an unfavorable prognosis. The data provide a first hint that elevated frequencies of activated NK cells at diagnosis might be associated with a better clinical outcome.

Oncotarget | https://doi.org/10.18632/oncotarget.11482 Stefanie Bette, Benedikt Wiestler, Johannes Kaesmacher, Thomas Huber, Julia Gerhardt, Melanie Barz, Claire Delbridge, Yu-Mi Ryang, Florian Ringel, Claus... Infarct volume after glioblastoma surgery as an independent prognostic factor

(1) Background: As resection of trigeminal schwannomas is challenging, due to anatomical involvement of the anterior, middle and posterior fossa, the appropriate approach is important. We report our experience with surgical resection of trigeminal schwannomas by simple and classic skull-base approaches. (2) Methods: We performed a retrospective single-center study including patients who underwent surgery for trigeminal schwannoma tumors between June 2007 and May 2020, concentrating on surgical technique, extent of resection, postoperative outcome and complications. (3) Results: We included 13 patients (median age 57.5 with range of 36-83 years, 53.8% (7/13) female. The most common preoperative clinical presentations were facial pain in six (46.2%), hypoacusis in four (30.8%), trigeminal nerve hypesthesia in 11 (V1 46.2% (6/13), V2 (61.5% (8/13), V3 46.2% (6/13)) and headache in three (23.1%) patients. In three cases, the tumor was resected in a two-stage technique. The intradural subtemporal approach was performed in six cases, the extradural technique in two cases, the retrosigmoid approach in five cases, a Kawase approach in two cases and the transnasal endoscopic approach in one case. The gross total resection rate was 76.9% (10/13) and the median follow-up time 24.0 (0–136) months. Three (23.1%) patients developed postoperative anesthesia in at least one branch of the trigeminal nerve. Trigeminal motor function was preserved in 11 (84.6%) patients. Ten of the 11 patients (76.9%) who reported decreased gustation, cerebellar ataxia, visual impairment, or headache improved postoperatively. Two (15.4%) patients exhibited minimal facial palsy (House and Brackmann II–III), which resolved during the follow-up. The total adverse event rate requiring surgical intervention during follow-up was 7.7%. Surgery-related mortality was 0%. (4) Conclusions: Trigeminal schwannomas are rare benign lesions with intra- and extracranial extension. Considering the low operative morbidity and satisfying functional outcome, gross total resection of trigeminal schwannomas is achievable by classic, but also individually tailored approaches. More invasive or combined techniques were not needed with meticulous surgical planning.