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Despite unprecedented survival in patients with glioblastoma (GB), the aggressive primary brain cancer remains largely incurable and its mechanisms of treatment resistance have gained particular attention. The cytokine interleukin 6 (IL-6) and its receptor weave through the hallmarks of malignant gliomas and may represent a key vulnerability to GB. Known for activating the STAT3 pathway in autocrine fashion, IL-6 is amplified in GB and has been recognized as a negative biomarker for GB prognosis, rendering it a putative target of novel GB therapies. While it has been recognized as a biologically active component of GB for three decades only with concurrent advances in understanding of complementary immunotherapy has the concept of targeting IL-6 for a human clinical trial gained scientific footing., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Glioblastoma multiforme (GBM) is one of the most aggressive and deadly forms of brain cancer, which has a very complex tumor microenvironment (TME) promoting tumor growth, immune evasion, and resistance to therapy. The main players within this environment are represented by cytokines such as Interleukin-4, Interleukin-6, and Interleukin-13, along with the costimulatory molecule CD40. The paper draws back the curtain on the complex interactions played out by these molecules in contributing to the formation of a TME within GBM. IL-4 and IL-13 induce an immunosuppressive environment through the polarization of tumor-associated macrophages (TAMs) into a pro-tumoral M2 phenotype. In contrast, IL-6 takes part in the activation of the JAK-STAT3 pathway, enhancing survival and proliferation of tumor cells. In this context, CD40 either induces anti-tumor immunity through APC activation or facilitates tumors by angiogenesis and survival pathways. The synergistic actions of these molecules create feedback loops that keep up the malignancy of GBM and present a big problem for therapy. Knowledge of these interactions opens new ways for the development of multi-targeted therapeutic strategies at the other end. This may result in the interruption of the tumor-supportive environment in GBM, reducing tumor growth and improving patient outcomes by targeting IL-4, IL-6, IL-13, and CD40 simultaneously., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Glioblastoma multiforme (GBM) patients continue to suffer a poor prognosis. The blood brain barrier (BBB) comprises one of the obstacles for therapy, creating a barrier that decreases the bioavailability of chemotherapeutic agents in the central nervous system. Previously, a vascularized temporoparietal fascial scalp flap (TPFF) lining the resection cavity was introduced in a trial conducted in our institution, in newly-diagnosed GBM patients in an attempt to bypass the BBB after initial resection. In this paper, we report on a new technique to bypass the BBB after re-resection and potentially to allow tumor antigens to be surveilled by the immune system. The study aims to assess the feasibility of performing a cranial transposition and revascularization of autologous omentum after re-resection of GBM. Laparoscopically harvested omental free flap was transposed to the resection cavity by a team consisting of neurosurgeons, otolaryngologists, and general surgeons. This was done as part of a single center, single arm, open-label, phase I study. Autologous abdominal omental tissue was harvested laparoscopically on its vascularized pedicle in 2 patients, transposed as a free flap, revascularized using external carotid artery, and carefully laid into the tumor resection cavity. Patients did well postoperatively returning to baseline activities. Graft viability was confirmed by cerebral angiogram. Omental cranial transposition of a laparoscopically harvested, vascularized flap, into the cavity of re-resected GBM patients is feasible and safe in the short term. Further studies are needed to ascertain whether such technique can improve progression free survival and overall survival in these patients., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The inevitable recurrence of glioblastoma (GBM) results in patients often undergoing multiple resections with questionable benefit to overall survival (OS)., Objective: To systematically review and analyze prior studies examining the potential added benefit of repeat resection (RR) in recurrent GBM., Methods: We performed a PRISMA-compliant systematic review of literature published between 1969 to 2019 involving patients undergoing RR at GBM recurrence., Results: The search yielded 3994 non-duplicate citations. Final abstraction included 43 articles, with 2 level II and 41 level III studies. The earliest paper we included was published in 1987 [1], and 35 identified papers (81.4%) were published within the last 10 years. The survival data of 9236 patients (55% male) were analyzed, with a median age of 56; 3726 patients underwent RR. In 31 studies with a comparable single-surgery-only cohort, 20 articles reported a statistically significant increase in OS with RR, 7 reported nonsignificant trends toward increased OS with RR, and 4 reported no significant increase in OS with RR. Twenty-two articles with multivariate analyses of Karnofsky performance scores and 17 articles with extent-of-resection reported these as significant prognostic factors of OS. In 26 studies, median OS among all patients was 17.85 months inclusive of median OS following RR totaling 9.6 months. Notably, in 10 studies with data on subsequent progressions (2+ recurrences), 6 studies reported significant increases in OS with subsequent repeat resection (sRR) compared to those not undergoing sRR., Conclusions: Recurrent GBM presents a treatment challenge. There appears to be an OS benefit for RR upon first recurrence as well as sRR. Such findings warrant further investigation of the potential benefits of continued surgical intervention after subsequent progressions of GBM.

The currently accepted standard of care for primary glioblastoma (GBM) consists of maximal surgical resection followed by fractionated external beam radiotherapy (EBRT) with concomitant temozolomide chemotherapy. The role of stereotactic radiosurgery (SRS) in the treatment of GBM is not well defined, but SRS has typically been applied as a salvage therapy for GBM recurrence. This paper reviews our single institution experience using gamma knife radiosurgery (GKRS) for the treatment of GBM. Thirty-six patients treated with GKRS for pathologically proven GBM at LSU Health in Shreveport from February 2000 to December 2013 were identified and analyzed. Patient characteristics, treatment variables, and survival were correlated. Seven patients received GKRS in the immediate postoperative period for an average tumor volume of 10.9 cm(3), and 29 patients were treated for a recurrent average tumor volume of 11.4 cm(3) with a prescribed dose ranging from 10 to 20 Gy at the 50 % isodose line. The median overall survival was significantly higher in recurrence group compared to up-front group [7.9 months (0.77-32.1 months) vs. 3.5 months (range 0.23-11.7 months) respectively, (p = 0.018)]. The predictive factors for improved survival in the patients with GBM were as follows: Karnofsky performance scale (KPS) > 70 (p = 0.026), age ≤ 50 years (p = 0.006), absence of neurodeficits (p = 0.01), and initial postoperative treatment with EBRT (p = 0.042). Adjuvant therapy with GKRS following GBM recurrence demonstrates statistical superiority over immediate postoperative boost therapy.