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Current standard of care treatment for patients with spine tumors includes multidisciplinary approaches, including the following: (1) surgical tumor debulking, epidural spinal cord decompression, and spine stabilization techniques; (2) systemic chemo/targeted therapies; (3) radiation therapy; and (4) surveillance imaging for local disease control and recurrence. Titanium pedicle screw and rod fixation have become commonplace in the spine surgeon's armamentarium for the stabilization of the spine following tumor resection and separation surgery. However, the high degree of imaging artifacts seen with titanium implants on postoperative CT and MRI scans can significantly hinder the accurate delineation of vertebral anatomy and adjacent neurovascular structures to allow for the safe and effective planning of downstream radiation therapies and detection of disease recurrence. Carbon fiber-reinforced polyetheretherketone (CFR-PEEK) spine implants have emerged as a promising alternative to titanium due to the lack of artifact signals on CT and MRI, allowing for more accurate and safe postoperative radiation planning. In this article, we review the tenants of the surgical and radiation management of spine tumors and discuss the safety, efficacy, and current limitations of CFR-PEEK spine implants in the multidisciplinary management of spine oncology patients. [ABSTRACT FROM AUTHOR]

The current standard of care for brain tumor management includes maximal safe surgical resection followed by concurrent chemotherapy and radiation therapy. Recent advances in image-guided surgical techniques have enhanced the precision of tumor resections, yet there remains a critical need for innovative technologies to further improve patient outcomes. Techniques such as fluorescence image-guided neurosurgery in combination with stereotactic radiosurgery have improved outcomes for patients with brain tumors. In this article for Brain Science's Special Issue Recent Advances in Translational Neuro-Oncology, we review the use of image-guided neurosurgery and stereotactic radiosurgery for the treatment of brain tumors. In addition, we summarize the emerging use of theranostic nanoparticles for the delivery of diagnostic and therapeutic technologies to enable the neurosurgeon to perform more precise surgical resections in the operating room, to specifically target the delivery of existing and novel treatments to tumor cells, and to augment the efficacy of stereotactic radiosurgery. These innovative translational tools will allow neurosurgeons, neuro-oncologists, and radiation oncologists to go "beyond the knife" to improve the survival of brain tumor patients. [ABSTRACT FROM AUTHOR]

Introduction: Intramedullary metastases to the conus medullaris spinalis (IMCM) pose a rare problem in neurosurgical oncology and are usually encountered as a complicated clinical scenario in the setting of advanced systemic malignancy with poor overall survival. Despite the progress in interdisciplinary oncological care, their management remains complicated. Research Question: We performed a PRISMA-guided literature search to achieve a pooled analysis of all previously reported IMCM cases that contained detailed clinical data on this problem to investigate the currently employed management options and respective outcomes. We obtained a clinical vignette and performed a comprehensive narrative review of IMCM management. Materials and Methods: The PubMed/MEDLINE/Google Scholar, Cochrane and Embase databases were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All relevant publications retrieved were subjected to full-text analysis in detail and pertinent information was extracted. Results: The most common systemic primary tumor site as the origin of IMCM was the lung, followed by the breast. Overall, the pooled median survival was 6 months (range 0.5–36 months). Patients who received both surgery and radiation therapy had the longest overall survival (OS) (mean 9.9 months) and those who received no oncological treatment (neither surgery nor adjuvant therapy) had the shortest OS (mean 3.6 months). In cases where surgical resection was performed as part of the treatment plan for metastases, those with partial tumor resection had a more favorable neurological outcome than patients who underwent aggressive gross total resection. Conclusions: Based on the results of our analysis, we find that diligent microsurgical resection (subtotal or total) followed by radiation therapy appears as an effective and suitable treatment in select patients with IMCM. When surgery is not feasible as part of the treatment algorithm, radiation therapy alone (conventional or radiosurgery) also appears to be a suitable treatment option that confers a benefit to the patient. [ABSTRACT FROM AUTHOR]

Background: There is currently no consensus in the field regarding whether a frontal or lateral approach is superior for microsurgical resection of olfactory groove meningiomas (OGM). Due to the lack of uniformity in classifying lesions and inherent differences in reporting outcomes after varying operative approaches, the best practice for approaching these lesions is yet to be determined. Objective: This study aimed to assess various surgical approaches undertaken for OGMs, investigate procedural aspects influencing the extent of resection, and analyze the respective complication rate associated with each approach. We performed a comprehensive literature review of presenting signs and symptoms in OGM patients, their surgical management, and the reported surgical outcomes. To address the lack of uniform data reporting across studies and to take more recent translational studies into account, we developed a new classification system for OGMs that can remedy the existing deficiencies in comparability of reporting. Methods: We conducted a PRISMA-guided literature search for surgical reports on OGMs published in the MRI era using broad search terms such as 'olfactory groove meningioma' and 'surgery', which yielded 20,672 results. After title screening and removal of duplicates, we assessed 871 studies on the specific surgical management of olfactory groove meningiomas. Following the application of exclusion criteria and abstract screening, a set of 27 studies was chosen for the final analysis of a pooled cohort of these reported patient outcomes. Results: The final twenty-seven studies included in our in-depth analysis identified a total of 1016 individual patients who underwent open microsurgical resection of OGMs. The approaches used included: pterional/unilateral, bifrontal with variations, and anterior interhemispheric approaches. Across all studies, gross total resection (Simpson Grades I or II) was achieved in 91.4% of cases, and subtotal resection (Grades III and IV) was reported in 8.6% of cases. A cumulative twenty-seven percent of surgical OGM patients sustained some form of complications. Minor issues accounted for 22.2% (CSF leak, seizures, infection, transient cranial nerve palsies, hydrocephalus), whereas major issues comprised 4.7% (hemorrhage, ischemic infarct, malignant cerebral edema). We then examined the correlation between these complications and the surgical approach chosen. Among pooled cohort of 426 patients who underwent unilateral approaches, 14% experienced minor complications, and 2.1% experienced major complications. For the mixed cohort of 410 patients who underwent bifrontal approaches, 24.6% experienced minor complications, and 7% experienced major complications. Conclusions: Unilateral approaches appear to have lower complication rates for the resection of OGMs compared to bilateral approaches. However, the extent of resection is not uniformly reported, making it difficult to identify differences. The use of an improved preoperative classification and scoring system can help establish a more coherent system to select the most suitable approach and to uniformly report surgical outcomes, such as EOR and complication rates specific to a given OGM and its surgical approach. [ABSTRACT FROM AUTHOR]

Author(s): Scott R. Floyd [sup.1] [sup.2] , Michael E. Pacold [sup.1] [sup.3] [sup.4] , Qiuying Huang [sup.1] , Scott M. Clarke [sup.1] , Fred C. Lam [sup.1] , Ian G. [...], Isoform B of the chromatin-binding protein Brd4 acts to suppress DNA damage response signalling. Brd4 modulates response to DNA damage The detection and repair of damaged DNA is vital for cell survival and the maintenance of an intact genome, but aberrant DNA damage signalling can be a cause of cancer. Here Michael Yaffe and colleagues examine the role of chromatin structure change in the activation of the DNA damage response (DDR). They find that the B isoform of the chromatin binding protein, Brd4, acts to suppress DDR signalling. As it is bound to acetylated histones, this Brd4 isoform recruits the condensin II chromatin remodelling complex, which prevents relaxation of the chromatin necessary for binding by factors that recognize and repair DNA damage. In this way, this Brd4 isoform regulates the strength of the DDR through mechanisms distinct from known transcriptional interactions with the P-TEFb transcriptional complex. DNA damage activates a signalling network that blocks cell-cycle progression, recruits DNA repair factors and/or triggers senescence or programmed cell death.sup.1. Alterations in chromatin structure are implicated in the initiation and propagation of the DNA damage response.sup.2. Here we further investigate the role of chromatin structure in the DNA damage response by monitoring ionizing-radiation-induced signalling and response events with a high-content multiplex RNA-mediated interference screen of chromatin-modifying and -interacting genes. We discover that an isoform of Brd4, a bromodomain and extra-terminal (BET) family member, functions as an endogenous inhibitor of DNA damage response signalling by recruiting the condensin II chromatin remodelling complex to acetylated histones through bromodomain interactions. Loss of this isoform results in relaxed chromatin structure, rapid cell-cycle checkpoint recovery and enhanced survival after irradiation, whereas functional gain of this isoform compacted chromatin, attenuated DNA damage response signalling and enhanced radiation-induced lethality. These data implicate Brd4, previously known for its role in transcriptional control, as an insulator of chromatin that can modulate the signalling response to DNA damage.

There is significant improvement in the outcomes following treatment with PARP inhibitors among patients with certain tumors that have BRCA mutations (BRCAm), homologous recombination repair (HRR) gene mutations, or homologous recombination deficiency (HRD) positivity. We performed a literature review and meta‐analysis to evaluate the prevalence of BRCA1/2m, HRR gene mutations, and HRD positivity across multiple cancers. There were 265 publications on BRCA1/2 mutation prevalence, 189 on HRR gene mutation prevalence, and 7 on HRD positivity prevalence. The prevalences of germline BRCA1m and BRCA2m were 7.8% and 5.7% for breast cancer, 13.5% and 6.6% for ovarian cancer, 0.5% and 3.5% for prostate cancer, and 1.1% and 4.1% for pancreatic cancer, respectively. The prevalences of somatic BRCA1m and BRCA2m were 3.4% and 2.7% for breast cancer, 4.7% and 2.9% for ovarian cancer, 5.7% and 3.2% for prostate cancer, and 1.2% and 2.9% for pancreatic cancer, respectively. We identified 189 studies with over 418,649 samples across 25 tumor types that examined mutations in one or more HRR genes other than BRCA1/2. The prevalence of mutations among HRR genes remained low (less than 1%), with ATM (5.2%), CHEK2 (1.6%), and PALB2 (0.9%) exhibiting the highest prevalence. Seven studies evaluated HRD positivity in breast, ovarian, and prostate cancer patients. The prevalence of HRD positivity was 56% overall (95% CI = 48%–64%). The understanding of biomarker prevalence across tumor types and standardization of biomarker assays could have important clinical implications. [ABSTRACT FROM AUTHOR]

Abstract Background Lymphocyte-depleted Hodgkin’s lymphoma is the rarest form of classical Hodgkin’s lymphoma, accounting for Case presentation An 88-year-old Caucasian female presented with a history of upper back pain for several months and new onset bilateral leg numbness and weakness. MRI of the spine showed a dorsal epidural lesion with cord compression at T1-T4 with involvement of the paraspinal muscles. The patient received urgent surgical decompression, with final histopathology showing a lymphocyte-depleted Hodgkin’s lymphoma. Systemic work-up did not show evidence of nodal disease. Following surgery, she received a course of radiotherapy with good outcome. Conclusion To the best of our knowledge, this is the first reported case of primary lymphocyte-depleted Hodgkin lymphoma presenting as epidural spinal cord compression. Our report, in conjunction with a review of the literature, suggests that surgical intervention is clearly indicated in de novo disease followed by radiotherapy.

R-loops are intermediate structures of transcription that can accumulate when transcriptional elongation is blocked by inhibiting BRD4. In normal cells, R-loop persistence suppresses firing of adjacent replication origins. This control is lost in a subset of cancer cells, where BRD4 inhibition results in R-loop accumulation, leading to transcription-replication collisions and DNA double-strand breaks during S-phase, followed by cell death. This finding sheds new light on the mechanisms by which BRD4 inhibitors function as cancer therapies, and indicates that targeting other cellular events to cause R-loop accumulation may be useful for cancer treatment. [ABSTRACT FROM AUTHOR]