Nuanced Management of a Skull Base Tumor in the Setting of Relapsed Acute Lymphoblastic Leukemia.

Introduction Relapsed acute lymphoblastic leukemia (ALL) involving the central nervous system (CNS) is a significant issue that contributes to both morbidity and mortality. Given the poor outcomes in patients with CNS relapse, understanding how ALL involving intracranial relapse presents and is treated is critical. Here, we present a complex case of relapsed recurrent ALL in a pediatric patient. Case Report An 11-year-old patient presented with double relapse of ALL in the form of an extensive skull base lesion and again with leptomeningeal disease. For the skull base lesion, she was treated nonsurgically with chemotherapy and radiation, which led to a remarkable reduction in the size of the lesion. However, she was found to have early recurrence with leptomeningeal enhancement resulting in hydrocephalus 5 months after completing therapy. A shunt was placed successfully. Currently, she is being managed with monthly intrathecal chemotherapy with cerebrospinal fluid sampling and bone marrow biopsies every 2 months. Discussion We report the significant effect of chemotherapy and radiotherapy in reducing the size of the extensive skull base lesion, saving the patient from the risks associated with surgery. This patient's initial relapse, with a large skull base lesion that had intracranial involvement, is an unusual presentation of relapsed ALL. The additional early recurrence of leptomeningeal disease further makes this case unique and the management even more nuanced. Here, we demonstrate a multidisciplinary approach for the successful treatment of our patient, which can help guide the management of similar patients in the future.

Clinical Features and Management of Skull Base Fractures in the Pediatric Population: A Systematic Review.

Pediatric basilar skull fractures (BSFs) are a rare type of traumatic head injury that can cause debilitating complications without prompt treatment. Here, we sought to review the literature and characterize the clinical features, management, and outcomes of pediatric BSFs. We identified 21 relevant studies, excluding reviews, meta-analyses, and non-English articles. The incidence of pediatric BSFs ranged from 0.0001% to 7.3%, with falls from multi-level heights and traffic accidents being the primary causes (9/21). The median presentation age ranged from 3.2 to 12.8 years, and the mean age of patients across all studies was 8.68 years. Up to 55% of pediatric BSFs presented with intracranial hematoma/hemorrhage, along with pneumocephalus and edema. Cranial nerve palsies were a common complication (9/21), with the facial nerve injured most frequently (7/21). While delayed cranial nerve palsy was reported in a few studies (4/21), most resolved within three months post-admission. Other complications included CSF leaks (10/21) and meningitis (4/21). Management included IV fluids, antiemetics, and surgery (8/21) to treat the fracture directly, address a CSF leak, or achieve cranial nerve compression. Despite their rarity, pediatric skull base fractures are associated with clinical complications, including CSF leaks and cranial nerve palsies. Given that some of these complications may be delayed, patient education is critical.

CCR2 and CCR5 co-inhibition modulates immunosuppressive myeloid milieu in glioma and synergizes with anti-PD-1 therapy.

Immunotherapy has revolutionized the treatment of cancers. Reinvigorating lymphocytes with checkpoint blockade has become a cornerstone of immunotherapy for multiple tumor types, but the treatment of glioblastoma has not yet shown clinical efficacy. A major hurdle to treat GBM with checkpoint blockade is the high degree of myeloid-mediated immunosuppression in brain tumors that limits CD8 T-cell activity. A potential strategy to improve anti-tumor efficacy against glioma is to use myeloid-modulating agents to target immunosuppressive cells, such as myeloid-derived suppressor cells (MDSCs) in the tumor microenvironment. We found that the co-inhibition of the chemokine receptors CCR2 and CCR5 in murine model of glioma improves the survival and synergizes robustly with anti-PD-1 therapy. Moreover, the treatment specifically reduced the infiltration of monocytic-MDSCs (M-MDSCs) into brain tumors and increased lymphocyte abundance and cytokine secretion by tumor-infiltrating CD8 T cells. The depletion of T-cell subsets and myeloid cells abrogated the effects of CCR2 and CCR5 blockade, indicating that while broad depletion of myeloid cells does not improve survival, specific reduction in the infiltration of immunosuppressive myeloid cells, such as M-MDSCs, can boost the anti-tumor immune response of lymphocytes. Our study highlights the potential of CCR2/CCR5 co-inhibition in reducing myeloid-mediated immunosuppression in GBM patients.

A Case Report of Infant-Type Hemispheric Glioma with a Novel GAB1-ABL2 Kinase Fusion Treated with Dasatinib.

INTRODUCTION: Infant-type hemispheric glioma (IHG) is a rare form of cancer that affects newborns and infants. It is classified as a pediatric-type high-grade glioma and typically harbors receptor tyrosine kinase (RTK) gene fusions. Here, we present the finding of a novel gene fusion IHG treated with a targeted therapy that has yet to be implemented for any other IHG case to date. CASE PRESENTATION: We report the case of a 12-month-old boy with IHG who presented with obstructive hydrocephalus due to a large mass in the right frontal lobe. The patient initially underwent mass resection, but subsequent imaging showed rapid interval progression of the residual tumor. Comprehensive molecular analysis of the tumor tissue revealed a novel GAB1-ABL2 gene fusion, and the patient was started on dasatinib, an ABL kinase inhibitor. Shortly after initiation of dasatinib treatment, there was a significant reduction in tumor size and enhancement, followed by stabilization of disease. DISCUSSION: The patient's robust response to treatment suggests that dasatinib is an effective targeted therapy for IHG harboring a GAB1-ABL2 gene fusion. This finding may inform future investigations into the disease processes of IHG and help guide the diagnosis and treatment of IHG in the absence of previously identified gene fusions, improving clinical management of this vulnerable patient population.

Effect of utilization of veno-venous bypass vs. cardiopulmonary bypass on complications for high level inferior vena cava tumor thrombectomy and concomitant radical nephrectomy

ABSTRACT Purpose: To determine if patients with renal cell carcinoma (RCC) with levels III and IV tumor thrombi are receive any reduction in complication rate utilizing veno-venous bypass (VVB) over cardiopulmonary bypass (CPB) for high level (III/IV) inferior vena cava (IVC) tumor thrombectomy and concomitant radical nephrectomy. Materials and Methods: From May 1990 to August 2011, we reviewed 21 patients that had been treated for RCC with radical nephrectomy and concomitant IVC thrombectomy employing either CPB (n =16) or VVB (n=5). We retrospectively reviewed our study population for complication rates and perioperative characteristics. Results: Our results are reported using the validated Dindo-Clavien Classification system comparing the VVB and CPB cohorts. No significant difference was noted in minor complication rate (60.0% versus 68.7%, P=1.0), major complication rate (40.0% versus 31.3%, P=1.0), or overall complication rate (60.0% versus 62.5%, P=1.0) comparing VVB versus CPB. We also demonstrated a trend towards decreased time on bypass (P=0.09) in the VVB cohort. Conclusion: The use of VVB over CPB provides no decrease in minor, major, or overall complication rate. The use of VVB however, can be employed on an individualized basis with final decision on vascular bypass selection left to the discretion of the surgeon based on specifics of the individual case.