Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: phase 1 trial interim results.

Recurrent glioblastoma (rGBM) remains a major unmet medical need, with a median overall survival of less than 1 year. Here we report the first six patients with rGBM treated in a phase 1 trial of intrathecally delivered bivalent chimeric antigen receptor (CAR) T cells targeting epidermal growth factor receptor (EGFR) and interleukin-13 receptor alpha 2 (IL13Rα2). The study's primary endpoints were safety and determination of the maximum tolerated dose. Secondary endpoints reported in this interim analysis include the frequency of manufacturing failures and objective radiographic response (ORR) according to modified Response Assessment in Neuro-Oncology criteria. All six patients had progressive, multifocal disease at the time of treatment. In both dose level 1 (1 ×107 cells; n = 3) and dose level 2 (2.5 × 107 cells; n = 3), administration of CART-EGFR-IL13Rα2 cells was associated with early-onset neurotoxicity, most consistent with immune effector cell-associated neurotoxicity syndrome (ICANS), and managed with high-dose dexamethasone and anakinra (anti-IL1R). One patient in dose level 2 experienced a dose-limiting toxicity (grade 3 anorexia, generalized muscle weakness and fatigue). Reductions in enhancement and tumor size at early magnetic resonance imaging timepoints were observed in all six patients; however, none met criteria for ORR. In exploratory endpoint analyses, substantial CAR T cell abundance and cytokine release in the cerebrospinal fluid were detected in all six patients. Taken together, these first-in-human data demonstrate the preliminary safety and bioactivity of CART-EGFR-IL13Rα2 cells in rGBM. An encouraging early efficacy signal was also detected and requires confirmation with additional patients and longer follow-up time. ClinicalTrials.gov identifier: NCT05168423 .

Case report of a giant cell tumor of the carotid sheath.

Giant cell tumor of the soft tissue (GCTST) is a neoplasm with low malignant potential and typically affects the trunk and extremities. Herein, we present a case of a palpable right neck mass diagnosed as a GCTST of the carotid sheath in a 38-year-old woman. A review of the imaging characteristics as well as of the differential diagnoses of primary neoplasms of the carotid space is presented.

Giant Iliac Artery Pseudoaneurysm Mimicking Postoperative Fluid Collection and Diskitis.

BACKGROUND: In this report, we describe an extremely rare case of a giant pseudoaneurysm of the internal iliac artery causing marked destructive changes at a disk space and mimicking diskitis-osteomyelitis. Only 2 other cases of pseudoaneurysms extending into the disk space have been reported, and those arose from the aorta and were relatively straightforward to diagnose. CASE DESCRIPTION: Our case is unique because the pseudoaneurysm arose from the internal iliac artery, an artery that is not usually included in the field of view of lumbar magnetic resonance imaging or computed tomography. However, the pseudoaneurysm was so large that it extended to the lumbosacral junction, where it eroded a disk space and caused findings of diskitis-osteomyelitis. CONCLUSIONS: Complex paraspinal fluid collections causing osseous erosions should raise the possibility of an aneurysm/pseudoaneurysm. Computed tomography or conventional angiography should be considered if the question of a vascular mass/collection cannot be answered on conventional cross-sectional imaging, as inadvertent biopsy of a pseudoaneurysm can cause catastrophic bleeding.

Muslin Granuloma Mimicking Parenchymal Hematoma in Patient with Seizures 30 Years After Aneurysm Wrapping.

Muslin foreign body granulomas are a known complication of muslin aneurysm wrapping and have been associated with vision loss from optochiasmatic arachnoiditis. Muslin granulomas have also been confused with abscesses due to surrounding inflammatory changes. In this clinical image, we present a unique case of a muslin granuloma mimicking an intraparenchymal hematoma.

Cranial Nerve Schwannomas: Diagnostic Imaging Approach.

Schwannomas are benign nerve sheath tumors that may arise along the complex course of the cranial nerves (CNs), anywhere in the head and neck. Sound knowledge of the CN anatomy and imaging features of schwannomas is paramount for making the correct diagnosis. In this article, we review approaches to diagnosing CN schwannomas by describing their imaging characteristics and the associated clinical presentations. Relevant anatomic considerations are highlighted by using illustrative examples and key differential diagnoses categorized according to regions, which include the anterior skull base, orbit, cavernous sinus, basal cisterns, and neck. The clinical presentations associated with CN schwannomas vary and range from no symptoms to symptoms caused by mass effect or CN deficits. Individuals with the inherited disorder neurofibromatosis type 2 are predisposed to multiple schwannomas. When a lesion follows the course of a CN, the radiologist's roles are to confirm the imaging features of schwannoma and exclude appropriate differential considerations. The characteristic imaging features of CN schwannomas reflect their slow growth as benign neoplasms and include circumscribed margins, displacement of local structures, and smooth expansion of osseous foramina. These neoplasms exhibit various degrees of solid enhancement, often with internal cystic spaces on magnetic resonance (MR) and computed tomographic (CT) images and heterogeneous high signal intensity specifically on T2-weighted MR images. Clinical and/or imaging evidence of end-organ compromise of the involved CN may exist and aid in the identification of the nerve of origin. With a detailed understanding of the course of the CNs, the diagnostic features of CN schwannomas, and the correlation between these data and the associated clinical presentations of these tumors, the radiologist can have a key role in the diagnosis of CN schwannomas and the treatment planning for affected patients. (©)RSNA, 2016.

Vertebral artery dissection and cerebral infarction in a patient with recurrent ovarian cancer receiving bevacizumab.

•Ovarian cancer patients receiving bevacizumab treatment can experience significant adverse events.•We report a case of vertebral artery dissection associated with bevacizumab treatment.

Ruptured pseudoaneurysm of the internal maxillary artery complicating CT-guided fine-needle aspiration in an irradiated, surgical bed.

BACKGROUND: CT-guided fine-needle aspiration (FNA) is a safe procedure, but major complications can occur rarely. Pseudoaneurysm rupture in the head and neck region following CT-guided FNA is an emergency that can result in life-threatening hemorrhage. This case emphasizes the salient risk factors for pseudoaneurysm formation and rupture in the head and neck region following CT-guided FNA. METHODS: A patient was seen with oral and facial hemorrhage as a result of a ruptured pseudoaneurysm 11 weeks following CT-guided FNA in a previously irradiated surgical bed. RESULTS: The patient was treated with coil embolization in and around the pseudoaneurysm and discharged without any further complications. CONCLUSIONS: Although CT-guided FNA is a safe and effective procedure, some patients may be at increased risk for rare but major complications. Caution should be used in proceeding with CT-guided FNA in an irradiated surgical bed of the head and neck.

Recurrent late cerebral necrosis with aggressive characteristics after radiosurgical treatment of an arteriovenous malformation. Case report.

/Late cerebral radiation necrosis usually occurs within 3 years of stereotactic radiosurgery. The authors report on a case of recurrent radiation necrosis with rapid clinical deterioration and imaging findings resembling those of a malignant glioma. This 68-year-old man, who had a history of a left posterior temporal and thalamic arteriovenous malformation (AVM) treated with linear accelerator radiosurgery 13 years before presentation and complicated by radiation necrosis 11 years before presentation, exhibited new-onset mixed aphasia, right hemiparesis, and right hemineglect. Imaging studies demonstrated hemorrhage and an enlarging, heterogeneously enhancing mass in the region of the previously treated AVM. The patient was treated medically with corticosteroid agents, and stabilized temporarily. Unfortunately, his condition worsened precipitously soon thereafter, requiring the placement of a shunt for relief of obstructive hydrocephalus. Further surgical intervention was offered, but the patient's family opted for hospice care instead. The patient died 10 weeks after initially presenting to the authors' institution, and the results of an autopsy demonstrated radiation necrosis. Symptomatic radiation necrosis can occur more than a decade after stereotactic radiosurgery, necessitating patient follow up during a longer period of time than currently practiced. Furthermore, there is a need for more careful reporting on the natural history of such cases to clarify the pathogenesis of very late and recurrent radiation necrosis after radiosurgery and to define patient groups with a higher risk for these entities.