Stereotactic needle biopsy provides a minimally invasive option for the diagnosis of intracranial lesions but is limited by inconclusive diagnoses on frozen pathology. For rapid pathology, ...5-aminovelunic acid and sodium fluorescein have previously demonstrated potential as diagnostic adjuvants. Stereotactic biopsy with near-infrared (NIR) fluorophores has not been reported. We identified 5 representative cases using NIR fluorescent dye indocyanine green (ICG) administered in a high dose, delayed manner.
Five patients underwent second window indocyanine green (SWIG)-guided stereotactic biopsy for diagnosis of suspected glioma or tumor recurrence. Up to 5 mg/kg ICG was administered approximately 24 hours prior to surgery. Biopsies were conducted in the standard fashion, targeting regions of suspected tumor using intraoperative frameless navigation. Samples were examined intraoperatively under standard visible light and for fluorescence using conventional NIR imaging platforms. Findings were correlated with frozen and final tumor pathology for all cases.
A total of 10 biopsy specimens were obtained. Three did not fluoresce and did not demonstrate tumor on preliminary or final pathology, including a non-gadolinium-enhancing sample taken proximal to the final target. The remaining 7 fluoresced, of which 6 contained tumor and 1 contained necrosis. Fluorescence was also noted in a patient with radiation treatment effect. Overall fluorescence characteristics were highly concordant with preliminary and final diagnoses.
SWIG provides rapid intraoperative confirmation of pathologic brain tissue by permeating neoplastic or inflammatory brain tissue via a mechanism similar to that of gadolinium enhancement. SWIG-guided stereotactic biopsy can improve surgical efficiency by enhancing confidence in acquisition of target tissue.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
BACKGROUND:Meningiomas are well-encapsulated benign brain tumors and surgical resection is often curative. Nevertheless, this is not always possible due to the difficulty of identifying residual ...disease intraoperatively. We hypothesized that meningiomas overexpress folate receptor alpha (FRα), allowing intraoperative molecular imaging by targeting FRα with a near-infrared (NIR) dye.
OBJECTIVE:To determine FRα expression in both human and canine meningioma cohorts to prepare for future clinical studies. Present a case study of a meningioma resection with intraoperative NIR fluorescence imaging.
METHODS:Tissue samples of 27 human meningioma specimens and 7 canine meningioma specimens were immunohistochemically stained for FRα along with normal dura, skeletal muscle, and kidney tissue. We then enrolled a patient with a pituitary adenoma and tuberculum sella meningioma in a clinical trial in which the patient received an infusion of folate-linked, NIR fluorescent dye prior to surgery.
RESULTS:In the cohort of human meningiomas, 9 WHO grade I, 12 grade II, and 6 grade III tumors were identified. Eighty-nine percent of WHO grade I, 67% of grade II, and 50% of grade III tumors overexpressed FRα. In the 7 canine meningioma samples, 100% stained positively for FRα. Both human and canine normal dura from autopsy samples demonstrated no evidence of FRα overexpression. In the case study, the meningioma demonstrated a high NIR signal-to-background-ratio of 4.0 and demonstrated strong FRα immunohistochemistry staining.
CONCLUSION:This study directly demonstrates FRα overexpression in both human and canine meningiomas. We also demonstrate superb intraoperative imaging of a meningioma using a FRα-targeting dye.
Glioblastoma (GBM) is an immunologically "cold" tumor characterized by poor responsiveness to immunotherapy. Standard of care for GBM is surgical resection followed by chemoradiotherapy and ...maintenance chemotherapy. However, tumor recurrence is the norm, and recurring tumors are found frequently to have acquired molecular changes (e.g., mutations) that may influence their immunobiology. Here, we compared the immune contexture of de novo GBM and recurrent GBM (rGBM) using high-dimensional cytometry and multiplex IHC. Although myeloid and T cells were similarly abundant in de novo and rGBM, their spatial organization within tumors differed and was linked to outcomes. In rGBM, T cells were enriched and activated in perivascular regions and clustered with activated macrophages and fewer regulatory T cells. Moreover, a higher expression of phosphorylated STAT1 by T cells in these regions at recurrence was associated with a favorable prognosis. Together, our data identify differences in the immunobiology of de novo GBM and rGBM and identify perivascular T cells as potential therapeutic targets. See related Spotlight by Bayik et al., p. 787.
The surgical resection of solid tumours can be enhanced by fluorescence-guided imaging. However, variable tumour uptake and incomplete clearance of fluorescent dyes reduces the accuracy of ...distinguishing tumour from normal tissue via conventional fluorescence intensity-based imaging. Here we show that, after systemic injection of the near-infrared dye indocyanine green in patients with various types of solid tumour, the fluorescence lifetime (FLT) of tumour tissue is longer than the FLT of non-cancerous tissue. This tumour-specific shift in FLT can be used to distinguish tumours from normal tissue with an accuracy of over 97% across tumour types, and can be visualized at the cellular level using microscopy and in larger specimens through wide-field imaging. Unlike fluorescence intensity, which depends on imaging-system parameters, tissue depth and the amount of dye taken up by tumours, FLT is a photophysical property that is largely independent of these factors. FLT imaging with indocyanine green may improve the accuracy of cancer surgeries.
ABSTRACTGlioblastoma (GBM) is the deadliest form of brain cancer and recurs uniformly. Despite aggressive treatment with maximal safe surgical resection, adjuvant radiation with temozolomide ...chemotherapy, and alternating electrical field therapy, median survival for newly diagnosed GBM remains <2 years. Novel therapies are desperately needed. Immunotherapy, which has led to significant improvement in patient outcomes across many tumor types, is currently being studied in a large number of GBM clinical trials. One of the biggest challenges in immunotherapy trials in GBM has been accurate response assessment using currently available imaging modalities, including magnetic resonance imaging. In this review, we will discuss the rationale for immunotherapy for GBM, immunotherapeutic modalities currently under clinical evaluation in GBM, and the challenges and recent advances in imaging response assessment in GBM immunotherapy.
Abstract Background and Importance Spinal meningiomas are typically extra-axial, slow-growing, benign tumors that arise from the arachnoid cap cells. Intramedullary spinal meningiomas are exceedingly ...rare with few cases reported in the literature. Clinical Presentation 64 year-old man with a history of Grade I thoracic meningioma at the T4 level resected initially in 1989 and who required re-operation in 2013 for intradural, extramedullary recurrence of tumor, presenting again in 2015 with gait difficulty. MRI revealed a soft tissue mass at the T3 to T4 levels on the left side of the canal that was mildly enhancing on T1 contrasted sequences. The patient was taken to the operating room where a purely intramedullary recurrence was discovered without extramedullary extension or a dural based attachment. The intramedullary tumor was completely resected and post-operatively the patient recovered well and was at his neurological baseline. The patient ultimately underwent proton beam radiotherapy given that this tumor, while benign, had recurred twice. Conclusion I ntramedullary spinal meningiomas, and in particular, intramedullary low-grade recurrence of a previously extramedullary tumor, is a rare phenomenon. While the pathogenic mechanisms are not well understood, intramedullary recurrence as described in this patient may reflect extrinsic factors related to prior surgical resections in addition to histologic progression. When operating on recurrent extramedullary lesions, aggressive arachnoid dissection may predispose patients to unusual patterns of recurrence.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Abstract
Background
Recurrent gliomas are therapeutically challenging diseases with few treatment options available. One area of potential therapeutic vulnerability is the presence of targetable ...oncogenic fusion proteins.
Methods
To better understand the clinical benefit of routinely testing for fusion proteins in adult glioma patients, we performed a retrospective review of 647 adult patients with glioma who underwent surgical resection at our center between August 2017 and May 2021 and whose tumors were analyzed with an in-house fusion transcript panel.
Results
Fifty-two patients (8%) were found to harbor a potentially targetable fusion with 11 (21%) of these patients receiving treatment with a fusion-targeted inhibitor. The targetable genes found to be involved in a fusion included FGFR3, MET, EGFR, NTRK1, NTRK2, BRAF, ROS1, and PIK3CA.
Conclusions
This analysis demonstrates that routine clinical testing for gene fusions identifies a diverse repertoire of potential therapeutic targets in adult patients with glioma and can offer rational therapeutic options for patients with recurrent disease.
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