Fluorescence-guided surgery for brain tumors

Hefti, Max

doi:10.2217/cns.12.35

Cited by 6 publications

(3 citation statements)

References 47 publications

(42 reference statements)

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“…5c. Similar results have been documented with PpIX fluorescence imaging near glioma tumors [43]. More importantly, though, this increased background from edema-based perfusion to normal brain did not significantly decrease the tumor˗-to-normal contrast (Fig.…”

Section: Discussionsupporting

confidence: 87%

Fluorescent Affibody Molecule Administered In Vivo at a Microdose Level Labels EGFR Expressing Glioma Tumor Regions

et al. 2016

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PurposeFluorescence guidance in surgical oncology provides the potential to realize enhanced molecular tumor contrast with dedicated targeted tracers, potentially with a microdose injection level. For most glioma tumors, the blood brain barrier is compromised allowing some exogenous drug/molecule delivery and accumulation for imaging. The aberrant overexpression and/or activation of epidermal growth factor receptor (EGFR) is associated with many types of cancers, including glioblastoma, and so the use of a near-infrared (NIR) fluorescent molecule targeted to the EGFR receptor provides the potential for improving tumor contrast during surgery. Fluorescently labeled affibody molecule (ABY-029) has high EGFR affinity and high potential specificity with reasonably fast plasma clearance. In this study, ABY-29 was evaluated in glioma versus normal brain uptake from intravenous injection at a range of doses, down to a microdose injection level.ProcedureNude rats were inoculated with the U251 human glioma cell line in the brain. Tumors were allowed to grow for 3–4 weeks. ABY-029 fluorescence ex vivo imaging of brain slices was acquired at different time points (1–48 h) and varying injection doses from 25 to 122 μg/kg (from human protein microdose equivalent to five times microdose levels).ResultsThe tumor was most clearly visualized at 1-h post-injection with 8- to 16-fold average contrast relative to normal brain. However, the tumor still could be identified after 48 h. In all cases, the ABY-029 fluorescence appeared to localize preferentially in EGFR-positive regions. Increasing the injected dose from a microdose level to five times, a microdose level increased the signal by 10-fold, and the contrast was from 8 to 16, showing that there was value in doses slightly higher than the microdose restriction. Normal tissue uptake was found to be affected by the tumor size, indicating that edema was a likely factor affecting the expected tumor to normal tissue contrast.ConclusionThese results suggest that the NIR-labeled affibody molecules provide an excellent potential to increase surgical visualization of EGFR-positive tumor regions.

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Section: Discussionsupporting

confidence: 87%

Fluorescent Affibody Molecule Administered In Vivo at a Microdose Level Labels EGFR Expressing Glioma Tumor Regions

et al. 2016

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“…However, maximum cytoreductive surgery has been shown to prolong survival in glioblastoma patients [26,27]. For complete resection of the contrast-enhancing tumor, fluorescence-guided resection has proven to be beneficial, being the current gold standard [28,29]. Thus, fluorescenceguided resection often exceeds the contrastenhancing tumor [30].…”

Section: Surgerymentioning

confidence: 99%

Treatment of glioblastoma in elderly patients

Stockhammer¹

2014

CNS Oncol.

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Although glioblastoma occurs mostly in elderly patients, there is a paucity of trials addressing patients older than 70 years of age. Age, by itself, constitutes an unfavorable prognostic factor, which is probably due to unpropitious genetic features, but also due to iatrogenic defeatism. However, many retrospective studies report a survival benefit achieved by aggressive surgical resection seeking gross total removal of contrast-enhancing tumor according to preoperative MRI. Combined radiochemotherapy with concomitant and adjuvant temozolomide has not been investigated in prospective trials. Numerous retrospective studies and a meta-analysis suggest benefit from combined treatment. Prospective randomized trials only evaluated either temozolomide or radiotherapy. Single-treatment hypofractionated radiotherapy performed superior to conventional fractionation. In patients with methylated MGMT promoter, first-line dose-dense temozolomide facilitates prolonged survival. However, there is no comparison with combined radiochemotherapy as the standard-of-care in adult patients. Comorbidity is more frequent in elderly patients, but does not correlate with preterm termination of temozolomide treatment. This review article compiles data proposing a straightforward glioblastoma treatment, irrespective of age.

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“…More data is needed on the ALA/PpIX metabolism and fluorescence of tumors other than GBM, although it is known that several other forms of malignant glioma such as anaplastic oligodendroglioma and ependymoma or some cancer metastases show PpIX fluorescence (Hefti, 2013, Ewelt et al, 2015. This implies that a variety of lesions suspected for malignant CNS tumor are within the category of possible detection by means of fluorescence spectroscopy.…”

Section: Discussionmentioning

confidence: 99%

Fluorescence Guided Resection of Brain Tumors: Evaluation of a Hand-held Spectroscopic Probe

Richter¹

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Malignant gliomas grow infiltrative in the brain and can therefore not be completely removed by neurosurgical means. However, for an optimized oncological treatment it has proven useful to resect as much as possible of the tumor tissue. The identification of the tumor in the marginal zone is difficult but crucial. Studies have shown that visualization of the specific enhancement of 5-aminolevulinic acid (5-ALA) in the tumor can help to maximize the resection. The Department of Biomedical Engineering, Linköping University, has developed an optical hand-held probe (HHP) to identify tumor tissue with a high sensitivity by means of fluorescence spectroscopy. The technical design and the optical properties of the probe were gradually developed in a standard neurosurgical setting during resection of malignant gliomas. The device could easily be implemented in the operating room, meeting all requirements in terms of sterile handling and without interference of any kind with other equipment. The integration of the device in a navigation system and its use in combination with a blue light surgical microscope were simple. Measurements in 27 operations during resection of malignant gliomas were compared to results from biopsies from the same tumor locations. The equipment was tested as a stand-alone device (n = 180), integrated in a navigation system or in combination with the blue light microscope (n = 190). A ratio calculated from the measurements enabled objective and comparable values for different tissue types, in correspondence with the findings from the histopathological examinations and in accordance with the navigation system as well as with the surgical microscope. The marginal zone was explored and tumor fluorescence could be identified beyond the fluorescence as seen through the microscope. A higher sensitivity of the HHP was confirmed; the specificity was lower. The combined use of the HHP with a navigation system and with a surgical microscope was beneficial. X XI SammanfattningMaligna hjärntumörer växer infiltrerande i hjärnan och kan därför inte helt avlägsnas genom kirurgiska operationer. För en optimerad behandling har det emellertid visat sig vara av värde att avlägsna så mycket som möjligt av tumörvävnaden. Identifiering av tumören i gränszonen är mycket svårt, men avgörande. Studier har visat att visualisering av den specifika laddningen av 5-aminolevulinsyra (5-ALA) i tumören kan bidra till att maximera resektionen. Institutionen för Medicinsk Teknik (IMT) på Linköpings universitet, har utvecklat en liten handhållen optisk prob (HHP) för att identifiera tumörvävnad med hög känslighet med hjälp av fluorescens-spektroskopi. Den tekniska konstruktionen och de optiska egenskaperna hos proben utvecklades stegvis genom testning i flera neurokirurgiska operationer för resektion av maligna gliom. Utrustningen uppfyllde alla krav när det gällde steril hantering i operationssalen och kunde användas utan störningar av något slag med annan operationsutrustning. Integreringen i ett navigerings-system och a...

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Fluorescence-guided surgery for brain tumors

Cited by 6 publications

References 47 publications

Fluorescent Affibody Molecule Administered In Vivo at a Microdose Level Labels EGFR Expressing Glioma Tumor Regions

Fluorescent Affibody Molecule Administered In Vivo at a Microdose Level Labels EGFR Expressing Glioma Tumor Regions

Treatment of glioblastoma in elderly patients

Fluorescence Guided Resection of Brain Tumors: Evaluation of a Hand-held Spectroscopic Probe

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