Intraoperative Use of I.V. Sodium Fluorescein in Suspected CNS Tumors

The FLUO.CER.TUM study is a prospective observational clinical trial conducted at the IRCCS Foundation Neurological Institute "Carlo Besta" in Milan, Italy. It investigates the intraoperative use of intravenous sodium fluorescein as a fluorescent tracer to assist in the surgical resection of suspected malignant tumors of the central nervous system (CNS). These tumors typically present as contrast-enhancing masses on pre-operative MRI or CT scans. Malignant brain tumors are notoriously difficult to fully resect due to challenges in distinguishing tumor margins from healthy tissue. Sodium fluorescein, a dye that accumulates in areas where the blood-brain barrier is disrupted, offers a promising solution by enhancing tumor visualization during surgery. When used with a dedicated surgical microscope equipped with a fluorescence filter, fluorescein can help surgeons identify and remove more tumor tissue, potentially improving patient outcomes. The study aims to evaluate the effectiveness and safety of fluorescein-guided surgery in a real-world clinical setting. Approximately 800 patients of any age and gender, with suspected aggressive CNS lesions, will be enrolled. Each patient will receive 5 mg/kg of sodium fluorescein intravenously at the induction of anesthesia. Surgery will be performed using fluorescence-guided techniques, and patients will undergo pre- and post-operative imaging to assess the extent of resection. Clinical and neurological evaluations will also be conducted to monitor outcomes and any adverse effects. The primary objective is to qualitatively assess the intraoperative fluorescence characteristics of CNS tumors. Secondary objectives include measuring the extent of tumor resection, evaluating post-operative neurological function, and documenting any side effects related to fluorescein administration. The study adheres to ethical standards, including informed consent and approval by an ethics committee, and will be conducted in accordance with Good Clinical Practice guidelines and the Declaration of Helsinki. Data will be anonymized and securely stored, with results potentially published following appropriate review and approval.

Sex

All

Inclusion Criteria:

1. Patients of both genders, at any age.
2. Patients with suspected aggressive lesion of the CNS, as suggested by pre-operative MRI or CT with i.v. contrast agent administration.

Exclusion Criteria:

1. Impossibility to give consent due to cognitive deficits or language disorder.
2. Known allergy to contrast agents and/or history of previous anaphylactic shocks.
3. Known severe previous adverse reactions to Fluorescein
4. Acute myocardial infarction or stroke in the last 90 days.
5. Severe renal failure;
6. Severe hepatic failure;
7. Women in their first trimester of pregnancy or lactation.

• BACKGROUNDRoberts DW, Hartov A, Kennedy FE, Miga MI, Paulsen KD. Intraoperative brain shift and deformation: a quantitative analysis of cortical displacement in 28 cases. Neurosurgery. 1998 Oct;43(4):749-58; discussion 758-60. doi: 10.1097/00006123-199810000-00010. PMID 9766300
• BACKGROUNDRasmussen IA Jr, Lindseth F, Rygh OM, Berntsen EM, Selbekk T, Xu J, Nagelhus Hernes TA, Harg E, Haberg A, Unsgaard G. Functional neuronavigation combined with intra-operative 3D ultrasound: initial experiences during surgical resections close to eloquent brain areas and future directions in automatic brain shift compensation of preoperative data. Acta Neurochir (Wien). 2007;149(4):365-78. doi: 10.1007/s00701-006-1110-0. Epub 2007 Feb 19. PMID 17308976
• BACKGROUNDRamirez C, Bowman C, Maurage CA, Dubois F, Blond S, Porchet N, Escande F. Loss of 1p, 19q, and 10q heterozygosity prospectively predicts prognosis of oligodendroglial tumors--towards individualized tumor treatment? Neuro Oncol. 2010 May;12(5):490-9. doi: 10.1093/neuonc/nop071. Epub 2010 Feb 14. PMID 20156805
• BACKGROUNDPedersen MW, Meltorn M, Damstrup L, Poulsen HS. The type III epidermal growth factor receptor mutation. Biological significance and potential target for anti-cancer therapy. Ann Oncol. 2001 Jun;12(6):745-60. doi: 10.1023/a:1011177318162. PMID 11484948
• BACKGROUNDOhue S, Kumon Y, Nagato S, Kohno S, Harada H, Nakagawa K, Kikuchi K, Miki H, Ohnishi T. Evaluation of intraoperative brain shift using an ultrasound-linked navigation system for brain tumor surgery. Neurol Med Chir (Tokyo). 2010;50(4):291-300. doi: 10.2176/nmc.50.291. PMID 20448420
• BACKGROUNDKwan AS, Barry C, McAllister IL, Constable I. Fluorescein angiography and adverse drug reactions revisited: the Lions Eye experience. Clin Exp Ophthalmol. 2006 Jan-Feb;34(1):33-8. doi: 10.1111/j.1442-9071.2006.01136.x. PMID 16451256