Combination of 5-ALA and iMRI in re-resection of recurrent glioblastoma

Abstract

Background Tumour resection plays a role in the initial treatment but also in the setting of recurrent glioblastoma (rGBM). To achieve maximum resection, 5-aminolevulinic acid (5-ALA) and intraoperative MRI (iMRI) are used as surgical tools. Aiming at complete tumour re-resection, we started combining iMRI with 5-ALA to find out if this leads to better surgical results. Methods We performed tumour resections in seven patients with rGBM, combining 5-ALA (20 mg/kg bodyweight) with iMRI (0.15 T). Radiologically complete resections were intended in all seven patients. We assessed intraoperative fluorescence findings and compared these with intraoperative imaging. All patients had early postoperative MRI (3 T) to verify final iMRI scans and received adjuvant treatment according to interdisciplinary tumour board decision. Results Median patient age was 63 years. Median KPS score was 90, and median tumour volume was 8.2 cm(3). In six of seven patients (85%), 5-ALA induced fluorescence of tumour-tissue was detected intraoperatively. All tumours were good to visualise with iMRI and contrast media. One patient received additional resection of residual contrast enhancing tissue on intraoperative imaging, which did not show fluorescence. Radiologically complete resections according to early postoperative MRI were achieved in all patients. Median survival since second surgery was 7.6 months and overall survival since diagnosis was 27.8 months. Conclusions 5-ALA and iMRI are important surgical tools to maximise tumour resection also in rGBM. However, not all rGBMs exhibit fluorescence after 5-ALA administration. We propose the combined use of 5-ALA and iMRI in the surgery of rGBM.

Agents for fluorescence-guided glioma surgery: a systematic review of preclinical and clinical results

“…Sixty-four studies describe the clinical use of fluorescent agents [1, 3, 5, 6, 9, 11, 13–16, 22–26, 28–31, 33–35, 37, 38, 40–42, 44, 49, 52–54, 58, 64–66, 69, 71, 74, 75, 78, 80–82, 84–87, 89, 92, 94, 97–101, 105–107, 109, 110, 113, 115, 118]. Three ways of labeling tumor cells were identified in the literature: (1) passive, (2) metabolic, and (3) molecular labeling.…”

“…Forty-four clinical studies described the use of 5-ALA for glioma surgery [3, 5, 6, 13–16, 22, 24–26, 28, 30, 31, 33, 34, 37, 40–42, 44, 66, 69, 74, 75, 78, 81, 82, 84, 85, 87, 89, 94, 97–101, 105, 106, 109, 110, 113, 115], of which only six studies included LGGs [28, 33, 84, 109, 110, 113]. 5-ALA is the only fluorescent agent that has been tested in an RCT.…”

“…To increase the accuracy of LGGs, FGS was combined with intra-operative confocal microscopy [84] or an intraoperative probe for quantitative fluorescence measurement [109]. Other intraoperative techniques used to increase the extent of glioma resection are photodynamic therapy (PDT) [26], iMRI [14, 30, 34, 40, 78, 85], intra-operative CT [5], exoscope imaging [6, 75], fluorescence spectrometry [37, 100], confocal microscopy [84], and intraoperative mapping [22, 89]. …”

Oncologic Procedures Amenable to Fluorescence-guided Surgery

“…34 Newer studies have demonstrated 5-ALA FGS combined with intraoperative MRI may be beneficial in maximizing resection of GBM. 35,36 This combination presents a potential solution to the problem encountered with 5-ALA in that not all GBM tissue uniformly exhibits 5-ALA fluorescence. 36 …”

Re-irradiation for recurrent glioblastoma multiforme

“…Novel resection techniques are also being explored to improve the rate of complete resection. For example, protoporphyrin IX (PpIX) is a fluorescent compound that preferentially concentrates in malignant glioma cells, allowing for successful intra-operative tumor visualization to guide surgical resection (10,11). Despite such advances, the principle of maximum safe resection is not always optimal in the setting of recurrent GBM, as the benefit of reoperation remains in question (12)(13)(14).…”