EGFR-targeted intraoperative fluorescence imaging detects high-grade glioma with panitumumab-IRDye800 in a phase 1 clinical trial.

Rationale: First-line therapy for high-grade gliomas (HGGs) includes maximal safe surgical resection. The extent of resection predicts overall survival, but current neuroimaging approaches lack tumor specificity. The epidermal growth factor receptor (EGFR) is a highly expressed HGG biomarker. We evaluated the safety and feasibility of an anti-EGFR antibody, panitumuab-IRDye800, at subtherapeutic doses as an imaging agent for HGG. Methods: Eleven patients with contrast-enhancing HGGs were systemically infused with panitumumab-IRDye800 at a low (50 mg) or high (100 mg) dose 1-5 days before surgery. Near-infrared fluorescence imaging was performed intraoperatively and ex vivo, to identify the optimal tumor-to-background ratio by comparing mean fluorescence intensities of tumor and histologically uninvolved tissue. Fluorescence was correlated with preoperative T1 contrast, tumor size, EGFR expression and other biomarkers. Results: No adverse events were attributed to panitumumab-IRDye800. Tumor fragments as small as 5 mg could be detected ex vivo and detection threshold was dose dependent. In tissue sections, panitumumab-IRDye800 was highly sensitive (95%) and specific (96%) for pathology confirmed tumor containing tissue. Cellular delivery of panitumumab-IRDye800 was correlated to EGFR overexpression and compromised blood-brain barrier in HGG, while normal brain tissue showed minimal fluorescence. Intraoperative fluorescence improved optical contrast in tumor tissue within and beyond the T1 contrast-enhancing margin, with contrast-to-noise ratios of 9.5 ± 2.1 and 3.6 ± 1.1, respectively. Conclusions: Panitumumab-IRDye800 provided excellent tumor contrast and was safe at both doses. Smaller fragments of tumor could be detected at the 100 mg dose and thus more suitable for intraoperative imaging.

The utility of three-dimensional models in complex microsurgical reconstruction.

BACKGROUND: Three-dimensional (3D) model printing improves visualization of anatomical structures in space compared to two-dimensional (2D) data and creates an exact model of the surgical site that can be used for reference during surgery. There is limited evidence on the effects of using 3D models in microsurgical reconstruction on improving clinical outcomes. METHODS: A retrospective review of patients undergoing reconstructive breast microsurgery procedures from 2017 to 2019 who received computed tomography angiography (CTA) scans only or with 3D models for preoperative surgical planning were performed. Preoperative decision-making to undergo a deep inferior epigastric perforator (DIEP) versus muscle-sparing transverse rectus abdominis myocutaneous (MS-TRAM) flap, as well as whether the decision changed during flap harvest and postoperative complications were tracked based on the preoperative imaging used. In addition, we describe three example cases showing direct application of 3D mold as an accurate model to guide intraoperative dissection in complex microsurgical reconstruction. RESULTS: Fifty-eight abdominal-based breast free-flaps performed using conventional CTA were compared with a matched cohort of 58 breast free-flaps performed with 3D model print. There was no flap loss in either group. There was a significant reduction in flap harvest time with use of 3D model (CTA vs. 3D, 117.7±14.2 minutes vs. 109.8±11.6 minutes; P=0.001). In addition, there was no change in preoperative decision on type of flap harvested in all cases in 3D print group (0%), compared with 24.1% change in conventional CTA group. CONCLUSIONS: Use of 3D print model improves accuracy of preoperative planning and reduces flap harvest time with similar postoperative complications in complex microsurgical reconstruction.

Magnetic resonance-guided focused ultrasound treatment of extra-abdominal desmoid tumors: a retrospective multicenter study.

OBJECTIVES: To assess the feasibility, safety and preliminary efficacy of magnetic resonance-guided focused ultrasound (MRgFUS) for the treatment of extra-abdominal desmoid tumours. METHODS: Fifteen patients with desmoid fibromatosis (six males, nine females; age range, 7-66 years) were treated with MRgFUS, with seven patients requiring multiple treatments (25 total treatments). Changes in viable and total tumour volumes were measured after treatment. Efficacy was evaluated using an exact one-sided Wilcoxon test to determine if the median reduction in viable tumour measured immediately after initial treatment exceeded a threshold of 50 % of the targeted volume. Median decrease after treatment of at least two points in numerical rating scale (NRS) worst and average pain scores was tested with an exact one-sided Wilcoxon test. Adverse events were recorded. RESULTS: After initial MRgFUS treatment, median viable targeted tumour volume decreased 63 %, significantly beyond our efficacy threshold (P = 0.0013). Median viable total tumour volume decreased (105 mL [interquartile range {IQR}, 217 mL] to 54 mL [IQR, 92 mL]) and pain improved (worst scores, 7.5 ± 1.9 vs 2.7 ± 2.6, P = 0.027; average scores, 6 ± 2.3 vs 1.3 ± 2, P = 0.021). Skin burn was the most common complication. CONCLUSIONS: MRgFUS significantly and durably reduced viable tumour volume and pain in this series of 15 patients with extra-abdominal desmoid fibromatosis. KEY POINTS: • Retrospective four-centre study shows MRgFUS safely and effectively treats extra-abdominal desmoid tumours • This non-invasive procedure can eradicate viable tumour in some cases • Alternatively, MRgFUS can provide durable control of tumour growth through repeated treatments • Compared to surgery or radiation, MRgFUS has relatively mild side effects.