5-aminolevulinic acid (5-ALA), Gleolan ®, is a photosensitizing agent used in fluorescence guided surgery (FGS) to facilitate visualization of tumors intraoperatively. 5-ALA is currently FDA approved for fluorescence-guided resection of WHO grade III and IV malignant gliomas, where it has been shown to improve margin status and survival rates. 5-ALA has previously been shown to induce fluorescence when topically applied to squamous cell carcinomas of the oral cavity, pharynx, and larynx, but to the authors’ knowledge, its use intraoperatively in the resection of aerodigestive head and neck squamous cell carcinoma (SCCa) via oral preoperative administration has never been studied. We present the first experience of an ongoing pilot trial to evaluate the feasibility and efficacy of oral 5-ALA administration to facilitate intraoperative head and neck SCCa resection.
Methods: This ongoing prospective pilot trial includes patients with biopsy proven aerodigestive head and neck SCCa from September 2021 onward with a projected end date of May 2022. Demographics, primary tumor pathology, intraoperative techniques, and adverse reactions will be collected. 5-ALA is administered in the form of an oral solution 3-5 hours before induction of anesthesia. Intraoperatively, 405 nm blue light is applied via headlight and operating microscope to visualize tumor fluorescence. Specimen fluorescence intensity is graded on a scale from 0-3 (0= no fluorescence, 3= intense fluorescence).
Results: 3 patients have been recruited. All 3 are male with an age range of 51-65 years (average: 58.3 years). The final pathology for all patient specimens was moderately differentiated squamous cell carcinoma. Use of 5-ALA yielded excellent fluorescence of squamous cell carcinoma in the nasal cavity, oral cavity, and larynx with all specimens demonstrating grade 3 fluorescence. The laryngectomy specimen demonstrated satellites of mucosal fluorescence which were notable for dysplasia. The absence of tumor in the deep margin, thus far, correlates with negative frozen section analysis and negative margin status on permanent pathological analysis of all patients. 2 patients had mild photosensitivity reactions and 1 patient had a mild liver function test elevation which normalized on postoperative day 2.
Conclusions: 5-ALA can successfully and safely induce intraoperative fluorescence of aerodigestive SCCa and possibly dysplastic mucosa. The utility of this agent may lie in early detection and localization of squamous cell carcinoma, as well as intraoperative assessment of margins and residual tumor in sensitive areas along the skull base, orbit, and neurovascular structures; however, this must be elucidated with further studies. Likely limitations will include detection of fluorescence with the human eye (as opposed to spectrophotometric devices) and background fluorescence of normal mucosa. Future uses in endoscopic skull base surgery, ablative head and neck surgery, parathyroidectomy, robotic surgery, neck dissections, as well as intraoperative margin status assessment and survival will be studied in forthcoming trials.