Work

Hiporfin (HpD) for fluorescence-guided resection of recurrent glioblastoma: diagnostic accuracy and feasibility of an integrated photodynamic strategy

Year: 2026

Type: preprint

Abstract: Background Hematoporphyrin derivative (HpD, Hiporfin) is used for photodynamic therapy (PDT) of solid tumors but had never been evaluated for fluorescence-guided resection (FGR) in glioma. We assessed Hiporfin fluorescence accuracy against histopathology in recurrent glioblastoma (rGBM) and the feasibility of adding cavity PDT to FGR. Methods In this prospective single-arm study, adults with rGBM received a single preoperative intravenous Hiporfin dose of 5 mg/kg before FGR under blue-light excitation and 630-nm cavity PDT. Intraoperative fluorescence assessment was the index test and histopathology the reference standard. Specimen-level diagnostic accuracy was pooled with bivariate random-effects modeling. Results Of 63 specimens, 35 were true positive, 7 false positive, 8 false negative and 13 true negative. Pooled sensitivity was 0.751 (95% confidence interval 0.600–0.858) and specificity 0.606 (0.407–0.775); the crude positive predictive value was 0.833 (0.694–0.917) and the negative predictive value 0.619 (0.409–0.792). All seven false-positive specimens were peritumoral tissue and the eight false negatives were non-fluorescent tumor. FGR combined with cavity PDT was completed in all six patients without new neurological deficits. Conclusions Hiporfin fluorescence identified rGBM with moderate accuracy: fluorescent regions were likely tumor, while non-fluorescent tissue often still contained tumor. The main source of error was peritumoral tissue of the treated cavity, and not the drug or the optics. Hiporfin is a new fluorescence agent for glioma. One drug provides both fluorescence guidance during resection and immediate cavity PDT. Key Points Hiporfin fluorescence in recurrent glioblastoma: sensitivity 0.75, specificity 0.61. Fluorescence predicted tumor with PPV 0.83, but its absence had NPV 0.62. First specimen-level accuracy estimated for Hiporfin fluorescence in recurrent glioblastoma. Importance of the Study Hiporfin (hematoporphyrin derivative) is used for photodynamic therapy of solid tumors, but its fluorescence had not been characterized in the operative field. We provide the first clinical fluorescence-guided resection data for this agent in glioma and pair it with immediate cavity photodynamic therapy in a single procedure. In this prospective six-patient series, pooled sensitivity was 0.75 and specificity 0.61, so more than a third of non-fluorescent specimens still contained tumor while every false-positive specimen was peritumoral tissue. That failure mode is intrinsic to reoperation in a treated cavity and not to the drug or the optics. The workflow was completed in every patient without new deficit; the one patient with both a newly diagnosed and a recurrent lesion suggests greater potential for Hiporfin in newly diagnosed glioblastoma, which warrants prospective evaluation.

Source: medRxiv

DOI: 10.64898/2026.10.07.26364687