Microsurgical Resection Combined With Photodynamic Therapy for Recurrent Glioblastoma

This single-center, prospective, single-arm, open-label clinical study evaluates the effectiveness and safety of microsurgical resection combined with photodynamic therapy (PDT) in patients with recurrent glioblastoma (GBM). Patients receive intravenous hematoporphyrin injection (Hiporfin) 5 mg/kg 48-72 hours before surgery. Standard craniotomy with microsurgical resection of the recurrent tumor is then performed, followed by intraoperative irradiation of the resection cavity with a 630-nm semiconductor laser (fluence 150-200 J/cm2). The primary outcome is the rate of tumor recurrence within 2 years after surgery. Participants are followed postoperatively for up to 24 months with contrast-enhanced brain MRI, neurological and quality-of-life assessments (EORTC QLQ-C30), and adverse event monitoring.

Inclusion Criteria: * Age 18-65 years, any sex * KPS score \>= 70 and ECOG performance status 0-2 * Patient and family members willing and able to provide written informed consent * Histopathologically confirmed glioblastoma (WHO grade IV) that has progressed or recurred after standard radiotherapy and chemotherapy, based on radiological evidence of measurable disease * More than 3 months since completion of brain radiotherapy * Hospitalized for recurrence/progression with a sizable lesion causing related symptoms and/or mass effect, for which gross-total or subtotal resection is considered feasible at reoperation * No concomitant malignancy, severe autoimmune disease or congenital immunodeficiency, severe active infection, cranial nerve disorder, or psychiatric disease * Life expectancy greater than 12 weeks * Cardiac function: essentially normal electrocardiogram, stable hemodynamics, left ventricular ejection fraction \> 55% * White blood cell count \> 3.5 x 10\^9/L, platelet count \> 100 x 10\^9/L, absolute neutrophil count \> 1.5 x 10\^9/L, hemoglobin \> 90 g/L * ALT and AST \< 2.5 x upper limit of normal (\< 5 x ULN if hepatic impairment mainly due to tumor infiltration), total bilirubin \< 1.5 x ULN, serum creatinine \< 1 x ULN * INR or prothrombin time \< 1.5 x ULN and APTT \< 1.5 x ULN (for patients on anticoagulation, PT/PTT within the expected therapeutic range) * Negative for HIV antibody, Treponema pallidum antibody, HBsAg, HCV antibody, and EBV-DNA * Female subjects must use effective contraception throughout the study, with negative serum or urine pregnancy test at screening and during the study * Able to attend regular follow-up visits at the study institution throughout the trial * Expected benefit of participation judged to outweigh the risks by the investigators Exclusion Criteria: * KPS score \< 70 * Prior or concurrent malignancy at other sites, unless disease-free for \>= 3 years * Pregnant or lactating women * History of allergy to photosensitizers or hematoporphyrin * Porphyria or soy allergy * Contraindications to surgery * Other uncontrolled active infection * Treatment with any investigational drug within 30 days before study entry * Psychiatric disease or other conditions (e.g., uncontrolled cardiac or pulmonary disease, diabetes) precluding compliance with study treatment and monitoring * Severe renal or hepatic impairment (bilirubin \> 1.5 x ULN, alkaline phosphatase and AST \> 2.5 x ULN, creatinine clearance \< 30 mL/min) * Prior allogeneic tissue or organ transplantation * Poor compliance or inability to follow skin photosensitivity precautions * HIV-positive or AIDS-related disease * Contraindications to magnetic resonance imaging * Follow-up impossible for psychological, family, social, or geographical reasons * Lack of legal capacity (deprived of liberty or under guardianship) * Refusal to participate or to provide consent * Any other condition judged unsuitable for enrollment by the investigator