First-In-Human Computer-Optimized Endobronchial Ultrasound-Guided Interstitial Photodynamic Therapy for Patients With...

Area of Science:

• Pulmonology
• Oncology
• Medical Imaging

Background:

• Patients with inoperable extrabronchial or endobronchial tumors face poor prognoses.
• Limited effective long-term treatment options exist for these patients, especially those unsuitable for curative radiotherapy.

Purpose of the Study:

• To evaluate the safety and potential effectiveness of computer-optimized interstitial photodynamic therapy (I-PDT) for inoperable central airway obstructions.
• To assess I-PDT's impact on patient survival and immune markers.

Main Methods:

• High-spatial resolution computer simulations personalized light dose for each tumor.
• Optical fibers were placed using endobronchial ultrasound and transbronchial needle based on individualized plans.
• Safety and overall survival were primary and secondary endpoints, respectively; immune marker changes were exploratory.

Main Results:

• I-PDT was declared safe across 10 patients (8 received I-PDT, 2 external beam PDT).
• Three of 10 patients survived at 26.3, 12, and 8.3 months post-I-PDT.
• Effective light dose delivery was achieved in most tumor volumes, with increased programmed death-ligand 1-expressing monocytic myeloid-derived suppressor cells in some patients.

Conclusions:

• Image-guided I-PDT using endobronchial ultrasound is safe and may improve survival in patients with inoperable airway malignancies.
• I-PDT demonstrates a positive effect on the immune response, specifically increasing PD-L1 expression on certain immune cells.