Transbronchial photodynamic therapy for peripheral lung cancer - A pilot study.

[OBJECTIVES] Photodynamic therapy (PDT) is an established treatment for centrally located early-stage lung cancer but remains limited for peripheral lung cancers in part due to restricted light penetration and the difficulty of precisely positioning optical fibers. Our team developed a novel light delivery technique involving the transbronchial infusion of Lipiodol to induce a waveguide effect, expanding the illumination field. We conducted two sequential pilot clinical trials to evaluate the feasibility and safety of this approach.

[METHODS] Two single-arm, Phase-0 feasibility studies were conducted. Eligible patients had peripheral lung malignancies (≤2 cm in Stage I; ≤3 cm in Stage II) and were unsuitable for or refractory to standard therapies. In Stage I, an electromagnetic navigation bronchoscope (ENB) was used to position a catheter for Lipiodol infusion and single-illumination PDT. Stage II employed an ultrathin bronchoscope to access multiple peripheral airways for repeated Lipiodol infusion and illumination from 3 to 6 angles. The primary endpoints were technical feasibility and safety (specifically lipoid pneumonia or hemoptysis).

[RESULTS] Six patients (three in each stage) were treated. Diagnoses included primary adenocarcinoma and metastatic lesions. All procedures were technically successful with complete Lipiodol encapsulation confirmed by cone-beam CT. No major acute complications occurred. Tumor response at 3 months varied: in Stage I, two patients had progressive disease (PD) and one had stable disease (SD); in Stage II, one PD, one partial response (PR), and one SD were observed. Lipiodol was gradually absorbed within 3-6 months.

[CONCLUSION] Lipiodol-assisted transbronchial PDT is technically feasible and demonstrated a favorable acute safety profile in this small pilot cohort. While the light dose (200 J/cm) resulted in modest tumor control, the technique successfully addressed the challenge of light delivery to peripheral lesions. Future Phase I trials with dose escalation are warranted.