Pulmonary Suffusion Refinements for Primary and Secondary Malignancies: Preliminary Analyses of Phase I Safety and Drug Delivery Data

<b>Objectives</b>: We sought to document interim methodologic improvements and preliminary results for pulmonary suffusion. <b>Methods</b>: A Phase I/II trial of thoracoscopic lung suffusion for resectable sarcoma and colorectal carcinoma metastases followed a pilot study on oligometastatic lung malignancy at a comprehensive cancer center. Primary-specific chemotherapy doses (cisplatin, oxaliplatin, doxorubicin, or gemcitabine) suffused unilaterally for 30 min were escalated to amplify regional deliveries three-fold. Drug delivery was measured with tissue, blood samples, and ⁹⁹Tc; pulmonary function tests and clinical adverse events (AEs) assessed safety and tolerance. <b>Results</b>: From 2008-2025, 31 ECOG 0-2 patients (10 male) aged 33-75 years had unilateral lung suffusion (16 right, 14 left, 1 aborted, and 8 sides selected randomly). Vascular occlusion intolerance was immediate or delayed (25 min) in two cases. Two catheter-positioning grade 3 AEs occurred: hypotension with troponin leak (1) and atrial fibrillation (1). Patients averaged 1.3 ± 1.2 metastasectomies (17 sub-lobar, 8 lobar resections, and 2 intentional open cytoreductive metastasectomies). Hospitalizations were brief (1-4 days) except for 6-7 day stays in the only two open cases and one doxorubicin (grade 4 hypoxic respiratory failure) case. Ninety-day survival was 100%, and the Phase I delivery goal of 12.75 mg/m² 65 (15% systemic) was achieved for oxaliplatin. Lung function was preserved according to ⁹⁹Tc differentials within 6.1 ± 7.1% of the predicted reductions at 30 days. Sampling delays, tracer discordances, and atypical pharmacokinetics reduced tissue drug detections. Recent pulmonary artery snaring cases (two) demonstrated in-flow control more stable than that of balloon occlusions. <b>Conclusions</b>: Suffusion for metastatic malignancies appears safe and warrants further investigation.