Percutaneous venovenous perfusion-induced systemic hyperthermia for advanced non-small cell lung cancer: Initial clinical experience

Background. Venovenous perfusion-induced systemic hyperthermia raises core body temperature by extracorporeal heating of the blood. Five patients with advanced non-small cell lung carcinoma stage IV (4.4 ± 1 months after initial diagnosis) received venovenous perfusion-induced systemic hyperthermia to 42.5°C (core temperature) to assess technical and patient risks. Methods. After general anesthesia and systemic heparinization (activated clotting time > 300 seconds), percutaneous cannulation of the right internal jugular vein (15F) for drainage and common femoral vein (15F) for reinfusion allowed extracorporeal flow rates up to 1,500 mL/min (20 mL · kg^-1 · min^-1) with the ThermoChem System. This device uses charcoal-based sorbent for electrolyte homeostasis. Six monitored sites (rectal, bladder, tympanic ×2, nasopharyngeal, and esophageal) determined average core temperature. Results. All patients achieved a core target temperature of 42.5°C for 2 hours. Electrolyte balance was maintained throughout hyperthermia (mean) in mmol/L: Na⁺, 136.2 ± 2.2 mmol/L; K⁺, 4.0 ± 0.3 mmol/L; Ca²⁺, 4.1 ± 0.2 mg/dL; Mg²⁺, 1.9 ± 0.1 mg/dL; PO₄^-, 4.5 ± 0.9 mg/dL). Plasma cytokine concentration revealed significant heat-induced activation of proinflammatory and antiinflammatory cascades. All patients exhibited systemic vasodilation requiring norepinephrine infusion, 4 of 5 patients required vigorous diuresis, and 3 of 5 required intubation for 24 to 36 hours because of pulmonary edema or somnolence, with full recovery. Average length of hospital stay was 5.4 days. Serial tumor measurements (1 patient withdrew) revealed a decrease (64.5% ± 18%) in tumor size in 2 patients, no change in 1, and enlargement in 1, with no 30-day mortality. Median survival after hyperthermia treatment was 172 days (range, 40 to 271 days). Conclusions. Venovenous perfusion-induced systemic hyperthermia is feasible and provides the following potential advantages for better tumoricidal effect: (1) homogeneous heating, and (2) a higher sustained temperature.