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Improved Tumor Destruction with Arsenic Trioxide and Radiofrequency Ablation in Three Animal Models¹

¹ From the Laboratory for Minimally Invasive Tumor Therapy, Department of Radiology (A.H., Z.j.L., S.N.G.), and Department of Medicine, Renal Division (V.S.), Beth Israel Deaconess Medical Center, 1 Deaconess Rd, WCC 308B, Boston, MA 02215; Department of Biostatistics and Computational Biology, Dana Farber Cancer Institute and the Renal Cancer Program of the Dana Farber/Harvard Cancer Center, Boston, Mass (M.R.); Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Mass (S.S.); and Harvard Medical School, Boston, Mass (A.H., V.S., M.R., S.S., Z.j.L., S.N.G.). Received May 9, 2005; revision requested July 7; revision received August 18; final version accepted September 14. Supported by National Cancer Institute Dana Farber/Harvard Cancer Center Renal Cancer SPORE grant 1 P50 CA10194-01. Address correspondence to S.N.G. (e-mail: sgoldber{at}caregroup.harvard.edu).

Purpose: To assess the extent of tumor blood flow reduction that is achievable with arsenic trioxide (As₂O₃) and the effect of As₂O₃ on radiofrequency (RF)-induced coagulation.

Materials and Methods: All animal protocols and experiments were approved by an institutional animal care and use committee before the start of the study. Experiments were conducted in three tumor models: intrarenal VX2 sarcoma in 27 rabbits, RCC 786-0 human renal cell carcinoma in 24 nude mice, and R3230 mammary adenocarcinoma in 40 rats. One dose (0–7.5 mg per kilogram of body weight) of As₂O₃ was administered (intraperitoneally in rodents, intravenously in rabbits) 1, 6, or 24 hours before standardized RF ablation, which was performed by using a 1-cm active tip, with mean temperatures of 70°C ± 2 (standard deviation) for 5 minutes in rodents and 90°C ± 2 for 6 minutes in rabbits. Laser Doppler flowmetry was used to quantify changes in blood flow, which were compared with diameters of induced tumor coagulation. Comparisons between groups were performed by using Student t tests or analysis of variance. The strengths of correlations between As₂O₃, tumor blood flow, and RF-induced coagulation were assessed by using linear and higher-order regression models and reported as R² computations.

Results: Administration of As₂O₃ significantly (P < .05) reduced blood flow and increased tumor destruction in all tumor models. In VX2 sarcoma tumors, 1 mg/kg As₂O₃ reduced mean tumor blood flow to 46% ± 13 of the normal value. The mean resultant coagulation (1.1 cm ± 0.1) was significantly greater than that achieved with RF ablation alone (0.6 cm ± 0.1, P < .01). In RCC 786-0 and R3230 tumors, 5 mg/kg As₂O₃ reduced mean tumor blood flow to 57% ± 6 and 46% ± 6 of normal, respectively, increasing mean ablation extent to 0.8 cm ± 0.1 for both models, compared with those achieved with the control treatment (0.6 cm ± 0.1 and 0.5 cm ± 0.1, respectively; P < .05 for both comparisons). Dose studies revealed correlations between drug dose, tumor blood flow, and RF-induced coagulation in all three tumor models (R² = 0.60–0.79). Maximal RF synergy was observed 1 hour after As₂O₃ administration.

Conclusion: As₂O₃ administration represents a transient noninvasive method of reducing tumor blood flow during RF ablation, enabling larger zones of tumor destruction in multiple tumor models.

© RSNA, 2006

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