Pulsed Radiotherapy with Concurrent Cisplatin results in Superior Tumor Growth Delay in a Head and Neck Squamous Cell Carcinoma Murine Model
Menée à l'aide d'une xénogreffe de carcinome épidermoïde de la tête et du cou sur un modèle murin, cette étude met en évidence l'intérêt d'un traitement combinant de manière concomitante une radiothérapie pulsée à faible dose de rayonnements et une chimiothérapie par cisplatine pour retarder la croissance tumorale
Purpose : To assess the efficacy of 3-week schedules of low-dose pulsed radiation treatment (PRT) and standard radiotherapy (SRT), with concurrent cisplatin (CDDP) in a head and neck squamous cell carcinoma (HNSCC) xenograft model. Methods and Materials : Subcutaneous UT-SCC-14 tumors were established in athymic NIH III HO female mice. 30 Gy was administered as 2 Gy/day (d), 5d/wk for 3 wks either by PRT (10x0.2 Gy/day, with a 3-min break between each 0.2 Gy dose) or SRT (2 Gy/day, non-interrupted delivery) in combination with concurrent 2 mg/kg CDDP 3 times/wk in the final 2 weeks of RT. Treatment-induced growth delays were defined from twice-weekly tumor volume measurements. Tumor hypoxia was assessed by 18F-FMISO PET imaging, and calculated SUVmax values compared with tumor histology. Tumor vessel density and hypoxia were measured by quantitative immunohistochemistry. Normal tissues effects were evaluated in gut and skin. Results : Non-treated tumors grew to 1000mm3 in 25.4d (±1.2), compared with delays of 62.3d (±3.5) for SRT+CDDP and 80.2d (±5.0) for PRT+CDDP. Time to reach 2x pre-treatment volume ranged from 8.2d (±1.8) for non-treated tumors to 67.1d (±4.7) after PRT+CDDP. Significant differences in tumor growth delay were observed for SRT vs SRT+CDDP (p=0.04), PRT vs PRT+CDDP (p=0.035) and SRT+CDDP vs PRT+CDDP (p=0.033), and for survival between PRT vs PRT+CDDP (p=0.017) and SRT+CDDP vs PRT+CDDP (p = 0.008). Differences in tumor hypoxia were evident by 18F-MISO PET imaging between SRT vs PRT (p=0.025), although not with concurrent CDDP. Tumor vessel density differed between SRT+CDDP vs PRT+CDDP (p=0.011). No differences in normal tissue parameters were seen. Conclusions : Concurrent CDDP was more effective in combination PRT than SRT at restricting tumor growth. Significant differences in tumor vascular density were evident between PRT and SRT, suggesting a preservation of vascular network with PRT.