title: Pulsed Radiation Therapy With Concurrent Cisplatin Results in Superior Tumor Growth Delay in a Head and Neck Squamous Cell Carcinoma Murine Model.
abstract: To assess the efficacy of 3-week schedules of low-dose pulsed radiation treatment (PRT) and standard radiation therapy (SRT), with concurrent cisplatin (CDDP) in a head and neck squamous cell carcinoma xenograft model.
  
  
  
  Subcutaneous UT-SCC-14 tumors were established in athymic NIH III HO female mice. A total of 30 Gy was administered as 2 Gy/d, 5 d/wk for 3 weeks, either by PRT (10 × 0.2 Gy/d, with a 3-minute break between each 0.2-Gy dose) or SRT (2 Gy/d, uninterrupted delivery) in combination with concurrent 2 mg/kg CDDP 3 times per week in the final 2 weeks of radiation therapy. Treatment-induced growth delays were defined from twice-weekly tumor volume measurements. Tumor hypoxia was assessed by (18)F-fluoromisonidazole positron emission tomography imaging, and calculated maximum standardized uptake values compared with tumor histology. Tumor vessel density and hypoxia were measured by quantitative immunohistochemistry. Normal tissues effects were evaluated in gut and skin.
  
  
  
  Untreated tumors grew to 1000 mm(3) in 25.4 days (±1.2), compared with delays of 62.3 days (±3.5) for SRT + CDDP and 80.2 days (±5.0) for PRT + CDDP. Time to reach 2× pretreatment volume ranged from 8.2 days (±1.8) for untreated tumors to 67.1 days (±4.7) after PRT + CDDP. Significant differences in tumor growth delay were observed for SRT versus SRT + CDDP (P=.04), PRT versus PRT + CDDP (P=.035), and SRT + CDDP versus PRT + CDDP (P=.033), and for survival between PRT versus PRT + CDDP (P=.017) and SRT + CDDP versus PRT + CDDP (P=.008). Differences in tumor hypoxia were evident by (18)F-fluoromisonidazole positron emission tomography imaging between SRT and PRT (P=.025), although not with concurrent CDDP. Tumor vessel density differed between SRT + CDDP and PRT + CDDP (P=.011). No differences in normal tissue parameters were seen.
  
  
  
  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.
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Kurt
authors: K
authors: Meyer
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Sarah A
authors: SA
authors: Krueger
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Jonathan L
authors: JL
authors: Kane
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Thomas G
authors: TG
authors: Wilson
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Alaa
authors: A
authors: Hanna
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Mohamad
authors: M
authors: Dabjan
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Katie M
authors: KM
authors: Hege
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: George D
authors: GD
authors: Wilson
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan.
authors: Inga
authors: I
authors: Grills
authors: Department of Radiation Oncology, William Beaumont Hospital, Royal Oak, Michigan. Electronic address: brian.marples@beaumont.edu.
authors: Brian
authors: B
authors: Marples
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000473:pathology* / Q000628:therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology* / Q000628:therapy*; D051379:Mice; D011879:Radiotherapy Dosage; D020266:Radiotherapy, Conformal / Q000379:methods*; D000077195:Squamous Cell Carcinoma of Head and Neck; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin