title: Hyperbaric Oxygen as Radiation Sensitizer for Locally Advanced Squamous Cell Carcinoma of the Oropharynx: A Phase 1 Dose-Escalation Study.
abstract: To explore, in a dose-escalation study, the feasibility of hyperbaric oxygen (HBO) treatments immediately before intensity modulated radiation therapy in conjunction with cisplatinum chemotherapy for squamous cell carcinoma of the head and neck (SCCHN).
  
  
  
  Eligible patients presented with SCCHN (stage III-IV [M0]), life expectancy >6 months, and Karnofsky performance status ≥70. Enrollees received intensity modulated radiation therapy, 70 Gy in 35 fractions over 7 weeks with weekly cisplatinum. Patients received HBO-100% oxygen, 2.4 atmospheres absolute (ATA) for 30 minutes-twice per week initially. Subsequent patients were escalated to 3 and then 5 times per week. Intensity modulated radiation therapy began within 15 minutes after HBO. Patients were followed for 2 years after RT with quality-of-life questionnaires (Performance Status Scale-Head and Neck Cancer and the Functional Assessment of Cancer Therapy-Head and Neck Cancer) and for 5+ years for local recurrence, distant metastases, disease-specific survival, and overall survival.
  
  
  
  Twelve subjects enrolled from 3 centers. Two withdrew during radiation therapy and 1 within 14 weeks after radiation therapy. The remaining 9 had primary oropharyngeal disease and were stage IVA (7) or IVB (2). No dose-limiting toxicities were observed with daily HBO. Two patients (22%) required pressure equalization tubes. The average time between HBO and radiation therapy was 8.5 minutes, with 2 of 231 administrations delivered beyond 15 minutes (0.5%). Per-protocol analysis showed a clinical complete response in 7 and a pathologic complete response without tumor in salvage neck dissections in 2. With minimum follow-up of 61 months, per-protocol 5-year overall survival was 100%, local recurrence 0%, and distant metastases 11%. Patient-reported outcomes for quality of life (Functional Assessment of Cancer Therapy-Head and Neck Cancer) were comparable to published results for chemoradiotherapy without HBO.
  
  
  
  While acknowledging the study's small size and early attrition of 3 patients, our in-depth review of the acquired data indicates the feasibility of combining HBO with chemoradiation.
authors.affiliation: Section of Radiation Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. Electronic address: Alan.C.Hartford@Hitchcock.org.
authors.forename: Alan C
authors.initials: AC
authors.lastname: Hartford
authors.affiliation: Section of Hematology-Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Davis
authors.affiliation: Section of Hyperbaric Medicine, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
authors.forename: Jay C
authors.initials: JC
authors.lastname: Buckey
authors.affiliation: Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Foote
authors.affiliation: Department of Radiation Oncology and Biophysics, Eastern Virginia Medical School, Norfolk, Virginia.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sinesi
authors.affiliation: Section of Radiation Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Williams
authors.affiliation: Section of Radiation Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
authors.forename: Anna K
authors.initials: AK
authors.lastname: Fariss
authors.affiliation: Section of Radiation Oncology, Department of Medicine, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.
authors.forename: Philip E
authors.initials: PE
authors.lastname: Schaner
authors.affiliation: Department of Aerospace Medicine, Mayo Clinic, Rochester, Minnesota.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Claus
authors.affiliation: Department of Medical Oncology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Okuno
authors.affiliation: Department of Biostatistics, Mayo Clinic, Rochester, Minnesota.
authors.forename: James R
authors.initials: JR
authors.lastname: Hussey
authors.affiliation: Baromedical Research Foundation, Columbia, South Carolina.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Clarke
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D059248:Chemoradiotherapy / Q000379:methods*; D002945:Cisplatin / Q000008:administration & dosage*; D019583:Dose Fractionation, Radiation; D004334:Drug Administration Schedule; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D006931:Hyperbaric Oxygenation / Q000379:methods*; D017567:Karnofsky Performance Status; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D011788:Quality of Life; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage*; D050397:Radiotherapy, Intensity-Modulated; D013997:Time Factors
chemical_list: D011838:Radiation-Sensitizing Agents; D002945:Cisplatin