title: Thermochemoradiotherapy improves oxygenation in locally advanced breast cancer.
abstract: OBJECTIVE
  The purpose of this research was to evaluate toxicity, response, and changes in oxygenation (pO(2)) in patients with locally advanced breast cancer (LABC) treated with concurrent taxol, hyperthermia (HT), and radiation therapy (RT) followed by mastectomy.
  
  
  METHODS
  Eighteen patients with LABC were enrolled from October 1995 through February 1999. Treatment consisted of taxol (175 mg/m(2)) given every 3 weeks for three cycles. Radiation therapy included the breast and regional nodes with a dose of 50 Gy, followed by a boost to 60-65 Gy for those not undergoing surgery. Mastectomy was performed for patients deemed resectable after this neoadjuvant program. HT was administered twice per week. Oxygenation was measured before the first HT treatment and 24 h after the first HT treatment.
  
  
  RESULTS
  Fifteen of 18 patients responded, 6 with a clinical complete response, 9 with a partial clinical response, and 3 nonresponders. Thirteen underwent mastectomy with 3 pathological complete responses. Tumor hypoxia was present in 8 of 13 patients (pO(2) = 4.7 +/- 1.2 mmHg). Five patients had well-oxygenated tumors (pO(2) = 27.6 +/- 7.8 mmHg). Patients with well-oxygenated tumors before treatment as well as those with significant reoxygenation had a favorable clinical response. Tumor reoxygenation appeared to be temperature dependent and associated with the lower thermal doses.
  
  
  CONCLUSIONS
  This novel therapeutic program resulted in a high response rate in patients with LABC. Hyperthermia may offer a strategy for improving tumor reoxygenation with consequent treatment response. However, the effect of hyperthermia on tumor reoxygenation appears to depend on thermal dose and requires additional investigation.
authors.affiliation: Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Jones
authors.forename: Leonard R
authors.initials: LR
authors.lastname: Prosnitz
authors.forename: Mark W
authors.initials: MW
authors.lastname: Dewhirst
authors.forename: P Kelly
authors.initials: PK
authors.lastname: Marcom
authors.forename: Patricia H
authors.initials: PH
authors.lastname: Hardenbergh
authors.forename: Lawrence B
authors.initials: LB
authors.lastname: Marks
authors.forename: David M
authors.initials: DM
authors.lastname: Brizel
authors.forename: Zeljko
authors.initials: Z
authors.lastname: Vujaskovic
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000628:therapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005334:Fever; D006801:Humans; D000860:Hypoxia; D008408:Mastectomy; D008875:Middle Aged; D010100:Oxygen / Q000378:metabolism*; D017239:Paclitaxel / Q000627:therapeutic use; D011446:Prospective Studies; D013696:Temperature; D013997:Time Factors
chemical_list: D017239:Paclitaxel; D010100:Oxygen