title: A prospective phase 2 trial of reirradiation with stereotactic body radiation therapy plus cetuximab in patients with previously irradiated recurrent squamous cell carcinoma of the head and neck.
abstract: OBJECTIVE
  Salvage options for unresectable locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. Although the addition of reirradiation may improve outcomes compared to chemotherapy alone, significant toxicities limit salvage reirradiation strategies, leading to suboptimal outcomes. We therefore designed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN.
  
  
  METHODS
  From July 2007 to March 2013, 50 patients >18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy, with a Zubrod performance status of 0 to 2, and normal hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m(2) on day -7 and then 250 mg/m(2) on days 0 and +8) plus SBRT (40-44 Gy in 5 fractions on alternating days over 1-2 weeks). Primary endpoints were 1-year locoregional progression-free survival and National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 graded toxicity.
  
  
  RESULTS
  Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS rate was 60% (95% confidence interval [CI]: 44%-75%), locoregional PFS was 37% (95% CI: 23%-53%), distant PFS was 71% (95% CI: 54%-85%), and PFS was 33% (95% CI: 20%-49%). The median overall survival was 10 months (95% CI: 7-16), with a 1-year overall survival of 40% (95% CI: 26%-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% were alive with progression. Acute and late grade 3 toxicity was observed in 6% of patients respectively.
  
  
  CONCLUSIONS
  SBRT with concurrent cetuximab appears to be a safe salvage treatment for rSCCHN of short overall treatment time.
authors: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors: John A
authors: JA
authors: Vargo
authors: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Robert L
authors: RL
authors: Ferris
authors: Division Medical Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: James
authors: J
authors: Ohr
authors: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania.
authors: David A
authors: DA
authors: Clump
authors: Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Kara S
authors: KS
authors: Davis
authors: Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Umamaheswar
authors: U
authors: Duvvuri
authors: Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Seungwon
authors: S
authors: Kim
authors: Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Jonas T
authors: JT
authors: Johnson
authors: Division Medical Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Julie E
authors: JE
authors: Bauman
authors: Division Medical Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
authors: Michael K
authors: MK
authors: Gibson
authors: Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors: Barton F
authors: BF
authors: Branstetter
authors: Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania; Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania. Electronic address: herond2@umpc.edu.
authors: Dwight E
authors: DE
authors: Heron
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery*; D000068818:Cetuximab; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery*; D018307:Neoplasms, Squamous Cell / Q000401:mortality / Q000532:radiotherapy / Q000601:surgery*; D011446:Prospective Studies; D011788:Quality of Life; D016634:Radiosurgery / Q000379:methods*; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted; D019233:Retreatment / Q000379:methods / Q000401:mortality; D016879:Salvage Therapy / Q000379:methods* / Q000401:mortality; D013997:Time Factors
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D000068818:Cetuximab