title: Correlation Between the Severity of Cetuximab-Induced Skin Rash and Clinical Outcome for Head and Neck Cancer Patients: The RTOG Experience.
abstract: To evaluate the severity of cetuximab-induced skin rash and its correlation with clinical outcome and late skin toxicity in patients with head and neck squamous cell carcinoma treated with chemoradiation therapy and cetuximab.
  
  
  
  Analysis included patients who received loading dose and ≥1 cetuximab dose concurrent with definitive chemoradiation therapy (70 Gy + cisplatin) or postoperative chemoradiation therapy (60-66 Gy + docetaxel or cisplatin).
  
  
  
  Six hundred two patients were analyzed; 383 (63.6%) developed grade 2 to 4 cetuximab rash. Patients manifesting grade 2 to 4 rash had younger age (P<.001), fewer pack-years smoking history (P<.001), were more likely to be males (P=.04), and had p16-negative (P=.04) oropharyngeal tumors (P=.003). In univariate analysis, grade 2 to 4 rash was associated with better overall survival (hazard ratio [HR] 0.58, P<.001) and progression-free survival (HR 0.75, P=.02), and reduced distant metastasis rate (HR 0.61, P=.03), but not local-regional failure (HR 0.79, P=.16) relative to grade 0 to 1 rash. In multivariable analysis, HRs for overall survival, progression-free survival, distant metastasis, and local-regional failure were, respectively, 0.68 (P=.008), 0.85 (P=.21), 0.64 (P=.06), and 0.89 (P=.48). Grade ≥2 rash was associated with improved survival in p16-negative patients (HR 0.28 [95% confidence interval 0.11-0.74]) but not in p16-positive patients (HR 1.10 [0.42-2.89]) (P=.05 for interaction). Twenty-five percent of patients with grade 2 to 4 acute in-field radiation dermatitis experienced grade 2 to 4 late skin fibrosis, versus 14% of patients with grade 0 to 1 acute in-field radiation dermatitis (P=.002).
  
  
  
  Grade 2 to 4 cetuximab rash was associated with better survival, possibly due to reduction of distant metastasis. This observation was noted mainly in p16-negative patients. Grade 2 to 4 acute in-field radiation dermatitis was associated with higher rate of late grade 2 to 4 skin fibrosis.
authors.affiliation: Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: voichita.bar-ad@jefferson.edu.
authors.forename: Voichita
authors.initials: V
authors.lastname: Bar-Ad
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Qiang Ed
authors.initials: QE
authors.lastname: Zhang
authors.affiliation: University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Harari
authors.affiliation: Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania.
authors.forename: Rita
authors.initials: R
authors.lastname: Axelrod
authors.affiliation: University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: David I
authors.initials: DI
authors.lastname: Rosenthal
authors.affiliation: H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Andy
authors.initials: A
authors.lastname: Trotti
authors.affiliation: Radiological Associates of Sacramento, Sacramento, California.
authors.forename: Christopher U
authors.initials: CU
authors.lastname: Jones
authors.affiliation: University of Texas M. D. Anderson Cancer Center, Houston, Texas.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Garden
authors.affiliation: Virginia Mason Medical Center, Seattle, Washington.
authors.forename: Guobin
authors.initials: G
authors.lastname: Song
authors.affiliation: Mayo Clinic, Rochester, Minnesota.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Foote
authors.affiliation: University of Colorado Comprehensive Cancer Center, Denver, Colorado.
authors.forename: David
authors.initials: D
authors.lastname: Raben
authors.affiliation: McGill University, Montreal, Quebec, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Shenouda
authors.affiliation: University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Spencer
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Harris
authors.affiliation: Stanford University Medical Center, Stanford, California.
authors.forename: Quynh-Thu
authors.initials: QT
authors.lastname: Le
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D015984:Causality; D000068818:Cetuximab / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D015897:Comorbidity; D018572:Disease-Free Survival; D003875:Drug Eruptions / Q000401:mortality*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011855:Radiodermatitis / Q000401:mortality* / Q000473:pathology; D011879:Radiotherapy Dosage; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D000077195:Squamous Cell Carcinoma of Head and Neck; D013223:Statistics as Topic; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D000068818:Cetuximab