title: Pre-treatment tumor-specific growth rate as a temporal biomarker that predicts treatment failure and improves risk stratification for oropharyngeal cancer.
abstract: OBJECTIVE
  To assess the relationship between tumor-specific growth rate (TSGR) and oropharyngeal cancer (OPC) outcomes in the HPV era.
  
  
  METHODS
  Primary tumor volume differences between a diagnostic and secondary scan separated ⩾7days without interval treatment were used to estimate TSGR, defined as percent volume growth/day derived from primary tumor volume doubling time for 85 OPC patients with known p16 status and smoking pack-years managed with (chemo)radiation. Variables were analyzed using Kruskal-Wallis or Fisher's exact test as appropriate. Log-rank tests and Cox proportional models analyzed endpoints. Using concordance probability estimates (CPE), TSGR was incorporated into RTOG 0129 risk grouping (0129RG) to assess whether TSGR could improve prognostic accuracy.
  
  
  RESULTS
  Median time between scans was 35days (range 8-314). Median follow up was 26months (range 1-76). The 0129RG classification was: 56% low, 25% intermediate, and 19% high risk. Median TSGR was 0.74%/day (range 0.01-4.25) and increased with 0129RG low (0.41%), intermediate (0.57%) and high (1.23%) risk, respectively (p=0.015). TSGR independently predicted for TF (TSGR: HR (95%CI)=2.79, 1.67-4.65, p<0.001) in the Cox model. On CPE, prognostic accuracy for TF, disease-free survival and overall survival was improved when 0129RG was combined with TSGR. Dichotomizing 0129RG by median TSGR yielded no observed recurrences in low risk patients with TSGR<0.74% and demonstrated significant difference for intermediate risk (8% vs. 50% for TSGR<0.74% vs. ⩾0.74%, respectively, p<0.001).
  
  
  CONCLUSIONS
  Tumor-specific growth rate correlates with increasing 0129RG and predicts treatment failure, potentially improving the prognostic strength and risk stratification of established 0129 risk groups.
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, United States.
authors.forename: Colin T
authors.initials: CT
authors.lastname: Murphy
authors.affiliation: Department of Biostatistics, Fox Chase Cancer Center, Philadelphia, PA, United States.
authors.forename: Karthik
authors.initials: K
authors.lastname: Devarajan
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, United States.
authors.forename: Lora S
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, United States.
authors.forename: Ranee
authors.initials: R
authors.lastname: Mehra
authors.affiliation: Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, United States.
authors.forename: John A
authors.initials: JA
authors.lastname: Ridge
authors.affiliation: Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA, United States.
authors.forename: Christopher
authors.initials: C
authors.lastname: Fundakowski
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, Philadelphia, PA, United States. Electronic address: thomas.galloway@fccc.edu.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Galloway
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000150:complications / Q000473:pathology* / Q000628:therapy; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009959:Oropharyngeal Neoplasms / Q000150:complications / Q000473:pathology* / Q000628:therapy; D030361:Papillomavirus Infections / Q000150:complications; D011379:Prognosis; D018570:Risk Assessment / Q000379:methods; D013997:Time Factors; D047368:Tumor Burden
keywords: Chemoradiation; Growth rate; HPV; Head and neck cancer; Oropharynx cancer; Radiation; p16