title: Older age impacts radiotherapy-related outcomes in soft tissue sarcoma.
abstract: BACKGROUND
  Radiation therapy (RT) is a standard component in the multimodality management of localized soft tissue sarcoma (STS). Increasing studies are focusing on biological modifiers that may influence the host's response to RT, including immunologic mechanisms known to change with the aging process. We hypothesized that the effects of RT would be influenced by age, contributing to differences in treatment outcome.
  
  
  METHODS
  Using Surveillance, Epidemiology, and End Results (1990-2011), we identified 30,898 adult patients (>18 y) with nonmetastatic STS undergoing initial surgery. We compared patient demographics, tumor characteristics, and treatments by age. Multivariable analyses were used to analyze overall survival (OS) and disease-specific survival (DSS). Hazard ratios (HRs) were calculated based on multivariable Cox proportional hazards models.
  
  
  RESULTS
  Mean age at diagnosis was 56.6 ± 16.8 y, and 33.6% of patients were ≥65 y. Of the total, 52.1% of patients were male and 67% were white; 59.9% of patients underwent surgery alone, 33.3% received adjuvant RT, and 6.8% neoadjuvant RT. On multivariable analysis, age, sex, year of diagnosis, histology, grade, size, marital status, and RT predicted OS, whereas age, year of diagnosis, ethnicity, histology, site, grade, RT, size, and marital status predicted DSS. In all patients, RT was associated with improved OS and DSS compared to surgery alone (median OS 136 ± 13 mo with RT versus 118 ± 9 mo without RT and 5-y OS 63.2 ± 1.4% with RT versus 60.5 ± 1.2% without, P < 0.01). Patients ≥65 y derived greater improvements in OS and DSS compared with patients <65 y. These benefits were most notable after neoadjuvant RT with patients ≥65 y having significantly better OS (HR = 0.63; 95% confidence interval = 0.53-0.75), whereas patients <65 y did not (HR = 0.96; 95% confidence interval = 0.83-1.10). In addition, interaction testing demonstrated a significant modifier effect between RT and age (P < 0.05).
  
  
  CONCLUSIONS
  RT is associated with improved survival in patients with STS undergoing surgical treatment, but improvements in oncologic outcome with RT were greatest among older patients. Further studies into the mechanism of these age-related effects are needed.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, UC Davis School of Medicine, Sacramento, California.
authors.forename: Noah K
authors.initials: NK
authors.lastname: Yuen
authors.affiliation: Division of Biostatistics, Department of Public Health Sciences, UC Davis, Sacramento, California.
authors.forename: Chin-Shang
authors.initials: CS
authors.lastname: Li
authors.affiliation: Department of Radiation Oncology, UC Davis School of Medicine, Sacramento, California.
authors.forename: Arta M
authors.initials: AM
authors.lastname: Monjazeb
authors.affiliation: Department of Pathology, Stritch School of Medicine, Loyola University, Chicago, Illinois.
authors.forename: Dariusz
authors.initials: D
authors.lastname: Borys
authors.affiliation: Division of Surgical Oncology, Department of Surgery, UC Davis School of Medicine, Sacramento, California.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bold
authors.affiliation: Division of Surgical Oncology, Department of Surgery, UC Davis School of Medicine, Sacramento, California. Electronic address: robert.canter@ucdmc.ucdavis.edu.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Canter
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018426:SEER Program; D012509:Sarcoma / Q000401:mortality* / Q000532:radiotherapy; D012983:Soft Tissue Neoplasms / Q000401:mortality* / Q000532:radiotherapy; D014481:United States / Q000453:epidemiology
keywords: Age; Radiotherapy; Soft tissue sarcoma; Surgery