title: Differences Between Colon Cancer Primaries and Metastases Using a Molecular Assay for Tumor Radiation Sensitivity Suggest Implications for Potential Oligometastatic SBRT Patient Selection.
abstract: OBJECTIVE
  We previously developed a multigene expression model of tumor radiation sensitivity index (RSI) with clinical validation in multiple independent cohorts (breast, rectal, esophageal, and head and neck patients). The purpose of this study was to assess differences between RSI scores in primary colon cancer and metastases.
  
  
  METHODS
  Patients were identified from our institutional review board-approved prospective observational protocol. A total of 704 metastatic and 1362 primary lesions were obtained from a de-identified metadata pool. RSI was calculated using the previously published rank-based algorithm. An independent cohort of 29 lung or liver colon metastases treated with 60 Gy in 5 fractions stereotactic body radiation therapy (SBRT) was used for validation.
  
  
  RESULTS
  The most common sites of metastases included liver (n=374; 53%), lung (n=116; 17%), and lymph nodes (n=40; 6%). Sixty percent of metastatic tumors, compared with 54% of primaries, were in the RSI radiation-resistant peak, suggesting metastatic tumors may be slightly more radiation resistant than primaries (P=.01). In contrast, when we analyzed metastases based on anatomical site, we uncovered large differences in RSI. The median RSIs for metastases in descending order of radiation resistance were ovary (0.48), abdomen (0.47), liver (0.43), brain (0.42), lung (0.32), and lymph nodes (0.31) (P<.0001). These findings were confirmed when the analysis was restricted to lesions from the same patient (n=139). In our independent cohort of treated lung and liver metastases, lung metastases had an improved local control rate compared to that in patients with liver metastases (2-year local control rate of 100% vs 73.0%, respectively; P=.026).
  
  
  CONCLUSIONS
  Assessment of radiation sensitivity between primary and metastatic tissues of colon cancer histology revealed significant differences based on anatomical location of metastases. These initial results warrant validation in a larger clinical cohort.
authors.affiliation: Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Kamran A
authors.initials: KA
authors.lastname: Ahmed
authors.affiliation: Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: William J
authors.initials: WJ
authors.lastname: Fulp
authors.affiliation: Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Anders E
authors.initials: AE
authors.lastname: Berglund
authors.affiliation: Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Hoffe
authors.affiliation: Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Dilling
authors.affiliation: Department of Bioinformatics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Eschrich
authors.affiliation: Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida.
authors.forename: Ravi
authors.initials: R
authors.lastname: Shridhar
authors.affiliation: Department of Radiation Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida. Electronic address: javier.torresroca@moffitt.org.
authors.forename: Javier F
authors.initials: JF
authors.lastname: Torres-Roca
mesh_terms: D000368:Aged; D003110:Colonic Neoplasms / Q000556:secondary / Q000601:surgery*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary / Q000601:surgery*; D008175:Lung Neoplasms / Q000556:secondary / Q000601:surgery*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D064887:Observational Studies as Topic; D011446:Prospective Studies; D011836:Radiation Tolerance / Q000235:genetics; D011879:Radiotherapy Dosage
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