title: Onset time of tumor repopulation for cervical cancer: first evidence from clinical data.
abstract: OBJECTIVE
  Accelerated tumor repopulation has significant implications in low-dose rate (LDR) brachytherapy. Repopulation onset time remains undetermined for cervical cancer. The purpose of this study was to determine the onset time of accelerated repopulation in cervical cancer, using clinical data.
  
  
  METHODS
  The linear quadratic (LQ) model extended for tumor repopulation was used to analyze clinical data and magnetic resonance imaging-based three-dimensional tumor volumetric regression data from 80 cervical cancer patients who received external beam radiotherapy (EBRT) and LDR brachytherapy. The LDR dose was converted to EBRT dose in 1.8-Gy fractions by using the LQ formula, and the total dose ranged from 61.4 to 99.7 Gy. Patients were divided into 11 groups according to total dose and treatment time. The tumor control probability (TCP) was calculated for each group. The least χ(2) method was used to fit the TCP data with two free parameters: onset time (T(k)) of accelerated repopulation and number of clonogens (K), while other LQ model parameters were adopted from the literature, due to the limited patient data.
  
  
  RESULTS
  Among the 11 patient groups, TCP varied from 33% to 100% as a function of radiation dose and overall treatment time. Higher dose and shorter treatment duration were associated with higher TCP. Using the LQ model, we achieved the best fit with onset time T(k) of 19 days and K of 139, with uncertainty ranges of (11, 22) days for T(k) and (48, 1822) for K, respectively.
  
  
  CONCLUSIONS
  This is the first report of accelerated repopulation onset time in cervical cancer, derived directly from clinical data by using the LQ model. Our study verifies the fact that accelerated repopulation does exist in cervical cancer and has a relatively short onset time. Dose escalation may be required to compensate for the effects of tumor repopulation if the radiation therapy course is protracted.
authors.affiliation: Department of Radiation Oncology, East Carolina University, Greenville, North Carolina 27834, USA. huangz@ecu.edu
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Huang
authors.forename: Nina A
authors.initials: NA
authors.lastname: Mayr
authors.forename: Mingcheng
authors.initials: M
authors.lastname: Gao
authors.forename: Simon S
authors.initials: SS
authors.lastname: Lo
authors.forename: Jian Z
authors.initials: JZ
authors.lastname: Wang
authors.forename: Guang
authors.initials: G
authors.lastname: Jia
authors.forename: William T C
authors.initials: WT
authors.lastname: Yuh
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000379:methods; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D002452:Cell Count; D049109:Cell Proliferation; D002999:Clone Cells / Q000473:pathology; D005260:Female; D006801:Humans; D016018:Least-Squares Analysis; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D008954:Models, Biological; D009367:Neoplasm Staging / Q000379:methods; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D013997:Time Factors; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy