title: Do differences in target volume definition in prostate cancer lead to clinically relevant differences in normal tissue toxicity?
abstract: OBJECTIVE
  Many studies have described the quantitated differences between clinicians in target volume definition in prostate cancer. However, few studies have looked at the clinical effects of this. We aimed to assess the relevance and sequelae of such differences.
  
  
  METHODS
  Five experienced radiation oncologists were given the clinical details of 5 patients with early-stage prostate cancer and asked to define the clinical target volume, consisting of the prostate and seminal vesicles (CTV1) and the prostate alone (CTV2), on specified planning CT scans of the pelvis. Planning target volumes (PTV1) were generated by automatic expansion of the CTV1 by a 1-cm margin. The PTV2 was defined as the CTV2. The rectum and bladder were defined by a single experienced clinician for each plan without knowledge of the involved clinician marking the CTVs. The Pinnacle planning system was used to generate the plans, using four-field conformal radiotherapy, to deliver 64 Gy in 32 fractions to the PTV1 followed by a boost of 10 Gy to the PTV2 (Medical Research Council RT01 trial protocol). Dose-volume histograms were generated for the whole bladder and rectum for each plan and the volume receiving a specific percentage of the dose (e.g., V(90)) calculated for 74 Gy, followed by estimates of normal tissue complication probabilities (NTCPs) for the bladder and rectum.
  
  
  RESULTS
  Statistically significant differences were found in the CTV1 and CTV2 and, consequently, the PTV1 among the 5 clinicians (p < 0.0005). Most of the discrepancies occurred at the delineation of the prostatic apex and seminal vesicles, with the smallest variance noted at the rectum-prostate and bladder-prostate interfaces. No statistically significant differences were found among clinicians for the rectal V(90), V(85), V(80), V(70), or V(50) or for the bladder V(85), V(80), V(70), or V(50). A difference was noted among consultants for the bladder V(90) (p = 0.015), although no correlation was found between the bladder V(90) and the size of the outlined volumes. No statistically significant differences were found between the estimates of bladder (p = 0.1) and rectal (p = 0.09) NTCPs.
  
  
  CONCLUSIONS
  The statistically significant difference in outlined volumes of the CTV1, CTV2, and PTV1 among the 5 clinicians is in keeping with the findings of previous studies. However, the interclinician variability did not result in clinically relevant outcomes with respect to the irradiated volume of rectum and bladder or NTCP. This may have been because the outlined areas in which interclinician differences were smallest (the rectal-prostate and prostate-bladder interfaces) are the areas that have the greatest effect on normal tissue toxicity. For the areas in which the interclinician correlation was lowest (the prostatic apex and distal seminal vesicles), the effects on normal tissue toxicity are smallest. The results of this study suggest that interclinician outlining differences in prostate cancer may have less clinical relevance than was previously thought.
authors.affiliation: Department of Clinical Oncology, Manchester, United Kingdom. jaclivsey@hotmail.com
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Livsey
authors.forename: James P
authors.initials: JP
authors.lastname: Wylie
authors.forename: Ric
authors.initials: R
authors.lastname: Swindell
authors.forename: Vincent S
authors.initials: VS
authors.lastname: Khoo
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cowan
authors.forename: John P
authors.initials: JP
authors.lastname: Logue
mesh_terms: D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D015588:Observer Variation; D011467:Prostate / Q000000981:diagnostic imaging* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy; D018787:Radiation Oncology / Q000592:standards*; D011859:Radiography; D011880:Radiotherapy Planning, Computer-Assisted; D020266:Radiotherapy, Conformal; D012007:Rectum / Q000000981:diagnostic imaging; D012669:Seminal Vesicles / Q000000981:diagnostic imaging*; D047368:Tumor Burden; D001743:Urinary Bladder / Q000000981:diagnostic imaging