title: Quantifying Unnecessary Normal Tissue Complication Risks due to Suboptimal Planning: A Secondary Study of RTOG 0126.
abstract: OBJECTIVE
  The purpose of this study was to quantify the frequency and clinical severity of quality deficiencies in intensity modulated radiation therapy (IMRT) planning in the Radiation Therapy Oncology Group 0126 protocol.
  
  
  METHODS
  A total of 219 IMRT patients from the high-dose arm (79.2 Gy) of RTOG 0126 were analyzed. To quantify plan quality, we used established knowledge-based methods for patient-specific dose-volume histogram (DVH) prediction of organs at risk and a Lyman-Kutcher-Burman (LKB) model for grade ≥2 rectal complications to convert DVHs into normal tissue complication probabilities (NTCPs). The LKB model was validated by fitting dose-response parameters relative to observed toxicities. The 90th percentile (22 of 219) of plans with the lowest excess risk (difference between clinical and model-predicted NTCP) were used to create a model for the presumed best practices in the protocol (pDVH0126,top10%). Applying the resultant model to the entire sample enabled comparisons between DVHs that patients could have received to DVHs they actually received. Excess risk quantified the clinical impact of suboptimal planning. Accuracy of pDVH predictions was validated by replanning 30 of 219 patients (13.7%), including equal numbers of presumed "high-quality," "low-quality," and randomly sampled plans. NTCP-predicted toxicities were compared to adverse events on protocol.
  
  
  RESULTS
  Existing models showed that bladder-sparing variations were less prevalent than rectum quality variations and that increased rectal sparing was not correlated with target metrics (dose received by 98% and 2% of the PTV, respectively). Observed toxicities were consistent with current LKB parameters. Converting DVH and pDVH0126,top10% to rectal NTCPs, we observed 94 of 219 patients (42.9%) with ≥5% excess risk, 20 of 219 patients (9.1%) with ≥10% excess risk, and 2 of 219 patients (0.9%) with ≥15% excess risk. Replanning demonstrated the predicted NTCP reductions while maintaining the volume of the PTV receiving prescription dose. An equivalent sample of high-quality plans showed fewer toxicities than low-quality plans, 6 of 73 versus 10 of 73 respectively, although these differences were not significant (P=.21) due to insufficient statistical power in this retrospective study.
  
  
  CONCLUSIONS
  Plan quality deficiencies in RTOG 0126 exposed patients to substantial excess risk for rectal complications.
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California. Electronic address: kevinmoore@ucsd.edu.
authors.forename: Kevin L
authors.initials: KL
authors.lastname: Moore
authors.affiliation: Department of Physics, Fort Hays State University, Hays, Kansas.
authors.forename: Rachel
authors.initials: R
authors.lastname: Schmidt
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.
authors.forename: Vitali
authors.initials: V
authors.lastname: Moiseenko
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Olsen
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: Jun
authors.initials: J
authors.lastname: Tan
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: James
authors.initials: J
authors.lastname: Galvin
authors.affiliation: NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Pugh
authors.affiliation: Akron City Hospital, Akron, Ohio.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Seider
authors.affiliation: Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Dicker
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: Walter
authors.initials: W
authors.lastname: Bosch
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: Jeff
authors.initials: J
authors.lastname: Michalski
authors.affiliation: Department of Radiation Oncology, Washington University in St. Louis, St. Louis, Missouri.
authors.forename: Sasa
authors.initials: S
authors.lastname: Mutic
mesh_terms: D019985:Benchmarking / Q000379:methods / Q000592:standards*; D004307:Dose-Response Relationship, Radiation; D006801:Humans; D008297:Male; D015233:Models, Statistical; D059351:Organ Sparing Treatments / Q000592:standards; D058958:Organs at Risk / Q000528:radiation effects*; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011787:Quality of Health Care; D011832:Radiation Injuries / Q000175:diagnosis* / Q000209:etiology; D011880:Radiotherapy Planning, Computer-Assisted / Q000009:adverse effects* / Q000592:standards; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects* / Q000379:methods / Q000592:standards; D012007:Rectum / Q000528:radiation effects*; D018570:Risk Assessment
references.citation: Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S116-22
references.pmid: 20171505
references.citation: Med Phys. 2009 Dec;36(12):5497-505
references.pmid: 20095262
references.citation: Radiother Oncol. 2012 Jan;102(1):38-44
references.pmid: 21680036
references.citation: J Natl Cancer Inst. 2013 Mar 20;105(6):387-93
references.pmid: 23468460
references.citation: Med Phys. 2012 Dec;39(12):7446-61
references.pmid: 23231294
references.citation: Int J Radiat Oncol Biol Phys. 2012 Oct 1;84(2):390-5
references.pmid: 22342302
references.citation: Int J Radiat Oncol Biol Phys. 2011 Oct 1;81(2):545-51
references.pmid: 21277097
references.citation: Semin Radiat Oncol. 2012 Jan;22(1):18-28
references.pmid: 22177875
references.citation: Pract Radiat Oncol. 2012 Oct-Dec;2(4):296-305
references.pmid: 24674168
references.citation: Int J Radiat Oncol Biol Phys. 2013 Oct 1;87(2):246-60
references.pmid: 23683829
references.citation: J Clin Oncol. 2010 Jun 20;28(18):2996-3001
references.pmid: 20479390
references.citation: Int J Radiat Oncol Biol Phys. 2012 Feb 1;82(2):809-16
references.pmid: 21277694
references.citation: Radiother Oncol. 2014 Feb;110(2):272-7
references.pmid: 24332020
references.citation: Med Phys. 2012 Nov;39(11):6868-78
references.pmid: 23127079
references.citation: Int J Radiat Oncol Biol Phys. 2013 Dec 1;87(5):932-8
references.pmid: 24113055
references.citation: Int J Radiat Oncol Biol Phys. 2011 Mar 15;79(4):1241-7
references.pmid: 20800382
references.citation: Int J Radiat Oncol Biol Phys. 2012 Dec 1;84(5):e647-53
references.pmid: 22867890
references.citation: Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3 Suppl):S123-9
references.pmid: 20171506
references.citation: Radiother Oncol. 1993 Oct;29(1):69-74
references.pmid: 8295990
references.citation: Med Phys. 2011 Feb;38(2):719-26
references.pmid: 21452709