title: Highly Efficient Training, Refinement, and Validation of a Knowledge-based Planning Quality-Control System for Radiation Therapy Clinical Trials.
abstract: To demonstrate an efficient method for training and validation of a knowledge-based planning (KBP) system as a radiation therapy clinical trial plan quality-control system.
  
  
  
  We analyzed 86 patients with stage IB through IVA cervical cancer treated with intensity modulated radiation therapy at 2 institutions according to the standards of the INTERTECC (International Evaluation of Radiotherapy Technology Effectiveness in Cervical Cancer, National Clinical Trials Network identifier: 01554397) protocol. The protocol used a planning target volume and 2 primary organs at risk: pelvic bone marrow (PBM) and bowel. Secondary organs at risk were rectum and bladder. Initial unfiltered dose-volume histogram (DVH) estimation models were trained using all 86 plans. Refined training sets were created by removing sub-optimal plans from the unfiltered sample, and DVH estimation models… and DVH estimation models were constructed by identifying 30 of 86 plans emphasizing PBM sparing (comparing protocol-specified dosimetric cutpoints V10(percentage volume of PBM receiving at least 10 Gy dose) and V20(percentage volume of PBM receiving at least 20 Gy dose) with unfiltered predictions) and another 30 of 86 plans emphasizing bowel sparing (comparing V40(absolute volume of bowel receiving at least 40 Gy dose) and V45(absolute volume of bowel receiving at least 45 Gy dose), 9 in common with the PBM set). To obtain deliverable KBP plans, refined models must inform patient-specific optimization objectives and/or priorities (an auto-planning "routine"). Four candidate routines emphasizing different tradeoffs were composed, and a script was developed to automatically re-plan multiple patients with each routine. After selection of the routine that best met protocol objectives in the 51-patient training sample (KBPFINAL), protocol-specific DVH metrics and normal tissue complication probability were compared for original versus KBPFINALplans across the 35-patient validation set. Paired t tests were used to test differences between planning sets.
  
  
  
  KBPFINALplans outperformed manual planning across the validation set in all protocol-specific DVH cutpoints. The mean normal tissue complication probability for gastrointestinal toxicity was lower for KBPFINALversus validation-set plans (48.7% vs 53.8%, P<.001). Similarly, the estimated mean white blood cell count nadir was higher (2.77 vs 2.49 k/mL, P<.001) with KBPFINALplans, indicating lowered probability of hematologic toxicity.
  
  
  
  This work demonstrates that a KBP system can be efficiently trained and refined for use in radiation therapy clinical trials with minimal effort. This patient-specific plan quality control resulted in improvements on protocol-specific dosimetric endpoints.
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.
authors.forename: Ruben
authors.initials: R
authors.lastname: Carmona
authors.affiliation: Department of Oncology and Radiotherapy, University Hospital, Hradec Kralove, Czech Republic.
authors.forename: Igor
authors.initials: I
authors.lastname: Sirak
authors.affiliation: Department of Oncology and Radiotherapy, University Hospital, Hradec Kralove, Czech Republic.
authors.forename: Linda
authors.initials: L
authors.lastname: Kasaova
authors.affiliation: Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: David
authors.initials: D
authors.lastname: Followill
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: Walter
authors.initials: W
authors.lastname: Bosch
authors.affiliation: Department of Radiation Oncology, Washington University in St Louis, St Louis, Missouri.
authors.forename: William
authors.initials: W
authors.lastname: Straube
authors.affiliation: Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, California.
authors.forename: Loren K
authors.initials: LK
authors.lastname: Mell
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
mesh_terms: D001853:Bone Marrow; D002986:Clinical Trials as Topic / Q000592:standards*; D005260:Female; D006801:Humans; D007422:Intestines; D059351:Organ Sparing Treatments / Q000379:methods / Q000592:standards*; D058958:Organs at Risk; D010384:Pelvic Bones; D011786:Quality Control; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods* / Q000592:standards*; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods / Q000592:standards*; D012007:Rectum; D047368:Tumor Burden; D001743:Urinary Bladder; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy*