title: Toward a model-based patient selection strategy for proton therapy: External validation of photon-derived normal tissue complication probability models in a head and neck proton therapy cohort.
abstract: To externally validate head and neck cancer (HNC) photon-derived normal tissue complication probability (NTCP) models in patients treated with proton beam therapy (PBT).
  
  
  
  This prospective cohort consisted of HNC patients treated with PBT at a single institution. NTCP models were selected based on the availability of data for validation and evaluated by using the leave-one-out cross-validated area under the curve (AUC) for the receiver operating characteristics curve.
  
  
  
  192 patients were included. The most prevalent tumor site was oropharynx (n=86, 45%), followed by sinonasal (n=28), nasopharyngeal (n=27) or parotid (n=27) tumors. Apart from the prediction of acute mucositis (reduction of AUC of 0.17), the models overall performed well. The validation (PBT) AUC and the published AUC were respectively 0.90 versus 0.88 for feeding tube 6months PBT; 0.70 versus 0.80 for physician-rated dysphagia 6months after PBT; 0.70 versus 0.68 for dry mouth 6months after PBT; and 0.73 versus 0.85 for hypothyroidism 12months after PBT.
  
  
  
  Although a drop in NTCP model performance was expected for PBT patients, the models showed robustness and remained valid. Further work is warranted, but these results support the validity of the model-based approach for selecting treatment for patients with HNC.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA; Department of Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Blanchard
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Wong
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: G Brandon
authors.initials: GB
authors.lastname: Gunn
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Garden
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Abdallah S R
authors.initials: ASR
authors.lastname: Mohamed
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: David I
authors.initials: DI
authors.lastname: Rosenthal
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Crutison
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: X Ronald
authors.initials: XR
authors.lastname: Zhu
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Radhe
authors.initials: R
authors.lastname: Mohan
authors.affiliation: Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: Mayankkumar V
authors.initials: MV
authors.lastname: Amin
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA.
authors.forename: C David
authors.initials: CD
authors.lastname: Fuller
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, USA. Electronic address: sjfrank@mdanderson.org.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Frank
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003680:Deglutition Disorders / Q000209:etiology; D005260:Female; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007037:Hypothyroidism / Q000209:etiology; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D052016:Mucositis / Q000209:etiology; D018579:Patient Selection; D017785:Photons; D011336:Probability; D011446:Prospective Studies; D061766:Proton Therapy / Q000009:adverse effects* / Q000379:methods*; D012372:ROC Curve; D011832:Radiation Injuries / Q000209:etiology; D011874:Radiometry / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods; D014987:Xerostomia / Q000209:etiology; D055815:Young Adult
keywords: Head and neck cancer; Intensity-modulated proton therapy; Late toxicity; Model; Prediction; Radiation therapy