title: The potential benefit of radiotherapy with protons in head and neck cancer with respect to normal tissue sparing: a systematic review of literature.
abstract: OBJECTIVE
  Clinical studies concerning head and neck cancer patients treated with protons reporting on radiation-induced side effects are scarce. Therefore, we reviewed the literature regarding the potential benefits of protons compared with the currently used photons in terms of lower doses to normal tissue and the potential for fewer subsequent radiation-induced side effects, with the main focus on in silico planning comparative (ISPC) studies.
  
  
  METHODS
  A literature search was performed by two independent researchers on ISPC studies that included proton-based and photon-based irradiation techniques.
  
  
  RESULTS
  Initially, 877 papers were retrieved and 14 relevant and eligible ISPC studies were identified and included in this review. Four studies included paranasal sinus cancer cases, three included nasopharyngeal cancer cases, and seven included oropharyngeal, hypopharyngeal, and/or laryngeal cancer cases. Seven studies compared the most sophisticated photon and proton techniques: intensity-modulated photon therapy versus intensity-modulated proton therapy (IMPT). Four studies compared different proton techniques. All studies showed that protons had a lower normal tissue dose, while keeping similar or better target coverage. Two studies found that these lower doses theoretically translated into a significantly lower incidence of salivary dysfunction.
  
  
  CONCLUSIONS
  The results of ISPC studies indicate that protons have the potential for a significantly lower normal tissue dose, while keeping similar or better target coverage. Scanned IMPT probably offers the most advantage and will allow for a substantially lower probability of radiation-induced side effects. The results of these ISPC studies should be confirmed in properly designed clinical trials.
authors.affiliation: Department of Radiation Oncology, University Medical Center Groningen, 9700 RB Groningen, The Netherlands. t.a.van.de.water@rt.umcg.nl
authors.forename: Tara A
authors.initials: TA
authors.lastname: van de Water
authors.forename: Hendrik P
authors.initials: HP
authors.lastname: Bijl
authors.forename: Cornelis
authors.initials: C
authors.lastname: Schilstra
authors.forename: Madelon
authors.initials: M
authors.lastname: Pijls-Johannesma
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Langendijk
mesh_terms: D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D061766:Proton Therapy; D018787:Radiation Oncology / Q000379:methods; D011522:Protons
chemical_list: D011522:Protons