title: Late toxicity of proton beam therapy for patients with the nasal cavity, para-nasal sinuses, or involving the skull base malignancy: importance of long-term follow-up.
abstract: BACKGROUND
  Although several reports have shown that proton beam therapy (PBT) offers promise for patients with skull base cancer, little is known about the frequency of late toxicity in clinical practice when PBT is used for these patients. Here, we conducted a retrospective analysis to clarify the late toxicity profile of PBT in patients with malignancies of the nasal cavity, para-nasal sinuses, or involving the skull base.
  
  
  METHODS
  Entry to this retrospective study was restricted to patients with (1) malignant tumors of the nasal cavity, para-nasal sinuses, or involving the skull base; (2) definitive or postoperative PBT (>50 GyE) from January 1999 through December 2008; and (3) more than 1 year of follow-up. Late toxicities were graded according to the common terminology criteria for adverse events v4.0 (CTCAE v4.0).
  
  
  RESULTS
  From January 1999 through December 2008, 90 patients satisfied all criteria. Median observation period was 57.5 months (range, 12.4-162.7 months), median time to onset of grade 2 or greater late toxicity except cataract was 39.2 months (range, 2.7-99.8 months), and 3 patients had toxicities that occurred more than 5 years after PBT. Grade 3 late toxicities occurred in 17 patients (19%), with 19 events, and grade 4 late toxicities in 6 patients (7%), with 6 events (encephalomyelitis infection 2, optic nerve disorder 4).
  
  
  CONCLUSIONS
  In conclusion, the late toxicity profile of PBT in patients with malignancy involving the nasal cavity, para-nasal sinuses, or skull base malignancy was partly clarified. Because late toxicity can still occur at 5 years after treatment, long-term follow-up is necessary.
authors.affiliation: Division of Radiation Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan, szenda@east.ncc.go.jp.
authors.forename: Sadamoto
authors.initials: S
authors.lastname: Zenda
authors.forename: Mitsuhiko
authors.initials: M
authors.lastname: Kawashima
authors.forename: Satoko
authors.initials: S
authors.lastname: Arahira
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Kohno
authors.forename: Teiji
authors.initials: T
authors.lastname: Nishio
authors.forename: Makoto
authors.initials: M
authors.lastname: Tahara
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Hayashi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Akimoto
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009296:Nasal Cavity; D009669:Nose Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D010255:Paranasal Sinus Neoplasms / Q000188:drug therapy / Q000532:radiotherapy; D061766:Proton Therapy / Q000009:adverse effects*; D012189:Retrospective Studies; D019292:Skull Base Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D055815:Young Adult