title: Effectiveness and safety of spot scanning proton radiation therapy for chordomas and chondrosarcomas of the skull base: first long-term report.
abstract: OBJECTIVE
  To evaluate effectiveness and safety of spot-scanning-based proton radiotherapy (PT) in skull-base chordomas and chondrosarcomas.
  
  
  METHODS
  Between October 1998 and November 2005, 64 patients with skull-base chordomas (n = 42) and chondrosarcomas (n = 22) were treated at Paul Scherrer Institute with PT using spot-scanning technique. Median total dose for chordomas was 73.5 Gy(RBE) and 68.4 Gy(RBE) for chondrosarcomas at 1.8-2.0 Gy(RBE) dose per fraction. Local control (LC), disease specific survival (DSS), and overall survival (OS) rates were calculated. Toxicity was assessed according to CTCAE, v. 3.0.
  
  
  RESULTS
  Mean follow-up period was 38 months (range, 14-92 months). Five patients with chordoma and one patient with chondrosarcoma experienced local recurrence. Actuarial 5-year LC rates were 81% for chordomas and 94% for chondrosarcomas. Brainstem compression at the time of PT (p = 0.007) and gross tumor volume >25 mL (p = 0.03) were associated with lower LC rates. Five years rates of DSS and OS were 81% and 62% for chordomas and 100% and 91% for chondrosarcomas, respectively. High-grade late toxicity consisted of one patient with Grade 3 and one patient with Grade 4 unilateral optic neuropathy, and two patients with Grade 3 central nervous system necrosis. No patient experienced brainstem toxicity. Actuarial 5-year freedom from high-grade toxicity was 94%.
  
  
  CONCLUSIONS
  Our data indicate safety and efficacy of spot-scanning based PT for skull-base chordomas and chondrosarcomas. With target definition, dose prescription and normal organ tolerance levels similar to passive-scattering based PT series, complication-free, tumor control and survival rates are at present comparable.
authors.affiliation: Center for Proton Radiation Therapy, Paul Scherrer Institute, Villigen, Switzerland. carmen.ares@psi.ch
authors.forename: Carmen
authors.initials: C
authors.lastname: Ares
authors.forename: Eugen B
authors.initials: EB
authors.lastname: Hug
authors.forename: Antony J
authors.initials: AJ
authors.lastname: Lomax
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bolsi
authors.forename: Beate
authors.initials: B
authors.lastname: Timmermann
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Rutz
authors.forename: Jan C
authors.initials: JC
authors.lastname: Schuller
authors.forename: Eros
authors.initials: E
authors.lastname: Pedroni
authors.forename: Gudrun
authors.initials: G
authors.lastname: Goitein
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D002648:Child; D002813:Chondrosarcoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D002817:Chordoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D018365:Neoplasm, Residual; D061766:Proton Therapy; D011522:Protons / Q000009:adverse effects; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D019292:Skull Base Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D015996:Survival Rate; D047368:Tumor Burden; D055815:Young Adult
chemical_list: D011522:Protons