title: Dose-escalation with proton/photon irradiation for Daumas-Duport lower-grade glioma: results of an institutional phase I/II trial.
abstract: OBJECTIVE
  The role of dose escalation with proton/photon radiotherapy in lower-grade gliomas was assessed in a prospective Phase I/II trial. We report the results in terms of local control, toxicity, and survival.
  
  
  METHODS
  Twenty patients with Grade 2/4 (n = 7) and Grade 3/4 (n = 13) gliomas according to the Daumas-Duport classification were treated on a prospective institutional protocol at Massachusetts General Hospital/Harvard Cyclotron Laboratory between 1993 and 1996. Doses prescribed to the target volumes were 68.2 cobalt Gray equivalent (CGE, 1 proton Gray = 1.1 CGE) to gross tumor in Grade 2 lesions and 79.7 CGE in Grade 3 lesions. Fractionation was conventional, with 1.8 to 1.92 CGE once per day. Eligibility criteria included age between 18 and 70 years, biopsy-proven Daumas-Duport Grade 2/4 or 3/4 malignant glioma, Karnofsky performance score of 70 or greater, and supratentorial tumor. Median age of the patient population at diagnosis was 35.9 years (range 19-49). Ten tumors were mixed gliomas, one an oligodendroglioma.
  
  
  RESULTS
  Five patients underwent biopsy, 12 a subtotal resection, and 3 a gross total resection. Median interval from surgery to first radiation treatment was 2.9 months. Actuarial 5-year survival rate for Grade 2 lesions was 71% as calculated from diagnosis (median survival not yet reached); actuarial 5-year survival for Grade 3 lesions was 23% (median 29 months). Median follow-up is 61 months and 55 months for 4 patients alive with Grade 2 and 3 patients alive with Grade 3 lesions, respectively. Three patients with Grade 2 lesions died from tumor recurrence, whereas 2 of the 4 survivors have evidence of radiation necrosis. Eight of 10 patients who have died with Grade 3 lesions died from tumor recurrence, 1 from pulmonary embolus, and 1 most likely from radiation necrosis. One of 3 survivors in this group has evidence of radiation necrosis.
  
  
  CONCLUSIONS
  Tumor recurrence was neither prevented nor noticeably delayed in our patients relative to published series on photon irradiation. Dose escalation using this fractionation scheme and total dose delivered failed to improve outcome for patients with Grade 2 and 3 gliomas.
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA
authors.forename: M M
authors.initials: MM
authors.lastname: Fitzek
authors.forename: A F
authors.initials: AF
authors.lastname: Thornton
authors.forename: G
authors.initials: G
authors.lastname: Harsh
authors.forename: J D
authors.initials: JD
authors.lastname: Rabinov
authors.forename: J E
authors.initials: JE
authors.lastname: Munzenrider
authors.forename: M
authors.initials: M
authors.lastname: Lev
authors.forename: M
authors.initials: M
authors.lastname: Ancukiewicz
authors.forename: M
authors.initials: M
authors.lastname: Bussiere
authors.forename: E T
authors.initials: ET
authors.lastname: Hedley-Whyte
authors.forename: F H
authors.initials: FH
authors.lastname: Hochberg
authors.forename: F S
authors.initials: FS
authors.lastname: Pardo
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005910:Glioma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis; D017785:Photons / Q000627:therapeutic use*; D011446:Prospective Studies; D061766:Proton Therapy; D011788:Quality of Life; D011879:Radiotherapy Dosage; D015173:Supratentorial Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy; D016019:Survival Analysis; D011522:Protons
chemical_list: D011522:Protons