title: Influence of Residual Tumor Volume and Radiation Dose Coverage in Outcomes for Clival Chordoma.
abstract: OBJECTIVE
  The purpose of this study was to evaluate factors associated with tumor control in clival chordomas.
  
  
  METHODS
  A retrospective review of 39 patients treated with surgery and proton therapy for clival chordomas between 2004 and 2014 was performed. The median prescribed dose was 77.4 Gy (relative biological effectiveness [RBE]); range was 70.2-79.2 Gy (RBE). Minimum and median doses to gross tumor volume (GTV), radiation dose received by 1 cm(3) of GTV (D1cm(3)), and the equivalent uniform dose were calculated. Receiver operating characteristics curves evaluated the predictive sensitivity and specificity for local failure of potential cutpoint values for GTV and D1cm(3).
  
  
  RESULTS
  After a median follow-up of 51 months, the 5-year estimate of local control (LC) was 69.6% (95% confidence interval [CI] 50.0%-89.2%), and overall survival (OS) was 81.4% (95% CI: 65.3%-97.5%). Tumor histology, GTV at the time of radiation, and prescribed radiation dose were significantly associated with local control on multivariate analysis, whereas D1cm(3) was associated with overall survival. Compared to those patients whose conditions remained controlled, patients experiencing tumor failure had statistically significant larger GTVs and lower D1cm(3), and prescribed and median doses to GTV. A subset of 21 patients with GTV of ≤20 cm(3) and D1cm(3) of >67 Gy (RBE) had a median follow-up of 47 months. The 5-year estimate of local control in this subset was 81.1% (95% CI: 61.7%-100%; P=.004, overall comparison by GTV ≤20 cm(3) stratified by D1cm(3)). A D1cm(3) of 74.5 Gy (RBE) had 80% sensitivity for local control and 60% specificity, whereas a GTV of 9.3 cm(3) had 80% sensitivity for local control and 66.7% specificity.
  
  
  CONCLUSIONS
  Local control of clival chordomas was associated with both smaller size of residual tumor and more complete high-dose coverage of residual tumor. Multidisciplinary care should seek maximal safe surgical resection, particularly to facilitate delivery of high-dose radiation therapy in proximity to critical structures. A D1cm(3) ≥74.5 Gy (RBE) represents a proposed treatment planning objective.
authors.affiliation: Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana; Indiana University Health Proton Therapy Center, Bloomington, Indiana. Electronic address: markmcdonaldmd@gmail.com.
authors.forename: Mark W
authors.initials: MW
authors.lastname: McDonald
authors.affiliation: Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Okechukwu R
authors.initials: OR
authors.lastname: Linton
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Moore
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana.
authors.forename: Jonathan Y
authors.initials: JY
authors.lastname: Ting
authors.affiliation: Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana; Goodman Campbell Brain and Spine, Indianapolis, Indiana.
authors.forename: Aaron A
authors.initials: AA
authors.lastname: Cohen-Gadol
authors.affiliation: Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, Indiana; Goodman Campbell Brain and Spine, Indianapolis, Indiana.
authors.forename: Mitesh V
authors.initials: MV
authors.lastname: Shah
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002817:Chordoma / Q000401:mortality / Q000473:pathology* / Q000532:radiotherapy* / Q000601:surgery; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D061766:Proton Therapy / Q000379:methods*; D012372:ROC Curve; D011879:Radiotherapy Dosage; D012062:Relative Biological Effectiveness; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D019292:Skull Base Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D013997:Time Factors; D047368:Tumor Burden