title: Volume of high-dose regions and likelihood of locoregional control after perioperative high-dose-rate brachytherapy: do hotter implants work better?
abstract: OBJECTIVE
  To determine whether perioperative high-dose-rate brachytherapy (PHDRB) implants with larger high-dose regions produce increased locoregional control.
  
  
  METHODS
  Patients (n=166) enrolled in several PHDRB prospective studies conducted at the University of Navarre were analyzed. The PHDRB was given to total doses of 16Gy/4 b.i.d. or 24Gy/6 b.i.d. treatments for negative or close/positive margins along with 45Gy/25 Rx of external beam radiation therapy. The histogram-based generalized equivalent uniform dose (EUD) formulism was used to quantify and standardize the dose-volume histogram into 2-Gy equivalents. The region of interest analyzed included: tissue volume encompassed by the prescription isodose of 4Gy (TV100). Routine dose reporting parameters such as physical dose and single-point 2-Gy equivalent dose were used for reference.
  
  
  RESULTS
  After a median followup of 7.4 years (range, 3-12+), 50 patients have failed, and 116 remain controlled at last followup. Overall, EUD was not different in the patients who failed compared with controls (89.1Gy vs. 86.5Gy; p=not significant). When patients were stratified by risk using the University of Navarre Predictive Model, very high-risk patients (i.e., tumors ≥3cm resected with close <1mm/positive margins) had an improved locoregional control with higher EUD values (p=0.028). This effect was not observed in low-, intermediate-, and high-risk University of Navarre Predictive Model categories.
  
  
  CONCLUSIONS
  In very high-risk patients, enlarged high-dose regions can produce a dose-response effect. Routine dose reporting methods such as physical dose and single-point 2-Gy equivalent dose may not show this effect, but it can be revealed by histogram-based EUD assessment.
authors.affiliation: Department of Radiation Oncology, Clínica Universidad de Navarra, Pamplona, Navarre, Spain. Electronic address: rmartinezm@unav.es.
authors.forename: Rafael
authors.initials: R
authors.lastname: Martínez-Monge
authors.affiliation: Department of Radiation Oncology, Clínica Universidad de Navarra, Pamplona, Navarre, Spain.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Cambeiro
authors.affiliation: Department of Radiation Oncology, Clínica Universidad de Navarra, Pamplona, Navarre, Spain.
authors.forename: Luis I
authors.initials: LI
authors.lastname: Ramos
authors.affiliation: Department of Radiation Oncology, Clínica Universidad de Navarra, Pamplona, Navarre, Spain.
authors.forename: Alicia
authors.initials: A
authors.lastname: Olarte
authors.affiliation: Department of Radiation Oncology, Clínica Universidad de Navarra, Pamplona, Navarre, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Valtueña
authors.affiliation: Department of Orthopedic Surgery, Clínica Universidad de Navarra, Pamplona, Navarre, Spain.
authors.forename: Mikel
authors.initials: M
authors.lastname: San-Julián
authors.affiliation: Department of Otolaryngology, Clínica Universidad de Navarra, Pamplona, Navarre, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Alcalde
authors.affiliation: Department of Oral Surgery, Clínica Universidad de Navarra, Pamplona, Navarre, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Naval-Gías
authors.affiliation: Department of Gynecology, Clínica Universidad de Navarra, Pamplona, Navarre, Spain.
authors.forename: Matías
authors.initials: M
authors.lastname: Jurado
mesh_terms: D000328:Adult; D000368:Aged; D001918:Brachytherapy / Q000379:methods*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009369:Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D009929:Organ Size; D011446:Prospective Studies; D012372:ROC Curve; D011879:Radiotherapy Dosage; D012509:Sarcoma / Q000532:radiotherapy
keywords: High-dose rate; High-dose regions; Locoregional control; Perioperative