title: Endorectal Brachytherapy Boost After External Beam Radiation Therapy in Elderly or Medically Inoperable Patients With Rectal Cancer: Primary Outcomes of the Phase 1 HERBERT Study.
abstract: To evaluate the toxicity and efficacy of the combination of external beam radiation therapy (EBRT) followed by high-dose-rate endorectal brachytherapy (HDREBT) boost in elderly and medically inoperable patients with rectal cancer.
  
  
  
  A phase 1 dose-escalation study was performed. Treatment consisted of EBRT (13 × 3 Gy) followed by 3 weekly brachytherapy applications 6 weeks later. The HDREBT dose started at 5 Gy per fraction, increasing with 1 Gy per fraction if dose-limiting toxicity (DLT, defined as grade ≥3 proctitis <6 weeks after HDREBT) occurred in ≤2 patients per dose level. The primary endpoint was the maximum tolerated dose, defined as 1 dose level below the dose at which 3 patients experienced DLT. Secondary endpoints were toxicity, clinical tumor response, freedom from local progression, and local progression-free and overall survival (L-PFS and OS).
  
  
  
  Thirty-eight patients with a median age of 83 years were included in the study. Thirty-two were evaluable for DLT and late toxicity and 33 for response evaluation. Maximum delivered dose was 8 Gy per fraction, resulting in a recommended dose of 7 Gy per fraction. Response occurred in 29 of 33 patients (87.9%), with 60.6% complete response (CR). The L-PFS and OS rates were 42% and 63%, respectively, at 2 years. Patients with CR showed a significantly improved L-PFS (60% at 2 years, P=.006) and a trend in improved OS (80% at 2 years, P=.11). Severe late toxicity occurred in 10 of 32 patients.
  
  
  
  We found that HDREBT after EBRT results in a high overall response rate, with improved L-PFS for patients with a CR. The high observed rate of severe late toxicity requires further evaluation of the risks and benefits of an HDREBT boost.
authors.affiliation: Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: e.c.rijkmans@lumc.nl.
authors.forename: Eva C
authors.initials: EC
authors.lastname: Rijkmans
authors.affiliation: Department of Gastroenterology and Hepatology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Annemieke
authors.initials: A
authors.lastname: Cats
authors.affiliation: Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Remi A
authors.initials: RA
authors.lastname: Nout
authors.affiliation: Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Desiree H J G
authors.initials: DHJG
authors.lastname: van den Bongard
authors.affiliation: Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Martijn
authors.initials: M
authors.lastname: Ketelaars
authors.affiliation: Department of Radiotherapy, MAASTRO Clinic, Maastricht, The Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Buijsen
authors.affiliation: Department of Radiotherapy, Verbeeten Institute, Tilburg, The Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: Rozema
authors.affiliation: Department of Radiotherapy, HAGA Hospital, The Hague, The Netherlands.
authors.forename: Jan-Huib
authors.initials: JH
authors.lastname: Franssen
authors.affiliation: Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Velema
authors.affiliation: Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Baukelien
authors.initials: B
authors.lastname: van Triest
authors.affiliation: Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Corrie A M
authors.initials: CAM
authors.lastname: Marijnen
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000379:methods*; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D016330:Frail Elderly; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011349:Proctitis / Q000209:etiology; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D016896:Treatment Outcome