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

• Published in: International journal of radiation oncology, biology, physics Vol. 98; no. 4; pp. 908 - 917
• Main Authors: Rijkmans, Eva C., MD, Cats, Annemieke, MD, PhD, Nout, Remi A., MD, PhD, van den Bongard, Desiree H.J.G., MD, PhD, Ketelaars, Martijn, PhD, Buijsen, Jeroen, MD, PhD, Rozema, Tom, MD, Franssen, Jan-Huib, MD, Velema, Laura A., MD, van Triest, Baukelien, MD, PhD, Marijnen, Corrie A.M., MD, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.07.2017
• Subjects: Adenocarcinoma - mortality; Adenocarcinoma - pathology; Adenocarcinoma - radiotherapy; Aged; Aged, 80 and over; Brachytherapy - methods; Disease-Free Survival; Dose Fractionation; Female; Frail Elderly; Hematology, Oncology and Palliative Medicine; Humans; Male; Maximum Tolerated Dose; Middle Aged; Proctitis - etiology; Radiology; Rectal Neoplasms - mortality; Rectal Neoplasms - pathology; Rectal Neoplasms - radiotherapy; Treatment Outcome
• ISSN: 0360-3016; 1879-355X
• DOI: 10.1016/j.ijrobp.2017.01.033

Purpose 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. Methods and Materials 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). Results 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. Conclusion 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.