Eva C Rijkmans1, Annemieke Cats2, Remi A Nout3, Desiree H J G van den Bongard4, Martijn Ketelaars3, Jeroen Buijsen5, Tom Rozema6, Jan-Huib Franssen7, Laura A Velema3, Baukelien van Triest8, Corrie A M Marijnen3. 1. Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands. Electronic address: e.c.rijkmans@lumc.nl. 2. Department of Gastroenterology and Hepatology, The Netherlands Cancer Institute, Amsterdam, The Netherlands. 3. Department of Radiotherapy, Leiden University Medical Center, Leiden, The Netherlands. 4. Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands. 5. Department of Radiotherapy, MAASTRO Clinic, Maastricht, The Netherlands. 6. Department of Radiotherapy, Verbeeten Institute, Tilburg, The Netherlands. 7. Department of Radiotherapy, HAGA Hospital, The Hague, The Netherlands. 8. Department of Radiotherapy, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Abstract
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.
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.
Authors: Stijn H J Ketelaers; Anne Jacobs; An-Sofie E Verrijssen; Jeltsje S Cnossen; Irene E G van Hellemond; Geert-Jan M Creemers; Ramon-Michel Schreuder; Harm J Scholten; Jip L Tolenaar; Johanne G Bloemen; Harm J T Rutten; Jacobus W A Burger Journal: Cancers (Basel) Date: 2022-05-11 Impact factor: 6.575
Authors: Petra A Custers; Barbara M Geubels; Inge L Huibregtse; Femke P Peters; Ellen G Engelhardt; Geerard L Beets; Corrie A M Marijnen; Monique E van Leerdam; Baukelien van Triest Journal: Cancers (Basel) Date: 2021-12-16 Impact factor: 6.639