D W Nathan Kim1, L Chinsoo Cho2, Christopher Straka1, Alana Christie3, Yair Lotan4, David Pistenmaa1, Brian D Kavanagh5, Akash Nanda6, Patrick Kueplian7, Jeffrey Brindle8, Susan Cooley1, Alida Perkins1, David Raben5, Xian-Jin Xie3, Robert D Timmerman9. 1. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. 2. Department of Radiation Oncology, University of Minnesota, Minneapolis, Minnesota. 3. Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas. 4. Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas. 5. Department of Radiation Oncology, University of Colorado, Denver, Colorado. 6. Department of Radiation Oncology, University of Florida Health Cancer Center at Orlando Health, Orlando, Florida. 7. Department of Radiation Oncology, University of California, Los Angeles, Los Angeles, California. 8. Prairie Lakes Hospital, Watertown, South Dakota. 9. Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: robert.timmerman@utsouthwestern.edu.
Abstract
PURPOSE: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury. METHODS AND MATERIALS: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer. RESULTS: At the highest dose level, 6.6% of patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm(3) (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010). CONCLUSION: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.
PURPOSE: To convey the occurrence of isolated cases of severe rectal toxicity at the highest dose level tested in 5-fraction stereotactic body radiation therapy (SBRT) for localized prostate cancer; and to rationally test potential causal mechanisms to guide future studies and experiments to aid in mitigating or altogether avoiding such severe bowel injury. METHODS AND MATERIALS: Clinical and treatment planning data were analyzed from 91 patients enrolled from 2006 to 2011 on a dose-escalation (45, 47.5, and 50 Gy in 5 fractions) phase 1/2 clinical study of SBRT for localized prostate cancer. RESULTS: At the highest dose level, 6.6% of patients treated (6 of 91) developed high-grade rectal toxicity, 5 of whom required colostomy. Grade 3+ delayed rectal toxicity was strongly correlated with volume of rectal wall receiving 50 Gy >3 cm(3) (P<.0001), and treatment of >35% circumference of rectal wall to 39 Gy (P=.003). Grade 2+ acute rectal toxicity was significantly correlated with treatment of >50% circumference of rectal wall to 24 Gy (P=.010). CONCLUSION: Caution is advised when considering high-dose SBRT for treatment of tumors near bowel structures, including prostate cancer. Threshold dose constraints developed from physiologic principles are defined, and if respected can minimize risk of severe rectal toxicity.
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