Predictors of rectal tolerance observed in a dose-escalated phase 1-2 trial of stereotactic body radiation therapy for prostate cancer

D. W Nathan Kim, L. Chinsoo Cho, Christopher Straka, Alana Christie, Yair Lotan, David Pistenmaa, Brian D. Kavanagh, Akash Nanda, Patrick Kueplian, Jeffrey Brindle, Susan Cooley, Alida Perkins, David Raben, Xian-Jin Xie, Robert Timmerman

Research output: Contribution to journalArticle

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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 cm3 (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.

Original languageEnglish (US)
Pages (from-to)509-517
Number of pages9
JournalInternational Journal of Radiation Oncology Biology Physics
Volume89
Issue number3
DOIs
StatePublished - Jul 1 2014

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toxicity
radiation therapy
Prostatic Neoplasms
Radiotherapy
cancer
dosage
predictions
grade
circumferences
Colostomy
Therapeutics
Wounds and Injuries
planning
tumors
occurrences
Neoplasms
thresholds
Clinical Studies

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Radiation
  • Cancer Research

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Predictors of rectal tolerance observed in a dose-escalated phase 1-2 trial of stereotactic body radiation therapy for prostate cancer. / Kim, D. W Nathan; Cho, L. Chinsoo; Straka, Christopher; Christie, Alana; Lotan, Yair; Pistenmaa, David; Kavanagh, Brian D.; Nanda, Akash; Kueplian, Patrick; Brindle, Jeffrey; Cooley, Susan; Perkins, Alida; Raben, David; Xie, Xian-Jin; Timmerman, Robert.

In: International Journal of Radiation Oncology Biology Physics, Vol. 89, No. 3, 01.07.2014, p. 509-517.

Research output: Contribution to journalArticle

Kim, DWN, Cho, LC, Straka, C, Christie, A, Lotan, Y, Pistenmaa, D, Kavanagh, BD, Nanda, A, Kueplian, P, Brindle, J, Cooley, S, Perkins, A, Raben, D, Xie, X-J & Timmerman, R 2014, 'Predictors of rectal tolerance observed in a dose-escalated phase 1-2 trial of stereotactic body radiation therapy for prostate cancer', International Journal of Radiation Oncology Biology Physics, vol. 89, no. 3, pp. 509-517. https://doi.org/10.1016/j.ijrobp.2014.03.012
Kim, D. W Nathan ; Cho, L. Chinsoo ; Straka, Christopher ; Christie, Alana ; Lotan, Yair ; Pistenmaa, David ; Kavanagh, Brian D. ; Nanda, Akash ; Kueplian, Patrick ; Brindle, Jeffrey ; Cooley, Susan ; Perkins, Alida ; Raben, David ; Xie, Xian-Jin ; Timmerman, Robert. / Predictors of rectal tolerance observed in a dose-escalated phase 1-2 trial of stereotactic body radiation therapy for prostate cancer. In: International Journal of Radiation Oncology Biology Physics. 2014 ; Vol. 89, No. 3. pp. 509-517.
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AB - 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 cm3 (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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