Parameters that Predict for High Grade Rectal Toxicity in Prostate Cancer Patients Undergoing Stereotactic Body Radiation Therapy- Analysis of Phase I/II at UT Southwestern

Date

2013-01-22

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Abstract

INTRODUCTION: Conventional radiation therapy (CRT) is a well-accepted option for PCa treatment with high disease control rate, and low (< 3-5%) risk of rectal toxicity. SBRT, unlike CRT, delivers higher doses of radiation in 1-5 fractions, reducing treatment time significantly (from 8-9 weeks to ~ 2 weeks). Benefits of SBRT include improved patient convenience, significant healthcare cost reduction, and it has strong biologic rationale. A dose escalation phase I study (Boike et. al, JCO 2011) established 45-50 Gy in 5 treatments as effective and safe. Phase II study at 50 Gy was recently completed. Interim analysis unexpectedly revealed a significant number of grade 3+ delayed rectal events. We performed a rigorous analysis to determine potential etiology and methods to avoid occurrence of such rectal events. METHODS: Clinical parameters evaluated include tumor stage, Gleason grade, prostate volume, comorbid conditions (diabetes, smoking history, immunosuppression), race, age, and baseline bowel function score. Treatment planning parameters collected and evaluated included rectal wall volume receiving high doses of radiation, target volume size, rectal wall size, and degree of circumferential radiation to the rectal wall. Uni/multivariate analysis and correlative studies were conducted. RESULTS: 59 low/intermediate risk Pca patients were enrolled in this phase I/II study at UTSW. Median follow-up for all patients is 25.5 months. Tumor control rate is 99% to date. No patients experienced high grade rectal toxicity at 45 and 47.5 Gy, but at 50 Gy 10.8% experienced ≥ grade 3 rectal toxicity. Significant parameters were rectal volume receiving 50 Gy, HR of 2.67 (1.25, 5.71), p=.0113; rectal circumference irradiated by 24 Gy, 39 Gy and 50 Gy, HR of 1.1 (1.01,1.2) (p=.03), 1.2 (1.01, 1.38) (p=.04), and 1.22 (1.01, 1.47) (p=.04) respectively; and possibly diabetes HR 6.86 (0.83, 56.8) (p=.074). All 4 patients with grade 3+ rectal toxicity had > 3.5 cm3 rectal wall irradiated by 50 Gy. All patients without rectal toxicity had < 3.5 cm3 rectal wall irradiated by 50 Gy. DISCUSSION: We have determined the absolute threshold dose volume constraint to avoid rectal toxicity for SBRT of Pca. These findings contribute significantly to the radiobiology of bowel tolerance. If anatomy does not permit safe rectal dose constraints, dose reduced SBRT or alternatively CRT should be considered. When rectal constraints are met, or when 45-47.5 Gy prescription dose is used, SBRT seems to be a potent, safe, convenient and cost effective treatment for patients with low/intermediate risk PCa.

General Notes

The 51st Annual Medical Student Research Forum at UT Southwestern Medical Center (Tuesday, January 22, 2013, 3-6 p.m., D1.602)

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Subjects

Clinical Research and Case Reports, Organs at Risk, Prostatic Neoplasms, Radiation Injuries, Radiation Tolerance, Radiosurgery, Rectum

Citation

Straka, C., Kim, D. N., Pistenmaa, D., Lotan, Y., Xie, X.-J., & Timmerman, R. (2013, January 22). Parameters that predict for high grade rectal toxicity in prostate cancer patients undergoing stereotactic body radiation therapy- analysis of phase I/II at UT Southwestern. Poster session presented at the 51st Annual Medical Student Research Forum, Dallas, TX. Retrieved from https://hdl.handle.net/2152.5/1634

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