The Effect of Dose Escalation on Clinical Outcomes
Several studies performed by the Radiation Therapy Oncology Group (RTOG) in the 1970s and 1980s established radiation doses in the range of 70 Gy as a standard. At least three trials were performed using a simple four-field technique to examine the use of higher doses of radiation.[7–9] However, these studies found unacceptably high toxicities to the rectum and bladder. Chism et al demonstrated late grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities at 3 years to be 12% and 38%, respectively, with doses of 79 to 84 Gy. Additionally, patterns of care analyses suggest that severe complication rates double when conventional techniques are used to treat at doses > 70 Gy.
In the 1980s, the advent of more sophisticated radiation therapy treatment planning software permitted the introduction of 3D CRT. For prostate cancer, this technique generally employs a six- or seven-beam configuration in which each of the beams is shaped to conform to the shape of the prostate in what is known as "the beam's eye view." The goal of delivering higher dose to tumor while minimizing the dose to normal tissue was the driving force behind the development of 3D CRT. Seminal work performed by Pollack et al at the M.D. Anderson Cancer Center culminated in one of the first randomized trials to utilize 3D CRT for the purposes of prostate radiation dose escalation. Their study evaluated 301 patients treated with 70 Gy vs those treated with 78 Gy using a 3D CRT boost. Kuban et al recently reported 10-year outcomes from this study, demonstrating biochemical and clinical freedom from failure rates of 73% vs 50% favoring the 78-Gy arm. Several other randomized trials employing 3D CRT to escalate doses between 78 to 81 Gy compared with 68 Gy to 70 Gy have supported these results.[1,5,6,18–20]
Although enhancing biochemical control, the delivery of higher doses using 3D CRT for prostate cancer has not come without costs. Despite the use of a more conformal treatment, normal tissue toxicities, specifically rectal toxicity, have been found to be higher. The M.D. Anderson Cancer Center trial found that late grade 2 rectal toxicities significantly increased from 11% to 19% and late grade 3 toxicities increased from 1% to 7% with the use of 78 Gy compared with 70 Gy.17 Dearnaley et al found late grade 2 and 3 rectal toxicity to increase from 14% and 4% to 20% and 6% in patients randomized to 64 Gy vs 74 Gy. Furthermore, Zelefsky et al reported that patients who were treated with 3D CRT at 75.6 or 81 Gy compared with those receiving 70.2 or 64.8 Gy had an increased late rectal toxicity of 17% vs 7% favoring lower doses. Though increases in rectal toxicity are evident with higher doses using a 3D CRT technique, whether there is an associated increase in GU toxicity is less clear. Dearnaley et al demonstrated a significant increase in late grade 2 and 3 GU toxicity with use of 74 Gy. Moreover, Zelefsky et al demonstrated a significantly higher rate of late grade 2 or higher GU toxicity of 15% vs 8% in patients who received doses > 75.6 Gy. However, several other randomized trials did not report a significant increase in late GU toxicity with increased doses using 3D CRT.[1,5,21–24]
Cancer Control. 2010;17(4):223-32. © 2010 H. Lee Moffitt Cancer Center and Research Institute, Inc.
Copyright by H. Lee Moffitt Cancer Center & Research Institute. All rights reserved.
Cite this: Emerging Technologies in Prostate Cancer Radiation Therapy: Improving the Therapeutic Window - Medscape - Oct 01, 2010.