Presenter:Jeff Michalski , MD Presenter's Affiliation: Washington University Medical Center, St. Louis, MO
Trial was funded by the NCI and run by RTOG.
Numerous dosimetric and several single institution retrospective studies have evaluated the role of IMRT in the treatment of prostate cancer as a mechanism of dose escalation while limiting GU and GI toxicity. IMRT utilizes multiple beams and computerized planning to modulate the radiation beam, increasing target coverage while decrease the radiation dose to organs at risk.
Dosimetric studies have consistently demonstrated decreased doses to bowel, bladder, and erectile structures with IMRT vs. 3D conformal radiation.
Single institution data demonstrate decreased GI and GU toxicities with IMRT.
The authors present preliminary analysis of clinical & treatment characteristics associated with acute & late toxicity in men receiving high dose RT on a phase III RTOG dose escalation trial.
The trial was designed to evaluate dose-escalation for 79.2 vs 70.2 Gy; however, after 1.5 years of enrollment, the trial was amended to allow IMRT planning. This was an unplanned analysis of toxicity of IMRT vs 3D conformal in the high dose arm.
Materials and Methods
1548 patients were included in the trial. 748 patients were treated on the high dose arm. Patients were enrolled with Gleason Score 6 and PSA 10-20 or Gleason Score 7 and PSA <15.
Patients treated with 3DCRT received 55.8 Gy to a PTV that included the prostate & proximal seminal vesicles (P+pSV) followed by a 23.4Gy to prostate only. IMRT patients were treated to the P+pSV to 79.2Gy.
All radiation treatment plans were centrally reviewed.
Physician reported toxicity was recorded.
748 of 763 patients were randomized to the 79.2 Gy arm of RTOG 0126 were eligible & evaluable. 491 & 257 patients were treated with 3DCRT & IMRT, respectively.
Median follow-up was 4.6 years & 3.5 years for 3DCRT & IMRT patients.
Dosimetry outcomes were statistically improved with IMRT:
The percent of the bladder receiving 65 Gy, 70 Gy and 75 Gy were 25.3%, 22.2%, and 17.7% for 3DCRT
The percent of the bladder receiving 65 Gy, 70 Gy and 75 Gy were 19.7%, 16.6% and 13.1% for IMRT.
The median rectum V65, V70 & V75 were 27.4%, 21.7%, & 15.8% for 3DCRT and 23.0%, 18.2% & 13.0% for IMRT.
Acute GI/ GU toxicity:
Late GI/GU toxicity:
For Grade 2+ acute GI/GU toxicity, both univariate and multivariate analyses, show a statistically significant decrease in Grade 2+ acute collective GI/GU toxicity for IMRT. This translates into a 39% reduction in acute Grade 2+ toxicity with IMRT.
There are no significant differences with 3DCRT or IMRT for acute or late Grade 2+ or 3+ GU toxicities.
Despite a small number of events, univariate analysis shows a statistically significant decrease in late Grade 2+ GI toxicity for IMRT (p=0.039). On multivariate analysis, IMRT shows a trend for a 28% reduction in Grade 2+ late GI toxicity (p=0.099).
Acute Grade 3+ toxicity was significantly associated with late Grade 3+ toxicity.
In the multivariate analysis, RT modality is not significant whereas white race & a rectal V70 (volume receiving greater than 70 Gy)>15% are significantly associated with Grade 2+ rectal toxicity.
IMRT is associated with a statistically significant reduction in high dose volume of bladder and rectum doses.
IMRT is associated with a statistically significant reduction in acute and late Grade 2+ GI toxicity.
Rectum V70 <15% and V75< 10% are associated with increased risks of late GI toxicity. The occurrence of acute GI toxicity and large (>15%) volumes of rectum exceeding 70Gy are associated with late rectal toxicity.
Race differences with increased toxicity documented in white patients was noted in the study.
Dose-escalation has been demonstrated in randomized trials to improved biochemical failure free survival with external beam radiation therapy for prostate cancer; however, it must be done with appropriate constraints in place to minimize toxicities.
Single institution data suggest IMRT allows dose escalation while decreasing acute and late toxicity.
This trial is the first multi-institutional trial that demonstrates IMRT can be used for dose-escalation with decreased rates of toxicity. This study was not randomizing IMRT vs conventional radiation, and results should be evaluated with this in mind. Additionally, these data were recorded prior to the use of daily imaging guidance radiation therapy.
Research should continued to attempt to develop mechanisms to allow dose escalation while minimizing dose to organs at risk.