Top Line: Do more frequent prostate SBRT treatments increase acute toxicity when delivering a simultaneous integrated boost to gross disease?
The Study: By now you’re probably aware of the FLAME trial that improved biochemical control without increasing toxicity via simultaneous integrated boost to MRI-defined gross disease. The hypo-FLAME trial was a single arm phase 2 study investigating the same approach using 5-fraction SBRT. It included men with intermediate and high risk prostate cancer with a visible target on MRI. The CTV consisted of the prostate and the MRI-defined GTV plus a 4 mm margin (but excluding OARs) to account for possible ECE. The seminal vesicles were included at physician discretion. An additional 4 mm PTV margin was used. The rectum and urethra also had a 2 mm PRV margin. The PTV received 33.25 Gy in 5 fractions, the prostate received 35 Gy, and the GTV received up to 50 Gy while still meeting OAR constraints. Those included rectum D0.03cc < 40 Gy, rectum PRV D0.03 cc < 42 Gy, rectum D2cc < 35 Gy. The urethra PRV was limited to a D0.03cc <42 Gy. In hypo-FLAME 1.0, one fraction was delivered weekly. The initial toxicity analysis found no acute grade 3+ toxicity, 34% grade 2 GU toxicity, and 5% grade 2 GI toxicity. Here we have the initial toxicity outcomes from hypo-FLAME 2.0, which used the same SBRT approach except that treatments were delivered twice per week instead of once. It included 124 patients, and at 90 days, there was no grade 3 toxicity, 47.5% grade 2 GU toxicity, and 7.4% grade 2 GI toxicity. Compared to hypo-FLAME 1.0 once weekly fractionation, the rate of grade 2 GU toxicity was significantly higher with twice weekly fractionation. However, there was no difference in GI toxicity. Recall, another recent randomized phase 2 study showed no difference in grade 2 toxicity with every other day versus weekly SBRT fractionation. This trial did not deliver a SIB, so the dose escalation used in hypo-FLAME could have contributed to a more noticeable difference in toxicity with more frequently scheduled treatments.
TBL: When delivering a dose-escalated simultaneous integrated boost to MRI-defined gross disease with prostate SBRT in the style of hypo-FLAME, twice weekly fractionation was associated with a higher rate of acute grade 2 toxicity than once per week fractionation. | De Cook, Radiother Oncol 2023
The Study: By now you’re probably aware of the FLAME trial that improved biochemical control without increasing toxicity via simultaneous integrated boost to MRI-defined gross disease. The hypo-FLAME trial was a single arm phase 2 study investigating the same approach using 5-fraction SBRT. It included men with intermediate and high risk prostate cancer with a visible target on MRI. The CTV consisted of the prostate and the MRI-defined GTV plus a 4 mm margin (but excluding OARs) to account for possible ECE. The seminal vesicles were included at physician discretion. An additional 4 mm PTV margin was used. The rectum and urethra also had a 2 mm PRV margin. The PTV received 33.25 Gy in 5 fractions, the prostate received 35 Gy, and the GTV received up to 50 Gy while still meeting OAR constraints. Those included rectum D0.03cc < 40 Gy, rectum PRV D0.03 cc < 42 Gy, rectum D2cc < 35 Gy. The urethra PRV was limited to a D0.03cc <42 Gy. In hypo-FLAME 1.0, one fraction was delivered weekly. The initial toxicity analysis found no acute grade 3+ toxicity, 34% grade 2 GU toxicity, and 5% grade 2 GI toxicity. Here we have the initial toxicity outcomes from hypo-FLAME 2.0, which used the same SBRT approach except that treatments were delivered twice per week instead of once. It included 124 patients, and at 90 days, there was no grade 3 toxicity, 47.5% grade 2 GU toxicity, and 7.4% grade 2 GI toxicity. Compared to hypo-FLAME 1.0 once weekly fractionation, the rate of grade 2 GU toxicity was significantly higher with twice weekly fractionation. However, there was no difference in GI toxicity. Recall, another recent randomized phase 2 study showed no difference in grade 2 toxicity with every other day versus weekly SBRT fractionation. This trial did not deliver a SIB, so the dose escalation used in hypo-FLAME could have contributed to a more noticeable difference in toxicity with more frequently scheduled treatments.
TBL: When delivering a dose-escalated simultaneous integrated boost to MRI-defined gross disease with prostate SBRT in the style of hypo-FLAME, twice weekly fractionation was associated with a higher rate of acute grade 2 toxicity than once per week fractionation. | De Cook, Radiother Oncol 2023