ORLANDO, FL, USA (UroToday.com) - Dr. Jeff Michalski, a radiation oncologist, from Washington University in Saint Louis presented on the concept of hypofractionation and stereotactic body radiation therapy in prostate cancer.
Initial response to radiation in human tissue is linear followed by quadratic “curviness.” This curviness is measured by the alpha/beta ratio. Low alpha/beta ratio indicates slow proliferation of tissue while high ratio means rapidly proliferative. Rapidly proliferative is not very sensitive to radiation while slowly proliferative is very sensitive. Prostate cancer has an alpha/beta ratio of 1.5 lower than 5-7 of the surrounding normal tissues (rectum or bladder). This would indicate that prostate cancer would have an advantage by hypofractionation—increasing the dose given per fraction—and, thus, total number of fractionations can be reduced.
Dr. Michalski then discussed 3 separate phase III superiority trials evaluating whether the hypofractionation is equivalent or superior to conventional fractionation. The Arcangeli, IJOBP 2010 trial is an Italian randomized trial that looked at high-risk patients who received conventional fractionations versus hypofractionation. The study hypothesis was that the tumor control would be equivalent. This study indicated that hypofractionation might lead to increased 3 year freedom from biochemical relapse (87% vs 79% conventional) which on longer duration was equivalent. Fox Chase Cancer Center Study (Pollack JCO 2013) looked at both intermediate-risk and high-risk prostate cancer and randomized patients in conventional and hypofractionation. Again, results indicated equivalency with respect to biochemical recurrences. However, in the high-risk group, the study indicates statistically significant increased hazard ratio of biochemical recurrence. Additionally, patients with IPSS > 12 had higher > Grade 2 toxicity. The M.D. Anderson group also showed no differences in PSA failure.
Stereotactic body radiation therapy (SBRT) is an extreme form of hypofractionation with literature suggesting studies with 6.7-10 Gy dose/fraction with total dose of 32-50 Gy. Katz RadOnc 2013 has a largest series of patients (n = 304) with stereotactic body radiation therapy. Their study indicates favorable biochemical disease-free survival of 97% in low risk and 90.7% in intermediate risk. However, it is about 74.1% in the high-risk patients, and it is associated with up to 20% urinary toxicity and 10% rectal toxicity. Medicare claims data by Yu, et.al JCO 2014 indicate that there may be treatment cost savings with SBRT compared to IMRT ($13 645 vs $21 023). However, SBRT is associated with up to 43.9% GU toxicity at 24 months compared to 36.3% in IMRT.
Dr. Michalski concluded that with hypofractionation biochemical control does not appear to be superior. Equivalencies seen in phase III studies need longer follow up. With SBRT, there is limited comparative data to support widespread adoption of extreme hypofractionation. Early data suggests SBRT is safe with doses less than 40 Gy. Doses over 45 Gy in 5 fractions appear to be associated with an unacceptable rate of high grade GI and GU toxicities.
Presented by Jeff M. Michalski, MD, MBA, FACR, FASTRO at the 2015 Genitourinary Cancers Symposium - "Integrating Biology Into Patient-Centric Care" - February 26 - 28, 2015 - Rosen Shingle Creek - Orlando, Florida USA
Washington University, St. Louis, MO USA
Reported by Mohammed Haseebuddin, MD, medical writer for UroToday.com