No need to go through 38-44 treatments with IMRT anymore

There have been several hypofractionation trials maturing in the last couple of years. With minor exception, they all tell the same story: external beam radiation therapy (EBRT) can be completed in less time without loss of efficacy or increase in toxicity. Hypofractionation means completing EBRT in fewer treatments or fractions using higher doses per fraction.

Catton et al. now report the 5-year outcomes of a multi-institutional, multinational (27 centers in Canada, Australia and France) randomized clinical trial (called the “PROFIT” trial) among 1,206 intermediate-risk patients treated from 2006 to 2011. All patients received radiation doses now considered curative: 78 Gy in 39 fractions (conventional fractionation - CFN) or 60 Gy in 20 fractions (hypofractionation - HFN). The doses are biologically equivalent for cancer control, no ADT was allowed. After median follow-up of 6.0 years:

• 5-year freedom from biochemical or clinical failure was 85% in both groups
• Acute urinary toxicity, grade 2: 27% in both groups; grade 3:4% in both groups 
• Acute rectal toxicity, grade 2: 16% for HFN*, 10% for CFN; grade 3: <1% in both groups 
• Late term urinary toxicity, grade 2: 20% for HFN, 19% for CFN; grade 3+:2% for HFN, 3% for CFN Late term rectal toxicity, grade 2: 7% for HFN, 11% for CFN*; grade 3+: 1% for HFN, 3% for CFN 

*Difference between arms was statistically significant, but not meaningful

The table below summarizes the key oncological and late-term toxicity outcomes of the various hypofractionation trials:

Randomized Clinical Trial	Risk Groups	Fractionation	5-yr bPFS	Urinary toxicity Grade 2+	Rectal toxicity Grade 2+	Ref.
PROFIT	100% intermediate	60 Gy/20fx 78 Gy/39fx	85% 85%	22% 21%	8% 14%	1
Fox Chase	67% Intermediate, 33% high	70.2 Gy/26fx 76 Gy/38fx	77% 79%	22% 13%	18% 23%	2
CHHiP	73% intermediate, 15% low, 12% high	60 Gy/20fx 74 Gy/37fx	91% 88%	12% 9%	12% 14%	3
MD Anderson	71% intermediate, 28% low, 1% high	72 Gy/30fx 75.6 Gy/42fx	96% 92%	16% 17%	10% 5%	4
RTOG 0415	100% low risk	70 Gy/28fx 73.8 Gy/41fx	94% 92%	30% 23%	22% 14%	5
HYPRO	>70% high, <30% intermediate	64.6 Gy/19fx 78 Gy/39fx	81% 77%	41% 39%	22% 18%	6, 7
Cleveland Clinic	49% low, 51% intermediate	70 Gy/28fx 78 Gy/39fx	94% 88%	1% 2%	5% 12%	8

Hypofractionation has demonstrated equal efficacy and side effects compared to conventional fractionation. Hypofractionation requires greater care on the part of the radiation oncologist. He must use advanced image guidance with placement of fiducials or radio transponders and localization with cone beam CT, set tighter margins, lower dose constraints for organs at risk, assure adequate bladder filling and lack of bowel distension at each treatment, use fused MRI/CT images if possible, and have very rapid linacs to minimize intrafractional motion. With this much cumulative level 1 evidence, it is hard to justify the use of conventionally fractionated EBRT anymore. Patients should not have to endure 38 or more treatments, and pay the extra cost of that, even if insurance or Medicare is willing to pay. Patients should shop for radiation oncologists who have experience with hypofractionation, or preferably, with extreme hypofractionation (SBRT).