Table 4.

Hypofractionated IMRT/IGRT trials

Reference	Study design	Number of patients	Fractionation (total dose/ singel dose/fractions)	EQD for tumor α/β-ratio 1.4Gy	EQD for normal tussues α/β-ratio 3Gy	IGRT	Follow-up	Acute GU toxicitiy	Late GU toxicity	Acute GI toxicity	Late GI toxicity	Therapeutic outcomes
Arcangeli, G. [14]	Phase III prospective	168 pat.	Arm I: 80Gy/2Gy/40 fractions, ArmII: 62Gy/3.1Gy/20 fractions, 4x/week.	82.1Gy	74.2Gy	daily portal imaging	70 months	-	Arm I: 16% ≥ II° GI, Arm II: 11% ≥ II° GI., at 3 years.	-	Arm I: 17% ≥ II° GI, Arm II: 14% ≥ II° GI, at 3 years.	Hypofraction-RT is not inferior to conventional RT.
Dearnaley, D. [15]	Phase III prospective	Arm I: 153 pat. 74Gy; Arm II 153 pat. 60Gy and 151 pat. 57Gy.	Arm I: 74Gy/2Gy/37 fx; Arm II: 57-60Gy/3Gy/19-20 fx.	Arm II: 73.8/77.6Gy	Arm II: 68.4/72Gy	no	50.5 months	-	At 2 years, 3 pat. (2 · 2%) in 74Gy group, 3 (2 · 2%) in 60Gy group, and 0 in 57Gy group ≥ II° GU.	-	At 2 years, 6 pat. (4 · 3%) in Arm I ≥ II° RTOG, 5 pat. (3 · 6%) in 60Gy group, 2 (1 · 4%) in 57Gy group.	-
Pollack, A. [16]	Phase III prospective	307 (ASTRO Update 2011)	Arm I: 76Gy/2Gy/28 fx; Arm II: 70.2Gy/2.7Gy/26 fx.	Arm II: 84.7Gy	Arm II: 80Gy.	no	5 years	Arm I: 54% > II°; 2% > III°; Arm II: 40% > II°; 8% > III°.	Arm I: 8.3%; Arm II: 18.3% at 5 years	Arm I: 8% ≥ II°; Arm II: 18% ≥ II°	4.5% ≥ II° GI.	biochem. recurrence 21.5% vs. 21.9% at 5 years
McDonald, A.M. [31]	Retrospective	57 PORT and 31 WPRT	70Gy/2.5Gy/ 28 fractions	80.3Gy	77Gy	CBCT daily	41 months	18/31(58%) in PORT, 28/57(49%) in WPRT ≥ II°	4/57(7%)in WPRT, 0% in PORT ≥ III° GU	7/31(23%) in PORT, 23/57 (40%) in WPRT ≥ II° GI	0% in PORT, 10/57(18%) in WPRT ≥ II° GI	-
Adkinson, J.B. [29]	Phase I prospective	53 pat.	70Gy/2.5Gy/28 fractions	80.3Gy	77Gy	yes	25.4 months	20/53(38%) ≥ II° GU	14/53(27%) ≥ II° GU	17/53(32%) ≥ II° GI	4/53(8%) ≥ II° GI	biochem. control (nadir +2) 81.2 ± 6.6%.
Jereczek-Fossa, B.A. [51]	Prospective longitudinal follow-up	337 pat. cT1-2, 40.9% low-risk; 43.3% intermed-risk; 14.2% high-risk.	70.2Gy/2.7Gy/26 frations	84.7Gy	80Gy	BAT 72%, stereo X-ray 16.4%, CBCT 11.9% pat.	19 months	35% ≥ II° GU, 6.2% ≥ III° GU.	10.4% ≥ II° GU, 1.6% ≥ III° GU.	11.3% ≥ II° GI, 1.2% ≥ III° GI.	7.5% ≥ II° GI, 1.3% ≥ III° GI.	-
Kupelian, P. A. [18]	Retrospective	770 pat, 34% low-risk, 28% intermed.-risk, 38% high-risk D'Amico criterien.	70Gy/2.5Gy/28 fractions, but mean target dose was 75.3Gy at 2.7Gy!	80.3Gy with 1.4Gy α/β-ratio (83.8Gy with 3.5Gy α/β-ratio in publication)	77Gy	IGRT with BAT tranabdominal ultrasound	45 months	33% Pat. 0°, 48% I°, 18% II°, 1% III° RTOG	90.5% pat. 0°, 4.3% I°, 5.1% II°, 0.1%(1 pat.) III° RTOG	51% pat. 0°, 40% I°, 9% II° RTOG	89.6% pat. 0°, 5.9% I°, 3.1% II°, 1.4% ≥ III° RTOG	At 5 years 94%, 83%, 72% for low-/intermed./high-risk respectively (Nadir + 2 ng/ml)
Quon, H. [33]	Prospective phase I-II	97 pat. High-risk	67.5Gy/2.7Gy/25 fractions	81.4Gy	77Gy	IGRT with gold marker	39 months median	8% pat. 0°, 50% I°, 39% II°, 4% III° CTCAE	82% pat. 0°, 9% I°, 5% II°, 3% III°, 1% IV°.	4% pat. 0°, 59% I°, 37% II°	54% pat. 0°, 40% I°, and 7% II°	4 year bFFS 90.5%.
Martin, J. [40]	Prospective phase I-II	92 pat., mainly intermed./low risk	60Gy/3Gy/20 fractions	77.6Gy	72Gy	IGRT with gold marker	38 months median	32% pat. 0°, 43% I°, 25% II° RTOG	90% pat. 0°, 7% I°, 3% II° RTOG	66% pat. 0°, 22% I°, 11% II°, 1% IV° RTOG	93% pat. 0°, 2% I°, 4% II° RTOG	3 year biochemical control 76%.