Table 2.

Literature review of dose-volume relationship for late rectal bleeding in radiotherapy of prostate cancer

Author	Patients	Follow up	Persription Doses	Treatment technique	Classification of toxicity	Endpoint	Events	Dosimetric parameter	Rectum delineation	Results
Hartford 1996 [29]	41	Minimum 4 years	50.4Gy 25.2CGE	4 field Perineal proton boost	RTOG	≥ Grad I rectal bleeding	14	DWH ant. RW	From superior limit of anus to 2 cm superior to prostate	Cut-off: Continuously between 60Gy to 70% and 75Gy to 30%
Boersma 1998 [30]	130	Median 24 months	70 – 76Gy	3 field 3D-CRT	SOMA/LENT and RTOG/EORTC	≥ Grad III rectal bleeding	2	DWH	15 mm caudal to the apex of the prostate to boarder to sigmoid	Cut-off: ≥ 65Gy to >40% ≥ 70Gy to >30% ≥ 75Gy to >5% (no correlation for grade I/II rectal bleeding)
Storey 2000 [31]	189	Minimum 2 years	70Gy 78Gy	4 field box 4 field box, 6 field 3D-CRT boost	Modified RTOG	≥ Grad II late rectal toxicity	28	DVH	Rectum included within 11 cm of initial APPA field	For patients treated to 78Gy: Cut-off: ≥ 70Gy to >25%
Jackson 2001 [32]	451	Minimum 30 months	70.2Gy 75.6Gy	6 field arrangement 3D-CRT	RTOG	≥ Grad III late rectal bleeding	49	DWH	below sigmoid flexure to above anal verge	Correlation with: # area under the average percent volume DWH # Exposure to ~62% and to ~102% of prescription dose
Fenwick 2001 [33]	79	Minimum 2 years	60 – 64Gy	3 field • 3D-CRT • Conventional	RTOG	Grade I – III rectal bleeding	?	DSH	up to level of rectosigmoid junction	Correlation with: % of RS exposed to > 57Gy
Wachter 2001 [34]	109	Median 30 months	66Gy	4 field 3D-CRT	EORTC/RTOG	Grade II rectal bleeding	15	DVH	From lower to upper boarder of 4 field	Cut-off: ≥ 60Gy to >57%
Kupelian 2002 [35]	128	Median 24 months	78Gy 70Gy	4 field (42Gy) 6 field boost (36Gy): 3D-CRT IMRT (SD 2.5Gy)	RTOG	Grade I – III rectal bleeding	9	DVH	From 1 cm above to 1 cm below the target	Cut-off: Absolute rectal volume: ≥ 78Gy to >15 cm3
Huang 2002 [36]	163	Median 62 months	74 – 78Gy	4 field conventional (46Gy) 6 field boost 3D-CRT	Modified RTOG	≥ Grad II late rectal toxicity	38	DVH	11 cm in length starting at 2 cm below the inferiormost aspect of the ischial tuberosities	Cut-off: V60 below 40% V70 below 25% V75.6 below 15% V78 below 5%
Fiorino 2003 [37]	245	Median 2 years	70 – 78Gy	3 to 4 field 3D-CRT	Modified RTOG	Grade II – III rectal bleeding	23	DVH	Above anal verge to sigmoid	Cut-off: V50 below 60–65% V60 below 50–55% V70 below 25–30%
Greco 2003 [38]	135	Median 28 months	76Gy	6 field 3D-CRT	RTOG	≥ Grad II late rectal toxicity	24	DVH	from just below the sigmoid flexure to just above the anal verge	Cut-off: V40 below 60% V50 below 50% V60 below 25% V72 below 15% V76 below 5%
Akimoto 2004 [39]	52	Median 31 months	69Gy SD 3Gy	unblocked 4 field technique to the prostate	RTOG	≥ Grad II late rectal toxicity	13	DVH	above anal verge to point at which it turns into the sigmoid colon	Cut-off (equivalent 83Gy prescription dose): V30 (V24.9) to ≥ 60% V50 (V41.5) to ≥ 40% V80 (V66.4) to ≥ 40% V90 (V74.7) to ≥ 15%
Koper 2004 [40]	266	Minimum 2 years	66Gy	Conventional (n = 125) 3 field 3D-CRT (n = 123)	RTOG	≥ Grad I late rectal toxicity	57% 47%	DVH (separately for proximal, middle and distal part of rectum)	length of intestinal structures was limited to cranial and caudal field borders	Correlation with: Distal rectal volume exposed to ≥ 90% tumor dose
Lee 2005 [41]	212	Median 86 months 35 months	66 70 – 74Gy	Conventional 3D-CRT	Modified RTOG/Lent and RTOG	≥ Grad II late rectal toxicity	34	DVH	?	Cut-offs: ≥ 60Gy to >51.5% ≥ 70Gy to >41.5%
Vargas 2005 [11]	331	Median 19 months	70.2Gy to 79.2Gy	Adaptive 3D-CRT	CTC 2.0	≥ Grad II late rectal toxicity	43	DVH, DWH	from the anal verge or ischial tuberosities (whichever was higher) to the sacroiliac joints or rectosigmoid junction (whichever was lower)	Association with: DWH: V50, V60, V66.6, V70, V72 DVH V60–V72
Peeters 2006 [42]	614	Median: 44 months	68Gy vs 78Gy	3D-CRT	Adapted RTOG/EORTC	≥ Grad II rectal bleeding	31	DWH	anorectal, rectal, and anal wall dose volume histogram	Correlation with: anorectal V55–V65