Table 3 Whole bowel and small bowel studies – significant findings and quality assessment

Deville [7]

Intestinal cavity

Intestinal cavity below L4–5

RTOG Gr ≥ 1

5/36 (14%)

Toxicity associated with total volume & V20. No constraints specified.

1,7

(n/a: 2–6)

None

Mouttet-Audouard [6]

“Small bowel” [outlined as abdominal cavity hence included in this section]

Entire abdominal cavity including all possible organ locations to iliac crests or D12/L1

CTCAE v4.0 Gr1–3 –diarrhoea or “whole digestive toxicity” (diarrhoea, gastritis, bleeding, pain, incontinence)

8/37 (21.6%)

17/37 (46%)

Larger volumes of bowel receiving 10–30Gy associated with diarrhoea & whole digestive toxicity. (No constraints specified)

“Whole digestive toxicity” associated with many parameters including D20%-D95%.

1, 7

(n/a 2–6)

2

Green [36]

Intestinal cavity

Not stated

CTCAE v4.0

9 (12%)

No dose-volume relationship found.

1 (n/a 2–6)

2

Deville [31]

Intestinal cavity

Large & small bowel below L4–5

RTOG Gr ≥ 2

2/30 (6%)

No dose-volume relationship found

1,7

(n/a 2–6)

None

Isohashi [10]

Peritoneal cavity

Volume surrounding small bowel loops to edge of peritoneum excluding bladder & rectum

RTOG/EORTC Gr ≥ 2

16/97 (16.5%)

No dose-volume relationship found

1,7

(n/a 2–6)

2

Poorvu [16]

1. Peritoneum

2. Peritoneum + Colon

1. Possible location of small bowel excluding solid organs & retroperitoneal structures.

2. Peritoneum (as above) plus asc & desc colon

CTCAE v4.0 Gr > 3

3/46 (6.5%)

No dose-volume relationship found

1, 7

(n/a 2–6)

2

Guerrero-Urbano [8]

Bowel loops

Loops from recto-sigmoid junction to 2 cm above PTV

RTOG Gr ≥ 2 diarrhoea; LENT-SOMA consistency & frequency- worst grade

21/79 (26%) RTOG diarrhoea; ≥gr2 6/79 (7.6%)

V40, V45, V60 and bowel volume of > 450 cc had both higher RTOG & LENTSOMA diarrhoea.

Constraints suggested: V40 < 124 cc, V45 < 71 cc, V60 < 0.5 cc for RTOG<gr 2

1,7

(n/a 2–3)

1

McDonald [9]

Bowel loops

Loops from recto-sigmoid junction to 2 cm above PTV

RTOG Gr ≥ 1

7/47 (14.9%) gr1; 3/47 (6.4%) gr2

Constraints for < 25% ≥ gr2 toxicity: V30 < 178 cc;V35 < 163 cc;V40 < 151 cc;V45 < 139c; V50 < 127 cc; V55 < 115 cc; V60 < 98 cc V65 < 40 cc

1,4,7

(n/a 2–3)

2

Chopra [11]

Small bowel

2 cm above target, individual small bowel loops (unclear how differentiated from large bowel)

CTCAE v3.0 Gr3+

9/71 (12.6%)

V15 associated with ≥gr3 toxicity. Recommend V15 < 275 cc, V30 < 190 cc, V40 < 150 cc reduces Gr3 toxicity from 23.6 to 5.6%.

1, 4, 6

(n/a 2,3)

2

Isohashi [10]

Small bowel

Bowel loops remaining after exclusion of large bowel loops

RTOG/EORTC Gr ≥ 2

16/97 (16.5%)

V40 best predictor of late toxicity; Recommend V40 < 340 ml to reduce toxicity from 46.2 to 8.7%

1,4,6,7

(n/a 2,3)

2

Lind [12]

Small bowel

All visible small bowel in small pelvic cavity to caudal part of sacroiliac joints

Defecation into clothing without warning > 1 in last 6 months

63/519 (12.1%)

Mean dose>50Gy to small bowel or sigmoid or anal sphincter region associated with symptom (findings for individual organs not clarified)

1, 7 (n/a 2,3)

1,2,3

Adkison [34]

Small bowel

Not clearly defined

CTCAE v3.0 Gr1 and Gr2

Gr1 16/53 (30%); Gr2 4/53 (8%)

No dose-volume relationship with V30-V60 small bowel

1

(n/a 2–6)

None

Fokdal [14]

Small bowel

Opacified & unopacified small intestine loops (outer contour & contents) from 1st slice to minor pelvis

LENT-SOMA G1–4

Symptom specific

No dose-volume relationship found

1,7

(n/a 2–6)

1,2,3

Fonteyne [17]

Small bowel

Not clearly defined

RTOG and “RILIT” Gr1 & Gr2

Gr1 112/241 (46%), Gr2 32/241(13%)

No dose-volume relationship found

1,

(n/a 2–6)

1,2

Poorvu [16]

Small bowel

Opacified & non-opacified small bowel loops

CTCAE v4.0 Gr3+

3/46 (6.5%)

No dose-volume relationship found

1,7

(n/a 2–6)

2

Huang [15]

Duodenum

Duodenal bulb to ligament of Treitz

CTCAE v4.0 Gr ≥ 3

8/46 (17.4%)

With a V25 > 45% toxicity rates increase from 8 to 48%

1,4,6,7

(n/a 2,3)

2

Kelly [13]

Duodenum

Gastric pylorus until end of duodenum 3 cm past midline

CTCAE v4.0 Gr ≥ 2

20/106 (18.9%)

With a V55 > 1 cc toxicity rates increase from 9 to 47%

1,4,6,7

(n/a 2,3)

2

Verma [30]

Duodenum

From gastric outlet through transverse portion of duodenum (ascending portion excluded)

RTOG, all grades

9 /105 (8.6%)

With a V55 > 15 cc toxicity rates increase from 7.4 to 48.6%

1,4,6,7

(n/a 2,3)

2

Poorvu [16]

Duodenal segments

D1 segment: bulblike shape & origin beyond gastric pylorus. Transitions between 2nd & 3rd segments was lateral border of IVC; Between 3rd & 4th was medial border of aorta

CTCAE v4.0 Gr ≥ 3

3/46 (6.5%)

No dose-volume relationship found with duodenum

1,7

(n/a 2–6)

2