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Table 4 Large Bowel studies - details and quality assessment

From: A systematic review of dose-volume predictors and constraints for late bowel toxicity following pelvic radiotherapy

       Quality Assessment
Author OAR studied OAR defined Toxicity definition Pts with toxicity Significant findings Statistical considerations met (1–7) Endpoint considerations met (1–3)
Chopra [11] Large bowel 2 cm above target, individual loops of large bowel (unclear how differentiated from small bowel) CTCAE v3.0 Gr ≥ 3 9/71 (12.6%) V15 associated with ≥gr 3 toxicity.
Constraints: V15 < 250 cc, V30 < 100 cc, V40 < 90 cc to reduce toxicity from 26.7 to 5.4%
1, 4, 6
(n/a 2,3)
2
Isohashi [10] Large bowel Single loop continuing from end of sigmoid to ascending colon RTOG/EORTC, Gr ≥ 2 16/97 (16.5%) No constraint found for large bowel 1,7
(n/a 2–6)
2
Fonteyne [17] Sigmoid colon Where rectum sweeps anteriorly to one slice above aortic bifurcation RTOG and “RILIT” Gr 1 and 2 Gr 1112/241 (46%), Gr 2 32/241 (13%). V40 associated with gr1 diarrhoea & blood loss.
Constraints: V40 < 10%, V30 < 16% to avoid gr1–2 diarrhoea
1, 7
(n/a 3)
1,2
Mouttet-Audouard [6] Sigmoid colon Anterior curvature of sigmoid colon to anterior abdominal wall CTCAE v4.0
Gr1–3 diarrhoea and “whole digestive toxicity”
8/37 (21.6%) diarrhoea; 17/37
(46%) (whole tox)
‘Whole late digestive toxicity’ associated with V30–40. No specific constraints. 1,7
(n/a 2–6)
1,2
Lind [12] Sigmoid colon From where rectum deviates from its mid- position to where it turns cranially in left abdomen connecting to colon descendens 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 2–6)
1,2,3
al-Abany [18] Anal sphincter region Caudal 3 cm of the rectum from anal verge (including filling) Own questionnaire; Faecal leakage >2X/week 9/65 (13.8%) faecal leakage Increased risk with mean dose of 45-55Gy.
Constraints: V35 < 60%, V40 < 40% associated with no risk of faecal leakage.
1, 7
(n/a 2,3)
1,2,3
Alsadius [19] Anal sphincter region Caudal part of large bowel, from end of rectal ampulla where bowel no longer had visible content or air. Own questionnaire;
Faecal leakage >once per month
51/403 (12.7%) faecal leakage Dmean<40Gy reduces risk from 17 to 4%. 1,2,4,7
(n/a 3)
1,2,3
Fokdal [14] Anal canal Outer contour of the structure extending from anal verge 2 cm cranially LENT SOMA score Urge: 27/71 (38%); Incontinence: 21/71 (30%) Urgency related to Dmed> 33.8: increases toxicity 31 to 47%
Incontinence related to Dmax> 53.8 increases 14 to 44%
1,2,4,5,7
(n/a 3)
1,2,3
Vordermark [23] Anal canal Anal verge to the section below visible rectal lumen, corresponding to the upper border of the
levator ani muscle
“Solid soiling” (Severe incontinence)
Own continence questionnaire
6/44 (14%) Severe incontinence
- associated with Dmin (23.1Gy)
- related to portals extending 2 mm below ischial tuberosities (compared with 5 mm above)
1, 7
(n/a 2–3)
1,2,3
Koper [25] Anal canal Caudal 3 cm of the intestine RTOG gr1 + 2;
Plus symptom questionnaire.
141/248 (57%) D90% (=54.9Gy) to associated with ≥ gr1 rectal toxicity 1, 7
(n/a 2–6)
2,3
Taussky [37] Anal canal Most distal 2-3 cm of rectum 10 questions from UCLA-PCI, FACT-P & EORTC QLQ -PR25 Unclear no relation with anal canal DVH found 7
(N/a: 2–3)
3
Buettner [20] Anal canal Caudal 3 cm of rectum Common grading scheme; subjective sphincter control at highest grade 57/388 (14.7%) DSH data: Toxicity correlated with dose to anal surface: lateral extent 53Gy > 56%.
DVH data: Dmean 47Gy to anal sphincter volume correlated with sphincter toxicity. Constraints: Dmean<30Gy.NTCP modeling to LKB model TD50 = 120, m = 0.42.
1,3,6,7
(n/a 2)
1,2,3
Peeters [21] Anal wall Wall of caudal 3 cm of anorectum (method described) RTOG/EORTC ≥ gr 2 and ≥ gr 3 Plus incontinence pad use>2x/wk. ≥gr 2165/641 (25.7%) ≥ gr 3 27/641 4.2% Dmean increase from 19Gy to 52Gy increased gr2 toxicity: 16 to 31%.
V65 & Dmean most significant for incontinence. Dmean increase by 33Gy increased incontinence by 12%
1,2,4,6,7
(n/a 3)
1,2
Mavroidis [27] Anal sphincter region Musculaure layer around the rectal aperture, 3 cm caudal from anal verge Own questionnaire faecal leakage 19/65 (29%); blood/mucus 22/65 (34%) Relative seriality NTCP model of anal sphincter for incontinence, blood/mucus. Parameters for incontinence: D50 = 70.2Gy, γ = 1.22, s = 0.35. Parameters for blood/mucus: D50 = 74.0Gy, γ = 0.75, s ≈ 0 1, 3, 5, 6, 7
(n/a 2)
1,3
Peeters [28] Anal canal wall Wall of caudal 3 cm of anorectum (method described) Incontinence requiring pad
use>2x/wk.;
32/368 (7%) NTCP LKB model of incontinence with anal wall dose. Parameters found were n = 7.48; TD50 = 105; m = 0.46 1,3,4,5,6,7
(n/a: 2)
1,3
Smeenk [26] Anal sphincter muscles Individual muscles defined (Internal anal sphincter (IAS), external anal sphincter (EAS), puborectalis & levator ani) Frequency, Urgency, Incontinence 21/48 (44%) For complication <5% Dmean<30Gy to IAS; <10Gy to EAS, < 50Gy to puborectalis, <40Gy to levator ani 1, 4,5
(n/a 2)
1,2,3
Smeenk [22] Anal wall Continuation of rectal wall from anal verge to slice below lowest slice with a rectal balloon Frequency, urgency, incontinence 39% frequency, 31% urgency, 31% incontinence For urgency:
Anal wall Dmean<38Gy risk < 15%, >38Gy risk is 62%
1,4,7
(n/a 2,3,5,6)
1,3
Lind [12] Anal sphincter region Inner muscle layer of the sphincter up to anal verge 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 this symptom
(findings for individual organs not clarified)
1, 7 (n/a 2,3) 1,2,3
Yeoh [24] Anal wall From anorectal junction (not clearly defined) LENT-SOMA total score 72% Anal wall V40 > 65% associated with chronic toxicity. 1,5 (n/a 2,3) 2,3
Thor [29] Anal sphincter Anal canal, inner and outer sphincter (not clearly defined) Questionnaire of 19 questions in 4 domains: pain urgency, mucus & incontinence. Specific to each of 19 question 5 LKB models proposed for anal sphincter doses.
Low anal sphincter dose associated with faecal leakage and pain. High anal sphincter dose associated with leakage.
1,3,6 (n/a 2) 1,2,3
Ebert [35] Anal Canal Caudal 3 cm of anorectum LENT-SOMA – 8 symptoms Specific to each symptom Bleeding associated with >40Gy, proctitis with 36-63Gy, frequency with 8-85Gy, urgency and tenesmus with 5-34Gy to anal canal. 1,5,7 (n/a 2) 1,2,3
  1. Abbreviations: Pts Patients, OAR Organs at risk, RT Radiotherapy, Gr Grade, CTCAE Common terminology criteria for adverse events, RTOG Radiation therapy oncology group, LENT-SOMA Late Effects of Normal Tissue – Subjective Objective Management Analytical, RILIT Radiation induced late intestinal toxicity, EORTC European Organisation for Research and Treatment of Cancer, Vx Volume receiving x Gy, AUC Area under curve, Dmean Mean dose, Dmax Maximal dose, DVH Dose volume histogram, DSH Dose surface histogram, NTCP Normal Tissue Complication Probability, LKB Lyman Kutcher Burman