Hyperbaric oxygen therapy as a complementary treatment for radiation proctitis: Useless or useful? – A literature review

Table 2 Summary of the case-series or clinical trials described in the literature regarding the use of hyperbaric oxygen therapy in the treatment of radiation proctitis

Ref.	Study design	Patients (n)	RP stages/grades, patients (n)	Other (previous) treatments (%)	HBOT protocol	Nº sessions	Overall response rate (%)	Complete response (%)	Follow-up period (mo)
Bouachour et al[45], 1990	Retrospective	8	NA	100%	2.5 ATA, 90 min, twice daily (4 wk)-> Once daily	80 ± 10	87.5%	75%	[4-20]
Feldmeier et al[46], 1996	Retrospective	7	RTOG/EORTC[36]: 4	28.6%	2.4 ATA, 90 min, 5 ×/wk	24 [3-50]	57%	57%	NA
Warren et al[47], 1997	Retrospective	14	Bleeding (n = 11); Diarrhoea (n = 5); Rectal pain (n = 4); Tenesmus (n = 2)	78.6%	2.0 ATA, 120 min, 5-6/wk; 2.35 ATA, 90 min, 5 ×/wk	39 [20-72]	64.3%	57.1%	14.6 [2-35]
Woo et al[48], 1997	Retrospective	18	Bleeding (n = 17); Diarrhoea (n = 8); Rectal pain (n = 4); Incontinence (n = 4)	77.7%	2.0 ATA, 105 min, 6 ×/wk	24 [40]	55.5%; Incontinence 75%; Diarrhoea 50%; Rectal pain 50%; Haemorrhage 41.2%	11.1%; 50%; 25%; 25%; 23.5%	14 [65]
Bredfeldt and Hampson[49], 1998	Retrospective	19	NA	NA	2.36 ATA, 90 min, 5 ×/wk	30	84%	47%	NA
Ugheoke et al[50], 1998	Retrospective	8	NA	NA	2.5 ATA, 90 min, 5 ×/wk	28 [20-40]	62.5%	NA	NA
Carl et al[51], 1998	Retrospective	2	Bleeding (n = 1); Rectal pain (n = 1)	NA	2.4 ATA, 90 min, 5 ×/wk	38, 40	50%	50%	NA
Gouëllo et al[52], 1999	Retrospective	36	LENT-SOMA: Grade 1 (n = 1); Grade 2 (n = 11); Grade 3 (n = 16); Grade 4 (n = 8)	NA	2.5 ATA, 90 min, 5 ×/wk	67 (mean)	66%	25%	52
Kitta et al[53], 2000	Retrospective	4	Bleeding (n = 3); Rectal pain (n = 1)	100%	2.0 ATA, 60 min, 5 ×/wk	37.5 [30-60]	75%	25%	NA
Bem et al[54], 2000	Retrospective	2	Dean and Taylor[28]: I-II	100%	2.4 ATA, 90 min, 5 ×/wk	60, 60	100%	100%	[3-48]
Roque et al[55], 2001	Retrospective	6	NA	NA	2.5 ATA, 90 min, 5 ×/wk	37 [20-60]	85%	NA	NA
Mayer et al[56], 2001	Retrospective	10	RTOG/EORTC[36]: Grade 2 (n = 4); Grade 3 (n = 6)	Majority (% not stated)	2.2-2.4 ATA, 60 min, 7 ×/wk	28 [13-60]	90%	30%	15.3 [7.5-26.9]
Boyle et al[57], 2002	Retrospective	19	NA	NA	2.0 ATA, 120 min, 5 ×/wk	59 [27-80]	68%	NA	NA
Jones et al[58], 2006	Retrospective	10	LENT-SOMA: Grade 2 (n = 7); Grade 3 (n = 3)	100%	2.0-2.5, 90 min, 5 ×/wk	40 [36-41]	77%; Haemorrhage 88.8%; Diarrhoea 80%; Rectal pain 80%	44.4%; 60%; 20%	25 [6-43]
Dall’Era et al[59], 2006	Retrospective	27	RTOG/EORTC[36]: 3-4	100%	2.4 ATA, 90 min, 7-7 ×/wk	36 [29-60]	66.6%; Haemorrhage 76%; Rectal pain 75%; Faecal urgency 75%; Rectal ulcer 50%	37%; 48%; 0%; 50%; 21%	13 [1-60]
Fink et al[60], 2006	Retrospective	4	NA	100%	2.4 ATA, 90 min, 5 ×/wk	31 [28-37]	75%	25%	33
Girnius et al[61], 2006	Retrospective	9	Bleeding Scale for Radiation-Induced Haemorrhagic Proctitis[33]: Grade 2 (n = 1); Grade 3 (n = 3); Grade 4 (n = 5)	100%	2.5 ATA, 90 min, 5 ×/wk	58 [22-80	100%	77.7%	17 [1-77]
Marshall et al[16], 2007	Retrospective	65 (15 with lesions beyond the rectum)	Bleeding (n = 54); Diarrhoea (n = 25); Rectal pain (n = 25); Tenesmus, urgency, incontinence (n = 13); Malnutrition, weight loss (n = 7); Bloating, cramping (n = 6); Nausea, emesis (n = 5); Fistulae (n = 2); Total parenteral nutrition (n = 2)	65%	2.36 ATA, 90 min, 5 ×/wk	30-> If partial response-> 60	68% (all patients); 65% (rectum); 73% (proximal sites); Haemorrhage 70%; Other symptoms 58% (including pain relief, improved nutritional status and intestinal transit, closure of fistulae)	43%; 39%; 60%; 75%; 33%	23 [1-70]
Sidik et al[62,63], 2007	Prospective, randomised clinical trial	HBOT 32; Comparator33	LENT-SOMA: HBOT, mean 7.7 ± 2.0; Control, mean 6.8 ± 2.3. Karnofsky scale: HBOT, mean 73.8 ± 6; Control, mean 74.6 ± 8.3	NA	HBOT, Protocol not reported vs Comparator described as “symptomatic treatment”	HBOT, Minimum 18 sessions	Outcomes poorly reported (losses to follow-up, not all patient data provided)	NA	6
Safra et al[64], 2008	Retrospective	6	NCI CTCAE[37]: Mean 3.3 [2-4]	100%	2.0 ATA, 90 min, 7 ×/wk	27 [16-40]. Not only RP	100%	16.7%	NA
Clarke et al[65], 2008	Randomised, double-blind, sham-controlled, crossover allowed (“HORTIS”)	HBOT 76; Comparator74	LENT-SOMA: HBOT, mean 12.55; Sham, mean 12.84	100%	HBOT, 2.0 ATA, 90 min, 5 ×/wk vs Sham treatment 1.34-> 1.1 ATA O2 21%, 90 min, 5 ×/wk	30-> 40	HBOT: 88.9%. Improved bowel-specific and bowel bother and function QoL scores (before crossover) vs Sham treatment: 62.5%	HBOT: 7.9% vs Sham: 0%	25 [12-60]
Alvaro-Villegas et al[66], 2011	Prospective, non-randomised clinical trial	HBOT 17; Comparator14	LENT-SOMA: HBOT, 12.1 ± 2.9; APC, 13.3 ± 2.9	NA	HBOT 2.0-2.5 ATA, 90 min, 5 ×/wk vs Non-contact APC, 2.3 mm diameter catheter, 1.6 L/min flow rate at 60 W, mean 3 ± 1 (SD) sessions	HBOT, 35 ± 5 vs APC, 3 ± 1	HBOT: 82% vs APC: 87%	NA	3
Oliai et al[67], 2012	Retrospective	4	LENT-SOMA: Mean 0.66 [0.36-0.93]. Severity of rectal bleeding: Persistent (n = 3), Occasional (n = 1)	100%	2.0 ATA, 90-105 min, 5 ×/wk	37.5 [30-40]	75%	50%	NA
Carvalho et al[68], 2014	Retrospective	30	NA	NA	2.5 ATA, 100 min, 5 ×/wk	66 [38-80]	96.7%	73.3%	NA
Tahir et al[69], 2015	Retrospective	59	NA	NA	2.4 ATA, 70 min, 7x/wk	NA	95%	51%	Major response 15 [2-76]. Minor response 20 [1-84]
Glover et al[70], 2016	Randomised, double-blind, sham-controlled phase 3 clinical trial (“HOT2”)	Ratio 2:1; HBOT 55; Comparator29	LENT-SOMA: Grade 2; Grade 1 with intermittent symptoms. IBDQ bowel function component (n/IQR): HBOT 48 (42-52); Sham 51 (44-59). IBDQ rectal bleeding (n/IQR): HBOT 3 (2-4); Sham 3 (2-4). NCI CTCAE[64]: Grade 1-3, 46 (55%). EORTC QLQ-CR38 Question 59: Grade 1-3, 47 (59%)	100%	HBOT 2.4 ATA, 90 min, 5 ×/wk vs Sham treatment 1.34 ATA O2 21%, 90 min, 5 ×/wk	40 (89% of patients) < 38 (11% of patients)	HBOT: IBDQ bowel function component (n/IQR): Δ 3.5 (-3-11). IBDQ rectal bleeding (n/IQR): Δ 3 (1-3) vs Sham treatment: IBDQ bowel function component (n/IQR): Δ 4 (-6-9); IBDQ rectal bleeding (n/IQR): Δ 1 (1-2)	NA	13.2 [12.4-14.2]
Yoshimizu et al[71], 2017	Retrospective	5	Sherman[27]: Grade II (n = 3); Grade III (n = 1); Grade IV (n = 1)	NA	2.5 ATA, 60 min, 5 ×/wk	76 [40-100]	100%	20%	NA

APC: Argon plasma coagulation; ATA: Atmosphere absolute; HBOT: Hyperbaric oxygen therapy; IBDQ: Inflammatory Bowel Disease Questionnaire; IQR: Interquartile range; min, minute; NA: Not available or not applicable; NCI CTCAE: National Cancer Institute Common Terminology Criteria for Adverse Events; O₂: Oxygen; QoL: Quality of life; RP: Radiation proctitis; SD: Standard deviation; Δ: Median change from baseline to 12 mo.