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.