Hyperbaric oxygen therapy for cancer treatment side effects.
Subject: Hyperbaric oxygenation (Complications and side effects)
Cancer (Care and treatment)
Cancer (Methods)
Cancer (Patient outcomes)
Author: Faass, Nancy
Pub Date: 08/01/2012
Publication: Name: Townsend Letter Publisher: The Townsend Letter Group Audience: General; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 The Townsend Letter Group ISSN: 1940-5464
Issue: Date: August-Sept, 2012 Source Issue: 349-350
Product: Product Code: 8000432 Cancer Therapy NAICS Code: 621 Ambulatory Health Care Services
Geographic: Geographic Scope: Japan Geographic Code: 9JAPA Japan
Accession Number: 303012896
Full Text: Recent studies report increasingly positive outcomes for the use of hyperbaric oxygen therapy with cancer patients. Of the ten latest studies published 2006 to 2012, nine found improved outcomes. In contrast, of ten preceding studies published 2000 to 2006, only four indicated favorable outcomes.

Hemorrhagic cystitis. Research published in 2012, conducted at a university hospital in Shanghai, evaluated outcomes of hyperbaric oxygen therapy for radiation-induced hemorrhagic cystitis. Investigators compared the efficacy of hyperbaric oxygen and hyaluronic acid in a randomized controlled trial involving 36 patients. Researchers found both treatments equally effective at 6-, 12-, and 18-month follow-ups. Decrease in urinary frequency was significant for both treatments at the 6-month follow-up, but at 12 months hyperbaric therapy was no longer effective. However, improvement in pain scores remained significant in both groups at 18 months. (1)

Post-surgical brain edema. A large randomized, controlled trial (2011) at a medical school in central China evaluated the effect of hyperbaric oxygen therapy on post-surgical brain edema in 232 patients. Following tumor resection for meningiomas, patients were randomized to a treatment or control group. Although no differences were observed on the third day following surgery, at 15 days after surgery those receiving hyperbaric therapy had "obviously higher" performance and "brain edema in the operative region was definitely smaller." Based on evaluation at the six-month follow-up, researchers reported, "[HBO.sub.2] therapy is effective in reducing edema formation and neurological deficits after resection." (2)

Wound healing following throat and neck surgery. A randomized controlled study of 83 patients (2011) at a medical college near Beijing assessed the effect of hyperbaric oxygen therapy on wound healing following pharyngeal and laryngeal cancer surgery. Hyperbaric oxygen was provided to 48 patients using the following protocol: HBO pressure 2 x 10(5) Pa, 110 minutes per day for 5 to 10 days. Patients receiving hyperbaric treatment experienced significantly better healing:

* Myocutaneous or forearm flaps--27.5 days to heal compared with 45 days in control group

* Pharyngeal fistulas--8.5 days compared with 14 days in controls

* Infected wounds--5.9 days compared with 8.6 days in controls

The study concluded that "hyperbaric therapy is an effective and powerful treatment for late healed post-operative wounds in carcinoma surgery." (3)

Radiotherapy side effects with oropharyngeal and nasopharyngeal cancer. A randomized trial (2009) conducted at an urban cancer center in the Netherlands evaluated quality of life and side effects for early hyperbaric oxygen therapy following radiotherapy. Nineteen patients were randomly assigned to a protocol of HBOT: 30 sessions at 2.5 ATA (15 msw) with oxygen for 90 minutes daily, 5 days per week. Follow-up questionnaires were obtained at 2, 4, and 6 weeks and 3, 6, 12, and 18 months. Researchers concluded, "Patients randomized for hyperbaric oxygen after radiotherapy had better quality of life scores for swallowing ... xerostomia, and pain in mouth." (4)

Liver resection. A Japanese study published in 2011 evaluated the effects of hyperbaric oxygen therapy on 41 patients following liver resection, provided to minimize the requirement for perioperative blood transfusions. Patients with similar preoperative assessments were randomly assigned to hyperbaric therapy. The treatment protocol consisted of HBOT at 2.0 atm. with inhalation of 100% oxygen for a duration of 60 minutes, performed at 3, 24, and/or 48 hours after the hepatectomy. In contrast with the control group, there were no fatal complications in the hyperbaric group, and patients had better blood chemistry markers and lower incidence of hyperbilirubinemia. (5)

Lymphedema after breast cancer surgery. A randomized study conducted in London (2010) evaluated the effects of hyperbaric oxygen therapy on 58 women post-surgery for early breast cancer. Protocol utilized was 100% oxygen at 2.4 atmospheres absolute for 100 minutes on 30 occasions over 6 weeks. In the final evaluation of 46 patients, no significant differences were observed between hyperbaric-treated patients and controls in terms of limb volume. Researchers concluded, "No evidence has been found of a beneficial effect of HBO on treatment of arm." (6)

Radiation proctitis. A randomized, controlled, double-blind crossover trial (2008) evaluated the long-term risk of radiation-induced injury in conditions such as refractory radiation proctitis. Based on a design by a research center in Columbia, SC, patients were randomized to hyperbaric oxygen at 2.0 atmospheres absolute or sham treatment at 1.1 atmospheres with subsequent crossover. Outcomes were evaluated at 3 and 6 months and at years 1 through 5. "Hyperbaric oxygen therapy significantly improved the healing responses in patients with refractory radiation proctitis, generating an absolute risk reduction of 32%. ... Other medical management requirements were discontinued and advanced interventions were largely avoided. Enhanced bowel-specific quality of life resulted." (7)

A second study of radiation proctitis, using an open, randomized, parallel, prospective design (2007), was conducted at Navy SEAL Hospital in Jakarta, Indonesia. Of the 65 patients studied, 32 patients received HBOT. Researchers concluded, "The study showed that HBOT decreased acute and late side effects, and also improved the quality of life of patients with radiation proctitis. (8)

A third study of radiation-induced hemorrhagic proctitis (2006) was conducted at the University of Cincinnati to evaluate nine patients. The median age was 75 (range 66 to 83); unresolved issues included chronic bleeding, and anemia. Symptoms had not resolved, despite hospitalization, transfusions, electrocautery, or coagulation therapy. At an average of 17 months after HBOT treatment, seven patients had complete resolution of rectal bleeding, and the other two exhibited partial resolution. (9)

Recurrent high-grade gliomas. The division of hyperbaric medicine at a university hospital in southern Japan conducted a study (2007) evaluating 25 consecutive patients who had previously received radiation with chemotherapy for gliomas. In this study, patients were treated with radiotherapy immediately following HBOT (2.5 atmospheres absolute for 60 minutes). Among 14 patients with anaplastic astrocytomas, median survival time was 19 months; among the 11 with glioblastoma multiforme, median survival was 11 months. (10) [For comparative survival rates, see the article by Gorter and Peper in this issue under Outcomes: Brain Cancer.]

An open question for clinicians. What accounts for these improved outcomes? Are treatment protocols better calibrated? Is the new technology more effective? In a field in which every gain is hard won, these outcomes suggest the value of further scrutiny.

Notes

(1.) Shao Y, Lu GL, Shen ZJ. Comparison of intravesical hyaluronic acid instillation and hyperbaric oxygen in the treatment of radiation-induced hemorrhagic cystitis. BJU Int. 2012 Mar;109(5):691-4. Epub 2011 Sep 2.

(2.) Tang X, Yin X, Zhang T, Peng H. The effect of hyperbaric oxygen on clinical outcome of patients after resection of meningiomas with conspicuous peritumoral brain edema. Undersea Hyperb Med. 2011 Mar-Apr;38(2):109-15.

(3.) Jiang W, Liang D, Zhang H, Shang W, Wang P, Li W. [The effect of hyperbaric oxygen therapy on treatment of late healed wounds after pharyngeal and laryngeal surgery] [Article in Chinese]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2011 Jan;25(1):14-5, 19.

(4.) Teguh DN, Levendag PC, Noever I, et al. Early hyperbaric oxygen therapy for reducing radiotherapy side effects: early results of a randomized trial in oropharyngeal and nasopharyngeal cancer. Int J Radiat Oncol Biol Phys. 2009 Nov 1;75(3):711-6. Epub 2009 Apr 20.

(5.) Ueno S, Sakoda M, Kurahara H, et al. Safety and efficacy of early postoperative hyperbaric oxygen therapy with restriction of transfusions in patients with HCC who have undergone partial hepatectomy. Langenbecks Arch Surg. 2011 Jan;396(1):99-106. Epub 2010 Nov 11.

(6.) Gothard L, Haviland J, Bryson P, et al. Randomised phase II trial of hyperbaric oxygen therapy in patients with chronic arm lymphoedema after radiotherapy for cancer. Radiother Oncol. 2010 Oct;97(1):101-7. Epub 2010 May 31.

(7.) Clarke RE, Tenorio LM, Hussey JR, et al. Hyperbaric oxygen treatment of chronic refractory radiation proctitis: a randomized and controlled double-blind crossover trial with long-term follow-up. Int J Radiat Oncol Biol Phys. 2008 Sep 1;72(1):134-43. Epub 2008 Mar 14.

(8.) Sidik S, Hardjodisastro D, Setiabudy R, Gondowiardjo S. Does hyperbaric oxygen administration decrease side effect and improve quality of life after pelvic radiation? Acta Med Indones. 2007 Oct-Dec;39(4):169-73.

(9.) Girnius S, Cersonsky N, Gesell L, Cico S, Barrett W. Treatment of refractory radiation-induced hemorrhagic proctitis with hyperbaric oxygen therapy. Am J Clin Oncol. 2006 Dec;29(6):588-92.

(10.) Kohshi K, Yamamoto H, Nakahara A, Katoh T, Takagi M. Fractionated stereotactic radiotherapy using gamma unit after hyperbaric oxygenation on recurrent high-grade gliomas. J Neurooncol. 2007 May;82(3):297-303. Epub 2006 Nov 22.

Nancy Faass, MSW, MPH
Side Effects & Quality of Life Scores

Post-Pelvic Radiation

                                    HBOT  Control
Acute side effects                   0.7     44.1

Late side effects                  -19.6     33.6

Quality of life post treatment      19.7      4.5

Quality of life 6-month follow-up   15.2      2.5
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