Original articleImproved Quality of Life with Hyperbaric Oxygen Therapy in Patients with Persistent Pelvic Radiation-induced Toxicity
Introduction
Pelvic irradiation is an essential part of the curative treatment of pelvic malignancies, including rectal, uterine and cervical carcinoma. In spite of all the precautions and advances that are taken in the implementation of radiation therapy, the adjacent healthy tissues do get damaged. The damage mechanisms include outright cell demise or lethal cellular damage with later cell death, as well as inappropriate cell reproduction or collagen production. Injuries are divided into two basic categories: those of soft tissue (fibroblast, endothelium, muscle, nerve, etc.) and radiation osteonecrosis (bone injury). Late complications appear in 5% of the irradiated population and up to 10% when surgery and radiation are combined [1].
The urinary and gastrointestinal systems are the main sites of post-radiation pelvic complications 2, 3, 4. Radiation cystitis presents as haematuria (recurrent), urinary urgency and pain. The primary treatment modality for haemorrhagic cystitis is bladder irrigation. Oral and intravenous agents, such as aminocaproic acid, oestrogens and sodium pentosanpolysulphate, have been tried with limited success [4]. Intravesical treatments with alumsilver nitrate, prostaglandins or formalin are sometimes used if bleeding persists [5]. Finally, selective embolisation of the hypogastric arteries, urinary diversion and cystectomy may be carried out as necessary in the most severe cases. Radiation proctitis presents as irregularity of bowel function, rectal blood loss and pain [6], and primary treatment includes anti-inflammatory agents in combination with rectal steroids, rectal sucralphate, short-chain fatty acid enemas and different types of thermal therapy [7].
In hyperbaric oxygen therapy (HBOT), patients are breathing 100% oxygen at pressures greater than normal atmospheric (sea level) pressure. Instead of topical application of oxygen into tissues at levels only slightly higher than atmospheric pressure, HBOT consists of the systemic (patients are breathing the oxygen into their body) delivery of oxygen at levels two to three times higher than atmospheric pressure.
There are a number of well-established indications for HBOT, such as decompression sickness, air embolism or carbon monoxide poisoning. Since the mid-1980s, experiences dealing with the treatment of radiation-induced changes at various sites have been published [8]; encouraging results were reported in the case of radionecrosis of the mandible [9], complications of wound healing after surgery in irradiated head and neck regions [10], radiation-induced necrosis of the brain [11], as well as radiation-induced proctitis and cystitis 12, 13.
We present the results of HBOT in patients with pelvic tumours suffering radiation-induced late side-effects, such as soft tissue necrosis (skin and vagina), cystitis, proctitis and fistulas.
Section snippets
Patients' Characteristics
Between January 2001 and December 2005, 108 patients underwent pelvic surgery and adjuvant postoperative pelvic radiotherapy for pelvic malignancy at the Institute of Radiotherapy, Tel-Aviv Sourasky Medical Center, Israel.
Twelve per cent of the patients (n = 13), with a median age of 60.3 years (range 32–88 years), suffered chronic radiation-induced toxicity after pelvic radiation. This group of patients was referred for HBOT. The clinical details are provided in Table 1.
Radiotherapy
All of the patients who
Results
The median time to occurrence of late radiation-induced toxicity was 10.1 months. Six patients suffered from proctitis/cystitis, five patients suffered from longstanding vaginal ulcers and fistulas and two patients suffered longstanding skin injuries (Table 1).
For radiation-induced toxicity grading we used the National Cancer Institute CTC grading system [14] (Table 2).
We used this grading system before and after HBOT. Details are shown in Table 3.
No adverse effects of HBOT were observed. After
Discussion
Late radiation damage is often characterised histologically by a loss of parenchymal cells and an overproduction of collagen. The classic theory of late radiation injury states that it is the depletion of these parenchymal cells that leads to late injury, and that the latent period preceding the development of late effects is caused by the long cell cycle time of many of these target cells. Recent evidence has highlighted the importance of microvascular endothelial damage as a major contributor
Acknowledgement
Esther Eshkol is thanked for editorial assistance. Julia Mondry is thanked for statistical analysis.
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Cited by (35)
Sexual and urinary dysfunction after proctectomy with or without abdominoperineal resection: Incidence and treatment
2021, Seminars in Colon and Rectal SurgeryCitation Excerpt :Use of lubricants for vaginal dryness and vaginal dilators to prevent stenosis can be used,36 and topical estrogens can be applied to reduce dyspareunia.37 Hyperbaric oxygen therapy may improve cases of necrotic injuries of the perineal area due to radiotherapy.38 Psychosexual counseling might also benefit women with sexual dysfunction.
Vaginal necrosis: A rare late toxicity after radiation therapy
2021, Gynecologic OncologyCitation Excerpt :In another report of 13 women treated for a gynecologic malignancy with persistent pelvic radiation-induced toxicities, there were three cases of vaginal necrosis and two cases of vagina fistula. HBOT (2.0 ATA, median of 27 sessions) was reported to heal one case of vaginal fistula and reduce the other from a grade 4 to grade 1, and resolve two cases of vaginal necrosis and reduce the third from a grade 3 to grade 1 [63]. There have been two recent Phase III randomized controlled trials designed to test the efficacy of HBOT in the management of chronic radiation-induced gastrointestinal injury.
Current Status of Targeted Radioprotection and Radiation Injury Mitigation and Treatment Agents: A Critical Review of the Literature
2017, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :Regarding the treatment of established radiation therapy–induced normal tissue injury, a 2016 meta-analysis with 14 studies that randomized patients to HBO or no therapy concluded that the data supported HBO use for osteoradionecrosis in the head and neck and for radiation proctitis but not for radiation therapy–induced lymphedema or central or peripheral nervous injury (141, 163, 165-176). For urinary, rectal, and gynecologic toxicity after pelvic radiation therapy, retrospective data have demonstrated benefit to HBO use (177-185). These reports indicate that HBO is a useful therapy for patients with existing injury, although further study is needed to determine whether it can mitigate radiation injury.
Hyperbaric oxygen therapy for chronic bowel dysfunction after pelvic radiotherapy
2016, The Lancet OncologyHyperbaric oxygen therapy: Can it prevent irradiation-induced necrosis?
2012, Experimental NeurologyCitation Excerpt :However, the clinical finding that HBOT is effective in preventing or reducing irradiation-induced neurological side when used before the irradiation-induced side effects become manifest is very promising for future clinical studies. Since there is no convincing clinical evidence that HBOT enhances or stimulates malignant growth or neurological side effects, (Hampson and Corman, 2007a, 2007b; Safra et al., 2008) and that HBOT does not increase tissue irradiation tolerance, (Sminia et al., 2003a, 2003b) initiating HBOT before the manifestation of necrosis should not be a clinical concern. However, it is clear that the use of HBOT is expensive, time consuming and inconvenient for the patient.
The efficacy of hyperbaric oxygen therapy in the treatment of medically refractory soft tissue necrosis after penile brachytherapy
2011, BrachytherapyCitation Excerpt :When medical therapies fail, a more radical option such as partial penectomy is often suggested. Hyperbaric oxygen therapy (HBO) has a well-defined role in the treatment of late radiation toxicities such as procititis (15–23) and cystitis (21, 24, 25) and in problematic wound healing in diabetic patients and burn injuries (26, 27). Some studies have shown that HBO can effectively treat postradiation soft tissue necrosis (5, 28–30).
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Dr Gutman and Dr Safra contribute equally to the paper.