International Journal of Radiation Oncology*Biology*Physics
Clinical investigationThe efficacy of hyperbaric oxygen therapy in the treatment of radiation-induced late side effects
Introduction
Radiation is a therapeutic modality commonly used in the management of cancer. Although most patients experience some acute side effects, it is a rare and serious event when severe late side effects develop (1). Acute side effects during or in the immediate postirradiation period are mostly self-limiting or amenable to simple medical management. On the other hand, late side effects, occurring after this period, are slower to heal and may lead to chronic debility. For example, osteoradionecrosis is one serious late effect present in the minority of head-and-neck cancer patients treated with radiation. Although 85% of cases resolve with conservative management, the remainder become refractory and can progress to involve a more extensive area of bony and soft tissue (2).
In recent years, our understanding of the underlying mechanisms of late radiation-induced side effects has increased 3, 4, 5, 6, 7. Although cellular depletion and tissue devascularization were originally thought of as being the predominant pathologic basis for these side effects (8), they represent merely a histopathologic marker for a far more complex and clinically diverse problem (9). Both patient- and treatment-related factors seem to contribute to this process. It is now known that the size of the radiation treatment field, dose per treatment, and total dose are important factors that are associated with the occurrence of radiation-related side effects 10, 11. Also different tissues have various levels of tolerance to radiation damage, possibly because of the structural organization of that tissue. More specifically, tissues whose functional subunits are arranged in series tend to display a lower degree of radiation tolerance than those with parallel arrangement, because serially arranged subunits depend on the well-being of all subunits before and after them (12). Patients' comorbid disease may also affect the ability to repair tissue damage caused by therapeutic radiation. Anecdotal data suggest a possible correlation between connective tissue diseases and increased radiosensitivity (13), though clinical evidence thus far has not conclusively confirmed any such relationship (14). Recent evidence suggests a role of an impaired genomic repair capacity of radiation-induced DNA damage in some patients with severe radiation-related late side effects (15).
Hyperbaric oxygen therapy (HBOT) has been used in the past to assist in the repair of radiation-induced damage (8). Besides improving temporarily the oxygenation of tissue and helping eradicate anaerobic bacteria, it is thought that high oxygen tension promotes neovascularization in damaged tissues of radiation-treated patients (16). Studies have shown that HBOT effectively treats irradiated soft tissue necrosis 17, 18 and has also been used empirically to treat mandibular osteoradionecrosis, radiation cystitis, radiation proctitis, and other radiation side effects 19, 20, 21, 22, 23, 24, 25, 26, 27, 28. HBOT has also been used for the other areas of problematic wound healing, such as ulcers in chronic diabetes and burns, besides its obvious role in the treatment of decompression disease 29, 30.
Certain chemotherapies sensitize cells to effects of radiation through various mechanisms 31, 32, 33. Combination chemoradiotherapy plays a valuable role in tumor downstaging, increasing surgical resectability, and potentially improving long-term prognosis 34, 35. However, associated with enhancing tumor response is a potentially equal sensitization of normal tissues to radiation resulting from a biologically more intense treatment. Recent data suggest that more intense therapy may prolong acute symptoms, leading to consequential late effects (36).
In this retrospective study, we aim to evaluate the efficacy of HBOT in the treatment of radiation-induced late side effects in a group of patients treated with radiation alone or in combination with chemotherapy.
Section snippets
Methods and materials
This study was granted institutional review board approval at UCLA in accordance with the Health Insurance Portability and Accountability Act of 1996. We recruited patients who were treated between January 1998 and August 2003 at the UCLA Hyperbaric Oxygen Unit for radiation late effects. From these patients we received written permission to access their medical records. Our inclusion criteria required that patients must have received radical radiation for their cancers or noncancerous
Results
From 75 eligible subjects, a total of 45 patients responded to the questionnaire (overall response rate of 60%). Of these, 31 patients (69%) had irradiation for head-and-neck (H&N) cancer. We also included in this group 3 patients with brain irradiation for past brain cancer diagnoses who experienced radiation-related late effects in the head-and-neck region (Table 1). Seven patients (16%) received radiation therapy to the pelvic area (prostate n = 5, uterus n = 1, and ovarian/perineum n = 1).
Discussion
We found that the majority of patients with radiation-induced late side effects showed improvement after either HBOT alone or HBOT followed by surgical or medical procedures. HBOT facilitated symptom improvement in all patients with pelvic symptoms, 4 of 7 patients (57%) with “other” symptoms, and the majority of H&N patients with late side effects (75%) (excluding 3 subjects treated with HBOT prophylactically). We were unable to obtain a control group in this study, because HBOT has currently
Conclusions
Our retrospective study indicates that HBOT seems to be an efficacious treatment modality for many radiation-induced late side effects. Clinicians may consider using this treatment in patients determined not to have tumor recurrence. Refractory bone symptoms arising from radiation treatment of the head and neck are highly amenable to HBOT, although success tends to require the maintenance of concurrent medical treatment, such as antibiotics and pain control, during the HBOT course. Severely
References (44)
- et al.
Changes in early and late radiation responses with altered dose fractionationImplications for dose-survival relationships
Int J Radiat Oncol Biol Phys
(1982) - et al.
Late complications of radiation only for advanced breast cancer
Int J Radiat Oncol Biol Phys
(1980) - et al.
The relationship of acute to late skin injury in 2 and 5 fraction/week gamma-ray therapy
Int J Radiat Oncol Biol Phys
(1978) - et al.
Alpha/beta value and the importance of size of dose per fraction for late complications in the supraglottic larynx
Radiother Oncol
(1986) The Franz Buschke lectureLate effects of chemotherapy and radiation therapy: A new hypothesis
Int J Radiat Oncol Biol Phys
(1984)- et al.
Tolerance of normal tissue to therapeutic irradiation
Int J Radiat Oncol Biol Phys
(1991) - et al.
Novel DNA sequence variants in the hHR21 DNA repair gene in radiosensitive cancer patients
Int J Radiat Oncol Biol Phys
(2001) - et al.
Relationship of oxygen dose to angiogenesis induction in irradiated tissue
Am J Surg
(1990) - et al.
Review of severe osteoradionecrosis treated by surgery alone or surgery with postoperative hyperbaric oxygenation
Br J Oral Maxillofac Surg
(2000) - et al.
The use of hyperbaric oxygen therapy in bony reconstruction of the irradiated and tissue-deficient patient
J Oral Maxillofac Surg
(1982)
Hyperbaric oxygen and postradiation osteonecrosis of the mandible
Eur J Cancer B Oral Oncol
Hyperbaric oxygen treatment of osteoradionecrosis of the mandible. Experience in 29 patients
Oral Surg Oral Med Oral Pathol Oral Radiol Endod
Do acute mucosal reactions lead to consequential late reactions in patients with head and neck cancer?
Radiother Oncol
Late effects of hyperfractionated radiotherapy for advanced head and neck cancerLong-term follow-up results of RTOG 83–13
Int J Radiat Oncol Biol Phys
Hyperbaric oxygen treatment for radiation proctitis
Int J Radiat Oncol Biol Phys
Hyperbaric oxygen—an effective tool to treat radiation morbidity in prostate cancer
Radiother Oncol
Osteoradionecrosis of the mandible
Ann Otol Rhinol Laryngol
Late sequelae and complications of electron therapy
J Radiol Electrol Med Nucl
Osteonecrosis in patients treated with definitive radiotherapy for squamous cell carcinomas of the oral cavity and naso- and oropharynx
Radiology
Treatment volume and tissue tolerance
Int J Radiat Oncol Biol Phys
Cited by (88)
Sexual dysfunction in female patients with anal cancer treated with curative intent: A systematic review of the literature
2023, Radiotherapy and OncologyAnalysis of Radiation Dose/Volume Effect Relationship for Anorectal Morbidity in Children Treated for Pelvic Malignancies
2021, International Journal of Radiation Oncology Biology PhysicsCitation Excerpt :For grade 3 rectal bleeding and proctitis, semi-invasive procedures were necessary. These approaches have demonstrated their effectiveness, although recurrence of symptoms is frequent.36,37 Prevention of rectal complications can be achieved by decreasing doses to the rectum, and our data can be viewed as a first step to integrate dose–volume constraints into brachytherapy treatment planning to reduce long-term morbidity.
Inhibitors of HIF-1α and CXCR4 Mitigate the Development of Radiation Necrosis in Mouse Brain
2018, International Journal of Radiation Oncology Biology PhysicsHyperbaric oxygen treatment did not significantly affect radiation injury in the mandibular area of rats
2018, Oral Surgery, Oral Medicine, Oral Pathology and Oral RadiologyCurrent 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.