Clinical investigation
The efficacy of hyperbaric oxygen therapy in the treatment of radiation-induced late side effects

https://doi.org/10.1016/j.ijrobp.2004.04.019Get rights and content

Abstract

Purpose

We investigated the efficacy of hyperbaric oxygen therapy (HBOT) in the management of patients with radiation-induced late side effects, the majority of whom had failed previous interventions.

Methods and materials

Of 105 eligible subjects, 30 had either died or were not contactable, leaving 75 who qualified for inclusion in this retrospective study. Patients answered a questionnaire documenting symptom severity before and after treatment (using Radiation Therapy Oncology Group criteria), duration of improvement, relapse incidence, and HBOT-related complications.

Results

The rate of participation was 60% (45/75). Improvement of principal presenting symptoms after HBOT was noted in 75% of head-and-neck, 100% of pelvic, and 57% of “other” subjects (median duration of response of 62, 72, and 68 weeks, respectively). Bone and bladder symptoms were most likely to benefit from HBOT (response rate, 81% and 83%, respectively). Fifty percent of subjects with soft tissue necrosis/mucous membrane side effects improved with HBOT. The low response rate of salivary (11%), neurologic (17%), laryngeal (17%), and upper gastrointestinal symptoms (22%) indicates that these were more resistant to HBOT. Relapse incidence was low (22%), and minor HBOT-related complications occurred in 31% of patients.

Conclusion

Hyperbaric oxygen therapy is a safe and effective treatment modality offering durable relief in the management of radiation-induced osteoradionecrosis either alone or as an adjunctive treatment. Radiation soft tissue necrosis, cystitis, and proctitis also seemed to benefit from HBOT, but the present study did not have sufficient numbers to reliably predict long-term response.

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

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