Evolving Treatment Options Prompt a Call for Better HBO Evidence
Localized/early stage mandibular osteoradionecrosis is commonly defined as superficial mucosal ulceration with minimal (2.0-2.5 cm) exposed devitalized bone, present for at least three months. (Clarke, 2019) Since the 1980’s, hyperbaric oxygen (HBO) has been employed as primary therapy, supported on occasion by limited surgical intervention. The genesis for HBO’s role was work by Robert Marx, which culminated in the Wilford Hall HBO ORN Protocol, better known today as the Marx Protocol. (Marx, 1983)
Over the ensuing decades, hyperbaric treatment facilities have routinely rendered care on behalf of this condition, and on an international scale. They have done so in the absence of formal evidence of efficacy, a measure of the value of a given intervention when tested at the highest level of clinical research enquiry. This ‘evidence-based’ demonstration of proof that an intervention works as advertised increasingly influences development of clinical practice guidelines, graduate medical education, governmental policy makers, and third-party health purchasers of health care. The strength of clinical evidence currently supporting HBO is largely the sum of retrospective and prospective case series. One group undertook formal assessment of HBO for localized ORN and reported that it was not beneficial. (Annane, et al. 2004) Despite attention-getting evidence-based medicine (EBM) buzz words within the published paper's title, this trial fell woefully short in terms of research design, patient selection, and study conduct. Several Letters to the Editor pointed out these shortcomings. (Moon et al, 2005, Feldmeier, 2005; Laden, 2005).
Unfortunately, then, when peer reviewed literature is searched for evidence of efficacy, it is this lone (surprising to many that there is but this single RCT addressing HBO for ORN) negative paper to serve as a principal determinant of HBO's relative value. Equally unfortunate, the associated 'counter-point' letters rarely feature. So, like it or not, EBM analyses increasingly view HBO therapy as largely unproven. (Teng & Futan, 2005; Pitak-Arnnop et al. 2008; Costa, et al. 2016; National Institute for Health and Care Excellence (NICE) Clinical Guidelines UK, 2016; Sultan et al. 2017; He et al. 2020). To be considered otherwise, better efficacy evidence is imperative. Government health care policy decisions in several countries have resulted in the delisting HBO, and no longer reimbursable for treatment for ORN.
Treatment alternatives to HBO exist. Medical management, in the form of antioxidant therapy, likewise lacking elevated evidence of efficacy, is increasingly advocated and prescribed. (Delanian et al. 2004) While this practice is more common in Europe, a recent systematic review and meta-analysis by a highly regarded oral maxillofacial group in the US was favorably disposed to this oral medication regimen. (Kolokythas et al. 2019) These authors noted that antioxidant therapy had proven effective in cases that failed to respond to HBO therapy. To their credit, they did emphasize the need for improved efficacy data. A recent report describes the use of free flaps, commonly associated with advanced ORN, to treat these localized cases, using small periosteal free flaps. (Bettoni et al. 2019) Several somewhat predictable complications were associated with this surgical approach, as they are for reconstruction of advanced ORN, but 11/12 cases otherwise refractory to conservative care were ultimately resolved.
Where does all of this leave the practice of hyperbaric medicine for localized ORN? If polled, my sense is that a large majority of hyperbaric providers would indicate their overall clinical outcomes experience as positive. They may also express satisfaction with supportive, although non-peer reviewed, medical textbook chapters to guide clinical decision-making. These two 'evidence levels', however, fall short of that increasingly sought in the modern era, namely high-quality efficacy data. There are challenges to studying HBO at the randomized and sham controlled level given that it is an otherwise de facto standard of care, at least in the USA. To allocate patients to a control (non-HBO) arm may represent too great an ethical dilemma for many within that large majority who are encouraged enough by their clinical experience. There is also the specter of medico legal risk should a sham/control patient suffer disease advancement during the study period, and who could have declined to enroll in the study and otherwise undergo HBO as ‘standard of care’. These concerns are surmountable when dealing with chronic conditions such as localized ORN, and successfully addresed in our earlier radiation proctitis RCT. (Clarke et al. 2008) Without much sought-after efficacy data, HBO therapy will increasingly struggle to gain traction within agencies that control health care spending and during conduct of EBM meta-analyses.
References available upon request
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