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Journal of Clinical Oncology, Vol 23, No 19 (July 1), 2005: pp. 4466-4468 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.01.4043
In Reply:Hyperbaric Chamber Unit, Raymond Poincaré Hospital (APHP), School of Medicine Paris Ile de France Ouest (UVSQ), Garches, France
Departement de Biostatistique et Informatique Médicale, Saint Louis Hospital (APHP), School of Medicine Saint Louis Lariboisière, Paris, France Dr Laden's statement that we exposed some patients to a serious risk of acute decompression sickness is wrong. First, the scientific accuracy of the protocol was carefully checked and recognized by independent experts in the field of hyperbaric medicine, therapeutic radiations, and head and neck cancer during the review process that preceded funding by the French Ministry of Health (protocol recorded under number P960114 AOM95211. On July 18, 1996, our regional ethics committee, the Comité Consultatif de Protection des Personnes dans la Recherche Biomédicale (CCPPRB), approved the study as a trial with major benefit for patients (reference No. 96,033). By French law (art. L.1123-1, previously L.209-11),1 this committee is made up of 12 members who have no link with either the sponsor or the investigators. It includes physicians from academic and nonacademic hospitals, nurses, sociologists, psychologists, philosophers, and jurists. An independent main end point and safety monitoring board was also set up before the beginning of inclusions. The study was therefore conducted under the supervision of the Délégation Régionale à la Recherche Clinique d'Ile de France (DRRC).2 The goals of this public institution, created by the French Ministry of Health in each region of France, are to promote clinical research in public hospitals and to guarantee that research is conducted according to the declaration of Helsinki, to the European directives, and to the French regulations. Secondly, to avoid any risk of acute decompression sickness, at the end of the pressure plateau, in both groups, the pressure was decreased from 2.4ATA to 1ATA in 30 minutes while patients were breathing room air, which is almost five times longer than what was recommended by the French Navy (Table M.N. 90). Thirdly, in practice, none of the patients had symptoms of acute decompression sickness. Dr Laden also misinterpreted data in Table 2. First of all, most patients completed the 30-dives protocol and the 30-plus-10 dives in patients who needed to be operated on. This is now more clearly displayed in Figure 1. In the current study, multiple patients were simultaneously treated in a hyperbaric chamber, and once a complication occurred (even in only one patient), the session was prematurely discontinued for all patients. Then, there were two patients with two sessions "discontinued due to complications" but only one patient who actually had hyperbaric oxygen therapy (HBO) session–related complication. Finally, with regards to the study design, we used a triangular test, which is a sequential approach allowing for measuring treatment difference as data accumulate along the trial while controlling for type I and type II error rates. At each inspection, two statistics were computed—one indicating the difference between treatment arms, and another indicating the amount of information in the trial (ie, approximately the sample size). Therefore, even in the first analyses of the trial, the small sample sizes involved in the triangular test were taken into account.
Also noted by van Merkesteyn et al, in the study by Marx et al on the prevention of mandibular osteoradionecrosis following dental extraction, HBO alone did better than penicillin alone,3 and not the combination of HBO plus penicillin as we mistakenly reported. We chose to treat the patients by two HBO dives per day to shorten the overall duration of treatment and to improve patients' compliance. There is no evidence from both experimental and clinical studies to suggest that one HBO session per day is superior to two sessions per day. Thus, awaiting such evidence from new investigations, there is no ground to debate the therapeutic protocol we have tested. We strongly disagree with the statement by van Merkesteyn et al that the definition for osteoradionecrosis used in this study was not valid. The definition was based on that proposed by Marx et al.3 More than half of the patients had areas of bone exposure, and all had bone sequestra. The progression of the disease, with only 19% to 32% of recovery at 1 year, and 62% of patients eventually operated on, strongly highlighted the presence of radionecrosis of the jaw in these patients. In addition, the diagnosis of osteoradionecrosis made at each participating center was double-checked by a surgeon at the core center. Finally, because entry into the study required exclusion of ongoing cancer, all patients had pre–random assignment biopsies of the mandible that confirmed bone necrosis and absence of malignant cells. Thus, there is no doubt that we studied only patients with true radionecrosis of the mandible. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
REFERENCES 1. Loi No. 88-1138 du 20 décembre 1988 relative à la protection des personnes qui se prêtent à des recherches biomédicales, modifiée par les lois No. 90-86 du 23 janvier 1990, No. 91-73 du 18 janvier 1991 et No. 94-630 du 25 juillet 1994. Code de la Santé Publique –Livre II bis 2. Délégation Régionale à la Recherche Clinique d'Ile de France. http://www.drrc.aphp.fr/ 3. Marx RE, Johnson RP, Kline SN. Prevention of osteoradionecrosis: A randomized prospective clinical trial of hyperbaric oxygen versus penicillin. J Am Dent Assoc 111:49-54, 1985[Abstract]
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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