ประสิทธิผลของการรักษาภาวะกระดูกตายจากรังสีรักษาบริเวณขากรรไกรด้วยออกซิเจนความดันสูง หรือแนวทาง PENTO/PENTOCLO: การทบทวนอย่างเป็นระบบและวิเคราะห์อภิมาน

Kanticha Lantomrattana; Donnapa Naprasert; Kannika Chukiatmun

Authors

Kanticha Lantomrattana Institute of Dentistry
Donnapa Naprasert Institute of Dentistry
Kannika Chukiatmun Institute of Dentistry

Keywords:

Osteoradionecrosis, Hyperbaric oxygen, Pentoxifylline, Tocopherol, Clodronate

Abstract

Background: Osteoradionecrosis (ORN) severe post-radiation therapy complication in head and neck cancer patients. Current non-surgical treatments include hyperbaric oxygen therapy (HBOT) and PENTO/PENTOCLO protocol, but empirical evidence of their effectiveness remains limited. Objective: To systematically analyze the effectiveness of HBOT and PENTO/PENTOCLO protocol in treating mandibular osteoradionecrosis. Method: A systematic review and meta-analysis were conducted via Cochrane Library, PubMed, Google Scholar and hand search, compiling studies on the effectiveness of HBOT or the PENTO/PENTOCLO protocol in treating mandibular ORN. Only studies published in English or Thai up to May 31^st, 2024. The quality of the studies was assessed, and outcomes were analyzed using a random-effects model. Results were reported as proportions and 95% confidence intervals of recovered patients. Subgroup analyses and association between outcome and treatment methods or disease stages were also examined. Result: 20 studies were identified, comprising 695 participants (HBOT=222, PENTO/PENTOCLO = 473). Most studies showed low to moderate bias risk. Overall patient recovery was 0.51 (95%CI: 0.34, 0.67, I²=97.21%). HBOT group recovery was 0.43 (95%CI: 0.27, 0.59), while PENTO/PENTOCLO group was 0.56 (95%CI: 0.44, 0.69). Furthermore, the proportion of patients who recovered in Notani I, II, III group was 0.50 (95%CI: 0.32, 0.69), 0.48 (95%CI: 0.35, 0.61), 0.39 (95%CI: 0.19, 0.59) respectively. No statistically significant differences were found between treatment methods (p = .231) or Notani staging criteria (p = .358) Conclusion: From the meta-analysis result, after receiving treatment, approximately half of the patients recovered with complete tissue coverage. Neither the treatment method nor the Notani staging significantly associated with treatment outcomes. However, due to data heterogeneity and limited study samples, a definitive conclusion about the effectiveness of HBOT or PENTO/PENTOCLO protocol in mandibular ORN treatment cannot be established.

References

Singh A, Huryn JM, Kronstadt KL, Yom SK, Randazzo JR, Estilo CL. Osteoradionecrosis of the jaw: a mini review. Front Oral Health 2022;3:980786.

Meyer I. Infectious diseases of the jaws. J Oral Surg 1970;28(1):17-26.

Marx RE. A new concept in the treatment of osteoradionecrosis. J Oral Maxillofac Surg 1983;41(6):351-7.

Delanian S, Lefaix JL. The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. Radiother Oncol 2004;73(2):119-31.

Annane D, Depondt J, Aubert P, Villart M, Gehanno P, Gajdos P, et al. Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group. J Clin Oncol 2004;22(24):4893-900.

Leesomprasong T, Thaweedej S. The effectiveness of hyperbaric oxygen therapy for management osteoradionecrosis in jaw: A Meta-Analysis. J DMS 2021;46(1):99-106.

Forner LE, Dieleman FJ, Shaw RJ, Kanatas A, Butterworth CJ, Kjeller G, et al. Hyperbaric oxygen treatment of mandibular osteoradionecrosis: Combined data from the two randomized clinical trials DAHANCA-21 and NWHHT2009-1. Radiother Oncol 2022;166:137-44.

Delanian S, Depondt J, Lefaix JL. Major healing of refractory mandible osteoradionecrosis after treatment combining pentoxifylline and tocopherol: a phase II trial. Head Neck 2005;27(2):114-23.

Delanian S, Chatel C, Porcher R, Depondt J, Lefaix JL. Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial. Int J Radiat Oncol Biol Phys 2011;80(3):832-9.

Robard L, Louis MY, Blanchard D, Babin E, Delanian S. Medical treatment of osteoradionecrosis of the mandible by PENTOCLO: preliminary results. Eur Ann Otorhinolaryngol Head Neck Dis 2014;131(6):333-8.

Dissard A, N PD, Barthelemy I, Delbet C, Puechmaille M, Depeyre A, et al. Efficacy of pentoxifylline-tocopherol-clodronate in mandibular osteoradionecrosis. Laryngoscope 2020;130(11):E559-E66.

Dos Anjos RS, de Padua Walfrido GN, de Hollanda Valente RO, Gueiros LA, Carvalho AAT, Patel P, et al. Pentoxifylline, tocopherol, and sequestrectomy are effective for the management of advanced osteoradionecrosis of the jaws-a case series. Support Care Cancer 2021;29(6):3311-7.

Arqueros-Lemus M, Marino-Recabarren D, Niklander S, Martinez-Flores R, Moraga V. Pentoxifylline and tocopherol for the treatment of osteoradionecrosis of the jaws. A systematic review. Med Oral Patol Oral Cir Bucal 2023;28(3):e293-e300.

Martos-Fernandez M, Saez-Barba M, Lopez-Lopez J, Estrugo-Devesa A, Balibrea-Del-Castillo JM, Bescos-Atin C. Pentoxifylline, tocopherol, and clodronate for the treatment of mandibular osteoradionecrosis: a systematic review. Oral Surg Oral Med Oral Pathol Oral Radiol 2018;125(5):431-9.

Kolokythas A, Rasmussen JT, Reardon J, Feng C. Management of osteoradionecrosis of the jaws with pentoxifylline-tocopherol: a systematic review of the literature and meta-analysis. Int J Oral Maxillofac Surg 2019;48(2):173-80.

D'Souza J, Lowe D, Rogers SN. Changing trends and the role of medical management on the outcome of patients treated for osteoradionecrosis of the mandible: experience from a regional head and neck unit. Br J Oral Maxillofac Surg 2014;52(4):356-62.

Ortega MA, Fraile-Martinez O, García-Montero C, Callejón-Peláez E, Sáez MA, Álvarez-Mon MA, et al. A general overview on the hyperbaric oxygen therapy: applications, mechanisms and translational opportunities. Medicina (Kaunas) 2021;57(9):864.

McCoy JM, Oreadi D. Diagnosis and management of pathological conditions. J Oral Maxillofac Surg 2017;75(8S):e224-e63.

Peterson DE, Koyfman SA, Yarom N, Lynggaard CD, Ismaila N, Forner LE, et al. Prevention and management of osteoradionecrosis in patients with head and neck cancer treated with radiation therapy: ISOO-MASCC-ASCO Guideline. J Clin Oncol 2024;42(16):1975-96.

Marx RE, Johnson RP, Kline SN. Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin. J Am Dent Assoc 1985;111(1):49-54.