Radiation Oncology/Toxicity/Osteoradionecrosis

Osteoradionecrosis Overview Nonvital bone in a site of prior radiation therapy Can be spontaneous or may develop after even minor trauma, such as denture-related injury, tooth extraction, or ulcers. It is believed that the reparative capacity of radiation-injured bone is exceeded Clinical presentation: pain, swelling, trismus, exposed bone, pathologic fracture, malocclusion, oral cutaneous fistula formation Grading Grade I: exposed alveolar bone Grade II: exposed alveolar bone that does not respond to HBO Grade III: full-thickness involvement and/or pathologic fracture On pathology, inferior alveolar artery (the predominant arterial blood supply to the body of the mandible) and periosteal arteries have significant intimal fibrosis and thrombosis Historically, 5-12% incidence but more recent frequency probably ~3% Rare in patients who receive <60 Gy Risk factors: preradiation or postradiation extraction or surgery, close to tumor, posterior mandible > anterior mandible > posterior maxilla > anterior maxilla, dental disease, dose > 60 Gy, time from preradiation extractions to start of RT < 14 days Work-up Rule out tumor recurrence, with biopsies as necessary Plain film, CT and/or MRI Prevention Full dental evaluation prior to RT Radiation carries: Daily fluoride treatment with 1% neutral sodium fluoride gel in prefabricated trays for 5 minutes each day, for life Medical management is supportive. Nutritional support, superficial debridement, oral saline irrigation. ABX only for definite secondary infection Use and efficacy of hyperbaric oxygen (HBO) is controversial. If used, typically 30 dives to 2.4 ATM x90 minutes, followed by surgery, and additional 10 dives Surgical reconstruction typically involves vascularized free tissue transfers MD Anderson 1980 PMID 7410128 — "Radiation necrosis of the mandible: a 10 year study. Part I. Factors influencing the onset of necrosis." Murray CG et al. Int J Radiat Oncol Biol Phys. 1980 May;6(5):543-8. 1980 PMID 6997243 "Radiation necrosis of the mandible: a 10 year study. Part II. Dental factors; onset, duration and management of necrosis." Int J Radiat Oncol Biol Phys. 1980 May;6(5):549-53. Reviews: 2006 PMID 16458773 — "Osteoradionecrosis prevention myths." Wahl MH et al. Int J Radiat Oncol Biol Phys. 2006 Mar 1;64(3):661-9. Hyperbaric Oxygen Randomized HOPON PMID 30851351 -- "HOPON (Hyperbaric Oxygen for the Prevention of Osteoradionecrosis): A Randomized Controlled Trial of Hyperbaric Oxygen to Prevent Osteoradionecrosis of the Irradiated Mandible After Dentoalveolar Surgery" (Shaw RJ, Int J Radiat Oncol Biol Phys . 2019 Jul 1;104(3):530-539. doi: 10.1016/j.ijrobp.2019.02.044. Epub 2019 Mar 7.) Randomized. 144 patients, who required dental extraction or implant placement in madible, had prior RT >50 Gy. Arm 1) HBO 30 daily dives @ 2.4 atmospheres 80-90 minutes. Arm 2) No HBO (control). Primary outcome ORN @ 6 months. Outcome: ORN HBO 6.4% vs control 5.7% (NS). Fewer acute symptoms in HBO group, but no difference in late pain or QOL Conclusion: Low incidence of ORN makes recommending HBO prior to dental work unnecessary French ORN96 (1997-2001) -- hyperbaric oxygen vs. placebo Randomized. Stopped early after 2nd interim analysis for lower HBO outcomes. 68 patients, history of RT for H&N cancer, with overt mandibular radionecrosis. Severe forms such as mandibular fracture or bony resorption excluded. Arm 1) 30 HBO exposures @ 2.4 ATM x90 min prior to surgery, with additional 10 HBO exposures post-operatively vs. Arm 2) placebo 2004 PMID 15520052 -- "Hyperbaric oxygen therapy for radionecrosis of the jaw: a randomized, placebo-controlled, double-blind trial from the ORN96 study group." (Annane D, J Clin Oncol. 2004 Dec 15;22(24):4893-900. Epub 2004 Nov 1.) Outcome: 1-year recovery HBO 19% vs. placebo 32% (NS) Conclusion: Patients with mild/moderate mandibular osteoradionecrosis didn't benefit from HBO University of Miami -- hyperbaric oxygen vs. penicillin Randomized. High risk patients, history of RT, who required tooth removal. Arm 1) hyperbaric oxygen vs. Arm 2) penicillin 1985 PMID 3897335 -- "Prevention of osteoradionecrosis: a randomized prospective clinical trial of hyperbaric oxygen versus penicillin." (Marx RE, J Am Dent Assoc. 1985 Jul;111(1):49-54.) Outcome: incidence of ORN: HBO 5% vs. penicillin 30% (SS) Conclusion: HBO should be considered a prophylactic measure when post-RT dental care involving trauma to tissue is necessary Review Liverpool; 2010 PMID 20347191 -- "Hyperbaric oxygen in the management of late radiation injury to the head and neck. Part I: treatment." (Shaw RJ, Br J Oral Maxillofac Surg. 2010 Mar 25. [Epub ahead of print]) Review