# Radiation Oncology/Toxicity/Osteoradionecrosis

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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

* 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