SA1 - Insights and a Retrospective Analysis from a Single Institution Using Pentoxifylline, Vitamin E and Sodium Clodronate in the Prevention and Management of ORN

Abstract: Osteoradionecrosis (ORN) of the jaws remains one of the most debilitating complications of radiotherapy (RT) in head and neck cancer (HNC) patients, affecting approximately 5.5% of patients. Prevention and management of ORN remains contentious with no consensus on the optimal approach. Medical management as a strategy using the PENTO/CLO regime (pentoxifylline, vitamin E with or without sodium clodronate) has grown in popularity considering the promising outcomes demonstrated in the literature.

The Oral Surgery department at Guy’s & St Thomas’ Hospital is a tertiary care unit providing a service for the prevention and management of ORN, receiving both internal and external referrals from hospitals within London and across the UK since 2008. A review of our patient registry revealed that we have implemented the PENTO/CLO regimen in 815 patients across various clinical scenarios in the prevention and management of ORN:
i) Treating established jaw and craniofacial ORN
ii) Prophylactic administration for dental surgery post-radiotherapy
iv) Employing a liquid formulation of PENTO for patients with dysphagia
v) Managing established ORN in patients with underlying cardiac/cerebrovascular conditions
vii) ORN with the additional risk factor of bone-modifying agents

Our retrospective analysis revealed that the jaws were most frequently affected, with a predilection for the mandible (7:1, mandible:maxilla). Most cases presented as Notani I (48%), followed by Notani III (36%) and Notani II (15%). Beyond the jaws, other craniofacial areas such as the temporal bone, zygoma, and cervical spine were also affected. Considering ORN for all sites, 48% of cases completely healed, 38% remained stable, while 14% showed disease progression.

In instances of disease progression, we noted significant challenges with control of infection, necessitating approximately four times more antibiotic prescriptions on average. Approximately 9% of patients reported side effects related to pentoxifylline, with gastric irritation being the most reported (42%), followed by dizziness (8%) and malaise (8%). 115 patients received the liquid formulation of the PENTO/CLO regimen due to dysphagia and had similar outcome measures compared to those on the tablet formulation. Furthermore, following the recommended absolute contraindications for pentoxifylline, we identified excellent tolerance to the medication with no adverse events reported in those with underlying cardiac- or cerebrovascular disease.

Beyond the management of ORN, we noted that the prophylactic use of this regime in ‘at risk’ patients prior to dental surgery reduced the risk of ORN development from 7% to 1%. Cost analysis revealed that PENTO costs $33/month (total cost in a healed case is $106) compared to alternative adjuncts such as hyperbaric oxygen at an estimated $10,098 per course.

In summary, medical management is increasingly recognized as a valuable approach in both the prevention and management of osteoradionecrosis (ORN), with mounting evidence supporting its efficacy, ease of administration, and cost-effectiveness compared to alternative strategies. We have demonstrated good outcomes with the use of this regime in a range of settings. However, we emphasize the importance of stringent infection control to ensure optimal outcomes.


References
1. Patel, Sagar, et al. "The use of pentoxifylline, tocopherol and clodronate in the management of osteoradionecrosis of the jaws." Radiotherapy and Oncology 156 (2021): 209-216.
2. Samani, Meera, et al. "Prophylactic pentoxifylline and vitamin E use for dental extractions in irradiated patients with head and neck cancer." Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology 133.3 (2022): e63-e71.