Evaluating Outcomes of Combination Pentoxifylline and Tocopherol in Preventing Osteradionecrosis of the Jaws

Statement of the problem

Osteoradionecrosis (ORN) is a significant complication of radiotherapy for head and neck cancer (HNC). It is characterized by the presence of exposed bone that fails to heal beyond 6 weeks in a previously irradiated area. ORN can have a devastating impact on quality of life. Pain, swelling, dysgeusia, lip/facial numbness, chewing and eating disturbance are frequently experienced. Pathological fracture and chronic orocutaneous fistula are seen in severe ORN, where major surgical intervention may be necessary to alleviate the problem.

Dental extraction and/or trauma are associated with the onset of ORN. There is huge emphasis in preventing ORN because treatment of established ORN is very challenging. Delanian (2005) suggests that established ORN may be amenable to medical management with combination of pentoxifylline (PTX) and tocopherol/vitamin E (VE). However, PTX-VE intervention has never been reported in the prevention of ORN. The purpose of this study was to evaluate the outcomes of PTX-PE intervention in preventing onset of ORN.

Materials & method

A retrospective case review at the University of Maryland Oral & Maxillofacial Surgery unit was undertaken. PTX-VE intervention was used prophylactically with elective dental extraction, implant placement and/or minor oral surgery (MOS) since April 2009. PTX (400mg BD)-VE (1000units OD) was prescribed 2 weeks prior to the planned procedure and continued for 4 weeks post-surgery.

Irradiated HNC patients who received PTX-VE intervention prior to extraction and/or implants/MOS undertaken at the unit, and attended a 8-week post-procedure follow-up were included in the study. Eligible patients were identified through the unit registry. Data collected from chart review include relevant demographic, clinicopathological and treatment parameters. The primary outcome measure was complete healing with mucosal coverage at the surgical site at 6-week follow up. We hypothesized that PTX-VE intervention would not prevent the development of ORN.

Methods of data analysis

Data analysis included summary statistics and comparison of proportions. Multivariate regression analysis was undertaken for predictive factors of outcomes.

Results

Ninety-one patients underwent 109 procedures from April 2009 to December 2015. In this cohort, males predominated (60/91, 65.9%) and the mean age at presentation was 62 years (range, 31-90). The most common diagnosis, primary site and stage at HNC presentation were squamous cell carcinoma (85%), lip/oral cavity (43%), and late stage (71%), respectively.  The mean radiation dose received was 63Gy, delivered with IMRT in 80%. The mean interval time from completion of radiation to procedure was 2045.5 days. Adjuvant chemotherapy was received in 60%.

Dental extraction alone and in combination accounted for 97/109 cases (90%) while implant alone and MOS alone were 8.3% and 2.8%, respectively. A total of 524 teeth were extracted (mean, 5) from the mandible only (54%), both jaws (25%) and maxilla only (21%).

Outcomes data

ORN occurred following 8/109 procedures (7.3%), indicating a PTX-VE prophylaxis success rate of 92.6% (101/109). Out of the 8 ORN cases, 5 cases stabilized at Notani stage 1 with continued PTX-VE therapy (5/109, 4.6%), while the remaining ORN cases (3/109, 2.7%) progressed and required major surgery for definitive treatment. Multivariate analysis found only smoking and longer interval times between radiotherapy completion to procedure were independent predictive for development of ORN (p<0.05).

Conclusions

This study provides early evidence of the efficacy of PTX-VE in preventing ORN after oral surgical procedures. A randomized control trial is required for definitive recommendation.

References

 

1. Lyons A, Ghazali N. Osteoradionecrosis of the jaws: current understanding of its pathophyisology and treatment. Br J Oral Maxillofac Surg 2008; 46:653–60.
2. 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; 27:114-23.