Adjuvant Antiangiogenic Treatment for Aggressive Giant Cell Lesions of the Jaw - 20 Years Experience at the Massachusetts General Hospital

Giant cell lesions (GCLs) are rare non-odontogenic osteolytic lesions that affect both maxillofacial and axial/appendicular skeletal structures. Aggressive lesions have a tendency to recur after surgical enucleation. To avoid en-bloc resection, adjuvant pharmacologic therapy has been used with local operative treatment. Based on the hypothesis that maxillofacial GCLs are proliferative vascular lesions and angiogenesis dependent, a protocol of at least 6 months subcutaneous interferon alpha-2a after enucleation sparing vital structures (i.e. teeth and nerves) has been used since 1999 in collaboration with a hematologist/oncologist.¹The purpose of this study was to evaluate the long-term results of this standardized treatment regimen in a homogenous cohort of patients with aggressive GCLs of the maxillofacial skeleton.

This was a retrospective cohort study of all patients treated with enucleation and adjuvant interferon alpha-2a for GCLs at Massachusetts General Hospital.  Subjects were included if they had a histologically confirmed GCL that was classified as aggressive by clinical and radiographic criteria,²completed the protocol, and had complete records.  Subjects with systemic diseases associated with GCLs (e.g. Cherubism, Noonan-like multiple giant cell syndrome) were excluded. The primary outcome variable was the long-term progression free survival rate, defined as the percentage of people with no new tumor growth after finishing treatment.  A secondary outcome variable was the occurrence and severity of side effects of adjuvant treatment as classified according to the Common Terminology Criteria for Adverse Events (CTCAE v. 4.0). Also the effect of the following predictor variables on progression free survival was assessed: age, location (mandible/maxilla), duration of treatment, amount of bone fill at the end of interferon treatment, need of additional treatment.

Descriptive statistics were computed to describe patient, tumor and response characteristics. Kaplan-Meier survival was calculated for progression free survival analysis. The Cox proportional hazards regression analysis was used to assess the relationship of the predictor variables on disease free survival. Statistical significance was set at p-value ≤ 0.05.  

Forty-four subjects (28 females) out of 47 undergoing the protocol were included in this study. Mean age of the subjects was 18.2 ± 12.7 years.  Lesions occurred in the maxilla (23%) and mandible (77%). Interferon alpha-2a was administered for an average of 8.0 ± 2.6 months. The mean follow up after the last interferon was 5.1 ± 3.4 years. Six patients developed a recurrence, leading to a failure rate of 13.6%. The progression free survival rate was 79.6%, when accounting for follow up time. Eighty percent of subjects had complete bone fill and 7% had >75% bone fill at the latest follow-up. None of the predictor variables had a significant effect on the progression free survival. In total 93.5%, 67.4%, and 37.0% of subjects experienced a grade I, II, or III side effect, respectively.

The results of this long-term outcome study indicate that enucleation and adjuvant interferon alpha-2a is an effective protocol for managing aggressive maxillofacial GCLs while sparing vital structures such as teeth and nerves.  Most patients experienced one or more side-effects during treatment, but completed the protocol and had no long-term side-effects.

REFERENCES

1. Kaban, L.B., et al., Antiangiogenic therapy of a recurrent giant cell tumor of the mandible with interferon alfa-2a. Pediatrics, 1999. 103(6): p. 1145-9.
2. Chuong, R., et al., Central giant cell lesions of the jaws: a clinicopathologic study. J Oral Maxillofac Surg, 1986. 44(9): p. 708-13.