Tag Archive | recurrence

Reducing Local Recurrence of Adamantinomas

The international multicenter study by Schutgens et al. in the October 7, 2020 issue of JBJS reports findings from an analysis of >300 cases of patients diagnosed with either classic adamantinomas (ADs) or osteofibrous dysplasia-like adamantinomas (OFD-ADs) who were followed for 7 to >10 years. The mean age at diagnosis was 17 years. The authors conclude that OFD-AD and AD are “parts of a disease spectrum but should be regarded as different entities.” Their findings, they say, also “support reclassification of OFD-AD into the intermediate locally aggressive [but non-metastatic] category” of bone tumors.

Perhaps the most clinically interesting findings in this study are related to local recurrence, which the authors describe as a “multifactorial” phenomenon in both tumor types. They found local recurrence in 22% of the OFD-AD cases and 24% of the AD cases. None of the recurrences in the OFD-AD group progressed to AD, which is a malignant disease with metastatic potential.

The authors found that the unadjusted cumulative incidence of local recurrence was higher if a pathological fracture was reported and if resection margins were contaminated. So, to reduce the risk of local recurrence in both tumor types, Schutgens et al. suggest “preventing pathological fracture after diagnosis and achieving uncontaminated margins with resection.”  The uncontaminated resection should include the periosteum of the involved bone at the time of surgery.

Giant-Cell Tumor Treatment: Curettage Without Denosumab Is Better

GCTB for OBuzzDenosumab is an FDA-approved drug for osteoporosis. It works by binding RANKL, thus inhibiting osteoclastic activity. Denosumab  has also been shown to have a favorable impact on tumor response in relatively small, short-term studies among patients with giant-cell tumor of bone (GCTB).

In the March 21, 2018 issue of The Journal, Errani et al. report on a longer-term follow up (minimum 24 months, median 85.6 months) in two cohorts of patients with GCTB who were treated with joint-preserving curettage: those treated with curettage plus denosumab and those treated with curettage alone. The study found that denosumab administration was significantly associated with unfavorable outcomes in patients treated with curettage. Specifically, the local GCTB recurrence rate was nearly 4 times higher (60% vs 16%) in patients treated with denosumab plus curettage, compared to those treated with curettage alone.

Recent in vitro studies have shown that denosumab only slows giant-cell multiplication to some degree. The authors point out that patients treated with denosumab in this cohort study had more severe GCTB disease, which would seem to further confirm that cellular proliferation of giant cells is ineffectively slowed by this RANKL-binding drug. What’s most important about the Errani et al. study is that it’s the first one to look at the longer-term outcomes of denosumab usage before and after curettage for GCTB.

The authors emphasize that while their study shows a strong and independent association between denosumab administration and a high level of local recurrence, “causation could not be evaluated.” Still, at a time when clinicians, payers, and patients are critically evaluating every facet of treatment, it seems difficult to recommend the use of denosumab in addition to curettage for GCTB. The data in this study should encourage the musculoskeletal oncology community to continue to investigate other adjunctive treatments to be used with curettage for this disease process.

Marc Swiontkowski, MD
JBJS Editor-in-Chief