Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study

Abstract

BackgroundGiant cell tumor of bone (GCTB) is an intermediate tumor known to be locally aggressive, but rarely metastasizing. To plan a prospective study of GCTB, we performed a questionnaire survey for institutions participating in the Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical Oncology Group (JCOG) in 2015.MethodsWe reviewed 158 consecutive patients with primary GCTB treated with curettage without perioperative denosumab from 2008 to 2010 in Japan. We investigated local and distant recurrence rates after definitive curettage. We also investigated the recurrence rate after treatment with preoperative and/or postoperative denosumab with curettage in recent years. There were 40 patients treated with perioperative denosumab, and the factors affecting recurrence in them were investigated.ResultsAnswers were available from 24 of 30 institutions (80.0%) participating in JCOG BSTTSG. Thirty (19.0%) and 4 (2.5%) of 158 patients developed local and distant recurrence after curettage without perioperative denosumab from 2008 to 2010, respectively. Campanacci grade and embolization before surgery were significantly associated with increasing incidence of local recurrence after curettage (p = 0.034 and p = 0.022, respectively). In patients treated with perioperative desnosumab, 120 mg denosumab was administered subcutaneously for a median 6 (2–41) and 6 (1–14) times in preoperative and postoperative settings, respectively. The recurrence rates were 6 of 21 (28.6%), 2 of 9 (22.2%), and 0 of 10 (0.0%) in the preoperative, postoperative, and both pre- and postoperative denosumab treatment groups, respectively. With all of the preoperative treatments, administration exceeding five times was significantly associated with a decreased incidence of local recurrence after curettage (p < 0.001).ConclusionThe recurrence rate of GCTB was still high after curettage, especially in Campanacci grade III, and improvements in the therapeutic strategy are needed in this cohort. There is a possibility that a sufficient dose of preoperative denosumab can reduce recurrence after curettage. Recently, we have started a clinical trial, JCOG1610, to investigate the efficacy of preoperative denosumab in patients who can be treated with curettage in GCTB.

Survival and prognostic factors analyses in malignant giant cell tumor of bone

“…Based on the Campanacci classification, which has been widely accepted in evaluating giant cell tumor, grade III represented the aggressive type. A series of studies reported Campanacci grade III as the risk factor for tumor recurrence [19,20] and lung metastasis [21,22]. The recurrence was also reported to be a risk factor for resulting in metastasis [21,22].…”

Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis

“…The total dosage given prior to surgery was inconsistent among included studies. Four studies [13,[15][16][17] administered denosumab pre-operatively and post-operatively. Overall, 61 cases in the denosumab group and 175 cases in the control group had local recurrence.…”

Pre-operative denosumab is associated with higher risk of local recurrence in giant cell tumor of bone: a systematic review and meta-analysis

“…1.16 to 4.85, p=0.02, I 2 =57%)(figure2) . Surgical choice was taken into account by comparing cases underwent curettage with denosumab and curettage alone in 4 studies [9,[16][17][18](OR: 2.13, 95% CI: 0.95 to 4.76, p=0.07, I 2 =29%)( Figure 3), though the result was not statistically significant. 7 studies [9,[15][16][17][18][19][20] reported outcome on primary lesions, which also suggest significantly higher risk of local recurrence in the denosumab group(OR: 1.91, 95% CI: 1.17 to 3.09, p=0.009, I 2 =36%)( Figure 4).…”

“…In 4 studies [13,[15][16][17] denosumab was administered both preoperatively and postoperatively, no statistically significant difference was found when comparing pre and post denosumab administration group and control group in terms of local recurrence(OR: 1.96, 95% CI: 0.63 to 6.07, p=0.24, I 2 =79%) ( Figure 5).…”

“…Chen et al [15] recommend the duration of medication should be shortened to the greatest extent to avoid formation of thick rim of new bone. Urakawa et al [17] applied denosumab both pre-operatively and post-operatively, in the 31 cases treated with denosumab, administration exceeding 5 times was significantly associated with lower risk of recurrence. When only studies applying preoperative and postoperative denosumab are included, pooled analysis showed no significant difference in recurrence comparing to the control group.…”