The online version of this article (https://doi.org/10.1186/s12957-018-1478-3) contains supplementary material, which is available to authorized users.
Denosumab has been shown to reduce tumor size and progression, reform mineralized bone, and increase intralesional bone density in patients with giant cell tumor of bone (GCTB); however, radiologic assessment of tumors in bone is challenging. The study objective was to assess tumor response to denosumab using three different imaging parameters in a prespecified analysis in patients with GCTB from two phase 2 studies.
The studies enrolled adults and adolescents (skeletally mature and at least 12 years of age) with radiographically measurable GCTB that were given denosumab 120 mg every 4 weeks, with additional doses on days 8 and 15 of cycle 1. The proportion of patients with an objective tumor response was assessed using either Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST), European Organisation for Research and Treatment of Cancer response criteria (positron emission tomography [PET] scan criteria), or inverse Choi density/size (ICDS) criteria. Target lesions were measured by computed tomography or magnetic resonance imaging (both studies), PET (study 2 only), or plain film radiograph (study 2 only).
Most patients (71.6%) had an objective tumor response by at least one response criteria. Per RECIST, 25.1% of patients had a response; per PET scan criteria, 96.2% had a response; per ICDS, 76.1% had a response. 68.5% had an objective tumor response ≥ 24 weeks. Using any criteria, crude incidence of response ranged from 56% (vertebrae/skull) to 91% (lung/soft tissue), and 98.2% had tumor control ≥ 24 weeks. Reduced PET avidity appeared to be an early sign of response to denosumab treatment.
Modified PET scan criteria and ICDS criteria indicate that most patients show responses and higher benefit rates than modified RECIST, and therefore may be useful for early assessment of response to denosumab.
Additional file 1: Figure S1. Postbaseline time point assessments for tumor response by study for patients with ≥ 1 evaluable time point assessment. Per protocol, the sites were instructed to perform CT or MRI scans of the lesion at baseline and quarterly during the treatment period. 18FDG-PET scans were performed at the discretion of the investigator. Because this was a retrospective, independent image review, no specific acquisition parameters were provided. Sites were instructed to use their standard acquisition parameters for CT, MRI, and 18FDG-PET. Consistent use of the imaging modalities, parameters, and contrast was recommended for reproducibility. CT computed tomography, 18FDG‑PET 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography; MRI magnetic resonance imaging. Figure S2. (a) Best percentage change in SLD for target lesions in the ICDS evaluation and (b) best percentage change in density for target lesions in the ICDS evaluation. ICDS inverse Choi density/size; LD longest diameter; SLD sum of longest diameter. (DOCX 233 kb)12957_2018_1478_MOESM1_ESM.docx
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- Assessment of denosumab treatment effects and imaging response in patients with giant cell tumor of bone
Zachary J. Roberts
Bruce A. Bach
- BioMed Central
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