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Modeling Primary Bone Tumors and Bone Metastasis with Solid Tumor Graft Implantation into Bone
Published on: September 9, 2020
Tumor localization and biochemical response to cure in tumor-induced osteomalacia
William H Chong1, Panagiota Andreopoulou, Clara C Chen
1Skeletal Clinical Studies Unit, Craniofacial and Skeletal Disease Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Abstract:
Tumor-induced osteomalacia (TIO) is a rare disorder of phosphate wasting due to fibroblast growth factor-23 (FGF23)-secreting tumors that are often difficult to locate. We present a systematic approach to tumor localization and postoperative biochemical changes in 31 subjects with TIO. All had failed either initial localization, or relocalization (in case of recurrence or metastases) at outside institutions. Functional imaging with ¹¹¹Indium-octreotide with single photon emission computed tomography (octreo-SPECT or SPECT/CT), and ¹⁸fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT) were performed, followed by anatomic imaging (CT, MRI). Selective venous sampling (VS) was performed when multiple suspicious lesions were identified or high surgical risk was a concern. Tumors were localized in 20 of 31 subjects (64.5%). Nineteen of 20 subjects underwent octreo-SPECT imaging, and 16 of 20 FDG-PET/CT imaging. Eighteen of 19 (95%) were positive on octreo-SPECT, and 14 of 16 (88%) on FDG-PET/CT. Twelve of 20 subjects underwent VS; 10 of 12 (83%) were positive. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were as follows: sensitivity = 0.95, specificity = 0.64, PPV = 0.82, and NPV = 0.88 for octreo-SPECT; sensitivity = 0.88, specificity = 0.36, PPV = 0.62, and NPV = 0.50 for FDG-PET/CT. Fifteen subjects had their tumor resected at our institution, and were disease-free at last follow-up. Serum phosphorus returned to normal in all subjects within 1 to 5 days. In 10 subjects who were followed for at least 7 days postoperatively, intact FGF23 (iFGF23) decreased to near undetectable within hours and returned to the normal range within 5 days. C-terminal FGF23 (cFGF23) decreased immediately but remained elevated, yielding a markedly elevated cFGF23/iFGF23 ratio. Serum 1,25-dihydroxyvitamin D₃ (1,25D) rose and exceeded the normal range. In this systematic approach to tumor localization in TIO, octreo-SPECT was more sensitive and specific, but in many cases FDG-PET/CT was complementary. VS can discriminate between multiple suspicious lesions and increase certainty prior to surgery. Sustained elevations in cFGF23 and 1,25D were observed, suggesting novel regulation of FGF23 processing and 1,25D generation.
Insights
Tumor-induced osteomalacia (TIO) diagnosis is improved by a systematic imaging approach. Octreotide single-photon emission computed tomography (octreo-SPECT) showed higher sensitivity and specificity for locating fibroblast growth factor-23 (FGF23)-secreting tumors.
Area of Science:
- Endocrinology
- Nuclear Medicine
- Oncology
Background:
- Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome.
- It results from fibroblast growth factor-23 (FGF23)-secreting tumors, which are often challenging to localize.
- Previous localization attempts at outside institutions frequently fail.
Purpose of the Study:
- To evaluate a systematic approach for localizing FGF23-secreting tumors in TIO patients.
- To assess postoperative biochemical changes following tumor resection.
Main Methods:
- A systematic imaging protocol including octreotide single-photon emission computed tomography/CT (octreo-SPECT/CT) and 18F-fluorodeoxyglucose positron emission tomography/CT (FDG-PET/CT).
- Anatomic imaging (CT, MRI) and selective venous sampling (VS) were employed.
- Biochemical markers including serum phosphorus, intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23), and 1,25-dihydroxyvitamin D3 (1,25D) were monitored.
Main Results:
- Tumors were localized in 64.5% of subjects using the systematic approach.
- Octreo-SPECT demonstrated higher sensitivity (95%) and specificity (64%) compared to FDG-PET/CT (88% sensitivity, 36% specificity).
- Postoperatively, serum phosphorus normalized within 1-5 days, iFGF23 decreased rapidly, while cFGF23 and 1,25D remained elevated, suggesting complex FGF23 processing and vitamin D regulation.
Conclusions:
- A systematic imaging strategy, particularly with octreo-SPECT, is effective for localizing elusive FGF23-secreting tumors in TIO.
- FDG-PET/CT can be complementary, and VS aids in localizing multiple lesions or in high-surgical-risk patients.
- Postoperative biochemical profiles indicate sustained FGF23 processing and 1,25D generation, warranting further investigation.
