Tumor localization and biochemical response to cure in tumor-induced osteomalacia

William H. Chong, Panagiota Andreopoulou, Clara C. Chen, James Reynolds, Lori Guthrie, Marilyn Kelly, Rachel I. Gafni, Nisan Bhattacharyya, Alison M. Boyce, Diala El-Maouche, Diana Ovejero Crespo, Richard Sherry, Richard Chang, Felasfa M. Wodajo, Gad B. Kletter, Andrew Dwyer, Michael T. Collins

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1386-1398
Number of pages13
JournalJournal of Bone and Mineral Research
Volume28
Issue number6
DOIs
StatePublished - Jun 2013
Externally publishedYes

Fingerprint

Single-Photon Emission-Computed Tomography
Neoplasms
Calcitriol
Sensitivity and Specificity
Reference Values
Fibroblast Growth Factor 1
Octreotide
Serum
Positron-Emission Tomography
Phosphorus
Oncogenic osteomalacia
Phosphates
Neoplasm Metastasis
Recurrence
fibroblast growth factor 23

Keywords

  • FGF23
  • HYPOPHOSPHATEMIA
  • MINERAL METABOLISM
  • OSTEOMALACIA
  • VITAMIN D

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Chong, W. H., Andreopoulou, P., Chen, C. C., Reynolds, J., Guthrie, L., Kelly, M., ... Collins, M. T. (2013). Tumor localization and biochemical response to cure in tumor-induced osteomalacia. Journal of Bone and Mineral Research, 28(6), 1386-1398. https://doi.org/10.1002/jbmr.1881

Tumor localization and biochemical response to cure in tumor-induced osteomalacia. / Chong, William H.; Andreopoulou, Panagiota; Chen, Clara C.; Reynolds, James; Guthrie, Lori; Kelly, Marilyn; Gafni, Rachel I.; Bhattacharyya, Nisan; Boyce, Alison M.; El-Maouche, Diala; Crespo, Diana Ovejero; Sherry, Richard; Chang, Richard; Wodajo, Felasfa M.; Kletter, Gad B.; Dwyer, Andrew; Collins, Michael T.

In: Journal of Bone and Mineral Research, Vol. 28, No. 6, 06.2013, p. 1386-1398.

Research output: Contribution to journalArticle

Chong, WH, Andreopoulou, P, Chen, CC, Reynolds, J, Guthrie, L, Kelly, M, Gafni, RI, Bhattacharyya, N, Boyce, AM, El-Maouche, D, Crespo, DO, Sherry, R, Chang, R, Wodajo, FM, Kletter, GB, Dwyer, A & Collins, MT 2013, 'Tumor localization and biochemical response to cure in tumor-induced osteomalacia', Journal of Bone and Mineral Research, vol. 28, no. 6, pp. 1386-1398. https://doi.org/10.1002/jbmr.1881
Chong WH, Andreopoulou P, Chen CC, Reynolds J, Guthrie L, Kelly M et al. Tumor localization and biochemical response to cure in tumor-induced osteomalacia. Journal of Bone and Mineral Research. 2013 Jun;28(6):1386-1398. https://doi.org/10.1002/jbmr.1881
Chong, William H. ; Andreopoulou, Panagiota ; Chen, Clara C. ; Reynolds, James ; Guthrie, Lori ; Kelly, Marilyn ; Gafni, Rachel I. ; Bhattacharyya, Nisan ; Boyce, Alison M. ; El-Maouche, Diala ; Crespo, Diana Ovejero ; Sherry, Richard ; Chang, Richard ; Wodajo, Felasfa M. ; Kletter, Gad B. ; Dwyer, Andrew ; Collins, Michael T. / Tumor localization and biochemical response to cure in tumor-induced osteomalacia. In: Journal of Bone and Mineral Research. 2013 ; Vol. 28, No. 6. pp. 1386-1398.
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AU - Andreopoulou, Panagiota

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AU - Reynolds, James

AU - Guthrie, Lori

AU - Kelly, Marilyn

AU - Gafni, Rachel I.

AU - Bhattacharyya, Nisan

AU - Boyce, Alison M.

AU - El-Maouche, Diala

AU - Crespo, Diana Ovejero

AU - Sherry, Richard

AU - Chang, Richard

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N2 - 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.

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