Detection Rate of Culprit Tumors Causing Osteomalacia Using Somatostatin Receptor PET/CT: Systematic Review and Meta-Analysis

Background: Tumor-induced or oncogenic osteomalacia (TIO) is a rare paraneoplastic syndrome in which osteomalacia is a consequence of fibroblast growth factor 23 (FGF23) secretion by a mesenchymal tumor. The localization of the culprit lesion in patients with TIO is often challenging. Several studies have evaluated the detection rate (DR) of these tumors using somatostatin receptor positron emission tomography (SSTR-PET/CT). We aimed to summarize literature findings on this topic providing pooled estimates of DR. Methods: A comprehensive literature search by screening PubMed, Embase and Cochrane library electronic databases through August 2019 was performed. The pooled DR of culprit tumors using SSTR-PET/CT in patients with TIO was calculated using a random-effects statistical model. Results: Fourteen studies on the use of SSTR-PET/CT in detecting the culprit tumor in patients with TIO were included in the qualitative analysis. The pooled DR of SSTR-PET/CT on a per-patient-based analysis calculated using eleven studies (166 patients) was 87.6% (95% confidence interval (95% CI) 80.2–95.1%). Statistical heterogeneity among studies was detected (I-square = 63%), likely due to the use of different radiolabeled somatostatin analogues, as demonstrated by a subgroup analysis. Conclusions: Despite limited literature data due to the rarity of the disease, SSTR-PET/CT demonstrated a very high DR of culprit tumors in patients with TIO and it could be used as first-line imaging method for this indication.

[1]  R. Dierckx,et al.  Somatostatin receptor imaging by SPECT and PET in patients with chronic inflammatory disorders: a systematic review , 2019, European Journal of Nuclear Medicine and Molecular Imaging.

[2]  G. Treglia Diagnostic Performance of 18F-FDG PET/CT in Infectious and Inflammatory Diseases according to Published Meta-Analyses , 2019, Contrast media & molecular imaging.

[3]  J. Hephzibah,et al.  Ga-68 DOTATATE Positron Emission Tomography-Computed Tomography Imaging in Oncogenic Osteomalacia: Experience from a Tertiary Level Hospital in South India , 2019, Indian journal of nuclear medicine : IJNM : the official journal of the Society of Nuclear Medicine, India.

[4]  A. Folpe Phosphaturic mesenchymal tumors: A review and update. , 2019, Seminars in diagnostic pathology.

[5]  M. Roarke,et al.  Molecular Imaging in Diagnosis of Tumor-induced Osteomalacia. , 2019, Current problems in diagnostic radiology.

[6]  F. Remotti,et al.  Tumor-induced osteomalacia - Current imaging modalities and a systematic approach for tumor localization. , 2019, Clinical imaging.

[7]  A. Schindeler,et al.  FGF23, Hypophosphatemia, and Emerging Treatments , 2019, JBMR plus.

[8]  L. Giovanella,et al.  Detection rate of unknown primary tumour by using somatostatin receptor PET/CT in patients with metastatic neuroendocrine tumours: a meta-analysis , 2019, Endocrine.

[9]  R. Busse,et al.  Evidence-based indications for the planning of PET or PET/CT capacities are needed , 2019, Clinical and Translational Imaging.

[10]  U. Saikia,et al.  Tumor-induced osteomalacia: experience from three tertiary care centers in India , 2019, Endocrine connections.

[11]  李方,et al.  68Ga-DOTA-TATE正电子发射断层显像/计算机断层显像对 99mTc-HYNIC-TOC单光子发射断层显像阴性瘤源性骨软化症致病肿瘤的定位价值 , 2019 .

[12]  L. Huo,et al.  Increased Activity Due to Fractures Does Not Significantly Affect the Accuracy of 68Ga-DOTATATE PET/CT in the Detection of Culprit Tumor in the Evaluation of Tumor-Induced Osteomalacia , 2018, Clinical nuclear medicine.

[13]  A. Piccardo,et al.  Role of positron emission tomography in thyroid and neuroendocrine tumors. , 2018, Minerva endocrinologica.

[14]  J. Talbot,et al.  Diagnostic performance and impact on patient management of 68Ga-DOTA-TOC PET/CT for detecting osteomalacia-associated tumours , 2018, European Journal of Nuclear Medicine and Molecular Imaging.

[15]  David Moher,et al.  Preferred Reporting Items for a Systematic Review and Meta-analysis of Diagnostic Test Accuracy Studies: The PRISMA-DTA Statement , 2018, JAMA.

[16]  G. Treglia,et al.  Systematic reviews and meta-analyses of diagnostic studies: a practical guideline , 2017, Clinical and Translational Imaging.

[17]  E. Bhatia,et al.  Oncogenic osteomalacia: role of Ga-68 DOTANOC PET/CT scan in identifying the culprit lesion and its management , 2017 .

[18]  N. Thomas,et al.  Musculoskeletal oncogenic osteomalacia-An experience from a single centre in South India. , 2017, Journal of orthopaedics.

[19]  E. Nakakura,et al.  Somatostatin receptor PET/MRI for the evaluation of neuroendocrine tumors , 2017, Clinical and Translational Imaging.

[20]  E. Kebebew,et al.  68Ga-DOTATATE for Tumor Localization in Tumor-Induced Osteomalacia. , 2016, The Journal of clinical endocrinology and metabolism.

[21]  U. Menon,et al.  Utility of Gallium‐68 DOTANOC PET/CT in the localization of Tumour‐induced osteomalacia , 2016, Clinical endocrinology.

[22]  H. Zhuang,et al.  68Ga DOTATATE PET/CT is an Accurate Imaging Modality in the Detection of Culprit Tumors Causing Osteomalacia , 2015, Clinical nuclear medicine.

[23]  S. Bhadada,et al.  Comparison of 18F-FDG and 68Ga DOTATATE PET/CT in Localization of Tumor Causing Oncogenic Osteomalacia , 2015, Clinical nuclear medicine.

[24]  M. Heiland,et al.  68Ga DOTA-TATE PET/CT allows tumor localization in patients with tumor-induced osteomalacia but negative 111In-octreotide SPECT/CT. , 2014, Bone.

[25]  V. Rangarajan,et al.  Functional imaging in primary tumour‐induced osteomalacia: relative performance of FDG PET/CT vs somatostatin receptor‐based functional scans: a series of nine patients , 2014, Clinical endocrinology.

[26]  G. Treglia,et al.  Meta-analyses and systematic reviews on PET and PET/CT in oncology: the state of the art , 2013, Clinical and Translational Imaging.

[27]  A. Gill,et al.  Improving diagnosis of tumor-induced osteomalacia with Gallium-68 DOTATATE PET/CT. , 2013, The Journal of clinical endocrinology and metabolism.

[28]  G. Rindi,et al.  Expression of somatostatin receptors may guide the use of somatostatin receptor imaging and therapy in differentiated thyroid cancer , 2012, Hormones.

[29]  P. Castaldi,et al.  Diagnostic performance of Gallium-68 somatostatin receptor PET and PET/CT in patients with thoracic and gastroenteropancreatic neuroendocrine tumours: a meta-analysis , 2012, Endocrine.

[30]  Susan Mallett,et al.  QUADAS-2: A Revised Tool for the Quality Assessment of Diagnostic Accuracy Studies , 2011, Annals of Internal Medicine.

[31]  Juan Du,et al.  Tumor-induced osteomalacia , 2008, Osteoporosis and sarcopenia.

[32]  Roger M Harbord,et al.  A modified test for small‐study effects in meta‐analyses of controlled trials with binary endpoints , 2006, Statistics in medicine.

[33]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.