Multimodality Image-Guided Cryoablation for Inoperable Tumor-Induced Osteomalacia

Abstract

Tumor-induced osteomalacia (TIO) is a debilitating paraneoplastic condition caused by small phosphaturic mesenchymal tumors (PMTs) that secrete large amounts of the phosphate-regulating and vitamin D-regulating hormone, FGF23. Tumor removal results in cure. However, because of high perioperative comorbidity, either from tumor location or host factors, surgery is sometimes not an option. Tumor destruction via cryoablation may be an effective option for inoperable PMTs. Three subjects with a confirmed diagnosis of TIO were studied. All three underwent cryoablation of suspected PMTs rather than surgery due to significant medical comorbidities or challenging anatomical location. Subject 3 had tumor embolization 24 hours prior to cryoablation because of the size and hypervascularity of the tumor. The success of the tumor cryoablation was defined by normalization of serum phosphate and FGF23. Cryoablation resulted in a rapid decrease in plasma intact FGF23 by 24 hours postprocedure in all three subjects (0, 2, and 9 pg/mL, respectively) with normalization of blood phosphate by postprocedure day 3. Three-day renal tubular reabsorption of phosphate increased to 76%, 94%, and 95.2%, respectively; 1, 25(OH)₂ vitamin D increased to 84, 138, and 196 pg/ml, respectively. All three had dramatic clinical improvement in pain and weakness. Two subjects tolerated the procedure well with no complications; one had significant prolonged procedure-related localized pain. Although surgery remains the treatment of choice, cryoablation may be an effective, less invasive, and safe treatment for patients with difficult to remove tumors or who are poor surgical candidates. © 2017 American Society for Bone and Mineral Research.

Keywords: CRYOABLATION; FGF23; TIO; TUMOR-INDUCED OSTEOMALACIA.

Figure 1

Localization studies subject 1: Panel A. FDG-PET coronal (A1) and sagittal image (A2) showing artifact from rod (orange arrow) and culprit tumor (white arrow). Panel B: Coronal view of FDG-PET scan localizing the lesion (white arrow), femoral head (yellow arrow) and rod (orange arrow). Panel c: Axial view of FDG-PET/CT fusion imaging localizing the lesion-white arrows point the tumor, yellow arrow points the femoral shaft and orange arrow points the side plate. Panel D. Selective venous sampling for intact FGF23. There was a significant step-up in FGF23 concentration as the suspected tumor venous drainage was approached anatomically. Panel E. CT-Scan sagittal view showing sternal collapse (white arrow), kyphosis (orange arrow), vertebral compression fractures (yellow arrow) and restrictive lung disease (asterisk).

Figure 2

Panels A1–A2 demonstrate cryoablation path in subject 1. Panels B1–B2 demonstrate cryoablation path in subject 2. Panels C1–C2 demonstrate cryoablation path in subject 3. * (asterisk) demonstrates cryoablation path in all the panels.

Figure 3

Biochemical changes in response to treatment. iFGF23, Phosphorus and 1, 25 (OH₂) Vitamin D are plotted on vertical axis and day relative to the treatment is plotted on horizontal axis. In all the patients, iFGF23 levels dropped below the normal range by day 1 after cryoablation, Phosphorous returned to normal by day 3 and remained normal at follow up. 1, 25 (OH₂) vitamin D levels showed the typical supraphysiologic rebound that is seen in TIO after tumor removal. Subject 3, was the subject who underwent embolization prior to ablation, and showed a large decrease in FGF23 following embolization, which went to undetectable after cryoablation. The patient was placed on IV phosphate replacement overnight before proceeding to cryoablation. Gray shadows indicate normal ranges. NA = Data not available.

Figure 4

Localization studies subject 2: Panels A, B: FDG PET demonstrating positive uptake in left proximal femur (white arrows). Panel C: Skull image demonstrating calcified duramater (yellow arrows). D. Orange arrows demonstrating calcified posterior longitudinal ligament in cervical spine area indicating the long-standing hypophosphatemia. E. Selective venous sampling for iFGF23. There was a significant step-up in iFGF23 concentration as the suspected tumor venous drainage was approached anatomically (lower left common and circumflex femoral veins).

Figure 5

Localization studies subject 3: Panels A, B, C: Ga⁶⁸ DOTATATE isotopic uptake in right ischium corresponding to the right ischial mass. Panel D: MRI of the pelvis confirmed the ischial location. Panel E. CT scan coronal view of pelvis confirmed the lesion location in right ischium budding the acetabulum. Panel F. Selective venous sampling for intact FGF23. There was a significant step-up in FGF23 concentration as the suspected tumor venous drainage was approached anatomically.