Background: Breast cancer has been the subject of many recent studies because it is a significant cause of death in women. This study was performed to clarify whether solitary skeletal metastasis has clinical significance compared with multiple skeletal metastasis. Patients and methods: Seven hundred and three patients who developed metastatic bone lesions up to September 2002 after beginning treatment for breast cancer from 1988 to 1998 were included. The lesions were classified first as solitary or multiple based on bone scan results and then according to anatomical distribution. Next, solitary-to-multiple conversion was investigated in patients with solitary skeletal metastasis. Then factors related to solitary or multiple skeletal metastasis were analyzed. The prognosis of skeletal metastasis was compared between patients with solitary or multiple metastatic bone lesions. A Cox proportional hazards model was used to test whether solitary skeletal metastasis compared with multiple skeletal metastasis was an independent factor of survival. Results: Two hundred and eighty-nine patients (41%) had solitary skeletal metastasis and 414 patients (59%) showed multiple skeletal metastasis. The sternum was a frequent site for solitary skeletal metastasis (98 of 289, 34%), while other skeletal sites were more frequent in patients with multiple metastatic bone lesions (P <0.001). Solitary sternal metastatic lesions remained solitary longer than solitary metastatic bone lesions to places other than the sternum (P <0.001), but did not lengthen patient survival times (P = 0.871). The factors related to solitary skeletal metastasis are TNM stage (tumor–node–metastasis) and histology. The patients with earlier stage and favorable histology tend to have solitary skeletal metastasis. The patients with solitary skeletal metastasis lived longer than those with multiple metastatic bone lesions (P <0.001). Multivariate analysis revealed that a solitary metastatic bone lesion (P = 0.002) is an independent favorable prognostic factor in patients with skeletal metastasis. Conclusions: Solitary skeletal metastasis has a different anatomical distribution and is an independent prognostic factor in patients with skeletal metastasis.

Objectives To establish a new three-dimensional quantitative evaluation method for bone metastasis, we applied bone single photon emission tomography with computed tomography (SPECT/CT). The total bone uptake (TBU), which measures active bone metastatic burden, was calculated as the sum of [mean uptake obtained as standardized uptake value (SUV) above a cut-off level] × (the volume of the lesion) in the trunk using bone SPECT/CT. We studied the threshold value and utility of TBU in prostate cancer patients treated with radium-223 (Ra-223) therapy. Methods To establish the threshold value of TBU, we compared bone metastatic and non-metastatic regions in 61 prostate cancer patients with bone metastasis and 69 without. Five fixed sites in each patient were selected as evaluation points and divided into bone metastatic and non-metastatic sites. Sensitivity and specificity analysis was applied to establish the threshold level. Using the obtained threshold value, we then calculated the TBU in nine prostate cancer patients who received Ra-223 therapy, and compared the results with the bone scan index (BSI) by BONENAVI^® and visual evaluation of bone scintigraphy. Results Uptake was significantly lower in non-metastatic sites in patients with bone metastasis than in patients without metastasis. Sensitivity and specificity analysis revealed SUV = 7.0 as the threshold level. There was a discrepancy between TBU and BSI change in two of the nine patients, in whom TBU change correlated with visual judgement, but BSI change did not. In two patients, BSI was nearly 0 throughout the course, but the TBU was positive and changed, although the change was not large. These results suggest that TBU may be more accurate and sensitive than BSI for quantitative evaluation of active bone metastatic burden. Conclusion We established a threshold value (SUV > 7.0) for three-dimensional TBU for evaluating active bone metastatic burden in prostate cancer patients using bone SPECT/CT. Despite the small number of patients, we expect the change in TBU could be more accurate and sensitive than the change in BSI among patients who received Ra-223.

Background: Two novel methods of image reconstruction, xSPECT Quant (xQ) and xSPECT Bone (xB), that use an ordered subset conjugate gradient minimizer (OSCGM) for SPECT/CT reconstruction have been proposed. The present study compares the performance characteristics of xQ, xB, and conventional Flash3D (F3D) reconstruction using images derived from phantoms and patients. Methods: A custom-designed body phantom for bone SPECT was scanned using a Symbia Intevo (Siemens Healthineers), and reconstructed xSPECT images were evaluated. The phantom experiments proceeded twice with different activity concentrations and sphere sizes. A phantom with 28-mm spheres containing a ^99mTc-background and tumor-to-normal bone ratios (TBR) of 1, 2, 4, and 10 were generated, and convergence property against various TBR was evaluated across 96 iterations. A phantom with four spheres (13-, 17-, 22-, and 28-mm diameters), containing a ^99mTc-background at TBR4, was also generated. The full width at half maximum of an imaged spinous process (10 mm), coefficients of variance (CV), contrast-to-noise ratio (CNR), and recovery coefficients (RC) were evaluated after reconstructing images of a spine using Flash 3D (F3D), xQ, and xB. We retrospectively analyzed images from 20 patients with suspected bone metastases (male, n = 13) which were acquired using [^99mTc]Tc-(H)MDP SPECT/CT, then CV and standardized uptake values (SUV) at the 4^th vertebral body (L4) were compared after xQ and xB reconstruction in a clinical setup. Results: Mean activity concentrations with various TBR converged according to increasing numbers of iterations. The spatial resolution of xB was considerably superior to xQ and F3D, and it approached almost the actual size regardless of the iteration numbers during reconstruction. The CV and RC were better for xQ and xB than for F3D. The CNR peaked at 24 iterations for xQ and 48 iterations for F3D and xB, respectively. The RC between xQ and xB significantly differed at lower numbers of iterations but were almost equivalent at higher numbers of iterations. The reconstructed xQ and xB images of the clinical patients showed a significant difference in the SUV_max and SUV_peak. Conclusions: The reconstructed xQ and xB images were more accurate than those reconstructed conventionally using F3D. The xB for bone SPECT imaging offered essentially unchanged spatial resolution even when the numbers of iterations did not converge. The xB reconstruction further enhanced SPECT image quality using CT data. Our findings provide important information for understanding the performance characteristics of the novel xQ and xB algorithms.

We recently showed that increased urinary excretion of the cross-linked, nonisomerized form of the C-telopeptide of collagen type I (ααCTX) could be a sensitive indicator of the presence of bone metastases in breast cancer patients. The present study was sought to investigate (a) the localization of αCTX epitopes in the proximity of a bone metastasis and (b) the relationship between number of metastases and the urinary excretion of ααCTX. Adjacent bone sections from breast cancer patients were stained for the presence of tumor cells (anti-cytokeratin antibody), osteoclasts (TRAcP activity), and αCTX (anti-αCTX antibody). The association between the extent of metastatic bone disease and urinary excretion of ααCTX measured with ELISA was assessed in 90 breast cancer patients (45 with bone metastasis and 45 without bone metastasis). Immunohistochemistry revealed accumulation of TRAcP-positive osteoclasts and intense staining for αCTX epitopes in the proximity of cytokeratin-positive bone metastasis. Areas of αCTX staining showed unstructured bone tissue under polarized light. In addition, there was a significant linear association between the number of bone metastases and the urinary levels of ααCTX in breast cancer patients with metastatic bone disease, independent of age and body mass index (r = 0.56, P < 0.001). The estimated relative increases in ααCTX associated with the presence of one, two, or three metastases are 38%, 57%, and 81%, respectively. Taken into account the 17% intraindividual variation of the assay, ααCTX could be a sensitive biochemical marker for the close monitoring of cancer patients aiming the facilitation of early metastasis detection. (Cancer Epidemiol Biomarkers Prev 2006;15(7):1392–5)