Abstract
Background and aim
Calcium-suppressed imaging with dual-energy CT can visualize subtle cellular changes in the bone marrow. The purpose of this study was to investigate the application value of calcium-suppressed images in the evaluation of cancellous bone metastasis treated by stereotactic ablative radiotherapy (SABR).
Patients and methods
Dual-energy CT was performed before and after SABR in 10 patients with cancellous bone metastasis from breast cancer. Signal intensities of cancellous bone metastases to skeletal muscle were compared using calcium-suppressed images.
Results
The relative signal intensity of cancellous bone metastasis before SABR was 0.99 ± 0.02, while after SABR it was 0.95 ± 0.06 (P < 0.05). Visual assessment of the signal intensity of cancellous bone metastases showed a decrease in signal intensity in all cases.
Conclusions
Calcium-suppressed imaging with dual-energy CT may be able to evaluate cancellous bone metastases treated by SABR.
Introduction
Cancellous bone consists of dense trabeculae that traverse the bone marrow-filled medullary cavity. On CT, trabeculae have the same density as cortical bone, but bone marrow has medium to low density. When a solid tumor metastasizes to the bone marrow, it can be difficult to assess cancellous bone metastases on CT due to the mixed density of tumor cells and trabeculae [1]. Dual-energy spectral CT can suppress the high attenuation of the trabeculae, allowing visualization of subtle changes in the underlying attenuation of the bone marrow [2–5]. However, as far as we know, there have been no reports using dual-energy spectral CT for the evaluation of stereotactic ablative radiotherapy (SABR) for cancellous bone metastasis from solid malignancies. In addition, it has never been evaluated in cancellous bone metastases of solid tumors that develop both osteolytic and osteoblastic metastases (e.g., breast cancer). The purpose of this study was to investigate the application value of calcium-suppressed images of dual-energy spectral CT in the evaluation of cancellous bone metastasis treated by SABR.
Patients and methods
Patients
This study was approved by the institutional review board (RO202020), and all procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Ten consecutive female patients with cancellous bone metastases of breast cancer who had undergone SABR at our institution in the past 12 months were included in this study. The median age was 55 years (range, 47–75 years), and all patients had hormone receptor-positive breast cancer, and one of them was also HER2/neu positive. SABR was indicated for five or fewer oligometastases and was allowed concurrent use with aromatase inhibitors, but not with chemotherapy. If multiple cancellous bone metastases were treated with SABR, only the largest lesion was evaluated. The lesions evaluated were the vertebrae (n = 8), ilium (n = 1), and sternum (n = 1).
Radiation treatment planning
CT was used for dose calculation, and short tau inversion recovery (STIR) MRI was used with CT to identify tumors and the surrounding normal structures. A rigid fusion of both CT and STIR MRI was performed by the Monaco software (Elekta Stockholm, Sweden). Gross tumor volume (GTV) was defined on the STIR images and clinical target volume (CTV) was defined as GTV with a 2–3 mm margin. Planning target volume (PTV) was defined as CTV plus a 2–3 mm margin in all directions excluding organs at risk (e.g., spinal cord, intestine, esophagus, stomach). All patients underwent SABR using helical tomotherapy (Hi-ART system, Accuray, Sunnyvale, CA, USA). Prescribed doses were 24–32 Gy in 3–8 fractions, and dose was defined as the minimum dose received by 95% volume (D95%) of PTV. No limit was set on the maximum dose for PTV. D0.1cc (the top dose delivered to a 0.1-ml volume) of the spinal cord was set to be less than 12 Gy.
Evaluation by dual-energy spectral CT
Ipre: Signal intensity of skeletal muscle on calcium-suppressed images before SABR.
Ipost: Signal intensity of skeletal muscle on calcium-suppressed images after SABR.
Regions of interest (ROI) setting. Referring to the single-energy CT images (A), ROIs were defined in the bone metastases (round ROI) and nearby skeletal muscle (square ROI) on the calcium-suppressed images (B). Both single-energy and calcium-suppressed CT was performed before and three months after stereotactic ablative radiotherapy
Citation: Imaging 2023; 10.1556/1647.2023.00127
Regions of interest (ROI) setting. Referring to the single-energy CT images (A), ROIs were defined in the bone metastases (round ROI) and nearby skeletal muscle (square ROI) on the calcium-suppressed images (B). Both single-energy and calcium-suppressed CT was performed before and three months after stereotactic ablative radiotherapy
Citation: Imaging 2023; 10.1556/1647.2023.00127
Regions of interest (ROI) setting. Referring to the single-energy CT images (A), ROIs were defined in the bone metastases (round ROI) and nearby skeletal muscle (square ROI) on the calcium-suppressed images (B). Both single-energy and calcium-suppressed CT was performed before and three months after stereotactic ablative radiotherapy
Citation: Imaging 2023; 10.1556/1647.2023.00127
Visual assessment of the signal intensity of bone metastases was also performed by two certified radiologists using single-energy and calcium-suppressed CT images, who classified the changes in signal intensity after SABR into three categories: increased, same, and decreased.
Statistical analysis
Data were expressed as mean ± standard deviation (SD). Signal intensity of metastatic bone tumors relative to skeletal muscle before and 3 months after SABR was compared using a Wilcoxon signed-rank test. Group differences were considered statistically significant if P < 0.05.
Results
The mean background signal intensity change (∆) after SABR was −0.25% ± 2.6% (range: −7.5%–2.1%). The relative signal intensity of cancellous bone metastasis before SABR was 0.99 ± 0.02, while after SABR it was 0.95 ± 0.06 (P < 0.05) (Fig. 2). Visual assessment of the signal intensity of cancellous bone metastases showed a decrease in signal intensity in all cases (Fig. 3).
Box plots of relative signal intensity of cancellous bone metastasis before and after stereotactic ablative radiotherapy (SABR). Relative Signal intensity decreased significantly after SABR. "×" marks correspond to the means. The central horizontal bars are the medians. The lower and upper limits of the box are the first and third quartiles, respectively. Points above or below the whiskers' lower bounds are outliers
Citation: Imaging 2023; 10.1556/1647.2023.00127
Box plots of relative signal intensity of cancellous bone metastasis before and after stereotactic ablative radiotherapy (SABR). Relative Signal intensity decreased significantly after SABR. "×" marks correspond to the means. The central horizontal bars are the medians. The lower and upper limits of the box are the first and third quartiles, respectively. Points above or below the whiskers' lower bounds are outliers
Citation: Imaging 2023; 10.1556/1647.2023.00127
Box plots of relative signal intensity of cancellous bone metastasis before and after stereotactic ablative radiotherapy (SABR). Relative Signal intensity decreased significantly after SABR. "×" marks correspond to the means. The central horizontal bars are the medians. The lower and upper limits of the box are the first and third quartiles, respectively. Points above or below the whiskers' lower bounds are outliers
Citation: Imaging 2023; 10.1556/1647.2023.00127
A representative case of visual assessment of signal intensity of cancellous bone metastases on calcium-suppressed images. (A) Single-energy CT before stereotactic ablative radiotherapy (SABR). (B) Calcium-suppressed image before SABR. (C) Single-energy CT after SABR. (D) Calcium-suppressed image after SABR. The signal intensity of cancellous bone metastases (arrows) decreased after SABR
Citation: Imaging 2023; 10.1556/1647.2023.00127
A representative case of visual assessment of signal intensity of cancellous bone metastases on calcium-suppressed images. (A) Single-energy CT before stereotactic ablative radiotherapy (SABR). (B) Calcium-suppressed image before SABR. (C) Single-energy CT after SABR. (D) Calcium-suppressed image after SABR. The signal intensity of cancellous bone metastases (arrows) decreased after SABR
Citation: Imaging 2023; 10.1556/1647.2023.00127
A representative case of visual assessment of signal intensity of cancellous bone metastases on calcium-suppressed images. (A) Single-energy CT before stereotactic ablative radiotherapy (SABR). (B) Calcium-suppressed image before SABR. (C) Single-energy CT after SABR. (D) Calcium-suppressed image after SABR. The signal intensity of cancellous bone metastases (arrows) decreased after SABR
Citation: Imaging 2023; 10.1556/1647.2023.00127
Discussion
There are few objective and convenient biomarkers to assess the efficacy of SABR for cancellous bone metastases. Magnetic resonance imaging (MRI) and positron emission tomography (PET) are useful for assessing the effects of radiotherapy, but are not as convenient as CT [6]. This is the first report of quantitative evaluation of cancellous bone metastases of breast cancer treated with SABR using dual-energy spectral CT. The results indicate the possibility of evaluating metastatic cancellous bone tumors even when tumor cells and trabeculae are intermingled within the bone marrow, or there is a mixture of osteolytic and osteoblastic lesions.
There are several interesting aspects to this study. First, all bone metastases evaluated were cancellous bone metastases. In addition, we limited our study to breast cancer that can cause both osteolytic and osteoblastic bone metastases. In the past, there have been a report that has evaluated the efficacy of radiation therapy for osteolytic lesions of multiple myeloma, including long bones as well as flat bones [3], but none have been limited to cancellous bone lesions. Second, the signal intensity of cancellous bone metastases was assessed after being adjusted by the background signal (skeletal muscle in this study). Even in skeletal muscle, where radiation absorption by calcium is negligible, there is a signal intensity change or error of −7.5% to +2.1% on the calcium-suppressed images in this study. This is the first report to quantitatively evaluate cancellous bone metastasis after adjusting for the uncertainties of background signal intensity on calcium-suppressed images. Although the present study was performed using dual-energy spectral CT, it is likely that similar studies will be performed using photon-counting CT in the future as photon-counting CT becomes more widely used [7]. This study has important implications for future research using photon-counting CT.
There are several limitations to this study. First, the number of patients is as small as ten. However, since the purpose of this study is to investigate the value of applying dual-energy spectral CT in cancellous bone metastases treated with SABR, the small number of participants is not a limitation for demonstrating proof-of-principle. Second, incomplete masking and filtering on calcium-suppressed images may limit quantitative evaluation of lesions that show less than 2 mm of bone or greater than 50% sclerosis [8]. To minimize these artifacts and pitfalls in calcium-suppressed images, we applied the background skeletal muscle signal intensity to adjust the lesion signal intensity. In the near future, photon-counting CT may resolve these limitations [9].
In conclusion, although a single preliminary study cannot be generalized to others without further scientific validation, dual-energy spectral CT may be able to evaluate cancellous bone metastases treated by SABR even when osteolytic and osteoblastic metastases and small trabeculae are intermingled within the lesion.
Authors' contribution
Conceptualization: YH, ET. Data curation: YH, ET. Formal analysis: YH, ET. Funding acquisition: N/A. Investigation: YH, ET. Methodology: YH, ET. Project administration: YH, ET. Resources: YH, ET. Software: YH. Supervision: YH. Validation: YH, ET. Visualization: YH, ET. Original draft: YH, ET. Writing - review & editing: YH, ET. All authors reviewed the final version of the manuscript and agreed to submit it to IMAGING for publication.
Conflict of interests
The authors have no conflict of interest to disclose.
Funding sources
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Ethical statement
This study was approved by the institutional review board (RO202020), and all procedures performed in this study were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
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