We retrospectively reviewed relevant data of patients treated with local RT for bone metastases between 2013 and 2019, and we selected 51 patients whose bone metastases had been confirmed by computed tomography (CT) or magnetic resonance imaging (MRI) and who had also undergone BS. This study was approved by our institutional Review Board; informed consent was obtained from all patients. We have read the Declaration of Helsinki and followed its guidelines in this investigation. The clinical data of all 51 patients are summarized in Table 1. Age at the time of BS ranged from 32 to 85 years (median 66 years) and there were 33 men (64.7%) and 18 women (35.3%). The most common primary tumor was lung cancer (21 patients, 41.2%) and the second most common liver (nine patients, 17.6%). Seven patients had solitary bone metastasis (13.7%) and 44 multiple bone metastases (86.3%). According to the CT findings, bone metastases were classified into the following three types (14, 15): osteoblastic (n = 6, 11.8%), osteolytic (n = 15, 29.4%), and mixed (n = 30, 58.8%). Concurrent visceral metastases were detected in 36 patients (70.6%).
Table 1
Characteristics of patients treated with radiation therapy for bone metastasis
Characteristics | n = 51 (%) |
Age at the time of bone scintigraphy, median years (range) | 66 (32–85) |
Gender | |
Male | 33 (64.7) |
Female | 18 (35.3) |
Primary tumor site | |
Lung | 21 (41.2) |
Liver | 9 (17.6) |
Kidney | 4 (7.7) |
Bile duct | 3 (5.8) |
Pancreas | 2 (3.9) |
Colon | 2 (3.9) |
Ovary | 2 (3.9) |
Thyroid | 1 (2.0) |
Stomach | 1 (2.0) |
Gallbladder | 1 (2.0) |
Uterine body | 1 (2.0) |
Uterine cervix | 1 (2.0) |
Bladder | 1 (2.0) |
Bone | 1 (2.0) |
Unknown | 1 (2.0) |
Number of bone metastasis | |
Solitary | 7 (13.7) |
Multiple | 44 (86.3) |
Type of bone metastasis | |
Osteoblastic | 6 (11.8) |
Osteolytic | 15 (29.4) |
Mixed | 30 (58.8) |
Bone scan index, mean % (range) | 2.50 (0.00-11.86) |
Visceral metastasis | |
Yes | 36 (70.6) |
No | 15 (29.4) |
Systemic chemotherapy before RT | |
Yes | 25 (49.0) |
No | 26 (51.0) |
Performance status at RT | |
0, 1 | 33 (64.7) |
2, 3, 4 | 18 (35.3) |
RT dose, median Gy (range) | 30 (6–40) |
Abbreviations: RT, radiation therapy. |
Bone scintigraphy
Each patient was injected with 740 MBq of 99mTc-methylene diphosphonate (Fujifilm RI Pharma, Tokyo, Japan) or 99mTc-hydroxymethylene diphosphonate (Nihon Medi-Physics, Tokyo, Japan). Whole-body scintigraphy was performed ≥ 3.5 hours after the administration, using a gamma camera at a speed of 12 or 13.3 cm/min with a low-energy high-resolution collimator, 512 × 1024 or 256 × 1024 matrix size, zoom factor 1.00, and 139 keV photopeak with 20% window or 140.5 keV photopeak with 10% window. One of the following two gamma camera units was used; Forte (Philips Japan, Tokyo, Japan) or Discovery NM/CT 670 (GE Healthcare Japan, Tokyo, Japan). Raw image data were transferred to a PC with VSBONE BSI software and analyzed.
VSBONE BSI
The database of VSBONE BSI comprises data of pairs of anterior and posterior BS images of Japanese patients with prostate cancer (16, 17). Additionally, skeletal segmentation from 246 patients with prostate cancer and hot spot extraction from 896 patients with prostate cancer were performed, using a butterfly-type network of fully convolutional networks. Fully convolutional networks have no threshold for hot spots unlike ANN. Hot spots suspected of being metastases are depicted in red, whereas lesions suspected of being false positives are depicted in blue. From these, the BSI is automatically calculated. The BSI of the 51 patients in this study ranged from 0.00–11.86% (mean 2.50%).
Radiation therapy
Systemic chemotherapy was administered to 25 patients (49.0%) after BS and prior to commencing RT. RT was performed to relieve pain or to prevent or improve spinal cord paralysis. Performance status (PS) at the start of RT was evaluated according to the Eastern Cooperative Oncology Group criteria (18). There were 33 patients with PS ≤ 1 (68.7%) and 18 with PS ≥ 2 (35.3%). Ten patients received irradiation to multiple sites in one treatment session and eight received irradiation in multiple sessions, the total RT dose ranging from 6 to 40 Gy (median 30 Gy).
Statistical analysis
SPSS version 21.0 (IBM, Armonk, NY, USA) was used for statistical analysis. To identify variables associated with high BSI, univariate analysis with the Mann–Whitney U test was performed using the following patient characteristics: age at BS (median <66 years vs. ≥66 years), sex, primary tumor site (lung cancer vs. other tumors), number of bone metastases (solitary vs. multiple), and type of bone metastasis (osteolytic vs. others). The Kaplan–Meier method was used to calculate the probability of overall survival (OS) from the date of BS. Differences in survival between subgroups of patients according to BSI (< mean 2.50% vs. ≥ mean), visceral or brain metastases at BS (yes vs. no), systemic chemotherapy before RT (yes vs. no), PS at RT (0, 1 vs. 2, 3, 4), and the above mentioned variables were analyzed using Mantel’s log-rank test and multivariate analyses Cox proportional hazard model. A P value of < 0.05 was considered to denote statistical significance.