Factors affecting local control of bone metastases from radioresistant tumors treated with palliative external beam radiotherapy

Abstract

Background This study aimed to evaluate the factors that affect the local control (LC) of bone metastases from radioresistant carcinomas (renal cell carcinoma, hepatocellular carcinoma [HCC], and colorectal carcinoma [CRC]) treated with palliative external-beam radiotherapy (EBRT). Methods and materials Between January 2010 and December 2020, 211 bone metastases in 134 patients were treated with EBRT in two hospitals (a cancer center and university hospital). Based on follow-up CT, these cases were reviewed retrospectively to evaluate LC at the EBRT site. Results The median EBRT dose (BED10) was 39.0 Gy (range, 14.4–66.3 Gy). The median follow-up time of the imaging studies was 6 months (range, 1–107 months). The 0.5-year overall survival and LC rates of the EBRT sites were 73% and 73%, respectively. Multivariate analysis revealed that the primary sites (HCC/CRC), low EBRT dose (BED10) (≤ 39.0 Gy), and non-administration of post-EBRT bone modifying agents (BMAs) and/or antineoplastic agents (ATs) were statistically significant factors that negatively affected the LC of EBRT sites. In the absence of BMAs or ATs, the EBRT dose (BED10) escalation from 39.0 Gy improved the LC of EBRT sites. Based on ATs administration, the LC of EBRT sites was significantly affected by tyrosine kinase inhibitors and/or immune checkpoint inhibitors. Conclusions Dose escalation improves LC in bone metastases from radioresistant carcinomas. Higher EBRT doses are needed to treat patients for whom few effective systemic therapies remain available.

Predictive Factors and the Role of Conventionally Fractionated Radiation Therapy for Bone Metastasis from Renal Cell Carcinoma in the Era of Targeted Therapy

“…Recently reported studies for bone metastasis from RCC are consistent with our improved treatment outcomes compared to early studies [22,23]; however, regarding the potential synergistic effect of combined targeted therapy, heterogeneous results were observed. Makita et al evaluated the palliative CF-RT effect on radioresistant carcinoma, including RCC; the 12-month LC rate was 62%, and the administration of TKIs was associated with improved LC in multivariate analysis (HR 2.19, p = 0.010) [22]. Lee et al reported the outcome of spinal metastases from RCC treated with CF-RT [23]; the 12-month LC rate was 87.5%, and the use of TKIs was the only independent predictor of improved overall survival (HR 0.47, p = 0.050).…”

“…Therefore, the addition of CF-RT appeared to initiate a treatment response and prolong the duration of nivolumab treatment [21]. Recently reported studies for bone metastasis from RCC are consistent with our improved treatment outcomes compared to early studies [22,23]; however, regarding the potential synergistic effect of combined targeted therapy, heterogeneous results were observed. Makita et al evaluated the palliative CF-RT effect on radioresistant carcinoma, including RCC; the 12-month LC rate was 62%, and the administration of TKIs was associated with improved LC in multivariate analysis (HR 2.19, p = 0.010) [22].…”

“…Several studies have evaluated the relationship between radiation dose and LC, showing heterogeneous results. Makita et al found that an elevated CF-RT dose has a significant impact on the 12-month LC rate (55% vs. 84%, p = 0.02) [22]. However, elevated doses did not show an additional LC benefit in other studies [15,26,27].…”