Transarterial Chemoembolization for the Palliation of Painful Bone Metastases Refractory to First-Line Radiotherapy

Clinical question
How do the efficacy and safety of transarterial chemoembolization (TACE) compare with re-radiotherapy (re-RT) in the palliative treatment of radiotherapy (RT)-failure bone metastases (BMs).

Take-away point
TACE achieved a superior response rate and longer duration of palliation in symptomatic RT-failure BMs without adverse events.

Reference
Heianna, J, Makino, W, Toguchi, M, et al. Transarterial Chemoembolization for the Palliation of Painful Bone Metastases Refractory to First-Line Radiotherapy. J Vasc Interv Radiol. 2021;32(3):384-392

Click here for abstract

Study design
Retrospective cohort study

Funding source
Self-funded or unfunded

Setting
Single institution, University of Ryukyus

Figure

Figure 2. A 63-year-old woman with radiotherapy (RT)-failure bone metastasis (BM) of the third thoracic spine from thyroid cancer who underwent transarterial chemoembolization. (a) T2-weighted magnetic resonance imaging showing severe spinal cord compression due to spinal BM. (b) Thoracic contrast-enhanced CT showing spinal cord compression due to BM (black and white arrow). (c) Localized intraoperative cone-beam CT of the left costocervical artery showing enhancement corresponding to the lesion (white arrows). (d) Selective angiography of the left costocervical artery showing a tumor blush corresponding to the lesion (black arrow). The vessel, which dorsally extends from the left costocervical artery (broken arrow), nourished the dorsal skin, as observed via angiography (no image). (e) After transarterial chemoembolization, selective angiography of the left costocervical artery shows the disappearance of the tumor blush in the upper left half of the lesion. The arrowheads indicate microcoils placed at the proximal part of the abovementioned branch vessel to prevent anticancer agent inflow and embolic material migration to the skin and muscle. (f) Thoracic contrast-enhanced CT images performed 1 month after transarterial chemoembolization showing the shrinkage of the BM with the resolution of spinal cord compression. This lesion was judged to have partially responded due to a tumor reduction rate of 40%.

Summary

Radiotherapy (RT) has been shown to be effective in treating pain caused by bone metastases (BMs) in a majority of patients. Unfortunately, recurrent pain from BM regrowth has been shown to occur in up to 50% of cases. In cases where palliative surgical excision of painful tumors is contraindicated, re-radiotherapy (re-RT) has been employed, but data demonstrates pain relief in only 58% of patients. Transarterial embolization (TACE), normally employed to reduce intraoperative bleeding, has been shown in isolated reports to temporarily reduce pain due to BMs in most patients. Its primary use for palliative treatment of BM pain, however, has not been established.

In this retrospective cohort study, 50 patients with RT-refractory BMs across various primary tumor locations who underwent a second therapy over a 6-year period were analyzed. 23 patients (46%) underwent repeat RT while 27 patients (54%) underwent TACE. All patients had severe pain after initial therapy and had disease that were refractory to medical therapy or analgesia and were surgically unresectable. Indication for TACE included predicted cumulative dose greater than 120 Gy2 after re-RT as well as hypervascular bone tumors with adequate bone marrow, hepatic, and renal function. Patients also needed an Eastern Cooperative Oncology Group performance status of ≤3. Patient demographics with statistically similar, including Katagiri score, which predicts survival of patients with BMs. Both re-RT and transarterial chemoemolization were performed with consistent methods between patients at a single center, although a variety of different chemotherapeutics were employed based on the primary cancer type. Measured outcomes included technical success, index lesion pain assessment within 2 weeks and at regular follow-up appointments, disease progression by imaging, and adverse events. Pain was assessed using a Numerical Rating Scale (NRS) to rate pain from 0 (no pain) to 10 (worst pain).

Primary tumor types included gastrointestinal (24%), urogenital (22%), head and neck (18%), sarcoma (16%), gynecological (10%), lung (4%), breast, thymus, and gastrointestinal stromal tumors (2%). 66% of patients had intermediate-risk Katagiri prognostic scores. TACE group tumors had a median diameter of 95 mm compared to 78 mm in the re-RT group (p = 0.04). Median initial RT dose to the lesion was 33 Gy in the re-RT group and 42 Gy in the TACE group (p = 0.003). NRS scores prior to treatment were 10 in all patients analyzed.

Technical success was achieved in 24 of 27 chemoembolization cases (89%). 1 treatment failure resulting from the tumor being fed by the anterior spinal artery while 2 failures were the result of difficult catheterizations secondary to atherosclerotic plaque burden. Pain relief was achieved in 92% and 57% of TACE and re-RT patients respectively (p = 0.006) with a median relief rate of 3 and 2 months respectively (p = 0.02). Median NRS scores were 3 in the TACE group and 7 in the re-RT group (p < 0.001). Median hospital stay was 1 day in the TACE group and 14 days in the re-RT group (p < 0.001). Pain-free survival at 6 months was 51% in the TACE group and 30% in the re-RT group (p = 0.08), but the difference was not statistically significant.

There were no significant adverse events recorded in the TACE cohort, including nerve injury, skin necrosis, muscle abscess, or death. Grade 3/4 leukopenia was observed in 4 (14%) re-RT patients and no TACE patients (p = 0.16). Grade 3/4 thrombocytopenia was observed in 2 (7%) re-RT patients and no TACE patients (p = 0.54). No patients in either cohort required blood transfusions. One (4%) patient experienced transient nausea after TACE.

Commentary

This study provides a comparison between the use of re-RT and TACE in patients undergoing subsequent therapy for painful BMs after initial RT. Despite its limited study size, the investigation demonstrated statistically-significant increase in time without pain in addition to decrease in hospital stay enjoyed by patients undergoing TACE versus re-RT. It also demonstrated a paucity of adverse events, signaling that this procedure is a safe alternative to RT when applicable. This study is limited, however, due to small sample size, making it difficult to draw comparisons between different types of primary cancer sources. There also exists a difference in tumor qualities between groups, including the required hypervascularity in TACE-treated BMs versus the BMs treated with re-RT. The promising reduction in pain over longer periods and decreased hospital stays, however, preliminarily suggest that TACE is a valuable treatment modality for BM pain control in a palliative care setting. Larger multicenter trials will not only elucidate a higher-resolution safety profile for TACE, but will also establish its efficacy on a larger scale.

Post Author
Jared Edwards, MD
General Surgery Intern (PGY-1)
Department of General Surgery
Naval Medical Center San Diego, San Diego, CA

@JaredRayEdwards