TRIBUTE Trial

In this prospective, multi-center, observational study, we are looking to evaluate real-world outcomes (e.g., pain, patient reported outcomes, skeletal related events, healthcare utilization, etc.) in patients treated with both percutaneous ablation and palliative radiation therapy (RT) for symptomatic, high-risk metastatic bone lesions.  Our hypothesis is that patients will have an improved combined Complete Response (CR)/Partial Response (PR) pain response rate estimated to be at least 65%.

This US-based study will enroll subjects who have one painful, high-risk, metastatic lesion involving the bone and who are scheduled to be treated with percutaneous ablation and RT.  A total of 120 subjects will be enrolled in this observational study and subjects will be followed out for one year.

Despite the steady decline of death related to cancer over the last 30 years, cancer incidence is on the rise for many common cancers. This increase is largely affected by a rise in diagnoses of 6 of the 10 most common cancers—breast, prostate, endometrial, pancreatic, kidney, and melanoma, as well as the aging and growth of the population. The first-time new cases of cancer in the US are expected to surpass 2 million cases and over 611,000 deaths are project in 2024 for the US. The 5-year relative survival rate for all cancers combined has increased from 49% during the mid-1970s to 69% during 2013–2019¹. 

Most patients with cancer die from metastatic disease. After the lung and liver, the most common site of metastases is bone. Approximately 400,000 new cases of malignant bone metastasis are diagnosed in the United States each year. Bone metastases often cause limb dysfunction, pathological fractures, spinal cord compression, and severe pain, seriously affecting the quality of life of patients with advanced cancer and poor prognoses².

During the past 2 decades, there have been substantial advances in percutaneous image-guided minimally invasive musculoskeletal interventions for the management of cancer.  These interventions are commonly performed in conjunction with or supplemented by adjuvant radiation therapy, chemotherapy, or surgery³.

Combined percutaneous ablation and RT has been used to treat metastatic lung cancer for years and has more recently been studied in the metastatic bone cancer population^4–6.  The combination of these two therapies seems to address the shortcomings of each individual therapy.

Percutaneous ablation and RT have different mechanisms of alleviating pain and causing tumor death that may work synergistically by compensating for the other’s shortcomings. Both RFA and cryoablation are effective in treating osseous metastatic disease, but are dependent on the conduction of energy which dissipates with distance from the probe tip, resulting in decreased efficacy around the tumor edge. Conversely, RT is dependent on oxygen for cytotoxicity and is thought to be deficient in killing centrally located tumor cells that are often hypoxic. 

Multiple studies in this area have shown positive outcomes for patients who undergo combined percutaneous ablation and RT therapies^7,8. 

We hypothesize that patients will have an improved combined CR/PR pain response rate estimated to be at least 65%.

Prospective, single-arm, non-randomized, multi-center, observational, open-label, study with sites in the United States.

Combined partial and complete pain response rate using the Brief Pain Inventory (BPI), worst pain 24-hour recall, at 3 months following percutaneous ablation and palliative RT as defined by International Consensus on Palliative Radiotherapy Endpoints in clinical trials (ICPRE).

• Partial response is defined as pain reduction of 2 or more at the treated site on a scale of 0 to 10 scale without analgesic increase, or analgesic reduction of 25% or more from Baseline without an increase in pain.
• Complete response is defined as a pain score of 0 at the treated site with no concomitant increase in analgesic intake (stable or reducing analgesics in daily OMED).

• Change in PROMIS® Physical Function (-PF) from Baseline to 2 weeks, 3, 6, 9, and 12 months post combined treatment.
• Change in PROMIS® Pain Intensity (-PAIN) from Baseline to 2 weeks, 3, 6, 9, and 12 months post combined treatment.
• Change in PROMIS® Pain Interference (-PI) from Baseline to 2 weeks, 3, 6, 9, and 12 months post combined treatment.
• Partial Response (PR): proportion of subjects with pain reduction of 2 or more from Baseline at the treated site on a scale of 0 to 10 scale without analgesic increase, or analgesic reduction of 25% or more from Baseline without an increase in pain at 2 weeks, 3, 6, 9, and 12 months post combined treatment
• Complete Response (CR): proportion of subjects with pain score of 0 at the treated site with no concomitant increase in analgesic intake (stable or reducing analgesics in daily OMED) at 2 weeks, 3 months, 6 months, 9 months, and 12 months post combined treatment
• Pain Progression (PP): proportion of subjects with an increase in pain score of 2 or more above Baseline at the treated site with stable OMED or an increase of 25% or more in OMED compared with Baseline with a pain score stable or 1 point above Baseline at 2 weeks, 3, 6, 9, and 12 months post combined treatment
• Indeterminate Response (IR): proportion of subjects with any response that is not captured by the complete response, partial response, or pain progression definitions
• Time to best pain response by PROMIS®-PAIN and BPI Score
• Time to pain relapse (≥ 2-point increase from nadir) by PROMIS®-PAIN and BPI Score
• Change in OMED and pain medication usage from Baseline through 12 months
• Treatment related Serious Adverse Event (SAE) rates after combined therapy through 12 months post treatment
• Treatment related Skeletal Related Event (SRE) rates after combined therapy through 12 months post treatment
• Pain related admission rate through 12 months related to treated tumor
• Patient reported COST-FACIT scores of financial toxicity from Baseline through 12 months
• Change in SOC imaging (e.g., CT, PET/CT, MRI) response at 3, 6, 9, and 12 months

This study is supported by grants funded by the following industry partners:
 

Exclusive Pioneer Trial Partner

Advocate Trial Partner

Catalyst Trial Partner
 

First-line therapy for patients with symptomatic skeletal metastases currently includes palliative radiation therapy. Although responses can be durable in a subset of patients, most patients do not achieve complete relief from pain, particularly among those with radioresistant tumors.  Additionally, increasing radiation doses are associated with increased risk of skeletal events such as vertebral compression fracture and can limit additional radiation therapy to the target lesion and or adjacent lesions especially in the spine. Percutaneous ablation offers a high rate of local pain control that is rapid and durable but, however, is not effective in all patients and can be limited by proximity to nerves or other critical structures.

Palliative radiation therapy and percutaneous ablation are standard-of-care (SOC) therapies which are commonly employed concurrently with the aim of improving symptom relief and durability, which may minimize treatment-related complications and healthcare utilization⁹. Furthermore, the NCCN Guidelines for Adult Cancer Pain states that the synergistic effect of radiation combined with ablation may prove to be complimentary¹⁰.

Though research has been conducted to study the outcomes of combined percutaneous ablation and RT, additional research is required to bolster the evidence on patients who undergo this combined treatment.

This observational study aims to evaluate real-world outcomes (e.g., pain, patient reported outcomes, skeletal related events, healthcare utilization, etc.) in a real-world patient population treated with both percutaneous ablation and palliative RT.

1. Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024;74(1):12-49. doi:10.3322/caac.21820
2.  Jiang W, Rixiati Y, Zhao B, Li Y, Tang C, Liu J. Incidence, prevalence, and outcomes of systemic malignancy with bone metastases. J Orthop Surg. 2020;28(2):230949902091598. doi:10.1177/2309499020915989
3. Tomasian A, Filippiadis DK, Tutton S, et al. Comprehensive Palliative Musculoskeletal Interventional Radiology Care for Patients with Cancer. RadioGraphics. 2022;42(6):1654-1669. doi:10.1148/rg.220009
4. Grieco CA, Simon CJ, Mayo-Smith WW, DiPetrillo TA, Ready NE, Dupuy DE. Percutaneous Image-guided Thermal Ablation and Radiation Therapy: Outcomes of Combined Treatment for 41 Patients with Inoperable Stage I/II Non–Small-Cell Lung Cancer. J Vasc Interv Radiol. 2006;17(7):1117-1124. doi:10.1097/01.RVI.0000228373.58498.6E
5. Dupuy DE, DiPetrillo T, Gandhi S, et al. Radiofrequency Ablation Followed by Conventional Radiotherapy for Medically Inoperable Stage I Non-small Cell Lung Cancer. Chest. 2006;129(3):738-745. doi:10.1378/chest.129.3.738
6. Steber CR, Hughes RT, Urbanic J, et al. Long-Term Outcomes From a Phase 2 Trial of Radiofrequency Ablation Combined With External Beam Radiation Therapy for Patients With Inoperable Non-Small Cell Lung Cancer. Int J Radiat Oncol. 2021;111(1):152-156. doi:10.1016/j.ijrobp.2021.04.020
7. Di Staso M, Zugaro L, Gravina GL, et al. A feasibility study of percutaneous radiofrequency ablation followed by radiotherapy in the management of painful osteolytic bone metastases. Eur Radiol. 2011;21(9):2004-2010. doi:10.1007/s00330-011-2133-3
8. Di Staso M, Gravina GL, Zugaro L, et al. Treatment of Solitary Painful Osseous Metastases with Radiotherapy, Cryoablation or Combined Therapy: Propensity Matching Analysis in 175 Patients. Sung SY, ed. PLOS ONE. 2015;10(6):e0129021. doi:10.1371/journal.pone.0129021
9. Filippiadis DK, Yevich S, Deschamps F, Jennings JW, Tutton S, Kelekis A. The Role of Ablation in Cancer Pain Relief. Curr Oncol Rep. 2019;21(12):105. doi:10.1007/s11912-019-0844-9
10. National Comprehensive Cancer Network. Adult Cancer Pain (Version 1.2024). http://www.nccn.org/professionals/physician_gls/pdf/adultcancerpain.pdf. Accessed February 2, 2024.

• 31 January 2025: SIO Announces Second Clinical Trial with Transformative Industry Support