Bone Metastases, Metastatic Solid Tumor
Conditions
Keywords
prophylactic radiotherapy, early radiotherapy
Brief summary
This is a prospective, randomized, single-center clinical trial evaluating whether early prophylactic radiotherapy to high-risk asymptomatic or minimally symptomatic bone metastases reduces the 1-year rate of skeletal-related events (SREs) in patients with metastatic solid cancers. Patients will be randomized in a 1:1 ratio to receive either standard of care systemic therapy or observation, or prophylactic radiotherapy in addition to standard of care. The primary endpoint is the 1-year rate of SREs. Secondary endpoints include adverse events, quality of life, economic burden, pain-free survival, and overall survival.
Detailed description
Bone metastases are a common complication in patients with metastatic solid cancers and are associated with significant morbidity, including skeletal-related events (SREs) such as pathological fractures, spinal cord compression, and severe pain requiring intervention. While palliative radiotherapy is an established treatment for symptomatic bone metastases, the role of prophylactic radiotherapy in asymptomatic or minimally symptomatic high-risk lesions remains insufficiently defined. This prospective, randomized, single-center phase II clinical trial evaluates the effectiveness of early prophylactic radiotherapy in reducing the incidence of SREs. Eligible patients with metastatic solid cancers and up to five high-risk asymptomatic or minimally symptomatic bone metastases will be randomized in a 1:1 ratio into two groups. The control group will receive standard of care systemic therapy or observation according to tumor type and clinical guidelines. The intervention group will receive prophylactic external-beam radiotherapy (25 Gy in 5 fractions) to selected high-risk bone metastases in addition to standard of care. Patients will be followed from baseline up to 12 months, with assessments conducted at predefined intervals. Study outcomes include the incidence of SREs, adverse events (graded according to CTCAE), patient-reported outcomes using validated questionnaires (EORTC QLQ-C30, EQ-5D-5L, BPI), economic burden, pain-free survival, and overall survival. This study aims to determine whether early radiotherapy intervention can prevent skeletal complications, reduce healthcare burden, and improve patient outcomes in metastatic bone disease.
Interventions
RADIATIONProphylactic External Beam Radiotherapy
External beam radiotherapy delivered to up to five high-risk asymptomatic or minimally symptomatic bone metastases at a total dose of 25 Gy in 5 fractions.
OTHERStandard of Care
Systemic therapy or observation according to tumor type and clinical guidelines.
Sponsors
Institute of Oncology Ljubljana
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Masking description
This is an open-label study due to the nature of the intervention (radiotherapy), which does not allow blinding of participants or investigators.
Intervention model description
Participants are randomized in a 1:1 ratio to one of two parallel groups: 1. standard of care systemic therapy or observation, or 2. prophylactic external-beam radiotherapy in addition to standard of care systemic therapy or observation.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Histologically confirmed solid malignancy * Metastatic disease confirmed by imaging (CT, MRI, or PET-CT) * Presence of up to five high-risk bone metastases * High-risk bone metastases defined according to protocol criteria * Asymptomatic or minimally symptomatic bone metastases (not requiring opioid analgesics) * ECOG performance status 0-2 * Ability to provide written informed consent
Exclusion criteria
* Prior radiotherapy to the index bone metastases preventing safe treatment planning * Symptomatic bone metastases requiring immediate palliative radiotherapy * Evidence of spinal cord compression * Bone metastases causing significant pain requiring opioid analgesics * Oligometastatic disease suitable for radical treatment * Leptomeningeal disease * ECOG performance status ≥3 * Life expectancy less than 3 months * Any condition that, in the investigator's opinion, would interfere with study participation or assessment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 1-year rate of skeletal-related events (SREs) | From randomization to 12 months after randomization | Number of participants experiencing at least one skeletal-related event (pathological fracture, spinal cord compression, need for radiation to bone, need for surgery to bone, or tumor-related hypercalcemia) within 12 months after randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of adverse events | Up to 12 months after randomization | Adverse events assessed and graded according to CTCAE version 6.0 |
| EORTC QLQ-C30 global health status score | Baseline, 3 months, 6 months, and 12 months after randomization | EORTC QLQ-C30 global health status score at each assessment time point (range: 0-100; higher scores indicate better quality of life). |
| EQ-5D-5L index score | Baseline and follow-up visits up to 12 months after randomization | EQ-5D-5L index score at each assessment time point (range typically from \<0 to 1; higher values indicate better health status). |
| Brief Pain Inventory (BPI) pain intensity score | Baseline and follow-up visits up to 12 months after randomization | Pain intensity score measured using the Brief Pain Inventory (scale 0-10; higher scores indicate worse pain). |
| Pain-free survival | From randomization to 12 months after randomization | Time from randomization to first occurrence of pain requiring opioid analgesics or death from any cause, whichever occurs first. |
| Overall survival | From randomization to 12 months after randomization | Time from randomization to death from any cause. |
| Healthcare resource utilization | From randomization to 12 months after randomization | Number and duration of hospitalizations, number of outpatient visits, and associated healthcare costs during the study period. |
Countries
Slovenia
Contacts
CONTACTEva Ćirić, MD
CONTACTKlavdija Korošec
Outcome results
None listed