Early palliative radiation versus observation for high-risk asymptomatic or minimally symptomatic bone metastases: study protocol for a randomized controlled trial

Abstract

Background In patients with metastatic cancer, the bone is the third-most common site of involvement. Radiation to painful bone metastases results in high rates of pain control and is an integral part of bone metastases management. Up to one-third of inpatient consults are requested for painful bone metastases, and up to 60% of these patients had evidence of these lesions visible on prior imaging. Meanwhile recent advances have reduced potential side effects of radiation. Therefore, there is an opportunity to further improve outcomes for patients using prophylactic palliative radiation to manage asymptomatic bone metastases. Methods/study design In this trial, 74 patients with metastatic solid tumors and high-risk asymptomatic or minimally symptomatic bone metastases will be enrolled and randomized to early palliative radiation or standard of care. This will be the first trial to assess the efficacy of prophylactic palliative radiation in preventing skeletal related events (SREs), the primary endpoint. This endpoint was selected to encompass patient-centered outcomes that impact quality of life including pathologic fracture, spinal cord compression, and intervention with surgery or radiation. Secondary endpoints include hospitalizations, Bone Pain Index, pain-free survival, pain-related quality of life, and side effects of radiation therapy. Discussion In this study, we propose a novel definition of high-risk bone metastases most likely to benefit from preventive radiation and use validated questionnaires to assess pain and impact on quality of life and health resource utilization. Observations from early patient enrollment have demonstrated robustness of the primary endpoint and need for minor modifications to Bone Pain Index and data collection for opioid use and hospitalizations. With increasing indications for radiation in the oligometastatic setting, this trial aims to improve patient-centered outcomes in the polymetastatic setting. Trial registration ISRCTN Number/Clinical trials.gov, ID:NCT03523351. Registered on 14 May 2018.

Prophylactic Radiation Therapy Versus Standard of Care for Patients With High-Risk Asymptomatic Bone Metastases: A Multicenter, Randomized Phase II Clinical Trial

“…The full study protocol has been previously published. 9 High risk was informed by previous research 5 and defined as (1) bulky site of disease in bone (≥2 cm); (2) disease involving the hip (acetabulum, femoral head, and femoral neck), shoulder (acromion, glenoid, and humeral head), or sacroiliac joints; (3) disease in long bones occupying one third to two third of the cortical thickness (humerus, radius, ulna, clavicle, femur, tibia, fibula, metacarpals, and phalanges); (4) disease in vertebrae of the junctional spine (C7-T1, T12-L1, and L5-S1) and/or disease with posterior element involvement. The presence of more than five metastatic lesions was required to avoid enrollment of patients with oligometastatic disease because of competing trials.…”

Multidisciplinary management of chronic pain in elderly oncology patients

“…Repeat radiotherapy is effective in 50-60% of patients, and 16-28% of patients experience complete pain relief [69,70]. Additional effects of radiotherapy in the treatment of bone metastases include a reduction in the incidence of pathological fractures (bone calcification effect in 30-40% of patients), a reduction in the risk of hypercalcaemia, prevention of core compression, and a reduction in the incidence of hospitalization [69,71,72].…”

“…Radiotherapy used with analgesic intention is an effective and valuable method. It allows good pain control, reduces the doses of analgesics used, leads to an improvement in quality of life (QOL), improvement in an emotional state, improvement in sleep quality, and reduces the risk of constipation [69,[71][72][73]. It may lead to a prolongation of the patients' overall survival (OS) [69].…”

The next unknown for patients with metastatic disease: optimal surveillance after palliative radiation therapy

“…In our patient cohort, most (74%, 2,266) patients survived to 3 months after radiation therapy completion and a minority of those patients (18%, 397) initiated another radiation treatment within 3 months. While capturing an opportunity for a subsequent radiation treatment may be beneficial (i.e., prophylactic in the setting of impending fracture), radiation treatment of asymptomatic (even high risk) lesions has an unclear benefit and is currently undergoing prospective investigation (16). Thus, the value of scheduled imaging for the purposes of surveillance is unclear and may put patients at a high risk of undue burden and financial toxicity, especially with long and expensive tests like MRI.…”