Challenges of Recruitment to Interventional MSK Oncology in Palliative Care – Focus on MRI Guided High Intensity Focused Ultrasound (MRg-HIFU) for Treating Skeletal Metastasis

Purpose: New innovations in musculoskeletal interventional oncology need validation and evidence to develop the most effective treatment options, pathways, and guidelines, thus optimizing outcomes and quality of life for patients, even more so for those in palliative care. Obstacles in patient recruitment exist in all trials, but the reasons for nonparticipation are less well understood. We reflect on our experience in magnetic resonance guided high-intensity focused ultrasound (MRg-HIFU) therapy of skeletal metastasis and correlate it with the current literature.

Methods and Materials: Eligibility criteria included adults only and a radiologic diagnosis of bony metastasis in the nonaxial skeleton presenting with pain following a 4- to 6-week interval after 8 Gy single-fraction radiotherapy (RT) to the lesion. Exclusion criteria included adjacent metalwork or fracture, life expectancy < 60 days, poor compliance status, approximation to neurovascular structures/bowel/skin, ≥ 10 cm depth, involvement in another clinical research trial, and/or hematologic malignancies and sarcoma (soft tissue/bone). Once deemed eligible, patients were seen in a preassessment clinic and either placed in a treatment group or a control group. Radiologic and clinical eligibility, noneligibility, and nonparticipation data were collected between June and November 2018 and analyzed.

Results: A total of 2,199 patients received RT. Of those, 234 received 8 Gy single-fraction RT, and 105 received RT to bone lesions. Overall, 52 patients were identified as potential patients with bone lesions (nonaxial skeleton) amenable to HIFU. Of these potential patients, 11 were identified with painful radiologically amenable lesions, yet only one could be recruited. The remaining patients could not participate due to poor performance status, inability to maintain position within the scanner, poor psychological health, and death. Sadly, most of the patients died following RT with an average survival of 1 month. One patient was successfully consented and recruited from the November cohort. Her lesion was located in the right ischium secondary to bronchogenic carcinoma.

Conclusion: Our study provides valuable insight into the challenges for researchers undertaking oncologic interventional therapies. Due to the limitations described, we advocate larger multicenter trials to increase the recruitment rates. Patients and oncologists’ access to information regarding such procedures are in the recruitment phase. Timelines between radiotherapy and evaluation for eligibility to MRg-HIFU are critical and require a proactive approach. Accurate prognoses for better patient selection are needed. Incorporating a wider range of histologic types of primaries into the recruitment criteria would be helpful. We also advocate patient and public involvement discussions to optimize the expectations of patients and caregivers; establishing dedicated international networks, facilitating collaborations; regular recorded meetings between research team members to evaluate and streamline the recruitment pathway, standardizing primary and secondary outcome measures, and correlating them with similar research projects published; and co-enrollment in multiple simultaneous trials. MRg-HIFU is an evolving and promising technique in interventional radiology oncology, among many others, but it remains the least invasive. Improving patient selection criteria and access to patients may improve outcomes, but recruitment remains a particular challenge.

Fig. 1 Ablation by magnetic resonance guided high-intensity focused ultrasound of the right scapula periosteum (diffusely infiltrated with metastatic disease). Left image depicts the planning sequence. On the right, real-time temperature mapping (thermometry) monitors changes in the surrounding tissues.

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