Radiation therapy alone versus radiation therapy plus radiofrequency ablation/vertebral augmentation for spine metastasis: study protocol for a randomized controlled trial

Background: Spine metastasis is a common occurrence in cancer patients and results in pain, neurologic deficits, decline in performance status, disability, inferior quality of life (QOL), and reduction in ability to receive cancer-directed therapies. Conventional external beam radiation therapy (EBRT) is associated with modest rates of pain relief, high rates of disease recurrence, low response rates for those with radioresistant histologies, and limited improvement in neurologic deficits. The addition of radiofrequency ablation/percutaneous vertebral augmentation (RFA/PVA) to index sites together with EBRT may improve pain response rates and corresponding quality of life. Methods/design: This is a single-center, prospective, randomized, controlled trial in patients with spine metastasis from T5-L5, stratified according to tumor type (radioresistant vs. radiosensitive) in which patients in each stratum will be randomized in a 2:1 ratio to either RFA/PVA and EBRT or EBRT alone. All patients will be treated with EBRT to a dose of 20-30 Gy in 5-10 fractions. The target parameters will be measured and recorded at the baseline clinic visit, and daily at home with collection of weekly measurements at 1, 2, and 3 weeks after treatment, and at 3, 6, 12, and 24 months following treatment with imaging and QOL assessments. Discussion: The primary objective of this randomized trial is to determine whether RFA/PVA in addition to EBRT improves pain control compared to palliative EBRT alone for patients with spine metastasis, defined as complete or partial pain relief (measured using the Numerical Rating Pain Scale [NRPS]) at 3 months. Secondary objectives include determining whether combined modality treatment improves the rapidity of pain response, duration of pain response, patient reported pain impact, health utility, and overall QOL. Trial registration: ClinicalTrials.gov NCT04375891 . Registered on 5 May 2020. Keywords: Bone metastasis; Radiation therapy; Radiofrequency ablation; Randomized controlled trial; Spine; Vertebrae; Vertebral augmentation

Radiation therapy alone versus radiation therapy plus radiofrequency ablation/vertebral augmentation for spine metastasis: trial in progress

BACKGROUND: Spine metastases are a common occurrence in cancer patients and result in pain, neurologic deficits, decline in performance status, disability, inferior quality of life (QOL), and reduction in ability to receive cancer-directed therapies. Conventional external beam radiation therapy (EBRT) is associated with modest rates of pain relief, high rates of disease recurrence, low response rates for those with radioresistant histologies, and limited improvement in neurologic deficits. The addition of radiofrequency ablation/percutaneous vertebral augmentation (RFA/PVA) to index sites together with EBRT may improve pain response rates and corresponding quality of life. METHODS/DESIGN: This is a single-center, prospective, randomized, controlled trial in patients with spine metastases from T5-L5, stratified according to tumor type (radioresistant vs. radiosensitive) in which patients in each stratum are randomized in a 2:1 ratio to either RFA/PVA and EBRT or EBRT alone. All patients are treated with EBRT to a dose of 20-30 Gy in 5-10 fractions. The target parameters are measured and recorded at the baseline clinic visit, and daily at home with collection of weekly measurements at 1, 2, and 3 weeks after treatment, and at 3, 6, 12, and 24 months following treatment with imaging and QOL assessments. DISCUSSION: The primary objective of this randomized trial is to determine whether RFA/PVA in addition to EBRT improves pain control compared to palliative EBRT alone for patients with spine metastases, defined as complete or partial pain relief (measured using the Numerical Rating Pain Scale [NRPS]) at 3 months. Secondary objectives include determining whether combined modality treatment improves the rapidity of pain response, duration of pain response, patient reported pain impact, health utility, and overall QOL. The results from this study will be used to allow for comparisons to alternative treatment approaches. This trial was activated 5/2020 and is open to accrual

Postoperative lead migration in deep brain stimulation surgery: Incidence, risk factors, and clinical impact.

Deep brain stimulation (DBS) is an effective treatment for multiple movement disorders and shows substantial promise for the treatment of some neuropsychiatric and other disorders of brain neurocircuitry. Optimal neuroanatomical lead position is a critical determinant of clinical outcomes in DBS surgery. Lead migration, defined as an unintended post-operative displacement of the DBS lead, has been previously reported. Despite several reports, however, there have been no systematic investigations of this issue. This study aimed to: 1) quantify the incidence of lead migration in a large series of DBS patients, 2) identify potential risk factors contributing to DBS lead migration, and 3) investigate the practical importance of this complication by correlating its occurrence with clinical outcomes.A database of all DBS procedures performed at UF was queried for patients who had undergone multiple post-operative DBS lead localization imaging studies separated by at least two months. Bilateral DBS implantation has commonly been performed as a staged procedure at UF, with an interval of six or more months between sides. To localize the position of each DBS lead, a head CT is acquired ~4 weeks after lead implantation and fused to the pre-operative targeting MRI. The fused targeting images (MR + stereotactic CT) acquired in preparation for the delayed second side lead implantation provide an opportunity to repeat the localization of the first implanted lead. This paradigm offers an ideal patient population for the study of delayed DBS lead migration because it provides a large cohort of patients with localization of the same implanted DBS lead at two time points. The position of the tip of each implanted DBS lead was measured on both the initial post-operative lead localization CT and the delayed CT. Lead tip displacement, intracranial lead length, and ventricular indices were collected and analyzed. Clinical outcomes were characterized with validated rating scales for all cases, and a comparison was made between outcomes of cases with lead migration versus those where migration of the lead did not occur.Data from 138 leads in 132 patients with initial and delayed lead localization CT scans were analyzed. The mean distance between initial and delayed DBS lead tip position was 2.2 mm and the mean change in intracranial lead length was 0.45 mm. Significant delayed migration (>3 mm) was observed in 17 leads in 16 patients (12.3% of leads, 12.1% of patients). Factors associated with lead migration were: technical error, repetitive dystonic head movement, and twiddler's syndrome. Outcomes were worse in dystonia patients with lead migration (p = 0.035). In the PD group, worse clinical outcomes trended in cases with lead migration.Over 10% of DBS leads in this large single center cohort were displaced by greater than 3 mm on delayed measurement, adversely affecting outcomes. Multiple risk factors emerged, including technical error during implantation of the DBS pulse generator and failure of lead fixation at the burr hole site. We hypothesize that a change in surgical technique and a more effective lead fixation device might mitigate this problem

Clinical outcomes (%improvement).

<p>Clinical outcomes (%improvement).</p

Representative images of dislocated leads.

<p><b>Cases described in the text. Case 1: A unique ventral lead migration due to repetitive dystonic head movements. Cases 3 and 5: Dorsal lead migrations secondary to “twiddler syndrome”</b>. Arrows and numbers indicate the direction and the distance of the movement, respectively.</p

Characteristics of patients with lead migration.

<p>Characteristics of patients with lead migration.</p

Correlation between ΔC and |ΔL|.

<p>A (left). Scatter plot of all values for ΔC and |ΔL|. The overall Spearman (non-parametric) correlation between ΔC and |ΔL| was 0.55 (p < .0001). B. (right) is an enlargement of the area near (0,0)–observations for which both ΔC and |ΔL| are less than 2. The correlation is tiny (0.06) and non-significant (p = 0.562). (ΔC = vector distance between the measured lead tip locations on serial CT scans, |ΔL| = measured change in intracranial lead length on serial CT scans).</p

DBS programming parameters and threshold levels of patients with lead migration.

<p>DBS programming parameters and threshold levels of patients with lead migration.</p

Methodology for measurement of the intracranial length of a curved DBS lead.

<p>ILL = intracranial lead length.</p