The spine is a common site of metastasis. Complications include pathologic fracture, spinal cord compression, and neurological deficits. Vertebroplasty (VP) and Balloon Kyphoplasty (KP) are minimally invasive stabilization procedures used as a palliative treatment to improve mechanical stability, quality of life, and reduce pain. Photodynamic therapy (PDT) is a tumour-ablative modality that may complement mechanical stability afforded by VP/KP. This first-in-human study evaluates PDT safety when applied in conjunction with VP/KP.

This dose escalation trial involved one light only control group and four light-drug doses (50,100,150,200J;n=6) delivered at 150mW from a 690nm diode laser by 800-micron optical fibers prior to KP/VP. Patients eligible for VP/KP in treating pathologic fracture or at-risk lesions at a single level were recruited. Exclusion criteria included spinal canal compromise or neurologic impairment. PDT is a two-step binary therapy of systemic drug followed by intravertebral light activation. Light was applied via bone trochar prior to cementation. This study used a benzoporphyrin derivative monoacid (BPD-MA), Verteporfin (VisudyneTm), as the photosensitizer drug in the therapy. Drug/light safety, neurologic safety, generic (SF-36), and disease-specific outcomes (VAS, EORTC-QLQ-BM22, EORTC-QLQ-C15-PAL) were recorded through six weeks. Phototoxicity and the side effects of the BPD-MA were also examined following PDT use.

Thirty (10 male, 20 female) patients were treated (13 KP, 17 VP). The average age was 61 and significantly different between genders (Male 70yrs vs. Female 57yrs: p 0.05), and tumour status (lytic vs. mixed blastic/lytic: p>0.05). In most cases, fluence rates were similar throughout PDT treatment time, indicating a relatively stable treatment. Twelve (40%) of patients experienced complications during the study, none of which were attributed to PDT therapy. This included two kyphoplasty failures due to progression of disease, one case of shingles, one ankle fracture, one prominent suture, one case of constipation due to a lung lesion, one case of fatigue, and five patients experienced pain that was surgically related or preceded therapy.

Vertebral PDT appears safe from pharmaceutical and neurologic perspectives. KP/VP failure rate is broadly in line with reported values and PDT did not compromise efficacy. The 50J group demonstrated an improved response. Ongoing study determining safe dose range and subsequent efficacy studies are necessary.

The impact of cement leakage during percutaneous vertebroplasty has not been well characterized. This study aimed to quantify and compare cement leakage and its clinical significance in osteoporotic and metastatic vertebrae treated with vertebroplasty. Cement leakage was quantified using semi-automated thresholding of digital CT scans for fouteen metastatic and nineteen osteoporotic vertebrae and compared to pain scores. Cement leakage was present in 90.9% of vertebrae. Cement leaked predominantly into the disc in the osteoporotic vertebrae but yielded more diffuse leakage patterns in the metastatic cases. Despite cement leakage, there was significant improvement in pain immediately following vertebroplasty for all patients.

This study aimed to quantify cement leakage in osteoporotic and metastatic vertebrae post-vertebroplasty and to determine whether leakage has clinical significance at follow-up.

Despite high incidences of cement leakage, both osteoporotic and metastatic patients experienced significant immediate pain relief post-vertebroplasty.

Cement leakage is investigated as a possible rationale for the higher rates of pain relief seen in osteoporotic vs metastatic patients undergoing percutaneous vertebroplasty.

Cement leakage was present in 90.9% of the vertebrae treated. The percent volume of cement leakage was 11.6±10.6 in the osteoporotic vertebrae and 19.4±19.1 in the metastatic vertebrae (p=0.144). Cement leaked predominantly into the disc in the osteoporotic vertebrae whereas leakage was more diffuse in the metastatic vertebrae. Pain scores were high prior to vertebroplasty and decreased significantly following the procedure in both groups irrespective of leakage (p< 0.05).

Digital CT scans were retrieved for osteoporotic (n=19) and metastatic (n=14) patients treated with percutaneous vertebroplasty. Volume of cement injected directly into the vertebral body and location of cement leakage (pedicle, disc, periphery, canal) was quantified using semi-automated thresholding techniques. Pain scores were collected at four stages of treatment (pre, immediately post, one day post, one week post-vertebroplasty).

Disruption of the endplate in the osteoporotic spine provides an easily accessible pathway for the leakage of cement into the disc. Elevated pressurization during cement injection into metastatically involved vertebrae may account for the more diffuse cement leakage seen in the metastatic group. Clinically, pain scores improved irrespective of leakage.

Using serial CT scans, this project aims to develop a clinical research tool that analyzes changes in vertebral density in spines involved with metastatic disease. Tracking of total vertebral body and tumor volume alone was investigated. A program was developed to semi-automate the segmentation of the region of interest followed by image registration to superimpose the segmentation onto spatially aligned serial scans. Based on analysis of a simulated metastatic vertebra, generating a voxel distribution histogram from the vertebral body best quantified density in serial scans. This quantification method may improve clinical decision-making and treatment options for patients with vertebral metastases.

To develop a clinical research tool to serially track tumor involvement in vertebrae with metastatic disease by quantifying changes in CT attenuation.

Segmentation of the vertebral body and analysis of the voxel distribution within the region provides the most accurate method of quantifying changes in tumor involvement for the metastatic spine.

A quantitative method to assess the progression or regression of disease may improve clinical decision–making and treatment options for patients with spinal metastases.

The vertebral body segmentation was more accurate at tracking tumor involvement (voxel distribution histogram: 96.8% +/− 0.75% accuracy, mean density error: 4.7% +/− 0.8%) than segmenting the tumor volume alone (voxel distribution histogram: 86.1% +/− 3.6% accuracy, mean density error: 14.1% +/− 4.8%).

A program was developed to semi-automatically segment the total vertebral body and tumor volume alone from CT scans of metastatically involved vertebrae. Image registration through user-defined landmarks and surface matching was used to spatially align serial scans, and the initial segmentation was superimposed with the aligned scans. Changes within the segmentation between CT scans were tracked using mean density and a voxel distribution histogram. A cadaveric vertebra with a simulated tumor was scanned at five orientations with 20° offsets to determine the accuracy of the methods. Error primarily resulted from unavoidable re-sampling during alignment of the scans.

The management of spinal metastases is palliative and aimed at improving quality of life at an acceptable risk. This population study uses administrative databases and measures survivorship and complication rates after surgery for spinal metastases. The effects of various potential predictor variables were evaluated. We identified 987 patients with a median survival for all types of cancer of 227 days. The one and three-month mortality was 9% and 29%, respectively. Increasing age, male gender and primary lung cancer were significant risk factors for death within 30 days of surgery. A preoperative neurological deficit contributed a 19% increase in mortality and a 71% increase in the risk of postoperative wound infection. We found an overall major complication rate of 27%. This information will provide patients, families and clinicians with objective data which will help in the choice of treatment and the understanding of the surgical risk and outcome.

A province-wide study designed to use administrative data to determine the rate of post-operative complications, the survival duration and predictors of outcome among patients undergoing surgery for metastatic disease of the spine.

Surgery for patients with spinal metastasis is primarily palliative. It is often fraught with complications, which may in fact diminish quality of life. Quantification of survival rates and the risk of potential complications following surgery is important to the clinician and the patient’s families for decision making.

All patients that underwent surgery for spinal metastasis between 1991 and 1998 were identified using the Ontario health insurance database and a hospital discharge registry.

The mean age at surgery was 60. 3 years (range: 13–92 years). The mortality files identified patients who were dead by October 1999. Information about individual inpatient admissions including post-operative complications was then collected. The survival rates and complications following surgery were quantified and the effect of several variables on these two parameters was computed.

The median and mean survival was 227 days and 793. 4 days respectively. The 30-day and 3-month mortality were 9% and 29% respectively. Advanced age at surgery, male sex, presence of a pre-operative neurological deficit and primary cancers of lung, gastrointestinal tract & melanoma are predictive of poor survival. 39% patients had complications. Pre-operative neurological deficit was associated with a 71% higher risk of developing post-op. wound infection.

In the past, surgery has been recommended in patients with an anticipated survival of at least three to six months. The current study shows that even patients preselected on the basis of predictions of longer survival, there is a potential for early mortality and significant complications. Hence, a careful estimation of the benefits of surgery versus surgery related morbidity must be made prior to offering surgery for palliation.