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VICS
H. Ashamalla, M. Macedon,, E. Cardoso, L. Weng,, B.
Mokhtar, A. Guirguis, N. Panigrahi.
Radiation Oncology and Neurosurgery departments
New York Methodist Hospital, Weill Medical college of
Cornell University, NY.

 Each year, more than 100,000 patients in the U.S. develop bone metastases.
 Bone is the third most common site of metastatic disease after liver and lung
 Up to 40% of patients presenting with bone mets. will have spinal/vertebral mets,
90% of whom will develop severe axial pain

Epidemiology - Etiology
Breast
Prostate
Bladder
Lung
Thyroid
Other
Total
Estimated Number of Persons Living with Cancer 1
Number of New
Cases in 2004 1
2,184,125 (24%)
1,838,653 (20%)
521,945 (6%)
388,538 (4%)
217,440 (16%)
230,110 (17%)
60,240 (4%)
173,770 (13%)
273,642 (3%)
4,013,458 (43%)
23,600 (2%)
705,160 (52%)
9,220,361 (100%) 1,368,030 (100%)
Incidence of
Bone
Metastases 2
65-75%
65-75%
40%
30-40%
60%
1. SEER Cancer Statistics Review 1975
– 2001, National Cancer Institute
2. Coleman, R.E. Cancer Treatment Reviews . 2001;27:165-176.

Metastasis Sites
 Most common sites of metastasis
 Vertebra (69%)
 Pelvis (41%)
 Femur (25%)
 Hip (14%)
 Median time from cancer diagnosis to bone metastasis is 30 months


Metastatic cancer in the bone causes skeletal complications every 3 to 4 months.
 17 – 50% of patients with metastatic breast cancer will develop VCFs annually.
 Median time to first fracture among breast cancer patients
(not on bisphosphonate) is 12.8 months.

Treatment Goals
 Reduce pain
 Eradicate or reduce tumor when primary tumors are involved
 Prevent neurologic complications
 Treat pathologic fractures and prevent recurrent fracture

 Operative Management
 Vertebral column reconstruction
 A or P decompression with internal fixation
 Oncology patients are generally poor candidates for open surgery due to soft bone/tumor mass and co-morbidities
 Minimally Invasive Procedures
 Kyphoplasty
 Vertebroplasty

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Patient placed in lateral decubitus position
Trochar inserted into anterior vertebral body under fluoroscopic guidence
Curretting performed for tissue sample
Balloon inflated to decompress the fracture and to open up space for cement injection
Balloon removed and PMMA bone cement injected into cavity to stabilize the vertebra

Balloon Kyphoplasty

 Shown to significantly reduce pain associated with VCF in patients with metastatic bony lesions
 However, this procedure does not address the neoplastic component of the problem

 External radiation
 Radionuclides – systemic administration, localize to all bony mets
 Strontium-90
 Samarium-153

 Created by bombarding Samarium-152
(stable) with neutrons
 Comes from manufacturer complexed to
EDTMP
 Beta particles from Sm-153 travel 3.1mm in tissue, 1.7mm in bone
 Typically administered at the dose of
1mCi/kg

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When given IV, Sm-153-EDTMP (Quadramet) has an affinity for bone and will concentrate in areas of high bone turnover, especially bony metastasis
Mechanism of relief of bone pain is unknown, but may be due to suppression of the growth of the tumor cells from radiation
Major adverse effect of systemic administration is hematologic toxicity with nadir at 3-4wks:
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Leukopenia 60%
Thrombocytopenia 69%
Decr. Hemoglobin 40%

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Procedure
Materials
Methods

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 A novel approach to bony metastasis
 Employs combination of balloon kyphoplasty and anti-tumoral activity of
Sm-153 injected directly into the affected vertebra

 Study feasibility of intravertebral administration of Sm-153 with kyphoplasty
 Assess procedure-related morbidities
(specifically hematological) related to procedure
 Monitor pain relief and durability of response

 Inclusion criteria:
 Documented bone mets with intact anterior wall of vertebra
 Recurrent pain or progression of metastases in areas treated by prior external RT
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Acceptable candidate for kyphoplasty
Good performance status, Karnofsky ≥ 60
 Exclusion criteria
 Epidural soft tissue component
 Cord impingement or compression
 Inability to undergo anesthesia

 IRB approval was obtained
 After signing consent, all patients were assessed for pre-op pain level.
 Pre-op MRI, CT and/or bone scan, confirming presence of bony metastasis.

 Insertion of trochar and balloon as with the balloon Kyphoplasty approach
 Under tight radiation safety measures, Sm-153 in escalating doses(1-4mCi) is co-injected and mixed with the cement as it is injected into the cavity of the vertebra using a three way valve.
 Equipment, drapes, and room are surveyed post-operatively. Contaminated needles etc. are taken to the radioactive lab to allow for safe decay

 Serial Samarium nuclear scans were obtained post-op on days 0, 1, 2, and 4.

F/U bone scans and MRI’s were obtained at least 1 month post procedure
 Serial blood counts were also monitored

 33 procedures were performed in 26 patients (18 males and 8 females).
 Seven patients had procedures performed in two vertebral levels.
 The mean age of the cohort was 64 years
(range 33 to 86).
 The mean pain score prior to treatment was 8.8/10.

Primary Cancer Site
2
1
1
1
1 1
2
5
12
Lung Prostate
Multiple Myeloma Urinary Bladder
Breast Stomach
Colon
Ovary
Head & neck
Type
Lung
Prostate
Colon
Multiple Myeloma
Urinary Bladder
Ovary
Breast
Stomach
Head & neck
#
2
2
1
12
5
1
1
1
1
%
46
19
7.5
7.5
4
4
4
4
4

 Of the 33 vertebrae treated, 20 were in the lumbar spine, 12 were in the thoracic spine and 1 was in the sacral spine.
Thoracic
Lubmar
Sacral

Dose of samarium
(mCi)
1
2
2.5
3
4
Number of Procedures
(Patients)
4(3)
7(7)
6(5)
8(5)
8(6)

 There was no mortality or procedurerelated complications.
 There was no hematological toxicity, no significant change in the WBC, Hg and platelets was seen at one month after the procedure.
 Estimation of dose contribution to spinal cord using diagrammatic and inverse square models was 40 ± 6 cGy.

 All patients tolerated procedure very well.
 The mean pain score (VAS) improved from
8.5 ( ±2) prior the procedure to 2.6 (±3.1) one day after the procedure (p<0.0001).
 The ECOG performance scores only improved marginally from 2.4 ( ±1) before to 2 ( ±1) after (p=0.035, one-sided test).

 Whole body Samarium scans confirmed the local absorption injected 153 Samarium-EDTMP in the intended vertebra in 32 out of the 33 injections.
 One patient did not demonstrate clear absorption of the 153 Samarium-EDTMP in the site with no evidence of spillage nor there was systemic absorption.
 No appreciable radiation leakage or spillage was encountered.

Localization of Sm-153 in the injected vertebra persistently shown at 3, 24,
48, and 96 hours of post injection.
3 hrs 24 hrs 48 hrs 96 hrs

 Prior to treatment (A
B) low-signal lesion and hyperintensity
(arrows) in the anterior aspect of the vertebral body.
 12 months after procedure (C , D): local control of the disease is observed

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On the left side there is evidence of targeting at the injected L2. Decrease in signal from day 1 to day 3 after treatment is observed.
The decline of radioactivity was consistent with the known half life of 153 Sm and followed the physical in-vitro decay. On the right side, the curve shows the mean in vivo decay of 153 Sm in 11 patients ( ± 1SD) as compared to in vitro decay.

 Variable systemic absorption was evident in
Samarium scans in all patients (9-75%). The mean ratio between the concentrations of 153 Sm in the target vertebrae and normal tissues was
37 ±26.3 (ranging from 9.3 to 92.1).
 Patients with wide spread bone disease had demonstrated Samarium absorption in distant metastatic sites.
 Asymptomatic extravasation of cement/Samarium was encountered in 6 vertebrae (6/33).

Absorbed Sm-153 targets other skeletal lesions: right clavicle, manubrium, and right posterior ilium. All these lesions were present on pre-treatment bone scan.
Ant.
Bone scan
Post Ant.
Post
Samarium scan

 Reduced intensity of bone tracer ( 99m Tc-
MDP) uptake was studied in 8 patients
 The ratio of mean counts in the intended vertebra to soft tissue after correction to background was 12.1 prior to the procedure dropped down to 6.9 at the last follow up scan (3-12 months)

 Whole-body bone scans before treatment, at 8 and 22 months post-treatment. The new scan reveals reduction of uptake at the treated vertebra L1, while new area of uptake appears at L2.

 Radiation Safety: Open liquid radiation source.
 Obtaining Sm-153 on a timely basis from manufacturer
 Unsuitable for open procedures

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Injection of Sm-153 is feasible and can be performed safely
 No adverse effects were seen as a result of the procedure
 No hematologic toxicities were seen
 Indirect evidence for the cytotoxicity of the procedure is observed through reduction of the intensity of uptake in bone scan.

 Need direct head-to-head comparison of
VICS with balloon Kyphoplasty to determine if there is any net change in the duration of response, or in level of pain relief