Vertebral Intracavitary Cement

1
Vertebral Intracavitary Cement Samarium
(VICS). A Novel Approach to treat Painful
Vertebral Metastases

• 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.

2
Background

• 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

3
Metastatic Bone DiseaseEpidemiology - Etiology
Estimated Number of Persons Living with Cancer1 Number of New Cases in 20041 Incidence of Bone Metastases2
Breast 2,184,125 (24) 217,440 (16) 65-75
Prostate 1,838,653 (20) 230,110 (17) 65-75
Bladder 521,945 (6) 60,240 (4) 40
Lung 388,538 (4) 173,770 (13) 30-40
Thyroid 273,642 (3) 23,600 (2) 60
Other 4,013,458 (43) 705,160 (52)
Total 9,220,361 (100) 1,368,030 (100)
1. SEER Cancer Statistics Review 1975 2001,
National Cancer Institute 2. Coleman, R.E.
Cancer Treatment Reviews. 200127165-176.
4
Metastatic Bone DiseaseMetastasis 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

5
Vertebral Compression fractures (VCF)-

• 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.

6
Metastatic Bone DiseaseTreatment Goals

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

7
A) Surgical Treatment

• 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

8
Balloon Kyphoplasty

• 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

9
Balloon Kyphoplasty

10
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

11
B) Radiation Treatment for Bony Metastasis

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

12
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

13
Samarium-153 (systemic)

• 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
• Leukopenia 60
• Thrombocytopenia 69
• Decr. Hemoglobin 40

14
Vertebral Intracavitary Cement and Samarium VICS

• Procedure
• Materials
• Methods

15
Vertebral Intracavitary Cement and Samarium
VICS

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

16
Objectives

• 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

17
Eligibility

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

18

• 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.

19
VICS Procedure

• 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

20
Procedure

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

21
Patients

• 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.

22
Patients
Type
Lung 12 46
Prostate 5 19
Colon 2 7.5
Multiple Myeloma 2 7.5
Urinary Bladder 1 4
Ovary 1 4
Breast 1 4
Stomach 1 4
Head neck 1 4
23
Distribution of Treated Vertebrae

• Of the 33 vertebrae treated, 20 were in the
  lumbar spine, 12 were in the thoracic spine and 1
  was in the sacral spine.

24
Escalating Doses of Samarium
Dose of samarium (mCi) Number of Procedures (Patients)
1 4(3)
2 7(7)
2.5 6(5)
3 8(5)
4 8(6)
25
A) Patients tolerance

• There was no mortality or procedure-related
  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.

26
B) Pain control

• 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 (plt0.0001).
• The ECOG performance scores only improved
  marginally from 2.4 (1) before to 2 (1) after
  (p0.035, one-sided test).

27
C) Accuracy and Feasibility

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

28
Localization of Sm-153 in the injected vertebra
persistently shown at 3, 24, 48, and 96 hours of
post injection.
48 hrs
96 hrs
24 hrs
3 hrs
29
C) Accuracy and Feasibility

• 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

30
C) Accuracy and Feasibility

• 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 153Sm and followed the
  physical in-vitro decay. On the right side, the
  curve shows the mean in vivo decay of 153Sm in 11
  patients ( 1SD) as compared to in vitro decay.

31
D) Systemic absorption

• Variable systemic absorption was evident in
  Samarium scans in all patients (9-75). The mean
  ratio between the concentrations of 153Sm in the
  target vertebrae and normal tissues was 3726.3
  (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).

32
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.
Post
Ant.
Post
Bone scan
Samarium scan
33
D) Cytotoxic effect

• Reduced intensity of bone tracer (99mTc-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)

34
D) Cytotoxic Effect

• 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.

35
Drawbacks to VICS

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

36
Conclusions Vertebral Intracavitary Cement and
Samarium VICS

• 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.

37
Future Directions

• 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