The Effect of Zoledronic Acid on Spine Metastases

15SProceedings of the NASS 27th Annual Meeting / The Spine Journal 12 (2012) 1S–21S

the potential impact of combined surgery and radiotherapy on health care

utilization given the frequency of this clinical problem.

PURPOSE: To assess quality of life outcomes in patients receiving surgi-

cal treatment for metastatic epidural spinal cord compression (MESCC).

STUDY DESIGN/SETTING: Patientswere enrolled in a prospectivemulti-

center, cohort study involving nine sites in North America. Patients were fol-

lowed at predetermined follow-up visits for 12 months or until they expired.

PATIENT SAMPLE: To date, 125 surgically treated patients with solitary

symptomatic MESCC confirmed by MRI.

OUTCOME MEASURES: Neurological, function, pain, utility and, quality

of lifeoutcomeswereprospectivelyassessedusingVASpainassessments,ASIA

scale, Oswestry Disability Index (ODI), SF-36v2, and EuroQol-5D (EQ-5D).

METHODS: Changes in outcome parameters were evaluated by paired t-

tests. Survival was modeled by Cox regression.

RESULTS: Theaverage age was 58 years (SD 11, range 30 - 82) with 58%

males. Common primary sites were lung (23%), breast (13%), prostate

(15%), kidney (12%) and, other genitourinary (9%). For 14% of the subjects

the location of primary cancer was unknown. Patients’ functional and health

status prior to the treatment was poor. The baseline Visual Analog Pain

(VAS) level was 7.1 (SD 2.5); the baselineODIwas 61.6 (SD 21.5); the base-

line SF36v2Physical Component Score (PCS)was 32.19 (SD7.7). The base-

line utility as measured by EQ-5Dwas.39 (SD.26). Only 41% of the subjects

had normal ASIA motor impairment grade ‘‘E’’; 39% had grade ‘‘D’’; 15%

‘‘C’’, 2% ‘‘B’’ and, 2% ‘‘A’’. Median survival was 213 days (95% CI

133d285 days). The estimated survival was as follows: 93% survived one

month; 66% survived 3 months, 53% 6 months, 45% survived 9 months

and, 30% survived 12 months. Survival was strongly associated with the site

of the primary neoplastic disease (P!.05). Subjects with breast cancer had

best survival experience while the subjects with lung cancer had the worst

survival. About 64% of patients with breast cancer and only 21% of patients

with lung cancer survived 12months.Median survivalswere 569 and 93 days

in the breast and lung cancer groups, respectively. Patients who survived 3

months experienced significant improvement in pain, function and health

utility. At 3 months, Pain VAS improved for 1.8 (SD 3.2, P!.01); ODI for

16.6 (SD 28.2; P!.01) and EQ5D for.16 (SD.30, P!.01). The improvement

in SF36v2 PCS was 1.46 (SD 11.0, P 5.36). The gains in EQ5D, ODI and

VAS Pain were maintained in patients who survived 6 months.

CONCLUSIONS: Surgically treated patients with MESCC are a diverse

group of patients with different prognoses. Some patients have poor sur-

vival while other have better prognosis and survive 12 months or longer.

A characteristic clearly associated with survival prognosis is type of pri-

mary cancer with lung cancer being associated with the poorest prognosis

and breast cancer with the best. The surviving patients experience clini-

cally relevant symptoms improvement and gains in function and utility.

At this stage of our analysis, the quality of life gains are of borderline sig-

nificance. Our analysis supports use of surgery in patients with survival ex-

pectancy of 3 months or more. We plan to undertake cost-effectiveness

analyses once a larger sample size has been accrued.

FDA DEVICE/DRUG STATUS: This abstract does not discuss or include

any applicable devices or drugs.

http://dx.doi.org/10.1016/j.spinee.2012.08.060

32. Outcome of Embolized Vascular Metastatic Spinal Tumors

Causing Cord Compression

NasirA.Quraishi,MD, SanjayPurushothamdas,FRCS,RobertLenthall,MD,

Michael P. Grevitt, MD, FRCS; Queens Medical Centre, Nottingham, UK

BACKGROUND CONTEXT: Blood loss remains a major concern in sur-

gical management of vascular metastatic spinal tumours. Surgical and func-

tional outcome is affected by this variable. Pre-operative embolization is

aimed at reducing blood loss, facilitating tumor surgery by providing a rela-

tively bloodless field and reducingmorbidity and thereby improve outcomes.

PURPOSE: To present the results of the surgical management of vascular

metastatic tumours of the spine with cord compression who underwent pre-

operative embolisation.

All referenced figures and tables will be available at the Annual Mee

STUDY DESIGN/SETTING: Retrospective cohort study by means of

a prospectively maintained database.

PATIENT SAMPLE: We studied 23 patients (mean age 59yrs (24-78);

19F,4 M) with metastatic spinal cord compression who had preoperative

embolisation and surgery. Embolisation was performed by a senior inter-

ventional radiologist using a combination of liquid and particulate agents.

OUTCOME MEASURES: We studied the degree and extent of emboli-

sation, estimated blood loss, transfusion requirements, neurological status

and survival time after surgery. Comparison was done on the basis of tim-

ing of surgery from embolisation (immediate vs. within 24-48 hours) and

extent of embolisation (number of vascular pedicles embolised).

METHODS: Methodology of the study included analysis of the database

of spinal tumours referred to our institution, study of the medical case re-

cords for operative and postoperative details and study of the radiological

records for embolisation details.

RESULTS: Renal cell carcinoma was the most common primary tumour

(n521). All the patients had posterior decompression/stabilisation and 8

had corpectomy with anterior column reconstruction. The estimated blood

loss was 2210 (400-10,000)mls; mean operating timewas 291 (90-840)min-

utes and an average of 3 (2-19) units of whole blood was transfused. The av-

erage survival following surgery was 16 months (2 weeks – 6 years).

Postoperatively, 48 %(11/23) had no change in neurological status, 26% (6/

23) showed improvement in neurological status by at least one Frankel grade

and 22% (5/23) had neurological deterioration by at least one Frankel grade.

Immediate surgery after embolisation (n510) was associated with less blood

loss, less operating time and fewer blood transfusionwhen compared to those

operated within 24-48 hours (n512). However, there was no statistically sig-

nificant difference in the survival period. Tumours where all major vascular

pedicles were embolised (n514), had higher blood loss and had higher trans-

fusion rate. However, operating time was less and survival was better when

compared to tumours with embolisation of fewer vascular pedicles (n59).

CONCLUSIONS: Blood loss remains amajor concern in the operative treat-

ment of vascular metastatic spinal cord compression. Paradoxically, higher

blood loss and transfusion rates were observed in patients who had all the vas-

cular pedicles to the tumour embolised compared to those who had reduced

number of pedicles embolised. Patients with complete embolisation showed

reduced operative time compared to those with incomplete embolisation.




33. The Effect of Zoledronic Acid on Spine Metastases

Kei Tateno, MD, PhD1, Koji Kanzaki, MD2, Junichi Ochiai, MD2,

Takayuki Nakajima, MD2, Kazuyuki Segami, MD3; 1Showa University

Fujigaoka Hospital Department of Orthopedics, Kanagawa-ken, Japan;2Showa University Fujigaoka Hospital, Yokohama, Kanagawa, Japan;3Yokohama, Japan

BACKGROUND CONTEXT: The spinemetastases patients suffer from lo-

cal pain caused by irritation of the periosteum due to rapid growth of the tumor

or subsequent pathologic fractures whichmay lead to compression and neuro-

logical impairmentwith paresthesia, paresis and paraplegia. Zoledronic acid is

a third-generation nitrogen-containing parenteral bisphosphonate indicated

for the treatment of bone metastases due to solid tumors. However, there

was no report about the effect of Zoledronic Acid on spine metastases.

PURPOSE: This study seeks define the effect of zoledronic acid on spine

metastases.

STUDY DESIGN/SETTING: Retrospective study.

PATIENT SAMPLE: Fifty-five patients receiving zoledronic acid for the

spine metastases consisted of 23 men and 32 women with a mean age of 63.3

years. The mean follow-up period was 14.3 months (3-45months). The origins

of the metastases were as follows: 24 breast, 8 lung, 9 prostate and 14 others.

OUTCOME MEASURES: Previously at NASS, we reported that

Tokuhashi’s prognostic scoring and Tomita’s surgical staging classification

are useful in the treatment of metastatic spine tumors. Tokuhashi’s

ting and will be included with the post-meeting online content.



16S Proceedings of the NASS 27th Annual Meeting / The Spine Journal 12 (2012) 1S–21S

prognostic score and Tomita’s surgical staging classification, Frankel clas-

sification, radiographs,computed tomography (CT) scan.

METHODS:Weevaluated 55 consecutive patientswithmetastatic spine tu-

mors who were treated with zoledronic acid. The prognosis of all patients

was evaluated by Tokuhashi’s score (15 points), Tomita’s surgical staging

classification, Frankel’s classification, CT scan and the side effect of drug.

RESULTS: The Tokuhashi Score was 9.9 (3-15) points, 42 patients

(76.4%) had multiple spine metastases, one patient (1.8%) had cervical me-

tastases, 4 patients (7.3%) had thoracic metastases, 5 patients (9.1%) had

lumbar metastases, 3 patients (5.5%) had sacral metastases. The progress

of the compression to the spinal cord were 10 patients(18.2%), the progress

of paralysis were 6 patients (10.9%), one case changed from Frankel E to

Frankel A during treatment. 4 patients (7.3%) had the progress of Tomita’s

surgical staging classification. All patients had chemotherapy or hormone

therapy, 31 patients (56.4%) had radiation therapy, 5 patients (9.1%) had

jaw osteonecrosis. On CT scan, 52 patients (94.5%) had the increased bone

density and 16 patients (29%) had the progress of pathological fracture.

CONCLUSIONS: Zoledronic acid effects segmental spine stability of the

spine metastases patient. Zoledronic acid is useful in the treatment of met-

astatic spine tumors.




34. Nanoparticle Mediated Thermoablation in Tumors of the Spinal

Column in a Rat Model of Metastatic Breast Cancer

Patricia L. Zadnik1, Camilo A. Molina2, Mari L. Groves, MD3,

Rachel Sarabia-Estrada, DVM, PhD4, Michele Wabler, BS1, Jana Mihalic1,

Edward McCarthy2, Robert Ivkov, PhD1, Daniel M. Sciubba, MD4; 1Johns

Hopkins Medicine, Baltimore, MD, US; 2Baltimore, MD, US; 3John

Hopkins University, Baltimore, MD, US; 4Johns Hopkins University School

of Medicine, Baltimore, MD, US

BACKGROUND CONTEXT: Among the 1.5 million new cases of cancer

diagnosed annually, approximately 3-9% of patients experience symptom-

atic spinal metastasis. Although advances have been made in the diagnosis

of metastatic spine disease, management has not advanced accordingly.

PURPOSE: The purpose of this study was to use an animal model of met-

astatic spine disease to investigate nanoparticle-based tumor thermoabla-

tion as a treatment modality for metastatic spine disease. Ferromagnetic

nanoparticles can be delivered by injection to target cancer tissue, and

when exposed to an alternating magnetic field (AMF), the magnetic mate-

rials can generate thermoablative heat. This thermoablation is minimally

toxic to surrounding cells but kills local tumor cells when injected directly

into the tumor, as evidenced in several recent trials.

OUTCOMEMEASURES: Outcome measures included ambulation post-

treatment, evidence of nanoparticles in lymphoreticular organs, evidence

of nanoparticles in tumor, total tumor necrosis, and temperature during

AMF treatment.

METHODS: Twenty-two female Fischer-rats were divided into two groups

(Group-1, n518andGroup-2,n54).Bothgroupsunderwent a transperitoneal

approach to the lumbar spine followedby implantationof rat breast-adenocar-

cinoma tissue (CRL-1666) into theL6vertebral body.Onpostoperative day9,

Group-1 received intratumoral nanoparticle injections (0.4 mg/cm3 of

tumor). Group-1 animals were sacrificed at 1,3,6,12,24, and 48 hours

following particle injection to study intratumoral and systemic particle distri-

bution. Lung, liver, and spleenwere harvested for immunohistochemistry. In-

ductively-coupled plasma mass spectrometry (ICP-MS) was performed on

blood and CSF samples to determine iron concentration. Group-2 animals

were given intratumoral nanoparticles on day 13 at a dose of 0.4 mg/cm3 then

exposed to an AMF having frequency of about 150 kHz and amplitude rang-

ing from 600-800 Gauss at approximately one hour post nanoparticle injec-

tion. Temperatures were measured with fiber-optic probes that were

inserted into the tumor and rectum of each rat. All animals in group 2 were

sacrificed at 24 hours post-treatment. A pathologist (E.M.) specializing in

bone was consulted to review all tumor histological specimens.

All referenced figures and tables will be available at the Annual Mee

RESULTS: Group-1 distribution analysis at 1,3,6,12,24 and 48 hours dem-

onstrated linear clearance of iron from blood and CSF as measured by ICP-

MS. There was an absence of nanoparticles in the spinal cord, lung, liver, or

spleen as demonstrated byH&E staining at all time points.Mean intratumor-

al-temperature in Group-2 animals was significantly higher than core tem-

perature. All Group 2 animals were ambulatory at 24-hours status-post

AMF treatment. A bone pathologist (E.M.) from the Johns Hopkins Hospital

reviewed all histology slides for Group 2 animals, and noted that there was

variable necrosis (25-50%) throughout all treated tumors. Macrophages

could be seen engulfing nanoparticles within the tumor. Some regions of tu-

mor demonstrated vacuole formation suggesting early stage cell death. Itwas

unclear if the extent of necrosis was greater than normal for this mammary

cancer tumor line. Histologic analysis of the spinal cord did not reveal any

evidence of damage at 24 hours post-nanoparticle/AMF treatment.

CONCLUSIONS: Nanoparticle and AMF therapy to spinal column tu-

mors is a safe treatment modality that results in limited systemic distribu-

tion. This treatment can generate high selective intratumoral temperatures

and variable tumor necrosis.

FDA DEVICE/DRUG STATUS: Ferromagnetic nanoparticles (Not ap-

proved for this indication).


35. Successful Treatment of Extensive Epidural Abscess with

a Percutaneously Introduced Catheter for Drainage

Michael T. Merrick, MD1, James R. Stubbart, MD2; 1Grand Rapids

Medical Education Partners, Grand Rapids, MI, US; 2Orthopaedic

Associates of Michigan, Grand Rapids, MI, US

BACKGROUND CONTEXT: Antimicrobial therapy has been advocated

as the treatment for spinal epidural abscesses in patients without neuro-

logic symptoms. However, in the face of neurologic deterioration, surgical

management is often utilized because of the risk of further neurologic

compromise. Clinical scenarios that may preclude surgical decompression

are poor surgical candidates and patients with massive panspinal abscesses.

In such instances, percutaneous drain placement may be a viable option.

PURPOSE: To define an alternative minimally invasive management ap-

proach for spinal epidural abscesses to traditional open decompression.

STUDY DESIGN/SETTING: Case Report.

PATIENT SAMPLE: Single Patient.

OUTCOME MEASURES: Resolution of spinal epidural abscess.

METHODS: The patient is a 53-year-old diabetic male who was admitted

to the hospital with intractable low back pain and methicillin-sensitive

staphylococcus aureus bacteremia. Despite appropriate IV antibiotic man-

agement, the patient developed quadriparesis. MRI imaging demonstrated

a massive epidural abscess spanning from C1 to the sacrum with multiple

areas of spinal cord compression. Given the difficulty of an open decom-

pression, an attempt at epidural drain placement was made. Two percuta-

neously placed epidural suction drains were placed under sedation.

RESULTS: After percutaneous placement of two 6-French catheters and

treatment with IVantibiotics, the patient’s neurologic function improved dra-

matically within 24 hours. Follow-upMRIwas performed at 5 days after drain

placement demonstrating resolutionof the entire abscess. The drainswere sub-

sequently removedwithout incident or recurrence. The patientwas discharged

home three days later on IVantibiotics. Resolution of the quadriparesis with

the exception of 4/5 unilateral hip flexor weakness was obtained by discharge.

CONCLUSIONS: Although surgical drainage remains the primary treat-

ment of spinal epidural abscess with neurologic involvement, consideration

can begiven to percutaneous catheter placement in patientswho are poor can-

didates for operative intervention. To the best of our knowledge, no previous

report has been published on percutaneous catheter drainage for extensive

panspinal epidural abscesses in a patient with neurologic compromise.




ting and will be included with the post-meeting online content.




The Effect of Zoledronic Acid on Spine Metastases

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