Radionuclide synovectomy

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Radionuclide Synovectomy (RS)
Herbert Marder
Jacqueline Hochman PGY4 Feb 22, 2005
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Outline

• History
• Indications for use
• Alternative procedures
• Principles of the procedure
• Complications
• Special considerations in the hemophilic patient
• Evidence based application

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Images of Radiation
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Radionuclide Synovectomy (RS)

• Radioactive
• Radioisotope
• Radiocolloid

• Synovectomy
• Synoviorthesis

Local form of radiotherapy to control resistant
synovitis recurrent hemarthrosis
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A brief history on radionuclide synovectomy

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RS

• First used by Fellinger et al. in 1952
• Die lokale Behandlung der rheumatischen
  Erkrankungen. (Wien Z Inn Med. 1952)
• Translation
• The local treatment of rheumatic illnesses

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History of radionuclide synovectomy

• 1971 Ahlberg et al. Radioactive Gold
  inhaemophilia
• Hypothesis radiation causes fibrosis of the
  synovium with diminuation of the extensive
  vasculature and might prevent the progression to
  arthropathy.
• 1991 Yttrium-90
• 1984, 1996 198Au, Rhenium-186, 90Y
• 1994 32P chromic phosphate
• 1997 RS is invaluable in hemophilic patients
  with inhibitors

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. 2005

• RS is the procedure of choice for haemophilic
  patients requiring synovectomy
• Role in refractory synovitis 2nd to other
  inflammatory conditions
• Particularly medical condition makes surgery
  dangerous or impossible

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Reflecting Radiation by Ellen Jantzen
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Indications for RS

• Rheumatoid Arthritis
• Seronegative spondyloarthropathy
• Chronic pyrophosphate arthropathy
• Pigmented villonodular synovitis
• Hemarthrosis or synovitis in the hemophiliac

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Contraindications

• pregnancy
• breastfeeding
• ruptured bakers cyst
• local skin infection
• massive hemarthrosis

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What are the alternatives?
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Radionuclide vs Surgical Synovectomy

• Surgical
• Surgical anaesthetic complications
• Incomplete removal of synovium
• Prolonged joint immobilization
• Loss ROM, fibrosis, scarring

• Radionuclide
• Less costly
• No general anaesthesia
• Day-procedure
• Minimally invasive
• Less risk of bleeding
• No age restriction (absolute)
• Can use in poor surgical candidates

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Chemical synovectomy

• Agents thiotepa, osmic acid
• Limited success in controlling synovitis
• May cause massive hemorrhaging in hemophiliacs

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Principles of the Procedure
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RS Goals of the procedure

• Deliver targeted radiation to synovium
• Homogenous distribution of radioisotope
• Phagocytosis by synovial cells leuks
• Minimize radiation to surrounding tissue
• Minimize leakage

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Mechanism of Action of RS

• Radioactive particles phagocytosed by superficial
  synovial cells
• Radiation causes
• coagulation necrosis
• sloughing of cells
• regression of synovium
• ? inflammatory infiltrate
• sclerosis

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Mechanism of Action of RS
(A) ß-Emitting colloidal particles (yellow stars)
phagocytized by inflamed hypertrophic synovial
lining with proliferating synoviocytes (pink).
Top cartilage layer remains unaffected. (B)
Subsequent cell damage and sclerosis of synovial
membrane.
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Clinical Outcome of RS

• Reduction in
• pain
• swelling
• stiffness
• Improvement in
• ROM
• QUALITY OF LIFE

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Theoretical Complications of RS

• Leakage
• Chromosomal defects
• Malignancy
• Bleeding
• Inflammatory reaction

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Minimize complications by

• Using larger particle, stable radiocolloid
• Prior to procedure, reduce inflammation
• Joint lavage or steroid injection days earlier
• Prophylactic factor infusion
• NSAIDS, PT, limited splinting
• Fluoroscopic guidance
• Flush the needle track with saline or steroids on
  withdrawal
• Joint immobilization post Rx

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SELF-PORTRAIT When I look in the mirror I can
foresee my own radiation death. ARTIST NATASHA
From the Chernobyl childrens project.
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Radioisotope Selection Factors

• Half-life
• Beta-emitting preferable
• Mean tissue penetrance
• Particle size
• Irreversible binding between particle
  radionuclide
• Particle biodegradability

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Radionuclide Options

• Gold (Au-198)
• Yttrium (Y-90)
• Chromic phosphate (P-32)
• Rhenium (Re-186)
• Erbium (Er-169)

Only P-32 has FDA approval for intra-cavitary
use in US
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Comparison of isotope properties
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Why use P32 for RS?

• Pure ?-emitter
• Large particle size gt500m?
• Long t1/2 ? no local inflammatory reaction
• Travels short distance, penetrance 3mm
• Predominately absorbed by synovium
• Moderately high energy -gt rapid uptake

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Other variables affectingradiation delivery

• Joint size
• Amount of synovial fluid
• Synovial thickness

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Radioactive Art by Lulu radiation can be your
friend
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How is it done?
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Technique

• Aseptic technique, fluoro for elbows ankles
• 21 guage needle/3-way stopcock
• Infiltrate site of injection with 1 lidocaine
• Confirm position of needle fluoro/contrast,
  aspirate jt
• Inject small amount depo-medrol to confirm free
  flow
• Inject 0.5-1ml 32P, flush w/ depo-medrol
• 37mBq for large joints, 18.5 for small, 50 less
  in kids
• Slowly withdraw while injecting steroid
• Local pressure, 2-3 passive ROM

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Management Post-procedure

• for bilateral procedures - admit
• 1hr post injection imaging for loculation
• OT splint x 48-72hrs, crutches for unilateral
• Crutches x 2weeks
• Special considerations in the hemophiliac patient
• Prophylaxis
• factor VIII
• FEIBA - factor eight inhibitor bypass
• factor VII

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Leakage Detection

• Immobilize x 1hr
• Scan local joint, adjacent l.node w/
  scintillation camera using bremsstrahlung energy
  window or
• Geiger Muller Counter sequential point counting
  over treated jts, LN, RE system
• ? radiation difficult to detect

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Chernobyl baby
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Who will benefit?What is the evidence?
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3 dancers by Picasso
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Meta-analysis of 2190 Treated Joints

• Literature search 1971-1999
• Break down of 1º disease in 2190 joints
• 1880 rheumatoid arthritis (RA)
• 121 osteoarthritis (OA)
• 37 seronegative arthritis (SA)
• 15 vonWillebrands disease (VWD)
• 116 haemophilia
• ? Pigmented villonodular synovitis (PVS)

Kresnik et al. Nuc med comm 2002.
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Steinbrocker Classification
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Results mean improvement rate

• RA 66.7 15.4
• OA 56 11
• Steinbrocker I 72.8 12.3
• Steinbrocker II 64 17.3
• Steinbrocker III IV 52.4 23.6
• Haemophilia, VWD 914.3
• PVS 77.325.3

Overall response rate in 1 year 72.517
Kresnik et al. Nuc med comm 2002.
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Imaging Before After RS
Kresnik et al. Nuc med comm 2002.
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Groups for RS
Kresnik et al. Nuc med comm 2002.
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Conclusions from Meta-Analysis

• Better results in
• RA gt OA
• In those with milder radiological changes
• Steibrocker I II vs III IV
• Reasonable to repeat in initial responders
• Consider surgery for deformed/unstable jts

Kresnik et al. Nuc med comm 2002.
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Anonymous Artist
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Multicenter study in inflammatory conditions
(2004)

• To evaluate the effectiveness of RS in RA (group
  A) vs other disorders (group B) using a
  questionnaire
• N691 pts, 803 procedures
• Ameliorations in joint pain, swelling/effusion,
  or ROM
• 80 of group A, effect lasted longer in this
  group
• 56 of group B, larger joints responded better in
  this grp only
• Quality of life improvement
• 78 group A
• 59 group B

Although slightly more efficient in RA, RS is an
effective treatment option in OA other
disorders with concomitant synovitis.
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The hemophiliac patient

• Recurrent joint
• bleeding synovitis

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Background

• Mod-severe hemophiliacs develop 1st bleed as
  young as 2-5 years old
• Followed by hemarthrosis-synovitis-hemarthrosis
  cycle
• Fe deposition ? synovitis? hypertrophy
• Rich vascularization ? rebleed ? Target joint
• Target joint
• Reduced range of motion
• Muscle atrophy
• Cumulative joint deformity

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Hemarthrosis-synovitis-hemarthrosis Cycle
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Special considerations in hemophilia

• Advantages of radionuclide synovectomy vs surgery
• Minimal factor requirement
• Several joints at once
• Factor replacement concurrent with or prior to
  procedure to 50 N level
• Tx 8-12hrs later to reduce chance of bleed
• Admit/immobilize LE injections, all inhibitor pts
• 80 success rate

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Treatment Algorithm for Hemophiliac
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Radiation anonymous artist
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Radionuclide Synovectomy for Hemophilic
Arthropathy A Comprehensive Review of Safety
Efficacy.

• Dunn et al. Comprehensive review of safety
  efficacy.
• Thrombosis and Haemostasis 2002.

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Comprehensive Review

• Study group hematologists, nuclear medicine
  specialists, orthopedic surgeons with expertise
  in RS
• Aim
• Develop standardized protocol
• Define research questions
• Literature review

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Experience with 32P Synovectomy
Outcome Joint bleeding Pain
ROM Radiographic AE Miscellaneous
Ref Dose No. Joint Age f/u pts
No. Yrs
Dunn et al. Thrombosis Haemostasis 2002
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Impact on Bleeding Rates

• Rivard and colleagues (1985) studied 14 pts, 22
  joints
• mean pre-RS bleeding rate 12.9 bleeds / yr
• Mean 1yr after RS 4.8/y
• Mean last f/u 2.5 bleeds / yr.
• 8 joints required repeat P-32 injections
• excluding these joints pre-RS rate 9.9 bleeds/yr
  2.2 bleeds/yr in f/u
• Rivard (1994) studied 29 pts, 38 joints, f/u up
  to 15yrs
• similar trends in ? bleeding rates,
• Pre - 12.1/y ?1yr post - 5.1/yr-gt last f/u -
  6.1/y
• Siegel and Luck (1999) studied 125 procedures
• 50 decline in rate of joint bleeding, 2-10yrs
  after procedure in 81
• No bleeding in 54 of joints
• Younger pts lt 18y had a greater reduction in
  bleeding than gt 40y pts
• Studies w/ P32 were similarly positve to gold

Dunn et al. Thrombosis Haemostasis 2002
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Impact on Pain

• 4 groups provided specific data on pain
• Rivard et al. (1994) on P32 RS
• Surveyed 40pts, from 1-15yrs post-P32 RS
• 73 reported less pain
• 27 reported no change in pain
• Overall, studies post-gold, yttrium, P32
• Showed majority had marked reduction in pain

Dunn et al. Thrombosis Haemostasis 2002
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Influence of P32 RS on ROM
Rivard GE. Recent advances in hemophilia care
1990.
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Impact of 32P RS on radiographs

• 6 groups reported on x-ray data
• Rivard et al.1994,(Pettersson scores)
• N23 jts, f/u 1-14yrs (mean 8.7)
• 2 joints improved by 1 point
• 3 joints unchanged
• 19 joints deteriorated by 1-7 points
• All jts scored ?2, worsened by 1-7 points

Dunn et al. Thrombosis Haemostasis 2002
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Potential Complications of P32 RS

• Small amount of leakage
• Chromosomal defects are rare
• Appear to resolve over time
• No published reports of malignancy
• Post-injection bleeds (Rivard et al. 1994)
• in 11/31 joints, all had high-titer inhibitors
• 20/31 were not pre-treated with factor
• Inflammatory reactions ameliorated by steroid
  injections
• Local skin soft-tissue radiation damage is rare

Dunn et al. Thrombosis Haemostasis 2002
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What does the future have in store?

• New radionuclides
• 188Re-microspheres,
• 153Sm-particulate hydroxyapatite
• Complex computer models w/ MRI to determine
  dosimetry more precisely

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Summary (I)

• RS is effective in reducing recurrent
  hemarthrosis
• In most reports, 80 of treated joints
• had gt 50 reduction in bleeding rate
• effect often sustained, may improve over time
• Many pts experience less pain
• Most (at least initially) maintain or improve ROM
• May slow radiographic progression in mild disease
• Most joints have radiographic progression

Dunn et al. Thrombosis Haemostasis 2002
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Summary(II)

• Effective and safe alternative to surgical
  synovectomy
• In inflammatory arthropathies causing resistant
  synovitis despite standard Rx
• In hemophiliacs for haemostasis and prevention of
  target joints

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References

• Dunn AL et al. Radionuclide synovectomy for
  hemophilic arthropathy A comprehensive review of
  safety and efficacy and recommendation for a
  standardized treatment protocal. Thromb Haemost
  200287383-93.
• Fischer M Modder D. Radionuclide therapy of
  inflammatory joint diseases. Nuclear Medicine
  Communications. 200223829-831.
• Kresnik et al. Clinical outcome of
  radiosynoviorthesis a meta-analysis including
  2190 treated joints. Nuclear Medicine
  Communications 200223683-688.
• Prahalad S Passo M. Long-term outcome among
  patients with Juvenile Rheumatoid Arthritis.
  Frontiers in Bioscience 1998313-22.
• Rau H et al. Nuklearmedizin-nuclear medicine
  200443 (2)57-62.
• Schneider et al. Radiosynovectomy in
  rheumatologu, orthopedics, and hemophilia. The J
  of Nuc Med 200546(N1suppl)48S-54S.

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Radionuclide Synovectomy
Jacqueline Hochman PGY4 Feb 22, 2005