Measuring Normal Tissue Effects of Radionuclide Therapy

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Measuring Normal Tissue Effectsof Radionuclide
Therapy

• Ruby Meredith, M.D., Ph.D.
• Department of Radiation Oncology
• University of Alabama at Birmingham

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What is the Tolerance of Normal Organs to
Radiation ?
Usually more tolerance for radionuclides than
external beam - but not well studied
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Organ Tolerance Data Comparison

• External Beam Radionuclide
• TD5/5, TD 50/5 any toxicity
• Severe Late complications acute late
• patients reported usually lt 50
• /- surgery failed multiple therapies

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Organ Tolerance Data Comparison

• External Beam Radionulcide 2Gy/d x
  5/week single dosegt1 MeV lower energyHigh
  dose rate low dose rateWhole/partial
  organ mostly whole

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Normal Organ Tolerance to Radiation (cGy)
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Normal Organ Tolerance to Radiation (cGy)
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Normal Organ Tolerance to Radiation (cGy)
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How Accurate are Radionuclide DoseEstimates and
Comparison Between Studies?

• 1. Radionuclide dosimetry is less accurate than
  external beam.
• 2. How accurate are tracer studies?
• 3. Calculated dose is ? biologic dose.
• 4. How accurate are comparisons of radionuclide
  dose estimates?

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Radionuclide Dosimetry Is Less Accurate Than
External Beam

• Radionuclide less precise. e.g. parenchymal
  lung tumor difference in attenuation between lung
  vs. more dense tissue, immediate full
  dose

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How Accurate Are Tracer Studies?

• Comparison of tracer-predicted vs. therapeutic
  radiation doses measured

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Calculated Dose Is ? Biologic Dose
Physical/biologic interaction factorsheterogeneou
s distribution dose rate effectseffective
range of radiation RBE, other characteristics
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Biologic Factors Affecting Tolerance

• age, prior therapies, time since prior Rx,
• disease status-e.g. anemia, marrow
  replacement genetic factors and/or
  physiologic conditions - hypoxia that affect
  radio-sensitivity repair

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Biologic Effectiveness ofRadionuclide Therapy

• Agents/factors not contributing to radiation dose
  estimates. Chemotherapy, other biologic response
  modifiers
• ? ? ?
• Radiosensitizers, Cytokines Growth
  Factor Inhibitors
• BuDR IL-1, IL-2 anti-EGFr

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90Y-ChL6 Therapy ofBreast Cancer Xenografts
DeNardo et al., PNAS 1997
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How Accurate are Comparisons of
Radionuclide Dose Estimates?
Variance in Dosimetry Methods Include
a) Measured organ volume as used in
myeloablative studies (U. Washington) vs
Phantom MIRD model b) Do calculations use
computer programs- MIRDOSE 2 or MIRDOSE 3
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How Accurate are Comparisons of
Radionuclide Dose Estimates?
Variance in Dosimetry Methods c) Was
attenuation correction applied for imaged ROI or
a transmission scan technique used d) Was
background subtraction correction performed
e) What was the frequency appropriateness of
data collection, if peak concentration missed ?
lower dose estimate
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How Accurate are Doses Reported -

• Wessels marrow /-700 in 1980s,
• 200 in 1990s, now 30
• reports of 7 institutions vs. his
  recalculation of their data? -35 - 6
• AAPM-Sgouros method, 0.19 blood in marrow ?
  200 cGy vs. report whole blood had marrow dose
  600 cGy

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When Does Imaging/Dosimetry Potential Have Great
Impact ?

• Good correlation of data with organ toxicity
  and/or anti-tumor effects.
• When normal organ that can be accurately
  assessed is dose limiting. e.g.myeloablative,
  lung, liver

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When Does Imaging/Dosimetry Potential Have Great
Impact ?

• Tumor adjacent critical organ
• Distribution highly variable - 131I-anti-CEA?
  gt2x faster T1/2 colorectal
• Unknown distribution

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Loculation, Then Resolved
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Catheter Eroded into Bowel
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RIT External Beam RT

• Hepatoma 2100cGy concurrent
• Adr/alternating 5-Fu Flagyl,
• 2 months ? dose chemo.
• 93-157mCi 131I-anti-ferritin?
• 400-1000cGy to nl liver (Order)

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Myeloablative RIT XRT

• Leukemia ( U. Washington) 76-612 mCi
  131I-anti-CD45 CY 1200cGy TBI, MTD liver
  1050cGy
• Breast, Prostate Ca 131I-anti-TAG-72 CY 1320cGy
  TBI /- Thiotepa, 131I-Ab ? 142-990cGy to liver,
  ? LFT also chemo only regimens (UAB)

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Tissue Tolerance to Re-Irradiation

• Acutely Responding Tolerate Full 2nd Course
  (Months)
• Late Responding Vary- No Recovery Heart,
  Bladder, Kidney.
• Partial Recovery Skin, Mucous, Lung, Spinal
  Cord
• Sem Rad Onc 10(3) 200-209 2000

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Tolerance for 2nd Radiation Course - May be Close
to that of Initial for Some Tissues
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Radionuclide Re-treatment

• 89Sr gt 5x, gt 6 wk
• 90Y2B8 40mCi(3 pt.) unfavorable factors
• 131I-LYM-1,177Lu-CC49, 131I-CC49
• Trend longer recovery, mildly increased
  toxicity with re-treatment at short interval

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Summary Conclusions

• More radionuclide data needed to improve
  dose/toxicity relationships.
• improved data collection/processing methods will
  increase accuracy of dose estimates.

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Summary Conclusions

• Modifiers ? chemotherapy- other
  radiosensitizing agents
• prior Rx, disease status affect toxicity
  tumor response without changing dose estimates