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Measuring Normal Tissue Effects of Radionuclide Therapy

Measuring Normal Tissue Effects of Radionuclide Therapy. Ruby Meredith, M.D., Ph.D. Department of Radiation Oncology University of Alabama at Birmingham. 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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Measuring Normal Tissue Effects of Radionuclide Therapy

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  1. Measuring Normal Tissue Effectsof Radionuclide Therapy Ruby Meredith, M.D., Ph.D. Department of Radiation Oncology University of Alabama at Birmingham

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

  3. Organ Tolerance Data Comparison External BeamRadionuclide TD5/5, TD 50/5 any toxicity Severe Late complications acute + late # patients reported usually < 50 +/- surgery failed multiple therapies

  4. Organ Tolerance Data Comparison External BeamRadionulcide2Gy/d x 5/week single dose>1 MeV lower energyHigh dose rate low dose rateWhole/partial organ mostly whole

  5. Normal Organ Tolerance to Radiation (cGy)

  6. Normal Organ Tolerance to Radiation (cGy)

  7. Normal Organ Tolerance to Radiation (cGy)

  8. 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?

  9. 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

  10. How Accurate Are Tracer Studies? Comparison of tracer-predicted vs. therapeutic radiation doses measured

  11. Calculated Dose Is  Biologic Dose Physical/biologic interaction factorsheterogeneous distribution dose rate effectseffective range of radiation RBE, other characteristics

  12. 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

  13. 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

  14. 90Y-ChL6 Therapy ofBreast Cancer Xenografts DeNardo et al., PNAS 1997

  15. 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

  16. 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

  17. How Accurate are Doses Reported - Wessels: marrow +/-700% in 1980’s, 200% in 1990’s, 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

  18. 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

  19. When Does Imaging/Dosimetry Potential Have Great Impact ? • Tumor adjacent critical organ • Distribution – highly variable - 131I-anti-CEA >2x faster T1/2 colorectal • Unknown distribution

  20. Loculation, Then Resolved

  21. Catheter Eroded into Bowel

  22. 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)

  23. 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)

  24. 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

  25. Tolerance for 2nd Radiation Course - May be Close to that of Initial for Some Tissues

  26. Radionuclide Re-treatment • 89Sr > 5x, > 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

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

  28. Summary & Conclusions • Modifiers  chemotherapy- other radiosensitizing agents • prior Rx, disease status affect toxicity & tumor response without changing dose estimates

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