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Darlene Gabeau

Darlene Gabeau

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Transcript

  • 1. Role of Radiation Therapy in Multidisciplinary Management of Hepatocellullar Carcinoma Darlene Gabeau, M.D., Ph.D. Assistant Professor Department of Radiation Oncology Department of Radiation Oncology
  • 2. HCC : Standard Treatment Algorithm Barcelona Clinic Liver Cancer System Llovet, J. M. et al. J. Natl. Cancer Inst. 2008 100:698-711
  • 3. HCC : Standard Treatment Algorithm Barcelona Clinic Liver Cancer System Llovet, J. M. et al. J. Natl. Cancer Inst. 2008 100:698-711
  • 4. HCC: Limitations of Standard Modalities Survival 50 - 70% Local Control <25%
  • 5. HCC: Limitations of Standard Modalities Survival 50 - 70% Local Control <25% Survival 50 - 80%
  • 6. HCC: Limitations of Standard Modalities Survival 50 - 70% Local Control <25% Survival 50 - 80% Ablation Survival 10 - 50%
  • 7. HCC: Limitations of Standard Modalities Survival 50 - 70% Local Control <25% Survival 50 - 80% Ablation Survival 10 - 50% TACE Survival 30 - 60%
  • 8.
        • Eligibility criteria: 1 lesion  5 cm or  3 lesions/< 3 cm
        • Long wait list  interim tumor progression  >20% dropout
    HCC: Limitations of Standard Modalities Survival 50 - 70% Local Control <25% Survival 50 - 80% Ablation Survival 10 - 50% TACE Survival 30 - 60%
  • 9.
        • Eligibility criteria: 1 lesion  5 cm or  3 lesions/< 3cm
        • Long wait list  interim tumor progression  >20% dropout
    HCC: Limitations of Standard Modalities Survival 50 - 70% Local Control <25% Survival 50 - 80% Ablation Survival 10 - 50% TACE Survival 30 - 60%
    • Might radiation therapy have a role:
    • Tumor downsizing?
    • Bridge to transplant?
  • 10. Radiation Therapy: Important therapeutic modality
    • Used to treat most solid tumors
    • Delivery of electromagnetic energy to a target volume
      • X-rays, Electrons, Protons
  • 11. Radiation Therapy: Important therapeutic modality
    • Cellular basis
    DNA repair Cell cycle regulation Apoptosis
  • 12. Radiation Therapy: Important therapeutic modality
    • Tumor Cell Kill
    • Must also consider normal tissues
  • 13. Radiation Therapy: Important therapeutic modality
    • Therapeutic Ratio: TCP/ NTCP
      • Tumor control probability/normal tissue complication probability
  • 14. Radiation Therapy: Important therapeutic modality
    • Improving the Therapeutic Ratio
      • Fractionation : aliquoting radiation dose
        • The “4 R’s” of radiation therapy
    Repair Normal Tissue > tumor Repopulation Normal Tissue, Some tumors Redistribution Not significant Reoxygenation Tumors
  • 15.
    • Improving the Therapeutic Ratio
      • Fractionation : aliquoting radiation dose
        • Standard: 1.8 - 2 Gy per fraction over 5 -7 weeks
        • Hyperfractionate: 1.5 Gy per fraction twice per day over shorter span
          • Normal tissues repair sublethal damage between doses
          • Minimizes repopulation of tumor
        • Hypofractionate : >3 Gy per fraction over shorter span
          • More lethal damage, less repopulation
          • Limited by ability to spare normal tissues
    Radiation Therapy: Important therapeutic modality
  • 16. Radiation Therapy: Important therapeutic modality
    • Improving the Therapeutic Ratio
      • Optimize treatment planning
        • Technology driven approach
        • Increase the conformality of the delivered radiation
        • Spare normal tissues relative to target
    TV IV Less conformal More conformal TV
  • 17. Emerging Role for Radiation Therapy in HCC: Why not in intra-hepatic malignancies?
    • Historical Data:
      • low therapeutic ratio, hepatotoxicity, unable to deliver curative doses
      • Radiation induced liver disease (RILD)
        • Triad of anicteric ascites, elevated alkaline phosphatase, hepatomegaly
        • Within 3 months of liver irradiation
    • Modern Clinical Data:
      • NTCP depends on volume of liver irradiated
      • small liver volumes can tolerate high radiation doses
  • 18. Emerging Role for Radiation Therapy in HCC
    • Small liver volumes can tolerate high radiation doses
  • 19. Emerging Role for Radiation Therapy in HCC
    • Small liver volumes can tolerate high radiation doses
  • 20. Emerging Role for Radiation Therapy in HCC:
    • C hallenges to safe radiation delivery:
      • Low whole liver tolerance to radiation
      • Other radiosensitive tissues in upper abdomen
      • Tumor and organ motion
      • Baseline compromised hepatic function
      • Advanced disease at presentation
  • 21. Emerging Role for Radiation Therapy in HCC:
    • C hallenges to safe radiation delivery:
      • Low whole liver tolerance to radiation  conformality
      • Other radiosensitive tissues in upper abdomen  conformality
      • Tumor and organ motion
      • Baseline compromised hepatic function
      • Advanced disease at presentation
  • 22. Emerging Role for Radiation Therapy in HCC:
    • C hallenges to safe radiation delivery:
      • Low whole liver tolerance to radiation  conformality
      • Other radiosensitive tissues in upper abdomen  conformality
      • Tumor and organ motion  motion management, image guidance
      • Baseline compromised hepatic function
      • Advanced disease at presentation
  • 23. Emerging Role for Radiation Therapy in HCC:
    • C hallenges to safe radiation delivery:
      • Low whole liver tolerance to radiation  conformality
      • Other radiosensitive tissues in upper abdomen  conformality
      • Tumor and organ motion  motion management, image guidance
      • Baseline compromised hepatic function  patient selection
      • Advanced disease at presentation  patient selection
  • 24. Emerging Role for Radiation Therapy in HCC: Dependent on Advances in imaging
    • Multi-modal imaging: CT, MR
      • Arterial phase imaging for HCC
      • Venous phase imaging for portal vein thrombus
    • Image registration and fusion  better target delineation
  • 25. Emerging Role for Radiation Therapy in HCC: Stereotactic Body Radiotherapy (SBRT)
    • Superior tumor imaging
    • Reliable patient immobilization
    • Respiratory motion management techniques
    • Real-time image guidance for conformal delivery (IGRT)
    • Minimize dose to uninvolved liver
    • Improve conformality
    • Safer radiation dose escalation  hypofractionate
  • 26.
    • Can liver SBRT be delivered safely for HCC?
    • Phase I studies demonstrate safety (RILD rare)
    • No standard fractionation scheme
    • Must establish institutional approach
    Emerging Role for Radiation Therapy in HCC: Experimental Questions
  • 27.
    • Can liver SBRT be delivered safely for HCC?
    • Phase I studies demonstrate safety (RILD rare)
    • No standard fractionation scheme
    • Must establish institutional approach
    • Can liver SBRT effectively bridge HCC patients awaiting transplant?
    Emerging Role for Radiation Therapy in HCC: Experimental Questions
  • 28.
    • Can liver SBRT be delivered safely for HCC?
    • Phase I studies demonstrate safety (RILD rare)
    • No standard fractionation scheme
    • Must establish institutional approach
    • Can liver SBRT effectively bridge HCC patients awaiting transplant?
    • Can liver SBRT downsize HCC lesions for patients outside of criteria?
    Emerging Role for Radiation Therapy in HCC: Experimental Questions
  • 29.
    • Can liver SBRT be delivered safely for HCC?
    • Phase I studies demonstrate safety (RILD rare)
    • No standard fractionation scheme
    • Must establish institutional approach
    • Can liver SBRT effectively bridge HCC patients awaiting transplant?
    • Can liver SBRT downsize HCC lesions for patients outside of criteria?
    • Are there serologic and tissue biomarkers of hepatic radiation response?
    Emerging Role for Radiation Therapy in HCC: Experimental Questions
  • 30.
    • Objective : Confirm feasibility and safety of liver SBRT as a therapeutic option for patients with unresectable HCC
    • Fractionation :
    • Effective liver volume irradiated (V eff ) Dose per fraction
        • < 0.3 9 Gy x 5
    • 0.3 - 0.4 7.5 Gy x 5
    • 0.4 - 0.5 6.25 Gy x 5
        • 0.5 - 0.6 5.5 Gy x 5
    • Primary safety endpoint : Treatment-related hepatic toxicity within 3 months of SBRT
    Emerging Role for Radiation Therapy in HCC: Montefiore-Einstein Liver SBRT Pilot Project
  • 31.
    • Secondary efficacy endpoints : radiographic response, time to progression, survival
    • Correlative endpoints : Serologic and explant biomarkers for radiation response
    • Acrrual : 20 patients over ≤20 months
    Emerging Role for Radiation Therapy in HCC: Montefiore-Einstein Liver SBRT Pilot Project
  • 32.
    • Investigate combined modality therapy:
    • -Liver SBRT + targeted agents?
    • -Liver SBRT + other locoregional therapies?
    • Profiling of human serologic and explant tissue for radiation response biomarkers?
      • Genomic, proteomic, metabolomic
    • Partner with cooperative clinical research groups for large prospective comparative effectiveness studies of liver SBRT?
    Emerging Role for Radiation Therapy in HCC: Potential Future Directions
  • 33. Multidisciplinary Team
    • Radiation Oncology
    • Niloy Deb
    • Chandan Guha
    • Linda Hong
    • Shalom Kalnicki
    • Nitika Thawani
    • Medical Oncology
    • Andreas Kaubisch
    • Epidemiology
    • Mimi Kim
    Hepatology Paul Gaglio John Reinus Pathology Quiang Lu Kathryn Tanaka Surgery Milan Kinkhabwala Funding: Paul Calabresi Award in Clinical Oncology (K12) Prinicipal Investigator: Roman Perez-Soler