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Hypofractionated Radiation Therapy for Early Stage Breast Cancer

Hypofractionated Radiation Therapy for Early Stage Breast Cancer. Patrick J. Gagnon, M.D. Resident, PGY-4 Radiation Medicine, OHSU Providence Hospital Breast Conference November 5, 2008. Outline. Hypofractionation Benefits Radiobiology Disadvantages Breast Conservation

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Hypofractionated Radiation Therapy for Early Stage Breast Cancer

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  1. Hypofractionated Radiation Therapy for Early Stage Breast Cancer Patrick J. Gagnon, M.D. Resident, PGY-4 Radiation Medicine, OHSU Providence Hospital Breast Conference November 5, 2008

  2. Outline • Hypofractionation • Benefits • Radiobiology • Disadvantages • Breast Conservation • Current Standard-of-Care • Hypofractionated Radiation • Whelan Data – JNCI (2002) • Whelan Update – ASTRO (2008)

  3. Hypofractionation - Defined • Larger doses of radiation per treatment fraction delivering a full course of treatment over a shorter period of time compared to conventional fractionation • Typical fraction sizes: 1.8 – 2.0 Gy per day • Hypofractionation: 2.25 - >20 Gy per day • SBRT (lung, liver), pre-op rectal, glottic larynx

  4. Hypofractionation - Benefits • Reduced cost (fewer fractions, increased throughput) • Increased convenience (1-3 weeks vs 6-7) • Decreased patient travel and lodging • Increased treatment compliance and acceptance of therapy • Improved access to care • Radiobiology

  5. Hypofractionation - Radiobiology • Increased dose per fraction, increased tumor kill • Relative dose to late-responding tissues is higher than to early-responding tissues (mucosa, tumor) raising concerns about late-tissue toxicity

  6. Hypofractionation - Disadvantages • Late normal tissue toxicity • Cosmesis • Loco-regional control • Biologically equivalent dose may actually be less than compared to standard fractionation

  7. Breast Applications • Standard BCT includes lumpectomy with negative margins followed by whole breast radiation therapy • Radiation doses typically 45-50 Gy +/- lumpectomy cavity boost to ~61 Gy • Fraction sizes 1.8 – 2.0 Gy, often 33 fractions delivered over 6.5 weeks • Excellent local control and cosmesis

  8. Long-term Results of a Randomized Trial of Accelerated Hypofractionated Whole Breast Irradiation Following Breast Conserving Surgery in Women with Node-Negative Breast Cancer • Whelan et. al., Canada • Plenary session, 50th annual ASTRO Meeting, Boston • Initial data published in JNCI in 2002 • 10 year follow-up data presented at ASTRO

  9. Randomized Trial of Breast Irradiation Schedules After Lumpectomy for Women With Lymph Node-Negative Breast Cancer • Results initially reported with median follow-up of 69 months (JNCI 2002;94:1143-50) • 1234 patients, T1-2 N0 disease, lumpectomy with negative margins, 2 arm randomization • 622 received 42.5 Gy in 16 fractions and 612 received 50 Gy in 25 fractions • Primary endpoint local recurrence • Secondary endpoints were distant recurrence, cosmesis, and late radiation toxicity

  10. Randomized Trial of Breast Irradiation Schedules After Lumpectomy for Women With Lymph Node-Negative Breast Cancer

  11. Randomized Trial of Breast Irradiation Schedules After Lumpectomy for Women With Lymph Node-Negative Breast Cancer Local in-breast recurrence data from original study with 5 year follow-up

  12. Long-term Results of a Randomized Trial of Accelerated Hypofractionated Whole Breast Irradiation Following Breast Conserving Surgery in Women with Node-Negative Breast Cancer • Median follow-up now 144 months • Local Recurrence at 10 years • 6.2% (hypofrac) • 6.7% (standard frac) • Cosmesis at 10 years (EORTC Rating System) • 70% excellent (hypofrac) • 71% excellent (standard frac) • Late mod-severe skin/sub-Q toxicity at 10 years • 6% skin & 8% sub-Q (hypofrac) • 3% skin & 4% sub-Q (standard frac)

  13. Long-term Results of a Randomized Trial of Accelerated Hypofractionated Whole Breast Irradiation Following Breast Conserving Surgery in Women with Node-Negative Breast Cancer • Conclusions • Accelerated hypofractionated whole breast irradiation provides excellent long-term local control and limited late morbidity • Benefits of convenience and cost • Questions over late normal tissue toxicity remain • Standard arm does not match typical U.S. whole breast regimen (higher whole breast dose, no boost) • Cosmesis based on physician assessment rather than patient assessment • Is this the new “standard-of-care” or do we rely on our mature data and extensive clinical experience with conventionally fractionated whole breast radiation?

  14. Acknowledgements • Thank you to Dr. Cha and the entire Providence Radiation Oncology Department • Providence Breast Conference • Dr. Charles Thomas, OHSU Radiation Medicine • Dr. Carol Marquez, OHSU Radiation Medicine • Dr. John Holland, OHSU Radiation Medicine

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