Hypofractionated Radiation Therapy for Early Stage Breast Cancer

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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

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Outline

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

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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 - gt20 Gy per day
• SBRT (lung, liver), pre-op rectal, glottic larynx

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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

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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

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Hypofractionation - Disadvantages

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

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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

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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

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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 2002941143-50)
• 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

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

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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?

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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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