Hypofractionated Radiation Therapy for Early Stage Breast Cancer
Patrick J. Gagnon, M.D.Resident, PGY-4Radiation Medicine, OHSUProvidence HospitalBreast ConferenceNovember 5, 2008
Outline
HypofractionationBenefitsRadiobiologyDisadvantages
Breast ConservationCurrent Standard-of-CareHypofractionated Radiation
Whelan Data – JNCI (2002)Whelan Update – ASTRO (2008)
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 dayHypofractionation: 2.25 - >20 Gy per day
SBRT (lung, liver), pre-op rectal, glottic larynx
Hypofractionation - Benefits
Reduced cost (fewer fractions, increased throughput)
Increased convenience (1-3 weeks vs 6-7)Decreased patient travel and lodgingIncreased treatment compliance and acceptance
of therapyImproved access to careRadiobiology
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
Hypofractionation - Disadvantages
Late normal tissue toxicityCosmesisLoco-regional control
Biologically equivalent dose may actually be less than compared to standard fractionation
Breast Applications
Standard BCT includes lumpectomy with negative margins followed by whole breast radiation therapyRadiation doses typically 45-50 Gy +/-
lumpectomy cavity boost to ~61 GyFraction sizes 1.8 – 2.0 Gy, often 33 fractions
delivered over 6.5 weeksExcellent local control and cosmesis
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., CanadaPlenary session, 50th annual ASTRO Meeting,
BostonInitial data published in JNCI in 200210 year follow-up data presented at ASTRO
Randomized Trial of Breast Irradiation Schedules After Lumpectomy for Women With Lymph Node-
Negative Breast CancerResults 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 randomization622 received 42.5 Gy in 16 fractions and 612
received 50 Gy in 25 fractionsPrimary endpoint local recurrenceSecondary endpoints were distant recurrence,
cosmesis, and late radiation toxicity
Randomized Trial of Breast Irradiation Schedules After Lumpectomy for Women With Lymph Node-
Negative Breast Cancer
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
Long-term Results of a Randomized Trial of Accelerated Hypofractionated Whole Breast Irradiation Following Breast Conserving Surgery in Women with Node-Negative Breast
CancerMedian follow-up now 144 monthsLocal 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 years6% skin & 8% sub-Q (hypofrac)3% skin & 4% sub-Q (standard frac)
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 costQuestions 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?
Acknowledgements
Thank you to Dr. Cha and the entire Providence Radiation Oncology Department
Providence Breast ConferenceDr. Charles Thomas, OHSU Radiation MedicineDr. Carol Marquez, OHSU Radiation MedicineDr. John Holland, OHSU Radiation Medicine