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