radiotherapy in carcinoma of the breast patrick s swift, md director, radiation oncology alta bates...

Radiotherapy in Carcinoma of the Breast

Patrick S Swift, MDDirector, Radiation Oncology

Alta Bates Comprehensive Cancer CenterBerkeley, CA

Breast Conserving Therapy BCT

70-80% of patients with stage I or II disease are candidates for BCT

6 major randomized trials comparing mastectomy to BCT No difference in DFS No difference in OS

Distant Failure

Trial # Time pt. Mast. BCT

WHO 1972-79 179 22 yrs 24% 23%

Milan I 1973-80 701 20 51% 54%

NSABP06 1976-84 1406 20 33% 40%

US NCI 1979-89 279 20 34% 39%

EORTC 10801

1980-86 903 10 34% 30%

Denmark 82TM

1983-89 859 6 32% 34%

Overall Survival

Trial # Time pt. Mast. BCT

WHO 1972-79 179 22 yrs 41% 42%

Milan I 1973-80 701 20 47% 46%

NSABP06 1976-84 1406 20 58% 53%

US NCI 1979-89 279 20 66% 65%

EORTC 10801

1980-86 903 10 79% 82%

Denmark 82TM

1983-89 859 6 67% 67%

Absolute Contraindications to BCT

Repeatedly positive marginsMulticentric disease ( >2 quadrants)Diffuse malignant calcifications on

mammogramPrior RT to breastPregnancy

Relative Contraindications to BCT

History of sclerodermaLarge tumor in small breast

Cosmetically undesirable

NOT contraindications to BCT

AgeSkin or nipple retractionHistology other than IDCExtensive intraductal component

As long as margins are clearPositive nodesLocation of primary in breastPositive family history

Positive Margins after Lumpectomy

Single most important predictor of local failure in BCT

Consider re-excision to get negative margins

Focal positivity - may be okay Especially if chemo or HT given

Extensive positivity - re-excise!

Extensive Intraductal Component (EIC)

Intraductal component a prominent part of the main tumor

Intraductal carcinoma extends BEYOND the infiltrating margin of the mass

Of uncertain significance if margins are clearly negative

Treatment by Stage

DCISDuctal Carcinoma in Situ

MRM is acceptable no node dissection

BCT is an acceptable approach if: Lesion is small (< 3 cm) Margins must be negative

preferably > 10 mm in all dimensions Nuclear grade is low to intermediate Adjuvant radiotherapy can be delivered

S alone can be considered if margins >10 mm controversial

NSABP-17

814 pts. with DCIS, negative marginsRandomized to RT v no RT

50 Gy to entire breast, no boostAt 12 years, local failure rates

31.7% for no RT 15.7% for RT

Only comedo necrosis was a significant factor predicting for local failure

EORTC 10853

500 pts with DCIS, clear marginsRandomized to 50 Gy whole breast or

no RTAt 4.25 years, local failure

16% no RT 9% with RT (p=0.005)

UKCCCR DCIS Working Group

1030 pts with DCIS, clear marginsS alone S + TamS + RTS + RT + TamAt 4.4.years, local failure

14% in no RT 6% in RT arm S + Tam intermediate

Radiation TechniqueDCIS

Opposed tangential fieldsBreast onlyNo boost1.8-2.0 Gy daily to 50 Gy2.65 Gy daily to 40 Gy

Van Nuys Prognostic Index

Scores of 3-4 - 98% local control without RTScores of 5-7 - 32% failed without RT, 16% with RTScores of 8-9 - 100% failure without RT, 60% with RT

Radiation TechniqueT1-2 N0

Opposed tangential fieldsBreast onlyBoost optional50 Gy in 25-28 fractions42.5 Gy in 16 fractions (Canadian)

ASTRO 2008 Plenary

42.5 Gy in 16 fractions v. 50 Gy in 25 fractions

ASTRO 2008 Plenary

Canadian Trial 1993-1996N= 1234 womenMedian followup - 12 yearsLocal recurrence at 10 years - 6%Excellent cosmesis at 10 yrs - 70%No difference between 16 and 25

fractions

If getting chemotherapy…

Radiation is usually withheld until after the systemic therapy is complete

Delay of up to 4-6 months from surgery generally not considered a problem

Possible problem with inflammatory cancer or other locally aggressive cancers

Hypofractionated schemes may allow for early RT while waiting for Oncotype

Surgery alone without RT?

Meta-analysis results Lancet. 2005 Dec 17, vol. 366(9503):2087-106 “Effects of radiotherapy and of differences in the

extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.”

An average of 75% reduction in local failure rates with the addition of RT, in even the lowest risk groups.

A survival benefit was seen in the meta-analysis

Surgery alone without RT?

One possible subset may benefitPatients > 70 years of age

with small ER+ tumors who will get tamoxifen

No survival benefit with RT

Radiation TechniqueT3-4 (after neoadjuvant chemo)

Opposed tangential fieldsBoost

10 Gy for neg margins 18 Gy for positive or close margins

50 Gy in 25-28 fractions

Nodal Irradiation

N0 - no role for axillary RTN+

1-3 nodes, “adequate sampling” - no RT > 4 nodes, RT to SCLV and axilla

IM Nodal RT > 4 axillary nodes positive Medial T3 tumors with any nodes positive

axillaAwaiting results of two large trials (France and

EORTC)

Full SCLV Field

IM Nodal Radiation Technique

Post-mastectomy RT

Indications T3 lesions with any positive nodes Smaller lesions with > 3 nodes T4 lesions Pectoralis fascia involvement

Technique Tangential beams for the chest wall Axillary/SCLV coverage IM node coverage for medial lesions or > 3 nodes

positive

Post-MRM RT Trials(all with chemo and modern RT)

Local failure

Overall Survival

Danish 82b 1708 RT 9% 54%

No RT 32% 45%

Vancouver 318 RT 13% 54%

No RT 33% 46%

Danish 82c 1375 RT 8% 45%

No RT 35% 36%

RT Complications

Lymphedema After full axillary dissection + RT - 37% Level I/II dissection + RT - 7%

Rib fracture - 1.8%Pneumonitis - 1-5%Cardiac toxicity - avoidableRadiation-induced sarcoma

0.78% at 30 yrs.

Reducing Risk

Respiratory Gating

IM nodal techniques

IMRT

Partial Breast Irradiation

RTOG / NSABP Trial comparing Standard whole breast RT 3D conformal technique Mammosite Interstitial Implant technique

5 days, twice daily radiationOutcome results pending