ACCELERATED BREAST IRRADIATION -...

ACCELERATED BREAST

IRRADIATIONEVOLVING PARADIGM FOR TREATMENT

OF EARLY STAGE BREAST CANCER

KHANH NGUYEN, MD, MA

DEPARTMENT OF RADIATION ONCOLOGY

BAYHEALTH CANCER CENTER

BREAST CANCER STATISTICS

Most common cancer in women

1 in 8 women

Estimated 253000 invasive and 64,000 non-invasivecancers in 2017

Leading cause of cancer deaths in women

In 2017, estimated 40,000 deaths from breast cancer

If diagnosed and treated early, five-year survival >98%

Source: American Cancer Society

EVOLUTION OF BREAST CANCER

TREATMENT

Radical Mastectomy as “GOLD STANDARD” Mastectomy still widely used for early stage breast cancer: Mastectomy rates increasing

for early stage breast cancer: latest SEER data from 2013

2000: 40.1%

2005: 35.6%

2008: 38.4%

( Source: Ann Surg Oncol. 2013 May; 20(5):1436-43)

Lack of access to standard EBRT

Inconvenient (Daily EBRT for 6-7 weeks; more recently, hypo-fractionation for three

weeks; M-F)

Lack of access to long-term follow-up care

Double Mastectomy: tripled to 12% from 2002 to 2012; “Angelina Jolie Effect”

EVOLUTION OF BREAST CANCER

TREATMENT

Radical Mastectomy as “GOLD STANDARD”

36% Mastectomy

For Early Stage

Is Radical Mastectomy too “Radical”?

Breast Conservation Surgery: “Less is More”

NSABP-B06: key study for invasive breast cancer; 1976-1984

NSABP-B17: key study for DCIS (non-invasive); 1985-1990

EVOLUTION OF BREAST CANCER

TREATMENT

BREAST CONSERVATION THERAPY

NSABP B-06: 20-YEAR FOLLOW UP DATA

N Engl J Med 2002; 347:1233-1241

Mastectomy does not improve survivalXRT decreases recurrences

EVOLUTION OF BREAST CANCER

TREATMENT

“EVOLVING STANDARDS”

Mastectomy

Breast conservation therapy

Lumpectomy with negative margins

Adjuvant chemotherapy as indicated: Oncotype Score

Adjuvant Whole Breast XRT

Five weeks of Whole Breast XRT +/- one week of tumor bed boost

EVOLUTION OF BREAST CANCER

TREATMENT

Questioning Whole Breast Radiation Dogmas

Duration: shorter than 6 weeks?

Impetus for hypo-fractionation trials in 1990’s

EVOLUTION OF BREAST CANCER

TREATMENT

Hypo-Fractionation Trials

Canadian Trial (Whelan): 3 vs 5 weeks of WBI

START A/B Trials: hypo-fractionation vs conventional WBI

HYPO-FRACTIONATION TRIALS

Shorter course with equivalent

Local Control and Survival

Canadian Trial: N Engl J Med 2010; 362:513-520

Forest Plot: high grade tumors

HYPO-FRACTIONATION TRIALS

Canadian Trial: N Engl J Med 2010; 362:513-520

No compromise in toxicity or

Cosmetic outcomes.

ACCELERATED PARTIAL BREAST

IRRADIATION:RATIONALE

Questioning Whole Breast Radiation Dogmas

Duration: shorter than 6 weeks? Hypo-fractionation

Volume: Why Whole breast?

Impetus for Accelerated Partial Breast Irradiation

ACCELERATED PARTIAL BREAST

IRRADIATION:

RATIONALE

Most breast cancer recurrences within same quadrant

of breast

80-90% of local recurrences are within 1-2 cm of the

tumor cavity

(Source:American Brachytherapy Society Report, 2002)

Inconvenience of standard fractionation WBI: 5-6 weeks

Even with hypo-fractionation, still 4 week commitment

New paradigm Shift: Accelerated Partial Breast Irradiation

ACCELERATED PARTIAL BREAST

IRRADIATION

Techniques: How is it done?

External Beam

Interstitial Brachytherapy

Intra-Cavitary Brachytherapy

ACCELERATED PARTIAL BREAST

IRRADIATION:EXTERNAL BEAM: EBRT/IGRT/SBRT

Treat tumor cavity

Use image guidance

Disadvantage: still treat more normal tissue than other PBI

techniques

Source: Varian

ACCELERATED PARTIAL BREAST

IRRADIATION:

INTERSTITIAL BRACHYTHERAPY

Treat tumor cavity

Use multiple needles, inpatient treatment

Disadvantage: inpatient procedure, cosmesis

Source: UCSD

ACCELERATED PARTIAL BREAST

IRRADIATION:

INTRA-CAVITARY BRACHYTHERAPY

Treat tumor cavity

Devices: Mammosite, Contura,

Savi

Disadvantage: highly selected

patients

ACCELERATED PARTIAL BREAST

IRRADIATION:

INTRA-CAVITARY DEVICES

Mammosite

Contura

Savi

Source: NCI

ACCELERATED PARTIAL BREAST

IRRADIATION

What are the data for APBI?

ACCELERATED PARTIAL BREAST

IRRADIATION:

PRELIMINARY DATA: 5-YEAR FOLLOW-UP

Source: Red Journal 85(5): 1179-1185, 2013

WHOLE BREAST VERSUS PARTIAL BREAST

IRRADIATIONHISTORICAL COMPARISON: NSABP B-06 VS APBI REGISTRY DATA

Caveat: 20-year randomized data versus 5-year registry data; Need longer follow up

ACCELERATED PARTIAL BREAST

IRRADIATION:

PROMISING PROSPECTIVE REGISTRY DATA

But what about Randomized Trials?

NSABP B-39: US trial, completed accrual 4/15/2014

GEC-ESTRO: 5-Year Data presented at 2017 ASTRO

Meeting

WHOLE BREAST VERSUS PARTIAL BREAST

IRRADIATIONRANDOMIZED DATA: GEC-ESTRO TRIAL

-Preliminary data suggest APBI just as effective as WBI

-Caveat: 5-year data; Need longer follow up

US B-39 Trial: completed 4/15/2014; Preliminary results due soon

ACCELERATED PARTIAL BREAST

IRRADIATION:RATIONALE

Who is a candidate for APBI?Highly selected candidates

Age, Tumor size, LN involvement, margin

status

Very strict dosimetric criteria

Cavity dose, limits on radiation doses to skin,

chest wall, rib dose, etc.

ACCELERATED PARTIAL BREAST

IRRADIATION:2016 ASTRO CONSENSUS: PATIENT SELECTION

NSABP B-39 HDR DOSIMETRIC

CRITERIA

ACCELERATED PARTIAL BREAST

IRRADIATION:

TREATMENT PROCEDURES

Surgical removal of tumor

Insertion of device into cavity

CT simulation for treatment planning

Daily Radiation Treatments

Twice a day for 5 days

Each daily treatment separated by 5-6 hrs

Removal of device after last treatment

ACCELERATED PARTIAL BREAST

IRRADIATION

SAVI TREATMENT ANIMATION

Courtesy: Lee Luchtel, Cienna Medical, SAVI

ACCELERATED PARTIAL BREAST

IRRADIATION:

TREATMENT FOLLOW-UP

Follow-Up schedule

1 week after APBI: look for infection, bleeding, skin

reactions, pain

1 & 3 months: side effects

6-12 months: side effects; ipsilateral mammograms

every six months for first 2 years

Annual mammos after 2 years

ACCELERATED PARTIAL BREAST

IRRADIATION:

TREATMENT FOLLOW-UP

Toxicity rates defined by CTCAE v.3

iHong R, et al. Results of the SAVI Collaborative Research Group Registry: Correlating Clinical Toxicity

with Dosimetric Parameters in Patients Treated with APBI using Strut-Based Brachytherapy. Poster session

presented at the American Society of Radiation Oncology annual meeting, Oct 28-31, 2012iiStrasser J, Jacob D, et al. Accelerated Partial Breast Irradiation Using a Strut-Based Brachytherapy Device: A

Multi-Institutional Initial Report on Acute and Late Toxicity. Presented at the American Society of Breast

Disease annual meeting, April 12-14, 2012.iiiYashar C, Scanderbeg D, et al. Initial Clinical Experience with the Strut-Adjusted Volume Implant (SAVI)

Breast Brachytherapy Device for Accelerated Partial-Breast Irradiation (APBI): First 100 Patients with More

than 1 Year of Follow Up. Int J Radiat Oncol Biol Phys. 2011 Jul 1; 80(3): 765-70.

Questioning Whole Breast Radiation Dogmas

Duration: shorter than 6 weeks? Hypo-fractionation

Volume: why Whole breast? APBI

XRT Omission: Is it needed in all cases?

EVOLUTION OF BREAST CANCER TREATMENT

Questioning Whole Breast Radiation Dogmas

Duration: shorter than 6 weeks? Hypo-fractionation

Volume: why Whole breast? APBI

XRT Omission: Is it needed in all cases?

EVOLUTION OF BREAST CANCER TREATMENT

Radiation Omission Trials NSABP B-21: TAM vs RT vs RT+TAM

<1.0 cm

IBTR: 17% vs 9% vs 3%, p<0.05

CALGB 9343: TAM vs RT+TAM in women over 70 y/o

LRR free survival: 90 vs 98%, p<0.001

DM, OS equal

PRIME II: TAM vs RT+TAM

IBTR: 4.1 vs 1.3%, p=0.001

DM, OS equal

Princess Margaret Hospital Trial: TAM vs RT+TAM

LR: 17.6 vs 3.6%, p<0.001

DFS: 75% vs 85%, p=0.004

OS: 92.8 vs 93.8%, p=NS

EVOLUTION OF BREAST CANCER TREATMENT

Conclusions:

-All these trials show benefit of XRT in

reducing local recurrence

-No survival benefit

Radiation Omission: Ultimate ultra-fractionation

Consider XRT omission in highly selected cases

Small tumors: <1 cm

Low grade

ER positive disease

Wide margins

Elderly >70 y/o

Poor performance status

Key: there is always a benefit to XRT, but to what extent?

EVOLUTION OF BREAST CANCER TREATMENT

SUMMARY

Continually evolving: surgery, systemic therapy, and radiation

Challenge conventional dogmas: quality, not quantity

Improve patient comfort

Provide convenient care

Hope for better cure