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