accelerated breast irradiation -...
TRANSCRIPT
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ACCELERATED BREAST
IRRADIATIONEVOLVING PARADIGM FOR TREATMENT
OF EARLY STAGE BREAST CANCER
KHANH NGUYEN, MD, MA
DEPARTMENT OF RADIATION ONCOLOGY
BAYHEALTH CANCER CENTER
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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
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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”
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EVOLUTION OF BREAST CANCER
TREATMENT
Radical Mastectomy as “GOLD STANDARD”
36% Mastectomy
For Early Stage
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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
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BREAST CONSERVATION THERAPY
NSABP B-06: 20-YEAR FOLLOW UP DATA
N Engl J Med 2002; 347:1233-1241
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Mastectomy does not improve survivalXRT decreases recurrences
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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
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EVOLUTION OF BREAST CANCER
TREATMENT
Questioning Whole Breast Radiation Dogmas
Duration: shorter than 6 weeks?
Impetus for hypo-fractionation trials in 1990’s
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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
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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
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HYPO-FRACTIONATION TRIALS
Canadian Trial: N Engl J Med 2010; 362:513-520
No compromise in toxicity or
Cosmetic outcomes.
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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
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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
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ACCELERATED PARTIAL BREAST
IRRADIATION
Techniques: How is it done?
External Beam
Interstitial Brachytherapy
Intra-Cavitary Brachytherapy
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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
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ACCELERATED PARTIAL BREAST
IRRADIATION:
INTERSTITIAL BRACHYTHERAPY
Treat tumor cavity
Use multiple needles, inpatient treatment
Disadvantage: inpatient procedure, cosmesis
Source: UCSD
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ACCELERATED PARTIAL BREAST
IRRADIATION:
INTRA-CAVITARY BRACHYTHERAPY
Treat tumor cavity
Devices: Mammosite, Contura,
Savi
Disadvantage: highly selected
patients
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ACCELERATED PARTIAL BREAST
IRRADIATION:
INTRA-CAVITARY DEVICES
Mammosite
Contura
Savi
Source: NCI
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ACCELERATED PARTIAL BREAST
IRRADIATION
What are the data for APBI?
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ACCELERATED PARTIAL BREAST
IRRADIATION:
PRELIMINARY DATA: 5-YEAR FOLLOW-UP
Source: Red Journal 85(5): 1179-1185, 2013
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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
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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
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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
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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.
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ACCELERATED PARTIAL BREAST
IRRADIATION:2016 ASTRO CONSENSUS: PATIENT SELECTION
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NSABP B-39 HDR DOSIMETRIC
CRITERIA
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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
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ACCELERATED PARTIAL BREAST
IRRADIATION
SAVI TREATMENT ANIMATION
Courtesy: Lee Luchtel, Cienna Medical, SAVI
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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
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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.
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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
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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
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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
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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
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SUMMARY
Continually evolving: surgery, systemic therapy, and radiation
Challenge conventional dogmas: quality, not quantity
Improve patient comfort
Provide convenient care
Hope for better cure