ACCELERATED BREAST IRRADIATION EVOLVING PARADIGM FOR TREATMENT OF EARLY STAGE BREAST CANCER
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1 ACCELERATED BREAST IRRADIATION EVOLVING PARADIGM FOR TREATMENT OF EARLY STAGE BREAST CANCER KHANH NGUYEN, MD, MA DEPARTMENT OF RADIATION ONCOLOGY BAYHEALTH CANCER CENTER
2 BREAST CANCER STATISTICS Most common cancer in women 1 in 8 women Estimated invasive and 64,000 non-invasive cancers 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
3 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 : 40.1% 2005: 35.6% 2008: 38.4% ( Source: Ann Surg Oncol May; 20(5): ) 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
4 EVOLUTION OF BREAST CANCER TREATMENT Radical Mastectomy as GOLD STANDARD 36% Mastectomy For Early Stage
5 EVOLUTION OF BREAST CANCER TREATMENT Is Radical Mastectomy too Radical? Breast Conservation Surgery: Less is More NSABP-B06: key study for invasive breast cancer; NSABP-B17: key study for DCIS (non-invasive);
6 BREAST CONSERVATION THERAPY NSABP B-06: 20-YEAR FOLLOW UP DATA N Engl J Med 2002; 347:
7 XRT decreases recurrences Mastectomy does not improve survival
8 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
9 EVOLUTION OF BREAST CANCER TREATMENT Questioning Whole Breast Radiation Dogmas Duration: shorter than 6 weeks? Impetus for hypo-fractionation trials in 1990 s
10 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
11 HYPO-FRACTIONATION TRIALS Forest Plot: high grade tumors Shorter course with equivalent Local Control and Survival Canadian Trial: N Engl J Med 2010; 362:
12 HYPO-FRACTIONATION TRIALS No compromise in toxicity or Cosmetic outcomes. Canadian Trial: N Engl J Med 2010; 362:
13 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
14 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
15 ACCELERATED PARTIAL BREAST IRRADIATION Techniques: How is it done? External Beam Interstitial Brachytherapy Intra-Cavitary Brachytherapy
16 ACCELERATED PARTIAL BREAST IRRADIATION: EXTERNAL BEAM: EBRT/IGRT/SBRT Treat tumor cavity Use image guidance Source: Varian Disadvantage: still treat more normal tissue than other PBI techniques
17 ACCELERATED PARTIAL BREAST IRRADIATION: INTERSTITIAL BRACHYTHERAPY Treat tumor cavity Use multiple needles, inpatient treatment Disadvantage: inpatient procedure, cosmesis Source: UCSD
18 ACCELERATED PARTIAL BREAST IRRADIATION: INTRA-CAVITARY BRACHYTHERAPY Treat tumor cavity Devices: Mammosite, Contura, Savi Disadvantage: highly selected patients
19 ACCELERATED PARTIAL BREAST IRRADIATION: INTRA-CAVITARY DEVICES Mammosite Contura Savi Source: NCI
20 ACCELERATED PARTIAL BREAST IRRADIATION What are the data for APBI?
21 ACCELERATED PARTIAL BREAST IRRADIATION: PRELIMINARY DATA: 5-YEAR FOLLOW-UP Source: Red Journal 85(5): , 2013
22 WHOLE BREAST VERSUS PARTIAL BREAST IRRADIATION HISTORICAL COMPARISON: NSABP B-06 VS APBI REGISTRY DATA Caveat: 20-year randomized data versus 5-year registry data; Need longer follow up
23 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
24 WHOLE BREAST VERSUS PARTIAL BREAST IRRADIATION RANDOMIZED 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
25 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.
26 ACCELERATED PARTIAL BREAST IRRADIATION: 2016 ASTRO CONSENSUS: PATIENT SELECTION
27 NSABP B-39 HDR DOSIMETRIC CRITERIA
28 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
29 ACCELERATED PARTIAL BREAST IRRADIATION SAVI TREATMENT ANIMATION Courtesy: Lee Luchtel, Cienna Medical, SAVI
30 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
31 ACCELERATED PARTIAL BREAST IRRADIATION: TREATMENT FOLLOW-UP Toxicity rates defined by CTCAE v.3 i Hong 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, 2012 ii Strasser 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, iii Yashar 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 Jul 1; 80(3):
32 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?
33 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?
34 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 Conclusions: -All these trials show benefit of XRT in reducing local recurrence -No survival benefit
35 EVOLUTION OF BREAST CANCER TREATMENT 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?
36 SUMMARY Continually evolving: surgery, systemic therapy, and radiation Challenge conventional dogmas: quality, not quantity Improve patient comfort Provide convenient care Hope for better cure
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