joint hospital surgical grand round accelerated partial breast irradiation: where should we go? dr...
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Joint Hospital Surgical Grand Round
Accelerated partial breast irradiation: where should we go?
Dr Ma Kwok Kuen
Queen Mary Hospital
Background
Early Breast Cancer Trialist’s Collaborative Group meta-analysis: Whole breast radiotherapy (WBRT) after breast conserving surgery (BCS) 19% absolute risk reduction of ipsilateral breast
recurrence in 5 years 5% absolute reduction in 15-year risk of death
Lancet 2005
Definitions
Conventional WBRT: 50Gy over 25 fractions (5 weeks)
Partial breast irradiation (PBI): irradiation of a limited volume of breast tissue around the tumor bed
Accelerated partial breast irradiation (APBI): deliver a larger than standard dose of radiation with each treatment, shortening the overall treatment time
Rationale of APBI
The spatial pattern of relapse after BCS with or without WBRT: 76-90% at “same site” Five prospective randomized trials
NSABP B06. Cancer 1986 Uppsala-Orebro. J Clin Oncol 1999 Ontario Clinical Oncology Group. J Natl Cancer Inst
1996 Milan III. Ann Oncol 2001 SweBCG 91-RT. Eur J Cancer 2003
Rationale of APBI
WBRT may not protect against the development of new primary cancer in the irradiated breast Milan I trial: comparing mastectomy with
quadrantectomy and WBRT Similar rate of other quadrant breast recurrence and
contralateral breast cancers (CLB) Yale group: at 15 years after BCT in 1152
patients, 13% incidence of other quadrant breast tumor compared with 10% incidence of CLB
New Engl Med 2002
Int J Radiation Oncology Biol Phys 2000
Potential advantages of APBI
Reduction of treatment time Convenient to patient Increase the use of BCS Shorten the waiting time Treatment costs
Reduce normal tissue toxicity Cosmesis
Questions to be answered
1. Which patients are best served by APBI?
2. What is the best technique?
3. What is the long term result?
1. Which patients are best served by accelerated partial breast irradiation?
Patient selection Patient with low risk of recurrence and multicentric
fociABS ASBS ASTRO
Age (years) >=45 >=45 >=60
Histology IDC IDC or DCIS IDC/ favourable subtype
Size <=3cm <=3cm <=2cm
Resection margin
No tumor at inked margin
Negative microscopic surgical margins
Negative by at least 2mm
Axillary LN status
Negative Negative Negative
2. What is the optimal technique of administration of APBI?
Methods of APBI
Interstitial brachytherapy Balloon brachytherapy Intraoperative radiotherapy External beam radiotherapy
Promising Phase I/II trials
Interstitial brachytherapy
10-20 catheters Requires high level of expertise
Balloon brachytherapy
MammoSite Contura SAVI
Inflatable balloon placed in lumpectomy cavity 34Gy/10 in 5 days
Intraoperative radiotherapy
Energy source (Electrons/Photons) Single dose 21Gy
External beam radiotherapy
3D conformal Other methods
(Intensity modulated radiotherapy (IMRT), tomotherapy)
3. What are the long-term effects on local control, survival and toxcity?
APBI vs WBRT (RCT)
Year Arm 1 Arm 2 Conclusion
Christie 1982-1987
WBRT
40 Gy/15
Electrons 42.5 Gy/8
WBRT superior
Yorkshire 1986-1990
WBRT 40Gy/15
EBRT 55Gy/20
WBRT superior
Hungary 1998-2004
WBRT 50Gy/25
HDR
36.4 Gy/7
Similar control, better cosmesis with HDR
TARGIT A 2000-2009
WBRT 40-56Gy
IORT
20 Gy/1
IORT non-inferior
Hungary WBRT (130) vs PBI (128) using HDR
multicatheter brachytherapy (69%) or EB (31%)
No statistically significant difference in 5 year local recurrence rate: 3.4% in WBRT vs 4.7% in
PBI Overall survival: 91.8% vs 96.4% Cancer specific survival: 96% vs 98.3% Disease free survival: 90.3% vs 88.3%
Better cosmesis with HDR APBI
Int. J. Radiation Oncology Biol. Phys. 2007
TARGIT A trial Year 2000-2009: 1113 IORT vs 1119 WBRT
Conclusion: IORT should be considered as an alternative to WBRT after BCS
Lancet 2010
Local recurrence at 4 years:
1.2% in IORT0.95% in WBRT
Ongoing RCT (APBI vs WBRT)
Trial APBI technique
NSABP B39 Multicatheter brachytherapy,
MammoSite balloon catheter,
3D conformal radiotherapy
ELIOT Intraoperative radiotherapy (Electron)
GEC-ESTRO Interstitial brachytherapy
RAPID 3D conformal radiotherapy
IRMA 3D conformal radiotherapy
IMPORT Low Intensity-modulated radiotherapy (IMRT)
Arm 1: primary tumor region + low risk region
Arm 2: primary tumor region
Is it a perfect solution?
Counterpoints
The spatial pattern of ipsilateral breast tumor relapse is not accurately defined Definition of “same site”: no generally accepted criteria (?
index quadrant ?tumor bed ?surgical field ?scar area)
Does not correspond closely to pathological findings Pathological studies suggest multifocal/multicentric foci are
relatively common (~45%) in patients with clinically unifocal tumors Holland R et al. Cancer 1985 Vaidya JS et al. Br J Cancer 1996
Counterpoints
The distinction between true recurrence and new primary tumor may not be reliable Vicini FA et al. Cancer 2007: Clinical and the
clonality classifications only show 65% concordance
7 randomized breast conservation trials suggests that other quadrant ipsilateral breast relapse is reduced by whole breast radiotherapy
What is the likely impact of APBI trials?
Conclusions
~16000 women Level I evidence for or against APBI in early
breast cancer Identification of patient subgroups with the
most and least to benefit from APBI APBI technique comparison (NSABP B39) Increase the understanding of ipsilateral
breast tumor relapse and the impact of radiotherapy (IMPORT Low)
Supplementary
ELIOT trial ELIOT (Electron Intraoperative Therapy) 2000
4-12MeV external beam electron applicator 21 Gy single dose to 10-30mm around the applicator Milan III trial – testing the effect of WBRT after
quadrantectomy, in which in the absence of radiotherapy, 85% of IBTR presented “in the scar area”
Milan I trial – comparing quadrantectomy and mastectomy, in which patients treated with quadrantectomy suffered comparable rates of other quadrant IBTR and contralateral breast cancer
Hypothesis – WBRT is not necessary, since most IBTRs occur in the vicinity of the primary tumor, and radiotherapy does not prevent other quadrant relapses which are mostly new primaries
TARGIT trial
TARGIT (TARGeted Intraoperative radioTherapy) 2000 Low energy photons (50kV maximum) 20Gy single dose to 2mm beyond the surface of applicator Clinical and pathological observation
IBTR occurs in >90% of the patients at the site of the original primary tumor regardless of surgical excision margin and WBRT
A pathological study of 30 mastectomy specimens from women eligible for BCS revealed multiple tumor foci in 19 specimens, and in 15 of these, foci were located outside the index quadrant
Hypothesis – Multicentric cancer foci remain dormant and are not generally responsible for IBTR
GEC-ESTRO trial
European Brachytherapy Breast Cancer GEC-ESTRO Working Group trial
2004 High dose rate (HDR) [32 Gy/8 or 30.3Gy/7
BD] or pulsed dose rate (PDR) [50 Gy hourly fractions of 0.6-0.8Gy] brachytherapy
Majority of IBTRs occur in close proximity to the tumor bed, and that other quadrant IBTR risk is low and unaffected by radiotherapy
NSABP B39/RTOG 0413 trial
2005 Three APBI technique
Multicatheter brachytherapy MammoSite balloon catheter 3D conformal radiotherapy
Rationals similar to ELIOT trial
RAPID and IRMA trials
RAPID (Randomised Trial of Accelerated Partial Breast Irradiation) 2006
IRMA (Innovazioni nella Radioterapia della MAmmella) 2007
Compare WBRT and 3D conformal radiotherapy
Rationals similar to ELIOT trial
IMPORT Low trial IMPORT (Intensity Modulated and Partial Organ
Radiotherapy) Low trial 2006 Fixed multisegmented tangential beams in all three
arms Whole breast (40Gy/15) Partial breast (40Gy/15) Partial breast (40Gy/15) + remainder of the whole breast
(36Gy/15) Testing
WBRT vs PBI Direct measure of RT effect against other quadrant
relapses