Post-mastectomy radiotherapy

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Post-mastectomy radiotherapy

• Sabine Balmer Majno
• Radiation Oncology
• Geneva University Hospital

SRO Tutorial 20/09/2006
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Post-mastectomy radiotherapy (PMRT)

• RT as post-operative adjuvant to total
  mastectomy (usually with axillary surgery)
• Historically (clinical trials), PMRT refers to
  comprehensive loco-regional RT
• chest wall
• axilla
• supraclavicular
• internal mammary

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PMRT technical requirements

• Megavoltage photon and electron beams of
  appropriate energies (linear accelerator)
• Beam simulation (conventional or CT)
• Computer-assisted dose optimisation
• Adjuvant dose prescription (EORTC) 50 Gy in
  25 2-Gy fractions, 5 weeks
  
  Other
  schedules may have comparable therapeutic ratios

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Set-up of the patient on the breast board
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Breast board
SINMED BV Posiboard-2

Posiboard-2

The
Posiboard-2 breast board is a
complete solution for the
positioning of
breast patients. It is made of a low
density
foam core covered with an ultra
thin layer of carbon
fiber. This allows
the beam to transfer the Posiboard-2
from
any angle with minimal attenuation. For
arm
positioning, several comfortable and
adjustable
supports are available. To
prevent the patient from
sliding down, an
adjustable bottom stop is integrated.
The
Posiboard-2 is compact , lightweight and
can be
positioned on any couch top with
the aid of
specifically designed couch top
fixation pieces. For
additional support, a
breast mask can be mounted using
a quick
release system. When the Posiboard-2 is
not in use,
it is hung on the wall with the
supplied wall mount
plate.
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Patient with radio-opaque markers on the skin
Red crosses (initial position for the scan) are
drawn on the skin to check the position of the
patient before marking the isocenters of the
different fields.
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CT Parameters

• Pilot scan

130 kV - 200 mA Pitch 2.00 Index 4 - Thickness 4
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Transfer of the data set to ACQSIM.
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Outline of the superior border slice of the
breast inferior border of the SC field.
Determining the isocenter for the SC field. SSD
100 cm.
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Rotation of the gantry to avoid the spinal
cord. A modification of the isocenter is possible.
ESTRO MARCONI
ESTRO MARCONI
Add shifts if necessary
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Coordinates of the isocenter - Add shifts if
necessary.
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Determination of the central slice for the
tangential beams. Drawing the box
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Automatic set-up of the isocenter.
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Displacement of isocenter, if needed.
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Virtual simulation software.
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The negative side of PMRT

• Cost, inconvenience, and transient acute
  reactions
• Chronic functional impairments arm oedema, rib
  fractures, shoulder stiffness, brachial plexus
  injury, lung fibrosis
• Increased second neoplasms
• Increased cardiovascular morbidity

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The negative side of PMRT

• Almost all serious complications of PMRT relate
  to irradiation of specific nodal fields (e.g.,
  arm oedema from axillary RT, brachial plexus
  injury from supraclavicular RT, cardiac injury
  from left-sided IMC RT)
• Properly conducted chest-wall RT has little
  serious morbidity

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The negative side of PMRT

• Functional complications of PMRT can be reduced
  by
• improved RT technique
• more restrictive indications for nodal RT
• Potentially fatal consequences of PMRT
  essentially limited to
• cardiac (and other vascular?) events
• secondary neoplasms

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EBCTCG 1995 OverviewLancet 2000

• Analysed long-term results from 20,000 women
  randomised in 40 adjuvant RT trials
• Statistically powerful, but heterogeneous
  regarding tumour stage, surgical approach, and RT
  technique
• Purports to provide conclusions relevant to
  contemporary practice

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EBCTCG 1995 OverviewLancet 2000

• Non-vascular non-breast-cancer mortality
  slightly, but not significantly, greater with RT
  (2p 0.08)
• Deaths from second non-breast cancers
• with RT 213/10,021 (2.1)
• without RT 173/10,154 (1.7) 2p gt 0.1

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EBCTCG 1995 OverviewLancet 2000

• Increased non-breast cancer mortality essentially
  due to excess of vascular deaths in irradiated
  patients
• with RT 437/10,021 (4.3)
• without RT 322/10,154 (3.2) 2p 0.0007
• Predominant effect thought to result from cardiac
  irradiation in left-sided tumours

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EBCTCG 1995 OverviewLancet 2000

• Increased non-breast-cancer mortality observed in
  irradiated patients
• Significant only in trials started before 1975
• lt 1975 6.4 absolute increase in non-BC
  deaths with RT
• gt1975 0.8 absolute increase in non-BC deaths
  with RT

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Randomised trials of the local management of
early breast cancer by various types of surgery
and/or radiotherapy

• Meta-analyses 42,000 women in 79 trials from the
  year 2000 EBCTCG meeting
• Richard Peto, Sarah Darby Paul McGale,
• on behalf of the Early Breast Cancer Trialists
  Collaborative Group (EBCTCG)

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EBCTCG 2000 trials of local therapy
Treatment comparison Available for the EBCTCG year 2000 meta-analyses Available for the EBCTCG year 2000 meta-analyses Available for the EBCTCG year 2000 meta-analyses
Treatment comparison Trials Women Deaths
Radiotherapy (RT) versus no RT 46 24,000 12,000
More surgery v less surgery 16 9,000 4000
More surgery v RT less surgery 17 9,000 5000
TOTAL 79 42,000 21,000
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Crude example any RT versus no RT

• Meta-analysis putting together the results from
  all (old or new) trials of radiotherapy
• Shows that breast cancer mortality can be
  affected by better local disease control

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Isolated local recurrence in the trials of any
type of radiotherapy (RT) versus no RT
Isolated local recurrence
Absolute difference in risk of isolated local
recurrence 20, mostly within the first 5 years.
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15-year breast cancer mortality in the trials of
any type of radiotherapy (RT) versus no
RT(total 24,000 women randomised in 46 trials)
Breast cancer mortality
Absolute difference in risk of death from breast
cancer 4, mostly after the first 5
years. Little difference in breast cancer
mortality during the first 5 years.
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EBCTCG local treatment comparisons (NB Absolute
5-year gain in local recurrence risk depends on
treatment comparison and on nodal status, N- or
N)

• Radiotherapy (RT) vs no radiotherapy (24,000
  women)
• Mastectomy Axillary Clearance (Mast ? AC) ? RT
• Mast ? Axillary Sampling / Partial C (AS / PC) ?
  RT
• Mast alone (with no routine axillary surgery) ?
  RT
• Breast-Conserving Surgery AC (BCS ? AC) ? RT
• More surgery vs less surgery (9000 women)
• Internal mammary node (IMN) removal vs not,
  neither with RT
• Pectoral muscle (PecM) removal l vs not, both
  with same RT or neither with RT
• AC vs not in N? disease, both with same RT
• AC vs not in N? disease, neither with axillary
  RT
• Mast ? AC vs BCS ? AC, neither with RT (NSABP
  B-06)
• Mast vs BCS, both with AC and RT
• More BCS vs less BCS, neither with AC
• More surgery vs radiotherapy and less surgery
  (9000 women)
• Mast ? AC vs Mast alone ? RT
• Mast ? AC vs BCS alone ? RT (Guys Hospital)

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24 meta-analyses
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Overall meta-analysis of 24 specific
meta-analyses

• Sort the 24 meta-analyses of particular types
  of local therapy comparisons into 3 categories,
• according to the absolute sizes of their
  reductions in 5-year local recurrence risk (lt10,
  10-20, gt20)
• Example N- BCS RT yields 10-20 gain,
• but N BCS RT yields gt20 gain

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Danish DBCG Trials 82b 82c

• Test the effect of 50 Gy loco-regional RT on
  survival of high-risk patients receiving systemic
  therapy after mastectomy
• RT technique explicitly chosen to avoid
  cardiopulmonary toxicity
• Sample size large enough to provide definitive
  evidence

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Danish DBCG Trials 82b 82c(Hojris et al,
Lancet 1999)N3,083, MFU 122 mo
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Meta-analysis of PMRT in patients receiving
systemic therapyWhelan et al, JCO 2000

• 6,367 patients randomised in 18 trials
  (1973-1984)
• Significant net benefit from PMRT
• 75 reduction in odds of LRF
• 31 reduction in odds of cancer recurrence
• 17 reduction in odds of death
• Multivariate analysis significant benefit for
  beginning RTlt6 months

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Superior results with 2 Gy fractionsEBCTCG 1995
Overview

• better local control
• risk reduction 73 vs 63
• less excess non-breast cancer deaths
• 1.4 versus 3.7
• more reduction in breast cancer mortality
• 4.5 versus 2.9

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Which anatomical regions should be irradiated in
PMRT?

• Most clinical trials used comprehensive RT.
• But overview analysis assumes that survival
  benefit is proportional to LRF reduction.
• LRF is observed most commonly on chest wall, less
  frequently in the supraclavicular area,
  uncommonly in the axilla, and rarely in the
  internal mammary area.
• It follows that chest wall RT is first priority.

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Sites of LRF after mastectomy(Recht et al, 1999)
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Axillary irradiation

• Axillary RT increases risk of arm lymphoedema
  after axillary clearance.
• Axillary failure is rare after adequate
  clearance.
• Axillary RT should be avoided after clearance,
  unless residual axillary disease is suspected.
• Axillary RT is recommended after axillary
  sampling in case of positive nodes.
• Other indications undissected axilla? positive
  sentinel node?

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Supraclavicular irradiation

• Risk of brachial plexus injury lt1 if dose does
  not exceed 50 Gy in 2 Gy fractions.
• Cerebro-vascular risk of supraclavicular RT?
• After axillary clearance, risk of supraclavicular
  recurrence lt10 in patients with less than 4
  positive nodes.
• Supraclavicular RT generally recommended for 4 or
  more positive nodes.

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Supraclavicular recurrence
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Internal mammary irradiation (1)

• IM nodes frequently involved when axillary nodes
  positive (particularly for medial T).
• Clinically, IM recurrence is rare.
• No direct evidence that IM treatment improves
  survival.
• IM RT (particularly left-sided) contributes to
  cardiac morbidity.

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Internal mammary irradiation (2)

• Benefits vs risks of IM irradiation under study
  in randomised trials.
• Major importance of RT technique
• CT-based treatment planning
• use of electron beams
• Future role for sentinel node techniques for
  planning IM RT?

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Which patients need PMRT?

• In appropriate patients PMRT reduces LRF and
  increases overall survival.
• EBCTCG Overview 5 fewer breast cancer deaths for
  every 20 LRF prevented by RT (more favourable
  estimates in newer trials).
• With modern RT techniques, excess non-breast
  cancer deaths assumed to be lt1, but longer
  follow-up needed in recent trials.

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Which patients need PMRT?

• The quality of both surgery and systemic therapy
  is important in reducing LRF risk
• But it is a fallacy to believe
• that correct surgical technique makes PMRT
  unnecessary
• that systemic therapy can totally replace PMRT

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Which patients need PMRT?

• PMRT should be recommdended for patients whose
  10-year LRF risk remains unacceptable despite
  optimal surgery and appropriate systemic therapy.
• What is unacceptable is arbitrary, but a
  threshold of 20 is proposed, as PMRT in such
  patients will reduce breast cancer mortality by
  5 (absolute).

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LRF after modified radical mastectomy and optimal
systemic therapy(Recht et al, 1999)
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Which patients need PMRT?

• PMRT strongly recommended for
• T1-2 tumours with 4 or more N.
• T3-4 tumours with N.
• For T1-2 tumours with lt 4 N, high-risk subgoups
  remain to be defined
• larger tumours, close margins, lt 10 nodes
  examined, extracapsular extension?
• unfavourable morphology (LV invasion, etc.)?

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PMRT Conclusions (1)

• 50 Gy PMRT reduces LRF by factor of 4.
• This reduction in LRF leads to a decrease in
  breast-cancer mortality.
• In appropriate high-risk patients, overall
  survival will also be improved if excess
  cardiovascular mortality is minimised.
• Meticulous planning and execution of PMRT is of
  major importance.

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PMRT Conclusions (2)

• Future questions
• indications for T1-2, N1-3?
• role of internal mammary nodal RT?
• role of axillary RT after sentinal node biopsy?
• safety of PMRT with anthracyclines, taxanes?
• optimal sequencing?
• optimisation of RT technique?