Professional Documents
Culture Documents
for
Non-Invasive Cancers and
Early Invasive Cancer
Dr Suranjan Maitra
PGT, Radiotherapy
NRSMCH
1
NonInvasive
Cancers
Early
Stage
Invasi
Non-Invasive Diseases
LCIS
DCIS
Pagets Disease
Lobular Ca in situ
<15% of non-invasive ca
Multicentric in 90% of specimens
Bilateral in 35-59% cases
10% Invasive ca has associated LCIS
ER positive
Must at diagnosis:
Bilateral Mammogram
Core Biopsy/FNAC
Pathology Review
Importance of Mammogram:
LCIS: A marker for increased risk for
subsequent development of invasive
(usually ductal carcinoma), equally
both for IBTR and CBTR
Lobular Ca in situ
Surgical Excision and Biopsy
is must to proceed for
management.
Management is done
according to associated DCIS
or Invasive Ca disregarding
the presence of LCIS.
If margins are positive for
LCIS, additional surgery to
obtain clear margins for LCIS
is not required.
7
Pagets Disease
Rare entity: <5% of all Breast
Ca cases; In fifth-sixth decade.
D/d: Eczema (B/L in Eczema)
Palpable mass present in 50%
cases (Invasive Ca in 90%).
If no palpable mass, 66-86%
underlying DCIS.
Prognosis and management
according to underlying
disease.
9
Ductal Ca in situ
DCIS - Recurrences
Recurrence is 50% DCIS and 50% Invasive Ca.
Risk Factors for Recurrence:
1)Age <50yrs
2)Palpable mass
3)Close (<1mm) or involved margins
4)High Grade
5)Diameter >1cm
6)Presence of Comedo Necrosis.
12
13
14
DCIS - Treatment
Whole Breast RT following lumpectomy
reduces the recurrence rate by 50% in DCIS.
Boost to tumor bed by 10 Gy is recommended
in cases with close margins and age <50yrs.
MRI may be advised in patients suspected to
have multi centric disease.
Patients without any high risk feature: Surgical
Excision alone is sufficient.
15
16
17
18
19
Definitive therapy of
Ca Breast
Evolution of
Breast Surgery
20
21
22
(Lumpectomy
+ Surgical Ax Staging)
reconstruction
Total Mastectomy
+ Surgical Ax Staging
reconstruction
Preoperative
chemotherapy
If,T2 or T3 tumor
fulfills criteria for BCT
23
Lumpectomy
Optimal extent of resection for treatment of EBC not clearly
defined.
Wide local excision with microscopically negative margins is
preferable
to segmental
or Quadrantectomy
Re-excision
at mastectomy
the primary tumor
site recommended when:
Surgical procedure was less than a complete lumpectomy.
Pathologic margins are positive.
Residual suspicious microcalcifications on a postlumpectomy
mammogram.
Extensive Intraductal Carcinoma (EIC).
Tumor size alone is not usually considered an indication for reexcision
For larger T2-T3 tumor NACT f/b breast conservation is
encouraged.
24
BCS+RT
Mastectomy is no longer a standard
of care in breast cancer surgery
BCS is possible in all EBC and is also
practised in LABC
Whole breast RT is compulsory in BCT
Results of BCS+RT and mastectomy
are equivalent
Local control rates are also
significantly improved by use of
boost to tumor bed
25
IGR
Milan
NSABP
B-06
NCI
EORTC
Danish
Stage
1,2
1,2
1,2
1,2,3
Surgery
2cm
gross
margin
Quadrantectom
y
Lumpectomy
Gross
excision
1 cm gross
margin
Wide
excision
Follow-up(y)
15
20
20
18
10
73
42
46
59
65
79
BCS
BCS followed
followed by
by RT
RT is
is
equivalent
equivalent to
to mastectomy
mastectomy for
for
OS:BCS+RT(%)
M(%)
appropriately
appropriately
selected
selected
patients
65
41
47
58 patients
66
LR: BCS+RT(%)
M(%)
14
14
22
with
with
EBC.
EBC.
10
82
20
12
26
BCS+RT vs BCS
27
78 RCTs of EBC.
N= 42 000
7300 had BCS
Local recurrence
rate at 5 years,
after BCS was
reduced by
post-op RT from
26% to 7%.
5 yr gain
16.1%
LR
15 yr gain
5.1%
OS
EBCTCG Lancet 2005,vol 366, 2093
29
5 yr gain
30.1%
OS
15 yr gain
7.1%
30
4 Ax Nodes (+)
Negative Ax nodes
RT to whole Breast
Tumor bed boost OR
Partial Breast
Irradiation
(PBI)
Negative Ax nodes +
Tumor 5cm OR
: RT to chest wall
Close margin(< 1cm)
Negative Ax nodes +
Tumor 5cm OR
: No Radiation therapy
Margin > 1cm.
Axillary Sampling :
Min. 4 nodes removed at Level I if metastatic AD or Axillary RT
Recognized as staging procedure
Significant morbidity and LR > 10%
33
Adequate ALND???
34
Sentinel Lymph
Node Biopsy in
Breast Cancer
Ten-Year
Results of a
Randomized
Controlled Study
Veronesi U et al , Ann Surg 2010;251: 595600
35
36
NSABP-32 Trial
Sentinel-lymph-node resection compared with conventional axillary-lymph-node
dissection in clinically node-negative patients with breast cancer: overall survival
findings from the NSABP B-32 randomised phase 3 trial
Findings
5611 women were randomly assigned to the treatment groups, 3989 had pathologically
negative SLN. 309 deaths were reported in the 3986 SLN-negative patients with follow-up
information: 140 of 1975 patients in group 1 and 169 of 2011 in group 2. Log-rank
comparison of overall survival in groups 1 and 2 yielded an unadjusted hazard ratio (HR) of
120 (95% CI 096150; p=012). 8-year Kaplan-Meier estimates for overall survival were
918% (95% CI 904933) in group 1 and 903% (888918) in group 2. Treatment
comparisons for disease-free survival yielded an unadjusted HR of 105 (95% CI 090122;
p=054). 8-year Kaplan-Meier estimates for disease-free survival were 824% (805844) in
group 1 and 815% (796834) in group 2. There were eight regional-node recurrences as
first events in group 1 and 14 in group 2 (p=022). Patients are continuing follow-up for
longer-term assessment of survival and regional control. The most common adverse events
were allergic reactions, mostly related to the administration of the blue dye.
Interpretation
Overall survival, disease-free survival, and regional control were statistically equivalent
between groups. When the SLN is negative, SLN surgery alone with no further ALND is an
appropriate, safe, and effective therapy for breast cancer patients with clinically negative
lymph nodes.
Krag et al, Lancet 2010 Vol.11.p 927-933
- Vol 252
CONCLUSION:
The maximum depth of the SC and AX lymph nodes varies widely and is related to
the patient's size represented by the A/P diameter. In most patients, the AX
lymph nodes lie at approximately the same depth or shallower than the SC.
Therefore, the rationale for a posterior axillary boost field needs to be further
assessed. When the AX and SC lymph nodes are deep, opposed supraclavicular
and axillary fields and/or the use of a higher energy beam might be reasonable.
Before
Offerin
g BCT
43
Breast imaging.
Details of specimen
46
Treatme
nt
volume
Whole
Breast
Supraclav
Axilla
Internal
Mammary
Indication
cN2-N3 ds
>4+LN after AD
1-3+LN with High RF
Node +SLN with no AD
High risk with no dissection
N+ with extensive ECE
SN+ with no dissection
Inadequate axillary
dissection
High risk with dissection
# size/
Total
technique dose
2Gy or 1.8
Gy/tangents
Wedges
/dynamic
wedges to
optimize
homogeneity
1.8-2Gy
AP or AP-PA
4550.4Gy
Comment
Consider omission
of RT
In elderly with stage
I (ER +) and co
morbidities
1.8-2 Gy
45-50.4 Gy Axilla may be
AP-consider
intentionally included
posterior axillary
With use of high
boost if
tangents
suboptimal
coverage only
Individualized but consider for 1.8-2Gy
45-50.4 Gy
+Ax. Nodes with Central &
Partially Wide
Medial quadrant lesions
tangents or
Stage III breast cancer
separate IM
+SLN in IMN chain
electron/photon
+SLN in axilla with drainage
47
to IM on Lymphoscintigraphy
Hypofractionated RT
Started as an empirical practice in
government-run health care systems of UK
and Canada
Initially, a purely logistical exercise to reduce
treatment duration & create machine space
Recently, 2 large trials, START-A and START-B,
have validated that clinically as well,
hypofractionated RT is safe and effective.
In fact, even while delivering a lower BED, the
hypofractionated regimens have shown a
survival advantage over conventional
fractionation!
START-A: (19982002)
N=2236
EBC (pT1-T3a, pN0N1, M0)
BCS=1900 (85%) &
MRM=336 (15%)
3 arms:
50 Gy/25#/5 weeks
41.6 Gy/13#/5 weeks
39 Gy/13#/5 weeks
Median FU=5.1 years
Locoregional relapse
rates were 3.6%, 3.5%
and 5.2%, respectively
Late effects, based on
photographs and patient
assessments, were
significantly lower with
39 Gy as compared to
50 Gy
This trial estimated /
of breast cancer as
4.6Gy for tumor control
and 3.4Gy for late
change in photographic
appearance.
START-B: (19992001)
N=2215
EBC (pT1-T3a, pN0N1, M0)
BCS=2038 (92%) &
MRM=177 (8%)
2 arms:
50 Gy/25#/5 weeks
40 Gy/15#/3 weeks
Median FU=6 years
Locoregional relapse
rates were 3.3% and
2.2%, respectively
Absolute differences
in locoregional
relapse was -0.7%
(95%CI -1.7% to
0.9%), meaning that
with 40Gy the
relapse rate would
be at most 1% worse
and at best 1.7%
BETTER!
Cosmesis
Is SCF RT required
at all?
Studies suggest that isolated SCF recurrences
are uncommon, for both pN1 and pN3 disease
The main risk for pN3 disease, is not SCF
recurrence but distant metastasis
54
tment position:
ne position- For reducing dose to underlying lung , heart & contrlat. breast
( Merchant and McCormick)
Treatment volume :
Targets
Whole breast , Chest wall + small lung tissue
Supraclavicular fossa
Axillary nodes
Breast
Internal mammary nodes ( if indicated)
OARs
Lung
Heart
Opposite
Skin55
56
dio-opaque clips placed at margins of tumor bed and/or scars are wired
Lower margins : Upper margin of tangential fields
per margins
Edge of: At
thethe
Head
of of
the
clavicle
Upper: margin
level
cricothyroid
groove
Medial
: 1cm
the midline
along the medial border of
wer margin
: 2margin
cm below
theacross
inframammary
fold
ipsilat. SCM
eral margin
: 2border
cm beyond
all palpable
breast
including
entire Medial
Lateral
: At Coracoid
process(
In tissue
case of( axillary
extension
2/3 rd of scar in post-mastectomy pts.)
Humeral head is included)
dial margin : With Int.mammmary field- at lat margin of int.mammary field
This field
is angled
approximately
5 to 10
from the
the midline
vertical
Without
Int.
mammary fieldAtdegrees
or 1cm over
toward the medial side to avoid treating the cervical spinal cord.
57
58
59
make the post. edge of the tang. beam follow to the downward sloping
our of the ant. chest wall
61
CLD
Ipsilat. Lung
included
(Predicted)
1.5 cm
2.5 cm
3.5
6%
16%
26%
63
ns at edge of sharp Linac beams produces Hot spots just beneath skin at
d junction (d/t divergence of Tangential fields and Supraclavicular field int
other.) SEVERE MATCHLINE FIBROSIS or RIB FRACTURE
hods of matching:
65
66
TUMOUR BED
BOOST
67
68
Boost modalities
ve
margin
:
15
mm
is adequate.
IMPT
Surgical clips usu 5
For LABC
: Not defined. An area of
Modulated
electrons
Ultrasonography
(MERT)
present
trials.
scan
Liberal margin (evenCT
extra 5 mm) will
MRI
double the
Per-op placement of catheters
CTV.
(Ref: ESTRO Recommendations, 2002)
69
APBI
Twin rationale:
(1) Most breast cancer recurrences
occur in the index quadrant.
(2) Many patients cannot come for
prolonged 5-6 week adjuvant
radiotherapy for logistic reasons.
71
APBI: Indications
(ASTRO recommendations)
Suitable outside clinical
trial
(ALL of)
Age>60 years
BRCA negative
T1N0M0 (pT<2cm)
EIC negative
Unifocal
IDC/ favourable histology
Margin negative (>2mm)
LCIS negative
ER positive
Suitable only in a
clinical trial
(ANY of)
Age 50-59 years
BRCA negative
T1/2,N0,M0 (pT2-3 cm)
EIC <3cm
Unifocal
ILC
Margin close (<2mm)
ER negative
72
T>3cm/T4 or N+
BRCA mutated
High grade
LVSI extensive
EIC+ve (>3cm)
Multifocal disease (contraindication to BCS
per se)
Margin positive
Received neoadjuvant chemotherapy
73
2
16
0
10
234 1112
5 7
74
2.7
Gy
3.4
Gy
5.1
Gy
75
4.25
Gy
5.1 Gy
76
77
TARGIT
TARGIT-A trial results
tractive because
1) Non invasive , 2) Homogeneous dose pattern , 3) Less toxicity
79
ELIOT
80
Veronesi U et al.(2008)
ecancermedicalscience 2:65
81
83
IMPORT trials
(phase III RCTs from UK)
IMPORT High: (2008-ongoing)IMPORT Low: (2006-2010)
To test dose-escalated IMRT To test PBI by IMRT in lowrisk EBC after BCS
in high-risk EBC after BCS
(ALL) IDC/no ILC/pN0/no
High risk by v/o (ANY)
LVE/pT<3cm/unifocal/grade
N+/grade III/T>2/NACT
I,II or III/margin>2mm
received/margin<5mm/age
3 arms:
18-49 yrs/LVE+
WBRT (15#/3 weeks)
3 arms:
WBRT followed by sequential WBRT +PBI (each 15#/3
weeks)
boost (56 Gy/23#)
WBRT with SIB (48Gy/15#) PBI (15#/3 weeks)
WBRT with SIB (53Gy/15#)
Primary endpoint: Local
control (ipsilateral)
Primary endpoint: Breast
fibrosis
84
Low Risk
Intermediate
Risk
High Risk
Endocrine
Responsive
ET or Nil
ET alone , or
CT+ ET
CT+ET
Endocrine
Response
Uncertain
ET or Nil
CT+ ET
CT+ ET
CT
CT
Endocrine
Non
responsive
Goldhrisch
NA
Follow up of BCT
Post radiation B/L mammogram - within first year.
H+Ph.Ex -3mnthly x 3yrs ;6mnthly x following 2yrs and annually thereafter.
After BCT, a diagnostic mammogram -6-12mnthly x 2yrs and yearly
Thereafter
Monthly self-breast examination (supine and upright position.)
At least yearly evaluation (even 10yrs after Rx)- d/t late breast relapses
and occasional distant metastasis
Unnecessary tests are discouraged
87
lumpectomy
nodal status
50 Gy
Compensators
wedge
supraclavi
electron boost
4-6 MV photons
diffuse
Take cancer
Breast
MLD MHD
WBI
Home
IMRT
boost
margins
heart
CHD
ALM ANAC
conservation therapy
T
APBI
isodose
sentinel node mammosi
i.e.
V30
EIC
conformal
multileaf
adjuvant collimator
TARGIT
systemic therapy
lung V20
pregnancy
local relapse
te
QUART
prone position
Overall survival
ELIOT
Her2-neu
interstiti
recurrenc
al
ER/
e PR
cosmesis
IOET
tamoxifen
breast
board
EORTC
NSABPtumor
B-06 volume gives improved local
4. Radiation Boost to primary
10801
tylectomy
single isocenter
Control but minimal
benefit
axillary survival
3-D
CRT
DCIS
divergence
opp. breast
nodes
dose
CO60
medial
breast
5.PBI/APBI though results are promising
, still not
accepted
as
inhomogeniety
standard of care and needs further evaluation
port technique
PTV
EBCTGG
BRCA 1/2
CTV therapy
6.Systemic
as Neoadjuvant
results in
Stage
I & II or adjuvant therapy
0 - 120
isocenter
mammogram
90as
better outcome
in terms of downMRM
staging as well
LRC0 abduction
7.Close and careful monitoring is essential during follow-up period
to detect
88
both local recurrence as well as distant metastasis
89