Intraoperative radiotherapy carcinoma breast

RECENT ADVANCES IN SURGERY
TOPIC: INTRA-OPERATIVE RADIOTHERAPY FOR
CARCINOMA BREAST(IORT)
SPEAKER: DR. ABHISHEK KUMAR THAKUR
PG general surgery

Breast cancer
 Breast cancer remains the
most common cancer that
affects women.
 Despite the evolution of
treatment, breast cancer
persists as the second most
common cause of cancer
death in women.
 Treatment modalities for
breast cancer have evolved
significantly over the past 25
years.

GENDER - All
women are
at risk
Age
Family/Personal
History
Reproductive
History
Menstrual
HistoryRace
Genetic
Factors
Breast Cancer Risk Factors
unalterable factors
Radiation
Treatment with
DES

All
women are
at risk
Obesity
Breastfeeding
Not having
children
Birth Control
Pills
Alcohol
Hormone
Replacement
Therapy
Exercise
All
women are
at risk
Obesity
Breastfeeding
Not having
children
Birth Control
Pills
Alcohol
Hormone
Replacement
Therapy
Breast Cancer Risk Factors
that can be controlled
Exercise

Causes of Hereditary
Susceptibility to Breast Cancer
Gene
BRCA1
BRCA2
TP53
PTEN
Undiscovered genes
Contribution to
Hereditary Breast
Cancer
20%–40%
10%–30%
<1%
<1%
30%–70%
5 to 10% of breast cancers can be attributed to inherited factors

The relationship of carcinoma of breast to the quadrants of the
breast

Ductal Carcinoma in situ (DCIS)
11
Illustration © Mary K. Bryson
Ductal
cancer
cells
Normal
ductal
cell

Invasive Ductal Carcinoma (IDC – 85% of
breast cancer)
• The cancer has spread to the
surrounding tissues
12Illustration © Mary K. Bryson
Ductal cancer cells
breaking through
the wall

Invasive Lobular Carcinoma (ILC)
13Illustration © Mary K. Bryson
Lobular cancer
cells breaking
through the
wall

DIAGNOSING BREAST CANCER
History and Physical Examination

Signs and Symptoms
16
Most common:
lump or
thickening in
breast. Often
painless
Change in color
or appearance
of areola
Redness or pitting
of skin over the
breast, like the
skin of an orange
Discharge
or
bleeding
Change in size
or contours of
breast

Mammography
• Use a low-dose x-ray system to examine breasts
• Digital mammography replaces x-ray film by solid-
state detectors that convert x-rays into electrical
signals. These signals are used to produce images
that can be displayed on a computer screen (similar
to digital cameras)
• Mammography can show changes in the breast up
to two years before a physician can feel them
20

What Mammograms Show
Two of the most important mammographic indicators of
breat cancers
– Masses
– Microcalcifications: Tiny flecks of calcium – like grains of salt –
in the soft tissue of the breast that can sometimes indicate an
early cancer.
25

Detection of Malignant Masses
Malignant masses have a more spiculated
appearance
26malignant benign

Impression
• Overall assessment of the radiological findings
often includes a classification of the
mammogram using the BI-RADS system
developed by the American College Of
Radiology(ACR)

Breast Imaging Reporting and Data
System(BI-RADS)
• Category0: additional view or ultrasound and
or compare prior film
• Category1: negative
• Category2: benign(noncancerous)
• Category3:probably benign,repeat in
6mth

BI-RADS category
• Category4: suspicious abnormality
consider biopsy
4A: finding with low suspicion of being cancer.
4B: finding with an intermediate suspicion of
being cancer
4C: finding of moderate concern of being cancer
but not as high as category5

BI-RADS category
• Category5: highly suggestive of malignancy,
biopsy is recommended
• Category6: known biopsy proven malignancy,
appropriate action should be taken. It is only
to see how well the cancer is responding to
treatment

Mammogram – Difficult Case*
• Heterogeneously dense breast
• Cancer can be difficult to detect
with this type of breast tissue
• The fibroglandular tissue (white
areas) may hide the tumor
• The breasts of younger women
contain more glands and ligaments
resulting in dense breast tissue
31

Mammogram – Easier Case*
• With age, breast tissue
becomes fattier and has
fewer glands
• Cancer is relatively easy to
detect in this type of breast
tissue
32

Breast Biopsy:
– Image-guided
– Fine-needle aspiration
(FNA) biopsy
• cytological evaluation
– Core-needle biopsy
• alternative to open
biopsy
• low complication rate,
avoidance of scarring,
and a lower cost.

FNAC under ultrasound
guidance

TNM Staging System for Breast Cancer
Primary tumor (T)
 TX - Primary tumor cannot be assessed
 T0 - No evidence of primary tumor
 Tis - Carcinoma in situ
Tis (DCIS) Ductal carcinoma in situ
Tis (LCIS) Lobular carcinoma in situ
Tis (Paget's) Paget's disease of the nipple with no
tumor (NOTE: Paget's disease associated
with a tumor is classified according to
the size of the tumor)

 T2 - Tumor >2 cm but not >5 cm in greatest dimension
 T3 - Tumor >5 cm in greatest dimension
 T4 - Tumor of any size with direct extension to (a) chest
wall and/or (b) skin(ulceration or skin nodules)
T4a Extension to chest wall, not including only
pectoralis muscle
T4b Edema (including peau d'orange), or ulceration of
the skin of the breast, or satellite skin nodules
confined to the same breast
T4c Both T4a and T4b
T4d Inflammatory carcinoma

Regional lymph nodes—Clinical (N)
 NX - Regional lymph nodes cannot be assessed (e.g.,
previously removed)
 N0 - No regional lymph node metastasis
 N1 - Metastasis to movable ipsilateral axillary lymph
node(s)
 N2 - Metastases in ipsilateral axillary lymph nodes fixed
or matted, or in clinically apparent ipsilateral
internal mammary nodes in the absence of
clinically evident axillary lymph node metastasis

 N2a - Metastasis in ipsilateral axillary lymph nodes
fixed to one another (matted) or to other
structures.
 N2b - Metastases only in clinically apparent ipsilateral
internal mammary nodes in the absence of
clinically evident axillary lymph node metastasis
 N3 - Metastasis in ipsilateral infraclavicular
lymphnode(s), or in clinically apparent ipsilateral
internal mammary node(s) and in the presence of
clinically evident axillary lymph node metastasis;

N3a-metastasis in ipsilateral infraclavicular lymph node
N3b-metastasis in ipsilateral internal mammary lymph
node(s) and axillary lymph node(s)
N3(c)-metastasis in ipsilateral supraclavicular lymph
node(s)
Distant metastasis (M)
 MX - Distant metastasis cannot be assessed
 M0 - No distant metastasis
 M1 - Distant metastasis

ANATOMIC STAGE/PROGNOSTIC GROUP

TREATMENT OPTIONS
• Depend on
– Size of the tumor
– Invasive or in situ
– Lymph node status
– Whether it has spread to other parts of the
body

HISTORY
William Stewart
Halsted, (September
23, 1852 –
September 7, 1922)

BREAST CONSERVATION SURGERY;
INDICATIONS
• Stage I & II
• Tumor less then 4 cm

METHODS
• Wide local excision+ RT
• Lumpectomy + Axillary dissection +RT
• Lumpectomy + SLN biopsy +RT
• QUART- Quadrantectomy + Axillary dissection
+RT

RADIATION THERAPY
• Adjuvant
• High energy rays used to kill cancer
cells
• Usually effective in killing fast growing
cells such as breast cancer cells

• 6 ½ weeks, daily treatments,
Monday through Friday
• 4500-5000 cGy to whole
Breast followed by a 1000–
2100 cGy boost to the
lumpectomy site bringing the
entire dose to the surgical bed
to between 6000 and 6600 cGy
External Beam Radiotherapy Treatment Course

Radiation treatment - Front view
Radiation treatment - Side view
Radiation treatment - Cross-sectional view

External Beam Radiotherapy;
indications
• After breast conservation surgery
• T3 tumor
• Positive margins
• High risk groups
• Inflammatory carcinoma
• 4 or more positive nodes

EXTERNAL BEAM RADIOTHERAPY: Side effects
Acute Side Effects
• Fatigue
• Skin changes
Chronic Side Effects
• Pneumonitis
• Lymphedema
• Rib Fracture
• Secondary Malignancy
• Skin Changes
• Pericarditis

BRACHYTHERAPY
• Small infiltrating duct cancers with uninvolved
nodes.
• Treated with interstitial brachytherapy with
radioactive wires.
• Recurrence rate is 0–4% at 2–5-year follow-up.
• This technique was found to be equivalent to
whole-breast radiotherapy at 30-month
follow-up

DRAWBACKS
• These techniques need after-loading of the
radioactive source in the wire or balloon
templates.
– This typically is done in 5–7 fractions delivered in
the postoperative period, over 4–5 days.
• uses interstitial implants necessitates the
treatment to be carried out in a specially
shielded room.
• cumbersome

Y IORT?
• Until the 1970s, surgical management of breast cancer
was based on the Halsted mastectomy, with minor
modifications. From the 1970s, studies showed that
breast-conserving surgery plus radiotherapy resulted in
much the same outcomes as the Halsted mastectomy for
tumours up to 5 cm in size; however, when radiotherapy
was omitted, women had an increased likelihood of local
recurrence.

• Many RCT have shown that more than 90% of
recurrent disease occurring in the breast is within
the index quadrant
• Thus, breast-conserving surgery followed by
whole breast irradiation became the mainstay of
surgical treatment for small breast carcinoma.
• In the past 10 years, studies have shown that the
duration of whole breast irradiation can be
abbreviated from 6 weeks to 3 weeks and partial
breast irradiation has reduced the irradiation field
to the quadrant in which the carcinoma arose.

• Despite these advances, most women are still
required to attend postoperative radiotherapy
for about 30 days consecutively. Many women
living a substantial distance from a
radiotherapy centre have serious difficulties
attending every day, especially those living in
small villages, mountainous regions, or
islands

• One striking fact about local recurrence after breast-
conserving surgery is that most occurs in the area of
breast immediately next to the primary tumour;
Thus, only the area adjacent to the tumour may
need treatment with radiotherapy.
• On the basis of this premise, clinical scientists have
used new technology to administer radiotherapy to
the area at greatest risk of local recurrence, with the
aim of completing the whole local treatment in one
sitting.
• If this approach is validated by the results of current
randomised trials, it could save time, money, and
breasts.

THE TECHNOLOGY:-
• The technique employs a miniature electron-
beam driven X-ray source that emits soft X-
rays (50 kV) from within the breast.

It employs a miniature electron-beam-driven X-ray source
called INTRABEAM TM(PeC) that emits soft X-rays (50 kV)
from within the breast. The X-rays are emitted from the
tip of a 10 cm ,63.2 mm diameter probe, that is enclosed
in a spherical applicator (available in 2.5±5 cm diameter
sizes), which in turn is inserted in the tumour bed and
intraoperative radiotherapy is delivered in about 25 min.

Intrabeam™ for Targeted Intraoperative Radiotherapy

THE INTRABEAM SYSTEM
• Radiation in the form of soft X-
rays (low energy 50 kV) is emitted
from the point source and is
modulated by spherical applicators
to give a uniform dose of
radiotherapy in a spherical field in
the tumour bed.
• There is quick attenuation of the
radiation within tissues which
reduces the damage to
surrounding normal tissues and
minimises the need for radiation
protection by the operating
personnel.

• Depending upon the size of the
surgical cavity, various sizes of
applicator spheres are available and,
for each size, the radiation received is
proportional to the time the machine
is switched on and left in situ.
• If necessary, the chest wall and skin
can be protected (95% shielding) by
radio- opaque, tungsten-filled
polyurethane caps, which can be cut
to size on the operation table –
another advantage of using soft X-
rays.

• A range of applicators from 2.5 cm to 5 cm
have been developed for use in the breast
• Its been found the shape of the cavity after
wide local excision resembles a multisided
pyramid with the base resting on the
posterior/deep wall. However, this cavity
could easily be made spherical if the pliable
breast tissue were wrapped around a rigid
applicator so that the tissue immediately
beyond the surgical excision would be closely
applied to the surface of the applicator and
thus get the highest dose of radiation

• The prescribed dose is 5 Gy at 1 cm.
This delivers a physical dose of about 20 Gy at
the surface of the applicator. The time to
deliver this dose depends upon the size of the
applicator Generally larger the applicator,
longer the duration.
• For a 3.5 cm applicator, it usually takes 24± 25
minutes and for a 5 cm applicator about 38
minutes. It is important that the X-ray source
(XRS) does not move at all during the
treatment since even a millimetre movement
can change the dosimetry.

Intraoperative Technique
Distance
Surface
PE probe (Gy) Conventional EBRT
Physical
Dose
BED Physical
Dose
BED
0.1 cm 15 165 50 60
0.5 cm 8.75 59 50 60
1.0 cm 5.0 21.7 50 60
BED= Physical Dose x [1+ (dose/fx) / a/b)]
a/b = 10 (early effects conventional EBRT)
a/b= 1.5 (assumed for TARGiT device)
Physical Dose Profile
Vaidya et al, Annals of Oncol, 2001; 12: 1075-1080

Operative technique:-
• A single prophylactic dose of intravenous
antibiotic (Cefuroxime l.5 gm) is given at
induction of anaesthetic.
• The wide local excision (WLE) is carried out in the
usual way and immaculate haemostasis
achieved.
• One or two gauze pieces are left in the breast
wound and axillary surgery is performed . This
consists of either the usual axillary dissection or
sentinel node biopsy

• Haemostasis of the breast wound is now
rechecked. This is very important because
even a tiny ooze from capillaries can collect
significant amount of blood over the duration
of radiotherapy and this could potentially
cause a distortion of the cavity around the
applicator. Distortion of the cavity can change
the dose that the target tissues receive.

• The diameter of the
cavity is now measured
with a disposable tape
measure cut to 4 cm or
5 cm This and the
judgement of how well
the breast wraps
around the applicator ±
actually inserting the
applicators in the
wound and visualizing
the apposition is very
useful ± will determine
the size of the
applicator. The usual
size of the applicator is
3.5, 4 or 4.5 cm Cavity is measured with a cut tape (above) and
the applicator is inserted in the cavity to assess
the closeness of fit
(below

• A purse-string stitch is now taken with a No 1 silk
mounted on a hand-held needle. This stitch should be
taken deep to the whole cavity edges, through the
breast tissue and not in the subcutaneous tissues,
such that on tightening the purse string, the skin
should not get pulled too close (1 cm) to the
applicator; at the same time, on pulling the purse
string, the breast tissue should appose to the surface
of the applicator and wrap around it.
Purse string suture
taken with a No 1
silk on a hand-held
needle

• If the tumour is on the left side, a tungsten-
impregnated rubber shield is used to cap the
applicator, to protect the heart and coronary vessels
• The applicator cap needs to be positioned such that it
apposes the bare muscle on the chest wall. Since the
Intrabeam device is not sterile, it is wrapped in a
sterile polyethylene bag. At first, a hole is cut at the
closed end of the bag for the applicator sphere to
come out which is taped at its neck.

• Once the purse string and position of the
gantry is ready, Intrabeam is attached to the
applicator and the bag reversed over the
Intrabeam to cover it and taped in place

• Once the applicator is in place, the position of
the chest wall shield is ascertained, the purse
string is tightened carefully
• Care is taken to ensure that all breast tissue in
the cavity apposes applicator and no part of
skin is less than 1 cm from the applicator
Purse
string is
now
tied
securely

• Three Thermo-Luminescent Detectors (TLD) and a
sheet of Radio-chromatic paper (RCP) is placed
adjacent to the skin edges and kept in place with
transparent tapes
• The minimum distance between skin at the site of
TLD/RCP and the applicator is measured. Care is taken
that this is not less than 1 cm
Prolene stitch everting skin edges Placement of purse-string, RCP and TLD.

• The position of the XRS should be usually
vertical and stay in its position once it is left
free to hang. Once the XRS and the applicator
is inserted and well balanced, a Tungsten
impregnated sheet covers the wound around
the applicator . This blocks 95% of radiation
and reduces the amount of radiation in the
operating theatre to very low levels and that
in the corridor to near zero levels.

• The anaesthesiologist wearing a lead gown
sits behind a portable lead shield and the
physicists are located just outside the
operating theatre, along with the portable
computer and monitoring equipment. The
surgeons and nurses un-scrub and go out of
the theatre

Intrabeam in place and site covered with
protective shield

• Once the radiotherapy is completed, the
shield is removed, the purse-string cut and the
XRS delivered to the Physics team. The TLDs
and Radiochromatic paper is handed over,
carefully mapping the position of each of the
TLD. Haemostasis is re-confirmed and wound
closed

[S4-2] Targeted Intraoperative Radiotherapy for
Early Breast Cancer: TARGIT-A Trial- Updated
Analysis of Local Recurrence and First Analysis of
Survival
Lancet 2010

• What is TARGIT IORT for breast cancer?
The TARGIT technique uses
the Intrabeam device for delivering precise
and timely dose of intraoperative
radiotherapy accurately to the tumour bed.
• Collaborative effort between University
College London and the Photoelectron
Corporation in 1990s.
It was first used on 2 July 1998 in the
Middlesex Hospital, UCL, London. Intrabeam is
currently manufactured by Carl Zeiss

What was done in the TARGIT-A trial
• The TARGIT-A trial was a randomised trial
testing an individualised approach of radiation
after lumpectomy for breast cancer.
• The comparison in the TARGIT-A trial was
between standard radiation therapy that is
given over several weeks after a lumpectomy
vs. a risk-adapted approach using single dose
of TARGeted Intraoperative radioTherapy
(TARGIT) given at the time of lumpectomy.

• The risk-adapted protocol recommended that
if the patients who had received TARGIT were
found to have high risk factors
postoperatively, they also received whole
breast radiation – which occurred in 15-20%
of cases as expected in the protocol;
otherwise, about 80% of such patients
completed their treatment (surgery and
radiation) during their lumpectomy.

• The pre-specified non-inferiority margin was an
absolute difference in local recurrence of breast
cancer between TARGIT and EBRT of 2.5% — in
simple terms, if the absolute difference in local
recurrence between the two treatments being
compared was less than 2.5%, they would be
considered non-inferior to each other in terms of
local control of breast cancer.
• Patient preference studies have suggests
majority of patients consider such a 2.5% margin
as appropriate.
• 3451 patients from 33 centres in 11 countries
participated in the TARGIT-A trial (UK, USA,
Germany, Italy, France Poland , Switzerland,
Norway, Denmark, Canada and Australia) from 24
March 2000 to 25 June 2012

What was found? Results of the
TARGIT-A trial
• When TARGIT is given with lumpectomy, the 5-year
local recurrence of breast cancer is similar to EBRT
• Breast cancer mortality with TARGIT were similar to
EBRT
• Mortality from other causes was significantly lower
with TARGIT due to fewer deaths from cardiovascular
causes and other cancers.
• The results remain stable with longer follow up. The
results were the same for the large number (1222)
patients who were treated between 2000-2008 and
had a median follow up of 5 years.

Is the follow up of the TARGIT-A trial
long enough?
• Although breast cancer can continue to recur beyond 5
years, the peak hazard is in the first 2-3 years.
• Thus, for local recurrence in radiotherapy trials, the 5-
year results are indicative of longer term results.
• The TARGIT-A trial has a large number of patients
(n=1222) with a median follow up of 5 years and even
larger 2232 with a median follow up of nearly 4 years.
• Therefore, these results can be relied upon to guide
the application of TARGIT using Intrabeam in routine
clinical practice in appropriate patients.

Intraoperative radiotherapy versus external
radiotherapy for
early breast cancer (ELIOT): a randomised controlled
equivalence trial
Umberto Veronesi, Roberto Orecchia, Patrick
Maisonneuve, Giuseppe Viale, Nicole Rotmensz, Claudia
Sangalli, Alberto Luini, Paolo Veronesi,
Viviana Galimberti, Stefano Zurrida, Maria Cristina
Leonardi, Roberta Lazzari, Federica Cattani, Oreste
Gentilini, Mattia Intra, Pietro Caldarella,
Bettina Ballardini

Background:-
• Intraoperative radiotherapy with electrons
allows the substitution of conventional
postoperative whole breast irradiation with
one session of radiotherapy with the same
equivalent dose during surgery. However, its
ability to control for recurrence of local
disease requires confirmation in a randomised
controlled trial.

Mobetron System
(Oncology Care
Systems Group of
Siemens Medical
Systems, Intraop
Medical Inc., Santa
Clara, CA, USA)

1305 patients were randomised (654 to external radiotherapy
and 651 to intraoperative radiotherapy) between
Nov 20, 2000, and Dec 27, 2007.
The 5-year event rate for IBRT was 4・4% (95% CI 2・7–6・1)
in the intraoperative radiotherapy group and 0・4% (0・0–1
・0) in the external radiotherapy group During the same
period, 34 women allocated to intraoperative radiotherapy
and 31 to external radiotherapy died (p=0・59).
5-year overall survival was 96・8% in the intraoperative
radiotherapy group and 96・9% in the external radiotherapy
group. In patients with data available (n=464 for intraoperative
radiotherapy; n=412 for external radiotherapy) we noted
signifi cantly fewer skin side-eff ects in women in the
intraoperative radiotherapy group than in those in the external
radiotherapy group (p=0·0002).

• other systems are mobile linear accelerators –
– the Novac-7 System (Hitesys SpA, Italy).

THE NOVAC-7 SYSTEM
• Novac-7 (Hitesys SpA, Italy) is a mobile, dedicated,
linear accelerator.
• Its radiating head can be moved by an articulated
arm which can work in an existing operating room.
• It only delivers electron beams at four different
nominal energies – 3, 5, 7, and 9 MeV radiation.

• Beams are collimated by means of a hard-docking
system, consisting of cylindrical perspex
applicators available in various diameters (4, 5, 6,
8, and 10 cm).
• The source-to-surface distance is 80–100 cm.
• For reasons of radiation protection, a primary
beam stopper (consisting of a lead shield, 15 cm
thick) mounted on a trolley and three mobile
barriers (100 cm length, 150 cm height and 1.5
cm lead thickness) are provided.

EARLY RESULTS
• introduced in July 1998, the technique of intra-
operative radiotherapy that is delivered as a
single-dose treatment using low energy X-rays,
• targeted to the peri-tumoural tissues from within
the breast.
– In patients with small breast cancers (now the
majority), this could be the sole treatment.
– In those with high risk of local recurrence, it would
avoid any geographical miss and,
– in combination with external beam radiotherapy, may
further reduce local recurrence.

HEALTH ECONOMICS
• Delivering intra-operative radiotherapy with
Intrabeam™ prolongs the primary operation
by 15–45 min and adds 1–2 h of radiotherapy
physicists’ time in preparation of the device.
• External beam radiotherapy, on the other
hand, costs about 9 man-hours, 6 h of
radiotherapy room time and 30–60 h of
patient time.

Discussion
• This large, international randomised trial provides
robust and mature evidence that substantiates
previous findings showing that targeted
intraoperative radiotherapy is safe.
• Rates of overall complications and major
complications were similar in the targeted IORT
and EBRT groups.
• Although there was a higher risk of seroma needing
aspiration in patients assigned to targeted
intraoperative radiotherapy than in those assigned
to conventional treatment, this event was more than
compensated for by significantly lower radiotherapy-
related complications in the targeted intraoperative
radiotherapy group (RTOG toxicity grade 3 or 4)

Key points for clinical practice
• The usual 6-week course of postoperative
radiotherapy after breast conserving surgery has
several disadvantages that reduces its general
applicability to a wide population, even amongst
the most advanced health economies.
• Since local recurrence after breast-conserving
surgery occurs mainly in the area around the
original primary tumour, it may be sufficient to
target adjuvant radiotherapy to peri-tumoural
tissues.

(continued)
• Modern technology has allowed development
of portable, powerful radiotherapy devices
that can be used in standard unmodified
operation theatres.
• Radiobiology of single-dose, intra-operative
radiotherapy is still being studied and the
optimum dose has not been established as
yet.

(continued)
• Results of pilot studies using modern intra-
operative radiotherapy techniques are
encouraging and several collaborating
international groups are recruiting patients in
randomised trials
• Used as a boost, targeted intra-operative
radiotherapy can avoid geographical miss and has
the potential to reduce local recurrence. Used as
a sole treatment for good prognosis breast
cancers, it could replace the whole 6-week course
of postoperative radiotherapy.

(continued)
• Unlike most modern medical technology,
some intra-operative systems may actually
save money for the health system.

Intraoperative radiotherapy carcinoma breast

Intraoperative radiotherapy carcinoma breast

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Intraoperative radiotherapy carcinoma breast

Similar to Intraoperative radiotherapy carcinoma breast (20)

Recently uploaded

Recently uploaded (20)

Intraoperative radiotherapy carcinoma breast