Accelerated Partial Breast Irradiation

ADVANTAGES :

 Improved patient convenience and acceptability

 Reduced treatment time, treatment cost, volume of normal tissue exposed to radiation(lung,
heart) and radiation toxicity
 Treatment focused to area of highest risk of residual occult disease/recurrence.
METHODS:

a) Interstitial brachytherapy
b) TARGIT
c) ELIOT
d) Mammosite
e) 3DCRT
f) IMRT

Interstitial Brachytherapy
 Oldest method
 Large and encouraging data
 Good target volume coverage with sparing of normal tissues
 Brachytherapy Machines more common .

 Requires technical expertise.

 Most commonly used method

 Post op interstitial brachytherapy within 8 weeks of primary surgery

 Dose- HDR dose-34Gy/10#/5days

Factor Suitable group Cautionary Unsuitable
Patient ≥60years 50-59 Age <50
Factors Age years

Pathologic factors
Tumor size ≤2cm 2.1-3 >3cm
T stage T1 T0, T2 T3,T4
Margins Negative (> 2 Close Positive
mm) (<2mm)
Grade Any
LVSI No Limited/focal Present
extensive
ER status Positive Negative
Multicentricity Unicentric only Present
Multifocality Unifocal >3cm
Histology Invasive Invasive >3cm
Pure ductal ,favo lobular >3cm
DCIS rable Not ≤3cm
EIC allowed ≤3cm
Not alowed
Nodal pNo PN1, N2, N3
factors N SN Bx or ALND
stage
Nodal
surgery
Treatment Not allowed Used
factors
Neoadjuvant
therapy
METHODS OF APPLICATION

 Template guided
 Single/double/three plane.

PROCEDURE:
• Needles are implanted parallel and equidistance from each other(Paris system)
• In most cases inserted in mediolateral direction
• In very medially or laterally located tumor sites, needles should be implanted in
craniocaudal direction to enable separate target area from skin points
• In some rare cases, upper outer quadrant has to be implanted with needle oriented in
45 degree angle to avoid overlap of source position and skin
• Single plane <12mm
• 2 planes of needles are usually needed to cover the PTV
• 3 planes are required in a large breast where the targeted breast tissue between
pectoral fascia and skin is thicker than 30mm
• 5-9 needles spaced 15-20mm are usually required
 • If superficial needles are too close to the skin, the templates are moved toward each
other so that overlying skin moves up and away from the needles
• If not sufficient, templates with smaller spacing between the needles are used,
resulting in compression of breast tissue and upward movement of skin
• Gauze is used between the templates and skin of thoracic wall at both sides of implant
to avoid skin necrosis secondary to continuous pressure of template
Advantages:
• Longest follow up.
• Better control and tailoring of radiation dose delivery to variation in lumpectomy
cavity, shape, location of breast.
• Limit toxicity to healthy tissue while delivering the maximum dose to at risk tissue.
GEC-ESTRO Randomized trial of APBI

Stage 0,I and II

Low risk and invasive breast carcinoma Treated with breast conserving therapy

Whole Breast RT + Tumor bed boost 50Gy Interstitial Multicatheter

+10Gy Brachytherapy HDR:32Gy/8#
WBRT APBI P va
PDR: 50Gy in pulses of0.6-
5 year Local Recurrence 0.97% 1.38% 0.53
0.8Gy/hr given hourly

5 year disease free 94.45% 95.03% 0.79

survival

5 year overall survival 95.5% 97.25% 0.11

Limitations:
• Considerable training and experiences
• Dose inhomogenity
• High skin dose
Thus not be viable treatment option for patients with superficial tumor or small breast
Complications:-
• Port site infection
• Abscess
• Bleeding
• Breast fibrosis
NSABP-B39/RTOG 0413:PBI OR WBI IN STAGE 0.I.II.BC
PBI was given 3.4-3.85Gy twice daily either with brachytherapy or 3DCRT. Noabsolute
difference in 10year rate of IBTR .
INTRACAVITARY BRACHYTHERAPY

Mammosite

• Balloon with single catheter

• Dose: 34Gy/10 fraction BID Advantage:
• Ease of application
• Problems:
 High skin dose and telengectesia Rib fractures
 Problem in non-uniform cavities
It is a dual-lumen spherical balloon catheter infl atable to 4–5 cm with a central lumen for the high
dose rate (HDR) iridium-192 (192Ir) source. The catheter is a silicone balloon and shaft
approximately 6 mm in diameter and 15 cm in length . The shaft contains a small infl ation channel
and a larger central “treatment” channel for passage of the HDR source

Criteria for patient selection

• T1,<2cm,N0,M0
• Edges of post surgical cavity must be more than 5-7mm from skin surface
• Cavity size >3 cm
• Negative surgical margin

INELIGIBLE:
• An extensive intraductal component
• pure intraductal cancers
• lobular histology
• collagen vascular disease
PROCEDURE
• After lumpectomy ,catheter is placed in breast cavity either during lumpectomy
procedure or later through closed technique
• Balloon is inflated with 35 to 70 ml of saline mixed with small amount of contrast
material, depending on size of lumpectomy cavity
• CT imaging to assess the adequate placement of the devices
• An Ir-192 radioactive source connected to computer controlled HDR remote after-
loader, is inserted through catheter into balloon to deliver the prescription radiation
dose
• Minimum balloon to skin distance for good cosmesis
• 5-7mm is required
• Symmetry is essential for adequate dosimetry
• A non symmetrical implant result in dose in homogeneity to surrounding tissue
• Dose - 34Gy over 10 #(@3.4 Gy/ fraction, twice daily)
• Prescription point is 1 cm from balloon surface
• Minimum 6 hours gap.

Advantages:

• Easily reproducible
• More user friendly technique for brachytherapy.

Disadvantage:
 • Inadequate skin sparing due to poor spacing
• Infection(16%)
• Recurrent seroma
• Balloon rupture

Mutli-channel Catheters

• Mutlichannel Balloon based brachytherapy

• Single balloon: to be inflated

• Coverage better than Mammosite
• Issues related to cavity coverage in irregularly shaped cavities

Intraoperative X rays
Targeted intraoperative therapy

Source: 50KV Xray source

Technique: Intraoperative radiation after wide excision

Dose: 20Gy in 1 fraction at 1mm Effective dose at 1cm: 5-7Gy
Advantage:

 simple technique
 sparing of normal tissues Problems:
 Issues of penetration
 Adequacy of cavity wall dose
 Encouraging early results
TARGIT trial

• Age > 45 years, T size upto 3 cm, unifocal tumors

• BCT+TARGIT vs BCT+ External RT
• Local recurrence rate at 4 years TARGIT group: 1.2%
• External RT group: 0.95%

5year outcome: Local Recurrence in TARGIT arm: 3.3%

Local recurrence in EBRT arm: 1.1%

 • TARGIT inferior to EBRT for Local Control

Intra-operative Electrons:

• Machine: Mobile linear accelerator

• Electron energy: 3-10MeV Technique: Wide excision
• Placement of shield to protect chest wall Reconstruction of the tumor bed
• Dose: 21Gy at 90% isodose Advantages: single fraction
• Problems: Issues of cavity wall coverage .
• Set up and expenses
• Violation of surgical planes
• Encouraging early results

ELIOT TRIAL(intraoperative electron) 2013

T<2.5CM,Age >48 years

BCT+ Whole Breast RT vs BCT+ ELIOT

5 year event rate for IBRT 4.4% in the IORT group and 0.4% in the EXRT group.
External Beam Radiation
Machine: Linear Accelerator

Technique: External Beam RT

3DCRT,IMRT,Tomotherapy Advantages:
Good coverage of target
Good dose homogeneity

Problems:
 Issues of movement with breathing .
 More margin
 Higher intergral dose-lungs, heart
Advantages:

• Non invasive(complication of surgery like seroma and infection can be

avoided)
• Widespread availability
• Technically less demanding

PLANNING

• CTV- Tumor bed on CT including ,surgical clips plus 1cm margin inside breast tissue
• PTV- CTV+1cm margin
• Prescribed dose-38.5 Gy in 10 fraction bd over 5-8 days(Minimum interfraction
interval 6 hrs)
 • Treated with 3-5 non-coplanar conformal fields

Interstitial 3DCRT/ Introperat Intraopera Mammosite

Brachythera IMRT ive tive Xrays
py electrons TARGIT
(ELIOT)

Covera Variable Best Good Good Good

ge of
target
volume
Thickne 1-2cm 2-2.5cm 1-2.5cm Dose 1cm
ss of prescribed at
target 1mm.
treated At 10mm:5-7Gy

Sparin good least good best good

g of
norma
l breast
Skin dose Least High Least Least (can Variable
shield)

Technical Axilla Almost Axilla, Large Large

limitations Nil brachial cavities, cavitie
plexus, skin irregular s,
cavities irregul
ar
cavitie
s,
close
to
skin,
peripher
y

Drawbacks Adequacy of High Histopathology Very limited Cavity

dose to dept shape
 and
target normal Wider h of irradiation, size
tissues,
coverage motion applicability cavity shape, Skin
dose
Wider size, no
applicability hitopathology

Accelerated Partial-Breast Irradiation Compared With Whole-Breast Irradiation for Early

Breast Cancer: Long-Term Results of the Randomized Phase III APBI-IMRT-Florence Trial

Eligible patients, as previously reported, were women age . 40 years with early BC (maximum
diameter, 2.5 cm) suitable for BCS.13 Extensive intraductal carcinoma, multiple foci cancer, and final
surgical margins , 5 mm represented the main exclusion criteria

The primary end point was to determine the 5-year difference in ipsilateral breast tumor recurrence
(IBTR) between 30 Gy in 5 once-daily fractions (APBI arm) and 50 Gy in 25 fractions with a tumor bed
boost (WBI arm) after breast-conserving surgery.

The 10-year cumulative IBTR incidence in early breast cancer treated with external APBI using IMRT
technique in 5 once-daily fractions is low and not different from that after WBI. Acute and late
treatmentrelated toxicity and cosmesis outcomes were significantly in favor of APBI.

Limitations of apbi

• Highly restrictive selection criteria

• Not many trials showing non inferiorty, none showing superiorty and many NOT
reaching the goal of non inferiorty
• Emergence of new hypofractionated schedules with broader selection criteria.

Sequelae of irradiation in breast cancer:

• Lymphedema and Breast Edema

• Skin and Breast Complications
• Brachial Plexopathy
• Pulmonary Sequelae
• Cardiac Sequelae
• Contralateral Breast Cancer and Irradiation
• Incidence of Other Second Malignancies
• Post irradiation Angiosarcoma of the Breast
CHEMO THERAPY IN BREAST CANCER:
• Adjuvant systemic therapies improved locoregional treatment,have contributed to a
decline in breast cancer mortality.
• The introduction of effective cytotoxic agents and targeted drugs (eg, endocrine and
anti-HER2 agents), given before and after surgery, has been instrumental in the
eradication of micrometastases,
• But also has limitations: overtreatment of patients already cured by locoregional
therapy; short-term toxicities
• Emergence of chronic, long-term, and sometimes life-threatening side-effects; and
financial toxicity.
• Two multigene signatures, a 21-gene recurrence score (Oncotype DX,
Exact Sciences, Madison, WI, USA) and a 70-gene prognosis signature (MammaPrint,
Agendia, Amsterdam,Netherlands), have shown level 1 clinical utility to identify patients with
preserved outcome when treated with adjuvant endocrine therapy and no chemotherapy.

• Mammaprint is a 70 gene assay that predicts the probability of long term breast
cancer specific survival, while Oncotype Dx is a 21 gene assay that estimates the
risk of recurrence.

• Results of the MINDACT and TAILORX studies to validate these assays

suggest that these signatures are accurate in predicting which patients may
safely forego chemotherapy.

Relatively inexpensive and less tedious measures (eg. Ki67 explression < 10% advocated
by the St Galen guidelines) also seen to be effective; no comparisons available.
1. MINDACT. Cardoso et al. NEJM, 2016.
2. TAILORX. Sparano et al. NEJM, 2015.

21-gene recurrence-score assay (Oncotype DX, Genomic Health) is one of several

commercially available gene-expression assays that provide prognostic information in
hormone-receptor–positive breast cancer

The Trial Assigning Individualized Options for Treatment (TAILORx) was designed to
address whether chemotherapy is beneficial for women with a mid-range recurrence
score of 11 to 25.
• The Oncotype DX test is a genomic test that analyzes the activity of a group of genes
that can affect how a cancer is likely to behave and respond to treatment. The
Oncotype DX is used in two ways:
 figure out a woman’s risk of early-stage, ER positive breast cancer recurrence, as
well as how likely she is to benefit from chemotherapy after breast cancer surgery
 figure out a woman’s risk of DCIS recurrence and/or the risk of a new invasive
cancer developing in the same breast, as well as how likely she is to benefit from
radiation therapy after DCIS surgery
• Of all the breast cancer genomic tests, the Oncotype DX test has the strongest
research behind it.

• The results of the Oncotype DX test, combined with other features of the cancer, can
help to make a more informed decision about whether or not to have chemotherapy
to treat
• early-stage,
• hormone-receptor-positive breast cancer, or
• radiation therapy to treat DCIS.
Eligible candidate for the Oncotype DX test if:

 stage I or II invasive breast cancer

 the cancer is ER positive
  lymph-node-negative breast cancer
• Most early-stage (stage I or II), estrogen-receptor-positive breast cancers that
haven’t spread to the lymph nodes are considered to be at low risk for recurrence.
• If you’ve been diagnosed with early-stage, estrogen-receptor-positive breast cancer,
the Oncotype DX test can help make a more informed decision about whether or not
you need chemotherapy. (Some research also suggests the test may help
postmenopausal women with estrogen-receptor-positive breast cancer that has
spread to the lymph nodes make chemotherapy decisions. ).

CONCLUSION

• Endocrine therapy was noninferior to chemoendocrine therapy in the analysis of invasive

disease–free survival (hazard ratio for invasive disease recurrence, second primary
cancer, or death.
The chemotherapy benefit for invasive disease–free survival varied with the combination of
recurrence score and age (P = 0.004), with some benefit of chemotherapy found in women 50 years
of age or younger with a recurrence score of 16 to 25.

MIND ACT TRIAL:

• The Mamma print test made by Agendia is a genomic test that analyses the activity
of certain genes in early breast cancer.
• Research suggests that Mamma print test may eventually be widely used to help to
make treatment decisions based on cancer’s risk of recurrence within 10years after
diagnosis.
•
ELIGIBLE CRITERIA
MammaPrint can only be used to analyze early-stage breast cancers. In the United
States, MammaPrint can be used on cancers that are:
 stage I or stage II
 invasive
 <5 centimeters
 ER-positive or -negative 
 three or fewer lymph nodes
HOW THIS TEST WORK?
• The MammaPrint test looks at the activity of 70 genes and then calculates a
recurrence score that is either low risk or high risk.
• If you decide to have the MammaPrint test, doctor and patient both will consider a
number of factors when deciding on whether to add chemotherapy to your treatment
plan, including:
  age
 the size of the cancer
 cancer grade
 whether cancer cells were found in nearby lymph nodes
 general health.
CONCLUSION

 The updated 5-year distant metastasis-free survival rate for patients with high
clinical risk and low genomic risk receiving no chemotherapy was 95·1%,
which is above the predefined non-inferiority boundary of 92%, supporting the
previous analysis and proving MINDACT as a positive de-escalation trial.
 Patients with hormone receptor-positive, HER2-negative disease,shows
different effects of chemotherapy administration on 8-year distant metastasis-
free survival according to age: 93·6% with chemotherapy versus 88·6%
without chemotherapy in women aged 50 years or younger versus 90·0% in
women older than 50 years.

 The 8-year distant metastasis-free survival in the exploratory analysis by nodal status
in these patients was 91·7% with chemotherapy and 89·2% without chemotherapy -
negative patients and 91·2% versus 89·9% for with one to three positive nodes.


 With a more mature follow-up approaching 9 years

 The 70-gene signature shows an intact ability of identifying among women with high
clinical risk, with a low genomic risk, with an excellent distant metastasis-free survival
when treated with endocrine therapy alone.

 For these women the magnitude of the benefit from adding chemotherapy to
endocrine therapy remains small (2·6 percentage points) and is not enhanced by
nodal positivity.

 This benefit appears to be age-dependent, as it is only seen in women younger than

50 years where it reaches a clinically relevant threshold of 5 percentage points.
CAN ASSIST SCORE (INDIAN ORIGIN)
• It is a test developed on patients of Indian origin and ethnicity and in Caucasian
patients.
• CAB predicts risk of distant recurrence in 5 years from diagnosis by segregating the
patients into low- and high-risk groups for distant recurrence; based on this
recurrence risk prediction an informed decision can be made on use of systemic anti-
cancer therapy for the patient.

ELIGIBLE:
• included
• younger patients (<50),
• node-positive patients and patients with luminal B characteristics,
• stage I-IIIA hormone receptor-positive and HER2/neu disease

• CAB uses 5 biomarkers (CD44-a stemness marker; N-Cadherin,pan-Cadherin-cell

adhesion and invasion markers; ABCC4 and ABCC11-drug exporters) which are reflective
 on biology of the tumor migration from a primary site to a distant site, drug resistance
and dormancy in tumor cells which causes metastasis.
• CAB test predicts risk of recurrence using IHC staining information of these 5 biomarkers
along with 3 clinical parameters-tumor size, grade and node-status.

CONCLUSION
• In clinically low-risk patients and with luminal A characteristics, CAB identified
>16% as high risk and with recurrence rate of upto 12%.
• In clinically high risk patients and with luminal B characteristics, CAB identified
>64% as low risk.
• CAB prognostification was significant in womemn with clinically low and high risk
disease.

There are other genomics tests used to analyze breast cancer tumors. To learn
more, click on the links below.
 The Breast Cancer Index test is used to predict the risk of node-negative,
hormone-receptor-positive breast cancer coming back 5 to 10 years after
diagnosis.
 The EndoPredict test is used to predict the risk of distant recurrence of early-
stage, hormone-receptor-positive, HER2-negative breast cancer that is either
node-negative or has up to three positive lymph nodes.
 The Mammostrat test is used to predict the risk of recurrence of early-stage,
hormone-receptor-positive breast cancer.
• The Prosigna Breast Cancer Prognostic Gene Signature Assay (formerly called
the PAM50 test) is used to predict the risk of distant recurrence for
postmenopausal women within 10 years of diagnosis of early-stage, hormone-
receptor positive disease with up to three positive lymph nodes after 5 years of
hormonal therapy