Radiotherapy in early stage invasive breast carcinoma

Dr Astha SrivastavaSenior Resident,SRMSIMS

Clinical presentation

• painless or slightly tender breast mass • Abnormal screening mammogram• breast tenderness, bloody nipple discharge, or

occasionally change in the shape and size of the breast

Diagnostic Work-up• General

History with emphasis on presenting symptoms, menstrual status, parity, family history of cancer, other risk factors Physical examination with emphasis on breast, axilla, supraclavicular area, abdomenSpecial tests Biopsy (core biopsy directed by physical examination, ultrasound, or mammography as indicated, or needle localization)Radiologic studies Before biopsy Mammography/ultrasonography Chest radiographs Magnetic resonance imaging of breast (selected cases) After positive biopsy Bone scan (when clinically indicated, for stage II or III disease or elevated serum alkaline phosphatase levels) Computed tomography of chest, abdomen and pelvis for stage II or III disease and/or abnormal liver function testsLaboratory studies Complete blood cell count, blood chemistry UrinalysisOther studies Hormone receptor status (ER, PR) HER2/neu status Consider genetic counseling/BRCA testing in selected cases

• Two major treatment options• – Mastectomy• – Breast conserving therapy Margin-negative lumpectomy+ ALND Adjuvant radiation therapy• Adjuvant therapy• – Dependent on pathologic variable Chemotherapy Hormonal therapy

Types of Mastectomies Used as Treatments for Breast Cancer

• Segmental mastectomy, lumpectomy, tylectomy: Removal of the primary tumor with a surrounding margin of breast tissue

• Total or simple mastectomy :Removal of the

breast but not the axillary contents

Indications:

– Stage I and stage IIa carcinoma

– Multifocal or multicentric CIS.

• Modified radical mastectomy: Removal of

the breast plus an axillary level I/II dissection

• Indications:

– LABC

– Multifocal or multicentric disease

Modified radical Mastectomy-procedure

1. Patey’s procedure:

– The P.minor is removed for better visualization and easy

dissection of level III lymph nodes.

2. Scanlon’s procedure:

– P.minor is retracted to expose level III nodes and dissected out.

3. Auchincloss procedure:

– Level I and II lymph nodes are cleared, level III nodes are left

behind.

• Radical mastectomy :Removal of the parenchyma breast tissue and pectoralis major muscle plus an axillary level I/II dissection

• Extended radical mastectomy :Removal of the breast and pectoralis major muscle plus an axillary level I/II and internal mammary lymph node dissection, may also include a level III axillary lymph node dissection

• Skin-sparing mastectomy :Total or modified radical

mastectomy with preservation of a significant component of the native skin of the breast to optimize the aesthetic result of an immediate reconstruction

Breast conserving therapy

– Wide local excision/Lumpectomy or

Quadrantectomy + axillary lymph node clearance +

Radiotherapy.

Contraindications to BCT

• Absolute:• Radiation therapy during pregnancy• Diffuse suspicious or malignant-appearing

microcalcifications• Widespread disease that cannot be incorporated

by local excision through a single incision that achieves negative margins with a satisfactory cosmetic result

• Positive pathologic margin

• Relative:• Prior radiation therapy to the chest wall or breast; knowledge of doses

and volumes prescribed is essential.• Active connective tissue disease involving the skin (especially

scleroderma and lupus)• Tumors >5 cm • Diffusely positive pathologic margins• Women with a known or suspected genetic predisposition to breast

cancer: -May have an increased risk of ipsilateral breast recurrence or

contralateral breast cancer with breast-conserving therapy -Prophylactic bilateral mastectomy for risk reduction may be considered

Treatment Policy for Conservative Management of Early Stage Invasive Breast

Cancer• Treatment Volume:Whole breast• Indication: routinely following BCS• Fraction Size/Technique: 200 or 180cGy/

tangents with wedges or dynamic wedges to optimize homogeneity

• Total Dose: 46 to 50 Gy/23-25 fractions

• Treatment Volume:Boost• Indication: routinely following whole breast• Fraction Size/Technique: 200 or

180cGy/electrons• Total Dose: 10-16 Gy/4-8 fractions

• Treatment Volume: Accelerated partial breast • Indication: On protocol or ASTRO guidelines • Fraction Size/Technique: 3.4-3.8 Gy/ext beam

conformal, interstitial, or MammoSite• Total Dose: 34-38 Gy /10 fractions.

Treatment Policy for Regional Nodes

• Treatment Volume:Supraclav • Indication: # Clinical N2 or N3 disease # >4 +LN after axillary dissection # 1-3 +LN with high risk features # T>5 cm # Node + sentinel lymph node with no dissection unless risk of

additional axillary disease is very small # High risk no dissection Fraction Size/Technique: 180-200 /AP or AP-PA • Total Dose: 45-50.4Gy

• Treatment Volume:Axilla• Indication: # N+ with extensive ECE # SN+ with no dissection # Inadequate axillary dissection # High risk with no dissection

• Fraction Size/Technique: 180-200/AP,consider posterior axillary boost if suboptimal coverage with AP only

• Total Dose: 4,500-5,040 cGy

• Treatment Volume:Internal mammary• Indication: Individualized but consider for- # Positive axillary nodes with central and medial lesions # Stage III breast cancer # +SLN in the IM chain # +SLN in axilla with drainage to IM on lymphosintigraphy

• Fraction Size/Technique: 180-200cGy/Partially wide tangents or separate IM electron/photon

• Total Dose: 46- 50Gy/23-25#

Barriers to BreastConservation

• Stage at diagnosis• Lack of screening• Physician and patient attitudes• Access to radiotherapy

Radiotherapy

• Treatment position:Most patients are treated in the supine position, with the arm abducted (90 degrees or greater)

• Radiation Beams:X-ray energies of 4 to 6 MV are preferred .

• Use of bolus results in impaired cosmetic results

• Wedges or compensating filters must be used for a portion of the treatment to achieve a uniform dose distribution in the breast

For tangential fields• Upper border – 2nd ICS (angle of Louis) when supra

clavicular field used. When SCF not irradiated – head of clavicle

• Medial border – at or 1cm away from midline

• Lateral border – 2-3cm beyond all palpable breast tissue – mid axillary line

• Lower border – 2cm below inframammary fold

SCF• Single anterior field is used.Field borders – • Upper border : thyrocricoid groove

• Medial border : at or 1cm across midline extending upward following medial border of SCM ms to thyrocricoid groove

• Lateral border: insertion of deltoid muscle

• Lower border : matched with upper order of tangential fields

Matching SCF and chest wall fields

AngulationBy inferior angulation of the tangential fields.

Half beam block technique Blocking the supraclav field’s inferior half, eliminating its divergence inferiorly .

Hanging block technique

Superior edge of tangential beam

made vertical by vertical

hanging block.

Single isocentre technique

• Isocentre placed at the junction

of tangential and supraclavicular field

• Inferior portion of field blocked for

supraclavicular treatment and

superior portion blocked for

tangential field

Internalmammary1. Extension of tangential fields– by extending medial border –

3cm across midline or by using imaging techniques

2. Separate field – • Medial border – midline , matching with tangential field

border• Lateral border – 5-6cm from midline• Superior border – abuts inferior border of supraclav field or

at 1st ICS (superior border of head of clavicle) if only IMNs are to be treated

• Inferior border – at xiphoid or higher if 1st three ICS covered

MRM vs. BCT (with RT)

6 RCT have shown no OS advantage after mastectomy or BCT

Whole Breast Radiotherapy Reduces Local failure

The benefit of tumor bed boost

• Most authors report that 65-80% of breast recurrence occurs around primary tumour site.

• Various studies suggest that patients treated with higher doses have a greater probability of tumor control.

Boost with electron beam

• Preferred over brachytherapy due to:-Relative ease in set up-Opd setting-Lower cost-Excellent results

Boost with interstitial implant

• large breast and deep tumors(>4 cm)• HDR is as effective as LDR

EORTC 22881-10882: RND Boost Trial

• Purpose: – Most large randomized trials providing long term IBTR did not

use tumor bed boost Example NSABP trials

• Single institution trials suggested a benefit of a tumor bed boost

• Endpoint: • •OS and IBTR

EORTC Boost vs. No Boost Trial

EORTC Boost trial: subgroup analysis Goal: Determine prognostic factors Central path review SM, LVI, grade, extend of DCIS, Mitotic Index + SM (14%), close (0-2mm) (27%, neg (> 2 mm) Median f/u 10 yrs

Results: MVA for LR: –Boost dose, high grade tumor, age < 50 y/o –10 yr Cumulative Incidence of IBTR: •7.3% (low) •8.4% (int) •13.7% (high)

Conclusions: -Patients at high risk for recurrence are those < 50 y/o and high grade tumor. Boost helps decrease the absolute risk most in these groups.

ASTRO Consensus Guidelines 2014 Margins for BCS With WBRT in Stages I and II Invasive Breast

Cancer

• Positive margins • A positive margin, defined as ink on invasive

cancer or DCIS -> 2-fold increase in IBTR. – This increased risk in IBTR is not nullified by:

Delivery of a boost dose of radiation – Delivery of systemic therapy (endocrine therapy,

chemotherapy, or biologic therapy), or – Favorable biology

• Margin Width • Negative margins (no ink on tumor) minimize the

risk of IBTR. • Wider margin widths do not significantly lower

this risk. • Systemic chemotherapy does NOT lower risk • The routine practice to obtain negative margin

widths wider than no ink on tumor is not indicated

Hypofractionation

• Short treatment course improves experience for patients • Improves access to breast conservation

• Biology :Increased dose per fraction without compromising BED

• Decreased cost to deliver care • Concerns: Toxicity

• START-A: (1998-2002)• N=2236• EBC (pT1-T3a, pN0-N1,

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 α/β of breast cancer as 4.6Gy for tumor control and 3.4Gy for late change in photographic appearance.

Lancet Online. March 19,2008

• START-B: (1999-2001)• N=2215• EBC (pT1-T3a, pN0-N1,

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!

Lancet Online. March 19,2008

UK START B (2001)

The “Canadian” Trial: Ontario

• 1234 Pts ~55yo • T1-2,N0 • 50Gy/25fx WBRT 42.6/16fx No boost

Accelerated Partial Breast Irradiation

• Rationale –Biology: Most recurrences occur within 2cm of

lumpectomy from prospective and RND trials.

• Decreased Treatment time and QOL • Potential reduction in treatment toxicity • Multiple techniques with short follow up

APBI - ASTRO Consensus Statement

• Established methods – External beam (3.85gy BID x 5 days) Most common

– Interstitial Brachytherapy: LDR, HDR Multi-catheter

– Intraoperative Electrons: ELIOT – Intraoperative Orthovoltage Photons: TARGIT-A – Mammosite

APBI: Current state

• Retrospective and registry studies demonstrate excellent local control

• Excellent cosmesis is reported• Meta-Analysis (2010) and Seer data (2014)

show decreased control

Comparison of APBI techniques

Mammosite

• Single lumen catheter – Typical dose (and on NSABP B31) RT: 34 Gy in 3.4 Gy fractions,

prescribed 1 cm from balloon – About 20% of RND trial – Needed balloon-to-skin dist >5 mm, cavity size < 6 cm

– Results at 3 years from registry: IBTR = 2.15% (4 yr=2.65%) – 3 yr axillary recurrence = 0.36% (4 yr=0.6%) – DM=1.1% – OS=95.6%

– Toxicity: infection: 9.5%, – Seroma: 27% (13% symptomatic) – 2% fat necrosis

• Cosmesis: Good or excellent at 4 yrs: 91% • Conclusions: Data consistent with other APBI techniques

Mammosite:results

Institution Dose Ipsilateral breast

recurrence rate

Cosmesis &Complications

American Society of Breast Surgeons Mammosite Breast Brachytherapy Registry trial (97 institutions)

34 Gy/10# 1.79% 3-yr actuarial LRR

Good-excellent cosmesis in >93%.

Rush University Medical Centre, Chicago, USA

34 Gy/10# 5.7% (crude) Good-excellent cosmesis in 93%.

Interstitial APBI

• Started as boost technique initially following WBRT

• Multiple catheters are placed at 1-1.5 cm interval.

HDR interstitial brachytherapy:results

Institution Dose Dose Rate Ipsilateral breast recurrence rate

Cosmesis & Complications

William Beaumont Hospital, USA

32-34 Gy/8-10#

50 Gy

HDR

LDR

2.1% (5-yr)

0.9% (5-yr)

>90% achieved good to excellent cosmesis

Ochsner Clinic, USA

32-34 Gy/8-10#

50 Gy

HDR

LDR

8% 75% achieved good to excellent cosmesis

London Regional Cancer Centre, Ontario, Canada

37.2 Gy/10# HDR 16.2% at 5 yrs* Median overall cosmetic score 89%.

HDR interstitial brachytherapy:results

Institution Dose Dose Rate Ipsilateral breast recurrence rate

Cosmesis & Complications

National Institute of Oncology, Hungary

30.3-36.4 Gy/7#

HDR 6.7% Excellent to good cosmesis in 84.4%.

Tufts New England, USA

34 Gy/10# HDR 6.1% (5-yr actuarial)

89% had excellent cosmesis at 5 years.

Guy’s Hospital, London

55 Gy LDR 37%* Cosmesis good to excellent in 85%.

*= inappropriate selection of patients for APBI

IORT:results

Institution Dose Modality Ipsilateral breast recurrence rate

Cosmesis & Complications

European Institute of Oncology, Milan

21 Gy Electrons 1% Mild/severe fibrosis in 3%.

State University of Buffalo, USA

15-20 Gy 120 kV X rays 29% Acceptable

University College, London(TARGIT)

20 Gy 50 kV X rays 0% Acceptable

Intra-op Conclusions

• Randomized data demonstrate safety and efficacy

• Allows post-surgery RT for high risk groups without toxicity

• Statistically Significant increase LRR vs WBRT • Long term data still lacking

Regional nodal contouring

IMRT

• Dosimetric advantages include:

(1) better dose homogeneity for whole breast RT

(2) better coverage of tumor cavity(3) feasibility of SIB