Breast Brachytherapy : Techniques and Advances

Anuj V Peddada, M.D. Director

Department of Radiation Oncology Penrose Cancer Center Colorado Springs, CO

USA

Elsewhere Failure (Outside

Lumpectomy Region)

No XRT XRT Randomized Trials (BCT)

#

Cases

Follow-up

Interval

(mos)

Crude % Crude %

Ontario

837 43 15/421 3.5 4/416 0.9

Milan III

579 109 8/280 2.8 2/299 0.6

NSABP B06

1265 144 17/636 2.7 24/629 3.8

Uppsala-Orebro

381 33 3/194 1.5 1/187 0.5

Finland 152 80 4/72 5.5 4/80 5.0

The majority of cancer recurrences in the treated breast occur at the lumpectomy site

Pattern of In-Breast Cancer Recurrences Following Breast Conserving Therapy

Rationale for Accelerated Partial Breast Irradiation (APBI)

10%-40% of those who are candidates for breast conservation therapy actually do not receive it.

Why? – Patient’s choice – Complex and prolonged treatment course can be

inconvenient for those with poor access to a radiation facility, the elderly and working women

– Physician bias

Potential Benefits of Accelerated Partial Breast Irradiation

Reduce time and inconvenience of BCT

Improve documented underutilization of breast conserving therapy (BCT)?

Reduce burden of care for patients (1 week)

Eliminate scheduling problems with systemic chemotherapy

Limited radiation exposure to normal tissue

Potentially reduce acute and chronic toxicity

Accelerated Partial Breast Irradiation

Limitations: – May require additional surgical

procedure

– Requires twice daily treatment

– Newer modality with far fewer patients treated and much shorter follow-up

– As of now, no direct comparison with standard radiation (NSAPB -39)

Techniques for Partial Breast Irradiation – Interstitial

– MammoSite

– SAVI

– Contura

– Xoft

– Permanent seed implants

– 3D radiation

– Intraoperative therapy – Intrabeam, ELIOT

Partial breast irradiation techniques

Multi-catheter Interstitial Brachytherapy

Intracavitary Brachythery

Intraop. RT

3D Conformal RT

Dose 34 Gy in 10 fx In 5 days

34Gy in 10 fx In 5 days

20-21Gy in single fraction

38.5 Gy in 10 fx. In 5 days

Target 1.5 cm margin around WLE cavity

1cm around WLE cavity

Visual by surgeon and radonc

2.5cm margin around WLE cavity

Pros Many dwell positions for Irreg. cavity

Ease of placement and planning

Single dose Spares skin

Fits with standard RT machines

Cons Operator dependent

High cost Fewer dwell positions

RT before path known specialized centers only

Larger fields (respiration) and more normal tissue

Patient Selection Criteria

ABS ASBS NSABP B39 -

RTOG 0413 GEC-ESTRO

Age >45 >50 >18 >40

Diagnosis

Unifocal,

invasive

ductal

carcinoma

Invasive ductal

carcinoma or

DCIS

Invasive

carcinoma or

DCIS

Invasive

adenocarcinoma

or DCIS

Tumor

size

<3cm <3cm <3cm

<3cm

Surgical

margins

Negative

microscopic

surgical

margins

Negative

microscopic

surgical

margins of at

least 2mm

Negative

microscopic

surgical margins

of excision by

NSABP definition

> 2mm or >5mm

for lobular or

DCIS

Nodal

status N0 N0

N0, N1 (1-3

nodes) pN0 or PNmi

ASTRO Guidelines ASTRO guidelines

strict

ASTRO

“with caution”

ASTRO

on trial

Age ≥ 60 50-59 < 50

Diagnosis

Invasive ductal,

mucinous, tubular, or

colloid, no EIC or LVI,

ER (+)

Invasive lobular, EIC

< 3 cm, limited or

focal LVI, ER (-),

DCIS < 3cm

Extensive LVI,

pure DCIS > 3 cm,

neoadjuvant

chemo

Tumor

size

cUnifocal, < 2 cm 2.1 - 3 cm

> 3cm, T3, T4 or

cmultifocal,

multicentric

Surgical

margins ≥ 2 mm < 2 mm (+)

Nodal

status N0 or IHC (+) only

N(+) or

undissected

Studies evaluating ASTRO guidelines

Limitations of the ASTRO guidelines on use of APBI – Vicini F IJROBP, 2010 in press – Found in a data base of 199 + 199, that all three groups

had an equally low risk of IBTR 5yr outcome in ASBS Registry using ASTRO guidelines

– Shaitelman S Cancer, 2010 (epub ahead of print) – Of 1449 cases, 41% suitable, 42% cautionary, 17%

unsuitable – LR5 2.59%, 5.43%, and 5.28% (p= 0.18)

DCIS outcomes on ASBS registry – Jeruss J Annals of Surg Oncol online June 25, 2010 – 194 patients, median 54.4 months (LR5 3.39%)

DCIS WBH IJROBP 10/1/11 LR at 3 yrs 2%

NSABP B-39/RTOG 0413 Trial Phase III

Stage 0, I-II breast cancer treated by lumpectomy

Randomization

WBI • 50-50.4 Gy (1.8-2.0 Gy)

Fractions to the whole breast followed by boost to 60 -66.6 Gy

PBI • 34 Gy in 3.4 Gy fxs bid

Mammosite® or Multicatheter brachytherapy

OR • 38.5 Gy in 3.85 Gy fxs bid

3D-CRT

Three Established Methods For PBI

Multi Catheter Mammosite®

3-D Conformal

Target definition

Interstitial brachytherapy

Catheters are placed intraoperatively or later; usually 2 planes

Typical doses with HDR = 30-36 Gy and LDR = 45-60 Gy

Treatment delivered

over one week.

Interstitial Breast Brachytherapy Multi-Catheter Placement Methods

Free-hand/template – with fluoro/US guidance – open cavity post-lumpectomy placement

Stereotactic mammo- guidance – ‘Kuske’ Technique

3D - CT based guidance

Preplan - catheter entrance and exit determination

- exam and CT to determine direction of catheters

- wide entrance and exit - provides peripheral coverage - allows straight catheter strike

- direction that will reduce number of catheters

- direction that reduces risk of traversing intercostal muscles

- comfort – end buttons and catheter leads

- cosmesis – location of potential punctate scarring

- goal: homogeneous coverage with least number of catheters

- target 1.5 -2 cm beyond lumpectomy cavity

dose can only be safely pushed ~.5cm beyond planes

intercatheter distance 1-1.5 cm

planar separation = 2.5cm

at least two catheters beyond cavity

Measure, Mark, Local anesthesia

Base plane

Compress and lift

Superficial Plane Flat of hand Allows arcing over

CT evaluation

prior to completion

- target coverage

- skin

- chest wall

- intercatheter

- interplanar

Multi-catheter Implant

Dose Distribution of MultiCatheter PBI

PTV

100% isodose

Post- Removal 1 month post implant

8 years post-therapy

Mammosite® Breast Brachytherapy Applicator

• Simplified brachytherapy method for PBI

• Dual lumen single catheter with expandable balloon at end

• Balloon expands to fill the lumpectomy cavity

• Radiation dose prescribed to 1 cm beyond balloon surface

• Uses 192Ir (HDR) as the source

• FDA approval May 2002

MammoSite PBI

MammoSite Placement

Time of Lumpectomy Post-lumpectomy

Open Cavity Scar Entry (SET) Ultrasound Guided

CT Planning for Mammosite Brachytherapy

Isodose Lines

50%

80%

100%

120%

140%

200%

Mammosite® balloon

Difficulties with MammoSite

Balloon must conform to cavity shape without air gaps. Device explanted in ~ 10-15% of pts.

Ideal is to have 7 mm b/w balloon and skin to decrease risk of skin complications

Very dependent on surgical cavity

Infections

Balloon ruptures

Day 2 on treatment

Breast Appearance after MammoSite®

3 years post treatment

MammoSite PBI

Institution Pt.

No.

Median

age

F/U

mo.

T size

(cm)

median

N+

%

ER +

%

Local

relapse

%

Exc/

good

Cosmesis

%

Initial Multi-

Institutional 43 69 48 1.0 0 - 0 80

Rush Univ. 112 64 - 88%

Tis-T-1 7 - 0 80

Tufts-NEMC/

VCU 28 62 19 1.1 0 100 0 86

St. Vincent

Hospital 32 62 11 97% T-1 9 94 - 86

Average: 64 y 26 mo 1 cm 4% 0% 83%

MammoSite 5 year registry data Vicini F, IJROBP 2010 (epub ahead of print)

• ASBS MammoSite Registry

• N= 1440, median f/u 54 mo.

• 87% Invasive (median size 10 mm), 13% DCIS

(median size 8 mm)

• LR5 3.8% (70% “new” tumors)

– 3.86% IDC, 3.39% DCIS

• Axillary recurrence5 0.84%

Toxicities of Mammosite

Seroma formation: Risk is increased with open technique for placement. In Beaumont series, found 60% risk with open cavity vs. 30% in closed cavity; overall rate of 45%, with 10% symptomatic.

Skin Toxicity

Next Generation:

SAVI

ClearPath™

Contura

MammoSite ML

Hybrid Approaches

MammoSite Classic Contura

Interstitial MC

MammoSite ML SAVI

Increasing Modulation

Case characteristics:

Skin Distance: 3 mm Skin Dose: 107 %

Rib Distance: 14 mm Rib Dose: 76%

V95: 95.6%

V150: 21.5 cc V200: 5.6 cc

MammoSite ML case

Contura

Inner struts that can be expanded to modulate the dose

Improvements in Critical Endpoints…..Phase IV trial Arthur IJROBP epub ahead of print, 2010

Skin

≥ 5mm,

< 7mm

d < 5mm

Skin <

7mm and

rib < 5mm

Median

skin dose 120% 124% 120.6%

Median

rib dose 136.5% 142%

EXTENDED TIP

Collapsed for insertion

SAVI

(Strut Adjusted Volume Implant)

Cosmesis

First 102 patients median follow-up 21 months Yashar C IJROBP, 2010 epub ahead of print

Skin <7mm 95.2 25.8 12.7 280cGy

CW and skin

<7mm 93% 19.9 10.6 272cGy

V90 V150 V200 Skin dose

all

patients 95.9 37.8 14

255cGy

(75%)

RR 1%

Gr 1 telangiectasias 1.9%

Gr 1 hyperpigmentation 9.8%

Gr 2 fibrosis 1.9%

Asx seromas 2%

Asx fat necrosis 1.9%

First 102 patients median follow-up 21 months Yashar C IJROBP, 2010 epub ahead of print

Xoft

A tiny 50 kV source

Advantages – Less shielding issues

Uses a single lumen balloon – Multiple dwell positions

Dosimetry of source makes higher dose at balloon with more rapid falloff

Experience with XOFT for APBI Mehta V Am J Clin Oncol April 2010 (epub ahead of print)

N=65, 32% not eligible, 44 treated

Follow-up 6 months in 43, 1 year in 36

>50, IDC or DCIS < 2.0 cm, NO, neg margins

Skin distance ≥ 7mm

4 (9%) grade 3 toxicities (blister, pain, moist desquamation)

Phase I/II permanent seed103Pd

Pignol JP IJROBP 73:1482, 2009

IDC ≤ 3 cm, ≥2mm margin, no EIC, no LVI and N0

Minimal peripheral dose 90Gy at margin of 1.5 cm

N=67 17% significant pain Moist desquamation, erythema,

induration 10%, 42%, 27% Year 1 telangiectasia grade 1

14% 1.5% abscess LR 0% at 32 months

Permanent seed implant

Trials of partial breast RT

Trial Target accrual RT Technique Duration of RT

NSABP B-39 9000 Multisource Ir-192 5 days

TARGIT 3000 Intraoperative Xrays

1 day

ELIOT 2000 Intraoperative electrons

1 day

IMPORT Low 2000 External beam IMRT

3 weeks

GEC-ESTRO 1170 Multisource Ir-192 HDR/PDR

2.5-4 days

Accelerated Partial Breast Irradiation: Summary

Accelerated partial breast irradiation allows patients to complete a course of treatment in one week as opposed to the standard six weeks.

Treatment limited to part of the breast may be associated with less morbidity of treatment and better cosmetic outcome.

Hopefully, the randomized, prospective NSABP trial will answer the question of equivalence of partial and standard breast irradiation.

Summary

APBI is a viable option for some early stage breast cancer patients

Studies are actively trying to define that population

A variety of “user friendly” devices are currently on the market with early data out….

Stay tuned…..