Prof. Giovanni Paganelli

Dipartimento delle procedure e tecnologie avanzate, IRST-IRCCS – Meldola.

Universita degli Studi Ferrara

Contributo della medicina nucleare nei tumori mammari: dal linfonodo

sentinella alla IART

Months

0 60 120 180 240 300

0.0

0.2

0.4

0.6

0.8

1.0

Halsted (349)

Breast conservation (352)Phase I: Milan I study

Veronesi U, et al. N Engl J Med, 2002

Twenty years ago the challenge was:

Can lymphoscintigraphy + radioguided SNB replace

axillary dissection?

Multiple SNs

lymphatic vessels to diaphragmatic and liver lymph nodes

lymphatic vessels to the controlateral breast

internal mammary chain (IMC)

subclavian axillary group

lymphatic vessels to

anterior mediastinal

lymph nodes

anterior

axillary

group

subscapular

axillary

group

lateral

axillary

group

central axillary group

interpettoral lymph nodes

99mTc-labelled colloids (0.3 mCi/0.2ml)

< 50 nm < 80 nm 200-1000 nmSulphide Human albumin Human albumin

AXILLARY DISSECTION SENTINEL NODE

N-166 SN-166N+93N+91

516 randomized cases

257 259

36% N+( Veronesi, Paganelli,Viale N Eng JMed ‘03)

USE OF SN IN BREAST CANCER

• 1999: 686/1655 41.4%• 2000: 940/1896 49.5%• 2001: 1126/1979 56.8%• 2002: 1428/2217 64.4%• 2003: 1521/2192 69.3%• 2004: 1759/2372 74.2%• 2005: 1810/2353 76.9%• 2006: 2001/2599 77.0%

Year N. of cases Percentage

SNB after breast surgery YesSNB in multicentric cancer YesSNB after chemotherapy Yes SNB after SNB Yes SNB in pregnancy Yes SNB in male breast cancer YesSNB in DCIS OPTIONAL

Indications to SN

The 2nd Challenge was:

Can non palpable breastlesions be localized with

radioisotopes?

In 1996 we pioneered a new technique to remove non palpable breast lesions

ROLL

Paganelli et al., Eur J Nucl Med 1996

lateralanterior

The surgeon can determine the best incision to reach the tumor with a better

aesthetic result

1 cm.

This results in high excision accuracy and centring of the lesion within specimen so that it is rarely necessary to radicalize the margins

THE FUTURE

From ROLL diagnosis to

IART® therapy

Quadrantectomy + SNB + EBRT

represent the standard therapy

in Early Breast Cancer

Open problems with EBRT• EBRT post-quadrantectomy requires 6 – 8

weeks to be completed

• EBRT may cause side effects and complications (lung – heart)

• The radiation centres are often not easy accessible

Acute skin toxicity during RT

Women receiving Postoperative Radiotherapy according to distance to RT

Center

< 25 8325 – 75 74> 75 51

% who received RT afterBreast Conservative Surgery

Distance(Miles)

From WF Athas, et al.,2000

Can we modify EBRT in early breast cancer?

IntraoperativeRadiotherapyIORT / ELIOT

Partial breastIrradiationPBI

➢There are obvious advantages in terms of overall treatment time, patients comfort, cosmetic results, quality of life.

➢ELIOT represents a step to improve the quality of life of breast cancer patients.

Electrons IntraOperative Therapy

Veronesi et al., Ann Surg 2005

However ELIOT is affected by some limitations:

➢Costs

➢Limited targeted area

Electrons IntraOperative Therapy

Collimator

Skin separator

Target

anterior lateral+

+

+

Are there other methods to deliver

electrons in the operated breast?

ROLL: too large injections of 99mTc-MAA

I.A.R.T.®

Avidin injection during surgery into the tumour bed area

Avidin

IART ®Intra-operative

Avidination for

Radionuclide

Theraphy

In the operative room…

Dedicated vial for90Y or 177Lu-biotin

16 to 48 hrs post-surgery 90Y-Biotin i.v. injection

…in the Nuclear Medicine Dept.

Total Body anterior view - pt no 25

1h 4h 24h 48h

Fig. 1a)

b)

IART Phase II study: summary on dosimetry

Tumour bed uptake: 8 % (4 %– 12%) of IA

Avidin injected 100 mg with dedicated syringe

Activity: 3.7 GBq of 90Y-biotin

Safe !

BED 23 Gy

Gy

20 (15 – 27)

3.7 (2.2 – 5.9)

5.2 (3.0 – 7.4)

Tumour quadrant:

Kidneys:

Ur. Bladder:

1

Pre surgery

2

Post surgery

3

3 weeks after IART

6 months after EBRT

4

Conclusions

• IART® is safe and it can be applied to allBC conserving surgery in any hospital without dedicated acellerator

Dosimetry calculation ,based on our phaseII trial, supports its use in early breastcancer.

The S.A.R.A. StudyStandard -vs –Accelerated- Radio

metabolic Avidinated therapy

Phase III, multicenter, randomized, clinical trial to evaluate IART with 90Y-Biotin compared to Standard RT in patients with breast cancer candidate to RT after conservative surgery

Giovanni Paganelli IRST, Meldola