Contributo della medicina nucleare nei tumori mammari: dal linfonodo sentinella alla IART Prof. Giovanni Paganelli Dipartimento delle procedure e tecnologie avanzate, IRST-IRCCS Meldola. Universita degli Studi Ferrara
Phase I: Milan I study 1.0 Breast conservation (352) 0.8 0.6 Halsted (349) 0.4 0.2 0.0 0 60 120 180 240 300 Months Veronesi U, et al. N Engl J Med, 2002
Twenty years ago the challenge was: Can lymphoscintigraphy + radioguided SNB replace axillary dissection?
Multiple SNs interpettoral lymph nodes central axillary group internal mammary chain (IMC) subclavian axillary group lateral axillary group subscapular axillary group anterior axillary group lymphatic vessels to anterior mediastinal lymph nodes lymphatic vessels to the controlateral breast lymphatic vessels to diaphragmatic and liver lymph nodes
99mTc-labelled colloids (0.3 mci/0.2ml) < 50 nm < 80 nm 200-1000 nm Sulphide Human albumin Human albumin
516 randomized cases AXILLARY DISSECTION SENTINEL NODE 257 259 N-166 N+91 N+93 SN-166 36% N+ ( Veronesi, Paganelli,Viale N Eng JMed 03)
USE OF SN IN BREAST CANCER Year N. of cases Percentage 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%
Indications to SN SNB after breast surgery SNB in multicentric cancer SNB after chemotherapy SNB after SNB SNB in pregnancy SNB in male breast cancer SNB in DCIS Yes Yes Yes Yes Yes Yes OPTIONAL
The 2nd Challenge was: Can non palpable breast lesions be localized with radioisotopes?
ROLL In 1996 we pioneered a new technique to remove non palpable breast lesions Paganelli et al., Eur J Nucl Med 1996
anterior lateral
The surgeon can determine the best incision to reach the tumor with a better aesthetic result
This results in high excision accuracy and centring of the lesion within specimen so that it is rarely necessary to radicalize the margins 1 cm.
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 Distance (Miles) % who received RT after Breast Conservative Surgery < 25 83 25 75 74 > 75 51 From WF Athas, et al.,2000
Can we modify EBRT in early breast cancer?
Partial breast Irradiation PBI Intraoperative Radiotherapy IORT / ELIOT
Electrons IntraOperative Therapy 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. Veronesi et al., Ann Surg 2005
Electrons IntraOperative Therapy However ELIOT is affected by some limitations: Costs Limited targeted area
Skin separator Target Collimator
Are there other methods to deliver electrons in the operated breast? anterior + + lateral + ROLL: too large injections of 99mTc -MAA
I.A.R.T. Avidin Avidin injection during surgery into the tumour bed area
IART Intra-operative Avidination for Radionuclide Theraphy
In the operative room
Dedicated vial for 90Y or 177Lubiotin
in the Nuclear Medicine Dept. 16 to 48 hrs post-surgery 90Y-Biotin i.v. injection
Total Body anterior view - pt no 25 1h 4h 24h 48h
a) Fig. 1 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 90 Y-biotin Gy Tumour quadrant: Kidneys: Ur. Bladder: 20 (15 27) 3.7 (2.2 5.9) 5.2 (3.0 7.4) BED 23 Gy Safe!
1 2 4 Pre surgery Post surgery 3 6 months after EBRT 3 weeks after IART
Conclusions IART is safe and it can be applied to all BC conserving surgery in any hospital without dedicated acellerator Dosimetry calculation,based on our phase II trial, supports its use in early breast cancer.
The S.A.R.A. Study Standard -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