ISOTOPE GUIDED SURGERY FOR NON PALPABLE BREAST CANCER 25-7-2009 Dr. MP Chow Department of Surgery Kwong Wah Hospital ISOTOPE GUIDED SURGERY FOR NON PALPABLE BREAST CANCER

Breast cancer Commonest cancer for female in Hong Kong (2004) >2000 new cases / year Commonest malignancy in women worldwide > 1 million new cases diagnosed in 2000

Opportunistic Screening Breast screening program No population screening Target group: All woman > 40 years old (<70 years old) 35-40 if +ve family history of a first degree relative at premenopausal age Detect early stage breast cancer Reported to reduce mortality in up to 30% in western country Lui et al Hong Kong Med J 2007

Management of non-palpable breast cancer Topic

Management Triple assessment History/Physical examination Imaging Breast complaints Risk factors e.g. Family history, OC pills, Previous breast disease, Date of menarche, Imaging Ultrasound Mammogram Cytology / Histology Fine Needle Aspiration Core Biopsy

Treatment options for occult breast cancer Surgery Mastectomy + Sentinel lymph node biopsy +/- Axillary dissection Breast conservative therapy + Sentinel lymph node biopsy + Post-operative radiotherapy +/- Axillary dissection Extent of disease Multifocality Previous radiation Patient’s wish

How Can we localize occult brest lesion? What choices?

How to localize the lesion? Hookwire localization Wire is deployed under stereotactic / ultrasound guidance within rigid over-shealth cannula preoperatively Potential disadvantages Uncomfortable for patient Displacement in fatty breast Wire transection Technical difficulty in dense breast Interference with surgical approach Required post-procedure mammogram to confirm position

Problems with HWL And sometimes… Hookwire tip retained after surgery

New advances Potential advantages Potential disadvantage Radio-guided surgery Introduced by European Institute of Oncology in Milan Luini et el, European Journal of Cancer 1998 Vol 34 No. 1 ROLL/SNOLL Radiologically Occult Lesion Localization Sentinel Lymph Node Occult Lesion Localization Method Intratumoural injection of radioactive isotope (e.g. Technetium labelled colloid) under radiological guidance Pre-operative lymphoscintigraphy (Lymph node mapping) Lesion excision and lymph node localization guided by radioactivity Potential advantages Simple and less invasive procedure “Killing Two Birds with One Stone”. Shorter localization time Potential disadvantage Radiation exposure

SNOLL <100 µm 100-200 µm Filtered Sulphur Colloid Sulphur Colloid The technique of injecting the isotope is identical to ROLL Use correct particle size ROLL The radiotracer used is immobile and remains at the site of injection SNOLL The radiotracer used can remain at injection site and move within the lymph ducts to accumulate in SN + + + + + + + + + + + + + 100-200 µm Sulphur Colloid <100 µm Filtered Sulphur Colloid

SNOLL

SNOLL

SNOLL Video

Radiation Issue Is it a problem?

Radiation Issue SNOLL is safe to patients and medical staff SNOLL MMG Short half life of Tc99m of only 6 hours Low dose gamma radiation used SNOLL MMG CXR Effective Dose 9.25 µSv or 0.009 mSv 1-2 mSv 0.02 mSv SNOLL <<< MMG or CXR Clinical Radiology (2005) 60, 681–686 Nucl Med Commun 1999; 20: 919–924

Radiation Issue Finger Dose Surgeon 9.3+/-3.3 µSv Radiologist If a surgeon performs 100 procedures per annum, a Finger Dose of approximately 1 mSv is received, well within the annual dose limit of 150 mSv. Breast. 2003 Apr;12(2):150-2

Literatrue REview

Monti et al Italy March 1997 to April 2004 N = 959 Methodology Injection and scintigraphic procedures for ROLL and SNB were performed separately on the day of surgery For ROLL Human serum albumin macroaggregate, particle size 100-150µm and labeled with Technetium was injected into the lesion. Scintigraphy was performed after injection of isotope. Procedure was repeated in cases of failure For SNB Human serum albumin macroaggregate, particle size 0.1-0.8µm and labeled with Technetium was injected peritumorally or subdermally. Lymphoscintigraphy was performed 15-30 mins and 3 hours. Procedure was repeated in cases of failure Monti et al Ann. Surg. Oncol Vol 14 No. 10. 2007

Result Margins status Number Percentage Positive 11 1.3% Close margins < 1cm 65 6.7% Negative margins >= 1cm 883 92% Total 959 100% Monti et al Ann. Surg. Oncol Vol 14 No. 10. 2007

Result Axillary SNs were identified in 958 of 959 (99.6%) Axillary dissection was performed for the case which the sentinel LN is not visualized in lymphscintigraphy SN Location Number Percentage Axilla 926 96.6% Axilla plus internal mammary chain 32 3.3% SN not visualized 1 0.1% Total 959 100% Monti et al Ann. Surg. Oncol Vol 14 No. 10. 2007

Other literatures Patel et al 20 90% 100% Yes Feggi et al 73 95% 97% Authors No. of patient Complete excision (%) Identification sentinel node (%) Supplementary Blue dye Confirmation specimen Patel et al 20 90% 100% Yes Radiography Feggi et al 73 95% 97% Scintigraphy + Mammography De Cicco et al 227 No Barros et al 112 98% I.M.C. van der Ploeg et al, EJSO 34 (2008)

EXPERIENCE IN KWONG WAH SURGERY

Kwong Wah Hospital SNOLL has been introduced since 2004 as operative technique for BCT of non-palpable breast cancer Interval 2004 – 2008 Total number of patient: 57 Inclusion criteria Clinically occult lesion Suitable for BCT Biopsy proven breast cancer

Methodology Stereotactic or ultrasonic guided intratumoral injection of 99mTc-labeled (<100 µm) filtered Sulphur Colloid will be performed by radiologist on the same day of surgery Lymphscintigraphy was performed after radioisotope injection (Navigator GPS) Gamma probe was used for localization of index lesion and sentinel lymph node Supplementary blue dye injection if failed localization of sentinel lymph node by gamma probe End points Complete excision was defined as tumour free margins >=1mm Successful breast lesion localization and sentinel lymph node localization

Result 21 (37%) patients had DCIS 36 (63%) patient had invasive carcinoma Index lesion localization rate = 100% Complete excision rate = 84% (48/57) 7 (12%) patient required 2nd operation

Sentinel Lymph Node Localization Sentinel LN localization by Lymphoscintigraphy 72% Sentinel LN localization by Gamma Probe 82% Overall sentinel LN localization (Both isotope and blue dye): 95%

Current Evidences Monti et al 959 92% 99.6% No Patel et al 20 90% 100% Authors No. of patient Complete excision (%) Identification sentinel node (%) Supplementary Blue dye Confirmation specimen Monti et al 959 92% 99.6% No Radiography Patel et al 20 90% 100% Yes Feggi et al 73 95% 97% Scintigraphy + Mammography De Cicco et al 227 Barros et al 112 98% Kwong Wah Hospital 57 84%

Conclusion Isotope surgery is a promising technique with good results in terms of sentinel lymph node and tumour localization. SNOLL provides an additional benefit of sentinel lymph node identification in one procedure.

The End. Thank you !

HWL vs ROLL (KWH) HWL (n=76) ROLL (n=89) P value Age 51.2 52.0 0.508 Success 75/76 (98.7%) 86/89 (96.6%) 0.6251 Mean localisation time 31 18 0.0000 Mean OT time 52 48 0.188 Need for further excision intraop. 22/75 (29.3%) 25/86 (29.1%) 1.0000 (due to unsatisfactory specimen mammogram) 12/75 (16%) 11/86 (12.8%) 0.6536 Involved or close margin in first specimen for malignant lesions 12/38 (31.6%) 9/55 (16.4%) 0.1290 0.0711 (1-tailed) Need for 2nd OT for malignant lesions Either intraop re-excision or 2nd OT 29/75 (38.7%) 31/86 (36.0%) 0.7466 Size of specimen 48.2 66.0 0.005 Therapeutic intention 23/76 (30.3%) 44/89 (49.4%) 0.0169 Size of DCIS 17.7mm (n=30) 8.8mm (n=25) 0.003 Size of invasive cancer 13.2mm (n=5) 12.7mm (n=28)

Cost Issue (in KWH, HK) HWL: Slightly lower cost Dose of Technetium SNOLL Hookwire Dose of Technetium 62 USD Spinal Needle 1 USD Gamma Probe (OT) (Capital Cost) 18000-20000 USD Hookwire BLN 20G(Promex) 13 USD Additional Mammograms 2 USD HWL: Slightly lower cost

Cost Issue (in Prescot, UK) SNOLL Hookwire Dose of Technetium £ 28 Spinal Needle £ 0.6 Gamma Probe (OT) (Capital Cost) £10,000 to £15,000 Hookwire Reedy Wire(Cook) £ 35 Additional Mammograms £ 7 ROLL: Slightly lower cost Clinical Radiology (2005) 60, 681–686