The GOSTT concept. (radio)guided intraoperative Scintigraphic Tumor Targeting. Emmanuel Deshayes. GOSTT = Radioguided Surgery

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1 IAEA WorkShop, November 2017 Emmanuel Deshayes With the kind help of Pr Francesco Giammarile The GOSTT concept GOSTT = Radioguided Surgery (radio)guided intraoperative Scintigraphic Tumor Targeting 1

2 Radioguided Surgery Aim: tailor surgical approaches to the different diseasespecific and patientspecific conditions Method: 1. preoperative labeling of target lesions; 2. intraoperative guidance (detecting probe); 3. minimal surgical access and probe aided assessment of the completeness of excision. 300 Medline-based search Synergistic collaboration of different specialties involved 2005 The GOSTT concept 1. Methods a. After interstitial injection Lymphatic (Sentinel node) Intra tumoral (ROLL) b. After systemic administration (SPECT or PET specific tracers) c. Others (leakage measurement during isolated limb perfusion ) 2. Materials a. Devices Preoperative imaging Intraoperative gamma probe Intraoperative imaging Multimodality preoperative imaging ("mixed reality" surgery) b. Tracers Radiopharmaceuticals Hybrid compounds 2

3 The sentinel node concept First node involved in metastatic spread of tumour Artery Tumor Sentinel Lymph Node: Hot Vein Lymphatic vessel Secondary Lymph Nodes Particles diffuse into interstitial fluid, drains into lymphatic vessels and regional nodes Sentinel Lymph Node Indications Common (guidelines) Breast Melanoma Gynecological malignancies Rare(research) Head and neck Urological malignancies Others 3

4 Imaging modalities Planar/dynamic No Consensus Landmarks Nothing! SPECT CT SPECT/CT: General indications Planar images difficult to interpret: unexpected unusual drainage patterns no or poor visualization of drainage (low or no activity, injection closer to nodes, depth, overweighed patients...) SPECT/CT Topographic localization and detection of additional SLNs areas of deep lymphatic drainage (pelvis, abdomen, or mediastinum) areas with complex anatomy (head and neck) identification of number, size, depth, and exact localization Advantages Surgical planning Sensitivity Specificity Attenuation correction Problems Cost and added time Additional radiation Non suitable for dynamic studies too much sensitive? Hybrid imaging with SPECT and CT including anatomical information improves the localization of SLNs and reduces misinterpretation of images. 4

5 SPECT/CT: Added Values Sensitivity Breast cancer Lymph node clearly shown only on SPECT-CT Sensitivity SPECT/CT: Added Values Breast cancer An intra-mamary lymph node is seen only in SPECT-CT 5

6 Specific location of the SLN SPECT/CT: Added Values Breast cancer Level I and Level II axillar lymph nodes clearly shown on SPECT-CT Specific location of the SLN SPECT/CT: Added Values Breast cancer Internal mammary lymph nodes 6

7 SPECT/CT: Added Values Anatomic Information for surgical planning Breast cancer SPECT/CT: Added Values Anatomic Information for surgical planning F.Giammarile 7

8 Superficial injections are easy to perform Injection method does not affect the identification of axillary SLN Deep injections may require ultrasound or sterotaxic guidance but allow detection of extraaxillary nodes Injection methods Superficial injections 20% Deep injections 4% 9% 99% 99% SPECT/CT: Added Values Pre-surgical imaging Breast cancer 8

9 SPECT/CT: Added Values Pre-surgical imaging Breast cancer Radioguided Occult Lesion Localisation (ROLL) Intratumoral administration guided by ultrasound/stereotaxis Followed by immediate surgical resection, guided by probe In non palpable suspected breast lesion replace hooked wired localization (SLN in separate occasion) 9

10 SPECT/CT: Added Values Pre-surgical imaging Melanoma Pre-surgical imaging The sentinel node concept Head and neck cancer 10

11 Pre-surgical imaging The sentinel node concept Cervical cancer Pre-surgical imaging The sentinel node concept Vulvar cancer 11

12 Pre-surgical imaging The sentinel node concept Penile cancer Pre-surgical imaging The sentinel node concept Testicular cancer 12

13 Latest technological knowledge Radiopharmaceuticals Methods and instrumentation Handle Optical camera Infrared localization system (Radio) pharmaceuticals for SLN Radiopharmaceuticals Blue Dyes 99m Tc colloids (nano, sulfur) 99m Tc phytates Better than colloids in breast cancer (533 patients, Surg Today, 2006) 198 Au colloïd Uniformity of size (20 nm): high lymph node uptake (15% vs 5%) (Nuc Med Biol, 2011) 99m Tc Tilmanocept Receptor imaging Diameter < 1nm Coloration of urines (12 24 hours) and teguments (24 48 hours) Long term tatooing effect Anaphylactic shock 0.4 1% Eckert et al,

14 Receptor targeting agent 99m Tc Tilmanocept High affinity for CD 206 receptor Small size: 7nm, 19kDa Accumulation on macrophages and dendritic cells Internalized in lymphatic tissue High uptake and fast clearance from injection site Two phase III study in breast cancer (Baker el al & Wallace et al. 2013): excellent concordance with blue and less surgically removed SLN. Sensitivity equal to colloids Lymphoseek The advantages of this tracer include rapid clearance from the injection depot and low accumulation in second echelon nodes. This novel radiopharmaceutical might be of particular utility in patients with head and neck melanoma. 14

15 Perspectives in Imaging Agents for Lymphatic Mapping Bimodal (hybrid) agents Simultaneous scintigraphic and optical imaging (near infrared fluorescence): Fluorescent agent (ICG) Tissue penetration signals Assembled nanoparticule Brouwer OR, Ann containing ICG Surg Oncol (2012) Intrumentation 15

16 Laparoscopic Gamma-Probe Prostate carcinoma Endoscopic detection Small field of view portable imaging devices Portable gamma camera: Sentinella ANT ANT axilar OBLIQUE axilar Laser pointer centers targets on the screen LATERAL Axilar 16

17 Small field of view portable imaging devices Portable gamma camera: breast 57 year old patient with a breast cancer in left upper outer quadrant Images obtained with the portable gamma camera before and after SLN excision: completeness of the SLN removal Small field of view portable imaging devices Portable gamma camera: melanoma No SLN on preoperative imaging Portable gamma camera: SLN is depicted Increased resolution and sensitivity 17

18 Small field of view portable imaging devices Portable gamma camera: melanoma Frontal melanoma with drainage to several nodes at different neck s level in right cervical basin Images obtained with the portable gamma camera before and after resection of 2 nodes: one more node is depicted added value for close monitoring of the surgical procedure 3 D volume rendering SPECT 3D/2D tracking assisted probes 18

19 3D/2D tracking assisted probes 3 D volume rendering SPECT "Mixed Reality" Surgery (better 3D perception) 3D/2D tracking assisted probes Portable gamma camera and laparoscopic Gamma-Probe 125I seed pointer (on the collimator) SLN localized in the operation room guided by SPECT/CT information and using a portable gamma camera for real time display SPECT CT: sentinel node near the left testicular vessels testicular cancer 19

20 Radioguided Surgery today Take home messages Multimodality preoperative molecular imaging Intraoperative imaging Non imaging procedures are essential for optimizing surgical approaches in patient and disease specific conditions to reduce the invasiveness of procedures (positively impact health economy) providing the standardization of the methods (guidelines) Radioguided Surgery tomorrow Take home messages Develop more specific tumor markers to delineate more precisely the extent of damage (bimodal radioactive and fluorescent agents) Develop more sensitive detectors, miniaturized and ergonomic Integrate different surgical methods (imaging modalities, resection, navigation) Robot assisted endoscopic surgery Virtual reality (mostly for training purposes), mixed reality and augmented reality 20

21 Conclusion: Evolution of Oncologic Surgery Historical: open and see Passed: open and listen Present: see, open and listen Future: see, open, listen and see with new eyes 21