GOSTT General concept

Transcription

1 GOSTT General concept Francesco GIAMMARILE «Aut tace aut loquere meliora silentio»

2 Presentation Outline Introduction: GOSTT and radioguided surgery The Sentinel Node Concept Latest technological knowledge I sort of thought your presentation was going to be in powerpoint. NO CONFLICT OF INTEREST

3 The GOSTT concept (radio)guided intraoperative Scintigraphic Tumor Targeting

4 Radioguided surgery Fundamental forces driving the growth of radioguided surgery Oncologic surgery is becoming as less invasive/mutilating as possible The emerging concept of the sentinel lymph node in oncologic surgery for staging parameter N Growing applications of non-sentinel lymph node radioguided surgery with different approaches to tumor targeting (interstitial or systemic routes) Growing applications of robotic surgery Aim: tailor surgical approaches to the different disease-specific and patient-specific conditions Base: growing collaboration of different specialties involved

5 Nuclear Medicine and Radioguided Surgery adequate radiopharmaceutical for preoperative labeling of the target tissue radioactivity-detecting probe for intraoperative guidance of the target tissue to be removed. minimal surgical access and probe-aided assessment of the completeness of excision

6 Nuclear Medicine and Radioguided Surgery A new concept in Nuclear Medicine?

7 Nuclear Medicine and Radioguided Surgery Author Year Tracer Pathology Comment Selverstone P Brain tumors Geiger-Müller detection Harris I Thyroid cancer β - counting probes Aitken I- anti ACE Ab Colorectal cancer First RIG surgery Krag m Tc-colloids Breast cancer First SL surgery Desai F-FDG Colorectal cancer Β + counting probes Late 1940s: pioneering experience in radioguided surgery of brain tumors using 32P and intra-operative β- Geiger-Müller detection. Early 1980s: adding a new intraoperative sense to the surgeon for radioimmunoguided surgery (sound pitch proportional to activity level). Early 2000s: intraoperative imaging probes and hybrid imaging (preoperative SPECT/CT). Early 2010s: growing integration of all modalities, including intraoperative optical imaging.

8 Evolution of oncologic surgery and radioguidance 1. open and see 2. open and listen 3. see, open and listen 4. see, open, listen and see with new eyes

9 Nuclear medicine applications of radioguided surgery 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

10 The sentinel node concept First node involved in metastatic spread of tumour Artery Tumor Sentinel Lymph Node Vein Lymphatic vessel Secondary Lymph Nodes Particles diffuse into interstitial fluid, drains into lymphatic vessels and regional nodes

11 The sentinel node concept Radiopharmaceuticals 99m Tc labeled colloids Size max Size mean range (nm) (nm) Antimony sulphide 80 -> 5-30 Albumin nanocolloid (Nanocoll ) 100 -> 5-80 Sulfide nanocolloid (Lymphoscint ) > Rhenium sulfide nanocolloid (Nanocis ) > Sulphur colloid (filtered) 5, > Colloidal tin hydroxide (Hepatate ) > Dextran > Human serum albumin > Particule size (µm) Target (i.v. injection) > 15 Lung < 8 Reticuloendothelial system > 0.6 Spleen Liver <0.3 Bone marrow Nonspecific, particle size-related phagocytosis by macrophages in lymph nodes Quality control: > 95% Activity: MBq (adjusted if 2 days)

12 The sentinel node concept Modalities for Localizing Anatomically the Sentinel Node on Lymphoscintigraphy Planar imaging without reference landmarks Planar imaging with contour of the body by moving a radioactive point source Planar imaging with transmission scan from a flood source beneath the patient s body SPECT SPECT/CT Intraoperative imaging devices for radioactive and optical guidance

13 The sentinel node concept Pre-surgical planar imaging

14 The sentinel node concept Pre-surgical SPECT/CT imaging

15 The sentinel node concept SPECT/CT: General indications No or poor visualization of drainage at planar imaging (low or no activity, injection closer to nodes, depth, overweighed patients...): attenuation correction in SPECT/CT Topographic localization and detection of additional SLNs in areas of deep lymphatic drainage (pelvis, abdomen, or mediastinum) or in areas with complex anatomy (head and neck): identification of number, size, depth, and exact localization Planar images difficult to interpret (unexpected unusual drainage patterns) Advantages Surgical planning Sensitivity Specificity Attenuation correction Problems Cost and added time Additional radiation Non suitable for dynamic studies too much sensitive?

16 The sentinel node concept SPECT/CT: Added Values Breast cancer faster intraoperative search (42%) overall improved accuracy (82%) additional SLNs in 13%, unexpected drainage patterns in 21%, and falsepositive sites in 9% of patients Cutaneous melanoma adjustment in surgical approach (36%) additional SLNs in 20%, better intraoperative search in 29%, and adjustment in surgical approach in 29% JNM 2015

17 The sentinel node concept SPECT/CT: advantages Sensitivity Breast cancer Lymph node clearly shown only on SPECT-CT

18 The sentinel node concept SPECT/CT: advantages Sensitivity Breast cancer An intra-mamary lymph node is seen only in SPECT-CT

19 The sentinel node concept SPECT/CT: advantages Specific location of the SLN Breast cancer Level I and Level II axillar lymph nodes clearly shown on SPECT-CT

20 The sentinel node concept SPECT/CT: advantages Specific location of the SLN Breast cancer Deep intra-mammary lymph nodes

21 The sentinel node concept SPECT/CT: advantages Anatomic Information for surgical planning Breast cancer

22 The sentinel node concept SPECT/CT: advantages Anatomic Information for tissue characterization Breast cancer Enlarged axillar lymph node with uptake of the tracer only at the pole clearly shown on SPECT-CT

23 Latest technological knowledge Dedicated small field of view portable imaging devices Provide high-resolution imaging of all hotspots in surgical field No role for intraoperative guide in the surgical bed (too bulky for surgical access) Important role for real-time assessing completeness of lesion removal, especially in locations close to the injection site Must meet several requirements: portable and stable design no delay between image acquisition and display (real time imaging) possibility for continuous monitoring, spatial orientation on screen, real time quantification and display of the counts recorded adequate spatial resolution, sensitivity and field of view.

24 Small field of view portable imaging devices Light weight portable gamma cameras (less than 1 kg), without support designed for intraoperative use

25 Small field of view portable imaging devices Gamma-Node (Clerad) Sentinella S102 (Oncovision) Last generation portable gamma camera fitted with a pin-hole collimator, with improved ergometrical details and adequate support system for intraoperative use

26 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

27 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

28 Latest technological knowledge 3D/2D tracking assisted probes Image acquisition is obtained with a standard, collimated intraoperative nuclear probe together with an optical tracking system (position and orientation) Intraoperative combined imaging used for precise localization and targeting Similarly to portable gamma cameras, possibility to ensure permanent assistance and transparent documentation of soft tissue removal during the intervention

29 3D/2D tracking assisted probes Handle Gamma probe with sterile tracking target Optical camera Infrared localization system Sterile patient target virtual reconstruction in a 3D environment Freehand SPECT CSS300 (SurgicEye s)

30 3D/2D tracking assisted probes 3-D tracking and optical/ radioactivity fusion Data with tracked gamma probe Non-uniform / non-symmetric set <180 covered

31 3D/2D tracking assisted probes 3-D volume rendering SPECT

32 Latest technological knowledge Radiopharmaceuticals van den Berg NS et al. Q J Nucl Med Mol Imaging 2014; 58:

33 Latest technological knowledge 99m Tc-labelled agents Colloids (passive phagocytosis) 99m Tc labelled phytates 99m Tc labelled gold particles: uniformity of size (20 nm) Tilmanocept (active phagocytosis) 99m Tc mannosylated dextran (7 nm) Paramagnetic, fluorescent and bimodal radioactive agents Hybrid tracers (radioactive and fluorescent) for simultaneous scintigraphic and optical imaging (near-infrared fluorescence): - Indocyanine-green/ 99m Tc-Nanocolloid - Indocyanine-green/ 99m Tc-Tilmanocept Added value for laparoscopic surgery or in case of complex lymphatic anatomy (head & neck)

34 Latest technological knowledge Tilmanocept Receptor targeting agent tilmanocept Protein CD 206 Active phagocytosis: binding to macrophages and dendritic cells in lymph nodes through nonsaturable mannose receptors (CD206)

35 Latest technological knowledge Tilmanocept Advantages Problems Higher specific radioactivity. Faster clearance from injection site. Faster migration to draining lymph nodes. Longer retention in lymph nodes. Greater scintigraphic contrast. Lesser migration to higher-tier lymph nodes. Greater signal-to-background ratio. Comparable sensitivity but greater specificity in sentinel node identification. Higher count-rate in tumor-positive lymph nodes? particular utility in patients with head and neck melanoma

36 Latest technological knowledge Paramagnetic tracers Phagocytosis in macrophages (internalization and accumulation)

37 Latest technological knowledge Fluorescent tracers Gastric cancer I. Miyashiro, J Gastric Cancer (2012) Breast cancer J. Sven, Ann Surg Oncol (2011) Endometrial cancer RW Halloway, Gynecol Oncol (2012)

38 Latest technological knowledge Bimodal (hybrid) agents Tissue penetration signals Electronically assembled nanoparticule containing ICG

39 Latest technological knowledge Bimodal (hybrid) agents Simultaneous radioguided and fluorescent detection Brouwer OR, Ann Surg Oncol (2012)

40 Conclusion Radioguided Surgery today Multimodality preoperative molecular imaging, intraoperative imaging and non-imaging procedures are essential for optimizing surgical approaches in patient- and disease-specific conditions To evaluate more precisely and in real time the resection margins (improving patient management and outcome) To reduce the invasiveness of procedures (positively impact health economy)

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