1. Sentinel Node Localization Yolonda L. Colson, MD, PhD Professor of Surgery, Harvard Medical School Vice Chair for Surgical Innovation Executive Director, Center for Surgical Innovation Associate Administrative Chief, Division of Thoracic Surgery at BWH Dana Farber Cancer Institute / Brigham & Women’s Cancer Center NIR Image-guided Lymphatic Mapping in Lung Cancer

2. Disclosures I have no equity, ownership, stock, options or any interest in any company I do not consult for any company We gratefully acknowledge Novadaq for the generous loan of the Pinpoint system. There has been no data preview or monetary sponsorship for this collaboration I have presented our NIH-funded data on NIR-imaging at a Novadaq-sponsored conference but without honorarium Use of ICG for NIR-imaging of SLN is NOT FDA-approved

3. Why Consider SLN Mapping in Lung Cancer? Almost 30% of Clinical stage I NSCLC patients upstaged at surgery due to occult nodal disease Sites of Missed Nodal disease ▫ Residual lymph nodes: only 50% of patients undergo a complete lymphadenectomy. ▫ Micrometastasis: 16-18% of “node negative” patients harbor positive LN disease with further histologic scrutiny. ▫ Skip Metastases: ~20% of “first tumor-draining lymph nodes” (i.e. SLN) at N2 station.

4. GroupYearTechniqueSuccess Little et al1999Single CenterBlue Dye47% Liptay et al2000Single CenterRadioisotope81% Liptay et al2009Multi-CenterRadioisotope51% Nomori et al2007Single CenterPre-op Radioisotope81% Schmidt et al2002Single CenterIntra-operative Blue Dye/ Radioisotope 81% Tiffet et al2005Single CenterIntra-operative Blue Dye/ Radioisotope 54% No Reliable SLN Technology for Lung Cancer SLN Mapping in Lung Cancer “Conventional Methods” Mixed Success ▫ Low Signal ▫ Anatomic Limitations

5. Lipid NIR Window Courtesy of J. Frangioni, BIDMC Advantages of NIR Fluorescent Imaging High signal-to-background ratio ▫ Low NIR Autoflourescence ▫ High Fluorophore Signal in NIR Invisible to the human eye ▫ No alteration of Surgical Field Increased Safety ▫ No radioactivity or laser risk Real-time visualization of target during surgical dissection Excitation of the Indocyanine Green (ICG) captured by a near-infrared camera

6. Indocyanine Green (ICG) emission in NIR spectra: 750-950nm ICG signal detection via NIR videoscopic camera Visualization of merged and single channel images in real-time Light Source Surgical Field NIR Camera Color Video Camera Video of Real-time Merged Images Courtesy of J. Frangioni, BIDMC. How Does it Work?

7. Lesion Characteristics Dictate NIR Approach

8. How I Do It

10. Summary 32 SLN in 20 patients ▫ ICG Dose Dependent ▫ Dose optimized at 2.5mg ▫ N1 Stations – 21 LN ▫ N2 Stations – 11 LN No Adverse events SLN status predictive of nodal metastases in all patients N=7n=13 0%

11. Conclusion NIR guided lymphatic mapping appears to be a safe & feasible approach to identify SLN Learning curve is initially high May improve intraoperative staging with identification of micrometastatic disease in lung cancer patients Still an experimental approach and has not been evaluated for long-term safety or for SLN accuracy in a sufficient number of patients to be standard of care Large prospective clinical trial is needed

12. Funding & Support National Cancer Institute – R01-CA131044 American College of Surgeons Clowes Award Edward M. Kennedy Award for Healthcare Innovation Center for Integration of Medicine & Innovative Technology (CIMIT) Talent Hisashi Tsukada (BWH), John Frangioni (BIDMC) Krista Hachey, Denis Gilmore, Onkar Khullar Katie Armstrong, David Owens Acknowledgments