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What is Light Guided Surgery (LGS)?

Light Guided Surgery uses fluorescent markers that make the tumor light up during surgery. We are currently investigating if this will help surgeons to remove tumor tissue.

Today surgeons rely on their vision and touch to assess what should be removed during tumor resection. However, 15-30% of all head and neck cancer patients leave the operation room with tumor cells left behind. For these patients, the chances of tumor recurrence are high and overall survival low.

We are currently investigating if Light Guided Surgery could help solve this problem.

How We Investigate in LGS

1) Infusion of fluorescent dye that reaches the tumor.

2) The tumor will light up with a special camera during surgery.

3) The surgeon will outline the tumor.

4) The surgeon will remove the tumor.

5) After tumor resection, the surgeon checks the wound bed for remaining cancer.

6) The tumor is removed.

Examples of How LGS Could Potentially Change Surgery in the Future

Assessment of tumor extent

25% of patients leave the operation room with tumor cells left behind.

Detection of a Second Tumor

Second tumors represent the second leading cause of death in head and neck cancer patients.

Clinical Trials

At Stanford, we are establishing Light Guided Surgery as tomorrows standard of care. Patients who are eligible can potentially join the research. To find out if you are eligible please contact your doctor. Currently, we are including patients in the following clinical trials:

Roan Raymundo
Study Coordinator

Email

Gordon Li, MD

Principle Investigator
Clinical Brain Cancer Trial

Eben L. Rosenthal, MD

Principle Investigator
Dual-Modality Imaging Clinical Trial

George A. Poultsides, MD

Principle Investigator
Clinical Pancreas Cancer Trial

Suspended Trials

Lung Cancer

Natalie Lui, MD

Principle Investigator
Clinical Lung Cancer Trial

Head & Neck Cancer

Fred Baik, MD PhD

Principle Investigator
Clinical Head and Neck Sentinel Node Trial

To be considered for these trials you must be:

  • Be 19 years or older
  • Not be pregnant or breastfeeding
  • Have a biopsy-proven diagnosis of Squamous Cell Carcinoma of the head and neck
  • Be planned for standard of care surgery of the tumor
  • Be determined a suitable candidate for the clinical trial by your physician

Dual-Modality Imaging Study

Cervical lymph node staging if of great prognostic value for patients with head and neck cancer. Currently, to identify the presence of metastatic lymph nodes during the surgical resection of head and neck cancer, patients undergo a neck dissection or sentinel node biopsy procedure whereby some or all of the lymph nodes are taken out of the neck and sent for pathological evaluation.

We hope to show that the combined use (i.e. dual-modality) of 89Zr‑panitumumab and panitumumab‑IRDye800 can help surgeons to identify metastatic lymph nodes prior to and during the surgical procedure with equal or better accuracy than the current methods.

Panitumumab‑IRDye800 is an investigational imaging agent that contains a dye molecule that surgeons and researchers can image using light waves both during surgery and after the surgery on removed tissues. Recently we have shown that using this drug, we can identify metastatic lymph nodes from benign, normal lymph nodes based on the fluorescent signal that comes from the panitumumab‑IRDye800. However, because of the limited penetration depth of the fluorescence signal, it is challenging to detect these lymph node(s) in the body.

89Zr‑panitumumab is an investigational imaging agent that contains a small amount of radiation, which makes it visible in positron emission tomography (PET) scans. We hypothesize that by using 89Zr‑panitumumab we can identify metastatic lymph nodes on preoperatively acquired (non-invasive) PET scans. If so, this information we can then use to guide us during the surgery. Because for the dual-modality study we will intravenously infuse both panitumumab-IRDye800 and 89Zr‑panitumumab, we can use the fluorescent signal coming from panitumumab-IRDye800 to precisely localize the metastatic lymph node(s).

Preoperative imaging 89Zr-panitumumab (radiotracer)

Day 0

At 2 hours we see the tracer mainly circulating in the blood. All the large blood vessels are clearly visible.We also see some excretion into the liver and kidneys.

Day 2

At 22 hours, besides the blood vessels and the liver we see some tracer accumulation at the primary tumor site.

Day 4

At 95 hours we hardly see any tracer circulating in the blood anymore (you don’t see the blood vessels anymore) and we see that excretion of the tracer has increased (liver, kidneys, intestine).

Intraoperative imaging panitumumab-IRDye800 (fluorescence)

Primary tumor prior to resection

Wound bed post re-resection of tumor

Fluorescence imaging of the tumor was performed prior to resection and after resection to “check” the wound bed. In the upper row the tumor is clearly visible with fluorescence and in the bottom row you can see that the wound bed is empty – there is no suspicious fluorescence left. The middle column of tiles show the fluorescence signal in black and white where the “white” represents the tumor and the black the background (= no fluorescence signal). The right column of tiles shows the overlay of the brightfield photo (in greyscale) and the fluorescence (red-yellow-blue heatmap). This image provides anatomical context to the surgeon – the surgeon can see where is the fluorescence located with regard to the tumor area.

The research study that we are conducting is looking for 14 patients with head and neck cancer that are scheduled to undergo surgery for removal of the primary tumor and/or lymph nodes of the neck. Should you be interested in participating in the study, please reach out to Dr. Eben Rosenthal at (650)-723-4250 and/or Ms. Roan Raymundo (650)-722-4071.

Fluorescently-labeled panitumumab to image brain cancer during surgery

Patients with glioma often undergo surgical procedures to reduce or remove their cancer.  Doctors who perform this type of surgery are well‑trained in removing all the cancer that can be seen during your operation. However, there are times when the tumor looks like normal brain tissue or there are cancer deposits that are too small to be seen by the surgeon.

We hope to show that panitumumab-IRDye800, an imaging agent, is safe to use in brain cancer patients. We will also evaluate if panitumumab-IRDye800 can help surgeons to better distinguish cancer cells from normal brain tissue and identify small cancer lesions that cannot be seen using current imaging methods.

Panitumumab‑IRDye800 is an investigational imaging agent that contains a dye molecule that surgeons and researchers can image using light waves both during surgery and after the surgery on removed tissues.

Skull Removed

Brain Exposed

Tumor Visible

Tumor Removed

White light

Fluorescence (heat map)

Fluorescence (black and white)

As the tumor was located beneath the brain surface (as indicated in presurgical MRI), minimal fluorescence was detected through the intact dura.

The tumor lied beneath the area (dashed line: expected incision path) where faint fluorescence signal showed up on the brain surface.

A clear fluorescence signal was visible in the tumor when the surgeon reached the tumor (dashed circle).

Very little fluorescence remained in the wound bed after surgical removal of the tumor.

The research study that we are conducting is looking for 22 participants undergoing surgery for removal of brain tumors. Enrollment will occur at Stanford University and the University of Alabama (Birmingham). Stanford will enroll up to 12 research participants. Should you be interested in participating in the study, please reach out to Dr. Gordon Li at (650-) 498-6000, Dr. Eben Rosenthal at (650)-723-4250, and/or the study coordinator for this study, Ms. Roan Raymundo (650)-721-4071.

You may also want to read the recent interview that was held with Dr. Li and Dr. Rosenthal on novel imaging technologies to identify brain cancer:

Dr. Li & Dr. Rosenthal interview

Fluorescently-labeled panitumumab to image pancreatic cancer during surgery

Patients with pancreatic cancer often undergo surgical procedures to reduce or remove their cancer.  Doctors who perform this type of surgery are well‑trained in removing all the cancer that can be seen during your operation.  However, there are times when there are cancer deposits that are too small to be seen by the surgeon.

We hope to show that panitumumab-IRDye800, an imaging agent, is safe to use in pancreatic cancer patients and learn whether panitumumab-IRDye800 can help surgeons identify small cancer lesions that cannot be seen using current imaging methods.

Panitumumab‑IRDye800 is an investigational imaging agent that contains a dye molecule that surgeons and researchers can image using light waves both during surgery and after the surgery on removed tissues.

Intraoperative fluorescence imaging of the pancreas part that contains tumor

The tumor area light up fluorescently and so does a lymph node (LN; red circle) that is located on top of the tumor area. We can also see some lymphatic ducts (green circle).

After removal of the pancreas tumor fluorescence imaging was performed to check that there was no residual fluorescence left in the wound bed. A little bit of background fluore-scence was found in the intestine.

The research study that we are conducting is looking for 27 participants undergoing surgery to remove pancreatic cancer.  Should you be interested in participating in the study, please reach out to Dr. Poultsides at (650) 723-2967Dr. Eben Rosenthal at (650)-723-4250, and/or the study coordinator for this study, Ms. Roan Raymundo (650)-721-4071.

Publications

  • Gao RW, Teraphongphom NT, van den Berg NS, et al. Determination of Tumor Margins with Surgical Specimen Mapping Using Near-Infrared Fluorescence. Cancer Res. 2018;78(17):5144-5154. doi:10.1158/0008-5472.CAN-18-0878 PMID: 29967260
  • Fakurnejad S, van Keulen S, Nishio N, et al. Fluorescence molecular imaging for identification of high-grade dysplasia in patients with head and neck cancer. Oral Oncology. 2019;97:50-55. doi:10.1016/j.oraloncology.2019.08.008 PMID: 31421471
  • Nishio N, van den Berg NS, van Keulen S, et al. Optical molecular imaging can differentiate metastatic from benign lymph nodes in head and neck cancer. Nat Commun. 2019;10(1):5044. doi:10.1038/s41467-019-13076-7 PMID: 31695030
  • van Keulen S, van den Berg NS, Nishio N, et al. Rapid, non-invasive fluorescence margin assessment: Optical specimen mapping in oral squamous cell carcinoma. Oral Oncology. 2019;88:58-65. doi:10.1016/j.oraloncology.2018.11.012 PMID: 30616798
  • Tummers WS, Warram JM, van den Berg NS, et al. Recommendations for reporting on emerging optical imaging agents to promote clinical approval. Theranostics. 2018;8(19):5336-5347. doi:10.7150/thno.27384 PMID: 30555550
  • Gao RW, Teraphongphom N, de Boer E, et al. Safety of panitumumab-IRDye800CW and cetuximab-IRDye800CW for fluorescence-guided surgical navigation in head and neck cancers. Theranostics. 2018;8(9):2488-2495. doi:10.7150/thno.24487 PMID: 29721094
  • van Keulen S, Nishio N, Fakurnejad S, et al. The Clinical Application of Fluorescence-Guided Surgery in Head and Neck Cancer. J Nucl Med. 2019;60(6):758-763. doi:10.2967/jnumed.118.222810 PMID: 30733319
  • van Keulen S, Nishio N, Birkeland A, et al. The Sentinel Margin: Intraoperative Ex Vivo Specimen Mapping Using Relative Fluorescence Intensity. Clin Cancer Res. 2019;25(15):4656-4662. doi:10.1158/1078-0432.CCR-19-0319 PMID: 31142505

Dr. Eben L. Rosenthal, PI

Dr. Rosenthal is committed to improve survival for patients that undergo surgery for cancer. As a surgeon-scientist, he has the unique opportunity to act as a direct bridge between science and the patient. He specializes in the treatment of head and neck cancer patients and has a strong interest in the development of imaging modalities to enhance successful tumor removal in all cancer types.

With a team of medical doctors, post-doctoral students and visiting scholars from all over the world, Dr. Rosenthal is working hard to take Light Guided Surgery into clinical practice.

Stanford Profile
Dr. A. Dimitrios Colevas

Dr. A. Dimitrios Colevas, Medical Oncologist

I am a board-certified medical oncologist with a particular interest in the multimodality of treatment of many types of cancers originating in the head and neck region and a secondary interest in early phase clinical trials of new chemical and biological entities. After graduating from Columbia University with a BA in chemistry, I attended medical school and internal medicine residency at Johns Hopkins Medical School and Johns Hopkins hospital, respectively. After an interim year practicing internal medicine in Fairbanks Alaska, I completed my medical oncology fellowship at Dana Farber Cancer Institute where I was mentored by Dr. Marshall Posner in the clinic and Dr. William Kaelin in the lab.

My interests relevant to the Rosenthal lab are trials presently involving the adenoviral vector AdPNP in combination with systemic fludarabine for the treatment of recurrent metastatic head and neck cancer and the study of fluorescently labeled or radiolabeled entities,  in particular, monoclonal antibodies against EGFR, in order to explore distribution of cancer cells in a manner  not possible using conventional methodologies .  We are also  using this platform to study the basic biology of monoclonal antibody bonding and  distribution in squamous cell carcinomas of the head and neck.

Stanford Profile

Team

With a team of medical doctors, post-doctoral students and visiting scholars from all over the world, professor E. Rosenthal is working hard to take Light Guided Surgery into clinical practice.

Giri Krishnan, MD

Giri is an Otolaryngology, Head and Neck Surgical trainee and PhD candidate from Adelaide, South Australia. He has conducted part of his research in the Rosenthal Laboratory, where he has focused on exploring emerging strategies for intraoperative tumor detection in head and neck cancer surgery using fluorescent imaging. His work has specifically looked into ex vivo margin analysis of oral cancer specimens and the use of systemically infused Panitumumab-IRDye800CW for sentinel lymph node mapping in the neck.

Naoki Nishio, MD PhD

Naoki is a board-certified head and neck surgeon with over ten years’ experience, who specializes in the surgical treatment of primary tumor and lymph node metastasis in head and neck cancer. He earned his MD (2005) and a PhD (2013) from the Nagoya University Graduate School of Medicine in Japan. Prior to joining Rosenthal lab at Stanford University, Dr. Nishio worked as an assistant professor at Nagoya University Hospital in Japan, where he developed a new approach to skull base malignancies using three-dimensional virtual surgical simulation. Presently, his research focuses on the clinical application of molecular fluorescence imaging using tumor-specific antibody with fluorescence tracer in several solid cancers.

Nynke van den Berg, PhD

Nynke obtained her bachelor in Health and Life Sciences (2009) and her masters in Oncology (2011) from the Free University in Amsterdam, the Netherlands. She obtained her PhD with greatest honors (cum laude) from the Leiden University in Leiden, the Netherlands in November 2016 – thesis: “Advancing surgical guidance: from (hybrid) molecule to man and beyond”. She joined the Rosenthal lab in January 2017 to continue her research on the clinical evaluation and validation of fluorescence- and/or radio-labeled imaging agents to improve primary tumor and metastatic lymph node detection in head and neck cancer.

Guolan Lu, PhD

Guolan is a postdoc in the Rosenthal Lab. She received her PhD degree from the joint Biomedical Engineering department of Georgia Institute of Technology and Emory University, where she worked on quantitative cancer detection with hyperspectral imaging and machine learning in both preclinical and clinical studies. Since joining the lab, Guolan has been working on the quantification and prediction of antibody penetration into solid tumors and running the clinical trial for fluorescence-guided surgery in pancreatic cancer.

Quan Zhou, PhD

Quan grew up in Nanjing, China. She attended Hong Kong Baptist University for her undergraduate training where she majored in applied biology and minored in chemistry, completing an honor’s thesis investigating the acute and prolonged effects of alcohol intake on dopamine receptor expression in mice substantia nigra. Moving to the other side of the Pacific, Quan then completed both her M.S. and Ph.D. training in biomedical engineering at the University of Michigan, Ann Arbor. Her doctoral research focused on optical and photoacoustic imaging for early detection of liver and colon cancers with molecular targeting probes such as peptides and nanoparticles. Quan is currently undertaking a postdoctoral training in the Rosenthal and Grant labs with the goal of translating fluorescence guided neurosurgery in human brain cancer patients and enhanced drug delivery across the blood-brain barrier via tight junction protein modulation and focused ultrasound.

Jacqueline Pei, BS

Jackie is a Bay Area native from Foster City, California. She graduated from UCLA with a BS in Molecular, Cell, and Developmental Biology in 2018. Since joining, she has been describing the pharmacokinetics of panitumumab-IRDye800CW and and investigating other markers in head and neck squamous cell carcinoma.

Roan Raymundo, BS

Roan graduated from University of California, Davis in 2018 with a Bachelor of Science in Human Development.  During her undergraduate career, she served as a research assistant for the Peer Relations human ecology lab and the Attraction and Relationships psychology lab.  She joined Stanford’s Clinical Cancer Trials Office and Rosenthal lab in October 2018 as a research coordinator.

Grace Yi, BS

Grace obtained her Bachelor of Science in Psychology with a concentration in Neuroscience in 2019  from the University of Massachusetts in Amherst. In college, she conducted research in the Translational Biomaterials and Tissue Engineering Laboratory, designing a microfluidics chip that mimics bone marrow microanatomy and cellular complexity to understand the interplay between normal and malignant cell dissemination. In 2018, at Johns Hopkins Medical School, she studied how aging endothelial cells contribute to cardiovascular diseases such as atherosclerosis. Later in June 2019, she joined Dr. Eben Rosenthal’s clinical trials team to investigate the use of intra-operative imaging agents for patients with head and neck cancer. Grace aspires to be both a physician and scientist who wishes to gain a deeper understanding of the protocols for delivery and implementation of new drugs and treatment methods.

Shrey Kapoor, BS

Shrey graduated Summa Cum Laude from Johns Hopkins University in 2019 with degrees in Public Health and Natural Sciences. Matriculating to Johns Hopkins School of Medicine in Fall of 2020. Bay Area native. Working on prospective study on using fluorescent imaging for intraoperative tumor margin assessment.

Contact Us

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Eben Rosenthal | Professor and Medical Director Stanford Cancer Center​
Email: erosenthal@stanfordhealthcare.org ​

Heather Restificar | Administrative assistant
Email: hrestificar@stanfordhealthcare.org

Roan Raymundo | Study Coordinator
Email: rcraymun@stanford.edu

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