Glowing tumor dye may distinguish tumors from healthy tissue among patients with head, neck cancers

Jason G. Newman 

Researchers have launched a first-of-its-kind trial that will assess the use of intraoperative molecular imaging — or glowing tumor dye — to help detect cancerous lymph nodes among patients with head and neck cancers.

More than 65,000 Americans will be diagnosed with head and neck cancers this year.

When these cancers metastasize or recur, lymph nodes are one of the most commonly involved areas. Yet, when suspicious lymph nodes are removed during surgery, there is risk for damage to healthy tissue.

Jason G. Newman, MD, FACS, associate professor of otorhinolaryngology at Perelman School of Medicine at University of Pennsylvania, and colleagues are evaluating the effectiveness of intraoperative molecular imaging (IMI) of lymph nodes for patients with head and neck cancer.

The researchers hypothesize that IMI will allow for real-time guidance during surgery to help remove as much cancer as possible without affecting healthy tissue.

“By using a dye that makes cancerous cells glow, we get real-time information about which lymph nodes are potentially dangerous and which ones we can leave alone,” Newman said in a press release. “[This] not only helps us remove more cancer from our patients during surgery, it also improves our ability to spare healthy tissue.

“We know that tumors hold onto this dye longer than most other tissues, so if it is administered to a patient several hours before surgery, the tumors will still glow long after it has disappeared from the rest of the body,” Newman added. “As we build this program, we will learn which dyes work best for which cancers.”

HemOnc Today spoke with Newman about the trial and the potential benefits of this approach if it is proven effective and safe.

 

Question: What prompted this study?

Answer: In the head and neck, the anatomy and tumor biology make the visualization of where the tumors are extremely significant. Because of this, we are always looking for ways to better detail the difference between tumor and nontumor, with the goal of preserving as much healthy tissue as possible. A lot of technology has come out to help guide our decision-making. When we first were exposed to IMI, it appeared to be the perfect fit for the head and neck.

 

Q: Can you describe the technology?

A: Based upon studies done my colleague — Sunil Singhal, MD, professor in surgical research in the department of thoracic surgery at University of Pennsylvania — has conducted in the thoracic arena, we realize that, if patients are injected with different fluorescent markers, these markers will bind to tumors. This allows us to visualize the tumor better than by using the naked eye. When thinking conceptually about the idea of making the tumor glow relative to the surrounding tissue, this could help a surgeon better distinguish normal tissue from tumor tissue. This is the premise of this concept. Can we help identify, with visual augmentation, the difference between normal and abnormal tissue. Early work has been done with this concept and a variety of approaches have been used. Some markers have been designed that are specific to individual tumor types and some are nonspecific markers that appear to make a variety of tumors fluoresce.

 

Q: How will this study be conducted?

A: We are early enough in our understanding of this technology that we are trying to determine where the biggest impact will be. We have patients with different tumors of the head and neck and we are in the early stage of determining which tumors are the most appropriate on which to use this imaging technology. We do not yet know where the ‘sweet spot’ of this technology is in the head and neck arena. We are enrolling patients for whom we are planning surgery for cancer — whether it be robotic, endoscopic or open surgery. We do not know which will be the most appropriate in the long term. We are following their intraoperative course very closely and are using indocyanine green as the IMI marker at this time. The plan is to use a variety of different markers that are specific to each tumor and grow our library of florescent markers. Specifically, with indocyanine green, the patients come into our infusion suite the day before the surgery. They get injected, go home and come back the next day for surgery. The only difference is that we use a camera to image the tissue, and we determine the utility of the florescent dye. We are not yet using this to make formal decisions during surgery, but we are using IMI to help determine what role the marker should or can play in the management of these cancers.

 

Q: What do you think you will find?

A: The hypothesis is that this augmented visualization — the ability to see an extra layer of information above what our native vision can do — ultimately will improve our ability to remove all of the cancer and minimize damage to normal tissue. These are principles that are meant to hold true in every surgery but, in certain body parts, the removal of additional tissue is likely to cause more damage.

 

Q: What implications might the findings have on practice?

A: Although this concept is in its infancy, it is taking hold in many areas of surgical oncology. Companies and academic institutions are starting to think that IMI technology is going to become a mainstay for how we treat cancers during surgery. Augmented visualization to allow us to see tumors more clearly is something we will be seeing a lot more of in the future.

 

Q: What is the anticipated timeline for results?

A: We have already had abstracts accepted for publication, and I think there will be many layers of results. The timeline is ongoing because — unlike a drug trial, where we’d have to wait for efficacy — we know the efficacy at the time of surgery and pathology. The most interesting information comes in that ‘sweet spot’ when tissue looks normal to the naked eye, but then imaging shows the tissue is fluorescing, we test it and we start to determine that the technology is doing a better job than our eyes distinguishing tumor from normal tissue.

 

Q: Is there anything else that you would like to mention?

A: Our hope is that these techniques will allow us to more thoroughly detect any nonvisible cancer in a patient’s body. If we begin to demonstrate that this technology is better than our eyes at detecting small cancers, this will fundamentally change how we perform surgery and how likely we are to cure someone’s cancer. – by Jennifer Southall

 

For more information:

Jason G. Newman, MD, FACS, can be reached at Perelman School of Medicine, University of Pennsylvania, 295 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104; email: jason.newman@uphs.upenn.edu.

 

Disclosure: Newman reports no relevant financial disclosures.

Jason G. Newman 

Researchers have launched a first-of-its-kind trial that will assess the use of intraoperative molecular imaging — or glowing tumor dye — to help detect cancerous lymph nodes among patients with head and neck cancers.

More than 65,000 Americans will be diagnosed with head and neck cancers this year.

When these cancers metastasize or recur, lymph nodes are one of the most commonly involved areas. Yet, when suspicious lymph nodes are removed during surgery, there is risk for damage to healthy tissue.

Jason G. Newman, MD, FACS, associate professor of otorhinolaryngology at Perelman School of Medicine at University of Pennsylvania, and colleagues are evaluating the effectiveness of intraoperative molecular imaging (IMI) of lymph nodes for patients with head and neck cancer.

The researchers hypothesize that IMI will allow for real-time guidance during surgery to help remove as much cancer as possible without affecting healthy tissue.

“By using a dye that makes cancerous cells glow, we get real-time information about which lymph nodes are potentially dangerous and which ones we can leave alone,” Newman said in a press release. “[This] not only helps us remove more cancer from our patients during surgery, it also improves our ability to spare healthy tissue.

“We know that tumors hold onto this dye longer than most other tissues, so if it is administered to a patient several hours before surgery, the tumors will still glow long after it has disappeared from the rest of the body,” Newman added. “As we build this program, we will learn which dyes work best for which cancers.”

HemOnc Today spoke with Newman about the trial and the potential benefits of this approach if it is proven effective and safe.

 

Question: What prompted this study?

Answer: In the head and neck, the anatomy and tumor biology make the visualization of where the tumors are extremely significant. Because of this, we are always looking for ways to better detail the difference between tumor and nontumor, with the goal of preserving as much healthy tissue as possible. A lot of technology has come out to help guide our decision-making. When we first were exposed to IMI, it appeared to be the perfect fit for the head and neck.

 

Q: Can you describe the technology?

A: Based upon studies done my colleague — Sunil Singhal, MD, professor in surgical research in the department of thoracic surgery at University of Pennsylvania — has conducted in the thoracic arena, we realize that, if patients are injected with different fluorescent markers, these markers will bind to tumors. This allows us to visualize the tumor better than by using the naked eye. When thinking conceptually about the idea of making the tumor glow relative to the surrounding tissue, this could help a surgeon better distinguish normal tissue from tumor tissue. This is the premise of this concept. Can we help identify, with visual augmentation, the difference between normal and abnormal tissue. Early work has been done with this concept and a variety of approaches have been used. Some markers have been designed that are specific to individual tumor types and some are nonspecific markers that appear to make a variety of tumors fluoresce.

PAGE BREAK

 

Q: How will this study be conducted?

A: We are early enough in our understanding of this technology that we are trying to determine where the biggest impact will be. We have patients with different tumors of the head and neck and we are in the early stage of determining which tumors are the most appropriate on which to use this imaging technology. We do not yet know where the ‘sweet spot’ of this technology is in the head and neck arena. We are enrolling patients for whom we are planning surgery for cancer — whether it be robotic, endoscopic or open surgery. We do not know which will be the most appropriate in the long term. We are following their intraoperative course very closely and are using indocyanine green as the IMI marker at this time. The plan is to use a variety of different markers that are specific to each tumor and grow our library of florescent markers. Specifically, with indocyanine green, the patients come into our infusion suite the day before the surgery. They get injected, go home and come back the next day for surgery. The only difference is that we use a camera to image the tissue, and we determine the utility of the florescent dye. We are not yet using this to make formal decisions during surgery, but we are using IMI to help determine what role the marker should or can play in the management of these cancers.

 

Q: What do you think you will find?

A: The hypothesis is that this augmented visualization — the ability to see an extra layer of information above what our native vision can do — ultimately will improve our ability to remove all of the cancer and minimize damage to normal tissue. These are principles that are meant to hold true in every surgery but, in certain body parts, the removal of additional tissue is likely to cause more damage.

 

Q: What implications might the findings have on practice?

A: Although this concept is in its infancy, it is taking hold in many areas of surgical oncology. Companies and academic institutions are starting to think that IMI technology is going to become a mainstay for how we treat cancers during surgery. Augmented visualization to allow us to see tumors more clearly is something we will be seeing a lot more of in the future.

PAGE BREAK

 

Q: What is the anticipated timeline for results?

A: We have already had abstracts accepted for publication, and I think there will be many layers of results. The timeline is ongoing because — unlike a drug trial, where we’d have to wait for efficacy — we know the efficacy at the time of surgery and pathology. The most interesting information comes in that ‘sweet spot’ when tissue looks normal to the naked eye, but then imaging shows the tissue is fluorescing, we test it and we start to determine that the technology is doing a better job than our eyes distinguishing tumor from normal tissue.

 

Q: Is there anything else that you would like to mention?

A: Our hope is that these techniques will allow us to more thoroughly detect any nonvisible cancer in a patient’s body. If we begin to demonstrate that this technology is better than our eyes at detecting small cancers, this will fundamentally change how we perform surgery and how likely we are to cure someone’s cancer. – by Jennifer Southall

 

For more information:

Jason G. Newman, MD, FACS, can be reached at Perelman School of Medicine, University of Pennsylvania, 295 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104; email: jason.newman@uphs.upenn.edu.

 

Disclosure: Newman reports no relevant financial disclosures.