Intraoperative molecular imaging helps identify more cancerous lung nodules

Jarrod D. Predina

The addition of intraoperative molecular imaging and preoperative PET scan led to the identification and removal of significantly more cancerous nodules than PET scan alone for patients with resectable lung cancer, according to study results published in Annals of Surgery.

“Surgically removing tumors still leads to the best outcomes in cancer patients, and this study shows intraoperative molecular imaging can improve the surgeries,” Jarrod D. Predina, MD, MS, postdoctoral research fellow in the Thoracic Surgery Research Laboratory at Abramson Cancer Center and University of Pennsylvania’s Center for Precision Surgery, said in a press release. “The more we can improve surgeries, the better the outcomes for these patients will be.”

Although PET scans are the standard for identifying malignancies before surgery to remove suspicious pulmonary nodules, these types of scans have known limitations. They are unable to identify tumors smaller than 1cm, they cannot differentiate between cancerous growths and benign inflammatory diseases, and scans taken before surgery do not give surgeons real-time guidance once the procedure begins.

For this reason, Predina and colleagues sought to assess the use of intraoperative molecular imaging — with a near-infrared contrast agent, OTL38, that makes tumor cells glow — combined with PET imaging for 50 patients undergoing surgery for lung nodules.

Results showed intraoperative molecular imaging identified 94.9% of malignant pulmonary nodules identified by PET scan. Moreover, nine nodules not previously detected with PET scan or traditional intraoperative imaging were found with intraoperative molecular imaging.

Nodules detected only by intraoperative molecular imaging were smaller than those detected preoperatively (0.5 cm vs. 2.4 cm; P < .01).

Sensitivity values were 95.6% for intraoperative molecular imaging and 73.5% for PET (P = .001). Positive predictive values were 94.2% for intraoperative molecular imaging and 89.3% for PET (P > .05).

Of note, intraoperative molecular imaging clinically upstaged 12% of patients and led to improvements in management of 30% of patients.

HemOnc Today spoke with Predina about the study and the potential implications of the findings.

 

Question: How did the idea for this research come about?

Answer: I am a resident at Massachusetts General Hospital and I worked with Sunil Singhal, MD, the William Maul Measey associate professor in surgical research and director of the Abramson Cancer Center’s Center for Precision Surgery, about 8 years ago when the idea of making tumors glow was really just an idea at the time. During the years I was completing my residency in Boston, this idea really took off. We decided to figure out what we could do to truly understand how this technology fits in with standard of care for lung cancer. Penn is one of the biggest imaging centers in the world, and it had imaged more than 600 patients at that point. They had already proven they could make tumors glow, but they had not determined how it impacted what we do on a regular basis for patients with lung cancer. The thought was to determine how the addition of molecular imaging would improve upon the standard of care.

Q: What did you find?

A: In 12% of the patients we enrolled, we identified invasive cancers with the new agent that were undetectable with preoperative imaging. This was the big finding. The other major finding that was a huge surprise was that the technology works well and is extremely sensitive for smaller cancers that are hard to find. The sensitivity of this technology was far superior than PET and CT scans for nodules smaller than 0.5 cm.

 

Q: What are the potential clinical implications of these findings?

A: The results are very early, but we have found that this technology does three things. First, it helps us to localize known nodules that we would otherwise have challenges trying to find with traditional techniques. Second, it helps us obtain more information to remove occult tumors that we would have otherwise missed. Third, the fluorescent feedback allows us to perform many of the tasks during minimally invasive surgery — something that is sometimes very challenging.

 

Q: Might this combination be used for other cancer types?

A: This technology is under phase 3 investigation for ovarian cancer and phase 2 investigation for lung cancer. We also have had preliminary success in osteosarcomas, which also upregulate the folate receptor. Theoretically, this approach may be applicable to any tumor that upregulates the folate receptor.

 

Q: What still needs to be confirmed in subsequent research?

A: Intraoperative molecular imaging is still investigational. There is only one FDA-approved cancer imaging agent in the United States. However, there are many other agents in the pipeline. I feel very fortunate to be working in one of the oncology laboratories that is the furthest in the game and has one of these agents under investigation now. We are in phase 2 right now for the agent in lung cancer and need to better understand how others can use this technology.

 

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

A: We are all very excited about this agent and happy that it is getting a lot of coverage, but I think the most important thing is that this is still in the very early stage of research and we continue to learn about this technology. So far, the data appear promising, but this is still investigational. I think most surgeons agree this will play a role in the future, and we are just beginning to understand how big that role may be. As we continue to evaluate this approach, I am hopeful we can really understand how this can improve the way we do surgery. – by Jennifer Southall

 

Reference:

Predina JD, et al. Annals of Surgery. 2017;doi:10.1097/SLA.0000000000002382.

 

For more information:

Jarrod D. Predina, MD, MS, can be reached at Abramson Cancer Center at University of Pennsylvania, 3400 Civic Center Blvd., West Pavilion, Philadelphia PA 19104; email: jpredina@partners.org.

 

Disclosure: The study was supported by the American Philosophical Society, the NIH and the Association for Academic Surgery Foundation. Predina reports no relevant financial disclosures.

Jarrod D. Predina

The addition of intraoperative molecular imaging and preoperative PET scan led to the identification and removal of significantly more cancerous nodules than PET scan alone for patients with resectable lung cancer, according to study results published in Annals of Surgery.

“Surgically removing tumors still leads to the best outcomes in cancer patients, and this study shows intraoperative molecular imaging can improve the surgeries,” Jarrod D. Predina, MD, MS, postdoctoral research fellow in the Thoracic Surgery Research Laboratory at Abramson Cancer Center and University of Pennsylvania’s Center for Precision Surgery, said in a press release. “The more we can improve surgeries, the better the outcomes for these patients will be.”

Although PET scans are the standard for identifying malignancies before surgery to remove suspicious pulmonary nodules, these types of scans have known limitations. They are unable to identify tumors smaller than 1cm, they cannot differentiate between cancerous growths and benign inflammatory diseases, and scans taken before surgery do not give surgeons real-time guidance once the procedure begins.

For this reason, Predina and colleagues sought to assess the use of intraoperative molecular imaging — with a near-infrared contrast agent, OTL38, that makes tumor cells glow — combined with PET imaging for 50 patients undergoing surgery for lung nodules.

Results showed intraoperative molecular imaging identified 94.9% of malignant pulmonary nodules identified by PET scan. Moreover, nine nodules not previously detected with PET scan or traditional intraoperative imaging were found with intraoperative molecular imaging.

Nodules detected only by intraoperative molecular imaging were smaller than those detected preoperatively (0.5 cm vs. 2.4 cm; P < .01).

Sensitivity values were 95.6% for intraoperative molecular imaging and 73.5% for PET (P = .001). Positive predictive values were 94.2% for intraoperative molecular imaging and 89.3% for PET (P > .05).

Of note, intraoperative molecular imaging clinically upstaged 12% of patients and led to improvements in management of 30% of patients.

HemOnc Today spoke with Predina about the study and the potential implications of the findings.

 

Question: How did the idea for this research come about?

Answer: I am a resident at Massachusetts General Hospital and I worked with Sunil Singhal, MD, the William Maul Measey associate professor in surgical research and director of the Abramson Cancer Center’s Center for Precision Surgery, about 8 years ago when the idea of making tumors glow was really just an idea at the time. During the years I was completing my residency in Boston, this idea really took off. We decided to figure out what we could do to truly understand how this technology fits in with standard of care for lung cancer. Penn is one of the biggest imaging centers in the world, and it had imaged more than 600 patients at that point. They had already proven they could make tumors glow, but they had not determined how it impacted what we do on a regular basis for patients with lung cancer. The thought was to determine how the addition of molecular imaging would improve upon the standard of care.

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Q: What did you find?

A: In 12% of the patients we enrolled, we identified invasive cancers with the new agent that were undetectable with preoperative imaging. This was the big finding. The other major finding that was a huge surprise was that the technology works well and is extremely sensitive for smaller cancers that are hard to find. The sensitivity of this technology was far superior than PET and CT scans for nodules smaller than 0.5 cm.

 

Q: What are the potential clinical implications of these findings?

A: The results are very early, but we have found that this technology does three things. First, it helps us to localize known nodules that we would otherwise have challenges trying to find with traditional techniques. Second, it helps us obtain more information to remove occult tumors that we would have otherwise missed. Third, the fluorescent feedback allows us to perform many of the tasks during minimally invasive surgery — something that is sometimes very challenging.

 

Q: Might this combination be used for other cancer types?

A: This technology is under phase 3 investigation for ovarian cancer and phase 2 investigation for lung cancer. We also have had preliminary success in osteosarcomas, which also upregulate the folate receptor. Theoretically, this approach may be applicable to any tumor that upregulates the folate receptor.

 

Q: What still needs to be confirmed in subsequent research?

A: Intraoperative molecular imaging is still investigational. There is only one FDA-approved cancer imaging agent in the United States. However, there are many other agents in the pipeline. I feel very fortunate to be working in one of the oncology laboratories that is the furthest in the game and has one of these agents under investigation now. We are in phase 2 right now for the agent in lung cancer and need to better understand how others can use this technology.

 

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

A: We are all very excited about this agent and happy that it is getting a lot of coverage, but I think the most important thing is that this is still in the very early stage of research and we continue to learn about this technology. So far, the data appear promising, but this is still investigational. I think most surgeons agree this will play a role in the future, and we are just beginning to understand how big that role may be. As we continue to evaluate this approach, I am hopeful we can really understand how this can improve the way we do surgery. – by Jennifer Southall

 

Reference:

Predina JD, et al. Annals of Surgery. 2017;doi:10.1097/SLA.0000000000002382.

 

For more information:

Jarrod D. Predina, MD, MS, can be reached at Abramson Cancer Center at University of Pennsylvania, 3400 Civic Center Blvd., West Pavilion, Philadelphia PA 19104; email: jpredina@partners.org.

 

Disclosure: The study was supported by the American Philosophical Society, the NIH and the Association for Academic Surgery Foundation. Predina reports no relevant financial disclosures.