Gastrointestinal Cancer: A Conversation with George Poultsides, MD
During Gastric and Pancreatic Cancer Awareness Month, we caught up with Stanford Cancer Institute (SCI) member and professor of surgery George Poultsides, MD, MS. Among his many hats, Poultsides is the co-lead of the Gastrointestinal (GI) Oncology Clinical Research Program at the SCI and serves as the program director of Stanford’s Complex General Surgical Oncology Fellowship.
Advancing early detection of pancreatic cancer
Pancreatic cancer is challenging to diagnose in its early stages. Since the pancreas lies deep within the body, small tumors cannot be seen or felt during routine physicals. Often, people display no symptoms until the cancer has advanced or metastasized. Poultsides and his team are working on an imaging technique to detect pancreatic cancer when it is smaller at its earlier stages. Poultsides’ project entitled “Highly Sensitive Detection of Occult Pancreatic Cancer Using Intraoperative Molecular Imaging” received a $2.7 million grant from the National Cancer Institute (NCI) earlier this year.
Current imaging methods can only detect tumors that are approximately 7-8 millimeters. At this size, the cancer is already well-established and has likely spread to different parts of the body. Poultsides’phase I/II trial is currently investigating the side effects, best dosage, and effectiveness of panitumumab-IRDye800 in detecting pancreatic cancer tumor foci that are not detectable through conventional surgical exploration or standard preoperative cross-sectional imaging. Panitumumab-IRDye800 is a combination of the antibody-drug panitumumab and IRDye800CW, an investigational fluorescent dye that near-infrared cameras can pick up during surgery. This investigational dye attaches to tumors, making them more visible during pancreatic cancer surgery. The team hopes the dye will help identify cancers at a much smaller size, 1-3 millimeters.
Clinical trial participants receive an infusion of the dye before surgery. In addition to conventional white light during surgery, surgeons use a near-infrared camera to identify fluorescent spots. This innovative approach serves as an additional navigation system for the surgeon, enabling enhanced visualization of the cancer. This can have significant implications for minimally invasive surgery, where surgeons can’t directly feel the tumor with their hands but must rely solely on their vision. The potential benefits of this approach include improved surgical margins and a more comprehensive resection of lymph nodes surrounding the tumor, which might be overlooked using only standard white light.
The research also holds promise for other potential advantages. Poultsides hopes to learn how the fluorescent antibody penetrates the dense stroma around the tumor. Pancreatic cancer is notorious for having a dense stroma around it that makes the tumor nearly impenetrable to chemotherapy. This may be why pancreatic cancer is chemo-resistant.
“Although the specific antibody we are testing is not therapeutic for pancreatic cancer, the mere insight into how and where it penetrates the tumor could hold significant promise in addressing drug-delivery challenges. This is why we're very enthusiastic about this new research direction,” states Poultsides.
The researchers are also investigating if this technology could be leveraged to develop a novel imaging modality similar to a positron emission tomography (PET) scan. The new test could potentially detect cancer at its earlier stages without the need for surgery.
GI oncology surgical trials
As the co-lead of the GI Oncology Clinical Research Program at the SCI, Poultsides provides oversight of the institution’s GI surgical clinical trials. Poultsides highlighted a few noteworthy trials within the SCI’s portfolio.
There are two ongoing National Clinical Trials Network (NCTN) studies. One focuses on resectable pancreatic cancer, and the second study is on resectable gallbladder cancer. The standard treatment for these cancers consists of giving chemotherapy after surgery. These two trials assess whether chemotherapy before and after surgery provides better outcomes than the standard of care. Poultsides believes these are important clinical questions for surgeons
Poultsides states, “We are one of the top accruing sites nationally for both trials. This is not only a testament to our robust clinical volume but also to our commitment to offering cutting-edge clinical trial opportunities to as many patients seeking treatment here as possible.”
SCI member Brendan Visser, MD, leads an investigator-initiated trial assessing Peptide Receptor Radiotherapy (PRRT), a newer targeted therapy designed for patients with neuroendocrine tumors undergoing surgical debulking. Similarly, the study seeks to determine whether administering PRRT before and after surgery is more beneficial than the standard of care, which provides PRRT after surgery alone.
Poultsides says, "As systemic therapies continue to improve in effectiveness, the goal is to integrate them earlier into the treatment sequence, ensuring they are available to patients both before and after their surgery, thus enhancing the overall benefits of the surgery.”
Poultsides reports, "One of the most exciting things we are currently working on revolves around personalized oncology. We are trying to identify biomarkers that can guide individualized treatment decisions.”
Poultsides and his collaborator, Niaz Banei, MD, are analyzing the microbiome in pancreatic cancer patients to determine whether it is associated with how individual patients respond to specific chemotherapy treatments.
They aim to uncover novel predictive biomarkers to help determine the most beneficial systemic treatment for each patient.
Cancer care often follows a one-size-fits-all approach. For example, cancer patients are typically initially offered chemotherapy regimen A. If that proves ineffective, they are then provided chemotherapy regimen B, and so on.
"Rather than starting with chemotherapy A for every patient, we aim to pinpoint cases where chemotherapy A is ineffective, but chemotherapy B will work best. This targeted approach holds significant potential. Therefore, we can give the patients the chemo that will work best for them initially and not waste time with an ineffective regimen," states Poultsides.
Complex General Surgical Oncology Fellowship program
Poultsides serves as the program director of Stanford’s Complex General Surgical Oncology Fellowship program.
One of the program's key strengths is its comprehensive clinical training. Roughly half of the two-year program is focused on clinical rotations. There is a strong focus on hepato-pancreato-biliary (HPB), complex upper gastrointestinal, and retroperitoneal sarcoma surgery. Furthermore, the program boasts a highly regarded Peritoneal Surface Malignancy Program led by Byrne Lee, MD, one of the busiest programs on the West Coast.
Fellows have the opportunity to participate in tumor board discussions at the SCI. Multidisciplinary teams consisting of surgeons, medical oncologists, radiation oncologists, pathologists, and radiologists collaborate to ensure that each patient receives a personalized treatment plan tailored to their condition and disease trajectory. Moreover, the program provides extensive research opportunities. Over half of the program’s faculty members have secured federal or extramural research funding, enabling the fellows to contribute to cutting-edge oncological research during their training.
Poultsides understands the significance and duty of inspiring the next generation of surgeons and offers some advice.
"For those faculty members who are just embarking on their careers or trainees who are setting out on their journey, my most significant advice is to discover what truly excites you and which problems you are eager to solve. Once you identify your passion, everything falls into place, and the long hours no longer seem like a burden."
Poultsides concludes with an affirmation of the SCI’s commitment to patient-centered care.
“At the epicenter of all our efforts is our dedication to our patients. Our research initiatives and work to educate the next generation of surgeons stems from our commitment to providing the best possible care to our patients. It’s important to know that our research questions are inspired by the patients we see in the clinic. It’s not just research for its own sake. We seek to translate it into better outcomes in our clinical practices. It’s highly rewarding to return to the clinic and assist each and every patient to the best of our ability. While an operation impacts one patient at a time, a research breakthrough can simultaneously benefit thousands of patients.”
November 2023 by Sarah Pelta