His labored breathing and exhaustion prompted him to see his physician, who ordered a battery of tests. Aster’s diagnosis: A rare cancer called a neuroendocrine tumor was causing a condition called carcinoid heart disease, and causing his heart to fail.

With treatment at the Cedars-Sinai Neuroendocrine Tumor Multidisciplinary Clinic, Aster is now back on the trail, his bike, his board and the court.

“I went from wondering how long I have to live to understanding that this can be managed,” Aster said. “I feel better than I have felt in years.”

Aster’s symptoms came on slowly over several months: crushing fatigue, bloating, loss of appetite and swelling in his legs and feet. Blood tests ordered by his primary doctor were normal, but a CT scan showed tumors in his liver, which were eventually diagnosed as stage 4 neuroendocrine cancer.

“We received the diagnosis the day we dropped the youngest of our four kids off at college,” Orr said. “We had other plans, so we just had to reset.”

Unable to sleep the night they got the news, Orr—who Aster said was his caregiver and support throughout this difficult time and credits with helping save his life—spent hours online. She clicked her way to the Neuroendocrine Tumor Research Foundation. The organization, a resource for research funding, patient education and support, directed the couple to  the Neuroendocrine Cancer Foundation, which referred them to Cedars-Sinai and its multidisciplinary clinic.

“We were concerned about Ken’s neuroendocrine tumors, which had spread to his liver and were making it difficult for his stomach to work normally,” said Andrew Hendifar, MD, who leads the clinic and is a professor of Medicine at Cedars-Sinai. “But we knew from experience that his heart failure would have to be treated first. We didn’t have a minute to lose.”

Neuroendocrine tumors begin in neuroendocrine cells, which connect the nervous system with the hormone-producing endocrine system. They can occur anywhere in the body.

Aster’s began in his small bowel and produced a hormone called serotonin, which thickened two of his heart valves and caused them to leak. The condition is called carcinoid heart disease.

Prashanth Venkatesh, MD, assistant professor of Cardiology in the Smidt Heart Institute at Cedars-Sinai, is the cardiologist on the neuroendocrine team.

“The pulmonary valve, which sends blood from the heart to the lungs, is notoriously difficult to evaluate with standard imaging techniques because of its location in the chest and the relative rarity of pulmonary valve disease in adults,” Venkatesh said. “Significant pulmonary valve involvement in carcinoid heart disease is hence very easily missed.”

Venkatesh, a congenital heart specialist, often employs more extensive imaging techniques for patients born with structural heart defects. Aster’s results showed there was a leak in his pulmonary valve as well as a leak in his tricuspid valve. Both valves needed to be replaced.

“When there is a leaky valve, which we call regurgitation, some of the blood in the heart goes in the wrong direction,” said Raj Makkar, MD, vice president of Cardiovascular Innovation and Intervention at Cedars-Sinai and the Karsh Distinguished Chair in Interventional Cardiology in the Smidt Heart Institute. “With leaky pulmonary and tricuspid valves, the blood that is supposed to go into the lungs can leak back toward the upper chamber of the heart.”

Aster’s pulmonary valve was replaced via a minimally invasive procedure in which a catheter was threaded up through an artery in the groin to maneuver the valve into its proper place. Four weeks later, Makkar replaced Aster’s tricuspid valve using a similar procedure. 

“Patients with carcinoid heart disease are going through a lot because of the neuroendocrine tumor, and traditional valve replacement surgery puts them at higher risk for complications,” Makkar said. “We pioneered testing of transcatheter tricuspid valve replacement around five years ago, and this was the option we chose for Mr. Aster.”

To address the neuroendocrine tumors on Aster’s liver, Alexandra Gangi, MD, director of the Division of Surgical Oncology and co-director of the Neuroendocrine Tumor Multidisciplinary Clinc, chose another minimally invasive approach: tumor embolization.

“We accessed the tumors with a catheter, through the artery in the groin,” Gangi said. “This allows us to block off the blood flow to the specific arteries that feed the tumors. This starves the tumors, and results in shrinking and tumor control.”

So far, Aster has avoided surgery and chemotherapy because of the nature of neuroendocrine tumors and the expertise of his care team in sequencing his therapies based on his sypmtoms.

“I think the difference between metastatic neuroendocrine tumors and most other types of gastrointestinal cancers is that we’re playing the long game,” Gangi said. “We often do the least invasive thing and save more aggressive options for when we really need them. These tumors tend to recur, but prognosis is generally good and patients can live a long time with them.”

Additional treatment or surgical procedures might be on the horizon, but today, Aster is doing well.

“We feel very fortunate that we were able to identify this as early as we did and intervene in the way that we did,” Hendifar said. “A few years ago, even six months ago, Ken wouldn't have been a candidate for minimally invasive valve replacements. He would have required open-heart surgery, and I'm not sure if the outcome would have been as good.”

Aster describes his current health as “great.”

“I just started cycling again in January, 13 months after the second valve replacement,” Aster said. “Now I'm doing a 25-mile ride in the hills two or three times a week with no problem. My heart feels as normal as can be.”

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Ulcerative colitis is a type of inflammatory bowel disease (IBD) that causes chronic inflammation and sores in the colon.

“Ulcerative colitis greatly increases a person’s risk of developing colorectal cancer, but we don’t have a noninvasive way to determine how great each patient’s risk might be,” said Hajar Hazime, PhD, a project scientist in the Abreu Lab at Cedars-Sinai and co-first author of the study. “Undergoing frequent surveillance colonoscopies can help, but preparing for that procedure is especially difficult for someone with ulcerative colitis.”

Additionally, colonoscopy results can be inconclusive, forcing the physician and patient to decide whether to remove all or part of the colon to prevent cancer from developing, Hazime said. Investigators hoped to find a more conclusive and less invasive way to screen these patients.

“Our physician-scientists are continually working to improve cancer screening for our patients,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “We treat more than 60 types of cancer, but our ultimate goal is prevention.”

Each person’s gut is populated with trillions of microbes—bacteria, viruses, fungi and other organisms too small to see with the naked eye. These interact with each other and appear to influence several aspects of a person’s health, including IBD.

Hazime said that these microbes use QSMs to communicate and coordinate their behavior, and that a goal of the study was to determine whether QSMs play a role in causing colon cancer in patients with ulcerative colitis.

When the investigators examined blood samples from human patients with ulcerative colitis and conducted experiments using colon organoids and laboratory mice, they found:

• In the blood of ulcerative colitis patients, there were higher levels of QSMs in patients at higher risk for cancer, who had experienced symptoms for 10 years or longer, than in patients at lower cancer risk, with symptoms for five years or less.
• In colon organoids—tiny clusters of cells that mimic some functions of the human colon—exposure to QSMs caused inflammation, which is a risk factor for tumor development. Because organoids do not contain gut microbes, this showed that elevated QSM levels and the activity of microbes they regulate can increase cancer risk.
• In laboratory mice with a condition that mirrors ulcerative colitis, investigators found higher levels of QSMs in the blood of those that developed tumors than in those that did not. Also, mice exposed to extra levels of QSMs developed more tumors, more quickly, than those not exposed.

“These results show us that quorum sensing molecules are not only associated with colon cancer risk in patients with ulcerative colitis, but that they actually contribute to the formation of these tumors,” said Maria T. Abreu, MD, executive director of the F. Widjaja Inflammatory Bowel Disease Institute and co-corresponding author of the study. “That makes these molecules a potential way to screen patients for cancer risk, but also a possible target for reducing risk.”

Investigators will next focus on pinpointing how QSMs contribute to tumor formation, studying the molecules as a biomarker to predict cancer development, and finding ways to target these molecules to disrupt cancer development, Abreu said.

Additional Cedars-Sinai authors include Irina Fernández, Katerina M. Faust, and Maria A. Quintero.

Other authors include Gregory O’Connor, Juan F. Burgueño, Ana M. Santander, Nivis Brito, Yuguang Ban, Sapna K. Deo, and Sylvia Daunert.

Funding: This work was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases (R01DK099076) and the Micky & Madeleine Arison Family Foundation Crohn's & Colitis Discovery Laboratory to MTA as well as from the National Institutes of Health (R01GM127706) and the Department of Defense (W81XWH-20-1-0697) to SD and SKD and the Lucille P. Markey Chair in Biochemistry and Molecular Biology to SD.

Disclosures: MTA is a consultant or on the advisory board of the following companies: AbbVie Inc., Alimentiv Inc., Amgen, Bristol Myers Squibb, Eli Lilly and Company, Genetech, Gilead Sciences, Janssen Pharmaceuticals, Pfizer Pharmaceutical, Takeda Pharmaceuticals, and UCB Pharma.

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

“These rising cancer rates are expected worldwide, and large-scale efforts need to be made to encourage lifestyle changes and develop screening programs to reduce them,” said Ju Dong Yang, MD, medical director of the Liver Cancer Program and professor of Medicine at Cedars-Sinai and co-corresponding author of the study.

Liver Cancer

Yang said that up to 70% of liver cancers could be prevented through lifestyle changes, because while hepatitis B and C were once leading causes of liver cancer in the U.S., they are being eclipsed.

“Metabolic dysfunction-associated steatotic liver disease, or MASLD, is emerging as a leading cause of liver cancer in Western countries, including the U.S.,” Yang said. “This is a buildup of fat in the liver that is associated with diabetes, obesity, and uncontrolled high cholesterol and high blood pressure.”

Taking steps to help control these risk factors is the best way to reduce risk, Yang said.

Yang said that only about 20% of people in the U.S. with cirrhosis from hepatitis and other chronic liver conditions receive liver cancer screening, which could help improve early detection and patient outcomes. Only about 30% of liver cancers are detected at an early enough stage for cure, Yang said.

Esophageal and Gastric Cancers

Lifestyle factors and limited screening also come into play in risk for esophageal and gastric cancers, said Alexandra Gangi, MD, director of the Division of Surgical Oncology in the Jim and Eleanor Randall Department of Surgery and director of the Gastrointestinal Tumor Program.

“These tumors cause few symptoms before the cancer has spread—and they tend to spread rapidly,” Gangi said. “To reduce risk, focus on preventable issues such as obesity, tobacco and alcohol use, and diet. And if you have other risk factors such as chronic acid reflux, gastritis or family history of these cancers, speak with your doctor about screening.”

Colorectal Cancer

Everyone should be screened for colorectal cancer by age 45—but those with a family history of the disease should begin sooner, said Alessio Pigazzi, MD, PhD, director of the Division of Colorectal Surgery. Results of that first screening, along with other risk factors, will help determine how often follow-up screenings are needed.

“Late diagnosis makes colorectal cancer highly lethal, while early diagnosis leads to very high cure rates,” Pigazzi said. “To reduce risk, everyone should eat a diet focused on whole foods that are high in fiber and low in sugars and animal fats, exercise regularly, keep up with screenings, and watch for colon cancer symptoms such as frequent rectal bleeding or unexplained changes in bowel habits.”

Pancreatic Cancer

Pancreatic cancer is another GI cancer usually diagnosed in advanced stages—with 50% of people diagnosed when the disease has already spread, said Arsen Osipov, MD, medical director of Pancreatic Cancer and Multidisciplinary Programs and Integration.

“There have been recent advances in early detection and treatment, including blood-based ‘liquid biopsy’ tests and structured screening programs for those with strong genetic risk,” Osipov said. “And multidisciplinary clinics, such as one pioneered at Cedars-Sinai, help accelerate diagnosis and treatment planning, and improve access to clinical trials and patient outcomes.”

To reduce pancreatic cancer risk, Osipov recommended paying attention to modifiable lifestyle factors similar to those for other GI cancers. He also suggested that people with chronic pancreatitis or family history of pancreatic cancer consider genetic counseling and participation in a high-risk surveillance program.

On the Horizon

Cedars-Sinai research is changing the landscape of GI cancer detection and treatment, said Katelyn Atkins, MD, PhD, interim chair and medical director of Radiation Oncology. Blood-based biomarkers such as circulating tumor DNA are improving early detection and allowing for tailored treatments and better detection of recurrence in colorectal cancer—and are now being leveraged for other GI sites, Atkins said.

“Improvements in radiation oncology techniques are allowing us to deliver the therapy more precisely and better protect nearby organs, making it safer to deliver more intense and effective treatment,” Atkins said. “There is also growing use of radiotherapy as an alternative to radical surgery in rectal, esophageal and gastroesophageal cancers.” 

Biomarker-driven treatment is also improving integration of radiotherapy into treatment regimens that also include surgery, chemotherapy and immunotherapy.  

“This shift toward more personalized, biology-driven treatment approaches helps us extend survival and preserve quality of life for patients with GI cancers,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “We will continue to work to improve treatment options and prevent cancer incidence in our community.”  

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

“After 35 years of marriage, my heart still sings when I look at her,” Philip said. “My cancer was much worse on Linda than it was on me, and her cancer was worse on me than it was on her. Whichever one of us was sick, the other one filled in the gaps. But that’s the way we normally live our lives. Whatever one needs, the other one provides.”

Philip’s pancreatic cancer was detected in early 2024 during an unrelated MRI of his kidneys. Arsen Osipov, MD, medical director of the Pancreatic Cancer Multidisciplinary Clinic and Multidisciplinary Cancer Programs and Integration at Cedars-Sinai, Philip’s oncologist, said it was a stroke of luck.

“He was diagnosed at a curable stage, before the cancer had spread,” Osipov said. “Only 10 to 20% of patients with pancreatic cancer are diagnosed this early.”

Philip was one of the first patients to visit the multidisciplinary clinic, where in a single day he met with medical oncologists, radiation oncologists, surgeons, gastroenterologists and other experts, and agreed on a treatment plan: four months of chemotherapy, followed by radiation and a complicated surgery called a Whipple procedure.

“This is a complex operation where we remove what’s called the head of the pancreas, the first part of the small intestine, the gallbladder and the bile duct,” said Nicholas Nissen, MD, director of Hepatobiliary and Pancreatic Surgery. “After removal, these structures are reattached to restore normal function.”

This procedure once required large incisions, but because radiation and chemotherapy successfully shrank Philip’s tumor, Nissen was able to perform the procedure robotically.

“This allows us to make smaller incisions, with lower risk of complications and a shorter recovery time for the patient,” Nissen said.

After four days in the hospital and two more months of chemotherapy, Philip was declared cancer-free in June.

But the couple had just a few days to celebrate.

Less than a week after Philip learned he was cancer-free, Linda was diagnosed with breast cancer after undergoing a routine mammogram.

“As a health system, we focus on screening and are always developing new ways to detect cancer early,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “For both of these patients, early detection was key to the best possible outcome.”

Still, the diagnosis was a bit of a shock to Philip and Linda.

“It was sort of unbelievable,” Linda said. “But we had been through the whole process with Phil, and his surgery was much more serious than mine, and he did so well that I felt much more comfortable.”

And she, too, was lucky, said Armando Giuliano, MD, director of Breast Surgical Oncology at Cedars-Sinai Cancer and Linda’s surgeon.

“She had a screen-detected cancer that has no symptoms. You can't feel it. It causes no pain, no discharge,” Giuliano said. “The only way you can detect a cancer like that is with breast cancer screening. And those cancers are the smallest cancers—the cancers that are the easiest to cure.”

Giuliano was able to perform a breast-sparing therapy known as a partial mastectomy or lumpectomy.

“We remove the area of the breast that has cancer, all the way around so that we have clean margins,” Giuliano said. “And then we do an internal reconstruction to make the breast look as natural as possible.”

Giuliano also performed a procedure he pioneered, which he continues to develop at Cedars-Sinai, called a sentinel lymph node biopsy, removing one or two lymph nodes to be certain the cancer had not spread beyond the breast.

“He did such a beautiful job that if you were to look at my breast, you would not know I had had surgery,” Linda said.

Linda’s cancer was an infiltrating ductal carcinoma, a cancer that starts in the breast ducts and can spread throughout the body. It was also HER2 positive, so it required further treatment.

“Around 20% of cancers have this overexpression of the HER2 protein, which makes them more aggressive and at higher risk of spreading,” said medical oncologist Philomena McAndrew, MD. “For this reason, after Linda’s surgery we treated her with chemotherapy and immunotherapy. We followed that with radiation therapy, and Linda did incredibly well throughout each of these steps.”

One important element for Linda was McAndrew’s recommendation to use a cooling cap to help avoid hair loss during chemotherapy.

“I'm so thrilled that I did,” Linda said. “Dr. McAndrew told me that when women lose their hair, it's very traumatic. When they look in the mirror, they realize how sick they are. Fortunately, that didn’t happen to me, and I was so grateful.”

Linda completed her final radiation treatment in January and will continue preventive therapy for five years. She and Philip will also have regular follow-up screenings.

But for now they are headed from their “city house” in Culver City to their main house in Lake Arrowhead, to spend time with friends they haven’t seen in a while.

Then they’ll continue their journey, in sickness and in health, together.

“We’re going on a cruise to Hawaii at the end of February,” Linda said. “We're just trying to pack some fun into the next 20 years.”

Cedars-Sinai Health Sciences University is advancing groundbreaking research and educating future leaders in medicine, biomedical sciences and allied health sciences. Learn more about the university.

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a special type of treatment for patients with certain cancers that have spread to the abdominal cavity (peritoneum).

Unlike regular chemotherapy, which is often delivered through an intravenous (IV) drip and then circulates throughout the entire body, HIPEC is delivered during a surgical procedure. Also called “hot chemotherapy,” HIPEC involves delivering high doses of heated chemotherapy directly to the abdomen during the surgical procedure. The chemotherapy solution is heated to about 41 to 42 degrees Celsius (about 108 F).

“Bathing the peritoneal cavity with heated chemotherapeutic agents helps to target and kill cancer cells that might be too small to remove through surgery alone,” said Alexandra Gangi, MD, director of the Gastrointestinal Tumor and Cancer Regional Therapies programs at Cedars-Sinai Cancer and associate professor at the Jim and Eleanor Randall Department of Surgery.

Gangi recently spoke with the Cedars-Sinai Newsroom about how HIPEC works and who can benefit from the targeted surgical procedure.

What is HIPEC and who gets it?

HIPEC is a regional therapy used for patients with peritoneal disease, where cancer spreads to the peritoneum—the smooth membrane lining the abdominal wall and surrounding organs. When cancer from sites like the colon or the peritoneum itself spreads into the abdominal cavity, after removing visible tumors through surgery, heated chemotherapy is circulated in the abdomen to target and destroy remaining cancer cells at a cellular level.

Who is a good candidate for the HIPEC procedure?

Good candidates for HIPEC are patients with certain cancers that have spread within the peritoneum, a membrane that lines the inside of the abdomen and pelvis abdominal cavity. These patients have stage 4 cancer. This can include appendix cancer, colon and rectal cancer, mesothelioma, and primary peritoneal cancer. Some patients with gastric and ovarian cancer are eligible for the procedure, as well.

What does the HIPEC procedure involve?

The procedure typically begins with a cytoreductive surgery, where visible tumors are removed. Afterward, large catheters are placed into the abdominal cavity and the abdomen is closed. Heated chemotherapy is then circulated for 30 minutes to about an hour and a half at temperatures between 41 to 42 degrees Celsius—the solution is really hot.

Once that's done, we drain all the fluid from the belly and we open the patient back up. If there are any new surgical connections we may need to create, as in scenarios where we have removed some colon or intestine, we do that. We rinse the abdomen with saline, and then we close up the abdomen, and the patient goes to recovery.

How is HIPEC different from regular chemotherapy?

The procedure offers a more focused approach compared to regular chemotherapy, which circulates through your bloodstream throughout your body. Typically, patients won't see major fluctuations in their blood count, and they’re not necessarily considered immunocompromised. Unlike IV chemotherapy, which requires repeated sessions every few weeks, HIPEC is typically a one-time procedure, but can be repeated in some cases.

Systemic chemotherapy, which is given through an IV, relies on blood flow to reach tumors, but small tumors may not receive enough blood flow to be effectively treated this way. In HIPEC, chemotherapy is used after the visible disease is removed to kill any remaining cancer cells that exist at a cellular level since it only penetrates about three millimeters into the abdominal wall.

How does HIPEC improve survival rates?

For certain late-stage cancers, the survival rate is quite a bit lower, at around the 20% range. However, for certain mucinous tumors like pseudomyxoma peritonei, a type of appendix cancer, HIPEC can be life changing. The surgery significantly improves survival rate and can reduce the risk of recurrence. In some cases, survival without recurrence can be over 80%. It's a huge range but it is dependent on what type of cancer we're ultimately trying to treat and the patient's overall response to treatment.

What is the recovery process following the HIPEC procedure?

After surgery, some patients experience delayed return of bowel function, where the intestines take time to "wake up." This might lead to symptoms like reduced appetite, constipation or diarrhea, depending on what was removed during the surgery. Patients may also experience some discomfort or bloating. It’s best to avoid heavy lifting for about 6-8 weeks to allow proper healing. I typically advise patients that the first three months are kind of tough. And then you kind of start to feel more like your normal self. It’s a marathon, not a sprint.

Read more on the Cedars-Sinai Blog: The Need for Colorectal Cancer Screening in the Hispanic Community

Pancreatic cancer is one of the most aggressive types of cancer, with an incidence rate that is steadily rising each year. While treatments have improved over the past decade, the five-year overall survival rate for the disease is still just 13%.

The research, led by Cristina Ferrone, MD, the Lippman Family Chair in Surgical Oncology and chair of the Cedars-Sinai Jim and Eleanor Randall Department of Surgery, sought to understand two elements of pancreatic cancers.

First, Ferrone and fellow investigators studied how human leukocyte antigen (HLA) class I complex—a system that presents targets to the immune system, thereby alerting the immune system that a cell is defective—is expressed to a varying degree in pancreatic cancers. If a patient has high levels of HLA class I expressed on the pancreatic cancer, it suggests that their body is better at fighting the cancer.

Next, investigators aimed to target a molecule called B7-H3, which is expressed on malignant cells to escape recognition and destruction by the immune system. In many patients, a high level of B7-H3 means that cancer cells can evade the body’s immune system.

The study, which was completed when Ferrone was a professor of Surgery at Harvard Medical School, found that B7-H3 was highly expressed in the majority of pancreatic cancers studied, and its immune-evading presence was associated with significantly worse patient survival.

Patients whose tumors had a low or negative B7-H3 expression but positive HLA class I expression—alerting the immune system of defective cells—had significantly improved survival.

However, patients with high B7-H3 expressions had consistently poor prognoses, regardless of their tumor’s HLA class I expression.

“Our research suggests that the positive impact provided by high HLA class I expression in pancreatic cancer may be overpowered by a high B7-H3 expression,” said Ferrone, corresponding author of the study. “These findings provide the rationale to leverage B7-H3 suppression as a target for immunotherapeutic approaches, such as CAR-T cells directed to B7-H3, as a strategy for pancreatic cancer patients to potentially improve survival.”

Ferrone said that, in recent years, physicians are trying to shift the therapeutic paradigm for the treatment of pancreatic cancer from a generalized chemotherapy approach to a more patient-specific precision medicine approach based on the individual characteristics of a patient’s tumor. She said that the results of this study indicate a rationale for the design of new Phase I/II clinical trials investigating the effectiveness of anti-B7-H3 monoclonal antibodies alone or in combination with standard of care chemotherapy regimens, as well as a CAR-T therapy aimed at B7-H3 for patients with pancreatic cancer.

“If trial results from this approach are positive,” Ferrone said, “targeting B7-H3 has the potential to significantly improve the efficacy of immunotherapies for pancreatic cancer patients and, eventually, overall survival rates for the disease.”

Additional authors include Giulia Cattaneo; Marco Ventin; Shahrzad Arya; Filippos Kontos; Theodoros Michelakos; Yurie Sekigami; Lei Cai; Vincenzo Villani; Francesco Sabbatino; Francine Chen; Ananthan Sadagopan; Vikram Deshpande; Paul A. Moore; David T. Ting; Nabeel Bardeesy; Xinhui Wang; Soldano Ferrone.

Funding: This work was supported by National Cancer Institute/National Institute of Health (NCI/NIH) grants [R03CA223886 and R03CA231766 to Cristina Ferrone and Soldano Ferrone; R01DE028172 and R01CA226981 to Xinhui Wang], Department of Defense Breakthrough Award Level 2 [W81XWH-16-1-0500 (BC190615) to Soldano Ferrone], Department of Defense Breakthrough Award Level 4 [W81XWH-20-1-0315 (BC190615) to Cristina Ferrone and Soldano Ferrone], Department of Defense Idea Award [W81XWH-20-PCRP-IDA (W81XWH2110433) to Xinhui Wang] grants, and Internal funding from the Department of Surgery at the Massachusetts General Hospital.

Read more from the Cedars-Sinai Blog: How to Manage Your Pancreatic Cancer Risk

Gastrointestinal cancers were once diagnosed primarily by location. A tumor in the liver was liver cancer, while one in the pancreas was pancreatic. The few chemotherapy treatments available affected the entire patient—sometimes causing difficult side effects. Today, these tumors are analyzed at the molecular level, and clinicians target them with precision treatments that fight the cancer cells and spare the healthy tissue.

Andrew Hendifar, MD, medical director of the Gastrointestinal Oncology Disease Research Group at Cedars-Sinai Cancer, is a physician-scientist who treats patients with cancers of the digestive tract and other abdominal organs and works to develop new therapies for these patients.

In advance of the fifth annual Cedars-Sinai Gastrointestinal Tumor Conference, an event for healthcare professionals seeking updates on the most recent advances in these therapies, Hendifar sat down with the Cedars-Sinai Newsroom to discuss the challenges and latest advances in treating this group of cancers.

What has changed about the way we diagnose gastrointestinal (GI) tumors?

We used to diagnose these tumors based on their approximate location and a review of the tissue under a microscope. Now we use molecular profiling. These tests look at the makeup of the tumor’s genes and protein expression through a biopsy or blood specimen. This helps us understand the biological underpinnings of the specific tumor. Molecular profiling is especially important in GI tumors because these tumors—liver, gastric, pancreatic, small bowel, colon—look similar and are often located in the same area.

Without molecular testing, it might not be possible to tell that you're dealing with a bile duct tumor rather than a liver cancer or a pancreatic cancer. The bile ducts travel through the liver, so a bile duct mass could be in the same position as a liver cancer, but the cellular makeup is quite different and the treatments they require are worlds apart.

We’re also using advanced imaging techniques that employ artificial intelligence to discern subtle pancreatic masses that might be invisible to the human eye, and special MRI sequences that can detect pancreas cancer at an earlier stage. Imaging can also tell us whether treatments are working and predict what a patient’s outcomes could be. Furthermore, we are working to develop blood and urine tests for early pancreas cancer detection.

How is treatment of GI tumors changing?

When I started treating patients 15 years ago, the only treatments available were a couple of different IV chemotherapies. Now, thanks to new diagnostic tools and more targeted forms of treatment, we can often turn a patient’s life around, and that's actually the best feeling in the world.

Immune therapy has been such a breath of fresh air. Treatment involves just an hourlong infusion with minimal side effects, so we no longer have to worry about whether a patient can tolerate the treatment. I have so many patients who are alive and well receiving immune therapy, who otherwise wouldn’t have made it. Through our continuing work to develop new biomarkers, we are able to pair more of our patients with immune therapy. And these biomarkers go across tumor boundaries, so we no longer need to think about the site of origin. If your tumor has the right biomarker, we can pair you with the right form of treatment.

At ASCO GI 2024 we presented a study comparing patients with localized liver cancer who received local therapy alone with those who received local therapy and immune therapy in combination. For patients receiving the combination therapy, progression-free survival was twice as long, so this has become the new standard of care.

There are also a lot of new antibody drug conjugates that are working their way through the pipelines, including options for various types of GI tumors. Antibody drug conjugates deliver chemotherapy directly to tumor cells by binding to specific proteins on the surface of the cells. This allows us to target the cancer without targeting healthy tissue. If we can identify the right protein on a patient’s tumor cells, we can use antibody drug conjugates to deliver very effective treatment.

What are some of the more challenging tumors to treat?

Bile duct tumors need more attention. They are often lumped in with pancreatic cancer but are completely different. And they are difficult to diagnose without advanced endoscopy.

We’re doing a lot of research to identify bile duct tumor biomarkers that help us pair patients with targeted therapy, especially antibody drug conjugates, to improve outcomes. There are many clinical trials now open for these therapies, and many patients do incredibly well.

What is the next frontier for GI tumor research?

The Molecular Twin Precision Oncology Platform, a unique precision medicine and AI tool developed at Cedars-Sinai, was validated on patients with pancreatic cancer and used to identify biomarkers that outperformed the current standard test for predicting patient survival. The platform has expanded to include all cancers, and we have enrolled at least 500 patients with GI cancers. All of my patients are enrolled and are contributing quite a bit to this project.

What topics will be covered at the upcoming conference, and what makes the event unique?

We are always thinking about the future of cancer treatment rather than about what’s currently available. We will be highlighting new technologies to detect and treat cancer, and will focus on using social media platforms to enhance the practice of medicine.

Read more on the Cedars-Sinai Blog: Pancreatic Cancer Clinic Saves Time and Lives