L-glutamine, an amino acid that occurs naturally in the body and plays an important role in digestion, has been studied as a potential way to ease side effects in other cancers. But this was the first trial to evaluate it as an anti-cancer therapy in human patients, said Jun Gong, MD, associate professor of Medicine, medical director of Colorectal Cancer at Cedars-Sinai Cancer and first author of the study.

“Current treatment for stage 4 pancreatic cancer is a cocktail of chemotherapy, with overall survival ranging from eight to 13 months,” Gong said. “We found that by adding L-glutamine to this treatment, we increased overall survival to as much as 22 months—and these positive results merit larger clinical trials of this combination.”

In this Phase I clinical trial, investigators studied 16 patients with advanced pancreatic cancer. All patients were treated with a standard chemotherapy combination of gemcitabine and nab-paclitaxel, along with clinical-grade L-glutamine supplements.

“We began the trial in the hope of improving gut health in these patients,” said Neil Bhowmick, PhD, Mark Goodson Chair in Oncology Research, professor of Medicine and Biomedical Sciences, research scientist at Cedars-Sinai Cancer, and senior author of the study. “Patients with pancreatic cancer do not absorb nutrients well, and often develop a condition called cachexia—a loss of weight and muscle that can be fatal. Glutamine is known to help the gut heal.”

Half of the patients in the study maintained their weight, and investigators found a correlation between the way the bacteria in the gut responded to the glutamine and patient outcomes, Gong said.

“At the time of our paper’s publication, the life expectancy of these patients taking glutamine and chemotherapy was more than double the average life expectancy associated with the historical standard of care,” Gong said. “The study did not compare the two options head-to-head, but our result is striking enough for us to advance to a larger randomized trial where patients are given glutamine or not.”

In the lab, investigators also found that cancer cells exposed to high-dose glutamine were particularly vulnerable to chemotherapy, a result in line with the reduction in tumor size seen in patients.

“It is really satisfying to see science from the bench translated so well into patient outcomes,” Bhowmick said.

The supplements used in the study are approved by the Food and Drug Administration for treatment of sickle cell disease, meaning they are federally regulated, Bhowmick and Gong said.

“The survival rate for advanced pancreatic cancer is poor,” said Robert Figlin, MD, interim director of Cedars-Sinai Cancer. “This trial points to a potential new option for optimizing first-line chemotherapy for patients while also opening up a number of new avenues for our physician-scientists to study.”

Additional Cedars-Sinai authors include Hayato Muranaka, So Yung Choi, Mourad Tighiouart, Aleksandr Stotland, Jennifer Van Eyk, Omer H.M. Elmadbouh, Mouad Edderkaoui, Sunao Tanaka, Hideki Furuya, Arsen Osipov, Jeremy Lorber, Sandrine Billet, Stephen J. Pandol, and Andrew Hendifar.

Other authors include Shrikant Bhute, Ezinne R. Aja, Jonathan P. Jacobs, Alexzandra Morris, Johanna ten Hoeve-Scott, and Thomas Graeber.

Funding: This project was funded by the 2019 Tower Cancer Research Foundation Experimental Therapeutics Endowed Fund/Cedars-Sinai Cancer 2019 Developmental Funds for Investigator-Initiated Trials (IITs; J.G.). This project was also supported in part by the NIH National Center for Advancing Translational Sciences (NCATS) UCLA CTSI (UL1 TR001881-01; M.T.) and NCI grants P01CA233452 (M.T., S.J.P., N.A.B.) and U01 grant CA232859-01 (M.T.).

Competing Interest Statement: H.M., N.A.B., J.G. and A.H. have a pending patent related to the work.

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.

Philip and Linda Simmons spent 35 years building their life together before facing their greatest challenge: back-to-back cancer diagnoses.

“Phil was diagnosed with pancreatic cancer. Then he was declared cancer-free on a Friday, and the following Monday, I was diagnosed with breast cancer,” Linda Simmons said.

The couple caught both cancers early thanks to routine medical testing—Philip's during screening for another condition and Linda's through her regular mammogram.

About 40% of cancer cases in the U.S. are preventable, according to an American Cancer Society study. To reduce the risk of developing the disease, experts recommend maintaining a healthy weight, staying physically active, avoiding tobacco and limiting alcohol use.

Osipov told Spectrum News 1 that if diagnosed early, cancers can be cured, but “if you diagnose cancers at a later stage, typically, let's say stage 4, where the cancer may have metastasized to a different organ, you're not really talking about cure, you're more talking about palliation or prolonging people's lives.”

Now healthy, Philip and Linda are back to living their lives, including doing puzzles, spending time with friends and visiting their mountain home in Lake Arrowhead. Philip recommends that people “make sure that nothing's growing that shouldn't be growing for early detection and early treatment,” he said.

Watch the complete segment from Spectrum News 1.

“Después de 35 años de matrimonio, mi corazón sigue cantando cuando la miro”, dijo Philip. “Mi cáncer fue más duro para Linda que para mí, y el cáncer de ella fue más duro para mí que para ella. Cuando uno de los dos estaba enfermo, el otro llenaba los vacíos. Así es como vivimos nuestras vidas: lo que uno necesita, el otro lo da”.

El cáncer de páncreas de Philip fue detectado a principios de 2024 durante una resonancia magnética no relacionada de sus riñones. Arsen Osipov, MD, director médico de la Clínica Multidisciplinaria de Cáncer de Páncreas y de los Programas Multidisciplinarios de Cáncer e Integración en Cedars-Sinai, y oncólogo de Philip, dijo que fue un golpe de suerte.

“Fue diagnosticado en una etapa curable, antes de que el cáncer se propagara”, explicó Osipov. “Solo entre el 10% y el 20% de los pacientes con cáncer de páncreas reciben un diagnóstico tan temprano”.

Philip fue uno de los primeros pacientes en acudir a la clínica multidisciplinaria, donde en un solo día se reunió con oncólogos médicos, oncólogos radioterapeutas, cirujanos, gastroenterólogos y otros especialistas. Juntos acordaron un plan de tratamiento: cuatro meses de quimioterapia, seguidos de radiación y una cirugía compleja conocida como el procedimiento de Whipple.

“Es una operación compleja en la que se extirpa lo que se conoce como la cabeza del páncreas, la primera parte del intestino delgado, la vesícula biliar y el conducto biliar”, explicó Nicholas Nissen, MD, director de Cirugía Hepatobiliar y Pancreática. “Luego, estas estructuras se reconectan para restaurar la función normal”.

Antes, este procedimiento requería incisiones grandes, pero gracias a que la radiación y la quimioterapia redujeron con éxito el tumor de Philip, Nissen pudo realizar la cirugía de forma robótica.

“Esto nos permite hacer incisiones más pequeñas, con menor riesgo de complicaciones y un tiempo de recuperación más corto para el paciente”, dijo Nissen.

Tras cuatro días en el hospital y dos meses más de quimioterapia, Philip fue declarado libre de cáncer en junio.

Pero la pareja solo tuvo unos días para celebrar.

Menos de una semana después de que Philip recibiera la noticia, Linda fue diagnosticada con cáncer de mama tras una mamografía de rutina.

“Como sistema de salud, nos enfocamos en la detección y siempre estamos desarrollando nuevas formas de identificar el cáncer de manera temprana”, dijo Robert Figlin, MD, director interino de Cedars-Sinai Cancer. “En ambos casos, la detección temprana fue clave para lograr el mejor resultado posible”.

Aun así, el diagnóstico fue un shock para Philip y Linda.

“Fue algo increíble”, dijo Linda. “Pero ya habíamos pasado por todo el proceso con Phil. Su cirugía fue mucho más seria que la mía, y le fue tan bien que me sentí mucho más tranquila”.

Ella también tuvo suerte, señaló Armando Giuliano, MD, director de Oncología Quirúrgica de Mama en Cedars-Sinai Cancer y cirujano de Linda.

“Era un cáncer detectado por estudios de rutina, sin síntomas. No se puede palpar, no causa dolor ni secreción”, explicó Giuliano. “La única forma de detectar un cáncer así es mediante pruebas de detección. Y esos son los cánceres más pequeños y los más fáciles de curar”.

Giuliano pudo realizar una terapia conservadora de mama conocida como mastectomía parcial o lumpectomía.

“Extirpamos el área del seno que contiene el cáncer, asegurándonos de obtener márgenes limpios”, dijo. “Luego realizamos una reconstrucción interna para que el seno luzca lo más natural posible”.

También realizó un procedimiento que él mismo desarrolló y continúa perfeccionando en Cedars-Sinai, llamado biopsia del ganglio linfático centinela, mediante el cual se extraen uno o dos ganglios para confirmar que el cáncer no se haya diseminado más allá del seno.

“Hizo un trabajo tan hermoso que, si alguien viera mi seno, no sabría que tuve una cirugía”, dijo Linda.

El cáncer de Linda era un carcinoma ductal infiltrante, un tipo de cáncer que comienza en los conductos mamarios y puede propagarse a otras partes del cuerpo. Además, era HER2 positivo, por lo que requirió tratamiento adicional.

“Aproximadamente el 20% de los cánceres presentan una sobreexpresión de la proteína HER2, lo que los hace más agresivos y con mayor riesgo de propagación”, explicó la oncóloga médica Philomena McAndrew, MD. “Por esta razón, después de la cirugía tratamos a Linda con quimioterapia e inmunoterapia, seguidas de radioterapia. Linda respondió increíblemente bien en cada etapa”.

Un elemento importante para Linda fue la recomendación de McAndrew de usar un gorro de enfriamiento para ayudar a prevenir la caída del cabello durante la quimioterapia.

“Estoy tan feliz de haberlo usado”, dijo Linda.“ La Dra. McAndrew me explicó que cuando las mujeres pierden el cabello, puede ser muy traumático. Al mirarse al espejo, se dan cuenta de lo enfermas que están. Afortunadamente, eso no me pasó, y estoy muy agradecida”.

Linda completó su último tratamiento de radiación en enero y continuará con terapia preventiva durante cinco años. Ella y Philip también se someterán a exámenes de seguimiento de forma regular.

Por ahora, planean viajar desde su “casa en la ciudad”, en Culver City, hasta su residencia principal en Lake Arrowhead para pasar tiempo con amigos que no han visto en un tiempo.

Y luego continuarán su camino juntos, en la salud y en la enfermedad.

“Nos vamos de crucero a Hawái a finales de febrero”, dijo Linda. “Estamos tratando de llenar de diversión los próximos 20 años”.

Cedars-Sinai Health Sciences University impulsa investigaciones innovadoras y forma a las futuras generaciones de líderes en medicina, ciencias biomédicas y ciencias de la salud. Conozca más sobre la universidad.

“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.

The findings, published in JAMA Surgery, provide a framework to better manage ongoing follow-up care of patients whose cancer has not spread to their lymph nodes and who have had their tumors surgically removed.

“We now have a way to identify patients whose higher risk of recurrence may have been previously overlooked,” said Cristina R. Ferrone, MD, chair of the Jim and Eleanor Randall Department of Surgery at Cedars-Sinai and corresponding author of the study. “This gives us the opportunity to change the way we care for this patient population in a meaningful way.”

Pancreatic neuroendocrine tumors are a less common and typically less aggressive form of pancreatic cancer. Patients whose cancer has not spread to the lymph nodes or outside the pancreas have a 91% five-year relative survival rate following surgical treatment, according to the American Cancer Society. However, the Cedars-Sinai study identified a distinct subset of those patients who remain at high risk for their cancer to return.

The multi-institutional study analyzed data from 770 patients across five high-volume institutions and found approximately 10% of patients without lymph node involvement would eventually experience a recurrence of their cancer, most commonly in the liver. This data allowed investigators to develop a 13-point risk score by identifying four key factors that predict a higher risk of recurrence: male sex, a tumor size of 3 centimeters or larger, World Health Organization grade of 2 or higher, and whether cancer cells had entered the blood or lymph vessels, called lymphovascular invasion.

By using the newly created risk score to stratify patients into low-, moderate- and high-risk groups, investigators say they can better predict which patients should receive more frequent and intensive monitoring.

“The current guidelines leave clinicians with a ‘one-size-fits-all’ approach, but it’s clear from our research that not all patients require the same intensity of surveillance,” Ferrone said. “The results address a critical gap in current practice and will hopefully influence future guideline development for well-managed, individualized and cost-effective care.”

Shlomo Melmed, MB, ChB, Cedars-Sinai’s dean of the Medical Faculty and executive vice president of Medicine and Health Sciences, who was not involved in the study, said the new risk score could help physicians and patients around the world.

“The exciting research outcomes of Dr. Ferrone and team will have a significant impact on enhancing the care and management of all patients with neuroendocrine tumors,” Melmed said.  

Additional Cedars-Sinai authors include Shahrzad Arya, MD; Liti Zhang, MD; Alexandra Gangi, MD; Andrew E. Hendifar, MD, MPH; Giulia Cattaneo, PhD; Luigi Liguori, MD; Arsen Osipov, MD; Nicholas N. Nissen, MD; and Kambiz Kosari, MD

Other authors include Marco Ventin, MD; Carlos Fernandez del-Castillo, MD; Motaz Qadan, MD, PhD; Francesco Sabbatino, MD, PhD; Keith D. Lillemoe, MD; Alice C. Wei, MD, MSc; Jin He, MD, PhD; and Amer H. Zureikat, MD

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.