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Prof. Dr. Thomas Seyfried, PhD

Thomas N. Seyfried received his Ph.D. in Genetics and Biochemistry from the University of Illinois, Urbana, in 1976. He did his undergraduate work at the University of New England, where he recently received the distinguished Alumni Achievement Award. He also holds a Master’s degree in Genetics from Illinois State University. Thomas Seyfried served with distinction in the United States Army’s First Cavalry Division during the Vietnam War and received numerous medals and commendations. He was a Postdoctoral Fellow in the Department of Neurology at the Yale University School of Medicine and then served on the faculty as an Assistant Professor in Neurology.

Other awards and honours have come from such diverse organisations as the American Oil Chemists Society, the National Institutes of Health, The American Society for Neurochemistry, the Ketogenic Diet Special Interest Group of the American Epilepsy Society, the Academy of Comprehensive and Complementary Medicine, and the American College of Nutrition.

Dr. Seyfried previously served as Chair, Scientific Advisory Committee for the National Tay-Sachs and Allied Diseases Association and presently serves on several editorial boards, including those for Nutrition & Metabolism, Neurochemical Research, the Journal of Lipid Research, and ASN Neuro, where he is a Senior Editor.

Dr. Seyfried has over 200 peer-reviewed publications and is the author of the book, Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer (Wiley, 1st ed., 2012). 

Books by Prof. Dr. Thomas Seyfried, PhD

Video Presentations of Prof. Dr. Thomas Seyfried, PhD

025: How KETO DIET Works in CANCER! – Prof. Dr. THOMAS SEYFRIED (Full Interview)

Prof. Dr. Thomas N. Seyfried is a distinguished American professor of biology, genetics, and biochemistry at Boston College. He holds a master's degree in Genetics from llinois State University and a PhD in Genetics and Biochemistry from the University of Illinois Urbana-Champaign. He further honed his expertise with postdoctoral studies in Neurochemistry and Genetics at Yale University School of Medicine’s Department of Neurology where he served as Assistant Professor.

Prof. Seyfried’s illustrious career spans over 200 peer-reviewed publications, focusing on the mechanisms underlying chronic diseases such as cancer, epilepsy, and neurodegenerative disorders. He currently serves on the editorial boards of several journals, including Nutrition and Metabolism, the Journal of Lipid Research, Neurochemical Research, and ASN Neuro. His groundbreaking work with his preeminent book on “Cancer as a Metabolic Disease - On the Origin, Prevention and Management of Cancer” has positioned him at the forefront of cancer research worldwide.

*PROF. SEYFRIED'S BOSTON COLLEGE PAGE 👉 https://www.bc.edu/bc-web/schools/morrissey/departments/biology/people/faculty-directory/thomas-seyfried.html

*PROF. SEYFRIED in the WEB 👉 https://tomseyfried.com

*LCHD DR. SEYFRIED PAGE: https://www.lowcarbhealthmd.com/resources/experts/seyfried

"Cancer as a Metabolic Disease" - Prof. Dr. Thomas Seyfried, PhD

Thomas N. Seyfried received his Ph.D. in Genetics and Biochemistry from the University of Illinois, Urbana, in 1976. He did his undergraduate work at the University of New England, where he recently received the distinguished Alumni Achievement Award. He also holds a Master’s degree in Genetics from Illinois State University. Thomas Seyfried served with distinction in the United States Army’s First Cavalry Division during the Vietnam War and received numerous medals and commendations. He was a Postdoctoral Fellow in the Department of Neurology at the Yale University School of Medicine and then served on the faculty as an Assistant Professor in Neurology.

Other awards and honours have come from such diverse organisations as the American Oil Chemists Society, the National Institutes of Health, The American Society for Neurochemistry, the Ketogenic Diet Special Interest Group of the American Epilepsy Society, the Academy of Comprehensive and Complementary Medicine, and the American College of Nutrition.

Dr. Seyfried previously served as Chair, Scientific Advisory Committee for the National Tay-Sachs and Allied Diseases Association and presently serves on several editorial boards, including those for Nutrition & Metabolism, Neurochemical Research, the Journal of Lipid Research, and ASN Neuro, where he is a Senior Editor.

Dr. Seyfried has over 150 peer-reviewed publications and is the author of the book, Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer (Wiley, 1st ed., 2012). 

"Cancer as a Metabolic Disease" - Interview with Prof. Dr. Thomas Seyfried, PhD

Current cancer research focuses on genetic origins of cancer, and standard treatments generally involve combinations of surgery, chemotherapy and radiation. In Cancer as Metabolic Disease, Dr. Thomas Seyfried presents an alternative origin of cancer based on the theories of Otto Warburg, wherein cancer is viewed as a disease of cellular metabolic dysfunction due to damaged mitochondria. In addition to pointing to new directions of research, Dr. Seyfried elaborates on a non toxic mode of treatment, the ketogenic diet, which capitalizes on the inability of the damaged cancer cell mitochondria to metabolize ketones, thus starving them while maintaining healthy cells.

Thomas Seyfried is Professor of Biology at Boston College. He is a senior editor of the American Society of Neurochemistry’s journal ASN Neuro and is on the editorial boards of Journal of Lipid Research, Neurochemical Research and Nutrition & Metabolism.

"Cancer: A Metabolic Disease with Metabolic Solutions" - Prof. Dr. Thomas Seyfried, PhD

Emerging evidence indicates that cancer is primarily a metabolic disease involving disturbances in energy production through respiration and fermentation. Cancer is suppressed following transfer of the nucleus from the tumor cell to cytoplasm of normal cells containing normal mitochondria. These findings indicate that nuclear genetic abnormalities cannot be responsible for cancer despite commonly held beliefs in the cancer field. The genomic instability observed in tumor cells and all other recognized hallmarks of cancer are considered downstream epiphenomena of the initial disturbance of cellular energy metabolism. The disturbances in tumor cell energy metabolism can be linked to abnormalities in the structure and function of the mitochondria. Cancer growth and progression can be managed following a whole-body transition from fermentable metabolites, primarily glucose and glutamine, to respiratory metabolites, primarily ketone bodies. This transition will reduce tumor vascularity and inflammation while enhancing tumor cell death. A novel “press-pulse” therapeutic strategy is in development for the non-toxic metabolic management of cancer. Malignant brain cancer in preclinical models and humans will be used to illustrate general concepts. As each individual is a unique metabolic entity, personalization of metabolic therapy as a broadbased cancer treatment strategy will require fine-tuning to match the therapy to an individual’s unique physiology.

Thomas N. Seyfried received his Ph.D. in Genetics and Biochemistry from the University of Illinois, Urbana, in 1976. He did his undergraduate work at the University of New England, where he recently received the distinguished Alumni Achievement Award. He also holds a Master’s degree in Genetics from Illinois State University. Thomas Seyfried served with distinction in the United States Army’s First Cavalry Division during the Vietnam War and received numerous medals and commendations. He was a Postdoctoral Fellow in the Department of Neurology at the Yale University School of Medicine and then served on the faculty as an Assistant Professor in Neurology. Other awards and honors have come from such diverse organizations as the American Oil Chemists Society, the National Institutes of Health, The American Society for Neurochemistry, and the Ketogenic Diet Special Interest Group of the American Epilepsy Society. Dr. Seyfried previously served as Chair, Scientific Advisory Committee for the National Tay-Sachs and Allied Diseases Association and presently serves on several editorial boards, including those for Nutrition & Metabolism, Neurochemical Research, the Journal of Lipid Research, and ASN Neuro, where he is a Senior Editor. Dr. Seyfried has over 150 peer-reviewed publications and is the author of the book “Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer (Wiley Press).” 

Cancer as a Mitochondrial Metabolic Disease - Dr. Thomas Seyfried

Thomas Seyfried, Ph.D., is a biochemical geneticist, professor of biology at Boston College, and author of the groundbreaking book Cancer as a Metabolic Disease. As part of a lecture delivered on July 31, 2018, at the annual CrossFit Health Conference, Seyfried presented a report card on our current approaches to treating cancer in the United States. Looking at data from the American Cancer Society on cancer incidence and deaths per day between 2013 and 2017, he noted death rates are actually on the rise. “The more money we raise for cancer, the more cancer we get,” he observed. “So you have to ask, ‘What is going on here?’ ... This is a failure of monumental proportions.”

The reason for the failure “has to do with a fundamental misunderstanding of what the nature of this disease is,” he explained. “We’ve been led to believe that this is a genetic disease, and I’ll present evidence to say that it’s not.”

The belief that cancer is a genetic disease associated with somatic mutation has become dogma, Seyfried explained, and this dogma shaped much of the cancer research and treatment protocols of the twentieth century. So-called cutting-edge treatments, such as personalized therapy and precision medicine, are based on this viewpoint.

Unfortunately, the viewpoint is wrong, as Seyfried explained in “Cancer as a Mitochondrial Metabolic Disease,” an article published in Frontiers in 2015. There, he aggregated existing research on cancer and reevaluated the information in light of the two competing theories on the origin of the disease (i.e., cancer as a genetic or metabolic disease).

The research he surveyed supported Otto Warburg’s theory that cancer develops as a result of disturbed energy metabolism. Seyfried and his colleagues compared nuclear-cytoplasmic transfer and mitochondrial transfer experiments and found that the mitochondria are “calling the shots, not the nucleus,” which is “the opposite of what we would expect if this were a genetic disease,” he explained.

Seyfried then described what he and his colleagues believe is the missing link in Warburg’s theory. Normal healthy cells derive energy from oxidative phosphorylation. Cancer cells, on the other hand, get energy through fermentation. What Seyfried and his colleagues discovered — and what Warburg did not know — is that cancer cells can ferment not only lactic acid but amino acids as well. That is to say, cancer cells can derive energy for proliferation from glucose and glutamine. Thus, to remove a cancer cell’s energy source, one has to remove its access to fermentable fuels, and an effective way to do this, Seyfried found, is through calorie restriction and ketosis.

Calorie restriction and ketosis, he explained, are anti-angiogenic, anti-inflammatory, and pro-apoptotic. “No cancer drug is known that can do this without toxicity,” he said. He then added that those who claim they don’t understand the mechanism by which calorie restriction and ketosis work are full of “bullshit.” “They don’t read the literature. Nor do they contribute to it,” he said.

Seyfried’s cancer research, particularly on aggressive forms of cancer such as glioblastoma multiforme (GBM) and other stage 4 cancers, led to his development of a glucose-ketone index calculator and the press-pulse therapeutic strategy. The calculator helps patients monitor their progress toward therapeutic ketosis. The press-pulse method pairs press therapies, such as following a keto diet while taking ketone supplements and practicing stress management, with pulse therapies, such as taking glucose and glutamine inhibitors while undergoing hyperbaric oxygen treatments. During his presentation, Seyfried explained how and why these methods are more effective for cancer patients than traditional standard of care.

“GBM and other stage 4 cancers — I don’t consider them as terminal cancers,” he said. 

Cancer as a Mitochondrial Metabolic Disease - Dr. Thomas Seyfried, PhD

Thomas N. Seyfried is Professor of Biology at Boston College. He received his Ph.D. in Genetics and Biochemistry from the University of Illinois, Urbana, in 1976. He did his undergraduate work at the University of New England where he recently received the distinguished Alumni Achievement Award. He also holds a Master’s degree in genetics from Illinois State University, Normal, IL. Thomas Seyfried served with distinction in the United States Army’s First Cavalry Division during the Vietnam War, and received numerous medals and commendations. He was a Postdoctoral Fellow in the Department of Neurology at the Yale University School of Medicine, and then served on the faculty as an Assistant Professor in Neurology. Other awards and honors have come from such diverse organizations as the American Oil Chemists Society, the National Institutes of Health, The American Society for Neurochemistry, and the Ketogenic Diet Special Interest Group of the American Epilepsy Society. Dr. Seyfried previously served as Chair, Scientific Advisory Committee for the National Tay-Sachs and Allied Diseases Association and presently serves on several editorial boards, including those for Nutrition & Metabolism, Neurochemical Research, the Journal of Lipid Research, and ASN Neuro. Dr. Seyfried has over 170 peer-reviewed publications and is author of the book, Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer (Wiley Press).

Controversial Discussion - Cancer as A Metabolic Mitochondrial Disease? - Prof. Dr. Thomas Seyfried, PhD

In this episode, Thomas Seyfried, a cancer researcher and professor of biology at Boston College, discusses a controversial view of cancer as a mitochondrial metabolic disease. Many topics related to the causes, treatments, and prevention of cancer are covered in this in-depth conversation.

A Radical & Controversial Approach to STARVING CANCER: The Two Root Causes - Prof. Dr. Thomas Seyfried, PhD

Over the years, it has become a widely held belief that cancer is predominantly genetic or simply the consequence of bad luck. An empowering evolution in cancer research, however, suggests we have far more control over our risk than previously thought. 

Today on The Dhru Purohit Podcast, Dhru sits down with cancer researcher and scientist Dr. Thomas Seyfried to discuss the underlying causes of cancer and why addressing metabolic dysfunction is a very important and often overlooked area of its prevention and treatment. 

In this episode, Dr. Seyfried shares the role that oxidative stress, mitochondrial health, and glucose play in the development and progression of cancer. He also discusses his research on ketogenic diets as a promising solution in helping to correct these imbalances. Dr. Seyfried describes the limitations of conventional cancer treatment, the role our modern-day society plays in the risk of cancer, and why diet and lifestyle strategies are an integral part of the solution for prevention and better treatment outcomes. 

Dr. Thomas Seyfried is an American professor of biology, genetics, and biochemistry at Boston College. He received his PhD from the University of Illinois Urbana-Champaign in 1976 and did his postdoctoral fellowship at the Yale University School of Medicine.

Dr. Seyfried has over 150 peer-reviewed publications, and his research focuses primarily on the mechanisms driving cancer, epilepsy, and neurodegenerative diseases and calorie-restricted ketogenic diets in their prevention and treatment. He is the author of Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer and presently serves on the Nutrition & Metabolism, Neurochemical Research, Journal of Lipid Research, and ASN Neuro editorial boards. 

In this episode, Dhru and Dr. Seyfried dive into:

-Beliefs about the origins of cancer not accepted by the mainstream 

-What cancer is and why it’s so pervasive today 

-Where Dr. Seyfried’s beliefs differ from the conventional cancer model 

-The antismoking campaign’s success in cancer prevention 

-Metabolic health as a driver of cancer 

-The discovery of glucose fermentation and oxidative stress and their link to cancer 

-Conventional cancer treatment: could it be causing more harm than good? 

-Mitochondrial damage and cancer 

-The ketogenic diet as a promising anticancer intervention 

-Dr. Seyfried’s research and case studies 

-Limitations in conventional cancer treatment 

-Diet and lifestyle strategies for cancer prevention 

-Navigating cancer resources, testing, and treatments 

-Invasive vs noninvasive tools for cancer detection 

-Dr. Seyfried’s research and the future of cancer treatment and prevention

The SHOCKING ROOT CAUSE of Cancer & How to STARVE It Naturally - Prof. Dr. Thomas Seyfried, PhD

Can a Keto Diet Eliminate Cancer Growth? Dr. Thomas Seyfried Says Yes

In this episode, Dr. Thomas Seyfried discusses metabolic approaches to cancer. Learn how depriving cancer cells of fermentable fuels like glucose and glutamine can starve and kill them. Challenge the genetic disease model and discover the impact of ketosis on mitochondrial health. Uncover the truth about cancer as a metabolic, not genetic, disease. Empower yourself with the knowledge to combat cancer through metabolic strategies and learn about the dangers surrounding us: processed foods.

Can We STARVE CANCER? What You NEED TO KNOW! | Dr. Thomas Seyfried

Over the years, it has become a widely held belief that cancer is predominately a genetic disease or simply the consequence of bad luck. An empowering evolution in cancer research, however, suggests we have far more control over our risk than previously thought. 

I’m excited to talk to Dr. Thomas Seyfried about the underlying causes of cancer and why addressing metabolic dysfunction is a very important and often overlooked area of its prevention and treatment. 

Dr. Thomas Seyfried is an American professor of biology, genetics, and biochemistry at Boston College. He received his Ph.D. from the University of Illinois Urbana-Champaign in 1976 and did his postdoctoral fellowship at the Yale University School of Medicine. Dr. Seyfried has over 150 peer-reviewed publications, and his research focuses primarily on the mechanisms driving cancer, epilepsy, and neurodegenerative diseases and calorie-restricted ketogenic diets in their prevention and treatment. He is the author of Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer and presently serves on the Nutrition & Metabolism, Neurochemical Research, Journal of Lipid Research, and ASN Neuro editorial boards.

Shocking Truth About Cancer: Fix Your Diet & Lifestyle To Starve It For Longevity | Thomas Seyfried

When I started medical school in 1995, we were taught that one in four people were likely to develop cancer in their lifetime. Today, that statistic has changed to one in two – a rapid rise that can’t be explained by genetics. But if our modern diet and lifestyles are the cause, we have more control than we might think. 

That’s the message my guest, Professor Thomas Seyfried, has worked tirelessly to prove and communicate over his four decades as a cancer researcher. Professor Seyfried is a professor of biology, genetics and biochemistry at Boston College, Massachusetts, and author of more than 150 peer-reviewed publications, as well as the 2012 book Cancer As A Metabolic Disease. 

Through his research, and in this conversation, he sets out to explain how it’s a malfunction in our mitochondria – the energy powerhouses in each of our cells – that’s at the root of every cancer he’s studied. Normal-functioning mitochondria, he explains, use oxygen to make energy. In cancer, this process is disrupted. Cancer cells cannot use oxygen, so they fall back on a primitive form of energy creation known as fermentation. 

It follows then, explains Professor Seyfried, that if we can somehow stop this fermentation process, then cancer cells will die. Cancer uses glucose and glutamine to fuel fermentation. While we don’t want to block glutamine, as it has other uses in the body, we can drastically lower our glucose levels to stop driving cancer growth. 

We discuss some of the ways in which we can start doing this – for example, using specific low-carb diets and nutritional ketosis. Professor Seyfried also talks us through his ground-breaking ‘metabolic therapy’ protocols for treating cancer – sometimes, alongside conventional treatments like chemotherapy and radiotherapy.

Professor Seyfried has spent decades researching and proving a metabolic cause for this devastating disease. This a compelling and optimistic conversation, packed with actions we can all take to reduce our risk not just of cancer, but all the chronic conditions driven by metabolic disruption.

Scholarly Articles from Prof. Dr. Thomas Seyfried, PhD

Nontoxic Targeting of Energy Metabolism in Preclinical VM-M3 Experimental GlioblastomaIntroduction: Temozolomide (TMZ) is part of the standard of care for treating glioblastoma multiforme (GBM), an aggressive primary brain tumor. New approaches are needed to enhance therapeutic efficacy and reduce toxicity. GBM tumor cells are dependent on glucose and glutamine while relying heavily on aerobic fermentation for energy metabolism. Restricted availability of glucose and glutamine may therefore reduce disease progression. Calorically restricted ketogenic diets (KD-R), which reduce glucose and elevate ketone bodies, offer a promising alternative in targeting energy metabolism because cancer cells cannot effectively burn ketones due to defects in the number, structure, and function of mitochondria. Similarly, oxaloacetate, which participates in the deamination of glutamate, has the potential to reduce the negative effects of excess glutamate found in many brain tumors, while hyperbaric oxygen therapy can reverse the hypoxic phenotype of tumors and reduce growth. We hypothesize that the combinatorial therapy of KD-R, hyperbaric oxygen, and oxaloacetate, could reduce or eliminate the need for TMZ in GBM patients.Methods: Our proposed approach for inhibiting tumor metabolism involved various combinations of the KD-R, oxaloacetate (2 mg/g), hyperbaric oxygen, and TMZ (20 mg/kg). This combinatorial therapy was tested on adult VM/Dk mice bearing the VM-M3/Fluc preclinical GBM model grown orthotopically. After 14 days, tumor growth was quantified via bioluminescence. A ...
Press-pulse: a novel therapeutic strategy for the metabolic management of cancer - Nutrition & MetabolismBackground A shift from respiration to fermentation is a common metabolic hallmark of cancer cells. As a result, glucose and glutamine become the prime fuels for driving the dysregulated growth of tumors. The simultaneous occurrence of “Press-Pulse” disturbances was considered the mechanism responsible for reduction of organic populations during prior evolutionary epochs. Press disturbances produce chronic stress, while pulse disturbances produce acute stress on populations. It was only when both disturbances coincide that population reduction occurred. Methods This general concept can be applied to the management of cancer by creating chronic metabolic stresses on tumor cell energy metabolism (press disturbance) that are coupled to a series of acute metabolic stressors that restrict glucose and glutamine availability while also stimulating cancer-specific oxidative stress (pulse disturbances). The elevation of non-fermentable ketone bodies protect normal cells from energy stress while further enhancing energy stress in tumor cells that lack the metabolic flexibility to use ketones as an efficient energy source. Mitochondrial abnormalities and genetic mutations make tumor cells vulnerable metabolic stress. Results The press-pulse therapeutic strategy for cancer management is illustrated with calorie restricted ketogenic diets (KD-R) used together with drugs and procedures that create both chronic and intermittent acute stress on tumor cell energy metabolism, while protecting and enhancing the energy metabolism of normal cells. Conclusions Optimization of dosing, timing, and scheduling of the press-pulse therapeutic strategy will facilitate the eradication of tumor cells with minimal patient toxicity. This therapeutic strategy can be used as a framework for the design of clinical trials for the non-toxic management of most cancers.
The glucose ketone index calculator: a simple tool to monitor therapeutic efficacy for metabolic management of brain cancer - Nutrition & MetabolismBackground Metabolic therapy using ketogenic diets (KD) is emerging as an alternative or complementary approach to the current standard of care for brain cancer management. This therapeutic strategy targets the aerobic fermentation of glucose (Warburg effect), which is the common metabolic malady of most cancers including brain tumors. The KD targets tumor energy metabolism by lowering blood glucose and elevating blood ketones (β-hydroxybutyrate). Brain tumor cells, unlike normal brain cells, cannot use ketone bodies effectively for energy when glucose becomes limiting. Although plasma levels of glucose and ketone bodies have been used separately to predict the therapeutic success of metabolic therapy, daily glucose levels can fluctuate widely in brain cancer patients. This can create difficulty in linking changes in blood glucose and ketones to efficacy of metabolic therapy. Methods A program was developed (Glucose Ketone Index Calculator, GKIC) that tracks the ratio of blood glucose to ketones as a single value. We have termed this ratio the Glucose Ketone Index (GKI). Results The GKIC was used to compute the GKI for data published on blood glucose and ketone levels in humans and mice with brain tumors. The results showed a clear relationship between the GKI and therapeutic efficacy using ketogenic diets and calorie restriction. Conclusions The GKIC is a simple tool that can help monitor the efficacy of metabolic therapy in preclinical animal models and in clinical trials for malignant brain cancer and possibly other cancers that express aerobic fermentation.
The Ketogenic Diet and Hyperbaric Oxygen Therapy Prolong Survival in Mice with Systemic Metastatic CancerIntroduction Abnormal cancer metabolism creates a glycolytic-dependency which can be exploited by lowering glucose availability to the tumor. The ketogenic diet (KD) is a low carbohydrate, high fat diet which decreases blood glucose and elevates blood ketones and has been shown to slow cancer progression in animals and humans. Abnormal tumor vasculature creates hypoxic pockets which promote cancer progression and further increase the glycolytic-dependency of cancers. Hyperbaric oxygen therapy (HBO2T) saturates tumors with oxygen, reversing the cancer promoting effects of tumor hypoxia. Since these non-toxic therapies exploit overlapping metabolic deficiencies of cancer, we tested their combined effects on cancer progression in a natural model of metastatic disease. Methods We used the firefly luciferase-tagged VM-M3 mouse model of metastatic cancer to compare tumor progression and survival in mice fed standard or KD ad libitum with or without HBO2T (2.5 ATM absolute, 90 min, 3x/week). Tumor growth was monitored by in vivo bioluminescent imaging. Results KD alone significantly decreased blood glucose, slowed tumor growth, and increased mean survival time by 56.7% in mice with systemic metastatic cancer. While HBO2T alone did not influence cancer progression, combining the KD with HBO2T elicited a significant decrease in blood glucose, tumor growth rate, and 77.9% increase in mean survival time compared to controls. Conclusions KD and HBO2T produce significant anti-cancer effects when combined in a natural model of systemic metastatic cancer. Our evidence suggests that these therapies should be further investigated as potential non-toxic treatments or adjuvant therapies to standard care for patients with systemic metastatic disease.