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williamscancerinstitute · 2 years

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Complete response in 12 Out of 12 Patients with Rectal Carcinoma using Immunotherapy

On June 5, published by Cercek et al. in The New England Journal of Medicine, a small trial of 12 patients with stage 2-3 rectal cancer was treated with the PD-1 inhibitor, dostarlimab. Amazingly, they reported that 12 out of 12 had a complete response. Clearly very exciting and goes with my feeling that most cancer patients need to be allowed to be treated with Immunotherapy, especially if other treatments have failed. There is one special consideration in the study; the patients had what is known as a mismatch repair deficient tumor. What is mismatch repair? It is the ability to fix incorrectly inserted bases of DNA that occur during the copying of the DNA. If this process does not function correctly, more DNA errors will accumulate. The more errors, the more different the cancer DNA will be from normal cells. This gives the immune system more targets, making cancer more receptive to Immunotherapy. Unfortunately, like many other cancers, mismatch deficiency is in the minority of colorectal cancer, 15% or less. Certainly, it is essential to identify patients with mismatch deficiency and consider Immunotherapy. That is undoubtedly a common practice in evaluating the biopsy of a tumor. There are also other aspects beyond mismatch repair, such as tumor mutational burden and other mutations associated with DNA repair. Also, in some cases, certain medications can be used to block DNA repair, potentially increasing the potential to respond to Immunotherapy.

There are a few questions that arise from this trial. One question is whether dostarlimab is superior to Opdivo or Keytruda, even though all are in the same class of drugs as PD-1 inhibitors. The results seemed similar in prior trials where dostarlimab and Keytruda were used. We may see more head-to-head trials to answer this question in the future. The next question is what can be done to make the majority of patients who don’t have mismatch deficiency respond as well. Though there are many complex aspects of the immune response, one key one is to increase the immune cell infiltration into cancer. One technique is injecting immune agents into the tumor that calls the immune cells to the tumor. This now alerts the immune cells to cancer and can increase the ability to respond to other Immunotherapy. This is a way to equalize the playing field for patients who don’t have mismatch repair to be more like those who do.

Certainly, this study further demonstrates to the public what we in the scientific community already knew, that it is possible to have incredible responses with Immunotherapy. And we know the playbook and can expand this out to the majority of other cancers. That is precisely what we are doing with our patients, bringing the treatments of the future to them today.

By Dr. Jason Williams

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williamscancerinstitute · 2 years

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IMMUNOTHERAPY AWARENESS MONTH | WILLIAMS CANCER INSTITUTE

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williamscancerinstitute · 2 years

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CANCER PREVENTION AND EARLY DETECTION.

Of all the causes of death, cancer remains the second-leading in the entire world. Maintaining a healthy diet and active lifestyle is vital in fighting this disease. Regular screenings such as mammograms, pap smears, colonoscopies, and prostate exams are essential for early detection, and early detection can be critical to treatment success.

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williamscancerinstitute · 2 years

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Immunotherapy vs Chemotherapy

IMMUNOTHERAPY VS CHEMOTHERAPY

When it comes to breaking down the differences between two cancer treatments and choosing which is best, the ultimate goal is to take into consideration the individual factors and circumstances each patient has. Each treatment will have its unique side effects and considerations. We’ve simplified a couple of differences amongst both chemotherapy and immunotherapy to help you better compare both treatments. Chemotherapy ● Depletes the body’s immune system ● Decreases white blood cells count ● Causes drastic hair loss ● Causes nausea and vomiting ● Causes chemo brain (disruption in focus and concentration) ● Can be combined with immunotherapy ● Low metronomic dosing is an option ● Reduces tumor burden, making it easier for the immune system to fight Immunotherapy ● May increase certain autoimmune diseases ● Can cause autoimmune pneumonitis ● Hormone imbalance may occur ● Cytokine Release Syndrome (CRS) ● Less invasive than chemotherapy ● When used in combination with other cancer treatments has been shown to improve the overall treatment process ● Fewer side effects compared to chemotherapy

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williamscancerinstitute · 2 years

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Immunotherapy treatment against breast cancer

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williamscancerinstitute · 2 years

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Early Detection of Cancer and Its Challenges

Treating early stage cancer is much easier and it has less invasive treatment choices than treating advanced stage cancer which will represent a higher challenge to both the patient and the physician. This is why we need to work on developing new technologies and strategies to early detection and treatment of cancer. This also may include the possibility of overdiagnosis and overtreatment, which could cause more harm to patients who had not developed malignant tumors or lesions and might see only traditional therapies (such as surgery, chemotherapy and radiotherapy alone) as their only choice.

However, detection and treatment of early stage cancer can get a higher rate of success and survival cases and yet around 50% of cancers are only detected at an advanced stage. The reason for this is that to be able to detect cancer early we need to consider some challenges we face. Understanding cancer itself and its behavior it’s one of the first things to achieve this goal. Determining the risk of developing cancer is also crucial, examining germline genomic susceptibility, family history, exposures, demographic, and behavioral data will give us an idea of what kind of patients should be getting cancer tests more often and as more therapies are coming out, considering which one or which combination might work best depending on the patients cancer.

Another difficulty in finding accurate signals of early cancer is finding and validating biomarkers, including circulating tumor DNA, circulating tumor cells, proteins, exosomes, and cancer metabolites. The combination and resolution of these factors with technological advancements and appropriate evaluation will be crucial to realizing the potential for early detection to inform treatment decisions and improve survival cases, while minimizing the risk of overtreatment. To conclude, our efforts and resources must be directed towards improving our knowledge and technology to a more efficient evaluation and implementation of newer treatment and technologies to early detection of cancer to get much better expected results of success and survival rate.

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williamscancerinstitute · 2 years

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Cryoablation Immunotherapy for Cancer.

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williamscancerinstitute · 2 years

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Interleukin 6 Blockade a “Win-Win” for Cancer Immunotherapy.

IL-6 blockade with Tocilizumab Increases Response to Cancer Immunotherapy While Reducing Side-Effects

Though we have suspected that blocking IL-6 with immune checkpoint blockade could be helpful in cancer treatment, a new study on May 9, 2022, from MD Anderson, Hailemichael, et al. published titled “Interleukin-6 blockade abrogates immunotherapy toxicity and promotes tumor immunity.”

This sounds like a win-win, with better response and fewer side effects. Indeed, we know that, in general, IL-6 can behave as an immune-suppressing cytokine. From checking on my patients, I know high IL-6 is very common in cancer patients. So, what key points did they show? This study had two parts, one a mouse study—the other a retrospective human study of patients on cancer immunotherapy and incidentally received tocilizumab. The added human part is nice since animal studies alone can be misleading. In their mouse study using one of my favorite technologies, NanoString, they determined the combination of CTLA-4 and IL-6 blockade resulted in increased infiltration of cancer attacking immune cells within the tumor. This heating up the immune environment is an essential fundamental principle necessary to start an effective immune response. They also observed that immune cells in the colon associated with causing colitis, inflammation of the colon, and a nagging problem for immunotherapy, were reduced. These results were certainly a surprise. The human patient’s review mainly included those who had immune-related adverse events, such as colitis, on PD-1 inhibitors but failed typical first-line treatment, such as high dose steroids and were escalated to anti-IL-6 to treat these immune events. The difference in response rates between patients who received IL-6 blockade and those that didn’t was just under 8%. Though modest, these patients mainly had been treated previously with a course of immune-suppressive drugs so that number could be a little higher. Indeed, this is not the magic bullet. However, we continue to gain ground in cancer treatments, piece by piece, adding a little more here and there. As our immunotherapy combination increases, side effects will be even more of a problem. If most of these side-effects can be subverted with IL-6 blockade, which FDA-approved drugs are already available, it will give us an even more significant advantage in our therapies. Indeed, for most doctors to use this, they will need to see more evidence and a specific FDA indication. We have already been measuring IL-6 levels and using tocilizumab when appropriate. We had already seen previously that drugs for rheumatoid arthritis, such as infliximab (Remicade), helped reduce adverse events and may improve response. Hopefully, these drugs will allow more protection against these adverse advents and will enable us to increase our aggressiveness on immunotherapy combinations putting us that much closer to a cure.

Jason R. Williams, MD, DABR

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williamscancerinstitute · 2 years

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Cancer Procedure: Intratumoral Vaccine Immune Response into the liver mass with SBRT.

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williamscancerinstitute · 2 years

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Vitamin E Boost Response of Cancer Immunotherapy

A recent study published by Yuan et al. from MD Anderson Cancer Center showed that natural Vitamin E (DL-a-tocopherol) enhanced the response rates of cancer immunotherapy by reinvigorating dendritic cells. I am going to break down the overall key highlights of the study. One is that they reviewed the electronic health records of cancer patients on immunotherapy and determined that one’s taking Vitamin E had improved survival. This led them to try to determine the mechanism in the mouse model. They discovered that Vitamin E entered the dendritic cells inhibiting a checkpoint within them called SHP1. This resulted in enhanced antigen presentation; as you may know, dendritic cells are involved in presenting foreign or tumor antigens to other immune cells, such as T cells, to activate an immune response. There has been much work on dendritic cell vaccines, which has been disappointing. This is because that is only one part of the activation of the immune response. In addition, like most immune cells, dendritic cells can also be regulatory to inhibit an immune response against cancer. However, in this situation described in the study, Vitamin E leads to an activation of mature dendritic cells presenting tumor antigen, and the overall response is enhanced due to the presence of traditional immunotherapy such as PD-1 CTLA-4 inhibitors. In previous studies, the benefits of Vitamin E were not clear.

Another study to keep in mind was published by Kang et al. in 2014, showing that Vitamin E reduced myeloid-derived suppressor cells (MDSC) and increased the effects of CD8+ T cells against tumors; as you may know from my book that MDSCs are immune cells that inhibit the anti-cancer immune response, essentially protecting cancer. High amounts of MDSC are associated with a poor prognosis and reduce potential response to immunotherapy. In the study by Kang, they showed that Vitamin E reduced the MDSCs, resulting in increased anti- cancer CD8+ T cells infiltrating the tumor. This study gives a different mechanism but adds more data backing the use of Vitamin E in conjunction with immunotherapy.

Indeed, supplementation with Vitamin E should be considered for patients on immunotherapy for cancer. However, not much has been discussed on dosing. The 2014 study showed benefits with dietary Vitamin E, but they also described a much more significant effect when injected into the tumor. They explain that injected Vitamin E can modify the tumor microenvironment to be more receptive to other immunotherapy treatments. As you can see, the theme of injection into the tumor site continues to be the most potent treatment option. Otherwise, a standard dose of 400 IU of natural Vitamin E orally a day is probably helpful.

Jason R. Williams, MD, DABR

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williamscancerinstitute · 2 years

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How and why optimizing your body’s immune

How and why optimizing your body’s immune system for preventing and treating Cancer?

Many may be wondering how exactly the immune system and cancer are interrelated. It’s quite complex given that it has taken decades of countless scientific research in search of a cure. The goal is to break this cancer into its basic mechanisms to fully understand its totality and appreciate its processes.

In general, the immune system works by fighting against any harmful substances such as bacteria, fungi, viruses, and cancer cells. Something important to note is that your own cells and immune system can and will betray you.

It could be easier to think of our cells as a double-sided sword. Take, for instance, antigen-presenting cells, specifically dendritic cells which act by collecting information and delivering it to the immune system. Whenever bad information is delivered it will cause the immune system to slow down, depleting the body’s overall vitality. As we can see, this dual-action a single cell can produce can either help or hurt the process. This is just one of the many examples that occur within the body with other cells.

Thankfully, there are different forms of therapy such as cryoablation which works by attacking such cells which cause harm to the body. Adjuvants are another tool that serves the positive stimulation of immune response. They are substances that can be injected into and around the ablated tumor.

But before jumping into these therapies, it’s recommended to strengthen the immune system in healthy ways to promote higher chances of immunotherapy to be effective in treating certain cancers.

However, due to the complexity of the immune response and regulatory cells it contains for autoimmunity protection, it is crucial to understand that these cells act like a double-sided sword. On its dark side, regulatory cells can be attacked by cancer and will serve as anti-cancer immune response blockers.

Overall, finding ways to optimize one’s immune system can be tedious in midst of so much chaos with busy work schedules, relationships, and currently dealing with a pandemic. Below is a compiled list of suggestions for boosting the immune system with the hope of preventing and/or curing cancer.

Vitamin D (sun exposure or supplement in conjunction with Vit. K)

Vitamin C (through diet or supplement)

Minimum of 30 minutes of physical activity (can be a light jog, yoga, pilates, Zumba, weight lifting, etc)

Healthy balanced diet according to body constitution

Consuming healthy fats such as fish oil or flaxseed oil to decrease inflammation

Limiting sugar intake

Receiving adequate sleep

Being outdoors in nature more often

The material contained on this site is for informational purposes only and DOES NOT CONSTITUTE THE PROVIDING OF MEDICAL ADVICE, and is not intended to be a substitute for independent professional medical judgment, advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare providers with any questions or concerns you may have regarding your health.

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williamscancerinstitute · 2 years

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Pentoxifylline an FDA Approved

Pentoxifylline an FDA Approved Drug for Vascular Disease That May Boost Immunotherapy

Pentoxifylline, sold under the brand name Trental is typically used for vascular disease to increase blood flow due to its effect in reducing blood viscosity. However, there is a gene called c-Rel that is important to maintain the function of regulatory cells such as Tregs and MDSC. As I have discussed, the immune system has two sides, one that is regulatory, which has been tricked by cancer to protect it. There is the other side that can attack cancer.

Our goal is to tip the balance in favor of attacking cancer. In a study published by Grinberg-Bleyer, et al in Cell, Sept 7, 2017, titled “NF-kB c-Rel Is Crucial for the Regulatory T Cell Immune Checkpoint in Cancer” they describe how blocking c-Rel can reduce the regulatory function of Tregs. In addition, Li, et al published in Nature Cancer, May 18, 2020, an article titled “c-Rel is a Myeloid Checkpoint for Cancer Immunotherapy” which discusses MDSC.

These two articles are describing how c-Rel is key to two of the main groups of immune cells that can inhibit an anti-cancer immune response. In turn, blocking c-Rel was demonstrated in animals to enhance standard immunotherapy, such as PD-1 inhibitors. Blocking both c-Rel and PD-1 together was better than either alone. The study by Grinberg-Bleyer showed that Pentoxifylline, a c-Rel inhibitor delayed tumor growth in the mouse model. When administered with a PD-1 inhibitor, the effects of both were enhanced. Though there are other c-Rel inhibitors in development, since Pentoxifylline is available and FDA approved, it may allow for off-label use which could improve the results of immunotherapy.

Jason R. Williams, MD, DABR

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The material contained on this site is for informational purposes only and DOES NOT CONSTITUTE THE PROVIDING OF MEDICAL ADVICE, and is not intended to be a substitute for independent professional medical judgment, advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare providers with any questions or concerns you may have regarding your health.

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williamscancerinstitute · 2 years

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How Does Breast Cancer Cryoablation Work

Cancer is a frightening word for anyone to hear. When it comes to breast cancer, many women feel an especially strong fear. Fortunately, treatments are improving every day and there are now a variety of treatment options available. One such option is Breast Cancer Cryoablation. This article will discuss what Cryoablation is, the benefits of this treatment method, and how it may be right for you.

Cryoablation is a surgical procedure that uses extreme cold to destroy breast cancer cells. This minimally invasive treatment is an alternative to traditional surgery for women with early-stage breast cancer. Cryoablation can be used to treat tumors that are too small to remove with traditional surgery or when traditional surgery is not possible.

Benefits of Cryoablation Over Traditional Surgery

Cryoablation surgery is a safe and effective treatment for breast cancer. It has been shown to be as effective as traditional surgery in removing tumors. Cryoablation also causes less damage to healthy tissue than traditional surgery. This can lead to fewer complications and a quicker recovery time.

Side Effects of Cryoablation

As with any surgical procedure, there are some risks associated with Cryoablation. These include infection, bleeding, and damage to healthy tissue. However, these risks are minimal and can be minimized by following your doctors’ instructions carefully.

It is important to discuss the benefits and risks of Cryoablation with your doctor before deciding if this is the right treatment for you.

Cryoablation surgery is a safe and effective treatment for breast cancer. If you are considering this procedure, please make an appointment with one of our specialists at Williams Cancer Institute to discuss your options. We are here to help you get the care that you need. Our team of experts will work with you to develop a treatment plan that meets your needs and provides the best possible outcome.

The material contained on this site is for informational purposes only and DOES NOT CONSTITUTE THE PROVIDING OF MEDICAL ADVICE, and is not intended to be a substitute for independent professional medical judgment, advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare providers with any questions or concerns you may have regarding your health.

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williamscancerinstitute · 2 years

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World Cancer Day

World Cancer Day has arrived and Williams Cancer Institute would like to thank each and every patient who has entrusted their health with our clinic and treatments. Williams Cancer Institute aims to help create a cancer-free world. Our team has been passionately working on developing continuous medical research to eradicate cancer. We value the courage and strength every cancer patient has, and we honor your resilience.

The more awareness we bring forth to the community about immunotherapy for cancer means more patients will have the opportunity to be treated with less invasive treatments. In this interview, Dr. Jason Williams explains the main advances in research that are being developed at the Williams Cancer Institute to fight cancer.

Jason R. Williams, MD, DABR

The material contained on this site is for informational purposes only and DOES NOT CONSTITUTE THE PROVIDING OF MEDICAL ADVICE, and is not intended to be a substitute for independent professional medical judgment, advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare providers with any questions or concerns you may have regarding your health.

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williamscancerinstitute · 2 years

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Immunotherapy for Cancer

Immune response in cancer treatments has been studied for over decades and to this day continues to be closely researched in an attempt to provide a less invasive treatment for patients. Thanks to medical research, patients and physicians have access to seventeen immunotherapy FDA approved treatments. This ongoing mission is one of great value and in today’s blog we will be exploring more interesting details about the immune system and cancer.

The immune system includes immune cells known as antigen presenting cells, such as a dendritic cell. It gathers information and distributes it to the immune system. Now, just as it will deliver good information, it can also deliver the bad information. When this happens, it alters the T effector cells. With this, the dendritic cells are more likely to slow the immune system down rather than help it. Due to this, there is an urgency for a more precise form of treatment.

Cryoablation

This fascinating medical advancement is used to destroy the malignant cell while also gathering important information. Having access to good information will allow this form of therapy to then destroy the cancer that’s affecting the body.

You may be wondering “what exactly is cryoablation?”

Well, it’s a form of immunotherapy that involves freezing a tumor directly with a thin needle. It works best when used for early stage cancer and is useful with immune-enhancing measures to reduce the risk of future metastasis. Cryoablation is so powerful that it can be used to generate strong immune responses which can lead to one of the most successful cancer treatments that exist, especially for patients with Stage III or IV cancer. Another important note is that combining cryoablation with other forms of immunotherapy enhances the overall success rate of the cancer treatment.

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Robert O. Dillman, Gary B. Fogel, Andrew N. Cornforth, Senthamil R. Selvan, Patric M. Schiltz, and Carol DePriest: Features associated with survival in metastatic melanoma patients treated with patient-specific dendritic cell vaccines. Cancer biother radiopharm 26:407-15 (2011)

DOI: 10.1089/cbr.2011.0973

The material contained on this site is for informational purposes only and DOES NOT CONSTITUTE THE PROVIDING OF MEDICAL ADVICE, and is not intended to be a substitute for independent professional medical judgment, advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare providers with any questions or concerns you may have regarding your health.

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williamscancerinstitute · 2 years

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A Simple Guide to Understanding Breast Cancer

Have you or a loved one previously been diagnosed with breast cancer?

Are you currently struggling on learning how to support your loved one through this battle?

If so, you have reached a great place where you will receive information that will assist you throughout this journey. Breast cancer is a type of cancer that mostly affects women. It is most common to see breast cancer in women the age 50 years and older. This does not mean it will not affect women of younger age.

Many factors can increase the risk of breast cancer such as:

-Family history of breast cancer

-Having dense breast

-Genetic mutations such as BRCA1 and BRCA2

Breast cancer can start at many different places throughout the breast. The most common one is ductal cancer which affects the ducts in the breast that carry milk to the nipple. Another place is in the glands of the breast which make breast milk. If cancer stays local there could possibly be less harm to the body. Unfortunately, there is a vast connection of lymph nodes in and around the breast that can be affected by these cancer cells. In some cases, the cancer cells travel into the lymphatic cells or the blood and this can potentially cause cancer to metastasize. This is why it is more promising to treat breast cancer at its earlier stages because there is less probability that the cancer cells have spread to the rest of the body.

Once screened, the physician will diagnose the patient with one of the two types of breast cancer: ductal carcinoma in situ or invasive breast cancer. The next blog will further go in depth to explain the difference between the two. Your doctor may use an MRI for the breast, a mammogram, or an ultrasound to diagnose breast cancer. Sometimes, multiple scans are necessary in order to rule out any confusion. Afterward, a process called staging is usually performed to detect what stage the cancer is at and whether it has spread to other parts of the breast area.

As noted, breast cancer can be very complex if it’s not broken down into simple steps. It’s a sensitive conversation to have especially with all the fear. Coming up in the next blog, the main topic will be the two most common types of breast cancer.

“What Are The Risk Factors For Breast Cancer?” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 20 Sep. 2021,

https://www.cdc.gov/cancer/breast/basic_info/risk_factors.htm.

Jason R. Williams, MD, DABR

The material contained on this site is for informational purposes only and DOES NOT CONSTITUTE THE PROVIDING OF MEDICAL ADVICE, and is not intended to be a substitute for independent professional medical judgment, advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare providers with any questions or concerns you may have regarding your health.

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williamscancerinstitute · 3 years

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Could a Group of Arthritis Drugs be a Game Changer in Cancer Immunotherapy?

The immune system produces proteins, known as chemokines, which are signals that can affect immune function. There is a chemokine named C-C motif ligand 20, also known as CCL20. It is known as an inflammatory protein, often associated with rheumatoid arthritis. However, new evidence links this cytokine with numerous cancers. It seems that CCL20 promotes cancer metastasis. In addition, it increases cancer stem cells and causes T cell exhaustion. These actions will suppress an immune response. There are studies in many cancer types indicating that blocking CCL20 is anti-cancer and may enhance the success of immunotherapy. Surprisingly enough, drugs that can block CCL20 may also reduce autoimmune side-effects from standard PD-1 immunotherapy, such as Opdivo and Keytruda. Unfortunately, patients with autoimmune side effects are typically given steroids to treat these issues, which can reduce the success of immunotherapy. It seems these arthritis medications would be a better choice because they reduce side effects and increase immunotherapy success. They appear on their own to be cancer immunotherapy.

So what drugs arthritis am I discussing? I am talking about three FDA-approved medications, Infliximab, Tocilizumab, and Etanercept. These drugs all indirectly block CCL20. Though more studies are needed, it seems using any of these with immunotherapy can increase response rates while possibly lowering autoimmune side effects. I am sure the potential benefits will lead to new drugs specifically designed to inhibit the CCL20-CCR6 axis. Also, some natural agents have inhibition of CCL20, including Epigallocatechin gallate (EGCG) and gallotannin. These arthritis drugs are a reasonable consideration that can be deployed right away since they already have approval for a different purpose. Indeed they may have great value in patients who have failed or developed autoimmune side effects from standard immunotherapy, such as Opdivo and Keytruda.

Jason R. Williams, MD, DABR

The material contained on this site is for informational purposes only and DOES NOT CONSTITUTE THE PROVIDING OF MEDICAL ADVICE, and is not intended to be a substitute for independent professional medical judgment, advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified healthcare providers with any questions or concerns you may have regarding your health.

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