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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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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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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