For Newly Diagnosed

This page is intended for people who have just been diagnosed with hemangioendothelioma (HE) and particularly epithelioid hemangioendothelioma (EHE) - the disease this author knows most about. CRAVAT hopes the following information will give you a starting point and basis for understanding EHE so that you can better cope with the diagnosis. Consider it your EHE orientation. I have divided it into an‘Introduction’ and a ‘More Advanced Stuff’ section to accommodate concerns that there is too much information here for the ‘beginner’ who might be overwhelmed. When EHE first came to visit my family, I couldn’t learn enough fast enough; the second section is aimed at like-minded people. Don’t expect to get it all at once. You can come back as often as needed. Continue to seek other resources and sources of information. The more you learn the better. I hope this serves as a good starting point.

Introduction

EHE is a rare disease characterized by tumors that can occur anywhere in the body. These are often very slow-growing and people can live for decades with EHE - there are even a few reports of the disease regressing or disappearing completely over time. Furthermore, it is a very unusual disease because the appearance of tumors in multiple body parts does not necessarily carry a poor outcome or indicate aggressive disease. Therefore, while EHE is usually considered a sarcoma (a form of cancer), it is very different from most cancers.

Now, let’s go back to the beginning The day you learned you or a loved one had EHE was undoubtedly tough - very tough. We know that from personal experience. However, there is much to be optimistic about. First, as mentioned above, EHE is usually slow to grow or spread, so you have time to adjust and plan. Furthermore, recently there have been important advances in understanding the disease – and this is considered the first step to finding an effective treatment.

You probably plan to spend some time learning about HE/EHE and what is currently known about it. However, because EHE is so rare, finding good information can be challenging and most doctors probably won’t be able to tell you very much about it. Unlike the common cancers like breast and prostate, there are few resources about EHE and only a handful of oncologists and surgeons have experience in treating EHE patients. In the US, the doctors with the most experience treating EHE generally practice at large academic medical centers. In countries with smaller populations, such as Australia, these doctors will be more difficult to find and patients are more reliant on word of mouth.

A Movie

A good example of the ways EHE both differs and is similar to other cancers can be found in the movie Crazy Sexy Cancer (crazysexycancer.com). Kris Carr has made a very informative documentary of her entire early experience with EHE, starting with the first trips to the doctor. If you haven’t seen it yet, I recommend this movie to you as another helpful starting point. You will probably recognize many things that you have already experienced. Our family found this an inspirational, funny and poignant film. It was a source of education and emotional support for us at a time of great need. It really hit the spot and I hope it does for you, too.

More Advanced Stuff

The Medical Literature Almost every paper about EHE begins with a statement that reads something like, “EHE is a vascular neoplasm intermediate between hemangioma (benign) and angiosarcoma”.  Although the first part of this description is correct, the second part is not entirely accurate. We call EHE a vascular tumor since it is caused by proliferation (unregulated growth) of endothelial cells – the cells that form the interior lining of blood vessels. However, EHE is entirely distinct from both hemangioma and angiosarcoma. We know this now because a genetic alteration responsible for EHE has recently been identified. It is entirely unique to EHE and is not seen in hemangiomas, angiosarcomas, or other vascular tumors. The overall notion is right though: EHE is neither benign like hemangioma nor is it usually aggressive like angiosarcoma.

Many medical journal papers about EHE describe only a single patient (“case reports”) and are therefore not very useful to you. Moreover, most focus only on surgical approaches to treatment. This is partly because there are no standard non-surgical treatments for EHE and not enough EHE patients to run clinical trials that compare effectiveness of various treatments. We don’t recommend focusing too much on any one given paper that describes only one patient since such reports aren’t usually very helpful in evaluating or comparing treatments or understanding the range of outcomes in EHE. This takes what doctors call a randomized controlled clinical trial (RCT), or more simply, Clinical Trial.

Unfortunately there are currently no Clinical Trials comparing treatments for EHE. However, there are two well-designed studies focused on liver transplant (generally very favorable results), though neither has a control group (no transplant) for comparison. Interestingly, outcomes among the transplanted patients are often favorable despite widespread disease . Therefore, the presence of tumors in other parts of the body is not usually considered a contraindication to transplant in EHE as it usually is in other forms of cancer. Finally, the HEARDsupport group in collaboration with physicians at the University of Illinois at Chicago recently published the cumulative clinical experiences of roughly 200 patients with EHE in a recent issue of the journal Chest. They show that information from such an on-line registry can provide potentially helpful insights into the disease.

What Causes EHE? This is an important question since the first step to treating a disease is knowing its cause. Many things have been speculated as potential causes of EHE, including hormonal effects, birth control pills, industrial exposures (vinyl chloride), and trauma among others. None of these associations has been confirmed. Fortunately, significant progress has been made very recently in our understanding of EHE. Two separate research groups published findings in late 2011 indicating a specific  chromosomal translocation that is virtually diagnostic for EHE. This swapping of genetic material between chromosomes 1 and 3 is seen in almost all EHE tumor cells and can be considered ‘disease defining’. This genetic alteration results in the production of a fusion gene and a resulting fusion protein: it  has part of a protein that is normally seen only in endothelial cells and a part that is normally found only in brain. This abnormal fusion protein presumably causes the cells to grow without normal regulation. It is this abnormal system that could theoretically be targeted for therapy. However, to begin testing possible treatments we need to develop laboratory models of of EHE: that is, cells or animals that contain the translocation and resulting fusion protein. CRAVAT Foundation has already funded important research in this area.

A different, less mainstream line of investigation has recently implicated a possible association between EHE and infection by Bartonella bacteria. This bacterium is unique in that it has the ability to cause endothelial cells to proliferate – the underlying biological problem in EHE. Many cancers are thought to result from “two hits” and it is possible that Bartonella infection comprises the other ‘hit’ after the disease defining translocation, possibly by stimulating synthesis of the fusion protein. This is entirely speculative it is good to know there are several possible lines of investigation that could lead to progress in a better understanding of EHE and, possibly a treatment.

Treatment:

Many cases of hemangioendothelioma are asymptomatic and are treated with a ‘wait and see’ approach. It is sometimes considered prudent to wait until the hemangioendothelioma declares its intentions, before starting to fight back. However, there are times when treatment may be indicated.

1) If you have isolated disease, ie a tumor in one place where it can be removed, then surgery to remove the one tumor can be the best chance for a cureand this is almost certainly the way to go. Surgery with wide margins is often the best option when possible.

2) Liver transplantation can be very helpful in controlling disease and symptoms when there are many tumors in the liver. The success with liver transplantation for EHE patients is generally good, however the disease can recur in the new liver in approximately 25-30% of cases.

3) Standard chemotherapy and radiation therapy are not usually very effective in EHE due to its slow growing nature. However, some success has been shown with localised treatments which are still experimental, such as irreversible electroporation (IRE).

4).Newer non-surgical therapies are currently being evaluated including various anti-angiogenics that inhibit formation of new blood vessels. Clinical trials are needed to test the efficacy of anti-angiogenics versus surgery or other treatments like interferon or kinase inhibitors. It might be useful to ask your doctor the exact mechanism of action of any drug he recommends so that you know what category of treatment it falls in.

5) Future treatments:  As the genetic alteration responsible for EHE has now been found, it is now possible to start research to identify the specific molecules that contribute to the growth of EHE. Then the approach, called “targeted therapy” might theoretically be applied to EHE; it has been successfully used to identify useful treatments for other cancers. Obviously, research is the key, including laboratory and clinical research. CRAVAT is currently looking for ways to fund this research through the CRAVAT foundation.  If you would like to contribute financially or if you have suggestions for possible research sponsors please contact CRAVATfoundation.org. Our goal is to fund research that will help lead to a treatment for EHE.

The Work Ahead

Most cancers are of epithelial origin. They are collectively called carcinomas and derive from cells that are from either ectoderm (the outer cell lining of the developing fetus; eg skin) or endoderm (the inner cell lining; e.g., colon cells). This does not mean cancers begin during fetal development, it’s merely a way of differentiating the cell-types of various cancers. Cancers that derive from cells of mesodermal origin (the middle layer of tissue in between the ectoderm and endoderm; e.g., muscle, blood vessels, bone) are called sarcomas and EHE falls into this group.  Sarcomas make up roughly 10% of all cancers.  However, almost all available research funding goes to study carcinomas, especially breast, prostate, lung and colon. Unfortunately sarcoma research is the poor cousin of cancer research and receives only a tiny amount of research funding, far less than the 10% it is entitled to.

It’s time for the community of sarcoma patients, their families and friends to raise a banner and be heard. It’s time for money for research to be spent proportionately. Sarcomas might be individually rare, but are common as a group and they are important scientifically as well. Understanding the biology of sarcomas has provided and will continue to provide important insights into the nature and possible treatment of all types of cancer. Let’s work together to improve the visibility of sarcomas and the need to support research in the field. If you want to help, contribute to fund research on EHE or other sarcomas. If you want the government to help, we must have our voices heard together. Your input and ideas are appreciated. We will probably need to launch a campaign to make politicians aware of these funding discrepancies and the importance of rectifying them.