How can cancer metastases be treated

Supra-local group practice for
Hematology and Internal Oncology
Dr. med. Heike Steiniger, Axel Schneider, Wilfried Mertins
Prof. Dr. med. Jochen Schütte & Dr. Gerhard Kummer
Bahnhofstrasse 64
46145 Oberhausen-Sterkrade
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Frequently asked questions about oncology and hematology

What is oncology and hematology?

Oncology deals with the treatment of malignant solid tumors, i.e. colon cancer, lung cancer, breast cancer, prostate carcinoma and many more. In hematology, it concerns on the one hand malignant tumors of the blood-forming cells such as leukemia and lymphomas and also non-tumor-related changes in the blood count that are congenital can be caused by a deficiency in iron, vitamins or in the context of other diseases.
The specialist in hematology and internal oncology is the one who deals full-time with the diagnosis and treatment of the diseases mentioned above.

 


Tumor diseases are becoming more and more common - why is that?

In relation to age, most tumor diseases do not occur more frequently than in the past. Gastric carcinoma was still the most common cause of cancer death in the USA in the 1930s and has since decreased by a factor of around 8 in Germany, among other things thanks to improved preservation techniques for food. However, since most tumor diseases (fortunately) tend to appear at an advanced age and more and more people are reaching an older age, because, for example, cardiovascular diseases have been treated increasingly better in the last few decades, the number of new tumor diseases is increasing significantly in absolute numbers, for example in men compared to 1980 by 90%.

The risk of developing a tumor disease within one year is about 200 to 300 times higher for an 80 year old compared to a 15 year old, and dying from it is even 1000 times higher.

The increase in tumor diseases is therefore not a sign of increasing exposure to nutrition, environmental toxins, work, etc., but on the contrary, a sign of better health and a longer life. If men often died of heart attacks in their late 50s / early 60s in the 1970s, they could no longer develop tumors by the age of 70.

In addition, many tumor diseases can be treated better than, for example, 30 years ago, so that there are more and more people who have been cured of a tumor disease or are living with a tumor disease.

Around half a million people in Germany are currently diagnosed with cancer every year, and around 1.5 out of 80 million people living in Germany were diagnosed with a tumor less than 5 years ago.

 


Are tumor diseases curable?

Overall - that is, cheap and less favorable, early and advanced stages taken together at initial diagnosis - more than half of people are cured of a malignant tumor disease or do not die from the disease. In the majority of common tumors (breast, colon, cervical cancer, etc.) that are discovered at a very early stage, 90% or more of those affected can be cured by surgery, radiation and / or chemotherapy.

 


Are metastases curable?

For a few tumor diseases (testicular tumors, lymphomas, thyroid carcinomas, few liver metastases in colon tumors, etc.) yes. In the majority of so-called solid tumors such as lung cancer or breast cancer, a cure is generally no longer possible if metastases have occurred, but treatment and a life with the tumor disease are possible.
Sugar disease or a heart attack caused by vascular calcification cannot be cured either and must be treated for life. However, many people live for many years with often only minor restrictions on sugar or after a heart attack. It works
through more and better tolerated therapies also increasingly for many tumor diseases, although often not as long as for diabetes or arteriosclerosis.

Are tumor diseases hereditary?

Mostly no. Tumor diseases usually occur because of various avoidable or unavoidable events in the course of life, such as the normal exposure to the environment, smoking and many more. came together, which then led to a tumor disease. A few cancers are hereditary. For example, about 5-10% of women with breast cancer have a genetic change (BRCA1 / 2, CHEK2, etc.), which can also increase the risk of other tumors such as ovarian, colon, pancreatic cancer and lymphoma. In these cases, genes that are responsible for repairing naturally occurring damage to the genetic material are usually affected.

 


Can I reduce my tumor risk, e.g. by changing my diet or using food supplements?

Apart from too much alcohol or being significantly overweight, the modifiable part of the diet plays a less important role than is generally assumed. By avoiding sugar in food, no tumor can be prevented from growing - except in the test tube. In particular, there is currently no vitamin or trace element that has been proven to lead to a reduction in the tumor risk or even to make a tumor cell behave like a normal cell again. On the contrary, an increased incidence of tumor diseases has been observed, e.g. with an increased intake of some vitamins.

For example, smokers shouldn't consume vitamin A as well. If you smoke, the most effective way of reducing your tumor risk is to stop smoking, and not just for lung cancer.
Information on preventive examinations such as colonoscopy, gynecological and urological screening, skin cancer screening, etc. can be found in the respective fields.

Is there anything else you can do after a tumor has been operated on?

In the case of some tumors, irradiation is often additionally carried out before or after an operation (especially in the case of breast cancer, rectal cancer, lung cancer, etc.) in order to improve control at the site of the operation or the surrounding area.
With most common tumors, depending on the stage of the tumor, there is a high risk that tumor cells will have detached before an operation and distributed via the bloodstream or the lymphatic system. These tiny settlements cannot be represented or proven, not even by computer or magnetic resonance imaging (CT / MRT) or PET. In the case of a colon tumor with settlements in the local lymph nodes, for example, you know that if you didn't do anything after the operation, the tumor would come back in about every second person in the liver, lungs or elsewhere. With an infusion chemotherapy (which does not cause nausea and usually does not lead to hair loss), this risk can be cut in half. Such a therapy is called adjuvant = safety chemotherapy.

 


In the media you hear about a particularly precise irradiation method that is offered in Heidelberg, for example. Could that help me?

The usual irradiation is currently carried out with X-rays (photons), which are generated with the help of a linear accelerator with high energy. A planning CT is usually carried out beforehand and computer planning precisely calculates which fields must be irradiated and how, so that the target area receives the desired dose and the surrounding tissue is spared as much as possible.
For most tumors, the above-mentioned method is the most favorable, precisely because a relatively high radiation dose sufficient to kill the tumor cells is still achieved in the immediate vicinity of the tumor, where tumor cells can be found, for example, in lymphatic crevices. This applies, for example, to the irradiation of bones, the chest, the head, lung tumors and much more.
For some time now, there have been several methods of focusing the radiation dose more on the target volume. On the one hand, this includes stereotactic radiation.
The oldest and best-known method is the gamma knife, which is often used for the irradiation of a single or a few brain metastases or for benign brain tumors. A target wreath made of metal is attached to the skull bone and a (or a few) target volume is irradiated very precisely with a very high dose via approx. 200 individual cobalt sources. The closest gamma knife center to Oberhausen is in Krefeld.


A linear accelerator can also be used to irradiate with great precision. In the case of head tumors, this is done similarly to the Gamma Knife with a more complex targeting and planning technique.

A newer technique is intensity-modulated radiation therapy (IMRT), in which irradiation is carried out over an even larger number of fields and with field boundaries that can be changed during the irradiation. This results in a greater decrease in the radiation dose in the environment. In addition to tumors in the head area, this method is also partly established for prostate carcinomas, some tumors in the head and neck area and when tissues that are very sensitive to radiation are adjacent.

The current reports about new buildings in the media mostly concern irradiation no longer with X-rays but with charged atomic nuclei such as protons (under construction e.g. in Essen) or with heavy ions (in Heidelberg) e.g. carbon. These particles, which are very large in comparison with photons, have certain physical advantages if a greater depth of penetration and a strong dose drop behind them are desired. Treated tumors currently affect the base of the skull, some sarcomas, some special head and neck tumors and prostate carcinomas.

The advantage of all targeted therapy methods is also their disadvantage. As mentioned above, the surrounding tissue is less irradiated. This means that tumors in which the irradiation is supposed to kill off protrusions in the surrounding tissue are less suitable. This is true of the majority of solid tumors. In addition, a very complex tumor localization is necessary during the irradiation, because e.g. the prostate position can change depending on the filling of the rectum every day and sometimes even during the irradiation. Under unfavorable circumstances, targeted irradiation without position control would otherwise no longer adequately hit part of the tumor.

 


The newspaper reports on a targeted therapy using a gene analysis, e.g. for lung cancer by the Cologne University Hospital. Can I get that too?

In the case of some tumors, an analysis of the gene or protein structure of the tumor cells can be used to determine whether a certain therapy is effective or not. The best-known example of this is the (mostly existing) expression of hormone receptors in breast cancer. If the tumor has this, anti-hormonal therapy can be used. In the last few years, a large number of genetic changes and the resulting differences in protein levels have also been identified in other tumors.
There are now drugs against some of these changes, but not yet against many others. All characteristics against which there are already drugs are routinely tested by us outside of research projects and the corresponding drugs are given.
The best-known examples of this are Her2 expression in breast cancer for therapy with trastuzumab / lapatinib / pertuzumab / trastuzumab emtansine or the determination of KRAS / NRAS changes for the treatment of colorectal carcinomas with cetuximab / panitumumab.

Until a few years ago, there was little progress in lung cancer, so the discovery of new treatments is very welcome. As early as the late 1990s, this led to the development of drugs against an enzyme that regulates cell growth - the EGF receptor thyrosine kinase (EGF = Epidermal Growth Factor). Initially, however, these drugs were given unselected to all people with lung cancer. In this way it helped very few patients, but some people experienced serious side effects, which significantly delayed the approval of the first drug Gefitinib / ZD1839. The second drug, Erlotinib, was approved in 2005. It was only a good 10 years after the first studies that it was shown that the very good effect occurs almost exclusively in tumors that have a change (mutation) in the EGF receptor gene that leads to permanent activation of the receptor. You can think of it as if, for example, the insulin receptor was always active even without insulin. An activating mutation of the EGF receptor leads to the growth of lung tumors. In the meantime there are also other drugs such as afatinib that can still work if a mutation has occurred against which Gefitinib or Erlotinib are not effective.
The second target structure in lung tumors, for which there is already a commonly available drug (since 10/2012 crizotinib, soon also ceritinib, etc.) is the enzyme that is created by changing the ALK gene (ALK = Anaplatic Lymphoma Kinase) or even more rarely ROS1.
The above-mentioned gene changes - EGF, ALK and ROS1 - have in common that they are mainly found in adenocarcinomas of the lungs in non-smokers and there also not in all, i.e. in a total of significantly less than 10% of all patients with lung tumors.
Another new therapeutic method, which works by influencing the regulatory points of the immune system (PD-1, PD-L1), could also be helpful against squamous cell carcinomas, which are more common in smokers.

While a good 10 years ago genetic examinations using the snager method looked similar to the one on the left (source: genome.gov) and were very time-consuming and expensive, the development of improved, faster examination methods (catchphrase NGS = next generation sequencing) has made the cheaper examination more extensive Gene collections possible in routine diagnostics.
At the University Clinic in Cologne, but also in Essen and many other places, lung tumors have been systematically examined for various genetic changes for several years. The University Clinic Cologne has the most active press work and a cooperation with the AOK Rhineland / Hamburg, through which patients of the health insurance fund can have their tumor examined there. As a research project, such investigations, as already mentioned above, are extremely helpful for the development of new substances, and often do not provide any acute helpful information to a patient who now has a lung tumor who has already been tested for the effectiveness of existing drugs.

The result of such a test looks like this - if an additional mutation is found - for example (wild type = unchanged gene):

geneExonMutation statusFrequency%interpretationTherapy option
ACT14Wild type   
ALK21-25Wild type   
BRAF11,15Exon11 mutation10%inactivatingno
CTNNB13Wild type   
DDR23-18Wild type   
EGFR18,19,21Wild type   
EGFR20Wild type   
Her219,20Wild type   
KRAS2,3Wild type   
MAP2K12Wild type   
MET14Wild type   
NRAS2,3Wild type   
PIK3CA9,20Exon 9 mutation5%activating Check study
PTEN1-8Wild type   
TP535-8Wild type   

- Wild type = no (previously known) change means that there is no therapeutic approach here.
- Inactivating mutation means that there is usually either no therapeutic approach or, as is the case with KRAS / NRAS for colon tumors, therapy should not be undertaken.
- Activating mutation means that there is a possible therapeutic approach, but except for EGFR and ALK, which have already been tested, no approved drug for lung tumors.
In the above-mentioned case there is a newly approved phosphatidylinositol-3-kinase (PI3K) inhibitor (Idelalisib), but it only helps with lymphomas, especially chronic lymphocytic leukemia. Other PI3K inhibitors are in development, but like other inhibitors of the same signaling pathway that have been known for a long time (PIK3-AKT-mTOR), they have so far been of more importance in hematological diseases.
At the time of the finding, there was a phase II study with docetaxel +/- buparlisib in squamous cell carcinoma (the tumor was an adeno-CA) and a study with GDC-0941 / pictilisib for untreated patients , but the tumor was pretreated. None of the studies had a place of study in North Rhine-Westphalia.
In summary: if your health insurance company offers it or if the opportunity arises as part of a study, have your tumor examined. However, you should not be disappointed if this usually does not result in an acute treatment option. In the press it usually sounds different in the short version.

 


Are blood transfusions harmful ("bad blood")?

A program recently ran on ARD that warned against blood transfusions in sometimes dramatic words and triggered corresponding inquiries and uncertainty in many patients. The text accompanying the program reflects the situation much more realistically: if the values ​​for the red blood pigment hemoglobin (Hb) are very low, be it acute due to an injury, an operation with very high blood loss or an illness, a blood transfusion saves life and the benefits outweigh the benefits the risks are considerable.
It is also correct that alternatives to a blood transfusion should be considered.Operations should be carried out with as little transfusion as possible and, in the case of planned interventions, options for increasing the hemoglobin value, such as iron infusions, should be used. These findings are not really new, but are being pursued with varying degrees of intensity. Funding of such activities is to be welcomed.
In the above broadcast, however, especially cancer patients were warned against blood transfusions because they could weaken the immune system. It has been known for many decades that blood transfusions have an impact on the immune system, especially if they are given more frequently.
Before there were effective drugs to suppress the immune system after kidney transplants, researchers looked to find out which patients had received a kidney transplant particularly well and for a long time. These were the patients with many blood transfusions and the resulting immunosuppression.
At that time, however, whole blood or blood with only a relatively low depleted proportion of white blood cells and blood plasma was given to the blood donors, which are mainly responsible for the immunosuppressive effect. For some years now, only red blood cells without white blood cells (leukocyte depletion) and largely without blood plasma have been given, so that the immunosuppressive effect has decreased considerably. Whether it is still measurable is possible, but is controversially discussed for its clinical relevance.
Tumor patients with a low hemoglobin level usually have a disease or therapy-related weakness of the bone marrow for the formation of new red blood cells, which usually cannot be positively influenced by iron infusions or is even associated with iron overload.
The broadcast warns against the growth of metastases due to immunosuppression, but conceals that, for example, the growth factor for red blood cells (EPO) can also have a positive effect on the growth of metastases. Other alternatives to blood transfusions in this situation are not mentioned in the report (nor are they known), which makes the show not really helpful for those affected.
In summary, blood transfusions are now indispensable for many people and are considerably safer and have fewer side effects than they were years ago. Treatment of many leukemias or tumor diseases is only possible with blood transfusions.

Dr. med. Heike Steiniger, Axel Schneider, Prof. Dr. med. Jochen Schütte and Dr. Gerhard Kummer-
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