Medicine

Introduction

We wanted our device to have the greatest positive potential impact on the patient's life, so we contacted several medical doctors to assess whether this diagnostic device could be useful for the doctor and for the patient. In order to do so we designed a survey focusing on these main points:

• How useful would it be to have an early detection of metastasis or cancer?
• Do you think it would improve survival rates of patients?
• What do you think is worse: to have a false positive or a false negative?
• Which psychological effects do you think people will have from knowing to have such a feared disease from that early?
• How do you usually detect cancer? Which stages is it usually found in?
• Our device requires of a period of incubation of the blood sample, before introducing it into the chip (4-5h). Do you think it would be possible to implement it in the clinics? Would it require trained staff?

We met Dr. MD Heinz Läubli in person, whereas Dr. Alexis Cortot and Dr. Elisabeth del Amo sent us back the answers electronically.

Talk with Dr. MD Heinz Läubli from Universitätsspital Basel

How useful would it be to have an early detection of metastasis or cancer?

It depends on where the cancer comes from, especially if there is metastasis. The device would be useful if it leads to a better treatment. In patients with a localized tumor we would be able to use systemic therapy, like chemotherapy. Chemotherapy is used when the tumor cells are already disseminated.

Currently there is a device called Cell Search for detecting cancer. Are you using it?

No, we are not using it. In the last 10 years there has been many publications about secreted tumour cells, but it is still not completely standardized and it is not clear whether it is meaningful. You would need to talk with a pathologist about that. In Switzerland it is not used clinically and probably nowhere in the world.

Do you think it will be useful to treat residual illness (such as CTCs) after a treatment in a patient if they are not showing any metastasis?

The treatment would be useful in a biological sense, as it shows presence of residual disease, but to know if it is in a medical sense we need a clinical trial. Some studies have shown that healthy people also present CTCs, and no trial has shown whether it is useful to treat only if CTCs are present. However, if this is proved, it would be very useful to treat the disease while it is still possible.

How do you usually detect cancer? Which stages is it usually found in?

Patients are usually diagnosed during emergency situations: they either come with a pneumonia or another derived problem, or their family doctor sent them. When the patient arrives to oncology department, they have already done a biopsy. This is the best for the patient, as it is less disturbing than being referred immediately to oncology. The stage of detection depends on the screening method and the symptoms. By screening we can detect cancer in early stage. In many cantons the screenings are not covered by the insurance but they are highly recommended. However, this is not possible for all cancers. For instance, for lung cancer there is no screening and many patients come later to the doctor because of their lifestyle (eg. smokers). In these cases we unfortunately cannot help the patient. It depends on the organ and if there symptoms. For example, if there is disturbance of the sight, it is easily detected because the patient will consult immediately the doctor, but for symptoms concerning the intestines, it is harder to diagnose. We have some screening methods for colon cancer and at certain age colonoscopy is recommended.

Do you test the predisposition of the patients to have cancer with DNA tests?

It depends. If we have a woman of 28-30 years old with breast cancer we will certainly do a genetic test for BRCA1 and BRCA2. For a woman with 55-60 years old with no big family history of cancer, no. Currently much is decided with scores of how many relatives with cancer a patient has, and then we decide whether to make the test according to that. Genetic testing has advanced quite quickly, and with next generation sequencing we can do this tests quickly in pathology, so we can see if there is any punctual mutation that we can target in about 40 genes. Now we can detect a 2% of mutated cells from a tumor sample, which is not bad. In the future many more than this 40 genes will be analysed and we have to learn what to do with this information.

What do you think is worse: to have a false positive or a false negative?

Well... (laughs) A false positive can have a big impact on the psychological level and it’s very stressful for the patient, so it depends on the consequence of a positive test. If you can improve the treatment then it’s ok and you can accept the psychological impact. It’s the same with tumor markers, like CA23-29 for breast cancer. There are no trials that show that it’s useful to measure them and they might be stressful for many patients. It is also not nice to say your patient: “look, you have CTC but we don’t know what it means”. We need to do some trials first and also some counseling for the patients with this type of tests.

How many tests do you usually perform before you confirm that a patient has cancer?

Usually with a biopsy and an histology it is sufficient, especially if the pathologist says that there is invasive growth. Then, histochemistry will show the type of cancer. We can do a DNA test to find punctual mutations.

Our device requires of a period of incubation of the blood sample, before introducing it into the chip (4-5h). Do you think it would be possible to implement it in the clinics? Would it require trained staff?

Probably trained staff will be required in the lab. You can go to the hematology department of the hospital where you want to implement the test, as they are the most experienced with blood sample preparation.

Electronic survey - Answers from Dr. Alexis Cortot, pneumo-oncologist, Lille, France

How useful would it be to have an early detection of metastasis or cancer?

It would be useful if it can be done easily (blood sample), rapidly and if it detects metastasis earlier than imaging. However, once metastasis are found, the countdown has started and no cure is expected. One important point is to be sure that this test is really associated with CTC and metastasis. Some CTC may be found and never induce metastasis (if they are destroyed by immune system for example).

Do you think it would improve survival rates of patients?

It won’t reduce long-term survival. All patients with metastasis will eventually die from their cancer. Finding metastasis earlier can help to improve the efficacy of the treatments, since the tumor burden is reduced. So it may improve the 1-year or 2-year survival rate. In my opinion, it would be more interesting to use such a technique after surgery or radiation therapy, in order to detect residual disease and to give adjuvant treatment to those patients.

Which psychological effects do you think people will have from knowing to have such a feared disease from that early?

It will have negative psychological effects : you will tell earlier to patients that they’re going to die from their cancer. And it will be hard to believe for them since you won’t see anything on CT scans.

What do you think is worse: to think that you have cancer when you don’t, or to think you are healthy when you have cancer?

It depends on patients. For clinicians, I think it is more important that patients think they are healthy whereas they have cancer rather than the opposite. It is just due to the lack of sensitivity of our techniques. This is something we are used to. Patients know that our techniques are not perfect and that you need time to detect a relapse. Inversely, I think they would not understand that you tell them they have metastasis – that they’re going to die – whereas it is not true.

How do you usually detect cancer? Which stages is it usually found in?

For lung cancer : based on symptoms (cough, weight loss, chest pain) or screening by chest CT-scan (not systematically performed). Then diagnosis is made by getting a tumor sample through bronchoscopy. Most of the patients are discovered at stage IV.

Our device requires of a period of incubation of the blood sample, before introducing it into the chip (4-5h). Do you think it would be possible to implement it in the clinics? Would it require trained staff?

Yes it could be easily implemented in routine practice.

Electronic survey - Answers from Dr. Elisabeth del Amo, medical coordinator of PASSIR, Parc Salut Mar, Barcelona

I think your project is very interesting and can contribute to new fast diagnostic tests of cancer, which would improve the survival rate of patients. Regarding the psychological effects for the patients, it can be possible that people would fear to know to have the disease although on the other hand it can calm him down to know that the treatment would be in a very early stage. It is always possible to make them think that the test is not so important before confirming the diagnostic, hence reducing the initial stress. The probability of implantation in the hospital will depend on how the final setup of the system will look like, and if it would require of trained staff or nor. It would be interesting if the technique could identify different types of neoplastic cells (adenocarcinoma, lymphoma, and so on).

Summary and insights

We retained the following from their answers:

• For the medical approach, the goal prevails on the mean. Here what is essential is that this technique could allow an earlier treatment or better treatment. If we just inform the patient that he has cancer but no treatments are available, then no doctor on this planet would use the device.
• Our device could have a great potential, especially in the cases when cancer is discovered really late such as lung cancer.
• The proportion of false positive should be diminished as much as possible, since informing a patient that he has cancer when he does not have dreadful psychological effects.
• If the diagnostics of CTCs leads to an anticipated treatment, it could improve the survival rate of patients. This fact still need to be confirmed by clinical trials.
• Our assay needs to be robust in order to be used by doctors. The current device on the market CellSearch is not widely applied because of the lack of reproducibility of the results between laboratories.
• The incubation time required for our device is not a problem for routine laboratory practices.