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CANCER

Cancer Statistics Cancer Biology

Strategies Against Cancer Diagnosis of Cancer Cancer Treatment

Version 1.1 – April 2007 for internal use only page 1TP-ROW-01

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In female breast cancer is the ‘earliest’ type of cancer with a high incidence already in the 30ies. After the menopause the incidence still increases with age but with a far smaller slope.


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The graphic shows the differences in incidence of cancer between men and women. Lung cancer is the most common in men (smoking) whereas it is breast cancer in women.

There are a lot of environmental factors contributing to the development of cancer, but most of them are lifestyle related such as smoking and bad eating and drinking habits (bowel cancer, liver cancer).


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4% of all cancers can be related to occupational factors such as asbestos. Viral infections accounts for 10-15% of human cancer. Epstein-Barr Virus (EBV), Human Herpes Virus (HHV) and Human Papiloma Virus (HPV) are among the viruses most clearly associated with cancer. HPV for example is related to cervical cancer in women. Hepatitis B is a virus transmitted by blood and sexual contact. It causes hepatitis and cirrhosis. Hepatocellular carcinoma occurs at 100 times the frequency of non-infected individuals. Hepatitis C also causes chronic hepatitis with a greatly increased incidence of hepatocellular carcinoma. Both viruses have a worldwide distribution but are especially prevalent in China and Taiwan. The two viruses are responsible for the majority of primary liver cancer deaths worldwide.

Cigarette smoking has also been implicated in the development of carcinoma of the bladder, larynx, pancreas and kidney and is considered to be responsible for 35% of all cancer deaths.


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Programmed cell death is called apoptosis.


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A genetic damage caused by a carcinogen leaves a potential malignant cell. Under normal conditions this damage will be repaired by the system. If a repair is not possible the damaged cell runs into the programmed cell death, the so-called apoptosis. Even if this mechanism fails because of other genetic damages (inherited or caused by carcinogens) the immune system will kill these malignant cells.

Only if all mechanisms fail, this malignant cell is a potential initiator for a solid tumour. A tumour in the early stage is hardly detectable. It can exist and grow for a couple of years before it becomes clinical obvious or causes any symptoms. As the tumour grows, tumour blood vessels proliferate under the influence of tumour angiogenesis factors (VEGF, PDGF).


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One result of local invasion is that tumour cells can enter vascular and other channels (such as lymphatic) and metastasize. Lymphatic spread follows invasion of lymphatic channels, and the tumour cells grow in cords and clumps in the lymphatic vessels and lymph nodes. From there, spread to distal lymph nodes readily occurs. Haematogenous spread occurs after tumour cells have entered the vessels near the primary tumour. The tumour cells are then trapped in the next capillary network, which is in the lung or liver.


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Relief of pain (for example in bones and limbs) is a particular important aspect of the management of cancer. Patients often have more than one cause of pain. In terminal cancer patients this pain often requires a treatment with morphine.


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Diagnosis of hepatic metastasis by ultrasound. Several large metastases are shown in this transverse scan of the liver.

CT scan of a thorax, showing a solitary metastasis (arrowed) behind the heart.

MRI scans showing a large brainstem tumour.


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PET scan using 18-fluorodeoxy-glucose (FDG) in non-small cell lung cancer (NSCLC) showing widespread metastasis (clinically undetectable) including both hilae, right supraclavicular fossa and porta hepatis.

Some tumours produce proteins, which can be detected in the blood and may serve as a marker both of the presence of the tumour and its size.

The TNM system is widely used for solid tumours including cancers of the breast, head and neck, non-small-cell lung cancer and genitourinary cancers. It has obvious limitations, for example in disorders such as diffuse lymphoma where the disease is often generalized, and is clearly inappropriate for leukaemias.


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Because of the importance of radiation therapy for SIRT it will be dealt with in a separate module. There are some local methods, which are applied in the treatment of liver cancer and therefore are dealt with in the corresponding module ‘Treatment of Liver Cancer’.


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After cell division cells may enter growth phase, G1, in preparation of a subsequent division. This lasts for a variable period of time in different tumours. Alternatively cells may rest in G0 phase (not shown). After G1 the cell moves into the phase of DNA synthesis, S phase, in which the amount of chromosomal material is doubled. The cell then passes through a premitotic phase, G2, and then into mitosis, M, in which the pairs of chromosomes separate and the cell divides. As with other tissues, tumours are heterogeneous with respect to cell division. Chemotherapy drugs are usually only able to kill tumour cells in a certain phase of the cell cycle, so not all cells can be killed at the same time.

In experimental systems a given dose of a cytotoxic drug kills a given proportion of cells and not a given number. This fractional cell kill hypothesis is shown in the figure above. A single dose of a drug might kill 99.9% of cells and will do so whether 10,000,000 cells are treated or 10,000.


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Repeated doses allow a more effective killing of the tumour without killing all physiological important cells like the bone marrow. Between two cycles the bone marrow has time to recover, but also the tumour will grow again. The aim is to allow a maximum time for the physiological cells to recover but a minimum time for the tumour to re-grow.

Even in sensitive tumours single-agent chemotherapy is rarely curative. It is therefore logical to try and improve response rate and duration by the use of drugs in combination. The intention behind the combined therapy is to target tumour cells in all phases of the cell cycle and to circumvent as many resistance mechanisms as possible.


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Most schedules are derived from an informed empiricism. Where possible, drugs with synergistic killing effects should be used which is normally not known in practice.

The flow diagram gives the proportion of new cancer cases, which might be expected to benefit from drug treatment. In the end one in four patients with cancer benefits from chemotherapy, but only 1 of 10 is being cured.

The taxoids are based on an extract from the bark of the Pacific yew, Taxus brevifolia.


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Acute and often life-threatening medical problems may arise as a result of the cancer and its treatment.


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Many chemotherapeutic agents are associated with hypersensitivity reactions that may be life-threatening and which, for some drugs, are quite frequent. They are hard to predict but most patients who have had a reaction will do so again if re-challenged. Cisplatin and carboplatin for example cause those reactions in about 10% of patients. Vomiting is quite common so that antiemetic agents are given with almost all chemotherapy regimens. Immune suppression due to bone marrow depression is a big problem and leads to a high rate of post treatment infections which might kill the patient.


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