2-[18F]fluoro-2-deoxy-D-glucose

Lung cancer

Lung cancer is one of the most common and most lethal types of cancer affecting both men and women. It is one of the most widespread types of tumour in industrialised countries. The most common cause of lung cancer is smoking. Lung cancer accounts for 22% of all types of cancer in men and 8% of all types of cancer in women. Only 13% of patients diagnosed with lung cancer survive the next 5 years.

According to their biological properties and histological composition, malignant lung tumours are divided into two groups: small cell tumours (small cell lung cancer, SCLC) and non-small cell tumours (non-small cell lung cancer, NSCLC).

a) Small cell carcinoma is characterised by rapid growth and tends to form metastases. This disease is usually not suitable for surgical removal. It mostly shows good sensitivity to chemotherapy and radiotherapy. After the end of treatment, recurrence cannot be ruled out.

b) Non-small cell carcinoma usually has slower growth and leads to metastasis later. In the early stages of its development it is suitable for surgical removal, but only 20% of patients are operable. In more advanced stages of the disease, palliative chemotherapy and radiotherapy are used. The sensitivity of the tumour to chemotherapy and radiotherapy may be lower than in small cell carcinoma.

Cancer of the colon and rectum

The Czech Republic is one of the countries where cancer of the colon and rectum, known by the professional name colorectal carcinoma, occurs exceptionally often. Compared with other countries, we in fact have the highest incidence of this disease. Every year in the Czech Republic, a malignant tumour of the colon or rectum is diagnosed in about 7,800 people, and it is the second most common tumour disease in the Czech Republic in both men and women.

The vast majority of colon tumours are adenocarcinomas. These are tumours arising from the glandular cells of the intestinal mucosa. Other malignant tumours, e.g. lymphoma or carcinoid, may rarely occur in the colon.

In a very early stage the tumour is confined only to the intestinal mucosa; it may then gradually penetrate the entire intestinal wall. In a further stage the tumour cells may reach the surrounding lymph nodes. In the highest stage of the disease, distant metastases develop. These appear most often in the liver and lungs.

In the treatment of colorectal carcinoma, surgical treatment, anti-tumour chemotherapy and radiotherapy treatment are used; targeted biological treatment with so-called monoclonal antibodies also has its place. A combination of these treatment methods is often necessary.

Imaging using [¹⁸F]FDG-PET helps to determine the spread of the primary tumour in the area of the colon and rectum and to identify possible metastases in the liver or lungs.

Melanoma

Skin cancer is a disease that first affects the skin and, in some cases, can establish secondary lesions (metastases) in other organs. Some of these tumours can act destructively only at the site of their origin and thus damage not only the skin but also the surrounding mucous membranes, muscle, bones and cartilage; others are life-threatening through metastasis.

Malignant skin tumours are the most common malignant tumours of all. The most common of them are tumours arising from the structures of the most superficial layer of the skin – the epidermis. This is basalioma, a tumour that damages almost exclusively the site of its origin and its immediate surroundings. The same applies in most cases, but unfortunately not 100%, also to spinalioma. This can create distant secondary lesions elsewhere in the body and thus damage not only the surroundings of its site of origin but also other organs, and thus threaten the patient's life.

From this point of view, the most dangerous form of skin cancer is malignant melanoma, which initially manifests as an at first sight inconspicuous small spot and can end in extensive organ metastases, e.g. in the skin, lymph nodes, brain, lungs, liver, etc.

Four main types of malignant melanoma are described:

• superficial spreading melanoma — the most common type of melanoma
• nodular melanoma — this type grows very rapidly
• lentigo maligna melanoma — is often found on the face, especially in elderly people. It grows slowly and it may take years for it to develop
• acral lentiginous melanoma — is usually found on the palms, soles of the feet and around the nails

Melanoma can arise anywhere on the body, but it most often arises in women on the lower limbs and in men on the trunk, mainly on the back. It most often affects women aged between 25 and 29 years and accounts for 18% of all types of cancer in young people aged 15–39 years. About 20% of patients with metastases in the lymph nodes without distant metastases are treated surgically. Surgical removal of distant and isolated metastases in the brain or lungs can also considerably increase the chance of survival. Here the role of [¹⁸F]FDG-PET in identifying isolated metastases is very important for rational decision-making about their radical surgical removal.

Lymphoma

Lymphoma is a general term for a tumour disease of the lymphatic system. The cells of the lymphatic system multiply uncontrollably — the affected node, or groups of nodes, begin to enlarge and, importantly, cease to serve the body as a whole and lose their original functions. Because lymphatic tissue is present throughout the body, the disease can also affect organs other than the nodes. The classification of lymphomas is quite complex and has undergone significant development over the last twenty years. Currently the classification published by the WHO in 2001 is used. From a practical point of view, the most commonly used division is into two groups — Hodgkin lymphoma and the group of non-Hodgkin lymphomas. Hodgkin lymphoma is divided into a further 4 subtypes, which, however, from a practical point of view do not lead to different treatment. It is currently accepted that this type of lymphoma originates in B lymphocytes.

Non-Hodgkin lymphomas form a substantially more heterogeneous group. They are divided into lymphomas arising from B lymphocytes and from T lymphocytes. In Europe, almost 80% of lymphomas are B-cell lymphomas. In total we recognise about thirty separate types of lymphoma, which differ in how they arose, but also in how they behave and what prognosis they have. The most common types of lymphoma are diffuse large B-cell lymphoma (in the Czech Republic it accounts for more than 40% of all types of lymphoma), follicular lymphoma (also from B lymphocytes, accounts for about 20%), marginal zone lymphomas (very often occurring outside the nodes, most often affecting the gastrointestinal tract, accounts for about 8–10% of lymphomas), mantle cell lymphoma (a B-cell lymphoma, accounts for roughly 5%), chronic lymphocytic leukaemia-type lymphoma (a B-cell lymphoma, 5%), peripheral T-cell lymphomas (lymphomas arising from T lymphocytes; the individual subtypes together account for 10–15% of all lymphomas). Determining the exact type of lymphoma, which is often further divided into other variants, is extremely important, because individual lymphomas often have a different type of behaviour, meaning that sometimes it is necessary to start intensive treatment as soon as possible, while at other times the patient can simply be monitored and treatment started only in the event of difficulties.

Lymphomas are not among common diseases; they account for a mere 6% of all newly diagnosed tumour diseases. Hodgkin lymphoma accounts for 1% of all newly diagnosed tumour diseases and non-Hodgkin lymphomas for approximately 5%. Hodgkin lymphoma affects younger patients more, more often men aged 20 to 30 years, but the disease can also develop in older patients over 60 years of age. Non-Hodgkin lymphomas can occur at any age, again more often in men, with a median age at diagnosis of around 50 years.

The basis of the development of lymphoma is, as with other tumours, acquired genetic changes, in this case in lymphocytes, which lead to the uncontrolled multiplication of a tumour population of lymphocytes. The development of lymphomas can have a number of causes. One of the significant causes is considered to be weakening of the immune system (the system of defence capacity). Other causes can include infections. In the last ten years, a relationship of certain lymphomas with the bacterial infection Helicobacter pylori has been demonstrated, which leads in the stomach to irritation of the lymphatic tissue and thus to its possible damage, and subsequently a lymphoma may develop in some patients. There are studies that point to the influence of certain environmental factors, such as chemical solvents and certain other chemical substances.

Lymphomas are considered a disease that can occur anywhere in the lymphatic tissue. Therefore, in the vast majority of cases, the basic treatment approach in patients is so-called “systemic treatment”. This includes chemotherapy, immunotherapy and radiotherapy. Special forms of chemotherapy and immunotherapy include high-dose treatment with autologous transplantation of haematopoietic cells and allogeneic transplantation of haematopoietic cells.

An examination using [¹⁸F]FDG-PET following chemotherapy shows whether the treatment was successful, whether the cancer cells have been destroyed, and significantly helps the physician in deciding on the further course of treatment.

Head and neck cancer

The term head and neck tumours is used particularly for tumours of the swallowing and respiratory tract, affecting the lips, oral cavity, nose, paranasal sinuses, pharynx, larynx, salivary glands and local lymphatic tissue; in this area we also encounter skin tumours, tumours of the ear and orbit, and tumours of the thyroid gland.

The development of the vast majority of head and neck tumours is related to smoking. Although most of these tumours are relatively easy to examine clinically, a large proportion of patients come to the physician only in advanced stages of the disease. Because of the considerable variability of the site of origin, the manner of local tumour growth, distant spread and thus also the symptoms are considerably different. For optimal assessment, diagnosis and treatment, the site of origin of the tumour is very important.

In the countries of the European Union, head and neck tumours are the fourth most common tumours in men. The incidence of head and neck tumours in women is significantly lower than in men. The development of carcinomas in the head and neck area can be provoked by a wide variety of causes; environmental influences act most strongly here. The vast majority occur in cigarette smokers. Earlier occurrence is demonstrated with the simultaneous overuse of tobacco and alcohol. Alcohol is attributed the role of a co-carcinogen here – a substance that does not itself have the ability to induce tumour growth but, in the presence of a carcinogen, even a very weak one, induces and supports the development of a malignant neoplasm.

The clinical symptoms of the disease are varied. The clinical differences between individual tumours cannot be explained solely by their anatomical localisation but also by biological differences. Speech, swallowing, smell, breathing and other important functions important for quality of life and survival may be affected to various degrees. Patients with head and neck tumours require the approach of a team consisting of many medical specialties, usually consisting of otorhinolaryngologists – head and neck surgeons, radiologists, clinical oncologists, imaging diagnostics specialists and pathologists. Sometimes the participation of a maxillofacial surgeon, plastic surgeon, neurosurgeon or ophthalmologist is also necessary.

The localisation of the primary tumour influences the early onset of symptoms and thus early diagnosis, which influences the prognosis and therefore also the possibility of a radical surgical solution. The prognosis is worse along an ascending gradient from the lips through the oral cavity to the pharynx. However, more significant for the prognosis is the extent of the primary tumour at the time of diagnosis. For example, a small tumour in the area of the vocal cords and lips has a 5-year survival of up to 80% of patients. Advanced tumours, however, have a very poor prognosis, with 5-year survival not exceeding 10–15%. Second tumours are described in the head and neck area in about 40% of patients treated for a first carcinoma who have not stopped smoking. Local recurrences occur in up to 66%, and most recurrences appear within 2 years of the start of treatment. Distant metastases are not common and usually develop late.

It follows from the above that, alongside other imaging techniques, [¹⁸F]FDG-PET diagnostics provides essential information about the depth and extent of tumour involvement and about the regional lymph nodes. [¹⁸F]FDG-PET is also often used for the detection of tumour recurrence and for monitoring the response to therapy.

Breast cancer

Malignant breast tumour is the most common malignant tumour disease of women in the Czech Republic. The incidence of malignant breast tumours has been steadily increasing in recent years, but at the same time the mortality (the number of deaths) is decreasing. According to localisation, malignant tumours are divided into ductal type (arising from the milk ducts) and lobular type (arising from the glandular lobules). An early stage of breast cancer is ductal carcinoma in situ, which, thanks to modern examination techniques, we currently encounter often. Lobular carcinoma in situ develops in the lobules; however, we do not consider this type of tumour malignant (despite its name), but it represents a high-risk terrain for the possible development of an invasive tumour and it needs to be monitored regularly. Invasive ductal carcinoma occurs most often. Breast tumours can further spread to the local lymph nodes in the armpit = axillary lymph nodes and to distant organs. The extent of axillary node involvement is one of the factors that determines the further treatment approach.

Brain tumours

CNS tumours are generally divided into primary tumours, which arise from the cells of the brain tissue or surrounding structures (e.g. the meninges — meningiomas), and a much more numerous group of secondary tumours, which are secondary tumours (so-called metastases) whose original tumour can be anywhere in the body (e.g. breast, lung, kidney). Primary brain tumours represent approximately 1–2% of all malignant tumours. Every year in the Czech Republic about 700 people develop a brain tumour, with a slight predominance in men. The occurrence of this disease is more frequent in two age groups — children under 5 years and adults over 60.

About 5% of tumours are hereditary, mainly in patients of childhood and younger age (e.g. neurofibromatosis — the occurrence of multiple formations along the nerves and subcutaneous tissue). The question of the influence of external factors on the development of brain tumours is still being investigated; there is evidence for radioactive radiation, and among chemical substances, e.g. polychlorinated biphenyls (PCBs), ethylnitrosourea and vinyl chloride are suspected; viruses also cannot be ruled out.

Primary brain tumours are a very heterogeneous group. They most often arise from the cells of the supporting brain tissue (neuroglia) — so-called gliomas, which account for more than 50% of all CNS tumours. According to certain histological features and the behaviour of the disease, gliomas are, in simplified terms, divided into low-grade gliomas and high-grade gliomas.

A low-grade glioma grows slowly (over years), occurs more often in younger age groups (20–40 years), but its growth is not well demarcated from the surrounding healthy brain tissue and therefore it often cannot be completely removed surgically. It may remain the same for years or grow slowly. Over time, as part of further genetic disorders, it may transform into a more aggressive form of glioma.

A high-grade glioma can arise in 2 ways. Either by natural development, via further genetic disorders from a low-grade glioma, or directly from healthy neuroglia. These highly malignant gliomas are typically characterised by rapid aggressive growth (weeks to months), affect older individuals more often (over 50 years of age), have indistinct growth borders, complete removal is rather impossible, and recurrences often occur.

Among the common brain tumours it is necessary to mention meningiomas — predominantly benign tumours arising from the cells of the brain coverings; they are more common in women over 50 years of age. Despite their benign nature, however, by their pressure on the surrounding structures they can cause major health problems. Furthermore, tumours of the cerebrospinal nerves — neuromas, mostly benign. Pituitary adenomas, which manifest as disorders of hormonal functions. Among tumours mainly of childhood, medulloblastomas and ependymomas are known, which can spread via the cerebrospinal fluid.

Cancer of the ovary, cervix and uterus

Tumours of the ovaries and fallopian tubes represent about 15% of all malignant neoplasms in women. The biological behaviour of ovarian tumours and of the rare tumours of the fallopian tubes is very similar, so they are listed together, and the treatment of these tumours is identical. Ovarian tumours are divided into two large groups, epithelial tumours and tumours arising from other structures of the ovaries, so-called non-epithelial. These tumours usually affect younger women and have a very good prognosis; they account for at most 10% of all ovarian tumours.

Cervical cancer is diagnosed annually in 1,050–1,100 cases. Cervical carcinomas almost always have pre-tumour stages (so-called precanceroses). These are cell changes that are confined only to the epithelial layer and do not yet have the ability to metastasise. We divide them into low-grade changes — LG lesions, which in most cases the woman's own body is able to eliminate even without a surgical procedure, and so-called high-grade changes — HG lesions, which can be treated only by a simple surgical procedure.

Tumours of the uterine body are the most common tumours of the female reproductive organs, accounting for over 40% of all gynaecological malignant tumours. There are several types of malignant tumours of the uterine body. Primary malignant neoplasm of the uterine body (a tumour that arises directly in the uterus) is in 98% represented by endometrial carcinoma, which arises from the glandular cells of the endometrium. Because of the influence of oestrogens on the growth of tumours of the uterine body, this type of tumour can be described as a hormone-dependent tumour. In terms of the action of oestrogens, we divide endometrial carcinoma into two main types.

Type 1: the tumour arises on the basis of a relative or absolute increase in the level of oestrogens; this tumour is diagnosed in early stages and has a relatively good prognosis.

Type 2: this type of tumour does not arise on the basis of a relative or absolute increase in the level of oestrogens; it is diagnosed in later stages and has a worse prognosis than type 1, occurring rather in late old age.

Among the rare primary tumours of the uterine body are sarcomas (leiomyosarcoma and the very rare rhabdomyosarcoma). Alongside primary tumours of the uterine body, secondary (metastatic) tumours are also found here, which arise in other parts of the body and reach the uterine body during their spread.

[¹⁸F]FDG-PET imaging is important particularly for staging the disease and the involvement of the relevant regional lymph nodes, for finding possible metastases in other affected organs (lungs, brain, liver), for determining recurrences of the disease after surgical procedures and radiotherapy, and for monitoring the response of the patient's body to treatment.

Bladder cancer

Bladder cancer is the most common tumour of the urinary tract. In the Czech Republic it is the 6th most common tumour in men and the 13th in women. It is estimated that 250,000 new cases appear worldwide per year. The incidence in all industrial countries is slowly increasing and the Czech Republic is no exception.

The most common tumours in the bladder are tumours arising from the urothelium. In shape they most often have the character of papillary tumours, i.e. growths bulging into the cavity of the bladder. Papillomas may remain only in the epithelium — then they are so-called superficial tumours — or they may grow into the deeper layers of the musculature and are then called infiltrating carcinomas of the bladder. In addition to the most common papillomas and papillocarcinomas (which account for more than 90%), other types of tumour may also occur in the bladder wall. These are, for example, adenomas, adenocarcinomas, squamous cell carcinomas, undifferentiated carcinomas, sarcomas and lymphomas. Papillomas and some papillocarcinomas do not grow into the depth of the wall, i.e. into the musculature of the bladder. Some tumours, on the contrary, grow through the wall. The difference between benign papillomas and malignant papillocarcinomas is very small.

Cancer of the oesophagus and stomach

Oesophageal tumours are diseases arising from the malignant transformation of the squamous epithelium of the oesophagus (epidermoid carcinoma) or of the epithelium of Barrett's oesophagus or the mucinous glands of the oesophageal wall (adenocarcinoma).

Stomach cancer is a tumour arising from the gradual tumour transformation of the cells of the gastric mucosa, known by the professional name carcinoma. More rarely, other kinds of malignant tumours also occur in the stomach, for example lymphoma, sarcoma or carcinoid.

The disease occurs more often in men than in women and, according to age-specific incidence, the maximum occurrence of the disease is between 50 and 70 years. In the Czech Republic about 450 new cases of the disease are reported annually. The increasing incidence of adenocarcinoma is contributed to by the increase in gastroesophageal reflux disease (GERD). The occurrence of GERD is related to an increase in body weight. In connection with reflux in the distal third of the oesophagus, metaplasia of the squamous epithelium to columnar epithelium occurs — this precancerosis (pre-cancer state) is called Barrett's oesophagus. Adenocarcinoma occurs 30–40 times more often in patients with Barrett's oesophagus.

[¹⁸F]FDG-PET contributes particularly to the diagnosis of distant lymphatic or haematogenous metastases. Even more precise information is provided by the combined PET/CT method.

Liver cancer

Liver tumours are among the rare diseases. They occur more often in men, where the incidence is up to twice that in women. Malignant tumours arising from liver tissue are divided into several types: the most common is a tumour arising directly from the liver cells (so-called hepatocellular tumour). Another variant is a tumour arising from the tumour transformation of the cells of the bile ducts (so-called cholangiocellular tumour). There is also a mixed form of tumour, which is a combination of the two types mentioned above. In addition to the actual malignant disease, the liver is a frequent site of metastases of a wide variety of malignant tumours, for example cancer of the lung, breast, colon and rectum. A tumour or metastasis growing in the liver obtains its nutrition directly from the hepatic artery.

To determine the exact extent of the disease using [¹⁸F]FDG-PET diagnostics, involvement of the lymph nodes and the presence of metastatic lesions in other organs are also monitored.

Tumours of muscles and connective tissues

This is a whole group of malignant tumours that arise from connective tissues in a wide variety of places in the body, i.e. in adipose tissue, muscle, cartilage or ligamentous tissue anywhere in the body. A special group is formed by sarcomas in the abdominal and thoracic cavities. Sarcomas are always a serious disease that threatens patients mainly by local uncontrollable growth into the surrounding structures and organs and by metastasis, especially to the lungs.

Microscopic examination of the tumour tissue can distinguish more than forty different types of sarcoma, which differ in their aggressiveness and prognosis. Among the relatively least malignant are, for example, liposarcomas; among the most malignant are fibrosarcoma and malignant fibrous histiocytoma. Between them stand dermatofibrosarcomas, leiomyosarcomas, synovial sarcomas, rhabdomyosarcomas, chondrosarcomas, osteosarcomas, angiosarcomas and others.

Pancreatic cancer

Most pancreatic tumours arise in the ducts through which the pancreatic juices pass. This type of tumour is called pancreatic carcinoma. Only very rarely does a pancreatic tumour arise in the cells that produce insulin. When tumour cells metastasise outside the pancreas, they appear first in the surrounding lymph nodes. They then most often spread to the liver, peritoneum and lungs. These new tumour lesions have the same type of tumour cells as the original tumour.

It is important to note that in some cases of inflammatory disease of the pancreas (pancreatitis), increased uptake of [¹⁸F]FDG by the pancreas may also occur, which is then indistinguishable from a tumour disease.

Prostate cancer

Prostate carcinoma is the second most common oncological disease of men in the Czech Republic. In the years 1990–2001 its incidence increased by approximately 100%. Although the increase in mortality from this disease is by far not as rapid compared with its incidence, it is the third most common cause of death from a malignant tumour in men in the Czech Republic. The majority of malignant prostate tumours are carcinoma, and on histopathological examination adenocarcinoma is most often found. The presence of the disease is usually indicated by an increased level of prostate-specific antigen (PSA).

A distinction is made between so-called early prostate carcinoma, in which the tumour is localised within the prostate and its capsule is not disrupted, and so-called locally advanced prostate carcinoma, in which the prostate capsule is affected by the tumour, which can also grow into the immediate surroundings of the prostate. In generalised carcinoma disease, metastatic spread of the tumour is found. The most common target of metastases is the pelvic lymph nodes and the skeleton. However, it can (although far less often) also spread to other organs.

[¹⁸F]FDG-PET diagnostics is generally not very suitable for this type of tumour, because prostate tumour cells show a low level of glycolysis; however, it is already well suited for locating metastases in the lymph nodes, bones or distant soft tissues.

Kidney cancer

Several kinds of malignant growth affect the kidney. However, the most common tumour is renal adenocarcinoma. It accounts for 86% of all malignant tumours of the renal parenchyma. The tumour affects both sides approximately equally, and more rarely is found simultaneously on both sides. Renal adenocarcinoma can be of various sizes, from the size of a cherry to huge irregular masses weighing several kilograms.

The tumour most often grows from a small nodule in one of the renal segments. For a long time it grows expansively and encapsulated, deforming the shape of the kidney, and gradually, through its growth, the kidney enlarges. In further phases of its development the tumour begins to grow through its capsule into the tissue of the kidney, into its vascular supply, especially into the veins, where it can form so-called tumour thrombi. Via the bloodstream the disease can spread throughout the body and establish metastases. The bones, lungs and central nervous system are most often affected. Furthermore, the tumour spreads via the lymphatic route into the nodes around the kidney in the abdominal cavity, but also to distant nodal locations. The biological behaviour of metastases is poorly predictable. They may appear even 10–15 years after removal of the primary tumour.

Testicular cancer

Testicular cancer arises from the abnormal division and maturation of germ cells in the testis. Malignant testicular tumours represent about 1% of all malignant tumours in men; they occur at every age but most often appear between 20 and 35 years of age. Testicular tumours are a disease with a marked racial, geographical and age-related occurrence. Long-term studies show that 90% of all testicular tumours in the world are found in the white race, 6.6% occur in the black race and the rest fall to the other racial groups. An increased risk of developing malignant testicular tumours exists in men born with undescended testicles, so-called cryptorchids.

Before treatment of a proven testicular tumour, further examinations need to be carried out to clarify the extent of the disease, i.e. to determine the presence of possible further secondary tumour lesions in the body, using [¹⁸F]FDG-PET diagnostics.

Thyroid cancer

Thyroid cancer is among the rare diseases, accounting for 0.5–1% of all carcinomas. In thyroid cancer, malignant tumours of the papillary, follicular, medullary and anaplastic types are distinguished. Those particularly at risk are people exposed to higher doses of radiation or after radiotherapy of tumours in the head and neck area. Although thyroid cancer occurs rarely, it is the most common disease of the endocrine system.

[¹⁸F]FDG-PET diagnostics is very helpful particularly in cases where the whole-body [131]I scan is negative but the level of thyroglobulin is rising, or also for a better assessment of medullary thyroid tumours, where the level of calcitonin is rising but the initial imaging using DMSA (dimercaptosuccinic acid) or metaiodobenzylguanidine is negative.