The Increasing Incidence of Cutaneous Malignant Melanoma (CMM) In Ireland

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How dangerous is CMM to the Irish population?

On average each year, about 375 new cases of malignant melanoma of the skin are diagnosed in Ireland each year, 235 in females, and 140 in males. Every year about 60 people in Ireland die of CMM, of these about 32 are female and 28 are male. This makes CMM the 6th most frequent category of malignant cancer in females, but only the 12th most frequent in males. European-age-standardised rates show it is also significantly higher among females than males, by about 52%. On average, an Irish female is estimated to have a 1-in-100 chance of developing this cancer by age 74, while males a 1-in-150 chance. CMM is now the most common cancer amongst Irish women aged 20-29 years. Irish females also have the third highest number of cases of this form of skin cancer in the EU, while Irish males have the sixth highest out of 15 other European nations. (EUCAN study Ferlay et al 1999). Rates of CMM amongst males in Northern Ireland are significantly higher than males in RoI (about 14%). Within the EU, a north-south gradient is evident with melanoma rates higher in the more northerly countries, especially Sweden. This is consistent with the hypothesis that intermittent sunlight exposure in sun-sensitive individuals may be a critical factor in melanoma development.

The condition becomes a significant cancer from about age 20 or 25 onwards and based on All-Ireland data, rates appear to rise gradually to about age 50, with a steeper increase in rates thereafter, reaching a peak in age-classes from 75 years onwards. Rates are substantially higher among females than males in all age-classes between 15 and 69 years, especially in the range 15-34 years. Although patterns are broadly consistent between NI and RoI, the age-profile of NI patients indicates, on average, earlier occurrence. It is interesting that mortality rates with European Age Standardised Incidence Rates (EASRs) do not differ significantly between males and females, despite higher incidence rates in females, thus reflecting lower average survival rates in males. On average, the risk of dying from melanoma of the skin in Ireland before age 75 is presently estimated to be 1 in 770 for women and 1 in 800 for men.

Risk Factors for Melanoma

Family history of melanoma

Dysplastic nevi

History of melanoma

Weakened immune system

Many ordinary moles (more than 50)

Ultraviolet (UV) radiation

Severe, blistering sunburns

Freckles

Fair skin

Diagnosis

Because melanoma usually begins on the surface of the skin, a trained health care worker often can detect it at an early stage with a total skin examination. A monthly skin self-exam is important for people who have any of the known risk factors, especially those with dysplastic naevi or those with a very large number of ordinary moles who are at an increased risk of developing a melanoma. A new scanning machine SolarScan, which can detect malignant melanomas early in their course without requirement for a biopsy has recently been launched in Australia. The new device works by capturing an image of a patient’s skin lesion and it was developed over a period of eight years. It apparently can diagnose a melanoma before it exhibits features detectable in a routine clinical examination. Around 1,000 Australians and 1,600 people in the UK are killed each year by melanoma. If detected early, melanoma has a cure rate of almost 100 per cent, however, late detection (melanoma > 3 millimetres deep) results in only a 59 per cent survival rate.

Doing a skin self-examination

(1) Stand in front of a full-length mirror in a well-lighted room, after a bath or shower and use a hand-held mirror to look at hard-to-see areas.

(2) Begin with the face and scalp and work downward. Check the head, neck, shoulders, back, chest, and be sure to check the front, back, and sides of the arms and legs. Check the groin, palms, fingernails, the soles of the feet, the toenails, and the area between the toes. A friend or relative may be able to help inspect areas such as the scalp and neck..

(3) Be aware of where your moles are and how they look. Look for any signs of change in outline, shape, size, colour (especially black) or feel of an existing mole. Also, note any new, unusual, or “ugly-looking” moles. Remember to check moles carefully during times of hormone changes, such as adolescence, pregnancy, and menopause. It is known that as hormone levels change, moles may also change.

Prevention of Melanoma

UV radiation from the sun and from sunlamps and tanning booths damages the skin and can lead to melanoma and other types of skin cancer. The intensity of UV radiation from the sun is greatest in the summer, particularly during midday hours. A simple rule is to avoid the sun or protect your skin whenever your shadow is shorter than you are. People who work or play in the sun should wear protective clothing, such as a hat and long sleeves. Many doctors believe sunscreens may help prevent melanoma, especially those that reflect, absorb, and/or scatter both types of ultraviolet radiation. Sunscreens are rated in strength according to a sun protection factor (SPF). Those with a SPF value of 2 to 11 provide minimal protection; those with a SPF of 12 to 29 provide moderate protection, while those with an SPF of 30 or higher provide high protection against sunburn. Sunglasses that have UV-absorbing lenses should also be worn. The label should specify that the lenses block at least 99 percent of UVA and UVB radiation. ROC offer a range of screens with MINESOL(TM) that protect the skin against the negative effects of UVAs and UVBs. People with a history of melanoma would be advised to look at their SPF 60 sunblock cream. Uvistat® is one of the top Irish sun care brands and was originally formulated for dermatologists to use with patients suffering from sun damaged skin. This product is marketed by Boehringer Ingelheim and offers balanced UVA and UVB protection, is hypo-allergenic, water resistant and lasts for about 85 minutes.

Methods of Treatment

Surgery is the standard treatment for this disease and it is necessary to remove not only the tumour but also some normal tissue around it in order to minimize the chances of metastases. The width and depth of surrounding skin that needs to be removed depends on the thickness of the melanoma and how deeply it has invaded the skin. If it is necessary to remove a large area of tissue, a skin graft may be done at the same time. Interestingly, new research suggests that people who have small melanomas, can be successfully treated with smaller excisions than was needed in the past. The Swedish research, published in the October 2001 issue of Cancer, found that patients with melanomas, 0.8 to 2.0 mms thick, did just as well if they had 2cms of healthy tissue removed rather than the accepted 5cms.

Sentinel Node Biopsy has now become part of the standard treatment for melanoma. Surgeons locate sentinel or guard nodes, by injecting a radioactive substance and a blue dye into the site of the melanoma. Once these agents have migrated to the sentinel nodes, the nodes can be identified by the presence of the blue dye and with the help of a hand-held radioisotope detector that beeps like a Geiger counter. Microscopic examination of tissue from the excised nodes determines whether the melanoma has metastasised from its original site. When metastasis has occurred, additional methods of treatment include chemotherapy, radiation therapy, and biological therapy may be used separately or in combination. One of the common combination regimens used more frequently is the so-called Darmouth regimen consisting of carmustine (BCNU), cisplatin, DTIC, and tamoxifen. Initial reports described response rates of 50%.

Biological therapy or immunotherapy uses biological response modifiers (BMRs) to reinforce the body’s immune system and guard against the recurrence of melanoma. For patients with a high risk of recurrence, interferon alfa (Roferon-A) is sometimes recommended after surgery. Interleukin-2 and melanoma vaccines are other BRMs under study. French scientists from the INSERM U 463 laboratories, in Nantes, have recently developed a treatment to boost the immune system of melanoma patients after they have had surgery to remove skin tumours. The treatment, is based on cells called TILS (tumour infiltrating lymphocytes) that produce a reaction against the cancer, has cut the number of relapses and increased the survival of patients who were given the treatment in early trials.

Genetic Therapy will become more prevelent as recent research from an international team of experts suggests that the majority of malignant melanomas have mutations in the BRAF gene. Dr Richard Wooster and colleagues, from the Wellcome Trust Sanger Institute in Cambridge, UK, undertook a genome-wide search for the genes that frequently prompt cancer-causing mutations. The authors state in the latest edition of Nature, that cancers arise due to the accumulation of mutations in critical genes that alter the normal programme of cell proliferation, differentiation and death. The researchers conclude that 66 per cent of malignant melanomas have mutations in the BRAF gene. The discovery of a new oncogene at such an early point in the project suggests that systematic searches through cancer cell genomes for mutations could provide a much clearer picture of the defects that underlie cancer. The results of their study follow an investigation that compared the BRAF sequence from 15 cancerous cell lines with healthy cells from the same donors. Significantly, the researchers found that the majority of the mutations can be located at a specific region of the BRAF protein. They disrupt the enzymatic activity of the BRAF protein and hence the growth of the affected cell. They conclude that the high frequency of BRAF mutations in malignant melanomas suggests that targeting this gene’s activity could represent a new treatment strategy for skin cancer.

What about the future?

Experts are optimistic for the discovery because the previously unknown mutation is very similar to another that helps cause a type of leukaemia. In trials, a drug, which blocks that gene, has already been outstandingly successful in treating leukaemia patients. Professor Mike Stratton, head of the Cancer Genome Project, also believes that this discovery could be a direct lead to new treatments for malignant melanoma. It could take about five years to identify a safe compound to use, followed by several years of clinical trials and it would be about 15 years before a drug became available. In the UK, 6,000 new cases of malignant melanoma are diagnosed each year and 1,700 people die from the disease. The number of new cases in the US is 54,000 and the number of deaths each year 7,400. Dr Mike Dexter, director of the Wellcome Trust, also expects information from the human genome to lead to a revolution in cancer treatment. This is an intriguing discovery that highlights the close association between genetics and cancer. The cause of this genetic mutation is unclear, but we do know that ultra-violet radiation damages DNA and triggers cancer. There is a direct link between sun exposure and melanoma, and people must remain alert to this danger.

Pointers of Melanoma

Large size – Most melanomas are usually at least 5 millimetres (about 1/4 inch) across when they are found; although many may be much larger. An unusually large mole may be melanoma.

Many colours – A mixture of tan, brown, white, pink, red, grey, blue, and especially black in a mole suggests melanoma.

Irregular border – If a mole has an edge that is irregular or notched, it may be melanoma.

Abnormal surface – If a mole is scaly, flaky, oozing, or bleeding, has an open sore that does not heal, or has a hard lump in it, it may be melanoma.

Unusual sensation – If a mole itches or is painful or tender, melanoma may be present.

Abnormal skin around mole – If colour from the mole spreads into the skin around it or if this skin becomes red or loses its colour (becomes white or grey), melanoma may be present.

Key facts about Malignant Melanoma in Ireland

* Average of 375 new cases per year, 1994-98: 235 in females, 140 in males.

* Average of 60 deaths per year: 32 in females, 28 in males.

* Age-standardised incidence rates about 50% higher in females than in males.

* 6th most frequent category for cancer incidence in females, 12th in males.

* 12th most frequent cause of cancer deaths in males, 15th in females.

* Median age at diagnosis 58 years for females and 60 years for males, lower than that for all cancers.

* Higher incidence rate among males in Northern Ireland (NI) than the Republic (RoI), by about 14%.

* Incidence rates higher than EU average for males and, especially, females.


write by Hypatia

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