Medical Oncologist

Singapore Oncology Consultant

Interviewed by Lian He Zhao Bao

Colon Cancer and Erbitux

Medical Oncologist

Singapore Oncology Consultants

TV Interview with Dr Hsieh Wen-Son on CNA AM Live!

Find out who is most at risk of developing head and neck cancer.

Visit- http://tinyurl.com/7j6s6nr

What Are Head and Neck Cancers?

A number of cancers can develop in the head and neck region.  The most common head and neck cancers in Singapore are nasopharyngeal cancer (NPC), squamous cell cancers of the head and neck (HNSCC), and thyroid cancer.  NPC more frequently occurs in men and is the seventh most common cancer in Singaporean men.  Thyroid carcinoma more frequently occurs in women and is the 10^th most common cancer in Singaporean women.  Due to the lower incidence of tobacco and alcohol use, HNSCC is less common in Singapore but there are still between 150 to 200 cases diagnosed and treated in Singapore annually. When head and neck cancers are diagnosed early, the results of available treatment are relatively good.  However, due to lack of public awareness of the signs and symptoms of head and neck cancers as well as the vague symptoms of head and neck cancers, these cancers are often diagnosed at relatively late stages, where the treatments required have lots of side effects and do not have the same good outcome as in the earlier stages.  Efforts to diagnose these cancers at earlier stages are ongoing to improve these results.

Figure 1.  Anatomy of the Head and Neck Area

The factors that predispose people to develop NPC are ethnic origin and family history, suggesting an inherited genetic tendency to develop the disease.  People of Southern Chinese ancestry are at highest risk (up to 30 times higher).  Studies in Hong Kong and Singapore have also found that people with a first degree relative with NPC have a 20 to 25 fold increase in risk of developing NPC, often within 5 years of a sibling developing NPC.  Men are twice as likely as women to develop NPC.  People of certain age groups are also more likely to develop NPC, with people in their late 30’s and early 40’s at highest risk.  NPC tumor cells almost always contain Epstein-Barr virus, an infection present in 95% of the adult population in the world.  Consumption of salted fish during childhood has been implicated as an environmental risk factor for NPC, as the cooking of salted meat or fish releases chemicals which are particularly harmful to the tissues of the nose in terms of creating cancer cells.

The greatest risk factor for developing HNSCC is the use of alcohol and of tobacco in form of cigarettes, cigars, and chewing tobacco.  Betel nut chewing, a practice common in Taiwan and India, is also associated with a high risk of developing squamous cell carcinomas of the mouth.   Recently, human papilloma virus (HPV), the virus which causes cervical cancer, has been found in up to 60% of the squamous cell cancers of the mouth and tongue.

In most people who develop thyroid cancer, the cause is unknown. Radiation exposure to the neck or inherited genetic predisposition increases the risk in only a minority of patients.    Women are three times as likely to develop thyroid cancer as men.

Symptoms and Screening

Symptoms of NPC include headaches, hearing loss (especially in one ear only), nasal stuffiness, facial pain, nosebleeds, difficulty opening the mouth, blurred or double vision, and a lump in the neck area.  Symptoms of HNSCC include a change in the voice, difficulty in or pain with swallowing, blood in the sputum, a growth or an ulcer that does not heal in the mouth or tongue, or a lump in the neck.  Symptoms of thyroid cancer include a lump in the front of the neck, near the Adam’s apple, difficulty swallowing or breathing, a lump in the side of the neck, pain in the neck or throat, and voice changes.  Thyroid Cancers are also increasingly more often found incidentally when ultrasounds or CT scans are done for other reasons.

Because of the fact that many of these symptoms are not specific for cancer, many patients ignore these symptoms or are treated for other problems such as infections for long periods of times before the correct diagnosis is made.  As a result, many of the patients who are diagnosed with head and neck cancers are diagnosed with late stage disease.  People with the symptoms listed above should seek prompt medical evaluation and treatment, especially if they belong to the high risk groups for developing these cancers.

People with early forms of these cancers often do not have any symptoms.  Although there are no accepted methods of routine screening for early detection of head and neck cancers, certain measures may be helpful.  For example careful examination of the mouth and tongue during routine dental treatments can help to find abnormal areas which may be cancerous.  Studies in Hong Kong and Singapore have shown that routine examinations of the back of the nose by an Ear, Nose, and Throat Specialist (ENT) can pick up NPC at an earlier stage.  However, it is not clear who should undergo such routine examinations and how often.  Currently, the most helpful way of diagnosing head and neck cancer early is still prompt evaluation of any suspicious symptoms which do not improve or resolve after 2 to 3 weeks.

Diagnosis

Diagnosis of head and neck cancers are made by careful examinations of the area which is affected and doing a biopsy of the area.  The examination of the nose, mouth, and throat area is done with fibro-optic scope, which is a flexible tube with a camera on the end that allows the specialist to see areas inside the body.   Diagnosis also involves CT scan, Magnetic Resonance Imaging (MRI), or Positron Emission Tomography (PET/CT), a new and more sensitive type of radiology scan involving the localization of tumor masses via the uptake of radioactively labeled sugar molecules

Treatment

Treatment and prognosis depend upon the location of the tumor, histological type of cancer, the stage (degree of spread), and the patient’s performance status (how well the patient is currently).  Very early HNSCC can be treated with surgery, radiotherapy, or laser therapy.  More advanced but still localized HNSCC (confined to the head and neck area) are often treated with surgery, which often involve taking out the whole area involved by the tumor followed by reconstruction surgery to preserve function and cosmetic appearance.  With tumors involving areas such as the vocal cord or back of tongue, where surgical removal of the tumor would result permanent loss of the ability to swallow or speak, chemotherapy with radiotherapy is often used to cure the tumor while preserving these important functions.  Drugs such as Erbitux are also combined with radiotherapy to increase the effectiveness of radiotherapy while minimizing side effects. Targeted agents such as Erbitux are important advances in the treatment of head and neck cancers.  Erbitux target the Epidermal Growth Factor Receptor (EGFR) pathway, which is important for the growth and survival of cancer cells.  Because normal cells are less dependent on the EGFR pathway, use of these medications leads to better control of the cancer with fewer side effects.  Combining Erbitux with radiotherapy greatly increases the chance of curing the tumor while causing no more side effects than the radiotherapy alone.

Fig 2:  EGFR pathway

A high percentage of patients with localized nasopharyngeal carcinoma (confined to the nose and the lymph nodes in the neck) can be cured with either radiotherapy alone or chemotherapy with radiotherapy.  Localized thyroid cancer is treated with partial or complete removal of the thyroid gland followed by administration of radioactive iodine.  Radioactive iodine treatment is also very effective in controlling thyroid cancer which has metastasized.

While new and better treatments for head and neck cancers are important in increasing rates of cure, prolonging life, and decreasing side effects associated with treatments, a greater impact can be made with higher rates of early diagnosis.  Creation of greater awareness of signs and symptoms associated with cancers in the head and neck region and development of screening tests are ongoing.

1. Introduction

Colorectal cancer is cancer of the large intestine (colon and rectum). The incidence of colorectal cancer has ranked second for both males and females in Singapore since 1983 and since 2003-2007 it has overtaken lung cancer as the leading cause of cancer incidence among Singapore males. It accounts for 17.8% of cancers in males and 14.5% in females, and is the most frequent cancer when both genders are combined (7277 cases in 2003-2007 compared to 5696 cases of lung cancer in the same period). The age-standardized incidence rate in Singapore Chinese is the highest among Chinese populations around the world and has exceeded those of whites in the US. They are also inching towards the rates in Australia, NSW, a region with one of the highest age-standardized incidence rates in the world. Among the ethnic groups, Malays and Indians have a risk between 20-60% that of Chinese. The age-specific rates for colorectal cancers begin to increase sharply in the 40-45 year age group and continues to rise after 50 years old.

2. What is colorectal cancer and what causes the cancer?

Most cases of colorectal cancer begin as non-cancerous (benign) polyps on the surface of the colon which can become cancerous over time. Polyps can appear mushroom-shaped or some can be flat recessed into the wall of the colon or rectum. Common types of intestinal polyps include adenomas, hyperplasic polyps and inflammatory polyps following a bout of ulcerative colitis. They develop when there are errors in the way cells grow and repair the lining of the colon. Most polyps remain benign, but some have the potential to turn cancerous. Removing them early prevents colorectal cancer. Yet, when colorectal cancer is found early, it is highly curable. This type of cancer occurs when abnormal cells grow in the lining of the large intestine (colon) or rectum.

3. What are the risk factors for colorectal cancer you can’t control?

Your risk of colorectal cancer depends on genetics and lifestyle. Factors you can’t control include:

• Age – most patients are older than 50
• Polyps or inflammatory bowel disease
• Family history of colorectal cancer
• History of ovarian or breast cancer

4. What are the risk factors for colorectal cancer you can control?

Some factors that raise the risk of colorectal cancer are within your control:

• Diet high in red, processed, or heavily cooked meats
• Being overweight (excess fat around the waist)
• Exercising too little
• Smoking or drinking alcohol

5. What are the signs and symptoms?

• Are there early warning signs for colorectal cancer?
• There are usually no early warning signs for colorectal cancer. For this reason it’s important to get screened. Detecting cancer early means it’s more curable.
• What are the symptoms?
• As the disease progresses, patients may notice blood in the stool, abdominal pain, a change in bowel habits (such as constipation or diarrhea), unexplained weight loss, or fatigue. By the time these symptoms appear, tumors tend to be larger and more difficult to treat
• If testing reveals a possible tumor, the next step is a biopsy. During a colonoscopy, your doctor will remove polyps and take tissue samples from any parts of the colon that look unusual. This tissue is examined under a microscope to determine whether or not it is cancerous.

6. Stages of colorectal cancer

What are the different stages in colorectal cancer?
If cancer is detected, it will be “staged”’ a process of finding out how far the cancer has spread. Tumour size may not correlate with the stage of cancer. Staging also enables your doctor to determine what type of treatment you will receive.

• Stage I – cancer has not spread beyond the inside of the colon or rectum
• Stage II – Cancer has spread into the muscle layer of the colon or rectum
• Stage III – Cancer has spread to one or more lymph nodes in the area
• Stage IV – Cancer has spread to other parts of the body, such as the liver, lung or bones. This stage does NOT depend on how deep the tumour has penetrated or if the disease has spread to the lymph nodes near the tumour.

7. What are the treatments available?

Can it be cured?

When colorectal cancer is detected early, it can often be cured
The descriptions of the most common treatment options for colorectal cancer are listed below

Is surgery always required?

The most common treatment for colorectal cancer is surgery to remove the tumor, called surgical resection. Part of the healthy colon or rectum and nearby lymph nodes will also be removed. While both general surgeons and specialists may perform colorectal surgery, many people consult specialists who have additional training and experience in colorectal surgery. A surgical oncologist is a doctor who specializes in treating cancer using surgery, and a colorectal surgeon has additional training beyond general surgery.

Some patients are able to undergo laparoscopic colorectal cancer surgery. This type of surgery involves smaller incisions and the recovery time is often shorter than standard colon surgery and the results can be as effective as conventional colon surgery in removing the cancer.. Less often, a person with rectal cancer may need colostomy and this is a surgical opening or stoma through which the colon is connected to the abdominal surface to provide a pathway for waste to exit the body; such waste is collected in a pouch worn by the patient. Sometimes the colostomy may be temporary to allow the rectum to heal but it may be permanent. With modern surgical
techniques and the use of radiation therapy and chemotherapy before surgery, most people treated for rectal cancer do not need permanent colostomy.

Some patients may be candidates for surgery on the liver or lungs to remove tumours that have spread to these organs. An alternative is to use radiofrequency ablation (RFA; energy in the form of radiofrequency waves to heat tumours). Not all liver or lung tumours can be treated with this approach. In some cases, RFA can be done through skin, in others RFA can be done during surgery. While this can allow preservation of liver and lung tissue that might be removed in regular surgical resection, there is also a chance that some portions of the tumour will not destroyed using this technique.

In general, the side effects of surgery include pain and tenderness in the area of the operation. The operation may also cause constipation or diarrhea, which usually goes away after a while. People who receive a colostomy may have irritation around the stoma. The doctor, nurse, or a specialist in colostomy management (called an enterostomal therapist) can teach the patient how to clean the area and prevent infection
What about radiation and chemotherapy?

Radiation therapy is the use of high-energy x-rays to kill cancer cells and is commonly used for treating rectal cancer because this tumour tends to recur locally. A radiation therapy regime (schedule) usually consists of a specific number of treatments given over a specific time. External beam radiation uses a machine to deliver x-rays to the site of the body where the cancer is located. Radiation treatment is given five days a week for several weeks and may be given at the hospital.

For rectal cancer, radiation therapy may be used before surgery (called neoadjuvant therapy) to shrink the tumor so that it is easier to remove or after surgery to destroy any remaining cancer cells, as both have shown value in treating this disease. One recent study found that pre-operative radiation therapy in combination with chemotherapy showed greater benefit compared with the same radiation therapy and chemotherapy given after surgery. The main benefits included a lower rate of the tumour coming back in the area where it started, fewer patients that needed permanent colostomies, and fewer problems with scarring of the bowel in the area where the radiation therapy was administered.

Chemotherapy is often given at the same time as radiation therapy (called chemoradiation therapy) to increase the effectiveness of the radiation therapy. Chemoradiation therapy is often used in rectal cancer before surgery to avoid

Chemotherapy is the use of drugs to kill cancer cells. Systemic chemotherapy is delivered through the blood stream, targeting cancer cells throughout the body. Chemotherapy is usually given by a medical oncologist in the doctor’s office or outpatient clinic. A chemotherapy regimen (schedule) usually consists of a specific number of cycles given over a specific time. Chemotherapy for colorectal cancer is
usually given into a vein, although some chemotherapy can be given as a pill.

Chemotherapy may be given after surgery to eliminate any remaining cancer cells. In some situations, for rectal cancer, a doctor will give chemotherapy and radiation before surgery to reduce the size of a rectal cancer and lower the chance of cancer returning.

Currently, six drugs are commonly used for the treatment of colorectal cancer in Singapore and they include fluorouracil (5-FU), capecitabine (Xeloda), irinotecan (Campto), oxaliplatin (Eloxatin), bevacizumab (Avastin) and cetuximab (Erbitux). The last two drugs are “targeted drugs”. 5-FU is often given by continuous infusion and may require a central line either in the form of Port-a-Cath or Hickman line. Many new drugs are in clinical trials and may provide future options. Some common treatments are:

• 5-FU infusion
• 5-FU infusion with leucovorin, a vitamin that improves the effectiveness of 5-FU
  Capecitabine, an oral form of 5-FU
• 5-FU infusion with leucovorin and oxaliplatin (FOLFOX)
• 5-FU infusion with leucovorin and irinotecan (FOLFIRI)
• Irinotecan alone
• Capecitabine with either irinotecan or oxaliplatin

Any of the above with either cetuximab or bevacizumab

The most common chemotherapy given for colorectal cancer may cause vomiting, nausea, diarrhea, or mouth sores. However, medications to prevent these side effects are available. Because of the way drugs are given, these side effects are less problematic than they have been in the past for most patients. In addition, patients may be unusually tired, and there is an increased risk of infection. Neuropathy (tingling or numbness in feet or hands) may also occur with some drugs. Hair loss is an uncommon side effect with the drugs used to treat colorectal cancer. Medications are available to ease most side effects, including nausea, neuropathy and diarrhoea. Most side effects usually go away once treatment is finished. If side effects are particularly difficult, the dose of drug may be lowered or a treatment

Targeted therapy is a treatment that targets specific genes, proteins or tissue environment that contributes to cancer growth and survival. These drugs are becoming important in the treatment of colorectal cancer.

Anti-angiogenesis therapy is focused on stopping angiogenesis, a process of making new blood vessels. A tumour needs the nutrients found in blood vessels to grow and spread, the goal of antiangiogenesis therapies is to “stare” the tumour. One such drug is bevacizumab (Avastin), a monoclonal antibody given with chemotherapy and it improves survival for patients with advanced colorectal cancer.

Another strategy is to give epidermal growth factor receptor (EGFR) inhibitor which is effective in shrinking or stabilizing the growth of colorectal cancer. Cetuximab (Erbitux) is a monoclonal antibody that blocks EGFR and it is usually given with chemotherapy. Recent studies show that cetuximab (Erbitux) is not effective in patients with tumours that have specific mutations (changes) to a gene called kras. Doctors using this drug should send the tumour for kras gene mutation and cetuximab (Erbitux) should be given to patients with tumours with non-mutated (sometimes called wild type) kras genes.

Chemotherapy can be given as adjuvant (preventive) after surgery or in advanced stage of cancer.

Colorectal cancer can spread to distant organs such as liver, lungs, peritoneum (tissue lining the abdomen) or to a woman’s ovaries. A combination of surgery, radiation therapy and chemotherapy (with targeted therapy) can be used to slow the spread of the disease and in many cases, can temporarily shrink a cancerous tumour. With metastatic colorectal cancer, it is particularly important to talk with doctors who are experienced in treating this disease. There can be different opinions about how to treat colorectal cancer, particularly in which combination of drugs. With current chemotherapies and targeted drugs, the median survival of patients with advanced colorectal cancer is more than 26 months.

8. Can Colorectal Cancer be prevented?

Can benign polyps removed by colonoscopy – When is this necessary?

Yes, colonic polyps are routinely removed by polypectomy during colonoscopy and sent for histopathology analysis. It is a simple surgery done during the procedure with minimal side effects.

 Soy foods have a lot of isoflavones, which is classified as phytoestrogens (weak estrogen-like compounds found in plants). Laboratory data show that isoflavones have a wide range of biological actions. They have an affinity for estrogen receptors in vitro, therefore potentially competing for the binding sites of estrogen receptors. In addition, they have been shown to be anti-proliferative, anti-angiogenic, anti-oxidative, and anti-inflammatory. These properties of soy have suggested many potential benefits in breast cancer. Nevertheless, there is some epidemiological evidence of an inverse association. Thus, no clear consensus has emerged regarding isoflavones and breast cancer.

 A number of reports have studied the preventive role of soy in breast cancer. We have consistently observed that country with high soy diet like Japan has historically much lower incidence of breast cancer than western countries. The incidence rate among Japanese immigrants rises as the length of time in the host country increases. This may possibly be due to both prepubertal or pubertal exposure as well as greater level of soy consumption among the Japanese as compared to the west. The Shanghai Women’s Health Study reported a cohort of more that 70,000 Chinese women using a validated food-frequency questionnaire showed strong evidence of a protective effect of soy food intake against premenopausal breast cancer (relative risk reduction of 43%). A similar study conducted in Singapore on 34,000 postmenopausal women reported a diet characterized by vegetables, fruit and soy has an early acting protective effect on breast cancer (relative risk of 30% and 43% with > 5 years follow up).

 Other studies on soy and breast cancer survivors were reported both in US and China.

A US study on a cohort of 1,954 breast cancer patients were prospectively followed up for >6 years. Increasing quintiles of soy intakes was associated with lower breast cancer recurrence compared to no intake among postmenopausal women and among Tamoxifen users. They concluded that soy isoflavones consumed at levels comparable to those in Asian populations may reduce the risk of cancer recurrence in survivors, even with Tamoxifen therapy. Moreover, soy does not appear to interfere with Tamoxifen efficacy.

 The most recent Shanghai Breast Cancer Survival Study reported a cohort of 5,042 breast cancer survivors in China in Oct 2009, aged 20 to 75 years old. With 4 years follow up, they reported the findings of an inverse correlation on mortality and recurrence among highest and lowest quartile of soy intake. (Relative risk of 29% for mortality and 32% for recurrence). The inverse association was evident among women with either estrogen receptor positive or negative breast cancer as well as both users and nonusers of Tamoxifen, in death and recurrence.  They also observed that women not taking Tamoxifen who ate the most soy seemed to have a better prognosis than women who took Tamoxifen and ate the least soy.  The associations did not vary by menopausal status, cancer stage, estrogen receptors of the breast cancer or intake of Tamoxifen. Of significance, the high soy protein intakes in this study were more than 15.3 mg of soy protein or more than 62.3 mg of isoflavones.

The relationship between soy and breast cancer is complicated by other factors. Most women living in Asia depend on soy as their main source of protein. They consume only small amounts of beef, chicken and pork. Also, compared to the average women in the US, the average Asian woman eats more fresh vegetables, is closer to her ideal body weight and is more physically active as well as less alcohol consumption. All these other factors may contribute to better breast cancer prognosis seen in the Chinese women in this study who ate the most soy.

  So far, these studies support the benefits of dietary soy in higher content of Asian diet while the probable benefit of supplemental soy in the western diet remains undetermined.

According to these population studies, soy consumption appears to be safe, and potentially  protective for women on breast cancer occurrence  as well as survival despite fears about estrogen-like effects.

 References

 1) Soy food intake and breast cancer survival. JAMA 2009 Dec 9; 302(22); 2437-43.

2) Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors: the Life After Cancer Epidemiology Study. Breast Cancer Research Treat 2009 Nov ;118(2) 395-405.

 3) A vegetable-fruit soy dietary pattern protects against breast cancer among postmenopausal Singapore Chinese women.  Am J of Clin Nutr 2010 91; 1013-1019.

 4) Adolescent and Adult soy food intake and breast cancer risk: results from the Shanghai Women’s Health Study.  Am J of Clin Nutr 2009; 89 (6); 1920-6.

Cancer of the bone is a general term used when cancer cells are seen in the bone. The cancer cells may be of several different types. Bone cancer begins when cells in the bone begin to change, grow without control, and no longer die, forming a mass called a tumor. Primary bone cancer is rare and accounts for less than 1% of all new cancers.  Osteosarcoma and chondrosarcoma each make up 35% of primary bone cancers, followed by Ewing’s family of tumors (10%), chordoma (5%), and malignant fibrous histocytoma (MFH)/fibrosarcoma (2%). The remaining cases represent other, rare types of bone cancer. Leukemias are cancers involving the marrow and affect production of blood cells. Lymphoma  is a term that refers to many, very different types of cancer of the lymph system. The lymph system carries lymph, a colorless fluid containing lymphocytes (white blood cells). These malignant lymph cells can spread to any organ in the body including the bone marrow. Multiple myeloma is a cancer of the plasma cells in the bone marrow, the spongy tissue inside of bones. Plasma cells are a part of the body’s immune system and produce antibodies that help the body fight infection. Myeloma often causes structural bone damage resulting in painful fractures. Therefore, primary bone cancer is a completely different type of cancer with very different treatments.

It is much more common for bones to be the site of metastasis (spreading) from other cancers, such as breast, lung, nasopharynx, thyroid, kidney, stomach or prostate cancer. Secondary bone cancer does not start in the bone, but is the result of cancer cells spreading to the bone from a primary tumour as described above. Sometimes only one area of bone is affected, but in some people a number of bone secondaries develop, often in different bones in the body. Not all the secondaries will cause symptoms or problems. Although a secondary bone cancer can occur in any bone in the body, the most commonly affected bones are those of the spine, ribs, pelvis, skull, and the upper bones of the arms (humerus) and the legs (femur).

    Symptoms of Secondary Bone Cancer

(i)      Bone pain

The most common symptom of secondary bone cancer is pain in the affected area. The pain may be a dull, persistent ache that often gets worse at night when the muscles are relaxed. There may also be swelling and tenderness in the area. If you experience this type of pain and it lasts for more than one to two weeks, it’s best to let your doctor know as soon as possible. Although bone secondaries can occur in several different bones at the same time, usually only one or two areas are painful.

(ii)     Weakened bones

Sometimes if a bone is weakened by cancer it will break (fracture), even if you have not had an accident or fall. This is known as a pathological fracture.

(iii)    Raised calcium level

When bones are affected by secondary cancer cells, increased amounts of calcium (the substance that helps to build bones) may be released into the blood. A raised level of calcium in the blood is called hypercalcaemia. It can cause symptoms such as tiredness, feeling sick (nausea), constipation, thirst and confusion. However, in many people hypercalcaemia is discovered with a blood test, before any symptoms develop.

(iv)    Pressure on the spinal cord

If secondary bone cancer affects the bones of the spine it can put pressure on the nerves in the spinal cord. This is called spinal cord compression and may cause symptoms such as pain, muscle weakness and sometimes tingling and numbness of the limbs. If the lower spine is affected, it may also affect how the bowel and bladder work. If you have weakness, pain, tingling or numbness in the legs it is very important to let your doctor know as soon as possible so that treatment can be given to prevent permanent damage.

(v)      Other symptoms

Sometimes secondary cancer in the bone can make you feel more tired than usual. Occasionally secondary cancer in the bone can affect the way that the bone marrow works. If the bone marrow is unable to produce enough blood cells you may become anaemic, and be more likely to get infections or to have bruising or bleeding.

    How Secondary Bone Cancer is Diagnosed   

Your doctor is likely to arrange a number of tests for you if they think it’s possible that your cancer has spread to the bones. You may worry that the cancer has come back or spread, but without the results of the tests you cannot know for sure. In this situation you may find yourself torn between believing there is some other cause for your symptoms and thinking the worst. The tests that can show that that you have secondary bone cancer include:

(a) blood test that may be done to check your general health and the level of calcium in your blood. Serum alkaline phosphatase is an enzyme made in the liver, bone and placenta. Abnormally high blood levels of alkaline phosphatase may indicate disease in bone or liver or bile duct obstruction.

(b) bone x-ray that can show up certain changes in the bone and may show that a secondary bone cancer is present. A cancer of the bone may not always show up on a plain bone x ray

(c) bone scan is a more sensitive test than a simple x ray and shows up any abnormal areas of bone more clearly. A small amount of a mildly radioactive substance is injected into a vein, usually in your arm. Abnormal bone absorbs more radioactivity than normal bone, so these areas are highlighted and picked up by the scanner as hot spots. The level of radioactivity used in the scan is very small and does not cause any harm to your body

(d) CT (computerised tomography) scan takes a series of x-rays, which build up a three-dimensional (3D) picture of the inside of the body

(e) MRI (magnetic resonance imaging) scan is similar to a CT scan, but uses magnetic fields instead of x-rays to build up a series of cross-sectional pictures of the body

(f) PET (positron emission tomography) – CT scan uses low-dose radioactive glucose (a type of sugar) to measure the activity of cells in different parts of the body together with CT scan. Before the scan, a very small amount of a mildly radioactive substance is injected into a vein, usually in your arm. Areas of cancer are usually more active than surrounding tissue and show up on the scan.

(g) Biopsy – is the removal of a small amount of tissue for examination under microscope. Only a biopsy can make a definite diagnosis of cancer in the bone. The sample removed from the biopsy is analyzed by a pathologist (doctor who specializing interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease). The type of biopsy (needle or open incisional) perform will depend on the location of the cancer. However, there are some cases where a biopsy may not be able to perform.

 If a Secondary Bone Cancer is Found Before the Primary Cancer, y0ur doctor may arrange for you to have tests to find where the primary cancer is in your body. Such tests may include mammogram to look for primary cancer in the breast, a chest x-ray and CT scan to check for lung cancer, a CT or ultrasound scan of abdomen and pelvis to look for kidney cancer or a prostate ultrasound and blood sample to check for prostate cancer.

  Treatment of Secondary Bone Cancer

A number of different types of treatment can be used to treat people with secondary bone cancer. The treatment you have will depend on which bone is affected, where the cancer first started (the primary cancer), how damaged and weakened the bone is and how the cancer is affecting you – the symptoms you have, size of the tumour and your overall health.

It is often a team of doctors will work with you to determine the best treatment plan. The aim of treatment for a secondary bone cancer is to: (i) relieve any symptoms and make you more comfortable (ii) reduce the number of cancer cells (iii) lower the risk of developing a bone fracture (iv) reduce the risk of developing a high calcium level in the blood

(i)       Relieving symptoms

Apart from using painkillers and other pain relieving drugs, the main method of relieving symptom is radiotherapy. Radiotherapy may be given by machine such as external beam radiotherapy or radioisotopes.

In the bone, osteoclasts destroy the old bone and osteoblasts deposit new minerals and build new bone. Cancer cells which have spread to the bone produce chemicals that change the activity of these cells, upsetting the normal balance. The osteoclasts (the cells that destroy old bone) become overactive and this commonly causes small holes in the bone. Bisphosphonates are drugs that restrict the action of the osteoclasts. Examples of bisphosphonates include zoledronic acid (Zometa^®), pamidronate (Aredia^®), ibandronate (Bandronat^®) and clodronate (Bonefos^®). They are bone strengthening drugs used to reduce the risk of fracture or hypercalcaemia and to relieve pain. Bisphosphonates may be given into a vein through a drip (intravenously) in the outpatient department, every 3–4 weeks. Some bisphosphonates can be taken as tablets, which must be taken on an empty stomach at least half an hour before food. Many clinical trials have shown the benefits of bisphosphonates in patients with secondary bone cancer in reducing these skeletal complications and hypercalcemia.

Recently, a new drug denosumab (Prolia^®), a fully humanized monoclonal antibody that blocks and inhibits activity of osteoclasts, decreasing bone resorption and increase bone density. This drug is showing promise in treatment of osteoporosis, bone metastasis, treatment induced bone loss and multiple myeloma.

  Types of Treatment for Secondary Bone Cancer

The type of treatment you have depends on where your cancer started. This is because the secondary cancer cells in the bone have come from where the primary cancer is and will usually respond to the same type of treatment as the primary cancer. To treat the cancer you may be offered:

• Chemotherapy – use of drugs to kill the cancer cells. Systemic chemotherapy is delivered through the bloodstream, targeting cancer cells throughout the body. Chemotherapy for bone cancer can usually be given as an outpatient treatment, which is treatment that can be given at a clinic or doctor’s office instead of being admitted to a hospital.
• Hormone therapy for breast and prostate cancer since they the growth of these cancer cells can be controlled by using hormones
• Combination of hormonal therapy and chemotherapy
• Surgery may be offered if x-ray shows that a secondary cancer has weakened a long bone such as the thigh bone (femur) or upper arm bone (humerus). If there’s a risk of the bone breaking, you may need an operation to strengthen it and prevent a break from happening. A metal pin or a locking nail (a nail with screws at each end) can be put down the middle of the weakened bone. This secures and strengthens the bone, holding it firm so that it won’t break. The pin or nail can stay in permanently to continually protect the bone. Whether this operation is appropriate for you will depend on which bone is affected by your secondary cancer.
• Vertebroplasty and kyphoplasty are procedures for patients with vertebral compression fractures. Vertebroplasty  is a procedure in which a needle is used to deliver a cement material into the collapsed vertebral body and thereby stabilize it. Ths procedure reduces vertebral body movement and the associated bone pain. Balloon kyphoplasty is a procedure that allowed placement of a needle in the collapsed vertebral body to place an inflated balloon which is then withdrawn to allow cement to be injected into the space. This ten stabilize the fracture and restore the height of the vertebra and reduce the bone pain

Regular communication with your doctor is important in making informed decisions about your health care. Consider asking the following questions of your doctor:

  What Questions to Ask Your Doctor?

• What type of bone cancer do I have?
• What stage is the bone cancer? What does that mean?
• Where exactly is the cancer located?
• Can you explain my pathology report (laboratory test results) to me?
• What are my treatment options?
• What clinical trials are open to me?
• Which treatment option do you recommend? Why?
• What are the possible side effects of this treatment, both in the short term and the long term?
• What is the expected timeline for my treatment plan?
• How will this treatment affect my daily life? Will I be able to work, exercise, and perform my usual activities?
• What follow-up tests will I need, and how often will I need them?
• What support services are available to me? To my family?

After examining the characteristics of her tumour, her medical oncologist, Dr Tan Yew Oo, recommended the use of an oral anti-cancer drug. Two months later, the woman was no longer coughing as much as she used to. Apart from acne rash on her face and diarrhoea at the start, she suffered minimal side effects.

Repeated chest X-Rays subsequently showed a dramatic improvement in her condition, with a reduction in size and number of cancer in both her lungs.

The woman joins a growing list of patients around the world who have benefited from a relatively new treatment strategy known as personalised medicine — whereby a patient is given a specific drugs based, among other things, on the genetic and molecular characteristics of the tumour.

In an interview with My Alvernia, Dr Tan explains what personalised medicine is all about and how it can help advanced lung cancer patients.

How serious is lung cancer as a health problem?

Lung cancer is the most common cause of cancer deaths around the world. About 1,500 people in Singapore were diagnosed with lung cancer in 2008. In that same year, more than 160,000 people were estimated to have died from the disease in the United States alone.

How do you define “advanced lung cancer”?

Lung cancer can be divided into Small cell lung cancer (SCLC), which accounts for less than 15% of lung cancers, and Non-small cell lung cancer (NSCLC), which comprises more than 80% of lung cancers.

Patients who are diagnosed with advanced NSCLC have either Stage III or Stage 4 of the disease and their chances of survival are very poor. Only about 8.4% of patients of Stage III patients and less than 1.6% of patients in Stage IV are expected to survive for more than five years.

Those with advanced SCLC are divided into limited and extensive stages. Less than 1% of those in the latter stage are expected to live beyond five years.

What are the standard methods of treating advanced lung cancer?

Chemotherapy, combined with occasional radiation if the patient is physically fit, is the usual course of treatment for advanced lung cancer.

However, studies have shown that such standard anti-cancer drug treatment – or what we call cytotoxic chemotherapy  —  while useful in some ways, is still insufficient in helping to boost a patient’s chances of beating the odds. The five-year overall survival rate based on such a treatment remains dismal – hence the need for us to turn to new therapies that have proven to be more effective.

What does a personalised approach to cancer treatment mean?

This means tailoring a patient’s treatment according to the biological make-up of the tumour as well as certain features of the patient.

As such, several factors –   his race, gender, smoking history, the type of lung cancer and whether there are mutations of the epidermal growth factor receptor (EGFR) gene in the cancer cells  – will be taken into account before the oncologist decides what is the best course of treatment for the patient.

Studies have shown that personalised medicine have  not only produced better results but also improved the patients’ quality of life.

Can you share with us some examples of personalised medicine?

Some advanced lung cancer patients may respond better when anti-angiogenic drugs such as bevacizumab – which kills cancer cells by starving them of their blood supply – are added to the chemotherapy process.

Others, such as extensive stage SCLC patients, may be responsive to drugs such as cisplatin and etoposide, coupled with radiation therapy.

If there is EGFR gene mutation in the cancer cells, drugs such as gefitinib or erlotinib can be used to kill the cancer cells in the lungs.

Recently, it was found that Asian patients who were non-smokers or were light smokers could be treated with gefitinib without having to undergo chemotherapy.

In what ways is the personalised approach to medicine different from the standard anti-cancer treatment?

In the past, patients with advanced lung cancer were treated only with combination cytotoxic chemotherapy and they tended to have uniformly poor results and poor survival rates.

Nowadays, the oncologist will first seek detailed information about the patient as well as examine closely the nature of the tumour in order to prescribe a treatment that is tailor-made for his/her condition.

How long does this personalised approach to treating lung cancer last?

The standard practice is to treat patients with advanced NSCLC with four to six courses of chemotherapy. If bevacizumab is deemed beneficial for the patient, this drug is given with chemotherapy and continued until the patient shows signs of improvement.

However, if there is EGFR gene mutation in the tumour, molecular targeted drugs  –  which target specific molecules involved in the tumour growth —  can be used instead of chemotherapy for as long as the patient is responding well to the drug. It can also be used as maintenance after the initial chemotherapy.

Radiation is recommended for some patients with Stage IIIA or Stage IV, where there is pain due to the cancer spread to the bones, or there’s obstruction of major blood vessels. The procedure varies according to the patient’s needs –  from 10 to 25 radiation treatments over two to five weeks.

Are there any side effects in using personalised medicine?

Personalised medicine has fewer side effects compared to past therapies. NSCLC patients who use the drug pemetrexed do not suffer from hair loss, extreme numbness or a significant drop in their white blood count  — which are normal occurrences during the standard chemotherapy treatment.

Drugs such as gefitinib or erlotinib can cause diarrhoea and acne rash but do not cause hair loss or a drop in blood count. Bevacizumab may cause high blood pressure or bleeding.

Does personalised therapy cost more than a standard cancer treatment?

Yes, although it also depends on how the drugs are used and how long the treatment lasts. On average, these drugs cost about  50% to 70% more than the standard cytotoxic chemotherapy. They may be used either on their own, or in combination with standard chemotherapy.

How long has personalised therapy been available in Singapore?

Personalised cancer therapy is an evolving trend in Oncology.  Some of these drugs have been available in Singapore for about six years,  but it is only recently that they have been better understood as to when they could be tailored for certain unique situations and clinical settings.

Many oncologists here, including my colleagues and I at the Singapore Oncology Consultants, are practising personalised therapies for cancer patients by using the latest evidence-based technology and drugs.

LUNG CANCER FACTS

-  Tobacco smoking has been linked to lung cancer since way back in the 1950s,  with nicotine acknowledged as the carcinogenic agent. Certain industrial chemicals, such as radon, vinyl chloride, nickel and chromium compounds and asbestos, may also have carcinogenic properties.

-  In Singapore, men are more likely to get lung cancer than women since there are more male smokers.

-  The most common reason for lung cancer causation is environmental factors. Hence, lung cancer will usually manifest in those who are in their 50s and 60s.

-   Unlike cervical cancer or breast cancer, there is no good, cost-effective screening test for early detection of lung cancer. Quite often, when a patient shows symptoms of the disease, he already has locally advanced or even widespread lung cancer. More than 75% of lung cancers are detected when they are in Stage III or IV.

- The most common symptoms of lung cancer are cough, breathlessness, weight loss and chest pain. The less common ones include chest pain, blood in sputum, bone pain, fatigue, difficulty in swallowing, wheezing and noisy breathing.

– Eating more fresh vegetables and fruits may lower the risk of getting lung cancer. Certain foods containing provitamin A carotenoids, particularly ?-carotene, may also be useful in keeping the disease at bay.