responding differently to irinotecan
Transcription
responding differently to irinotecan
Issue No. 12 • MICA (P) 149/10/2009 AN NCCS BI-MONTHLY PUBLICATION September / October 2010 ...HELPING R E A DERS TO ACHIEV E GOOD HE A LTH Salubris is a Latin word which means healthy, in good condition (body) and wholesome. Higher concentration of SN-38 in blood causes neutropenia CPT-11 Higher concentration of SN-38 in intestines causes severe diarrhoea CE SN-38 SN-38 UGT1A1 UGT1A9 ENTERIC BACTERIA SN-38G SN-38G RESPONDING DIFFERENTLY TO IRINOTECAN UNDERSTANDING WHY EACH OF US RESPONDS DIFFERENTLY TO DIFFERENT DRUGS PAGE A2 In Other Words SALUBRIS September / October 2010 The genetic make-up of individuals has increasingly become the reason for more in-depth research into why human beings respond to drugs differently. VERONICA LEE speaks with A/PROF BALRAM CHOWBAY on his research on Irinotecan, which led to a change in its labeling by the Ministry of Health. I rinotecan has long intrigued A/Prof Balram Chowbay, Principal Pharmacologist, from the Laboratory of Clinical Pharmacology at NCCS, so much so that he now uses it as a model drug to learn more about the interactions between pharmacogenetics and pharmacokinetics of pharmacological agents. Prof Chowbay joined SGH in 1990 and moved over to NCCS in 1999. The quest into the varying responses had come during his early days in the ICU, when he had often wondered why patients responded differently to therapeutic agents when they are given a standard dose of drug. During that time, there was not much information about the role genes played in influencing drug action and how genomic factors caused variations in drug metabolism and response. PHARMACOLOGY OF IRINOTECAN IV CPT-11 SYSTEMIC CIRCULATION LIVER CPT-11 CES SN-38 CYP3A4 SN-38 UGT1A1 UGT1A9 NEUTROPENIA SN-38G ENTEROHEPATIC CIRCULATION CESs NPC CYP3A4/5 APC CPT-11 SN-38 EFFLUX TRANSPORTERS ABCB1 ABCC1 ABCC2 ABCG2 SN-38 SN-38G -GLUCURONIDASE SN-38G SN-38 SN-38G CPT-11 SN-38 COLON SMALL INTESTINE SN-38 DIARRHOEA With the knowledge that drugs are metabolized by specific enzymes that are encoded by specific genes, he began studying the variability present in genes that were responsible for encoding drug metabolizing enzymes and drug transporters involved in regulating the pharmacokinetics of drugs to assess the therapeutic outcomes for patients. Thus began an arduous journey into translational research. In a recent research, Prof Chowbay has found that Uridine Diphosphate Glucuronosyl Transferase 1A1 (UGT1A1), a type of gene in the liver, can affect the way Irinotecan, a drug that is used to treat colon cancer, is metabolized to its active metabolite, SN-38 in the liver. The UGT1A1 gene exists in two different forms, the normal (so-called wild-type form) and the homozygous variant form. Two different defective alleles, UGT1A1*6 and UGT1A1*28 are responsible for the low enzymatic activity of the encoded UGT1A1 protein in humans. Patients carrying two copies of the homozygous variant form of UGT1A1*6 or UGT1A1*28 allele have low amounts of the UGT1A1 enzyme in the liver and are unable to detoxify the SN-38 effectively. This leads to severe toxicity such as low white blood cells which compromises the defense mechanism in the body and severe diarrhea. PAGE A3 In Other Words SALUBRIS September / October 2010 Following studies done in the US and Japan, which suggested that Irinotecan toxicity is linked to variants of UGT1A1, such as UGT1A1*6 and UGT1A1*28, Prof Chowbay examined the situation in local contexts. It was found that the frequency of UGT1A1*6 was similar in all the Chinese, Malays and Indians at approximately 1%. However, the frequency of UGT1A1*28 was approximately 13% in Indians compared with 2% to 4% in Chinese and Malays. Similar to studies done abroad, the genotype distribution of UGT1A1*28 polymorphism in Indians are similar to Caucasians, while the Chinese have similar distribution as the Japanese. The study pointed to the fact that patients carrying this defective genetic constitution in the UGT1A1 gene can have higher levels of the cytotoxic metabolite of Irinotecan, SN-38 which is approximately 100 to 1,000-fold more active than Irinotecan and may be more susceptible to irinotecan induced serious toxicity. It also highlighted that ethnic differences to irinotecan induced toxicity exist in the Asian population. It has also helped doctors to better identify patients who will most likely tolerate Irinotecan vis-à-vis those who can’t when they send their patients’ blood samples for genetic test before receiving the drug. Explaining why he chose to embark on such a study, Prof Chowbay elaborated, “There is wide individual variability in the pharmacokinetics, pharmacodynamics, and tolerance to anticancer agents within a particular ethnic group and ever greater variability among different ethnic groups. Understanding the contribution of genetic factors to drug action has the potential to provide personalized therapy based on an individual’s genetic makeup and hence maximize efficacy and reduce adverse events. Thus it makes sense to study the inherent variability present in genes responsible for encoding the different proteins involved in regulating the actions of drugs.” Although the study has made some headway in clinical care of patients, Prof Chowbay revealed that the study had been a challenging one. To begin with, it was difficult to examine the influence of UGT1A1 polymorphisms on the pharmacokinetics of Irinotecan in the different ethnic groups in Singapore as the majority of patients belong to the Chinese ethnic group. Another challenge was working with the Health Sciences Authority and the Pharmacogenetics Advisory Committee to recommend a suitable package insert update for the drug based on his findings. This was effected early this year in Singapore. Despite the challenges, Prof Chowbay is able to envisage the light at the end of the tunnel. He sees the potential in continuing such studies. “Singapore, with its multi-ethnic population, can be regarded as a mini-global research hub. Studying the impact of pharmacogenetic factors on the pharmacokinetics of drugs in such a multi-racial society is fantastic. This is exactly what the industry is interested in and I think we should capitalize on this advantage that we already have,” he said. “Singapore, with its multiethnic population, can be regarded as a miniglobal research hub. Studying the impact of pharmacogenetic factors on the pharmacokinetics of drugs in such a multi-racial society is fantastic. This is exactly what the industry is interested in and I think we should capitalize on this advantage that we already have.” A/Prof Balram Chowbay Continued on page A4 UNDERSTANDING WHY EACH OF US RESPONDS DIFFERENTLY TO DIFFERENT DRUGS PAGE A4 In Other Words SALUBRIS September / October 2010 Continued from page A3. While it can be said that Prof Chowbay has made progress in his field and feels he has arrived to an extent, the straight-talking man thinks that there is a lot more to be done. “Healthcare cost is high and finding ways to select the right patients for the right drug will certainly help to reduce the financial burden on patients as well as decrease morbidity and mortality. Furthermore, this translational approach to treatment is becoming more important with the newly available molecularly targeted agents. The latter are drugs designed to hit certain deregulated pathways in cancer cells and they are very costly. Identifying patients who would benefit most from these new drugs is of paramount importance. This would depend on the identification of specific biomarkers that can tell us the nature of the activated or deregulated pathway in a patient’s tumor. Such information can aid in the selection of patients who would respond optimally to a selected targeted agent. We are still working on that.” IRINOTECAN GENOTYPE-DIRECTED DOSING IN ASIAN CANCER PATIENTS UNIFORM PATIENT POPULATION UGT1A1 *28/*28 + UGT1A1 *6/*6 UGT1A1 *1/*1 UGT1A1 *1/*28 UGT1A1 *1/*6 As an extension of his achievements, Prof Chowbay is now investigating how genetic polymorphism in genes affects clinical outcomes for breast cancer patients who are on tamoxifen therapy. While tamoxifen is a cheap and effective drug, its active metabolite, endoxifen, which is mediated by the CYP2D6 enzyme, is highly polymorphic. Interim studies have found that approximately 50% of the Chinese population carries the deficient CYP2D6*10 form which decreases CYP2D6 enzymatic activity. Such patients may produce limited amounts of endoxifen (the active metabolite of tamoxifen) and hence may derive limited therapeutic benefit from tamoxifen. “The goal is to identify patients who may not derive optimal benefit from tamoxifen and channel them to other treatment modalities,” he said. UGT1A1 *1/*1 UGT1A1 *28/*28 UGT1A1 *1/*6 UGT1A1 *1/*1 UGT1A1 *6/*6 UGT1A1 *1/*28 Aside from this and other on-going Phase 1 and 2 studies involving combinations of anticancer agents based on their mechanism of actions and pharmacokinetics among the ethnic groups in Singapore, of paramount importance to Prof Chowbay is the continual research on suitable biomarkers that will be useful in designing scientifically sound and early phase proof-of-concept type of clinical trials and treatment modalities. PARTIAL BREAST IRRADIATION: EVOLUTION OR REVOLUTION? About four Singaporean women are diagnosed with breast cancer daily. Not only is breast cancer already the number one cancer among Singaporean women, it is also the most rapidly increasing one. Many women owe their lives to life saving surgery in the form of radical mastectomy pioneered by William Halsted. However, although cured of breast cancer, many of these patients suffer from the physiological, psychological and emotional side effects of this mutilating, albeit necessary surgery. In the last 20 years, Breast Conserving Therapy (BCT) has supplanted mastectomy as the standard of care for a large proportion of patients, especially those diagnosed with early stage disease. In BCT, the breast cancer is excised with a rim of normal tissue. This is then followed by the application of radiation to the breast. Typically, five to six weeks of radiation is delivered daily to the entire breast. Long term results from many studies have convincingly demonstrated the safety and equivalent survival of BCT as compared to mastectomy with the distinct advantage of allowing patients to keep their breasts. This evolutionary (some would say ‘revolutionary’) leap in shrinking the extent of surgery for breast cancer is being mirrored in post-operative radiotherapy in BCT. The paradigm shift of Partial Breast Irradiation (PBI) is based on a better understanding of how breast cancers behave and their pattern of recurrence. Studies have shown that even in the absence of radiotherapy, nearly 80-90% of recurrences are in close proximity to the original tumour bed. Although pathological and imaging studies have demonstrated the presence of cancerous and pre-cancerous foci in other quadrants of mastectomy specimens, it remains unclear as to the natural history of these occult foci and their impact on disease recurrence in the same breast. Certainly, their progression rate is manifestly low as evidenced by the disproportionate high frequency of recurrence in the index quadrants as compared to that of ‘other-quadrants’. Furthermore, there is no evidence that pre-emptive treatment of these occult foci impacts on their progression; patients with Whole Breast Irradiation (WBI) have similar rates of ‘other-quadrants’ recurrence as the un-irradiated contralateral breast! Hence our understanding suggests that there may not be any need to irradiate breast tissue beyond the proximity of the tumour bed. One of the central tenets of radiotherapy is the avoidance of unnecessary irradiation to normal tissue or at least ALARA (As Low As Reasonably Achievable). This is an increasingly important issue when dealing with disease such as early breast cancer where most patients are expected to survive. Therefore, the minimization of radiation dose and hence, risk of long term iatrogenic side effects to surrounding normal tissue argues for the use of more curtailed radiation volumes, as long as equivalent disease control and survival are achieved. PAGE C1 Under The Microscope SALUBRIS September / October 2010 Dr Wong Fuh Yong Associate Consultant Department of Radiation Oncology NCCS Partial Breast Irradiation holds for both clinicians and patients alike, other attractions. For the patient, the attraction of a vastly shortened postoperative course of radiation and the decreased treatment burden it implies is immediately obvious. For the clinician, it is extremely appealing to consider a shortened treatment that places less demand on expensive treatment machine time and manpower, which can then be diverted for other purposes. Even more compelling is the ability to schedule post-operative radiotherapy in close succession to the surgery when disease burden is at its theoretical minimum. Contrast this with the delay of 4 to 6 months imposed by an intervening chemotherapy course that is increasingly required as part of a multipronged treatment of breast cancer. On top of this, the ability to deliver the radiation doses in fewer fractions (as few as one fraction) is supported from the standpoint of the radiobiology of breast cancer where fewer but larger fractions of radiation may be preferential to many but smaller fractions in terms of tumour cure probability. Continued on page C2. PAGE C2 Under The Microscope SALUBRIS September / October 2010 PARTIAL BREAST IRRADIATION: EVOLUTION OR REVOLUTION? Continued from page C1. Figure 1: Intrabeam applicator (TARGIT trial) placed in tumour bed immediately after tumour excision. The practice of PBI is not without its share of pitfalls and criticism. Initial studies with interstitial implants and single electron fields were met with increased local recurrences. The hard earned lesson from these studies is that patient selection is critical. Earlier trials have failed because of their lack of stringent excision margins assessment and inclusion of tumour with pathological characteristics that portends a more aggressive biological course. This knowledge has led to further finetuning in the eligible criteria for patient inclusion in latter trials, the results of some of which has recently became available. As an example of how accelerated PBI can be achieved, Intra-operative radiotherapy (IORT) epitomizes the benefits of PBI. Like the name suggested, TARGIT potentially delivers all the radiation that is needed in a single fraction immediately after surgical excision of the breast cancer while the patient is still under anaesthesia (Figure 1). The way the delivery is achieved virtually eliminates any possibility of missing the tumour bed and the surrounding normal tissue that does not need radiation can be either shielded, retracted away or have their exposure minimized from the steep dose fall-off from the radiation probe. As an illustration, the publication of the TARGIT Trial (TARGeted Intraoperative radioTherapy) (JS Vaidya et al, Lancet 2010) has generated substantial interest from both the media as well as among the medical fraternity. PBI, in all its varied forms, potentially represents the most significant advancement in the thinking and delivery of post-operative radiotherapy for breast cancer. In line with NCCS commitment to deliver the most up to date and cost effective treatment to our patients, we are making plans to introduce PBI and IORT as therapeutic options for a carefully selected group of patients in the not too distant future. The TARGIT trial demonstrated that with careful patient selection, it is possible to achieve rates of locoregional disease control and survival using PBI that is indistinguishable from WBI without an increase in acute and medium term side effects. The authors were prudent to acknowledge the need for “longer term followup of our own trial to monitor the clinical appearance of new primary tumours outside the index quadrant or delayed recurrences inside the index quadrant” although in the accompanying editorial, Azria and Bourgier opined that “in elderly patients, we are already convinced that accelerated partial-breast irradiation is the new standard and intraoperative radiotherapy an excellent approach.” While many trials are still on-going to test PBI against WBI and we await their long term results with interest, the American Society for Radiation Oncology (ASTRO) in their 2010 guidelines already allows for a well selected group of low risk patients to receive PBI outside of a clinical trial. SOFT TISSUE SARCOMAS PAGE C3 Spotlight SALUBRIS September / October 2010 DISTRIBUTION AND AETIOLOGY OF STS Soft tissue sarcomas (STS) are rare malignant tumours that arise from mesenchymal tissues. They comprise only of 1% of all malignancies and are a heterogenous group of tumours that are generally classified based on the tissues that they resemble. STS arise from the extremities in 50%, the viscera in 20%, retroperitoneum in 15%, trunk in 10% and other sites in 20%. Occasionally, when they arise from the gastrointestinal track or stromal tissue, they are known as Gastrointestinal Stromal Tumours (GIST). GISTs, whilst being mesenchymal in origin, are distinct as they express a growth factor receptor known as c-kit. They stain positively for CD34 and CD 117, making them identifiable on histology. As this growth factor receptor has tyrosine kinase activity, tyrosine kinase inhibitors (TKIs), such as imatinib and sunitinib, have considerable activity in targeting GISTs. The prognosis of these tumours is determined by the size and grade of the tumour, its mitotic index and the site of the tumour. GISTs arising from the stomach and rectum tend to have a poorer prognosis compared to small bowel GISTs. STS may be associated with several syndromes. These include neurofibromatosis, Gardner’s syndrome (familial adenomatous polyposis syndrome with intra-abdominal desmoids), Li-Fraumeni syndrome (p53 mutation) and tuberous sclerosis, amongst others. Gentic abnormalities in the form of chromosomal translocation are displayed by some STS, for example, synovial sarcoma t(x; 18) and myxoid liposarcoma t (12; 16). Other risk factors for the development of STS include previous radiation therapy for other cancers, for example, head, neck or breast. This sarcoma often develops many years later, not within the first few years after the radiation therapy has been administered. The secondary sarcoma that develops as a result is usually a high grade tumour (90%), and often an undifferentiated sarcoma. Trauma or chronic lymphadema may also result in the development of a STS, as is exemplified in the Steward Treves syndrome. HISTOLOGY OF STS Certain types of STS occur more commonly in children and these include rhabdomyosarcomas, Ewing’s sarcoma and osteosarcoma. Whilst the principles for treatment remain the same as STS that arise in adults, and the prognosis is still highly dependent on the tumour biology, which is influenced by the histology and grade of tumour. Some childhood sarcomas, for example, fibrosarcoma, are very chemosensitive and may show a significant response when accorded the appropriate treatment. The commonest histologic type of soft tissue sarcoma in adults is that of malignant fibrous histocytoma (although this has recently been reclassified as undifferentiated pleomorphic sarcoma by the current WHO classification). This comprises of 25% of all STS and is followed by liposarcoma at 14%, sarcoma (not otherwise specified) at 12%, leiomyosarcoma at 8%, malignant schwannoma and dermatofibrosarcoma protuberans (DFSP) at 6% each, synovial sarcoma at 5% and fibrosarcoma at 4%. By Melissa Teo Consultant Department of Surgical Oncology NCCS The highly aggressive angiosarcoma makes an appearance at 2%, whilst rhabdomyosarcoma and epithelioid sarcoma are seen at frequencies of 2% and 1% respectively. Histological subtype is an important prognostic factor, as some sarcomas tend to have very aggressive courses, with a great propensity for metastasis compared to others. Other contributing factors for prognosis include the grade, the size, the depth (superficial/ deep) and the location of the sarcoma. High grade tumours are characterized by poor differentiation, cellular pleomorphism, multiple mitoses and significant necrosis and often have a dismal prognosis, with less than half of these patients attaining long term survival. Nodal metastases are rare in STS, as most of these tumours metastasize haematogenously. 3% of all STS do have nodal metastases, with angiosarcomas, epithelioid sarcomas, rhabdosarcomas and synovial sarcomas have an increased chance of contributing to this statistic. The malignancy of each tumour is characterized by their local invasiveness and their likelihood for metastasis. Beyond examination of the histological subtype and grade of the tumour, other proliferation indices, such as Ki-67, may also give an indication of the aggressiveness of the tumour. The level of this proliferation marker has been shown to be inversely proportional to survival, with higher levels leading to a more dismal outcome. Continued on page C4. PAGE C4 Spotlight SOFT TISSUE SARCOMAS SALUBRIS September / October 2010 Continued from page C3. PRINCIPLES OF BIOPSY/ OBTAINING HISTOLOGY Establishing a diagnosis is hence paramount to predicting prognosis and administration of the appropriate treatment. In most instances, a biopsy is required and this can be obtained in a closed fashion, through a trucut core needle biopsy, or as an open biopsy, either incisional or excisional. It is important that this biopsy is taken by one who understands the behaviour and the treatment concept of STS, as the biopsy pathway and incision needs to be placed such that the entire “contaminated” track can be completely excised during the definitive surgery. In the extremity, this includes making a longitudinal incision when performing the biopsy. Subsequent definitive surgery can then easily incorporate the first incision when a compartmental resection is required. Deep to fascial extremity sarcomas should be resected en-bloc with the components within the compartment in which it lies. This entails resection of the muscles from origin to insertion. Excisional biopsy, with complete resection is usually only performed for the small (<5cm), and superficial lesions of the extremity and trunk. Most other biopsies do not attempt to remove the entire lesion, as wide resection with at least a few centimeters of clear margin is necessary for adequate surgical management of a STS. Low grade tumours may often be sufficiently treated surgically, if a complete resection can be guaranteed. High grade tumours, however, often require addition therapy in the form of radiation and/or chemotherapy. These may be administered in a pre-operative or post-operative setting, without conclusive studies favouring the scheduling of one over another. Function and quality of life are issues that need to be considered, especially for extremity sarcoma. Neoadjuvant treatment with chemotherapy and radiation are often used, in order that limb salvage surgery can be performed safely. Staging of RPS depends on the location of the primary sarcoma. Extremity sarcomas are often best evaluated with a magnetic resonance imaging (MRI) scan, whilst RPS and trunk sarcomas may be adequately visualized on computed tomographic (CT) scans. CT scans of the chest and liver to exclude common sites of metastases may be useful, especially for high grade lesions. RETROPERITONEAL SARCOMAS (RPS) RPS comprises of 15% of STS. As many of the lesions are deep-seated, most patients present in an advanced stage, remaining asymptomatic until the mass is well over 10cm. The patients may present with a vague abdominal mass, pain or symptoms of partial bowel obstruction. They may also develop symptoms secondary to a large mass in the retroperitoneum, reaching down to the pelvis, such as urinary frequency and urgency and lower limb swelling. Occasionally, RPS are discovered as incidental findings on imaging performed for the investigation of other conditions. A CT scan of the abdomen is often the modality of imaging used to evaluate an RPS. In addition to the location, characteristics such as a significant fatty component in the tumour may allude to the diagnosis of an RPS. The commonest RPS histology are leiomyosarcoma and liposarcoma, with well-differentiated, low grade tumours faring much better than their poorly- differentiated, high grade counterparts. Other differential diagnoses that should be considered include adrenal tumours such as pheochromocytoma and neuroendocrine tumours, and renal tumours. When reviewing the CT scan, it is important to determine the possible involvement of the ipsilateral kidney and large vascular structures such as the inferior vena cava, the aorta and its branches. A differential renal perfusion scan may be obtained pre-operatively to ensure adequate function of the contralateral kidney if a nephrectomy is anticipated. Similarly, the urinary markers for a phaeochromocytoma should be obtained to exclude that diagnosis prior to subjecting the patient to surgery. Many RPS lie in close proximity to adjacent organs and a clear margin is often not possible, without performing an en-bloc multivisceral resection of contiguous organs. A complete resection is critical in decreasing the risk of local recurrence, both in low and high grade tumours, although metastasis is much more common in the latter. High grade lesions may be more commonly associated with decreased resectability. The roles of chemotherapy and radiation in the management of RPS have been extensively explored but appear more limited than in extremity and head and neck sarcomas. The presence of small bowel, as well as other organs lying in close proximity to the radiation field hinders the delivery of a high dose of radiation. Pre-operative radiation has been advocated as a result, as the presence of the tumour prevents the small bowel from falling into the radiated field as much. In addition, oxygenation to the undisrupted field is expected to be better, allowing for a decreased dosage of radiation, perhaps leading to a better sterilization of the predicted resection margins. SUMMARY Soft tissue sarcomas are rare malignant tumours that can occur in the extremities, the retroperitoneum, the trunk and the viscera. Prognostic factors include the histological subtype, the grade, size and depth of the tumour, and importantly, the completeness of resection of the sarcoma with clear margins. Establishment of a diagnosis is often conducted through the performance of a carefully planned core, incisional or excisional biopsy, whereby the incision can be easily incorporated in the definitive surgery. Low grade lesions are often adequately treated with complete surgical excision whilst high grade lesions often require additional radiation and/or chemotherapy, either in the pre- or postoperative setting. ENGAGING THE YOUNG FOR LICAM 2010 PAGE A5 Community SALUBRIS September / October 2010 How are you at risk of liver cancer? Have you been vaccinated against hepatitis B virus? If the answer is "No", perhaps it is time to find out more. S ince 2008, the National Cancer Centre Singapore has, through its Liver Cancer Awareness Month (LiCAM), relentlessly been drawing the public’s attention to the risk factors, symptoms, prevention and treatment of liver cancer. Cancer of the liver is the fourth most common and third most fatal cancer among Singaporean men, having claimed the lives of 1,507 men between 2003 and 2007, according to the Singapore Cancer Registry. The majority of patients with liver cancer do not develop any symptoms until it is too late to treat, by which time treatment options are limited. The disease is discovered often by chance when the patient is examined for other unrelated problem using imaging methods such as a Computed Tomography (CT) scan or Ultrasound (US). Risk factors for liver cancer include: • Having hepatitis B • Having cirrhosis (liver hardening) from any cause including hepatitis C, excessive alcohol consumption or obesity • Eating foods with Aflatoxin (poison from a fungus that can grow on grains and nuts that have not been stored properly) The hepatitis B vaccination was incorporated into the national immunisation programme to protect those born in 1987 and after. The disease is commonly caused by the hepatitis virus, which causes inflammation (swelling) of the liver. Damage to the liver resulting from hepatitis will affect the liver in the long run and increase the risk of developing cancer. Individuals with hepatitis B or C are 100 times more likely to develop liver cancer than others. “Our past efforts for liver cancer awareness targeted those born before 1987, especially the elderly. This year, we decided to engage school-going children so that they can also learn about the disease and play a part by bringing the message home to their parents and relatives,” said Professor London Lucien Ooi, Organising Chair, LiCAM 2010. The contest kicked off in March and drew numerous well designed and meaningful entries for the three categories namely, primary school, secondary school and the junior college, preuniversity, polytechnic and ITE. Judging has concluded and the winners are: PRIMARY SCHOOL Winner Au Wei Hoe, Fuhua Primary School Consolations Tian Bo Lun, Fuhua Primary School Koh Wayne Gareth, Saint Andrew’s Junior School SECONDARY SCHOOL Winner Consolations Chew Tian Wei Valerie, Dunman High School Ahmad Nazaruddin Bin Abdul Rahim, Raffles Institute TERTIARY Winner NCCS together with Singapore General Hospital and Bayer Schering Pharma invited students to participate in its inaugural logo design contest where winners stood a chance to win attractive cash prizes. Chong Yu Shan, Yuan Ching Secondary School Tham May Peng Marilyn, Nanyang Polytechnic Consolations Lim Soon Keong Allon, Singapore Polytechnic Lee Anne, Nanyang Polytechnic By Carol Ang PAGE A6 People SALUBRIS September / October 2010 LEVERAGING FROM THE BEST IN CANCER CARE As he spoke of his stint, there were lighthearted moments that he was able to recall fondly, especially dealing with patients who were celebrities, senior politicians and billionaires. “A famous singer for whom we did a thyroidectomy gave me a private performance of “Amazing Grace”, just to prove that his voice was not affected by the surgery,” he confessed with a dry laugh. Going to Memorial SloanKettering Cancer Center has long been a dream for Dr Gopal Iyer. And, this dream was fulfilled recently when he returned from a one-year stint from New York and to share his experience with one of the leading cancer institutions. T Despite having been on his feet for extended hours each day, he found time to jog down the east river with a friend on alternate days and spend his evenings catching up on research projects and writing papers. To that, he had 11 papers, six book chapters and one online course to his name. here was every reason for Dr Gopal Iyer to lap everything up while he was in New York, a place which needs no introduction for its great offerings of art and culture. More so for an oncologist, as the Memorial Sloan-Kettering Cancer Center is one of the sought-after stops as far as cancer care and training is concerned. The man himself had been a role model for Dr Gopal who took to his meticulous nature, obsessive traits, organizational skills and drive for perfection. “The only thing I couldn’t emulate was that he could function with only 3-4 hours of sleep. I can’t imagine giving up my sleep,” he figured. He chanced upon the opportunity after obtaining a fellowship from the American Head and Neck Society in 2009. The opportunity to be in the best cancer centre had come with some sacrifices such as spending more time at work. Typically, each day began at 6am, doing rounds at the wards. Then from 7am, it was off to the operating theatre till 7pm, most times alternating between surgeries and minor procedures in the ward or seeing patients needing urgent care. After 7pm, it would be post-operative ward rounds. “It has traditionally been the Mecca for advanced head and neck surgery training. I was glad to have met Dr Jatin Shah, who is considered one of the masters of the subspecialty and was the author of numerous textbooks. I was first introduced to MSKCC as a wee third year medical student by Prof Soo Khee Chee, the director of NCCS…the fact that he was trained there as well spoke volumes about the centre.” The stint had been an eye opener in many ways. At MSKCC, he was fortunate to be in the company of some of the best medical professionals in the industry and managed to catch them in action. He had the privilege of working with Dr Jatin Shah. “Each operation done with Dr Shah was straight out of a textbook – clean, perfect, efficient and as beautiful as a painting or symphony,” he said. It is little wonder that he chalked up over 600 surgical cases which he said was equivalent to 4-5 years’ volume and met his objective for the fellowship- to increase the number of cases under his belt, fine tune surgical skills and learn selective techniques like laser surgery for laryngeal cancers and transoral robotic surgery for pharyngeal cancers, which were new to him. The one-year stint had been more than what he had expected when he was accorded the Michael E Burt Award by MSKCC, conferred to fellows with the best operative skills, outstanding teaching with a fine research output. With 60-70 surgical fellows contending for the award, it had come as a big surprise and as the icing on the cake. In the award presentation, Dr Shah had also cited him as “the best fellow that the centre had seen in 20 years.” The award, with its triple threads on clinical excellence, education and research had reminded him of the similarities NCCS had with MSKCC. Like Dr Gopal, many clinicians at NCCS now embark on research projects and share their expertise apart from doing clinical work. So much so that Dr Gopal finds the triple combination a big challenge. To transcend the challenge, he thinks that passion is important. “The key is to always enjoy what you are doing and be passionate about work. It is no point spending half of our waking hours of our life at a place where we don’t want to be,” said the enthusiastic Dr Gopal. Apart from clinical work, Dr Gopal is also heading the Wee Kim Wee Laboratory of Surgical Oncology and is involved research in head and neck cancers, with grants from NMRC and SingHealth. By Veronica Lee GIVING HOPE PAGE A7 NCC Foundation SALUBRIS September / October 2010 In a bid to demonstrate their support for cancer research and the importance of hope in the patient’s healing process, five healthcare professionals and cancer survivors have offered to become ambassadors for cancer research. They are the Faces of Hope for the forthcoming charity event – Run for Hope 2010. Ms Flora Yong G iving hope is more than just pounding the tarmac at a charity run. The five ambassadors are going to be part of this year’s Run for Hope to encourage others to have hope and advocate the causes that they believe in, namely, importance of research in the fight against cancer. The ambassadors are Ms Flora Yong, Mr Teo Thiam Chye, Dr Patricia Thong, Dr Gopal Iyer and Ms Tan Li Leng. For one of the ambassadors, Ms Flora Yong, was diagnosed with a benign cyst in the bladder a few years ago. Her first encounter with cancer had come early, when her father was diagnosed with cancer while she was graduating from cancer nursing school. She learnt to deal with it and as a professional, continues to wage war on the disease by conducting public education programmes for those who are affected by cancer. She also spends her free time supporting other patient causes. At the ‘Healing In Another Dimension’ Art exhibition in July 2010, she painted and donated her artwork to raise funds for patient support programmes. Mr Teo Thiam Chye Dr Patricia Thong Dr Gopal Iyer Ms Tan Li Leng Continued on page A8. GIVING HOPE PAGE A8 NCC Foundation SALUBRIS September / October 2010 Continued from page A7. It is heartening that healthcare professionals and cancer survivors alike, coming from different sides of the healthcare chain are united for one common cause. It goes to show that helping others in need has no boundaries. Helping cancer patients deal with their condition was the premise why Mr Teo Thiam Chye, a programme director with a statutory board, has committed so much of his time at NCCS. Having been diagnosed with nasopharyngeal cancer in 2003 and survived the disease, he felt that it was a terrible thing for patients to struggle with the disease alone. He then became one of the pioneers who formed the NPC support group, creating a safe haven for patients and their caregivers to come together to learn and support each other. Since then the NPC group now boasts of 155 members and continues to reach out to fellow survivors and victims of the disease. Indeed, a common adage subscribed by the quintet is that each of their work has the potential of improving patients’ lives and quality of life no matter what their professions might be. In the case of Dr Patricia Thong, a research fellow at the laboratory of Optical Imaging and Photodynamic Therapy at NCCS, though she has little contact with patients, she sees her work as equally important as that of doctors and nurses as she assist doctors in giving alternative treatment to patients with no effective treatment. She is instrumental in looking for non-invasive optical methods for cancer diagnosis and therapy for oral and bladder cancers. This requires extensive research and in spite of a long wait for impactful discoveries, she feels that small results have their merits in improving the standard of medical care. Editorial Advisors Dr Kon Oi Lian Prof Soo Khee Chee Executive Editors Ms Veronica Lee Mr Joshua Tan Mr Sunny Wee Having a finger in every pie for cancer cure is how Dr Gopal Iyer, a Consultant with the Department of Surgical Oncology at NCCS, describes his work as a clinician and researcher. As a clinician he has found satisfaction in providing clinical care to patients, being in the frontline to treat cancer. Although Dr Gopal admits that treatment modalities may have limitations and that patients’ conditions may not improve from them, giving comfort to them could be an alternative. At the backend, he is working very hard to identify molecular pathways that can be harnessed in demolishing cancerous tumours in head and neck cancers. Sometimes, helping others offers instant gratification. Such was Li Leng’s reward whenever she spends time with cancer survivors whom she meets at dance classes. Dance and exercise are her passions and conducting classes for them was fun for her. Under the auspices of the Breast Cancer Foundation, she does this once a week and also choreographs dances whenever they have performances. As these survivors are a source of inspiration for her, Li Leng feels that doing her bit is but a mere drop of hope to alleviate their sufferings. Since five years ago, she has been paddling with three dragon boat teams of cancer survivors and has never faltered under the strenuous sport, seeing that many more fragile than her could do it as well as others. It is heartening that healthcare professionals and cancer survivors alike, coming from different sides of the healthcare chain are united for one common cause. It goes to show that helping others in need has no boundaries. Contributing Editor Dr Wong Nan Soon Medical Editor Dr Richard Yeo Members, Editorial Board Ms Audrey-Anne Oei Ms Sharon Leow Ms Flora Yong Members, Medical Editorial Board Ms Lita Chew Dr Mohd Farid Dr Melissa Teo Dr Teo Tze Hern Dr Deborah Watkinson SALUBRIS is produced with you in mind. If there are other topics related to cancer that you would like to read about or if you would like to provide some feedback on the articles covered, please email to [email protected]. NATIONAL CANCER CENTRE SINGAPORE Reg No 199801562Z 11 Hospital Drive Singapore 169610 Tel: (65) 6436 8000 Fax: (65) 6225 6283 www.nccs.com.sg
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