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 salubris@nccs.com.sg.
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