Anita Zarina Bustam

Lectin-based electrophoretic analysis of the expression of the 35 kDa inter-α-trypsin inhibitor heavy chain H4 fragment in sera of patients with five different malignancies

A 35 kDa glycoprotein whose abundance was previously demonstrated to be enhanced in sera of patients with endometrial adenocarcinoma (n = 12), was isolated from pooled sera of three of the cancer patients using champedak galactose‐binding lectin affinity chromatography in the present study. Subjecting it to 2‐DE and MS/MS, the glycoprotein was identified as the O‐glycosylated fragment of inter‐α‐trypsin inhibitor heavy chain H4 (ITIH4). When compared to control sera (n = 17), expression of the 35 kDa ITIH4 cleavage fragment was demonstrated to be significantly enhanced in sera of patients with breast carcinoma (n = 10), epithelial ovarian carcinoma (n = 10), and germ cell ovarian carcinoma (n = 10) but not in patients with nasopharyngeal carcinoma (n = 13) and osteosarcoma (n = 7). The lectin‐based electrophoretic bioanalytical method adopted in the present study may be used to assess the physiological relevance of ITIH4 fragmentation and its correlation with different malignancies, their stages and progression.

Application of champedak mannose-binding lectin in the glycoproteomic profiling of serum samples unmasks reduced expression of alpha-2 macroglobulin and complement factor B in patients with nasopharyngeal carcinoma

The use of lectin affinity chromatography prior to 2‐DE separation forms an alternative method to unmask the expression of targeted glycoproteins of lower abundance in serum samples. Reduced expression of α‐2 macroglobulin (AMG) and complement factor B (CFB) was detected in sera of patients with nasopharyngeal carcinoma (NPC) when pooled serum samples of the patients and those of healthy individuals were subjected to affinity isolation using immobilized champedak mannose‐binding lectin and analyzed by 2‐DE and densitometry. The AMG and CFB spots were not detected in the 2‐DE protein profiles when the same pooled serum samples were subjected to albumin and IgG depletion and neither were they detected when the depleted samples were analyzed by western blotting and lectin detection. Together with other acute‐phase response proteins that were previously reported to be altered in expression in NPC patients, AMG and CFB may serve as useful complementary biomarkers for NPC.

Prevalence of distress in cancer patients undergoing chemotherapy

Aim:  Feeling distressed is often a normal reaction to the diagnosis of cancer and cancer treatment. However, if excessive, distress may lead to more disabling conditions such as depression and anxiety. The aims of the study were to determine the prevalence and level of distress in patients with cancer who were undergoing chemotherapy and to examine the associated factors related to psychological distress in these patients.

An oral cancer biobank initiative: a platform for multidisciplinary research in a developing country

Identification of diagnostic markers for early detection and development of novel and therapeutic agents for effective patient management are the main motivation for cancer research. Biological specimens from large cohort and case-control studies which are crucial in providing successful research outcomes are often the limiting factor that hinders research efforts, especially in developing countries. Therefore, the Malaysian Oral Cancer Database and Tissue Bank System (MOCDTBS) were established to systematically collect large number of samples with comprehensive sociodemographic, clinicopathological, management strategies, quality of life and associated patient follow-up data to facilitate oral cancer research in Malaysia. The MOCDTBS also promotes sharing among researchers and the development of a multidisciplinary research team. The following article aims to describe the process of setting-up and managing the MOCDTBS.

Multi-Institutional Phase II Clinical Study of Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer in East and Southeast Asia

PURPOSE To evaluate the toxicity and efficacy of concurrent chemoradiotherapy using weekly cisplatin for patients with locally advanced cervical cancer in East and Southeast Asia, a multi-institutional Phase II clinical study was conducted among eight Asian countries. METHODS AND MATERIALS Between April 2003 and March 2006, 120 patients (60 with bulky Stage IIB and 60 with Stage IIIB) with previously untreated squamous cell carcinoma of the cervix were enrolled in the present study. Radiotherapy consisted of pelvic external beam radiotherapy (total dose, 50 Gy) and either high-dose-rate or low-dose-rate intracavitary brachytherapy according to institutional practice. The planned Point A dose was 24-28 Gy in four fractions for high-dose-rate-intracavitary brachytherapy and 40-45 Gy in one to two fractions for low-dose-rate-intracavitary brachytherapy. Five cycles of weekly cisplatin (40 mg/m(2)) were administered during the radiotherapy course. RESULTS All patients were eligible for the study. The median follow-up was 27.3 months. Of the 120 patients, 100 (83%) received four or five cycles of chemotherapy. Acute Grade 3 leukopenia was observed in 21% of the patients, and Grade 3 gastrointestinal toxicity was observed in 6%. No patient failed to complete the radiotherapy course because of toxicity. The 2-year local control and overall survival rate for all patients was 87.1% and 79.6%, respectively. The 2-year major late rectal and bladder complication rate was 2.5% and 0%, respectively. CONCLUSION The results have suggested that concurrent chemoradiotherapy using weekly cisplatin is feasible and effective for patients with locally advanced cervical cancer in East and Southeast Asia.

Risk of Treatment Related Death and Febrile Neutropaenia with Taxane-Based Adjuvant Chemotherapy for Breast Cancer in a Middle Income Country Outside a Clinical Trial Setting

BACKGROUND The risk of treatment-related death (TRD) and febrile neutropaenia (FN) with adjuvant taxane- based chemotherapy for early breast cancer is unknown in Malaysia despite its widespread usage in recent years. This study aims to determine these rates in patients treated in University Malaya Medical Centre (UMMC). PATIENTS AND METHODS Patients who were treated with adjuvant taxane-based chemotherapy for early breast cancer stages I, II or III from 2007-2011 in UMMC were identified from our UMMC Breast Cancer Registry. The TRD and FN rates were then determined retrospectively from medical records. TRD was defined as death occurring during or within 30 days of completing chemotherapy as a consequence of the chemotherapy treatment. FN was defined as an oral temperature >38.5°C or two consecutive readings of >38.0°C for 2 hours and an absolute neutrophil count <0.5x109/L, or expected to fall below 0.5x109/L. RESULTS A total of 622 patients received adjuvant chemotherapy during this period. Of these patients 209 (33.6%) received taxane-based chemotherapy. 4 taxane-based regimens were used namely the FEC-D, TC, TAC and AC-PCX regimens. The commonest regimen employed was the FEC-D regimen accounting for 79.9% of the patients. The FN rate was 10% and there was no TRD. CONCLUSION Adjuvant taxane-based chemotherapy in UMMC for early breast cancer has a FN rate of 10%. Primary prophylactic G-CSF should be considered for patients with any additional risk factor for FN.

Symptom Experiences and Coping Strategies among Multi- ethnic Solid Tumor Patients Undergoing Chemotherapy in Malaysia

BACKGROUND This study was performed to assess patient symptoms prevalence, frequency and severity, as well as distress and coping strategies used, and to identify the relationships between coping strategies and psychological and physical symptoms distress and demographic data of cancer patients. This cross-sectional descriptive study involved a total of 268 cancer patients with various types of cancer and chemotherapy identified in the oncology unit of an urban tertiary hospital. MATERIALS AND METHODS Data were collected using questionnaires (demographic questionnaire, Medical characteristics, Memorial Symptom Assessment Scale (MSAS) and Brief COPE scales and analyzed for demographic, and disease-related variable effects on symptom prevalence, severity, distress and coping strategies. RESULTS Symptom prevalence was relatively high and ranged from 14.9% for swelling of arms and legs to 88.1% for lack of energy. This latter was the highest rated symptom in the study. The level of distress was found to be low in three domains. Problem-focused coping strategies were found to be more commonly employed compared to emotion-focused strategies, demonstrating significant associations with sex, age group, educational levels and race. However, there was a positive correlation between emotion-focused strategies and physical and psychological distress, indicating that patients would choose emotion-focused strategies when symptom distress increased. CONCLUSIONS These findings demonstrate that high symptom prevalence rates and coping strategies used render an improvement in current nursing management. Therefore development of symptoms management groups, encouraging the use of self-care diaries and enhancing the quality of psycho- oncology services provided are to be recommended.

Risk of treatment related death (TRD) with adjuvant chemotherapy for breast cancer: A study in University Malaya Medical Centre (UMMC)

Background: The risk of TRD with adjuvant chemotherapy for early breast cancer is unknown in Malaysia despite its widespread usage. This study aims to determine this rate in a large cohort of patients treated in UMMC. Patients & Methods: Patients who were treated with neoadjuvant or adjuvant chemotherapy for early breast cancer stages I, II or III from 2000-2007 in UMMC were identified from our UMMC Breast Cancer Registry. The TRD rate and 5 years overall survival (OS) were determined. TRD is defined as death occurring during or within 30 days of completing chemotherapy as a consequence of the chemotherapy treatment. OS was defined as death from any cause from the date of diagnosis to the date of death. OS was determined using the Kaplan-Meier method and differences between AJCC stages were compared by log-rank test. Results: A total of 1317 were identified for analysis. The median age at diagnosis was 49 years with a range of 24 to 74 years. The rate of TRD was 0.1%. The 5 years OS rate was 77.3% with a median follow up of 62 months. The 5 years OS according to AJCC stage were 90.7% for stage I, 83.9% for stage II and 62.2% for stage III disease. The commonest chemotherapy regimen used was the FEC (5-Fluorouracil, Epirubicin, Cyclophosphamide) regimen accounting for approximately 90% of the cases. Conclusion: Adjuvant chemotherapy for early breast cancer with the FEC regimen is safe with a TRD rate of 0.1% in our centre. Background The role of chemotherapy in cancer treatment is highly misunderstood not just in the public domain but also amongst medical practitioners. The fact that chemotherapy only plays a minor role as a definitive modality of cancer treatment is not well understood and it is mainly limited to haematological malignancies and germ cell tumours. Chemotherapys role in the treatment of solid tumours is mainly confined to neoadjuvant, adjuvant and palliative settings. As such, it is of utmost importance to be cognizant to the rate of TRDs with chemotherapy other than being aware of its potential benefits when used in these settings. Informing patients that this risk is negligible or less than one percent which is the figure often quoted by clinicians may be inadequate as this gives the impression that it is extremely rare. Moreover less than 1% can mean anywhere between 1 in 1001, 1 in 10000, 1 in 100000, 1 in 1000000 and so forth. Patients deserve to fully understand the real risk of TRDs and equally important is the need for clinicians to realize that TRDs are much commoner than perceived. There are various definitions of TRD used in the literature. For the purpose of this study the TRD was defined as deaths that occurred less than or equal to 30 days after the last cycle of chemotherapy, death of which was due to the chemotherapy itself. This definition was chosen as it was commonly used in many reported phase 3 trials and it is the least ambiguous amongst all definitions encountered in the literature. One major drawback is the fact that it does not take into account deaths that may be related to the long term side effects of chemotherapy for example deaths due to cardiac events which is especially relevant for anthracycline drugs commonly used for breast cancer treatment. Having said that, it is very difficult to prove that these deaths are directly due to the effect of chemotherapy alone as there are frequently many other confounding factors. Breast cancer is the commonest cancer treated with adjuvant chemotherapy in Malaysia. A commonly used regimen is the FAC regime (5 Fluorouracil, Adriamycin, Cyclophosphamide). In a trial involving 1491 patients in node positive breast cancer patients post definitive surgery, 745 patients received adjuvant TAC (Docetaxel, Adriamycin, Cyclophosphamide) and 746 patients received FAC. The TRDs for the TAC group and FAC group was similar at 0.3%. (1). The commonest regime used in our center is the FEC regime (5 Fluorouracil, Epirubicin, Cyclophosphamide). A pivotal phase 3 study, PACS 01 trial compared the FEC regime for 6 cycles with the FEC-D regime (FEC3-Docetaxel3) involving 996 patients in the FEC arm and 1003 patients in the FEC-D arm. Although significant high rates of febrile neutropaenia at 8.4% and 11.2% were reported in the FEC and FEC-D arms respectively, there were no early TRDs. However, there was one delayed cardiac death in each

Monte Carlo skin dose simulation in intraoperative radiotherapy of breast cancer using spherical applicators

The relatively new treatment modality electronic intraoperative radiotherapy (IORT) is gaining popularity, irradiation being obtained within a surgically produced cavity being delivered via a low-energy x-ray source and spherical applicators, primarily for early stage breast cancer. Due to the spatially dramatic dose-rate fall off with radial distance from the source and effects related to changes in the beam quality of the low keV photon spectra, dosimetric account of the Intrabeam system is rather complex. Skin dose monitoring in IORT is important due to the high dose prescription per treatment fraction. In this study, modeling of the x-ray source and related applicators were performed using the Monte Carlo N-Particle transport code. The dosimetric characteristics of the model were validated against measured data obtained using an ionization chamber and EBT3 film as dosimeters. By using a simulated breast phantom, absorbed doses to the skin for different combinations of applicator size (1.5-5 cm) and treatment depth (0.5-3 cm) were calculated. Simulation results showed overdosing of the skin (>30% of prescribed dose) at a treatment depth of 0.5 cm using applicator sizes larger than 1.5 cm. Skin doses were significantly increased with applicator size, insofar as delivering 12 Gy (60% of the prescribed dose) to skin for the largest sized applicator (5 cm diameter) and treatment depth of 0.5 cm. It is concluded that the recommended 0.5-1 cm distance between the skin and applicator surface does not guarantee skin safety and skin dose is generally more significant in cases with the larger applicators. HIGHLIGHTS • Intrabeam x-ray source and spherical applicators were simulated and skin dose was calculated. • Skin dose for constant skin to applicator distance strongly depends on applicator size. • Use of larger applicators generally results in higher skin dose. • The recommended 0.5-1 cm skin to applicator distance does not guarantee skin safety.

Oral cancer and precancer research in Malaysia - the database and tissue resource bank

Introduction: Uncoordinated data collection by different research groups prompted the initiation of Malaysian oral cancer Research Initiative (MOCRI) group. Objectives: To coordinate and standardize data and tissue collection and storage, develop a minimum dataset on risk factors, intervention techniques and quality of life of oral cancer patients. Materials and Methods: A computer software programme is currently being developed to accommodate multi-centre data collection and research activities in eight hospitals. The complete dataset includes parameters on sociodemographic, clinical, pathological, quality of life measures, details of treatment methods, vital status and dietary intake. Tissues are being collected, stored and catalogued as fresh and formalin-fixed tissues for future use in satellite researches. The networking in tissue and data collection includes the establishment of oral cancer cell-lines. These tissues are being planned for studies on genetic profile, genetic polymorphism, diagnostic and prognostic markers. Results: Tissues and data on 115 oral cancers, 9 leukoplakia and 13 lichen planus has been collected since 2003. Preliminary data from 2004 were analysed for 58 cancer patients. Majority of them are more than 60 years old (65.5%) with a mean age of 63.3. Twenty-four (41.4%) were males, 34 (58.6%) females with the majority of them being Indians (56.9%) followed by Chinese and Malays (15.5% each), Indigenous people of Sabah and Sarawak (12.1%). Eighteen (31%) respondents were smokers, 17 (29.3%) alcohol drinkers and 31 (53.4%) betel quid chewers. Five patients have had histories of family cancers where 3 included immediate family members with head and neck cancers. For the quality of life measure, only 30.2% felt that their daily activities were disrupted despite having advanced cancers. Satellite researches are in progress on genetic polymorphism and tumour markers. One oral cancer cell-line has been established. Conclusion: The establishment of oral cancer database and tissue bank in encouraging and supports on-going satellite researches.