ABSTRACT
AIMS: To determine the trend of cancer cases referred to the Department of Clinical Oncology in UMMC in terms of patient volumes over a period of 10 years. To define the stage at presentation of the top five cancers in males and females, respectively. To determine the overall radiotherapy utilization rates. METHODS AND MATERIAL: This is a retrospective analysis of all new cases seen at the Department of Clinical Oncology, University of Malaya Medical Centre (UMMC), from the year 2009 to 2018 inclusive. The top five cancers in males and females were defined in terms of patient volumes and stage at presentation. The overall actual radiotherapy utilization rates were determined. RESULTS: A total of 12,672 patients were included for analysis. A total of 62.9% of the cases were females and 37.1% were males. The median age of presentation was 59 years old. Breast cancer was the most common cancer, followed by colorectal, lung, thyroid, and prostate cancer. The most common presenting stage was stage 4. The overall actual radiotherapy utilization rate (aRTU) was 40.1%. Curative intent makes up 74.3% of radiotherapy and 66.6% of chemotherapy utilization. CONCLUSIONS: The cancer distribution and trends among our patients are comparable with national and regional data. The overall actual radiotherapy utilization rate in the UMMC was lower than the estimated optimal rate of 53% but higher than the actual rate of 28% for Malaysia. This study provides valuable insight into current cancer trends and treatment demands to facilitate service planning.
Subject(s)
Breast Neoplasms , Prostatic Neoplasms , Male , Humans , Middle Aged , Retrospective Studies , Malaysia/epidemiology , Tertiary Care CentersABSTRACT
BACKGROUND: There is a paucity of data on the use of intraoperative radiotherapy (IORT) with low-energy X-rays in Malaysian women with early breast cancer. The aim of this study is to evaluate the clinical, cosmetic, and patient-reported outcomes in low- and high-risk early breast cancer patients treated with breast conserving surgery (BCS) and IORT. METHODOLOGY: Patients suitable for BCS who were treated with IORT between January 2016 and June 2019 from three centres were analysed. They were divided into low-risk and high-risk groups based on the risk of recurrence according to the TARGeted Intraoperative radioTherapy (TARGIT) A and B study criteria. Outcomes of interest included local recurrence, wound complications, and radiation toxicity, with a subset analysed for cosmetic and patient-reported outcomes. RESULTS: Within a median follow-up of 31 months, there were 104 and 211 patients in the low- and high-risk groups, respectively. No significant difference was observed in local recurrence rates (low-risk, 1.0% vs. high-risk, 1.4%; p = 1.000). Both cohorts exhibited low frequencies of severe wound complications ranging between 1.4 and 1.9%. No major radiation toxicities were reported in either group. In the subgroup analysis, low-risk patients had significantly better mean scores in the subscales of inframammary fold and scar. Based on the BREAST-Q patient-reported outcomes questionnaire, seven out of nine parameters were scored similarly between both groups with no significant difference. CONCLUSION: This study showed that the use of IORT in both low- and high-risk early breast cancers is efficacious and safe with low recurrence rates and an acceptable toxicity profile.
Subject(s)
Breast Neoplasms , Female , Humans , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Prospective StudiesABSTRACT
PURPOSE: This study aims to evaluate in vivo skin dose delivered by intraoperative radiotherapy (IORT) and determine the factors associated with an increased risk of radiation-induced skin toxicity. METHODOLOGY: A total of 21 breast cancer patients who underwent breast-conserving surgery and IORT, either as IORT alone or IORT boost plus external beam radiotherapy (EBRT), were recruited in this prospective study. EBT3 film was calibrated in water and used to measure skin dose during IORT at concentric circles of 5 mm and 40 mm away from the applicator. For patients who also had EBRT, the maximum skin dose was estimated using the radiotherapy treatment planning system. Mid-term skin toxicities were evaluated at 3 and 6 months post-IORT. RESULTS: The average skin dose at 5 mm and 40 mm away from the applicator was 3.07 ± 0.82 Gy and 0.99 ± 0.28 Gy, respectively. Patients treated with IORT boost plus EBRT received an additional skin dose of 41.07 ± 1.57 Gy from the EBRT component. At 3 months post-IORT, 86% of patients showed no evidence of skin toxicity. However, the number of patients suffering from skin toxicity increased from 15% to 38% at 6 months post-IORT. We found no association between the IORT alone or with the IORT boost plus EBRT and skin toxicity. Older age was associated with increased risk of skin toxicities. A mathematical model was derived to predict skin dose. CONCLUSION: EBT3 film is a suitable dosimeter for in vivo skin dosimetry in IORT, providing patient-specific skin doses. Both IORT alone and IORT boost techniques resulted in similar skin toxicity rates.
Subject(s)
Breast Neoplasms , Radiation Injuries , Aged , Breast Neoplasms/radiotherapy , Breast Neoplasms/surgery , Female , Humans , Mastectomy, Segmental , Neoplasm Recurrence, Local , Prospective StudiesABSTRACT
Percutaneous biopsy in breast cancer has been associated with an increased risk of malignant cell seeding. However, the importance of these observations remains obscure due to lack of corroborating evidence from clinical studies. We determined whether method of biopsy is associated with breast cancer survival. This hospital registry-based cohort study included 3416 non-metastatic breast cancer patients diagnosed from 1993 to 2011 in a tertiary setting. Factors associated with biopsy methods were assessed. Multivariable Cox regression analysis was used to determine the independent prognostic impact of method of biopsy. Overall, 990 patients were diagnosed by core needle biopsy (CNB), 1364 by fine needle aspiration cytology (FNAC), and 1062 by excision biopsy. Excision biopsy was significantly associated with more favorable tumor characteristics. Radiotherapy modified the prognostic impact of biopsy method (Pinteractionâ<â.001). Following multivariable analysis, excision biopsy was consistently associated with lower risk of mortality compared to FNAC in women receiving adjuvant radiotherapy (adjusted hazard ratio: 0.81, 95%CI: 0.66-0.99), but not in those who did not receive adjuvant radiotherapy (adjusted hazard ratio: 0.87, 95%CI: 0.65-1.17). While the risk of mortality was not different between patients undergoing FNAC and CNB when radiotherapy is administered, in the absence of radiotherapy, CNB was associated with higher risk of mortality than FNAC (adjusted hazard ratio: 1.57, 95%CI: 1.16-2.12). Given that our results contradict with findings of previous clinical studies assessing the prognostic impact of method of biopsy in women with breast cancer, further studies are warranted.
Subject(s)
Biopsy/methods , Breast Neoplasms/diagnosis , Adult , Biopsy/adverse effects , Biopsy, Fine-Needle/adverse effects , Biopsy, Fine-Needle/methods , Biopsy, Needle/adverse effects , Biopsy, Needle/methods , Breast/pathology , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Proportional Hazards Models , Registries , Survival AnalysisABSTRACT
Previous studies found that ethnicity influences oral cancer patients' survival; however, most studies were limited to certain ethnic groups particularly from the West, thus of limited relevance to Asians where the disease is most prevalent. We investigated the relationship between ethnicity and patient survival in multi-racial Malaysia. 5-year survival rate was 40.9%. No statistically significant difference was observed in survival between Malays, Chinese, Indians and Indigenous peoples (45.7%, 44.0%, 41.3%, 27.7% respectively). Increased tumor size, lymph node involvement and advanced tumor were predictive of poor survival. We conclude that ethnicity has no effect on survival or its prognostic indicators.
Subject(s)
Mouth Neoplasms/ethnology , Mouth Neoplasms/mortality , Adult , Aged , Cohort Studies , Ethnicity/statistics & numerical data , Female , Humans , Malaysia/ethnology , Male , Middle Aged , Mouth Neoplasms/pathology , Prognosis , Survival Rate , Tumor BurdenABSTRACT
Aim: To evaluate the efficacy and safety of neratinib as extended adjuvant therapy in patients from Asia based on exploratory analyses of the Phase III ExteNET trial. Patients & methods: A total of 2840 women with early stage HER2-positive breast cancer were randomly assigned to neratinib 240 mg/day or placebo for 1 year after trastuzumab-based adjuvant therapy. Results: A total of 341 patients were from Asia (neratinib, n = 165; placebo, n = 176). 2-year invasive disease-free survival rates were 92.8 and 90.8% with neratinib and placebo, respectively (HR: 0.70; 95% CI: 0.31-1.55), and 5-year rates were 91.9 and 87.2%, respectively (HR: 0.57; 95% CI: 0.27-1.13). Diarrhea was the most common adverse event with neratinib. Conclusion: Extended adjuvant therapy with neratinib reduces disease recurrences in Asian women with HER2-positive breast cancer. Trial registration: Clinicaltrials.gov NCT00878709.
Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Protein Kinase Inhibitors/therapeutic use , Quinolines/therapeutic use , Receptor, ErbB-2/metabolism , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Female , Humans , Kaplan-Meier Estimate , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards Models , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Quinolines/administration & dosage , Quinolines/adverse effects , Retreatment , Trastuzumab/administration & dosage , Treatment OutcomeABSTRACT
BACKGROUND: Scalp cooling has been shown in several studies to be an effective method in preventing chemotherapy-induced alopecia (CIA). Data on the use of scalp cooling in Asian countries are limited, and evidence for its use and efficacy among our patients are not available. OBJECTIVE: The aim of this study was to assess the effectiveness and tolerability of scalp cooling among breast cancer patients in our study population. METHODS: Consecutive breast cancer patients receiving FE75C, FE100C, FE100C-D, docetaxel75 or docetaxel, and cyclophosphamide (TC) at our treatment center were recruited and allocated to the treatment (scalp cooling, DigniCapTM system) or control group in this prospective nonrandomized controlled study. The assessment of alopecia was carried out using the World Health Organization grading system and clinical photographs. RESULTS: Seventy patients were recruited, but only 25 completed the study and were evaluable for analysis. Five of 12 patients (42%) in the scalp cooling group managed to preserve hair. Two of three patients who received FE75C and TC regimens had minimal hair loss. All patients treated with FE100C had severe hair loss. Half of all patients who received scalp cooling throughout chemotherapy rated the treatment as reasonably well tolerated. The most common reason for discontinuing scalp cooling was intolerance to its side effects. CONCLUSION: Scalp cooling is potentially effective in reducing CIA caused by docetaxel, TC, and FE75C chemotherapy regimen. However, it was not well tolerated by our study population. The dropout rate was high, and this needs to be taken into consideration when pursuing further trials in a similar setting.
Subject(s)
Alopecia/therapy , Anthracyclines/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/complications , Bridged-Ring Compounds/therapeutic use , Scalp/blood supply , Taxoids/therapeutic use , Anthracyclines/pharmacology , Asian People , Bridged-Ring Compounds/pharmacology , Female , Humans , Taxoids/pharmacologyABSTRACT
BACKGROUND: Oral capecitabine is increasingly replacing intravenous 5-fluorouracil in many chemotherapy regimens. However, data on the risk of febrile neutropaenia (FN) and treatment related death (TRD) with the drug remain sparse outside of clinical trial settings despite its widespread usage. This study aimed to determine these rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC). MATERIALS AND METHODS: We reviewed the clinical notes of all patients prescribed with oral capecitabine chemotherapy for any tumour sites in University Malaya Medical Centre (UMMC) from 1st January 2009 till 31st June 2010. Information collected included patient demographics, histopathological features, treatment received including the different chemotherapy regimens and intent of treatment whether the chemotherapy was given for neoadjuvant, concurrent with radiation, adjuvant or palliative intent. The aim of this study is to establish the pattern of usage, FN and TRD rates with capecitabine in clinical practice outside of clinical trial setting. FN is defined as an oral temperature >38.5°or two consecutive readings of >38.0° for 2 hours and an absolute neutrophil count <0.5 x 109/L, or expected to fall below 0.5 x 109/L (de Naurois et al., 2010). Treatment related death was defined as death occurring during or within 30 days of last chemotherapy treatment. RESULTS: Between 1st January 2009 and 30th June 2010, 274 patients were treated with capecitabine chemotherapy in UMMC. The mean age was 58 years (range 22 to 82 years). Capecitabine was used in 14 different tumour sites with the colorectal site predominating with a total of 128 cases (46.7%), followed by breast cancer (35.8%). Capecitabine was most commonly used in the palliative setting accounting for 63.9% of the cases, followed by the adjuvant setting (19.7%). The most common regimen was single agent capecitabine with 129 cases (47.1%). The other common regimens were XELOX (21.5%) and ECX (10.2%). The main result of this study showed an overall FN rate of 2.2% (6/274). The overall TRD rate was 5.1% (14/274). The FN rate for the single agent capecitabine regimen was 1.6% (2/129) and the TRD rate was 5.4% (7/129). All the TRDs were with single agent capecitabine regimen were used for palliative intent. CONCLUSIONS: Oral capecitabine is used widely in clinical practice in a myriad of tumour sites and bears a low risk of febrile neutropaenia. However, capecitabine like any other intravenous chemotherapeutic agent carries a significant risk of treatment related death.
Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Capecitabine/adverse effects , Chemotherapy-Induced Febrile Neutropenia/etiology , Chemotherapy-Induced Febrile Neutropenia/mortality , Drug Utilization/statistics & numerical data , Practice Patterns, Physicians' , Administration, Oral , Adult , Aged , Aged, 80 and over , Antimetabolites, Antineoplastic/administration & dosage , Capecitabine/administration & dosage , Female , Follow-Up Studies , Humans , Malaysia , Male , Middle Aged , Prognosis , Survival Rate , Young AdultABSTRACT
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.
Subject(s)
Adaptation, Psychological , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Ethnicity/psychology , Neoplasms/psychology , Stress, Psychological/psychology , Symptom Assessment , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Follow-Up Studies , Humans , Malaysia , Male , Middle Aged , Neoplasm Staging , Neoplasms/drug therapy , Neoplasms/pathology , Prognosis , Self Care , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Body image dissatisfaction among breast cancer survivors has been associated with psychological stress resultant from breast cancer and resultant surgery. This study aimed to examine the psychometric properties of the Malay Version of the Breast-Impact of Treatment Scale (MVBITS) and to investigate the associations of retained factors with the Hospital Anxiety and Depression Scale (HADS) and the Rosenberg Self-Esteem Scale (RSES). MATERIALS AND METHODS: The MVBITS was 'forward-backward' translated from English to Malay and then administered to 70 female breast cancer patients who came to the Oncology Clinic of University Malaya Medical Centre, Kuala Lumpur, Malaysia to undergo chemotherapy. Principal component analysis (PCA) with varimax rotation was performed to explore the factor structure of the MVBITS. Associations of retained factors were estimated with reference to Spearman correlation coefficients. RESULTS: The internal consistency reliability of MVBITS was good (Cronbach's alpha 0.945) and showed temporal stability over a 3-week period. Principal component analysis suggested two factors termed as 'Intrusion' and 'Avoidance' domains. These factors explained 70.3% of the variance. Factor 1 comprised the effects of breast cancer treatment on the emotion and thought, while Factor 2 informed attempts to limit exposure of the body to self or others. The Factor 1 of MVBITS was positively correlated with total, depression and anxiety sub-scores of HADS. Factor 2 was positively correlated with total and anxiety sub-scores of HADS. MVBITS was also positively correlated with the RSES scores. CONCLUSIONS: The results showed that the Malay Version of Breast-Impact of Treatment Scale possesses satisfactory psychometric properties suggesting that this instrument is appropriate for assessment of body change stress among female breast cancer patients in Malaysia.
Subject(s)
Body Image/psychology , Breast Neoplasms/psychology , Breast Neoplasms/surgery , Surveys and Questionnaires , Adult , Antineoplastic Agents/adverse effects , Anxiety/etiology , Anxiety/psychology , Breast Neoplasms/drug therapy , Cross-Sectional Studies , Depression/etiology , Depression/psychology , Female , Humans , Malaysia , Mastectomy, Segmental , Middle Aged , Principal Component Analysis , Psychometrics , Reproducibility of Results , Self Concept , Statistics, NonparametricABSTRACT
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.
Subject(s)
Developing Countries , Interdisciplinary Communication , Mouth Neoplasms/pathology , Tissue Banks , Databases as Topic , Humans , MalaysiaABSTRACT
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.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Bridged-Ring Compounds/adverse effects , Chemotherapy, Adjuvant/adverse effects , Taxoids/adverse effects , Aged , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Bridged-Ring Compounds/administration & dosage , Carboplatin/adverse effects , Cause of Death , Cyclophosphamide/adverse effects , Docetaxel , Doxorubicin/adverse effects , Epirubicin/adverse effects , Female , Fever/chemically induced , Fluorouracil/adverse effects , Humans , Malaysia , Middle Aged , Neutropenia/chemically induced , Paclitaxel/adverse effects , Retrospective Studies , Risk Factors , Taxoids/administration & dosageABSTRACT
BACKGROUND: Locally advanced breast cancer (LABC) is characterized by the presence of a large primary tumour (>5 cm) associated with or without skin or chest-wall involvement (T4) or with fixed (matted) axillary lymph nodes in the absence of any evidence of distant metastases. These cancers are classified as stage IIIA and IIIB according to the AJCC Staging System. Treatment of choice involves combinations of surgery, chemotherapy, radiotherapy and/or hormonal therapy. Current guidelines recommend primary surgery or neoadjuvant therapy followed by surgery. The primary objective of this study was to compare the outcome of LABC patients subjected to neoadjuvant chemotherapy before surgery and those who underwent surgery as the primary treatment and to determine prognostic predictors. Secondary objectives were to evaluate the response after neoadjuvant therapy and to determine the treatment compliance rate. METHODS: This retrospective study of Stage III breast cancer patients was conducted over a 5 year period from 1998 to 2002. The survival data were obtained from the National Registry of Births and Deaths with the end-point of the study in April 2006. The Kaplan Meier method was applied for survival analysis. Cox regression analysis by stepwise selection was performed to identify important prognostic factors. RESULTS: Out of a 155 evaluable patients, 74 (47.7%) had primary surgery, 62 (40%) had neoadjuvant chemotherapy, 10 patients (6.5%) were given Tamoxifen as the primary treatment, while 9 patients (5.8%) defaulted any form of treatment. After neoadjuvant chemotherapy, 9 patients defaulted further treatment, leaving 53 evaluable patients. Out of these 53 evaluable patients, 5 patients (9.4%) had complete pathological response, 5 (9.4%) a complete clinical response, and 26 (49.1%) had partial response after neoadjuvant chemotherapy. The 5-year survival in the primary surgery group was 56.7 % compared to 44.7% in the neoadjuvant chemotherapy group (p<0.01). The important prognostic factors were race, size of tumour, nodal status, estrogen receptor status and response to neoadjuvant chemotherapy. CONCLUSION: Patients who had primary surgery had better survival than those who underwent neoadjuvant chemotherapy, which may be due to bias in the selection of patients for neoadjuvant chemotherapy. Out of a total of 155 patients, 25.1% defaulted part of the treatment, or did not receive optimal treatment, emphasizing the importance of psychosocial support and counselling for this group of patients.
Subject(s)
Antineoplastic Agents, Hormonal/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Tamoxifen/administration & dosage , Adult , Aged, 80 and over , Antineoplastic Agents, Hormonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/mortality , Chemotherapy, Adjuvant , Combined Modality Therapy/methods , Critical Pathways , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Epirubicin/administration & dosage , Female , Fluorouracil/administration & dosage , Humans , Kaplan-Meier Estimate , Malaysia , Middle Aged , Neoadjuvant Therapy/methods , Proportional Hazards Models , Retrospective Studies , Survival Rate , Tamoxifen/therapeutic use , Taxoids/administration & dosage , Treatment Outcome , Treatment RefusalABSTRACT
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 alpha-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.
Subject(s)
Chromatography, Affinity/methods , Complement Factor B/metabolism , Mannose-Binding Lectin , Nasopharyngeal Neoplasms/metabolism , Proteome/metabolism , alpha-Macroglobulins/metabolism , Complement Factor B/isolation & purification , Electrophoresis, Gel, Two-Dimensional/methods , Humans , Mannose-Binding Lectin/metabolism , alpha-Macroglobulins/isolation & purificationABSTRACT
BACKGROUND: Locoregional recurrence after mastectomy for breast cancer may predict distant recurrence and mortality. This study examined the pattern and rates of post-mastectomy locoregional recurrence (PMLRR), survival outcome and prognostic factors for isolated PMLRR (ILR) in a breast cancer cohort in University of Malaya Medical Center (UMMC). METHODS: We studied 522 patients who underwent mastectomy between 1998 and 2002 and followed them up until 2008. We defined PMLRR as recurrence to the axilla, supraclavicular nodes and or chest wall. ILR was defined as PMLRR occurring as an isolated event. Prognostic factors for locoregional recurrence were determined using the Cox proportional hazards regression model. RESULTS: The overall PMLRR rate was 16.4%. ILR developed in 42 of 522 patients (8.0%). Within this subgroup, 25 (59.5%) remained disease free after treatment while 17 (40.5%) suffered disease progression. Univariate analyses identified race, age, size, stage, margin involvement, lymph node involvement, grade, lymphovascular invasion and ER status as probable prognostic factors for ILR. Cox regression resulted in only stage III disease and margin involvement as independent prognostic factors. The hazard of ILR was 2.5 times higher when the margins were involved compared to when they were clear (aHRR 2.5; 95% CI 1.3 to 5.0). Similarly, compared with stage I those with Stage II (aHRR 2.1; 95%CI 0.6 to 6.8) and stage III (aHRR 4.6; 95%CI 1.4 to 15.9) had worse prognosis for ILR. CONCLUSION: Margin involvement and stage III disease were identified to be independent prognostic factors for ILR. Close follow-up of high risk patients and prompt treatment of locoregional recurrence were recommended.
Subject(s)
Breast Neoplasms/pathology , Mastectomy , Neoplasm Recurrence, Local , Adult , Aged , Aged, 80 and over , Breast Neoplasms/surgery , Disease Progression , Female , Humans , Malaysia , Middle Aged , Neoplasm Staging , Prognosis , Proportional Hazards ModelsABSTRACT
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.
Subject(s)
Carcinoma, Squamous Cell/drug therapy , Carcinoma, Squamous Cell/radiotherapy , Uterine Cervical Neoplasms/drug therapy , Uterine Cervical Neoplasms/radiotherapy , Adult , Aged , Antineoplastic Agents/therapeutic use , Asia , Brachytherapy/methods , Carcinoma, Squamous Cell/pathology , Cisplatin/therapeutic use , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Feasibility Studies , Female , Humans , Leukopenia/etiology , Middle Aged , Neutropenia/etiology , Radiotherapy Dosage , Survival Rate , Uterine Cervical Neoplasms/pathologyABSTRACT
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-alpha-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.
Subject(s)
Alpha-Globulins/biosynthesis , Biomarkers, Tumor/biosynthesis , Galectins , Plant Lectins , Adolescent , Adult , Aged , Biomarkers, Tumor/blood , Bone Neoplasms/metabolism , Breast Neoplasms/metabolism , Electrophoresis, Gel, Two-Dimensional , Female , Glycosylation , Humans , Male , Middle Aged , Nasopharyngeal Neoplasms/metabolism , Neoplasms, Germ Cell and Embryonal/metabolism , Neoplasms, Glandular and Epithelial/metabolism , Osteosarcoma/metabolism , Ovarian Neoplasms/metabolism , Tandem Mass SpectrometryABSTRACT
PURPOSE: The purpose was to evaluate the activity and toxicity of split-dose paclitaxel or docetaxel in combination with gemcitabine in patients with metastatic breast cancer (MBC) who had previously received anthracyclines. PATIENTS AND METHODS: A total of 210 patients were randomly assigned to one of three treatment arms: gemcitabine 1,250 mg/m(2) Days 1 and 8 and paclitaxel 175 mg/m(2) as a 3-h infusion on Day 1 (GP1); gemcitabine 1,000 mg/m(2) Days 1 and 8 and paclitaxel 100 mg/m(2) as a 1-h infusion on Days 1 and 8 (GP2); gemcitabine 1,000 mg/m(2) Days 1 and 8 and docetaxel 40 mg/m(2) as a 1-h infusion on Days 1 and 8 (GD). Cycles were repeated every 3 weeks. RESULTS: For the 204 patients evaluable for response assessment, the response rates were 48.6% for GP1, 52.2% for GP2, and 52.3% for GD. Median response duration, time to treatment failure, and time to progression (TTP) were similar in each arm. Median TTP for GP1, GP2 and GD was 7.5, 7.0 and 7.4 months, respectively. For the 208 patients evaluable for safety, the most common grade 3/4 toxicity for each regimen was neutropaenia, with 64%, 57%, and 68% for GP1, GP2, and GD, respectively. Grade 4 neutropaenia, grade 3/4 anaemia, febrile neutropaenia, and diarrhoea were more common in the docetaxel arm, as was the use of intravenous antibiotics and blood transfusions. CONCLUSION: The study confirmed the high activity of gemcitabine-taxane combinations in MBC. Split-dose paclitaxel had similar activity and toxicity to the 3-weekly administration. The split-dose docetaxel regimen had similar activity to the paclitaxel combinations though associated with higher toxicity.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adolescent , Adult , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Docetaxel , Female , Humans , Middle Aged , Neoplasm Metastasis , Paclitaxel/administration & dosage , Paclitaxel/adverse effects , Taxoids/administration & dosage , Taxoids/adverse effects , Treatment Failure , GemcitabineABSTRACT
The proteomics approach was adopted to study the simultaneous expression of serum proteins in patients with nasopharyngeal carcinoma (NPC). We have subjected unfractionated whole sera of ten newly diagnosed Malaysian Chinese patients with WHO type III NPC to two-dimensional gel electrophoresis (2-DE) and image analysis. The results obtained were then compared to that generated from sera of ten normal healthy controls of the same ethnic group and range of age. Our data demonstrated that the serum high abundance 2-DE protein profiles of NPC patients were generally similar to that of the controls, with exception of the ceruloplasmin (CPL) spots (identified by mass spectrometric analysis and MASCOT database search), which showed higher expression. The enhanced expression of CPL in the patients' sera was confirmed by competitive ELISA. Immunohistochemical analysis of nasopharyngeal lesions of NPC patients demonstrated moderate to strong positive CPL staining in the cytoplasm of cells at the regions of malignancy but only weak cytoplasmic staining at normal epithelial lining areas. When follow-up 2-DE and ELISA studies were performed on five of the NPC patients who responded positively to six months treatment, the difference in CPL expression was no longer significant.