exudates and Carcinoma--Non-Small-Cell-Lung

In the recent years, increased understanding of the molecular profiles of non-small cell lung cancer (NSCLC) has allowed for targeted treatment of actionable genetic mutations. The management of NSCLC now requires multiple molecular tests to guide the treatment strategy. In the light of this, there is a need to establish a molecular testing consensus statement for advanced NSCLC patients in Malaysia. This Malaysian consensus statement was developed by a panel of experts, chaired by a pathologist and composed of three other pathologists, four respiratory physicians and three oncologists. It reflects currently available scientific data and adaptations of recommendations from international guidelines to the local landscape. Expert recommendations on different aspects of molecular testing agreed upon by the panel are provided as structured discussions. These recommendations address the appropriate patients and samples to be tested, as well as when and how these tests should be performed. The algorithms for molecular testing in metastatic NSCLC, in the first line setting and upon disease progression beyond first line therapy, were developed.

Topics: Biomarkers, Tumor; Biopsy; Carcinoma, Non-Small-Cell Lung; Female; Genetic Predisposition to Disease; Genome-Wide Association Study; High-Throughput Nucleotide Sequencing; Humans; Lung Neoplasms; Malaysia; Male; Molecular Diagnostic Techniques; Neoplasm Staging

To propose a novel robust radiogenomics approach to the identification of epidermal growth factor receptor (EGFR) mutations among patients with non-small cell lung cancer (NSCLC) using Betti numbers (BNs).. Contrast enhanced computed tomography (CT) images of 194 multi-racial NSCLC patients (79 EGFR mutants and 115 wildtypes) were collected from three different countries using 5 manufacturers' scanners with a variety of scanning parameters. Ninety-nine cases obtained from the University of Malaya Medical Centre (UMMC) in Malaysia were used for training and validation procedures. Forty-one cases collected from the Kyushu University Hospital (KUH) in Japan and fifty-four cases obtained from The Cancer Imaging Archive (TCIA) in America were used for a test procedure. Radiomic features were obtained from BN maps, which represent topologically invariant heterogeneous characteristics of lung cancer on CT images, by applying histogram- and texture-based feature computations. A BN-based signature was determined using support vector machine (SVM) models with the best combination of features that maximized a robustness index (RI) which defined a higher total area under receiver operating characteristics curves (AUCs) and lower difference of AUCs between the training and the validation. The SVM model was built using the signature and optimized in a five-fold cross validation. The BN-based model was compared to conventional original image (OI)- and wavelet-decomposition (WD)-based models with respect to the RI between the validation and the test.. The BN-based model showed a higher RI of 1.51 compared with the models based on the OI (RI: 1.33) and the WD (RI: 1.29).. The proposed model showed higher robustness than the conventional models in the identification of EGFR mutations among NSCLC patients. The results suggested the robustness of the BN-based approach against variations in image scanner/scanning parameters.

Topics: Adult; Aged; Aged, 80 and over; Area Under Curve; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Female; Humans; Image Processing, Computer-Assisted; Japan; Lung Neoplasms; Malaysia; Male; Middle Aged; Mutation; ROC Curve; Support Vector Machine; Tomography, X-Ray Computed; United States

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of early and locally-advanced non-small-cell lung cancer (NSCLC) was published in 2017, and covered the diagnosis, staging, management and treatment of both early stage I and II disease and locally-advanced stage III disease. At the ESMO Asia Meeting in November 2018, it was decided by both the ESMO and the Korean Society of Medical Oncology (KSMO) to convene a special face-to-face guidelines meeting in 2019 in Seoul. The aim was to adapt the ESMO 2017 guidelines to take into account potential differences related to ethnicity, cancer biology and standard practices associated with the treatment of locally-advanced, unresectable NSCLC in Asian patients. These guidelines represent the consensus opinions reached by those experts in the treatment of patients with lung cancer who represented the oncology societies of Korea (KSMO), China (CSCO), India (ISMPO), Japan (JSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and it was independent of both local current treatment practices and the treatment availability and reimbursement situations in the individual participating Asian countries.

Topics: Asia; Carcinoma, Non-Small-Cell Lung; China; Humans; India; Japan; Lung Neoplasms; Malaysia; Medical Oncology; Republic of Korea; Taiwan

Brain metastases occur in about 20-40% of patients with non-small-cell lung carcinoma (NSCLC), and are usually associated with a poor outcome. Whole brain radiotherapy (WBRT) is widely used but increasingly, more aggressive local treatments such as surgery or stereotactic radiosurgery (SRS) or stereotactic radiotherapy (SRT) are being employed. In our study we aimed to describe the various factors affecting outcomes in NSCLC patients receiving local therapy for brain metastases.. The case records of 125 patients with NSCLC and brain metastases consecutively treated with radiotherapy at two tertiary centres from January 2006 to June 2012 were analysed for patient, tumour and treatment-related prognostic factors. Patients receiving SRS/SRT were treated using Cyberknife. Variables were examined in univariate and multivariate testing.. Overall median survival was 3.4 months (95%CI: 1.7-5.1). Median survival for patients with multiple metastases receiving WBRT was 1.5 months, 1-3 metastases receiving WBRT was 3.6 months and 1-3 metastases receiving surgery or SRS/SRT was 8.9 months. ECOG score (≤2 vs >2, p=0.001), presence of seizure (yes versus no, p=0.031), treatment modality according to number of brain metastases (1-3 metastases+surgery or SRS/SRT±WBRT vs 1-3 metastases+WBRT only vs multiple metastases+WBRT only, p=0.007) and the use of post-therapy systemic treatment (yes versus no, p=0.001) emerged as significant on univariate analysis. All four factors remained statistically significant on multivariate analysis.. ECOG ≤2, presence of seizures, oligometastatic disease treated with aggressive local therapy (surgery or SRS/SRT) and the use of post-therapy systemic treatment are favourable prognostic factors in NSCLC patients with brain metastases.

Topics: Aged; Brain; Brain Neoplasms; Carcinoma, Non-Small-Cell Lung; Combined Modality Therapy; Female; Humans; Lung Neoplasms; Malaysia; Male; Radiosurgery; Retrospective Studies; Treatment Outcome

Mutations in the tyrosine kinase domain of the epidermal growth factor receptor (EGFR) in non- small cell lung cancer (NSCLC) are predictive of response to EGFR-targeted therapy in advanced stages of disease. This study aimed to determine the frequency of EGFR mutations in NSCLCs and to correlate their presence with clinical characteristics in multiethnic Malaysian patients.. In this prospective study, EGFR mutations in exons 18, 19, 20 and 21 in formalin-fixed paraffin-embedded biopsy specimens of consecutive NSCLC patients were asessed by real-time polymerase chain reaction.. EGFR mutations were detected in NSCLCs from 55 (36.4%) of a total of 151 patients, being significantly more common in females (62.5%) than in males (17.2%) [odds ratio (OR), 8.00; 95% confidence interval (CI), 3.77-16.98; p<0.001] and in never smokers (62.5%) than in ever smokers (12.7%) (OR, 11.50; 95%CI, 5.08-26.03; p<0.001). Mutations were more common in adenocarcinoma (39.4%) compared to non-adenocarcinoma NSCLCs (15.8%) (p=0.072). The mutation rates in patients of different ethnicities were not significantly different (p=0.08). Never smoking status was the only clinical feature that independently predicted the presence of EGFR mutations (adjusted OR, 5.94; 95%CI, 1.94- 18.17; p=0.002).. In Malaysian patients with NSCLC, the EGFR mutation rate was similar to that in other Asian populations. EGFR mutations were significantly more common in female patients and in never smokers. Never smoking status was the only independent predictor for the presence of EGFR mutations.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Asian People; Carcinoma, Non-Small-Cell Lung; ErbB Receptors; Exons; Female; Humans; Lung Neoplasms; Malaysia; Male; Middle Aged; Mutation; Mutation Rate; Prospective Studies; Sex Factors; Smoking

Typhonium flagelliforme (Lodd.) Blume (Araceae) is a Malaysian plant used locally to combat cancer. In order to evaluate its antiproliferative activity in vitro and to possibly identify the active chemical constituents, a bioactivity guided study was conducted on the extracts of this plant.. The active extracts of Typhonium flagelliforme were fractionated by flash column chromatography and each fraction was evaluated for antiproliferative activity using MTT assay. The apoptotic effect of the active fraction was determined microscopically and by using TUNEL colorimetric assay. GC-MS and NMR were used to determine the chemical constituents of this active fraction.. Several fractions of the hexane and dichloromethane extracts were found to inhibit the growth of NCI-H23 non-small cell lung carcinoma cell line significantly, with IC(50)<15 microg/ml. However, most of these active fractions were also found to inhibit the growth of non-tumorigenic BALB/c 3T3 mouse fibroblast cell line except for fraction 21 of the dichloromethane extract (D/F21). This particular fraction was not only less cytotoxic to the non-tumorigenic cells, where the IC(50) was 48.6 microg/ml compared to IC(50) 7.5 microg/ml for NCI-H23, but it was also found to induce apoptosis in the cancer cell line. GC-MS analysis revealed that D/F21 contains hexadecanoic acid, 1-hexadecene, phytol and a derivative of phytol. The presence of non-saturated fatty acids in this fraction was confirmed by nuclear magnetic resonance spectroscopy.. D/F21 was found to be the active and cancer cell line specific fraction of Typhonium flagelliforme. Its major chemical constituents had been determined spectroscopically.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Araceae; BALB 3T3 Cells; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Drug Screening Assays, Antitumor; Humans; Inhibitory Concentration 50; Malaysia; Medicine, East Asian Traditional; Mice; Plant Extracts

The objectives of the present study were (i) to study the pharmacogenetics of UGT1A1*6, UGT1A1*28 and ABCG2 c.421C>A in three distinct healthy Asian populations (Chinese, Malays and Indians), and (ii) to investigate the polygenic influence of these polymorphic variants in irinotecan-induced neutropenia in Asian cancer patients. Pharmacokinetic and pharmacogenetic analyses were done after administration of irinotecan as a 90-min intravenous infusion of 375 mg/m(2) once every 3 weeks (n = 45). Genotypic-phenotypic correlates showed a non-significant influence of UGT1A1*28 and ABCG2 c.421C>A polymorphisms on the pharmacokinetics of SN-38 (P > 0.05), as well as severity of neutropenia (P > 0.05). Significantly higher exposure levels to SN-38 (P = 0.018), lower relative extent of glucuronidation (REG; P = 0.006) and higher biliary index (BI; P = 0.003) were found in cancer patients homozygous for the UGT1A1*6 allele compared with patients harboring the reference genotype. The mean absolute neutrophil count (ANC) was 85% lower and the prevalence of grade 4 neutropenia (ANC < or = 500/microL) was 27% in patients homozygous for UGT1A1*6 compared with the reference group. Furthermore, the presence of the UGT1A1*6 allele was associated with an approximately 3-fold increased risk of developing severe grade 4 neutropenia compared with patients harboring the reference genotype. These exploratory findings suggest that homozygosity for UGT1A1*6 allele may be associated with altered SN-38 disposition and may increase the risk of severe neutropenia in Asian cancer patients, particularly in the Chinese cancer patients who comprised 80% (n = 36) of the patient population in the present study.

Topics: Adult; Aged; Alleles; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Camptothecin; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Female; Genetic Predisposition to Disease; Glucuronosyltransferase; Humans; India; Irinotecan; Lung Neoplasms; Malaysia; Male; Middle Aged; Neoplasm Proteins; Neutropenia; Polymorphism, Genetic; Singapore; Urogenital Neoplasms

A comparison of patients with lung cancer diagnosed at the University of Malaya Medical Centre, Kuala Lumpur, Malaysia from October 1991 to September 1999 with another group of lung cancer patients diagnosed at the same hospital during an earlier period of 1967-1976 was undertaken to determine whether there had been a change in the distribution of lung cancer cell types and patient demography. The number of histologically and/or cytologically proven lung cancer cases was 583 from October 1991 to September 1999 and 278 from 1967 to 1976. The mean (S.D.) age of the patients during the period 1991-1999, 60.1 (12.0) years was similar to that of patients during the period 1967-1976, 60.3 (12.2) years. There was no shift of the peak age distribution of lung cancer (i.e., the 7th decade) between the two periods. In the recent period, the percentage of patients with adenocarcinoma had increased significantly to 43.2% from 25.2% while that of large cell carcinoma had decreased to 3.3% from 11.9%. The percentages of patients with squamous cell carcinoma (SCC) and small cell lung cancer remained stable. In the period 1967-1976, SCC was the commonest cell type in men and in smokers while adenocarcinoma was the commonest cell type in women and in never smokers. In the period 1991-1999, adenocarcinoma was the commonest cell type in both men and women as well as in smokers and never smokers.

Topics: Adenocarcinoma; Adult; Age Distribution; Aged; Aged, 80 and over; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Demography; Female; Hospitals, Teaching; Hospitals, University; Humans; Lung Neoplasms; Malaysia; Male; Middle Aged; Retrospective Studies; Sex Distribution; Smoking

The aim of the study was to evaluate the response, survival advantage and toxicity profile of gemcitabine-carboplatin combination cytotoxic chemotherapy in patients with locally advanced and metastatic non-small cell lung cancer (NSCLC).. Patients who received gemcitabine-carboplatin combination chemotherapy over a 2.5-years period were analyzed. Carboplatin at a dose of 5 mg/mL/min (area under the concentration-time curve) was given on day 1 and gemcitabine (1000 mg/m(2)) on days 1 and 8, every 3 weeks.. Of 49 chemotherapy-naive patients (median age, 62 years) who received this treatment, 57% were males, 12% had stage IIIa, 39% stage IIIb and 49% metastatic disease. The Eastern Cooperative Oncology Group (ECOG) performance status of 70% of the patients was 1 at the time of commencement of chemotherapy and 2 for the remaining 30% of patients. The overall response rate, based on 33 evaluable patients, was 27.3%. The response rate was not affected by age, stage of disease or performance status. The median survival was 9 months. Median survival among patients with an ECOG performance status of 1 was 11 months, as compared with 4 months for patients with an ECOG performance status of 2 (P < 0.001). Toxicity was generally well tolerated and there were no treatment-related deaths.. Gemcitabine-carboplatin combination chemotherapy is an effective and well-tolerated cytotoxic regimen among Malaysian patients with advanced NSCLC. A performance status of 1 or less was associated with a better survival.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Deoxycytidine; Drug Administration Schedule; Female; Gemcitabine; Humans; Lung Neoplasms; Malaysia; Male; Middle Aged; Neoplasm Metastasis; Retrospective Studies; Survival Rate

Topics: Adult; Age Factors; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Malaysia; Male; Middle Aged; Risk Factors; Smoking

This study aimed to determine whether the clinicopathological features of lung cancer in patients younger than 40 years differ from that of older patients in an Asian country.. We undertook a review of the clinicopathological data of all patients with confirmed primary lung cancer at the Department of Medicine, University of Malaya Medical Centre, Kuala Lumpur, Malaysia, from October 1991 to September 1999.. Of the 580 patients with lung cancer, 36 (6.2%; 23 males, 13 females) were 21-39 years old at diagnosis. The percentage of people who had never smoked was higher among the younger patients (58.3% vs 19.1%, P < 0.001). Although adenocarcinoma was the most common cell type in both groups, its incidence was higher in the younger patients (24/36 (66.7%) vs 228/544 (41.9%), P = 0.007). The mean World Health Organization performance status at presentation was worse in the younger patients (2.4 vs 2, P = 0.007). In the case of non-small cell lung cancer, all the younger patients presented with either stage IIIb or metastatic disease compared to 77.2% of the older patients (P < 0.001).. Younger lung cancer patients were more likely than older patients to have never smoked, to have adenocarcinoma, and to present with poorer performance status and with more advanced-stage non-small cell lung cancer.

Topics: Adenocarcinoma; Adult; Age Distribution; Aged; Aged, 80 and over; Carcinoma, Large Cell; Carcinoma, Non-Small-Cell Lung; Carcinoma, Small Cell; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Malaysia; Male; Middle Aged; Neoplasm Staging; Population Surveillance; Prospective Studies; Sex Distribution; Smoking