Non-small Cell Lung Cancer In Taiwan Research Articles

The prognosis of clinical stage IIIa non-small cell lung cancer in Taiwan.

Lung cancer is the leading cause of cancer death. The treatment of stage IIIa remained the most controversial of all stages of non-small cell lung cancer (NSCLC). We reported on the heterogenicity and current treatment strategies of stage IIIa NSCLC in Taiwan. This study is a retrospective analysis using data from the Taiwan Society of Cancer Registry between January 2010 and December 2018. 4232 patients with stage IIIa NSCLC were included. Based on cell type, the best 5-year OS (40.40%) occurred among adenocarcinoma victims. The heterogenicity of T1N2 had the best 5-year OS (47.62%), followed by T4N0 (39.82%), and the others. Patients who underwent operations had better 5-year OS (over 50%) than those who did not (less than 30%). Segmentectomy (75.28%) and lobectomy (54.06%) showed better 5-year OS than other surgical methods (less than 50%). In multivariable analysis, young age, female, lower Charlson Comorbidity Index score, adenocarcinoma cell type, well differentiated, T1N2/T4N0 heterogenicity, treatment with operation, and segmentectomy/lobectomy/bilobectomy were significant factors. In conclusions, the heterogenicity of T1N2 had the best outcomes followed by T4N0. Patients received surgical treatment revealed much better outcomes than those did not. As always, multimodal therapies with individualized treatment tend to provide better survival outcomes.

Characteristics and immune checkpoint inhibitor effects on non-smoking non-small cell lung cancer with KRAS mutation: A single center cohort (STROBE-compliant).

Kirsten rat sarcoma (KRAS) mutation (KRASm) is associated with poor prognosis in non-small cell lung cancer (NSCLC) patients. We have aimed to survey NSCLC patients harboring KRASm in Taiwan, where never-smoking lung adenocarcinoma predominates, and analyze the immune checkpoint inhibitor effect on NSCLC harboring KRASm.NSCLC patients with KRASm were enrolled and tested on programmed death-ligand 1 (PD-L1) expression using available tissue. We analyzed their clinical features, PD-L1 status, responses to ICIs, and overall survival (OS).We studied 93 patients with a median age 66.0 years, 23.7% of whom were women, and 22.6% were never-smokers. The results showed that G12C (36.6%) was the most common KRASm. In 47 patients with available tissue for PD-L1 testing, PD-L1 expression was positive in 66.0% of patients, while PD-L1 ≥50% was higher in ever-smokers (P = .038). Among 23 patients receiving ICI treatment, those with PD-L1 ≥50% experience a 45.5% response rate to ICI. There were benefits from ICI treatment on OS compared with no ICI treatment (median OS 35.6 vs 9.8 months, P = .002) for all of our patients, and for patients with PD-L1 ≥50% (median OS not-reached vs 8.4 months, P = .008). There were no differences in survival across different KRAS subtypes (P = .666).Never-smokers composed more than one-fifth of KRASm in NSCLC in Taiwan. A high PD-L1 expression was related to smoking history and responded well to ICI. ICI treatment improved the OS in NSCLC patients with KRASm, particularly those with PD-L1 ≥50%.

Conventional treatment integrated with Chinese herbal medicine improves the survival rate of patients with advanced non-small cell lung cancer

ObjectivesThe main objective of this study was to assess whether treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) combined with Chinese herbal medicine (CHM), can improve the five-year survival rate in patients suffering from advanced non-small cell lung cancer (NSCLC), compared to patients treated by EGFR-TKIs alone. Interventions and main outcome measuresThe study is based on information in the sub-dataset of the National Health Insurance Research Database (NHIRD) from years 2000 to 2010, during which time a total of 14,244 patients were diagnosed with NSCLC in Taiwan. After selection by exclusion criteria and matching process, 2,616 NSCLC patients were included in the study. Statistical analysis was utilized to evaluate the differences in characteristic distribution, and to compare the survival rates between the CHM cohort and non-CHM cohort. ResultsPatients with advanced NSCLC using CHM as an adjunct therapy exhibited a significantly improved survival rate [hazard ration (HR) = 0.8; 95% confidence interval (CI): 0.73-0.87, p value<0.001], compared with non-CHM users. Based on a survival analysis by Kaplan-Meier method, the 5-year survival rate of CHM users was 4.9% higher, with the most notable difference being an elevated 2-year survival rate of up to 12.75%. In addition to the survival rate analysis, we provide the ten most used single herbs and herbal formulas prescribed for patients with advanced NSCLC. ConclusionsThis nationwide retrospective cohort study provides evidence supporting CHM as an effective adjunctive therapy to ameliorate the side effects of target therapy and prolong the five-year survival rate of patients with advanced NSCLC.

P3.07-009 Use of Adjuvant Chemotherapy for Non-Small Cell Lung Cancer: The Real-World Clinical Practice in Taiwan: Topic: Therapy and Economics

Adjuvant chemotherapy is the standard treatment for selected patients with non-small cell lung cancer (NSCLC) following curative surgery. This study evaluated the use of adjuvant chemotherapy for these cases among the general population in Taiwan. A population-based cohort was established by searching the database of the Taiwan Cancer Registry System to identify patients newly diagnosed with NSCLC for the period covering 2005 to 2009. Our target was patients with stage I, II and IIIA NSCLC who had undergone curative surgery. Medication prescription data were retrieved from the National Health Insurance Research Database, Taiwan. Chemotherapy administered within 3 months after the surgery was defined as adjuvant chemotherapy. A total of 5789 patients received curative surgery for NSCLC, and the 1277 (22.1%) who had undergone adjuvant chemotherapy were included in this study. Overall, the most common adjuvant chemotherapy regimen was platinum plus gemcitabine (P + G) (25.7%), followed by platinum plus vinorelbine (P + V) (18.4%). For patients with stage II or IIIA disease, P + G remained the most common regimen, respectively (29.0% and 29.0%). However, for patients with stage I disease, the most common regimen was tegafur/uracil (30.7%). Analyzed by the diagnosis year, P + G was the most common adjuvant chemotherapy regimen until overtaken by P + V in 2009. Platinum plus gemcitabine regimen was the most commonly used adjuvant chemotherapy regimen in patients with operated stage II and IIIA NSCLC in Taiwan from 2005 to 2009.

Comparison of gefitinib and erlotinib efficacies as third-line therapy for advanced non-small-cell lung cancer

PurposeThe epidermal growth factor receptor inhibitors, gefitinib and erlotinib, are used as standard salvage therapy for advanced non-small-cell lung cancer (NSCLC). The aim of the present study was to compare their efficacies in this population. Patients and methodsThe Taiwan Cancer Registry and the National Health Insurance claim databases were searched for newly diagnosed patients with NSCLC from 2004 to 2007 who received gefitinib or erlotinib as third-line therapy. Overall survival (OS) and time to treatment failure (TTF) were determined from registered parameters. Treatment efficacies were compared by the log-rank test in total population and subsets with different clinical characteristics. The Cox’s proportion hazard model was used to estimate the adjusted hazard ratios in multivariate analyses. ResultsA total of 984 patients who received gefitinib (67%) or erlotinib (33%) were included. Patients receiving gefitinib or erlotinib had similar OS (median, 10.2 versus 9.9months, p=0.524) and TTF (median, 5.5 versus 3.4months, p=0.103). In multivariate analyses, both treatment groups had similar risk of overall mortality (adjusted hazard ratio [HR]=1.04, p=0.629) and treatment failure (adjusted HR=0.94, p=0.417). Comparing the treatments in subgroups based on age, tumour histology and gender also revealed no differences in OS and TTF. For patients who received gefitinib or erlotinib for more than 3 or 6months, there was no difference in TTF but patients who received erlotinib had longer OS. ConclusionsGefitinib and erlotinib had similar efficacies as salvage therapy for advanced NSCLC in Taiwan.

High efficacy of erlotinib in Taiwanese NSCLC patients in an expanded access program study previously treated with chemotherapy

Erlotinib is the first epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) which has demonstrated a survival benefit in non-small-cell lung cancer (NSCLC) patients. An open label phase II study was conducted in Taiwanese patients with NSCLC to evaluate its efficacy. Patients with proven stage IIIB/IV NSCLC who had received at least one line of standard chemotherapy or radiotherapy were enrolled into this study. All patients were given oral erlotinib, 150mg/day till disease progression. From May 2005 to July 2006, 300 patients were entered from 14 hospitals in Taiwan. This analysis was based on 299 patients who received at least one dose of erlotinib. The best response rates were a 29% partial response and 44% stable disease in 273 patients who had response data available. Non-smoking (p=0.033), adenocarcinoma/BAC (p=0.0027), female (p=0.0013), aged less than 65 years (p=0.0115), stage IV (p=0.0492), patients with skin rash (p=0.0216), and a higher grade of skin rash (p=0.003) were significantly correlated with response to treatment. Skin rash was a common adverse event (any grade: 84%, Gr 3-4: 16%). The median time to disease progression was 5.6 months. Cox regression model for progression free survival showed patients most at risk of early progression were males of low performance status having squamous cell carcinoma. This was the largest multicenter prospective clinical study of NSCLC in Taiwan. The results demonstrated the excellent response rates, time-to-progression and overall survival of erlotinib in a large population of Taiwanese NSCLC patients who had been previously treated with chemotherapy or radiotherapy.

High frequency of frameshift mutation on p53 gene in Taiwanese with non small cell lung cancer

Extensive researches have found that the mutation of p53 tumor suppressor gene is the most frequent event in many human cancers and associated with a poor clinical outcome in lung cancer patients. Because the p53 molecular mutation involved in tumorigenesis of patients with lung cancer in Taiwan remains poorly defined, the aim of this study was to assess the p53 mutation spectrum and possible etiological factors of Taiwan's patients with Non-Small Cell Lung Cancer (NSCLC). Cancer specimens were obtained surgically from 61 patients with pathologically proven NSCLC. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing were used to study p53 mutations in exon 4-8. We also performed immunohistochemistry (IHC) to detect p53 protein expression. Our results provided that 34 mutations of p53 gene were found in 27 cases with a mutation rate of 44% (27/61). There were six cases having more than two p53 mutations. Among the 34 mutations, 19 were point mutations (56%, 19/34) consisted of a majority of missense mutations including transversion (13/19, 68%) and transitions (6/19, 32%) with four cases (4/6, 67%) occurring in the CpG sequence. One of the most important finding in our study was the high frequency of frameshift (44%, 15/34) which included 11 insertions and 4 deletions of p53 in NSCLC in Taiwan. Surprisingly, our results disclosed distinct novel mutations at codon 181, 185, 208 (Exon 5-6) of p53. Especially, 4 cases with mutation at codon181 and codon 185 seemed to have more advanced clinical outcome with survival time less than 6 months. In addition, there were two recurring mutations at codon 168 and three at condon193. The different mutation spectrum in our series, including a high frequency of frameshift mutations and distinctly novel hot spots suggested the heterogenous entity of exogenous mutagens in NSCLC in Taiwan.

Loss of p16 and/or pRb protein expression in NSCLC: An immunohistochemical and prognostic study

The disruption of p16/pRb pathway has been reported in several types of human cancer including lung cancer. However, the etiological and prognostic involvement of this pathway remains poorly defined in lung tumorigenesis in Taiwan. Therefore, we investigated the expressions of p16 and pRb in 107 non-small cell lung cancer (NSCLC) patients by immunohistochemical analysis. The associations of altered p16 and pRb expressions with prognosis were also examined. Sixty-four specimens (59.8%) exhibited alteration of p16 and/or pRb expression, with 49.5 and 22.4% of the tumors failing to express p16 and pRb, respectively. However, there was no reciprocally correlated expression of p16 and pRb. Negative p16 and pRb expression did not correlate well with patients’ clinicopathological parameters such as age, sex, smoking habit, tumor type, and tumor stage. In addition, negative p16 and pRb expression was not statistically associated with poor prognosis (P=0.10 and P=0.74, respectively). Our results suggested that the disruption of the p16/pRb pathway plays a significant role in NSCLC tumorigenesis whereas it may not have significant importance in the prognostic evaluation of NSCLC in Taiwan.

Exon 8 mutation of p53 gene associated with nodal metastasis in non-small-cell lung cancer.

The epidemiologic characteristics of lung cancer in Taiwan differ from those in other parts of the world in low male-to-female ratio, the high percentage of adenocarcinoma, and the relatively high percentage of nonsmokers who are victims. To investigate possible correlation between p53 gene alteration and the unique characteristics of lung cancer here, p53 gene status of 36 patients with primary, resected non-small-cell lung cancer (NSCLC) was studied by directly sequencing the cDNA of the p53 gene, then acquiring clinical and pathologic data to correlate p53 gene status with clinical parameters and pathologic staging. Missense mutations were present in 42% (15 of 36) of patients with NSCLC, including 42% (10 of 24) with adenocarcinomas, and 45% (five of 11) with squamous cell carcinomas. The frequency of p53 mutation was 50% in smokers and 29% in nonsmokers (p = 0.355). The mutation occurred most frequently in exon 8 (56%), and G:C to A:T transitions in non-CpG or CpG sites were the most commonly observed base changes (56%). These findings differ from the high prevalence of G to T transversion found in previous reports. The frequency of metastasis in hilar and mediastinal lymph nodes was significantly higher in tumors with p53 mutations. The association with nodal stage was strong for mutations within exon 8, but it was less apparent for mutations in other exons probably because of the small number. This study suggests that p53 gene missense is common in NSCLC in Taiwan, but smoking is probably not the sole contributing factor. More interestingly, p53 gene mutations, especially those in exon 8, may be associated with regional nodal metastasis.