Using an Improved Residual Network to Identify PIK3CA Mutation Status in Breast Cancer on Ultrasound Image.

Background: The detection of phosphatidylinositol-3 kinase catalytic alpha (PIK3CA) gene mutations in breast cancer is a key step to design personalizing an optimal treatment strategy. Traditional genetic testing methods are invasive and time-consuming. It is urgent to find a non-invasive method to estimate the PIK3CA mutation status. Ultrasound (US), one of the most common methods for breast cancer screening, has the advantages of being non-invasive, fast imaging, and inexpensive. In this study, we propose to develop a deep convolutional neural network (DCNN) to identify PIK3CA mutations in breast cancer based on US images. Materials and Methods: We retrospectively collected 312 patients with pathologically confirmed breast cancer who underwent genetic testing. All US images (n=800) of breast cancer patients were collected and divided into the training set (n=600) and test set (n=200). A DCNN-Improved Residual Network (ImResNet) was designed to identify the PIK3CA mutations. We also compared the ImResNet model with the original ResNet50 model, classical machine learning models, and other deep learning models. Results: The proposed ImResNet model has the ability to identify PIK3CA mutations in breast cancer based on US images. Notably, our ImResNet model outperforms the original ResNet50, DenseNet201, Xception, MobileNetv2, and two machine learning models (SVM and KNN), with an average area under the curve (AUC) of 0.775. Moreover, the overall accuracy, average precision, recall rate, and F1-score of the ImResNet model achieved 74.50%, 74.17%, 73.35%, and 73.76%, respectively. All of these measures were significantly higher than other models. Conclusion: The ImResNet model gives an encouraging performance in predicting PIK3CA mutations based on breast US images, providing a new method for noninvasive gene prediction. In addition, this model could provide the basis for clinical adjustments and precision treatment.

Clinicopathologic and Genomic Features in Triple-Negative Breast Cancer Between Special and No-Special Morphologic Pattern.

Background: Triple-negative breast cancer (TNBC) is refractory and heterogeneous, comprising various entities with divergent phenotype, biology, and clinical presentation. As an aggressive subtype, Chinese TNBC patients with special morphologic patterns (STs) were restricted to its incidence of 10-15% in total TNBC population. Methods: We recruited 89 patients with TNBC at Guangdong Provincial People's Hospital (GDPH) from October 2014 to May 2021, comprising 72 cases of invasive ductal carcinoma of no-special type (NSTs) and 17 cases of STs. The clinical data of these patients was collected and statistically analyzed. Formalin-fixed, paraffin-embedded (FFPE) tumor tissues and matched blood samples were collected for targeted next-generation sequencing (NGS) with cancer-related, 520- or 33-gene assay. Immunohistochemical analysis of FFPE tissue sections was performed using anti-programmed cell death-ligand 1(PD-L1) and anti-androgen receptor antibodies. Results: Cases with NSTs presented with higher histologic grade and Ki-67 index rate than ST patients (NSTs to STs: grade I/II/III 1.4%, 16.7%,81.9% vs 0%, 29.4%, 58.8%; p<0.05; Ki-67 ≥30%: 83.3% vs. 58.8%, p<0.05), while androgen receptor (AR) and PD-L1 positive (combined positive score≥10) rates were lower than of STs cases (AR: 11.1% vs. 47.1%; PD-L1: 9.6% vs. 33.3%, p<0.05). The most commonly altered genes were TP53 (88.7%), PIK3CA (26.8%), MYC (18.3%) in NSTs, and TP53 (68.8%), PIK3CA (50%), JAK3 (18.8%), KMT2C (18.8%) in STs respectively. Compared with NSTs, PIK3CA and TP53 mutation frequency showed difference in STs (47.1% vs 19.4%, p=0.039; 64.7% vs 87.5%, p=0.035). Conclusions: In TNBC patients with STs, decrease in histologic grade and ki-67 index, as well as increase in PD-L1 and AR expression were observed when compared to those with NSTs, suggesting that TNBC patients with STs may better benefit from immune checkpoint inhibitors and/or AR inhibitors. Additionally, lower TP53 and higher PIK3CA mutation rates were also found in STs patients, providing genetic evidence for deciphering at least partly potential mechanism of action.

Tau expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy.

The purpose of this study was to investigate the correlation between tau expression in primary breast cancer and sensitivity to taxanes during neoadjuvant chemotherapy in patients with breast cancer. We used immunohistochemistry to examine tau expression in breast cancer biopsies from 113 primary breast cancer patients and evaluated the correlation between tau expression and taxane sensitivity. Twenty-eight (24.78 %, 28/113) patients were positive for tau expression. After taxanes-based neoadjuvant chemotherapy, 40 patients achieved pathological complete response (pCR) (35.4 %). Among the 40 patients with pCR, five (12.5 %) were positive for tau expression. In univariate analysis, estrogen receptor (ER), progesterone receptor, human epidermal growth factor receptor 2 (HER2), and tau were found to be significantly predictive of a pCR (P = 0.001, 0.030, 0.002, and 0.025, respectively). Tau, ER, and HER2 status were significant for pCR on multivariate analysis (P = 0.025, 0.005, and 0.043, respectively). Tau expression was positively related to ER (P = 0.007) and progestin receptor (P = 0.008). In conclusion, tau protein expression correlated with breast cancer sensitivity to taxanes-based neoadjuvant chemotherapy; patients negative for tau expression were more likely to achieve pCR.

Accuracy and axilla sparing potentials of sentinel lymph node biopsy with methylene blue alone performed before versus after neoadjuvant chemotherapy in breast cancer: a single institution experience.

INTRODUCTION: The timing of sentinel lymph node biopsy (SLNB) of breast cancer in the neoadjuvant setting is still controversial. We retrospectively analyzed a Chinese patient cohort with neoadjuvant chemotherapy (NAC) to evaluate the accuracy and axilla sparing potentials of different SLNB timings with methylene blue alone for lymphatic mapping. MATERIALS AND METHODS: Patients with NAC and axillary lymph node dissection (ALND) and either pre- or post-NAC SLNB were eligible. Clinicopathological characteristics, identification rate (IR), false-negative rate (FNR), accuracy, and positive-predictive value were calculated and compared between the pre- and post-NAC SLNB group using appropriate statistical methods. Axilla sparing potentials of different SLNB timings were evaluated and compared. RESULTS: One hundred and fifteen eligible cases were included, and 58 had pre-NAC SLNB while the other 57 had post-NAC SLNB. Both groups were comparable in clinicopathological characteristics, neoadjuvant treatments and pathologic complete response rate. IR, FNR, and accuracy of SLNB, as pre-NAC versus post-NAC, were 100 versus 98.2 % (P = 0.496), 0 versus 8.0 % (P = 0.181), and 100 versus 96.4 % (P = 0.239), respectively. Post-NAC SLNB had significantly higher positive-predictive value for ALNs than pre-NAC SLNB (70.0 vs. 36.4 %, P = 0.014), suggesting as high as 63.6 % of ALND performed in the pre-NAC group could have been avoided while only 30 % of ALND in the post-NAC group were theoretically unnecessary. CONCLUSIONS: Both SLNB timings of breast cancer patients with NAC were feasible and accurate. Although pre-NAC SLNB tends to be better in accuracy, post-NAC SLNB is significantly superior in terms of axilla sparing.

Bis(5-methyl-pyrazine-2-carboxyl-ato-κ²N,O)nickel(II).

In the title complex, [Ni(C6H5O2N2)2], the Ni(II) atom is situated on an inversion centre and is coordinated in a square-planar geometry by four O atoms and two N atoms of the chelating ligands.

2-(5-Amino-2H-tetra-zol-2-yl)acetic acid.

In the title mol-ecule, C(3)H(5)N(5)O(2), the tetra-zole ring and carboxyl group form a dihedral angle of 82.25 (14)°. In the crystal, adjacent mol-ecules are linked through O-H⋯N, N-H⋯O and N-H⋯N hydrogen bonds into layers parallel to the bc plane.

Pre-treatment hormonal receptor status and Ki67 index predict pathologic complete response to neoadjuvant trastuzumab/taxanes but not disease-free survival in HER2-positive breast cancer patients.

Trastuzumab-containing neoadjuvant chemotherapy achieves a pathologic complete response (pCR) rate of about 40 % in HER2-positive breast cancers, and pCR predicts better survival. A cohort of 102 consecutive Chinese HER2-positive stage II/III patients with neoadjuvant trastuzumab/taxanes were retrospectively analyzed, to evaluate the role of hormonal receptor (HR) status and Ki67 index, along with other parameters, in pCR and survival prediction. pCR rate of the cohort was 44.1 % (45/102). Fifty-three patients were HR-positive and 49 were HR-negative. Median Ki67 index was 40 %, and 49 patients had a high Ki67 index (>40 %) whereas 53 had a low Ki67 index (≤40 %). HR status and Ki67 index were confirmed as the only two parameters associated with pCR in multivariate analysis (hazard ratio = 2.952; 95 % CI, 1.227-7.105; P = 0.016 for HR status and hazard ratio = 2.583, 95 % CI 1.107-6.026, P = 0.028 for Ki67 index). Patients with coexisting HR-negative and high Ki67 index had higher pCR rate (69.2 %), compared to those with either HR-negative alone or high Ki67 alone (hazard ratio = 3.038; 95 % CI, 1.102-8.372; P = 0.029), and to those with coexisting HR-positive and low Ki67 index as well (hazard ratio = 7.071; 95 % CI, 2.150-23.253; P = 0.001). In a median follow-up duration of 25.9 months, 11 disease-free survival events (DFS) were recorded. pCR predicted better DFS (log rank P = 0.018) and was the only significant factor in Cox regression analysis (hazard ratio = 0.184; 95 % CI, 0.038-0.893; P = 0.036). Our study indicates that HR status and Ki67 index are predictors for pCR but not for DFS in HER2-positive patients with neoadjuvant trastuzumab/taxanes, which deserves further investigations.

[Microstructure study on bismuth triborate crystal and its melt at high temperature by Raman spectroscopy].

Temperature dependent Raman spectra of BiB3 O6 crystal and its melt were recorded and the microstructure of BiB3 O6 melt was predicted. Multiple theoretical methods including quantum chemistry ab initio calculation and DFT (Density Function Theory) methods were applied to simulate the BiB3 O6 crystal and melt structure and Raman spectra. It was demonstrated that B-O triangles and Bi lattice in the crystal reveal little affected in structure while B-O tetrahedra shows severe distortion with increasing temperature, especially B-O tetrahedra disappears after being completely melt. The microstructure of BiB3 O6 melt consists of six-member ring, [B6 O12](6-), which varies in bond lengths and angles individually. Cation Bi behaves to balance the charge of anion cluster, and the oxygen coordination number of cation Bi is 3, different from the crystal situation in which cation Bi is coordinated with 6 oxygens.

Diaqua-bis-(5-methyl-pyrazine-2-carboxyl-ato-κN,O)cobalt(II) dihydrate.

In the title complex, [Co(C(6)H(5)N(2)O(2))(2)(H(2)O)(2)]·2H(2)O, the coordination geometry of the Co(2+) cation is distorted octa-hedral, with two N atoms and two O atoms from two 5-methyl-pyrazine-2-carboxyl-ate ligands in the equatorial plane. The two remaining coordination sites are occupied by two water mol-ecules. In addition, there are two uncoordinated water mol-ecules in the asymmetric unit. The crystal structure is stabilized by a network of O-H⋯O and O-H⋯N hydrogen-bonding inter-actions, forming a three-dimensional structure.

HER2-positive status is an independent predictor for coexisting invasion of ductal carcinoma in situ of the breast presenting extensive DCIS component.

DCIS of the breast with coexisting invasion is commonly seen, and no consensus on any biomarker capable of discriminating this subgroup has been reached yet. We retrospectively examined the receptor status and the histological grade in Chinese DCIS patients to identify any independent predictor in order to discriminate a subgroup with coexisting invasion from pure DCIS patients. A consecutive Chinese DCIS patient cohort registered at a single institution was included for ER, PR, and HER2 status, as well as for evaluation of the histological grade. Patients with invasion foci >1cm in diameter were excluded. The HER2 gene amplification status was further examined by FISH when the IHC result was HER2 (2+). Molecular subtypes were also profiled. Age, histological grade, ER, PR, and HER2 status were included in association analyses. In total, 183 patients were included. A hundred and forty patients had pure DCIS, and 43 patients had DCIS with invasion. The luminal A subtype accounted for 49.7% of all cases, the HER2-positive subtype for 27.9%, and only 10.4% and 12.0% represented the luminal B and basal-like subtypes, respectively. Univariate analyses showed that histological Grade 2, Grade 3, and HER2-positive status were associated with DCIS with invasion, odds ratios 5.1 (P = 0.017), 5.2 (P = 0.01) and 3.34 (P = 0.001), respectively. However, only the HER2-positive status was of statistical significance in the multivariate logistic regression analyses after adjustment for other markers, odds ratio 3.8 (95%CI 1.4-10, P = 0.008). The 43 cases with invasion were further stratified into extensive or small DCIS components according to the percentage of DCIS to total tumor area using 25% as the cutoff point. Multinomial logistic regression with pure DCIS cases as reference showed that the HER2-positive status was associated only with the group showing an extensive DCIS component, odds ratio 6.2 (95%CI 1.8-21, P = 0.003), but not with the group having a small DCIS component. Our study demonstrates that HER2-positive status is an independent predictor for DCIS, with invasion presenting an extensive DCIS component, and favors the hypothesis that HER2 overexpression or gene amplification is involved in the transition from DCIS to invasive disease.

[Efficacy and safety assessment of neoadjuvant paclitaxel and trastuzumab in Chinese women with Her-2 positive operable breast cancer].

OBJECTIVE: To assess the efficacy and safety of neoadjuvant 3-weekly paclitaxel plus trastuzumab (TH) in Chinese women with Her-2 overexpressing operable breast cancer. METHODS: This is a single center open-label phase II clinical trial. The included patients underwent 4 cycles of neoadjuvant 3-weekly TH before surgery. The primary endpoint was pathologic complete response rate (pCR rate) and the secondary endpoint was overall response rate (OR rate). Patients were also stratified according to hormone receptor status, and pCR rate and OR rate were compared between subgroups. Adverse events were graded according to CTCAE v3.0. RESULTS: There were 40 eligible patients entering this study with median age of 49 years. All patients completed 4 cycles of neoadjuvant treatment. pCR rate was 52.5% and OR rate was 87.5%. The differences of pCR and OR rates between subgroups were of no statistical significance. No cardiac toxicity event severer than grade 2 was recorded. CONCLUSION: 3-weekly TH regimen has satisfactory pCR rate and OR rate in Chinese patients with Her-2 overexpressing operable breast cancer and reliable safety.

Efficacy of intraoperative GeneSearch Breast Lymph Node (BLN) Assay for breast cancer metastasis detection in sentinel lymph node in Chinese patients.

UNLABELLED: Although intraoperative assessment of the sentinel lymph node (SLN) is useful, it has not gained popularity in China as it involves a heavy workload for pathologists. We conducted a prospective clinical feasibility study of the GeneSearch Breast Lymph Node (BLN) Assay performed in 158 SLNs from 97 patients by comparison with postoperative permanent section histopathology, to validate its potential usefulness in China. Every SLN was cut into alternating 1.5 to 3.0 mm slabs. The BLN assay processed 50% of the fresh alternating slabs to detect the presence of cytokeratin 19 and mammaglobin mRNA. Assay results were compared with those for permanent section histopathology and intraoperative imprint cytology. Slides for imprint cytology were prepared from the BLN assay node tissue before it was processed. Full axillary lymph node (ALN) dissections were performed on some patients after a SLN biopsy. The BLN assay was successfully performed on 158 SLNs from 97 patients. Overall performance of the BLN assay compared with permanent section histopathology was sensitivity 83.9% (26/31), specificity 95.5% (63/66), positive predictive value 89.7% (26/29), negative predictive value 92.6% (63/68), and overall agreement 91.8% (89/97). The BLN assay detected about 25% more metastases than imprint cytology. Moreover, the BLN assay correctly identified most of the additional non-sentinel ALNs metastases (P = 0.005). Our results from a large series of Chinese patients with breast cancer indicate that the BLN assay may be a viable alternative for the standard intraoperative procedures used for metastases detection, especially in early stage breast cancer patients. Name of the trial register: GeneSearch Breast Lymph Node (BLN) Assay China Registration Study. CLINICAL TRIAL REGISTRATION NUMBER: NCT00869674.

[Soil nitrogen mineralization and primary productivity in Rhododendron aureum community of snowpacks in alpine tundra of Changbai Mountain].

Based on continuous observation of soil temperature and in situ incubation, this paper studied the effects of snow packs on soil temperature, soil nitrogen (N) mineralization, and primary productivity of Rhododendron aureum community alpine tundra in Changbai Mountain. During the snow-covered period of non-growth season (from last October to early May), test soil had an increasing N content, and accumulated sufficient mineralized N for plant growth in the coming year. The soil under snow packs in snow-covered period had a mean temperature -3.0 degrees C, and its N mineralization was more vigorous, with available N increased by 3.88 g x m(-2); while the soil with no snowpack had a mean temperature -7.5 degrees C, and the available N only increased by 1.21 g x m(-2). During growth season (from mid May to late August), soil N content decreased. In autumn when plants stopped growing, soil available N content tended to increase. In winter, the soil temperature under snowpacks kept at around 0 degrees C or a little lower, which promoted soil N mineralization, while that with no snowpack was in a frozen status. The difference in soil N mineralization was the key factor resulting in the higher primary productivity of snowpack Rh. aureum community and the driving force for the spatial variation of vegetation.

[A meta-analysis of neoadjuvant chemotherapy combined with trastuzumab for HER2-positive breast cancers].

OBJECTIVE: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with trastuzumab for HER2 positive breast cancers. METHODS: PubMed online database, ASCO abstract database, SABCS abstract database, ESMO abstract database and CBMdisc database were searched for literatures related to trastuzumab in neoadjuvant chemotherapy for breast cancers. A meta-analysis was performed for retrieved literatures meeting the inclusion criteria. RESULTS: Three clinical trials were included. Meta-analysis showed that compared to chemotherapy only, regimens combined with trastuzumab could significantly improved the pCR rate of HER2-positive breast cancers (RR=1.65, 95% CI 1.28-2.13, P<0.0001) without increasing the frequencies of cardiac toxicity (RR=1.16, 95% CI 0.82-1.64, P=0.41). CONCLUSION: In neoadjuvant chemotherapy for HER2-positive breast cancers, chemotherapy combined with trastuzumab is superior to exclusive chemotherapy.

Expression of cyclin D1 splice variants is differentially associated with outcome in non-small cell lung cancer patients.

Real-time reverse transcription polymerase chain reaction and immunohistochemistry were used to evaluate the messenger RNA (mRNA) and protein expression levels of total cyclin D1 and its splice variants (cyclin D1a and cyclin D1b) in 102 paired malignant and nonmalignant tissues from patients with non-small cell lung cancer, respectively. The expression levels of total cyclin D1 and its splice variants were significantly up-regulated in malignant tissues than in nonmalignant tissues at both mRNA and protein levels. Although the expression levels of cyclin D1a were higher than those of cyclin D1b, the relative expression ratios of cyclin D1b mRNA between malignant and nonmalignant lung tissues were obviously higher than those of cyclin D1a mRNA. Analysis of variance showed that cyclin D1b mRNA expression was significantly associated with the histologic grade, lymph node metastasis, distant metastasis, and tumor stage of patients, whereas cyclin D1a mRNA expression was not related to clinicopathologic characteristics except sex. Patients with cyclin D1b mRNA expression above the median value had shorter survival than those below the median value (P = .033). Similarly, cyclin D1b immunopositivity was also associated with histologic grade, and patients with immunostaining positivity for cyclin D1b showed poor survival (P = .005). Multivariate analysis demonstrated that cyclin D1b immunopositivity was an independent risk factor in survival of patients with non-small cell lung cancer (P = .018). Our data show that cyclin D1b, rather than canonical cyclin D1a, might contribute to the development of non-small cell lung cancer. Cyclin D1b would be a better prognostic indicator for non-small cell lung cancer as compared to total cyclin D1 or cyclin D1a.

Better survival with EGFR exon 19 than exon 21 mutations in gefitinib-treated non-small cell lung cancer patients is due to differential inhibition of downstream signals.

Somatic mutations in the epidermal growth factor receptor (EGFR) kinase domain are associated with sensitivity to tyrosine kinase inhibitors (TKIs) in patients with non-small cell lung cancer (NSCLC). Our clinical data showed NSCLC patients with exon 19 deletions survived longer following gefitinib treatment than those with exon 21 point mutations. We aimed to investigate whether these two mutations produced differences in phosphorylation of EGFR and downstream signals. Two stable cell lines expressing these mutations were obtained by transfection. Inhibition of phosphorylation of EGFR, Akt, and Erk by gefitinib was detected using Western blotting, and cell inhibition tests were conducted to evaluate the bio-behavior. Gefitinib inhibited the phosphorylation of EGFR, Akt, and Erk to a greater degree in exon 19 deletion cells than in L858R cells. Gefitinib produced G1 arrest in more of the cells with exon 19 deletion than with L858R. This might be attributable to patient selection in TKIs therapy.

EGFR/KRAS mutations and gefitinib therapy in Chinese NSCLC patients.

BACKGROUND: For gefitinib treatment for non-small cell lung cancer (NSCLC), KRAS mutations reportedly behave as a resistance marker, and the epidermal growth factor receptor (EGFR) as a responsive marker. It is known that Asians and Caucasians have different responses to gefitinib. We investigated the KRAS and EGFR mutation status in a group of Chinese patients with advanced NSCLC who were treated with gefitinib after a failed chemotherapy. MATERIAL AND METHODS: Genomic DNA extracted from tumor specimens of 24 patients with advanced NSCLC, who failed at least 1 prior platinum-based chemotherapy regimen before gefitinib treatment, was subjected to nested polymerase chain reaction (PCR) to amplify codons 12, 13, 59, and 61 of the KRAS gene and exons 18-21 of the EGFR gene for direct sequencing. RESULTS: For the 24 patients, no KRAS gene mutation was found. 15 patients (62.5%, 15/24) harbored EGFR mutations which included deletion mutations in exon 19 and missense mutations in exon 21. CONCLUSION: KRAS mutation may occur at a very low frequency in Chinese NSCLC patients regardless of pathology, smoking status, or gender. Unlike EGFR, the low incidence of KRAS mutations may undermine its role in predicting the clinical response to EGFR tyrosine kinase inhibitors.

catena-Poly[[dichloridonickel(II)]-µ-1,3-di-4-pyridylpropane].

The title compound, [NiCl(2)(C(13)H(14)N(2))](n), is a one-dimensional polymer built up from alternating NiCl(2) units and bridging 1,3-di-4-pyridylpropane ligands. The Ni atom has a distorted tetra-hedral coordination formed by the Cl atoms and two N atoms from two ligands. A mirror plane pases through the central methylene group of the propyl chain.

The epidermal growth factor receptor intron1 (CA) n microsatellite polymorphism is a potential predictor of treatment outcome in patients with advanced lung cancer treated with Gefitinib.

The goal of our study was to assess the association between R497K and intron1 (CA) n repeat genetic polymorphisms of the EGF (epidermal growth factor) receptor and the clinical outcome of patients with advanced non-small cell lung cancer treated with EGF receptor tyrosine kinase inhibitor. We determined the genotypes for R497K and intron1 (CA) n repeat genetic polymorphisms of 70 Chinese patients with advanced non-small cell lung cancer. Genetic polymorphisms were correlated with the clinical outcome of treatment with EGF receptor tyrosine kinase inhibitor. In a subgroup of patients whose tumor tissues were available for mutation analysis and IHC (immunohistochemistry) assay, the associations between the EGF receptor mutations, the EGF receptor protein expression levels and EGF receptor polymorphisms were analyzed. The results indicated that patients with a lower number of EGF receptor CA repeats (any allele < or =16 CA) were more likely to have higher EGF receptor protein expression levels, better response, and longer survival time than were patients with a higher number of CA repeats (both alleles >16 CA) after therapy targeted at the EGF receptor (P=0.021; P=0.014; P=0.0392, respectively). In contrast, the R497K polymorphism had no relationship with EGF receptor protein expression levels or the clinical outcome of the patients treated with EGF receptor tyrosine kinase inhibitor (P=0.49; P=0.452, respectively), and there were no associations between the two polymorphisms and somatic mutations (P=0.916; P=0.562, respectively). Overall, our data suggest that the intron1 (CA) n polymorphism of the EGF receptor gene may be associated with the sensitivity to and the prognosis of non-small cell lung cancer after EGF receptor targeted inhibitor treatment.

Epidermal growth factor receptor mutations and their correlation with gefitinib therapy in patients with non-small cell lung cancer: a meta-analysis based on updated individual patient data from six medical centers in mainland China.

BACKGROUND: Convincing data on epidermal growth factor receptor (EGFR) mutations in Chinese patients with non-small-cell lung cancer (NSCLC) remain limited. We investigated the relevance of demographic characteristics and EGFR mutations, correlations between the efficacy of gefitinib and EGFR mutations in NSCLC, and to identify individuals who would likely benefit from gefitinib. METHODS: We conducted a meta-analysis based on updated individual patient data from six medical centers in mainland China. Outcome measures included the EGFR mutation status, demographic characteristics, response, and survival. RESULTS: Among 506 patients with NSCLC who received EGFR mutation analysis, the EGFR mutation rate was 30.04%. Patients with adenocarcinoma had a higher mutation rate than those with non-adenocarcinoma (44.1% vs 9.2%; p < 0.00001). The EGFR mutation rate for smokers was 15.1%, lower than that for non-smokers (45.5%) (p < 0.00001). Male patients had a lower mutation rate than female patients (23.1% vs 42.9%; p < 0.0001). Multivariate analysis showed that "adenocarcinoma" and "non-smoker" were independent predictors of EGFR mutations. In a subgroup of 57 patients with complete treatment data, the response rate to gefitinib in the EGFR mutant group was 60.7%, significantly higher than that in the wild-type EGFR group (17.2%) (odds ratio, 5.78; 95% CI, 1.95-17.13; p = 0.002). "EGFR mutation", "adenocarcinoma," and "non-smoker" were independent predictors of response. Overall survival in the EGFR mutant group and the wild-type group did not differ significantly (hazard ratio, 0.60; 95% CI, 0.32-1.12; p = 0.110). "Adenocarcinoma status" was an independent prognostic factor for survival. CONCLUSIONS: In mainland China, "adenocarcinoma" and "non-smoker" are independent predictors for EGFR mutations. Response to gefitinib favors patients with EGFR mutations. The clinical selected populations for gefitinib are non-smokers with adenocarcinoma.