[show abstract][hide abstract] ABSTRACT: Lineage transition in adenocarcinoma (ADC) and squamous cell carcinoma (SCC) of non-small cell lung cancer, as implicated by clinical observation of mixed ADC and SCC pathologies in adenosquamous cell carcinoma, remains a fundamental yet unsolved question. Here we provide in vivo evidence showing the transdifferentiation of lung cancer from ADC to SCC in mice: Lkb1-deficient lung ADC progressively transdifferentiates into SCC, via a pathologically mixed mAd-SCC intermediate. We find that reduction of lysyl oxidase (Lox) in Lkb1-deficient lung ADC decreases collagen disposition and triggers extracellular matrix remodelling and upregulates p63 expression, a SCC lineage survival oncogene. Pharmacological Lox inhibition promotes the transdifferentiation, whereas ectopic Lox expression significantly inhibits this process. Notably, ADC and SCC show differential responses to Lox inhibition. Collectively, our findings demonstrate the de novo transdifferentiation of lung ADC to SCC in mice and provide mechanistic insight that may have important implications for lung cancer treatment.
[show abstract][hide abstract] ABSTRACT: Liver kinase B1 (LKB1) genetic alteration in lung cancer involves not only point mutations and small deletion of several base pairs but also exonic loss. However, most of recent studies in LKB1 gene status only focus on point mutations and small deletion, and thus may underestimate the actual frequency of LKB1 genetic alteration in lung cancer. Thus, an integrative analysis of LKB1 genetic alteration is timely and important for providing a better estimate for the incidence of genetic alterations in this important tumor suppressor gene. One hundred and seven lung adenocarcinomas with more than 70% tumor have been analyzed for mutation of LKB1 as well as LKB1 large deletions detection by using multiplex ligation-dependent probe amplification analysis. These samples were also analyzed for EGFR, KRAS, HER2, BRAF, ALK, ROS1, and RET status in stepwise method. Among 107 lung adenocarcinomas analyzed, 29 (27.1%) harbored LKB1 genetic alteration. Twenty-three (21.5%) harbored LKB1 large exonic deletions and eight (7.48%) had LKB1 points mutations, two samples harbored both LKB1 large exonic deletions and point mutations. Eighty-seven samples (81.31%) harbored known driver mutations and 20 samples (18.69%) had no identifiable driver mutations. A high rate of LKB1 genetic alteration in Chinese lung adenocarcinomas is revealed by the integrative analysis of point mutation and exonic deletion. Moreover, LKB1 genetic alterations are concurrent with EGFR, KRAS, HER2, and CD74-ROS fusions.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2014; 9(2):254-8. · 4.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Genotyping for driver mutations is now routinely used to guide clinical care of patients with lung cancer. Adenosquamous lung carcinoma (AdSqLC) is a subtype of cancer that contains both adenocarcinoma and squamous cell carcinoma. However, the incidence, clinicopathologic characteristics, and prognostic implications of major driver mutations in AdSqLCs are not well established.
Seventy-six resected AdSqLCs and 646 lung adenocarcinomas were screened for known genetic alterations involving EGFR, ERBB2, KRAS, BRAF, PIK3CA, AKT1, RET, and ALK. Tumors showing acinar, lepidic, micropapillary, or papillary growth in glandular component were classified as classical AdSqLC.
Of the 76 AdSqLCs, 43 (56.6%) harbored known mutant kinases, including 24 (31.6%) with EGFR mutations, eight (10.5%) with KRAS mutations, two (2.6%) with AKT1 (2.6%) mutations, one (1.3%) with ERBB2 insertion mutation, one (1.3%) with PIK3CA mutation, four (5.3%) with ALK fusions, and three (4%) with KIF5B-RET fusions. No mutation was found in BRAF. The mutational profiles and clinicopathologic characteristics of classical AdSqLC were strikingly similar to that of poorly differentiated adenocarcinoma. However, AdSqLCs with solid growth pattern in glandular component had high frequency of ALK or RET fusions and low EGFR mutation rate.
To our knowledge, this is the first comprehensive study investigating major oncogenic driver mutations in a large cohort of AdSqLC patients in a Chinese population. The findings suggest that it will be clinically valuable to investigate the growth pattern of glandular component in AdSqLCs.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 01/2014; · 4.55 Impact Factor
[show abstract][hide abstract] ABSTRACT: Lung cancer is one of the most devastating diseases worldwide with high incidence and mortality. Hippo (Hpo) pathway is a conserved regulator of organ size in both Drosophila and mammals. Emerging evidence has suggested the significance of Hpo pathway in cancer development. In this study, we identify VGLL4 as a novel tumor suppressor in lung carcinogenesis through negatively regulating the formation of YAP-TEAD complex, the core component of Hpo pathway. Our data show that VGLL4 is frequently observed to be lowly expressed in both mouse and human lung cancer specimens. Ectopic expression of VGLL4 significantly suppresses the growth of lung cancer cells in vitro. More importantly, VGLL4 significantly inhibits lung cancer progression in de novo mouse model. We further find that VGLL4 inhibits the activity of the YAP-TEAD transcriptional complex. Our data show that VGLL4 directly competes with YAP in binding to TEADs and executes its growth-inhibitory function through two TDU domains. Collectively, our study demonstrates that VGLL4 is a novel tumor suppressor for lung cancer through negatively regulating the YAP-TEAD complex formation and thus the Hpo pathway.Cell Research advance online publication 24 January 2014; doi:10.1038/cr.2014.10.
[show abstract][hide abstract] ABSTRACT: To define the prevalence, clinicopathologic characteristics and molecular associations of epidermal growth factor receptor (EGFR) exon 20 insertion mutations in East Asian lung adenocarcinoma patients.
A total of 1,086 lung adenocarcinomas were sequenced for EGFR mutations. EGFR and HER2 copy number variations; total and phosphorylated (p) protein expression of ErbB family members including EGFR, HER2, and HER3; phosphorylated protein expression of downstream signaling molecules including Akt and Erk; and clinicopathologic features in lung adenocarcinomas with EGFR exon 20 insertion mutations were all investigated.
EGFR exon 20 insertion mutations were present in 2.9 % of lung adenocarcinomas and 4.7 % of all the EGFR mutations. Compared to those with classic activating EGFR mutations, lung adenocarcinomas with exon 20 insertion mutations were characterized by significantly younger age at diagnosis (P = 0.032 for exon 20 insertions vs. L858R) and shorter relapse-free survival [P = 0.045 for exon 20 insertions versus (vs) exon 19 deletions]. Molecularly, samples harboring exon 20 insertion mutations had lower expression of phosphorylated (p)-EGFR (P < 0.001) and HER3 (P = 0.016). In addition, higher expression of p-Akt (P = 0.007) and lower expression of p-Erk (P = 0.009) were observed in tumors with exon 20 insertion mutations.
Lung adenocarcinomas with EGFR exon 20 insertion mutations were present in a substantial proportion. This subset showed distinct clinicopathologic features, less dependence on EGFR molecularly, and different pathway activation patterns compared to those with classic EGFR activating mutations.
Annals of Surgical Oncology 01/2014; · 4.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: PIK3CA gene encoding a catalytic subunit of the phosphatidylinositol-3-kinase (PI3K) is mutated and/or amplified in various neoplasia, including lung cancer. Here we investigated PIK3CA gene alterations, the expression of core components of PI3K pathway, and evaluated their clinical importance in non-small cell lung cancer (NSCLC).
Oncogenic mutations/rearrangements in PIK3CA, EGFR, KRAS, HER2, BRAF, AKT1 and ALK genes were detected in tumors from 1117 patients with NSCLC. PIK3CA gene copy number was examined by fluorescent in situ hybridization and the expression of PI3K p110 subunit alpha (PI3K p110α), p-Akt, mTOR, PTEN was determined by immunohistochemistry in PIK3CA mutant cases and 108 patients without PIK3CA mutation.
PIK3CA mutation was found in 3.9% of squamous cell carcinoma and 2.7% of adenocarcinoma. Among 34 PIK3CA mutant cases, 17 tumors harbored concurrent EGFR mutations and 4 had KRAS mutations. PIK3CA mutation was significantly associated with high expression of PI3K p110α (p<0.0001), p-Akt (p = 0.024) and mTOR (p = 0.001), but not correlated with PIK3CA amplification (p = 0.463). Patients with single PIK3CA mutation had shorter overall survival than those with PIK3CA-EGFR/KRAS co-mutation or wildtype PIK3CA (p = 0.004). A significantly worse survival was also found in patients with PIK3CA mutations than those without PIK3CA mutations in the EGFR/KRAS wildtype subgroup (p = 0.043).
PIK3CA mutations frequently coexist with EGFR/KRAS mutations. The poor prognosis of patients with single PIK3CA mutation in NSCLC and the prognostic value of PIK3CA mutation in EGFR/KRAS wildtype subgroup suggest the distinct mutation status of PIK3CA gene should be determined for individual therapeutic strategies in NSCLC.
PLoS ONE 01/2014; 9(2):e88291. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Background
To have a comprehensive investigation of the clinicopathologic, histologic and cytologic features of fusion-positive lung adenocarcinomas.
Quantitative real-time reverse transcriptase PCR (qRT-PCR) and reverse transcriptase PCR (RT-PCR) were simultaneously performed to screen ALK, ROS1 and RET fusions in resected tumor samples from 1139 Chinese lung adenocarcinoma patients, with validation of positive results using fluorescent in situ hybridization. Clinicopathologic characteristics, predominant histologic subtype and cytomorphology were assessed in fusion-positive lung adenocarcinomas and compared to those harboring EGFR, KRAS, HER2 or BRAF mutations.
There were 58 (5.1%) ALK fusions, 11 (1.0%) ROS1 fusions and 15 (1.3%) RET fusions. Tumors with ROS1 fusions had significantly larger diameter than ROS1 fusion-negative tumors (P = 0.007), whereas all the 15 tumors harboring RET fusions were ≤ 3 cm in diameter (P = 0.001). The three fusion genes were all more prevalent in solid-predominant adenocarcinoma. Compared to fusion-negative lung adenocarcinomas, tumors harboring a fusion gene had significantly higher prevalence of extracellular mucin (P < 0.001), cribriform pattern (P < 0.001), signet ring cells (P < 0.001) and hepatoid cytology (P < 0.001). No significant difference in relapse-free survival (P = 0.147) and overall survival (P = 0.444) was observed between fusion-positive and fusion-negative patients.
This study showed fusion-positive lung adenocarcinomas had identifiable common and fusion-pattern specific clinicopathologic, histologic and cytologic features, offering implications for fusion genes screening.
[show abstract][hide abstract] ABSTRACT: The mutations in oncogenic genes, such as EGFR, ALK, BRAF, HER2, DDR2, RET and AKT1, defined subsets of non-small cell lung cancers (NSCLC) with potential sensitivity to targeted therapies. At present, the mutational spectrum, prevalence and clinicopathologic characteristics in squamous cell carcinomas with minor (<10%) glandular component (SQCC-mGC) are not well established.
Three hundred and ten surgically resected lung squamous cell carcinoma (SQCC) specimens were collected. The histology of all cases was re-evaluated using hematoxylin-eosin (H&E) and immunohistochemistry (IHC) staining. EGFR, KRAS, HER2, BRAF, PIK3CA, AKT1 and DDR2 mutations, as well as ALK and RET rearrangements, were examined in 310 SQCCs by directed sequencing.
Ninety-five SQCC-mGCs (30.6%) and 215 pure SQCCs (69.4%) were identified. Of the 95 SQCC-mGCs, 26 (27.4%; 95%CI, 18.7%-37.4%) were found to harbor known oncogenic mutations, including 10 with EGFR, 7 with KRAS, 3 with PIK3CA, 1 with BRAF, 1 with HER2, 1 each with EGFR/PIK3CA and KRAS/PIK3CA double mutations and 2 with EML4-ALK fusions. Ten of 215 pure SQCCs (4.7%; 95%CI, 2.3%-8.4%) harbored mutations, including 7 with PIK3CA, 1 each with AKT1, DDR2, and EGFR. No RET rearrangements were detected in SQCCs. SQCC-mGCs had a significantly higher rate of mutations in known oncogenic genes than that in pure SQCCs (27.4% vs. 4.7%, p<0.001). All KRAS mutations occurred in SQCC-mGCs.
Our results demonstrated that oncogenic mutations in EGFR, KRAS, BRAF, HER2 and ALK were extremely rare or absent in patients with pure SQCC, while SQCC-mGC had relatively high frequency of EGFR, ALK or KRAS mutations. Prospective identification of these known oncogenic mutations in SQCC-mGC before the initiation of treatment is an essential step to identify which patient could benefit from targeted therapies.
[show abstract][hide abstract] ABSTRACT: Driven by high throughput next generation sequencing technologies and the pressing need to decipher cancer genomes, computational approaches for detecting somatic single nucleotide variants (sSNVs) have undergone dramatic improvements during the past two years. The recently developed tools typically compare a tumor sample directly with a matched normal sample at each variant locus in order to increase the accuracy of sSNV calling. These programs also address the detection of sSNVs at low allele frequencies, allowing for the study of tumor heterogeneity, cancer subclones, and mutation evolution in cancer development.
We used whole genome sequencing (Illumina Genome Analyzer IIx platform) of a melanoma sample and matched blood, whole exome sequencing (Illumina HiSeq 2000 platform) of 18 lung tumor-normal pairs and 7 lung cancer cell lines to evaluate 6 tools for sSNV detection: EBCall, JointSNVMix, MuTect, SomaticSniper, Strelka, and VarScan 2, with a focus on MuTect and VarScan 2, two widely used publicly available software tools. Default/suggested parameters were used to run these tools. The missense sSNVs detected in these samples were validated through PCR and direct sequencing of genomic DNA from the samples. We also simulated 10 tumor-normal pairs to explore the ability of these programs to detect low allelic-frequency sSNVs.
Out of the 237 sSNVs successfully validated in our cancer samples, VarScan 2 and MuTect detected the most of any tools, i.e. 204 and 192, respectively. MuTect identified 11 more low-coverage validated sSNVs than VarScan 2, but missed 11 more sSNVs with alternate alleles in normal samples than VarScan 2. When examining the false calls of each tool using 169 invalidated sSNVs, we observed >63% false calls detected in the lung cancer cell lines had alternate alleles in normal samples. Additionally, from our simulation data, VarScan 2 identified more sSNVs than other tools, while MuTect characterized most low allelic-fraction sSNVs.
Our study explored the typical false positive and false negative detections that arise from the use of sSNV-calling tools. Our results suggest that despite recent progress, these tools have significant room for improvement, especially in the discrimination of low coverage/allelic-frequency sSNVs and sSNVs with alternate alleles in normal samples.
Genome Medicine 10/2013; 5(10):91. · 3.40 Impact Factor
[show abstract][hide abstract] ABSTRACT: There have been many controversies about the optimal extent of lymphadenectomy for thoracic esophageal cancer, whether three-field lymphadenectomy is superior to two-field lymphadenectomy with respect to the 5-year survival rate and perioperative morbidities and mortality.
A comprehensive search of PubMed and Embase for relevant studies comparing three-field and two-field lymphadenectomies for thoracic esophageal cancer was conducted using the Preferred Reporting Items for Systemic Reviews and Meta-Analyses standards. Hazard ratios (HRs) were extracted from these studies to give pooled estimates of the effect of the two surgical procedures on the 5-year survival rate and perioperative morbidities and mortality.
Thirteen studies were included for analysis. Compared with two-field lymphadenectomy, three-field lymphadenectomy provided a higher 5-year survival rate (HR 0.64, 95% confidence interval [CI]: 0.56 to 0.73, p = 0.000) and incidence of anastomotic leakage (HR 1.46, 95% CI: 1.19 to 1.79, p = 0.000), with a comparative perioperative mortality (HR 0.64, 95% CI: 0.38 to 1.10, p = 0.110) and incidence of vocal cord palsy (HR 1.12, 95% CI: 0.82 to 1.54, p = 0.470) and pulmonary complications (HR 1.00, 95% CI: 0.89 to 1.12, p = 0.760).
Published evidence indicated that three-field lymphadenectomy could be a priority for thoracic esophageal cancer, especially for tumors with positive lymph nodes. Given the lack of large-sample randomized controlled studies, further evaluations are necessary.
The Annals of thoracic surgery 09/2013; · 3.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Endoscopic treatment of superficial esophageal carcinoma has been increasingly conducted around the world. Because no lymph nodes are removed in such a procedure, the risk of lymph node metastases (LNMs) should be clearly understood. The aim of the present study was to accurately clarify the pattern of lymphatic spread in patients with superficial esophageal squamous cell carcinoma and analyze the factors potentially related to LNMs.
The pattern of lymphatic spread was studied in 189 patients who had undergone radical lymphadenectomy from 2006 to 2011. The risk factors associated with LNMs were determined by multivariate logistic regression analysis. According to the depth of tumor invasion, mucosal tumors were classified as M1, M2, and M3 and submucosal tumors as SM1, SM2, and SM3.
A total of 4252 lymph nodes were resected (average, 23 ± 9; range, 12-68). LNMs occurred in 49 patients (25.9%). The frequency of LNMs was 4.3% in those with mucosal and 33.1% in those with submucosal cancer. LNMs were found in 0%, 0%, 11.8%, 24.0%, 20.5%, and 43.8% of the M1, M2, M3, SM1, SM2, and SM3 cancer, respectively. For submucosal cancer, SM3 cancer (P = .006) and lymphovascular invasion (P = .001) were significant independent risk factors for LNMs. Paratracheal nodes were the most frequently involved. "Skip" metastases occurred in 20 of 49 patients (40.8%).
Endoscopic treatment can be attempted when the tumor is limited to the lamina propria mucosa. However, 2-field radical lymphadenectomy with careful upper mediastinal lymph node resection should be conducted for submucosal squamous cell carcinoma.
The Journal of thoracic and cardiovascular surgery 08/2013; · 3.41 Impact Factor
[show abstract][hide abstract] ABSTRACT: Germline mutations are responsible for familial cancer syndromes which account for approximately 5∼10% of all types of cancers. These mutations mainly occur at tumor suppressor genes or genome stability genes, such as DNA repair genes. Here we have identified a cancer predisposition family, in which eight members were inflicted with a wide spectrum of cancer including one diagnosed with lung cancer at 22 years old. Sequencing analysis of tumor samples as well as histologically normal specimens identified two germline mutations co-existing in the familial cancer syndrome, the mutation of tumor suppressor gene P53 V157D and mismatch repair gene PMS2 R20Q. We further demonstrate that P53 V157D and/or PMS2 R20Q mutant promotes lung cancer cell proliferation. These two mutants are capable of promoting colony formation in soft agar as well as tumor formation in transgenic drosophila system. Collectively, these data have uncovered the important role of co-existing germline P53 and PMS2 mutations in the familial cancer syndrome development.
[show abstract][hide abstract] ABSTRACT: Benign metastasizing leiomyoma (BML) occurs in a low proportion of uterine leiomyomas and treatment methods for BML are diverse and controversial. The study introduces preliminary experiences in the diagnosis and treatment of BML with the purpose of finding a suitable management strategy for these patients.
Three patients with BML were treated in our department from April 2008 to July 2012. Each of these patients presented with multiple nodules in both lungs, where we performed video-assisted thoracoscopic wedge resection to harvest enough tissue for histopathologic and immunohistochemical examination. The patients were treated with medical castration or surgical castration after the diagnosis of BML.
The ultimate pathologic results ruled out the possibility of leiomyosarcoma and other metastatic diseases, and confirmed that the pulmonary lesions were BML. The lung lesions remained stable in two patients who were treated by surgical castration, and the lung nodules regressed in one patient treated with gonadotropin-releasing hormone analogues.
The diagnosis of BML is based on the medical history of uterine myomas and histopathologic and immunohistochemical examination of lung nodules. Video-assisted thoracoscopic wedge resection is the best way to harvest tissue for diagnosis. The better outcomes in BML seem to call for medical intervention, either chemical or surgical, after diagnosis is made.
World Journal of Surgical Oncology 07/2013; 11(1):163. · 1.09 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: AAA+ nuclear coregulator cancer associated (ANCCA) is found to be overexpressed in various cancer types and could play a role in common and fundamental cellular processes. A recent study suggested that ANCCA was a likely driver whose expression explained the behavior of differentially expressed proliferation-related genes in lung adenocarcinoma. However, protein expression of ANCCA in lung adenocarcinoma and its association with clinicopathologic parameters and commonly reported driver mutations remains unexplored. METHODS: ANCCA expression was evaluated by immunohistochemistry in 143 surgically resected lung adenocarcinomas and was correlated with clinicopathologic and molecular variables including adenocarcinoma histologic subtypes, tumor, node, metastasis status, relapse-free survival, overall survival, EGFR mutations, KRAS mutations, HER2 mutations and ALK fusions. RESULTS: Positive ANCCA expression was significantly associated with male sex, smokers, poorly differentiated tumors, nonlepidic predominant subtype, more advanced T stage, lymph nodal metastasis and late disease stage. Cox multivariate analysis revealed that ANCCA-positive expression was an independent predictor of worse relapse-free survival [hazard ratio (HR) 1.736, 95 % confidence interval (CI) 1.075-2.804; P = .024) and overall survival (HR 7.758, 95 % CI 2.955-20.370; P < .001). The addition of ANCCA protein expression to the prognostic model using pathologic stage markedly improved the prognostic accuracy; the concordance index increased from .692 to .788, and the Akaike information criterion decreased from 354.20 to 336.11. CONCLUSIONS: We have identified ANCCA protein expression as a novel independent poor prognostic indicator in lung adenocarcinoma. Prospective studies are warranted to validate its potential prognostic value in combination with the current staging system.
Annals of Surgical Oncology 06/2013; · 4.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: The presence of nodal skip metastasis (NSM) has been found to be of clinical importance in non-small cell lung cancer, but the study of this phenomenon in esophageal carcinoma is relatively rare. The purpose of this study was to identify risk factors influencing NSM and to assess its prognostic value in thoracic esophageal squamous cell carcinoma (ESCC). METHODS: A total of 207 patients with thoracic ESCC who underwent three-field lymphadenectomy and who had lymph node metastasis were reviewed. Associations of NSM occurrence with the clinicopathological characteristics of patients and primary tumors were evaluated using logistic regression analysis. The influence of NSM on the overall survival (OS) was assessed by log-rank tests and Cox regression analysis. RESULTS: NSM were present in 58 (26 %) patients. No factor was significantly associated with the incidence of NSM except for the location of primary tumor. There were no NSMs in the 29 patients from our study with upper thoracic ESCC, and the rates of tumors occurrence in the middle and lower third of the esophagus were 38.9 and 14.9 %, respectively. The median OS was 30 months, and no significant difference in OS was found between the patients with or without NSM (p = 0.767). Only N status was found to be the independent risk factor for OS by Cox multivariate analysis. CONCLUSIONS: NSM is common in thoracic ESCC, especially in patients with tumors located in the middle and lower third of the esophagus. However, the presence of NSM did not predict prognosis.
Annals of Surgical Oncology 05/2013; · 4.12 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND AND OBJECTIVE: The aims of our study were to evaluate the occult nodal metastasis in clinical stage I patients by PET/CT, further investigate the potential risk factors for nodal involvement, since a successful prediction could be helpful in selection appropriate candidates for SABR or limited surgery. METHODS: We retrospectively reviewed the records of 189 patients who diagnosed as clinical stage I NSCLC by (18)F-FDG PET/CT from January 2004 to July 2011. All patients underwent lobectomy and systematic lymph node dissection and preoperative (18)F-FDG PET/CT scanning. The prevalence of occult nodal metastasis in patients as clinical N0 was analyzed according to clinicopathological factors such as tumor location, tumor size, tumor subtype, grade of differentiation and primary tumor SUVmax. Risk factors for occult nodal metastasis were defined by univariate and multivariate analysis. RESULTS: Occult nodal metastasis was detected in 18.0% (34/189) of the patients. SUVmax of the primary tumor and tumor size were independent predictors of occult nodal metastasis for patients with clinical N0 NSCLC by FDG PET/CT. Accordingly we divided our patients into three groups: group 1 (low-risk group) ~T≤3cm and SUVmax≤4.3; group 2 (moderate-risk group) ~T≤3cm and SUVmax>4.3 or SUVmax≤4.3 and T>3cm; group 3 (high-risk group) ~T>3cm and SUVmax>4.3. The occult lymph node metastasis rate in groups 1, 2, 3 was 1/82 (1.2%), 19/75 (25.3%) and 14/32 (43%) respectively. CONCLUSIONS: T1-2N0M0 NSCLC patients by PET/CT showing larger tumor size and high SUVmax constitute a high-risk group for occult nodal metastasis. The combined information of primary tumor SUVmax and tumor size before treatment have potential values in the clinic. These findings would be helpful in selection of SABR or limited surgery candidates.
Lung cancer (Amsterdam, Netherlands) 05/2013; · 3.14 Impact Factor
[show abstract][hide abstract] ABSTRACT: This aim of this study was to compare the efficacy of first-line tyrosine kinase inhibitor therapy followed, upon progression, by chemotherapy with the reverse sequence in patients with EGFR-mutated non-small cell lung cancer (NSCLC) in terms of overall survival.
We performed a meta-analysis of studies that met the following criteria: Phase III clinical trial comparing the sequencing of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors with chemotherapy in the treatment of advanced EGFR-mutated NSCLC; activating mutations reported; and availability of hazard ratio estimates with 95% confidence intervals (CIs) for overall survival.
Six clinical trials were included in this study. The pooled hazard ratio for overall survival of the EGFR-mutated population that completed sequential treatment was 1.03 (95% CI 0.86-1.22, P=0.776). There was no statistically significant heterogeneity between the studies (tau(2) =0; I(2)=0, 95% CI 0-0.37, P=0.548). Evidence of marked publication bias for the two treatment sequences was insufficient (P=0.145).
In patients with advanced NSCLC and activating EGFR mutations, first-line chemotherapy followed upon progression by a tyrosine kinase inhibitor was not inferior in terms of overall survival compared with the inverse sequence. This may serve as an indication that chemotherapy could be employed initially if mutation testing results are unavailable.
OncoTargets and Therapy 01/2013; 6:1771-1777. · 2.07 Impact Factor