Functional testing is a complementary tool for the diagnosis of vaginitis.

OBJECTIVE: Vaginal microbiota evaluation is a methodology widely used in China to diagnose various vaginal inflammatory diseases. Although vaginal microbiota evaluation has many advantages, it is time-consuming and requires highly skilled and experienced operators. Here, we investigated a six-index functional test that analyzed pH, hydrogen peroxide (H2O2), leukocyte esterase (LEU), sialidase (SNA), ß-glucuronidase (GUS), and acetylglucossidase (NAG), and determined its diagnostic value by comparing it with morphological tests of vaginal microbiota. MATERIALS AND METHODS: The research was conducted using data extracted from the Laboratory Information System of Women and Children's Hospital. A total of 4902 subjects, ranging in age from 35.4 ± 9.7 years, were analyzed. During the consultation, a minimum of two vaginal swab specimens per patient were collected for both functional and morphological testing. Fisher's exact was used to analyze data using SPSS. RESULTS: Of the 4,902 patients, 2,454 were considered to have normal Lactobacillus morphotypes and 3,334 were considered to have normal dominant microbiota. The sensitivity and specificity of H2O2-indicating Lactobacillus morphotypes were 91.3% and 25.28%, respectively, while those of pH-indicating Lactobacillus morphotypes were 88.09% and 59.52%, respectively. The sensitivity and specificity of H2O2-indicating dominant microbiota were 91.3% and 25.3%, respectively, while those of pH-indicating dominant microbiota were 86.27% and 64.45%, respectively. The sensitivity and specificity of NAG for vulvovaginal candidiasis were 40.64% and 84.8%, respectively. For aerobic vaginitis, GUS sensitivity was low at 0.52%, while its specificity was high at 99.93%; the LEU sensitivity and specificity values were 94.73% and 27.49%, respectively. Finally, SNA sensitivity and specificity for bacterial vaginosis were 80.72% and 96.78%, respectively. CONCLUSION: Functional tests (pH, SNA, H2O2, LEU) showed satisfactory sensitivity for the detection of vaginal inflammatory diseases. However, these tests lacked specificity, making it difficult to accurately identify specific pathologies. By contrast, NAG and GUS showed excellent specificity in identifying vaginal inflammatory diseases, but their sensitivity was limited. Therefore, functional tests alone are not sufficient to diagnose various vaginal inflammatory diseases. When functional and morphological tests are inconsistent, morphological tests are currently considered the preferred reference method.

Laryngeal function-preserving of frontolateral vertical partial laryngectomy (FLVPL) for selected T4a glottic cancer with thyroid cartilage invasion adherence to the anterior commissure: an innovative attempt.

OBJECTIVE: To evaluate the feasibility and efficacy in selected T4a glottic cancer (thyroid cartilage invasion adherence to the anterior commissure) treated with frontolateral vertical partial laryngectomy (FLVPL) and laryngeal framework reconstruction using titanium mesh. METHODS: Six patients with the limited T4a glottic cancer with thyroid cartilage destruction adherence to the anterior commissure, underwent FLVPL from 2009 to 2016 in Sun Yat-Sen University Cancer Center. All patients were followed up postoperatively. RESULTS: All patients comprised radical tumor resection and favorable functional outcomes, and no aspiration and laryngeal stenosis were observed. According to postoperative pathology, four patients should go through postsurgical radiotherapy with a mean dose of 66 Gy. But one of them refused to undergo postoperative radiotherapy, who observed local recurrence in postcricoid area underwent total laryngectomy (TL) and ipsilateral selected neck dissection in post-surgery two year. During follow-up period, all patients were still alive, and five patients without local recurrence and distant metastases. CONCLUSION: FLVPL and laryngeal framework reconstruction using titanium mesh is one viable surgical procedure to obtain adequate oncologic and functional outcomes.

Retrospective study on bevacizumab in the treatment of non-small cell lung cancer with brain metastases.

BACKGROUND: Bevacizumab was demonstrated to have efficacy in patients with non-small cell lung cancer (NSCLC) and brain metastases. However, cerebral toxicities were a major concern. This study aims to investigate the efficacy and risk factors of toxicity of bevacizumab in brain metastases. METHODS: All patients with advanced NSCLC hospitalized in our institute were screened and only those, who underwent bevacizumab administration after the diagnosis of brain metastases, were included. RESULTS: Fifty-one patients, who were treatment naïve or pretreated prior to bevacizumab regimens, were enrolled. Regardless of treatment lines, the objective response rate (ORR) was 62.7% (32/51), progression free survival (PFS) and overall survival were 6.2 months (95%CI, 5.0-7.4) and 14.0 months (95%CI, 9.6-18.4), respectively, and intracranial PFS was 7.8 months (95%CI, 7.1-8.5). For 41 patients with measurable brain metastatic lesions, the intracranial ORR was 46.3% (19/41). Ten patients (19.6%, 10/51) experienced cerebral toxicities (seven cases of grade 1 and three cases of grade 3), including cerebral or intratumoral hemorrhage and ischemic stroke. Cardiovascular disease was the risk factor contributing to cerebral toxicities (OR 16.645; 95%CI, 2.443-113.430; P = 0.004). CONCLUSIONS: This retrospective study shows that bevacizumab has efficacy and favorable toxicity in patients with NSCLC and brain metastases and cardiovascular disease might be a risk factor for cerebral toxicity.

Recursive partitioning analysis of patients with oligometastatic non-small cell lung cancer: a retrospective study.

BACKGROUND: Local consolidative treatment (LCT) is important for oligometastasis, defined as the restricted metastatic capacity of a tumor. This study aimed to determine the effects and prognostic heterogeneity of LCT in oligometastatic non-small cell lung cancer. METHODS: This retrospective study identified 436 eligible patients treated for oligometastatic disease at the Guangdong Provincial People's Hospital during 2009-2016. A Cox regression analysis was used to identify potential predictors of overall survival (OS). After splitting cases randomly into training and testing sets, risk stratification was performed using recursive partitioning analysis with a training dataset. The findings were confirmed using a validation dataset. The effects of LCT in different risk groups were evaluated using the Kaplan-Meier method. RESULTS: The T stage (p = 0.001), N stage (p = 0.008), number of metastatic sites (p = 0.031), and EGFR status (p = 0.043) were identified as significant predictors of OS. A recursive partitioning analysis was used to establish a prognostic risk model with the following four risk groups: Group I included never smokers with N0 disease (3-year OS: 55.6%, median survival time [MST]: 42.8 months), Group II included never smokers with N+ disease (3-year OS: 32.8%, MST: 26.5 months), Group III included smokers with T0-2 disease (3-year OS: 23.3%, MST: 19.4 months), and Group IV included smokers with T3/4 disease (3-year OS: 12.5%, MST: 11.1 months). Significant differences in OS according to LCT status were observed in all risk groups except Group IV (p = 0.45). CONCLUSIONS: Smokers with T3/4 oligometastatic non-small cell lung cancer may not benefit from LCT.

Intratumoral heterogeneity of EGFR-activating mutations in advanced NSCLC patients at the single-cell level.

BACKGROUND: Intratumoral epidermal growth factor receptor (EGFR) mutational heterogeneity is yet controversial in non-small cell lung cancer (NSCLC) patients. Single-cell analysis provides the genetic profile of single cancer cells and an in-depth understanding of the heterogeneity of a tumor. METHODS: Firstly, single H1975 cells harboring the EGFR L858R mutation were submitted to flow cytometry isolation, nested polymerase chain reaction (nested-PCR) amplification, and direct DNA sequencing to assess the feasibility of single-cell direct DNA sequencing. Then, the single cells of patients with lung adenocarcinoma receiving gefitinib were captured by laser capture microdissection and analyzed by the above methods to identify the intratumoral heterogeneity of the EGFR L858R mutant. Three patients with progression-free survival (PFS) > 14 months were categorized as the long PFS group, and 3 patients with PFS < 6 months as the short PFS group. The correlation between the abundance of EGFR L858R mutant and PFS was analyzed. RESULTS: 104 single H1975 cells were isolated. 100/104 were amplified by nested-PCR and confirmed by direct sequencing. We captured 135 tumor cells from the tissues of six patients. 120 single tumor cells were successfully amplified and sequenced. The rate of EGFR exon 21 mutation was only 77.5% (93/120). Furthermore, the rate of mutation in exon 21 of EGFR was significantly higher in the long PFS group than in the short PFS group (86.4 ± 4.9% vs. 68.9 ± 2.8%, P = 0.021). CONCLUSION: Our study suggested the intratumoral heterogeneity of EGFR-activating mutations in lung adenocarcinoma confirmed on the single-cell level, which might be associated with EGFR-TKIs response in lung adenocarcinoma patients harboring the EGFR L858R mutation.

Gefitinib versus vinorelbine plus cisplatin as adjuvant treatment for stage II-IIIA (N1-N2) EGFR-mutant NSCLC (ADJUVANT/CTONG1104): a randomised, open-label, phase 3 study.

BACKGROUND: Cisplatin-based adjuvant chemotherapy is the standard of care for patients with resected stage II-IIIA non-small-cell lung cancer (NSCLC). RADIANT and SELECT trial data suggest patients with EGFR-mutant stage IB-IIIA resected NSCLC could benefit from adjuvant EGFR tyrosine kinase inhibitor treatment. We aimed to compare the efficacy of adjuvant gefitinib versus vinorelbine plus cisplatin in patients with completely resected EGFR-mutant stage II-IIIA (N1-N2) NSCLC. METHODS: We did a randomised, open-label, phase 3 trial at 27 centres in China. We enrolled patients aged 18-75 years with completely resected (R0), stage II-IIIA (N1-N2), EGFR-mutant (exon 19 deletion or exon 21 Leu858Arg) NSCLC. Patients were stratified by N stage and EGFR mutation status and randomised (1:1) by Pocock and Simon minimisation with a random element to either gefitinib (250 mg once daily) for 24 months or intravenous vinorelbine (25 mg/m2 on days 1 and 8) plus intravenous cisplatin (75 mg/m2 on day 1) every 3 weeks for four cycles. The primary endpoint was disease-free survival in the intention-to-treat population, which comprised all randomised patients; the safety population included all randomised patients who received at least one dose of study medication. Enrolment to the study is closed but survival follow-up is ongoing. The study is registered with ClinicalTrials.gov, number NCT01405079. FINDINGS: Between Sept 19, 2011, and April 24, 2014, 483 patients were screened and 222 patients were randomised, 111 to gefitinib and 111 to vinorelbine plus cisplatin. Median follow-up was 36·5 months (IQR 23·8-44·8). Median disease-free survival was significantly longer with gefitinib (28·7 months [95% CI 24·9-32·5]) than with vinorelbine plus cisplatin (18·0 months [13·6-22·3]; hazard ratio [HR] 0·60, 95% CI 0·42-0·87; p=0·0054). In the safety population, the most commonly reported grade 3 or worse adverse events in the gefitinib group (n=106) were raised alanine aminotransferase and asparate aminotransferase (two [2%] patients with each event vs none with vinorelbine plus cisplatin). In the vinorelbine plus cisplatin group (n=87), the most frequently reported grade 3 or worse adverse events were neutropenia (30 [34%] patients vs none with gefitinib), leucopenia (14 [16%] vs none), and vomiting (eight [9%] vs none). Serious adverse events were reported for seven (7%) patients who received gefitinib and 20 (23%) patients who received vinorelbine plus cisplatin. No interstitial lung disease was noted with gefitinib. No deaths were treatment related. INTERPRETATION: Adjuvant gefitinib led to significantly longer disease-free survival compared with that for vinorelbine plus cisplatin in patients with completely resected stage II-IIIA (N1-N2) EGFR-mutant NSCLC. Based on the superior disease-free survival, reduced toxicity, and improved quality of life, adjuvant gefitinib could be a potential treatment option compared with adjuvant chemotherapy in these patients. However, the duration of benefit with gefitinib after 24 months might be limited and overall survival data are not yet mature. FUNDING: Guangdong Provincial Key Laboratory of Lung Cancer Translational Medicine; National Health and Family Planning Commission of People's Republic of China; Guangzhou Science and Technology Bureau; AstraZeneca China.

Decreased expression of protein tyrosine kinase 6 contributes to tumor progression and metastasis in laryngeal squamous cell carcinoma.

BACKGROUND: PTK6 is involved in cell proliferation, invasion and migration. Patients with lower PTK6 expression predicts poor prognosis of LSCC. However, the mechanism of PTK6 in LSCC progression remains unclear. We investigated the role of PTK6 in the pathogenesis of LSCC. METHODS: Human LSCC tissues and paired adjacent non-tumor tissues were obtained to evaluate PTK6 expression. The biological function of PTK6 in LSCC was determined by overexpression of PTK6 in Hep-2 cells in vitro and in nude mice. The potential PTK6 target factors and signaling pathways were identified by Western blotting assay and immunohistochemical staining. RESULTS: PTK6 was downregulated in tissues of human LSCC. Biological function investigation of PTK6 demonstrated that overexpression of PTK6 significantly decreased cell growth, clonogenicity, invasion and migration capacity in vitro and suppressed xenograft tumor growth as well as lung metastasis in vivo. PTK6 suppresses LSCC proliferation mainly by inhibiting c-myc and cyclinD1 expression. In addition, PTK6 promotes cell apoptosis in LSCC. Moreover, PTK6 mitigated LSCC invasion and migration through regulating EMT and MMP-9. CONCLUSION: PTK6 plays a tumor suppressor role in LSCC by regulating c-myc and cyclinD1 expression, cell apoptosis, EMT and MMP-9.

Crizotinib in advanced non-small-cell lung cancer with concomitant ALK rearrangement and c-Met overexpression.

OBJECTIVE: Crizotinib can target against mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK), which has been considered as a multi-targeted tyrosine kinase inhibitor (TKI). The objective of this study was to explore the efficacy of crizotinib in advanced non-small-cell lung cancer (NSCLC) with concomitant ALK rearrangement and c-Met overexpression. METHODS: Totally, 4622 advanced NSCLC patients from two institutes (3762 patients at the Guangdong Lung Cancer Institute from January 2011 to December 2016 and 860 cases at the Perking Cancer Hospital from January 2015 to December 2016) were screened for ALK rearrangement with any method of IHC, RACE-coupled PCR or FISH. C-Met expression was performed by IHC in ALK-rearranged patients, and more than 50% of cells with high staining were defined as c-Met overexpression. The efficacy of crizotinib was explored in the ALK-rearranged patients with or without c-Met overexpression. RESULTS: Sixteen patients were identified with c-Met overexpression in 160 ALK-rearranged cases, with the incidence of 10.0% (16/160). A total of 116 ALK-rearranged patients received the treatment of crizotinib. Objective response rate (ORR) was 86.7% (13/15) in ALK-rearranged patients with c-Met overexpression and 59.4% (60/101)in those without c-Met overexpression, P = 0.041. Median PFS showed a trend of superiority in c-Met overexpression group (15.2 versus 11.0 months, P = 0.263). Median overall survival (OS) showed a significant difference for ALK-rearranged patients with c-Met overexpression group of 33.5 months with the hazard ratio (HR) of 3.2. CONCLUSIONS: C-Met overexpression co-exists with ALK rearrangement in a small population of advanced NSCLC. There may be a trend of favorable efficacy of crizotinib in such co-altered patients.

Mixed Responses to Systemic Therapy Revealed Potential Genetic Heterogeneity and Poor Survival in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: A subset of patients with non-small cell lung cancer (NSCLC) fosters mixed responses (MRs) to epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) or chemotherapy. However, little is known about the clinical and molecular features or the prognostic significance and potential mechanisms. METHODS: The records of 246 consecutive patients with NSCLC receiving single-line chemotherapy or TKI treatment and who were assessed by baseline and interim positron emission tomography/computed tomography scans were collected retrospectively. The clinicopathological correlations of the MR were analyzed, and a multivariate analysis was performed to explore the prognostic significance of MR. RESULTS: The overall incidence of MR to systemic therapy was 21.5% (53/246) and predominated in patients with stage IIIB-IV, EGFR mutations and those who received TKI therapy (p < .05). Subgroup analyses based on MR classification (efficacious versus inefficacious) showed significant differences in subsequent treatment between the two groups (p < .001) and preferable progression-free survival (PFS) and overall survival (OS) in the efficacious MR group. Multivariate analyses demonstrated that the presence of MR was an independent unfavorable prognostic factor for PFS (hazard ratio [HR], 1.474; 95% confidence interval [CI], 1.018-2.134; p = .040) and OS (HR, 1.849; 95% CI, 1.190-2.871; p = .006) in patients with NSCLC. Induced by former systemic therapy, there were more T790M (18%), concomitant EGFR mutations (15%), and changes to EGFR wild type (19%) in the MR group among patients with EGFR mutations, which indicated higher incidence of genetic heterogeneity. CONCLUSION: MR was not a rare event in patients with NSCLC and tended to occur in those with advanced lung adenocarcinoma treated with a TKI. MR may result from genetic heterogeneity and is an unfavorable prognostic factor for survival. Further studies are imperative to explore subsequent treatment strategies. The Oncologist 2017;22:61-69Implications for Practice: Tumor heterogeneity tends to produce mixed responses (MR) to systemic therapy, including TKI and chemotherapy; however, the clinical significance and potential mechanisms are not fully understood, and the subsequent treatment after MR is also a clinical concern. The present study systemically assessed patients by PET/CT and differentiated MR and therapies. The study identified a relatively high incidence of MR in patients with advanced NSCLC, particularly those treated with targeted therapies. An MR may be an unfavorable prognostic factor and originate from genetic heterogeneity. Further studies are imperative to explore subsequent treatment strategies.

Supraclavicular lymph node incisional biopsies have no influence on the prognosis of advanced non-small cell lung cancer patients: a retrospective study.

BACKGROUND: Supraclavicular lymph node (SCLN) biopsies play an important role in diagnosing and staging lung cancer. However, not all patients with SCLN metastasis can have a complete resection. It is still unknown whether SCLN incisional biopsies affect the prognosis of non-small cell lung cancer (NSCLC) patients. METHODS: Patients who were histologically confirmed to have NSCLC with SCLN metastasis were enrolled in the study from January 2007 to December 2012 at Guangdong Lung Cancer Institute. The primary endpoint was OS, and the secondary endpoints were complications and local recurrence/progression. RESULTS: Two hundred two consecutive patients who had histologically confirmed NSCLC with SCLN metastasis were identified, 163 with excisional and 39 with incisional biopsies. The median OS was not significantly different between the excisional (10.9 months, 95% CI 8.7-13.2) and incisional biopsy groups (10.1 months, 95% CI 6.3-13.9), P = 0.569. Multivariable analysis showed that an Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 (HR = 2.75, 95% CI 1.71-4.38, P < 0.001) indicated a worse prognosis. Having an epidermal growth factor receptor (EGFR) mutation (HR = 0.58, 95% CI 0.40-0.84, P = 0.004) and receiving systemic treatment (HR = 0.36, 95% CI 0.25-0.53, P < 0.001) were associated with a favorable OS. Neither the number (multiple vs. single) nor site (bilateral vs. unilateral) of SCLNs was associated with an unfavorable OS, and SCLN size or fixed SCLNs did not affect OS. CONCLUSIONS: SCLN incisional biopsies did not negatively influence the prognosis of NSCLC patients. It was safe and feasible to partly remove a metastatic SCLN as a last resort in advanced NSCLC.

Comparing overall survival between first generation EGFR-TKIs and chemotherapy in lung cancer patients with Del19/L858R.

OBJECTIVE: Combined overall survival (OS) analysis of Lux-Lung 3 and Lux-Lung 6 demonstrated that patients with epidermal growth factor receptor (EGFR) exon 19 deletions (Del19) would benefit from first-line second generation EGFR tyrosine kinase inhibitors (TKIs) afatinib but not for those with L858R. This study was to investigate the survival difference between first-line first generation EGFR-TKIs and chemotherapy in patients with either Del19 or L858R, and to directly compare OS in these two mutation groups. METHODS: Eligibles were all prospective and retrospective studies comparing EGFR-TKIs with conventional chemotherapy or receiving single agent EGFR-TKIs and demonstrating survival analysis based on mutation types. The primary outcome was OS measured as pooled hazard ratios (HRs). All measures were pooled using randomeffects models and 95% confidential interval (95% CI) was calculated. RESULTS: A total of 14 studies incorporating 1,706 patients with either Del19 or L858R were included. Enrolling patients with Del19 or L858R in randomized controlled trials (RCTs), first-line first generation EGFR-TKIs were associated with no OS benefit, compared with chemotherapy (pooled HRTKI/Chemo for Del19: 0.82, 95% CI: 0.64-1.06, P = 0.14; pooled HRTKI/Chemo for L858R: 1.15, 95% CI: 0.85-1.56, P = 0.38). Direct comparison of Del19 with L858R receiving with first-line first generation EGFR-TKIs demonstrated no significant survival difference (pooled HR19/21: 0.88, 95% CI: 0.67-1.16, P = 0.37). CONCLUSIONS: Among patients with advanced non-small cell lung cancer (NSCLC) harboring Del19 and L858R, first-line first generation EGFR-TKIs demonstrated no survival benefit comparing with chemotherapy. Direct comparison between Del19 and L858R revealed no significant survival difference after first-line first generation EGFR-TKIs.

Multiple primary malignancies involving lung cancer.

BACKGROUND: The incidence of multiple primary malignancies (MPM) has increased sharply in recent decades. However, the clinical characteristics and prognosis of MPM patients involving lung cancer were not fully elucidated. This retrospective study was designed to explore the clinical characteristics and prognosis of MPM patients involving lung cancer in the People's Republic of China. METHODS: Of 5405 lung cancer cases diagnosed at the Guangdong Lung Cancer Institute between 2005 and 2013, we analyzed 185 patients (3.4 %) with MPM involving lung cancer. RESULTS: Among 185 patients with MPM involving lung cancer, 10 (5.4 %)had three malignancies and 175 (94.6 %) had two malignancies. 10 patients with three malignancies were excluded from the analysis to avoid misunderstanding. Of 175 accompanying malignancies, 64 (36.6 %) were synchronous MPM patients and 111 (63.4 %) were metachronous MPM patients; 49 (28.0 %) were lung cancer first MPM patients and 126 (72.0 %) were other cancer first MPM patients. The most frequent accompanying malignancy was colon cancer (25/175), followed by rectal cancer (18/175), esophageal cancer (17/175), and thyroid cancer (13/175). Metachronous MPM patients showed significantly better overall survival (OS) than synchronous MPM, with a median OS of 72.8 (range 12.2-391.0) and 12.9 (range 0.8-86.3)months, respectively (P < 0.001). Cox regression analysis revealed that time of occurrence and stage were independent factors for OS. CONCLUSIONS: Colorectal cancer, esophageal cancer, and thyroid cancer were the tumors that most frequently accompanying lung cancer. Metachronous MPM patients showed significantly better OS compared with synchronous MPM patients.

Venous thromboembolism risk factors in Chinese non-small cell lung cancer patients.

PURPOSE: Certain clinicopathological factors contribute to the development of venous thromboembolism (VTE) in lung cancer. The aim of the current study was to assess the incidence of and the potential risk factors associated with the development of VTE in Chinese lung cancer patients. METHODS: Patients with lung cancer in our center were screened for VTE from January 2004 to July 2013. One VTE case was matched with two controls according to gender, pathology, clinical stage, and anticancer therapy. RESULTS: Among the 4,726 patient records screened, 61 (1.3 %) VTE cases with non-small cell lung cancer (NSCLC) were identified, including 58 (95.1 %) with adenocarcinoma and 59 (96.7 %) with advanced stage tumors (IIIb and IV). Serous effusion (OR 2.089, 95 % CI 1.022-4.270, P = 0.043), fever (OR 8.999, 95 % CI 1.688-47.968, P = 0.010), increased leukocytes (OR 4.136, 95 % CI 1.957-8.738, P < 0.001), hyponatremia (< 130 mmol/L, OR 5.335, 95 % CI 1.366-20.833, P = 0.016), and increased alanine aminotransferase (ALT) (OR 3.879, 95 % CI 1.514-9.936, P = 0.005) were associated with an increased risk of VTE. Patients with poor performance status (PS) (≥ 2 vs. < 1) (HR 1.574, 95 % CI 1.112-2.228, P = 0.010) and serous effusion (HR 1.571, 95% CI 1.114-2.215, P = 0.010) tended to have a poor prognosis. There was no difference in overall survival between VTE (median 15.2 months, 95 % CI 11.6-18.9) and control patients (median 16.3 months, 95 % CI 14.1-18.4, P = 0.184; HR 1.273, 95 % CI 0.890-1.820, P = 0.185). CONCLUSIONS: Clinical characteristics such as serous effusion, fever, increased leukocytes, hyponatremia, and increased ALT are potential risk factors for VTE in NSCLC. Poor PS and serous effusion imply poor prognosis for NSCLC patients, most of which have adenocarcinomas and advanced stage.

Lung cancer treatment disparities in China: a question in need of an answer.

BACKGROUND: Substantial progress has been made in the treatment of malignancies in the People's Republic of China in recent years. The goal of this study was to identify the extent to which national treatment guidelines are being used to customize patient care in lung cancer and to analyze the reasons for treatment disparities. METHODS: Patient characteristics and treatments were investigated retrospectively for the period from October 2004 to January 2013 using the outpatient database of the Guangdong Lung Cancer Institute (GLCI) in China. RESULTS: A total of 2,535 outpatients with lung cancer were studied in this retrospective analysis. The treatment disparity was 45.3%. Overall, 20.6% of patients with stage I non-small cell lung cancer (NSCLC) were overtreated, and 20.1% of stage II patients were undertreated. Only 19.6% of stage IIIA patients and 30.7% of stage IIIB patients underwent the recommended combination of chemotherapy and radiotherapy, respectively. For advanced NSCLC, the greatest treatment disparity appeared in the second-line setting and beyond. Patients who were positive for epidermal growth factor receptor (EGFR) and receiving EGFR tyrosine kinase inhibitors experienced significant prolongation of survival compared with patients who were EGFR negative or whose EGFR mutation status was unknown (hazard ratio: 0.79; p = .037). The treatment disparities were significantly larger among patients aged younger than 65 years and in patients from developing regions compared with patients aged 65 years and older and from developed regions, respectively (p < .001, p = .046). The difference in treatment disparity was statistically significant between GLCI and other hospitals (p < .001). CONCLUSION: This retrospective study of a large number of patients from an outpatient oncology database demonstrated large disparities in the treatment of lung cancer in China. It is important to develop a new guideline for recommendations that are based on resource classification.

A randomized phase II clinical trial of nab-paclitaxel and carboplatin compared with gemcitabine and carboplatin as first-line therapy in locally advanced or metastatic squamous cell carcinoma of lung.

BACKGROUND: Recent advances have shown that histology and genetic biomarkers are important in patient selection, which have led to significantly better outcomes for lung cancer patients. However, most new treatments only apply to adenocarcinoma or non-squamous, and in squamous carcinoma there is little breakthrough. In a phase III trial nab-paclitaxel plus carboplatin showed superior response rate over paclitaxel and carboplatin. In subgroup analysis the squamous histology appeared to be a predictive factor to nab-paclitaxel treatment. METHODS/DESIGN: This is an open-label, randomized, active controlled phase II trial. A total of 120 untreated advanced squamous lung cancer patients are randomized at a 1:1 ratio to receive nab-paclitaxel (135 mg/m2, d1, 8, q3w) plus carboplatin (AUC 5, d1, q3w) or gemcitabine (1,250 mg/m2, d1, 8, q3w) and carboplatin (AUC 5, d1, q3w). The primary endpoint is objective response rate and the second endpoints are progression free survival, overall survival, safety and biomarkers associated with nab-paclitaxel. The treatment will continue up to six cycles or intolerable toxicity. DISCUSSION: This ongoing trial will be the first prospective randomized trial to explore the efficacy of nab-paclitaxel as the first-line treatment specifically in squamous carcinoma of lung. STUDY NUMBER: CTONG1002 TRIAL REGISTRATION: Clinicaltrials.gov reference: NCT01236716.

Probucol combined with valsartan in immunoglobulin A nephropathy: a multi-centre, open labelled, randomized controlled study.

AIM: Angiotensin receptor antagonists (ARBs) and anti-oxidants reduce urinary protein excretion and delay progression of immunoglobulin A (IgA) nephropathy. We investigated the efficacy and safety of probucol (an anti-oxidant) combined with valsartan (an ARB) on the progression of IgA nephropathy. METHODS: Patients with IgA nephropathy (n = 69) were recruited from five centres and randomly assigned to a treatment group (750 mg/day probucol plus 160 mg/day valsartan) or a control group (160 mg/day valsartan) and were followed for 3 years. RESULTS: At baseline, the two groups in any measured clinical information were comparable. The primary endpoint (doubling serum creatinine) showed no significant difference between the two groups during 3-year follow-up. The secondary endpoint (50% reduction in 24-h urinary protein) occurred in 23 patients in the treatment group and 20 patients in the control group. The time to the secondary end-point was shorter in the treatment group than the control group (8.13 months vs 19.63 months, P = 0.019). However, at the 3-year follow-up, the 24-h urinary protein levels were not significantly different from the baseline levels (P = 0.99 and P = 0.66, respectively). At the 1-year follow-up, plasma cholesterol in the treatment group was markedly lower than in the control group (4.12 ± 1.28 vs 5.03 ± 1.01, P = 0.02). CONCLUSION: Kidney function remained stable and there was no significant difference in two group patients. Probucol combined with valsartan led to a more rapid decrease of 24-h urinary protein excretion than valsartan alone. However, the long-term effect needs further investigation.

Detecting the spectrum of multigene mutations in non-small cell lung cancer by Snapshot assay.

As molecular targets continue to be identified and more targeted inhibitors are developed for personalized treatment of non-small cell lung cancer (NSCLC), multigene mutation determination will be needed for routine oncology practice and for clinical trials. In this study, we evaluated the sensitivity and specificity of multigene mutation testing by using the Snapshot assay in NSCLC. We retrospectively reviewed a cohort of 110 consecutive NSCLC specimens for which epidermal growth factor receptor (EGFR) mutation testing was performed between November 2011 and December 2011 using Sanger sequencing. Using the Snapshot assay, mutation statuses were detected for EGFR, Kirsten rate sarcoma viral oncogene homolog (KRAS), phosphoinositide-3-kinase catalytic alpha polypeptide (PIK3CA), v-Raf murine sarcoma viral oncogene homolog B1 (BRAF), v-ras neuroblastoma viral oncogene homolog (NRAS), dual specificity mitogen activated protein kinase kinase 1 (MEK1), phosphatase and tensin homolog (PTEN), and human epidermal growth factor receptor 2 (HER2) in patient specimens and cell line DNA. Snapshot data were compared to Sanger sequencing data. Of the 110 samples, 51 (46.4%) harbored at least one mutation. The mutation frequency in adenocarcinoma specimens was 55.6%, and the frequencies of EGFR, KRAS, PIK3CA, PTEN, and MEK1 mutations were 35.5%, 9.1%, 3.6%, 0.9%, and 0.9%, respectively. No mutation was found in the HER2, NRAS, or BRAF genes. Three of the 51 mutant samples harbored double mutations: two PIK3CA mutations coexisted with KRAS or EGFR mutations, and another KRAS mutation coexisted with a PTEN mutation. Among the 110 samples, 47 were surgical specimens, 60 were biopsy specimens, and 3 were cytological specimens; the corresponding mutation frequencies were 51.1%, 41.7%, and 66.7%, respectively (P = 0.532). Compared to Sanger sequencing, Snapshot specificity was 98.4% and sensitivity was 100% (positive predictive value, 97.9%; negative predictive value, 100%). The Snapshot assay is a sensitive and easily customized assay for multigene mutation testing in clinical practice.

[Efficacies of gefitinib versus paclitaxel/carboplatin for patients with advanced pulmonary adenocarcinoma].

OBJECTIVE: To compare the clinical efficacies of gefitinib versus paclitaxel/carboplatin in patients with advanced pulmonary adenocarcinoma. METHODS: A total of 51 advanced pulmonary adenocarcinoma patients were recruited from Guangdong General Hospital during October 2006 to September 2007. Eligible patients were ≥ 18 years old, either non-smokers or former light smokers and receiving no prior chemotherapy or biological/immunological therapy. According to performance status, smoking status and gender, they were selected with dynamic equilibrium randomized method 1: 1 to receive first-line gefitinib (250 mg/d) in gefitinib arm or carboplatin/paclitaxel (carboplatin, area under the curve 5 mg × ml⁻¹ × min⁻¹, 21-day cycle; paclitaxel, 200 mg/m², 21-day cycle in chemotherapy arm. The primary endpoint was progression free survival (PFS). And the secondary endpoints were objective response rate (ORR) and overall survival (OS). RESULTS: They were randomized into gefitinib arm (n = 25) and paclitaxel/carboplatin arm (n = 26). The median PFS was 4.2 months in gefitinib arm and 8.3 months in paclitaxel/carboplatin arm (P = 0.422); ORR 36.0% in gefitinib arm and 42.3% in paclitaxel/carboplatin arm (P = 0.645); Median OS 14.4 months in gefitinib arm and 15.0 months in paclitaxel/carboplatin arm (P = 0.290). Multifactorial Cox regression analysis showed that age (P = 0.004), epidermal growth factor receptor (EGFR) gene mutation status (P = 0.012) and subsequent treatments (platinum-based chemotherapy, P = 0.001; EGFR-tyrosine kinase inhibitors (TKI), P = 0.005) were the significant predictors of OS. CONCLUSIONS: No significant differences exist in terms of efficacy and survival between first-line gefitinib and paclitaxel/carboplatin for Chinese patients with pulmonary adenocarcinoma who are non-smokers or former light smokers. And age, EGFR gene mutation status and subsequent treatments are significant predictor of OS. However, first-line gefitinib should not be recommended for advanced non-small cell lung cancer (NSCLC) patients only based on clinical factors, due to a very small sample-size in our study.

Comparison of three mathematical prediction models in patients with a solitary pulmonary nodule.

BACKGROUND: Effective methods for managing patients with solitary pulmonary nodules (SPNs) depend critically on the predictive probability of malignancy. METHODS: Between July 2009 and June 2011, data on gender, age, cancer history, tumor familial history, smoking status, tumor location, nodule size, spiculation, calcification, the tumor border, and the final pathological diagnosis were collected retrospectively from 154 surgical patients with an SPN measuring 3-30 mm. Each final diagnosis was compared with the probability calculated by three predicted models-the Mayo, VA, and Peking University (PU) models. The accuracy of each model was assessed using area under the receiver operating characteristics (ROC) and calibration curves. RESULTS: The area under the ROC curve of the PU model [0.800; 95% confidence interval (CI): 0.708-0.891] was higher than that of the Mayo model (0.753; 95% CI: 0.650-0.857) or VA model (0.728; 95% CI: 0.623-0.833); however, this finding was not statistically significant. To varying degrees, calibration curves showed that all three models overestimated malignancy. CONCLUSIONS: The three predicted models have similar accuracy for prediction of SPN malignancy, although the accuracy is not sufficient. For Chinese patients, the PU model may has greater predictive power.

Plasma ddPCR for the detection of MET amplification in advanced NSCLC patients: a comparative real-world study.

Background: Mesenchymal-epithelial transition (MET) amplification is a crucial oncogenic driver and a resistance mechanism to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) of non-small-cell lung cancer (NSCLC). Fluorescence in situ hybridization (FISH) is the gold standard for MET amplification detection. However, it is inapplicable when tissue samples are unavailable. Objective: This study assessed the performance of plasma droplet digital polymerase chain reaction (ddPCR) in MET amplification detection in NSCLC patients. Design and methods: A total of 87 NSCLC patients were enrolled, and 94 paired tissue and plasma samples were analyzed for the concordance between FISH and plasma ddPCR/tissue next-generation sequencing (NGS) in detecting MET amplification. In addition, the efficacy of patients with MET amplification using different detection methods who were treated with MET-TKIs was evaluated. Results: Plasma ddPCR showed substantial concordance with FISH (74.1% sensitivity, 92.5% specificity, and 87.2% accuracy with a kappa value of 0.68) and outperformed tissue NGS (kappa value of 0.64) in MET amplification detection. Combined plasma ddPCR and tissue NGS showed substantial concordance with FISH (92.3% sensitivity, 89.2% specificity, and an accuracy of 90.1% with a kappa value of 0.77). The efficacy is comparable in these NSCLC patients with MET amplification detected by FISH and plasma ddPCR who were treated with MET-TKIs. Conclusion: Plasma ddPCR is a potentially reliable method for detecting MET amplification in advanced NSCLC patients. Combined plasma ddPCR and tissue NGS might be an alternative or complementary method to MET amplification detection.