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Background/purpose: Lung cancer patients can have advanced-stages at diagnosis, even the tumor size is ≤2 cm. We aimed to study the relationship between image characteristics, clinical, and patholoigcal results.Methods: We retrospectively enrolled patients with lung adenocarcinoma at Taichung Veterans General Hospital and Chang Gung Memorial Hospital from 2007 to 2015, who were diagnosed with treatment naïve primary tumor lesions at sizes less than 2 cm, as measured by computed tomography (CT) scans. The patient was analyzed for lymph node (LN) and distant metastasis evaluation, with clinicopathological characteristics, including tumor-disappearance ratio (TDR) (tumor diameter at the mediastinal/lung window) over chest CT scans, pathological diagnosis, disease-free survival (DFS), and overall survival (OS).Results: Totally 280 patients were surveyed initially and showed significantly increase of clinical LN involvement and distant metastasis when TDR ≤75% compared with >75% (21.6% vs 0% for LN involvement; 27.1% vs 0% for distant metastasis; both p < 0.001). We included 199 patients having surgical treatment and follow-up for the survival analysis. With a TDR ≤75%, significantly worse DFS (HR, 19.23; 95% CI, 2.60-142.01; p = 0.004) and a trend of worse OS (HR, 4.97; 95% CI, 0.61-40.61; p = 0.134) were noted by Kaplan-Meier method. TDR ≤75% revealed more advanced pathological stage, and more tumors containing micropapillary or solid subtypes when diagnosed adenocarcinoma.Conclusion: For lung cancer patients with primary tumor ≤2 cm, TDR ≤75% was related to more advanced stages, the presence of micropapillary or solid components of adenocarcinoma subtypes, worse DFS, and a trend of worse OS. [ABSTRACT FROM AUTHOR]

Introduction Smoking status is an important determinant of the prevalence of epidermal growth factor receptor ( EGFR ) mutations in lung cancer patients. However, it is unclear whether smoking status could also influence the spectrum of EGFR mutations. Methods We enrolled patients with lung adenocarcinoma from three medical centers in Taiwan. EGFR mutations were assessed by Sanger direct sequencing. The objective of this study was to evaluate the influence of smoking status on both the frequency and patterns of EGFR mutations. Results From 2001 to 2013, a total of 1175 patients with lung adenocarcinoma were enrolled for EGFR mutation analysis. The overall EGFR mutation rate was 59.6%, which was significantly higher in females than males (69.1% vs. 49.8%) and in non-smokers than current/former smokers (73.8% vs. 29.8%) (both P < 0.001). Among patients harboring EGFR mutations, smokers expressed L858R mutation less frequently (35.2% vs. 50.2%, P = 0.005) and exon 19 deletions more frequently (52.8% vs 38.8%, P = 0.008) than non-smokers. Smokers and non-smokers also had divergent exon 19 deletions subtypes (Del E746-A750 82.5% vs. 57.6%, respectively, P < 0.001). Among subgroup patients harboring the L858R mutation, smokers were associated with a higher rate of complex mutations than non-smokers (34.2% vs. 8.4%, P < 0.001). Conclusions Our results suggested that smoking status could influence not only the frequency but also the spectrum of EGFR mutations. These findings provide a clue for further investigation of EGFR mutagenesis. [ABSTRACT FROM AUTHOR]

Abstract: Background: The effective targeted therapy for lung squamous cell carcinoma (SCC) is needed. The epidermal growth factor receptor (EGFR) mutation rate is low in lung SCC. The aim of this study was to evaluate the status of erlotinib treatment and EGFR mutation in lung SCC patients. Methods: We retrospectively enrolled lung cancer patients with SCC histology and history of erlotinib treatment. The primary objective was to assess overall response rate (ORR) and disease control rate (DCR) and the secondary objective was to assess progression-free survival (PFS) and overall survival (OS). EGFR mutations were assessed in parts of patients using both direct sequencing and protein nucleic acid-locked nucleic acid polymerase chain reaction (PNA-LNA PCR) clamp methods. Results: In total, 92 patients were analyzed (75 men and 17 women, median age 69 years, and 74 current or former smokers). Sixteen patients achieved partial response and 9 had stable disease. The ORR was 17.4% and the DCR was 27.2%. The PFS and OS were longer in patients with disease control than with progressive disease (PFS 7.8 versus 1.3 months and OS 20.7 versus 2.7 months, both p <0.0001). The 1-year survival rate was 21.7%. In 27 patients with adequate specimens for molecular analysis (including 4 PR and 4 SD), two (7.4%) had EGFR complex mutations. One patient experienced response to erlotinib and the other did not. Conclusions: A significant proportion of lung SCC patients would derive a clinical benefit from erlotinib treatment. The relatively higher response rate than the EGFR mutation rate in present study needs further evaluation. [Copyright &y& Elsevier]

Abstract: The trapped fourth ventricle is caused by occlusion of outlets of fourth ventricle, including cerebral aqueduct and foramina of Luschka and Magendie. It is an uncommon entity that mainly occurs in children with hydrocephalus after successful shunting of lateral ventricles. The most common etiologies of obstruction to outflow of the fourth ventricle are infection and hemorrhage. Typical manifestation of trapped fourth ventricle is posterior fossa syndrome. Here, we report a 22-year-old man with hydrocephalus developed after successful removal of traumatic subdural hemorrhage. After shunting of lateral ventricles, hydrocephalus resolved initially. However, trapped fourth ventricle occurred 9 months later. Unlike previous reports of trapped fourth ventricle, his presentation was motor neuron disease-like syndrome, including hand muscle weakness and atrophy, generalized brisk deep tendon reflexes, and absence of sensory deficits. Imaging study showed isolated dilatation of fourth ventricle and edema of cervical cord from obex to C7 level. After surgical decompression and lysis of adhesion of posterior fossa, neurological deficits well recovered. The pathogenesis of hand muscle atrophy is secondary to cervical cord edema caused by trapped fourth ventricle and obstruction of cerebrospinal fluid (CSF) pathway. Furthermore, the anterior horn cells and lateral corticospinal tract are located in the highly vulnerable region of spinal cord, either possibly due to venous engorgement or arterial insufficiency. [Copyright &y& Elsevier]

Highlights • The level of PD-L1 expression can predict efficacy of EGFR-TKI. • Higher PD-L1 expression had high incidence of primary resistance to EGFR TKI. • Higher PD-L1 expression had shorter progression-free survival. Abstract Objectives The main objective was to investigate the relationship between Programmed cell Death-ligand 1 (PD-L1) expression levels and the frequency of primary resistance to Epidermal Growth Factor Receptor (EGFR)-Tyrosine Kinase Inhibitor (TKI) in treatment naïve advanced EGFR -mutant lung adenocarcinoma patients. Materials and methods From 2012–2017, we enrolled advanced EGFR -mutant lung adenocarcinoma patients who displayed primary resistance to EGFR-TKI therapy, along with patients with disease control, and patients experiencing either stable disease or partial response to EGFR-TKI treatment. Results Sixty-six patients were enrolled as the primary resistance group, while 57 patients were included as the disease control group. Fifteen-five (22.7%) patients had a PD-L1 Tumor Proportion Score (TPS) ≧50% in the primary resistance group, with only one patient (1.8%) having that score in the disease control group (P＜0.001). Twenty (30.3%) patients had a PD-L1 ≧25% in the primary resistance group, with 2 (3.5%) patients having that level in the disease control group (P＜0.001). Thirty (45.5%) patients had a PD-L1 ≧1% in the primary resistance group, with 7 (12.3%) patients at that level in the disease control group (P = 0.001). Patients with a PD-L1≧1% displayed a higher incidence of primary resistance to EGFR-TKIs than those with a PD-L1＜1% (Odds Ratio (OR), 5.95; 95% Confidence Interval (CI), 2.35–15.05; P＜0.001). The phenomenon existed still when the cutoff value was changed to both 25% (OR, 11.96; 95% CI, 2.65–53.87; P = 0.001) and 50% (OR, 16.47; 95% CI, 2.10–129.16; P = 0.008). The estimated median Progression-free Survival (PFS) rate was 7.3 months in patients with a PD-L1＜1%, 2.1 months in patients with a PD-L1≧1%, 1.8 months in patients with a PD-L1≧25%, and 1.6 months in patients with a PD-L1≧50%. Conclusions Treatment for advanced EGFR -mutant lung adenocarcinoma patients displaying a higher PD-L1 expression level experienced a higher frequency of primary resistance to EGFR-TKIs. [ABSTRACT FROM AUTHOR]

Background Acquired resistance occurs in most non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor ( EGFR) mutations experiencing a response to EGFR -tyrosine kinase inhibitor (TKI) initially. We investigated EGFR -TKI retreatment in patients who had previously received EGFR -TKI followed by chemotherapy. Materials and methods This was a retrospective multicenter study. Patients with locally advanced or metastatic adenocarcinoma or TTF-1 (+) NSCLC, positive EGFR sensitive mutation, and EGFR -TKI reuse after initial EGFR-TKI followed by chemotherapy were enrolled. The objectives were to assess the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) of EGFR TKI switched retreatment. Results In total, 205 patients were enrolled, with a median age of 61.8 years (range 31.4–92.9). There was a larger proportion of females (62.9%) than males, and more never-smokers (73.2%) than ever-smokers. In the initial EGFR -TKI administration, 57.6% of patients showed a complete response (CR) or partial response (PR), and 34.6% had stable disease (SD); in the second-line chemotherapy, 13.7% had PR, and 58.0% had SD; in the EGFR -TKI retreatment, 7.3% had PR, and 37.1% had SD. The median PFS of first-line EGFR -TKI was 8.0 months (95% CI 7.3–8.2), and retreatment EGFR -TKI was 4.1 months (95% CI 2.7–4.6). The median OS since the start of the first-line EGFR -TKI therapy was 35.9 months (95% CI 28.8–50.9), and since the start of EGFR -TKI retreatment was 12.6 months (95% CI 10.4–20.9). In the univariable and multivariable regression analysis of factors associated with PFS of EGFR -TKI retreatment, time interval between the two EGFR TKIs equal to or more than 7 months was statistically significant (HR = 0.62, 95% CI 0.44-0.86; HR = 0.6, 95% CI 0.43–0.86), both p < 0.01. Females with exon 21 mutation also showed a significant difference between the two groups (HR = 0.51, 95% CI 0.30–0.86; HR = 0.52 (0.31–0.88), both p < 0.05). Conclusions EGFR -TKI retreatment was effective in prolonging survival, and was shown to be a worthwhile option for EGFR- mutated NSCLC patients after failure of first-line EGFR -TKI and chemotherapy. The survival benefit was especially pronounced in patients with longer drug holidays from the initial EGFR -TKI and in females with the exon 21 mutation. [ABSTRACT FROM AUTHOR]