Identification of risk factors for venous thromboembolism and validation of the Khorana score in patients with advanced lung cancer: based on the multicenter, prospective Rising-VTE/NEJ037 study data.

BACKGROUND: Management of cancer-associated venous thromboembolism (VTE) is essential in cancer treatment selection and prognosis. However, currently, no method exists for assessing VTE risk associated with advanced lung cancer. Therefore, we assessed VTE risk, including driver gene mutation, in advanced lung cancer and performed a Khorana score validation. METHODS: The Rising-VTE/NEJ037 study was a multicenter prospective observational study that included patients with advanced lung cancer. In the Rising-VTE/NEJ037 study, the Khorana score was calculated for enrolled patients with available data on all Khorana score components. The modified Khorana score was based on the body mass index of ≥ 25 kg/m2, according to the Japanese obesity standard. A multivariate logistic regression analysis, including patient background characteristics, was performed to evaluate the presence of VTE 2 years after the lung cancer diagnosis. RESULTS: This study included 1008 patients with lung cancer, of whom 100 (9.9%) developed VTE. From the receiver operating characteristic curve analysis, VTE risk could not be determined because both the Khorana score (0.518) and modified Khorana score (0.516) showed very low areas under the curve. The risk factors for VTE in the multivariate analysis included female sex, adenocarcinoma, performance status, N factor, lymphocyte count, platelet count, prothrombin fragment 1 + 2 and diastolic blood pressure. CONCLUSION: The Khorana score, which is widely used in cancer-VTE risk assessment, was less useful for Japanese patients with advanced lung cancer. Prothrombin fragment 1 + 2, a serum marker involved in coagulation, was more suitable for risk identification. CLINICAL TRIAL INFORMATION: jRCTs061180025.

[An Autopsy Case of IGF‒⠡ Secreting Gastric Cancer with Non‒Islet Cell Tumor Hypoglycemia].

We present the case of a 72‒year‒old male patient with anorexia who was diagnosed with advanced gastric cancer with multiple liver metastasis. He had marked hypoglycemia and lightheadedness from the time of admission. The serum insulin level was very low and other endocrinology test results were normal. He was finally diagnosed with non‒islet cell tumor hypoglycemia(NICTH)based on IHC findings that tumor cells expressed insulin‒like growth factor (IGF)Ⅱ. After the patient received intravenous glucocorticoid therapy along with S‒1 plus CDDP combination chemotherapy, the hypoglycemia was quickly resolved. However, he developed septic shock in reaction to the chemotherapy and died on the 35th day of hospitalization. The autopsy showed the presence of IGF‒Ⅱ in the liver metastasis, as well as in the primary tumor.

Intrascleral fixation of intraocular lens haptics: histological advantages in a comparison with scleral suture fixation in rabbits.

PURPOSE: To disclose histological advantages of intrascleral fixation of intraocular lens haptics, in comparison with scleral suture fixation, in a study with rabbits. METHODS: Ten white rabbits, 10 weeks of age, were used in this experimental histopathological study. After unilateral lensectomy and anterior vitrectomy, an intraocular lens haptic was inserted into one eye of each rabbit. Intrascleral fixation was performed in five rabbits, whereas scleral suture fixation was performed in the others. At postoperative 1 week, the globe was enucleated in two rabbits in each group; at postoperative 8 weeks, the globe was enucleated in the remaining three rabbits in each group. Sections of the sclera around haptics and sutures were evaluated with haematoxylin and eosin and immunohistochemical staining methods. We assessed severity of inflammation on histopathological photos, taken near the haptic or suture in the sclera, by counting white blood cells. The Mann-Whitney U test was performed to analyse differences in the severity of inflammation between the groups. RESULTS: Samples in the intrascleral fixation group demonstrated reduced irregularity of collagen fibres; reduced infiltration of fibroblasts, giant cells, lymphocytes, neovascular cells, neutrophils and eosinophils and weaker staining for fibronectin (indicating tissue repair) and heat shock protein 70 (indicating cell damage). In addition, reduced white blood cell infiltration was observed in the intrascleral fixation samples at 8 weeks in both shallow sclera (p = 0.001) and deep sclera (p = 0.002). CONCLUSIONS: Histological analysis showed that intrascleral fixation caused fewer inflammatory changes than scleral suture fixation, with reduced fibroblast migration and production of cytotoxic factors.

The occhiolino (occ) mutant Zebrafish, a model for development of the optical function in the biological lens.

BACKGROUND: Zebrafish visual function depends on quality optics. An F3 screen for developmental mutations in the Zebrafish nervous system was conducted in wild-type (wt) AB Zebrafish exposed to 3 mM of N-ethyl-N-nitrosourea (ENU). RESULTS: Mutant offspring, identified in an F3 screen, were characterized by a small pupil, resulting from retinal hypertrophy or hyperplasia and a small lens. Deficits in visual function made feeding difficult after hatching at approximately 5-6 days postfertilization (dpf). Special feeding conditions were necessary for survival of the occhiolino (occ) mutants after 6 dpf. Optokinetic response (OKR) tests measured defects in visual function in the occ mutant, although electroretinograms (ERGs) were normal in the mutant and wt. Consistent with the ERGs, histology found normal retinal structure in the occ mutant and wt Zebrafish. However, lens development was abnormal. Multiphoton imaging of the developmental stages of live embryos confirmed the formation of a secondary mass of lens cells in the developing eye of the mutant Zebrafish at 3-4 dpf, and laminin immunohistochemistry indicated the lens capsule was thin and disorganized in the mutant Zebrafish. CONCLUSIONS: The occ Zebrafish is a novel disease model for visual defects associated with abnormal lens development. Developmental Dynamics 246:915-924, 2017. © 2017 Wiley Periodicals, Inc.

Histological Quantification of Gene Silencing by Intratracheal Administration of Dry Powdered Small-Interfering RNA/Chitosan Complexes in the Murine Lung.

PURPOSE: The use of small-interfering RNA (siRNA) as an inhalation therapy has recently received much attention. Some reports have confirmed the suppression of gene expression in whole lungs following intratracheal administration of dry powdered siRNA; however, the anatomical location in the lung where gene silencing occurs has not been precisely identified. Here, we aimed to histologically evaluate gene silencing efficacy in murine lungs by intratracheal administration of an siRNA/chitosan complex as a dry powder. METHODS: Enhanced green fluorescence protein (EGFP)-specific siRNA (EGFP-siRNA)/chitosan powder was prepared and administered intratracheally to EGFP transgenic mice or mice carrying metastatic lung tumors consisting of Lewis lung carcinoma (LLC) cells stably expressing EGFP (EGFP-LLCs). Thereafter, green fluorescence intensities were quantified in the airways, parenchyma, and lung tumors. RESULTS: Intratracheal administration of the EGFP-siRNA/chitosan powder suppressed EGFP expression in the bronchi, bronchioles, and alveolar walls of EGFP transgenic mice. Additionally, EGFP-siRNA/chitosan effectively silenced EGFP expression in lung tumors consisting of EGFP-LLC cells. CONCLUSIONS: Pulmonary administration of siRNA/chitosan powder suppressed gene expression throughout the lung and in lung tumors. Therefore, this may become a powerful strategy to target genes expressed in a wide range of respiratory diseases involving the airways, parenchyma, and lung tumors.

Stability of ascorbic acid in human aqueous humor.

OBJECTIVE: The stability of ascorbic acid (AA) in the human aqueous humor (AqH) remains unclear. This study aimed to investigate the stability of AqH AA under varying conditions (27, 4, - 20, and - 80 °C) without acidification. RESULTS: Rapid AA degradation occurred at 27 °C. At 4 °C, a significant 12.2% degradation was observed after 24 h. Storage at - 20 °C resulted in a notable 37.5% degradation after 28 days, whereas storage at - 80 °C resulted in 10.7% degradation after 28 days. Unacidified AqH samples recorded early decomposition at 27 °C and 4 °C. In conclusion, it is recommended to conduct measurements within 28 days for samples stored at - 80 °C.

Relationship between anterior capsule opening and direction of intraocular lens decentration.

PURPOSE: To compare intraocular lens (IOL) decentration between patients in whom the continuous curvilinear capsulorhexis (CCC) completely covers the IOL optic and those in whom it incompletely covers the IOL optic and determine how an incompletely covered CCC affects the IOL position. SETTING: Tertiary hospital in Japan. DESIGN: Single-center retrospective study. METHODS: 57 eyes of 57 patients (mean age 70.8 ± 6.2 years) that underwent phacoemulsification and IOL (SN60WF) implantation in the bag between April 2010 and April 2015 were included in this study. The patients were classified based on whether the CCC completely (CC group) or incompletely (NCC group) covered the IOL optic using an anterior eye segment analysis system (EAS-1000). The IOL decentration of the groups was analyzed using EAS-1000 at 1 week, 1 month, 3 months, and 6 months postoperatively and compared. The relationship between the NCC location and the IOL direction at 3 months postoperatively was analyzed. RESULTS: The NCC group (25 eyes) had a significantly higher amount of IOL decentration than the CC group (32 eyes) at 1 week, 1 month, 3 months, and 6 months postoperatively ( P < .05). There was a correlation between the direction of IOL decentration and the NCC location, and IOL decentration in the NCC group occurred in the opposite direction to the NCC area. CONCLUSIONS: An anterior capsule opening that completely covers the IOL optic is important to control IOL decentration.

Inhibition of anterior capsule opacification and contraction by the elevated anterior rim of the intraocular lens optic.

PURPOSE: To verify the anterior capsule opacification (ACO) and contraction (ACC) of the ZCB00V intraocular lens (IOL), made of the same material as the AR40e with a high ACC rate. STUDY DESIGN: Retrospective cohort study. METHODS: We evaluated 35 patients at 1 week, 1, 3 and 6 months post phacoemulsification with either a ZCB00V (n = 35) or FY-60AD (n = 34) IOL implantation. The ACC rate was calculated using retroillumination images of the anterior segment, and the ACO was measured using anterior segment photographs and image analysis software. The contact grade between the IOL and anterior capsule was estimated from the Pentacam® images. RESULTS: The postoperative ACC rates (mean ± standard deviation) at 3 months were 1.03%±2.54% for the ZCB00V and, and 7.12%±9.47% for the FY-60AD. The ZCB00V-implanted eyes showed a significantly lower postoperative ACC at 1 week, 3 months, and 6 months (P < 0.01). On the other hand, the FY-60AD-implanted eyes had more pronounced ACO, and a significantly larger area of opacification (62.24%±21.32% vs. 16.90%±8.34%; P = 0.0005). Pentacam® analysis revealed a space between the anterior capsule and IOL surface in the ZCB00V-implanted eyes, whereas the anterior capsule firmly adhered to the IOL surface in the FY-60AD-implanted eyes. CONCLUSION: The ACC and ACO were significantly lower in eyes with ZCB00V IOLs compared to those with the FY-60AD. The anterior segment image analysis revealed that the elevated anterior rim of the ZCB00V IOL prevented adhesion between the anterior capsule and IOL optic surface, suggesting an open capsule effect.

Clinical Features of Syphilis Patients with Ocular Symptoms as the Initial Manifestation.

Purpose: This study aimed to investigate the clinical features of patients with syphilis having ocular symptoms as the initial manifestation. Patients and Methods: Eleven patients diagnosed with ocular syphilis at Dokkyo Medical University Hospital and Jichi Medical University Hospital between November 2018 and April 2022 were studied retrospectively. Results: Six patients were diagnosed with secondary, three were latent, and one was tertiary stage syphilis. Ten out of 11 patients underwent cerebrospinal fluid analysis, and 1 refused. Nine out of 10 patients tested positive, of which 4 presented with neurological symptoms and the others were asymptomatic. Nine out of 11 patients tested negative for human immunodeficiency virus. Antiluetic therapy was administered to 10 out of 11 patients, which improved or maintained visual acuity at -0.1 logMAR in 9 patients. One patient achieved the best-corrected visual acuity -0.1 logMAR in one eye, whereas the other showed no improvement due to severe chorioretinal degeneration. Conclusion: Ocular syphilis presents with various clinical findings and has no significant ocular manifestations without acute syphilitic posterior placoid chorioretinitis. Patients diagnosed with syphilis based on ocular symptoms should undergo cerebrospinal fluid analysis.

Invasive Mucinous Adenocarcinoma with Acute Respiratory Distress Syndrome Diagnosed by Autopsy Findings.

We herein report a fatal case of invasive mucinous adenocarcinoma (IMA) with acute respiratory distress syndrome (ARDS) diagnosed based on autopsy findings. A 76-year-old man presented with severe respiratory discomfort on admission. Computed tomography (CT) revealed a peripheral distribution of consolidation. Although his respiratory status improved after steroid therapy, re-exacerbation occurred, and the patient died on day 131. A bronchoscopic lung biopsy had shown organizing pneumonia, but a post-mortem examination surprisingly revealed IMA with organizing pneumonia. IMA presenting with ARDS as the first symptom is extremely rare.

[Application of biological adhesives for corneal perforation treatment].

OBJECTIVE: To investigate of the effectiveness of biological adhesives in corneal perforation treatment. METHOD: Three types of surgical treatment of corneal perforation were performed on albino rabbits. Procedure 1 involved perforation closure using cyanoacrylate adhesive (DERMABOND), Procedure 2 involved a gelatinous glue adhesive, gelatin resorcin and formaldehyde (GRF), and Procedure 3 involved routine perforation repair using 10-0 nylon sutures. The healing status of the wounds was examined by comparing anterior eye photos taken before and after perforation. Pathological changes were also observed. RESULTS: 1) The closure using DERMABOND showed less inflammation in pathological findings, resulting in the best corneal clarity. 2) Pathological findings from the wounds closed using GRF showed early cell necrosis (possibly due to the formaldehyde), resulting in corneal vascularization and minor corneal opacity. 3) The outcome of the suturing procedure depended highly on the surgeon's skills; chronic physical stimulation from the sutures caused corneal vascularization and corneal opacity. CONCLUSIONS: The application of biological adhesives is effective in treating corneal perforations, with minimal effect on wound healing, and is recommended as a treatment option for these injuries.

A Case of Pigment Dispersion Syndrome after Placement of Sulcus Intraocular Lens with 7-mm Optic Diameter after Posterior Capsule Rupture.

A 48-year-old woman diagnosed with primary angle closure suspect (PACS) in the right eye underwent cataract surgery, and a 7-mm optic diameter intraocular lens (IOL) was placed in the ciliary sulcus after intraoperative posterior capsule rupture. The patient developed uveitis and blurred vision the next day. The IOL was fixed between the iris and the anterior capsule. Irregularly shaped pupils due to posterior synechia and pigmentation on the IOL surface were observed. In the Scheimpflug image, the IOL on the anterior capsule was observed and the anterior chamber depth was 2.92 mm. A diagnosis of pigment dispersion syndrome and elevated intraocular pressure due to sulcus IOL placement was made. The patient underwent intrascleral IOL fixation surgery using an already inserted IOL to reposition the IOL under the anterior capsule. After 1 week, the blurred vision, anterior chamber inflammation, and IOL surface pigmentation were resolved. The right eye IOP was 15 mm Hg and the pupil became a regular circle. Scheimpflug images showed the IOL located behind the anterior capsule and an anterior chamber depth of 3.88 mm. Because the patient had a slightly shorter axial length of 22.89 mm and PACS, pigment dispersion may have occurred due to friction between the iris and the shape of the optic edge with a large optic diameter. In cases of posterior capsule rupture with short axial length and PACS, the use of a 7-mm optic diameter IOL in the sulcus should be avoided, or intrascleral IOL fixation should be selected as the surgical technique.

Incidence of venous thromboembolism in advanced lung cancer and efficacy and safety of direct oral anticoagulants: a multicenter, prospective, observational study (Rising-VTE/NEJ037 study).

Background: Venous thromboembolism (VTE) is a well-known type of cancer-associated thrombosis and a common complication of malignancy. However, the incidence of VTE associated with lung cancer and the effectiveness of direct oral anticoagulants remain unclear. This study aimed to identify the incidence of VTE associated with lung cancer at the time of diagnosis or during treatment, the efficacy and safety of edoxaban, and associated risk factors. Methods: The Rising-VTE/NEJ037 study was a multicenter prospective observational study. Altogether, 1021 patients with lung cancer who were unsuitable for radical resection or radiation were enrolled and followed up for 2 years. Patients with VTE at the time of lung cancer diagnosis started treatment with edoxaban. The primary endpoint of this trial was the rate of newly diagnosed VTE after enrollment or recurrence rate 6 months after treatment initiation. Results: Data were available for 1008 patients. The median age was 70 years (range: 30-94 years), and 70.8% were men. Sixty-two patients had VTE at the time of lung cancer diagnosis, and 38 (9.9%) developed VTE at follow-up. No cases of VTE recurrence were recorded 6 months after treatment initiation with edoxaban. Major and clinically relevant non-major bleeding events occurred in 4.9% of patients and increased to 22.7% in the edoxaban treatment group. Conclusions: VTE occurrence should be monitored during lung cancer treatment. Although treatment with edoxaban was highly effective in preventing VTE recurrence, its administration should be cautiously considered because of the high bleeding rate. Trial registration: jRCTs061180025.

A new risk-assessment tool for venous thromboembolism in advanced lung cancer: a prospective, observational study.

Management of cancer-associated venous thromboembolism (VTE) is essential in treatment selection and cancer prognosis. However, to date, there is no method to assess the risk of VTE specifically associated with advanced lung cancer. Our aim was to create a new risk assessment scoring system that can predict the concomitant or incidence of VTE in advanced lung cancer. We used the dataset of 1008 patients with lung cancer in the Rising-VTE/NEJ037 study, of which 100 (9.9%) developed VTE. The items extracted in the multivariate analysis included female sex, adenocarcinoma, performance status, N factor, lymphocyte count, platelet count, prothrombin fragment 1 + 2, and diastolic blood pressure. This model had a maximum score of 8 points, with ≥ 5 points indicating a high risk of VTE. This simple risk-assessment model for VTE complications with advanced lung cancer could help identify cases that required monitoring for VTE.

Intra-airway administration of small interfering RNA targeting plasminogen activator inhibitor-1 attenuates allergic asthma in mice.

Recent studies suggest that plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system, may promote the development of asthma. To further investigate the significance of PAI-1 in the pathogenesis of asthma and determine the possibility that PAI-1 could be a therapeutic target for asthma, this study was conducted. First, PAI-1 levels in induced sputum (IS) from asthmatic subjects and healthy controls were measured. In asthmatic subjects, IS PAI-1 levels were elevated, compared with that of healthy controls, and were significantly higher in patients with long-duration asthma compared with short-duration asthma. PAI-1 levels were also found to correlate with IS transforming growth factor-ß levels. Then, acute and chronic asthma models induced by ovalbumin were established in PAI-1-deficient mice and wild-type mice that received intra-airway administrations of small interfering RNA against PAI-1 (PAI-1-siRNA). We could demonstrate that eosinophilic airway inflammation and airway hyperresponsiveness were reduced in an acute asthma model, and airway remodeling was suppressed in a chronic asthma model in both PAI-1-deficient mice and wild-type mice that received intra-airway administration of PAI-1-siRNA. These results indicate that PAI-1 is strongly involved in the pathogenesis of asthma, and intra-airway administration of PAI-1-siRNA may be able to become a new therapeutic approach for asthma.

Developmental factors of fibrous opacification in the atopic cataract lens capsule.

AIM: We investigated the developmental factors of fibrous opacification in the atopic cataract lens capsule. METHOD: We examined the expression of transforming growth factor (TGF)-ß signals (phosphorylated Smad2/3 and Smad7) and plasminogen activator inhibitor (PAI)-1 in atopic cataract lenses by immunohistochemistry. The PAI-1 concentration in aqueous humor was also measured. RESULTS: Lens epithelial cells of the atopic cataract lens capsule showed positive immunohistochemical staining for phosphorylated Smad2/3 and Smad7. Lens epithelial cells of the age-related cataract lens capsule were positive for phosphorylated Smad2/3, but negative for Smad7 by immunohistochemistry. All cells were negative for PAI-1. However, high concentrations of PAI-1 were detected in the aqueous humor of atopic cataract patients. CONCLUSION: We suggest that TGF-ß and PAI-1 contribute to fibrous opacification in the atopic cataract lens capsule.

Evaluation of the incidence of endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor.

AIMS: To report the incidence of infectious and noninfectious endophthalmitis after intravitreal injection of anti-vascular endothelial growth factor (VEGF) from a multicenter clinical trial in Japan. METHODS: A retrospective multicenter review of the data of patients who received intravitreal anti-VEGF injections between January 2007 and March 2011 was undertaken. Cases with the clinical diagnosis of endophthalmitis resulting from intravitreal injection were identified and reviewed. RESULTS: A total of 5,236 intravitreal anti-VEGF injections (1,209 intravitreal injections of bevacizumab, 3,827 injections of ranibizumab, and 200 injections of pegaptanib sodium) had been administered. Five patients (0.095%), all of whom had received bevacizumab, were diagnosed as having endophthalmitis after the intravitreal injection. All patients visited the institutes for re-examination within 1-2 days after the injection. Among the 5 patients, 2 (0.038%) were culture positive for Streptococcus oralis and Enterococcus faecalis, respectively. The remaining 3 eyes (0.057%) developed presumed noninfectious endophthalmitis. CONCLUSION: Although endophthalmitis is a rare complication associated with intravitreal injection, in this series intravitreal anti-VEGF injection caused infectious or noninfectious endophthalmitis at a relatively high frequency. Further investigations are needed to consider an appropriate injection protocol for minimizing the incidence rates of endophthalmitis, and to assess the optimal treatment protocol for intravitreal injection-related endophthalmitis although it was difficult to differentiate these two entities.

Conversion from Positive to Negative EGFR Mutation due to Clonal Selection during Long-Term Treatment with Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors: A Case Report.

A 77-year-old woman with postoperative recurrent non-small cell lung adenocarcinoma, which exhibited an epidermal growth factor receptor (EGFR) L858R mutation, was treated with gefitinib and erlotinib. Seven years after the start of treatment, the patient experienced a recurrence of malignant pleural effusion. However, 3 different genetic tests revealed that the lung adenocarcinoma cells in the pleural effusion had lost EGFR L858R mutation, suggesting that long-term treatment with EGFR-tyrosine kinase inhibitors (TKIs) converted EGFR mutation from positive to negative. The negative conversion of EGFR mutation as a mechanism of acquired resistance to EGFR-TKIs is considered rare and needs to be further investigated.

Systemic Inflammatory Score Predicts Response and Prognosis in Patients With Lung Cancer Treated With Immunotherapy.

AIM: This study aimed to investigate useful prognostic factors of immunotherapy in patients with lung cancer. PATIENTS AND METHODS: We retrospectively observed 73 patients who underwent immunotherapy (nivolumab, pembrolizumab, and atezolizumab) for lung cancer. The systemic inflammatory score (SIS) was calculated as the sum of the following factors scored one point each: Hemoglobin <12.5 g/dl and serum albumin <3.6 g/dl, resulting in scores of 0-2. We examined the correlation between the SIS and initial tumor response and progression-free and overall survival with other existing markers, namely tumor programmed death-ligand 1 (PD-L1) expression level; neutrophil-to-lymphocyte ratio (NLR); modified Glasgow prognostic score; and prognostic nutritional index, etc. Results: SIS ≤1 was significantly associated with better initial tumor response. In multivariate analysis, PD-L1 expression ≥50% (p=0.010), SIS ≤1 (p=0.028) and NLR <5.6 (p=0.047) were significantly associated with longer progression-free survival, and SIS ≤1 (p=0.030) and NLR <5.6 (p=0.037) were associated with longer overall survival. CONCLUSION: SIS is a useful marker of the efficacy of immunotherapy that can be obtained via routine blood tests.

Prognostic Significance of EGFR Gene Mutation in Patients With EGFR Mutated Non-small Cell Lung Cancer Who Received Best Supportive Care Alone.

BACKGROUND/AIM: The significance of epidermal growth factor receptor (EGFR) mutation in untreated patients with non-small cell lung cancer (NSCLC) remains uncertain. We aimed to determine the significance of EGFR mutation in patients who received best supportive care (BSC) alone, and compare the outcomes of only EGFR- tyrosine kinase inhibitors (TKI)-treated vs. BSC patients. PATIENTS AND METHODS: Between April 1991-August 2018, 1,197 patients diagnosed with unresectable NSCLC at our institutions were enrolled in the study. RESULTS: Among 226 patients who underwent EGFR mutation analysis and received BSC alone, 35 and 191 did and did not harbor the mutation, and the median survival times (MST) did not differ significantly between these groups. A comparison of only EGFR-TKI-treated and BSC patients with EGFR mutation revealed that the former had a three times longer MST than the latter. CONCLUSION: Our results may help explain the benefit of EGFR-TKI for patients who would be directed towards BSC.