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PurposeIdentification of lymph node (LN) metastasis in non-small cell lung cancer (NSCLC) is critical for disease staging and selection of therapeutic modalities. Sometimes it is not possible to obtain LN core tissue by endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA), resulting in low diagnostic yield.Materials and methodsIn this study, 138 specimens were collected from 108 patients who underwent EBUS-TBNA under the suspicion of LN metastasis of NSCLC. Diagnostic yields of anti-CD45 and anti-methionyl-tRNA synthetase (MRS), immunofluorescent (IF) staining on cytology specimens were compared with those of conventional cytology and positron emission tomography-computed tomography (PET-CT).ResultsMRS was strongly expressed in NSCLC cells metastasized to LNs, but weakly expressed in cells at the periphery of the LN germinal center. The majority of cells were CD20 positive, although a few cells were either CD3 or CD14 positive, indicating that CD45 staining is required for discrimination of non-malignant LN constituent cells from NSCLC cells. When the diagnostic efficacy of MRS/CD45 IF staining was evaluated using 138 LN cellular aspirates from 108 patients through EBUS-TBNA, the sensitivity was 76.7% and specificity was 90.8%, whereas those of conventional cytology test were 71.8% and 100.0%, respectively. Combining the results of conventional cytology testing and those of PET-CT showed a sensitivity and specificity of 71.6% and 100%, and the addition of MRS/CD45 dual IF data to this combination increased sensitivity and specificity to 85.1% and 97.8%, respectively.ConclusionMRS/CD45 dual IF staining showed good diagnostic performance and may be a good tool complementing conventional cytology test for determining LN metastasis of NSCLC.

Aminoacyl-tRNA synthetase-interacting multi-functional protein 2 (AIMP2) works as potent tumor suppressor, while its splicing variant lacking exon 2 (AIMP2-DX2) competes with AIMP2 for binding to target proteins and compromises its anti-tumor activity. Assuming that AIMP2 and its variant AIMP2-DX2 could be released out to human sera in pathological condition, we investigated the diagnostic and prognostic usefulness of autoantibodies against AIMP2 and AIMP2-DX2 by measuring their serum levels in 80 normal and lung cancer samples that were matched in age, gender and smoking status. The area under the curve of AIMP2-DX2, AIMP2, and AIMP2-DX2/AIMP2 autoantibody ratio was low (0.416, 0.579, and 0.357, respectively), suggesting limited diagnostic value. A total of 165 lung cancer patients were classified into low and high AIMP2-DX2, AIMP2, and AIMP2-DX2/AIMP2 based on the median expression of each parameter. The high AIMP2-DX2 group was older and had larger tumors (>3 cm) than the low AIMP2-DX2 group. The high AIMP2-DX2/AIMP2 group had higher CYFRA-21 levels and significantly shorter overall survival than the low AIMP2-DX2/AIMP2 group (18.6 vs. 48.9 months, P = 0.021, Log Rank Test). Taken together, autoantibodies against AIMP2-DX2 and AIMP2 are detectable in the human blood and the increased ratio of AIMP2-DX2/AIMP2 is related to poor clinical outcome of lung cancer.

Background: The clinical staging of non‐small cell lung cancer (NSCLC) is well known to be related to their prognosis. However, there is usually a discrepancy between clinical staging and pathological staging. There are few analyses of clinical staging accuracy in patients with NSCLC. We compared the concordance rate between clinical and pathological staging of NSCLC and evaluated factors affecting the accuracy in real‐world data. Methods: Altogether, 811 patients with primary NSCLC who had undergone curative lung resection surgery in Severance Hospital from January 2019 to December 2020 were retrospectively reviewed. We used the eighth edition of the American Joint Committee on Cancer TNM staging. Results: Among 811 patients, endobronchial ultrasound (EBUS) and positron emission tomography (PET‐CT) were performed in 31.6% and 96.7%, respectively. The concordance rates between clinical and pathological TNM staging, T factor, and N factor, were 68.7%, 77.7%, and 85.8%, respectively. With multivariable logistic regression analysis, current smokers (OR 0.49; 95% CI: 0.32–0.76, p = 0.001) and a higher clinical stage (p < 0.001) contributed to the clinical staging inaccuracy. Additionally, the presence of a bronchoscopy specialist was significantly associated with clinical staging accuracy (OR 1.53; 95% CI: 1.10–2.13, p = 0.011). Conclusion: Clinical staging accuracy in NSCLC improved compared to before the widespread use of PET‐CT and EBUS in clinical staging work‐up. Smoking history and absence of expert bronchoscopy specialists showed a meaningful correlation with the inaccuracy of clinical staging. Thus, training more bronchoscopy experts would improve the staging accuracy of NSCLC, which could positively affect the prognosis of NSCLC. [ABSTRACT FROM AUTHOR]

Simple Summary: Crizotinib, an oral tyrosine kinase inhibitor that targets ALK, MET, and ROS1 kinase, has emerged as an effective treatment for ROS1-rearranged NSCLC. In South Korea's real-world setting, characterized by a higher elderly population and increased brain/central nervous system metastasis rates, crizotinib remains a cornerstone in treating ROS1-rearranged NSCLC, providing lasting clinical benefits with a favorable safety profile. Liquid biopsies, utilizing biomarkers, are instrumental in detecting targetable mutations, monitoring the disease burden, and identifying resistance mechanisms. In our study, next-generation sequencing using cell-free total nucleic acids enables the detection of ROS1 fusions and the identification of resistance mechanisms during disease progression. Real-world data on the use and outcomes of crizotinib in ROS1-rearranged non-small-cell lung cancer (NSCLC) are limited. This study aims to analyze the real-world efficacy of crizotinib in South Korea and explore the utilization of liquid biopsies that implement next-generation sequencing (NGS) using cell-free total nucleic acids. In this prospective multicenter cohort study, 40 patients with ROS1-rearranged NSCLC, either starting or already on crizotinib, were enrolled. Patients had a median age of 61 years, with 32.5% presenting brain/central nervous system (CNS) metastases at treatment initiation. At the data cutoff, 48.0% were still in treatment; four continued with it even after disease progression due to the clinical benefits. The objective response rate was 70.0%, with a median duration of response of 27.8 months. The median progression-free survival was 24.1 months, while the median overall survival was not reached. Adverse events occurred in 90.0% of patients, primarily with elevated transaminases, yet these were mostly manageable. The NGS assay detected a CD74–ROS1 fusion in 2 of the 14 patients at treatment initiation and identified emerging mutations, such as ROS1 G2032R, ROS1 D2033N, and KRAS G12D, during disease progression. These findings confirm crizotinib's sustained clinical efficacy and safety in a real-world context, which was characterized by a higher elderly population and higher rates of brain/CNS metastases. The study highlights the clinical relevance of liquid biopsy for detecting resistance mechanisms, suggesting its value in personalized treatment strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Potential application of CDK12/13 inhibitor in overcoming resistance to osimertinib, a third-generation EGFR TKI, in vitro and in vivo. Osimertinib is a third-generation epidermal growth factor receptor and tyrosine kinase inhibitor (EGFR-TKI) approved for the treatment of lung adenocarcinoma patients harboring EGFR mutations. However, acquired resistance to this targeted therapy is inevitable, leading to disease relapse within a few years. Therefore, understanding the molecular mechanisms of osimertinib resistance and identifying novel targets to overcome such resistance are unmet needs of cancer patients. Here, we investigated the efficacy of two novel CDK12/13 inhibitors, AU-15506 and AU-16770, in osimertinib-resistant EGFR mutant lung adenocarcinoma cells in culture and xenograft models in vivo. We demonstrate that these drugs, either alone or in combination with osimertinib, are potent inhibitors of osimertinib-resistant as well as -sensitive lung adenocarcinoma cells in culture. Interestingly, only the CDK12/13 inhibitor in combination with osimertinib, although not as monotherapy, suppresses the growth of resistant tumors in xenograft models in vivo. Taken together, the results of this study suggest that inhibition of CDK12/13 in combination with osimertinib has the potential to overcome osimertinib resistance in EGFR mutant lung adenocarcinoma patients. [ABSTRACT FROM AUTHOR]

Introduction: The PACIFIC study demonstrated that durvalumab consolidation therapy significantly improved progression‐free survival (PFS) and overall survival (OS) in patients with unresectable stage III non‐small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT). However, there was no clinical benefit in both PFS and OS in epidermal growth factor receptor (EGFR) mutation‐positive patient groups in a post hoc exploratory analysis. Moreover, the clinical effects of immune checkpoint inhibitors (ICIs) in EGFR mutation‐positive stage IV NSCLC were demonstrated to be poor. Personalized treatment according to the mutation status is also required in stage III NSCLC. Lazertinib, a third‐generation EGFR tyrosine kinase inhibitor (TKI), is newly developed and approved for use in Korea. Methods: This prospective, open, single‐arm, multicenter, phase II clinical trial aims to evaluate the efficacy and safety of lazertinib as a consolidative therapy after CCRT treatment in unresectable, EGFR mutation‐positive NSCLC stage III patients. The primary endpoint of this study is PFS, and the secondary endpoints are OS, objective response rate (ORR), duration of response (DoR), time to death or distant metastasis (TTDM), and safety profiles. Discussion: Our study may extend the indications for third‐generation EGFR‐TKIs to treat patients with stage III NSCLC. Moreover, using this drug to treat stage III NSCLC would emphasize the value of mutation analysis and personalized medicine. [ABSTRACT FROM AUTHOR]

This study aimed to assess the diagnostic accuracy and safety of CT-guided percutaneous core needle biopsy (PCNB) with a coaxial needle for the diagnosis of lung cancer in patients with an usual interstitial pneumonia (UIP) pattern of interstitial lung disease. This study included 70 patients with UIP and suspected to have lung cancer. CT-guided PCNB was performed using a 20-gauge coaxial cutting needle. The diagnostic accuracy, sensitivity, specificity, and percentage of nondiagnostic results for PCNB were determined in comparison with the final diagnosis. PCNB-related complications were evaluated. Additionally, the risk factors for nondiagnostic results and pneumothorax were analyzed. The overall diagnostic accuracy, sensitivity, and specificity were 85.7%, 85.5%, and 87.5%, respectively. The percentage of nondiagnostic results was 18.6% (13/70). Two or less biopsy sampling was a risk factor for nondiagnostic results (p = 0.003). The overall complication rate was 35.7% (25/70), and pneumothorax developed in 22 patients (31.4%). A long transpulmonary needle path was a risk factor for the development of pneumothorax (p = 0.007). CT-guided PCNB using a coaxial needle is an effective method with reasonable accuracy and an acceptable complication rate for the diagnosis of lung cancer, even in patients with UIP. [ABSTRACT FROM AUTHOR]

Background: Skeletal muscle depletion (sarcopenia) is associated with poor prognosis in patients with lung cancer. We analyzed changes in skeletal muscle area using serial computed tomography (CT) until the death of patients with advanced squamous cell lung cancer (SQCLC). Methods: This retrospective study comprised 70 consecutive patients who underwent palliative chemotherapy for SQCLC. The cross‐sectional area of the skeletal muscle at the level of the first lumbar vertebra (L1) was measured using chest CT. An artificial intelligence algorithm was developed and used for the serial assessment of the muscle area. Sarcopenia was defined as an L1 skeletal muscle index <46 cm2/m2 in men and < 29 cm2/m2 in women. Results: The median age was 69 years; 62 patients (89%) had metastatic disease at the time of initial diagnosis. Sarcopenia was present in 58 patients (82.9%) at baseline; all patients experienced net muscle loss over the disease trajectory. The median overall survival was 8.7 (95% confidence interval 5.9–11.5) months. The mean percentage loss of skeletal muscle between the first and last CT was 16.5 ± 11.0%. Skeletal muscle loss accelerated over time and was the highest in the last 3 months of life (p < 0.001). Patients losing skeletal muscle rapidly (upper tertile, >3.24 cm2/month) had shorter overall survival than patients losing skeletal muscle slowly (median, 5.7 vs. 12.0 months, p < 0.001). Conclusions: Patients with advanced SQCLC lose a significant amount of skeletal muscle until death. The rate of muscle area reduction is faster at the end of life. Patients with advanced SQCLC lose a significant amount of skeletal muscle until death. The rate of muscle area reduction is faster at the end of life. [ABSTRACT FROM AUTHOR]

Background: Hyperprogressive disease (HPD) is a paradoxical acceleration of tumor growth after immune checkpoint inhibitor (ICI) treatment. This study aimed to identify the risk factors and to present a predictive model for HPD in patients treated with ICIs. Methods: A total of 78 non‐small cell lung cancer (NSCLC) cases, treated with at least two cycles of ICIs who underwent computed tomography (CT) for response assessment were recruited into the study from January 2016 to August 2019. HPD was defined by the following criteria: (i) time‐to‐treatment failure <2 months; (ii) a 50% increase in the sum of target lesion diameters; (iii) new development of at least two lesions in an already involved organ; (iv) appearance of a new organ lesion; and (v) a decrease in ECOG PS 2. Results: Of the 78 total patients, 15 (19.2%) had HPD. The risk factors of HPD were age; primary lesion size; and metastases in the contralateral lung, pleura, liver, and bone in multivariable logistic regression (odds ratio [OR]; 0.9038, 1.6619, 28.5913, 23.8264, 14.5711, and 20.1533, respectively, all P‐values < 0.05). By using these risk factors, we developed a prediction model for HPD and the area under the receiver operating characteristic curve of the model was 0.9556 (95% confidence interval [CI]: 0.9133–0.9978). Conclusions: HPD is relatively common and associated with a grave clinical outcome, requiring a careful monitoring in lung cancer patients treated with ICIs. Moreover, risk factors such as age, size of tumor and number of various metastatic lesions should be taken into consideration before ICI administration. Key points: Significant findings of the study: Age, primary lesion size, and number of metastases are risk factors of HPD. HPD is strongly associated with poor prognosis. HPD during ICI use needs comprehensive monitoring. What this study adds: This is the first study to develop a prediction model. The area under the curve of the prediction model for HPD was 0.9556. [ABSTRACT FROM AUTHOR]

Background: Although the use of radial endobronchial ultrasound (R‐EBUS) with a guide sheath has shown improved diagnostic capability in peripheral pulmonary lesions, its utility is still low due to variable performance. To overcome its limitation, we evaluated the feasibility and efficacy of R‐EBUS combined with transbronchial biopsy (TBB) under fluoroscopic guidance. Methods: We retrospectively reviewed medical records of 74 patients with non‐small cell lung cancer (NSCLC) who underwent R‐EBUS combined with TBB or TBB alone as a diagnostic technique. Subjects were grouped according to the diagnostic modality used (R‐EBUS combined with TBB vs. TBB alone). Each group was matched for age, sex, and location of the biopsy. The chi‐square test and paired t‐test were used to compare characteristics and identify factors that affected the diagnostic yield. Results: The mean age of the study cohort was 67.4 ± 12.8 years, with 21 (56.8%) men and 16 (43.2%) women in each group. The lesion size was significantly smaller in the R‐EBUS group (23.6 vs. 33.9, P < 0.001). The diagnostic yield with the combined use of R‐EBUS and TBB (27/37, 72.9%) was significantly higher than that with standard TBB alone (22/37, 59.4%). Lung lesions with a positive bronchus sign were associated with a higher diagnostic yield (odds ratio = 3.52 [1.17–10.62]; P = 0.025). Conclusions: The combination of R‐EBUS with TBB resulted in a higher diagnostic yield than either technique alone. Thus, the addition of R‐EBUS biopsy would be helpful to improve the diagnostic yield of TBB. Key points: Significant findings of the study: The combination of R‐EBUS with TBB under fluoroscopic guidance improved the diagnostic yield of PPLs compared to TBB alone. A tissue diagnosis was more likely in pulmonary lesions with the air‐bronchus sign. What this study adds: The use of R‐EBUS could help improve the low diagnostic yield of TBB under fluoroscopic guidance without increasing the incidence of complications. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is prevalent and a known adverse prognostic effector in lung cancer (LCA). However, the relationship between sarcopenia and histology remains uncertain in LCA. Methods: Consecutive patients with newly diagnosed LCA (n = 778) between June 2012 and February 2015 were retrospectively reviewed to identify factors associated with sarcopenia. Sarcopenia was defined as CT-determined L3 muscle index (muscle area at L3/height2) of < 55 cm2/m2 for men and < 39 cm2/m2 for women. Results: Mean patient age was 67.7 ± 10.8 years, and most (73.1%) were male. The most prevalent histology was adenocarcinoma (44.0%) and 71.6% of patients had stage III or IV disease. The overall prevalence of sarcopenia was 48.2% (60.3% in men, and 15.3% in women). Univariable analysis showed sarcopenia was significantly associated with male gender, age (≥ 65 years), smoking status, lower BMI (< 23 kg/m2), advanced stage (III and IV), and high comorbidity score (Charlson index ≥ 3). Furthermore, the prevalence of sarcopenia was higher in squamous cell carcinoma (54.9%) and small cell LCA (56.4%) than in adenocarcinoma (39.8%). Multivariable analyses showed sarcopenia was independently associated with a male gender (odds ratio [OR], 11.13), elderly (OR, 2.02) and low BMI (OR, 6.28), stage IV (OR, 1.98), and high comorbidity (OR, 1.93). However, no significant association was found between histologic subtypes and sarcopenia. Conclusions: Sarcopenia was found to be significantly associated with old age, male gender, an advanced stage, comorbidities, and low BMI in LCA. However, histology subtype was not an independent factor for the presence of sarcopenia. [ABSTRACT FROM AUTHOR]

Lung cancer specialists play an important role in designing and implementing lung cancer screening. We aimed to describe their 1) attitudes toward low-dose lung computed tomography (LDCT) screening, 2) current practices and experiences of LDCT screening and 3) attitudes and opinions towards national lung cancer screening program (NLCSP). We conducted a national web-based survey of pulmonologists, thoracic surgeons, medical oncologists, and radiological oncologists who are members of Korean Association for Lung Cancer (N = 183). Almost all respondents agreed that LDCT screening increases early detection (100%), improves survival (95.1%), and gives a good smoking cessation counseling opportunity (88.6%). Most were concerned about its high false positive results (79.8%) and the subsequent negative effects. Less than half were concerned about radiation hazard (37.2%). Overall, most (89.1%) believed that the benefits outweigh the risks and harms. Most (79.2%) stated that they proactively recommend LDCT screening to those who are eligible for the current guidelines, but the screening propensity varied considerably. The majority (77.6%) agreed with the idea of NLCSP and its beneficial effect, but had concerns about the quality control of CT devices (74.9%), quality assurance of radiologic interpretation (63.3%), poor access to LDCT (56.3%), and difficulties in selecting eligible population using self-report history (66.7%). Most (79.2%) thought that program need to be funded by a specialized fund rather than by the National Health Insurance. The opinions on the level of copayment for screening varied. Our findings would be an important source for health policy decision when considering for NLCSP in Korea. [ABSTRACT FROM AUTHOR]

Background: Methionyl-tRNA synthetase (MRS) plays a critical role in initiating translation by transferring Met to the initiator tRNA (tRNAiMet) and protection against ROS-mediated damage, suggesting that its overexpression is related to cancer growth and drug resistance. In this study, the clinical implication of MRS expression in non-small cell lung cancer (NSCLC) was evaluated.Methods: Immunoblot and immunohistochemical (IHC) analyses were performed using tissue lysates and formalin-fixed paraffin embedded (FFPE) tissue blocks from wild type C57BL/6, LSL-Kras G12D, and LSL-Kras G12D:p53fl/fl mice. For human studies, 12 paired adjacent normal appearing lung tissue lysates and cancer tissue lysates, in addition to 231 FFPE tissue samples, were used.Results: MRS was weakly expressed in the spleen and intestinal epithelium and only marginally expressed in the kidney, liver, and lungs of wild type C57BL/6 mice. On the other hand, MRS was strongly expressed in the neoplastic region of lung tissue from LSL-Kras G12D and LSL-Kras G12D:p53fl/fl mice. Immunoblot analysis of the human normal appearing adjacent and lung cancer paired tissue lysates revealed cancer-specific MRS overexpression, which was related to mTORC1 activity. IHC analysis of the 231 FFPE lung cancer tissue samples showed that MRS expression was frequently detected in the cytoplasm of lung cancer cells (179 out of 231, 77.4%), with a small proportion (73 out of 231, 31.6%) also showing nuclear expression. The proportion of cases with positive MRS expression was higher in the advanced pStage subgroup (P = 0.018, χ2-test) and cases with MRS expression also had shorter DFS (161.6 vs 142.3, P = 0.014, log-rank test).Conclusions: Taken together, MRS is frequently overexpressed in NSCLC. Moreover, MRS is related to mTORC1 activity and its overexpression is associated with poor clinical outcomes, indicating that it has potential as a putative therapeutic target. [ABSTRACT FROM AUTHOR]

Objectives: Despite a sharp increase in e-cigarette use, there is debate about whether e-cigarettes are a viable alternative for harm reduction, and the forms that regulation should take. Healthcare providers can be effective in offering guidance to patients and their families and shaping regulatory policy. We described lung cancer specialists’ attitudes toward e-cigarettes and its regulation. Methods: We undertook a nationwide survey of pulmonologists, thoracic surgeons, medical and radiological oncologists who are members of Korean Association for Lung Cancer. Survey items included beliefs and attitudes toward e-cigarettes, attitudes toward e-cigarette regulation and preparedness on discussing e-cigarettes with their patients. Results: Most respondents believed that e-cigarettes are not safer than conventional tobacco cigarettes (75.7%) or smokeless tobacco (83.2%), and feared that discussing e-cigarettes with the patients would encourage use (65.4%). They did not consider it a smoking cessation treatment (78.3%), and thus would not recommend it to smokers who do not want to quit (82.2%) or who failed to quit with conventional smoking cessation treatment (74.1%). Most respondents supported all examples of e-cigarette regulations, including the safety and quality check (97.8%), warning label (97.8%), advertisement ban (95.1%), restriction of flavoring (78.4%), minimum purchasing age (99.5%), and restriction of indoor use (94.6%). Most learned about e-cigarettes from media and advertisements, or conversation with patients rather than through professional scientific resources, and reported discomfort when discussing e-cigarette with patients. Conclusion: Lung cancer specialist physicians in Korea doubt the safety of e-cigarette and use of e-cigarette as smoking cessation treatment, and supported strict regulation. However, only 20% reported that they obtained information on e-cigarettes from the scientific literature and many lacked adequate knowledge based on scientific evidence, suggesting the need for better preparedness. Nevertheless, the views of professionals revealed from our study could help to develop clinical guidelines and regulatory guidance. [ABSTRACT FROM AUTHOR]

Durvalumab is an immune checkpoint inhibitor that blocks PD‐L1. Unlike cytotoxic chemotherapy or molecularly targeted agents, immune checkpoint inhibitors occasionally present distinct response patterns, including radiologic pseudoprogression (initial tumor enlargement with subsequent tumor regression) and immune‐related adverse events in normal tissues. We report a case of unusual computed tomography (CT) findings of pseudoprogression of pulmonary metastases in a patient with metastatic bladder cancer after durvalumab treatment: multiple pulmonary metastases turned into ground‐glass opacity on first follow‐up CT; on second follow‐up CT, and after sustained treatment of the PD‐L1 inhibitor, the lesion was resolved. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the clinical implications of lymph node (LN) density on 18F-FDG PET/CT for mediastinal LN characterization in non-small cell lung cancer (NSCLC).Methods: One hundred and fifty-two patients with 271 mediastinal LNs who underwent PET/CT and endobronchial ultrasound-guided transbronchial needle aspiration for staging were enrolled. Maximum standardized uptake value (SUVmax), short axis diameter, LN-to-primary cancer ratio of SUVmax, and median Hounsfield unit (HU) based on CT histogram were correlated to histopathology.Results: Of 271 nodes, 162 (59.8 %) were malignant. SUVmax, short axis diameter, and LPR of malignant LNs were higher than those of benign nodes. Among malignant LNs, 71.0 % had median HU between 25 and 45, while 78.9 % of benign LNs had values <25 HU or >45 HU. Using a cutoff value of 4.0, SUVmax showed the highest diagnostic ability for detecting malignant LNs with a specificity of 94.5 %, but showing a sensitivity of 70.4 %. Using additional density criteria (median HU 25-45) in LNs with 2.0< SUVmax ≤4.0, the sensitivity increased to 88.3 % with the specificity of 82.6 %.Conclusions: LN density is useful for the characterization of LNs with mild 18F-FDG uptake. The risk of mediastinal LN metastasis in NSCLC patients could be further stratified using both 18F-FDG uptake and LN density.Key Points: • SUVmax showed the highest diagnostic ability for detecting malignant LNs. • LN density was useful in characterization of LNs with mild FDG uptake. • SUVmax and LN density together could stratify the risk of LN metastasis. [ABSTRACT FROM AUTHOR]

Background: Single cross-sectional area of muscle at the third lumbar vertebra (L3MA) is gold standard to estimate skeletal muscle mass (SMM), and L3 muscle index (L3MI, L3MA/height(2)) is used to determine sarcopenia. The purposes of this study were to evaluate the relationship between SMM indices determined by routine chest CT and L3MI in patients with small-cell lung cancer (SCLC) and to suggest chest CT-derived diagnostic criteria for sarcopenia.Methods: Area of pectoralis muscles at the aortic arch (PMA) and at L1 (L1MA) was retrospectively measured on chest CT images of 90 consecutive SCLC patients. Pearson's correlation and multiple linear regression analysis were used to assess relationships between L3MI determined by PET/CT and pectoralis muscle index (PMI) and L1 muscle index (L1MI) determined by chest CT.Results: The correlation between L1MI and L3MI was stronger than that between PMI and L3MI (r = 0.851 vs. r = 0.447, p < 0.001). Multivariable regression analysis showed that L1MI was the only significant predictor of L3MI; L3MI = 0.963 × L1MI + 10.336 (R (2)  = 0.689, p < 0.001) for male and L3MI = 0.772 × L1MI + 16.518 (R (2)  = 0.777, p < 0.001) for female. Using this relationship, estimated cutoffs of L1MI for sarcopenia were 46 cm(2)/m(2) for male and 29 cm(2)/m(2) for female (L3MI cutoffs for sarcopenia are 55 cm(2)/m(2) for male and 39 cm(2)/m(2) for female). The sensitivity and specificity of L1MI cutoffs to determine sarcopenia were 98.2 and 100 %, respectively.Conclusions: Chest CT-determined L1MI is highly correlated with L3MI in SCLC patients. L1MI, as determined by chest CT, could be used to determine the presence of sarcopenia with suggested cutoffs of 46 cm(2)/m(2) for men and 29 cm(2)/m(2) for women. [ABSTRACT FROM AUTHOR]

Although cisplatin has been widely used as a component of standard treatments for advanced non-small cell lung cancers (NSCLC) with KRAS -activating mutations, clinical outcomes remain suboptimal. Among the resistance mechanisms to cisplatin, activation of the MAPK cascade, which plays an important role in cancer cell stress and death, offers a promising therapeutic target. Using KRAS -mutant NSCLC cells and a mouse model, we evaluated the efficacy of adding the MEK1/2 inhibitor AZD6244 as an addition for cisplatin-based chemotherapy. Cisplatin increased phosphorylation of MEK1/2 and ERK1/2 and reduced Bcl-2 like 11 (BIM) expression in NSCLC cells and the mouse model. BIM silencing in NSCLC cells using sh RNA led to a blunted cytotoxic response to cisplatin, while prevention of BIM loss with the MEK1/2 inhibitor synergized cisplatin-mediated cell death. The combination of cisplatin and AZD6244 yielded a superior response to cisplatin alone in K-ras mice. In conclusion, an MEK1/2 inhibitor potentiated the anti-tumor effects of cisplatin in KRAS -dependent lung cancer cells and an animal model through inhibition of BIM degradation. These findings warrant further studies of clinical applications of MEK1/2 inhibitors in cisplatin-based chemotherapy for lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: The objective of the study was to evaluate the computed tomographic (CT) features and growth rates of pulmonary metastases from colorectal cancer (CRC) on serial CT scans. The study included 17 patients (28 pulmonary metastases) who underwent metastasectomy from CRC. The characteristic CT features include well-defined round or oval nodules in the peripheral or subpleural/fissural lung with frequent feeding vessel sign. The mean tumor volume doubling time was calculated as 160 days. With these growth rates, short-term follow-up (i.e., 5–6 months) would be helpful. [Copyright &y& Elsevier]

Objectives Disruption in the stability of respiratory microbiota is known to be associated with many chronic respiratory diseases. However, only few studies have examined microbiomes in lung cancer. Therefore, we characterized and compared the microbiomes of patients with lung cancer and those with benign mass-like lesions. Materials and methods Bronchoalveolar fluid was collected prospectively to evaluate lung masses in patients who had undergone bronchoscopies from May to September 2015. Twenty-eight patients (20 male, 8 female) were enrolled: 20 diagnosed with lung cancer and 8 diagnosed with benign diseases. Samples were analysed by 16S rRNA-based next-generation sequencing. Results The participants’ mean age was 64 ± 11 years. Bacterial operational taxonomic units were classified into 26 phyla, 44 classes, 81 orders, 153 families, 288 genera, and 797 species. The relative abundance of two phyla ( Firmicutes and TM7 ) was significantly increased in patients with lung cancer (p = 0.037 and 0.035, respectively). Furthermore, two genera ( Veillonella and Megasphaera ) were relatively more abundant in lung cancer patients (p = 0.003 and 0.022, respectively). The area under the curve of a combination of these two genera used to predict lung cancer was 0.888 (sensitivity = 95.0%, specificity = 75.0% and sensitivity = 70.0%, specificity = 100.0%; p = 0.002). Conclusion The results indicate that differences exist in the bacterial communities of patients with lung cancer and those with benign mass-like lesions. The genera Veillonella and Megasphaera showed the potential to serve as biomarkers to predict lung cancer. Thus, the lung microbiota may change the environment in patients with lung cancer. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The aim of this study is to evaluate the predictive impact of cigarette smoking on treatment outcomes of EGFR-tyrosine kinase inhibitors (TKIs) in lung adenocarcinoma patients with activating EGFR mutations. Methods: We retrospectively analyzed 222 consecutive recurrent or unresectable lung adenocarcinoma patients who harbored activating EGFR mutations (exon 19 deletion or exon 21 L858R) and had received gefitinib or erlotinib. Detailed smoking histories were obtained from all patients according to a standard protocol. Results: Of 222 EGFR-mutated patients, 65.3% were never-smokers, 19.8% were smokers with <30 pack-years, and 14.9% were smokers with ≥30 pack-years smoking dosage. The disease control rate (DCR) and objective response rate (ORR) of smokers with ≥30 pack-years were significantly lower than never-smokers and smokers with <30 pack-years (DCR, 78.8% vs. 93.1%, p =0.016; ORR, 45.5% vs. 62.4%, p =0.020). Smokers with ≥30 pack-years showed significantly shorter PFS than never-smokers (6.4 vs. 11.8 months, p =0.001) and smokers with <30 pack-years (6.4 vs. 11.4 months, p =0.033), as well as shorter overall survival from the time of metastatic diagnosis than never-smokers (33.6 vs. 46.2 months, p =0.003). There was no survival difference between smokers with <30 pack-year and never smokers. In the multivariate analysis adjusted for age, sex, performance status, initial stage, and line of EGFR-TKI, the presence of smoking dosage ≥30 pack-years was an independent predictive factor for the disease progression to EGFR-TKIs (hazard ratio, 1.87; 95% confidence interval, 1.15–3.05; p =0.012). Conclusions: Cigarette smoking dosage of ≥30 pack-years is an independent negative predictive factor of EGFR-TKI treatment outcome in lung adenocarcinoma patients with activating EGFR mutations. [Copyright &y& Elsevier]