Cases Of Primary Lung Cancer Research Articles

Evaluation of solid portions in non-small cell lung cancer-the solid part is not always measurable for clinical T factor.

Solid component size on thin-section computed tomography is used for T-staging according to the eighth edition of the Tumor Node Metastasis classification of lung cancer. However, the feasibility of using the solid component to measure clinical T-factor remains controversial. We evaluated the feasibility of measuring the solid component in 859 tumours, which were suspected cases of primary lung cancers, requiring surgical resection regardless of the procedure or clinical stage. After excluding 126 pure ground-glass opacity tumours and 450 solid tumours, 283 part-solid tumours were analysed to determine the frequency of cases where the measurement of the solid portion was difficult along with the associated cause. Pathological invasiveness was also evaluated. The solid portion of 10 lesions in 283 part-solid nodules was difficult to measure due to an underlying lung disease (emphysema and pneumonitis). The solid portion of 62 lesions (21.9%) without emphysema and pneumonitis was difficult to measure due to imaging features of the tumours. Among the 62 patients, five had no malignancy and one with a tumour size of 33mm had nodal metastasis. There were 56 lesions with a tumour size of ≤30mm, wherein nodal metastases, vascular and/or lymphatic invasions were not observed. For one-fifth of the part-solid tumours, measurement of the solid component was difficult. Moreover, these lesions had low invasiveness, especially in T1. The measurement of the solid portion and the classification of T1 in 1-cm increments may be complex.

A Case of Primary Lung Cancer with a Thin-walled Cavitary Growth Process Under Four-year Observation

A Case of Primary Lung Cancer with a Thin-walled Cavitary Growth Process Under Four-year Observation

Abstract 2343: The incidence of BRAF mutation in non-small cell lung cancers is low in Korean patients

Abstract Introduction: BRAF mutation is present in about 8% of all cancer. Oncogenic activity of BRAF V600E mutation was established in lung cancers. Dabrafenib and trametinib combination therapy is preferred first line therapy for advanced or metastatic lung cancer with BRAF V600E mutation. However, there is only little basic knowledge of BRAF mutational status among Korean population. In this study, BRAF mutation, particularly BRAF V600E mutational status was explored among Korean non-small cell lung cancer patients. The clinical and pathologic characteristics of BRAF V600E mutation in non-small cell lung cancers were also investigated. Materials and Methods: The final cohort was 378 cases of primary non-small cell lung cancers. Fromalin-fixed paraffin embedded (FFPE) tissue blocks were used. PNA-mediated clamping PCR for BRAF V600, BRAF V600E real-time PCR and immunohistochemistry for mutation specific monoclonal antibody of Ventana VE1 were performed on all 378 cases of non-small cell lung cancers. For positive cases, direct sequencing was performed for validation. Results: BRAF V600 mutation was detected in five cases using PNA clamping method among 378 non-small cell carcinoma cases. By using BRAF real-time PCR, a BRAF V600E mutation was detected in 3 patients among total 378 cohort. There were 2 discordant cases between PNA clamping and real-time PCR. On immunohistochemistry, 3 patients showed positive staining for tumor cytoplasm and all positive cases also had positive results in real-time PCR. Direct Sanger sequencing was done in 5 cases that had any positive results for 3 methods. The results of Sanger sequencing was the same with those of real-time PCR and immunohistochemistry. Direct sequencing using PAN PCR product was performed on 2 negative cases for validation. On sequencing using PNA clamping PCR product, all cases showed mutation for BRAF gene other than V600E genotype. Finally, there were 3 cases (0.8%) of BRAF V600E mutation and 2 cases of BRAF mutation (0.5%) other than V600E genotype. Among BRAF mutated patients, there were 2 never smokers and 3 ever smokers. All patients harboring BRAF mutation had no concomitant EGFR or ALK aberrations. Conclusion: BRAF mutation incidence is relatively lower than that of Western data set and similar to that of Japanese report. Immunohistochemistry for Ventana VE1 antibody can be a useful screening method to detect BRAF V600E mutation. Citation Format: Ahrong Kim, Hyo Yeong Ahn, Chang Hun Lee, Young Dae Kim, Min Ki Lee, Yeon Joo Jeong, So Jeong Lee. The incidence of BRAF mutation in non-small cell lung cancers is low in Korean patients [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2343.

Abstract 2298: Is smoking a risk factor for second primary lung cancer

Abstract Background: Lung cancer (LC) survivors in the U.S. are increasing in number, with 5-year survival rates improving by 26% over the past decade. Although LC survivors are at high risk of developing a second primary lung cancer (SPLC), risk factors for SPLC have not been established and the impact of tobacco smoking remains controversial. In this study, we examined risk factors for SPLC among participants in the Multiethnic Cohort (MEC) study, validated our findings with two epidemiologic cohorts–the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) and the European Prospective Investigation into Cancer and Nutrition (EPIC)–and evaluated the impact of smoking cessation on SPLC risk. Methods: We analyzed data from 7,299 initial primary lung cancer (IPLC) cases in MEC who were diagnosed from 1993-2017. Incident IPLC and SPLC were identified via linkage to SEER registries, with SPLC defined by Martini and Melamed criteria. Baseline smoking data were obtained at the time of enrollment (1993-1996) and updated with 10-year follow-up data close to IPLC diagnosis, if available. Fine-Gray regression was used to take into account competing risks and to evaluate the associations between risk factors and SPLC, adjusting for age at IPLC diagnosis and IPLC histology and stage. We conducted validation studies with PLCO (N=3,423 LC patients) and EPIC (N=4,605 LC patients) and evaluated the combined effects of risk factors from all three cohorts using meta-analysis. Results: Among 7,299 MEC participants with IPLC, 167 (2.3%) developed a SPLC. Fine-Gray regression analyses identified several factors that were significantly associated with SPLC risk (P<0.05), which included smoking pack-years (HR 1.12 per 10 pack-years (PY); P=0.004) and smoking intensity (HR 1.21 per 10 cigarettes per day (CPD); P=0.017). Individuals who met the U.S. Preventative Services Task Force's (USPSTF) screening criteria (i.e., aged 55-80, smoked ≥30 PY, and ≤15 years since smoking cessation) at the time of IPLC had a 68% increase in SPLC risk (HR 1.68; P=0.001). Validation studies with PLCO and EPIC showed consistent results; the combined effects based on meta-analysis showed a HR 1.15 per 10 PY (Pmeta=0.022) for smoking pack-years, HR 1.18 per 10 CPD (Pmeta=6.0x10-4) for smoking intensity, and HR 1.70 (Pmeta = 1.9x10-5) for meeting the USPSTF criteria. Subset analysis of MEC participants (N=156) who were current smokers at baseline, had 10-year follow-up smoking data, and were diagnosed with IPLC between baseline and 10-year follow-up showed that smoking cessation was associated with a reduced risk of SPLC (HR=0.25; P=0.005). Conclusions: Smoking is a risk factor for SPLC among LC patients and the USPSTF criteria can potentially aid in identifying those at high risk of SPLC. Smoking cessation may reduce SPLC risk after IPLC diagnosis. Further analysis is required to stratify SPLC risk based on comprehensive risk factors and identify LC survivors at high risk of SPLC for CT screening. Citation Format: Jacqueline V. Aredo, Sophia J. Luo, Rebecca Gardner, Thomas P. Hickey, Thomas L. Riley, Lynne R. Wilkens, Loic Le Marchand, Christopher I. Amos, Rayjean J. Hung, Mattias Johansson, Iona Cheng, Heather A. Wakelee, Summer S. Han. Is smoking a risk factor for second primary lung cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2298.

Abstract 2333: Mutational landscape of multiple primary lung cancers and its correlation with environmental factors

Abstract Background: Multiple primary lung cancers (MPLC) are reported to occur in 0.2-20 % of all primary lung cancer cases. MPLC are considered to harbor various genetic profiling patterns among the tumors even within the same individuals, though they developed from the same occupational and environmental exposure. In this study, we performed paired mutational analyses to clarify genetic mutations in MPLC and its relationship with environmental factors. Materials and methods: We obtained 38 surgical specimens from 17 patients who were pathologically diagnosed as MPLC and underwent surgery at Osaka City University Hospital between October 2007 and March 2019. In addition to the clinicopathological features, the patients' age, sex, smoking history, body mass index, radiologic features and surgical procedures were reviewed. Four of the 17 MPLC patients had metachronous lesions, whereas 13 patients only had synchronous lesions. For genetic profiling of MPLC patients, the extracted DNAs were deep-sequenced on Ion S5 sequencer (Thermo Fisher) for somatic mutations in 409 cancer-associated genes (Ion AmpliSeq Comprehensive Cancer Panel). The study was approved by institutional review board of Osaka City University Hospital and written informed consent was obtained from all of the patients. For statistically analyses, we assumed genetic mutations occurred by chance and calculated the frequency of concomitant mutations in multiple tumors within the same individuals based on a previous study (JME study; Kawaguchi T et al, J Clin Oncol 2016). Comparing the assumed frequency of mutations with the actual data, statistically analyses whether mutations would occur concomitantly or randomly were performed using an exact test. Results: Deep sequencing was successfully performed in all of the specimens with the mean coverage of 823. Results from comprehensive genetic analyses suggested that the mutation profiles differed among the tumors within the same individuals, whereas EGFR, KRAS, TP53, and PARP1 mutations were concomitantly detected in multiple tumors within the same individuals. In this study, the frequency of EGFR mutations was significantly higher in never or light -smokers and females. The occurrence of concomitant EGFR or KRAS mutations in multiple tumors within the same individuals was significantly more frequent than expected by chance (EGFR, P = .0023; KRAS, P = .0049), suggesting environmental factors play more role in EGFR and KRAS mutations than the other mutations including TP53 which occurred more randomly in individual tumors. Concomitant EGFR or KRAS mutations were particularly prominent in never or light-smokers and males. Conclusions: Results from our MPLC study confirmed that the development of EGFR or KRAS-mutated tumors were strongly related to environmental factors such as sex and smoking history, and suggested that the other mutations may occur randomly. Citation Format: Motohiro Izumi, Jun Oyanagi, Kenji Sawa, Mitsuru Fukui, Koichi Ogawa, Yoshiya Matsumoto, Yoko Tani, Tomohiro Suzumura, Tetsuya Watanabe, Hiroyasu Kaneda, Shigeki Mitsuoka, Kazuhisa Asai, Tatsuo Kimura, Nobuyuki Yamamoto, Tomoya Kawaguchi, Yasuhiro Koh. Mutational landscape of multiple primary lung cancers and its correlation with environmental factors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2333.

Looking through the eyes of the multidisciplinary team: the design and clinical evaluation of a decision support system for lung cancer care.

BackgroundDecision-making in lung cancer is complex due to a rapidly increasing amount of diagnostic data and treatment options. The need for timely and accurate diagnosis and delivery of care demands high-quality multidisciplinary team (MDT) collaboration and coordination. Clinical decision support systems (CDSSs) can potentially support MDTs in constructing a shared mental model of a patient case. This enables the team to assess the strength and completeness of collected diagnostic data, stratification for the right personalized therapy driven by clinical stage and other treatment-influencing factors, and adapt care management strategies when needed. Current CDSSs often have a suboptimal fit into the decision-making workflow, which hampers their impact in clinical practice.MethodsA CDSS for multidisciplinary decision-making in lung cancer was designed to support the abovementioned goals through presentation of relevant clinical data in line with existing mental model structures of the MDT members. The CDSS was tested in a simulated multidisciplinary tumor board meeting for primary diagnosis and treatment selection, based on de-identified primary lung cancer cases (n=8). Decision course analysis, eye-tracking data and questionnaires were used to assess the impact of the CDSS on constructing shared mental models to improve the decision-making process and outcome.ResultsThe CDSS supported the team in their self-correcting capacity for accurate diagnosis and TNM classification. It enabled cross-validation of diagnostic findings, surfaced discordance between diagnostic tests and facilitated cancer staging according the diagnostic evidence, as well as spotting contra-indications for personalized treatment selection.ConclusionsThis study shows the potential of CDSS on clinical decision making, when these systems are properly designed in line with clinical thinking. The presented setup enables assessment of the impact of CDSS design on clinical decision making and optimization of CDSSs to maximize their effect on decision quality and confidence.

Different driver gene mutations in patients with synchronous multiple primary lung cancers: a case report

BackgroundRoutine clinical and pathological examinations usually cannot fully conclusively determine the relationship between different lesions of lung cancer. Detailed genetic analysis of tumor samples may supply important additional information and identify second primary lung cancers.Case presentationIn the present study, we report a case of synchronous multiple primary lung cancer (MPLC) composed of two distinct pathological subtypes with epidermal growth factor receptor (EGFR) gene mutations L858R of the acinar adenocarcinoma subtype and EML4–ALK rearrangement of the squamous cell carcinoma.ConclusionThe present report highlights the clinical importance of molecular cancer biomarkers detection to guide management decisions in MPLC cases.

A case of primary lung cancer treated without interruption of aspirin monotherapy after dual antiplatelet therapy following myocardial infarction

A case of primary lung cancer treated without interruption of aspirin monotherapy after dual antiplatelet therapy following myocardial infarction

Genetic features and application value of next generation sequencing in the diagnosis of synchronous multifocal lung adenocarcinoma.

The present study aimed to elucidate the genetic features of multiple lung cancer (MLC) and identify effective molecular markers for diagnosis using next generation sequencing (NGS). The present data may also inform patient treatment and prognosis. A total of 35 lesions were obtained from 17 patients with MLC. Based on lesion histology and NGS, 13 cases of multiple primary lung cancer (MPLC) were identified and 4 cases were classified as intrapulmonary metastasis (IPM). All 4 patients with IPM exhibited an epidermal growth factor receptor (EGFR) mutation and synchronous mutation of at least one tumor suppressor gene. The frequency and percentage of EGFR mutations, accompanied with tumor suppressor genes, were significantly higher in patients with IPM compared with MPLC. Furthermore, a high EGFR-heterogeneity score and male sex were risk factors of IPM occurrence. There were significant differences in mean EGFR mutation abundance alone, mutations of tumor suppressor genes and mutations of EGFR combined with tumor suppressor genes between patients with adenocarcinoma (ADC) and adenocarcinoma in situ (AIS). In conclusion, histological characteristics combined with genetic alterations may be an effective method for the diagnosis of MPLC and IPM, and NGS may serve as a useful diagnostic tool. MLC exhibited unique molecular characteristics, including higher rates of EGFR mutations, EGFR driver mutations accompanied with tumor suppressor gene mutations and the absence of anaplastic lymphoma kinase mutations, which may help distinguish between patients with MPLC or IPM. The present study hypothesized that the mean frequency of EGFR mutations, mutations of tumor suppressor genes and mutations of both EGFR and tumor suppressor genes may serve an important role in the development of AIS to ADC. The results of the present study highlight the potential underlying mechanisms of lung ADC development, which may assist with future elucidation of effective treatments to prevent the progression of lung cancer.

Contrast-enhanced T1-weighted image radiomics of brain metastases may predict EGFR mutation status in primary lung cancer

Identification of EGFR mutations is critical to the treatment of primary lung cancer and brain metastases (BMs). Here, we explored whether radiomic features of contrast-enhanced T1-weighted images (T1WIs) of BMs predict EGFR mutation status in primary lung cancer cases. In total, 1209 features were extracted from the contrast-enhanced T1WIs of 61 patients with 210 measurable BMs. Feature selection and classification were optimized using several machine learning algorithms. Ten-fold cross-validation was applied to the T1WI BM dataset (189 BMs for training and 21 BMs for the test set). Area under receiver operating characteristic curves (AUC), accuracy, sensitivity, and specificity were calculated. Subgroup analyses were also performed according to metastasis size. For all measurable BMs, random forest (RF) classification with RF selection demonstrated the highest diagnostic performance for identifying EGFR mutation (AUC: 86.81). Support vector machine and AdaBoost were comparable to RF classification. Subgroup analyses revealed that small BMs had the highest AUC (89.09). The diagnostic performance for large BMs was lower than that for small BMs (the highest AUC: 78.22). Contrast-enhanced T1-weighted image radiomics of brain metastases predicted the EGFR mutation status of lung cancer BMs with good diagnostic performance. However, further study is necessary to apply this algorithm more widely and to larger BMs.

Community-based practice of early lung cancer screening with low-dose spiral computed tomography in Jiaxing city from Zhejiang Province.

e13557 Background: As one of the most frequent malignant tumors in China, the morbidity and mortality of lung cancer remain high. Early diagnosis and normative treatment is the key to improve the prognosis of lung cancer. The aim of this study is to explore the practice of early lung cancer screening with low-dose spiral computed tomography (CT) based on the current situation in community health service, with integration of superior resources of medical institutions at all levels in Jiaxing City from Zhejiang Province. Methods: From Jan. 2017 to Dec. 2019, we screened 13491 (male 8783, female 4708) individuals high-risk population in selected communities of Nanhu District, Pinghu County and Haiyan County, Zhejiang Province, for early diagnosis of lung cancer with low-dose spiral CT combined with multidisciplinary comprehensive treatment models including minimally invasive surgery, exploring the medical service network covering prevention, diagnosis, treatment, rehabilitation and follow-up. Results: Screening resulted in a diagnosis of cancer in 27 participants. Of these participants, 24 cases of primary lung cancer, 1 case of lung metastasis, 1 case of breast cancer, 1 case of thyroid cancer. The morbidity of primary lung cancer is 224.53×10-5. There were 20 cases of Stage 0-Ⅰlung cancer accounting for 83.33% of all diagnosed primary lung cancer. Conclusions: Based on community health service, screening with LDCT could improve the early diagnosis rate of lung cancer in both smokers and nonsmokers with feasibility and validity, which could be applicable in qualified eligible medical centers and communities in China. It is not reasonable to exclude nonsmokers from screening with LDCT.

Epidemiology of lung cancer in Northern Greece: An 18-year hospital-based cohort study focused on the differences between smokers and non-smokers.

INTRODUCTIONLung cancer remains a leading cause of cancer incidence, yet, in Greece, country-level registry-based data are limited. We have thus investigated the epidemiology of lung cancer and its trends in the George Papanikolaou Hospital, Northern Greece over 18 years (2000–2018).METHODSWe analyzed all the cases reported in the Bronchoscopy Unit of the Hospital for the period 2000–2018. In total, 15131 subjects (12300 males and 2831 females) that presented with a mass in the imaging, were submitted to bronchoscopy. Characteristics of patients such as age, sex, smoking history and occupation were collected. Statistical analysis was performed with SPSS 21.0 software package.RESULTSAmong all subjects, a total of 5628 (37.2%; mean age: 65.85 ± 9.6 years) cases of primary lung cancer were identified with a male to female ratio of 2:1 (41.1% to 20.4%) (p<0.001). Squamous cell lung cancer was the most common type of lung cancer identified in this population (44%) with a higher proportion in males compared to females (p<0.001). Furthermore, adenocarcinoma was mostly observed in female non-smokers compared to males (p<0.001). The majority of lung cancer cases were identified in patients occupied with agriculture and livestock breeding (41.1%). The mean age at lung cancer diagnosis was 66.13 ± 9.19 years for the whole study population. Lung cancer cases observed with a higher mean of 43.93 ± 10.84 years of smoking compared to cancer-free patients with 39.64 ± 13.23 years of smoking (p<0.001).CONCLUSIONSApart from smoking, demographic characteristics including age, sex and occupation appear to have an impact on lung cancer development in this population. Smoking history alone could not predict the development of lung cancer in the studied northern Greek population.

Synchronous multiple primary non-small cell lung cancer or intrapulmonary metastasis from an index lesion: a dilemma—case report

: Lung cancer is considered one of the major causes of cancer-related mortality. Our case report wishes to highlight the confusion one may have when faced with a lesion that could be a synchronous lesion or metastasis from an index lesion, and its management including whether re-do VATS is a good option. We report our case of a 68 years old male who came to our attention in March 2018 with history of weight loss and repeated chest infections. He was smoking until he was reviewed in our clinic, with a 40-pack year history. PET scan revealed an intense uptake of left lower nodule of size 3.5 cm (cT2aN0M0). He underwent uniportal VATS left basal segmentectomy and lymphadenectomy with the histopathology confirming a squamous cell carcinoma (SCC) (pT2aN0M0R0). During his follow-up, a new left upper lobe lesion was noticed in February 2019. PET scan showed increased uptake in the lesion and CT guided biopsy showed poorly differentiated SCC (cT1cN0M0). The patient underwent uniportal VATS left upper trisegmentectomy and lymphadenectomy with histopathology revealing the presence of two different lesions this time around: the larger one being a SCC with a staging of pT1cN0M0R0 and the smaller being a basaloid type of SCC with a staging of pT1aN0M0. In our opinion, the three cancerous nodules the patient developed represented multiple primary tumours arising on a background of field change rather than intrapulmonary metastasis from an index lesion (differentiating this was important from management point of view). Moreover, we managed to safely perform a redo surgery via uniportal VATS for the same sided lung lesion. This is feasible as long as the patient has an adequate cardiorespiratory function. We wish to take this opportunity to add to the literature our experience with this case of multiple primary lung cancer (MPLC).

Five-year survival and prognostic factors according to histology in 6101 non-small-cell lung cancer patients

ObjectiveTo estimate five-year survival in non-small-cell lung cancer (NSCLC) patients according to histology and to identify independent prognostic factors by histology. MethodsData were obtained during the KBP-2010-CPHG study, which included all new cases of primary lung cancer diagnosed in 2010 in 104 non-academic hospitals. ResultsIn all, 3199 patients had adenocarcinoma (ADC), 1852 squamous cell carcinoma (SCC), 754 large cell carcinoma (LCC). Five-year survival was 13.3% [12.1%–14.5%] for ADC, 14.3% [12.7%–16.0%] for SCC, 9.6% [7.6%–11.9%] for LCC (P<0.001). Performance status, weight loss prior to diagnosis and tumour stage were consistently significant independent prognostic factors. Age (>70 years; P=0.004), male gender (P<0.001), and smoking (P<0.001) were independent negative prognostic factors for ADC. Epidermal Growth Factor Receptor (EGFR)-mutation tests, performed in 1638 ADC patients, were positive for 186. Five-year survival was 14.7% [10.3%–21%] and 10.9% [9.4%–12.6%] for mutated and wild-type EGFR, respectively (P<0.001). EFGR mutation was an independent positive prognostic factor (HR=0.5 [0.4–0.6], P<0.001); however, the proportional hazards assumption was not fulfilled and hazards were inverted after 35 months. ConclusionsFive-year survival in patients managed in French non-academic hospitals for primary NSCLC in 2010 remained poor (<15%), whatever the histologic type. The independent negative prognostic factors for five-year survival were: weight, particularly weight loss prior to diagnosis; smoking (active or former) at diagnosis in ADC and LCC and smoking level at diagnosis in smoker patients with SCC. The independent positive prognostic factors were young age and female gender for ADC.

ES12.01 Multiple Lung Nodules

Advanced imaging techniques resulted in increased detection of multiple tumors of the lung. Distinguishing synchronous primary lung cancers from intrapulmonary metastases (separate nodules) is important because treatments are very different. In addition, patients with independent primary tumors are expected to have better prognosis. Staging of such tumors as independent primary tumors or intrapulmonary metastases is often challenging, particularly in squamous cell carcinomas. Martini and Melamed modified criteria were used as the main approach for many decades with the idea that morphology of metastases should match the primary tumor, while different morphology supports classification of tumors as unrelated separate primaries. The 8th edition of the AJCC staging of the lung cancer pretty much has replaced this classification by establishing a multidisciplinary approach to these tumors as a standard of care and by promoting the tools such as comprehensive histologic assessment, imaging studies and molecular characterization either by CGH or biomarker testing. Comprehensive histologic assessment is based on the 2015 WHO classification of lung cancers and includes determination of the main histologic tumor type, quantitative subtyping particularly of lung adenocarcinomas, and assessment of cytologic and stromal characteristics. This approach can be relatively easily applied in lung adenocarcinomas, while squamous cell carcinoma remains a great challenge. A recent study conducted by the IASLC Pathology committee showed a good agreement (κ score 0.60) among thoracic pathologists in the histologic assessment of independent primary tumors from intrapulmonary metastasis. Despite a good agreement, there were cases with split opinions supporting a need for ancillary studies. Over the past decade many studies reported different molecular approaches to analysis of multiple lung tumor nodules including DNA microsatellite analysis, CGH/aCHG and most recently next generation sequencing. The data from published reports indicate a highly variable percentage of multifocal tumors identified as clonally related (up to 70%). Discrepancy between clinical and molecular classification of originally presumed cases of multiple primary lung cancers ranged in different series from 18% to 30%. Recent recommendations for routine molecular profiling of lung adenocarcinoma resulted in a widespread use of targeted mutational profiling for oncogenic mutations (i.e. EGFR, KRAS, BRAF etc) and gene rearrangements (i.e.ALK, ROS1) which results can be used in staging of multiple lung cancers. A different mutation profile in oncogenic mutations strongly indicates two separate primary tumors. However, the presence of a common driver mutation does not necessarily indicate tumors of similar origin. Therefore, limited molecular panels may not be sufficient in some cases. The detection of shared identical breakpoints by whole genome sequencing has been recently proposed as potentially more accurate and specific for lineage determination than the analysis of driver mutations alone. Also whole exome and whole genome sequencing approaches have been reported, but these assays may be technically challenging and turnaround time may not be suitable for routine clinical use.

EP1.01-106 A Special Case of Synchronous Multiple Primary Lung Cancer with Mediastinal Lymph Node Metastases of Unknown Primary Origin

EP1.01-106 A Special Case of Synchronous Multiple Primary Lung Cancer with Mediastinal Lymph Node Metastases of Unknown Primary Origin

Epidemiology of Lung Cancer in Oman: 20-Year Trends and Tumor Characteristics.

ObjectivesWe sought to investigate the epidemiology of lung cancer and its trends in Oman over 20 years.MethodsWe analyzed all cases of primary lung cancer reported to the Oman National Cancer Registry between 1996 and 2015. The World Standard Population was used to obtain age-standardized incidence rates (ASR) of lung cancer per 100 000. Analyses were conducted using univariate statistics.ResultsA total of 956 cases of primary lung cancer cases were registered in Oman between 1996 and 2015, with a male to female ratio of 3:1. In men, the ASR was 8.2 per 100 000, while in females it was 2.6 per 100 000 over the entire study period. There were no statistically significant differences in the ASR among men or women when the data was divided over three calendar periods (1996–2005, 2006–2015, and 1996–2015) (p = 0.332 and p = 0.577, respectively). There was also no increasing trend in the incidence of lung cancer. The risk of lung cancer onset commenced in the 30–34 year age group and the mean age at diagnosis was 60.0 years for men and 61.0 years for women. Adenocarcinoma was the most common type of lung cancer among Omanis with a higher proportion in females compared to males.ConclusionsOman has one of the lowest incidence rates of lung cancer in the world with no evidence of an increasing trend of this cancer type. This could be attributed to low uptake of tobacco smoking among both sexes. National authorities should capitalize on this finding to avoid any future lung cancer epidemics especially those driven by tobacco use.

High expression of DLC family proteins predicts better prognosis and inhibits tumor progression in NSCLC.

The incidence of primary lung cancer (PLC) is increasing and is becoming a leading cause of cancer-associated mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for ~80% of PLC cases and has the worst prognosis among malignant tumors. Deleted in liver cancer (DLC) proteins belong to the RhoGTPase-activating protein family and are considered to be tumor suppressor genes. However, the role of the proteins, particularly DLC2 and DLC3, in NSCLC, has not been fully elucidated. The present study investigated the expression levels and prognostic values of DLCs in NSCLC using The Cancer Genome Atlas, the Genotype-Tissue Expression project and Kaplan-Meier plotter datasets. The current study demonstrated that the three DLCs were downregulated in NSCLC. High expression levels of DLC1 and DLC2 were associated with an improved survival in NSCLC. Additionally, the effects of DLCs on the proliferation and apoptosis of the lung cancer cell line A-549 were investigated in vitro using a Cell Counting Kit-8 assay and flow cytometry analysis. DLC2 and DLC3 overexpression inhibited proliferation and induced apoptosis in A549 cells. To the best of our knowledge, the current study was the first to investigate the expression level and prognostic values of DLC2 and DLC3 in NSCLC. The results indicated that DLC1 DLC2 and DLC3 serve specific roles in the occurrence and development of NSCLC, and may be considered as potential prognostic indicators in NSCLC.

Lung cancer imaging methods in China from 2005 to 2014: A national, multicenter study.

BackgroundThe study was conducted to examine changes in diagnostic and staging imaging methods for lung cancer in China over a 10‐year period and to determine the relationships between such changes and socioeconomic development.MethodsThis was a hospital‐based, nationwide, multicenter retrospective study of primary lung cancer cases. The data were extracted from the 10‐year primary lung cancer databases at eight tertiary hospitals from various geographic areas in China. The chi‐squared test was used to assess the differences and the Cochran–Armitage trend test was used to estimate the trends of changes.ResultsA total of 7184 lung cancer cases were analyzed. Over the 10‐year period, the utilization ratio of diagnostic imaging methods, such as chest computed tomography (CT) and chest magnetic resonance imaging (MRI), increased from 65.79% to 81.42% and from 0.73% to 1.96%, respectively, while the utilization ratio of chest X‐ray declined from 50.15% to 30.93%. Staging imaging methods, such as positron emission tomography‐CT, neck ultrasound, brain MRI, bone scintigraphy, and bone MRI increased from 0.73% to 9.29%, 22.95% to 47.92%, 8.77% to 40.71%, 42.40% to 62.22%, and 0.88% to 4.65%, respectively; abdominal ultrasound declined from 83.33% to 59.9%. These trends were more notable in less developed areas than in areas with substantial economic development.ConclusionOverall, chest CT was the most common radiological diagnostic method for lung cancer in China. Imaging methods for lung cancer tend to be used in a diverse, rational, and regionally balanced manner.

Initial presentation of lung cancer in the emergency department: a descriptive analysis.

Guidelines aimed at improving care for lung cancer, the leading cause of cancer-related death in Canada and worldwide, require accurate knowledge of the diagnostic setting or pathway. We sought to determine how often lung cancer is initially diagnosed through the emergency department. We performed a descriptive study that included all cases of primary lung cancer diagnosed in residents of Nova Scotia in 2014. Cancer registry data included diagnostic data and date of death to Aug. 31, 2016. We reviewed linked hospital records, including laboratory and imaging results, to identify the first positive diagnostic study and the route of presentation (emergency department v. other). We evaluated time from diagnosis to death as a function of presentation route using Kaplan-Meier curves and Cox regression (hazard rate ratios [HRRs]). Sufficient data were available for 946 of 951 cases identified, of which 336 (35.5%) were diagnosed through the emergency department. Cases diagnosed via the emergency department were more likely to be at an advanced stage (stage IV, 59.5% v. 43.4%), with patients experiencing shorter survival (1-yr survival, 28.4% v. 49.5%), including stage-specific survival. Mortality for cases diagnosed in the emergency department was 54% higher than for the non-emergency department group after adjusting for age and stage (HRR 1.54, 95% confidence interval 1.32-1.81). Few patients (7.1%, n = 24) who presented to the emergency department reported having no family physician. The emergency department is a common route of presentation for lung cancer and is associated with advanced stage at diagnosis and reduced survival time. Strategies are needed to encourage pre-emergent diagnosis and to ensure that emergency providers are supported in the initial care of patients with lung cancer.