Initial Diagnosis Of Lung Cancer Research Articles

Blood Neurofilament Light Chain and Glial Fibrillary Acidic Protein as Promising Screening Biomarkers for Brain Metastases in Patients with Lung Cancer.

The diagnosis of brain metastases (BMs) in patients with lung cancer (LC) predominantly relies on magnetic resonance imaging (MRI), a method that is constrained by high costs and limited accessibility. This study explores the potential of serum neurofilament light chain (sNfL) and serum glial fibrillary acidic protein (sGFAP) as screening biomarkers for BMs in LC patients. We conducted a retrospective analysis of 700 LC cases at the National Cancer Center, Korea, from July 2020 to June 2022, measuring sNfL and sGFAP levels at initial LC diagnosis. The likelihood of BM was evaluated using multivariate analysis and a predictive nomogram. Additionally, we prospectively monitored 177 samples from 46 LC patients initially without BM. Patients with BMs (n= 135) had significantly higher median sNfL (52.5 pg/mL) and sGFAP (239.2 pg/mL) levels compared to those without BMs (n = 565), with medians of 17.8 pg/mL and 141.1 pg/mL, respectively (p < 0.001 for both). The nomogram, incorporating age, sNfL, and sGFAP, predicted BM with an area under the curve (AUC) of 0.877 (95% CI 0.84-0.914), showing 74.8% sensitivity and 83.5% specificity. Over nine months, 93% of samples from patients without BM remained below the cutoff, while all patients developing BMs showed increased levels at detection. A nomogram incorporating age, sNfL, and sGFAP provides a valuable tool for identifying LC patients at high risk for BM, thereby enabling targeted MRI screenings and enhancing diagnostic efficiency.

Predicting lung cancer survival prognosis based on the conditional survival bayesian network.

Lung cancer is a leading cause of cancer deaths and imposes an enormous economic burden on patients. It is important to develop an accurate risk assessment model to determine the appropriate treatment for patients after an initial lung cancer diagnosis. The Cox proportional hazards model is mainly employed in survival analysis. However, real-world medical data are usually incomplete, posing a great challenge to the application of this model. Commonly used imputation methods cannot achieve sufficient accuracy when data are missing, so we investigated novel methods for the development of clinical prediction models. In this article, we present a novel model for survival prediction in missing scenarios. We collected data from 5,240 patients diagnosed with lung cancer at the Weihai Municipal Hospital, China. Then, we applied a joint model that combined a BN and a Cox model to predict mortality risk in individual patients with lung cancer. The established prognostic model achieved good predictive performance in discrimination and calibration. We showed that combining the BN with the Cox proportional hazards model is highly beneficial and provides a more efficient tool for risk prediction.

Clinical characteristics and their influences on the survival of leptomeningeal metastasis derived from lung adenocarcinoma harboring epithelial growth factor receptor mutation

Objective: To analyze the clinical characteristics of leptomeningeal metastasis (LM) patients from epithelial growth factor receptor (EGFR)-mutated lung adenocarcinoma, and their impacts on the survival of the patients. Methods: From July 2018 to July 2022, the clinicopathological data of 81 patients diagnosed as EGFR-mutated lung adenocarcinoma LM by cytopathology who admitted to the Department of Oncology of Xiangya Hospital of Central South University were retrospectively analyzed, including 33 males and 48 females. The age ranged from 31 to 76 years, with a median age of 54 years. All the 81 patients were followed up, with a median follow-up of 21.0 months (95%CI: 12.5 to 29.5 months). The Kaplan Meier method was used to draw survival curve. Cox proportional hazards regression model was used to analyze the impact of the factors on the survival of patients. Results: Among the 81 patients, the interval between the initial diagnosis of lung cancer and the pathological diagnosis of LM in cerebrospinal fluid (CSF) was 0-108 months, with a median interval of 14 months. Fifty-two patients (64.2%) used the third-generation epithelial growth factor receptor tyrosine kinase inhibitor (EGFR-TKIs), while 17 patients (21.0%) used EGFR-TKIs in combination with other drugs, and 12 patients (14.8%) were treated with best supportive care (BSC). Sixty patients (74.1%) had a Kanofsky performance status (KPS) score of less than 60 points, and 71 patients (87.7%) had brain parenchymal metastasis and/or spinal metastasis. Twenty-two patients (27.2%) used pemetrexed through intrathecal CSF, and 17 patients (21.0%) used pemetrexed through the Ommaya sac to the CSF of the ventricle. The incidence of adverse event related to the administration of pemetrexed through CSF was 64.1% (25/39), mainly manifested as myelosuppression, including 22 patients of leukocyte reduction, 25 patients of hemoglobin reduction, and 14 patients of platelet reduction. The median post-leptomeningeal metastasis overall survival (pLM-OS) in 81 patients was 11.0 (95%CI: 7.7-14.3) months. KPS score≥60 points (HR=0.407, 95%CI: 0.170-0.973, P=0.043), CSF cytology negative after treatment (vs persistent positive, HR=0.351, 95%CI: 0.155-0.792, P=0.012), intraventricular administration of pemetrexed (vs non intraventricular administration of pemetrexed, HR=0.319, 95%CI: 0.137-0.745, P=0.008) and the treatment with third-generation EGFR-TKIs after LM (vs EGFR-TKIs in combination with other drugs, HR=0.486, 95%CI: 0.237-0.998, P=0.049) were a factor affecting pLM-OS of patients. Conclusions: Brain parenchyma, or/and spine are the most sites where the LM patients concurrently metastasize. KPS score≥60 points and CSF cytology negative after treatment, intraventricular administration of pemetrexed and the treatment with third-generation EGFR-TKIs are indictors affecting pLM-OS of the patients.

Retrospective review of patients with lung cancer presenting emergently

BackgroundA significant proportion of lung cancer patients receive their diagnosis as part of an emergency presentation (EPs) to emergency departments (EDs). ObjectivesThis study aimed to describe EPs of lung cancer at a safety-net hospital system. MethodsWe conducted a retrospective analysis of patients with lung cancer at a safety-net ED. EP was defined as a diagnosis of lung cancer due to an acute presentation with symptoms of undiagnosed lung cancer (e.g., cough, hemoptysis, shortness of breath). Non-EPs were the result of either incidental findings (trauma pan-scan) or as part of lung cancer screening. ResultsA total of 333 patient charts were reviewed who had lung cancer. Of those, 248 (74.5%) were defined as having an EP. EPs were more likely stage IV than non-EPs (50.4% vs 32.9%). The percent mortality was higher for EP versus non-EP, 60.0% vs 49.4%. which is driven by a high mortality rate for stage IV EPs (77.5%). Most patients with an EP were seen in the ED (177, 71.4%) as the location of initial visit that had a workup concerning for lung cancer. Most of the EPs were admitted for completion of either their diagnostic work up and/or for symptom management (117, 66.5%). Logistic regression identified significant predictors for an EP including stage IV at diagnosis (OR 2.49, 95% CI 1.39–4.48) and lack of primary care (OR 0.07, 95% CI 0.009–0.53). ConclusionMost patients with lung cancer present acutely as an EP with advanced stage in a safety-net health care setting. The ED plays an important role in the initial diagnosis of lung cancer and coordinating subsequent cancer care.

New prognostic system specific for epidermal growth factor receptor-mutated lung cancer brain metastasis.

Brain metastases (BM) from lung cancer are heterogeneous, and accurate prognosis is required for effective treatment strategies. This study aimed to identify prognostic factors and develop a prognostic system exclusively for epidermal growth factor receptor (EGFR)-mutated lung cancer BM. In total, 173 patients with EGFR-mutated lung cancer from two hospitals who developed BM and received tyrosine kinase inhibitor (TKI) and brain radiation therapy (RT) were included. Univariate and multivariate analyses were performed to identify significant EGFR-mutated BM prognostic factors to construct a new EGFR recursive partitioning analysis (RPA) prognostic index. The predictive discrimination of five prognostic scoring systems including RPA, diagnosis-specific prognostic factors indexes (DS-GPA), basic score for brain metastases (BS-BM), lung cancer using molecular markers (lung-mol GPA) and EGFR-RPA were analyzed using log-rank test, concordance index (C-index), and receiver operating characteristic curve (ROC). The potential predictive factors in the multivariable analysis to construct a prognostic index included Karnofsky performance status, BM at initial lung cancer diagnosis, BM progression after TKI, EGFR mutation type, uncontrolled primary tumors, and number of BM. In the log-rank test, indices of RPA, DS-GPA, lung-mol GPA, BS-BM, and EGFR-RPA were all significant predictors of overall survival (OS) (p ≤ 0.05). The C-indices of each prognostic score were 0.603, 0.569, 0.613, 0.595, and 0.671, respectively; The area under the curve (AUC) values predicting 1-year OS were 0.565 (p=0.215), 0.572 (p=0.174), 0.641 (p=0.007), 0.585 (p=0.106), and 0.781 (p=0.000), respectively. Furthermore, EGFR-RPA performed better in terms of calibration than other prognostic indices.BM progression after TKI and EGFR mutation type were specific prognostic factors for EGFR-mutated lung cancer BM. EGFR-RPA was more precise than other models, and useful for personal treatment.

Abstract A023: Racial differences in lung cancer burden: A retrospective analysis of TriNetX data

Abstract Background. Lung cancer is the number one cause of cancer-related deaths in the U.S. and many other countries. Lung cancer incidence and mortality rates have decreased for all races over the past 20 years, in part because of decreased tobacco use. Yet, there have been few clinical studies of lung cancer morbidity and mortality by race. The purpose of this study is to examine racial differences in lung cancer mortality in the U.S. using the electronic health records (EHR) database, TriNetX. Method. This retrospective cohort study was conducted based on the data from US Collaborative Network in TriNetX, a real-time, EHR database providing 42.7-million patient data from 49 health care organizations (HCOs). The cohort of interest was lung cancer patients in the U.S., which were identified using the ICD-10 code of C34 with an index diagnosis date of January 1, 2010. Kaplan-Meier curves, log-rank chi-square statistics, and hazard ratio (HR) were compared among different racial groups in the EHR data. Results. Of 42.7-million patients in the U.S., the majority (60.3%) were people who are non-Hispanic white (NHW) followed by people who are Black/African American (15.4%), Hispanic (7.2%), Asian (4.6%), and others (Native Hawaiian/Pacific Islander, 0.5%). 394,560 lung cancer patients were identified. Kaplan-Meier survival curves showed that Asians had the highest survival probability with median overall survival (OS) from the initial lung cancer diagnosis of 127.3 months, compared to 92.1 months for Hispanic, 69.1 months for African American/Black, 61.4 months for others, and 53.8 months for NHW. The HR was highest among NHW (HR=1.71, 95% CI=1.62-1.81), others (HR=1.62, 95% CI=1.41-1.85), African American/Black (HR=1.52, 95% CI=1.43-1.61), and Hispanic patients (HR=1.40, 95% CI=1.30-1.52) compared to Asian patients Conclusion. These findings suggest racial disparities in lung cancer survival, with NHW having the lowest and Asians having the highest median survival. These findings are inconsistent with the results from the Multiethnic Cohort study (prospective population based study), which reported blacks having the lowest median survival. It indicates that there are different racial burdens of lung cancer from clinical data and population data. Further analyses are needed to adjust potential confounders such as smoking status and stage of diagnosis. Citation Format: SoHye Park, Zachary Urdang, Julie Barta, Kuang-Yi Wen, Joseph Curry, Hee-Soon Juon. Racial differences in lung cancer burden: A retrospective analysis of TriNetX data [abstract]. In: Proceedings of the 15th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2022 Sep 16-19; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr A023.

State of the Art: Lung Cancer Staging Using Updated Imaging Modalities.

Lung cancer is among the most common mortality causes worldwide. This scientific article is a comprehensive review of current knowledge regarding screening, subtyping, imaging, staging, and management of treatment response for lung cancer. The traditional imaging modality for screening and initial lung cancer diagnosis is computed tomography (CT). Recently, a dual-energy CT was proven to enhance the categorization of variable pulmonary lesions. The National Comprehensive Cancer Network (NCCN) recommends usage of fluorodeoxyglucose positron emission tomography (FDG PET) in concert with CT to properly stage lung cancer and to prevent fruitless thoracotomies. Diffusion MR is an alternative to FDG PET/CT that is radiation-free and has a comparable diagnostic performance. For response evaluation after treatment, FDG PET/CT is a potent modality which predicts survival better than CT. Updated knowledge of lung cancer genomic abnormalities and treatment regimens helps to improve the radiologists’ skills. Incorporating the radiologic experience is crucial for precise diagnosis, therapy planning, and surveillance of lung cancer.

Concurrent Androgen Deprivation Therapy for Prostate Cancer Improves Survival for Synchronous or Metachronous Non-Small Cell Lung Cancer: A SEER-Medicare Database Analysis.

Simple SummaryThe study showed that androgen deprivation therapy for a preceding diagnosis of prostate cancer is associated with prolonged survival among patients who subsequently develop lung cancer. These population-level findings support a role of the androgen receptor in lung cancer.Introduction: The crosstalk between receptor kinase signaling, such as EGFR and androgen receptor signaling, suggests a potential interaction between androgen deprivation therapy (ADT) and lung cancer outcome. Methods: We employed the SEER–Medicare data of lung cancer patients diagnosed between 1988 and 2005 to test for an association between ADT for prostate cancer and lung cancer outcome. We employed the Kaplan–Meier method and Cox proportional hazard with log-rank test model to assess any significant impact of ADT on survival. Results: We included data from 367,750 lung cancer patients; 17.4%, 2.9%, 33.6% and 46.1% with stages I, II, III and IV, respectively; 84.5% were >65 years; 57.2% males; 84.2% Caucasians and 9.3% Blacks. There were 11,061 patients (3%) with an initial prostate cancer diagnosis followed by lung cancer (P-L group); 3017 (0.8%) with an initial diagnosis of lung cancer and subsequent prostate cancer diagnosis (L-P group); the remainder had only lung cancer (L group). Stage I lung cancer was most common in the L-P group compared to the L and P-L groups—54% vs. 17.13% vs. 17.92%, p < 0.0001 for L-P, L and P-L, respectively. The median OS for lung cancer diagnosis was 93 months versus 10 and 9 months, respectively, for the L-P, L and P-L subgroups. ADT was associated with improved survival on multivariate analysis, especially in Caucasian patients (HR of death: 0.86; 95% CI: 0.76–0.97; p = 0.012). Conclusion: ADT was associated with improved outcome for NSCLC, in line with the hypothesis of a role for the androgen receptor in lung cancer. Our findings support a systematic evaluation of the potential benefit of ADT as a therapy for lung cancer.

Use of algorithms for identifying patients in a German claims database: learnings from a lung cancer case

BackgroundThe analysis of statutory health insurance (SHI) data is a little-used approach for understanding treatment and care as well as resource use of lung cancer (LC) patients in Germany. The aims of this observational, retrospective, longitudinal analysis of structured data were to analyze the healthcare situation of LC patients in Germany based on routine data from SHI funds, to develop an algorithm that sheds light on LC types (non-small cell / NSCLC vs. small cell / SCLC), and to gain new knowledge to improve needs-based care.MethodsAnonymized billing data of approximately four million people with SHI were analyzed regarding ICD-10 (German modification), documented medical interventions based on the outpatient SHI Uniform Assessment Standard Tariff (EBM) or the inpatient Operations and Procedure Code (OPS), and the dispensing of prescription drugs to outpatients (ATC classification). The study included patients who were members of 64 SHI funds between Jan-1st, 2015 and Dec-31st, 2016 and who received the initial diagnosis of LC in 2015 and 2016.ResultsThe analysis shows that neither the cancer type nor the cancer stage can be unambiguously described by the ICD-10 coding. Furthermore, an assignment based on the prescribed medication provides only limited information: many of the drugs are either approved for both LC types or are used off-label, making it difficult to assign them to a specific LC type. Overall, 25% of the LC patients were unambiguously identifiable as NSCLC vs SCLC based on the ICD-10 code, the drug therapy, and the billing data.ConclusionsThe current coding system appears to be of limited suitability for drawing conclusions about LC and therefore the SHI patient population. This makes it difficult to analyze the healthcare data with the aim of gathering new knowledge to improve needs-based care. The approach chosen for this study did not allow for development of a LC differentiation algorithm based on the available healthcare data. However, a better overview of patient specific needs could make it possible to modify the range of services provided by the SHI funds. From this perspective, it makes sense, in a first step, to refine the ICD-10 system to facilitate NSCLC vs. SCLC classification.

Thoracic CT radiomics analysis for predicting synchronous brain metastasis in patients with lung cancer.

We aimed to assess the feasibility of radiomics analysis based on non-contrast-enhanced thoracic CT images in predicting synchronous brain metastasis (SBM) in lung cancer patients at initial diagnosis. This retrospective study enrolled 371 lung cancer patients (with SBM n=147, without SBM n=224) confirmed by histopathology. Patients were allocated to the training set (n=258) and testing set (n=113). The optimal radiomics features were selected by using the least absolute shrinkage and selection operator (LASSO) algorithm. The radiomics, clinicoradiologic, and combined models were developed to predict SBM using multivariable logistic regression. Then the discrimination ability of the models was assessed. Furthermore, the prediction performance of the abovementioned three models for oligometastatic (1-3 lesions) or multiple (>3 lesions) brain metastases in SBM, metachronous brain metastasis (MBM), and total (SBM and MBM) groups were investigated. Six radiomics features and two clinicoradiologic characteristics were chosen for predicting SBM. Both the radiomics model (area under the receiver operating characteristic curve [AUC] = 0.870 and 0.824 in the training and testing sets, respectively) and the combined model (AUC = 0.912 and 0.859, respectively) presented better predictive ability for SBM than the clinicoradiologic model (AUC = 0.712 and 0.692, respectively). The decision curve analysis (DCA) demonstrated the clinical usefulness of the radiomics-based models. The radiomics model can also be used to predict oligometastatic or multiple brain metastases in SBM, MBM, and total groups (P = .045, P = .022, and P = .030, respectively). The radiomics model and the combined model we presented can be used as valuable imaging markers for predicting patients at high risk of SBM at the initial diagnosis of lung cancer. Furthermore, the radiomics model can also be utilized as an indicator for identifying oligometastatic or multiple brain metastases.

Gamma Knife Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer Patients Treated with Immunotherapy or Targeted Therapy.

Simple SummaryIn non-small cell lung cancer patients with brain metastases, combined Gamma Knife radiosurgery and immunotherapy or targeted therapy showed an increase in overall survival. The combination of Gamma Knife radiosurgery and immunotherapy or targeted therapy did not increase complications related to radiosurgery. Therefore, the combined treatment seems to be a safe and powerful treatment option for non-small cell lung cancer patients with brain metastases.The combination of Gamma Knife radiosurgery (GKRS) and systemic immunotherapy (IT) or targeted therapy (TT) is a novel treatment method for brain metastases (BMs) in non-small cell lung cancer (NSCLC). To elucidate the safety and efficacy of concomitant IT or TT on the outcome after GKRS, 496 NSCLC patients with BMs, who were treated with GKRS were retrospectively reviewed. The median time between the initial lung cancer diagnosis and the diagnosis of brain metastases was one month. The survival after the initial BM diagnosis was significantly longer than the survival predicted by prognostic BM scores. After the first Gamma Knife radiosurgery treatment (GKRS1), the estimated median survival was 9.9 months (95% CI = 8.3–11.4). Patients with concurrent IT or TT presented with a significantly longer survival after GKRS1 than patients without IT or TT (p < 0.001). These significant differences in the survival were also apparent among the four treatment groups and remained significant after adjustment for Karnofsky performance status scale (KPS), recursive partitioning analysis (RPA) class, sex, and multiple BMs. About half of all our patients (46%) developed new distant BMs after GKRS1. Of note, no statistically significant differences in the occurrence of radiation reaction, radiation necrosis, or intralesional hemorrhage in association with IT or TT at or after GKRS1 were observed. In NSCLC-BM patients, the concomitant use of GKRS and IT or TT showed an increase in overall survival without increased complications related to GKRS. Therefore, the combined treatment with GKRS and IT or TT seems to be a safe and powerful treatment option and emphasizes the role of radiosurgery in modern BM treatment.

Coprevalence and Incidence of Lung Cancer in Patients Screened for Abdominal Aortic Aneurysm.

Lung diseases are common in patients with abdominal aortic aneurysms (AAA). This study evaluates the prevalence of lung cancer (LC) in high-risk patients screened for AAA. Six hundred and one male patients (≥65 years of age, cardiovascular high-risk profile) were enrolled and followed prospectively over a median of 16.5 months. In 29 patients (4.8%) LC and in another 50 patients (8.3%) AAA were found. The prevalence of LC among patients with AAA was even higher (9 of 50, 18.0%). Twenty-one patients had an initial diagnosis of LC, with an incidence of 12.0% (6 of 50) in patients with AAA. During follow-up, 14 of 70 patients with AAA and/ or LC (20.0%) deceased. The highest mortality was found in patients with LC only (8 of 20, 40.0%), followed by patients with both AAA and LC (3 of 9, 33.3%), while patients with AAA only had the lowest mortality rate (3 of 41, 7.3%). In patients with a high cardiovascular risk profile, a high prevalence of both AAA and LC were found, whereby the prognosis is largely determined by the LC. Therefore, LC is of particular importance in the setting of screening and surveillance of AAA.

Impact of clinicopathologic features on leptomeningeal metastasis from lung adenocarcinoma and treatment efficacy with epidermal growth factor receptor tyrosine kinase inhibitor.

BackgroundWe investigated the risk factors for leptomeningeal carcinomatosis (LMC) and compared clinical efficacies of various treatment modalities including intrathecal (IT) chemotherapy in patients with lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) mutations.MethodsUsing clinical research data from the Asan Medical Center, we retrospectively analyzed data of patients diagnosed with LMC, confirmed via cerebrospinal fluid (CSF) analysis from January 2008 to December 2017.ResultsWe identified 1189 patients with lung adenocarcinoma harboring EGFR mutations. Among these, 9.8% had a median duration of 13.5 (interquartile range [IQR] 6.8–23.6) months from the initial lung cancer diagnosis to LMC occurrence. Younger age (hazard ratio [HR] 1.043, P < 0.001), initial metastatic disease (HR 3.768, P < 0.001), and metastasis to the brain (HR 8.682, P < 0.001) or lung (HR 2.317, P = 0.004) were risk factors associated with LMC. Median survival duration from LMC diagnosis was 3.8 (IQR 1.5–8.6) months. Eastern Cooperative Oncology Group performance status score ≤ 2 (HR 0.505, P = 0.007) and insertion of Ommaya reservoir (HR 0.445, P = 0.005) were associated with longer survival. EGFR‐tyrosine kinase inhibitor (TKI) conferred survival benefits compared to cytotoxic chemotherapy or best supportive care (HR 2.222, P = 0.018; HR 5.638, P < 0.001, respectively). Although IT chemotherapy showed no survival benefit, it was associated with improved neurologic symptoms and signs and CSF negative conversion.ConclusionsYounger age, initial diagnosis of metastatic disease, and metastasis to the brain or different lobes were associated with LMC in patients with EGFR‐mutant lung adenocarcinoma. Therapeutic interventions including EGFR‐TKIs, cytotoxic chemotherapy, or Ommaya reservoir, and good performance status were related to favorable survival outcomes.Key pointsAge and disease status were associated with LMC in patients with EGFR‐mutant adenocarcinoma, and EGFR‐TKI, Ommaya reservoir, and good performance status were related to survival benefit.

Abstract 2191: Reduced clonogenic potential of patient-derived lung adenocarcinoma brain metastasis cells after in vitro application of Tumor Treating Fields (TTFields)

Abstract Up to 40% of all non-small cell lung cancer (NSCLC) patients will develop brain metastases during their disease, with ~25% of patients presenting with brain metastases at the time of their initial lung cancer diagnosis. For the latter patient population, median survival is a dismal 8 months. Systemic therapies are typically ineffective at treating the brain metastases, even in cases when the extracranial disease responds to the therapy. Clinical trials utilizing TTFields therapy in patients with lung cancer brain metastases are underway. For these trials, TTFields are delivered at 150 kHz, as that is the frequency that has been determined for the treatment of primary lung cancer. In contrast, for the FDA-approved treatment of the most common malignant primary brain tumor, glioblastoma, TTFields are delivered at 200 kHz. In our previous study, we found that 150 kHz TTFields decreased proliferation of patient-derived lung adenocarcinoma brain metastasis cells to a greater degree than 200 kHz. In this study, patient-derived lung adenocarcinoma brain metastasis cells were assessed for clonogenic potential after in vitro TTFields application at either 150 or 200 kHz and compared to untreated control cells. Methods: Use of patient tumor tissue for this study was approved by the Institutional Review Board and written informed consent was obtained from the patient. A lung adenocarcinoma brain metastasis tumor was collected immediately following microsurgical resection. A single-cell suspension from the tumor tissue was prepared by enzymatic and mechanical disruption. After 3-6 passages in vitro, cells were plated on plastic coverslips (5x104each) in DMEM/F12 media supplemented with 10% fetal bovine serum. TTFields were applied at ~1.6 V/cm at 150 or 200 kHz (groups n=3-6) with one control group. Culture media was replaced every day. After 14 days of in vitro TTFields application, cells were assayed for lactase dehydrogenase (LDH) release into the media and cells were harvested and replated for the clonogenic assay. Control vs. TTFields-treated groups were compared with one-way ANOVA. Results: TTFields application reduced LDH in the media ~15% at 150 kHz and ~30% at 200 kHz (p=0.0011). In the clonogenic assay, cell counts were markedly reduced after TTFields in both the 150 kHz (142.4±120.1) and 200 kHz (457.2±431.9) compared to the controls (9136±2735; p=0.0007) although the post-hoc Tukey analysis found no statistical difference between the two TTFields-treated groups. Conclusions: Application of TTFields in vitro at 150 and 200 kHz reduced LDH release into the media as well as the clonogenic potential of the patient-derived lung adenocarcinoma brain metastasis cells. Citation Format: Sharon K. Michelhaugh, Sam Kiousis, Sandeep Mittal. Reduced clonogenic potential of patient-derived lung adenocarcinoma brain metastasis cells after in vitro application of Tumor Treating Fields (TTFields) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2191.

Clinical outcomes of NSCLC patients with acquired RET rearrangement after resistance to osimertinib.

e20626 Background: Resistance mechanisms to osimertinib have raised growing concerns, but those with acquired RET rearrangement is poorly characterized. Methods: We retrospectively identified advanced, EGFR-mutant NSCLC (non-small-cell lung cancer) patients treated with osimertinib between April 9th, 2015 and November 1st, 2018 at our institute. Clinicopathologic features and clinical outcomes were analyzed. Subsequent genetic profiling was performed at the time of progression by next-generation sequencing (NGS). Overall survival (OS) since 1st line treatment was calculated from first-line treatment start to death or last follow up, and OS post-progression was calculated from osimertinib progression. Median follow-up time was 43.4 months. Results: In the 192 patients treated with osimertinib, 57 had follow-up NGS information after progression, and six harboured acquired RET rearrangement (11%, 6/57). For patients with RET rearrangements when progressed on osimertinib, OS since 1st line treatment (22.9m vs 59.5m, P = 0.021) and OS post-progression (2.1m vs 10.0m, P = 0.031) were significantly shorter compared with non- RET-rearranged cases, whereas no significant difference was found in demographics at the initial lung cancer diagnosis or progression-free survival (PFS) of osimertinib (12.1m vs 5.8m, P = 0.34). Among these six patients, one received best supportive care, two continued to use drugs targeting EGFR but deteriorating soon, three patients tried osimertinib combined with cabozantinib with one benefit from this combination approach. Conclusions: RET rearrangements could exist in EGFR-mutant NSCLC with acquired resistance to osimertinib and linked to inferior survival. Study on the molecular evolution and heterogeneity during treatment course are warranted for further therapeutic strategies. [Table: see text]

Incidence of second and higher order smoking-related primary cancers following lung cancer: a population-based cohort study

BackgroundLung cancer 5-year survival has doubled over 15 years. Although the risk of second primary cancer is recognised, quantification over time is lacking. We describe the incidence of second and...

Higher Age Puts Lung Cancer Patients at Risk for Not Receiving Anti-cancer Treatment.

PurposeWe aimed to determine the demographic and epidemiologic variables that are associated with no treatment in lung cancer patients.Materials and MethodsPatient data were collected from the Korean National Health Insurance Database. The lung cancer group included patients with an initial diagnosis of lung cancer between January 2009 and December 2014. Treated cases were defined as those that underwent surgery, radiation, or chemotherapy until death, after the diagnosis of lung cancer. Risk of no treatment was calculated by multiple logistic regression analysis. ResultsAmong the 2,148 new cases of lung cancer from 2009 to 2104, 612 (28.4%) were not treated. Risk of no treatment was higher in the following patients: patients in their 60s (odds ratio [OR], 1.18; 95% confidence interval [CI], 0.75 to 1.84), 70s (OR, 3.64; 95% CI, 2.41 to 5.50), and >80 years old (OR, 16.55; 95% CI, 10.53 to 25.03) than those in their 50s; patients with previous myocardial infarction (OR, 2.07; 95% CI, 1.01 to 4.25) or chronic kidney disease (OR, 2.88; 95% CI, 1.57 to 5.30); and patients diagnosed at a non-referral hospital (OR, 1.40; 95% CI, 1.01 to 1.92) or primary care provider (OR, 1.81; 95% CI, 1.43 to 2.29) compared with referral hospital. Low-income patients receiving Medicaid were 1.75 times (95% CI, 1.14 to 2.68) more likely to forgo treatment than high-income patients (upper 20%). Risk was not associated with sex or the year in which the lung cancer was diagnosed.ConclusionAge predominantly determines whether patients with lung cancer undergo anti-cancer treatment.

Incidence trends and risk prediction nomogram of metachronous second primary lung cancer in lung cancer survivors.

BackgroundThis study was designed to estimate the trends in 5-year incidence of metachronous second primary lung cancer(SPLC) and to establish a risk prediction model to identify candidates who were at high risk of developing metachronous SPLC.MethodsIncidence data between 2004 and 2007 were obtained from SEER database, including 42453 participants who survived ≥ 2 years after the initial diagnosis of lung cancer. Joinpoint regression analysis was used to calculate the 5-year incidence rates of metachronous SPLC per 100 000 population. Related risk factors of the survivors who developed MSPLC during five years were identified through logistic regression analysis, followed by establishment of risk prediction nomogram. Discrimination (C-index), calibration and decision analysis were further performed to assess the validation and clinical net benefit of risk prediction nomogram.ResultsA total of 1412 survivors with lung cancer developed MSPLC during five years, with 3546 per 100 000 population of age-adjusted 5-year incidence. Age, histology, tumor stage, and radiation were recognized as risk factors of metachronous SPLC, as indicated by logistic regression analysis. The risk prediction nomogram of metachronous SPLC harbored moderate discrimination(C-index = 0.67) and good calibration, with the risk of 0.01 to 0.11.The decision curve analysis showed that clinical net benefit of this risk prediction nomogram in a range of risk thresholds (0.01 to 0.06) was higher compared to all-screening or no-screening strategies.ConclusionsCollectively, the cumulative risk of metachronous SPLC of the survivors increased over time. The risk prediction nomogram was available to select high-risk survivors who should regularly undergo computed tomography screening.

EGFR-Mutant Adenocarcinomas That Transform to Small-Cell Lung Cancer and Other Neuroendocrine Carcinomas: Clinical Outcomes.

Approximately 3% to 10% of EGFR (epidermal growth factor receptor) -mutant non-small cell lung cancers (NSCLCs) undergo transformation to small-cell lung cancer (SCLC), but their clinical course is poorly characterized. We retrospectively identified patients with EGFR-mutant SCLC and other high-grade neuroendocrine carcinomas seen at our eight institutions. Demographics, disease features, and outcomes were analyzed. We included 67 patients-38 women and 29 men; EGFR mutations included exon 19 deletion (69%), L858R (25%), and other (6%). At the initial lung cancer diagnosis, 58 patients had NSCLC and nine had de novo SCLC or mixed histology. All but these nine patients received one or more EGFR tyrosine kinase inhibitor before SCLC transformation. Median time to transformation was 17.8 months (95% CI, 14.3 to 26.2 months). After transformation, both platinum-etoposide and taxanes yielded high response rates, but none of 17 patients who received immunotherapy experienced a response. Median overall survival since diagnosis was 31.5 months (95% CI, 24.8 to 41.3 months), whereas median survival since the time of SCLC transformation was 10.9 months (95% CI, 8.0 to 13.7 months). Fifty-nine patients had tissue genotyping at first evidence of SCLC. All maintained their founder EGFR mutation, and 15 of 19 with prior EGFR T790M positivity were T790 wild-type at transformation. Other recurrent mutations included TP53, Rb1, and PIK3CA. Re-emergence of NSCLC clones was identified in some cases. CNS metastases were frequent after transformation. There is a growing appreciation that EGFR-mutant NSCLCs can undergo SCLC transformation. We demonstrate that this occurs at an average of 17.8 months after diagnosis and cases are often characterized by Rb1, TP53, and PIK3CA mutations. Responses to platinum-etoposide and taxanes are frequent, but checkpoint inhibitors yielded no responses. Additional investigation is needed to better elucidate optimal strategies for this group.

Psychometric evaluation of the Taiwanese version of the functional assessment of cancer therapy: a questionnaire for patients with lung cancer.

The Functional Assessment of Cancer Therapy-Lung (FACT-L) consists of the Functional Assessment of Cancer Therapy-General (FACT-G) and the Lung Cancer Subscale. The FACT-L is commonly used to measure quality of life in patients with lung cancer. This study evaluated the reliability and validity of the FACT-L in examining patients with lung cancer in Taiwan. This was a methodology study. Patients with lung cancer at a regional hospital in Northern Taiwan. Patients who had received an early diagnosis of lung cancer between 2013 and 2015 were recruited as respondents. None. To verify the reliability and validity of the Taiwanese version of the FACT-L. A total of 104 patients who had received an initial diagnosis of lung cancer were recruited. The overall internal consistency of the FACT-L, as assessed using Cronbach's α, was 0.82. Among the patients, 64 had a test-retest reliability (r) of 0.45 (P < 0.001) at 6 weeks after treatment. Moreover, longitudinal research indicated that the FACT-L detected score differences before and after treatment in these patients (Cohen's d = -0.26). The Taiwanese version of the FACT-L considers 2-year survival as the gold standard, and the optimal combination of sensitivity and specificity was obtained when the receiver operating characteristic curve revealed cutoff points of 80 and 68 for the FACT-L and FACT-G, respectively. The Taiwanese version of the FACT-L can be widely applied to assess the quality of life of patients with lung cancer.