Selected Lung Cancer Patients Research Articles

Machine learning classification of mediastinal lymph node metastasis in NSCLC: a multicentre study in a Western European patient population

Background[18F] FDG PET-CT has an important role in the initial staging of lung cancer; however, accurate differentiation between activity in malignant and benign intrathoracic lymph nodes on PET-CT scans can be challenging. The purpose of the current study was to investigate the effect of incorporating primary tumour data and clinical features to differentiate between [18F] FDG-avid malignant and benign intrathoracic lymph nodes.MethodsWe retrospectively selected lung cancer patients who underwent PET-CT for initial staging in two centres in the Netherlands. The primary tumour and suspected lymph node metastases were annotated and cross-referenced with pathology results. Lymph nodes were classified as malignant or benign. From the image data, we extracted radiomic features and trained the classifier model using the extreme gradient boost (XGB) algorithm. Various scenarios were defined by selecting different combinations of data input and clinical features. Data from centre 1 were used for training and validation of the models using the XGB algorithm. To determine the performance of the model in a different hospital, the XGB model was tested using data from centre 2.ResultsAdding primary tumour data resulted in a significant gain in the performance of the trained classifier model. Adding the clinical information about distant metastases did not lead to significant improvement. The performance of the model in the test set (centre 2) was slightly but statistically significantly lower than in the validation set (centre 1).ConclusionsUsing the XGB algorithm potentially leads to an improved model for the classification of intrathoracic lymph nodes. The inclusion of primary tumour data improved the performance of the model, while additional knowledge of distant metastases did not. In patients in whom metastases are limited to lymph nodes in the thorax, this may reduce costly and invasive procedures such as endobronchial ultrasound or mediastinoscopy procedures.

Adherence to Oral Targeted Anti-Lung Cancer Therapy: A Qualitative Interview Study.

ObjectiveOral targeted antineoplastic drugs (OTADs) are becoming more and more acceptable for lung cancer treatment due to their advantages such as the convenience of administration and milder side effects. However, medication adherence represents a major issue for prolonged OTAD treatment. In this study, the factors associated with treatment adherence to OTAD were explored through the Adherence Influencing Factor Framework suggested by WHO. Based on these results, we further examined the potential factors related to social psychological cognition in OTAD adherence in patients with lung cancer.MethodsThis qualitative study was conducted in public hospitals in Henan, China. Data were collected through semi-structured interviews with selected lung cancer patients. Face-to-face interviews were audio-recorded and transcribed for thematic analysis.ResultsOf the 21 patients interviewed, 17 were males and 4 were females. The analysis of the data led to four themes, ie, patient-related factors (medication-taking introspection, family structure, weigh the pros and cons of OTAD treatment), medication-related factors (medication experience, adverse reactions, information access), physician/nurse-related factors (shared decision making, doctor’s reaction, nurse’s inquiry) and society-related factors (fear, stigma).ConclusionFamily structure, weigh the pros and cons of OTAD treatment, information access, shared decision making, nurse’s inquiry are potential factors affecting OTAD adherence in lung cancer patients. Providing drug information support to patients, inviting patients to join in shared decision-making and strengthening doctor-patient-nurse cooperation are important for improving medication adherence. Further research should be conducted to help healthcare providers to promote the medication adherence of lung cancer patients to OTAD treatment.

Deep Learning to Predict EGFR Mutation and PD-L1 Expression Status in Non-Small-Cell Lung Cancer on Computed Tomography Images.

Objective The detection of epidermal growth factor receptor (EGFR) mutation and programmed death ligand-1 (PD-L1) expression status is crucial to determine the treatment strategies for patients with non-small-cell lung cancer (NSCLC). Recently, the rapid development of radiomics including but not limited to deep learning techniques has indicated the potential role of medical images in the diagnosis and treatment of diseases. Methods Eligible patients diagnosed/treated at the West China Hospital of Sichuan University from January 2013 to April 2019 were identified retrospectively. The preoperative CT images were obtained, as well as the gene status regarding EGFR mutation and PD-L1 expression. Tumor region of interest (ROI) was delineated manually by experienced respiratory specialists. We used 3D convolutional neural network (CNN) with ROI information as input to construct a classification model and established a prognostic model combining deep learning features and clinical features to stratify survival risk of lung cancer patients. Results The whole cohort (N = 1262) was divided into a training set (N = 882, 70%), validation set (N = 125, 10%), and test set (N = 255, 20%). We used a 3D convolutional neural network (CNN) to construct a prediction model, with AUCs of 0.96 (95% CI: 0.94–0.98), 0.80 (95% CI: 0.72–0.88), and 0.73 (95% CI: 0.63–0.83) in the training, validation, and test cohorts, respectively. The combined prognostic model showed a good performance on survival prediction in NSCLC patients (C-index: 0.71). Conclusion In this study, a noninvasive and effective model was proposed to predict EGFR mutation and PD-L1 expression status as a clinical decision support tool. Additionally, the combination of deep learning features with clinical features demonstrated great stratification capabilities in the prognostic model. Our team would continue to explore the application of imaging markers for treatment selection of lung cancer patients.

Drainless Thoracoscopic Lobectomy for Lung Cancer.

OBJECTIVES: Drainless video-assisted thoracoscopic (VATS) wedge resection has been demonstrated as feasible in treating various lung diseases. However, it remains unknown whether this surgical technique can be effectively applied to lobectomy. In the current study, we evaluated the perioperative outcome of drainless, minimally invasive lobectomy in patients with lung cancer. METHODS: A total of 26 lung cancer patients who received surgery-performed pulmonary lobectomy were enrolled. The perioperative outcomes were analyzed based on a propensity score matching a comparison with those who had chest drainage. RESULTS: No major surgical morbidity and mortality was noted during the perioperative period. The mean of postoperative hospital stay was 5.08 ± 2.48 days. There was no significant difference in postoperative hospital stay between the two groups of patients. However, the presence of significant postoperative pain (VAS score > 30) on the first day after surgery was less in the drainless group (34.6% vs. 3.8%; p = 0.005). CONCLUSIONS: Our results demonstrated that drainless, minimally invasive lobectomy for selected lung cancer patients is feasible. Further evaluation of its impact on short- and long-term surgical outcomes is required in the future.

Uniportal video-assisted thoracoscopic left pneumonectomy: Retrospective analysis of eighteen consecutive patients from a single center.

BackgroundUniportal video‐assisted thoracoscopic surgery (VATS) is being more widely used in lung cancer, yet reports on its application in pneumonectomies are limited. This study aimed to evaluate the safety and feasibility of uniportal video‐assisted thoracoscopic left pneumonectomy for lung cancer.MethodsA series of 18 lung cancer patients who had received uniportal video‐assisted thoracoscopic left pneumonectomies were included in the study. Their clinical, pathological, and surgical features, as well as postoperative recovery, were analyzed.ResultsThe majority of the patients were male and smokers and their average age was 62.0 ± 8.9 years. All had primary lung cancer, while three (16.7%) had received neoadjuvant therapy. A total of 16 (88.9%) patients had stage II–III disease, with an average tumor size of 3.6 ± 1.5 cm. The average surgery time was 137.4 ± 47.0 minutes, with a 16.7% (3/18) conversion rate. The mean blood loss was 37.5 ± 59.4 mL and no patients needed blood transfusion during, or after, surgery. There was no perioperative death and the overall complication rate was 22.2% (4/18). Two (11.1%) patients needed to stay in the intensive care unit after surgery, and the average length of hospital stay after surgery was 6.3 ± 1.1 days (range 4–7 days).ConclusionsUniportal video‐assisted thoracoscopic left pneumonectomy is a safe and feasible procedure for selected lung cancer patients. The use of uniportal VATS in right pneumonectomies and the effect of uniportal video‐assisted thoracoscopic pneumonectomy on the survival of patients merits further study.Patients receiving uniportal VATS pneumonectomies had standard surgical results and recovery. Uniportal VATS pneumonectomy is safe for properly selected lung cancer patients.Key points Significant findings of the study: • Patients receiving uniportal VATS left pneumonectomies had standard surgical results and recovery. What this study adds: • Uniportal VATS left pneumonectomy is safe for properly selected lung cancer patients.

Scoping the Problem

Scoping the Problem

Clinical validation of ring-mounted halcyon linac for lung SBRT: comparison to SBRT-dedicated C-arm linac treatments.

Stereotactic body radiotherapy (SBRT) of lung tumors via the ring‐mounted Halcyon Linac, a fast kilovoltage cone beam CT‐guided treatment with coplanar geometry, a single energy 6MV flattening filter free (FFF) beam and volumetric modulated arc therapy (VMAT) is a fast, safe, and feasible treatment modality for selected lung cancer patients. Four‐dimensional (4D) CT‐based treatment plans were generated using advanced AcurosXB algorithm with heterogeneity corrections using an SBRT board and Halcyon couch insert. Halcyon VMAT‐SBRT plans with stacked and staggered multileaf collimators produced highly conformal radiosurgical dose distribution to the target, lower intermediate dose spillage, and similar dose to adjacent organs at risks (OARs) compared to SBRT‐dedicated highly conformal clinical noncoplanar Truebeam VMAT plans following the RTOG‐0813 requirements. Due to low monitor units per fraction and less multileaf collimator (MLC) modulation, the Halcyon VMAT plan can deliver lung SBRT fractions with an overall treatment time of less than 15 min (for 50 Gy in five fractions), significantly improving patient comfort and clinic workflow. Higher pass rates of quality assurance results demonstrate a more accurate treatment delivery on Halcyon. We have implemented Halcyon for lung SBRT treatment in our clinic. We suggest others use Halcyon for lung SBRT treatments using abdominal compression or 4D CT‐based treatment planning, thus expanding the access of curative ultra‐hypofractionated treatments to other centers with only a Halcyon Linac. Clinical follow‐up results for patients treated on Halcyon Linac with lung SBRT is ongoing.

OTUD7B suppresses Smac mimetic-induced lung cancer cell invasion and migration via deubiquitinating TRAF3

BackgroundSmac mimetics are a type of drug that can induce apoptosis by antagonizing IAP family members in cancer treatment. However, a recent study showed that Smac mimetics can trigger cell invasion and migration in cancer cells by activating the NF-κB pathway.MethodsWe assessed lung cancer cell elongation, invasion and migration under treatment with the Smac mimetic LCL161. Functional analyses (in vitro and in vivo) were performed to detect the contribution of NIK and OTUD7B to LCL161-induced cell invasion and migration. The role of OTUD7B in regulation of the TRAF3/NIK/NF-κB pathway under LCL161 treatment was analysed by immunoblotting, immunoprecipitation, luciferase and ubiquitin assays, shRNA silencing and plasmid overexpression. Expression levels of OTUD7B, NIK and TRAF3 in tissue samples from lung cancer patients were examined by immunohistochemistry.ResultsWe found that LCL161 stimulates lung cancer cell elongation, invasion and migration at non-toxic concentrations. Mechanistically, LCL161 results in NIK accumulation and activates the non-canonical rather than the canonical NF-κB pathway to enhance the transcription of target genes, such as IL-2 and MMP-9. Importantly, knockdown of NIK dramatically suppresses LCL161-induced cell invasion and migration by reducing the proteolytic processing of p100 to p52 and target gene transcription. Interestingly, we discovered that OTUD7B increases TRAF3 and decreases NIK to inhibit the non-canonical NF-κB pathway and that overexpression of OTUD7B suppresses LCL161-induced cell invasion and migration. Notably, OTUD7B directly binds to TRAF3 rather than to NIK and deubiquitinates TRAF3, thereby inhibiting TRAF3 proteolysis and preventing NIK accumulation and NF-κB pathway activation. Furthermore, the OTU domain of OTUD7B is required for the inhibition of LCL161-induced cell invasion and migration, as demonstrated by transfection of the C194S/H358R(CH) mutant OTUD7B. Finally, we investigated whether OTUD7B inhibits LCL161-induced lung cancer cell intrapulmonary metastasis in vivo, and our analysis of clinical samples was consistent with the above findings.ConclusionsOur study highlights the importance of OTUD7B in the suppression of LCL161-induced lung cancer cell invasion and migration, and the results are meaningful for selecting lung cancer patients suitable for LCL161 treatment.

Abstract 5796: Therapeutic effects of statins against lung adenocarcinoma via mutant p53 mediated apoptosis

Abstract Introduction The p53 gene is well known as an important tumor suppressor gene. Mutant p53 genes account for about half of all lung cancer cases. There is increasing evidence for the anti-tumor effects of statins via inhibition of the mevalonate pathway. However, the cancer prevention and protection effects of statinsin population-based studies are controversial. Previous population-based studies have shown protective effects of statins in advanced lung cancer patients; however, the effects in early lung cancer patients are unclear. Methods We investigated the correlation between statin use and lung cancer prognosis using the Taiwanese National Health Insurance Research Database retrospectively, mainly focusing on early-stage lung cancer. Cell viability, lipid raft changes, and motile activity from simvastatin-treated cell lines were examined to determine the effect of simvastatin under different p53 mutations. Apoptotic pathways and autophagy in lung cancer cells treated with simvastatin were analyzed using a western blot assay. Results Statin treatments reduced the 5-year mortality (odds ratio, 0.43; 95% confidence interval [CI], 0.37-0.49;P< 0.001) in this population-based study. Simvastatin inhibited cell growth, especially in mutant p53 lung cancer cell lines. Significantly higher levels of cellular apoptosis and decreased lipid rafts were shown in mutant p53 lung cancer cells treated with simvastatin. Further, simvastatin increased activity of the caspase-dependent apoptotic pathway in lung cancer cells containing mutant p53. In addition, simvastatin reduced migration in cells with a mutated p53 gene. Conclusion This study reports the protective effects of statin use in early-stage lung cancer patients regardless of chemotherapy. Simvastatin induced cellular apoptosis and regulated lipid raft content; further, motile activity was reduced in lung cancer cells with p53 missense mutations. These data suggest that statin use in selected lung cancer patients may have clinical benefits. Citation Format: Cheng-wei Chou, Ching-Heng Lin, Tzu-Hung Hsiao, Chia-Chien Lo, Chih-Ying Hsieh, Cheng-Chung Huang, Yuh-Pyng Sher. Therapeutic effects of statins against lung adenocarcinoma via mutant p53 mediated apoptosis [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 5796.

Abstract 3044: The novel bi-specific antibody CKD-702 is a potential agent for NSCLC patients with aberrant cMET and EGFR signaling

Abstract Development of drug resistance is one of the main causes of poor prognosis and therapeutic failure in NSCLC. Mutual synergism between cMET and EGFR is known to promote acquired drug resistance. In NSCLC, cMET gene amplification is reported in 2-4% previously untreated patients and in 5-20% of patients with EGFR mutation and acquired resistance to EGFR TKIs. Because of this crosstalk between cMET and EGFR pathways, dual inhibition of these targets holds promise as a treatment for NSCLC patients, especially those with acquired cMET activation. CKD-702 is a bispecific antibody designed to dually target cMET and EGFR. It is tetravalent IgG1-like bispecific antibody, in which single-chain variable fragment specific to EGFR is genetically fused to the c-terminus of a conventional IgG1 of a cMET. The antibody binds to extracellular domains of cMET and EGFR with high affinity and inhibits signaling by blocking ligand binding. CKD-702 also induces internalization and degradation of both receptors. There are various types of cMET activation in NSCLC patients, including point mutations and amplification. An emerging aberrant cMET activation is through a splice site mutation of cMET that leads to skipping of exon 14, inducing prolonged signaling and oncogenic activity. In this study, we carried out genetic analysis of cMET activation in cancer cell line as well as PDX model with or without EGFR mutation, and the efficacy of CKD-702 in each model for NSCLC was determined. CKD-702 showed complete tumor regression as monotherapy in tumor models that have primary/secondary activating EGFR mutations and cMET amplification. Also, CKD-702 resulted in complete tumor regression in models where cMET is activated by either skipping of exon 14 or amplification. Interestingly, unlike other previously developed EGFR-targeting agents, CKD-702 showed limited skin rash in GLP toxicity study. In summary, CKD-702 is confirmed to inhibit tumors with activated cMET pathway such as cMET amplification and exon 14 skipping as well as with EGFR-activating mutations. This profile of preclinical data supports the clinical trial of CKD-702 as monotherapy in selected lung cancer patients with aberrant cMET and EGFR signaling. A Phase I study of CKD-702 is planned to initiate in 2020. Citation Format: kyu jin park, Eun-Ju Jeon, Ji-Hye Choi, Kwan-Woo Lee, Kyung-Woo Lee, Gun-Woo Park, Hae-Jin Hong, In-Chang Hwang, Seung-Kee Moon, Yeo-Wook Koh. The novel bi-specific antibody CKD-702 is a potential agent for NSCLC patients with aberrant cMET and EGFR signaling [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 3044.

Lung cancer biomarker tests: the history and perspective in Japan.

Biomarker testing is recognized as being indispensable for selecting patients with advanced lung cancer. EGFR mutation is the first biomarker for therapeutic selection of lung cancer patients since the identification of the correlation between EGFR TKI response and EGFR mutation status. The biomarker testing in Japan mostly follows those corresponding to the US. However, there are some differences due to the national health care program and the medical environment. In this review, we introduce the history and current status of the biomarker testing for lung cancer in Japan and discuss perspectives, focusing on cell-free DNA (cfDNA)-based panel testing.

Targeting AXL-JAK1 in tumor and immune ecosystem of lung cancer

Abstract Intercellular crosstalk between lung adenocarcinoma cells (LACs) and tumor-associated macrophages (TAMs) has been implicated in promoting cancer metastasis; however, how oncogenic signaling networks corroborate in this tumorigenic process remains unexplored. Our findings suggest that coordinated activation of AXL and JAK1-pSTAT3 signaling engenders a vicious cycle of dependence between LACs and TAMs for tumor progression. AXL-overexpressing LACs polarize TAMs to an M2-like phenotype in a JAK1-STAT3-dependent manner, facilitating the development of a proinflammatory tumor microenvironment. Conversely, M2-like TAMs release Gas6 ligand to enhance AXL-mediated cancer stemness and epithelial-to-mesenchymal transition (EMT) in LACs. Cytometry by time-of-flight (CyTOF) is a single-cell detection technology that allows for measurement of multiple protein markers in diverse cell subpopulations. We designed a 34-antibody CyTOF panel to identify immune cells, stromal cells, epithelial cells, oncogenic signaling, stemness and EMT components for LAC tumor profiling. CyTOF profiling of ~642,241 single cells detected 55 subpopulations among LAC cell lines (n=4 with co-culture conditions) and lung tumors (n=12), which were further differentiated based on their cell types (LACs, TAMs, stromal cells, granulocytes, natural killer, B and T lymphocytes). High AXL expression was noticed in tumor cell subpopulation while high pSTAT3 expression was detected in the TAM subpopulation. Moreover, pSTAT3 expression levels were increased in U937 differentiated macrophage after co-culture with A549 cells. This novel platform may facilitate the optimal selection of lung cancer patients for dual targeting of AXL and JAK1-pSTAT3.

Therapeutic effects of statins against lung adenocarcinoma via p53 mutant-mediated apoptosis

The p53 gene is an important tumour suppressor gene. Mutant p53 genes account for about half of all lung cancer cases. There is increasing evidence for the anti-tumour effects of statins via inhibition of the mevalonate pathway. We retrospectively investigated the correlation between statin use and lung cancer prognosis using the Taiwanese National Health Insurance Research Database, mainly focusing on early-stage lung cancer. This study reports the protective effects of statin use in early-stage lung cancer patients regardless of chemotherapy. Statin treatments reduced the 5-year mortality (odds ratio, 0.43; P < 0.001) in this population-based study. Significantly higher levels of cellular apoptosis, inhibited cell growth, and regulated lipid raft content were observed in mutant p53 lung cancer cells treated with simvastatin. Further, simvastatin increased the caspase-dependent apoptotic pathway, promotes mutant p53 protein degradation, and decreased motile activity in lung cancer cells with p53 missense mutations. These data suggest that statin use in selected lung cancer patients may have clinical benefits.

Ultrasound guided fine-needle aspiration biopsy of metastases in nonpalpable supraclavicular lymph nodes in lung cancer patients

&#x0D; &#x0D; &#x0D; Background and objectives: To assess frequency and signifi- cance of enlarged nonpalpable supraclavicular lymph nodes with routine ultrasound (US) evaluation and US-guided fine- needle aspiration biopsy (FNAB) for the diagnosis and staging of patients with lung cancer.&#x0D; Materials and methods: 106 consecutive patients with lung cancer and nonpalpable supraclavicular lymph nodes were evaluated with cervical US for the presence of pathological lymph nodes. FNAB was performed in patients with nodes with short-axis &gt; 5 mm, rounded shape and missing echogenic hilum.&#x0D; Results: 27 (25.5%) patients had enlarged supraclavicular lymph nodes on US. Fourteen patients (13.2%) had cytologically proven lymph node involvement. Supraclavicular lymph node metastasis was more frequent in patients with medi- astinal invasion (p = 0.0001) and patients with enlarged lymph nodes on upper paratracheal stations on thorax CT (p = 0.0001). No relation was found between supraclavicular lymph node involvement and T stage (p = 0.27), distant metastasis (p = 0.50) or histological type (p = 0.80). Three patients were upstaged from IIIA to IIIB status. US-guided FNAB was the only diagnostic method in 2 patients.&#x0D; Conclusion: US-guided FNAB is a simple and safe procedure which can document N3 stage of disease in lung cancer patients. Thereby more invasive and expensive diagnostic procedures can be avoided in selected lung cancer patients.&#x0D; &#x0D; &#x0D;

MS02.03 Achieving Effective Lung Cancer Genotyping While Balancing Constrained Resources

Modern oncologic practice for patients with non-small cell lung carcinoma (NSCLC) demands real time data for an increasing numbers of tumor biomarkers. As a result, laboratories are embracing panel-based approaches to tumor molecular profiling, a trend that is facilitated by the adoption of next generation sequencing (NGS) assays. NGS assays may be designed for highly sensitive and focused detection of hotspot mutations (typically by amplicon sequencing) or broader, more comprehensive profiling for detection of a wide variety of alterations in oncogenes and tumor suppressor genes (typically by hybrid capture technology). There are benefits and drawbacks to both approaches. In general, amplicon sequencing offers speed and sensitivity but limited scope and a propensity for PCR-related artifacts that may adversely affect detection of certain mutation types. In contrast, hybrid capture techniques offer tremendous breadth, enabling capture of 100s of genes to whole genomes, but are limited by sensitivity and longer turnaround time.1 Preanalytic steps including sample acquisition, pathologist review to confirm sample adequacy, and nucleic acid extraction often comprise the majority of the turnaround time required to complete focused tumor tissue molecular profiling. Some assays have been optimized for turnaround times of just a few hours- these assays bypass the separate nucleic acid extraction step,2 but are limited by the few number of mutational targets detected, ultimately requiring the use of multiple simultaneous or sequential focused panels.3 This practice, while perhaps the optimal current model from the standpoint of patient care, may be financially prohibitive for many laboratories. This approach additionally requires careful stewardship of patient tissues, as the use of multiple competing assays and may lead to exhaustion of tumor tissue and incomplete tumor molecular profiling. For patients with limited tissue, a considered plan incorporating input from the treating physician, surgical pathologist, and molecular laboratorian should developed early in order to guide assay priority and ensure adequate tissue is available to confirm any unexpected or contradictory results. When the turnaround time for comprehensive large panel testing is clinically acceptable, this approach may be theoretically more cost effective and in most cases will deliver information for essential and emerging biomarkers.4 It is important to keep in mind, however, that even comprehensive DNA-based assays may lack optimal sensitivity for certain structural variants (fusions, large insertion-deletion events), and it may be necessary to couple these tests with focused RNA-based panels optimized for transcript fusion detection.5 1. Rizzo JM, Buck MJ. Key principles and clinical applications of "next-generation" DNA sequencing. Cancer Prev Res (Phila). 2012;5(7):887-900. 2. Ilie M, Butori C, Lassalle S, et al. Optimization of EGFR mutation detection by the fully-automated qPCR-based Idylla system on tumor tissue from patients with non-small cell lung cancer. Oncotarget. 2017;8(61):103055-103062. 3. Lindeman NI, Cagle PT, Aisner DL, et al. Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer, and the Association for Molecular Pathology. J Mol Diagn. 2018;20(2):129-159. 4. Sireci AN. Single Genes, Panels, and Next-Generation Sequencing Platforms: A Financial Perspective. Arch Pathol Lab Med. 2018;142(7):790-791. 5. Benayed R, Offin M, Mullaney K, et al. High Yield of RNA Sequencing for Targetable Kinase Fusions in Lung Adenocarcinomas with No Mitogenic Driver Alteration Detected by DNA Sequencing and Low Tumor Mutation Burden. Clin Cancer Res. 2019. amplicon sequencing, hybrid capture, turnaround time

ES07.04 Predictive Molecular Testing on Small Biopsy Samples

ES07.04 Predictive Molecular Testing on Small Biopsy Samples

MS05.05 Harnessing Oncogene Dependencies in Lung Cancer

The introduction of precision medicine had a dramatic impact on the overall survival of genomically selected lung cancer patients. This is primarily true for lung adenocarcinomas in which druggable targets like mutant EGFR or rearranged ALK are frequently oncogenically activated. The major challenge in these patients is the inevitable emergence of drug resistant clones that abrogate the effects of selected tyrosine kinase inhibitors. Through a detailed characterization of patients that relapse under osimertinib treatment we identified novel routes to overcome individual resistance mutations in EGFR. At the same time, the majority of lung lacks directly druggbale targets and thus remains largely unaffected by this therapeutic revolution. The induction of programmed cell death by perturbing the pro- and anti-apoptotic members of the BCL-2 family may represent an attractive strategy to circumvent this medical need. We sought to explore dependencies on individual BCL-2 family members with different therapeutic strategies to identify therapeutically relevant pathways in lung cancer models. resistance, BCL-2 family

SP-0355 Selection of lung cancer patients for adaptive radiotherapy using cone-beam CT imaging

SP-0355 Selection of lung cancer patients for adaptive radiotherapy using cone-beam CT imaging

RESECTION OF TRACHEAL BIFURCATION IN TREATMENT OF NON-SMALL CELL LUNG CANCER (LITERATURE REVIEW)

Over the past few years, significant advances in surgical and anesthetic techniques as well as appropriate selection of patients have led to an improvement in the immediate and long-term treatment outcomes in patients with non-small cell lung cancer with involvement of tracheal bifurcation. In accordance with the current selection criteria, patients with contralateral lymph node metastases (lung root, aortic window, paratracheal area) require chemotherapy or chemoradiotherapy with subsequent estimation of follow-up and treatment strategy. Surgeries with resection of tracheobronchial bifurcation are considered technically complicated, and they should be performed in carefully selected lung cancer patients and only in specialized centers with extensive experience. It allows the incidence of intra-and postoperative complications to be significantly reduced.

The role of indocyanine green fluorescence for intersegmental plane identification during video-assisted thoracoscopic surgery segmentectomies.

According to recent studies, thoracoscopic segmentectomy is an acceptable alternative to lobectomy for treating different lung diseases. This approach appears to have equivalent rates of postoperative morbidity with potentially similar long-term results even in selected lung cancer patients. At the same time, surgical success is highly dependent on intraoperative interpretation of segmental anatomy. We aimed to analyze our lung segmentectomy experience and identify the role of indocyanine green (ICG)-fluorescence for intersegmental plane detection. A total of 86 consecutive patients who underwent 90 thoracoscopic segmentectomies with near-infrared-indocyanine green (NIR-ICG) method between September 2015 and December 2017 were investigated. According to the preoperative 3D lung hilar model, vascular and bronchial branches of the target segment were divided. ICG was thereafter injected into the central or peripheral vein. The boundary lines between the areas with and without fluorescence was marked on the visceral pleura by electrocautery. The fluorescence was detected immediately after bolus ICG injection in the central vein in all patients but had a time delay of 10-25 seconds in cases of peripheral vein administration. The median duration of intensive ICG staining was 90 seconds, regardless of the injection method. Well-defined fluorescence borders were observed in 86 of 90 (95.6%) segmentectomies due to technical reasons in three cases and severe emphysema in one. Chronic obstructive pulmonary disease (COPD) in other patients did not impair the boundary line identification, but reduced the duration of intensive ICG staining. No ICG-related complications were observed. The ICG-fluorescence technology is safe and effective for verification of anatomic segment borders for video-assisted thoracoscopic surgery (VATS). The perfusion-based ICG fluorescence technique has advantages for thoracoscopic surgeries compared to other methods. Doubling the dose of ICG allows clear detection of the intersegmental plane, even in certain suboptimal conditions.