Stage Lung Cancer Patients Research Articles

Levels of Extracellular Vesicles in Pulmonary and Peripheral Blood Correlate with Stages of Lung Cancer Patients.

The extracellular vesicle (EV) concentration is known to be higher in cancer patients than in healthy individuals. Herein, we report that EV levels differ in the tumor-draining pulmonary vein blood and the peripheral blood of animal models and human subjects at different pathological stages of lung cancer. Ten rabbits and 40 humans formed the study cohorts. Blood was collected from the peripheral vein of members of all groups. Pulmonary blood was collected intraoperatively from all groups except for the healthy human controls. Quantitative analysis of EV levels was performed using a nanoparticle tracking assay, a CD63 enzyme-linked immunosorbent assay, and western blotting. The EV levels in the peripheral blood of animals and patients with lung cancer were higher than those in the peripheral blood of healthy controls (p < 0.01 and p < 0.001, respectively). Moreover, for both animals and patients with lung cancer, the EV levels in the pulmonary blood were significantly higher than those in the preoperative peripheral blood (p < 0.01 and p < 0.0001, respectively). In patients, the pathological stages of lung cancer showed a higher correlation with the pulmonary EV levels than the peripheral EV levels. EV levels increased with increasing lung cancer grade, and this trend was more prominent in the pulmonary blood than in the peripheral blood.

Comparison of the Clinical Effect of Uniportal Video-assisted Thoracoscopic Lobectomy and Biportal Video-assisted Thoracoscopic Lobectomy in the Treatment of Lung Cancer

背景与目的近年来单孔胸腔镜肺癌根治术逐渐兴起，作为一种新的手术方式，其可行性及安全性尚未得到普遍认可。本研究拟探讨单孔胸腔镜肺癌根治术在治疗Ⅰ期至部分Ⅲa期肺癌病例中的可行性及安全性。方法回顾性分析苏州大学附属第一医院胸外科同一治疗组在2018年5月-2019年3月连续进行的胸腔镜肺癌根治术患者的临床资料。排除部分不符合要求的病例后，根据手术方式分为单孔组（55例）和单操作孔组（87例），共142例。分析两组患者的临床数据，进行统计学分析。结果142例患者均行肺叶切除+淋巴结清扫术，术后顺利出院，未有围手术期死亡。单孔组和单操作孔组比较，年龄、肿瘤位置、术后病理类型、肿瘤大小、肿瘤的病理性原发灶-淋巴结-转移（pathological tumor-node-metastasis, pTNM）分期的差异均无统计学意义（P > 0.05）。单孔组手术时间更短[(167.65±43.85) min vs (181.71±51.28) min]，术中出血量更少[(57.45±50.19) mL vs (87.47±132.54) mL]，术后引流管留置时间[(4.82±2.82) d vs (5.84±3.43) d]及术后住院天数[(6.91±3.88) d vs (7.74±3.87) d]更短，但差异无统计学意义（P > 0.05）。单孔组的术后总引流量显著低于单操作孔组[(1, 064.82±776.38) mL vs (1, 658.71±1, 722.38) mL]，术后24 h及72 h视觉疼痛评分明显更低[（4.73±0.73）分vs（5.25±0.74）分；（2.16±0.71）分vs（2.55±0.86）分]，差异有统计学意义（P < 0.05）。结论在Ⅰ期至部分Ⅲa期肺癌病例中，单孔胸腔镜肺癌根治术安全可行。

Correlation of levels of extracellular vesicles in peripheral and pulmonary blood plasma with pathological stages of lung cancer patients.

e15558 Background: Exosome concentration is known to be higher in cancer patients than in healthy individuals. In this study, we observed that the levels of exosomes differ in tumor-draining pulmonary blood and in peripheral blood in animal models and human subjects at different pathological stages of lung cancer. Methods: Ten rabbits and 40 humans formed the study cohorts. Blood was collected from a peripheral vein in all groups, and pulmonary blood was collected intraoperatively from all groups, except the healthy human controls. Quantitative analysis of exosomes was performed by nanoparticle tracking assay, CD63 enzyme-linked immunosorbent assay, and western blotting. Results: The peripheral blood of lung cancer-bearing animals and patients with lung cancer carried higher amounts of exosome than that from healthy controls ( p &lt; 0.01 and p &lt; 0.001, respectively). Moreover, pulmonary blood from lung cancer-bearing animals and patients had significantly higher exosome levels, compared to preoperative peripheral blood ( p &lt; 0.01 and p &lt; 0.0001, respectively). In patients, pulmonary exosome levels showed higher correlation with pathological stages of lung cancer than the peripheral exosome levels. Conclusions: Exosome levels increased with increasing grade of lung cancer, and this trend was more prominent in the pulmonary than in the peripheral blood.

Lung cancer exosome specific protein 1(LESP-1) as a potential factor for diagnosis and treatment of non-small cell lung cancer.

e15550 Background: Exosomes are endosome-derived nano size (30-150 nm) extracellular microvesicles released from many cell types including cancer cells and encapsulated by cell membrane play a key role for cell to cell communication. Use of exosomes as a biomarkers in lung cancer is a rising nanotechnology in a liquid biopsy. We explored a role of an exosome specific marker and the relationship between pathological stage of lung cancer patients who underwent surgery and lung cancer specific exosome markers. Methods: Conditioned medium from non-small cell lung cancer (NSCLC) cells and human pulmonary alveolar endothelial cell (HPAEpiC) was collected and exosomes were isolated by size exclusion chromatography. Proteomics analysis was performed to investigate lung cancer specific proteins. Written informed consent was obtained from all human subjects (17 controls and 54 patients), approved by the Korea University Guro Hospital Institutional Review Bored. Plasma exosomes were isolated using dual size exclusion chromatography. We validated proteomics results with lung cancer exosome-specific protein 1 (LESP-1) ELISA assay and western blot assay in lung cancer patients with healthy control. Cancer cell lines with pCMV-CD63-GFP were transduced by lentiviral vectors containing LESP-1 shRNA. The distribution of GFP+ exosomes and cell migration were examined by immunocytochemistry (ICC) and cell migration assay. Results: We identified LESP1 by the proteomics analysis of exosomes from NSCLC cell lines, but not in HPAEpiC cell. Level of LESP1 was dramatically increased in exosomes from NSCLC cell lines and from NSCLC patients. LESP-1 concentration increased in lung cancer patients than healthy controls ( p &lt; 0.0001) and increased according to the grade of lung cancer stage in peripheral blood ( p &lt; 0.0001). Western blot results confirmed the presence of the LESP1 with higher intensity band at each grade of lung cancer stage than healthy controls. Interestingly, we found that the number of GFP+ exosomes was decreased and cell migration was inhibited when the LESP1 was suppressed in NSCLC cells. Conclusions: The LESP-1 in exosomes was highly expressed in blood plasma of lung cancer patients, and the exosome release and cancer cell migration was inhibited by the LESP-1, which suggest that LESP-1 could be a feasible factor for diagnosis and treatment of non-small cell lung cancer.

Variant allele frequency of circulating tumor DNA mutations detected in preoperative blood is indicator for lymph node metastasis in early stage lung cancer.

e21057 Background: The advances in deep sequencing technologies makes circulating tumor DNA (ctDNA) detection in preoperative plasma a more and more significant indicator in early stage cancers. In particular, it allows us to learn a lot about tumor progression before surgery. Plasma variant allele frequency (VAF) of preoperative ctDNA mutations had been verified to correlate with tumor sizes in early lung cancers. Identification of lymph node (LN) metastasis status before surgery in patients with lung cancer is valuable for prognosis and treatment strategy decisions. To evaluate whether ctDNA predict the LN metastasis status, we conducted this analysis. Methods: Preoperative plasma and the matched leukocyte before treatment were collected from 38 early stage lung cancer patients, in which 8 cases with lymph node metastasis. 150-gene panel sequencing were performed on the specimens and the sequencing data were used as primary cohort. Multivariable logistic regression analysis was used to develop a prediction model based on the DNA and other clinical characteristics. The performance of the model was assessed by its calibration, discrimination and clinical usefulness in the public TRACERx 100 early lung cancers cohort. Results: The proportion of high variant allele frequency (HAF proportion) of mutations was significantly associated with LN status (p &lt; 0.05, for both primary and validation cohorts). A prediction model was developed and predictors included the HAF proportion, smoking status and tumor size. The C-index of the model was 0.419 in primary cohort. In external validation cohort, the AUCs for LN positive was 0.678. Conclusions: Based on pan-gene panel deep sequencing, a big proportion of high variant allele frequency mutations in a single patient indicates advanced disease progression, which may reflect in LN involvement status. A logistic regression model was constructed using ctDNA and clinical characteristics. It showed considerable performance in the prediction of LN metastasis in early lung cancers.

Neighborhood disparities in timeliness of treatment for early stage lung cancer patients.

e19017 Background: Lung cancer is the second most commonly diagnosed cancer and the leading cause of cancer-related death in the United States, accounting for approximately 25% of all cancer deaths. The National Comprehensive Cancer Network (NCCN) provides evidence-based cancer treatment recommendations. Evidence suggests that a patient’s receipt of guideline-concordant treatment (GCT) increases survival, especially for screen-detected, earlier stage cancers. Neighborhoods are key determinants of health and the neighborhood social and built environments can influence cancer treatment and outcomes. Minority segregated neighborhoods often have limited health resource availability. The objective of this study is to estimate the relationship between neighborhood segregation on racial and ethnic disparities in timely receipt of GCT in early-stage lung cancer patients in California. Methods: We studied 22,903 patients diagnosed with stage I/II non-small cell lung cancer (2006-2015) in the California Cancer Registry. The primary outcome of the study is receipt of GCT according to the 2016 NCCN guidelines defined as the administration of proper initial and adjuvant treatment(s) according to cancer site and stage, and measured using surgery type, chemotherapy type, and radiation type. The secondary outcome was timely receipt of care as defined as the initiation of surgery, radiation, or chemotherapy within 45 days of diagnosis for initial treatment and the initiation of chemotherapy +/- radiation within 6 months of initial surgery for N1 patients for adjuvant treatment. Multivariable hierarchical logistic regression will be used to estimate the effect of neighborhood segregation on timely receipt of GCT, adjusting for individual- and neighborhood-level covariates, and stratified by patient race/ethnicity. Results: Overall, 81.39% of patients received GCT; 57.63% of them within 45 days of diagnosis. Under-treatment and treatment delay were more frequent in patients who were black or Hispanic, had public insurance, and were of lower socioeconomic status. We hypothesize that increased neighborhood segregation will decrease a patient’s likelihood of adherence to GCT and timely GCT. Conclusions: This research is vital to improving our understanding of cancer-related health disparities and promoting health in vulnerable neighborhoods. With rising numbers of early stage lung cancers due to screening smokers, administration of timely proper treatment is critical.

Clinical value of seven autoantibodies combined detection in the diagnosis of lung cancer.

BackgroundTo analyze the clinical value of seven autoantibodies (p53, PGP9.5, SOX2, GAGE7, GBU4‐5, MAGE A1 and CAGE) in lung cancer patients.MethodsELISA was used to determine serum levels of seven autoantibodies in 177 patients with lung cancer, 201 healthy persons, and 210 patients with benign pulmonary diseases. Positive rates of 7 autoantibodies were analyzed; receiver operating characteristic (ROC) curves were drawn to analyze their diagnostic efficiency in lung cancer and to compare the positive rate of seven kinds of autoantibody combined detection of lung cancer patients with different clinicopathological features.ResultsThe positive rate of seven autoantibodies in all subjects was 13.44%. The positive rate of seven autoantibodies in lung cancer was 25.42%. The positive rate of the combined detection of seven autoantibodies in the lung cancer group was significantly higher than that in healthy control group (χ2 = 19.76, P < .001) and benign lung disease group (χ2 = 21.44, P < .001). Sensitivity, specificity, and AUCROC of the seven autoantibodies were 25.42%, 91.75%, and 0.683, respectively. Sensitivity and AUCROC were higher than those of the single autoantibody detection. Positive rates of seven autoantibodies in different pathological types and clinical stages of lung cancer patients were significantly different (P < .05).ConclusionsThe combined detection of 7 autoantibodies in lung cancer has some clinical value for the auxiliary diagnosis of lung cancer.

Pushing the boundaries: transesophageal endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of intraparenchymal pulmonary micronodules

Endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS-TBNA) is nowadays considered widely reliable for mediastinal lymph nodal staging in lung cancer patients. In a few years it has deeply changed the diagnostic algorithms for thoracic diseases and can guide the choice of therapeutic protocols. The use of an EBUS videobronchoscope for transesophageal exploration (EUS-B-FNA) is less conventional. Here we report the case of a patient who underwent transesophageal EUS-B-FNA of a periesophageal pulmonary nodule in order to confirm systemic recurrence of a tracheal tumor. EUS-B-FNA is a reliable alternative technique for the diagnosis of pulmonary lesions, being effective and well tolerated by patients. The versatility of the EBUS bronchoscope gives reason, among others, for the key role it plays in the management of lung cancer patients.

Simvastatin is beneficial to lung cancer progression by inducing METTL3-induced m6A modification on EZH2 mRNA.

To elucidate the molecular mechanism of Simvastatin on inhibiting malignant progression of lung cancer. Relative levels of METTL3 and EZH2 in lung cancer tissues and adjacent normal ones were detected by quantitative real-time polymerase chain reaction (qRT-PCR). In addition, their levels in lung cancer patients with different pathological stages were determined as well. A549 cells were induced with different doses of Simvastatin for 24 h. Subsequently, relative levels of METTL3 and EZH2 in cells were detected. Proliferative and metastatic abilities in A549 cells were examined by cell counting kit-8 (CCK-8), 5-Ethynyl-2'- deoxyuridine (EdU) and transwell assay, respectively. RIP assay was conducted to detect the presence of m6A modification on EZH2 mRNA and the interaction between IGF2BP2 and EZH2. Relative levels of EZH2 and epithelial-mesenchymal transition (EMT)-associated genes (E-cadherin and N-cadherin), and metastatic abilities were detected in Simvastatin-induced A549 cells transfected with pcDNA-METTL3. METTL3 and EZH2 levels were upregulated in lung cancer tissues, which were higher in advanced stage lung cancer patients. Their levels, as well as cell proliferative and metastatic abilities, were dose-dependently inhibited in Simvastatin-induced A549 cells. METTL3 positively regulated EZH2 level, and m6A modification on its mRNA. Moreover, the interaction between IGF2BP2 and EZH2 could be inhibited by knockdown of METTL3. Simvastatin could abolish the role of METTL3 in regulating relative levels of EZH2 and EMT-associated genes, as well as metastatic abilities in A549 cells. Simvastatin induces METTL3 down-regulation in lung cancer tissues, which further influences EMT via m6A modification on EZH2 mRNA and thus inhibits the malignant progression of lung cancer.

Abstract No. 536 Effectiveness observation for lung cancer patients in middle and advanced stage receiving bronchial arterial infusion chemotherapy and CalliSpheres drug-eluting beads for embolization

Abstract No. 536 Effectiveness observation for lung cancer patients in middle and advanced stage receiving bronchial arterial infusion chemotherapy and CalliSpheres drug-eluting beads for embolization

Is Thiol-Disulphide Homeostasis an Indicative Marker in Prediction of Metastasis in Lung Cancer Patients.

Thiol/disulfide (SH/SS) homeostasis plays an essential and dynamic role in our body and in various cellular activities and pathways such as cell death, regulation of enzyme activities, mechanisms of transcription and cellular signal transduction. Lung cancer is the most commonly seen cancer type in the adult population. Therefore, prediction of metastases gains importance in this population. We included 150 patients with lung cancer who attended Kirikkale University Medical Faculty Hospital between June 2017 and June 2018. Our purpose was to evaluate whether metastases can be predicted in lung cancer patients by testing SH/SS homeostasis as a novel and easily applicable biochemical test. The mean age of the patients was 63.8 ± 8.1 (41 - 71) years. Advanced stage lung cancer, adenocarcinoma, squamous-cell and small cell lung cancers, and other types were detected in 54.7%, 42.7%, 41.3%, 13.3%, and 2.7% of the patients, respectively. SS values of the patients with advanced stage lung cancer were higher than in patients with early stage lung cancer (p < 0.001). It was determined that the patients with advanced stage lung cancer had statistically significantly higher mean values of SS, SS/SH (%), and SS/total SH (%) than patients with early stage lung cancer and that a statistically significantly lower mean value of SH/total SH (%) was found in advanced stage compared with early stage lung cancer patients. No statistically significant difference was found between the patient groups with advanced and early stage lung cancer regarding mean values of native SH and total SH levels. It can be concluded that SH/SS parameters may vary in advanced and early stage lung cancer patients; however, further studies should be conducted with SH/SS parameters in order to use them as indicators of cancer severity in lung cancer patients.

Differences in optimal timing of post-surgical surveillance for limited stage lung cancer patients and associations with outcomes

Background: Guidelines for post-operative surveillance for non-small cell lung cancer (NSCLC) are variable. Historically, providers have used a one-size fits all approach, such that surveillance guidelines incorporated few important prognostic indicators for recurrence and survival. The goal of this study was to determine optimal timing for detection of recurrence by CT scan and the association between surveillance CT and overall survival. Methods: This was a retrospective, single institution series of patients undergoing surgical resection [2008– 2012] with stage I or II disease (AJCC 7th edition) with at least 6 months of follow-up. Results: Recurrence occurred in 27.2% of patients at a median of 29.5 months following surgery. Recurrences peaked at 2–3 years following surgery for the entire cohort. For those detected on CT scan surveillance, stage I the peak timing for recurrence was at 25–36 months (year 3) whereas stage II peak timing was at 19–24 months (year 2) following resection. Timing of recurrences detected by any means differed significantly based on cancer stage with 81% (n=27) of recurrences occurring more than 24 months following surgery for stage I patients compared to 41% (n=17) of stage II patients (P Conclusions: The timing of recurrence differs significantly based on stage such that few stage I patients have recurrences within 2 years following surgical resection. Additionally, rates of recurrence detected by surveillance CT scans performed less than 24 months following surgery is significantly lower for stage I patients compared to stage 2 which would favor delaying routine surveillance in this select group. Optimal timing of CT surveillance based on peak recurrence rates has the potential to eliminate unnecessary testing and expense for healthcare systems.

Significance of the lobe-specific emphysema index to predict prolonged air leak after anatomical segmentectomy.

Prolonged air leak (PAL) is a major complication of pulmonary resection. Emphysema quantification with computed tomography is regarded as an important predictor of PAL for patients undergoing lobectomy. Therefore, we investigated whether this predictor might be applicable for segmentectomy. Herein, we characterized the factors that influence PAL in early stage lung cancer patients undergoing anatomical segmentectomy. Forty-one patients who underwent anatomical segmentectomy for early lung cancer between January 2014 and July 2017 were included for analysis. Several baseline and surgical variables were evaluated. In particular, the emphysema index (EI, %) and lobe-specific emphysema index (LEI, %) were assessed by using three-dimensional volumetric CT scan. PAL was observed in 13 patients (31.7%). There were statistically significant differences in DLCO (97.3% ± 18.3% vs. 111.7% ± 15.9%, p = 0.014), EI (4.61% ± 4.66% vs. 1.17% ± 1.76%, p = 0.023), and LEI (5.81% ± 5.78% vs. 0.76% ± 1.17%, p = 0.009) between patients with and without PAL. According to logistic regression analysis, both EI and LEI were significantly associated with PAL (p = 0.028 and p < 0.001, respectively). We found that EI and LEI significantly influenced the development of PAL after pulmonary resection. In particular, LEI showed stronger association with PAL, compared with EI, suggesting the importance of LEI in the prediction of PAL after anatomical segmentectomy.

Screening for fear of cancer recurrence: Instrument validation and current status in early stage lung cancer patients

Fear of cancer recurrence (FCR) is one of the most distressing concerns for cancer patients. A psychometrically validated brief scale is urgently needed for use in busy clinical oncology settings. This study aimed to (1) develop and validate the 7-item fear of cancer recurrence scale Chinese version (FCR7-C), and (2) explore the severity of FCR in post-operative early-stage lung cancer patients in Taiwan. Early-stage lung cancer patients were recruited from a medical center in Taiwan. The FCR7-C was evaluated for content and construct validity and internal consistency reliability. Construct validity of FCR7-C was determined by the empirically supported correlation and confirmatory factor analysis (CFA). A total of 160 subjects were recruited. The FCR7-C was shown to have satisfactory content validity and internal consistency reliability (Cronbach's α=0.9). The uni-dimensional structure was confirmed by CFA that showed a good fit for the model. The FCR7-C score correlates positively with the degree of most of the physical symptoms, anxiety, and depression, but correlates negatively with patient age, performance status, and quality of life. We found that 81.9% of patients reported at least some FCR, with a mean FCR severity of 15.18 (SD=7.78). FCR7-C is a brief screening tool with good psychometrics. Patients with early-stage lung cancer still revealed mild to moderate level of FCR. Applying the FCR7-C for to screen cancer patients' distress and further develop personalized psychological interventions would be strongly suggested.

Identification of Risk Factors and Likelihood of Benefit from Adjuvant Chemotherapy for Early Stage Lung Cancer Patients

ABSTRACTThe purpose of the research is to develop a statistical decision support algorithm for patients who may benefit from Adjuvant Cisplatin/Vinorelbine (ACT) and improve their survival rates. Genome-wide microarray data are used to identify feasible sets of genes and probe sets that constitute the gene signature. The data are available at the National Center for Biotechnology Information Gene Expression Omnibus (GSE14814). Preliminary studies have shown that high-risk patients who received ACT resulted in an improved prognosis. However, low-risk patients showed no benefit from ACT, and the treatment was possibly detrimental to the patient. Studies using tree-based ensemble statistical learning algorithms have shown that genomic markers could potentially identify a patient’s risk factor and likelihood to benefit from ACT; however, it was noted that tree-based ensemble statistical learning algorithms do not provide an estimate of the strength of the treatment effect, nor is it possible to clearly identify subgroups of patients with similar responses to ACT treatment. Building on this idea, Accelerated Failure Time models are used to predict the probability of benefit from receiving chemotherapy or surgery only and provide a treatment recommendation for a new patient. We showed that regardless of whether the model recommended chemotherapy or surgery only, patients who followed the predicted treatment recommendation had significantly longer survival times than patients who did not. The proposed approach provides the likelihood of benefit for each treatment based on a small number of genomic biomarkers.

Outpatient Anesthesia Facilitates Stereotactic Body Radiation Therapy for Early Stage Lung Cancer Patients With Advanced Cognitive Impairments

PurposeTo report on the use of outpatient anesthesia (OPA) facilitating delivery of stereotactic body radiation therapy (SBRT) in patients with severe cognitive impairments (CI) diagnosed with inoperable early stage lung cancer. Methods and MaterialsWe surveyed our institutional review board–approved prospective lung SBRT data registry to document the feasibility of using anesthesia in CI patients and to determine their SBRT outcomes. ResultsFrom 2004 to 2018, 8 from a total 2084 patients were identified for this analysis. The median age at treatment was 68 years (range, 44-78). Most patients were female (62.5%). CI diagnoses included Alzheimer-related dementia (3 patients), chronic schizophrenia (3 patients), severe anxiety disorder (1 patient), and severe developmental disability (1 patient). The median tumor size was 3.4 cm (range, 1.1-10.5), and 7 patients (87.5 %) had central lesions. The median follow-up time was 22.5 months. The most common (50%) SBRT schedule used was 50 Gy in 5 fractions. Intravenous propofol (10 mg/mL) was used for OPA in all cases at the time of simulation and with daily treatments. OPA was well tolerated and all patients completed SBRT as prescribed. There was one grade 5 but no other grade 3 or higher SBRT-related toxicities. One patient died with local failure and one of distant failure. ConclusionsOPA made lung SBRT feasible for patients with CIs. SBRT outcomes were in keeping with those reported in the literature. CI should not be considered a contraindication per se to SBRT delivery in patients otherwise appropriate for this modality.

P2.11-42 A Prospective Multicenter Study to Assess Combined 6 Tumor Markers for Early Stage Lung Cancer in Patients with Lung Nodule

P2.11-42 A Prospective Multicenter Study to Assess Combined 6 Tumor Markers for Early Stage Lung Cancer in Patients with Lung Nodule

111P - Combined genomic and epigenomic assessment of cell-free circulating tumour DNA (cfDNA) for cancer diagnosis and recurrence-risk assessment in early-stage lung cancer

BackgroundCirculating tumor DNA (ctDNA) analysis has been successfully applied to therapy selection and treatment monitoring in advanced cancer patients. However, it is not yet established whether ctDNA can be used clinically for early cancer detection or recurrence prediction in early stage lung cancer patients. MethodsWe analyzed pre-operative plasma samples from 55 early stage NSCLC patients (stages I-IIIA) using next-generation sequencing assay incorporating somatic and epigenomic analysis, and a bioinformatic classifier to filter non-tumor derived variants.Table: 111PTable: 111PCell typeStageSomatic mutationEpigenetic patternTotal numberRecurrence+, n (%)Site of recurrenceAdenocarcinomastage 1ctDNA-methylation-91 (11)Lungn=17methylation+62 (33.3)Stump, bonectDNA+21 (50)lungstage 2ctDNA-methylation-00 (0)n=2methylation+00(0)ctDNA+11 (100)multiplestage 3ctDNA-methylation-00 (0)n=4methylation+20 (0)ctDNA+22 (100)brain, multipleSqaumous cell carcinomastage1ctDNA-methylation-00 (0)n=7methylation+30 (0)ctDNA+41 (25)multiplestage2ctDNA-methylation-00 (0)n=9methylation+00 (0)ctDNA+92 (22.2)multiple, lungstage3ctDNA-methylation-00 (0)n=4methylation+10 (0)ctDNA+31 (33.3)Mediastinal LNs ResultsSomatic mutation analysis alone detected ctDNA in 42% (23/55) of patients, whereas combined mutational and epigenomic analysis detected ctDNA in 67% (37/55). ctDNA detection rate varied by pathological subtypes; using combined approach, ctDNA was detected in all squamous cell carcinoma patients, while only 55% (12/22) in adenocarcinoma (ADC) (p=0.006). Within the ADC subgroup, ctDNA detection rates using the combined approach were dependent on disease stage: 47% (8/17) in stage I, 100% (2/2) in stage II, and 100% (2/2) in stage IIIA. Importantly, within 2 years of follow-up, pre-operative ctDNA status was correlated with tumor recurrence after resection; among 17 stage I ADC patients, three of eight (38%) ctDNA-positive cases showed recurrence, while only one of nine (11%) ctDNA-negative cased did (p=0.29). Interestingly, patients with somatic mutation in their ctDNA have shown higher recurrence rate. ConclusionUtilizing a plasma-only sequencing assay incorporating somatic genomic and epigenomic analysis, ctDNA detection rate in early stage lung cancer (stage I-III) can far outperform the detection rate of somatic sequence variant detection alone. And, the presence of pre-operative ctDNA in patients with early stage lung adenocarcinoma may identify those who are more likely to have disease recurrence.Legal entity responsible for the study: Guradant Health, Inc. FundingGuardant Health, Redwood City, CA, USA. DisclosureI. Kim: Full / Part-time employment, Officer / Board of Directors: Guardant Health. M. Shultz: Officer / Board of Directors: Guardant Health. A. Jaimovich: Officer / Board of Directors: Guardant Health. J. Odegaard: Officer / Board of Directors: Guardant health, Inc. S. Olsen: Officer / Board of Directors: Guardant Health, Inc. A. Talasaz: Officer / Board of Directors: Guardant health. J. Kim: Research grant / Funding (self): Guardant health, Inc. All other authors have declared no conflicts of interest.

EP1.17-35 CBCT Radiomics May Predict Short-Term SBRT Effect in Early Stage Lung Cancer Patients

EP1.17-35 CBCT Radiomics May Predict Short-Term SBRT Effect in Early Stage Lung Cancer Patients

Quality of medical care in end-of-life lung cancer patients previously received immunotherapy

Abstract Background Immuno-oncology has changed disease trajectory as well as prognosis. End-of-life(EOL) care and EOL discussion must be changed, but little is known about current situation in the real world. The aim of this study is to explore the quality of medical care in end stage lung cancer patients who had received immunotherapy (IT). Methods This is a retrospective chart review. We reviewed the data of lung cancer patients who had received IT and died in our hospital between January 2014 and December 2018. The coprimary outcome are the length of stay in hospital and at home within 30 days from death. Results We identified 77 patients who met the eligible criteria. Their characteristics were as follows: median age, 63(34-78) years, male/female, 53/24 cases, histology type were Ad/Sq/Others, 55/14/8 cases. Patient received 1(1-2) regimens and 2(1-41) cycles of IT. Nivolumab, 46 cases (59%), was the most used IT agent. Most of the patients (92%) lived with their family and about half (52%) of them lived in Tokyo. The median overall survival from the initial diagnosis was 474 (25-4889) days and the median duration between final administration of IT and death was 58 (2-626) days. Within 30 days of death, the number of emergency hospitalizations was 1 (0-2) times, the length of hospital stay was 18 (1-30) days, the length of staying at home was 12 (0-29) days. Eighteen cases (23%) were hospitalized for 30 days or more consecutively until the death. Although fifteen(83%) out of 18 cases hospitalized for palliative care, only 6 cases received palliative care team (PCT) intervention. The most common reasons for emergency hospitalization were dyspnea (33 cases, 42%). Forty-five patients (58%) had meetings with medical social workers(MSWs). Six cases were able to go back home with visiting medical care. Conclusion Percentage of intervention by PCT is low. And the intervention of MSWs is too late. To improve this situation, EOL discussion should be started earlier.