Stage III-IV Lung Cancer Research Articles

Construction and validation of a nomogram of risk factors for new-onset atrial fibrillation in advanced lung cancer patients after non-surgical therapy.

Risk factors of new-onset atrial fibrillation (NOAF) in advanced lung cancer patients are not well defined. We aim to construct and validate a nomogram model between NOAF and advanced lung cancer. We retrospectively enrolled 19484 patients with Stage III-IV lung cancer undergoing first-line antitumor therapy in Shanghai Chest Hospital between January 2016 and December 2020 (15837 in training set, and 3647 in testing set). Patients with pre-existing AF, valvular heart disease, cardiomyopathy were excluded. Logistic regression analysis and propensity score matching (PSM) were performed to identify predictors of NOAF, and nomogram model was constructed and validated. A total of 1089 patients were included in this study (807 in the training set, and 282 in the testing set). Multivariate logistic regression analysis showed that age, c-reactive protein, centric pulmonary carcinoma, and pericardial effusion were independent risk factors, the last two of which were important independent risk factors as confirmed by PSM analysis. Nomogram included independent risk factors of age, c-reactive protein, centric pulmonary carcinoma, and pericardial effusion. The AUC was 0.716 (95% CI 0.661-0.770) and further evaluation of this model showed that the C-index was 0.716, while the bias-corrected C-index after internal validation was 0.748 in the training set. The calibration curves presented good concordance between the predicted and actual outcomes. Centric pulmonary carcinoma and pericardial effusion were important independent risk factors for NOAF besides common ones in advanced lung cancer patients. Furthermore, the new nomogram model contributed to the prediction of NOAF.

Blood-Derived Exosomal hTERT mRNA in Patients with Lung Cancer: Characterization and Correlation with Response to Therapy.

Background: Telomerase (human telomerase reverse transcriptase (hTERT) is considered a hallmark of cancer, being active in cancer cells but repressed in human somatic cells. As such, it has the potential to serve as a valid cancer biomarker. Exosomal hTERT mRNA can be detected in the serum of patients with solid malignancies but not in healthy individuals. We sought to evaluate the feasibility of measuring serum exosomal hTERT transcripts levels in patients with lung cancer. Methods: A prospective analysis of exosomal hTERT mRNA levels was determined in serum-derived exosomes from 76 patients with stage III-IV lung cancer (11 SCLC and 65 NSCLC). An hTERT level above RQ = 1.2 was considered "detectable" according to a previous receiver operating characteristic curve (ROC) curve. Sequential measurements were obtained in 33 patients. Demographic and clinical data were collected retrospectively from patients' charts. Data on response to systemic therapy (chemotherapy, immunotherapy, and tyrosine kinase inhibitors) were collected by the treating physicians. Results: hTERT was detected in 53% (40/76) of patients with lung cancer (89% of SCLC and 46% of NSLCC). The mean hTERT levels were 3.7 in all 76 patients, 5.87 in SCLC patients, and 3.62 in NSCLC patients. In total, 25 of 43 patients with sequential measurements had detectable levels of hTERT. The sequential exosomal hTERT mRNA levels reflected the clinical course in 23 of them. Decreases in hTERT levels were detected in 17 and 5 patients with partial and complete response, respectively. Eleven patients with a progressive disease had an increase in the level of exosomal hTERT, and seven with stable disease presented increases in its exosomal levels. Another patient who progressed on the first line of treatment and had a partial response to the second line of treatment exhibited an increase in exosomal hTERT mRNA levels during the progression and a decrease during the response. Conclusions: Exosomal hTERT mRNA levels are elevated in over half of patients with lung cancer. The potential association between hTERT levels and response to therapy suggests its utility as a promising cancer biomarker for response to therapy. This issue should be further explored in future studies.

Remote symptom-monitoring of patients with advanced lung cancer: A Danish national randomized controlled trial—The ProWide study.

1508 Background: Symptom-monitoring of patients with lung cancer has previously been shown to improve clinical outcomes. We conducted a national randomized controlled trial to evaluate the effects of remote symptom-monitoring of patients with advanced lung cancer completing induction treatment in a Danish setting. Methods: Patients with stage III-IV lung cancer treated with palliative intention, ECOG performance status ≤2, internet access and non-progressive disease after completed induction treatment were eligible. Patients were randomized 1:1 to remote symptom-monitoring (intervention arm) added to standard of care or standard of care alone (control arm). Maintenance therapy was allowed. Patients in the intervention arm weekly completed an electronic questionnaire from home covering 13 common symptoms related to lung cancer. A severity-threshold was applied to each question. When a threshold was exceeded, a notification was sent to a clinical nurse. The nurse was instructed to contact the patient and offer best supportive care. If disease progression was suspected, a computerized tomography (CT) scan was performed. Primary outcome was overall survival. Secondary endpoints included Health-related Quality of Life (HRQoL) measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire EORTC QLQ-C30/LC13 and Hospital Anxiety and Depression Scale (HADS) scales. Results: Of 494 randomized patients, recruited from 8 departments, 239 were assigned to the intervention and 254 to standard of care (inclusion rate 75%). Weekly compliance to symptom-monitoring during the first year was 82% in the intention-to-monitor population. At a median follow-up of 2.6 years, no significant improvement in overall survival (OS) was found in the intervention arm compared to the control arm (hazard ratio (HR) 0.93, 95% confidence interval (CI); 0.75 to 1.16; p = 0.54). Sub-group analyses indicated improved OS for patients treated with carboplatin/vinorelbine (HR 0.65, CI 95%; 0.44-0.96, p = 0.03) and for patients treated in a department with prior implementation and use of patient-reported outcomes in clinical decision-making (HR 0.68, CI 95%; 0.46-1.01, p = 0.054). For prespecified scales in the HRQoL-analyses, no clinically meaningful effects were found. For physical functioning, mean overall change from baseline was 3.1 points (95% CI 0.1 to 6.2, p = 0.043), for pain, -3.9 points (95% CI; -8.4 to 0.7, p = 0.096) and for HADS-anxiety, -0.5 points (95% CI; -1.0 to 0.0, p = 0.070). Conclusions: Remote symptom-monitoring did not significantly improve clinical outcomes for patients with advanced lung cancer in a Danish population. The results indicated benefits for a sub-group of patients not receiving maintenance therapy and that prior organizational experiences may be a prerequisite for improving outcomes of symptom-monitoring. Clinical trial information: NCT03608410 .

Contribution of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) measurements in determining response to treatment in lung cancer

Purpose: The purpose of this study was to evaluate the role of diffusion-weighted imaging (DWI) in evaluating tumor response to chemotherapy in stage III-IV lung cancer.
 Materials and Methods: Chest and DWI were performed with 3T MRI before and after 3 courses of chemotherapy on 32 patients diagnosed with stage III-IV lung cancer. DWI were acquired with a b factor of 50, 400 and 800 s/mm using a single-shot echo-planar sequence. Histopathological types before and after chemotherapy were compared by measuring mean apparent diffusion coefficient (mADC) values on the basis of regression and progression groups.
 Results: 32 cases, 7 (18.5%) were in the progression group (PG), and 25 (81.5%) were in the regression group (RG). mADC in the PG was 1.06±0.43 x 10ˉ³ before chemotherapy and 0.85±0.24 x 10ˉ³ after chemotherapy. mADC in the RG was 0.92±0.27 x 10ˉ³ before chemotherapy and 1.20±0.26 x 10ˉ³ after chemotherapy. There was a statistically significant difference between the mADC values in the PG and RG before and after chemotherapy. There was no statistically significant difference in mADC values before and after chemotherapy in small cell lung cancer (SCLC) tumor type in the PG . There was a statistically significant difference in mADC values before and after chemotherapy in SCLC and non-small cell lung cancer (NSCLC) tumor types in the RG and NSCLC tumor type in the PG
 Conclusion: DWI and ADC measurements can be used in assessing response to treatment in malignant pulmonary tumors.

Cardiac toxicity in patients with lung cancer receiving thoracic radiotherapy and immunotherapy.

Immune checkpoint inhibitors (ICIs) are used to treat locally-advanced and metastatic lung cancer, which can lead to severe immunogenic-related cardiotoxicities. We assessed the risk of cardiotoxicity in ICI-treated lung cancer patients with or without cardiac radiation from thoracic radiotherapy. Retrospective data was collected on Stage III-IV lung cancer patients who received ICIs between 2015 and 2018. All cardiotoxicities associated with ICI were assessed in correlation with the timing of radiotherapy (RT) in relation to ICI, and the mean RT heart dose. The rate of cardiac events in relation to RT timing and heart dose was compared using multiple logistic regression including the Framingham risk score and steroid use prior to ICI therapy. Of 194 ICI-treated patients evaluated, 55.2% (n=107/194) patients had received thoracic RT at a median dose of 60.4 Gy (range, 15-75). Cardiotoxicities such as non-ST elevated myocardial infarction and new onset supraventricular tachycardias were observed in 13 (12.2%) of those who had thoracic RT versus 9 (10.3%) who did not (p=0.87). 38 patients who received RT concurrently with ICI did not develop any cardiotoxicity whereas 14.1% (n=22/156) of those who did not receive concurrent RT developed cardiotoxicities (univariate, p=0.030; multivariate, p=0.055). There were no significant differences in the mean heart RT dose, Framingham risk score, and steroid treatment between patients that received concurrent RT with ICI versus non-concurrent RT/ICI. ICI-related cardiotoxicities were not significantly associated with patients who received concurrent thoracic radiotherapy in this retrospective review. Further validation of prospective studies is needed to confirm these results.

A nomogram for predicting hyperprogressive disease after immune checkpoint inhibitor treatment in lung cancer

BackgroundImmune checkpoint inhibitor (ICI) therapy is an emerging type of treatment for lung cancer (LC). However, hyperprogressive disease (HPD) has been observed in patients treated with ICIs that lacks a prognostic prediction model. There is an urgent need for a simple and easily implementable predictive model to predict the occurrence of HPD. This study aimed to establish a novel scoring system based on a nomogram for the occurrence of HPD.MethodsWe retrospectively identified 1473 patients with stage III–IV LC or inoperable stage I–II LC (1147 in training set, and 326 in testing set), who had undergone ICI therapy at the Shanghai Chest Hospital between January 2017 and March 2022. Available computed tomography (CT) data from the previous treatment, before ICI administration, and at least 2 months after the first the course of ICI administration is collected to confirm HPD. Data from these patients’ common blood laboratory test results before ICI administration were analyzed by the univariable and multivariable logistic regression analysis, then used to develop nomogram predictive model, and made validation in testing set.ResultsA total of 1,055 patients were included in this study (844 in the training set, and 211 in the testing set). In the training set, 93 were HPD and 751were non-HPD. Multivariate logistic regression analyses demonstrated that lactate dehydrogenase [LDH, P<0.001; odds ratio (OR) =0.987; 95% confidence interval (CI): 0.980–0.995], mean corpuscular hemoglobin concentration (MCHC, P=0.038; OR =1.021; 95% CI: 1.003–1.033), and erythrocyte sedimentation rate (ESR, P=0.012; OR =0.989; 95% CI: 0.977–0.997) were significantly different. The prediction model was established and validated based on these 3 variables. The concordance index were 0.899 (95% CI: 0.859–0.918) and 0.924 (95% CI: 0.866–0.983) in training set and testing set, and the calibration curve was acceptable.ConclusionsThis model, which was developed from a laboratory examination of LC patients undergoing ICI treatment, is the first nomogram model to be developed to predict HPD occurrence and exhibited good sensitivity and specificity.

Comparison of Radiation Pneumonitis in Lung Cancer Patients Treated with HT versus IMRT and Circulating Lymphocyte Subsets as Predicting Risk Factors.

PurposeWe sought to compare the symptomatic radiation pneumonitis (RP) in lung cancer patients treated with helical tomotherapy (HT) versus intensity-modulated radiotherapy (IMRT), and examine the predictive value of circulating lymphocyte subsets affecting the occurrence of RP.Patients and MethodsCirculating lymphocyte subsets, clinical characteristics, dosimetric parameters and pulmonary function were collected from 130 lung cancer patients treated with HT (n = 53) or IMRT (n = 77) from 2016 through 2020. Symptomatic RP was compared between groups. Binary logistic regression was used to identify predictors of RP.ResultsThe IMRT group had larger planning target volume (319.9 vs 240.8 cc, P = 0.041); more ECOG performance status 0–1 (96.1% vs 79.2%, P = 0.002); more stage III–IV disease (94.8% vs 37.6%, P = 0.028); and more combined systemic therapy (85.7% vs 69.8%, P = 0.022). Grade ≥2 RP were comparable between IMRT and HT groups (16.9% vs 15.1%, P = 0.785). For stage III–IV disease, IMRT was associated with lower lung V10 (31.9% vs 35.8%, P = 0.047) and lower incidence of grade 5 RP (0% vs 9.1%, P = 0.018). All lymphocyte subsets reduced after radiotherapy. The decrease degree of total T cell count and CD4+ T cell count were larger after IMRT than HT (P = 0.043, P = 0.021). In univariate analysis, the smoking status, lower baseline FEV1, and higher total T cell count, higher CD8+ T cell count, lower total B cell count, lower CD4+/CD8+ ratio after radiotherapy were associated with the development of grade ≥2 RP. The higher CD8+T cell count after radiotherapy was the only risk factor associated with grade ≥2 RP in multivariable analysis (OR 1.003; 95% CI: 1.000–1.005; P = 0.044).ConclusionIMRT was associated with lower lung V10 and less grade 5 RP than HT for stage III–IV lung cancer. Higher CD8+ T cell count after radiotherapy was associated with an increased risk of RP. HT may better preserve total T cell and CD4+ T cell than IMRT.

Performance of the EarlyCDT® Lung test in detection of lung cancer and pulmonary metastases in a high-risk cohort

ObjectivesEarly detection of lung cancer is pivotal for an optimal prognosis. CT screening is currently implemented in USA. To decrease the amount of CT scans, the application of a blood-based biomarker as part of screening criteria is desirable. Materials and methodsThe EarlyCDT® Lung test was performed in a high-risk cohort composed 246 patients referred from their GP on suspicion of lung cancer. Blood samples were taken at first visit and patients underwent diagnostic workup on suspicion of lung cancer resulting in either a malignant diagnosis or ruled out cancer. Sensitivity and specificity of the EarlyCDT® Lung were calculated in the cohort and subgroups based on age, smoking history, sex and lung cancer stage. ResultsOverall sensitivity in the cohort was 33 % for lung cancer and 31 % for primary lung cancer and lung metastases combined. Sensitivity in age groups was 11 % (60 years or below), 31 % (61−75 years) and 55 % (>75 years). In patients with at least 10 tobacco pack years, sensitivity was 33 % while the sensitivity in patients with at least 50 tobacco pack years was 44 %. The assay sensitivity in stage I-II lung cancer patients was 21 %, while this was 40 % in stage III-IV lung cancer patients.In a subgroup of patients that met current CT screening criteria (age 55–80 years and minimum 30 tobacco pack years) the sensitivity was 37 %. ConclusionThe rationale of screening for lung cancer is to find patients in an early and resectable stage. However, the EarlyCDT® Lung test performed best in elderly, late stage lung cancer patients with a heavy smoking history. Based on these results, the current study finds insufficient sensitivity of the EarlyCDT® Lung test to be used as part of inclusion criteria in a low-dose CT program for detection of lung cancer.

Severe OSA associated with higher risk of mortality in stage III and IV lung cancer.

OSA has been associated with increased cancer incidence and mortality. The aim of this study was to investigate cancer-related mortality, overall survival, and progression-free survival in patients with suspected OSA and lung cancer. This was a case series analysis of lung cancer from a sleep cohort with suspected OSA between 2009 and 2014. The AHI, hypoxia index, and survival outcome were recorded. Immunohistochemistry was used to analyze hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor expression in tumor pathology. In the sleep cohort comprising 8,261 patients, a total of 23 patients had lung cancer. The incidence of lung cancer was significantly higher in the sleep cohort than in the entire adult population in Taiwan (crude incidence rate: 242.1 vs 51.5 per 10⁵ persons, P < .01). The 3-year cancer-related mortality was 25% in AHI < 15 events/h, 50% in AHI 15-29 events/h, and 80% in AHI ≥ 30 events/h (χ² test for trend, P = .03). In Kaplan-Meier survival analysis, patients with stage III-IV lung cancer and AHI < 30 events/h exhibited significantly better overall survival (P = .02) and progression-free survival (P = .02) than patients with severe OSA. Overexpression of HIF-1α and vascular endothelial growth factor was shown in 63% and 45% of lung tumor samples. Overexpression of HIF-1α was positively associated with AHI (P = .04). In this preliminary case series, severe OSA is associated with an increased risk of cancer mortality in patients with stage III-IV lung cancer. AHI was significantly associated with HIF-1α overexpression.

Severe obstructive sleep apnea associated with stage iii-iv lung cancer mortality: a cohort study

Severe obstructive sleep apnea associated with stage iii-iv lung cancer mortality: a cohort study

Expression levels of serum osteopontin, adenosine kinase 1 and Dikkopf 1 in patients with lung cancer and their clinical significances

Objective To observe the expression levels of serum osteopontin (OPN), adenosine kinase 1 (TK1) and secretory protein Dikkopf 1 (DKK1) in patients with lung cancer and their clinical significances. Methods Lung cancer patients treated in the First Affiliated Hospital of Xi'an Medical University from February 2017 to April 2018 were selected as the lung cancer group (60 cases), and 60 healthy adults who received physical examination in the same period were selected as the control group. The differences of serum OPN, TK1 and DKK1 levels between the lung cancer group and the control group and lung cancer patients with different characteristics were compared. Measurement data were compared by using t test. Results The levels of serum OPN, TK1 and DKK1 in lung cancer patients were (38.56±3.18) μg/L, (4.69±1.03) pmol/L and (3.76±0.89) ng/ml, respectively, which were higher than those in the control group [(15.98±2.06) μg/L, (1.01±0.22)pmol/L, (1.21±0.24) ng/ml; t=-46.162, -27.064, -21.428, all P 0.05). The levels of serum OPN, TK 1 and DKK1 in stage Ⅲ-Ⅳ lung cancer patients were (57.18 ±3.12) μg/L, (6.26±1.28) pmol/L and (4.98±1.03) ng/ml, respectively, which were higher than those in stage Ⅰ-Ⅱ lung cancer patients [(30.35±2.96) μg/L, (3.49±0.67) pmol/L, (3.01±0.96) ng/ml; t= -34.156, -10.690, -7.665, all P < 0.01]. The levels of serum OPN, TK 1 and DKK1 in non-small cell lung cancer (NSCLC) patients were (55.13±5.02) μg/L, (5.96±1.11) pmol/L and (5.02±1.32) ng/ml, respectively, which were higher than those in small cell lung cancer (SCLC) patients [(29.68±3.16) μg/L, (3.13±0.98) pmol/L, (2.86±0.56) ng/ml; t = -22.353, -10.213, -7.688, all P < 0.01]. Conclusion The levels of serum OPN, TK1 and DKK1 in patients with lung cancer are higher, which are related to the type and stage of lung cancer. Key words: Lung neoplasms; Small cell lung carcinoma; Carcinoma, non-small-cell lung; Osteopontin; Adenosine kinase; Dikkopf 1

Impact of a mature palliative service for patients with lung cancer admitted to the ICU.

102 Background: In 2012 ASCO made the clinical recommendation for patients with stage IV solid organ cancer to receive palliative care consultation (PCC) at the time of detection. This was intended to increase utilization and effectiveness of palliative care. In this study, we estimate the proportion and impact of late "brink of death" PCC for patients with stage III-IV lung cancer admitted to the ICU of a hospital with a Joint Commission approved palliative care program. Methods: Retrospective review of patients with advanced lung cancer (stage III-IV) admitted to ICU in 2015-17. IRB approval was obtained. There were no exclusion criteria within this population. Areas assessed were age, stage, reason for admission, interventions, disposition, length of stay, days in the intensive care unit, palliative care consultation, code status, and documented end of life discussion. Results: A total of 13 patient met inclusion criteria. They were 38% male 62% female with a mean age of 67 years (SD: 14.9). All had prior diagnosis of advanced lung cancer and 92% were stage IV. The most common indication for admission was sepsis (38%). Less than half (46%) had a PCC, and fewer (31%) had a documented end of life care discussion. Even in the minority of patients with PCC, 33% received the PCC on day of death. Full code status was maintained in 77%. 53% expired during admission with only 57% of those that died having palliative care discussion. Conclusions: Even in a mature TJC certified PCC program, less than half of these terminally ill patients received a PCC. There is a chasm between ASCO's goal of early PCC and the reality of palliative care utilization in ICU admitted patients with advanced lung cancer. A possible solution is to initiate triggered palliative consultation for this high mortality population upon admission, with possible expansion to other terminally ill groups. In a world of electronic medical records, it should be possible to arrange a system to flag these patients for direct review by the palliative team to determine appropriateness and then notify the primary team in order to coordinate care.[Table: see text]

Prevalence and number of circulating tumour cells and microemboli at diagnosis of advanced NSCLC.

Timing and magnitude of blood release of circulating tumour cells (CTC) and circulating tumour microemboli (CTM) from primary solid cancers are uncertain. We investigated prevalence and number of CTC and CTM at diagnosis of advanced non-small cell lung cancer (NSCLC). Twenty-eight consecutive patients with suspected stage III-IV lung cancer gave consent to provide 15 mL of peripheral blood soon before diagnostic CT-guided fine-needle aspiration biopsy (FNAB). CTC and CTM (clusters of ≥3 CTC) were isolated by cell size filtration (ScreenCell), identified and counted by cytopathologists using morphometric criteria and (in 6 cases) immunostained for vimentin. FNAB demonstrated NSCLC in 26 cases. At least one CTC/3 mL blood (mean 6.8 ± 3.7) was detected in 17 (65 %) and one CTM (mean 4.5 ± 3.3) in 15 (58 %) of 26 NSCLC cases. No correlation between number of CTC or CTM and tumour type or stage was observed. Neoplastic cells from both FNA and CTC/CTM were positive for vimentin but heterogeneously. CTC can be detected in two-thirds and CTM in more than half of patients with advanced NSCLC at diagnosis. Reasons underlying lack of CTC and CTM in some advanced lung cancers deserve further investigations.

Abstract 77: Genetic variations in the stem cell pathway predict for toxicity following radiotherapy in lung cancer.

Abstract Lung cancer is a devastating malignancy leading to over 150,000 deaths in the US annually. One primary modality in the treatment of locally advanced lung cancer is radiotherapy in combination with chemotherapy. However, this treatment can lead to significant local toxicity in as many as 50% of all patients and, in some cases, is fatal. Though post-radiation toxicity significantly affects adherence to treatment, quality of life and clinical outcome, it is difficult to predict. Further, no genetic markers have yet been found to be useful in a clinical setting. Because stem cell recruitment is part of the post-radiation tissue repair response, we hypothesize that alterations in stem cell signaling may predict for toxicity following radiotherapy. To investigate this question we examined 441 SNPs related to stem cell signaling in the peripheral blood lymphocytes in 159 patients with stage III-IV lung cancer treated with chemoradiotherapy. After adjusting for treatment-related and demographic factors, we found 47 SNPs significantly associated with symptomatic radiation pneumonitis (p&amp;lt;0.05) and 51 SNPs associated with symptomatic esophagitis (p&amp;lt;0.05). For example, patients with at least one risk allele for WNT9Brs:2165846 had a 46% risk of symptomatic pneumonitis, compared to 31% in those who did not, for a 2.23 fold increase in risk (CI: 1.05-4.07, p=0.04). On analysis of a 141 patient validation set with similar characteristics, variant WNT9Brs:2165846 was confirmed to be associated with symptomatic radiation pneumonitis (OR 2.6, CI: 1.1-6.16, p=0.03). Analysis on this confirmation set is ongoing; however, the preliminary results are indicative of the importance of stem cell signaling in modulating repair following radiotherapy and, in combination with clinical factors, may allow for better management of these patients. Citation Format: Heath D. Skinner, Xia Pu, Joe Chang, Charles Lu, Ritsuko Komaki, Xifeng Wu. Genetic variations in the stem cell pathway predict for toxicity following radiotherapy in lung cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 77. doi:10.1158/1538-7445.AM2013-77

CK-coated magnetic-based beads as a tool to isolate circulating tumor cells (CTCs) in human tumors.

Circulating tumor cells (CTCs) can be detected in the blood of many cancer patients and play a key role in metastasis. In addition, after the development of technologies with the necessary sensitivity and reproducibility, the diagnostic potential of these cells is being actively explored. Recently, the U.S. Food and Drug Administration has approved the CellSearch(®) System, based on magnetic beads coated with epithelial cell-adhesion molecule (EpCAM) antibody. Despite its usefulness, this system can miss CTCs that lose epithelial antigens due to the epithelial-mesenchymal transition and, in the case of advanced NSCLC, CTCs positivity can be demonstrated only in 30-50% of patients. In an effort to overcome these drawbacks, new methods are being developed. In this study, we have evaluated CK-coated beads as a system to isolate CTCs from lung cancer patients in the clinical setting, and have evaluated if they can be a useful source of material for genetic testing. We were able to identify CTCs in 17 of the 30 patients included in the study (57%), with a range of 1 to 7 cells. In two of them, we found only CTCs with an EMT pattern. CTC positivity seemed to correlate with the clinical history of the malignancy. CTCs could be detected in more than 80% of stage III-IV lung cancer patients at presentation or in blood samples taken immediately after surgery. The percentage dropped to 13% in patients responding to chemotherapy or TKIs, raising again to 57% after tumor progression. Finally, we tested the CTCs isolated from 8 patients for EGFR and k-ras mutations, but gene amplification was successful only in the 3 patients with 4 or more CTCs.

Autologous cytokine-induced killer and dentritic cells in treatment of advanced and unresectable lung cancer.

e13069 Background: Both experimental and clinical studies showed cytokine-induced killer (CIK) cells have been shown capable of efficiently lysing target tumor cells, which activity can be enhanced by dendritic cell (DC) stimulation. This study demonstrated that co-cultured autologous CIK and tumor antigen-pulsed DC are effective in in treatment of advanced and unresectable lung cancer Methods: Sixteen patients having stage III-IV lung cancer with a malignant pleural effusion, 9 females and 7 males with an average age of 54.3 years old, were included in this study. Autologous CIK and DC were prepared from isolated peripheral blood mononuclear cells and were induced by multiple cytokines. Generated DCs were pulsed by the antigen generated from tumor tissues and co-cultured with CIK. Those patients received 4-6 times of CIK-DC intravenous infusion, 2-3 ×109 cells each time. Results: Eleven (68.8%) patients achieved a partial remission. The pleural effusion decreased in all those patients, and in 9 of them the effusion decreased over 50%. The clinical symptoms were relieved in all the patients. There were no significant adverse effects were found. Those patients are still followed for long-term survival outcome. Conclusions: CIK-DCs immunotherapy provides a new and effective treatment for the late stage lung cancer.