Clinical, pathological and molecular characterization of long-term survivors with advanced non-small cell lung cancer in a multicenter experience in Madrid: Final results.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20621-e20621
Author(s):  
Juan Moreno ◽  
Santiago Ponce Aix ◽  
Rosa Maria Alvarez Alvarez ◽  
Maria Eugenia Olmedo Garcia ◽  
Sandra Falagan ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Genetic Analysis ◽  
Small Cell Lung Cancer ◽  
Small Cell ◽  
Surfactant Proteins ◽  
Rna Seq ◽  
Wild Type ◽  
Rt Pcr ◽  
Small Cell Lung ◽  
Transcriptome Expression

e20621 Background: Long survivors (LS) in non-small-cell lung cancer (NSCLC), defined as an overall survival (OS) greater than 2 years, are less than 10% in most series. Classical prognosis factors include stage, weight loss and ECOG, but more information is missing in the literature. Recently, EGFR, ALK and ROS 1 population (less than 20%) reach OS longer than 2 years. Immunotherapy has demonstrated very promising results with more LS compared to chemotherapy in first and second line setting. In this study, we focused in the analysis of LS patients with advanced NSCLC EGFR wt (wild type) and ALK nt (non-translocated), defined as those with OS greater than 36 months, in 7 hospitals in Madrid. Methods: In this serie, first of all, we will try to make a clinical, histopathological characterization collecting data from clinical reports according to a previously defined information. In a second step, we will carry out a genetic analysis of these patient samples comparing to an opposite extreme short survivors (SS) samples (OS less than 9 months). Initially, we used a NGS method of RNA-seq technology to identify differentiating profiles of gene expression between the two opposite populations. And finally, we confirmed this preliminary profile by RT-PCR in the rest of samples. Results: Ninety-six patients were initially included. The majority were men, smokers or former with adenocarcinoma and ECOG 0- 1. We have obtained a differential transcriptome expression between samples from 6 LS and 6 SS, resulting 13 over-expressed and 42 down-expressed genes in LS comparing to SS transcriptome expression. Some of the genes involved in this initial profile belong to different cellular pathways: Secretin Receptor, Surfactant Protein, Trefoil Factor 1, Serpin Family, Ca-bindings Protein channel and Toll like Receptor family. Finally, we carried on by RT-PCR in 40 samples of SS and LS survivors and only four genes were significantly down-regulated in SS compared to LS in the multivariate analysis. These 4 genes were related to Surfactant Proteins: SFTPA1 (p = 0.023), SFTPA2 (p = 0.027), SFTPB (p = 0.02) and SFTPC (p = 0.047). Conclusions: We present a sequential genetic analysis of a LS population with NSCLC EGFR wt (wild type) and ALK nt (non-translocated), obtaining a differential RNA seq- and RT-PCR gene profile based on different surfactant proteins expression. A further confirmation in a larger sample is ongoing.

A Case of EGFR-wild-type Adenocarcinoma of Recurrent Non-small Cell Lung Cancer Responding to Erlotinib

Haigan ◽  
2012 ◽  
Vol 52 (3) ◽  
pp. 315-319
Author(s):  
Masami Morimoto ◽  
Naoki Hino ◽  
Hisashi Matsuoka ◽  
Takanori Miyoshi ◽  
Masaru Tsuyuguchi
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Wild Type ◽  
Small Cell Lung

Successful treatment of pulmonary lymphangitic carcinomatosis by anlotinib in 14 Chinese patients with advanced non-small cell lung cancer.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21064-e21064
Author(s):  
Shencun Fang ◽  
Wanwan Cheng ◽  
Yingming Zhang ◽  
Haitao Zhang ◽  
Si Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Lymphatic Metastasis ◽  
Small Cell ◽  
Smoking History ◽  
Wild Type ◽  
Small Cell Lung ◽  
The Impact ◽  
Lymphangitic Carcinomatosis

e21064 Background: Pulmonary lymphangitic carcinomatosis (PLC) occurs in 6%-8% of intrathoracic metastases among malignant tumor. The median survival was only 2.0 months from time of pulmonary symptoms to death in cases during 2000-2018, which is a poor prognosis. Effective interventions were needed besides standard chemotherapy and symptomatic support. Anlotinib showed a critical effect on lymphangiogenesis, and lymphatic metastasis in mouse models of lung adenocarcinoma, it might be a therapeutic option for tumor lymphatic metastasis. In this study, we retrospectively analyzed the efficacy and safety of anlotinib for PLC in patients with Non-small Cell Lung Cancer (NSCLC). Methods: We retrospectively investigated NSCLC patients with PLC at our hospital between May 2018 and November 2020, who received anlotinib monotherapy or combined therapy for PLC. Data were analyzed for progression-free survival (PFS), overall survival (OS), objective response rate(ORR), disease control rate(DCR) and adverse events (AE). The impact of clinical and genomic factors on PFS and OS were also assessed. Results: A total of 14 patients were enrolled with a median age of 64 years. 10(71.4%) were male, 4(28.6%) has smoking history, 10(71.4%) of patients had a performance status of 2-3. 9, 3, 2 patients had TP53 mutation, EGFR mutation, ALK fusion respectively. 9(64.3%) patients received anlotinib monotherapy. Of 14 patients, 8 achieved partial response (PR), 5 presented stable disease (SD), 1 had progressed disease. The ORR and DCR were 57.1% and 92.9% respectively. The median PFS was 3.1 months (95% CI: 2.0-4.2), the median OS for 1, 2, ≥3 line were 13 months, 7.2 months, 5.2 months, respectively. Median PFS and OS (≥3 line) were significantly longer for patients with TP53-mutant tumors compared with those with TP53–wild-type tumors (median PFS: 7 vs. 1.1 months, median OS (≥3 line): 6.8 vs. 1.9 months). No difference of PFS and OS (≥3 line) was found between EGFR or ALK alteration and the corresponding wild type patients. The most frequently reported AEs were high blood pressure (11, 78.6%), hand foot syndrome (6, 42.9%), diarrhea (5, 35.7%), fatigue (4, 28.6%), hoarseness (3, 21.4%), proteinuria (2, 14.3%) and stomatitis (2, 14.3%). Conclusions: Anlotinib presented favorable efficacy in patients with pulmonary lymphangitic carcinomatosis and conferred considerable survival benefit compared with previous studies, especially in patients harboring TP53 mutations. The AEs were manageable. These indicated that anlotinib can be a promising therapeutic treatment of PLC. More clinical data is needed to validate this finding.

scholarly journals 562 Real-world assessment of current treatment patterns and clinical outcomes among patients with EGFR and ALK wild type non-small cell lung cancer (NSCLC) in the US

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A591-A591
Author(s):  
Lyudmila Bazhenova ◽  
Jonathan Kish ◽  
Beilei Cai ◽  
Nydia Caro ◽  
Bruce Feinberg
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Treatment Patterns ◽  
Small Cell ◽  
Wild Type ◽  
Small Cell Lung ◽  
First Line ◽  
The Us ◽  
Nsclc Patients

BackgroundTreatment for advanced non-small cell lung cancer (NSCLC) has dramatically advanced in the past 5 years with the advent of immunotherapy (IO). This study sought to describe treatment patterns and clinical outcomes in a representative sample of NSCLC patients.MethodsPatients were identified by physicians from a voluntary sample of community practices across the US. Stage IIIB/IV NSCLC patients with EGFR/ALK wild-type initiating any first-line (1L) systemic therapy between 01/01/2016 and 12/31/2019 with at least 2 months of follow-up (unless deceased) were included, and were followed until November 2020. Sampling quotas included 250 patients who initiated 1L in 2016/2017 and 250 patients who did so in 2018/2019. Best tumor response was collected from patient charts during each line of therapy (LOT). Progression-free survival (PFS) and overall survival (OS) were calculated from initiation of 1L by Kaplan-Meier method. Baseline characteristics and clinical outcomes are described and presented by treatment regimen received.ResultsOf 500 submitted patients, 497 were included post QA/QC. Across all patients, mean age at 1L initiation was 65 years, 57.3% were male, 92.9% had stage IV disease, and 68.6% were ECOG-OS 0/1 (Table 1). Overall, 60.2% (n=299), 33.2% (n=165), and 6.6% (n=33) received 1, 2, or =3 LOTs during the study period. Most common 1L regimens (%) were platinum-doublet chemotherapy plus IO (PDC+IO) (40.6%), PDC (29.4%), IO monotherapy (20.7%), PDC+bevacizumab (6.2%); while most common 2L regimens were IO monotherapy (42.4%), single-agent chemotherapy (SAC) (18.2%), SAC+VEGF inhibitor (15.7%), PDC (8.1%), and PDC+bevacizumab (5.6%). Over 90% of pts who received IO monotherapy had PD-L1 >50%. Moving from 2016/2017 to 2018/2019, utilization of 1L PDC declined from 45.0% to 13.7% while utilization of 1L PDC+IO increased from 27.3% to 54.0%. Among those who received only one LOT (n=299), 44.5% were still on 1L, 14.0% stopped receiving 1L, and 41.5% were deceased. Overall response rates were 67.3%, 35.6%, 60.2%, and 61.3% for 1L PDC+IO, PDC, IO monotherapy, and PDC+bevacizumab, respectively (Table 1). First-line median PFS/OS (months) was 15.6/26.5, 5.3/13.7, 17.8/NR, and 10.8/18.6, respectively for PDC+IO, PDC, IO monotherapy, and PDC+bevacizumab (table 1).Abstract 562 Table 1ConclusionsData from 2016 to 2020 was used provide a contemporary assessment of treatment patterns among EGFR/ALK wild-type NSCLC patients. Although 1L treatment utilization shifted to IO-based regimens in recent years, 41.5% of patients did not survive to receive second-line therapy, 1L PFS did not exceed 1.5 years, and median OS remained limited across all 1L treatment groups.Ethics ApprovalOn August 20, 2020, Western Institutional Review Board (WIRB) approved a request for a waiver of authorization for use and disclosure of protected health information (PHI) for this research. The study is exempt under 45 CFR § 46.104(d)(4).

scholarly journals Micheliolide Enhances Radiosensitivities of p53-Deficient Non-Small-Cell Lung Cancer via Promoting HIF-1α Degradation

2020 ◽  
Vol 21 (9) ◽  
pp. 3392
Author(s):  
Peizhong Kong ◽  
K.N. Yu ◽  
Miaomiao Yang ◽  
Waleed Abdelbagi Almahi ◽  
Lili Nie ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Hypoxic Exposure ◽  
Dependent Manner ◽  
Wild Type ◽  
Small Cell Lung ◽  
H460 Cells ◽  
Wild Type P53

Micheliolide (MCL) has shown promising anti-inflammatory and anti-tumor efficacy. However, whether and how MCL enhances the sensitivity of non-small-cell lung cancer (NSCLC) to radiotherapy are still unknown. In the present paper, we found that MCL exerted a tumor cell killing effect on NSCLC cells in a dose-dependent manner, and MCL strongly sensitized p53-deficient NSCLC cells, but not the cells with wild-type p53 to irradiation (IR). Meanwhile, MCL markedly inhibited the expression of hypoxia-inducible factor-1α (HIF-1α) after IR and hypoxic exposure in H1299 and Calu-1 cells rather than in H460 cells. Consistently, radiation- or hypoxia-induced expression of vascular endothelial growth factor (VEGF) was also significantly inhibited by MCL in H1299 and Calu-1 cells, but not in H460 cells. Therefore, inhibition of the HIF-1α pathway might, at least in part, contribute to the radiosensitizing effect of MCL. Further study showed that MCL could accelerate the degradation of HIF-1α through the ubiquitin-proteosome system. In addition, the transfection of wild-type p53 into p53-null cells (H1299) attenuated the effect of MCL on inhibiting HIF-1α expression. These results suggest MCL effectively sensitizes p53-deficient NSCLC cells to IR in a manner of inhibiting the HIF-1α pathway via promoting HIF-1α degradation, and p53 played a negative role in MCL-induced HIF-1α degradation.

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