Immune Checkpoint Inhibitor for Non-small Cell Lung Cancer With Negative or Low Tumor PD-L1 Expression

2021 ◽  
Vol 1 (3) ◽  
pp. 173-177
Author(s):  
MINEHIKO INOMATA ◽  
NAOKI TAKATA ◽  
ISAMI MIZUSHIMA ◽  
KENJI AZECHI ◽  
KANA HAYASHI ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Cox Proportional Hazards Model ◽  
Small Cell Lung ◽  
Hazards Model

Background/Aim: We conducted a retrospective analysis of the survival durations of 25 patients diagnosed as having non-squamous cell non-small cell lung cancer with negative or low tumor programmed death-ligand 1 (PD-L1) expression treated with immune checkpoint inhibitor (ICI) monotherapy. Patients and Methods: The progression-free (PFS) and overall (OS) survival were calculated from the initiation of ICI monotherapy. The association between the patient characteristics and the PFS was analyzed using Cox proportional hazards model. Results: The median PFS was 2.6 months, and the 12-month PFS rate was 9.3%. The median OS was 5.5 months, and the 12-month OS rate was 39.8%. A Cox proportional hazards model identified the neutrophil/lymphocyte ratio and presence of liver metastasis as being significantly associated with PFS. Conclusion: Our findings suggest that a subset of patients with non-squamous cell non-small cell lung cancer who show negative or low tumor PD-L1 expression could benefit from ICI monotherapy.

scholarly journals Heregulin expression and its clinical implication for patients with EGFR-mutant non-small cell lung cancer treated with EGFR-tyrosine kinase inhibitors

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Kimio Yonesaka ◽  
Eiji Iwama ◽  
Hidetoshi Hayashi ◽  
Shinichiro Suzuki ◽  
Ryoji Kato ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Kinase Inhibitors ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Cox Proportional Hazards Model ◽  
Small Cell Lung ◽  
Hazards Model ◽  
Egfr Tkis

AbstractEpidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are standard therapy for EGFR-mutant non-small cell lung cancer (NSCLC). Preclinically, HER3 ligand heregulin induces resistance to EGFR-TKIs, whereas the pan-human EGFR family inhibitor afatinib remains effective. Here, we examined whether soluble heregulin levels have clinical implications for EGFR-mutant NSCLC treated with EGFR-TKIs. Soluble heregulin was immunologically measured in plasma from EGFR-mutant NSCLC patients. Cutoff values were determined by 1-year PFS ROC curve. The relationship between soluble heregulin and PFS following EGFR-TKI therapy was analyzed by Cox proportional hazards model. Seventy-three patients were enrolled: 44 were treated with 1st-generation and 29 with 2nd-generation EGFR-TKIs. Soluble heregulin levels varied (range: 274–7,138 pg/mL, median: 739 pg/mL). Among patients treated with 1st-generation EGFR-TKIs, those with high heregulin (n = 20, >800 pg/mL) had a tendency for shorter PFS than those with low heregulin (n = 24, <800 pg/mL), with median PFS of 322 and 671 days, respectively. Cox proportional hazards model also indicated a trend toward resistance against 1st-generation EGFR-TKIs (HR: 1.825, 95% CI: 0.865–4.318) but not against 2nd-generation EGFR-TKIs. Soluble heregulin potentially correlates with resistance to EGFR-TKIs but not 2nd-generation EGFR-TKIs in patients with EGFR-mutant NSCLC.

scholarly journals Analysis of Prognostic Factors of Patients with Small Cell Lung Cancer using Cox's Proportional Hazards Model.

Haigan ◽  
1993 ◽  
Vol 33 (7) ◽  
pp. 1011-1016
Author(s):  
Masahiko Takenaka ◽  
Noriaki Iwahashi ◽  
Takashi Nakano ◽  
Juichiro Maeda ◽  
Nobuyuki Aihara ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Small Cell ◽  
Small Cell Lung ◽  
Hazards Model ◽  
Cox's Proportional Hazards Model

scholarly journals Lobectomy Versus Segmentectomy in Patients with Stage T (>2 cm and ≤3 cm) N0M0 Non-small Cell Lung Cancer: A Propensity Score Matching Study

2020 ◽  
Author(s):  
Linlin Wang ◽  
Lihui Ge ◽  
Guofeng Zhang ◽  
Yi Ren ◽  
Yongyu Liu
Keyword(s):  
Lung Cancer ◽  
Propensity Score ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Seer Database ◽  
Regression Analyses ◽  
Small Cell Lung

Abstract Background: Whether lung segmentectomy is a safe and effective surgical treatment in patients with early non-small cell lung cancer (NSCLC) remains controversial. We have therefore reviewed the clinicopathologic characteristics and survival outcomes of patients receiving a lobectomy vs. segmentectomy to treat early T (>2 cm and ≤3 cm) N0M0 NSCLC.Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database for patients who underwent lobectomy or segmentectomy between 2004 and 2015. To reduce bias and imbalance between the treatment groups, propensity score matching (PSM) analysis was performed. We used Kaplan-Meier curves to estimate overall survival (OS) and lung cancer-specific survival (LCSS), performed univariate and multivariate Cox proportional hazards regression analyses to identify independent prognostic factors for OS and CSS, and applied the Cox proportional hazards model to create forest plots. Results: A total of 5783 patients from the SEER database were included. Of these, 5531 patients underwent lobectomy, and 252 patients underwent segmentectomy. Before matching, both univariate and multivariate Cox regression analyses showed that patients who underwent lobectomy had better OS (hazard ratio [HR]: 1.561; 95% confidence interval [CI] 1.292-1.885; P <0.001) and LCSS (HR: 1.551; 95% CI 1.198-2.009; P=0.001) than patients who underwent segmentectomy. However, survival differences between the groups were not significant; OS (P=0.160) and LCSS (P=0.097) after matching. Regression analyses revealed that age, sex, lymph node dissection, and grade were independent predictors of OS and LCSS (P <0.05).Conclusions: For patients with stage T (>2 cm and ≤3 cm) N0M0 non-small cell lung cancer, segmentectomy can achieve the same OS and LCSS compared with lobectomy. A large number of patients require further long-term follow-up analyses.

The incidence and predictors of new brain metastases in patients with non–small cell lung cancer following discontinuation of systemic therapy

2021 ◽  
pp. 1-11
Author(s):  
Dennis London ◽  
Dev N. Patel ◽  
Bernadine Donahue ◽  
Ralph E. Navarro ◽  
Jason Gurewitz ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Systemic Therapy ◽  
Recurrent Events ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Small Cell Lung

OBJECTIVE Patients with non–small cell lung cancer (NSCLC) metastatic to the brain are living longer. The risk of new brain metastases when these patients stop systemic therapy is unknown. The authors hypothesized that the risk of new brain metastases remains constant for as long as patients are off systemic therapy. METHODS A prospectively collected registry of patients undergoing radiosurgery for brain metastases was analyzed. Of 606 patients with NSCLC, 63 met the inclusion criteria of discontinuing systemic therapy for at least 90 days and undergoing active surveillance. The risk factors for the development of new tumors were determined using Cox proportional hazards and recurrent events models. RESULTS The median duration to new brain metastases off systemic therapy was 16.0 months. The probability of developing an additional new tumor at 6, 12, and 18 months was 26%, 40%, and 53%, respectively. There were no additional new tumors 22 months after stopping therapy. Patients who discontinued therapy due to intolerance or progression of the disease and those with mutations in RAS or receptor tyrosine kinase (RTK) pathways (e.g., KRAS, EGFR) were more likely to develop new tumors (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33–3.81, p = 2.5 × 10−3; HR 2.51, 95% CI 1.45–4.34, p = 9.8 × 10−4, respectively). CONCLUSIONS The rate of new brain metastases from NSCLC in patients off systemic therapy decreases over time and is uncommon 2 years after cessation of cancer therapy. Patients who stop therapy due to toxicity or who have RAS or RTK pathway mutations have a higher rate of new metastases and should be followed more closely.

Irinotecan in combination with platinum in refractory or relapsed small cell lung cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e18504-e18504
Author(s):  
Shufei Yu ◽  
Yan Wang
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Progression Free Survival ◽  
Small Cell ◽  
Hematologic Toxicity ◽  
Small Cell Lung ◽  
Cox's Regression

e18504 Background: To evaluate the efficacy and safety of irinotecan in combination with platinum against refractory or relapsed small cell lung cancer. Methods: In this retrospective study, we analyzed the data of 1,140 patients who diagnosed small cell lung cancer at our hospital between 2009 and 2012. Of all the patients, 34 were treated with irinotecan and nedaplatin (irinotecan 60mg/m2 on days 1,8 nedaplatin 85mg/m2 day 1,every 3 weeks), and 20 patients were treated with irinotecan and cisplatin (irinotecan 60mg/m2 on days 1,8 cisplatin 75mg/m2day 1,every 3 weeks ) as the second line treatment. Prognostic factors of overall survival (OS) were estimated by Kaplan-Meier and Cox's Regression-proportional hazards model. Results: Of 54 eligible patients, median progression free survival (PFS) was 21weeks, and median OS was 58 weeks. Median PFS was 23 weeks for irinotecan plus nedaplatin and 19 weeks for irinotecan plus cisplatin (P=0.410). Median OS was 62 weeks and 58 weeks, respectively (P=0.714).The response rate (RR) was 29% and 33.3%, respectively (HR 0.818,95%CI 0.234to2.855; P=0.753). In multivariate analysis, younger age, extensive stage while diagnosed, brain metastasis, treated with 3 cycles of irinotecan in combination with platinum or less, and PS≥1 were all associated with a statistically significant increase in the mortality harzard. Toxicity profile was slightly different for each of the arms: hematologic toxicity was higher with nedaplatin, and diarrhea was higher with cisplatin. Conclusions: Irinotecan plus platinum is effective and tolerable for refractory and relapsed small cell lung cancer. [Table: see text]

scholarly journals Interstitial lung abnormalities in patients with stage I non-small cell lung cancer are associated with shorter overall survival: the Boston lung cancer study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tomoyuki Hida ◽  
Akinori Hata ◽  
Junwei Lu ◽  
Vladimir I. Valtchinov ◽  
Takuya Hino ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Stage I ◽  
Small Cell Lung ◽  
Lung Abnormalities

Abstract Background Interstitial lung abnormalities (ILA) can be detected on computed tomography (CT) in lung cancer patients and have an association with mortality in advanced non-small cell lung cancer (NSCLC) patients. The aim of this study is to demonstrate the significance of ILA for mortality in patients with stage I NSCLC using Boston Lung Cancer Study cohort. Methods Two hundred and thirty-one patients with stage I NSCLC from 2000 to 2011 were investigated in this retrospective study (median age, 69 years; 93 males, 138 females). ILA was scored on baseline CT scans prior to treatment using a 3-point scale (0 = no evidence of ILA, 1 = equivocal for ILA, 2 = ILA) by a sequential reading method. ILA score 2 was considered the presence of ILA. The difference of overall survival (OS) for patients with different ILA scores were tested via log-rank test and multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) including ILA score, age, sex, smoking status, and treatment as the confounding variables. Results ILA was present in 22 out of 231 patients (9.5%) with stage I NSCLC. The presence of ILA was associated with shorter OS (patients with ILA score 2, median 3.85 years [95% confidence interval (CI): 3.36 – not reached (NR)]; patients with ILA score 0 or 1, median 10.16 years [95%CI: 8.65 - NR]; P <  0.0001). In a Cox proportional hazards model, the presence of ILA remained significant for increased risk for death (HR = 2.88, P = 0.005) after adjusting for age, sex, smoking and treatment. Conclusions ILA was detected on CT in 9.5% of patients with stage I NSCLC. The presence of ILA was significantly associated with a shorter OS and could be an imaging marker of shorter survival in stage I NSCLC.

Identification of a prognostic immune-related signature for small cell lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21041-e21041
Author(s):  
JUN WANG ◽  
Bicheng Zhang ◽  
Jianguo Sun ◽  
Jing Liang ◽  
Xiaolin Liu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Cancer Type ◽  
Small Cell Lung ◽  
Immune Related Genes ◽  
Testing Set

e21041 Background: As a subgroup of lung cancer, small cell lung cancer (SCLC) is characterized by a short tumor doubling time, high rates of early occurred distant cancer spread, and poor outcome. Despite its exquisite sensitivity to chemotherapy and radiotherapy, acquired drug resistance and tumor progression was impossibly avoided. This study aimed to develop a robust signature based on immune-related genes to predict the outcome of patients with SCLC. Methods: The expression data of 77 SCLC patients from George’s cohort were divided into training and testing set, and 1,534 immune-related genes from ImmPort database were used to generate and validate the signature. The Cox proportional hazards model was developed to determine the best gene model and construct the signature. The Kaplan-Meier survival analysis and Cox proportional hazards were used to test the prognostic significance of the signature. Results: A 10-genes model comprising NR3C1, NR1D2, TANK, ARAF, HDGF, INHBE, LRSAM1, PLXNA1, PML and SP1 with the highest frequency after 1,000 interactions, was chosen to construct an immune-related signature. This signature showed robust predictive value for SCLC patients’ survival in both training and testing set. This signature was closely associated with the activation of immune signal pathways, but not TNM stage. Furthermore, patients with high immune risk score presented with poor survival, whereas had high specific tumor-infiltrating immune cells such as NK CD56 bright cells. Conclusions: The present developed immune-related signature could predict the prognosis of SCLC patients, which to some extent reflect individual immune microenvironment phenotype in this highly lethal cancer type.

Therapeutic effect of cranial radiotherapy with or without anlotinib treatment for lung cancer patients with brain metastasis and non-EGFR/ALK-TKIs indication

2020 ◽  
Author(s):  
Zelai He ◽  
Jia Liu ◽  
Hongwei Li ◽  
Jing Qian ◽  
Zhen Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Factors ◽  
Brain Metastasis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Small Cell ◽  
Cox Proportional Hazards Model ◽  
Cranial Radiotherapy ◽  
Hazards Model

Abstract Background: Cranial radiotherapy (CRT) is the main treatment for lung malignant tumor with brain metastasis (BM) and lacking EGFR/ALK-TKIs indication. For non-small cell lung cancer with BM, anlotinib can improve progression free survival (PFS). We retrospectively analyzed the clinical effects of anlotinib + CRT versus CRT alone.Methods: In patients with lung cancer (adenocarcinoma, squamous carcinoma, or small cell carcinoma) with BM and non-EGFR/ALK-TKIs indication, the overall survival (OS) and PFS of anlotinib + CRT treatment versus CRT treatment alone were separately calculated and compared. The Cox proportional hazards model was used to analyze the independent prognostic factors for intracranial PFS (iPFS) and OS. All confounding factors were adjusted, including age, gender, Karnofsky Performance Status (KPS) score, smoking history, physiological characteristics, T/N stage, histology, metastases, and pathological characteristics. Subgroup analysis for iPFS and OS was performed to assess the effects on BM of treatment pattern.Results: The study included 100 patients with BM at baseline and the follow-up data. Of the 100 patients, 67 patients received CRT treatment alone and 33 patients received CRT + anlotinib treatment. The overall response rates of the CRT + anlotinib group and the CRT alone group were 90.91% and 83.58%, respectively. There was significantly more iPFS in the CRT + anlotinib group compared to CRT alone (median iPFS [miPFS]: 9.0 vs 3.0 months; hazard ratio [HR] 1.59; 95% confidence interval [CI] 1.01-2.52; p = 0.038). The OS, extracranial PFS (ePFS), and systematic PFS (sPFS) of CRT + anlotinib group were longer than those of the CRT alone group, but there was no significant statistical difference (median OS [mOS]: 9.0 vs 7.0 months, HR 1.17, 95% CI 0.74-1.85; median ePFS [mePFS]: 9.0 vs 7.0 months, HR 1.23, 95% CI 0.72-2.11; median sPFS [msPFS]: 7.0 vs 4.0 months, HR 1.37, 95% CI 0.82-2.30). The Cox proportional hazards model analysis revealed that age was an independent prognostic factor of iPFS (HR 1.65, 95% CI 1.05-2.59, p = 0.03). Age (HR 1.74, 95% CI 1.09-2.77, p = 0.02) and KPS score (HR 1.88, 95% CI 1.17-3.01, p = 0.01) were identified as independent prognostic factors of OS. Further subgroup analysis of iPFS showed that when the number of BM in the CRT + anlotinib group was less than or equal to three lesions (≤ 3), the miPFS (12.0 months) was significantly longer than that for CRT alone (> 3) (3.0 months), for CRT alone (≤ 3) (3.0 months), and for CRT + anlotinib (> 3) (7.0 months) (p = 0.014). The OS of the CRT + anlotinib group (≤ 3) (mOS 37.0 months) was much longer than that in CRT alone (> 3) (mOS 6.0 months), CRT alone (≤ 3) (mOS 7.5 months), and CRT + anlotinib (> 3) (mOS 8.5 months) groups, but this difference was not statistically significant (p = 0.051).Conclusion: Anlotinib can improve the survival of patients with lung cancer BM, with better efficacy of a combined treatment of anlotinib + CRT compared to that of CRT alone, especially for the iPFS of patients with BM ≤ 3.

scholarly journals MicroRNA-222 Expression and Its Prognostic Potential in Non-Small Cell Lung Cancer

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Kai-ping Mao ◽  
Wei-na Zhang ◽  
Xiao-min Liang ◽  
Yu-rong Ma
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Poor Prognosis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Small Cell ◽  
Expression Level ◽  
Small Cell Lung ◽  
Nsclc Tissue

Overexpression of miR-222 has been found in several types of cancers; however, the expression of miR-222 in non-small cell lung cancer (NSCLC) and its prognostic values are unclear. This study aimed to investigate whether the miR-222 expression level is related to clinicopathological factors and prognosis of NSCLC. Through a prospective study, 100 pairs of NSCLC tissues and adjacent normal tissues were examined by quantitative reverse-transcription polymerase chain reaction. The correlation between miR-222 expression and clinicopathological features was analyzed, and the significance of miR-222 as a prognostic factor and its relationship with survival were determined. Results showed that the expression levels of miR-222 were significantly elevated in the NSCLC tissue compared with that in adjacent normal tissue. In addition, Cox’s proportional hazards model analysis confirmed that miR-222 high expression level was an independent predictor of poor prognosis. In conclusion, miR-222 overexpression is involved in the poor prognosis of NSCLC and can be used as a biomarker for selection of cases requiring especial attention.

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