Venous thromboembolism among patients with advanced lung cancer randomized to prinomastat or placebo, plus chemotherapy

2003 ◽  
Vol 90 (10) ◽  
pp. 734-737 ◽  
Author(s):  
Rolando Ruiz ◽  
Carolyn Behrendt
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Venous Thromboembolism ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Univariate Analysis ◽  
Combined Treatment ◽  
Advanced Lung Cancer ◽  
Double Blind

SummaryTwo clinical trials have suggested that the combination of vascular endothelial growth factor inhibitor with chemotherapy is associated with venous thromboembolism (VTE). This retrospective cohort study investigates whether a similar association exists when matrix metalloproteinase inhibitor (prinomastat) is combined with chemotherapy.Patients (n=1,023) with stage IIIB, IV, or recurrent non-small cell lung cancer (NSCLC) were followed during 2 randomized, double-blind trials of prinomastat versus placebo orally bid, plus gemcitabine/cisplatin (GC) or paclitaxel/carboplatin (PC). VTE included deep venous thrombosis (DVT) or pulmonary embolism (PE) confirmed by imaging or autopsy. Risks identified in univariate analysis (incidence densities compared by t test) were confirmed in multivariate analysis (proportional hazards model).During 7,500.3 patient-months, 58 VTE (31 PE, 27 isolated DVT) were confirmed in 54 patients. On univariate analysis, VTE was associated with central venous catheter placed within 3 months,15 mg prinomastat plus GC, and to a lesser extent, 15 mg prinomastat plus PC, baseline performance status, and histologic type. VTE incidence was not increased by 15 mg prinomastat alone (post-discontinuation of chemotherapy), by chemotherapy plus placebo, or by 5 or 10 mg prinomastat plus chemotherapy. On multivariate analysis, VTE hazards (95% confidence interval) were 5.69 (2.61, 12.40) with recently placed central catheter, 2.78 (1.42, 5.43) with 15 mg prinomastat plus GC, and 2.06 (0.98, 4.31) with 15 mg prinomastat plus PC; performance status and histology were nonsignificant.We can conclude that combined treatment with 15 mg prinomastat plus chemotherapy approximately doubles the hazard of VTE among patients with advanced NSCLC.Research support: Pfizer Inc

Clusterin expression (CLU) as a prognostic marker in colorectal carcinoma (CCR).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 563-563
Author(s):  
Julia Alcaide ◽  
Antonio Rueda ◽  
Isabel Rodrigo ◽  
Teresa Tellez ◽  
Rafael Funez ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Normal Mucosa ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Staining Procedure ◽  
Positive Staining

563 Background: Increased CLU is involved in malignant progression and anticlusterin treatment with antisense oligonucleotides enhances apoptosis induced by several citotoxics. However, clinical significance of CLU expression in human CRCs has been scarcely studied. We investigated whether changes in CLU could be related to carcinogenesis and survival (sv) of CRC patients (pts). Methods: Formalin-fixed and paraffin-embedded specimens were examined from 31 adenomas and 103 CRCs resected at Costa del Sol Hospital. The study was approved by Research Ethics Committee. Immunohistochemistry using monoclonal anti-α chain clusterin antibody (Upstate-Millipore, Watford, England) was performed, following standard staining procedure. CLU was scored as negative (CLU–) (no staining) or positive (CLU +) (>10% of tumor cells with strong staining). Cytoplasmic CLU in tumors was evaluated for cancer cells only, and in normal mucosa for epithelial cells only. Sv curves were calculated and plotted according to Kaplan-Meier method. Predictors that were significant at p<0.10 in univariate analysis, were entered into a Cox proportional hazards model for multivariate analysis, remaining significant at p<0.05. Results: Median follow-up was 54 months. Median age was 70 years (45-91). TNM stage distribution was: I (13%), II (48%), III (25%) and IV (14%). Epithelial normal cells were always CLU-, but 16% (5/31) of adenomas was CLU+ and this percentage increased in CRCs (30%, 31/103). Positive staining always presented an apical cytoplasmic pattern. Recurrence was more frequent in CLU+ (61%,19/ 31) than in CLU- tumors (37%, 27/72) and CLU was significantly associated with lower disease-free survival (DFS) (p<0.05). In multivariate analysis, CLU and stage remained significant independent prognostic factors for DFS (Table). Conclusions: CLU has a role in colon carcinogenesis and prognostic value. CLU is associated with decreased DFS among pts with CRCs. These findings have important implications for identifying CRC pts with more aggressive tumors who may benefit from targeted therapy against clusterin. [Table: see text]

Advanced Lung Cancer Inflammation Index: Prognostic value in a retrospective lung cancer cohort.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21624-e21624
Author(s):  
Konstantinos N. Syrigos ◽  
Stavroula Patsilinakou ◽  
Dimitra Grapsa ◽  
Evangelia Chrysanthopoulou ◽  
Ioannis Gkiozos ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Prognostic Value ◽  
Performance Status ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Stage ◽  
Smoking History ◽  
Advanced Lung Cancer ◽  
Routine Practice ◽  
Cancer Inflammation

e21624 Background: As shown in recent studies, inflammation plays a key role in lung cancer (LC) pathogenesis and evolution, while the potential prognostic and predictive value of various inflammation markers in different disease stages is being extensively studied. We herein aimed to further evaluate the potential prognostic value of a new inflammation marker (ALI, Advanced Lung Cancer Inflammation Index = BMI x Alb / NLR), which combines previous markers of systematic inflammation with markers of nutrition or cachexia at the time of LC diagnosis. Methods: The medical records of 67 patients, diagnosed with LC in Sismanoglio Athens General hospital, within a two-year period (January 2016-January 2017) were retrospectively studied. Demographic, clinicopathological and laboratory features of patients, including pre-treatment ALI, were recorded and correlated with prognosis (overall survival, OS). Results: A total of 67 patients were included with a mean age of 60 (± 8) years. The majority of cases were men (39/67,58.2 %), with positive smoking history (62/67, 92.5%), performance status (PS) 1-2 (43/67, 64.2%) and disease stage IV (54/67, 80.6%). Adenocarcinoma was the commonest histological type observed (19/67, 28.5%). Values of ALI ranged from 7.8 to 37.2 (mean: 21±6). The cut-off point of ALI was 19 (based on ROC curve analysis) and patients were divided into two groups: those with ALI < 19 and those with ALI ≥ 19. In univariate analysis, PS and the presence of metastatic disease, as well as ALI values < 19, were all correlated with reduced survival (p = 0.002, p = 0.028 and p = 0.018, respectively). In multivariate analysis, PS was the only parameter that retained its statistically significant correlation with an adverse prognosis (p = 0.048), although its prognostic significance was increased when combined with ALI. Conclusions: Although failing to confirm an independent prognostic value for ALI, the results of our study suggest that combination of ALI with standard prognostic predictors such as PS may improve prediction of patients’ survival. Additional prospective studies are warranted to validate the prognostic significance of this promising biomarker and expand its use in routine practice.

scholarly journals Anorexia as a Risk Factor of Mortality in Patients with Advanced Lung Cancer Receiving Home-Base Palliative Care

2021 ◽  
Author(s):  
Jiaxin Cui ◽  
Lanhui Tan ◽  
Pei Fang ◽  
Zifen An ◽  
Jiayi Du ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Palliative Care ◽  
Cancer Patients ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Advanced Lung Cancer ◽  
Lung Cancer Patients ◽  
Home Based

Abstract Purpose To determine the prevalence of anorexia among advanced lung cancer patients at the beginning of receiving home-based palliative care and to examine the predictive role of anorexia in survival of patients with advanced lung cancer. Methods In this retrospective study, we analyzed data from 918 advanced lung cancer patients who had received home-based palliative care between March 2010 and March 2020. We used Kaplan-Meier survival curves to determine the factors associated with survival time and applied the Cox proportional hazards model to examine the effect of anorexia on survival. Results The study included 918 patients with a mean age of 63.5 years; and 72.2% of them were men. Factors associated with shortened survival included gender, place of residence, weight loss, anorexia, nausea and Karnofsky performance status (KPS). In a multivariable Cox proportional hazards model, after adjusting for male gender, patient lives in city, and low KPS, we found that anorexia was an independent negative predictor of survival. Conclusions As an independent factor predicting the survival of patients with advanced lung cancer, anorexia should be taken seriously by medical staff. This predictive factor may serve as early risk identification indicator for healthcare workers who provide home-based palliative care, thereby providing personalized palliative care for advanced lung cancer patients.

Analysis of the GERCOR index in KRAS Exon2 WT patients with mCRC treated with salvage-line cetuximab-based chemotherapy: HGCSG0901.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 781-781
Author(s):  
Ayumu Hosokawa ◽  
Satoshi Yuki ◽  
Hiroshi Nakatsumi ◽  
Kazuteru Hatanaka ◽  
Yasushi Tsuji ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Progression Free Survival ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Prognostic Impact ◽  
Significant Difference

781 Background: The GERCOR index (GI) based on performance status and serum LDH was reported to be useful to predict survival for patients with previously untreated mCRC. However, in the salvage setting, the validity of the GI has not been reported in patients treated with cetuximab (Cmab)-based chemotherapy. Methods: 269 patients with mCRC treated with Cmab contained chemotherapy were retrospectively registered from 27 centers in Japan. This analysis was included in the KRAS Exon2 wild type patients who were refractory to or intolerant of 5-FU / irinotecan/ oxaliplatin and were never administered anti-EGFR-antibody. Univariate and multivariate analysis for overall survival (OS) were performed using patient characteristics. Survival analyses were performed with the Kaplan-Meier method, log-rank test and the Cox proportional hazards model. The analysis was also designed to determine whether the GERCOR index could be extended to progression-free survival (PFS). Results: All data were available for prognostic categorization in 132 patients. Median OS and PFS were 9.8 and 4.3 months. The distribution and median OS / PFS for GI were as follows: low risk (L)(n = 28; 17.9/3.8 months), intermediate risk (I)(n = 52; 12.2/5.0 months), and high risk (H)(n = 52; 7.5/4.1 months). For OS, there was significant difference between L and H (p < 0.001) and between I and H (p < 0.001), but not between L and I (p = 0.076). For PFS, there was significant difference between I and H (p = 0.017), but not between L and I (p = 0.407), and between L and H (p = 0.222). In the Cox multivariate analysis, GI showed an independent prognostic impact (L vs. I ; HR 2.195, p=0.003 / L vs. H ; HR 4.028, p<0.001), but not predictive impact (L vs. I ; HR 0.987, p=0.958 / L vs. H ; HR 1.314, p=0.268). Conclusions: In this analysis, GI might be a prognostic factor in salvage treatment with Cmab-based chemotherapy.

Prognostic role of neutrophil-to-lymphocyte ratio (NLR) dynamics during first-line FOLFOXIRI in advanced pancreatic cancer (aPC).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15754-e15754
Author(s):  
Irene Pecora ◽  
Gianna Musettini ◽  
Silvia Catanese ◽  
Caterina Vivaldi ◽  
Giulia Pasquini ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Advanced Pancreatic Cancer ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
First Line ◽  
Poor Prognostic Factor

e15754 Background: Elevated pre-treatment NLR is a well-known poor prognostic factor in several tumours, including aPC. However, the role of NLR changes during first-line chemotherapy is less investigated. Methods: We retrospectively evaluated aPC patients (pts) treated with FOLFOXIRI (infusional 5-fluorouracil, oxaliplatin, irinotecan). NLR was calculated before the first (NLR-0) and the fourth (NLR-3) cycle, high NLR being defined as > 4. We evaluated the correlation between NLR change and overall survival (OS), progression-free survival (PFS), response rate (RR) and disease-control-rate (DCR). Survival curves were estimated using the Kaplan-Meier method. Log-rank and chi-square tests were applied. Multivariate analysis was performed by Cox proportional hazards model. Results: Ninety-four pts were evaluable. Median age was 62 years; at diagnosis, 38 (40.4%) pts had unresectable stage III and 56 (59.6%) had stage IV disease. In the overall population, median PFS (mPFS) and OS (mOS) were 8.0 and 12.9 months, respectively. NLR-0 was significantly associated with poor prognosis: among the 12 pts with NLR-0 > 4 mOS was 5.1 months compared with 13.5 months for the 82 pts with NLR-0 ≤4 (p < 0.001). As regards NLR dynamics, NLR-3 remained high or was increased (H/I) in 5 pts (5.3%) while was stably low or decreased (L/D) in 89 pts (94.7%). mOS was 5.1 months (95%CI 0.4-9.8) in H/I and 13.5 months (95%CI 10.9-16.1) in L/D (p < 0.001) pts. The same association was found for PFS, with 4.7 (95%CI 2.1-7.3) vs 8.3 months (95%CI 6.2-10.4, p = 0.004), respectively, but not for RR and DCR. At multivariate analysis, NLR change was confirmed as independent predictor of OS (HR 6.854, 95%CI 2.109-22.269, p = 0.001) and, when added to performance status, liver metastases and NLR-0, allowed a better risk stratification in good (no negative factors), intermediate (1-2 factors) and poor (3-4 factors) risk groups, with mOS of 18.0, 10.0 and 5.1 months, respectively (p = 0.012). Conclusions: Not only NLR-0, but also changes after 3 cycles of first-line FOLFOXIRI could predict OS in aPC pts. Early variations in NLR might be a cheap, reproducible and useful factor to predict prognosis and to better refine treatment strategy.

scholarly journals Advanced Lung Cancer Inflammation Index Predicts Survival Outcomes of Patients With Oral Cavity Cancer Following Curative Surgery

2021 ◽  
Vol 11 ◽  
Author(s):  
Yao-Te Tsai ◽  
Cheng-Ming Hsu ◽  
Geng-He Chang ◽  
Ming-Shao Tsai ◽  
Yi-Chan Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Multivariate Analysis ◽  
Oral Cavity ◽  
Proportional Hazards Model ◽  
Disease Free Survival ◽  
Cox Proportional Hazards Model ◽  
Advanced Lung Cancer ◽  
Survival Outcomes ◽  
Curative Surgery ◽  
Cancer Inflammation

AimThe aim of our study was to investigate the prognostic value of preoperative advanced lung cancer inflammation index (ALI) and to establish prognostic nomograms for the prediction of survival outcomes in patients with oral cavity squamous cell carcinoma (OSCC).Materials and MethodsA total of 372 patients who received primary curative surgery for OSCC during 2008–2017 at a tertiary referral center were enrolled. We used the receiver operating characteristic curve to determine the optimal cutoff point of ALI. Through a Cox proportional hazards model and Kaplan–Meier analysis, we elucidated the ALI–overall survival (OS) and ALI–disease-free survival (DFS) associations. Prognostic nomograms based on ALI and the results of multivariate analysis were created to predict the OS and DFS. We used the concordance indices (C-indices) and calibration plots to assess the discriminatory and predictive ability.ResultsThe results revealed that the ALI cutoff was 33.6, and 105 and 267 patients had ALI values of &lt;33.6 and ≥33.6, respectively. ALI &lt; 33.6 significantly indicated lower OS (44.0% vs. 80.1%, p &lt; 0.001) and DFS (33.6% vs. 62.8%; p &lt; 0.001). In multivariate analysis, ALI &lt; 33.6 was independently associated with poor OS and DFS (both p &lt; 0.001). The C-indices of established nomograms were 0.773 and 0.674 for OS and DFS, respectively; moreover, the calibration plots revealed good consistency between nomogram-predicted and actual observed OS and DFS.ConclusionALI is a promising prognostic biomarker in patients undergoing primary surgery for OSCC; moreover, ALI-based nomograms may be a useful prognostic tool for individualized OS and DFS estimations.

Multivariate analysis including biomarkers in the phase III RADIANT-2 study of octreotide LAR plus everolimus (E+O) or placebo (P+O) among patients with advanced neuroendocrine tumors (NET).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4014-4014 ◽  
Author(s):  
James C. Yao ◽  
John D. Hainsworth ◽  
Edward M. Wolin ◽  
Marianne E. Pavel ◽  
Eric Baudin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Univariate Analysis ◽  
Primary Site ◽  
Cox Proportional Hazards Model ◽  
Bone Involvement ◽  
Phase Iii ◽  
Rank Test

4014 Background: In this large phase III trial, median progression-free survival (PFS) improved by 5.1 mo with E+O compared to P+O in patients (pts) with NET associated with carcinoid syndrome. Baseline imbalances including WHO performance status (PS) and primary site favoring P+O confounded primary analysis. Chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) are important biomarkers in NET. Analyses were performed to identify prognostic factors and adjust for baseline imbalances. Methods: Pts were randomized to E+O (n=216) or P+O (n=213). Potential prognostic factors including baseline CgA (≤2×ULN vs >2×ULN), baseline 5-HIAA (≤median vs >median at baseline), age (<65 vs ≥65), gender, race, WHO PS (0 vs 1, 2), primary site (lung vs other), prior somatostatin analog use (yes vs no), duration from diagnosis (<6 mo, 6-24 mo, 2-5 yr, >5 yr), and organs involved (liver, bone) were assessed in univariate analysis using the log rank test and stepwise regression using Cox proportional hazards model. Results: Median PFS (mo) was significantly longer for pts with nonelevated CgA (27 vs 11; p<.001) and nonelevated 5-HIAA (17 vs 11; p<.001). Analyses also indicated age (14 vs 12; p=.01), WHO PS (17 vs 11; p=.004), liver involvement (14 vs not reached; p=.02), bone metastases (8 vs 15; p<.001), and lung as primary site (11 vs 14; p=.06) as potentially prognostic. Multivariate analysis indicated that significant prognostic factors for PFS included baseline CgA (HR, 0.47; CI, 0.34-0.65; p<.001), WHO PS (HR, 0.69; CI, 0.52-0.90; p=.006), bone involvement (HR, 1.52; CI, 1.06-2.18; p=.02), and lung as primary site (HR, 1.55; CI, 1.01-2.36; p=.04). Adjusted for covariates, a 38% reduction in risk of progression was observed for E+O (HR, 0.62; 95% CI, 0.51-0.87; p=.003). Conclusions: In the phase III RADIANT-2 trial, baseline CgA levels, WHO PS, lung as primary site, and bone involvement were important prognostic factors. Exploratory analysis adjusted for these prognostic factors indicated significant benefit of everolimus therapy.

Multivariate analysis including biomarkers in the phase III RADIANT-2 study of octreotide LAR plus everolimus (E+O) or placebo (P+O) among patients with advanced neuroendocrine tumors (NET).

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 157-157 ◽  
Author(s):  
James C. Yao ◽  
John D. Hainsworth ◽  
Edward M. Wolin ◽  
Marianne E. Pavel ◽  
Eric Baudin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Proportional Hazards Model ◽  
Performance Status ◽  
Univariate Analysis ◽  
Primary Site ◽  
Cox Proportional Hazards Model ◽  
Bone Involvement ◽  
Phase Iii ◽  
Rank Test

157 Background: In this large phase III trial, median progression-free survival (PFS) improved by 5.1 mo with E+O compared to P+O in patients (pts) with NET associated with carcinoid syndrome. Randomization imbalances including WHO performance status (PS), and primary site favoring P+O confounded primary analysis. Chromogranin A (CgA) and 5-hydroxyindoleacetic acid (5-HIAA) are important biomarkers in NET. Analyses were performed to identify prognostic factors and adjust for randomization imbalances. Methods: Pts were randomized to E+O (n=216) or P+O (n=213). Potential prognostic factors including baseline CgA (≤2×ULN vs >2×ULN), baseline 5-HIAA (≤median vs >median), age (<65 vs ≥65), gender, race, WHO PS (0 vs 1, 2), primary site (lung vs other), prior somatostatin analog use (yes vs no), duration from diagnosis (<6 mo, 6-24 mo, 2-5 yr, >5 yr), and organs involved (liver, bone) were assessed in univariate analysis using the log rank test and a stepwise regression using Cox proportional hazards model. Results: Randomization resulted in significant imbalance in baseline CgA (median [ng/mL], 251 E+O vs 137 P+O). Median PFS (mo) was significantly longer for pts with nonelevated CgA (27 vs 11; P<.001) and nonelevated 5-HIAA (17 vs 11; P<.001). Analyses also indicated age (14 vs 12; P=.01), WHO PS (17 vs 11; P=.004), liver involvement (14 vs not reached; P=.02), bone metastases (8 vs 15; P<.001), and lung as primary site (11 vs 14; P=.06) as potentially prognostic. Multivariate analysis indicated that significant prognostic factors for PFS included baseline CgA (HR, 0.47; CI, 0.34-0.65; P<.001), WHO PS (HR, 0.69; CI, 0.52-0.90; P=.006), bone involvement (HR, 1.52; CI, 1.06-2.18; P=.02), and lung as primary site (HR, 1.55; CI, 1.01-2.36; P=.04). Adjusted for covariates, a 38% reduction in risk of progression was observed for E+O (HR, 0.62; 95% CI, 0.51-0.87; P=.003). Conclusions: In the phase III RADIANT-2 trial, baseline CgA levels, WHO PS, lung as primary site, and bone involvement were important prognostic factors. Exploratory analysis adjusted for these prognostic factors indicated significant benefit for everolimus therapy.

Predictive Factors for the Development of Dyspnea Within 7 Days After Admission Among Terminally Ill Cancer Patients

2021 ◽  
pp. 104990912110288
Author(s):  
Ryo Matsunuma ◽  
Takashi Yamaguchi ◽  
Masanori Mori ◽  
Tomoo Ikari ◽  
Kozue Suzuki ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Predictive Factors ◽  
Performance Status ◽  
Univariate Analysis ◽  
Terminally Ill ◽  
Primary Lung Cancer ◽  
Poor Performance Status ◽  
Terminally Ill Cancer Patients ◽  
Development Group

Background: Predictive factors for the development of dyspnea have not been reported among terminally ill cancer patients. Objective: This current study aimed to identify the predictive factors attributed to the development of dyspnea within 7 days after admission among patients with cancer. Methods: This was a secondary analysis of a multicenter prospective observational study on the dying process among patients admitted in inpatient hospices/palliative care units. Patients were divided into 2 groups: those who developed dyspnea (development group) and those who did not (non-development group). To determine independent predictive factors, univariate and multivariate analyses using the logistic regression model were performed. Results: From January 2017 to December 2017, 1159 patients were included in this analysis. Univariate analysis showed that male participants, those with primary lung cancer, ascites, and Karnofsky Performance Status score (KPS) of ≤40, smokers, and benzodiazepine users were significantly higher in the development group. Multivariate analysis revealed that primary lung cancer (odds ratio [OR]: 2.80, 95% confidence interval [95% CI]: 1.47-5.31; p = 0.002), KPS score (≤40) (OR: 1.84, 95% CI: 1.02-3.31; p = 0.044), and presence of ascites (OR: 2.34, 95% CI: 1.36-4.02; p = 0.002) were independent predictive factors for the development of dyspnea. Conclusions: Lung cancer, poor performance status, and ascites may be predictive factors for the development of dyspnea among terminally ill cancer patients. However, further studies should be performed to validate these findings.

scholarly journals Expanded human NK cells from lung cancer patients sensitize patients’ PDL1−negative tumors to PD1-blockade therapy

2021 ◽  
Vol 9 (1) ◽  
pp. e001933
Author(s):  
Sophie M Poznanski ◽  
Tyrah M Ritchie ◽  
Isabella Y Fan ◽  
Abdullah El-Sayes ◽  
Ana L Portillo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Microenvironment ◽  
Nk Cells ◽  
Tumor Regression ◽  
Checkpoint Inhibitors ◽  
Combined Treatment ◽  
Death Receptor ◽  
High Rate ◽  
Advanced Lung Cancer ◽  
Pd1 Blockade

Lung cancer remains the leading cause of cancer death worldwide despite the significant progress made by immune checkpoint inhibitors, including programmed death receptor-1 (PD1)/PD ligand 1 (PDL1)-blockade therapy. PD1/PDL1−blockade has achieved unprecedented tumor regression in some patients with advanced lung cancer. However, the majority of patients fail to respond to PD1/PDL1 inhibitors. The high rate of therapy non-response results from insufficient PDL1 expression on most patients’ tumors and the presence of further immunosuppressive mechanisms in the tumor microenvironment. Here, we sensitize non-responding tumors from patients with lung cancer to PD1-blockade therapy using highly cytotoxic expanded natural killer (NK) cells. We uncover that NK cells expanded from patients with lung cancer dismantle the immunosuppressive tumor microenvironment by maintaining strong antitumor activity against both PDL1+ and PDL1− patient tumors. In the process, through a contact-independent mechanism involving interferon γ, expanded NK cells rescued tumor killing by exhausted endogenous TILs and upregulated the tumor proportion score of PDL1 across patient tumors. In contrast, unexpanded NK cells, which are susceptible to tumor-induced immunosuppression, had no effect on tumor PDL1. As a result, combined treatment of expanded NK cells and PD1-blockade resulted in robust synergistic tumor destruction of initially non-responding patient tumors. Thus, expanded NK cells may overcome the critical roadblocks to extending the prodigious benefits of PD1-blockade therapy to more patients with lung cancer and other tumor types.

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