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Chinese Clinical Trial Registry ChiCTR-IPR-15006164.
Chinese Clinical Trial Registry ChiCTR-IPR-15006164.
To investigate the differences in treatment effect sizes between progression-free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) treated with programmed cell death 1 (PD-1) and its ligand (PD-L1) blockade-based treatments.
The differences in treatment effect sizes between PFS and OS were assessed by using a ratio of hazard ratio (rHR) the HR for PFS to that for OS. A random effects meta-analysis across trials was conducted to generate the combined rHR. momordin-Ic datasheet We also evaluated the feasibility of adopting PFS as the surrogate of OS by using Spearman correlation coefficient (
) between logHR
and logHR
.
A total of 27 randomized controlled trials (RCTs) with 15,590 patients were included. Treatment effect sizes were comparable, on average, for OS than for PFS (pooled rHR, 0.98; 95% CI, 0.91 to 1.08). Subgroup analysis revealed that treatment effect sizes were greater for OS than for PFS for trials with immunotherapy as second or above line treatment (rHR, 1.17; 95% CI,S in trials with immunotherapy as first-line setting, but PFS should be cautiously interpreted without OS data for trials with immunotherapy as second or above line treatment.
Although liver metastasis occurs in approximately 15% of metastatic non-small cell lung cancer (NSCLC) patients with poor prognosis, its prognostic effect in patients who receive immunotherapy is unclear. This study aimed to verify the effects of liver metastasis on the prognosis of metastatic NSCLC patients according to their first-line treatment.
Patients who were initially diagnosed with stage 4 NSCLC from January 2015 to December 2019 were analyzed in this retrospective real-world data-based study. The patients were divided into three groups according to the type of first-line chemotherapy they received cytotoxic, targeted, and immunotherapy. Prognosis was then compared depending on the presence of liver metastasis in each treatment group.
Among the 1,470 patients, 723 (49.2%) received cytotoxic chemotherapy, 678 (46.1%) received targeted therapy, and 69 (4.7%) received immunotherapy as their first-line chemotherapy. A total of 234 (15.9%) patients had liver metastasis at the initial diagnosis. The s who received immunotherapy.
Evidence of the clinical impact of programmed death-ligand 1 (PD-L1) expression in small cell lung cancer (SCLC) is scarce and conflicting, even though atezolizumab became the first PD-L1 inhibitor approved by the US Food and Drug Administration (FDA) in recent years for the initial treatment of extensive-stage (ES)-SCLC.
We investigated PD-L1 expression in SCLC tumors using the three validated PD-L1 immunohistochemistry (IHC) assays (SP263, SP142, and 22C3) and assessed the correlation between PD-L1 expression and clinicopathological factors to determine the prognostic value of PD-L1 expression. The three PD-L1 IHC analyses were prospectively used to assess tumor samples of patients with SCLC at diagnosis.
Of the total of 59 patients, 47 patients received the active treatment beyond platinum-based chemotherapy at our institution. PD-L1 expression was positive in 39.0% with SP263, 37.3% with SP142, and 22.0% with 22C3. In a univariate analysis, the positive result of at least one of the three PD-L1 assays and the positive result of the SP142 assay were associated with longer overall survival (OS). A multivariable analysis confirmed that performance status, stage, and the SP142 assay were independent predictors of OS. In subgroup analysis, these results revealed more significant prognostic factors in ES than in limited-stage (LS). In patients with SCLC, especially those with ES, the expression of the SP142 assay is a significant independent prognostic factor.
Although these results need to be further validated in larger cohorts, this information will benefit clinicians and patients in determining the immunotherapy for patients with ES-SCLC.
Although these results need to be further validated in larger cohorts, this information will benefit clinicians and patients in determining the immunotherapy for patients with ES-SCLC.
Lung cancer remains the major cause of cancer related death worldwide. The discovery of targeted therapies against activating mutations in genes like EGFR considerably improved the prognosis for a subgroup of patients but still leaves a large part without a targeted therapy. One carbon metabolism (1CM) has been investigated in several cancer entities and its increased activity has been linked to higher tumor aggressiveness and reduced prognosis. In spite of 1CM enzymes role and correlation to cancer cells progression, comprehensive analysis for the diagnostic and functional role of the complete 1CM enzymes in lung cancer has not been conducted so far.
We investigated the prognostic and functional relevance of five major 1CM factors (MTHFD2, PGDH3, SHMT2, MTHFD1 and TYMS) in the three major subclasses of lung cancer [pulmonary adenocarcinoma (AC), squamous cell lung cancer (SQCLC) and small cell lung cancer (SCLC)]. We analyzed 1CM enzymes expression and clinicopathological correlation in patient derived tapeutic strategy to surround pemetrexed resistance in AC.
Expression of MTHFD2 significantly reduces the prognosis of AC patients. Furthermore, MTHFD2 expression is crucial for survival of AC cell lines and its expression correlates with resistance against Pemetrexed. As MTHFD2 is almost not expressed in healthy adult tissue, we therefore suggest that the inhibition of MTHFD2 might be a potential therapeutic strategy to surround pemetrexed resistance in AC.
Immune checkpoint inhibitors (ICIs) are currently the standard therapy in advanced non-small cell lung cancer (NSCLC); however, there is no well-established prognostic biomarker. We investigated the relationship between survival outcomes and three peripheral blood biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), as well as a new score termed the risk blood biomarker (RBB), calculated from the combination of the neutrophil-monocyte-to-lymphocyte ratio (NMLR) and white blood cell count (WBC).
This study included patients with stage IV or recurrent NSCLC confirmed with programmed death ligand 1 (PD-L1) expression ≥50% who received pembrolizumab monotherapy as first-line treatment at the Virgen del Rocío University Hospital in Seville, Spain. To establish the relationship between baseline peripheral blood biomarkers and survival outcomes, progression free survival (PFS) and overall survival (OS), we used the Kaplan-Meierrvival outcomes and response to therapy.
Low baseline NLR, MLR and PLR are significantly associated with better PFS, and low baseline NLR and PLR are associated with better OS. Additionally, we identified three subgroups of patients using the RBB score, and low scores were associated with improved survival outcomes and response to therapy.
Malignant pleural effusion (MPE) portends a poor prognosis in non-small cell lung cancer (NSCLC). However, the yield of pleural fluid cytology as well as survival of patients with MPE associated with squamous cell carcinoma versus adenocarcinoma is not well understood. We conducted this study to assess the diagnostic yield of pleural cytology and survival of patients with NSCLC related MPE.
We performed a single-center, retrospective analysis of patients with NSCLC related MPE between 2010 and 2017. Kaplan-Meier method was used to compare survival and Cox proportional hazards analysis to assess if squamous cell cytopathology was associated with mortality.
We identified 277 patients, 29 with squamous cell and 248 with adenocarcinoma MPE. Pleural fluid cytology from initial thoracentesis was diagnostic in 13.8% (4/29) patients with squamous cell and 80.2% (199/248) with adenocarcinoma (P<0.001). Cytology from second thoracentesis was diagnostic in 13.3% (2/15) patients with squamous cell carcinoma, compared to 37.5% (12/32) with adenocarcinoma (P=0.17). There was no statistically significant difference in the pleural biopsy yield from medical pleuroscopy or video-assisted thoracoscopic surgery (VATS) in the two groups. The median survival of patients with squamous cell MPE was 112 [interquartile range (IQR) 44-220] days versus 194 (IQR 54-523) days in adenocarcinoma (Log-rank test P=0.04). Multivariate Cox proportional hazards analysis showed that squamous cell cytopathology was independent predictor of mortality (hazard ratio for death of 1.73, 95% CI 1.1-2.6; P=0.01).
Pleural fluid cytology has a low diagnostic yield in squamous cell carcinoma MPE, and these patients have a poor survival compared to lung adenocarcinoma.
Pleural fluid cytology has a low diagnostic yield in squamous cell carcinoma MPE, and these patients have a poor survival compared to lung adenocarcinoma.
Indication for sublobar resections in early-stage lung adenocarcinomas has been controversial. The purpose of this study was to find appropriate selection criteria for sublobar resections in ground glass opacity (GGO)-containing early-stage lung adenocarcinomas.
We retrospectively studied 985 consecutive patients with clinical stage IA, peripheral GGO-containing lung adenocarcinomas ≤3 cm in size. According to their radiological appearance, they were divided into a pure GGO group and a part-solid nodule (PSN) group. The PSN group was further divided into a GGO-predominant subgroup and a solid-predominant subgroup. Propensity-score matching (PSM) was conducted first in PSNs with similar total lesion size and then in those with similar solid component size to eliminate potential confounders. Histological characteristics and prognosis were compared between matched patients to investigate the prognostic value of total lesion size and solid component size. Then solid component size was chosen as the selection r after sublobar resections or lobectomy (95.0%
93.6%, P=0.592). The results remained similar for PSNs of total lesion size >2 cm but solid component size ≤2 cm (88.9%
90.0%, P=0.893).
Solid component size better predicts histological characteristics and prognosis than total lesion size in early-stage GGO-containing lung adenocarcinomas. Instead of total lesion size, solid component size ≤2 cm may be a more appropriate selection criterion for sublobar resections in such patients.
Solid component size better predicts histological characteristics and prognosis than total lesion size in early-stage GGO-containing lung adenocarcinomas. Instead of total lesion size, solid component size ≤2 cm may be a more appropriate selection criterion for sublobar resections in such patients.
Immunogenic cell death (ICD) characterized by the release of damage-associated molecular patterns (DAMPs) from dying cancer cells may contribute to the synergistic antitumor effect of cytotoxic chemotherapy combined with an immune checkpoint inhibitor. The kinetics of circulating DAMP levels in cancer patients have remained largely uncharacterized, however.
We evaluated the possible effects of various systemic anticancer therapy modalities on the kinetics of plasma DAMP concentrations in a prospective observational study of patients with advanced lung cancer. The plasma concentrations of high-mobility group box 1 (HMGB1), calreticulin (CRT), heat shock protein 70 (HSP70), annexin A1, and histone H3 were thus determined in 121 such patients at four time points during the first cycle of treatment.
The mean of the maximum fold change in HMGB1, HSP70, or annexin A1 concentration observed during treatment was significantly greater than the corresponding baseline value (P<0.005). The maximum fold changes in HMGB1 and CRT concentrations tended to be associated with clinical response as evaluated by RECIST criteria, although the changes in the levels of these two DAMPs were not correlated, suggestive of differential induction mechanisms.
