Neutrophil‐to‐lymphocyte ratio (NLR) is associated with poor prognosis in patients with lung cancer, but the predictive role of NLR on the risk of developing lung cancer is unknown. We investigated ...the association between NLR and lung cancer mortality in lung cancer‐free adults. A cohort study was performed with 527,124 Korean adults who were free of lung cancer and were followed for up to 16 years. Vital status and lung cancer‐related deaths were ascertained through national death records. Hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer mortality were estimated using a Cox proportional hazards model. During 4,567,495.8 person‐years of follow‐up, 574 lung cancer deaths were identified. A higher NLR was positively associated with lung cancer mortality. The multivariable‐adjusted HR (95% CI) for lung cancer mortality comparing quintiles 2, 3, 4 and 5 of NLR to the lowest quintile were 1.26 (0.96–1.67), 1.23 (0.93–1.63), 1.33 (1.01–1.75) and 1.47 (1.13–1.92), respectively. The highest risk of lung cancer mortality was also observed in the highest NLR quintile among never‐smokers and low‐risk individuals after adjusting for lung function and other possible confounders. Platelet‐to‐lymphocyte ratio showed an inverse J‐shaped association with lung cancer mortality in men but the trends in women, low‐risk individuals or never‐smokers were neither linear nor U‐shaped. In this large cohort of young and middle‐aged individuals, NLR was independently associated with increased risk of lung cancer mortality in low‐risk individuals, indicating a role of systemic inflammation in lung cancer mortality in our study population.
What's new?
Neutrophil‐to‐lymphocyte ratio (NLR) is associated with poor prognosis in patients with lung cancer, but the predictive role of NLR on the risk of developing lung cancer is unknown. Here, the authors investigated the association between NLR and lung cancer mortality in a large prospective cohort study of 527,124 cancer‐free adults. The study reveals the association of elevated NLR with increased risk of lung cancer mortality, which was consistently observed in both never‐smokers and low‐risk individuals. NLR, a systemic inflammation marker, may thus play a role as an independent predictor of lung cancer mortality in never‐smokers as well as low‐risk populations.
Background
KEYNOTE‐063 (NCT03019588) investigated pembrolizumab versus paclitaxel as second‐line therapy in Asian patients with advanced programmed death ligand 1 (PD‐L1)–positive (combined positive ...score ≥1) gastric/gastroesophageal junction (GEJ) cancer.
Methods
This randomized, open‐label, phase 3 study was conducted at 36 medical centers in China (mainland), Malaysia, South Korea, and Taiwan. Patients were randomly assigned 1:1 to 200 mg of pembrolizumab intravenously every 3 weeks for ≤2 years or 80 mg/m2 of paclitaxel intravenously every week. Primary end points were overall survival (OS) and progression‐free survival (PFS). Secondary end points were objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 and safety.
Results
Between February 16, 2017, and March 12, 2018, 94 patients were randomly assigned (47 pembrolizumab/47 paclitaxel) after screening; enrollment was stopped on March 12, 2018, based on the results of the global KEYNOTE‐061 study, and patients were followed until the last patient's last visit. Median OS was 8 months (95% confidence interval CI, 4‐10 months) with pembrolizumab versus 8 months (95% CI, 5‐11 months) with paclitaxel (hazard ratio HR, 0.99; 95% CI, 0.63‐1.54). Median PFS was 2 months (95% CI, 1‐3 months) with pembrolizumab versus 4 months (95% CI, 3‐6 months) with paclitaxel (HR, 1.62; 95% CI, 1.04‐2.52). ORR was 13% for pembrolizumab versus 19% for paclitaxel. Any‐grade treatment‐related adverse events occurred in 28 pembrolizumab‐treated patients (60%) and 42 paclitaxel‐treated patients (96%); grades 3 to 5 events occurred in 5 patients (11%) and 28 patients (64%), respectively.
Conclusions
Definitive conclusions about the efficacy of second‐line pembrolizumab in Asian patients with advanced PD‐L1–positive gastric/GEJ cancer are limited because of insufficient power, but pembrolizumab was well tolerated in this patient population. Efficacy followed a trend similar to that observed in the phase 3 KEYNOTE‐061 trial.
In this small sample of Asian patients with advanced PD‐L1–positive (combined positive score CPS ≥1) gastric/gastroesophageal junction (GEJ) cancer enrolled in the randomized, open‐label, phase 3 KEYNOTE‐063 study, definitive conclusions on clinical outcomes are limited; however, second‐line pembrolizumab monotherapy seems to be well tolerated in this patient population. These findings are consistent with those of the larger global KEYNOTE‐061 study in patients with CPS ≥1 gastric/GEJ cancer.
Abstract
Context
It has been unclear whether the risk of pancreatic cancer is different according to glucose levels.
Objective
To determine the association between fasting glucose levels and ...pancreatic cancer risk using prospectively collected nationwide population-based cohort data in Korea.
Design
The National Health Insurance Service database of claims and preventive health check-up data recorded was used between 2009 and 2015.
Setting and Participants
A total of 25.4 million patients who had participated in a preventive health check-up between 2009 and 2013 were evaluated for pancreatic cancer incidence rates according to fasting glucose level.
Main Outcomes Measures
The cumulative incidence rate for pancreatic cancer was calculated after grouping according to fasting glucose levels as follows: (i) low normal (<90 mg/dL), (ii) high normal (90 to 99 mg/dL), (iii) prediabetes level 1 (100 to 109 mg/dL), (iv) prediabetes level 2 (110 to 125 mg/dL), (v) diabetes (≥126 mg/dL), and (vi) diabetes on anti-diabetic medications.
Results
The 5-year cumulative incidence rates (per 100,000) were as follows: (i) low normal = 32; (ii) high normal = 41; (iii) prediabetes level 1 = 50; (iv) prediabetes level 2 = 64; (v) diabetes = 75; and (vi) on anti-diabetic medications = 121. The risk of pancreatic cancer increased continuously with elevating fasting glucose levels (P < 0.0001). The incidence of pancreatic cancer increased significantly with increasing fasting blood glucose levels even after adjusting for age, sex, smoking, drinking, exercise, body mass index, and diabetes duration (P < 0.0001).
Conclusions
The cumulative incidence rate of pancreatic cancer significantly increased as the fasting glucose level elevated, even in populations with a normal glucose level range.
As the fasting glucose level elevated, the incidence of pancreatic cancer significantly increased, not only in diabetic populations but also in those with prediabetes or normal glucose levels.
Abstract
In this multi-center phase II trial, we evaluated the efficacy and safety of a quadruplet regimen (pembrolizumab, trastuzumab, and doublet chemotherapy) as first-line therapy for ...unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC) (NCT02901301). The primary endpoints were recommended phase 2 dose (RP2D) for phase Ib and objective response rate (ORR) for phase II. The secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response, time to response and safety. Without dose-limiting or unexpected toxicities, the starting dose in the phase Ib trial was selected as RP2D. In 43 patients, the primary endpoint was achieved: the objective response rate was 76.7% (95% confidence interval CI: 61.4–88.2), with complete and partial responses in 14% and 62.8% of patients, respectively. The median progression-free survival, overall survival, and duration of response were 8.6 months, 19.3 months, and 10.8 months, respectively. No patients discontinued pembrolizumab because of immune-related adverse events. Programmed death ligand-1 status was not related to survival.
Post hoc
analyses of pretreatment tumor specimens via targeted sequencing indicated that
ERBB2
amplification, RTK/RAS pathway alterations, and high neoantigen load corrected by HLA-B were positively related to survival. The current quadruplet regimen shows durable efficacy and safety for patients with HER2-positive AGC.
Background
Ramucirumab improves survival in gastric cancer patients. The efficacy and safety of ramucirumab outside of a clinical trial were evaluated using an expanded access program (EAP).
Methods
...Advanced gastric cancer patients treated with ramucirumab in combination with paclitaxel or with ramucirumab monotherapy in a Korean EAP were evaluated. Baseline characteristics were assessed for progression-free survival (PFS) and overall survival (OS), and adverse events were evaluated according to the treatment regimen.
Results
Of 265 patients, 228 received ramucirumab plus paclitaxel, and 37 received ramucirumab monotherapy. Grade 3 or 4 neutropenia was more common with ramucirumab plus paclitaxel than with ramucirumab monotherapy (46.7 vs. 8.1%). Gastrointestinal (GI) perforation developed in seven patients (3.1%) in the ramucirumab plus paclitaxel group. The overall response and disease control rates were 16.6 and 66.3% in the ramucirumab plus paclitaxel group, and 5.4 and 37.8% in the ramucirumab monotherapy group, respectively. PFS and OS were 3.8 and 8.6 months in the ramucirumab plus paclitaxel group, and 1.8 and 6.4 months in the ramucirumab monotherapy group, respectively. In multivariate analysis, alkaline phosphatase, albumin, and neutrophil-to-lymphocyte ratio (NLR) were the independent prognostic factors for PFS, while albumin, NLR, number of metastatic sites, and large amount of ascites were independent prognostic factors for OS.
Conclusion
In the Korean EAP cohort, ramucirumab showed similar efficacy to the results of the previous trials for gastric cancer. However, the level of GI perforation was slightly increased in the ramucirumab plus paclitaxel group.
Fentanyl buccal tablets (FBTs) are a rapid-onset opioid indicated for breakthrough cancer pain (BTcP) and FBT titration is needed to optimize BTcP management. We aimed to predict which patients could ...tolerate a high dose of FBT (400 μg or more at a time).
A retrospective analysis was performed to assess the final FBT dose. The final FBT doses were compared according to the clinical features. The prediction accuracy of patients tolerant of 400 μg or higher FBT was compared using the area under the receiver operating characteristic (ROC) curves. A risk scoring model based on the odds ratio (OR) was developed from the final multivariable model, and patients were assigned into two groups: low tolerance (0-1 point) and high tolerance (2-3 points).
Among 131 patients, the most frequently effective dose of FBT was 200 μg (54%), followed by 100 μg (30%). The median value of morphine equivalent daily doses (MEDD) was 60 mg/day, and the most common daily use was 3-4 times/day. In multivariable analysis, male sex, younger age, and use of FBTs three or more times per day were independently associated with high-dose FBT. According to the risk scoring model, the patients with a final FBT of 400 μg or higher were significantly more in the high tolerance group (17%) compared to the low tolerance group (3%; p = 0.023).
According to the dose relationship between the final FBT dose and the clinical features, three factors (sex, age, daily use of FBT) were independently associated with the final dose of FBT. Our risk score model could help predict tolerance to high-dose FBT and guide the titration plan for BTcP.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Aim
Radiofrequency ablation (RFA) has been increasingly used for the treatment of pulmonary metastases in various malignancies.
Methods
A retrospective analysis was performed to establish ...the safety and efficacy of cone‐beam computed tomography (CBCT)‐guided RFA in patients with metastatic colorectal cancer between 2016 and 2019, and the prognostic factors of local tumor control were assessed.
Results
A total of 31 patients with colorectal cancer underwent 48 sessions of lung RFA. The mean diameter of metastases targeted for RFA was 11 mm (range: 4–32), and the RFA was technically successful in 43 sessions (90%). There were 14 complications (29%), the majority of which required no intervention, with no cases of mortality. The median follow‐up duration from RFA in the surviving 29 patients was 18.0 months. Only two patients (6%) died of disease progression, and the 3‐year overall survival rate was 91% (95% CI: 83–99). Local tumor progression (LTP) of the RFA site was observed in 27%, and the LTP‐free survival rates at 1 and 2 years were 81% (95% CI: 70–82) and 64% (95% CI: 50–77), respectively. Multivariate analysis showed that the progression of extra‐RFA sites and the presence of extrapulmonary metastasis were independent prognostic factors significantly associated with LTP at RFA site.
Conclusion
Lung RFA using CBCT guidance is a comparatively safe and effective option for the treatment of lung metastases from colorectal cancer. However, the control of extrapulmonary metastases should be accompanied by combined or sequential systemic treatment and local treatment.
Abstract Objective This study aims to comprehensively assess the publication of clinical trial results and factors associated with their publication. Study Design and Setting Phase II and phase III ...trials of advanced breast cancer registered on ClinicalTrials.gov between October 1, 2000, and September 30, 2012 were identified. Publications were searched by using PubMed and reviewing those listed on the registry site. The main outcomes were publication rate, public availability of results, and time to publication. Results Of 352 phase II and 74 phase III trials, 12.5% and 31.1% were published, while 46.9% and 58.1% had publicly available results, respectively. Compared to those with significant results, studies with non-significant results had delays in time to publication ( P < 0.001). Even after adjusting for funding source and phase type, the significance of study outcomes was a significant factor that affected time to publication (hazard ratio = 6.02, 95% CI, 3.59-10.07; P < 0.001), with trials with significant outcomes taking less time to publish than those with non-significant outcomes. Conclusion Underreporting of results and non-publication or delays in the publication of negative results were identified in registered trials of advanced breast cancer. Thus, further initiatives appear necessary to urgently address such publication bias.
Progranulin (PGRN) is known to promote tumorigenesis and proliferation of several types of cancer cells. However, little is known about the clinicopathological features of patients with ...gastrointestinal stromal tumors (GISTs) with regard to PGRN expression.
A retrospective analysis was performed on patients with GISTs who underwent curative surgical resection between 2007 and 2017. PGRN expression was evaluated by immunohistochemical (IHC) analysis and semi-quantitatively categorized (no expression, 0; weak, 1+; moderate, 2+; strong, 3+). Tumors with a staining intensity of 2+ or 3+ were considered high PGRN expression.
Fifty-four patients were analyzed; 31 patients (57%) were male. The median age at surgery was 60 years (range, 33-79), and the most common primary site was the stomach (67%). Thirty-five patients (65%) had spindle histology; 42 patients (78%) were separated as a high-risk group according to the modified National Institutes of Health (NIH) classification. High PGRN-expressing tumors were observed in 27 patients (50%), had more epithelioid/mixed histology (68% vs. 32%; p = 0.046), and KIT exon 11 mutations (76% vs. 24%; p = 0.037). Patients with high PGRN-expressing tumors had a worse recurrence-free survival (RFS) (36% of 5-year RFS) compared to those with low PGRN-expressing tumors (96%; p<0.001). Multivariate analysis showed that high PGRN expression and old age (>60 years) were independent prognostic factors for poor RFS.
High PGRN-expressing GISTs showed more epithelioid/mixed histology and KIT exon 11 mutations. PGRN overexpression was significantly associated with poor RFS in patients with GISTs who underwent curative resection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The role of sodium caprate (C10) in enhancing drug absorption is well established; however, little information is available on its role as an anticancer drug. This study aimed to evaluate the ...anticancer effect of C10 in gastric cancer cells. The mechanism of cytotoxicity of C10 was evaluated by western blotting following treatment of the gastric cancer cells with various concentrations of C10. C10 cytotoxicity was measured via MTS (3-(4, 5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium), lactate dehydrogenase (LDH), cAMP, and ATP assays. Gastric cancer cells were observed by electron microscopy following treatment with C10. Then, xenograft mice that were inoculated with gastric cancer cells were treated with C10 for 4 weeks, after which the changes in tumor size were measured. C10 triggered apoptosis in the gastric cancer cells through the mitochondrial pathway at concentrations of more than 0.2 mM. However, 15 mM of C10 induced necrosis in gastric cancer cells by causing cellular swelling and the formation of holes in the cell membrane. Levels of cAMP and ATP decreased significantly following exposure to 15 mM C10 for 1 h. Additionally, the size of the xenograft tumors was significantly reduced by 24% after 4 weeks of C10 treatment (p < 0.05). This study indicates that C10 induces apoptosis and necrosis in a concentration-dependent manner and has clear anticancer effects on gastric cancer cells.
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