•Recommended phase II dose is binimetinib 30 mg BID with carboplatin/pemetrexed in non-squamous NSCLC.•Manageable toxicities observed with the combination of carboplatin, pemetrexed and ...binimetinib.•Objective response rate 50 % and disease control rate 83.3 % with chemotherapy plus binimetinib.
MEK inhibition is a potential therapeutic strategy in non-small cell lung cancer (NSCLC). This phase I study evaluates the MEK inhibitor binimetinib plus carboplatin and pemetrexed in stage IV non-squamous NSCLC patients (NCT02185690).
A standard 3 + 3 dose-escalation design was used. Binimetinib 30 mg BID (dose level 1 DL1) or 45 mg BID (dose level 2 DL2) was given with standard doses of carboplatin and pemetrexed using an intermittent dosing schedule. The primary outcome was determination of the recommended phase II dose (RP2D) and safety of binimetinib. Secondary outcomes included efficacy, pharmacokinetics, and an exploratory analysis of response based on mutation subtype.
Thirteen patients (6 DL1, 7 DL2) were enrolled: 7 KRAS, 5 EGFR, and 1 NRAS mutation. The RP2D was binimetinib 30 mg BID. Eight patients (61.5%) had grade 3/4 adverse events, with dose limiting toxicities in 2 patients at DL2. Twelve patients were evaluated for response, with an investigator-assessed objective response rate (ORR) of 50% (95% CI 21.1%-78.9%; ORR 33.3% by independent-review, IR), and disease control rate 83.3% (95% CI 51.6%-97.9%). Median progression free survival (PFS) was 4.5 months (95% CI 2.6 months–NA), with a 6-month and 12-month PFS rate of 38.5% (95% CI 19.3%-76.5%) and 25.6% (95% CI 8.9%-73.6%), respectively. In an exploratory analysis, KRAS/NRAS-mutated patients had an ORR of 62.5% (ORR 37.5% by IR) vs. 25% in KRAS/NRAS wild-type patients. In MAP2K1–mutated patients, the ORR was 42.8%.
The addition of binimetinib to carboplatin and pemetrexed appears to have manageable toxicity with evidence of activity in advanced non-squamous NSCLC.
The aims of the study were to identify predictors of locoregional failure (LRF) following surgery for pancreatic adenocarcinoma, develop a prediction risk score model of LRF and evaluate the impact ...of postoperative radiation therapy (PORT) on LRF.
A retrospective review was conducted on patients with stages I–III pancreatic adenocarcinoma who underwent surgery at our institution (2005–2016). Univariable and then multivariable analyses were used to evaluate clinicopathological factors associated with LRF for patients who did not receive PORT. The risk score of LRF was calculated based on the sum of coefficients of the predictors of LRF. The model was applied to the entire cohort to evaluate the impact of PORT on the high- and low-risk groups for LRF.
In total, 467 patients were identified (median follow-up 22 months). Among patients who did not receive PORT (n = 440), predictors of LRF were pN+, involved or close ≤1 mm margin(s), moderately and poorly differentiated tumour grade and lymphovascular invasion. After adding patients who received PORT, the 2-year LRF in the high-risk group was 57% for patients who did not receive PORT (n = 242) and 32% among patients who received PORT (n = 22), with an absolute benefit to LRF of 25% (95% confidence interval 5–52%, P = 0.07). The 2-year overall survival for the high-versus the low-risk group was 36% versus 67% (P < 0.001).
This risk group classification could be used to identify pancreatic adenocarcinoma patients with higher risk of LRF who may benefit from PORT. However, validation and prospective evaluation are warranted.
•Locoregional failure jeopardizes clinical outcome in resectable pancreatic adenocarcinoma following upfront surgery.•Predictors of locoregional failure (pN+, positive/close resection margin, high tumor grade and lymphovascular invasion).•Among high-risk group, there was an absolute risk reduction of locoregional failure by 25% with postoperative radiation.•Patients in the high-risk group had poorer survival compared with the low-risk group.
In this study, we aimed to show the protective effect of a single-dose Fosfomycin from infective complications against the standard usage of cephalosporine before retrograde intrarenal surgery.
A ...total of 186 patients who underwent retrograde intrarenal surgery between 2020 and 2021, included the study. Patients were divided into two groups: group 1(n=49), patients who received an oral dose of 3g Fosfomycin tromethamine powder administered 4-6h before the operation; and group 2 (n=137): patients who received Cephalosporin 30min before surgery and an additional dose 6h after surgery.
The median age and stone size were significantly higher in the cephalosporin group (P=0.006 and P=0.008, respectively). There was no statistically significant difference between the groups in terms of postoperative fever and postoperative UTI (P=0.408 and P=0.438). Additionally, no patient developed sepsis. and no adverse event was seen in either group. Preoperative urinary tract infection (UTI) and previous Extracorporeal Shock Wave lithotripsy (ESWL) were independent risk factors and increased postoperative infectious complications (O.R. 2.929 95% C.I. 0.723, P<0.001, and O.R. 2.860 95% C.I. 0.985, P=0.004, respectively).
Infectious is still one of the important complications after RIRS, and preoperative UTI is an independent risk factors for infections. Fosfomycin monotherapy could be sufficient and is also effective in patients with preoperative culture positive.
The impact of the right ventricular (RV) structure and function on the in-hospital outcomes in patients with COVID-19 infection has not been rigorously investigated.
The main aim of our study was to ...investigate in-hospital outcomes including mortality, ICU admission, mechanical ventilation, pressor support, associated with RV dilatation, and RV systolic dysfunction in COVID-19 patients without a history of pulmonary hypertension.
It was a single academic tertiary center, retrospective cohort study of 997 PCR-confirmed COVID-19 patients. One hundred ninty-four of those patients did not have a history of pulmonary hypertension and underwent transthoracic echocardiography at the request of the treating physicians for clinical indications. Clinical endpoints which included mortality, ICU admission, need for mechanical ventilation or pressor support were abstracted from the electronic charts.
Patients’ mean age was 68+/-16 years old and 42% of the study population were females. COPD was reported in 13% of the study population, whereas asthma was 10%, and CAD was 25%. The mean BMI was 29.8+/-9.5 kg/m2. Overall mortality was 27%, 46% in ICU patients, and 9% in the rest of the cohort. There were no significant differences in co-morbidities between expired patients and the survivors. A total of 19% of patients had evidence of RV dilatation and 17% manifested decreased RV systolic function. RV dilatation or decreased RV systolic function were noted in 24% of the total study population. RV dilatation was significantly more common in expired patients (15% vs 29%, p = 0.026) and was associated with increased mortality in patients treated in the ICU (HR 2.966, 95%CI 1.067–8.243, p = 0.037), who did not need require positive pressure ventilation, IV pressor support or acute hemodialysis.
In hospitalized COVID-19 patients without a history of pulmonary hypertension, RV dilatation is associated with a 2-fold increase in inpatient mortality and a 3-fold increase in ICU mortality.
There is a paucity of studies examining the prevalence and clinical characteristics of rhabdomyolysis in hospitalized patients with COVID-19 infection. The purpose of this study is to examine the ...incidence, clinical characteristics, and outcome of hospitalized patients with COVID-19 infection who develop rhabdomyolysis.
This is a single-center retrospective analysis of all hospitalized patients with COVID-19 admitted between March 8, 2020, and January 11, 2021. All patients with creatinine kinase (CK) levels available during the hospital admission were included. Rhabdomyolysis was defined as an elevation in CK level higher than five times the upper limit of normal (i.e., 1125 U/L). We compared clinical characteristics and outcomes of patients who developed rhabdomyolysis with patients who did not develop rhabdomyolysis.
The incidence of rhabdomyolysis in hospitalized patients with COVID-19 infection was 9.2%. There was no significant difference noted in comorbidities and clinical characteristics between the two groups. Moreover, there was no significant difference noted in the presence of severe COVID-19 infection (72.7% vs 54.6%, p = 0.1), mortality (27.3% vs 23.9%, p = 0.72), acute kidney injury (59.1% vs 42.7%, p = 0.14), or need for intensive care unit (ICU) care (72.7% vs 51.4%, p = 0.051). However, a higher percentage of patients in the rhabdomyolysis group required physical rehabilitation after discharge (40.9% vs 19.3%, p = 0.02).
The overall incidence of rhabdomyolysis in hospitalized patients with COVID-19 infection was high (9.2%). The presence of rhabdomyolysis was not associated with the increased severity of the disease. Patients with rhabdomyolysis more frequently required physical rehabilitation compared to those without rhabdomyolysis.
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