bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of life outcomes including neuropathy‐associated scale from a phase II, multicenter, randomized trial of eribulin plus gemcitabine versus paclitaxel plus gemcitabine as first‐line chemotherapy for HER2‐negative metastatic breast cancer: Korean Cancer Study Group Trial (KCSG BR13‐11)
Authors: Kim Ji‐Yeon , Park Seri , Im Seock‐Ah , Kim Sung‐Bae , Sohn Joohyuk , Lee Keun Seok , Chae Yee Soo , Lee Ki Hyeong , Kim Jee Hyun , Im Young‐Hyuck , Kim Tae‐Yong , Lee Kyung‐Hun , Ahn Jin‐Hee , Kim Gun Min , Park In Hae , Lee Soo Jung , Han Hye Sook , Kim Se Hyun , Jung Kyung Hae , Park Yeon Hee ,   Korean Cancer Study Group
Published: May 2019

AbstractBackgroundA phase II clinical trial of the comparison between eribulin plus gemcitabine (EG) and paclitaxel plus gemcitabine (PG) as first‐line chemotherapy for patients with metastatic breast cancer (MBC) found that the EG regimen was less neurotoxic, but was similar in efficacy to the PG regimen. In the present study, we analyzed functional assessment of cancer therapy‐taxane (FACT‐Taxane) questionnaires from patients in this clinical trial to determine their quality of life (QoL).MethodsQoL was assessed using the Korean version of the FACT‐Taxane questionnaires. After baseline assessment, QoL was assessed every 2 cycles for 12 cycles and every 3 cycles thereafter. The linear mixed model was used to evaluate the difference in QoL between the EG and PG arms.ResultsOf the 118 enrolled patients, 117 responded to the FACT‐Taxane questionnaires at baseline, 1 in the PG arm did not. Baseline QoL scores were not different between the EG and PG arms. During treatment, taxane subscale scores were significantly higher in the PG arm than in the EG arm after 2–13 cycles of chemotherapy (all P < 0.05), except for the 11th cycle. Neuropathy‐specific analysis showed that patients in the PG arm had earlier and more severe neuropathic symptoms than those in the EG arm (P< 0.001).ConclusionsIn our QoL analysis, the EG regimen delayed and decreased neuropathy as compared with the PG regimen. Therefore, eribulin would be a reasonable substitute for paclitaxel as first‐line chemotherapy for MBC.
Immunohistochemical expression of GRP78 in relation to angiogenesis markers VEGF-a and CD31 and other histopathological parameters in NSCLC.
Authors: Al-Keilani Maha S. , Almomani Basima A. , Alqudah Mohammad A. , Alrjoub Moath M. , Alzoubi Hiba W. , Shhabat Batool A. 
Published: May 2019

e20500 Background: Neovascularization is essential for the growth and progression of tumor tissues. GRP78 is frequently overexpressed in various types of cancers and has been suggested as a proangiogenic factor. Methods: In order to evaluate GRP78 expression and its role in angiogenesis of non-small cell lung cancer (NSCLC), paraffin-embedded NSCLC tissue samples (66 adenocarcinoma and 24 squamous cell carcinoma) were retrospectively collected from 90 patients who underwent surgical resection between 2008 and 2015; and did not receive chemotherapy or radiotherapy prior to surgery. Then we performed immunohistochemistry to examine GRP78 expression and we analyzed the relationships between GRP78 and the angiogenesis marker VEGF-A and the microvessel density marker (MVD) CD31. Additionally, we analyzed the association of GRP78 with clinicopathological characteristics of the patients. Results: Strong GRP78 expression was evident in about 86% of the tumor tissues (77/90). There was significant difference in GRP78 expression between poorly-differentiated and well-differentiated tumors (OR = 0.023, 95% CI = 0.001-0.419, p = 0.011). Moreover, there was a statistically significant association between VEGF-A and CD31 (χ² = 12.00, p = 0.001). Indeed, CD31 and VEGF-A expression significantly associated with histological type. Among the tissues expressing high CD31, approximately 86% of them were adenocarcinoma (χ² = 5.009, p = 0.025); and among the tissues expressing positive VEGF-A, about 79% were adenocarcinoma tissues (χ² = 6.545, p = 0.021). Conclusions: Strong GRP78 may be related to good prognosis of NSCLC. Nevertheless, further studies investigating large number of samples of all histological subtypes are required.
The depth of response was associated with the progression-free survival in advanced non-small cell lung cancer patients treated with EGFR-TKI.
Authors: Liu Yutao , Zhang Kai , Li Chengcheng , Hu Xingsheng , Jiang Jun , Hao Xuezhi , Wang Yan , Li Junling , Xing Puyuan , Yang Sheng , Zhang Xin , Wang Guoqiang , Cai Shangli , Shi Yuankai 
Published: May 2019

e20509 Background: Response Evaluation Criteria in Solid Tumors (RECIST) has been widely utilized to evaluate the new therapeutic strategies in cancer, however, RECIST fails to differentiate the heterogeneity of response in highly active therapies. Depth of response (DepOR), defined as maximum percent change in tumor size compared with baseline, may provide a new strategy to evaluate disease response. In the present study, we studied the association between DepOR and progression-free survival (PFS) in patients with advanced non-small cell lung cancer (NSCLC) treated with epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). Methods: Advanced NSCLC patients harboring EGFR driver mutation (L858R or 19del) treated with EGFR-TKI from August 2014 to July 2017 in two sites were retrospetively collected for analysis. Patients were divided into four groups by maximal tumor shrinkage (Q1 = 1-25%, Q2 = 26-50%, Q3 = 51-75%, Q4 = 76-100%). Kaplan-Meier curves were plotted for PFS by DepOR and the hazard ratio (HR) was determined through univariable and multivariable Cox regression models. Results: In total, 265 patients were included for analysis. The number for Group Q1-Q4 was 91, 73, 65 and 36, respectively. The greater DepOR was significantly associated with a longer PFS (Log-rank P for trend < 0.0001). The DepOR vs PFS analyses HR were 0.58 (0.42-0.80) for Q2, 0.49 (0.35-0.69) for Q3 and 0.33 (0.22-0.50) for Q4 compared with Q1. In the multivariable cox regression model, abnormal LDH, brain metastasis and male were also found to be associated with poorer PFS (P < 0.05). Conclusions: Greater DepOR was significantly associated with a longer PFS in advanced NSCLC treated with EGFR-TKI, suggesting that it may be a useful clinical outcome to more efficiently evaluate the response of targeted therapy.
PD-1 versus PD-L1 inhibitors for previously treated advanced non-small cell lung cancer (NSCLC): Bayesian network meta-analysis (NMA).
Authors: Almutairi Abdulaali , McBride Ali , Garland Linda L. , Abraham Ivo 
Published: May 2019

e20511 Background: PD-1 (pembrolizumab, nivolumab; PD-1i) and PD-L1(atezolizumab, avelumab; PD-L1i) inhibitors have been evaluated in patients with advanced NSCLC who failed first line therapy. We performed a Bayesian NMA to compare PD-1i and PD-L1i as groups as to efficacy and safety. Methods: Medline and Embase were searched for phase 2/3 randomized controlled trials (RCT) of PD-1i/PD-L1i in pretreated NSCLC setting. Bayesian NMA with fixed effect model was used to compare efficacy (overall survival (OS), progression-free survival (PFS), objective response rate (ORR)) and safety (grade 3-5 adverse events (AE), pneumonitis, and discontinuation rate due to AEs ). Outcomes were expressed as hazard (HR) or odds ratio (OR) with 95% credible interval (Crl). Results: 6 RCTs (3 PD-1i, 3 PD-L1i) involved comparison to docetaxel and were included. Table summarizes the results. PD-1i were ranked as the first therapy for the efficacy measures (OS (96.5%), PFS (98%), and ORR (99.92%)), and for the rate of grade3-5 AEs (60.17%). PD-L1 ranked first for the discontinuation rate due to AEs (56,51%) and docetaxel ranked first for pneumonitis (99.98%). Conclusions: PD-1i had better PFS/ORR benefits and similar OS benefit and safety profile compared to PD-L1i. Compared to docetaxel, PD-1i showed better PFS/ORR benefits and both PD-1i/PD-L1i had better OS benefit, lower grade 3-5 AEs and AE related discontinuation rate, and higher risk of pneumonitis. [Table: see text]
Angiotensin-converting enzyme inhibitor prescription is associated with decreased progression-free survival (PFS) and overall survival (OS) in patients with lung cancers treated with PD-1/PD-L1 immune checkpoint blockers.
Authors: Medjebar Soleine , Richard Corentin , Fumet Jean-David , Malo Julie , Elkrief Arielle , Blais Normand , Tehfe Mustapha , Florescu Marie , Boidot Romain , Truntzer Caroline , Routy Bertrand , Ghiringhelli François 
Published: May 2019

e20512 Background: Angiotensin converting enzyme (ACE) inhibitors are used to treat hyperblood pressure and congestive heart failure. Preclinical evidence show that ACE has a role in both innate and adaptive responses thus suggesting a capacity of ACE to promote antitumor immunity. Interaction between ACE inhibitors and Immune checkpoint blockers (ICB) has not been investigated in cancer patients (pts). Our study evaluated the effect of ACE inhibitors in Non Small cell lung cancer (NSCLC) pts treated with PD-1/PD-L1 inhibitors. Methods: We conducted a retrospective multicohort retrospective analysis of pts treated with PD-1/PD-L1 inhibitors for NSCLC at Dijon Cancer Center, and at the University of Montreal Hospital. ACE inhibitors groups were defined as pts treated with ACE inhibitors given during the treatment with ICB. PFS and OS were compared between both groups among all pts. Statistical analyses were performed using the Kaplan-Meier method and Cox univariate analysis. Multivariate Cox regression analyses was used to adjust for classical prognostic factors. Tumor RNA sequencing were performed and CIBERSORT was used to estimate immune cell infiltration in ACE inhibitors group and None ACE inhibitors group. Results: Among 283 pts included (177 pts from Dijon, and 106 pts from Montreal), 27 (10%) received ACE inhibitors. ACE inhibitors group did not differ from None ACE inhibitors group for main clinical prognostic characteristics. However, ACE inhibitors group are more frequently treated with statin, beta blocker and metformin. ACE inhibitors group had shorter median PFS compared to None ACE inhibitors group : 2.5 vs. 3.8 months, p = 0.02 (HR = 1.7 IC95% 1.1-2.5 p = 0.02 Cox Univariate). The negative impact of ACE inhibitors group was maintained after multivariate analyses adjusting for risk factors (HR = 1.9 IC95% 1.1-3.5 p = 0.02 for PFS and HR = 2.3 IC95% 1.2-4.4 p = 0.01 for OS). RNA sequencing and CIBERSORT analysis underlines that ACE inhibitors group has lower M1 macrophage, activated Mast cells, NK cells and memory activated T cells thus suggesting an immunosuppressive state. Conclusions: ACE inhibitors prescription concomitant to the PD-1/PD-L1 inhibitors treatment impairs the outcome in patients with advanced NSCLC pts. This reduction is independent of classical prognostic factors. Biological date underlines an immunosuppressive state in ACE inhibitors group. These data should be validated in larger cohort.
EGFR extracellular domain mutation in patients with lung cancer.
Authors: Guo Renhua , Gu Dejian , Zhao Jun , Zhu Lingjun , Chen Mingjiu , Liu Shuoyan , Tang Bo , Chen Rongrong , Xia Xuefeng 
Published: May 2019

e20532 Background: Missense mutations in the EGFR extracellular (EC) domain are found in 10% to 15% of glioblastomas(GBM). However, little is known about EGFR EC domain mutations in lung cancer. In this study, we retrospectively analyzed distribution of EGFR EC domain mutation in lung cancer. Methods: A total of 10100 lung cancer patients were analyzed in this study. EGFR mutations were detected by hybridization capture-based NGS panel sequencing with tumor biopsy, ctDNA or pleural effusion samples. Results: We identified gain-of-function mutations in the EC domain of EGFR in 36 (0.36%, 36/10100) patients with 23 patients carrying EGFR A289D/V/T/Y mutation, 10 patients harboring EGFR R108K/S mutation, 2 patients having EGFR T263P mutation, and 1 patient with EGFR G598R mutation. The EGFR EC domain mutation was detected in 23 patients with lung adenocarcinoma and 13 patients with other types of lung cancer (P = 0.018). Notably, 29 (80.56%) patients were detected with EGFR EC domain mutation and EGFR intracellular kinase domain (KD) mutation (P = 2.15×10-7). The incidence of L858R concomitant EC domain mutation was significantly higher compared with 19del (72.41% vs 17.24%, p = 28.64×10-5) or other EGFR KD mutations (72.41% vs 10.34%, p = 6.79×10-6). To further study whether L858R concomitant with EC domain mutation affected the efficiency of targeted therapy, we analyzed 6 patients who were treated with EGFR-TKIs. Among them, disease control rate of 2 months was 83.33% (5/6). Two patients had 10 months PFS. Three patients have been treated for 2, 5 and 12 months respectively, and are still on treatment. Conclusions: Our study reveals the distribution of EGFR EC domain mutation in lung cancer. EGFR EC domain mutation are more likely to occur concomitantly EGFR KD mutation, especial L858R. Meanwhile, our study shows that concomitant EC domain mutation and L858R may not affect the efficiency of targeted therapy.
Overall survival in PEMVITASTART randomized trial comparing immediate vs. conventional strategies of vitamin supplementation in NSCLC patients on 1st line pemetrexed-platinum chemotherapy.
Authors: Singh Navneet , Muthu Valliappan , Prasad Kuruswamy Thurai , Baldi Milind 
Published: May 2019

e20538 Background: PEMVITASTART ( NCT02679443 ) was an open label phase II randomized trial [Singh N, et al. Cancer (DOI: 10.1002/cncr.32028)] involving locally advanced/metastatic non-squamous NSCLC patients treated with 1st line pemetrexed-platinum chemotherapy (CTx). The trial assessed the hematological toxicity profile in Delayed Arm (DA; conventional strategy) in whom CTx was initiated after 5-7 days of vitamin B12/folate supplementation (B12-FAS) vs. Immediate Arm (IA) in whom patients received B12-FAS simultaneously (≤24 hours) with CTx initiation. All outcomes were reported in modified ITT population (patients who received ≥1 cycle). A non-significant trend towards better radiological responses was observed in IA (PR 33% vs. 18%; p = 0.06). Herein, we report exploratory post-hoc analysis of overall survival (OS) for the mITT population (n = 150; 77 IA, 73 DA) of PEMVITASTART. Methods: OS was calculated from date of enrolment to date of death/last follow up. Survival cutoff date was 28 months after last patient enrolment. Median OS was calculated by Kaplan-Meier method and group differences analyzed by log-rank test. Factors affecting OS were assessed by Cox proportional hazards (CPH) analysis and hazard ratios [HRs] with 95% confidence intervals (CIs) calculated (from univariate and stepwise multivariate models). Results: Median OS was 12.7 m (95% CI 8.0–17.4) and did not differ between IA [15.0 m (10.5-19.4)] and DA [11.7 m (4.1-19.3)]. 1 yr and 2 yr survival rates were similar (IA 42% and 21% vs. DA 44% and 23%). On univariate CPH analysis, factors associated with better OS were female gender, ECOG PS 0, absence of metastatic disease and receipt of maintenance pemetrexed CTx (mPEM) while current/ex-smoker status, disease progression (as best response) and age ≥70 years were a/w worse OS. Baseline Hb and homocysteine (both assessed as continuous variables) and receipt of packed RBC transfusions/ESAs for anemia correction did not influence OS. On multivariate CPH analysis, current/ex-smokers HR 2.2 (95% CI 1.3-3.7; p < 0.01) and mPEM HR 0.5 (95% CI 0.3-0.9; p = 0.01) were both significant. Median OS for current/ex-smokers was 7.4m (95% CI 5.4-9.4) vs. 25.6m (95% CI 16.2-35.0) for non-smokers (log rank p < 0.001) while for patients receiving mPEM, it was 22.7m (95% CI 9.9-35.4) vs. 9.7m (95% CI 4.9-14.5) for those not receiving mPEM (log rank p = 0.02). Conclusions: Smoking status and mPEM were strong and independent prognostic factors for OS in the PEMVITASTART trial. Clinical trial information: NCT02679443.
Multiple mutations in the EGFR gene in patients diagnosed with lung cancer.
Authors: Omelchuk Ekaterina P. , Kit Oleg I. , Petrusenko Natalia A. , Timoshkina Natalya N. , Gvaldin Dmitry Yu. , Kalabanova Elena Aleksandrovna , Kabanov Sergey N. , Svetitskaya Yana V. , Snezhko Tatiana A. , Mitashok Irina S , Vladimirova Liubov Yu 
Published: May 2019

e20542 Background: Lung cancer is the most common malignant tumor after breast cancer and is the main cause of cancer mortality. Mutations in the EGFR gene typical of lung cancer lead to constitutive activation of the epidermal growth factor receptor and malignant cell transformation. The purpose of this study was to identify associations between double and triple mutations in EGFR and clinical and pathological characteristics of patients in the South of Russia diagnosed with lung cancer. Methods: DNA was extracted from FFPE samples of 240 patients. Mutations in EGFR were detected using Cobas EGFR Mutation Test detection kit (Roche). Results: The mutant type of EGFR was identified in 24.6% of cases, and the most common activating mutations were ex19del (47.5%) and L858R (30.5%). Insertion in exon 20 was detected in 5.1% of mutation cases, G719X - in 3.4%. We also registered cases of identification of two or three mutations in one tumor: ex19del - L858R, ex19del - T790M, L858R - T790M with a frequency of 3.4% and G719X - ex20ins, ex19del - L858R - ex20ins with a frequency of 1.7%. Similar frequency is characteristic of the Caucasoid population of the USA. Multiple mutations in EGFR are associated with early manifestations of lung cancer and rapid progression of the disease. Two patients with two mutations EGFR T790M and L858R were of particular interest. According to the literature data, T790M is the most common somatic mutation that causes resistance to targeted therapy; however, rare cases could be associated with germinal variation of T790M. The primary T790M mutation is more common in patients with two or three mutations in EGFR. Conclusions: Mutations in the EGFR gene were detected in 24.6% of lung cancer cases in a patient population in the South of Russia. The frequency of two or three mutations in the EGFR gene was 0.33%. The timely detection of these mutations is particularly important for family cases when the risk group can be determined.
Cost-effectiveness analysis of icotinib versus whole-brain irradiation with or without chemotherapy in EGFR-mutant NSCLC patients with brain metastases.
Authors: Li Wenqian , Bai Rilan , Qian Lei , Chen Naifei , Zhao Yuguang , Han Fujun , Bai Ling , Li Jiaxuan , Yu Yu , Cui Jiuwei 
Published: May 2019

e20556 Background: Non-small-cell lung cancer (NSCLC) patients with brain metastases had a poor prognosis. Despite the traditional methods including radiotherapy and chemotherapy, epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) might benefit patients on survival and quality of life. We investigated the cost-effectiveness of icotinib compared with WBI with or without chemotherapy for NSCLC patients with brain metastases. Methods: A markov model was conducted based on the data of BRAIN trial. We compared the economic benefit between icotinib and the combination of WBI and WBI plus chemotherapy group. We considered disease progression as intracranial progression and overall progression separately. Sensitivity analyses were performed to observe the stability of the model. The willingness-to-pay (WTP) was set as 3× per capita gross domestic product ($25929/quality-adjusted life year [QALY]). Results: When considering progression as intracranial progression and overall progression respectively, the incremental cost-effectiveness ratio (ICER) was $930.17/QALY and $842.76/QALY between icotinib and WBI/WBI-chemotherapy. Besides, both of the average cost-effective ratio (average CE) and net benefit showed advantage of icotinib (average CE: $2157.59/QALY for intracranial progression, $2285.16/QALY for overall progression; net benefit: $372153.35 for intracranial progression, $349938.32 for overall progression). One-way sensitivity analyses demonstrated the impact of the utilities of icotinib group. The probabilistic sensitivity analyses showed even at a WTP under $6000/QALY, icotinib could be cost-effective. Conclusions: Icotinib was cost-effective compared with WBI with or without chemotherapy. [Table: see text]
Chemotherapy in combination with immune checkpoint inhibitors for the first-line treatment of patients with advanced non-small cell lung cancer: A systematic review and literature-based meta-analysis.
Authors: Addeo Alfredo , Banna Giuseppe Luigi , Metro Giulio , Di Maio Massimo 
Published: May 2019

e20565 Background: Checkpoint inhibitors plus platinum-based chemotherapy have shown superiority compared to chemotherapy alone as first-line therapy in advanced non–small cell lung carcinoma (NSCLC),To evaluate the relative benefit in term of Overall Survival (OS) and Progression-free Survival (PFS) of checkpoint inhibitors plus chemotherapy versus chemotherapy alone, overall and in subgroups defined by PDL1 expression we have performed a meta-analysis Methods: This meta-analysis searched PubMed and checked references of the selected English language articles to identify further eligible trials. Furthermore, proceedings of the main International meetings (American Society of Clinical Oncology [ASCO] annual meeting, European Society of Medical Oncology [ESMO] annual meeting, International Association for the Study of Lung Cancer [IASLC] World Conference on Lung Cancer), were searched from 2010 onwards for relevant abstracts. Data collection for this study took place from October 1 to October 24, 2018. Results: In total, 8 trials involving 4646 patients with advanced NSCLC, 3.314 (71%) and 1.332 (29%) with a non-squamous and squamous histology, respectively, were included in this meta-analysis. Four trials used atezolizumab, 3 pembrolizumab and 1 nivolumab, accounting for 2.985 (64%), 1.298 (28%) and 363 (8%) of patients, respectively. Checkpoint inhibitors plus chemotherapy were associated with prolonged OS, compared with chemotherapy in the ITT population (HR, 0.74; 95% CI, 0.64-0.87; p = 0.0002, with significant heterogeneity among trials). Within the PDL1 low group (1-49) there was a significant heterogeneity (p = 0.06) between type of drug and efficacy: the combination of chemotherapy plus pembrolizumab showed an OS benefit (HR, 0.56; 95% CI, 0.40-0.78; P< .00007) unlike the atezolizumab backbone trials (HR, 0.92; 95% CI, 0.62-1.37; P< 0.69). However, checkpoint inhibitors plus chemotherapy were associated with prolonged PFS in the ITT (HR, 0.61; 95% CI, 0.56-0.66; P < 0.00001) and across PDL1 subgroups. Conclusions: Checkpoint inhibitors plus chemotherapy compared with chemotherapy, are associated with significantly prolonged OS and PFS in first-line therapy in NSCLC. In the low PDL1 subgroups the benefit was statistically significant only in the pembrolizumab backbone trials.