bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of PFS with levels of pretreatment lactate dehydrogenase in patients with EML4-ALK rearrangement non-small cell lung cancer treated with ALK tyrosine kinase inhibitor.
Authors: Liang Hongge , Ma Di , Xu Yan , Zhao Jing , Chen Minjiang , Liu Xiaoyan , Zhong Wei , Wang Mengzhao , Junling Li 
Published: May 2019

e20513 Background: We performed a retrospective analysis to investigate the association between the lactate dehydrogenase (LDH) levels and progression-free survival (PFS) in patients with echinoderm microtubule-associated protein-like 4-anaplasticlymphoma kinase (EML4-ALK) rearrangement non-small cell lung cancer (NSCLC) receiving treatment with crizotinib. Methods: Advanced NSCLC patients with EML4-ALK rearrangement receiving treatment with crizotinib were enrolled at Peking Union Medical College and Cancer Hospital Chinese Academy of Medical Sciences between January 2007 and January 2016. Pre-treatment or post-treatment serum LDH levels were analyzed with progression-free survival (PFS) and patients’ clinical parameters. Results: Overall, 212 patients were studied. Kaplan-Meier univariate analysis showed that elevated pre-treatment LDH level (7.9 vs. 14.1 months, P = 0.004) were associated with PFS, while the mean value of post-treatment LDH level (14.3 vs. 13.3 months, P = 0.970) were not associated with PFS. Coxproportional hazards model also identified that pre-treatment LDH level (hazard ratio [HR] = 1.841, 95% confidence interval [CI] 1.062-3.190, P = 0.030) was associated with the PFS. Logistic regression analysis showed that post-treatment LDH level was associated with creatine kinase(OR = 6.712, 95% CI 3.395-13.273, P < 0.01), CKMB (OR = 6.297, 95% CI 2.953-13.427, P < 0.01), and hemoglobin(OR = 4.163, 1.741-9.956, P = 0.001). Conclusions: An elevated pre-treatment serum LDH level ( > 250U/L) is significantly associated with shorter PFS in patients with EML4-ALK rearrangement NSCLC. Post-treatment elevated serum LDH level is associated with multiple factors including muscle damage and anemia, rather than PFS.
Economic evaluation of anaplastic lymphoma kinase (ALK) inhibitors brigatinib, alectinib and crizotinib in non-small cell lung cancer (NSCLC): Analysis for intracranial metastasis-related progression free survival (CNSPFS).
Authors: Alkhatib Nimer S , Choi Briana , Pae Elizabeth , Babiker Hani M. , Garland Linda L. , Henglefelt Alyssa , McBride Ali , Abraham Ivo 
Published: May 2019

e20515 Background: ALK inhibitors (ALKI) have shown clinical benefit in preventing progression or death related to central nervous system (CNS) metastasis in NSCLC. We performed cost-effectiveness/utility analyses that consider CNS progression in comparing ALKIs. Methods: The Bücher method was used to indirectly estimate comparative hazard ratios (HR) for CNSPFS between the 3 agents. A 2-state Markov model (CNSPFS, CNS progression or death) was specified, survival curves were digitized, and Weibull distributions fitted with life time horizon. Drug costs were per RedBook (US$ 2018). Cost of adverse event management, disease progression and follow up were per published data. Outcomes included CNSPFS life years (CNSPFS LY) and quality adjusted life years (CNSPFS QALY). Incremental cost effectiveness/utility ratios (ICER/ICUR) of CNSPFS LY and CNSPFS QALY gained were estimated. Deterministic results were verified in probabilistic sensitivity analyses (PSA). Analyses were from the US payer perspective. Results: In indirect comparisons brigatinib was superior over crizotinib (CNSPFS HR = 0.27, 95%CI = 0.13-0.54) but comparable to alectinib (CNSPFS HR = 0.39, 95%CI = 0.12-1.31) in CNSPFS; whereas alectinib was comparable to crizotinib (CNSPFS HR = 0.68, 95%CI = 0.26-1.77). Deterministic (PSA) CNSPFS LY, CNSPFS QALY and cost estimates were 0.56 (0.69), 0.35 (0.42) and $126,430 ($153,870) for crizotinib; 0.68 (0.82), 0.39 (0.49) and $115,776 ($148,904) for alectinib; 0.80 (1.02), 0.51 (0.64) and $318,114 ($402,442) for brigatinib. See table for deterministic (PSA) ICER/ICUR results ($ in parentheses denote savings). Conclusions: This independent economic evaluation suggests that, despite the lower costs of per-label alectinib and crizotinib, greater gains in CNSPFS LYs and QALYs are achieved with per-label brigatinib in the setting of CNS metastasis. This assumes willingness to pay thresholds up to $1,152,445/CNSPFS LY and up to $1,198,025/CNSPFS QALY gained, which is above prevailing standards. [Table: see text]
Afatinib in the treatment of advanced NSCLC with EGFR mutation: An observational real-world study.
Authors: Li Yun , Wang Xiaohua , Wang Li , Kou Yingying , Ma Xianglei , Feng Ji Feng , Xiao Mingzhe , Shi Meiqi , Tang Yiqun 
Published: May 2019

e20518 Background: Compared with the first generation of EGFR-TKI, Afatinib has a broader spectrum of activity and can better inhibit tumor growth. At present, the therapeutic effects of Afatinib varies on patients with different EGFR mutations and studies on the mechanism of acquired Afatinib resistance are limited. The aim of this study was to evaluate the efficacy and safety of Afatinib in the treatment of EGFR-mutation NSCLC who hadn’t received EGFR-TKI in the past. Methods: 88 patients with advanced NSCLC who had EGFR mutations were enrolled and given oral 40 mg Afatinib daily until disease progression or adverse events that could not be handled by dosage reduction. Efficacy and safety in different subgroups were analyzed. Results: Among 88 patients, the common mutation rate of EGFR was 79.5%, and the rare mutation rate was 20.5%. The objective remission rate (ORR) was 54.5%, and the disease control rate (DCR) was 92.0%. The median progression-free survival (PFS) was 14.2 months (95% CI 11.4-18.5), 27 patients (30.7%) continued Afatinib treatment after tumor progression, and the median time to progression of clinical symptoms (TTSP) was 16.3 months (95% CI 12.7-19.3). A total of 13 patients (14.8%) reduced Afatinib dosage of due to adverse events. Subgroup analysis showed that Afatinib had better effect on patients harboring common EGFR mutation but not exon 20 mutation, and was not affected by brain metastasis, dosage and lines of therapy. Among patients who progressed on Afatinib, 65.4% harbored T790M mutation. Most T790M patients received the third generation EGFR-TKI including AZD9291 and oxetinib treatment. The most common adverse reactions were diarrhea, rash, paronychia and stomatitis. Conclusions: Afatinib showed good efficacy and tolerance in advanced NSCLC patients with EGFR mutations. Continuation of Afatinib treatment after cancer progression could delay the progression of disease symptoms. The third generation EGFR-TKI could become a treatment option after Afatinib resistance. These findings reflected the real-world clinical practice of Afatinib.
Impact of antibiotics and proton pump inhibitors on clinical outcomes of immune check point blockers in advanced non-small cell lung cancers and metastatic renal cell cancer.
Authors: Kulkarni Amit , Kumar Manoj , Pease Daniel Fellows , Wang Ying , DeFor Todd E. , Patel Manish 
Published: May 2019

e20520 Background: Studies have suggested that antibiotics can negatively influence efficacy of immune check-point blockers (ICB) but the results are inconsistent. The impact of concomitant proton pump inhibitors (PPI) is not known. We evaluated whether antibiotic and PPI use in patients with advanced non-small-cell lung cancer (NSCLC) and metastatic renal cell cancer (RCC) affects ICB efficacy. Methods: We identified advanced NSCLC and RCC patients treated with anti-PD1/PD-L1 at our institution between 5/2015 to 1/2019. Data regarding systemic antibiotics and PPI use < 1 month or during ICB treatment were collected. The primary outcome was progression free survival (PFS) per response evaluation criteria in solid tumors (RECIST 1.1). Secondary outcomes were overall survival (OS) and objective response rate (ORR). Logistic regression and cox proportional hazards model were used for statistical analysis. Results: 87/148 (58%) and 40/55 (72%) patients received antibiotics and 57/148 (39%) and 17/55 (31%) received PPI < 1 month or during ICI therapy in NSCLC and RCC respectively. In RCC, antibiotic use was associated with inferior PFS (2.9 v 5.0 months, HR = 2.3 95%CI 1.0-5.0; p = 0.04) but OS and ORR were not affected. In NSCLC, antibiotic exposure was associated with superior PFS (5.0 v 2.5 months, HR = 0.5, 95% CI 0.3-0.7; p < 0.01), OS (13.0 v 8.0 months, HR = 0.5, 95% CI 0.3-0.8; p < 0.01) and ORR (33% v 11%, OR = 4.6, p < 0.01). On univariate analysis, there was trend towards inferior OS in NSCLC (9.0 v 13.0 months, p = 0.05) with PPI use. PPI use was not associated with other primary or secondary outcomes in both the cohorts. The antibiotic effect remained significant for PFS in NSCLC and RCC in multivariate analysis. Conclusions: Antibiotic use significantly affected PFS in both NSCLC and RCC. PPI use did not affect outcomes. In contrast to previous studies, this is the first study to show that antibiotic use was associated with favorable outcomes in NSCLC. More studies are needed to explain this association. Future clinical trials with ICB should consider stratification of patients based on antibiotic exposure.
Correlation between PD-L1 level and immunotherapy outcome in NSCLC in Lebanon, 2012-2018: A multicenter observational review.
Authors: Ghoche Ahmad , Nasr Lewis , Diab Saada , Nasr Fadi 
Published: May 2019

e20524 Background: Immunotherapy targeting the PD1/PDL1 checkpoint pathway represents an important innovation in lung cancer treatment. In our research, we evaluate the correlation of PD-L1 expression with clinical outcomes (progression free survival, overall survival, objective response rate) in lung cancer patients in 4 centers in Lebanon. Methods: The 57 patients enrolled in this observational study were stage IIIB/IV NSCLC and SCLC who received immunotherapy with nivolumab, pembrolizumab or atezolizumab at any line of treatment, and were recruited between February 2012 and august 2018. Immunotherapy was continued until progression, death or unacceptable toxicity. PD-L1 expression was assessed on tumor samples either on diagnosis or at progression. Patients were divided into 3 categories according to PD-L1 level (< 1, 1-49, > 50%). Progression free survival defines the time from randomization to disease progression after each line of therapy. Overall survival defines time from randomization to death from any cause. Results: 70.18% had adenocarcinoma, 26.32% had squamous cell carcinoma, 1.75% had small cell lung cancer and one pathology was missing from the file. 66.66% were stage IV at diagnosis, 26.31% were stage 3. PD-L1 expression was > 50% in 40.35% of patients, 24.56% had a level between 1 and 50% and the remaining had a value of less than 1%. PD-L1 was missing or not done in 15.79%. Median PFS was 13.9 months. Median OS was 14.2 months. 22.81% received immunotherapy as first line and 75% of the remaining patients upon first progression. PFS1 was 4.2 months. Mean time to first progression on immunotherapy was 3.6 months in patients with PD-L1 > 50%, 10.5 months in PD-L1 between 1 and 50% and 14.3 months in those who had PD-L1 < 1%. At the date of data cutoff, 49.12 % of patients were still receiving immunotherapy. No grade 3 or 4 immune related adverse events were seen during follow-up. Conclusions: The efficacy and safety of anti-PD-1 medications for advanced NSCLC were comparable in real-world and clinical settings. Prediction of treatment response from tumor PD-L1 expression seemed less practical than that was expected
Comprehensive analysis of genomic alterations detected by next-generation sequencing-based tissue and circulating tumor DNA assays in Chinese patients with non-small cell lung cancer.
Authors: Yang Hua , Zhang Junjie , Zhang Lemeng , Wen Xiaoping , Luo Yongzhong , Yao Dingquan , Cheng Tianli , Cheng Huanqing , Wang Huina , Lou Feng , Guo Jing , Liang Xiayuan , Cao Shanbo , Chen Jianhua 
Published: May 2019

e20534 Background: While tumor genotyping is the standard treatment for patients with non-small cell lung cancer (NSCLC), spatial and temporal tumor heterogeneity and insufficient specimens can lead to limitations in the use of tissue-based sequencing. Circulating tumor DNA (ctDNA) fully encompasses tumor-specific sequence alterations and offers an alternative to tissue sample biopsies. The aim of the study was to evaluate whether the frequency of multiple genomic alterations observed following ctDNA sequencing was similar to that observed following tissue sequencing in NSCLC. Methods: A total of 99 NSCLC patients were enrolled in this study, including 40 tissue and 59 plasma samples. All kinds of variants of oncogenic drivers in NSCLC were identified by next-generation sequencing (NGS) with Acornmed panel. Results: The frequencies of genetic alterations detected in ctDNA were significantly correlated to those detected via tissue profiling (Spearman’s r = 0.812, P = 0.022). Genomic data revealed significant mutual exclusivity between alterations in epidermal growth factor receptor ( EGFR) and tumor protein 53 ( TP53; P = 0.020) and between those in EGFR and Kirsten rat sarcoma viral oncogene homolog ( KRAS; P = 0.008), as well as potential mutual exclusivity between alterations in EGFR and Erb-B2 receptor tyrosine kinase 2 ( ERBB2; P = 0.059). Furthermore, the EGFR mutant allele frequency (MAF) was strongly correlated with the TP53 MAF in individual tumors (Spearman’s r = 0.773, P = 0.005), and there was a marked difference in the EGFR MAF between patients with and without the TP53 mutation (P = 0.001). Levels of the tumor serum marker CA242 in patients with ctDNA-detectable mutations were higher than those in patients without ctDNA-detectable mutations. Conclusions: This study provides a better understanding of the spectra of genomic alterations detected by tissue and plasma ctDNA assays in Chinese patients with NSCLC. The present data also highlights the importance of tissue and plasma ctDNA screening by NGS to guide personalized therapy and promote the clinical management of NSCLC patients.
Real-world immuno-oncology treatment patterns and outcomes in US patients with metastatic non-small-cell lung cancer.
Authors: Bruno Amanda , Bell Kelly , Stafkey-Mailey Dana , Murty Sharanya , Ballas Marc S. 
Published: May 2019

e20537 Background: Three immune-oncology (IO) agents are approved by the FDA to treat metastatic NCSLC (mNSCLC). This retrospective observational study aimed to observe treatment patterns and real-world outcomes of mNSCLC patients treated in the community setting, predominantly in the southern region of the U.S. Methods: Electronic health records and charts were reviewed for patients with a diagnosis of mNSCLC initiating an IO between September 1, 2015 to September 30, 2017. Patient data were examined from the date of IO therapy initiation until death, loss to follow-up, or study end date (December 31, 2017), whichever was earliest. This study was hypothesis generating thus no statistical tests were performed. Results: Of the 2,864 patients who met initial study criteria, 750 were randomly chosen for full chart review and 577 met inclusion/exclusion criteria among whom 571 had metastatic NSCLC prior to initiating IO therapy. 464, 97, and 16 patients were initiated on nivolumab, pembrolizumab, and atezolizumab, respectively. Average age was 69.7 years and 65% of patients initiated treatment in 2015 or 2016. At diagnosis, 36% of patients had an Eastern Cooperative Oncology Group performance status of 0 versus 16% at time of therapy initiation. Duration of IO therapy was 5.15 months among all metastatic patients (5.37 months for 1L only) and 4.13. months among those who completed therapy during the study period. Median real world progression free survival (rwPFS) was 5.53 (4.31. 7.20) months for 1L patients and 3.32(2.76, 4.01) months for 2L+. Real world overall survival (rwOS) was 19.04 (13.03, NR) months for 1L patients and 12.01 (8.82, 15.92) months for 2L+. Conclusions: Median rwPFS and rwOS were slightly higher than published clinical trials, yet patients were older and with poorer performance status compared to clinical trial enrollees. Despite the differences in patient characteristics, results suggest that clinical real world outcomes for this population fall within the range of median OS and PFS values observed in immune checkpoint inhibitor trials. Future research should explore the use of EHR, chart and other data sources to confirm benefit and risk in the real world.
The clinical analysis of pulmonary lymphoepithelioma-like carcinoma with epithelioid granuloma: Fourteen cases and literature review.
Authors: Qin Yinyin 
Published: May 2019

e20545 Background: Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small cell lung cancer associated with Epstein-bar virus (EBV) infection. Even less reported were those with Epithelioid granuloma (EG) and were frequently misdiagnosed. Current study aimed at investigating the clinical presentation, pathological characteristics and treatments of PLELC complicated with EG to improve our understanding of this disease. Methods: Data was collected from January 2013 to December 2017. A total of 105 patients were diagnosed as PLELC, in which 14 patients were with EG. Their clinical features, pathological characteristics and treatment were analyzed. Results: The 14 patients with EG (13.3%) in our group were followed-up 15 months (10-31 months).The median age was 48.5 year-old (38-67 year-old) and 85.7% were under the age of 60, meanwhile females had a slightly higher proportion than males (1.8:1). Most patients were at early stage (71.4%) with nonspecific manifestations such as cough, expectoration and lack of rich-lewis phenomenon. EG were often located in tumor or beside the tumor (71.4%), others were located in lymph node. It was all negative in specific stain of pathology and all positive in situ hybridization of EBV-encoded RNA (EBER). In our study, two patients received palliative chemotherapy with the duration of progression-free survival in 8 and 10 months, respectively. Twelve patients underwent surgical resection including ten with adjuvant or neo-adjuvant chemotherapy. Three patients had disease relapsed in 8, 13 and 25 months after surgery, respectively. None of them had tuberculosis occurring, progression or relapse, even if anti-tuberculosis therapy were not taken. Conclusions: PLELC complicated with EG, a rare phenomenon, was lack of rich-lewis phenomenon and specific clinical characteristic compared with those without EG. The formation of EG may be caused by immunological hypersensitivity to tumor cell or EBV infection instead of tuberculosis. It was important for us to make an exact pathological diagnosis, and attention should be paid to obtain samples by biopsy and make differential diagnosis. PLELC complicated with EG could receive multimodality therapy such as chemotherapy and surgery. However, anti-tuberculosis therapy was not necessary.
BIOLUMA: A phase II trial of nivolumab in combination with ipilimumab to evaluate efficacy and safety in lung cancer and to evaluate biomarkers predictive for response—Preliminary results from the NSCLC cohort.
Authors: Fischer Rieke Nila , George Julie , Scheel Andreas H. , Schloesser Hans Anton , Vehreschild Maria , Brossart Peter , Engel-Riedel Walburga , Griesinger Frank , Grohé Christian , Kambartel Karl-Otto , Kern Jens , Hermes Barbara , Nachtkamp Kathrin , Panse Jens Peter , Sebastian Martin , Lehmann Markus , Wiewrodt Rainer Gerhard , Büttner Reinhard , Thomas Roman K. , Wolf Juergen 
Published: May 2019

e20550 Background: Patient selection, dosing regimens and resistance mechanisms for immune checkpoint inhibitor combination therapy remain unmet medical needs in lung cancer. Combining blockade of PD-1 and CTLA-4 can be more effective than monotherapy but is accompanied by an increase in toxicity. Thus, to circumvent unnecessary toxicity it is of great interest to identify patients who will benefit from PD-1/PD-L1 blockade alone and to add ipilimumab only in case of primary or secondary progression. We present interim data from the non-small-cell lung cancer (NSCLC) cohort of the ongoing BIOLUMA trial which evaluates efficacy and safety of nivolumab and ipilimumab in lung cancer with a broad translational program to identify potential biomarkers predictive of response and/or resistance including whole exome sequencing (WES) of serial biopsies, functional analysis of peripheral T-cells and gut microbiome analyses. Methods: BIOLUMA is a multicentre non-randomised phase II trial in 2nd line patients with non-squamous NSCLC. Patients are treated with nivolumab 240 mg until disease progression and subsequently with a combination therapy of nivolumab 3 mg/kg q2w and ipilimumab 1mg/kg q6w. Primary endpoint is overall response rate (ORR) after addition of ipilimumab to nivolumab treatment. Analysis of sequential tumor biopsies, blood and gut microbiome is performed at different timepoints. Results: To date, 26 patients have been enrolled and 9 patients were transferred to the combination therapy after progression on nivolumab monotherapy. Drop out rate between the treatment arms is high, mainly due to rapid disease progression and adverse events which don’t allow addition of ipilimumab. ORR is available for 8 of these patients: 6 patients (75%) had PD as best response, and 1 (12.5%) each had a stable disease and partial response, respectively. The patient who achieved a PR had experienced primary tumor progression on nivolumab monotherapy before. Toxicity rate was similar to what has been reported from other trials. Conclusions: In NSCLC, addition of ipilimumab to nivolumab in nivolumab refractory patients seems to be safe, but the response rate is low and the drop out between the treatment parts high. Given these data, early termination of this cohort is currently discussed. Clinical trial information: NCT03083691.