bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using a multiplexed immunofluorescence approach to compare immune cell populations in subtypes of non-small cell lung cancer.
Authors: Juncker-Jensen Anna , Reddy Vivek , Parnell Erinn , Nagy Mate Levente , Kuo Judy , Leones Eric , Sahafi Flora , Hoe Nicholas , William Josette 
Published: March 2020

e20702 Background: Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancer cases, and is characterized by a poor response to chemotherapy and a low survival rate. While immunotherapy has recently emerged as a successful approach in the treatment of NSCLC patients only 20-25% of patients show a positive response to anti-PD/PDL1 therapy, stressing the urgent need for additional immunotherapy options. NSCLC is a very heterogeneous disease with the two most common types being adenocarcinoma (ADCA) and squamous cell carcinoma (SCC). While a study using flow cytometry to analyze NSCLC on protein level reported the immune cell composition to be fundamentally different in ADCA compared with SCC (Daraselia et al. Am J Cancer Res, 2012 2(1):93), to the best of our knowledge this study will be the first of its kind performing an extensive analysis of NSCLS immune cell composition in tissue. Methods: In order to perform this comprehensive immunoprofiling of the NSCLC subtypes ADCA and SCC we will be using MultiOmyx™, an immunofluorescence (IF) multiplexing assay with similar staining characteristics as standard IHC stains but with the significant advantage that up to 60 protein biomarkers can be interrogated from a single FFPE section. Proprietary cell segmentation algorithms generate unique IDs for every cell and deep learning based cell classification algorithms then identify positive cells for each biomarker. Results: Using a 16-marker panel consisting of CD3, CD4, CD8, FoxP3, CD20, CD68, CD163, CD15, PD1, PDL1, ICOS, OX40, LAG-3, TIM-3, and PanCK we will analyze the proportion of B cells, T cell subtypes, M1/M2-type tumor-associated macrophages, as well as the expression of PD1/PDL1, in addition to novel immunotherapy targets LAG3, TIM3, ICOS, and OX40 in 20 samples from patients with NSCLC (10 ADCA and 10 SCC). Finally, from the same FFPE blocks that we will use to profile the immune cell composition on protein level we will also be extracting DNA/RNA in order to perform T cell receptor (TCR) sequencing, which will provide additional information on the diversity of T cells present in these tumors. Conclusions: It is our hope that these data will help provide new insights into the biology of ADCA and SCC that can ultimately be used to explore novel immunotherapeutic interventions for lung cancer treatment.
Cost-effectiveness of first-line pembrolizumab plus chemotherapy for metastatic squamous non-small cell lung cancer (NSCLC).
Authors: Kim Ashley , Devine Beth , Roth Joshua A. 
Published: March 2020

e20703 Background: Trial results from KEYNOTE-407 have recently led to the FDA approval for pembrolizumab + carboplatin + paclitaxel/nab-paclitaxel (pembrolizumab+chemo) in previously untreated metastatic squamous NSCLC. This is the only first-line indication for squamous NSCLC regardless of tumor expression status. Our objective was to evaluate the cost-effectiveness of pembrolizumab combination therapy in this setting from the US payer perspective. Methods: Using data from KEYNOTE-407, we developed a partitioned survival decision model to estimate the lifetime costs and effectiveness of pembrolizumab+chemo vs. chemo alone in the first-line treatment of metastatic squamous NSCLC. The base case used a Weibull curve selected based on minimum AIC/BIC and best graphical fit to extrapolate in-trial survival to a lifetime horizon. First- and second-line therapy resource use and adverse event (AE) rates were derived from KEYNOTE-407. Utility data and AE management were obtained from published literature and national sources. Direct medical costs were adjusted to 2018 US dollars, and future costs and outcomes were discounted at 3% per year. We estimated life years (LY), quality-adjusted life years (QALYs), and costs over a lifetime horizon. One-way and probabilistic sensitivity analyses were also conducted. Results: In the base case, pembrolizumab+chemo resulted in 0.51 more LYs, 0.36 more QALYs, and $233,246 in healthcare costs vs. chemo alone. Costs per LY and QALY gained were $216,180 and $309,004, respectively. One-way sensitivity analyses indicated that the results were most sensitive to survival and pre-progression utility inputs. In a threshold analysis, we found that the cost of pembrolizumab+chemo would need to be reduced by 24% per course of therapy ($176,175) in order to be cost-effective at $150,000/QALY. Conclusions: Based on current available data, our analysis suggests first-line pembrolizumab-based combination therapy in metastatic squamous NSCLC is unlikely to be cost-effective relative to implied willingness to pay in cancer in the U.S. (ie < $150,000 per QALY). Future studies should reassess cost-effectiveness as trial data mature.
Incidence and patterns of immune related adverse events (irAEs) during chemoimmunotherapy (ChemoIO) in patients with advanced nonsquamous NSCLC.
Authors: Patil Pradnya Dinkar , Zagouras Alexia , Wei Wei (Auston) , Pennell Nathan A. 
Published: March 2020

e20705 Background: Based on superior outcomes noted in KEYNOTE-189 with the addition of pembrolizumab to platinum doublet chemotherapy, a majority of pts with nonsquamous NSCLC are now treated with chemoIO. irAEs can cause significant morbidity and occasionally mortality in pts treated with immunotherapy. Since chemotherapy is immunosuppressive, it is plausible that incidence of irAEs would be lower in pts receiving chemoIO compared to immunotherapy. The incidence of irAEs in KEYNOTE-189 was 22.7% vs 29.2% in KEYNOTE-024 with pembrolizumab monotherapy. We sought to evaluate the incidence and patterns of irAEs in pts with advanced nonsquamous NSCLC treated with chemoIO at our institution and to determine if the rate varied with the intensity of chemotherapy [carboplatin/ pemetrexed/ pembrolizumab (CPP) vs pemetrexed/ pembrolizumab (PP)]. Methods: We retrospectively reviewed the charts of 73 pts with advanced nonsquamous NSCLC who received CPP followed by maintenance PP. In addition to clinicopathologic variables, we noted the date, incidence, type and grade of irAEs. Descriptive statistics were used to report the incidence and patterns of irAEs. McNemar’s test was used to determine if there was a significant difference in rate of irAEs during CPP vs PP. Results: Of the 73 pts, 52% were females, 67% former smokers, 49% had previously received radiation and 11% had a history of autoimmune disease. 35 pts received 4 cycles of CPP. 21 patients (28%) developed irAEs, of which 6 had irAEs during CPP and 15 developed irAEs on PP. The rate of irAEs was significantly higher after stopping carboplatin (p = 0.049). 10 pts (13%) stopped pembrolizumab due to irAEs. Organ systems involved and grade of irAEs are listed below. Conclusions: The immunosuppressive effects of intensive chemotherapy may be protective against irAEs in pts receiving chemoIO. [Table: see text]
Treatment delay and outcomes in stage IV lung cancer: The reality of a public hospital in a developing country.
Authors: Peruzzo Nicolas , Ce Coelho Juliano , Gössling Gustavo , Buiar Pedro Grachinski , Macedo Gabriel de Souza , Lenz Gabriel , Rocha Débora Leite , Liedke Pedro Emanuel Rubini , Schwartsmann Gilberto 
Published: March 2020

e20709 Background: Lung cancer is the leading cause of cancer deaths globally. Despite the development of a number of new therapeutic options for stage IV non-small cell lung cancer (NSCLC), many patients (pts) still face difficulties in accessing proper treatment in adequate time, especially in developing countries. We analyzed clinical outcomes in a population with stage IV NSCLC treated at a public hospital in Southern Brazil. Methods: In this retrospective cohort study, we enrolled 57 pts with stage IV NSCLC treated at Hospital de Clinicas de Porto Alegre (HCPA) between 2016 and 2018. Results: Median follow-up was 20.3 months, 53% were men, mean age was 65 years, 86% had smoked, 84% had de novo metastatic disease, 96% had non-squamous histology, and 16% had EGFR mutations. At the point of therapeutic decision-making, 72% had ECOG performance status (PS) 0-2 (deemed as good), whereas 28% had PS 3-4 (poor). Among pts diagnosed at HCPA (91%), median time from symptoms to diagnosis was 23 days, and median time from diagnosis to palliative systemic therapy (PST) was 65 days. PST was delivered to 60% of pts, and the most used first-line protocol was Taxol-Carboplatin (79%). Two or more lines of PST were delivered to 23% of pts. In the subgroup of pts with sensitizing EGFR mutations, 75% received anti-EGFR therapy (Gefitinib). The main reason for upfront best supportive care (BSC) was poor PS. In the poor PS subgroup, 44% initially presented at HCPA with good PS; however, PS deterioration precluded them from starting PST. No pts with poor PS received PST. In the whole cohort, median overall survival (OS) was 7.7 months. In the Cox regression multivariate analysis, poor PS (HR 3.80, P < 0.0001, 95% CI 1.90–7.61) and second-line PST (HR 0.23, P = 0.002, 95% CI 0.09–0.58) were independent predictors of OS. Median OS was 10.3 months vs. 2.4 months in PST and BSC subgroups, respectively. Conclusions: In our cohort, which reflects the reality of a publicly insured population and thus most of Brazilian lung cancer pts, poor PS deprives nearly one-third of pts from PST and is associated with a worse prognosis. Postponement of PST may lead to a loss of opportunity for pts to being treated; therefore, it is crucial to develop strategies to improve time to PST.
Erlotinib monotherapy in the treatment of advanced non-small cell lung carcinoma: A single center experience with 187 patients from 2005-2018.
Authors: Matsunaga Felipe , Pfau David , Laukamp Kai , Kikano Elias , Ramaiya Nikhil H. , Dowlati Afshin 
Published: March 2020

e20718 Background: Inhibition of epidermal growth factor receptors (EGFR) bearing somatic mutations in the tyrosine kinase domain is an important molecular target in the treatment of advanced non-small cell lung carcinoma (NSCLC). As such, first generation tyrosine kinase inhibitors such as erlotinib have been adopted as standard of care in the treatment of EGFR mutation positive advanced NSCLC. Herein we describe our experience with erlotinib monotherapy since its approval for clinical use in the United States in late 2004. Methods: A retrospective analysis of 187 patients with a diagnosis of NSCLC who underwent erlotinib monotherapy from 2005-2018 was performed. Clinical variables including patient age, disease stage, EGFR genomic status, adverse events and survival were analyzed. Likelihood Ratio Chi-Square test was applied and statistical significance was set to p < 0.05. Results: Among all patients who received erlotinib monotherapy (n = 187), treatment duration longer than 3 months was associated with EGFR mutant status (p < 0.001), increased rates of repeat lung biopsies (p < 0.002) as well as pulmonary (p = 0.008), gastrointestinal (p = 0.005) and cutaneous adverse events (p = 0.005). Subgroup analysis based on EGFR genomic status (n = 71) revealed that EGFR mutation positive patients remained on erlotinib for at least three months at a higher rate than wildtypes (p < 0.001), but also sustained higher rates of lung re-biopsy (p = 0.0121) and concomitant gastrointestinal (diarrhea) and cutaneous (acneiform, maculopapular rashes) adverse events (grades 1-3) (p = 0.003). EGFR mutant status was associated with increased rates of survival of 12 months or greater since the initiation of erlotinib (p < 0.001). Conclusions: Erlotinib monotherapy duration greater than 3 months and EGFR mutant status are associated with significantly higher rates of repeat lung biopsies and gastrointestinal and cutaneous adverse events. EGFR mutant status is further associated with survival of greater than 1 year.
Real-world clinical burden of aggressive disease (AD) in advanced/metastatic non small cell lung cancer (aNSCLC).
Authors: Batus Marta , Stefaniak Victoria Jennifer , Molife Cliff , Clarke Jeffrey Melson , Winfree Katherine B. , Mitchell Lucy , Cui Zhanglin Lin , Bonomi Philip D. 
Published: March 2020

e20723 Background: Clinical trials have shown that aNSCLC patients (pts) with AD, including those with rapid disease progression (RDP) on initial therapy (time to progression ≤ 12 weeks), have poor prognosis. This retrospective study evaluates the real world clinical burden associated with AD, defined as the difference in clinical effectiveness outcomes during subsequent treatment following RDP v non-RDP on platinum-based (Pt) therapy. Methods: Adult aNSCLC pts receiving standard post-Pt progression therapy (immune checkpoint inhibitors, single agent chemo, ramucirumab) between 03/01/2015 and 06/30/2018, after Pt therapy, with ≥ 3 months of potential follow up, were identified in the Flatiron EHR-derived deidentified database and assigned to RDP (n = 158) and non-RDP (n = 518) cohorts. Real-world tumor response (rwTR) was collected using technology-enabled abstraction. Overall survival (OS) from start of 1L, and real-world (rw) progression free survival (PFS) & rw tumor response outcomes (rw objective response rate [rwORR], rw disease control rate [rwDCR], rw time to first response [rwTTFR], rw duration of response [rwDOR] & rw best response [rwBR]) during post-Pt progression therapy were estimated. Results: Of 676 eligible pts, 23% had RDP. Clinical outcomes in the RDP and non-RDP cohorts are shown in table. Conclusions: Findings from this real world cohort underscore the clinical burden & unmet medical need for more effective treatment strategies in pts with aggressive aNSCLC pts who rapidly progress on initial therapy. As the treatment landscape evolves, characterization of these pts is warranted to identify potential risk factors. [Table: see text]
Impact of next-generation sequencing on clinical outcomes in advanced EGFR-mutant lung cancer patients after resistance to osimertinib.
Authors: Cheng Jia-Tao , Yang Jin-Ji , Wu Yi-Long 
Published: March 2020

e20726 Background: Osimertinib is used to treat EGFR-mutant non–small-cell lung cancer (NSCLC) with acquired T790M mutation. Next-generation sequencing (NGS) is helpful to understand mechanisms of resistance to osimertinib. However, whether NGS after resistance to osimertinib has an impact on clinical outcomes of patients treated with subsequent treatments has been elusive. Methods: We retrospectively identified advanced, EGFR-mutant T790M positive NSCLC patients treated with the 2nd or further-line osimertinib from January 27th, 2015 to January 31th, 2019 at our institute. Genetic profiles and clinical outcomes were analyzed. These patients were divided into 2 groups based on NGS data after resistance to osimertinib. Progression-free survival1 (PFS1) was calculated from the start of osimertinib to progression or death. PFS2 was calculated from the start of subsequent-line treatment to progression or death. Objective response rate (ORR) of subsequent-line treatments was evaluated by RECIST1.1. Results: Among 187 patients treated with osimertinib, 66 had NGS data and 27 had no NGS data after progression. Maintained EGFR T790M was detected in 23 patients (34.8%), and loss of T790M was seen in 43 patients (65.2%). Mutations of EGFR C797S were detected in 12 patients (18.1% overall; 52.2% of those with retained T790M), 11 in cis with a maintained T790M, 1 in trans with a maintained T790M. There was no significant difference in median PFS1 between the maintained T790M group and the loss of T790M group (10.8 vs. 7.0 months, P = 0.085).The NGS group was treated with TKIs according to the results of NGS strictly (n = 36), the non-NGS group received chemotherapy or best supportive care (n = 11).There was a significant difference in median PFS2 between the NGS and non-NGS groups (5.4 vs. 2.9 months, P = 0.043). The ORR of the NGS group was significantly superior to that of the non-NGS group (16.2% vs 11.1%, P < 0.001). Conclusions: NGS after resistance to osimertinib might favor clinical outcomes of advanced EGFR-mutant NSCLC patients. Further more investigations are warranted.
Bevacizumab biosimilar and reference bevacizumab in subjects with stage IIIB/IV non-squamous non-small cell lung cancer (STELLA): Design of a confirmatory, double-blind, randomized, controlled study.
Authors: Shparyk Yaroslav V. , Bondarenko Igor , Paravisini Alexandra , Florez Amalia , Huerga Camino , Abad Marta , Bullo Felicitas , Millan Susana 
Published: March 2020

e20731 Background: MB02 is a bevacizumab biosimilar developed to stringent guidelines, including non-clinical and preclinical investigations and a clinical trial as first-line treatment in metastatic colorectal cancer (Romera A et al. Lancet Gastroenterol Hepatol 2018;3 (12): 845-855). A clinical trial (STELLA) has been initiated to confirm there are no clinically meaningful differences between MB02 and reference bevacizumab (Avastin) in terms of efficacy, safety, and immunogenicity (NCT03296163). Methods: STELLA study is a multinational, double-blind, randomized, parallel-group, equivalence study comparing the efficacy and safety of MB02 vs reference bevacizumab plus chemotherapy in subjects with stage IIIB/IV non-squamous non-small cell lung cancer (NSCLC). Subjects aged 18-80 years, with ECOG status ≤1 and histologically confirmed NSCLC not receiving curative intent surgery or systemic therapy for advanced disease are randomized (1:1) to receive: chemotherapy (paclitaxel 200 mg/m2 and carboplatin AUC6) and either MB02 or reference bevacizumab 15 mg/kg every 3 weeks for up to 6 cycles (unless disease progression or treatment intolerance). Randomization is stratified by sex, smoking status, disease diagnosis (newly/recurrent), and stage. After 6 cycles, subjects can continue to receive MB02/reference bevacizumab in monotherapy every 3 weeks (until disease progression, treatment intolerance, death, withdrawal or end of study). The primary objective is to compare the objective response rate (ORR) between arms by week 18 (independently assessed) measured by RECIST v1.1. Progression free survival and overall survival (at 18 and 52 weeks), safety and immunogenicity will be assessed as secondary objectives. A sample size of 600 subjects was assumed providing about 89% power to show equivalence of MB02 plus chemotherapy with reference bevacizumab plus chemotherapy on a primary endpoint of risk ratio based on ORR. To date, 596 subjects have been recruited from more than 15 countries worldwide (Europe, Asia, Latin-America, Africa and Middle-East). At their last meeting in September, 2018 the independent data safety monitoring board (DSMB) recommended that the study continue without change. Clinical trial information: NCT03296163.
Off label targeted therapy use in adolescents and young adults with sarcoma.
Authors: Kopp Lisa M. , Saboda Kathylynn , Setty Bhuvana , Wedekind Mary Frances , Weiser Daniel , Schwartz Leya , Isakoff Michael , Harrison Douglas James , Gill Jonathan Benjamin , Hingorani Pooja 
Published: March 2020

e21504 Background: Outcomes for patients with metastatic or recurrent sarcomas remains dismal with < 20% overall survival. Due to the rarity of sarcomas, the development, testing, and approval of new therapies takes years. Most early phase clinical trials are restricted to adults leaving young patients with limited options. Little is known about the prevalence and clinical characteristics of patients receiving off-label targeted therapy (OLTT). In this multi-institutional retrospective review we evaluated OLTT use in this population. Methods: Patients with recurrent sarcoma diagnosed between the years of 2008 – 2016 were identified at six institutions. Charts were reviewed for OLTT use and additional clinical characteristics. ANOVA [Analysis of Variance] and Kruskal Wallis Rank sum tests were used for normally and non-normally distributed continuous data. Categorical data was analyzed using chi-squared tests or fisher exact tests. Results: The prevalence of OLTT use was 29% for the patients included in our analysis. Of the 99 cases, the mean age for OLTT was 18 years, ranging 3 – 34 years. Nearly half had recurrent tumor in multiple sites at the time of OLTT use, and 64% did not undergo resection prior to OLTT. Lack of clinical trial availability was the most common reason for OLTT use (31% of cases). The most common OLTT drug class used were tyrosine kinase inhibitors. Progression in 81% of cases was the primary reason for stopping OLTT and toxicity limited use in 12% of cases. One case had a complete response, 5 cases had a partial response and 4 cases had stable disease per RECIST. Conclusions: OLTT use is exceedingly prevalent in patients with recurrent sarcoma. Clinical trials for children and adolescents with recurrent sarcoma will identify optimal agents to improve outcomes in this understudied population.
Pediatric Cancer Registry in Turkey 2009-2018 (TPOG & TPHD).
Authors: Kutluk M. Tezer , Yeşilipek Akif 
Published: March 2020

e21510 Background: In Children and adolescents aged 0-14, each year more than 200.000 new cancer cases are expected at global level. For the planning and implementation of an effective pediatric cancer control program, pediatric cancer registries are essential. The long term survival rates have been improved to 85% in high income countries, however it is still less than this in LMICs. This work presents the most updated results of the pediatric cancer registry in Turkey. Methods: Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Association has established the Pediatric Cancer Registry in 2002. The childhood cancer cases registered between 2009-2018 was included in this analysis. International Childhood Cancer Classification System was used for the classification. Essential demographic findings, ICD-O-3 morphology and topography codes were recorded for each case. Results: During the 10 years from 2009 to 2018, 15713 cases were registered. For all cases, median age was 6.7 year (0-17; M/F 8838/6867, 3 hermaphrodite, 5 unknown). Age distribution was 0-4 yrs, 40.7%; 5-9 yrs, 24.4%; 10-14 yrs, 23.2%; 15-19 yrs, 11.7%) The distribution of the tumor types were [number of cases, percentage of total, median age yrs, M/F]: Leukemia (4368, 27.8%, 5.4, 2519/1849); Lymphoma & other RES tumors (2996, 19.1%, 9.7, 2012/979, 1 hermaphrodite & 4 unknown); CNS [brain & spinal] (2089, 13.3%, 7.1, 1142/947); Symphatetic system (1243, 7.9%, 2.4, 650/593); Retinoblastoma (358, 2.3%, 1.4, 204/154); Renal (788, 5.0%, 3.3, 369/419); Liver (260, 1.7%, 1.8, 143/117); Malignant bone (1030, 6.6%, 12.6, 566/464); Soft tissue sarcomas (1052, 6.7%, 7.4, 611/441); Germ cell (971, 6.2%, 8.4, 346/622, 2 hermaphrodite, 1 unknown); Carcinoma & other malignant epithelial (462, 2.9%, 13.7, 226/236); Other/non-specific malignant (96, 0.5%, 7.8, 50/46). Five year survival rate was found as 70.8%. Conclusions: This registry has been used widely among health care professionals since its establishment in 2002. Survival rates for children and adolescents has been improved to 70%. This level of survival is at the acceptable level for an upper middle income country. This registry became a useful source for investigator and decision makers at national and international level.