bluuebunny/crossref_metadata_2025_split huggingface dataset:
Trends in immunotherapy use and survival impact in stage IV non-small cell lung cancer.
Authors: Otaibi Zachary , Kamran Amir , Wegner Rodney E , Colonias Athanasios , Weksler Benny , Finley Gene Grant 
Published: March 2020

e20715 Background: Lung cancer is the leading cause of cancer-related mortality in the United States and worldwide. 5-year survival rate for metastatic non-small cell lung cancer (NSCLC) is estimated at 4%. For patients who lack a driver mutation, platinum based chemotherapy had been the cornerstone treatment, but the addition of immunotherapy has altered the treatment landscape for many advanced NSCLC patients. Immunotherapy, with or without chemotherapy, has been demonstrated in many clinical trials to extend survival in both the first-line setting as well as subsequent lines of therapy. While the clinical trial data over the past several years has been robust, less is known about how these agents have fared in routine clinical practice. To understand this better, we utilized the National Cancer Data Base (NCDB) to examine the survival of patients who received immunotherapy for stage IV NSCLC. Methods: We queried the NCDB from 2004-2015 for patients with stage IV NSCLC treated with chemotherapy and at least 3 months of follow-up. Multivariable logistic regression was used to determine predictors of immunotherapy use. Multivariable cox regression was used to determine predictors of overall survival. A propensity score was calculated and used to mitigate indication bias. Results: Of 203,069 eligible patients, 5,877 received immunotherapy. The median age was 65 years (40-90). The median follow up was 10.6 months (3-154). Patients were more likely to receive immunotherapy if they were younger, had a lower comorbidity score, received treatment at an academic facility, had adenocarcinoma histology, private insurance, Caucasian race, and a more recent treatment year. The use of immunotherapy rose steadily across the dataset years, rising from 1% to 12%. Predictors of survival were younger age, lower comorbidity score, lower grade tumor, treatment at an academic facility, higher education, higher income, private insurance, metropolitan location, immunotherapy use, adenocarcinoma histology, and more recent year of treatment. On propensity-matched Kaplan-Meier analysis patients treated with immunotherapy in addition to chemotherapy had improved survival, 13.7 months compared to 11.8 months, p < 0.0001. Conclusions: This analysis demonstrates improved overall survival in stage IV NSCLC patients who received immunotherapy. There are inherent limitations of retrospective analyses of data from large databases, however the survival improvement noted in this study is concordant with the more robust prospective clinical research published to date.
Mature, real world progression-free survival (PFS) and overall survival (OS) milestones in stage IV, non-squamous, non-small cell lung cancer patients (nsqNSCLC) treated with first line pemetrexed(Pem)/platinum(Plat) followed by pem+/-bevacizumab(Bev) maintenance.
Authors: Bhatt Parva Kiran , Fughhi Ibtihaj , Basu Sanjib , Fidler Mary J. , Borgia Jeffrey Allen , Bonomi Philip D. , Batus Marta 
Published: March 2020

e20721 Background: Pemetrexed maintenance therapy is associated with superior survival in stage IV nsqNSCLC patients. We have observed long term disease control in some patients treated with at least one cycle of Pem/Plat with potential for maintenance pem. There are no reports of data regarding long term PFS and OS in patients treated with Pem regimens. The objectives of our retrospective analysis are to determine the frequency of long term disease control on Pem maintenance and to identify parameters associated with longer PFS/OS. Methods: We included all patients with Stage IV nsqNSCLC who received at least one cycle of pem/plat between May 2010 and Nov 2013. We identified 240 patients from our database and analyzed their demographics, lab values, dates of therapy, and dates of progression. PFS/OS was estimated by the Kaplan-Meier method and associations with patient characteristics were assessed by log-rank tests and Cox proportional hazards analysis. The shortest potential follow up was 5 years. Results: Median age was 66 years, 60% were female, and 72% were Caucasian. Baseline ECOG performance status was 0(22%), 1(50%) and ≥ 2(22%). Median PFS was 6.2 months. At 1, 2, 3, 4, and 5 years of follow up absence of disease progression was seen in 33%, 14%, 7.5%, 4%, and 3%, respectively. Additionally, in terms of OS at 1-5 years, we observed 54.5%, 35%, 21%, 14%, and 11%. Lower baseline neutrophil: lymphocyte ratio (NLR) was strongly associated with improved PFS when using NLR≤5 vs > 5 (median PFS 13.2 mo vs 5.6 mo) Additionally, baseline Hemoglobin (mean = 12.03 g/dL, HR = .904, p = .0046) and Albumin (mean 3.3 g/dL, HR = .7722, p = .024) were associated with better PFS. Conclusions: The similarity in median PFS in our patients (6.2 mo) and clinical trial data suggests that our group of real world patients did not have uniquely favorable baseline characteristics. However, the patients most likely to reach long PFS/OS milestones had favorable baseline prognostic indicators suggesting that this patient subset might also be most likely to benefit from the recently approved regimen which combined Pembrolizumab with Pemetrexed/Carboplatin.
Real-world tumor response (rwTR) to ramucirumab plus docetaxel (R+D) post platinum-based (Pt) and immune checkpoint inhibitor (ICI) therapy in advanced non-small cell lung cancer (aNSCLC) patients (pts).
Authors: Clarke Jeffrey Melson , Mathur Raina , Molife Cliff , Batus Marta , Stefaniak Victoria Jennifer , Winfree Katherine B. , Baxi Shrujal , Cui Zhanglin Lin , Lenis David , Bonomi Philip D. 
Published: March 2020

e20725 Background: In REVEL, adding ramucirumab to docetaxel improved response rates among Pt-treated aNSCLC pts. This observational study evaluated rwTR in aNSCLC pts treated with R+D after Pt & ICI or other (non-ICI) therapies. Methods: Adult aNSCLC pts receiving 2L/3L R+D between 3/1/15 & 6/30/18, after 1L/2L Pt therapy, with ≥ 1 documented rwTR assessment, & ≥ 3 months of potential follow-up were selected from the Flatiron Health EHR-derived de-identified database (n = 172). Based on prior ICI exposure, pts were assigned to either the R+D post-ICI or the R+D post non-ICI [other] unmatched cohort. Study endpoints during R+D therapy included real-world (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]. Results: Overall, median age was 66.0 years and most pts were male (54.7%), white (70.3%), treated in the community (99.4%), had nonsquamous histology (79.7%), were stage IV at diagnosis (70.9%), had a low (≤ 1) Charlson comorbidity index (90.7%) & ECOG ≤ 1 (57.6%). Among tested pts, most were negative for EGFR (93.0%), ALK (94.9%) ROS1 (96.6%), or PD-L1 (75.0%). Baseline characteristics were similar between cohorts. Table shows significant differences in rwBR & rwDCR when stratified by cohort. Conclusions: Pts receiving R+D in the post-ICI setting had improved rwDCR compared to the R+D post-Other group, driven by a greater proportion of rwPR & a higher rate of rwSD as rwBR. The proportion of rwPD as rwBR was lower in R+D post-ICI pts. rwTR rates were generally similar to tumor response outcomes reported in REVEL. Understanding impact on OS is warranted given the increasing use of ICIs in earlier lines of therapy. [Table: see text]
Effects of COJEC induction on neuroblastoma patient-derived xenografts (PDX).
Authors: Manas Nunez Adriana , Aaltonen Kristina , Hansson Karin , Radke Katarzyna , Esfandyari Javanshir , Gisselsson David , Bexell Daniel 
Published: March 2020

e21503 Background: Neuroblastoma (NB) is a solid pediatric tumor that causes 15% of childhood cancer deaths. High-risk patients have 50 to 70% mortality after 5 years. Currently, the standard way to treat high risk patients is COJEC induction followed by surgery, chemotherapy with stem cell transplants, irradiation and immunotherapy. This intense treatment has significantly increased overall survival, but mortality is still high, survivors are prone to relapse and treatment resistance is a major clinical problem. COJEC induction consists in the cycled administration of the chemotherapeutics Cisplatin, Vincristine, Etoposide, Cyclophosphamide and Carboplatin. These drugs have been long used in the clinic, but a comprehensive preclinical study combining all of them had not been done. The aim of this project was to establish a PDX model for chemotherapy induction in high-risk NB and investigate tumor characteristics and response upon treatment. Methods: NB cells from previously developed high-risk PDX models were injected subcutaneously in nude mice. When tumors reached an appropriate size, they were treated with either a COJEC-like protocol or single agent induction with high dose cisplatin. After treatment, tumors were analyzed by immunohistochemistry, chromosomal copy number analysis and RNA sequencing. Results: Most mice responded well to COJEC induction and 8/10 tumors were reduced. Within the reduced tumors, 4 were subjected to total resection and relapsed after several weeks, mimicking the clinical situation. Cisplatin treatment alone led to no significant tumor reduction and 6/10 tumors were highly resistant. Thus, as for humans, multidrug induction is more successful in reducing tumor size but presents an uneven response with high relapse rate. The responsive tumors show a higher degree of cellular differentiation when compared to resistant tumors. Cisplatin treated tumors have accumulation of chromosomal aberrations when compared to controls, and subclonal dynamics are enhanced in resistant tumors. Conclusions: We established a PDX model for chemotherapy induction in high-risk NB. The results mimic clinical findings seen in high-risk NB patients. The model is useful to understand the mechanisms of treatment resistance and for the testing of novel therapies against high-risk NB.
MRI based radiomic signature to predict treatment response to intraventricular natural killer (NK) cell infusion therapy for recurrent/refractory pediatric brain tumors.
Authors: Khatua Soumen , Idris Tagwa , Kotrotsou Aikaterini , Gupta Sumit , Zaky Wafik Tharwat , Gopalakrishnan Vidya , Lee Dean Anthony , Colen Rivka R. 
Published: March 2020

e21511 Background: NK cell therapy is a novel immunotherapeutic strategy used in cancer therapy. We conducted first-in-human, loco-regional infusion of autologous ex-vivo expanded NK cell directly into the brain in children with recurrent medulloblastoma (MB) and ependymoma (EP). Radiomics is considered an emerging method to predict treatment response as well as evaluate prognosis and tumor milieu. This is the first study evaluating the ability of radiomics to predict response to intraventricular infusions of NK cell in children with recurrent/refractory posterior fossa malignant brain tumors. Methods: We evaluated 7 patients (5 males: 2 females; mean age 11.8 years) with refractory/recurrent MB or EP (MBs = 3, EPs = 4), who were enrolled on a Phase-1 trial (NCT02271711) and received 3 cycles of intraventricular NK cell infusions. Patients were categorized based on their clinical response into responders (N = 2) and non-responders (N = 5). After semiautomatic segmentation of the tumor, 3,660 radiomic features were extracted from the baseline (before treatment) MRI scan. The least absolute shrinkage and selection operator regression was used for feature selection, and the radiomics signature was built using the unsupervised anomaly detection algorithm. The performance of the radiomics model was assessed using leave-one-out cross-validation. Results: The radiomic signature/model was comprised of 6 radiomic features and demonstrated high discriminatory performance in predicting response to NK cell therapy with an area under the curve, sensitivity, and specificity of 100% ( P = 0.09486). In addition, patients clustered into responders and non-responders using unsupervised hierarchical clustering. Conclusions: To our knowledge, this is the first study to identify the ability of radiomics to predict those who will likely benefit from NK cell therapy. Though this small study did not attain statistical significance, the robust discriminatory results warrant larger prospective studies, evaluating radiomics as a potential tool to identify responders to NK cell therapy at diagnosis.
Factors impacting time to diagnosis in pediatric, adolescent and young adult (AYA) patients with solid tumors.
Authors: Alvarez Elysia Marie , Winestone Lena , McPheeters Jeffrey , Puccetti Diane , Wilkes Jennifer Jill , Henk Henry J. , Bhatia Smita , Ginsberg Jill P. , Keegan Theresa , Pollock Brad H. 
Published: March 2020

e21515 Background: While cancer is the leading cause of non-accidental death in children and AYAs, factors associated with delays in diagnosis in young patients with cancer are poorly understood; we sought to fill this knowledge gap. Methods: Using the OptumLabs Data Warehouse’s claims data for commercially insured enrollees in a large US health plan—we identified pediatric [0-14 years (y)] and AYA (15–39 y) patients diagnosed with soft tissue sarcomas (STS), bone tumors (BT) and germ cell tumors (GCT) during 2001–17 and continuously enrolled 6 months prior to diagnosis. Time to diagnosis was calculated as days between first medical encounter associated with a possible cancer symptom and diagnosis date. Median times from first symptom to diagnosis were compared using Wilcoxon Rank Sum test. Multivariable logistic regression identified sociodemographic and clinical factors associated with longer time ( > 3 months) from symptom to diagnosis. Results: Of the 11,395 patients, 86% presented to medical care with symptoms prior to diagnosis [STS: 2,228 (89%); BT: 1,565 (87%); GCT: 5,904 (84%)]. The most common symptoms were pain and swelling. STS had the longest median days to diagnosis (92), followed by BT (91) and GCT (49). There was a significant difference (p < 0.001) in median days to diagnosis by age for BT (0–14y: 69; 15–21y: 77; 22–39y: 105) and GCT (0–14y: 96; 15–21y: 34; 22–39y: 49), but not for STS. Patients in households with ≥ a college degree (OR 1.96, 95% CI 1.06–3.64, vs < high school) and seeing a specialist (excluding oncologists) (OR 2.54, CI 2.03–3.19, vs primary care) at first symptom presentation was associated with a longer delay, while older age (22–39y: OR 0.77, CI 0.63–0.94, vs 0-14y) and male sex (OR 0.58, CI 0.51–0.66) were associated with a shorter delay in diagnosis. Conclusions: This study demonstrates that, in a commercially insured population, time to diagnosis varies by cancer type and is impacted by clinical and sociodemographic factors. Shorter time to diagnosis may represent delays in presenting to medical care or more acute presentations of symptoms, therefore patient-reported symptoms and barriers to care data should be collected to better define strategies to reduce delays in diagnosis.
Modeling and identifying therapeutic targets in Hepatoblastoma.
Authors: Smith Jordan L. , Mou Haiwei , Zhang Xiao-Ou , Ozata Deniz , Xue Wen 
Published: March 2020

e21518 Background: Hepatoblastoma, an aggressive pediatric liver tumor, most often affects young children under five years of age. Surgical resection and chemotherapy have saved many children’s lives; yet, the overall five-year survival rate is 70%, and worse for children who present with unresectable tumors. Addressing the clinical need for HB-targeted therapies requires a better understanding of how HB tumors maintain their tumorigenic potential. Recent studies suggest that YAP1, the transcriptional co-regulator, and the Wnt/β-catenin pathway cooperate for HB tumor initiation. Further YAP1 is hyperactivated in nearly 80% of children’s HB tumors; however, will YAP1 inhibition result in therapeutic benefit for pediatric patients? Methods: To assess the role of YAP1 signaling in HB tumor maintenance, we generated a conditional mouse model of HB driven by doxycycline-inducible YAP1S127A and constitutively active β-Catenin. Delivery of doxycycline induces YAP1S127A expression and mice develop HB tumors within six weeks. After tumor formation, doxycycline is withdrawn, turning off YAP1 expression, and tumor progression is monitored using in vivo bioluminescent imaging. Results: Here we show in our conditional mouse model of HB that YAP1 is essential for tumor maintenance. In vivo YAP1 withdrawal leads to > 90% tumor regression within 10 weeks. Transcriptional analyses reveal that YAP1 withdraw in regressing tumors potently induces hepatocyte differentiation and metabolism genes, including HNF4a and FoxA2 target genes. Conclusions: Establishment of a luminescent conditional model of HB provides a new platform to critically address and explore therapeutic vulnerabilities in HB. Specifically, our data suggest HB tumor maintenance requires YAP1. Finally, in vivo tumor regression following YAP1 withdraw serves as preclinical evidence for the therapeutic potential of YAP1 inhibitory therapies in children with HB.
Assessment of knowledge, attitude and practice and associated factors towards palliative care among health care providers to the pediatric oncology patients in southern Philippines.
Authors: Pasaol Jayson Cagadas 
Published: March 2020

e21536 Background: Palliative care (PC) aims to prevent, relieve and manage the symptoms of cancer and the adverse effects of cancer treatment; however, lack of education is among the biggest challenges facing PC in Philippines. Education and Awareness are dismal, especially in Southern Philippines. This study aimed to assess the level of knowledge, attitude, and practice of Health Care Provider towards pediatric PC. And to discover associated factors that limits the pediatric oncology patients to receive PC and identify the barriers in providing PC by the cancer centers to the pediatric oncology patients. Methods: A cross-sectional study design, conducted at tertiary care hospital that offers PC to pediatric oncology patients at Southern Philippines. Structured questionnaire was circulated to identify the barriers of PC, and assess the Knowledge, Attitude and Practices (KAP) of health care provider using a systematic random sampling method. The data was entered, cleaned and analyzed using excel and SPSS version 19.0 software. The chisquare test was employed to assess the association between variables. A p-value of less than 0.05 was considered as statistically significant. Results: From the total of 508 health care providers selected, a response rate of 500 (98.4%) were registered. Among the respondents 287(57.4%) had good knowledge and 259 (58.1%) had favorable attitude towards pediatric PC. In contrast, the level of practice showed that the majority 384 (76.8%) of health care providers had poor practice towards PC. Results showed that 94% to 99% of health care providers believed that the inadequate research evidence base to guide and measure the quality of life and lack of staff training in pediatric PC were the major barriers in providing PC by the cancer centers to the pediatric oncology patients. And 100% health care providers affirmed that the ignorance and lack of awareness about the existing program and resources of PC were the major factors that limits the pediatric oncology patients to receive pediatric PC in Southern Philippines. Conclusions: The health care providers had poor training and knowledge aspect of practice, but their attitude towards PC was favorable. Recommendations are the needs to be incorporated in the Department of Health through Continuing Professional Development to promote regular training for PC. Also, Educational awareness to assist healthcare professionals and pediatric oncology patients involved in PC needs to be regulated and provide.
Comprehensive genomic profiling of patients with favorable prognosis in osteosarcoma.
Authors: Liu Weifeng , Huang Zhen , Ding Yi , Yang Yongkun , Jin Tao , Deng Zhiping , Xu Hairong , Wang Xuan , Zhang Yanrui , Wang Huina , Lou Feng , Cao Shanbo , Niu Xiaohui 
Published: March 2020

e22501 Background: Osteosarcoma (OS) is characterized by complex genetic features and mysterious biological behavior. Genomic technologies are starting to give more insights. However, recent investigations have focused on patients with the advanced or metastatic disease. This study intended to evaluate the genetic landscape and identify new prognostic biomarkers in OS pts with good prognosis. Methods: This study conducted in-depth genomic profiling in a cohort of 21 patients (MSTS stage II) with long-term follow-up. Whole exome sequencing of primary tumors with matched normal tissues were performed. Sequencing data were analyzed to call tumor specific single nucleotide variants (SNV), small insertions and deletions (Indels), copy number variations (CNV) and chromosomal rearrangements and their prevalence was compared to the pts with metastatic disease reported before (Wang et al, 2018). Tumor mutation burden (TMB) and microsatellite instability (MSI) was analyzed, with additional analysis for mutational signatures. The endpoint was disease free survival (DFS). Results: 21 participants were enrolled between July. 23th, 2008 and Aug. 19th, 2013. 21 pts (M/F 13/8), median age 17y (5-33). Median DFS was 88.4 (95% CI 61.27–111.77) months. The top ranked altered genes were MUC4 (67%), FRG1 (62%), TXNDC2 (62%), ZNF717 (62%), ANKRD20A4 (57%), IGSF3 (52%), MUC16 (52%), NBPF10 (52%), MUC12 (48%) and ARID1A (43%). TMB was evaluated as lower level with a median value of 1.11 muts/MB (range from 0.78 to 3.58), relative to the other solid tumors. None pathogenic and likely pathogenic germline mutations were detected. Mutation signature 5 and 6 were most prevalent. CNV were frequently happened in stage II OS with an incidence of 80.9% (17/21). Among these, The co-occurrence of copy number gain (CNG) and copy number loss (CNL) significantly correlated with DFS (p = 0.0164), comparing with pts of either CNG or CNL . While CNV of driver genes in stage II OS were different from those of stage III published before (Wang et al, 2018), TP53 (0% vs 30% ), RB1 (4.5% vs 60%), CDKN2A (0% vs 30% ), MYC (0% vs 60%) and MDM2 (0% vs 60%). Conclusions: Stage II OS with favorable prognosis has unique genetic characterizes relative to metastatic OS. This study indicates that MUC family could be one of prognostic indicators. Genes with CNV, and the state which CNV occurs could provide clinical significance for the discovery of prognostic markers, which need to be validated by prospective prognostic data.