bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting T790M mutation of tissue and plasma ctDNA samples by ARMS in EGFR-mutant NSCLC patients after disease progression.
Authors: Wu Ya-Lan , Tong Rui-Zhan , Zhang Yan , Hu Bin-Bin , Zhen Ke , Zhao Qian , Zhou Xiao-Juan , Ding Zhen-Yu , Peng Feng , Gong You-Ling , Xu Yong , Wang Jin , Ren Li , Liu Yong-Mei , Lu You 
Published: September 2018

e20625 Background: T790M mutation is the most common mechanism of acquired EGFR TKI resistance. The use of T790M-targeted EGFR TKIs needs re-biopsy to confirm the existence of sensitive mutation. People wonder whether blood can replace tissue to diagnose acquired T790M mutation. Methods: We performed a prospective study in our institution (West China Hospital, Chengdu, China) between 2014 and 2016. Patients were eligible if they have advanced EGFR-mutant NSCLC, clinical resistance to EGFR TKIs, and were undergoing a re-biopsy for EGFR genotyping as part of their routine clinical care. We used ARMS to sequence EGFR of tissue and blood sample. Blood collection was performed within 2 weeks of the repeat biopsy. Measurement of diagnostic concordance among two different methods was done using cohen’s kappa, and the McNemar test used to judge significance. All statistical analysis was performed with the use of SPSS 20.0. Results: Forty-five patients were enrolled in this study. Thirty-eight patients received tissue test, thirty-one patients received plasma ctDNA test, and twenty-four patients received both tissue and plasma ctDNA tests. 26/38 (38.4%) reported positive T790M mutation by tissue test, and 13/31 (41.9%) by plasma ctDNA test. In 24 patients received both tissue and plasma ctDNA tests, 10/24 (41.7%) were concordant for T790M mutation status (κ = 0.006, p = 0.013). The positive rate of T790M mutation is 70.8% by tissue test, and 37.5% by plasma ctDNA test. In 17 patients reported positive T790M mutation by tissue test, 7/17 (41.2%) also reported positive T790M mutation by plasma ctDNA test, and 3 of the 7 positive ctDNA tests (42.9%) reported weakly positive T790M mutation. In the other 7 patients reported negative T790M mutation by tissue test, 2/7 (28.6%) reported positive T790M mutation by plasma ctDNA test. Conclusions: The positive rate of ARMS in our study is high than that of some reported new technologies. The level of plasma ctDNA was reported to relate to prognosis. Hence, plasma ctDNA cannot fully replace tissue to diagnose acquired T790M mutation after disease progression. It is important and significant to develop new technology to improve the safety of tissue biopsy.
Apatinib monotherapy for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy.
Authors: Wang Si-Yu , Liu Zui , Ou Wei , Li Ning , Wu Hui-qi , Mao Xiao-Yong , Yuan Cheng 
Published: September 2018

e20626 Background: Apatinib, a small-molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), has been proved to be effective and safe in treating patients with advanced gastric cancer who failed to second-line chemotherapy. As the VEGFR-2 targeted therapy has made encouraging progress in the treatment of a broad range of malignancies, we aimed to explore the efficacy and safety of apatinib in treatment of advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. Methods: In this open-label single-arm, phase II study, patients were treated with apatinib alone in daily dose of 250 mg, po, in the second- or third-line setting. The primary endpoint was progression-free-survival (PFS) and the tumor response was determined according to the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. Results: From January 28, 2016 to December 31, 2016, 33 patients were enrolled, including 9 patients with squamous carcinoma and 24 patients with adenocarcinoma. Fourteen patients were detected as EGFR mutations and all the cases have no anaplastic lymphoma kinase (ALK) fusion gene. The median progression free survival (mPFS) of the whole group was 4.0 (95% confidence interval [CI], 0-8.2) months, while the mPFS of adenocarcinoma was 4.0 (95% CI, 2.1-5.9) months and the mPFS of squamous carcinoma was 5.5 (95% CI, 0-13.9) months (P = 0.245). Among the 33 patients, partial response was noted in 3 patients (9.09 %) and stable disease in 14 (42.42%). The disease control rate (DCR) was 51.52%. The common side effects of apatinib were hypertension, hand-foot syndrome and proteinuria, which accounted for 33.33%, 24.24%, and 15.15%, and no grade 3/4 adverse reactions occurred. The toxicity of apatinib was controllable and tolerable. Conclusions: Apatinib appears to be effective and safe for advanced non-small cell lung cancer after the failure of chemotherapy or other targeted therapy. Prospective studies are needed for further investigation.
In vivo effect of the parasite derived peptide GK-1, anti-PD-L1 and GK-1/anti-PD-L1 combination in experimental melanoma. Potential novel treatment pathways.
Authors: Vera Aguilera Jesus , Perez-Torres Armando , Vera Aguilera Carlos , Block Matthew Stephen , Duma Narjust , Ventolini Gary , Martinez-Zaguilan Raul , Sennoune Souad R. 
Published: September 2018

e21038 Background: Several studies of advanced melanoma patients suggest that combining therapies that target tumor mechanisms of immune evasion with activation of normal immune cell functionality may provide optimal benefits for patients. The synthetic parasite derived GK1 peptide in combination with anti-PD-L1 showed significant longer survival (34 days) compared to GK1 or Anti-PD-L1 alone (23-27 days) in a murine melanoma model (p < 0.05). This means an increase survival increased in 47.82% in the mice treated with GK-1 + anti-PD-L1, 21.7% treated with GK-1, and 6.08% treated with anti-PD-L1. Methods: To elucidate the potential mechanism by which this combination treatment exerts its anti-melanoma effects, C57BL/6 mice were injected with B16-F10-luc2 cells and separated according to treatments in four groups: control, GK-1, anti-PD-L1 and GK-1/anti-PDL-1.Blood samples were collected at day 0, 14, and at euthanization or end of the experiment and monitored for serum cytokines using mice-specific V-PLEX Pro-inflammatory Panel. Results: On day 14, TNF-α levels in the Anti-PD-L1 and GK-1 therapy group was significantly lower compared to control mice. At sacrifice, the combined treatment group demonstrated significant decrease cytokine production in IL-6 and IL-10. Conclusions: The decreased cytokine levels observed in the GK-1/anti-PD-L1 group may explain the significant improved survival. GK-1 is a Th1 response inductor both in vitro and in vivo as it increases IFN-γ, IL-2 but not IL-4 and IL-10. It is noteworthy that when PD-L1 signaling is reduced in T cells these cells proliferate extensively in vitro and produce increased levels of IFN-γ and IL-17, suggesting an enhanced pro-inflammatory phenotype. It has been established that cytokines of Th2 response such as IL-4 and IL-5 and IL-6, have tumor-promoting activity. The anti-melanoma effect of the GK-1/anti-PD-L1 combination observed in the present study could be mediated by decreasing the pro-tumor Th2 response. These results provide novel alternative pathways and potential targets to enhance the clinical effect of the PD-1/PD-L1 blockade pathway.
Retrospective review of metastatic uveal melanoma (mUM) at NYU Perlmutter Cancer Center (NYU-PCC).
Authors: Kavecansky Juraj , Finger Paul , Wilson Melissa , Madden Kathleen M. , Kannan Rajni , Pavlick Anna C. 
Published: September 2018

e21040 Background: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, despite its rare incidence of 5 per 1,000,000. UM metastasis (mets) occurs in approximately 50% of patients (pts). The published median survival from the time of mets is only 6 to 12 months (mos). To date there is no curative therapy for pts with mUM. Methods: This is a retrospective review of pts evaluated at NYU-PCC with UM between January 1, 2011 and December 31, 2016. Data collected include: ophthalmic treatment, time from ophthalmic diagnosis, systemic metastatic sites, genetic mutations (muts), systemic treatment and survival. Results: During this 5-year interval, 100 UM pts were referred to NYU-PCC. 58 pts were diagnosed with high-risk primary T3/T4 sized tumors and remained disease-free during this period. For the remaining 42 pts that developed mUM, primary ophthalmic treatments included: 12 enucleations, 27 brachytherapy and 3 received none since they had synchronous UM and mUM. Therapy for mUM included liver-directed therapy (LDT) such as TACE, 90Y brachytherapy, or radiofrequency ablation; or systemic therapy. These mUM pts had a median survival of 17 mos. 20 mUM pts are male; 22 pts are female; Ages: 33-96; 24 deceased and 18 alive. Of the latter, 5 are NED and 13 are alive with disease on treatment. 24 deceased mUM pts treated initially with LDT lived on average 14 mos longer than those treated with any systemic therapy alone; pts with LDT had a median survival of 24 mos, compared to 10 mos for those treated only with systemic therapy (p = 0.0075). There was no correlation between time of ophthalmic diagnosis and time to onset of mets and survival (R2value 0.00243). Genetic analysis of met tumors was available on 9 pts. 3 of 5 pts with GNA11 muts are alive compared to 1 of 4 pts with GNAQ muts. Conclusions: Pts with mUM treated initially with LDT had significantly longer survival compared to pts treated with systemic therapy alone. Whether longer survival in these pts is an effect of LDT, earlier treatment of mets, or a more indolent disease remains to be determined. Our study demonstrates mUM pts survive an average of 17 mos, which is higher than historically reported. Significance of GNAQ or GNA11 requires further investigation.
BRAF mutation and PD-L1 expression in melanoma: Comparison between multiple PD-L1 IHC clones and BRAF mutation evalutated by FDA-approved kits versus NGS.
Authors: O'Malley Dennis , Sudarsanam Sucha , Chizhevsky Vladislav , Ma Wanlong , Jiang Shiping , Chen Wayne , Funari Vincent Anthony , Agersborg Sally , Albitar Maher 
Published: September 2018

e21050 Background: BRAF mutation and PD-L1 expression appear independent in melanoma. We have established that PD-L1 clones 22C3 and 28.8 show almost identical results. In this study we correlated between BRAF mutation and PD-L1 expression as detected by 22C3/28.8 and SP142 in melanoma clinical samples. Methods: Melanoma samples were tested for PD-L1 expression and BRAF mutation. IHC testing for PD-L1 22C3 or 28.8 were tested using FDA-approved kits as recommended. Testing with SP142 (Spring Biosciences; LDT) was performed using standard techniques. BRAF testing in combination with SP142 PD-L1 testing was performed using next generation sequencing covering exons 11 and 15. Samples tested with 22C3 and 28.8 clones were tested using FDA-cleared BRAF kits (Cobas, Therascreen) testing V600 only. Results: 68 samples were tested for PD-L1 expression with clone 22C3, 67 with 28.8, and 56 with SP142. There was no overall statistical difference between the three clones in PD-L1 expression (P = 0.41). For combined 22C3 and 28.8, 61 of 135 cases (45%) had PD-L1 expression and 31 (23%) had BRAF mutation detected using FDA kits (V600). There was no statistical correlation between PD-L1 expression and BRAF mutation in this group (P = 0.9) at any cut-off. In cases tested with SP142 clone, BRAF mutation was detected in 31 cases (55%) by NGS, higher than using the FDA kit (P < 0.0001). In V600 mutations by NGS, 14 cases (25%) were positive, similar FDA kits. In SP142 cases, PD-L1 was positive in 45% of cases. There was no correlation between BRAF mutation and PD-L1 using SP142 expression as a continuous variable (P = 0.59) or cut-off points of 5% or 50%. When cut-off of 20% was used, significant inverse correlation with BRAF mutation (P = 0.004) was identified and was maintained if V600 codon only was evaluated. Conclusions: There is no correlation between BRAF mutation and PD-L1 expression as detected using clones 22C3 and 28.8. With SP142, a negative correlation between PD-L1 expression and BRAF mutation is identified with a 20% cut-off. The rate of BRAF mutations practically doubles when NGS is used and exons 11 and 15 are included in the testing, in contrast to FDA approved testing.
The prognostic role of preoperative serum lactate dehydrogenase (LDH) in patients with resected advanced melanoma.
Authors: Majithia Neil , Velazquez Manana Ana , Yan Yiyi , Kottschade Lisa A. , Dronca Roxana Stefania , Block Matthew Stephen , Nevala Wendy Kay , Markovic Svetomir 
Published: September 2018

e21054 Background: Up to 50% of patients undergoing resection for advanced melanoma experience recurrence. Identification of preoperative prognostic biomarkers is needed to ascertain risk of relapse and guide postoperative management. Lactate dehydrogenase (LDH) represents a strong prognostic factor in unresectable metastatic (stage IV) melanoma, but its relevance in patients with resected stage III or IV disease remains unknown. Methods: We retrospectively analyzed data from patients with stage III and IV melanoma who had undergone complete resection of disease and received follow-up treatment at Mayo Clinic, Rochester between January 1, 2000 and January 31, 2012. Clinical data were collected from electronic records. Survival data were estimated using the Kaplan-Meier method. Associations of preoperative LDH with time to relapse and death were evaluated using Cox proportional hazards regression models and summarized with hazard ratios and 95% confidence intervals. Results: A total of 154 subjects with resectable stage III or IV melanoma were included in the study. Median age at the time of resection was 58; 54 (35.1%) were female. One-hundred sixteen (75.3%) patients were classified as stage III and 38 (24.7%) stage IV. Adjuvant systemic treatment was administered in 75 (48.7%) patients and adjuvant radiation in 32 (20.7%). Median duration of follow-up was 4.0 years. Sixteen (10.3%) patients had preoperative LDH above the upper limit of normal. Each 50-unit increase in LDH was associated with a 15% increased risk of relapse (HR 1.15; p = 0.040) and 23% increased risk of death (HR 1.23; p = 0.001). After adjusting for age, gender, stage, number of sites, adjuvant systemic treatment, and adjuvant radiation, preoperative LDH remained associated with time to death (HR 1.25; p = 0.002). Preoperative LDH greater than the upper limit of normal was associated with increased hazard of death, both with univariate (HR 2.44; p = 0.005) and multivariate (HR 2.17; p = 0.017) analyses. Conclusions: This study supports the role of elevated preoperative LDH as a predictor of inferior outcomes in patients with advanced melanoma. Further study to correlate LDH to outcomes in the era of adjuvant immunotherapy is required.
Patient experiences with avelumab vs chemotherapy for treating merkel cell carcinoma: Results from protocol-specified qualitative research.
Authors: Kaufman Howard , Lambert Jeremy , Barbosa Carla Dias , Guillemin Isabelle , Mahnke Lisa , Bharmal Murtuza 
Published: September 2018

e21065 Background: Avelumab is a fully human anti–PD-L1 monoclonal antibody that has shown durable responses and a manageable safety profile in patients (pts) with various tumors, including metastatic Merkel cell carcinoma (mMCC). We report findings from qualitative interviews with mMCC pts about their experiences with avelumab or chemotherapy. Methods: Pts with mMCC who progressed after chemotherapy were enrolled in a registrational, single-arm, multicenter, international phase 2 trial (NCT02155647). Protocol-specified semi-structured phone interviews were conducted at baseline (to document experiences with chemotherapy) and during avelumab treatment at Weeks 13 and 25. Interview transcripts were analyzed qualitatively using a thematic approach. Results: Interviews were conducted with 19 pts at baseline and 10 pts at Weeks 13 and 25. At baseline, most pts (n = 12) reported that chemotherapy was initially successful prior to relapse. At Week 13, pts generally were “optimistic,” but “cautious,” and had “high hopes” regarding avelumab treatment. Pts most frequently reported having no or fewer side effects (n = 6) with avelumab vs prior chemotherapy. At Week 13, fatigue was the most frequently reported impact of avelumab (n = 8); at Week 25, 3 pts still reported fatigue, but 5 “felt less tired” than at Week 13. Most pts (n = 12) had experienced fatigue with chemotherapy; having “less energy” was the most-reported effect (n = 4) when compared with avelumab. Most pts did not report any negative impact of avelumab on everyday lives (n = 7); 3 reported a need “to rest more often after activities.” In contrast, only 6/19 pts reported that chemotherapy had no negative impact or a” very small” negative impact on everyday lives. Eight pts reported feeling “slowed down” or “being limited” in physical capacities during chemotherapy. Eight pts thought that chemotherapy had substantial negative impact on their lives, describing it as “very disruptive,” “debilitating,” or “devastating.” Conclusions: Pts had a more positive experience with avelumab than chemotherapy; it had a minimal detrimental impact on their lives. Clinical trial information: NCT02155647.
Exploring the form of change: A latent growth curve model of distress in oncologic patients undergoing specific cancer-related psychological intervention—A preliminary study.
Authors: Rossi Alessandro , Marconi Maria , Di Lucca Giuseppe , Morena Raffaella , Pogliani Claudia , Parati Maria Chiara , Rossini Chiara , Verusio Claudio 
Published: September 2018

e21556 Background: Psychological distress is one of the most important indexes of suffering in oncological patients – due to its severe negative impacts on medical treatments. Thus, the attention to this topic has increased constantly – focusing on the observed outcomes of (psychological) cares. However, very few studies investigated the (latent) pattern ( form) of change in distress within oncological patients receiving psychological intervention. The aim of the study was to test a Latent Growth Curve Model to explore the form of change in distress. Methods: A longitudinal research design was used. Patients ( N= 122, mean age: 68.3, SD= 12.3, 63 female-59 male) were enrolled at the Department of Medical Oncology at Presidio Ospedaliero of Saronno, ASST Valle Olona, Italy, and assessed for the presence of distress with Psychological Distress Inventory (PDI). As clinical routine, all patients received a specific cancer-related psychological intervention (CBT, mainly; mean of sessions: 27.4, SD= 13.5) and were tested at the beginning (T1; α= .88) and at the end of treatment (T2; α= .86) and at timed-balanced follow-up (T3; α= .87). Results: First, longitudinal invariance of measurement was performed to test whether (A) factor structure of PDI and (B) factor loadings of indicators were constant across time. PDI showed metric measurement invariance: Δχ2= 20.4; Δχ2 df= 24; p(Δχ2) = 0.67. Afterward, a LGCM was performed testing different trends of growth (no growth vs. linear vs. free) – controlling for age, number of sessions received, type and localization of tumor. The comparison of growth curves reveal that the linear trends of change had the best model fit to the data: χ2= 4.124, p= .248; RMSEA = .055(.000–.171), p(RMSEA < .05) = .372, CFI = .990, SRMR = .027. Conclusions: These findings highlight that the (latent) linear growth better explain true change of distress – among oncological patients receiving a specific cancer-related psychological intervention. These results outline the possibility to improve the structure of psychological and medical treatments for oncological settings, to reduce psychological suffering and increase quality of life.
Neo-adjuvant chemotherapy and distress in breast cancer patients: The moderating role of generalized self-efficacy.
Authors: Magno Stefano , Carnevale Stefania , Dentale Francesco , Belella Daniela , Linardos Marinella , Masetti Riccardo 
Published: September 2018

e21570 Background: Neo-Adjuvant Chemotherapy (NAC) is commonly recommended as a preoperative treatment for patients with locally advanced breast cancers (BC). However, several studies have shown that NAC can increase patients’ distress. A first aim of this study was to evaluate if BC patients treated with NAC show higher levels of distress as compared to patients undergoing primary surgery (PS). A secondary aim was to evaluate if distress could be significantly correlated with patients’ depression and anxiety, and if generalized self-efficacy (GSE) may moderate these relationships. Methods: one hundred and twenty-four BC patients (61 waiting for PS and 63 undergoing NAC), with a mean age of 51.64 (SD = 9.67), were instructed to complete a series of questionnaires evaluating socio-demographic data, anxiety, depression, distress and GSE. Results: An analysis of covariance was conducted, including treatment condition (NAC vs PS) as an independent variable, patients’ distress as a dependent variable, and age as a covariate. A significant mean difference emerged between groups [F(1, 121) = 5.66, p < .05)]. In particular, NAC patients showed a higher distress (Mean = 6.79) than PS ones (Mean = 5.72). Moreover, patients’ distress appeared moderately correlated with both anxiety (r = .34, p < .05) and depression (r = .36 < .05). Finally, results revealed a significant interaction effect of distress and GSE on depression (β = -.19, p < .05), confirming the moderating role of GSE. In particular, for low levels of GSE (-1 SD), the correlation between distress and depression was large and significant (r = .53, p < .001), while for high level of GSE (+1 SD) this relationship was definitively lower (r = .14, p = .03). No significant moderating effects of GSE were found for stress-anxiety relationship. Conclusions: Results of this study seems to confirm that NAC may induce distress in BC patients. Moreover, distress, significantly related to anxiety and depression, may play a detrimental role for patients’ psychological well-being. Finally, GSE emerged as a moderator of distress-depression relationship, suggesting that negative consequences of stress could be reduced during NAC using GSE-based psychological intervention.