Clinical and molecular characteristics of TSC1/2 mutant lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21647-e21647
Author(s):  
Yanye Wang ◽  
Song Xu ◽  
Shikang Zhao ◽  
Shuai Zhu ◽  
Xiongfei Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Smoking History ◽  
Rank Test ◽  
Molecular Characteristics ◽  
Fisher Exact Test ◽  
Continuous Variables ◽  
Cancer Dataset ◽  
Kaplan Meier ◽  
Oncogenic Gene ◽  
Gene Alterations

e21647 Background: Tumor suppressor genes TSC1 and TSC2 inhibit cell growth through inactivation the function of mTORC1. Previous studies have demonstrated that loss of function mutation of either TSC1 or TSC2 gene result in formation of neoplasm in multiple tissues. However, the clinical significance of TSC1 and TSC2 in non-small-cell lung cancer (NSCLC) remains unknown. This study aimed to investigate the clinical and molecular characteristics of TSC1 and TSC2 mutation in NSCLC patients. Methods: We retrieved the clinical and genomic information of 1144 NSCLC from the Pan-Lung cancer dataset through the cBioportal ( www.cbioportal.org) . The cohorts of TSC1 and TSC2 mutant patients were identified. We compared baseline characteristics of patients with the Fisher exact test for categorical data and the Mann-Whitney U test for continuous variables. Overall survival (OS) was estimated with Kaplan-Meier curves, and differences were compared with the log-rank test. Results: Among 1144 patients, 27(2.36%) of them had TSC1 mutation and 40 (3.50%) had TSC2 mutation. Most patients with TSC1 and TSC2 mutations coexisted with other oncogenic gene alterations. TP53 was the most frequent concurrent gene (n = 53), followed with ERBB family genes (n = 24) and KRAS (n = 15). Compared to squamous cell carcinoma, TSC1/2 mutation was slightly more common in adenocarcinoma (53.7% vs 46.3%). 61.2% TSC1/2 mutant patients were male and 88.1% patients had former/current smoking history. Kaplan–Meier analysis showed that the patients harboring TSC1 mutation had a median OS of 14.1 months, whereas patients with TSC2 mutation had a median OS 110.6 months. However, there was not a statistically difference (P = 0.201). Conclusions: TSC1/2 mutation may define a unique population of NSCLC, which often coexists with other oncogenic gene alterations such as TP53 mutation. The function of TSC1/2 mutation and the value of TSC1/2 as therapeutic target in NSCLC are under investigation.

KRAS mutations and outcomes for patients with stage IV NSCLC treated with frontline platinum/pemetrexed based chemotherapy.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e18139-e18139 ◽  
Author(s):  
Benjamin Levy ◽  
Nagashree Seetharamu ◽  
Stacie Richardson ◽  
Daniel Jacob Becker ◽  
Walter Choi ◽  
...  
Keyword(s):  
Stage Iv ◽  
Retrospective Chart Review ◽  
Rank Test ◽  
Fisher Exact Test ◽  
Kras Mutations ◽  
Exact Test ◽  
Kaplan Meier ◽  
Mutational Status ◽  
Former Smokers ◽  
Few Data

e18139 Background: KRAS mutations are the most common driver mutation indentified in NSCLC, occurring in 20 - 30% of adenocarcinomas. While several studies suggest KRAS predicts for lack of response to TKI therapy, few data exist regarding its association with outcomes for patients treated with cytotoxic chemotherapy. This study explores the association between KRAS mutations and outcomes (RR, PFS) in a cohort of patients treated with frontline platinum/pemetrexed (PPm) based therapy. Methods: In this retrospective chart review, we evaluated RR and PFS for 16 KRAS + EGFR – pts treated with carboplatin (AUC 5-6) or Cisplatin 75mg/m2 and (Pm)pemetrexed (500 mg/m2) +/- (B)bevacizumab 15mg/kg. For comparators, we identified 19 KRAS - EGFR - patients treated with the same regimen. Maintenance therapy with Pm or Pm+B was given at the discretion of the treating physician. KRAS and EGFR mutational status were assessed by RT-PCR on tumor tissue collected at first diagnosis. RR was assessed using RECIST criteria. Kaplan-Meier estimates for PFS were evaluating using log rank test. Fisher exact test was used to assess the association between KRAS mutation status and response rate. Results: The groups were similar in age (KRAS + mean 61 vs. 60; p=0.87), gender (62% vs. 57% F; p= 0.9), ECOG 2 (0 vs. 10%,p=0.47), smoking hx (93% vs. 94% current/former smokers, p=0.7), brain mets (0% vs. 18% p=0.22), mean number induction cycles (4 in each, p=0.6), cisplatin and bevacizumab use (12% vs 10%, p > 0.1;10% vs. 40%, p=0.10). Pm maintenance was used in 31% KRAS+ (5/16) and 26% KRAS-(5/19) (p=0.79). P+B maintenance was used in 12% (2/16) and 5% (1/19) (p=0.70). RR was 56% in the KRAS + (9/16) vs. 36% KRAS- (7/19) respectively (p=0.3). There was a statistically significant improvement in PFS in the KRAS + group (10.3 mos vs. 5.7 mos, p =0.03). Conclusions: In this small retrospective review, KRAS mutations appeared to be associated with a non-significant improvement in RR and significant improvement in PFS for patients treated with frontline PPm based therapy. Future prospective studies should investigate and validate the predictive value of KRAS for this cytotoxic regimen. [Table: see text]

Predictors of immune-related adverse events associated with checkpoint inhibitors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15159-e15159
Author(s):  
Alhareth Alsayed ◽  
Ashish Manne ◽  
Daisy E Escobar ◽  
Gaurav Sharma ◽  
Pranitha Prodduturvar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Lymphocyte Count ◽  
Checkpoint Inhibitors ◽  
Hematological Parameters ◽  
White Blood Count ◽  
Categorical Variables ◽  
Fisher Exact Test ◽  
Continuous Variables ◽  
Grade 3

e15159 Background: Immune-related adverse events (irAE) remain a significant challenge with the expansion of checkpoint inhibitors (ICI) indications. Unlike previous studies published, we investigated risk factors for irAE development, including lymphocytes and neutrophils counts in lung cancer and melanoma treated with all available ICIs in current clinical practice. Methods: This is a retrospective study conducted at the University of South Alabama Mitchell Cancer Institute. Between 2015-2019. A total of 160 patients with a diagnosis of melanoma (N = 54) or lung cancer (N = 106) who received at least two doses of ICI including ipilimumab (15%), nivolumab (32%), pembrolizumab (35%), dual nivolumab/ipilimumab (5%), durvalumab (9%) and atezolizumab (4%). The patient's baseline characteristics were extracted with irAE (grade 3/4) details and survival outcomes. Descriptive statistics were used, Fisher exact test to compare categorical variables, and Wilcoxon rank sum test for continuous variables using JMP software. Results: The median age at diagnosis was 64 years (range 17-93), with 51% females. Race distribution with 76% Caucasians and 26% African Americans. Around 30% of the cohort was treated for recurrence, and 39% did receive prior systemic chemotherapy. Median overall survival (OS) was 13.5 months (m) for melanoma and 16 m for lung cancer with CI 95% [16-24] and [15-23], respectively. Twenty-nine (29%) percent of the cohort (N = 46) had grade 3/4 irAEs. Median of baseline hematological parameters including total white blood count (WBC), absolute neutrophil count (ANC), absolute lymphocyte count (ALC), ANC to ALC ratio, and platelet to ALC ratio of these patients were not statistically different from the cohort without grade 3/4 irAEs. Interestingly, if a patient has baseline ALC < 1K/μL, the risk of irAE recurrence is low when ICI is re-initiated, p = .0143 (after symptomatic recovery from irAEs). Conclusions: Irrespective of ICI used, baseline lymphocyte count, and its relation to other blood counts have no clear impact on irAE. Larger cohorts or prospective studies are needed to make stronger conclusions about the relationship between the immune system and the occurrence of irAEs

scholarly journals Marital Status Independently Predicts Survival in Patients with Small Cell Lung Cancer: A SEER Database Analysis

2021 ◽  
Author(s):  
Pei Luo ◽  
Yan Mao ◽  
Liping Yang ◽  
Chao Pan ◽  
Jun Guo
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Marital Status ◽  
Cell Lung Cancer ◽  
Cox Regression ◽  
Small Cell ◽  
Rank Test ◽  
Seer Database ◽  
Small Cell Lung ◽  
Kaplan Meier

Abstract Purpose This study will investigate the relationship between marital status and prognosis in small cell lung cancer patients. Methods Patients of SCLC was selected from the SEER database (1973-2013) and the patient sinformation. Kaplan-Meier analysis, log-rank test and Cox regression model were used for studying patientprognosis. Result 27069 SCLC patients eligible for inclusion were screened from the SEER database. Kaplan-meier test showed that the median OS values were 8, 7, 6 months in married, single and SDW patients, respectively. Conclusion This study shows that marital status is an independent prognostic factor for overall survival in SCLC patients. Married patients with small cell lung cancer have better prognosis than those who were divorced/separated, widowed and single.

scholarly journals Efficacy of Apatinib+Radiotherapy vs. Radiotherapy alone in Patients with Advanced Multiline Therapy Failure for NSCLC

2021 ◽  
Author(s):  
Huanle Pan ◽  
Su Chenxian ◽  
Yunhao Li ◽  
Xinyi Wu ◽  
Chaoyi Wei ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Central Nervous System ◽  
Small Cell ◽  
Rank Test ◽  
Small Cell Lung ◽  
Therapy Failure ◽  
Log Rank Test ◽  
Kaplan Meier ◽  
Intracranial Metastases ◽  
Radiotherapy Alone

Abstract Background: Lung cancer is the leading cause of cancer-associated mortality worldwide, and in China. Central nervous system (CNS) metastasis is a prevalent and serious complication. The most common treatment for BM is still radiation therapy (RT). An increasing number of drugs have been shown to have intracranial activity or to sensitize tumours to radiotherapy.Methods: Our study aims to demonstrate the clinical efficacy of apatinib combined with radiotherapy vs. radiotherapy alone in the treatment of patients with advanced multiline failure for non-small-cell lung cancer with brain metastasis (BM). Eligible patients were divided into two groups: Apatinib + RT group and RT group. In the apatinib + RT group. Intracranial PFS and OS were analysed using the Kaplan-Meier method. Differences between groups were compared by the log-rank test.Results: The median intracranial PFS for the RT group and Apatinib+RT group was 5.83 months and 11.81 months (p=0.034). The median OS for the RT group and Apatinib+RT group was 9.02 months and 13.62 months (p=0.311). The Apatinib+RT group had a better intracranial PFS, but there were no significant differences between the two arms in OS. The Apatinib+RT group had significantly reduced symptoms caused by BM, mainly headache and vomiting. Most patients tolerated the side effects well. Conclusion: RT combined with apatinib could help to control intracranial metastases. The Apatinib+RT group had significantly reduced symptoms caused by BM, the safety of the two treatments was similar.

Evaluation of the pattern of SOX2 expression in non-small cell lung cancer (NSCLC) and correlation with clinicopathologic (CP) features and prognosis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21106-e21106
Author(s):  
Vamsidhar Velcheti ◽  
Huan Cheng ◽  
Xiaopan Yao ◽  
Yanhong Deng ◽  
Scott N. Gettinger ◽  
...  
Keyword(s):  
Embryonic Stem ◽  
University Hospital ◽  
Rank Test ◽  
Molecular Characteristics ◽  
Test Results ◽  
New Haven ◽  
Sox2 Expression ◽  
Kaplan Meier ◽  
Quantitative Immunofluorescence ◽  
Independent Cohort

e21106 Background: SOX2 is an embryonic stem cell transcription factor that plays a crucial role in differentiation and maintaining pluripotency. We examine the pattern of SOX2 expression and assess correlation with CP features in NSCLC. Methods: Using the AQUA method of automated quantitative immunofluorescence we measured SOX2 expression in two cohorts (in a tissue microarray format), from Yale New Haven Hospital (YTMA 79) and an independent cohort from Patras University Hospital in Greece (YTMA 140) (196 and 342 cases, respectively). YTMA 140 had high percentage of Squamous cell carcinoma (SCC) (48.8%) as opposed to 17.9% in YTMA 79. There were more stage III & IV pts in YTMA 140 (41.3%) compared to YTMA79 (30.6%). 88% of pts in the YTMA 140 were male compared to 52.5% in YTMA79. Survival analysis was done using Kaplan-Meier analysis with log-rank test. The associations between SOX2 expression level and CP features were evaluated by using non-parametric Kruskal-Wallis test. Results: In both cohorts, we found significantly higher SOX2 expression in SCC compared to adenocarcinoma. There was no correlation with gender or stage. Using the threshold of specific signal detection as the cut point, we divided the cohorts into expressers and non-expressers. YTMA 140 cohort which is enriched in SCC showed that 28/161(17.3%) pts with SCC were SOX2 non-expressers. Pts who were SOX2 non-expressers had a worse median overall survival (15 months) compared to pts who were SOX2 expressers (23.5 months) (p=0.015). Conclusions: Our data reveals that pts who have SCC have significantly higher expression of SOX2 and higher SOX2 expression correlates with better outcome. Further studies to define the molecular characteristics of SCC may elucidate more effective markers and effective classification for NSCLC.

RASA1 and NF1 co-mutated non-small cell lung carcinomas: Cancer genomic data and evaluation of sensitivity to MEK inhibition.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11600-11600
Author(s):  
Takuo Hayashi ◽  
Patrice Desmeules ◽  
Roger Smith ◽  
Alexander E. Drilon ◽  
Romel Somwar ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Mapk Pathway ◽  
Negative Control ◽  
Small Cell ◽  
Molecular Characteristics ◽  
Loss Of Function ◽  
Small Cell Lung ◽  
Cancer Dataset ◽  
Lung Carcinomas ◽  
Mek Inhibition

11600 Background: Ras-GTPase activating proteins (RasGAPs), notably NF1 and RASA1, mediate negative control of the RAS/MAPK pathway. While NF1 mutations are enriched in non-small cell lung carcinomas (NSCLC) lacking KRAS alterations, they are not completely mutually exclusive. We evaluated clinical and molecular characteristics of NSCLC with RASA1 mutations in comparison with NF1-mutated cases. Methods: Large genomic datasets of NSCLC [MSK-IMPACT™ dataset at MSKCC (n = 2004), TCGA combined lung cancer dataset (n = 1144)] were analyzed to define concurrent mutations and clinical features of RASA1-mutated NSCLCs. Functional studies were performed using immortalized human bronchial epithelial cells (HBECs) and NSCLC lines with RasGAP truncating mutations, in RASA1 (RERFLCKJ), NF1 (LCLC103H and H1838), or both (EPLC272H). Results: Overall, approximately 2% of NSCLCs had RASA1 truncating mutations, and this alteration was statistically, but not completely, mutually exclusive with known activating EGFR (p = .02) and KRAS (p = .02) mutations. Unexpectedly, RASA1 truncating mutations had a strong tendency to co-occur with NF1 truncating mutations (p < .001), suggesting selection for loss of more than one RasGAP. Furthermore, all patients (16/16) with concurrent RASA1/NF1 truncating mutations lacked other known lung cancer drivers, including KRAS. Knockdown of RASA1 in HBECs activated signaling downstream of RAS and promoted cell growth. Conversely, restoration of RASA1 expression in RERFLCKJ cells reduced MAPK and PI3K signaling. While growth of cell lines with inactivation of only one of these two RasGAPs showed moderate and variable sensitivity to inhibitors of MEK (trametinib) or PI3K (GDC0941, PI103), EPLC272H cells (with concurrent RASA1/NF1 mutations) showed notably more profound sensitivity (IC50: 0.040µM trametinib). Finally, simultaneous silencing of RASA1 and NF1 sensitized both HBECs and NSCLC cells to MEK inhibition. Conclusions: Cancer genomic and functional data nominate concurrent RASA1/NF1 loss of function mutations as a strong mitogenic driver in NSCLC. Patients whose tumors show this distinctive genotype should be considered for trials of MEK inhibitors.

scholarly journals Survival in a cohort of patients with lung cancer: the role of age and gender in prognosis

2017 ◽  
Vol 43 (6) ◽  
pp. 431-436 ◽  
Author(s):  
Juliana Pereira Franceschini ◽  
Sérgio Jamnik ◽  
Ilka Lopes Santoro
Keyword(s):  
Lung Cancer ◽  
Age Distribution ◽  
Age Groups ◽  
Rank Test ◽  
Age Group ◽  
Tertiary Referral Hospital ◽  
Kaplan Meier ◽  
Stage Disease ◽  
And Gender ◽  
Disease Stages

ABSTRACT Objective: To determine the demographic and clinical characteristics of patients with non-small cell lung cancer (NSCLC), as well as their disease course, by age group and gender. Methods: This was a retrospective cohort study of patients diagnosed with NSCLC from 2000 to 2012 and followed until July 2015 in a tertiary referral hospital in the city of São Paulo, Brazil. Based on the 25th and 75th percentiles of the age distribution, patients were stratified into three age groups: < 55 years; ≥ 55 and < 72 years; and ≥ 72 years. Survival time was evaluated during the follow-up period of the study. Functions of overall and gender-specific survival stratified by age groups (event: all-cause mortality) were calculated using the Kaplan-Meier method. Differences among survival curves were assessed via the log-rank test. Results: We included 790 patients with the following age distribution: < 55 years, 165 patients; ≥ 55 and < 72 years, 423; and ≥ 72 years, 202. In the entire sample, there were 493 men (62.4%). Adenocarcinoma was the most common histological pattern in the < 72-year age groups; 575 patients (73%) presented with advanced disease (stages IIIB-IV). The median 5-year survival was 12 months (95% CI: 4-46 months), with no significant differences among the age groups studied. Conclusions: NSCLC remains more common in men, although we found an increase in the proportion of the disease in women in the < 55-year age group. Adenocarcinoma predominated in women. In men, squamous cell carcinoma predominated in the ≥ 72-year age group. Most patients presented with advanced-stage disease at diagnosis. There were no statistical differences in survival between genders or among age groups.

scholarly journals CLINICAL, DEMOGRAPHIC, ANATOMOPATHOLOGICAL, AND MOLECULAR FINDINGS IN PATIENTS WITH MEDULLOBLASTOMA TREATED IN A SINGLE HEALTH FACILITY

2021 ◽  
Vol 39 ◽  
Author(s):  
Iva Loureiro Hoffmann ◽  
Izilda Aparecida Cardinalli ◽  
José Andrés Yunes ◽  
Ana Luiza Seidinger ◽  
Ricardo Mendes Pereira
Keyword(s):  
Overall Survival ◽  
Tumor Resection ◽  
Signs And Symptoms ◽  
Molecular Profile ◽  
Rank Test ◽  
Molecular Characteristics ◽  
Incomplete Resection ◽  
Event Free Survival ◽  
Free Survival ◽  
Kaplan Meier

ABSTRACT Objective: To describe the clinical, demographic, anatomopathological, molecular, and survival characteristics of patients with medulloblastoma. Methods: Retrospective study based on patient information obtained from the review of medical records. Overall and event-free survival were analyzed using the Kaplan-Meier estimator, and the curves were compared by the log-rank test. Results: Among the patients investigated, 70 were male (66%), and age at diagnosis ranged from 2 months to 22 years. The most frequent signs and symptoms were headache (80.8%) and vomiting (75.8%). Regarding treatment, most patients (63.2%) underwent complete surgical resection, with a predominance of classic histology (63.2%). The 5-year overall survival rate was 67.9%, and the 10-year rate was 64.2%. Patients with molecular profile characteristic of the wingless (WNT) subgroup had a better prognosis, with 5-year overall survival of 75%. Conclusions: The clinical, demographic, anatomopathological, and molecular characteristics of patients with medulloblastoma described in the present study were mostly similar to those reported in the literature. Patients submitted to complete tumor resection had better clinical outcomes than those who underwent incomplete resection/biopsy. Patients classified as high-risk showed worse overall and event-free survival than those in the standard-risk group, and the presence of metastasis at diagnosis was associated with recurrence.

scholarly journals Absence of Survival Improvement for Patients with Esthesioneuroblastoma Over the Past Two Decades: A Population-based Study

2021 ◽  
Author(s):  
Huy Gia Vuong ◽  
Duy Duc Nguyen ◽  
Edward El-Rassi ◽  
Tam N. M. Ngo ◽  
Ian F. Dunn
Keyword(s):  
Adjuvant Radiotherapy ◽  
Proportional Hazards Model ◽  
Tumor Resection ◽  
Cox Proportional Hazards Model ◽  
Rank Test ◽  
Tumor Diameter ◽  
Continuous Variables ◽  
The Past ◽  
Kaplan Meier ◽  
The Impact

Abstract Introduction: Esthesioneuroblastoma (ENB) is a rare malignancy of the sinonasal tract and its infrequency has confounded efforts at clearly describing the survival trends associated with this neoplasm over the years. In this study, we studied survival trends in ENB and investigated the impact of treatment extent and modality on patient outcomes.Methods: We accessed the Surveillance, Epidemiology, and End Result (SEER) program to identify ENB cases from 1998 to 2016. A Chi-square test was used to compare the categorical covariates whereas a t-test or Mann-Whitney U test was utilized for continuous variables. The impact of prognostic factors on survival was computed using a Kaplan-Meier analysis and multivariate Cox proportional hazards model. We divided ENB patients into four periods including 1998-2002, 2003-2007, 2008-2012, and 2013-2016, and investigated survival trends using the Kaplan-Meier curve and log-rank test.Results: ENB patients who underwent biopsy alone were associated with older age, larger tumor diameter, increased rates of tumor extension, nodal/distant metastases, and advanced stages as compared to patients undergoing tumor resection. Our results also demonstrated that surgical resection and adjuvant radiotherapy could confer survival advantages whereas chemotherapy was associated with reduced survival in patients with ENB. Over the past two decades, surprisingly, there has been no change in survival rates for patient with ENB (p = 0.793).Conclusion: Despite advanced diagnostic studies and modernized treatment approaches, ENB survival has remained unchanged over the years, calling for improved efforts to develop appropriate individualized interventions for this rare tumor entity. Our results also confirmed that surgery and adjuvant radiotherapy is associated with improved patient survival whereas the use of chemotherapy should be considered carefully.

scholarly journals Prognostic factors of patients with advanced lung cancer treated with anlotinib: a retrospective cohort study

2021 ◽  
Vol 49 (10) ◽  
pp. 030006052110461
Author(s):  
Bijun Fan ◽  
Xiaoming Tan ◽  
Yueyan Lou ◽  
Yu Zheng ◽  
Liyan Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Locally Advanced ◽  
Prognostic Nutritional Index ◽  
Progression Free Survival ◽  
Advanced Lung Cancer ◽  
Rank Test ◽  
Factors Affecting ◽  
Kaplan Meier ◽  
Hand Foot Syndrome ◽  
Cox Proportional Hazard Regression

Objective Our study aimed to evaluate the main factors affecting the efficacy of anlotinib to determine the therapeutically dominant populations. Methods The medical records of patients with lung cancer who were treated with anlotinib from July 2018 to February 2020 at Renji Hospital, School of Medicine, Shanghai Jiaotong University were retrospectively reviewed. The optimal cutoff prognostic nutritional index (PNI) value for predicting efficacy was determined according to receiver operating characteristic curves. Progression-free survival (PFS) and overall survival (OS) were calculated and compared using the Kaplan–Meier method and log‐rank test. The prognostic values of each variable were evaluated with univariate and multivariate Cox proportional hazard regression analyses. Results The overall disease control rate of 44 patients with lung cancer was 93.2% (41/44). The median PFS was 5.0 months (95% [confidence interval] CI: 2.2–7.8), and the median OS was 6.5 months (95% CI: 3.6–9.3). The multivariate analysis results indicated that hand–foot syndrome and high PNI values were independent protective factors of PFS and OS. Conclusions Anlotinib was effective in treating locally advanced or advanced lung cancer. High pretreatment PNI scores and the presence of hand–foot syndrome after treatment were independent prognostic markers for favorable OS and PFS.

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