The alteration of TERT in 10,000 Chinese patients with solid tumors.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13655-e13655
Author(s):  
Jie Lin ◽  
Yuehua Li ◽  
Hao Zou ◽  
Li Zhang ◽  
Yanbin Xiao ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Biliary Tract ◽  
Solid Tumor ◽  
Promoter Region ◽  
Chinese Patients ◽  
Tumor Patients ◽  
Lung Cancers ◽  
Liver Cancers ◽  
Biliary Tract Tumors ◽  
And Gender

e13655 Background: The reactivation of telomerase reverse transcriptase ( TERT) is one of the characters that make cancer cells immortal. TERT expression has been shown in various human cancers.However, the landscape of TERT alterations in Chinese patients with solid tumors still remains unclear. Here, we illustrated the profile of TERT variations of Chinese solid tumor patients by using next generation sequencing (NGS)-based targeted sequencing. Methods: Formalin fixed, paraffin embedded (FFPE) tumor tissues and matching blood samples were collected from 9874 Chinese patients and subjected to a NGS-based panel at a College of American Pathologists (CAP) accredited and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. All classes of alterations were assessed. Results: FFPE samples from 9874 Chinese solid tumor patients included lung cancers (39.7%), liver cancers (12.5%), colorectal cancers (10.8%), gastric cancers (5.7%), pancreatic cancers (4.9%), biliary tract tumors (4.6%), and other 18 cancer types (21.7%) were assessed. And 1187 (12.0%) out of 9874 cancer samples had TERT variations. TERT variations occurred in all types of cancer with various frequencies: urothelial neoplasms (52.0%), central nervous system tumors (40.0%), melanomas (38.9%), liver cancers (30.7%), thyroid tumors (24.3%), cervical cancers (20.6%), biliary tract tumors (16.3%), head and neck tumors (14.6%), soft tissue tumors (12.2%) and lung cancers (10.3%). Substitution was the most common variation of TERT and accounted for 58.7% of all the alterations, followed by gene amplification (38.8%) and fusions (2.4%). There were 86.8% of substitution variations presented in TERT promoter region comprising of c.-124C > T (70.7%) and c.-146C > T (13.1%). Patients with TERT alterations included 414 females and 773 males with a median age of 59 years old (range: 8-88). Tumors included stage IV (34.0%), stage III (22.2%), stage II (12.7%), stage I (18.7%) and stage 0 (12.3%). TERT variations were correlated with patients’ age (p = 0.00083) and gender (p = 5.59×10−7). There was no significant correlation of TERT alterations with the highly mutated TP53. The frequencies of TERT alterations were similar in patients with mutated and wild type TP53 (12.7% vs 11.1%). Conclusions: Our study revealed that 12.0% Chinese solid tumor patients harbored TERT alterations, especially two hotspots mutations (c.-124C > T and c.-146C > T) in the promoter region. TERT variations had a correlation with patients’ age and gender, but no correlation with hotspot TP53 mutations.

Updated safety and efficacy of MSB2311 (an anti-programmed death-ligand 1 antibody) in Chinese patients with advanced solid tumors and hematological malignancies from a phase 1 study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14547-e14547
Author(s):  
Lin Shen ◽  
Jifang Gong ◽  
Jian Zhang ◽  
Dongmei Ji ◽  
Haijun Zhong ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Solid Tumor ◽  
Phase 1 ◽  
Chinese Patients ◽  
Binding Property ◽  
Advanced Solid Tumors ◽  
Tumor Patients ◽  
Durable Response ◽  
Programmed Death ◽  
Grade 3

e14547 Background: MSB2311 is a novel humanized PD-L1 antibody with a unique pH-dependent antigen binding property that enables intra-tumor recycling and potentiates tumor penetration. Methods: Patients with metastatic solid tumors or selected lymphoma progressed on or after standard treatments were enrolled in this phase I study. In dose escalation part, MSB2311 was given at dose levels of 3, 10, and 20 mg/kg intravenously every 3 weeks. At the dose expansion part, patients with enriched biomarker expression, including EBV+, PD-L1+ (TPS≥50%), MSI-High or TMB-High (≥10muts/Mb), were dosed at 20mg/kg Q3W or 10mg/kg Q2W. Primary objectives are to evaluate the safety and tolerability and to identify MTD and RP2D. Secondary objectives include the assessment of pharmacokinetic parameter, immunogenicity, and preliminary anti-cancer activity per RECIST1.1. Results: As of data cutoff by Aug 31, 2020, 33 Chinese patients had been treated, including 27 heavily pre-treated solid tumor patients and 6 lymphoma patients. No dose limiting toxicity was reported and MTD has not been reached. The most common AEs (>20%) included: anemia, hypothyroidism, aspartate aminotransferase elevated, proteinuria, weight loss. 13 patients (39.4%) experienced grade 3 AEs, and 6 patients (18.2%) experienced SAEs. No treatment related grade 4 or 5 event was reported. Of the 17 efficacy evaluable solid tumor patients with biomarker selection, 6 achieved confirmed partial response with 35% ORR: 2/8 (25%) at 10 mg/kg Q2W and 4/9 (44%) at 20 mg/kg Q3W. Additionally, one patient achieved sustained iPR via iRECIST. 4 out of 7 responding patients (including one iPR) achieved tumor shrinkage of more than 50%, 3 of them got durable response (≥24 weeks).1 out of 6 lymphoma patients achieved PR. Conclusions: MSB2311 demonstrated a manageable safety profile and promising preliminary antitumor activity in patients with advanced solid tumors and selected lymphomas. Clinical trial information: NCT04272944.

CX1003 quantification by ultra-performance LC–MS/MS in human plasma and its application to a pharmacokinetic study in solid tumor patients

Bioanalysis ◽  
2019 ◽  
Vol 11 (16) ◽  
pp. 1483-1493
Author(s):  
Yu Li ◽  
Qian Zhao ◽  
Pei Hu ◽  
Ji Jiang
Keyword(s):  
Cancer Patients ◽  
Human Plasma ◽  
Solid Tumors ◽  
Pharmacokinetic Study ◽  
Solid Tumor ◽  
Receptor Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Chinese Patients ◽  
Good Sensitivity ◽  
Tumor Patients

Aim: CX1003 is a novel multitargeted receptor tyrosine kinase inhibitor targeting cancer patients with relapsed or metastatic malignant solid tumors. The study aimed to develop a robust and rapid assay approach to quantify CX1003 in human plasma. Methodology & results: Samples of plasma were purified by SPE where the diluted eluates were then separated by a Waters Acquity CSH C18 column and thereafter detected using positive electrospray ionization via an ultra performance LC–MS/MS. Conclusion: The method to quantify CX1003 in human plasma was first exploited and validated with good sensitivity and specificity, and successfully fulfilled the requirement of the first-in-human clinical pharmacokinetic study of CX1003 in Chinese patients with relapsed or metastatic malignant solid tumors.

Clinical prediction of bacteremia and early antibiotics therapy in patients with solid tumors

2021 ◽  
pp. 1-7
Author(s):  
Jonathan M. Hyak ◽  
Mayar Al Mohajer ◽  
Daniel M. Musher ◽  
Benjamin L. Musher
Keyword(s):  
Solid Tumors ◽  
Solid Tumor ◽  
Cardiopulmonary Arrest ◽  
Tertiary Care ◽  
Organ Transplant ◽  
Antibiotic Use ◽  
Care Hospital ◽  
Tumor Patients ◽  
Binomial Regression ◽  
Sirs Criteria

Abstract Objective: To investigate the relationship between the systemic inflammatory response syndrome (SIRS), early antibiotic use, and bacteremia in solid-tumor patients. Design, setting, and participants: We conducted a retrospective observational study of adults with solid tumors admitted to a tertiary-care hospital through the emergency department over a 2-year period. Patients with neutropenic fever, organ transplant, trauma, or cardiopulmonary arrest were excluded. Methods: Rates of SIRS, bacteremia, and early antibiotics (initiation within 8 hours of presentation) were compared using the χ2 and Student t tests. Binomial regression and receiver operator curves were analyzed to assess predictors of bacteremia and early antibiotics. Results: Early antibiotics were administered in 507 (37%) of 1,344 SIRS-positive cases and 492 (22%) of 2,236 SIRS-negative cases (P < .0001). Of SIRS-positive cases, 70% had blood cultures drawn within 48 hours and 19% were positive; among SIRS negative cases, 35% had cultures and 13% were positive (19% vs 13%; P = .003). Bacteremic cases were more often SIRS positive than nonbacteremic cases (60% vs 50%; P =.003), but they received early antibiotics at similar rates (50% vs 49%, P = .72). Three SIRS components predicted early antibiotics: temperature (OR, 1.7; 95% CI, 1.31–2.29; P = .0001), tachycardia (OR, 1.4; 95% CI, 1.10–1.69; P < .0001), and white blood-cell count (OR, 1.8; 95% CI, 1.56–2.14; P < .0001). Only temperature (OR, 1.6; 95% CI, 1.09–2.41; P = .01) and tachycardia (OR, 1.5; 95% CI, 1.09–2.06; P = .01) predicted bacteremia. SIRS criteria as a composite were poorly predictive of bacteremia (AUC, 0.57). Conclusions: SIRS criteria are frequently used to determine the need for early antibiotics, but they are poor predictors of bacteremia in solid-tumor patients. More reliable models are needed to guide judicious use of antibiotics in this population.

Characteristics and outcomes of cancer patients ≥80 years treated with chemotherapy at a comprehensive cancer center

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8548-8548
Author(s):  
P. Jiang ◽  
M. Choi ◽  
D. Smith ◽  
L. Heilbrun ◽  
S. M. Gadgeel
Keyword(s):  
Cancer Patients ◽  
Solid Tumors ◽  
Solid Tumor ◽  
Hematologic Malignancy ◽  
Survival Rates ◽  
The United States ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Tumor Patients ◽  
Hematologic Cancer

8548 Background: The percentage of cancer patients ≥ 80 years old is expected to rise in the United States. However data are limited on use of chemotherapy in this group of patients. Methods: Retrospective identification of patients who received systemic chemotherapy at our cancer center between 1/1/2000 to 12/31/2004 was performed using the computer generated pharmacy data and medical records. Patients who had diagnosis of cancer and ≥ 80 years were included in the study; patients receiving only supportive care, hormonal therapy, or oral chemotherapy were excluded. The protocol for this study was approved by the Wayne State University IRB. Results: A total of 133 patients ≥ 80 years who received chemotherapy was analyzed. The median age was 83 and 31% of the patients were ≥ 85 years. There were more females (61%) than males (39%). The gender distribution was more even (47% v. 53%) after excluding gender specific tumors. The racial distribution was diverse- Whites 65 (49%); Blacks 41 (31%); Other 18 (13%); Unknown 9 (7%). 16% of the patients had hematologic malignancy and 84% had solid tumors. Gynecological cancers (32%) followed by aerodigestive cancers (26%) were the most common solid tumors. Solid tumor patients primarily had regional (48%) or distant (45%) disease. During the first regimen, 512 cycles of chemotherapy was delivered with a median of 3 cycles per patient (range 1–24 cycles); 40% of patients received only 2 cycles of chemotherapy. 64% of patients were able to receive chemotherapy without 2nd cycle delay. The distribution of single or multidrug regimens was fairly similar; Solid tumors 52% v. 48%; Hematologic cancers 43% v. 57%. Carboplatin and paclitaxel (22%) was the most common regimen among solid tumor patients. 26% of all patients received a second regimen. The 1 year survival rates among hematologic cancer and solid tumor patients were 65% and 48%, respectively. Stage of disease was the only statistically significant factor predicting survival. Conclusions: In this diverse group of cancer patients ≥ 80 years old and selected for chemotherapy, the treatment was feasible. The survival outcomes in this elderly population were comparable to those of a younger patient population suggesting that the treatment is beneficial. No significant financial relationships to disclose.

Oncogenic FGFR3 gene fusions in solid tumors among Chinese cancer patients.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e15072-e15072
Author(s):  
Libin Xu ◽  
Ming Liu ◽  
Jingxian Duan ◽  
Tao Wang
Keyword(s):  
Cancer Patients ◽  
Solid Tumors ◽  
Solid Tumor ◽  
Coiled Coil ◽  
Genetic Alterations ◽  
Chinese Patients ◽  
Driver Mutations ◽  
Gene Fusions ◽  
Fgfr3 Gene ◽  
Tumor Types

e15072 Background: Oncogenic FGFR3 (fibroblast growth factor receptor 3) gene fusions have been identified as driver mutations that lead to the activation of FGFR3 in many solid tumor types and serve as a novel therapeutic target for FGFR inhibitors in clinical development. TACC3 (transforming acid coiled coil 3) is the most common partner of these FGFR3 fusions. Methods: The study enrolled over ten thousand cases of Chinese patients with different types of solid tumors. We performed targeted sequencing assay with our 605 gene panel that covered all the exon and intron regions of the FGFR3 gene, so that we could identify nearly all the FGFR3 translocation events. Results: The prevalence and form of FGFR3 fusions in different tumor types were shown in Table. We identified seven patients harboring FGFR3 fusion events, with six cases of FGFR3-TACC3 and one case of FGFR3-UBE2K. In the seven patients, three of them were also harbored concomitant TP53 gene mutations, and six of them were microsatellite stability (MSS), and one was microsatellite instability-low (MSI-L). Conclusions: FGFR3 gene rearrangements were identified in different solid tumor types in our study, and they were relatively rare compared to other novel mutations. However, clinical testing for the identification of FGFR3 fusions should be prioritized in bladder cancer patients. Consistent with other studies, the most common FGFR3 fusion form was FGFR3-TACC3. Co-occurring genetic alterations in FGFR3 gene fusions cases were also common. From our limited number of cases, most of FGFR3 gene fusions patients were MSS.[Table: see text]

In-hospital mortality of patients admitted through the emergency department of a comprehensive cancer center.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6125-6125 ◽  
Author(s):  
Ahmed F. Elsayem ◽  
Carmen E. Gonzalez ◽  
S. J. Yeung ◽  
Kelly W. Merriman ◽  
Knox H. Todd
Keyword(s):  
Mortality Rate ◽  
Hospital Mortality ◽  
Cancer Patients ◽  
Solid Tumors ◽  
Solid Tumor ◽  
Hematologic Malignancies ◽  
Comprehensive Cancer Center ◽  
Cancer Center ◽  
Intractable Pain ◽  
Tumor Patients

6125 Background: Cancer is a common presenting condition for emergency departments (EDs); however, there is limited information on outcomes of ED cancer patients subsequently admitted to the hospital. The purpose of this study is to describe outcomes of patients with hematologic malignancies versus those with solid tumors admitted through the ED of a comprehensive cancer center. Methods: We queried the ED database of The University of Texas MD Anderson Cancer Center for calendar year 2010 and linked it to our institutional data warehouse, including tumor registry data. We classified all leukemia and related disorders, lymphoma, multiple myeloma, and bone marrow transplant patients as hematologic malignancies, and remaining cancers as solid tumors. Descriptive statistics, including chi-square, and t-tests were used in two-sided comparisons. All statistical analyses were performed using SPSS version 15. Results: 20,732 total ED visits were made by 9,320 unique cancer patients. Of these, 5,364 (58%) were admitted to the hospital at least once (range 1-13 admits). ED admissions constituted 39% of total unique patients admitted (N=13,753). The main admission indications for solid tumor patients were infectious complications (particularly pneumonia), intractable pain, or dehydration. For hematologic malignancies, the main indication was neutropenic fever. 211/1656 (13%) of liquid tumor patients were admitted to the Intensive Care Unit (ICU) compared to 484/3708 (13%) of solid tumor patients (P=NS). Of all patients admitted through the ED, 587/5364 (10.9%) died during hospitalization. The hematologic hospital mortality rate was 225/1653 (13.6%) versus 362/3708 (9.8%) for solid tumors (P<0.001). Only 242/8389 (3%) of patients admitted directly from outpatient clinics died during the hospitalization (p<0.001). Conclusions: Patients admitted through the ED, particularly those with hematologic malignancies, have a high hospital mortality rate. ED-based palliative care interventions may be justified to improve quality of life and prevent unnecessary costly interventions and ICU admission. Further research should define predictors of poor outcomes in cancer patients admitted through the ED.

scholarly journals Investigation of spleen CXCR4 expression by [68Ga]Pentixafor PET in a cohort of 145 solid cancer patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Richard Lewis ◽  
Stefan Habringer ◽  
Malte Kircher ◽  
Maike Hefter ◽  
Caroline Anna Peuker ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Solid Tumors ◽  
Neuroendocrine Tumors ◽  
Cell Lung Cancer ◽  
Solid Tumor ◽  
Small Cell ◽  
Cxcr4 Expression ◽  
Small Cell Lung ◽  
Tumor Patients

Abstract Background The chemokine receptor CXCR4 is frequently overexpressed and associated with adverse prognosis in most hematopoietic malignancies and solid cancers. Recently, CXCR4 molecular imaging using the CXCR4-specific positron emission tomography (PET) tracer Pentixafor ([68Ga]Pentixafor) has become a well-established method to non-invasively measure CXCR4 expression in vivo. In previous Pentixafor imaging studies, highly variable CXCR4 tracer uptake to the spleen was observed. Results We investigated the hypothesis that enhanced spleen [68Ga]Pentixafor uptake and thus CXCR4 expression in patients with solid tumors would indicate an activated spleen state and/or an association with clinical and prognostic features and survival parameters. In this retrospective study, [68Ga]Pentixafor-PET images and patient records of 145 solid tumor patients representing 27 cancer entities were investigated for an association of spleen [68Ga]Pentixafor uptake and clinical characteristics and outcome. Based on this assessment, we did not observe differences in clinical outcomes, measured by progression-free survival, overall survival and remission status neither within the entire cohort nor within subgroups of adrenal cancer, desmoplastic small round cell tumor, neuroendocrine tumors, non-small cell lung cancer, small cell lung cancer and pancreatic adenocarcinoma patients. No tumor entity showed especially high levels of spleen [68Ga]Pentixafor uptake compared to others or a control cohort. However, when investigating laboratory parameters, there was a positive correlation of high spleen [68Ga]Pentixafor uptake with leukocyte and/or platelet counts in neuroendocrine tumors, non-small cell lung cancer and small cell lung cancer. Conclusion Spleen [68Ga]Pentixafor uptake was not associated with stage of disease and clinical outcomes in solid tumor patients. We identified positively associated platelet and/or leukocyte counts with spleen [68Ga]Pentixafor uptake in neuroendocrine tumors, non-small cell lung cancer and small cell lung cancer, suggesting that splenic CXCR4 expression could possibly play a role in systemic immunity/inflammation in some types of solid tumors or a subgroup of patients within solid tumor entities.

Neuraxis imaging in leptomeningeal metastasis: A retrospective case series.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2046-2046 ◽  
Author(s):  
Marc C. Chamberlain
Keyword(s):  
Flow Cytometry ◽  
Solid Tumors ◽  
Solid Tumor ◽  
Case Series ◽  
Leptomeningeal Metastasis ◽  
Csf Cytology ◽  
Csf Flow ◽  
Retrospective Case ◽  
Tumor Patients ◽  
Spine Mri

2046 Background: (and Objective) Leptomeningeal metastasis (LM) is a central nervous system metastatic complication of cancer that affects the entire neuraxis. Quantify imaging (brain and spine MRI and radio-isotope cerebrospinal fluid [CSF] flow study) abnormalities in a retrospective case series of patients with LM. Methods: 240 adult patients with LM (125 non-brain solid tumor patients with positive CSF cytology; 40 non-brain solid tumor patients with negative CSF cytology; 50 lymphoma and 40 leukemia patients with positive CSF flow cytometry) underwent prior to treatment brain and entire spine MRI and radio-isotope CSF flow studies (FS). Results: Neuraxis MRI in pathologically defined patients was more often normal in hematologic tumors (80-84%) compared to solid tumors (60%). Similarly, FS was more often normal in hematologic tumors (90-92%) compared to solid tumors (72-75%). However, neuraxis MRI and FS abnormalities (i.e. CSF flow obstruction; nodular subarachnoid or parenchymal disease; hydrocephalus) altered therapy by requiring CSF diversion, site specific radiotherapy, systemic chemotherapy or recommending no further therapy in one third of CSF cytology positive solid tumors and 15% of CSF flow cytometry positive hematologic tumors. Conclusions: Notwithstanding less frequent imaging abnormalities in hematologic tumors, similar to solid tumors imaging abnormalities frequently result in treatment alteration for patients with LM. Consequently, neuraxis imaging is recommended in both tumor categories in patients being considered for LM-directed and in particular intra-CSF chemotherapy treatment.

scholarly journals Targeting Solid Tumors With BTK Inhibitors

2021 ◽  
Vol 9 ◽  
Author(s):  
Fatih M. Uckun ◽  
Taracad Venkatachalam
Keyword(s):  
Solid Tumors ◽  
Solid Tumor ◽  
Tumor Therapy ◽  
Tumor Patients ◽  
Effective Combination ◽  
Solid Tumor Therapy ◽  
Refractory Solid Tumor ◽  
Clinical Potential ◽  
Combination Regimens ◽  
Btk Inhibitors

The repurposing of FDA-approved Bruton’s tyrosine kinase (BTK) inhibitors as therapeutic agents for solid tumors may offer renewed hope for chemotherapy-resistant cancer patients. Here we review the emerging evidence regarding the clinical potential of BTK inhibitors in solid tumor therapy. The use of BTK inhibitors may through lead optimization and translational research lead to the development of new and effective combination regimens for metastatic and/or therapy-refractory solid tumor patients.

scholarly journals Clinical sequencing to assess tumor mutational burden as a useful biomarker to immunotherapy in various solid tumors

2021 ◽  
Vol 13 ◽  
pp. 175883592199299
Author(s):  
Hana Kim ◽  
Jung Yong Hong ◽  
Jeeyun Lee ◽  
Se Hoon Park ◽  
Joon Oh Park ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Solid Tumors ◽  
Solid Tumor ◽  
Routine Clinical Practice ◽  
High Status ◽  
Tumor Patients ◽  
Mutational Burden ◽  
The Status ◽  
Tumor Mutational Burden ◽  
Cancer Panel

Background: Immune checkpoint inhibitors (ICIs) have become established as a new therapeutic paradigm in various solid cancers. Predictive biomarkers to ICIs have not yet been fully established. Tumor mutational burden (TMB) has been considered as a useful marker to indicate patients who benefit from ICIs. Methods: We performed next-generation sequencing, including TMB analysis, as a routine clinical practice in 501 patients with advanced gastrointestinal (GI), genitourinary (GU), or rare cancers. The TruSight™ Oncology 500 assay from Illumina was used as a cancer panel. Results: In total, 11.6% (58/501) were identified with tumors with high TMB and MSI-high status was confirmed in seven out of 501 cases (1.4%). High TMB was observed in 11.6% of patients with various solid tumors, including: GU cancers (36.0%, 9/25), colorectal cancer (15.2%, 23/151), biliary tract cancer (14.6%, 7/48), melanoma (14.3%, 3/21), gastric cancer (11.2%, 13/116), hepatocellular carcinoma (8.3%, 1/12), other GI tract cancers (4.5%, 1/22), and sarcoma (1.7%, 1/60). The objective response rate (ORR) to ICIs was 75% (nine out of 12) in solid tumor patients with high TMB and 25% (30 out of 40) in those with non-high TMB. Patients with high TMB had better ORR to ICIs than those with non-high TMB ( p = 0.004). Univariate analysis revealed that the status of PD-L1 expression and of TMB (high versus non-high) had significant association in response to ICIs. However, in multivariate analysis, the status of TMB (high versus non-high) was only significantly related to the response to ICIs ( p = 0.036). Conclusion: In the present study, we analyzed the TMB using a cancer panel for various solid tumor patients in routine clinical practice and also demonstrated the usefulness of TMB to predict the efficacy for ICIs.

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