Association of dynamic changes of methylated SFRP2 in ctDNA with prognosis in advanced gastric cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15051-e15051
Author(s):  
Yan Haijiao ◽  
Kele Ge ◽  
Wenyu Chen ◽  
Xizheng Mao ◽  
Xiaodong Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dynamic Change ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Suppressor Gene ◽  
Stage Iii ◽  
Dynamic Monitoring ◽  
Free Survival ◽  
Potential Biomarker

e15051 Background: Secreted frizzled-related protein 2 (SFRP2) is a tumor suppressor gene and its hyper methylation could cause its inactivation and promote cancer development. However, whether methylated SFRP2 (mSFRP2) in ctDNA could serve as prognostic biomarker for patients with gastric cancer has not been thoroughly studied. Methods: Stage III or IV gastric cancer patients treated with systemic chemotherapy in the Third Affiliated Hospital of Soochow University from 2015 to 2017 were included. The mSFRP2 before and during chemotherapy were dynamically detected from ctDNA by digital polymerase chain reaction-based technologies. Results: In total, 121 patients were enrolled, with 63 in stage III and 58 in stage IV. Baseline median mSFRP2 was higher in stage IV than stage III (64 VS 18 copies/ng, P < 0.001). In stage III GC, the top 50% mSFRP2 population had shorter median disease-free survival (DFS, 11.0 months VS NR; HR, 13.05; 95% CI, 3.05-55.95;) and overall survival (OS, 17.0 months VS NR; HR, 7.80; 95% CI, 1.81-33.60). Similar results were observed in stage IV GC that the median progression-free survival (PFS, 4.0 VS 7.0 months; HR, 2.74; 95% CI, 1.58-4.78) and OS (12.0 VS 16.0 months; HR, 3.14; 95% CI, 1.67-5.92) was shorter in patients with top 50% mSFRP2. During the dynamic monitor along treatment, elevated mSFPR2 was associated with worse PFS (5.0 VS 7.0 months; HR, 2.17; 95% CI, 1.25-3.76) and OS (12.0 VS 15.5 months; HR, 3.51; 95% CI, 1.94-6.35) in stage IV patients. Conclusions: Our study shows the association between SFRP2 methylation and its dynamic change and prognosis in patients with gastric cancer. Our results provide a potential biomarker in ctDNA for prognosis and dynamic monitoring in patients with gastric cancer.

scholarly journals Anlotinib combined with SOX regimen (S1 (tegafur, gimeracil and oteracil porassium capsules) + oxaliplatin) in treating stage IV gastric cancer: study protocol for a single-armed and single-centred clinical trial

BMJ Open ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. e034685 ◽  
Author(s):  
Juan Wang ◽  
Dong Xue Wu ◽  
Lu Meng ◽  
Gang Ji
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Free Survival ◽  
Stage Iv Gastric Cancer ◽  
Before And After

IntroductionAnlotinib hydrochloride is a multi-targeted receptor tyrosine kinase inhibitor that targets angiogenesis-related kinases and has already showed good safety and efficacy in some solid tumours. However, evidence on the safety and feasibility of anlotinib in patients with stage IV gastric cancer is scarce.Methods and analysisThis study is a single-armed and single-centred clinical study being designed to include 150 patients of stage IV gastric cancer. The patients’ demographics, pathological characteristics, test results of blood, biochemistry and tumour markers before and after medication, disease-free survival and overall survival will be collected and analysed. The primary and main efficacy outcomes are objective response rate, progression-free survival, disease control rate and overall survival. The secondary efficacy outcome is safety indicator including the incidence of adverse drug reactions and adverse events after administration.Ethics and disseminationEthics approval has been obtained from the Ethics Committee at the First Affiliated Hospital (Xijing Hospital) of Fourth Military Medical University (KY20192111-F-1). The results of this study will be disseminated at several research conferences and as published articles in peer-reviewed journals.Trial registration numberChiCTR1900026291 (registration date: 29 September 2019).

scholarly journals HOTAIR as a Prognostic Predictor for Diverse Human Cancers: A Meta- and Bioinformatics Analysis

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 778 ◽  
Author(s):  
Halil Ibrahim Toy ◽  
Didem Okmen ◽  
Panagiota I. Kontou ◽  
Alexandros G. Georgakilas ◽  
Athanasia Pavlopoulou
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Bioinformatics Analysis ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Predictive Biomarker ◽  
Free Survival ◽  
Human Cancers ◽  
Potential Biomarker

Several studies suggest that upregulated expression of the long non-coding RNA HOX transcript antisense RNA (HOTAIR) is a negative predictive biomarker for numerous cancers. Herein, we performed a meta-analysis to further investigate the prognostic value of HOTAIR expression in diverse human cancers. To this end, a systematic literature review was conducted in order to select scientific studies relevant to the association between HOTAIR expression and clinical outcomes, including overall survival (OS), recurrence-free survival (RFS)/disease-free survival (DFS), and progression-free survival (PFS)/metastasis-free survival (MFS) of cancer patients. Collectively, 53 eligible studies including a total of 4873 patients were enrolled in the current meta-analysis. Pooled hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were calculated to assess the relationship between HOTAIR and cancer patients’ survival. Elevated HOTAIR expression was found to be significantly associated with OS, RFS/DFS and PFS/MFS in diverse types of cancers. These findings were also corroborated by the results of bioinformatics analysis on overall survival. Therefore, based on our findings, HOTAIR could serve as a potential biomarker for the prediction of cancer patient survival in many different types of human cancers.

scholarly journals 300 Final analysis of a prospective, randomized, double-blind, placebo-controlled phase IIb trial of tumor lysate, particle-loaded, dendritic cell vaccine in stage III/IV melanoma: 36-month analysis

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A327-A327
Author(s):  
Lexy Adams ◽  
Robert Chick ◽  
Guy Clifton ◽  
Timothy Vreeland ◽  
Patrick McCarthy ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Stage Iv ◽  
Standard Of Care ◽  
Stage Iii ◽  
Tumor Lysate ◽  
Double Blind ◽  
Free Survival ◽  
Resected Stage ◽  
Disease Free ◽  
Stage Iv Melanoma

BackgroundThe tumor lysate, particle-loaded, dendritic cell (TLPLDC) vaccine is created ex vivo by loading autologous dendritic cells (DC) with yeast cell wall particles (YCWP) containing autologous tumor lysate, thus delivering tumor antigens to the DC cytoplasm via phagocytosis. TLPLDC then activates a robust T cell response against the unique antigens for each patient. The primary analysis of the prospective, randomized, multi-center, double-blind, placebo-controlled phase IIb trial in patients with resected stage III/IV melanoma showed TLPLDC improved 24-month disease-free survival (DFS) in the per-treatment (PT) analysis (patients completing the 6-month primary vaccine series). Here, we examine the secondary endpoint of 36-month DFS and overall survival (OS).MethodsPatients with resected stage III/IV melanoma were randomized 2:1 to TLPLDC vaccine or placebo (autologous DC loaded with empty YCWP). Treatments were given at 0, 1, 2, 6, 12 and 18 months. The protocol was amended to include patients receiving concurrent checkpoint inhibitors (CPIs) to follow changes in standard of care. The co-primary endpoints were 24-month DFS by intention-to-treat (IT) analysis and per-treatment (PT) analysis, with secondary endpoints including 36-month DFS and OS by ITT and PT analysis, pre-specified analysis by stage, and safety as measured by CTCAE v4.03.ResultsOverall, 103 patients received TLPLDC and 41 placebo. In PT analysis, 65 patients received TLPLDC and 32 placebo. Total adverse events (AEs), grade 3+ AEs, and serious AEs (SAEs) were similar in placebo vs TLPLDC groups, with one related SAE per treatment arm. By ITT analysis, 36-month OS was 76.2% for TLPLDC vs 70.3% for placebo (HR 0.72, p=0.437) and 36-month DFS was 35.6% vs 27.1% (HR 0.95, p=0.841). By PT analysis, 36-month DFS was improved with TLPLDC (57.5% vs 35.0%; HR 0.50, p=0.025, figure 1). This effect was even more dramatic in resected stage IV patients (36-month DFS: 60.9% vs 0%; HR 0.12, p=0.001, figure 2).ConclusionsThis phase IIb trial again demonstrates the safety of the TLPLDC vaccine, and an improved 36-month DFS in patients with resected stage III/IV melanoma who complete the primary vaccine series, particularly in the stage IV subgroup. Next, a phase III trial will evaluate the efficacy of TLPLDC vaccine as adjuvant treatment for resected stage IV melanoma, with patients randomized to receive standard of care PD-1 inhibitors + TLPLDC versus PD-1 inhibitors + placebo.Abstract 300 Figure 136-month disease free survival for patients receiving TLPLDC vs placebo by PT analysisAbstract 300 Figure 236-month disease free survival for subset of stage IV melanoma patients receiving TLPLDC vs placebo by PT analysisTrial RegistrationThis is a phase IIb clinical trial registered under NCT02301611Ethics ApprovalThis study was approved by Western IRB, protocol 20141932.

Randomized Clinical Trial of Adjuvant Mitomycin Plus Tegafur in Patients With Resected Stage III Gastric Cancer

1999 ◽  
Vol 17 (12) ◽  
pp. 3810-3815 ◽  
Author(s):  
Lluís Cirera ◽  
Anna Balil ◽  
Eduard Batiste-Alentorn ◽  
Ignasi Tusquets ◽  
Teresa Cardona ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Clinical Trial ◽  
Overall Survival ◽  
Survival Rate ◽  
Adjuvant Chemotherapy ◽  
Disease Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Resected Stage ◽  
Disease Free

PURPOSE: The efficacy of adjuvant chemotherapy in gastric cancer is controversial. We conducted a phase III, randomized, multicentric clinical trial with the goal of assessing the efficacy of the combination of mitomycin plus tegafur in prolonging the disease-free survival and overall survival of patients with resected stage III gastric cancer. PATIENTS AND METHODS: Patients with resected stage III gastric adenocarcinoma were randomly assigned, using sealed envelopes, to receive either chemotherapy or no further treatment. Chemotherapy was started within 28 days after surgery according to the following schedule: mitomycin 20 mg/m2 intravenously (bolus) at day 1 of chemotherapy; 30 days later, oral tegafur at 400 mg bid daily for 3 months. Disease-free survival and overall survival were estimated using the Kaplan-Meier analysis and the Cox proportional hazards model. RESULTS: Between January 1988 and September 1994, 148 patients from 10 hospitals in Catalonia, Spain, were included in the study. The median follow-up period was 37 months. The tolerability of the treatment was excellent. The overall survival and disease-free survival were higher in the group of patients treated with chemotherapy (P = .04 for survival and P = .01 for disease-free survival in the log-rank test). The overall 5-year survival rate and the 5-year disease-free survival rate were, respectively, 56% and 51% in the treatment group and 36% and 31% in the control group. CONCLUSION: Our positive results are consistent with the results of recent studies; which conclude that there is a potential benefit from adjuvant chemotherapy in resected gastric cancer.

Dose intensive chemotherapy (Cx) in advanced thymoma: Initial report of Japan Clinical Oncology Group trials (JCOG 9605 and 9606)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7080-7080
Author(s):  
H. Kunitoh ◽  
T. Tamura ◽  
H. Fukuda ◽  
K. Nakagawa ◽  
K. Takeda ◽  
...  
Keyword(s):  
Thymic Carcinoma ◽  
Local Therapy ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Initial Report ◽  
Free Survival ◽  
Unresectable Stage ◽  
Short Course ◽  
Ecog Ps

7080 Background: Thymoma is considered to be sensitive to Cx. Dose intensive Cx might well be suitable for such tumors, especially in combination with local therapy. Objectives of the trials were to evaluate the safety and efficacy of the dose intensive CODE (cisplatin[C]- vincristine[O]- doxorubicin[D]- etoposide[E]) Cx in thymoma. The primary endpoint was progression-free survival time (PFS). Methods: Patients (pts) with 15–70 years of age with histologically documented Cx-naïve thymoma with stage IVa/IVb disease (JCOG 9605) or unresectable stage III disease (JCOG 9606) were eligible. Tumors of other histology, such as thymic carcinoma, carcinoid or lymphoma were excluded; pts were to have ample organ function and ECOG PS of 0–2. Myasthenia was allowed. Signed consent form was obtained. Pts received CODE Cx of 9 weeks (w): C 25 mg/m2 Cx day 1 on each w1–9; O 1mg/m2 d1 on w1,2,4,6,8; D 40 mg/m2 d1 and E 80 mg/m2 d1,2,3 on w 1,3,5,7,9. Cx courses were supported by GCSF. Steroids were used only for antiemesis. Those with stage III disease (JCOG 9606) went on to surgery, if judged to be resectable, and post-operative radiotherapy (RT) of 48Gy; those with unresectable disease received 60Gy RT. Results: From Jul./97 to Apr./05, 53 pts were entered to the studies. Five were found ineligible because of different histology. Pt characteristics and response to the Cx were summarized in the table . Toxicity of the Cx was mainly hematologic and generally well tolerated, with no toxic death; 70% of the pts completed planned 9 weeks. Thirteen pts in JCOG 9606 (stage III) received thoracotomy; tumor was resected in 11 pts, completely in 9 (39% of enrolled pts). Pathologic CR was observed in 3. The median PFS was 9.5m for stage IV and 4.5 y for stage III diseases. Overall survival at 2 & 5 yrs were 82% & 57% for stage IV and 96% & 77% for stage III pts. Conclusions: Short-course, dose intensive Cx was active against thymoma. Although it does not seem to bring long PFS in stage IV pts, it could improve resectability in limited disease. [Table: see text] No significant financial relationships to disclose.

HPV and survival in patients with oropharyngeal squamous cell cancer of the head and neck (OPC) treated with induction chemotherapy followed by chemoradiotherapy (ST) versus chemoradiotherapy alone (CRT): The Dana-Farber experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5582-5582
Author(s):  
Jochen H. Lorch ◽  
Glenn Hanna ◽  
Wei Dai ◽  
Vijaya Thotakura ◽  
Vidya Nair ◽  
...  
Keyword(s):  
Cell Cancer ◽  
Stage Iv ◽  
Clinical Information ◽  
Progression Free Survival ◽  
Stage Iii ◽  
Free Survival ◽  
Group Outcomes ◽  
Hpv Status ◽  
Stage Iv Disease ◽  
Versus Stage

5582 Background: HPV status is a major prognostic marker for survival in patients with OPC. We examined overall survival (OS) and progression free survival (PFS) in patients with OPC and known HPV status treated at Dana-Farber Cancer Institute with ST and CRT between 2002 and 2011. Methods: 280 patients with OPC and known HPV status were identified retrospectively and clinical information was recorded. Results: 174 patients were treated with CRT (124 HPV positive, 50 HPV negative) and 106 patients were treated with ST (77 HPV positive, 29 HPV negative). For all 280 patients, OS and PFS were significantly better for patients who were HPV positive compared to those who were HPV negative. 3 year OS was 89.1% for HPV positive (95% CI, 83.8-94.7) and 70.5% for HPV negative patients (95%CI, 59.9-83%, HR 0.37, p=0.0007). Among HPV positive patients treated with CRT, 13/124 had died at 3 years (OS 88.5%, 95%CI 81.7-95.9) while 13 deaths were recorded among 50 HPV negative patients (OS 72.2%, 95% CI 59.1-88.2, HR 0.38, p=0.011). PFS at 3 years was also significantly better for HPV positive versus HPV negative patients(81.7% vs 58.8%, HR 0.42, p=0.006). In the group treated with ST, outcomes were similar despite a higher rate of stage IV versus stage III disease compared to the group treated with CRT (100% stage IV in ST versus 77% stage IV and 23% stage III disease in CRT group). Three year OS was 89.7% for HPV positive and 68.2% in the HPV negative group (8/77 HPV pos vs 10/29 HPV neg, HR 0.33, p=0.015). PFS was borderline better for HPV positive patients (81% vs 61.7%, HR 0.48, p= 0.058). Conclusions: We present the DFCI experience treating OPC with ST and CRT for patients with known HPV status over one decade.OS and PFS were superior for HPV positive versus HPV negative patients. Outcomes were virtually identical for patients treated with CRT versus ST despite a higher rate of stage IV disease in the ST group. Outcomes for the HPV negative patients in particular were superior compared to the published literature.

scholarly journals Risk tolerance in adjuvant and metastatic melanoma settings: a patient perspective study using the threshold technique

2021 ◽  
Author(s):  
Carol Mansfield ◽  
Kelley Myers ◽  
Kathleen Klein ◽  
Jeetvan Patel ◽  
Antonio Nakasato ◽  
...  
Keyword(s):  
Stage Iv ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Risk Tolerance ◽  
Stage Iii ◽  
Acceptable Risk ◽  
Treatment Benefit ◽  
Free Survival ◽  
Unresectable Stage ◽  
Melanoma Patients

Background: Adverse events (e.g., pyrexia) may affect treatment patterns and adherence. This study explored pyrexia risk tolerance among melanoma patients when treatment benefit is unknown versus known. Materials & methods: US respondents with stage III (n = 100) or stage III unresectable/stage IV melanoma (n = 125) chose between hypothetical melanoma treatments, defined by reoccurrence/progression-free survival and pyrexia risk, one resembling standard-of-care and one resembling dabrafenib + trametinib. Respondents chose first when efficacy was unknown and then when efficacy was known; pyrexia risk was varied systematically to define maximum acceptable risk. Results: Maximum acceptable risk of pyrexia was statistically significantly higher when efficacy was known versus unknown in stage III patients (85 vs 34%) and stage III unresectable/stage IV patients (66 vs 57%). Conclusion: Patients accepted higher levels of pyrexia risk when they understood treatment benefit.

scholarly journals Clinical Profile and Treatment Outcomes in Patients Treated with Intensity-Modulated Radiotherapy (IMRT) for Carcinoma Nasopharynx: A Retrospective Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Farida Nazeer ◽  
R. Rejnish Kumar ◽  
Malu Rafi ◽  
Tapesh Bhattacharya ◽  
Aparna Mullangath Prakasan ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Distant Metastasis ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Stage I ◽  
Stage Ii ◽  
Stage Iii ◽  
Pattern Of Failure ◽  
Free Survival

Objective. To retrospectively evaluate the clinical outcome of carcinoma nasopharynx patients treated with the IMRT technique. Methods. Eighty-one nasopharyngeal carcinoma patients who were treated with IMRT with or without chemotherapy between the period January 2011 and December 2014 at a comprehensive tertiary cancer center, Kerala, India, were included in the study. The mean age was 43 years (range 13–77 years), and majority of the patients were males (67.9%). The stagewise distribution of disease at presentation was 2 (2.5%) in stage I, 19 in stage II (23.5%), 31 (38.3%) in stage III, and 29 (35.8%) in stage IV. All patients were treated using simultaneous integrated boost (SIB) schedule using IMRT with 6 MV photon to a dose of 66 Gy in 30 fractions, 2.2 Gy per fraction prescribed to high-risk PTV; 60 Gy in 30 fractions, 2 Gy per fraction to intermediate risk PTV; and 54 Gy in 30 fractions, 1.8 Gy per fraction to low-risk PTV. Concurrent chemotherapy with cisplatin was offered to patients with stage II and above disease. Neoadjuvant chemotherapy with cisplatin and 5FU was given to patients with initially advanced disease (T3, T4, N2, and N3). Survival estimates were generated using the Kaplan–Meier method. The univariate analysis was performed using log-rank tests. Results. The 5-year locoregional control (LRC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 87.5%, 87%, 61.6%, and 62.5%, respectively. The 5-year OS was 100% for stage I (n = 2), 67% for stage II (n = 19), 70.4% for stage III (n = 31), and 68.1% for stage IV (n = 29). The DFS at 5 years was 100% for stage I, 61.1% for stage II, 56.2% for stage III, and 84.8% for stage IV disease. The univariate analysis showed that age, nodal stage, and use of induction chemotherapy showed an improved trend towards OS, though the results were not statistically significant. The predominant pattern of failure in the present study was distant metastasis. Most patients who developed distant metastasis in our study had either an advanced T stage or N3 disease at presentation. Conclusion. The present study shows our initial experience with IMRT for nasopharyngeal carcinoma. The compliance to RT was good in this study. The 5-year LRC and OS rate of nasopharyngeal carcinoma patients treated with IMRT were 87.5% and 62.5%. Distant metastasis was the main pattern of failure.

Postoperative LV5FU2 combination chemotherapy in patients with curative resected advanced gastric cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15660-e15660
Author(s):  
H. Lee ◽  
K. Lee ◽  
E. Park ◽  
I. Hwang ◽  
J. Jang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Continuous Infusion ◽  
Advanced Gastric Cancer ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Stage Iv ◽  
Postoperative Chemotherapy ◽  
Free Survival ◽  
Grade 3

e15660 Background: To illuminate the effect and toxicity of fortnightly low-dose leucovorin(LV) and fluorouracil(5FU) bolus plus continuous infusion(LV5FU2) postoperative chemotherapy(adjuvant) in patients with curative resected, advanced gastric cancer. Methods: Total 40 patients were enrolled in this study. All patients received LV 20mg/m2(bolus), 5FU 400mg/m2(bolus), 5FU 600mg/m2(24-hour continuous infusion) on day 1, 2, 15, and 16, every 4 weeks(LV5FU2), total 6 cycles. Results: Postoperative chemotherapy was initiated median 19 days after surgery. Total of 238 cycles were administered and median follow-up was 602 days. The median disease-free survival time was 728 days (95% CI, 411∼1045) and 2-year overall survival was 77%. Relapses were reported in 18 (45%) of the patients : Two of 9 patients relapsed in stage IIIA (22.2%), seven of 12 patients relapsed in stage IIIB (58.3%) and nine of 17 patients relapsed in stage IV (52.9%). They were all distant relapsed. Eight patients died. 7 patients died as a result of cancer progression and 1 patient suicided while receiving palliative chemotheraphy for cancer relapse. The grade 3∼4 toxicity of neutropenia 8.4% and anemia 0.4%, neutropenic fever 0.4% were observed. Conclusions: Postoperative LV5FU2 adjuvant chemotherapy is effective and tolerable for the patients with curative resected, advanced gastric cancer. No significant financial relationships to disclose.

Disassociation of ARID1A with genomic ancestry and prognostic impact in an admixed cohort of Brazilian patients with gastric cancer (GC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15585-e15585
Author(s):  
Helano C. Freitas ◽  
Diana Noronha Nunes ◽  
Thais Fernanda Bartelli ◽  
Maria Galli de Amorim ◽  
Luiza Ferreira Araujo ◽  
...  
Keyword(s):  
Disease Free Survival ◽  
Stage Iv ◽  
Suppressor Gene ◽  
Tumor Location ◽  
Cancer Center ◽  
Prognostic Impact ◽  
Ancestry Informative Markers ◽  
Free Survival ◽  
Protein Inactivation ◽  
Worse Prognosis

e15585 Background: Loss of expression of ARID1A, a tumor suppressor gene involved in chromatin remodeling and transcription activation, has been associated with worse prognosis in Asian GC patients (Yang et al. 2016). Mutations in ARID1A have been found in 8-27% of GC, usually leading to gene/protein inactivation. Here we evaluated the possible involvement of ARID1A mutations and clinical characteristics, while considering genomic ancestry and survival, in a cohort of Brazilian GC patients. Methods: We included 112 pts diagnosed with GC and treated at AC Camargo Cancer Center before 2013. The study was approved by local IRB. Genomic DNA was used for capture-based enrichment of a customized gene panel including 99 genes. Libraries were sequenced in the NextSeq 500 platform (Illumina), using paired-end reads (2x75bp). For ancestry inference we used a set of ancestry informative markers, covered by target and off-target reads, described by Elhaik et al. (2014). Results: Median age was 64y (37-91), 63% were male, M:F ratio was 1.73. Most cases were classified as Diffuse (47.3%) followed by Intestinal (41.1%), Mixed (2.7%) and 8.9% were deemed unclassifiable by Lauren´s classification. 22.3% were stage I, 20.5% stage II, 42.9% stage III and 14.3% stage IV. 11.6% were in the GEJ and 80.4% were in corpus/antrum. Five patients were EBV positive (4.5%). Genomic ancestry was as follows: 55.4% European, 27.7% Asian, 8.9% African and 8% were highly admixed ( < 50% of any ancestry). ARID1A was mutated in 19% of cases and showed no association with age at diagnosis (p = 0.21), gender (p = 0.76), tumor location (p = 0.55), staging (p = 0.42), Lauren (p = 0.14) or EBV (p = 0.42). ARID1A had no impact on overall survival (OS) (HR 1.17; 95%CI 0.59-2.31; p = 0.6) or disease-free survival (DFS) (HR 1.24; 95%CI 0.66-2.32; p = 0.5), including the subgroup with Asian genomic background: OS-Asia (HR 1.08; 95%CI 0.31-3.81; p = 0.9), DFS-Asia (HR 1.15; 95%CI 0.32-4.12; p = 0.8). Conclusions: ARID1A is a common driver in GC among Brazilian patients. Unlike in Asians, ARID1A was not prognostic in this Brazilian cohort even in the subgroup with a predominant ( > 50%) Asian genomic ancestry.

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