scholarly journals Pathology and Prognosis of Colonic Adenocarcinomas With Intermediate Primary Tumor Stage Between pT2 and pT3

2021 ◽  
Author(s):  
John D. Paulsen ◽  
Alexandros D. Polydorides
Keyword(s):  
Primary Tumor ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Muscularis Propria ◽  
Disease Free Survival ◽  
Venous Invasion ◽  
Tumor Stage ◽  
Rank Test ◽  
Clinicopathologic Characteristics ◽  
Colonic Adenocarcinomas

Context.— Primary tumor stage (pT) is an important prognostic indicator in colonic adenocarcinomas; however, cases that have no muscle fibers beyond the advancing tumor edge but also show no extension beyond the apparent outer border of muscularis propria (termed pT2int), have not been previously studied. Objective.— To address the clinicopathologic characteristics and prognosis of pT2int tumors. Design.— We recharacterized 168 colon carcinomas and compared pT2int cases to bona fide pT2 and pT3 tumors. Results.— In side-by-side analysis, 21 pT2int cases diverged from 29 pT2 tumors only in terms of larger size (P = .03), but they were less likely to show high-grade (P = .03), lymphovascular (P < .001), and extramural venous invasion (P = .04); discontinuous tumor deposits (P = .02); lymph node involvement (P = .001); and advanced stage (P = .001), compared with 118 pT3 tumors. Combining pT2int with pT2 cases (versus pT3) was a better independent predictor of negative lymph nodes in multivariate analysis (P = .04; odds ratio [OR], 3.96; CI, 1.09–14.42) and absent distant metastasis in univariate analysis (P = .04), compared with sorting pT2int with pT3 cases (versus pT2). Proportional hazards regression showed that pT2 and pT2int cases together were associated with better disease-free survival compared with pT3 tumors (P = .04; OR, 3.65; CI, 1.05–12.70). Kaplan-Meier analysis demonstrated that when pT2int were grouped with pT2 tumors, they were significantly less likely to show disease progression compared with pT3 (P = .002; log-rank test) and showed a trend toward better disease-specific survival (P = .06), during a mean patient follow-up of 44.9 months. Conclusions.— These data support the conclusion that pT2int carcinomas have clinicopathologic characteristics and are associated with patient outcomes more closely aligned with pT2 rather than pT3 tumors.

Clinicopathologic characteristics and impact of oophorectomy for ovarian metastases (ovmets) in colorectal cancer (CRC).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 779-779
Author(s):  
Carling Jade Ursem ◽  
Margaret Zhou ◽  
Alan T Paciorek ◽  
Chloe Evelyn Atreya ◽  
Andrew H. Ko ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Primary Tumor ◽  
Proportional Hazards ◽  
Clinical Care ◽  
Univariate Analysis ◽  
Operative Management ◽  
Cox Proportional Hazards ◽  
Clinicopathologic Characteristics ◽  
Ovarian Metastases ◽  
Significant Difference

779 Background: As overall survival (OS) with metastatic colorectal cancer (mCRC) and imaging modalities improve, detection of ovmets may be increasing. The ovary is often a sanctuary site for mCRC; however, there is a paucity of data to guide decision-making regarding the role for oophorectomy. Methods: This is a single-institution retrospective review of patients (pts) who received care for mCRC (incl. appendiceal primaries) with ovmets from 2009-2017. Pts were identified through a hospital-based cancer registry, provider recall, and pathology and radiology databases. Clinicopathologic and treatment data were abstracted. Cox proportional hazards models were used to evaluate for associations with OS. Results: Of 108 pts, median age was 50 (range 19-106), 62 (57%) were Caucasian, and 69 (64%) had ovmets at initial CRC diagnosis. Primary tumor location was left-sided in 54 (50%), right-sided in 27 (25%), appendiceal in 18 (17%), and unknown in 9 (8%). Median OS from diagnosis of mCRC was 29.6 months (mo) with median follow-up of 21.9 mo (range 0.77-172.47). Younger age, absence of signet-ring or mucinous features, well/moderately differentiated grade, and resection of primary tumor were associated with improved OS (p < 0.05). Of 83 (76%) pts who underwent oophorectomy median OS was 36.7 mo vs. 25 mo in those who underwent non-operative management (HR 0.54, 95% CI 0.31-0.94, p = 0.03). Among 94 pts with extra-ovarian disease, 70 (74%) underwent oophorectomy; however, no significant difference in median OS was detected vs. those who did not (30.9 vs 25.0 mo, p = 0.07). In a multivariate model, oophorectomy was not associated with OS (HR 0.63, 95% CI 0.29-1.36, p = 0.24). Conclusions: While ovmets have been previously reported as associated with a poor prognosis, the median OS for this cohort was comparable to existing OS data for mCRC pts. Although oophorectomy for ovmets from mCRC was associated with improved OS in univariate analysis, this effect was not significant in the presence of extra-ovarian metastases. Ovmets from mCRC remain a difficult challenge in clinical care. Oophorectomy may improve OS in select cases; however, further evaluation of predictors of benefit is needed.

scholarly journals IgG Fc Binding Protein (FCGBP) Is Down-Regulated in Metastatic Lesions and Predicts Survival in Metastatic Colorectal Cancer Patients

2020 ◽  
Author(s):  
Ziming Yuan ◽  
Zhixun Zhao ◽  
Hanqing Hu ◽  
Tianyu Qiao ◽  
Tianyi Ma ◽  
...  
Keyword(s):  
Liver Metastasis ◽  
Primary Tumor ◽  
Proportional Hazards ◽  
Binding Protein ◽  
Disease Free Survival ◽  
Metastatic Lesion ◽  
Cox Proportional Hazards ◽  
Primary Lesion ◽  
Rank Test ◽  
Tumor Tissues

Abstract Background: Liver is the most frequent metastatic spread sites for CRC patients and these patients have much poorer prognosis compared to those without metastasis. Previous studies have shown that IgG Fc binding protein (FCGBP) plays important roles in tumorigenesis, progression and prognosis. In this study, we are aimed to explore the significance of FCGBP in liver metastatic CRC (LMCRC) patients. Methods: The expression data of FCGBP was obtained from GEO and TCGA database, FCGBP RNA expression was evaluated between primary lesions (PC) and liver metastatic lesion (LM). 135 paired specimens including normal mucosa, primary tumor and liver metastasis tissues were all collected from CRC patients and adopted in Tissue microarrays (TMAs). Immunohistochemical staining was performed on the TMAs slides with FCGBP and the immunohistochemistry score (SI) was calculated by the staining intensity multiplied by the positive rate of stained cells. Survival curves were calculated by Kaplan–Meier method and the log-rank test was used to compare the overall survival (OS) and disease-free survival (DFS). Univariate and multivariate analysis for prognosis were using Cox proportional hazards regression model.Results: FCGBP RNA was down-regulated in PC and LM, and especially lower in LM in database. We also found FCGBP protein was down-regulated in primary lesion and metastatic lesion, especially in metastatic lesion in 135 paired tumor tissues. According to immunohistochemistry score (SI), each cohort (primary lesion and metastatic lesion) was divided into FCGBP-positive (SI=4-12) and FCGBP-negative (SI=0-3) group. In both groups, the level of CEA (PC group, 3.880 vs 77.049, p<0.001; LM group, 3.890 vs 14.239, p=0.008) and CA19-9 (PC group, 8.610 vs 111.700, p<0.001; LM group, 7.660 vs 19.380, p=0.037) was lower than those in FCGBP-negative group. FCGBP-positive in LM cohort was an independent risk factor both in OS (HR 1.573, 95% Cl [1.017-2.433], p=0.042) and DFS (HR 1.869, 95% Cl [1.256-2.781], p=0.002). Conclusions: This study has found the relationship between FCGBP and clinical information of LMCRC patients. FCGBP expression was much lower in liver metastasis tumor tissues compared with primary tumor tissues in liver metastatic CRC patients and associated with the OS and PFS. Our works illustrate that FCGBP can be a promising prognostic factor for LMCRC.

Predictors of overall survival (OS) in patients (pts) with melanoma brain metastasis (MBM) in the modern era.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9540-9540
Author(s):  
Merve Hasanov ◽  
Denai R. Milton ◽  
Alicia Bea Davies ◽  
Elizabeth Sirmans ◽  
Chantal M Saberian ◽  
...  
Keyword(s):  
Primary Tumor ◽  
Proportional Hazards ◽  
Statistical Tests ◽  
Univariate Analysis ◽  
Elevated Serum ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Cancer Center ◽  
Leptomeningeal Disease ◽  
Significance Level

9540 Background: The management and OS of pts with metastatic melanoma have improved due to new systemic therapies. However, relatively little is known about the use of these treatments (tx) and their association with OS in pts with MBMs. We reviewed a large cohort of MBM pts to assess how pt demographics, disease characteristics, and MBM tx impact OS in the current era. Methods: Under an institutional review board-approved protocol, retrospective data were curated and analyzed from pts diagnosed with, and received tx for, MBM from 2014 to 2018 at the MD Anderson Cancer Center (MDA). Pts diagnosed with uveal or mucosal melanoma or other cancers were excluded. Pt demographics; timing and features of initial melanoma dx; timing and features of initial MBM dx; prior, initial and subsequent tx; and OS were collected. OS was determined from MBM dx to last clinical follow-up (FU). Pts alive at last FU were censored. The Kaplan-Meier method and log-rank test were used to estimate OS and to assess univariate group differences, respectively. Multivariable (MV) associations of OS with variables of interest were investigated with Cox proportional hazards models. Initial treatment of MBM was assessed as a time-varying covariate. All statistical tests used a significance level of 5%. Results: A total of 401 MBM pts were identified. The median age at MBM dx was 61; 67% were male and 46% had a BRAF V600 mutation. At MBM diagnosis dx, most (70%) pts were asymptomatic; 70% had concurrent uncontrolled extracranial disease; 36% had elevated serum LDH. Prior tx included immunotherapy (IMT) for 39% and targeted therapy (TTX) for 17%. The median number of MBMs was 2; 31% had > 3 MBMs. Median largest MBM diameter was 1.0 cm, 9% had MBM > 3.0 cm, and 5% had concurrent leptomeningeal disease (LMD). Tx received after MBM dx included stereotactic radiosurgery (SRS; 53% as initial tx for MBM, 67% at any time after MBM dx), whole brain radiation therapy (WBRT; 16%, 35%), craniotomy (12%, 19%), IMT (37%, 74%), and/or TTX (22%, 40%). 31% received steroids during initial MBM tx. At a median FU of 13.4 (0.0 - 82.8) months (mos), the median OS was 15.1 mos, and 1- and 2-year OS rates were 56% and 40%. Notably, gender, time to MBM dx, and BRAF status were not associated with OS (univariate analysis). On MV analysis, clinical features associated with worse OS included increased age, increased primary tumor thickness, elevated LDH, > 3 MBMs, +LMD, +symptoms, and prior tx with IMT. Among tx used at any time after MBM dx, WBRT (HR 1.9, 95% CI 1.5-2.5) was associated with worse OS; SRS (HR 0.7, 95% CI 0.5-0.8) and IMT (HR 0.6, 95% CI 0.5-0.8) were associated with improved OS. Conclusions: In one of the largest cohorts of MBM pts described to date, OS has improved in MBM pts in the current era. Prognostic factors for OS include pt age, primary tumor and MBM features, prior tx, and tx for MBM. Additional analyses to assess the interaction of tx, disease features, and OS will be presented.

Chemoradiotherapy is an Alternative Choice for Patients with Primary Mediastinal Seminoma

2021 ◽  
Author(s):  
Yirui Zhai ◽  
Bo Chen ◽  
Xiaoli Feng ◽  
Kan Liu ◽  
Shulian Wang ◽  
...  
Keyword(s):  
Univariate Analysis ◽  
Progression Free Survival ◽  
Poor Performance ◽  
Rank Test ◽  
Clinicopathologic Characteristics ◽  
Cancer Specific Survival ◽  
Adjacent Structures ◽  
Significant Difference ◽  
Mediastinal Seminoma ◽  
Alternative Choice

Abstract Background: The low incidence of primary mediastinal seminomas has precluded the development of clinical trials on mediastinal seminomas. We investigated the clinicopathologic characteristics, prognosis of patients with primary mediastinal seminomas as well as the efficiency of nonsurgical treatments compared with treatments containing surgery.Methods: We retrospectively collected data on the clinicopathologic characteristics, treatments, toxicities, and survival of 27 patients from a single center between 2000 and 2018. Patients were divided into two groups according to whether they received operation. Survivals were assessed using the Kaplan-Meier method. Univariate analysis was performed using the log-rank test.Results: The median age was 28 (13-63) years. The most common symptoms were chest pain (29.6%), cough (25.9%), and dyspnea (22.2%). There were 13 and 14 patients in surgery and non-surgery group. Patients in the non-surgical group were more likely to be with poor performance scores (100% vs.76.9%) and disease invaded to adjacent structures(100% vs.76.9%) especially great vessels(100% vs.46.2%).The median follow-up period was 32.23 (2.7-198.2) months. There was no significant difference of overall survival (5-year 100% vs 100%), cancer-specific survival (5-year 100% vs.100%), local regional survival (5-year 91.7% vs.90.0%, p=0.948) , distant metastasis survival (5-year 100.0% vs. 90.9%, p=0.340) and progression-free survival (82.5% vs.90.0%, p=0.245) between patients with and without surgery. Conclusions: Primary mediastinal seminoma was with favorable prognosis, even though frequently invasion into adjacent structures brings difficulties to surgery administration. Chemoradiotherapy is an alternative treatment with both efficacy and safety.

scholarly journals Long interspersed nuclear element 1 hypomethylation has novel prognostic value and potential utility in liquid biopsy for oral cavity cancer

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Kiyoshi Misawa ◽  
Satoshi Yamada ◽  
Masato Mima ◽  
Takuya Nakagawa ◽  
Tomoya Kurokawa ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Real Time ◽  
Oral Cavity Cancer ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Inverse Correlation ◽  
Predictive Biomarker ◽  
Rank Test ◽  
Dna Hypomethylation ◽  
Prognostic Implications

Abstract Background New biomarkers are urgently needed to improve personalized treatment approaches for head and neck squamous cell carcinoma (HNSCC). Global DNA hypomethylation has wide-ranging functions in multistep carcinogenesis, and the hypomethylation of long interspersed nucleotide element-1 (LINE-1) is related to increased retrotransposon activity and induced genome instability. However, little information is available regarding LINE-1 hypomethylation and its prognostic implications in HNSCC. Methods In this study, we analyzed LINE-1 hypomethylation levels in a well-characterized dataset of 317 primary HNSCC tissues and 225 matched pairs of normal mucosa tissues, along with five oral cavity cancer (OCC) circulating tumor DNA (ctDNA) samples using quantitative real-time methylation and unmethylation PCR. The analysis was performed according to various clinical characteristics and prognostic implications. Results The results demonstrated that LINE-1 hypomethylation levels were significantly higher in the HNSCC tissues than in corresponding normal tissues from the same individuals (P < 0.001). Univariate analysis revealed that high levels of LINE-1 hypomethylation were correlated with poor disease-free survival (DFS; log-rank test, P = 0.038), whereas multivariate analysis demonstrated that they were significant independent prognostic factor for DFS (hazard ratio: 2.10, 95% confidence interval: 1.02–4.36; P = 0.045). Moreover, samples with high LINE-1 hypomethylation levels exhibited the greatest decrease in 5-hydroxymethylcytosine (5-hmC) levels and increase in tumor-suppressor gene methylation index (P = 0.006 and P < 0.001, respectively). Further, ctDNA studies also showed that LINE-1 hypomethylation had high predictive ability in OCC. Conclusions LINE-1 hypomethylation is associated with a higher risk of early OCC relapse, and is hence, a potential predictive biomarker for OCC. Furthermore, 5-hmC levels also exhibited predictive potential in OCC, based on their inverse correlation with LINE-1 hypomethylation levels. LINE-1 hypomethylation analysis, therefore, has applications in determining patient prognosis and real-time surveillance of disease recurrence, and could serve as an alternative method for OCC screening.

Expression of L1CAM and KI-67 in Endometrial Cancer of Egyptian Females: Clinical Impact and Survival

2020 ◽  
Vol 106 (1_suppl) ◽  
pp. 36-36
Author(s):  
Fatma Gharib ◽  
Dareen Abd elaziz mohamed ◽  
Basma Saed Amer
Keyword(s):  
Endometrial Cancer ◽  
Endometrial Adenocarcinoma ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Rank Test ◽  
Significant Heterogeneity ◽  
Ki 67 ◽  
Free Survival ◽  
Disease Free ◽  
L1cam Expression

Introduction: Endometrial adenocarcinoma is characterized by a good prognosis. However, the disease response shows a significant heterogeneity. Treatment of endometrial cancer (EC) is still based on clinico-pathological parameters, which have limited role in risk stratification. There is a need for more determinant markers, such as L1 Cell Adhesion Molecule (L1CAM), to identify patients at higher risk of relapse and tailor a more convenient treatment. L1CAM has a capacity to enhance cell motility and promote tumor invasion in different malignancies. In Egypt, the incidence rate of EC is growing over time. Especially in Elgharbiah governorate (home of this study). L1CAM expression and Ki-67 was reported and compared with other clinico-pathological criteria. Method: Seventy-six female patients of endometrial carcinomas were involved in this prospective study. The patients were treated and followed up at Tanta University Hospitals in the period between January 2015 to April 2019. L1CAM expression and Ki-67 was detected by immuno-histochemical exam and compared with other clinico-pathological criteria. Survival was assessed and compared by Kaplan-Meier curves and log-rank test. Results: Positive L1CAM expression was detected in 17 patients (22.4%) and was significantly correlated with unfavorable prognostic factors such as higher stage and grade ( P= 0.021 and P =0.001 respectively), lympo-vascular invasion ( P <0.001), non-endometroid type ( P <0.027) and Ki-67 ( P= 0.003). Univariate analysis revealed that: positive L1CAM; higher tumor grade; high stage; and non-endometrioid type were significantly associated with shorter disease-free survival (DFS) but no significant correlation was detected between Ki-67 and DFS. In multivariate analysis, positive L1CAM remained statistically significant with DFS [P =0.045; 95%CI (1.028:11.17); HR=3.38]. Conclusion: Our study indicates that L1CAM expression and Ki-67 are significantly associated with poor tumor characteristics. L1CAM is significantly associated with shorter disease-free survival and may be a helpful tool as a part of a simple clinical molecular classification for EC.

Impact of tumor site on the prognosis of small bowel adenocarcinoma

2019 ◽  
Vol 105 (6) ◽  
pp. 524-528 ◽  
Author(s):  
Rosa Falcone ◽  
Adriana Romiti ◽  
Marco Filetti ◽  
Michela Roberto ◽  
Riccardo Righini ◽  
...  
Keyword(s):  
Small Bowel ◽  
Clinical Outcome ◽  
Primary Tumor ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Rank Test ◽  
Small Bowel Adenocarcinoma ◽  
Tumor Site ◽  
Primary Tumor Site ◽  
Early Stage Disease

Background: Because of a lack of large-scale prospective studies there is no clear indication about the management of patients with small bowel adenocarcinoma (SBA). This study evaluated clinical outcome of patients diagnosed with SBA at our institution. Methods: Clinicopathologic features, treatments, and clinical outcome of patients diagnosed with SBA between 2006 and 2017 were retrospectively analyzed. Median time of survival was calculated and compared using the log-rank test. Multivariate Cox regression was used to test independence of significant factors in univariate analysis. Results: Forty patients were included in the study; the majority (82.5%) had a tumor in the duodenum (including ampulla of Vater) and an early stage disease at the diagnosis. Median overall survival (OS) in the whole study population was 26.5 months. Patients with a tumor of the lower part of the small intestine (jejunum, ileum, and appendix) showed a better OS compared with that of patients with upper SBA (40 months vs 26 months, respectively; P=0.09). Primary tumor site and stage were independent predictors of OS. Conclusions: Our results suggest a prognostic role for the primary tumor site. This finding deserves to be further investigated to ensure better classification as well as more effective management strategies for SBA.

Pharmacogenetics of Tamoxifen Biotransformation Is Associated With Clinical Outcomes of Efficacy and Hot Flashes

2005 ◽  
Vol 23 (36) ◽  
pp. 9312-9318 ◽  
Author(s):  
Matthew P. Goetz ◽  
James M. Rae ◽  
Vera J. Suman ◽  
Stephanie L. Safgren ◽  
Matthew M. Ames ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Proportional Hazards ◽  
Hot Flashes ◽  
Disease Free Survival ◽  
Metabolic Activation ◽  
Cox Proportional Hazards ◽  
Rank Test ◽  
Buccal Cells ◽  
Cancer Trial ◽  
Adjuvant Breast Cancer

Purpose Polymorphisms in tamoxifen metabolizing genes affect the plasma concentration of tamoxifen metabolites, but their effect on clinical outcome is unknown. Methods We determined cytochrome P450 (CYP)2D6 (*4 and *6) and CYP3A5 (*3) genotype from paraffin-embedded tumor samples and buccal cells (living patients) in tamoxifen-treated women enrolled onto a North Central Cancer Treatment Group adjuvant breast cancer trial. The relationship between genotype and disease outcome was determined using the log-rank test and Cox proportional hazards modeling. Results Paraffin blocks were obtained from 223 of 256 eligible patients, and buccal cells were obtained from 17 living women. CYP2D6 (*4 and *6) and CYP3A5 (*3) genotypes were determined from 190, 194, and 205 patient samples and in 17 living women. The concordance rate between buccal and tumor genotype was 100%. Women with the CYP2D6 *4/*4 genotype had worse relapse-free time (RF-time; P = .023) and disease-free survival (DFS; P = .012), but not overall survival (P = .169) and did not experience moderate to severe hot flashes relative to women heterozygous or homozygous for the wild-type allele. In the multivariate analysis, women with the CYP2D6 *4/*4 genotype still tended to have worse RFS (hazard ratio [HR], 1.85; P = .176) and DFS (HR, 1.86; P = .089). The CYP3A5*3 variant was not associated with any of these clinical outcomes. Conclusion In tamoxifen-treated patients, women with the CYP2D6 *4/*4 genotype tend to have a higher risk of disease relapse and a lower incidence of hot flashes, which is consistent with our previous observation that CYP2D6 is responsible for the metabolic activation of tamoxifen to endoxifen.

Prognostic value of BRAFV600 mutations in melanoma patients after resection of metastatic lymph nodes.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8540-8540
Author(s):  
Philippe Saiag ◽  
Stephanie Moreau ◽  
Philippe Aegerter ◽  
Daphne Bosset ◽  
Christine Longvert ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Prognostic Value ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Primary Melanoma ◽  
Stage Iv ◽  
Cox Proportional Hazards ◽  
Stage Iii ◽  
Rank Test ◽  
Braf Mutations

8540 Background: Prognosis of AJCC stage III melanoma is heterogeneous. BRAFV600 mutations are frequent in melanomas. BRAFV600-targeted therapy has dramatic, but often transitory, efficacy in stage IV patients (pts). We aimed to determine for the first time the prognostic value of BRAFV600 mutations and other known prognostic criteria in stage III pts with sufficient nodal invasion. Methods: We searched all pts with cutaneous melanoma who had radical lymphadenectomy in our institution between 1/1/00 and 15/6/10 and included those with a nodal deposit >2 mm. BRAFV600 mutations were detected by DNA sequencing and pyrosequencing in formalin-fixed nodal samples containing >60% melanoma cells. Samples were considered mutated when >15% of DNA was positive. Endpoints were overall survival (OS) and distant metastasis free survival (DMFS). 92 patients had to be included to demonstrate a doubling of OS in patients without (40 months (m)) and with BRAFV600 mutation (20 m). Log-rank test and multivariate Cox proportional hazards regression model were used. Results: 105 consecutive pts were included, with 72% prospectively followed-up pts. BRAFV600 mutations (E: 83%; K: 14% of pts) were detected in 40% of pts. Median follow-up was 19 m (range: 3-139). Death occurred in 83% and 60% of pts with and without BRAF mutations, respectively, with median OS of 1.4 and 2.8 years. Pts’ age, primary melanoma ulceration, number of invaded nodes, AJCC staging, and BRAF status influenced OS and DMFS in the univariate analysis. The multivariate analysis showed the major prognostic role of BRAF status and of the number of invaded nodes (table). Conclusions: Provided our findings are independently replicated, BRAFV600 status should be used to stage melanoma pts with nodal metastasis. Our results also help to plan adjuvant trials with BRAFV600-targeted therapy in such patients, for whom the low tumor load may induce longer efficacy of BRAF-targeted therapies. [Table: see text]

Prognostic value of lemur tyrosine kinase-3 (LMTK3) polymorphism in Japanese (J) patients (PTS) with localized gastric adenocarcinoma (GAC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4088-4088
Author(s):  
Afsaneh Barzi ◽  
Takeru Wakatsuki ◽  
Wu Zhang ◽  
Dongyun Yang ◽  
Fotios Loupakis ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Univariate Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Gender Disparity ◽  
Rank Test ◽  
Tissue Samples ◽  
Direct Dna Sequencing ◽  
Estrogen Exposure ◽  
Increased Risk

4088 Background: LMTK3 is an estrogen receptor α (ERα) regulator. Recent studies show that [rs808419(r8) and rs9989661(r9)] and LMTK3 expression are prognostic in breast and colon cancers. Our group demonstrated that r9AA is associated with shorter time to recurrence in Caucasian(C) and Hispanic(H) females(F) with GAC. We investigated the significance of LMTK3 polymorphism in J PTS with GAC. Methods: Blood or tissue samples of 169 J PTS who had surgery with/without adjuvant chemotherapy (ACT) were analyzed. Genomic DNA was extracted using the QIAmp kit; all samples were analyzed using PCR-based direct DNA-sequencing. The endpoints of the study were disease-free survival (DFS) and overall survival (OS). Kaplan-Meier curves and log-rank test were used for univariate analysis. Multivariate analysis was performed to test the interaction between polymorphism and gender adjusting for other variables. Results: 60 F and 109 males were enrolled in this study, 17% stage(s) IB, 31% s II, 36% s III, 17% s IV (AJCC-6). The median age was 67(31-88). 65% of PTS received S-1 based ACT. Median follow-up was 4 years(ys). Prognosis was worse in men with r9 AA than AG/GG, at 1 year 67% (95% CI 40-83%) with AA vs 99% (95% CI 91-99%) of AG/GG were alive (p= 0.039). Median survival was not reached in the AG/GG group; in the AA group median DFS and OS was 1yr (p= 0.03) and 2ys (p= 0.039) respectively. In the multivariate analysis adjusting for s, age, and ACT, males carrying AA had increased risk of disease recurrence (HR 3.84 95%CI 1.86-7.92, p< 0.001) and dying (HR 3.47 95%CI 1.58-7.62 p=0.002) compared to those with AG/GG (HR=1, reference). Conclusions: r9 AA was associated with significantly worse DFS and OS in J male with GAC. These results confirm our previous findings that LMTK3 is an independent prognostic factor for localized GAC; interestingly the relationship between gender and prognostic significance is the opposite in J vs. C/H. The gender disparity can be due to the differences in the etiology (histological subtypes), management strategies, allele frequency, and degree of estrogen exposure in the two populations. Additional studies are warranted to identify the underlying biological mechanism.

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