Positive Surgical Margins in Submandibular Malignancies: Facility and Practice Variation

Objectives Identify positive margin rate in a national cohort of patients with submandibular carcinoma, identify predictors of positive margins, and associate margins with overall survival. Study Design Retrospective cohort. Setting Commission on Cancer–accredited hospitals. Subjects and Methods We included patients in the National Cancer Database from 2004 to 2014 who were diagnosed with submandibular carcinoma and underwent primary surgical resection. We determined the rate of positive surgical margins and associated patient, tumor, and treatment factors with positive margins via univariable and multivariable logistic regression analysis. We associated margin status with overall survival by Kaplan-Meier curve and Cox proportional hazards regression. Results We identified 1150 patients with submandibular malignancy undergoing surgical resection. Positive margin rate was 41.0%. Increased odds of positive margins were seen in patients with advanced T stage (vs T1, T3: odds ratio [OR] = 3.04, P < .001; T4a: OR = 2.89, P < .001), adenoid cystic carcinoma histology (OR = 1.54, P = .020), and those treated at nonacademic facilities (OR = 1.41, P = .008). Patients who underwent a preoperative diagnostic biopsy had decreased odds of positive margins (OR = 0.72, P = .014). Positive margins were associated with reduced overall survival (58% vs 69% 5-year overall survival, P < .001; hazard ratio = 1.49, P = .001) when controlling for patient, tumor, and management factors. Conclusions The national positive margin rate of submandibular carcinoma is 41.0%. Preoperative biopsy and treatment at academic institutions independently decreased the risk of positive margins, and positive margins were independently associated with diminished overall survival. Positive margin rate for submandibular carcinoma may be considered a benchmark for quality of care.

Download Full-text

Value of surgical resection and timing of therapy in patients with pancreatic cancer at high risk for positive margins

ESMO Open ◽

10.1136/esmoopen-2017-000282 ◽

2018 ◽

Vol 3 (1) ◽

pp. e000282 ◽

Cited By ~ 12

Author(s):

Anna Torgeson ◽

Ignacio Garrido-Laguna ◽

Randa Tao ◽

George M Cannon ◽

Courtney L Scaife ◽

...

Keyword(s):

Pancreatic Cancer ◽

Surgical Resection ◽

Proportional Hazards ◽

Clinical Stage ◽

Positive Margin ◽

Cox Proportional Hazards ◽

Stage Iii ◽

Term Survival ◽

Additional Therapy ◽

Margin Positive

BackgroundSurgical resection remains the best chance at long-term survival in pancreatic cancer, though margin-positive resections are associated with diminished survival. We examined the effect of margin-positive resection on survival, as well as the role and timing of additional therapies through the National Cancer Database (NCDB).Patients and methodsPatients with stage IIA–III pancreatic adenocarcinoma diagnosed from 2004 to 2013 were identified in NCDB. Survival was compared using univariate and multivariate Cox proportional hazards modelling for patients who underwent surgery with negative (R0), microscopically positive (R1) and macroscopically positive (R2) margins or non-surgical treatment. We further analysed patients by margin status, timing of additional therapy (neoadjuvant therapy (NAT) vs adjuvant therapy (AT) vs none) and clinical stage.ResultsWe analysed 44 852 patients. Median survival (MS) for patients who did not undergo surgery was 10.3 months, compared with 19.7 months for R0 (P<0.001), 14.3 months for R1 (P<0.001) and 9.8 months (P=0.07) for R2 resections. NAT (MS 23.2 months) was associated with improved survival compared with AT (MS 21.5 months) in negative-margin patients and equivalent (MS 17.6 months) to AT (MS 16.8 months) in positive-margin patients. Survival for stage III NAT positive-margin patients (MS 19.8 months) was equivalent to AT after negative margins (MS 18.4 months, P=1.00). Improved R0 rates were seen with NAT (88% vs 81%, P<0.001), especially in stage III patients (85% vs 59%, P<0.001).ConclusionR1 resections portend poorer survival than R0 but do not negate the benefit of surgery when additional therapy is given. NAT was associated with improved R0 rates and improved survival for stage III positive-margin patients.

Download Full-text

Does up-front definitive surgical resection with delayed chemotherapy in patients with stage IV rectal cancer compromise overall survival?

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.586 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 586-586

Author(s):

Bindu V. Manyam ◽

Shlomo A. Koyfman ◽

Davendra Sohal ◽

Ismail Mallick ◽

Chandana A. Reddy ◽

...

Keyword(s):

Rectal Cancer ◽

Overall Survival ◽

Surgical Resection ◽

Proportional Hazards ◽

Performance Status ◽

Rectal Adenocarcinoma ◽

Stage Iv ◽

Cox Proportional Hazards ◽

Significant Difference ◽

Poorly Differentiated

586 Background: Definitive resection of the primary is frequently part of the management of patients (pts) with stage IV rectal cancer with good performance status and low volume of systemic metastases. It is unclear whether delaying systemic therapy for up front surgical management of the primary compromises overall survival (OS). Methods: Pts with metastatic rectal adenocarcinoma who received definitive surgical resection between 1998-2011 were identified in an IRB approved registry. The sequencing of CT and surgery, and the use of perioperative radiation therapy (RT), was at the discretion of treating physicians. Preoperative chemotherapy (Pre-CT) regimens included 5-fluorouracil (5-FU) +/- leukovorin (LV), capecitabine, 5-FU/LV/oxaliplatin +/- avastin, or 5-FU/LV/irinocetan. RT dose was typically 50.4 Gy. OS was measured from the date of diagnosis. Baseline variables were compared using the Chi-square and unpaired t-tests. OS was calculated using the Kaplan Meier method. Univariate (UVA) and multivariate analysis (MVA) were performed using Cox proportional hazards regression to identify variables associated with OS. Results: In this study of 115 pts, 75 (65%) were treated with pre-CT, while 40 (35%) were treated with up front surgery. Of the pts who received surgery up front, 3 (8%) received RT and of the pts who received pre-CT, 62 (83%) received RT. The cohort was predominantly male (70%) with a median age of 57, median KPS of 80, and median follow-up of 24.1 months. 94% of pts had T3/T4 tumors, 80% had N+ disease, and 33% had poorly differentiated tumors. Liver directed therapy (LDT) was performed in 61% of pts. There was no significant difference in OS (32.3 vs. 32 months; p = 0.24) between pts treated with pre-CT and those who received surgery up front, respectively. UVA demonstrated that pre-CT was not associated with OS (HR 1.26; p = 0.544). MVA demonstrated that pts with poorly differentiated tumors (HR 2.04; p = 0.007) and those that did not undergo LDT (HR 2.45; p = 0.001) had inferior survival. Conclusions: Delaying systemic chemotherapy in order to achieve local control with surgical resection up front does not appear to impact OS in pts with stage IV rectal cancer.

Download Full-text

The timing of chemoradiotherapy after surgical resection and its impact on overall survival in glioblastoma.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.2051 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 2051-2051

Author(s):

Robert H. Press ◽

Sarah L. Shafer ◽

Renjian Jiang ◽

Zachary S. Buchwald ◽

Mustafa Abugideiri ◽

...

Keyword(s):

Overall Survival ◽

Surgical Resection ◽

Proportional Hazards ◽

Radiation Therapy Oncology Group ◽

Cox Proportional Hazards ◽

Class I ◽

Optimal Timing ◽

Class Iii ◽

Entire Cohort ◽

Immortal Time Bias

2051 Background: Prior studies examining time to initiate chemoradiotherapy (CRT) after surgical resection (S) in glioblastoma (GBM) have not provided clear consensus on its clinical impact. We sought to evaluate the effect that differential timing of adjuvant therapy may have on overall survival (OS). Methods: With the National Cancer Database (NCDB), patients (pts) with GBM who underwent S and adjuvant CRT from 2004-2013 were analyzed. Analysis was performed for the entire cohort as well as by Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis (RPA) classes (i.e. I, II, and III). Time from S to CRT was grouped weekly (i.e. 0-1, 1-2, 2-3, 3-4, 4-5, 5-6, 6-7, 7-8, and > 8 weeks). Pts were excluded if they died within the first 8 weeks to account for immortal time bias. Kaplan-Meier analysis, log-rank testing, and multivariate (MVA) Cox proportional hazards regression were performed with OS as the primary outcome. Results: A total of 30,414 pts were included for analysis. RPA class I, II, and III contained 903, 4,347, and 25,164 pts, respectively. The most common time to initiate CRT was week 4-5 (n = 7389), and this group served as reference for survival analysis. On MVA, weeks 0-1 (hazard ratio [HR] 1.18, 95% confidence interval [CI] 1.02-1.35), 1-2 (HR 1.24, CI 1.17-1.32), and 2-3 (HR 1.11, CI 1.07-1.15) demonstrated worse OS (all p < 0.03). For RPA class I pts, week 1-2 (HR 2.07, CI 1.08-3.95) was associated with worse OS (p = 0.028). For RPA class II pts, weeks 1-2 (HR 1.34, CI 1.14-1.57), 2-3 (HR 1.18, CI 1.07-1.31), and 3-4 (HR 1.10, CI 1.0-1.21) were associated with worse OS (all p < 0.05). For RPA class III pts, weeks 0-1 (HR 1.18, CI 1.02-1.38), 1-2 (HR 1.22, CI 1.14-1.3), and 2-3 (HR 1.09, CI 1.05-1.14) were associated with worse OS (all p < 0.03). No time point after week 5 was associated with change in OS for the overall cohort or any RPA class subgroup. Conclusions: These data provide insight into the optimal timing of CRT in GBM and describe RPA-class specific outcomes. In general, OS was negatively impacted if CRT started less than 3 weeks from S. Waiting up to 8 weeks, however, was not detrimental to OS and suggests delaying CRT beyond week 4-5 should be considered if clinically indicated without undue concern.

Download Full-text

Single institutional analysis of resectable pancreatic cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.4_suppl.706 ◽

2020 ◽

Vol 38 (4_suppl) ◽

pp. 706-706

Author(s):

Jeff Wiisanen ◽

Patrick Navin ◽

Moustafa El Khatib ◽

William R Bamlet ◽

Sean P. Cleary ◽

...

Keyword(s):

Pancreatic Cancer ◽

Overall Survival ◽

Pancreatic Adenocarcinoma ◽

Surgical Resection ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Resectable Pancreatic Cancer ◽

Time To Recurrence ◽

Kaplan Meier ◽

Resectable Cancer

706 Background: In recent years, there has been a shift towards neo-adjuvant treatment (NAT) of non-metastatic pancreas cancer in the hopes of improving negative margin rate, lymph node negativity, recurrence and survival. Even patients deemed resectable based on NCCN criteria are receiving NAT but data for these patients remains limited. This current study evaluated the outcomes of patients diagnosed with resectable pancreatic adenocarcinoma. Methods: Patients were retrospectively identified through the Mayo Clinic, Rochester SPORE pancreatic cancer registry as well as search of the electronic medical record via Advanced Cohort Explorer from May 2011 to 2016. Baseline demographics, tumor characteristics, treatments rendered, and outcomes were collected. Variables were analyzed for association with recurrence from time of surgery and survival from time of diagnosis using Kaplan-Meier curves and Cox proportional hazards regression. Results: A total of 520 patients with resectable pancreatic adenocarcinoma were identified. 72 patients received upfront chemotherapy with 44 (61.1%) proceeding to surgical resection. 62 patients received upfront chemotherapy followed by radiation with 33 (53.2%) proceeding to surgical resection. 12 patients received upfront radiation alone with 7 (58.3%) proceeding to surgical resection. 374 patients did not receive any NAT with 293 (78.3%) proceeding to surgical resection. In total, 377 (72.5%) went to resection. Median time to recurrence from surgery was 27.7 months vs. 21.7 months for NAT and upfront resection, respectively (HR 0.87, 95% CI 0.60-1.72, p = 0.48). Median overall survival from diagnosis for those receiving NAT was 40.6 months vs. 24.7 months for those receiving upfront resection (HR 0.62, 95% CI 0.41-0.92, p = 0.02). Conclusions: This study shows an approximate 16 month improvement in overall survival of patients receiving upfront NAT for resectable pancreatic adenocarcinoma. This might be due to a better selection of patients. It also highlights that not all patients with resectable cancer undergo resection. Further studies are warranted to identify why resectable patients are not proceeding to resection and which specific NAT approaches benefit patients the most.

Download Full-text

Prognostic Significance of Preoperative Fibrinogen-to-Prealbumin Ratio in Patients with Stage I–III Colorectal Cancer Undergoing Surgical Resection: A Retrospective Cohort Study

BioMed Research International ◽

10.1155/2021/3905353 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Hailun Xie ◽

Shizhen Huang ◽

Guanghui Yuan ◽

Shuangyi Tang ◽

Jialiang Gan

Keyword(s):

Overall Survival ◽

Surgical Resection ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Disease Free Survival ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Stage I ◽

Free Survival ◽

Disease Free

Background. The objective of this study was to explore the role of preoperative fibrinogen-to-prealbumin ratio (FPR) in evaluating the prognosis of patients with stage I–III colorectal cancer (CRC). Methods. This retrospective study enrolled 584 stage I–III CRC patients undergoing surgical resection. Logistic regression analysis was used to explore the correlation between FPR and postoperative complications. The Kaplan-Meier curve and Cox proportional hazards model were used to identify the prognostic factors. The nomograms were constructed based on the prognostic factors. The concordance index and calibration curve were used to determine the accuracy of the nomograms. Time-dependent receiver operating characteristic was used to compare the predictive prognostic efficacy of nomograms and TNM stage. Results. FPR was determined to be an independent factor affecting postoperative complications. Patients with a low-FPR had a significantly better prognosis than those with a high-FPR (disease-free survival, p = 0.028 ; overall survival, p = 0.027 ), especially patients with stage I CRC (disease-free survival, p = 0.015 ; overall survival, p = 0.017 ). The Cox proportional hazards model identified FPR as an independent poor prognostic factor of disease-free survival (hazard ratio HR = 1.459 , 95% confidence interval CI = 1.074 –1.954, p = 0.011 ) and overall survival ( HR = 1.405 , 95% CI = 1.034 –1.909, p = 0.030 ). The prognostic nomograms had good accuracy and were superior to the traditional TNM stage. Conclusions. FPR is a potential indicator for predicting short- and long-term prognosis of stage I–III CRC patients undergoing surgical resection.

Download Full-text

Epilepsy as a Comorbidity in Polymyositis and Dermatomyositis—A Cross-Sectional Study

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18083983 ◽

2021 ◽

Vol 18 (8) ◽

pp. 3983

Author(s):

Ella Nissan ◽

Abdulla Watad ◽

Arnon D. Cohen ◽

Kassem Sharif ◽

Johnatan Nissan ◽

...

Keyword(s):

Proportional Hazards ◽

Cross Sectional Study ◽

Cox Proportional Hazards ◽

Categorical Variables ◽

Rank Test ◽

Control Group ◽

Multivariable Logistic Regression Analysis ◽

Positive Trend ◽

Continuous Variables ◽

Cross Sectional

Polymyositis (PM) and dermatomyositis (DM) are autoimmune-mediated multisystemic myopathies, characterized mainly by proximal muscle weakness. A connection between epilepsy and PM/DM has not been reported previously. Our study aim is to evaluate this association. A case–control study was conducted, enrolling a total of 12,278 patients with 2085 cases (17.0%) and 10,193 subjects in the control group (83.0%). Student’s t-test was used to evaluate continuous variables, while the chi-square test was applied for the distribution of categorical variables. Log-rank test, Kaplan–Meier curves and multivariate Cox proportional hazards method were performed for the analysis regarding survival. Of the studied 2085 cases, 1475 subjects (70.7%) were diagnosed with DM, and 610 patients (29.3%) with PM. Participants enrolled as cases had a significantly higher rate of epilepsy (n = 48 [2.3%]) as compared to controls (n = 141 [1.4%], p < 0.0005). Using multivariable logistic regression analysis, PM was found only to be significantly associated with epilepsy (OR 2.2 [95%CI 1.36 to 3.55], p = 0.0014), whereas a non-significant positive trend was noted in DM (OR 1.51 [95%CI 0.99 to 2.30], p = 0.0547). Our data suggest that PM is associated with a higher rate of epilepsy compared to controls. Physicians should be aware of this comorbidity in patients with immune-mediated myopathies.

Download Full-text

Survival rates and prognostic factors in right- and left-sided colon cancer stage I–IV: an unselected retrospective single-center trial

International Journal of Colorectal Disease ◽

10.1007/s00384-021-04005-6 ◽

2021 ◽

Author(s):

Claudius E. Degro ◽

Richard Strozynski ◽

Florian N. Loch ◽

Christian Schineis ◽

Fiona Speichinger ◽

...

Keyword(s):

Colon Cancer ◽

Overall Survival ◽

Blood Level ◽

Proportional Hazards ◽

Survival Rates ◽

Cox Proportional Hazards ◽

Stage I ◽

Cancer Stage ◽

Single Center ◽

Significant Difference

Abstract Purpose Colorectal cancer revealed over the last decades a remarkable shift with an increasing proportion of a right- compared to a left-sided tumor location. In the current study, we aimed to disclose clinicopathological differences between right- and left-sided colon cancer (rCC and lCC) with respect to mortality and outcome predictors. Methods In total, 417 patients with colon cancer stage I–IV were analyzed in the present retrospective single-center study. Survival rates were assessed using the Kaplan–Meier method and uni/multivariate analyses were performed with a Cox proportional hazards regression model. Results Our study showed no significant difference of the overall survival between rCC and lCC stage I–IV (p = 0.354). Multivariate analysis revealed in the rCC cohort the worst outcome for ASA (American Society of Anesthesiologists) score IV patients (hazard ratio [HR]: 16.0; CI 95%: 2.1–123.5), CEA (carcinoembryonic antigen) blood level > 100 µg/l (HR: 3.3; CI 95%: 1.2–9.0), increased lymph node ratio of 0.6–1.0 (HR: 5.3; CI 95%: 1.7–16.1), and grade 4 tumors (G4) (HR: 120.6; CI 95%: 6.7–2179.6) whereas in the lCC population, ASA score IV (HR: 8.9; CI 95%: 0.9–91.9), CEA blood level 20.1–100 µg/l (HR: 5.4; CI 95%: 2.4–12.4), conversion to laparotomy (HR: 14.1; CI 95%: 4.0–49.0), and severe surgical complications (Clavien-Dindo III–IV) (HR: 2.9; CI 95%: 1.5–5.5) were identified as predictors of a diminished overall survival. Conclusion Laterality disclosed no significant effect on the overall prognosis of colon cancer patients. However, group differences and distinct survival predictors could be identified in rCC and lCC patients.

Download Full-text

Patterns of Care and Outcomes of Primary Adenoid Cystic Carcinoma of the Trachea

Annals of Otology Rhinology & Laryngology ◽

10.1177/00034894211008101 ◽

2021 ◽

pp. 000348942110081

Author(s):

Sara Behbahani ◽

Gregory L. Barinsky ◽

David Wassef ◽

Boris Paskhover ◽

Rachel Kaye

Keyword(s):

Radiation Therapy ◽

Adenoid Cystic Carcinoma ◽

Surgical Resection ◽

Proportional Hazards ◽

Invasive Disease ◽

Cox Proportional Hazards ◽

Tumor Diameter ◽

Adenoid Cystic ◽

Cox Proportional Hazards Models ◽

Age Of Diagnosis

Objective: Primary tracheal malignancies are relatively rare cancers, representing 0.1% to 0.4% of all malignancies. Adenoid cystic carcinoma (ACC) is the second most common histology of primary tracheal malignancy, after squamous cell carcinoma. This study aims to analyze demographic characteristics and potential influencing factors on survival of tracheal ACC (TACC). Methods: This was a retrospective cohort study utilizing the National Cancer Database (NCDB). The NCDB was queried for all cases of TACC diagnosed from 2004 to 2016 (n = 394). Kaplan-Meier (KM) and Cox proportional-hazards models were used to determine clinicopathological and treatment factors associated with survival outcomes. Results: Median age of diagnosis was 56 (IQR: 44.75-66.00). Females were affected slightly more than males (53.8% vs 46.2%). The most prevalent tumor diameter range was 20 to 39 mm (34.8%) followed by greater than 40 mm in diameter (17.8%). Median overall survival (OS) was 9.72 years with a 5- and 10-year OS of 70% and 47.5%, respectively. Localized disease was not associated with a survival benefit over invasive disease ( P = .388). The most common intervention was surgery combined with radiation therapy (RT) at 46.2%, followed by surgery alone (16.8%), and standalone RT (8.9%). When adjusting for confounders, surgical resection was independently associated with improved OS (HR 0.461, 95% CI 0.225-0.946). Tumor size greater than 40 mm was independently associated with worse OS (HR 2.808; 95% CI 1.096-7.194). Conclusion: Our data suggests that surgical resection, possibly in conjunction with radiation therapy, is associated with improved survival, and tumor larger than 40 mm are associated with worse survival.

Download Full-text

Longer duration of symptoms at the time of presentation is not associated with worse survival in primary bone sarcoma

The Bone & Joint Journal ◽

10.1302/0301-620x.100b5.bjj-2017-1235.r1 ◽

2018 ◽

Vol 100-B (5) ◽

pp. 652-661 ◽

Cited By ~ 6

Author(s):

J. M. Lawrenz ◽

J. F. Styron ◽

M. Parry ◽

R. J. Grimer ◽

N. W. Mesko

Keyword(s):

Overall Survival ◽

Proportional Hazards ◽

Bone Sarcoma ◽

Axial Skeleton ◽

Cox Proportional Hazards ◽

Low Grade ◽

Duration Of Symptoms ◽

Negative Effect ◽

Primary Bone Sarcoma ◽

Primary Bone

Aims The primary aim of this study was to determine the effect of the duration of symptoms (DOS) prior to diagnosis on the overall survival in patients with a primary bone sarcoma. Patients and Methods In a retrospective analysis of a sarcoma database at a single institution between 1990 and 2014, we identified 1446 patients with non-metastatic and 346 with metastatic bone sarcoma. Low-grade types of tumour were excluded. Our data included the demographics of the patients, the characteristics of the tumour, and the survival outcome of patients. Cox proportional hazards analysis and Kaplan–Meier survival analysis were performed, and the survivorship of the non-metastatic and metastatic cohorts were compared. Results In the non-metastatic cohort, a longer DOS was associated with a slightly more favourable survival (hazard ratio (HR) 0.996, 95% confidence interval (CI) 0.994 to 0.998, p < 0.001). In all types of tumour, there was no difference in survival between patients with a DOS of greater than four months and those with a DOS of less than four months (p = 0.566). There was no correlation between the year of diagnosis and survival (p = 0.741). A diagnosis of chondrosarcoma (HR 0.636, 95% CI 0.474 to 0.854, p = 0.003) had the strongest positive effect on survival, while location in the axial skeleton (HR 1.76, 95% CI 1.36 to 2.29, p < 0.001) had the strongest negative effect on survival. Larger size of tumour (HR 1.05, 95% CI 1.03 to 1.06, p < 0.001) and increased age of the patient (HR 1.02, 95% CI 1.01 to 1.03, p < 0.001) had a slightly negative effect on survival. Metastatic and non-metastatic cohorts had similar median DOS (16 weeks, p = 0.277), although the median survival (15.5 months vs 41 months) and rates of survival at one year (69% vs 89%) and five years (20% vs 59%) were significantly shorter in the metastatic cohort. Conclusion A longer DOS prior to diagnosis is not associated with a poorer overall survival in patients with a primary bone sarcoma. Location in the axial skeleton remains the strongest predictor of a worse prognosis. This may be helpful in counselling patients referred for evaluation on a delayed basis. Cite this article: Bone Joint J 2018;100-B:652–61.

Download Full-text

Eps15 Homology Domain-Containing Protein 3 Hypermethylation as a Prognostic and Predictive Marker for Colorectal Cancer

Biomedicines ◽

10.3390/biomedicines9050453 ◽

2021 ◽

Vol 9 (5) ◽

pp. 453

Author(s):

Yu-Han Wang ◽

Shih-Ching Chang ◽

Muhamad Ansar ◽

Chin-Sheng Hung ◽

Ruo-Kai Lin

Keyword(s):

Colorectal Cancer ◽

Overall Survival ◽

Mrna Expression ◽

Proportional Hazards ◽

Uterine Cancer ◽

Colonic Polyps ◽

Predictive Marker ◽

Cox Proportional Hazards ◽

The Cancer Genome Atlas ◽

Eps15 Homology Domain

Colorectal cancer (CRC) arises from chromosomal instability, resulting from aberrant hypermethylation in tumor suppressor genes. This study identified hypermethylated genes in CRC and investigated how they affect clinical outcomes. Methylation levels of specific genes were analyzed from The Cancer Genome Atlas dataset and 20 breast cancer, 16 esophageal cancer, 33 lung cancer, 15 uterine cancer, 504 CRC, and 9 colon polyp tissues and 102 CRC plasma samples from a Taiwanese cohort. In the Asian cohort, Eps15 homology domain-containing protein 3 (EHD3) had twofold higher methylation in 44.4% of patients with colonic polyps, 37.3% of plasma from CRC patients, and 72.6% of CRC tissues, which was connected to vascular invasion and high microsatellite instability. Furthermore, EHD3 hypermethylation was detected in other gastrointestinal cancers. In the Asian CRC cohort, low EHD3 mRNA expression was found in 45.1% of patients and was connected to lymph node metastasis. Multivariate Cox proportional-hazards survival analysis revealed that hypermethylation in women and low mRNA expression were associated with overall survival. In the Western CRC cohort, EHD3 hypermethylation was also connected to overall survival and lower chemotherapy and antimetabolite response rates. In conclusion, EHD3 hypermethylation contributes to the development of CRC in both Asian and Western populations.

Download Full-text