scholarly journals 8-Oxoguanine DNA Glycosylase (OGG1) Cys326 Variant: Increased Risk for Worse Outcome of Patients with Locally Advanced Rectal Cancer after Multimodal Therapy

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2805
Author(s):  
Martin Leu ◽  
Theresa Riebeling ◽  
Leif Hendrik Dröge ◽  
Laura Hubert ◽  
Manuel Guhlich ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Clinical Outcome ◽  
Cox Regression ◽  
Locally Advanced ◽  
Multivariable Analysis ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Rank Test ◽  
Neoadjuvant Radiochemotherapy ◽  
Increased Risk

Despite excellent loco-regional control by multimodal treatment of locally advanced rectal cancer, a substantial portion of patients succumb to this disease. As many treatment effects are mediated via reactive oxygen species (ROS), we evaluated the effect of single nucleotide polymorphisms (SNPs) in ROS-related genes on clinical outcome. Based on the literature, eight SNPs in seven ROS-related genes were assayed. Eligible patients (n = 287) diagnosed with UICC stage II/III rectal cancer were treated multimodally starting with neoadjuvant radiochemotherapy (N-RCT) according to the clinical trial protocols of CAO/ARO/AIO-94, CAO/ARO/AIO-04, TransValid-A, and TransValid-B. The median follow-up was 64.4 months. The Ser326Cys polymorphism in the human OGG1 gene affected clinical outcome, in particular cancer-specific survival (CSS). This effect was comparable in extent to the ypN status, an already established strong prognosticator for patient outcome. Homozygous and heterozygous carriers of the Cys326 variant (n = 105) encountered a significantly worse CSS (p = 0.0004 according to the log-rank test, p = 0.01 upon multiple testing adjustment). Cox regression elicited a hazard ratio for CSS of 3.64 (95% confidence interval 1.70–7.78) for patients harboring the Cys326 allele. In a multivariable analysis, the effect of Cys326 on CSS was preserved. We propose the genetic polymorphism Ser326Cys as a promising biomarker for outcome in rectal cancer.

A nomogram based on clinical factors to predict locally advanced stage of rectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 376-376
Author(s):  
Guoxiang Cai ◽  
Baorong Song ◽  
Liyong Huang ◽  
Ye Xu ◽  
Zuqing Guan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Preoperative Staging ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Radiochemotherapy ◽  
Advanced Stage ◽  
Serum Cea ◽  
Magnetic Resonance Imaging Mri

376 Background: Preoperative staging of rectal cancer is important for designing treatment strategy. The standard treatment for locally advanced rectal cancer is neoadjuvant radiochemotherapy followed by surgery. Magnetic resonance imaging (MRI) and transrectal ultrasonography are major staging approaches with a prediction accuracy of about 70-80% but not widely available in hospitals in China. We sought to define possible clinicopathological predictors and establish a simple nomogram as a reference tool for patients and clinicians to predict stage of rectal cancer and make decisions about neoadjuvant therapy. Methods: Preoperative staging of rectal cancer is important for designing treatment strategy. The standard treatment for locally advanced rectal cancer is neoadjuvant radiochemotherapy followed by surgery. Magnetic resonance imaging (MRI) and transrectal ultrasonography are major staging approaches with a prediction accuracy of about 70-80% but not widely available in hospitals in China. We sought to define possible clinicopathological predictors and establish a simple nomogram as a reference tool for patients and clinicians to predict stage of rectal cancer and make decisions about neoadjuvant therapy. Results: In the training set, 77.1% of patients had locally advanced stage by pathology. The multivariate analysis indicated that tumor size (Odds ratio (OR)=1.55, p< 0.001), differentiation (OR =0.38, p< 0.001), location (OR =1.06, p=0.038), serum CEA (OR =0.24, p< 0.001) and CA19-9 level (OR =0.13, p< 0.001) were associated with tumor stage. A nomogram consisting of these 5 factors was developed and predicted locally advanced stage with a concordance index of 0.756. The concordance index of this nomogram was 0.800 in the validation set. Conclusions: Large tumor size, far from anal verge, poor differentiation, elevated serum CEA and CA19-9 level were high-risk factors of locally advanced stage of rectal cancer. The nomogram based on these clinical factors can predicte locally advanced rectal cancer with a considerable accuracy and thus helpful for making neoadjuvant therapy recommendations.

Clinical outcome in patients who did not accept complementary surgery after neoadjuvant chemoradiotherapy (QT-RT) in locally advanced rectal cancer (LARC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e15144-e15144
Author(s):  
German Caderillo-Ruiz ◽  
Dr. Consuelo Diaz ◽  
Horacio Noe López-Basave ◽  
MaryTere Herrera ◽  
Erika Ruiz Garcia ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Clinical Outcome ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

Impact of adjuvant treatment in elderly patients with locally advanced rectal cancer: A population-based retrospective study.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 3613-3613
Author(s):  
Shiru Lucy Liu ◽  
Pierre O'Brien ◽  
Yizhou Zhao ◽  
Wilma M Hopman ◽  
Nathan William Dana Lamond ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Elderly Patients ◽  
Cox Regression ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
The Elderly ◽  
Population Based ◽  
Locally Advanced Rectal Cancer ◽  
Curative Intent ◽  
Kaplan Meier

3613 Background: Little is known about the benefit and use of adjuvant chemotherapy (ADJ) in the elderly population (age ≥ 65) with locally advanced rectal cancer (LARC). We undertook a provincial review of LARC patients to evaluate the potential benefits, including survival and time to relapse (TTR), of ADJ in elderly patients. Methods: We performed a retrospective analysis of 286 LARC patients (stage 2 and 3) diagnosed between January 2010 and December 2013 from Nova Scotia, Canada, who underwent curative-intent surgery. Baseline patient, tumor and treatment characteristics were collected. Survival and TTR analysis were performed using Kaplan-Meier and Cox-regression statistics. Results: 152 patients were age ≥65, and 92 age ≥70. Median follow-up was 46 months. 178 patients (62%) received neoadjuvant chemo-radiation (NEOADJ). While 109 patients (81%) age < 65 received ADJ, only 68 patients (45%) age ≥ 65 received ADJ. Kaplan-Meier analysis revealed a significant survival and TTR advantage for ADJ irrespective of age (table). In cox-regression multivariate analysis, ECOG status, T stage, and ADJ were significant predictors of survival (p < 0.04), while age was not. Similarly, N stage, NEOADJ, and ADJ were significant predictors of TTR (p < 0.007). Poor ECOG status was the most common cause of ADJ omission. There was a significantly higher amount of grade≥ 1 chemotherapy-related toxicity experienced by patients age ≥ 65 treated with ADJ compared to no ADJ (77% vs 32%, p < 0.0001), which consisted mostly of diarrhea and mucositis. Toxicity was the main reason for non-completion of ADJ in the elderly. Conclusions: Elderly patients with LARC have significantly improved overall survival with ADJ, but the use of ADJ is lower than in patients age < 65. However, elderly patients experience more chemotherapy-related toxicities, leading to higher rates of early treatment discontinuation. [Table: see text]

Tumor necrosis as prognostic values in neoadjuvant chemoradiotherapy and laparoscopic surgery for locally advanced rectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 722-722
Author(s):  
Ji Han Jung ◽  
Hyung Jin Kim ◽  
Ho Jung An ◽  
Sung Whan Kim ◽  
Hyun Min Cho ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Treatment Response ◽  
Tumor Necrosis ◽  
Cox Regression ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Tissue Response ◽  
Response Factor ◽  
Pathologic Stage

722 Background: Association between treatment response on the basis of pathologic stage evaluated after radical tumor resection and patient prognosis was well established. The object of this study is that tumor necrosis factor after CRT is also important as treatment response. Methods: A total of 243 patients with locally advanced rectal cancer that underwent neoadjuvant CRT was included. Three treatment response groups were classified by their pathologic stage results: complete treatment response (CTR), intermediate treatment response (ITR), and poor treatment response (PTR). Three tissue necrosis groups were classified by tissue pathologic results: complete necrosis response (CNR), intermediate necrosis response (INR), and poor necrosis response (PNR). Results: Overall survival (OS) and recurrence free survival (RFS) rate at 3 years were 74.5% and 61.3%, respectively. The 3-year OS rates of the CTR, ITR, and PTR were 83.7%, 75.9%, and 69.7%, respectively (p<0.001); the 3-year RFS rates were 76.7%, 69.0%, and 52.1%, respectively (p<0.001). The 3-year OS rates of the CNR, INR, and PNR were 83.7%, 80.6%, and 61.8%, respectively (p<0.001); the 3-year RFS rates were 76.7%, 68.9%, and 44.3%, respectively (p<0.001). When compared to CTR / CNR, PTR / PNR was strongly related to an increased risk of recurrence (hazard ratio, 5.53; 95% CI, 2.01 to 15.23 / 6.37; 95% CI, 2.29 to 17.74) respectively in the univariate Cox regression. Therefore in the two models using multivariate Cox regression, both PTR and PNR were strongly associated to RFS and OS compared with CTR and CNR. Conclusions: The tissue response factor to neoadjuvant CRT is one surrogate marker for recurrence and oncologic outcomes and almost as important as the treatment response factor in rectal cancer patients treated with neo-adjuvant CRT.

Microsatellite instability (MSI) as an independent predictor of pathologic complete response (PCR) in locally advanced rectal cancer: A National Cancer Database (NCDB) analysis.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 616-616 ◽  
Author(s):  
Shaakir Hasan ◽  
Paul Renz ◽  
Rodney E Wegner ◽  
Gene Grant Finley ◽  
Moses S. Raj ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Microsatellite Instability ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Multivariable Analysis ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
National Cancer Database

616 Background: The relationship between microsatellite instability (MSI) and response to neoadjuvant chemoradiation in rectal cancer is not well understood. We therefore utilized the national cancer database (NCDB) to investigate the association between MSI and pathologic complete response (pCR) in this patient population. Methods: We analyzed 5,086 patients between 2010-2015 with locally advanced rectal cancer who were tested for MSI and treated definitively with chemoradiation followed by surgery. Primary comparison groups were between 4,450 MSI-negative(-) and 636 MSI-positive(+) patients. Multivariable regression analysis was conducted to identify demographic, therapeutic, and clinical characteristics predictive of pCR. Cox proportional hazard ratios were used for survival. Results: All patients were treated with definitive chemoradiation (median dose 50.4 Gy) followed by resection within 4 months. MSI(+) patients were associated with earlier year of diagnosis and higher grade tumors (P < 0.05). The overall pCR rate was 8.6%, including 8.9% for MSI(-) and 5.9% for MSI(+) tumors (P = 0.01). Along with lower T stage, MSI(+) cases were significantly associated with a reduced pCR rate (OR = 0.65, 95% CI 0.43 – 0.96) with multivariable analysis. The 5-year survival for patients with pCR was 93% compared to 73% without it (< 0.001). Conclusions: Microsatellite instability was independently associated with a reduction in pathologic complete response for locally advanced rectal cancer following neoadjuvant chemoradiation in this NCDB-based analysis.[Table: see text]

Sign in / Sign up

Export Citation Format

Share Document