scholarly journals The prognostic capacities of CBP and p300 in locally advanced rectal cancer

2019 ◽  
Vol 17 (1) ◽  
Author(s):  
Felix Rühlmann ◽  
Indra Maria Windhof-Jaidhauser ◽  
Cornelius Menze ◽  
Tim Beißbarth ◽  
Hanibal Bohnenberger ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
High Expression ◽  
Creb Binding Protein ◽  
Cancer Specific Survival ◽  
Tissue Samples ◽  
Oncological Treatment

Abstract Background CREB-binding protein (CBP) and p300 represent histone acetyltransferases (HATs) and transcriptional coactivators that play essential roles in tumour initiation and progression. Both proteins are generally thought to function as tumour suppressors, although their distinct roles in colorectal cancer (CRC) remain inconsistent and ambiguous. Thus, we analysed the expression of these two HATs in human tissue samples from patients with locally advanced rectal cancer via immunohistochemistry and evaluated their potential impacts on future CRC diagnosis and treatment. Methods In our analysis, we included ninety-three (n = 93) patients diagnosed with adenocarcinoma in the upper third of the rectum. None of the patients received preoperative chemoradiotherapy, but the patients did undergo primary resection of the tumour within the phase II GAST-05 trial. By using H-scores, the expression of both proteins was visualised via immunohistochemistry in resected specimens from the patients. CBP and p300 expression were correlated with clinical and follow-up data. Results Our analysis showed that high expression of CBP was significantly associated with prolonged cancer-specific survival (CSS; p = 0.002). In univariate analysis, CBP was an independent prognostic parameter for CSS (p = 0.042). High nuclear CBP expression was observed in two-thirds of patients. In contrast, we could not find any significant correlation between the expression of p300 and cancer-specific survival in this cohort of patients (p = 0.09). We did not observe any cooperation between CBP and p300 in our analysis. Conclusions High expression of CBP was significantly associated with improved oncological outcomes. This finding could help to stratify patients in the future for CRC treatment. Histone deacetylase (HDAC) inhibitors are increasingly playing a role in oncological treatment and could additionally become therapeutic options in CRC. Our findings need to be further evaluated and verified in future clinical analyses.

scholarly journals The Elevated Pre-Treatment C-Reactive Protein Predicts Poor Prognosis in Patients with Locally Advanced Rectal Cancer Treated with Neo-Adjuvant Radiochemotherapy

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 780
Author(s):  
Richard Partl ◽  
Katarzyna Lukasiak ◽  
Eva-Maria Thurner ◽  
Wilfried Renner ◽  
Heidi Stranzl-Lawatsch ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
C Reactive Protein ◽  
Adjuvant Radiochemotherapy ◽  
Free Survival ◽  
Reactive Protein ◽  
Pre Treatment

The aim of the present study was to investigate the association of the pre-treatment C-reactive protein (CRP) plasma level with survival outcomes in a cohort of 423 consecutive patients with locally advanced rectal cancer treated with neo-adjuvant radiochemotherapy followed by surgical resection. To evaluate the prognostic value of the CRP level for clinical endpoints recurrence-free survival (RFS), local-regional control (LC), metastases-free survival (MFS), and overall survival (OS), uni- and multivariate Cox regression analyses were applied, and survival rates were calculated using Kaplan–Meier analysis. The median follow-up time was 73 months. In univariate analyses, the pre-treatment CRP level was a significant predictor of RFS (hazard ratio (HR) 1.015, 95% CI 1.006–1.023; p < 0.001), LC (HR 1.015, 95% CI 1.004–1.027; p = 0.009), MFS (HR 1.014, 95% CI 1.004–1.023; p = 0.004), and OS (HR 1.016, 95% CI 1.007–1.024; p < 0.001). Additionally, univariate analysis identified the MRI circumferential resection margin (mrCRM) and pre-treatment carcinoembryonic antigen (CEA) as significant predictor of RFS (HR 2.082, 95% CI 1.106–3.919; p = 0.023 and HR 1.005, 95% CI 1.002–1.008; p < 0.001). Univariate analysis also revealed a significant association of the mrCRM (HR 2.089, 95% CI 1.052–4.147; p = 0.035) and CEA (HR 1.006, 95% CI 1.003–1.008; p < 0.001) with MFS. Age and CEA were prognostic factors for OS (HR 1.039, 95% CI 1.013–1.066; p = 0.003 and HR 1.005, 95% CI 1.002–1.008; p < 0.001). In multivariate analysis that included parameters with a p-level < 0.20 in univariate analysis, the pre-treatment CRP remained a significant prognostic factor for RFS (HR 1.013, 95%CI 1.001–1.025; p = 0.036), LC (HR 1.014, 95% CI 1.001–1.027; p = 0.031), and MFS (HR 1.013, 95% CI 1.000–1.027; p = 0.046). The results support the hypothesis that an elevated pre-treatment CRP level is a predictor of poor outcome. If confirmed by additional studies, this easily measurable biomarker could contribute to the identification of patients who might be candidates for more aggressive local or systemic treatment approaches or the administration of anti-inflammatory drugs.

The prognostic value of an early response in chemoradiation of locally advanced rectal cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14134-e14134
Author(s):  
John Ploeen ◽  
Jan Lindebjerg ◽  
Jens Christian Riis Joergensen ◽  
Anders Kristian Moeller Jakobsen
Keyword(s):  
Rectal Cancer ◽  
Clinical Examination ◽  
Anal Verge ◽  
Locally Advanced ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Clinical Value ◽  
Cancer Specific Survival ◽  
End Of Treatment

e14134 Background: Preoperative chemoradiation is standard treatment of locally advanced rectal cancer, and there is an obvious need for new methods of assessing the effect. Evaluation by clinical examination with endoscopy is controversial. In most papers the assessment of effect has been performed after the end of treatment. The aim of the present study was to investigate the clinical value of an examination during chemoradiation. Methods: The study included 128 patients with histopathologically verified rectal cancer. Further inclusion criteria were a T3 tumor with a circumferential margin ≤ 5 mm by MRI or a T4 tumor, a distance of < 10 cm from the anal verge and localized diseased only by abdominal and chest CT scan. The treatment was 50.4 Gy/28 fractions or the same treatment with the addition of endorectal brachytherapy 10 Gy/2 fractions in a randomized trial. The concomitant chemotherapy was UFT 300 mg/m2 and L-leucovorin 22.5 mg daily. Both drugs were given five days a week. Clinical examination with endoscopy was performed week 4 during treatment. The clinical effect was classified into complete response (CR) or not complete response with clinical residual tumor (NCR). The patients were operated eight weeks after end of treatment and the pathological tumor response was classified according to Mandard (TRG). Results: CR was found in 14% of the patients. Comparison with TRG showed that 82% with CR had TRG1 as compared to the NCR group where only 9% had TRG1 (p<10-4). The risk of lymph node metastasis was also different with 94% pN0 in the group with CR compared to 57% in the NCR group (p=0.02). The rate of CR translated to a major difference in the risk of recurrence (local and distant). No patients with CR experienced recurrence as compared to 19% in the NCR group (p<0.05). The CR also correlated with cancer specific survival. None of the patients with CR died from rectal cancer with a median observation time of 36 months compared to 30% in the NCR group. Conclusions: CR is a major prognostic parameter in locally advanced rectal cancer treated with chemoradiation. Early CR should be considered in the selection of patients for Watchful Waiting.

Predicting the pathologic complete regression with hematologic markers during neoadjuvant chemoradiotherapy in the locally advanced rectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 583-583
Author(s):  
Jae-Sung Kim ◽  
Joo Ho Lee ◽  
Changhoon Song
Keyword(s):  
Rectal Cancer ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
P Value ◽  
Complete Regression ◽  
Operating Characteristics ◽  
Predictive Values

583 Background: The present study aimed to evaluate the hematologic markers for predicting the pathologic complete regression during and after neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. Methods: Total 297 patients with rectal cancer underwent neoadjuvant CRT followed by surgical resection and performed complete blood counts (CBC) serially during and after CRT. The timepoints of CBC were before CRT (pre-), three weeks after the day of starting CRT (intra-), and four weeks after CRT (post-). We calculated the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte (NLR), derived neutrophil-to-lymphocyte (dNLR) using the serial CBC test. The ratio of change in PLR (cPLR), NLR (cNLR), and dNLR (cdNLR) was calculated as the change of value/pre-value. Chi-square and T-test for univariate analysis and multivariate logistic regression were performed to identify the significant predictor for pCR. Receiver operating characteristics (ROC) analysis was used to compare the predictive values. Results: The overall rate of pCR was 15.9%. The Pre-Hb, pre-NLR, intra-PLR, intra-NLR, intra-cPLR, intra-cNLR, post-WBC, post-Hb, and post-cPLR were significantly different between patients with pCR and no pCR. In the multivariate logstic regression, pre-Hb (OR 1.456 p-value .026), intra-cPLR (OR 4.949, p-value < .001), post-WBC (OR 0.664, p-value .008), and post-PLR (OR 1.011 p-value .001) were significant predictors for pCR. In the comparison of ROCs, intra-cPLR was the most accurate predictor for pCR among the hematologic variables (AUC = 0.74, p ≤ .001). Conclusions: Change of PLR during neoadjuvant CRT is the clinically applicable and significant predictor for pCR with high negative predictive value in the patients with LRC.

scholarly journals Prognostic significance of tumor regression in locally advanced rectal cancer after preoperative radiochemotherapy

2017 ◽  
Vol 52 (1) ◽  
pp. 30-35 ◽  
Author(s):  
Mirko Omejc ◽  
Maja Potisek
Keyword(s):  
Rectal Cancer ◽  
Multivariate Analysis ◽  
Tumor Regression ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Preoperative Radiochemotherapy ◽  
Term Survival

AbstractBackgroundThe majority of rectal cancers are discovered in locally advanced forms (UICC stage II, III). Treatment consists of preoperative radiochemotherapy, followed by surgery 6–8 weeks later and finally by postoperative chemotherapy. The aim of this study was to find out if tumor regression affected long-term survival in patients with localy advanced rectal cancer, treated with neoadjuvant radiochemotherapy.Patients and methodsPatients with rectal cancer stage II or III, treated between 2006 and 2010, were included in a retrospective study. Clinical and pathohistologic data were acquired from computer databases and information about survival from Cancer Registry. Survival was estimated according to Kaplan-Meier method. Significance of prognostic factors was evaluated in univariate analysis; comparison was carried out with log-rank test. The multivariate analysis was performed according to the Cox regression model; statistically significant variables from univariate analysis were included.ResultsTwo hundred and two patients met inclusion criteria. Median follow-up was 53.2 months. Stage ypT0N0 (pathologic complete response, pCR) was observed in 14.8% of patients. Pathohistologic stage had statistically significant impact on survival (p = 0.001). 5-year survival in patients with pCR was>90%. Postoperative T and N status were also found to be statistically significant (p = 0.011 for ypT and p < 0.001 for ypN). According to multivariate analysis, tumor response to neoadjuvant therapy was the only independent prognostic factor (p = 0.003).ConclusionsPathologic response of tumor to preoperative radiochemotherapy is an important prognostic factor for prediction of long-term survival of patients with locally advanced rectal cancer.

scholarly journals The Heterogeneity of Skewness in T2W-Based Radiomics Predicts the Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 795
Author(s):  
Francesca Coppola ◽  
Margherita Mottola ◽  
Silvia Lo Monaco ◽  
Arrigo Cattabriga ◽  
Maria Adriana Cocozza ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Youden Index ◽  
Tumour Regression ◽  
P Value ◽  
Tumour Regression Grade

Our study aimed to investigate whether radiomics on MRI sequences can differentiate responder (R) and non-responder (NR) patients based on the tumour regression grade (TRG) assigned after surgical resection in locally advanced rectal cancer (LARC) treated with neoadjuvant chemoradiotherapy (nCRT). Eighty-five patients undergoing primary staging with MRI were retrospectively evaluated, and 40 patients were finally selected. The ROIs were manually outlined in the tumour site on T2w sequences in the oblique-axial plane. Based on the TRG, patients were grouped as having either a complete or a partial response (TRG = (0,1), n = 15). NR patients had a minimal or poor nCRT response (TRG = (2,3), n = 25). Eighty-four local first-order radiomic features (RFs) were extracted from tumour ROIs. Only single RFs were investigated. Each feature was selected using univariate analysis guided by a one-tailed Wilcoxon rank-sum. ROC curve analysis was performed, using AUC computation and the Youden index (YI) for sensitivity and specificity. The RF measuring the heterogeneity of local skewness of T2w values from tumour ROIs differentiated Rs and NRs with a p-value ≈ 10−5; AUC = 0.90 (95%CI, 0.73–0.96); and YI = 0.68, corresponding to 80% sensitivity and 88% specificity. In conclusion, higher heterogeneity in skewness maps of the baseline tumour correlated with a greater benefit from nCRT.

Neoadjuvant treatment in a Mexican cohort of patients with locally advanced rectal cancer: Oncologic outcomes and prognostic factors.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 704-704
Author(s):  
ZULEYMA NIETO GARCIA ◽  
Edgar Omar Martos Armendáriz ◽  
Vanessa Rosas Camargo ◽  
Christian Haydeé Flores Balcázar ◽  
Mónica Isabel Meneses Medina ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Prognostic Factors ◽  
Survival Rate ◽  
Neoadjuvant Therapy ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Oncologic Outcomes ◽  
Nodal Disease

704 Background: Preoperative chemoradiotherapy (CRT) followed by total mesorectal excision (TME) and adjuvant chemotherapy (CT) is the standard of care for locally advanced rectal cancer (LARC). Total neoadjuvant therapy (TNT) consists of induction CT followed by CRT prior to surgery. This is an alternative strategy recommended in guidelines. Objective: To describe neoadjuvant strategies, oncologic outcomes and prognostic factors in a cohort of patients (pts) with LARC treated at a referral center in Mexico City. Methods: We retrospectively reviewed medical records from pts with LARC (T3-T4 or N+) treated with any neoadjuvant strategy at Instituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán” from January 2010 to December 2015. Clinical and pathological information was registered. Survival was estimated by Kaplan-Meier method. Univariate analysis for prognostic factors was performed and survival was compared by the log rank test. Results: 43 pts were included. Median age was 62 y/o (19-83), 51% were female. Clinical stage (CS) II 9% and CS III 91%. 36 pts were T3-4 and N+(86%). Localization was lower third 30%, middle third 56% and upper third 12%. 63% were moderately differentiated adenocarcinoma. 84% had TNT: induction CT with FOLFOX-4 regimen for 3 months followed by CRT (50.4 Gy in 28 fractions concurrently with fluoropyrimidines) and TME. Surgery: ultra-low anterior resection (AR) 48%, low AR 28% and abdominoperineal resection 24%. One patient did not accept surgery. Of the 32 pts with ultra-low and low AR, 94% had protective ileostomy. The pathologic complete response (pCR) ypT0ypN0 rate was 45% (19/42). Median follow-up was 48 months. There were 8/42 recurrences (19%): local-only 2.3%, systemic only 12% and both 5%. None of the pts with pCR recurred. All pts with residual nodal disease recurred (5/5). The 5-year relapse-free survival rate was 73%. There were 6 deaths, one patient died without disease. The 5-year overall survival rate was 83%. Conclusions: In pts with LARC the TNT is associated with high rates of pCR and favorable oncological outcomes. pCR and residual nodal disease after neoadjuvant therapy were strongly associated with recurrence and survival.

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