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.

Intensification of neoadjuvant therapy in patients with locally advanced rectal cancer

2021 ◽  
Vol 11 (2) ◽  
pp. 19-28
Author(s):  
Z. Z. Mamedli ◽  
A. V. Polynovskiy ◽  
D. V. Kuzmichev ◽  
S. I. Tkachev ◽  
A. A. Aniskin
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Control Group ◽  
Free Survival ◽  
Disease Free

The aim of the study: to increase the frequency of achieving pathologic complete response and increase disease-free survival in the investigational group of patients with locally advanced rectal cancer T3(MRF+)–4N0–2M0 by developing a new strategy for neoadjuvant therapy.Materials and methods. In total, 414 patients were assigned to treatment. Control group I included 89 patients who underwent radiotherapy (RT) 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week. Control group II included 160 patients who underwent RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and oxaliplatin once a week, during the course of RT. Study group III consisted of 165 patients. This group combined RT 52–56 Gy/26–28 fractions with concurrent capecitabine twice daily 5 days per week and additional consecutive CapOx cycles. This group was divided into 2 subgroups: subgroup IIIa included 106 patients with consolidating chemotherapy (after CRT); subgroup IIIb included 59 patients who underwent “sandwich” treatment. Therapy consisted of conducting from 1 to 2 cycles of induction CapOx (up to CRT) and from 1 to 2 cycles of consolidating CapOx with an interval of 7 days. In the interval between the courses of drug therapy, RT 52–56 Gy/26–28 fractions was performed. According to the results of the control examination, further treatment tactics were determined. The primary end points were 5-year disease-free survival and the achievement of a pathologic complete response.Results. Pathologic complete response was significantly more often recorded in patients in the investigational group III (17.48 %; p = 0.021) compared with control groups (7.95 % in the I group and 8.28 % in the II group). 5-year disease-free survival in patients in the study groups was: 71.5 % in the III group, 65.6 % in the II group and 56.9 % in the I group.Conclusion. The shift in emphasis on strengthening the neoadjuvant effect on the tumor and improving approaches to drug therapy regimens have significantly improved disease-free survival of patients with locally advanced rectal cancer.

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.

Pelvic side wall nodes in locally advanced rectal cancer as a prognostic indicator.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 613-613
Author(s):  
Kirsten Elizabeth Jean Laws ◽  
Christina Wilson ◽  
Stephen Harrow
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Locally Advanced ◽  
Side Wall ◽  
Distant Metastases ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Pre Treatment ◽  
Long Course ◽  
Patterns Of Recurrence

613 Background: Neoadjuvant long course chemoradiotherapy is a well recognised treatment in locally advanced rectal cancer. Patients with pelvic side wall nodes are often considered for neoadjuvant treatment. We investigated whether pelvic side wall nodes identified on pre-treatment imaging is a poor prognostic factor and whether there are different patterns of recurrence compared to patients without pelvic side wall node involvement. Methods: All patients treated with long course chemoradiotherapy between January 2008 and December 2009 were identified. Patients were excluded if treatment indication was for inoperable disease, postoperative, recurrence, or palliative intent. 231 patients were identified and a retrospective analysis performed investigating patterns of recurrence and survival for patients with pelvic side wall nodes identified on pre-treatment imaging. Results: Kaplan Meier curves are presented showing patients with pelvic side wall nodes identified on pre-treatment imaging appear to have poorer outcomes and overall survival compared with those with only mesorectal nodes or no nodes. Patterns of recurrence are presented, showing patients with pelvic side wall nodes identified on pre-treatment imaging have a non significant trend to increased rates of disease recurrence (local and distal recurrence combined, 45.7% versus 27.9% for pelvic side wall nodes versus no pelvic side wall nodes). Patients with pelvic side wall nodes identified on pre-treatment imaging appear to be more likely to develop distant metastases compared to those patients who have mesorectal nodes or no nodal involvement (37% versus 23%). Conclusions: Our study highlights that patients with pelvic side wall nodes identified on pre-treatment imaging appear to have a trend to poorer overall survival, are more likely to recur and develop distant metastases. These results were not statistically significant, due to the small number of patients, and the data is consequently limited. We intend to further investigate current management strategies for this subgroup of patients, with assessment of radiotherapy treatment plans, current use of integral boosts, and surgical procedures for this subgroup of patients.

Association of perineural invasion with outcomes after neodjuvant chemoradiation for locally advanced rectal adenocarcinoma.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 750-750
Author(s):  
Priyanka Vinod Chablani ◽  
Phuong Nguyen ◽  
Charles Andrew Robinson ◽  
Xueliang Jeff Pan ◽  
Steve Andrew Walston ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Perineural Invasion ◽  
Locally Advanced ◽  
Prognostic Significance ◽  
Rectal Adenocarcinoma ◽  
Residual Tumor ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Resected Specimen ◽  
Free Survival

750 Background: Perineural invasion (PNI) as a prognostic indicator has not been well studied in patients with rectal adenocarcinoma treated with neoadjuvant chemoradiation (nCRT). In this study, we investigated the incidence and prognostic significance of PNI in patients with stages II-III locally advanced rectal cancer treated with nCRT. Methods: We performed a retrospective study of 110 consecutive patients treated with nCRT for locally advanced rectal adenocarcinoma at a single institution from 2004 to 2011. 88 of these patients had residual tumor in the resected specimen after nCRT. We evaluated the association of PNI with clinical outcomes, including disease-free survival (DFS), distant-metastasis-free survival (DMFS), and overall survival (OS), using log-rank and Cox proportional hazard modeling. Results: Of the 88 patients with residual tumor at surgery, 14 patients (16%) had PNI and 74 patients (84%) did not. Baseline distribution of selected variables in the PNI+ and PNI- groups are shown in Table 1. Median follow-up was 27 months (range 0.9 to 84 months). The median DFS was 13.5 months for PNI+ patients and 39.8 months for PNI- patients (p<0.0001). The median DMFS was 13.5 months for PNI+ patients and median not reached (> 40 months) for PNI- patients (p<0.0001). We did not detect a significant association between the presence of PNI and worse OS, perhaps due to a high rate of censored patients in the OS analysis. In a multivariate model including pT stage, pN stage, tumor location, tumor size, type of surgery, and radial margin status, PNI remained a significant predictor of DFS (HR 16.8, 95% CI, 3.7–75.5, p<0.0002) and DMFS (HR 18.9, 95% CI, 4.4–81.9, p<0.0001). Conclusions: For patients with locally advanced rectal cancer treated with nCRT prior to surgical resection, PNI found at the time of surgery is significantly associated with worse DFS and DMFS. [Table: see text]

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 Systematic Review: Adjuvant Chemotherapy for Locally Advanced Rectal Cancer with respect to Stage of Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-10
Author(s):  
Shahab Hajibandeh ◽  
Shahin Hajibandeh
Keyword(s):  
Rectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Stage Ii ◽  
Stage Iii ◽  
Free Survival ◽  
Disease Free

Background. Recent meta-analysis of 21 randomised controlled trials (RCTs) supports the use of adjuvant chemotherapy for nonmetastatic rectal carcinoma. In order to define a subgroup of patients who can potentially benefit from postoperative adjuvant chemotherapy, this study aims to review trials investigating adjuvant chemotherapy with respect to stage of disease in patients with locally advanced rectal cancer who had undergone surgery for cure (stage II and stage III). Methods. We searched electronic information sources to identify randomised trials evaluating adjuvant chemotherapy in patients with stages II and III rectal cancer with overall survival or disease-free survival as outcomes. Scottish Intercollegiate Guidelines Network notes on methodology were used to assess the methodological quality of the selected studies. Random-effects models were applied to calculate pooled outcome data. Results. Eight studies reporting total of 5527 patients were selected for analysis. Adjuvant chemotherapy was associated with statistically significant improvement in disease-free survival and overall survival compared to surgery alone in both stage II and stage III cancer. Conclusions. This study indicates that both stage II and stage III rectal cancer patients may benefit from postoperative adjuvant chemotherapy. However, the benefits of adjuvant chemotherapy for patients who already had neoadjuvant chemoradiation still remain unknown.

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