Disease-free Survival In Rectal Cancer Research Articles

Expression profile and prognostic significance of HOXB13 in rectal cancer.

This study aimed to investigate the expression pattern and prognostic significance of HOXB13 in rectal cancer. HOXB13 expression in rectal cancer and normal adjacent tissues was detected by reverse transcriptase-polymerase chain reaction and immunohistochemistry, and its clinicopathological characteristics and prognosis were statistically tested. Furthermore, we evaluated the association between tumor immune infiltrating cells and HOXB13 using the tumor immune estimation resource (TIMER) database. The potential biological mechanism associated with HOXB13 overexpression was investigated by gene set enrichment analysis (GSEA). The expression of HOXB13 messenger RNA and protein in human rectal cancer tissues were significantly higher than those in the normal adjacent tissues (P < 0.05). HOXB13 expression was significantly correlated with depth of invasion, lymphatic invasion, lymph node metastasis, distant metastasis, and pathological tumor node metastasis stage (P < 0.05). Kaplan-Meier survival curves confirmed that HOXB13 overexpression was correlated negatively with overall survival and disease-free survival in rectal cancer (P < 0.05). Also, multivariate Cox regression analysis demonstrated that HOXB13 expression, age, and lymphatic invasion were independent prognostic factors in rectal cancer (P < 0.05). Plus, the results from the TIMER database indicated that HOXB13 expression has a significant association with several immune cell infiltrates. Finally, the GSEA results indicated that HOXB13 participated in the various immune-associated processes, including natural killer cell-mediated cytotoxicity and the T-cell receptor signaling pathway. Our study showed an essential role of HOXB13 in rectal cancer immunity and prognosis. Significantly, the overexpression of HOXB13 leads to the worse prognosis for patients with rectal cancer, which will contribute to understanding molecular mechanisms associated with tumor pathogenesis and prognosis in this disease.

“Rectal cancer survival: A retrospective analysis of MRI features and their association with prognosis”

PurposeTo assess rectal cancer aggressiveness using magnetic resonance (MR) imaging features and to investigate their relationship with patient prognosis. Materials and methodsClinical information and Pelvic MR scans of 106 consecutive patients with primary rectal cancer (RC) were analyzed. Clinical symptoms, age, sex, tumor location, and patient´s survival were recorded. The variables investigated by MR were: depth or mural/extramural tumor involvement, distance to mesorectal margin, lymph node involvement, vascular, peritoneal or sphincter complex infiltration. The association between imaging features and disease-free survival (DFS) was also assessed using a Kaplan-Meier model. Differences between survival curves were tested for significance using the Mantel-Cox LogRank test. ResultsThe final study population was 106 patients (65 males, 41 females). The median age was 69.5 years (range, 39-92 years). No significant differences were found between death risk and sex, age or tumor location (p>0,05). However, the relative risk (RR) of tumor mortality increased significantly with the presence of the variables: vascular infiltration (×5), T4 tumors (× 4.57), N2 lymph node involvement (more than 3 affected nodes × 4.11) and mesorectal fascia involvement (× 3,77). ConclusionTumor extension, number of pathological lymph nodes, mesorectal fascia involvement and vascular infiltration values obtained on initial MR imaging staging showed a significant difference for disease-free survival in RC at six years of control.

An up-to-date predictive model for rectal cancer survivorship reflecting tumor biology and clinical factors

IntroductionOur aim was to develop a nomogram taking into account factors such as tumor biology to predict overall and disease-free survival for patients with primary rectal adenocarcinoma undergoing curative intent surgical resection. MethodsPatients undergoing resection for primary rectal adenocarcinoma (2007–2017) were included. Factors reflecting tumor biology and important clinical prognosticators were included in nomogram development. Prognostic factors were assessed with multivariable analysis using Cox regression. The impact of each was assessed using Kaplan Meier survival curves. ResultsOverall, 1688 patients (male, 61%) with a mean age of 59.8 years (±13.5) and a median follow-up of 34.8 months (range, 12–132) were included. The only significant factors affecting the overall and disease-free survival were age at diagnosis, pathological staging, regression grade, resection margin, and tumor deposits. ConclusionThe current model incorporates histopathological and clinical factors. It emphasizes the importance of tumor biological factors like tumor deposits in predicting overall and disease-free survival in rectal cancer. SummaryRectal cancer outcomes are associated with certain clinical and pathological factors that can be evaluated. Tumor deposits are one such factor that can affect overall and disease-free survival.

Neoadjuvant rectal score as individual-level surrogate for disease-free survival in rectal cancer in the CAO/ARO/AIO-04 randomized phase III trial

BackgroundSurrogate end points in rectal cancer after preoperative chemoradiation are lacking as their statistical validation poses major challenges, including confirmation based on large phase III trials. We examined the prognostic role and individual-level surrogacy of neoadjuvant rectal (NAR) score that incorporates weighted cT, ypT and ypN categories for disease-free survival (DFS) in 1191 patients with rectal carcinoma treated within the CAO/ARO/AIO-04 phase III trial. Patients and methodsCox regression models adjusted for treatment arm, resection status, and NAR score were used in multivariable analysis. The four Prentice criteria (PC1–4) were used to assess individual-level surrogacy of NAR for DFS. ResultsAfter a median follow-up of 50months, the addition of oxaliplatin to fluorouracil-based chemoradiotherapy (CRT) significantly improved 3-year DFS [75.9% (95% confidence interval [CI] 72.30% to 79.50%) versus 71.3% (95% CI 67.60% to 74.90%); P=0.034; PC 1) and resulted in a shift toward lower NAR groups (P=0.034, PC 2) compared with fluorouracil-only CRT. The 3-year DFS was 91.7% (95% CI 88.2% to 95.2%), 81.8% (95% CI 78.4% to 85.1%), and 58.1% (95% CI 52.4% to 63.9%) for low, intermediate, and high NAR score, respectively (P<0.001; PC 3). NAR score remained an independent prognostic factor for DFS [low versus high NAR: hazard ratio (HR) 4.670; 95% CI 3.106–7.020; P<0.001; low versus intermediate NAR: HR 1.971; 95% CI 1.303–2.98; P=0.001] in multivariable analysis. Notwithstanding the inherent methodological difficulty in interpretation of PC 4 to establish surrogacy, the treatment effect on DFS was captured by NAR, supporting satisfaction of individual-level PC 4. ConclusionOur study validates the prognostic role and individual-level surrogacy of NAR score for DFS within a large randomized phase III trial. NAR score could help oncologists to speed up response-adapted therapeutic decision, and further large phase III trial data sets should aim to confirm trial-level surrogacy.

Prognostic Value of Diffusion MR Imaging and Clinical-Pathologic Factors in Patients with Rectal Cancer

Background: Apparent diffusion coefficient (ADC) value measured from diffusion-weighted magnetic resonance (MR) images are highly correlated with pathological T or N stage, tumor differentiation grade, and extramural depth of tumor in patients with rectal cancer. Objectives: To assess the prognostic value of diffusion MR imaging and clinical-pathologic risk factors in patients with rectal cancer. Patients and Methods: This retrospective study was approved by our institutional review board and written informed consent was waived. Sixty-one consecutive patients with rectal cancer (41 men and 20 women; mean age, 64.5 ± 12.1 years; range, 32 - 86 years) underwent pelvic MR imaging. Tumor ADC value and clinical-pathologic risk factors were tested as possible risk factors for postoperative local recurrence or distant metastasis (LRDM) as well as disease-free survival outcome. Results: Of 62 tumors, 12 (19.4%) had postoperative LRDM (median follow-up 38.5 months). Plasmatic CA19-9 level (P = 0.0027), pathological N stage (P = 0.0018), lymphatic invasion (P < 0.0001), and tumor ADC value (P = 0.0076) were independently associated with postoperative LDRM. High plasmatic CA19-9 level (≥ 37 U/mL) (P = 0.010), ly2 (P = 0.020), ly3 (P < 0.0001), pathological N2 (P = 0.006), and low tumor ADC value (< 0.996 × 10-3 mm2/sec) (P = 0.0026) were associated with reduced disease-free survival. Conclusion: Preoperative tumor ADC and plasmatic CA19-9 were significantly associated with postoperative LRDM and disease-free survival in rectal cancer.

GLUT-1 overexpression as an unfavorable prognostic biomarker in patients with colorectal cancer.

BackgroundGlucose transporter-1 (GLUT-1) exhibits altered expression in colorectal cancer (CRC). The aim of this study was to explore the association between GLUT-1 and survival conditions, as well as clinical features in CRC by meta-analysis.Materials and MethodsRelevant studies were searched through predefined strategies, hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs) were used as effective measures.ResultsA total of 14 studies with 2,077 patients were included in this meta-analysis. The results showed that GLUT-1 was not significantly associated with overall survival (OS) (HR=1.28, 95% CI=0.86–1.91, p=0.22) or disease-free survival (DFS) (HR=1.71, 95% CI=0.78–3.72, p=0.179). However, subgroup analysis indicated that GLUT-1 was a significant biomarker for poor DFS in rectal cancer (HR=2.47, 95% CI=1.21–5.05, p=0.013). GLUT-1 expression was also found to be significantly correlated with the presence of lymph node metastasis (n=8, OR=2.14, 95% CI=1.66–2.75, p<0.001), T stage (n=6, OR=1.73, 95% CI=1.17–2.58, p=0.007), higher Dukes stage (n=5, OR=2.92, 95% CI=2.16–3.95, p<0.001), female sex (n=4, OR=2.92, 95% CI=2.16–3.95, p<0.001), and presence of liver metastasis (n=3, OR=1.82, 95% CI=1.06–3.12, p=0.03).ConclusionIn conclusion, this meta-analysis showed that GLUT-1 was associated with poor DFS in rectal cancer (RC). Furthermore, GLUT-1 was also an indicator of aggressive clinical features in CRC.

Prognostic value of tumor shrinkage versus fragmentation following radiochemotherapy and surgery for rectal cancer.

Most patients with rectal cancer receive neoadjuvant radiochemotherapy (RCT), causing a variable decrease in tumor mass. We evaluated the prognostic impact of pathologic parameters reflecting tumor response to RCT, either directly or indirectly. Seventy-six rectal cancer patients receiving neoadjuvant RCT between 2006 and 2009 were included. We studied the association between disease-free survival (DFS) and the "classical" clinicopathologic features as well as tumor deposits, circumferential resection margin (CRM), Dworak regression grade, and tumor and nodal downstaging. Patients with tumor downstaging had a longer DFS (p = 0.05), indicating a more favorable prognosis when regression was accompanied by a decrease in tumor infiltrative depth, referred to as tumor shrinkage. Moreover, tumor downstaging was significantly associated with larger CRM and nodal downstaging (p = 0.02), suggesting that shrinkage of the primary tumor was associated with a decreased nodal tumor load. Higher Dworak grade did not correlate with tumor downstaging, nor with higher CRM or prolonged DFS. This implies that tumor mass decrease was sometimes due to fragmentation rather than shrinkage of the primary tumor. Lastly, the presence of tumor deposits was clearly associated with reduced DFS (p = 0.01). Assessment of tumor shrinkage after RCT via tumor downstaging and CRM is a good way of predicting DFS in rectal cancer, and shrinkage of the primary tumor is associated with a decreased nodal tumor load. Assessing regression based on the amount of tumor in relation to stromal fibrosis does not accurately discern tumor fragmentation from tumor shrinkage, which is most likely the reason why Dworak grade had less prognostic relevance.

Prognostic Significance of Partial Tumor Regression After Preoperative Chemoradiotherapy for Rectal Cancer

Complete tumor regression after preoperative chemoradiotherapy for rectal cancer has been associated with better disease-free and overall survival. The survival experience for patients with partial tumor regression is less clear. The aim of this meta-analysis was to evaluate the prognostic significance of partial response after preoperative chemotherapy on disease-free survival in rectal cancer patients. Relevant studies were identified by a search of MEDLINE and EMBASE databases with no restrictions to October 31, 2012. We included long-course radiotherapy that reported the association between degree of tumor regression and disease-free survival of rectal cancer. Direct, indirect, and graph methods were used to extract HRs. Study-specific HRs on the disease-free survival were pooled using a random-effects model. Eleven articles in total were selected. Analysis was performed first among the 6 studies that separated partial response from the complete response and later among all 11 of the studies. Pooled HR was 0.49 (95% CI, 0.28-0.85) for the 6 studies that compared partial response with poor response. It was 0.41 (95% CI, 0.25-0.67) when all 11 of the studies were analyzed together. The studies were limited by not being prospective, randomized trials, and the tumor regression grades were not uniform. Partial tumor response is associated with a 50% improvement in disease-free survival and should be considered as a favorable prognostic factor.

W1655 Pathologic Nodal Status is an Independent Predictor of Disease-Free Survival in Rectal Cancer Treated by Neoadjuvant Chemoradiation

W1655 Pathologic Nodal Status is an Independent Predictor of Disease-Free Survival in Rectal Cancer Treated by Neoadjuvant Chemoradiation

Predictors of disease‐free survival in rectal cancer patients undergoing curative proctectomy

To identify the factors that affect the disease-free survival (DFS) of rectal cancer patients. Patients from an IRB approved rectal cancer database were reviewed (1990-2000). All patients underwent either abdominoperineal resection or low anterior resection using total mesorectal excision with curative intent. Univariate and multivariate analyses were performed to analyse the factors that influenced DFS. A total of 304 patients were reviewed (mean age 64, 52% male). Seventy-seven per cent of patients received neoadjuvant therapy (28.6% short-course radiation therapy (RT), 35.5% long-course RT, 12.5% chemo-RT). The radial margin was involved with tumour in 5.2% of patients (final pathology). The overall survival rate was 85.2% with a mean follow-up time of 33 +/- 26 months. The mean time to death was 34.8 +/- 26.8 months. Local recurrence (+/- distant recurrence) occurred in 4%. Anastomotic leaks occurred in 3.6% of patients. Overall pathologic stage, pathologic T stage, nodal status, the use of adjuvant chemotherapy, tumour fixation, involvement of the radial margin, the presence of mucin, and lymphatic and perineural invasion (PNI) were predictors of DFS by univariate analysis. Of note, anastomotic leaks and obstructing cancers did not influence DFS. Using multivariate analysis with backward elimination, overall pathologic stage, radial margin status, adjuvant chemotherapy, and PNI predicted the DFS. Major predictors of DFS in rectal cancer are the overall pathologic stage, adjuvant chemotherapy, radial margin status and PNI. Radial margin status may be a marker of tumour aggressiveness and should be considered in deciding on adjuvant chemotherapy.