Tumor Karyotype Predicts Clinical Outcome in Colorectal Cancer Patients

2004 ◽  
Vol 22 (13) ◽  
pp. 2623-2634 ◽  
Author(s):  
Georgia Bardi ◽  
Claus Fenger ◽  
Bertil Johansson ◽  
Felix Mitelman ◽  
Sverre Heim

Purpose To investigate the prognostic value of the overall karyotypic features and specific chromosome aberrations in colorectal cancer (CRC). Patients and Methods Cytogenetic features of 150 primary CRCs investigated at the time of surgery were correlated with patient survival by univariate and multivariate analyses, using classical clinicopathologic parameters as covariates. Results In univariate analysis, in addition to tumor grade and clinical stage, structural aberrations as well as rearrangements of chromosomes 8 and 16 were significantly correlated with shorter overall survival. Karyotypic complexity, rearrangements of chromosomes 8 and 16, and loss of chromosome 4 were significantly correlated with shorter disease-free survival. In multivariate analysis, in addition to tumor grade, the type of chromosome aberrations (structural or numerical), ploidy, and loss of chromosome 18 came across as independent prognostic factors in the group of all patients. In the subset of patients with stage I and II carcinomas, none of the clinicopathologic variables could independently predict patient survival, whereas the presence of structural chromosomal aberrations was the only independent predictor of poor prognosis. In the subset of patients with stage III carcinomas, the presence of structural changes of chromosome 8 was a stronger independent predictor of prognosis than was tumor grade. Conclusion Cytogenetic tumor features are valuable predictors of prognosis in CRC patients. The tumor karyotype should therefore be taken into account in the clinical management of patients with this disease, especially for patients having cancers of the early or intermediate stages I, II, and III.

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21097-21097
Author(s):  
L. Zhou ◽  
W. Yin ◽  
J. Lu ◽  
D. Shi ◽  
G. Liu ◽  
...  

21097 Background: Although breast caner patients with any one of the two sex hormone receptors positive can be treated with endocrine therapy, many clinical data showed that there was different response to endocrine therapy for patients with ER+/PR+ and with ER+/PR- tumors. The aim of this study was to find out the factors related to PR expression by comparing the ER+/PR+ tumors and ER+/PR- tumors clinically and biologically. Methods: Between January 1990 to August 2006, 5,191 female breast cancer patients with known ER/PR expression status who received operation in our hospital were enrolled onto this retrospective study. Clinical and biological features of 2,227 patients with ER+/PR+ tumors were compared with those of 909 patients with ER+/PR- tumors. χ2 test was used for univariate analysis and logistic regression for multivariate analysis. Disease-free survival (DFS) and overall survival (OS) was calculated using Kaplan-Meier analyses, and all statistical tests were two-sided. Results: The peak onset age of patients with ER+/PR+ tumors and ER+/PR- tumors was 50, and it was significantly higher than that of patients with ER- tumors, which is 48(P=0.001). Univariate analysis showed that ER+/PR- tumors were larger in size, had more lymph nodes of metastasis, were higher in tumor grade than ER+/PR+ tumors. Furthermore, the expression of ER and CathepsinD was significantly lower, and CerbB-2 expression was higher in ER+/PR- tumors than in ER+/PR+ tumors. Multivariate analysis indicated that positive PR expression was associated with the level of ER(OR=1.792, P=0.000), CathepsinD(OR=1.380, P=0.035)and CerbB-2(OR=0.639, P=0.007). DFS(P=0.004) and OS(P=0.009) were higher among patients with PR-expressing tumors than with PR- negative tumors. Conclusions: ER+/PR+ tumors and ER+/PR- tumors may have the same etiology which is different from that of ER- tumors. Because of low ER level and changes of the expression of CerbB-2 and CathepsinD, the tumors that lacked PR expression display more aggressive features and have worse prognosis. According to these differences, new target of therapy and endocrine regimen may provide the possibility of improving the response and prognosis of endocrine therapy for patients with ER+/PR- tumors. No significant financial relationships to disclose.


2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 355-355 ◽  
Author(s):  
Christopher Michael Tully ◽  
Bernard H. Bochner ◽  
Guido Dalbagni ◽  
Emily C. Zabor ◽  
Harry W. Herr ◽  
...  

355 Background: NAC and RC-PLND improves survival in MIBC and GC is a standard NAC option. However, little is known about GC efficacy endpoints and the individual contribution of NAC and surgery. Methods: Pts with clinical T2-T4aN0M0 MIBC treated from 1/2000 to 10/2012 with a planned 4 cycles of GC plus RC-PLND within 90 days (D) of NAC were evaluated retrospectively for the number (#) of cycles, dose delivered, D from end of NAC to RC-PLND, margin status, LN status and # of LN identified. Post-NAC pathologic endpoints included complete response (pT0), residual Non-MIBC disease (pTa/Tis/T1;N0) and ≥MIBC disease (≥pT2N0). Associations with overall survival (OS) and disease-free survival were analyzed using Cox regression; non-linear associations with # of resected LN used linear and quadratic terms. Results: 154 pts met inclusion criteria. 5-year (yr) OS was 61% (95% CI 53-71%). Post-NAC pT0 was achieved in 21% (32/154) and Non-MIBC in 25% (39/154 - pTa (2), pTis (25), pT1 (12)). Post-NAC pT0 and Non-MIBC had similar 5-yr OS (85% and 89%, respectively) and combined (<pT2) pts differed significantly from pts with ≥pT2, (87% (95% CI 78, 98%) and 38% (95% CI 27, 53%), respectively; p<0.001). Median D from NAC to RC-PLND was 34 and median # of resected LN was 19. On univariate analysis, # of cycles (4 vs <4), GC dose intensity and total dose, clinical stage (cT2 vs cT3/cT4), # of resected LN, positive (+) LN and + margins were significant for OS. In multivariate analysis, post-NAC pathology ≥pT2 (HR 6.7; 95% CI 2.6-17.4; p<0.001), + LN (HR 3.21; 95% CI 1.6-6.4; p=0.001) and + margins (HR 3.2; 95% CI 1.4-7.5; p=0.007) were significant for increased risk of death. Using a model with these 3 predictors to estimate the benefit of PLND, the hazard ratio decreased with each LN resected until 25 and then plateaued beyond 25 (p=0.016). Conclusions: NAC with GC has excellent drug delivery, permits rapid RC-PLND and achieves meaningful pathologic responses. Survival is similar with <pT2N0 and pT0N0 post NAC pathology. Pts with post NAC ≥pT2, + margins, and + LN do poorly. Increasing LN yield on PLND contributes to OS.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15078-e15078
Author(s):  
Mathias Holsey Gramkow ◽  
Reetta Peltonen ◽  
Christian Dehlendorff ◽  
Pia J. Osterlund ◽  
Julia S. Johansen ◽  
...  

e15078 Background: IL-6 and YKL-40, markers of inflammation and cancer growth, are high in serum in patients with colorectal cancer (CRC) and associated with shorter overall survival (OS). We hypothesized that preoperative serum IL-6, YKL-40 and CEA are associated with disease free survival (DFS) and OS in patients with metastatic (mCRC) treated with liver resection. Methods: 457 patients (male/female: 267 (58%)/190 (42%), median age 65 [IQR: 58-71]) diagnosed with mCRC who underwent liver resection were included between March 1998 and February 2013. Preoperative serum samples were collected and stored at -80°C until analysis. Serum IL-6 (R&D Systems, UK) and YKL-40 (Quidel, USA) were determined by ELISA. For DFS and OS we estimated crude and adjusted hazard ratios (HR) and corresponding 95% confidence intervals (CIs) with Cox regression for each biomarker separately. The biomarkers were included as log2-transformed continuous variables and adjustment included mutual adjustment between the biomarkers in addition to adjusting for sex and age. Results: The median (IQR) preoperative biomarker levels were: IL-6 (3.5 pg/ml, 2.1-6.1), YKL-40 (75 ng/ml, 48-127) and CEA (5.2 kU/L, 2.6-18.8). Univariate analysis showed that high serum IL-6 and YKL-40 were associated with shorter DFS (IL-6: HR = 1.18, 1.06-1.31, p < 0.01; YKL-40: HR = 1.19, 1.08-1.32, p < 0.01). Serum CEA was not (p = 0.80). Multivariate analysis (all biomarkers) showed that high IL-6 was associated with shorter DFS (HR = 1.15, 1.02-1.29, p = 0.02), whereas YKL-40 (p = 0.08) and CEA (p = 0.51) were not. Univariate analysis showed that high preoperative serum IL-6 and YKL-40 were associated with shorter OS (IL-6: HR = 1.16, 1.03-1.29, p = 0.01; YKL-40: HR = 1.27, 1.14-1.42, p < 0.01). Serum CEA was not associated with OS (p = 0.16). Multivariate analysis (all biomarkers) showed that high YKL-40 was associated with shorter OS (HR = 1.19, 1.05-1.34, p = 0.01), whereas IL-6 (p = 0.25) and CEA (p = 0.26) were not. Patients with elevated serum levels of all 3 biomarkers had the shortest OS (HR = 2.12; 1.29-3.50, p < 0.01). Conclusions: Serum IL-6 and YKL-40 determined before liver resection may be valuable prognostic biomarkers in patients with metastatic CRC.


2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e17130-e17130 ◽  
Author(s):  
Rüdiger Klapdor ◽  
Peter Hillemanns ◽  
Linn Lena Woelber ◽  
Julia Kathrin Jueckstock ◽  
Felix Hilpert ◽  
...  

e17130 Background: Obesity is associated with worse patients’ survival in several cancer entities. Vulvar cancer as well as obesity show increasing incidence over the last years. The influence of obesity on prognosis of vulvar cancer patients is not clear. However, knowledge about this may have consequences on prevention, treatment, and follow-up. Methods: This is an analysis of the large AGO-CaRE-1 study. Patients suffering from squamous cell vulvar cancer (UICC stage IB and higher), treated in 29 cancer centers between 1998 and 2008, were categorized in a database, in order to analyze treatment patterns and prognostic factors in a retrospective setting. Results: In total, 849 patients with documented height and weight were divided into two groups depending on their body mass index (BMI, < 30 vs. ≥30 kg/m²). There was no difference in the baseline variables (age, tumor diameter, depth of infiltration, tumor stage, nodal invasion, tumor grade) between both groups (p > 0.05). However, we identified differences regarding ECOG status and preexistent comorbidities (cardiovascular, dementia) towards healthier patients with BMI < 30 kg/m². Treatment variables (R0 resection, chemotherapy, radiotherapy, continuation of adjuvant therapy) did not differ (p > 0.05). Patients with BMI ≥30 kg/m² underwent radical vulvectomy more often (61.1 % vs. 51.8%, p = 0.042). During follow-up, there was a higher recurrence rate in the group having a BMI ≥30 kg/m² (43.4%, vs. 28.3%, p < 0.01) due to an increased rate of local recurrences (33.3% vs. 18.5%, p < 0.01). The rate of groin and distant recurrences was similar between both groups (p > 0.05). Noteworthy, we observed a significantly shorter disease free survival (DSF) of the obese patients in univariate analysis (HR 1.362, 95%CI 1.093-1.696, p = 0.006). Even in multivariate Cox-regression analysis including age, ECOG, tumor stage, type of surgery, nodal invasion, tumor grade, and comorbidities patients with BMI ≥30 kg/m² had a significantly shorter DFS (HR 1.811, 95%CI 1.005-3.262, p = 0.048). Conclusions: In this first large study about the association between obesity and prognosis of vulvar cancer patients, we observed that a BMI ≥30kg/m² was associated with shorter DFS, mainly attributed to a higher risk for local recurrence.


2015 ◽  
Vol 100 (1) ◽  
pp. 77-86 ◽  
Author(s):  
John Hogan ◽  
Georges Samaha ◽  
John Burke ◽  
Kah Hoong Chang ◽  
Eoghan Condon ◽  
...  

Abstract Twenty percent of colon cancers present as an emergency. However, the association between emergency presentation and disease-free survival (DFS) remains uncertain. Consecutive patients who underwent elective (CC) and emergent (eCC) resection for colon cancer were included in the analysis. Survival outcomes were compared between the 2 groups in univariate/multivariate analyses. A total of 439 patients underwent colonic resection for colon cancer during the interval 2000−2010; 97 (22.1%) presented as an emergency. eCC tumors were more often located at the splenic flexure (P = 0.017) and descending colon (P = 0.004). The eCC group displayed features of more advanced disease with a higher proportion of T4 (P = 0.009), N2 tumors (P &lt; 0.01) and lymphovascular invasion (P&lt; 0.01). eCC was associated with adverse locoregional recurrence (P = 0.02) and adverse DFS (P &lt; 0.01 ) on univariate analysis. eCC remained an independent predictor of adverse locoregional recurrence (HR 1.86, 95% CI 1.50–3.30, P = 0.03) and DFS (HR 1.30, 95% CI 0.88–1.92, P = 0.05) on multivariate analysis. eCC was not associated with adverse overall survival and systemic recurrence. eCC is an independent predictor of adverse locoregional recurrence and DFS.


2020 ◽  
Author(s):  
Gordon Chun-Kau CHAN ◽  
Jack Kit-Chung NG ◽  
Kai-Ming CHOW ◽  
Bonnie CH Kwan ◽  
Vickie Wai-Ki KWONG ◽  
...  

Abstract Background Depression and frailty contribute to the adverse clinical outcome of peritoneal dialysis (PD) patients. However, the interaction between depression and frailty in PD patients remains uncertain. We determined the prevalence of depression and frailty in prevalent Chinese PD patients, dissected the internal relationship between depression and frailty, and determined their relative contribution to the adverse clinical outcome in PD patients. Methods In a prospective observational study, we recruited 267 prevalent PD patients. Depression was identified by Patient Health Questionnaire (PHQ-9). Frailty was identified by a validated Frailty Score. All cases were followed for one year. Outcome measures included number and duration of hospitalization, peritonitis rate, and all-cause mortality. Results Of the 267 patients, 197 patients (73.8%) were depressed, and 157 (58.8%) were frail. There was a substantial overlap between depression and frailty. Although depression and frailty were associated the number and duration of hospitalization by univariate analysis, the association became insignificant after adjusting for confounding factors by multivariate analysis. Both depression and frailty were associated with one-year mortality by univariate analysis. One-year patient survival was 95.9%, 86.5%, 82.4% and 71.0% for patients with nil, mild, moderate and severe frailty, respectively (p = 0.001). Frailty was an independent predictor of patient survival by multivariate analysis (adjusted hazard ratio 1.424, 95% confidence interval 1.011-2.005. p = 0.043), while the prognostic effect of depression disappears after adjusting for frailty score. Conclusion Depression and frailty were common among Chinese PD patients. Frailty, but not depression, was an independent predictor of one-year mortality.


2020 ◽  
Author(s):  
Gordon Chun-Kau CHAN ◽  
Jack Kit-Chung NG ◽  
Kai-Ming CHOW ◽  
Bonnie CH Kwan ◽  
Vickie Wai-Ki KWONG ◽  
...  

Abstract Background Depression and frailty contribute to the adverse clinical outcome of peritoneal dialysis (PD) patients. However, the interaction between depression and frailty in PD patients remains uncertain. We determined the prevalence of depression and frailty in prevalent Chinese PD patients, dissected the internal relationship between depression and frailty, and determined their relative contribution to the adverse clinical outcome in PD patients. Methods In a prospective observational study, we recruited 267 prevalent PD patients. Depression was identified by Patient Health Questionnaire (PHQ-9). Frailty was identified by a validated Frailty Score. All cases were followed for one year. Outcome measures included number and duration of hospitalization, peritonitis rate, and all-cause mortality. Results Of the 267 patients, 197 patients (73.8%) were depressed, and 157 (58.8%) were frail. There was a substantial overlap between depression and frailty. Although depression and frailty were associated the number and duration of hospitalization by univariate analysis, the association became insignificant after adjusting for confounding factors by multivariate analysis. Both depression and frailty were associated with one-year mortality by univariate analysis. One-year patient survival was 95.9%, 86.5%, 82.4% and 71.0% for patients with nil, mild, moderate and severe frailty, respectively (p = 0.001). Frailty was an independent predictor of patient survival by multivariate analysis (adjusted hazard ratio 1.424, 95% confidence interval 1.011-2.005. p = 0.043), while the prognostic effect of depression disappears after adjusting for frailty score. Conclusion Depression and frailty were common among Chinese PD patients. Frailty, but not depression, was an independent predictor of one-year mortality.


2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 321-321
Author(s):  
George Van Buren ◽  
Herbert Zeh ◽  
Alyssa M Krasinskas ◽  
William E. Gooding ◽  
Jennifer Steve ◽  
...  

321 Background: Microscopic tumor at the surgical margin is a predictor of recurrence and poor survival for pancreatic ductal adenocarcinoma (PDA). However, the impact of distance between the surgical margin and microscopic tumor on survival remains controversial. We hypothesized that margin distance (MD) would correlate with disease free survival (DFS) and overall survival (OS) in R0 resected PDA. Methods: Retrospective analysis of 191 resections for PDA. Margin distance was measured (0-1, 1-2, 2-4, 4-10, and > 10 mm) and categorized by location. Parameters including age, gender, BMI, TNM, AJCC stage, lymph node (LN) ratio, vascular and perineural invasion, vein resection, and adjuvant therapy were analyzed. Primary endpoints were DFS and disease specific OS. Univariate analysis was used to estimate factors associated with outcomes. The log rank test was applied to selected group comparisons. Results: 149 (78%) R0 outcomes were analyzed. 118 (79%) patients received adjuvant chemotherapy, 31 of whom also received XRT. Univariate analysis demonstrated reduced DFS (HR = 1.65, 95% CI = 1.13 – 2.48, p = .009) and OS (HR = 1.52 95% CI =.98 – 2.35, p = .059) among patients with margins ≤ 2mm compared to margins > 2mm. In addition LN status, LN ratio, tumor size, AJCC stage, vascular invasion, perineural invasion and adjuvant chemotherapy were found to influence OS on univariate analysis. Adjuvant XRT had no measurable effect on DFS or OS. Following adjustment for covariates in a multivariate model, margin distance >2mm did not correlate with DFS (HR = 1.14, 95%CI = .73 – 1.78, p = .57) or OS (HR = 1.13 95% CI = .69 – 1.85, p = .63), whereas adjuvant chemotherapy and presence of vascular invasion significantly affected OS (P=0.0006 and P=0.008 respectively). The retroperitoneal margin was the margin most commonly in close proximity to tumor (43% of Whipple), although there was no correlation between the closest margin and DFS (p=0.94) or OS (p=0.94). Conclusions: Margin distance is not an independent predictor of DFS or OS after R0 resection for PDA. Irrespective of margin distance, adjuvant chemotherapy, but not XRT, was associated with improved OS.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kajsa Björkman ◽  
Sirpa Jalkanen ◽  
Marko Salmi ◽  
Harri Mustonen ◽  
Tuomas Kaprio ◽  
...  

AbstractMortality in colorectal cancer (CRC) remains high, resulting in 860,000 deaths annually. Carcinoembryonic antigen is widely used in clinics for CRC patient follow-up, despite carrying a limited prognostic value. Thus, an obvious need exists for multivariate prognostic models. We analyzed 48 biomarkers using a multiplex immunoassay panel in preoperative serum samples from 328 CRC patients who underwent surgery at Helsinki University Hospital between 1998 and 2003. We performed a multivariate prognostic forward-stepping background model based on basic clinicopathological data, and a multivariate machine-learned prognostic model based on clinicopathological data and biomarker variables, calculating the disease-free survival using the value of importance score. From the 48 analyzed biomarkers, only IL-8 emerged as a significant prognostic factor for CRC patients in univariate analysis (HR 4.88; 95% CI 2.00–11.92; p = 0.024) after correcting for multiple comparisons. We also developed a multivariate model based on all 48 biomarkers using a random survival forest analysis. Variable selection based on a minimal depth and the value of importance yielded two tentative candidate CRC prognostic markers: IL-2Ra and IL-8. A multivariate prognostic model using machine-learning technologies improves the prognostic assessment of survival among surgically treated CRC patients.


2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 422-422
Author(s):  
Jae-Im Lee ◽  
Chang Hyeok An ◽  
Hyung Jin Kim ◽  
Sang Chul Lee ◽  
Seong-Taek Oh

422 Background: Tumor budding was defined as an isolated single cancer cell or a small cluster of cancer cells at the invasive margins. We assessed the clinical significance of tumor budding, as a predictor of outcomes in patients with non-metastatic colorectal cancer. Methods: We studied a total of 148 patients with colorectal cancer who underwent curative resection. Tumor budding was assessed on slides stained with hematoxylin and eosin (H&E). Tissue specimens including the entire invasive margin from largest cut sections of the whole tumor were examined. Tumor budding was not classified according to previously described classification. The actual number of tumor budding along the entire invasive margin was counted at a magnification of x200 with the use of light microscopy. We determined cut-off point of tumor budding, lymph node ratio and carcinoembryonic antigen (CEA) with receiver operating characteristic (ROC) curve. Results: Univariate analysis revealed that poorly differentiation (p=0.009), lymphatic invasion (p=0.035) venous invasion (p=0.007), CEA >6.3 (p=0.0007) and tumor budding >13 (p=0.0006) were significantly related to poor survival. Cumulative five survival rates differed significantly between patients with tumor budding ≤13 (92.3%) and those with tumor budding >13 (73.1 %). Multivariate analysis with Cox’s regression analysis demonstrated that tumor budding >13 (hazard ratio=4.925, p=0.003), poorly differentiation (hazard ratio=3.696, p=0.01) and CEA >6.3 (hazard ratio=3.085, p=0.024) were independent prognostic factors for overall survival. CEA >6.3 (hazard ratio=2.361, p=0.034) and tumor budding >20 (hazard ratio=3.293, p=0.008) were significant prognostic predictors for disease free survival Conclusions: Tumor budding is useful for prognosis and identifying patients with colorectal cancer who have a high-risk of disease recurrence after curative surgery. The proper cut-off level of tumor budding is 13.


Sign in / Sign up

Export Citation Format

Share Document