DNA Image cytometry as a prognostic tool in stage II and stage III colorectal cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13565-13565
Author(s):  
A. Buhmeida ◽  
A. Ålgars ◽  
R. Ristamäki ◽  
Y. Collan ◽  
K. Syrjänen ◽  
...  

13565 Background: We assessed the prognostic value of nuclear DNA content measured in the primary tumors of 123 patients with stage II or stage III colorectal cancer (CRC). Methods: Isolated nuclei from paraffin sections were stained with Feulgen and DNA was measured using a computer-assisted image analysis cytometry system (Ahrens ACAS). We applied 4 different approaches in analysis of DNA histograms: ABCDE approach, histogram range, peak evaluation, and DNA cut-off values. Results: Using the histogram range, narrow range was rare (3.7%) in patients who died of disease as compared with 16.4% among those alive (p=0.017). Modal peak evaluation was a significant predictor of disease free survival (DFS) (Kaplan-Meier log-rank p=0.0235). In the range evaluation, the first set (low-start gates) was a significant predictor of DFS (log-rank p=0.0121), where disease recurrence was closely associated the widest range (1.8c->10c) gates. Recurrence-free survival was markedly better among patients with narrow gate histograms than wide range histograms than among patients with wide range histograms (p<0.03). The first set also proved to be significant predictor of disease specific survival (DSS) (log-rank p=0.0045), being markedly better (78–90.0%) among the patients with the narrow-gate histograms. Grading of the histogram range into two categories (with 6.0c as cut-off for low and wide range), was a powerful predictor of both DSS (log-rank p= 0.0092) and 5-year DFS (p=0.0106) in the whole series, and separately in Stage III (but not Stage II) disease; p=0.0131 and p=0.0201, respectively. Conclusions: The DNA image cytometry with careful analysis of the histograms may provide valuable prognostic information in CRC, with potential clinical implications in patient management, particularly in predicting the patients at high risk for recurrence who should be considered as candidates for adjuvant therapy. No significant financial relationships to disclose.


Oncology ◽  
2006 ◽  
Vol 70 (6) ◽  
pp. 427-437 ◽  
Author(s):  
A. Buhmeida ◽  
A. Ålgars ◽  
R. Ristamäki ◽  
Y. Collan ◽  
K. Syrjänen ◽  
...  


2011 ◽  
Vol 25 (1) ◽  
pp. 1 ◽  
Author(s):  
Abdelbaset Buhmeida ◽  
Yrjo Collan ◽  
Kari Syrjanen ◽  
Seppo Pyrhonen

The role of DNA content as a prognostic factor in colorectal cancer (CRC) is highly controversial. Some of these controversies are due to purely technical reasons, e.g. variable practices in interpreting the DNA histograms, which is problematic particularly in advanced cases. In this report, we give a detailed account on various options how these histograms could be optimally interpreted, with the idea of establishing the potential value of DNA image cytometry in prognosis and in selection of proper treatment. Material consists of nuclei isolated from 50 ƒĘm paraffin sections from 160 patients with stage II, III or IV CRC diagnosed, treated and followed-up in our clinic. The nuclei were stained with the Feulgen stain. Nuclear DNA was measured using computer-assisted image cytometry. We applied 4 different approaches to analyse the DNA histograms: 1) appearance of the histogram (ABCDE approach), 2) range of DNA values, 3) peak evaluation, and 4) events present at high DNA values. Intra-observer reproducibility of these four histogram interpretation was 89%, 95%, 96%, and 100%, respectively. We depicted selected histograms to illustrate the four analytical approaches in cases with different stages of CRC, with variable disease outcome. In our analysis, the range of DNA values was the best prognosticator, i.e., the tumours with the widest histograms had the most ominous prognosis. These data implicate that DNA cytometry based on isolated nuclei is valuable in predicting the prognosis of CRC. Different interpretation techniques differed in their reproducibility, but the method showing the best prognostic value also had high reproducibility in our analysis.



2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 784-784
Author(s):  
Ik Yong Kim ◽  
Young Wan Kim

784 Background: To date, reasons for adjuvant chemotherapy (AC) omission and delay have not been extensively studies. This study aimed to evaluate factors affecting chemotherapy use and delay (≥8 weeks) after colorectal cancer surgery and their impact on survival. Methods: Between 2008 and 2013, consecutive 584 patients undergoing major resection for stage II and III colorectal cancer in a single tertiary referral center. Results: Among 584 patients with stage II and III diseases, AC was performed in 460 (78.8%) patients. Regimens included fluorouracil with folinic acid (n=257, 55.9%), FOLFOX (n=134, 29.1%), capecitabline (n=62, 13.5%), and tegafur-uracil (n=7, 1.5%). Factors affecting not receiving AC were older age (>80 years), American Society of Anesthesiologists score (≥3), presence of postoperative complication, and not receiving preoperative chemoradiation. Overall survival was 87.2% (AC +) and 58.5% (no AC, p<0.001) in stage II disease, and 79.5% (AC +) and 24.6% (no AC, p<0.001) in stage III disease, respectively. Recurrence-free survival was 83.7% (AC +) and 61.9% (no AC, p=0.003) in stage II disease, and 60.5%(AC +) and 21.8% (no AC, p<0.001) in stage III disease, respectively. Among 460 patients undergoing AC, AC was initiated within 8 weeks in 438 patients (95.2%) and after 8 weeks in 22 patients (4.8%). Factors affecting AC delay were male gender, rectal primary, intraoperative blood loss (>100ml), and presence of postoperative complications. Overall survival was 90.8% (AC +) and 40.0% (no AC, p=0.111) in stage II disease, and 82% (AC +) and 35.6% (no AC, p=0.275) in stage III disease, respectively. Recurrence-free survival 80.1% (AC +) and 54.5% (no AC, p=0.133) in stage II disease, and 64.4% (AC +) and 0.0% (no AC, p=0.014), respectively. Conclusions: In stage II, III patients, it appears that use of AC is more closely related patient’s survival rather than the time of AC initiation. To improve oncologic outcomes after curative resection, it is important to increase the proporation of AC use.



2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4090-4090
Author(s):  
J. Xu ◽  
Y. Zhong ◽  
W. Niu ◽  
X. Qin ◽  
Y. Wei ◽  
...  

4090 Background: To investigate whether preoperative hepatic and regional arterial chemotherapy are able to prevent liver metastasis and improve overall survival in patients receiving curative colorectal cancer resection. Methods: Patients with Stage II or Stage III colorectal cancer (CRC) were randomly assigned to receive preoperative hepatic and regional arterial chemotherapy (PHRAC group, n=256) or surgery alone (control group, n=253). The primary endpoint was disease-free survival, whereas the secondary endpoints included liver metastasis-free survival and overall survival. Results: There were no significant differences in overall morbidity between PHRAC and Control groups. During the follow-up period (median, 42 months), the median liver metastasis time for patients with stage III CRC was significantly longer in the PHRAC group (16±3 months v.s. 8±1 months, P=0.01). In stage III patients, there was also significant difference between the two groups with regard to the incidence of liver metastasis (18.9% vs 27.3%, P=0.01), 5-year disease-free survival (70.2% vs 52.0%, P=0.0076), 5-year overall survival (80.3% vs 69.5%, P=0.020) and the median survival time (40.1± 4.6 months vs 36.3 ± 3.2 months, P=0.03). In the PHRAC arm, the risk ratio of recurrence was 0.63 (95% CI, 0.51–0.79, P=0.0001), of death was 0.50(95% CI, 0.32–0.67; P=0.005), and of liver metastasis was 0.70 (95% CI, 0.52–0.86; p=0.01). In contrast, PHRAC seemed to be no benefit for stage II patients. Toxicities, such as hepatic toxicity and leucocyte decreasing, were mild and could be cured with medicine. Conclusions: Preoperative hepatic and regional arterial chemotherapy, in combination with surgical resection, could be able to reduce and delay the occurrence of liver metastasis and therefore improve survival rate in patients with stage III colorectal cancer. No significant financial relationships to disclose.



Author(s):  
Kosuke Mima ◽  
Nobutomo Miyanari ◽  
Keisuke Kosumi ◽  
Takuya Tajiri ◽  
Kosuke Kanemitsu ◽  
...  


2022 ◽  
pp. 000313482110547
Author(s):  
Chelsea Knotts ◽  
Alexandra Van Horn ◽  
Krysta Orminski ◽  
Stephanie Thompson ◽  
Jacob Minor ◽  
...  

Background Previous literature demonstrates correlations between comorbidities and failure to complete adjuvant chemotherapy. Frailty and socioeconomic disparities have also been implicated in affecting cancer treatment outcomes. This study examines the effect of demographics, comorbidities, frailty, and socioeconomic status on chemotherapy completion rates in colorectal cancer patients. Methods This was an observational case-control study using retrospective data from Stage II and III colorectal cancer patients offered chemotherapy between January 01, 2013 and January 01, 2018. Data was obtained using the cancer registry, supplemented with chart review. Patients were divided based on treatment completion and compared with respect to comorbidities, age, Eastern Cooperative Oncology Group (ECOG) score, and insurance status using univariate and multivariate analyses. Results 228 patients were identified: 53 Stage II and 175 Stage III. Of these, 24.5% of Stage II and 30.3% of Stage III patients did not complete chemotherapy. Neither ECOG status nor any comorbidity predicted failure to complete treatment. Those failing to complete chemotherapy were older (64.4 vs 60.8 years, P = .043). Additionally, those with public assistance or self-pay were less likely to complete chemotherapy than those with private insurance ( P = .049). Both factors (older age/insurance status) remained significant on multivariate analysis (increasing age at diagnosis: OR 1.03, P =.034; public insurance: OR 1.84, P = .07; and self-pay status: OR 4.49, P = .03). Conclusions No comorbidity was associated with failure to complete therapy, nor was frailty, as assessed by ECOG score. Though frailty was not significant, increasing age was, possibly reflecting negative attitudes toward chemotherapy in older populations. Insurance status also predicted failure to complete treatment, suggesting disparities in access to treatment, affected by socioeconomic factors.



2005 ◽  
Vol 91 (2) ◽  
pp. 168-172 ◽  
Author(s):  
Mahmut Gumus ◽  
Perran Fulden Yumuk ◽  
Gul Atalay ◽  
Mehmet Aliustaoglu ◽  
Beyza Macunluoglu ◽  
...  

Background Regional lymph node (LN) involvement in colorectal cancer (CRC) identifies the stage and the subset of patients who would benefit from adjuvant chemotherapy. We performed a retrospective analysis to determine if the number of recovered LNs was associated with long-term outcome in patients operated on for stage II and III CRC. Patients and methods Hospital records of 179 patients with CRC followed in our unit from 1997 to April 2003 were reviewed. Results On average 11.68 ± 7.3 LNs were sampled per surgical specimen. Sampling of at least nine LNs appeared to be the minimum number required for accurately predicting LN involvement ( P = 0.002). Three-year rates of disease-free survival (DFS), local recurrence-free survival (LRFS) and overall survival (OS) were lower in patients with fewer than nine LNs sampled ( P = 0.032, P = 0.006 and P = 0.04, respectively). However, this had no impact on the three-year distant metastasis-free survival rate (DMFS) ( P = 0.472). In stage II disease, patients with nine or more LNs dissected had significantly higher three year DFS and LRFS rates than the subgroup with fewer than nine LNs dissected ( P = 0.024 and P = 0.015, respectively), but this did not have any effect on DMFS or OS ( P = 0.406 and P = 0.353, respectively). Conclusion Current protocols provide adjuvant treatment in stage III patients; the problem is to correctly determine stage by recovering as many LNs as possible.



2019 ◽  
Vol 49 (10) ◽  
pp. 985-990 ◽  
Author(s):  
Kenichi Miyamoto ◽  
Atsuo Takashima ◽  
Junki Mizusawa ◽  
Yuya Sato ◽  
Yasuhiro Shimada ◽  
...  

Abstract Adjuvant chemotherapy is the current standard treatment for stage III colorectal cancer after curative resection. However, the prognosis of stage III colorectal cancer is still poor even after curative resection and adjuvant chemotherapy. Several observational studies suggested that the anti-tumor effect of aspirin. Therefore, we planned a randomized double-blind placebo-controlled phase III trial, which commenced in Japan in March 2018, to confirm the superiority of aspirin over placebo added to adjuvant chemotherapy in terms of disease-free survival (DFS) for stage III colorectal cancer patients after curative resection. A total of 880 patients will be accrued from 20 Japanese institutions within 3 years. The primary endpoint is DFS and the secondary endpoints are overall survival, relapse-free survival, relative dose intensity, adverse events, and serious adverse events. This trial has been registered at Japan Registry of Clinical Trials as jRCTs031180009 (https://jrct.niph.go.jp/detail/589).



2010 ◽  
Vol 127 (10) ◽  
pp. 2292-2299 ◽  
Author(s):  
Takatoshi Matsuyama ◽  
Toshiaki Ishikawa ◽  
Kaoru Mogushi ◽  
Tsuyoshi Yoshida ◽  
Satoru Iida ◽  
...  


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4121-4121
Author(s):  
G. Des Guetz ◽  
B. Uzzan ◽  
P. Nicolas ◽  
K. Chouahnia ◽  
G. Perret ◽  
...  

4121 Background: Microsatellite instability (MSI) is a prognostic factor in colorectal cancer. Whether it predicts the effect of adjuvant chemotherapy (CT) on overall survival (OS) and relapse-free survival (RFS) is controversial. Methods: Studies were identified by an electronic search using online PubMed, with simultaneous keywords (colorectal neoplasm, microsatellite instability, chemotherapy, prognosis). Abstracts from ASCO and AACR proceedings were reviewed. Articles were obtained from cross-checking of references and from a previous prognostic meta-analysis (MA) (Popat, 2005). We used EasyMA software, available online. A Hazard Ratio (HR) < 1 for MSI-high (MSI-H) status compared with microsatellite stable (MSS) meant a better survival. Results: Our MA found 21 studies (4 abstracts). Statistical calculations were performed in 11 studies (5087 patients including 2879 receiving 5FU-based CT; mean age: 63 years; 1489 stage II, 2648 stage III (64%)). MSI-H was found in 644 patients (15% of total), MSS in 3624. Seven studies (2 randomized) assessed 2 cohorts receiving or not adjuvant CT, 4 studies only included patients receiving CT. Global HR OS (9 studies) was 0.79 (95% confidence interval or CI: 0.64–0.98; p = 0.03). Global HR RFS (8 studies) was 0.67 (95% CI: 0.54–0.83; p < 0.001). A MA on stage III patients (4 studies, 719 patients, 137 MSI-H) found a higher survival among MSI-H than MSS patients receiving CT (HR OS: 0.71, 95% CI 0.49–1.03; HR RFS 0.56, 95% CI 0.42–0.75). Interaction between MSI status and CT status was statistically significant on OS and RFS (4 studies). A MA among MSI-H patients (7 studies) found no survival difference between patients under CT or not: HR OS: 0.70 (95% CI 0.44–1.09), HR RFS: 0.96 (95% CI: 0.62–1.49). Conclusions: Adjuvant CT significantly improved survival in MSI-H compared with MSS patients. MSI-H stage III patients receiving CT survived more than MSS. MSI-H status did not predict response to CT compared with no treatment. No significant financial relationships to disclose.



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