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529
Background: Colorectal signet-ring cell carcinoma (SRCC) has been associated with a poor survival compared to mucinous adenocarcinoma (MC) and the common adenocarcinoma (AC). ...Prognostic impact of tumor localization is unknown and efficacy of adjuvant chemotherapy in SRCC has never been assessed. This study analyses prognostic impact of SRCC and determines whether SRCC patients benefit from adjuvant chemotherapy for colon cancer equally compared with AC. Methods: Data on 196,757 patients with CRC in the Netherlands in the period 1989 and 2010 was included in this nationwide population-based study. Five-year relative survival estimates were calculated and multivariate relative survival analyses using a multiple regression model of relative excess risk (RER) were performed. Results: SRCC was found in 1.0% of CRC patients. SRCC patients presented more frequently with stage III or IV disease than AC (75.2% versus 43.6%, P<0.0001) and SRCC was more frequently found in the proximal colon (57.7% versus 32.0%, P<0.0001). SRCC patients had a poor 5-year relative survival of 31% in colon and 20% in the rectum compared to 57% and 59% in AC (P<0.0001). This poorer survival for SRCC was found in stage II, III and IV. In comparison with AC, there was no significant interaction between SRCC and adjuvant chemotherapy (RER 1.10, 95% CI 0.81-1.51), suggesting a comparable benefit from adjuvant chemotherapy in AC and SRCC. Conclusions: Prognostic impact of SRCC is dismal in both colon and rectal cancer patients, but colonic SRCC patients seem to benefit from adjuvant chemotherapy equally compared with AC. Reduced efficacy of adjuvant chemotherapy therefore does not seem to explain the poor outcome in SRCC patients. We recommend to adhere to adjuvant treatment guidelines for all histological subtypes, but encourage clinical trials to take histological subtype into account for stratification.
A standardized detailed surgical pathology report is the cornerstone of gastric cancer management.
To guide management and prognostication for patients with gastric carcinomas globally, the ...International Collaboration on Cancer Reporting aimed to produce an evidence-based international pathology reporting data set with a panel of globally recognized expert pathologists and clinicians.
Based on published guidelines/data sets for gastric carcinomas, a working draft was developed by the chair of the expert panel of pathologists and clinicians. The draft was then circulated to the panel and discussed in a series of teleconferences and email communications until consensus was achieved. The draft data set was uploaded on the International Collaboration on Cancer Reporting Web site for public comment. The data set was reviewed in consideration of the feedback, and a final version was approved by the panel.
This data set was developed for gastrectomy specimens for primary gastric carcinomas, including neuroendocrine carcinomas and mixed neuroendocrine-nonneuroendocrine neoplasms. Well-differentiated neuroendocrine tumors, nonepithelial malignancies, and secondary tumors were excluded from this data set. The final data set contains 15 core (required) elements and 8 noncore (recommended) elements. A commentary is provided for each element.
The International Collaboration on Cancer Reporting has published freely available, evidence-based data sets for gastric cancer reporting. Standardized reporting has been shown to improve patient care and facilitates data exchange and analysis for quality assurance, cancer epidemiology, and clinical and basic research.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
The condition of pneumatosis intestinalis is characterized by gas in the intestinal wall, with a variety of causes.
A septic patient with intestinal pneumatosis, locally advanced ovarian cancer, and ...Sister Joseph's Nodule.
The clinical significance of this rare combination of symptoms and signs is discussed.
Abstract
Objective: Metastasis is a complex process that remains an obstacle in the management of colorectal cancer (CRC). Over the years many models have been developed to explain the metastatic ...process in detail, however, the molecular basis is still poorly understood. To gain better insight into the biology of metastases we investigated genomic aberrations in matched triplets of normal, CRC primaries and metastases of various distant sites. Methods: In total, 63 primary colorectal tumours, 63 matched normal specimens, and 69 matched metastases (liver, lung, ovarian, omentum and distant lymph nodes) were analysed by high resolution array comparative genomic hybridization (array CGH). Our findings were validated in a publicly available dataset consisting of 21 matched primary tumours and liver metastases.1 Fluorescence in situ hybridization (FISH) was used to confirm our findings and to evaluate intra-tumour heterogeneity of the observed copy number differences. Results: The overall pattern of copy number aberrations was highly similar between primary tumours and their metastases. However, higher deflections were observed in the metastases compared to the primary tumours, which was confirmed in the validation set. Across all patients, 17 regions showed significantly lower DNA copy number ratio and 2 regions showed significantly higher DNA copy number ratio in the metastases compared to the primary tumour. None of these significant DNA copy number changes occurred in a substantial percentage of our patients. In the training set we did not detect a higher frequency of chromosome 11p15.5 gain in liver metastasis compared to the primary tumour, as previously reported in the validation set. In two different patients, two specific regions showed amplifications in the three metastases (one patient with two metastatic sites) which were absent in the primary tumours. One of these regions harboured the MYC oncogene. FISH analysis confirmed the extensive MYC amplification in the three metastases, but also showed tumour cell populations with smaller MYC amplifications within the primary tumour, which were not detected by array CGH. Conclusions: Highly similar patterns of DNA copy number profiles between metastatic and primary CRC were observed using array CGH. Focal differences that were observed in individual patients are probably explained by heterogeneity within the primary tumour in contrast to the metastatic sub clone. True additional copy number aberrations are rare and rather specific for individual patients, which is consistent with the hypothesis that the metastatic potential is already present in the primary tumour. Referentie: 1. Stange DE, Engel F, Longerich T et al. Expression of an ASCL2 related stem cell signature and IGF2 in colorectal cancer liver metastases with 11p15.5 gain. Gut 2011;59:1236-44.
Citation Format: {Authors}. {Abstract title} abstract. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3397. doi:1538-7445.AM2012-3397
Purpose:
In vitro, ionizing radiation of epithelial cells leads to upregulation of wild-type p53 and subsequent induction of p21
waf1. The effect of radiotherapy (RT) on the expression of these ...proteins in patients is unknown. We assessed the influence of RT on the expression of p53 and p21
waf1 in normal mucosa and rectal carcinomas
in vivo.
Methods:
Tumor and normal tissue samples were derived from rectal cancer patients randomized in a clinical trial in which the value of preoperative RT was evaluated. p53 and p21
waf1 expression was determined in 51 irradiated and 52 nonirradiated patients using immunohistochemistry.
Results:
In normal mucosa, both p53 and p21
waf1 were strongly upregulated after RT compared with the expression in unirradiated normal tissue (
p <0.001). In tumor cells, no significant difference in the expression of p53 or p21
waf1 was found in the irradiated vs. nonirradiated group. In the few rectal tumors with wild-type p53, induction of p53 after RT did not necessarily lead to upregulation of p21
waf1.
Conclusion:
These findings demonstrate that in normal mucosa, a functional p53–p21
waf1 pathway is present, whereas in tumor cells it is defective in almost all cases because of either p53 mutation or down- or upstream disruption in tumors with wild-type p53. Therefore, we believe that the role of p53 expression as a single prognostic marker in rectal cancer needs reconsideration.
Abstract only
3552
Background: Heterogeneity in the biology of colorectal cancer (CRC) is associated with variable responses to standard chemotherapy. We aimed to identify DNA hypermethylated genes ...as predictive biomarkers for irinotecan treatment of patients with metastatic CRC. Methods: The presence of DNA methylation for a selected panel of 22 genes was assessed by methylation specific PCR (MSP) on primary tumors of 185 patients with metastatic CRC treated with first-line capecitabine (CAP, n=90) or a combination of capecitabine and irinotecan (CAPIRI, n=95) in the phase 3 CAIRO trial. Methylation status of each gene was correlated to progression free survival (PFS) by treatment regimen. Genes for which methylation status associated with response to irinotecan, were validated in 166 patients treated with first-line CAP (n=78) or CAPIRI (n=88). Results: Decoy Receptor 1 (DCR1) was identified as a novel hypermethylated gene in CRC. In CAPIRI treated patients, DCR1 methylation was correlated to a shorter PFS compared to patients with unmethylated DCR1 (hazard ratio HR=0.4 (95%CI =0.3-0.7), p = 0.0009). In patients with methylated DCR1 PFS did not improve with CAPIRI treatment, compared to treatment with CAP (discovery set: HR=0.8 (95%CI=0.5-1.3, p=0.4); validation set: HR=1.1 (95%CI 0.7-1.7, p=0.6)), in contrast to patients with unmethylated DCR1 (discovery set: HR=2.5 (95%CI 1.7-3.3, p=0.00004); validation set: HR=1.7 (95%CI 1.1-2.0, p=0.004)). Conclusions: CRC patients with methylated DCR1 did not benefit from adding irinotecan to capecitabine therapy, indicating that DCR1 methylation status may guide selecting metastatic CRC patients for irinotecan-based therapy.
The CARTS study is a multicenter feasibility study, investigating the role of rectum saving surgery for distal rectal cancer.
Patients with a clinical T1-3 N0 M0 rectal adenocarcinoma below 10 cm ...from the anal verge will receive neoadjuvant chemoradiation therapy (25 fractions of 2 Gy with concurrent capecitabine). Transanal Endoscopic Microsurgery (TEM) will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response.Primary objective is to determine the number of patients with a (near) complete pathological response after chemoradiation therapy and TEM. Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality. A three-step analysis will be performed after 20, 33 and 55 patients to ensure the feasibility of this treatment protocol.
The CARTS-study is one of the first prospective multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision. The CARTS study is registered at clinicaltrials.gov (NCT01273051).
Abstract
Background
Heterogeneity in the biology of colorectal cancer (CRC) is associated with variable responses to standard chemotherapy. We aimed to identify DNA hypermethylated genes as ...predictive biomarkers for irinotecan treatment of patients with metastatic CRC.
Material and Methods
The presence of DNA methylation for a selected panel of 22 genes was assessed by methylation specific PCR (MSP) on primary tumors of 185 patients with metastatic CRC treated with first-line capecitabine (CAP, n=90) or a combination of capecitabine and irinotecan (CAPIRI, n=95) in the phase III CAIRO trial. Methylation status of each gene was correlated to progression free survival (PFS) by treatment regimen. Genes for which methylation status associated with response to irinotecan, were validated in 166 patients treated with first-line CAP (n=78) or CAPIRI (n=88).
Results
Decoy Receptor 1 (DCR1) was identified as a novel hypermethylated gene in CRC. In CAPIRI treated patients, DCR1 methylation was correlated to a shorter PFS compared to patients with unmethylated DCR1 (hazard ratio HR=0.4 (95%CI =0.3-0.7), p = 0.0009). In patients with methylated DCR1 PFS did not improve with CAPIRI treatment, compared to treatment with CAP (discovery set: HR=0.8 (95%CI=0.5-1.3, p=0.4); validation set: HR=1.1 (95%CI 0.7-1.7, p=0.6)), in contrast to patients with unmethylated DCR1 (discovery set: HR=2.5 (95%CI 1.7-3.3, p=0.00004); validation set: HR=1.7 (95%CI 1.1-2.0, p=0.004)).
Conclusion
CRC patients with methylated DCR1 did not benefit from adding irinotecan to capecitabine therapy, indicating that DCR1 methylation status may guide selecting metastatic CRC patients for irinotecan-based therapy.
Citation Format: Linda JW Bosch, Geert Trooskens, Petur Snaebjornsson, Josien C. Haan, Lorraine Pelosof, Miriam Koopman, Jolien Tol, Joost Louwagie, Luc Dehaspe, Bauke Ylstra, Henk Verheul, Manon van Engeland, Iris D. Nagtegaal, James G. Herman, Cornelis JA Punt, Wim van Criekinge, Beatriz Carvalho, Gerrit A. Meijer. Promoter CpG island hypermethylation of Decoy Receptor 1 (DCR1) is associated with poor response to irinotecan in colorectal cancer. abstract. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1155. doi:10.1158/1538-7445.AM2013-1155
Abstract
Introduction: KRAS mutation is a negative predictive factor for treatment with anti-epidermal growth factor receptor (EGFR) antibodies in metastatic colorectal cancer (mCRC). Novel ...predictive markers are required to further improve the selection of patients for this treatment. We assessed the influence of modification of KRAS by gene copy number aberration (CNA) and microRNAs (miRNAs) in correlation to clinical outcome in mCRC patients treated with cetuximab in combination with chemotherapy and bevacizumab.
Patients and methods: Formalin-fixed paraffin-embedded primary tumor tissue was used of 34 mCRC patients from a phase III trial (CAIRO2), who were selected based upon their good (n=17) and poor (n=17) progression-free survival (PFS) upon treatment with cetuximab in combination with capecitabine, oxaliplatin, and bevacizumab. Gene CNA at the KRAS locus was assessed using a high resolution genome-wide array CGH and the expression levels of 17 miRNAs targeting KRAS were determined by real-time PCR.
Results: Copy number loss of the KRAS locus was observed in the tumor of 5 patients who were all good responders including patients with a KRAS mutation. Copy number gains in two wild type-KRAS tumors were associated with a poor PFS. Increased expression of several miRNAs (presented at the meeting) targeting KRAS correlated with PFS of patients treated with cetuximab, bevacizumab and chemotherapy.
Conclusion: Our results indicate that the assessment of KRAS CNA and miRNAs targeting KRAS further optimize the selection of mCRC eligible for anti-EGFR therapy, in addition to KRAS mutation status.
Citation Format: {Authors}. {Abstract title} abstract. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 235. doi:10.1158/1538-7445.AM2011-235
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