Who to treat with adjuvant therapy in Dukes B/stage II colorectal cancer? The need for high quality pathology

Morris, Eva; Maughan, Nicola; Forman, David; Quirke, Philip

doi:10.1136/gut.2006.116830

Cited by 118 publications

(94 citation statements)

References 29 publications

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“…Intra or extramural vascular invasion, peritoneal involvement and margin involvement were allocated a score of 1, and tumour perforation was allocated a score of 2. The cumulative total is calculated and the PI considered low risk, in which the score is between 0 and 1 and high risk with the score between 2 and 5 (Petersen et al, 2002;Morris et al, 2007).…”

Section: Methodsmentioning

confidence: 99%

Comparison of tumour-based (Petersen Index) and inflammation-based (Glasgow Prognostic Score) scoring systems in patients undergoing curative resection for colon cancer

et al. 2009

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After resection, it is important to identify colon cancer patients, who are at a high risk of recurrence and who may benefit from adjuvant treatment. The Petersen Index (PI), a prognostic model based on pathological criteria is validated in Dukes' B and C disease. Similarly, the modified Glasgow Prognostic Score (mGPS) based on biochemical criteria has also been validated. This study compares both the scores in patients undergoing curative resection of colon cancer. A total of 244 patients underwent elective resection between 1997 and 2005. The PI was constructed from pathological reports; the mGPS was measured pre-operatively. The median follow-up was 67 months (minimum 36 months) during which 109 patients died; 68 of them from cancer. On multivariate analysis of age, Dukes' stage, PI and mGPS, age (hazard ratio, HR, 1.74, P ¼ 0.001), Dukes' stage (HR, 3.63, Po0.001), PI (HR, 2.05, P ¼ 0.010) and mGPS (HR, 2.34, Po0.001) were associated independently with cancer-specific survival. Three-year cancer-specific survival rates for Dukes' B patients with the low-risk PI were 98, 92 and 82% for the mGPS of 0, 1 and 2, respectively (Po0.05). The high-risk PI population is small, in particular for Dukes' B disease (9%). The mGPS further stratifies those patients classified as low risk by the PI. Combining both the scoring systems could identify patients who have undergone curative surgery but are at high-risk of cancerrelated death, therefore guiding management and trial stratification.

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Section: Methodsmentioning

confidence: 99%

Comparison of tumour-based (Petersen Index) and inflammation-based (Glasgow Prognostic Score) scoring systems in patients undergoing curative resection for colon cancer

et al. 2009

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“…This situation is caused by two factors: firstly, understaging of regional lymph node status for the reason of insufficient number of resected and/or examined lymph nodes, secondly, the TNM classification does not include biological characteristics and predictors of tumor behaviour. Multicentric studies based on cancer registers, in which thousands of patients are included, have proved that number of examined lymph nodes has a significant impact on the prognosis, even if lymph nodes were not infiltrated by tumor cells (2)(3)(4)(5)(6)(7). For the purposes of the TNM classification UICC (International Union Against Cancer) has recommended that the histological examination of samples from regional lymphadenectomy should involve twelve or more regional lymph nodes.…”

Section: Introductionmentioning

confidence: 99%

Significant overexpression of Hsp110 gene during colorectal cancer progression

Slabý

Sobková²,

Svoboda³

et al. 2009

Oncol Rep

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Abstract. Colorectal cancer (CRC) is one of the most frequent malignant diseases in the world. Metastatic spread of the cancer to the lymph nodes is a crucial factor for progression and therapeutic management of the disease. We analysed gene expression profiles of CRC patiens by lowdensity cancer-focused oligonucleotide microarrays to identify new predictive markers of the extent of the disease and for better understanding of CRC progression. Relative expression levels of 440 genes known to be involved in cancer biology were obtained by low-density oligonucleotide microarrays from 20 tumor samples. Statistical analysis of gene expression data identified 3 genes (HSP110, HYOU1 and TCTP) significantly up-regulated in primary tumors of patients who developed lymph node metastasis. We have shown, for the first time, that up-regulation HSP110 and HYOU1 expression is associated with lymph node involvement in CRC. We validated the differences in HSP110 expression in an independent group of 30 patients of all clinical stages by real-time PCR. We identified significant up-regulation of HSP110 expression in colorectal tumors compared to adjacent non-tumoral tissue (p<0.0003). We observed significant differences of HSP110 gene expression between metastatic and localized disease (p=0.031) and negative trend of HSP110 gene expression and overall survival of CRC patients. We suggest that HSP110 gene is a promising molecular predictor in CRC. IntroductionColorectal cancer (CRC) is one of the most frequent malignant diseases in the world. With the incidence rate ~78 per 100,000 people, the Czech Republic is a country with one of the highest incidence of CRC in the world and the highest in Europe (1). The prognosis of these patients depends largely on the extent of the disease and a possibility of curative surgical intervention which is feasible only in patients with disease limited to the primary tumor and regional lymph nodes. Spread of the cancer to lymph nodes has been considered a crucial factor for progression and further therapeutic management of the disease. While in the case of clinical stage I and IV, the prognostic significance of the TNM classification is evident, for the group of patients diagnosed at stages II (without dissemination to regional lymph nodes) and III (with dissemination to lymph nodes) the prognostic information of clinical stage is much lower. The fact, that 30% of patients with clinical stage II of CRC will progress within five years and only 45% of the patients with clinical stage III will reach a 5-year survival, although undergoing radical surgery, implies that recent staging of CRC based on TNM classification is not optimal and failed for a significant proportion of non-advanced CRC patients. This situation is caused by two factors: firstly, understaging of regional lymph node status for the reason of insufficient number of resected and/or examined lymph nodes, secondly, the TNM classification does not include biological characteristics and predictors of tumor behaviour. Multicentric studies ba...

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“…Recent figures show that CRC is now the second commonest cause of cancer related mortality in the United Kingdom with over 16 000 deaths occurring annually (Cancer Research UK, 2009). Staging systems such as Dukes (Gabriel et al, 1935) and tumour, node, metastasis (TNM) (Sobin and Wittekind, 1997, pp 66-69) are routinely used to predict prognosis following surgery, however, patients diagnosed at the same stage of disease often have markedly different outcomes (Morris et al, 2007). Current research aims to identify additional prognostic markers that can be used to stratify CRC patients and identify those which may benefit from adjuvant therapy.…”

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confidence: 99%

The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients

et al. 2010

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BACKGROUND: The proportion of epithelial and stromal cells in tumours is thought to have an important role in the progression of epithelial malignancy. We aimed to determine whether the relative proportion of tumour (PoT) was related to survival in colorectal cancer. METHODS: The PoT at the luminal surface was measured by point counting using virtual tissue sections in a series of 145 colorectal cancer cases. The relationship of PoT to clinicopathological parameters including cancer-specific survival was analysed. Modified receiver operating characteristic curves were used to determine the optimum cut off points to dichotomise the data for survival analyses. RESULTS: Tumours with PoT-low (p47%) were associated with significantly lower cancer-specific survival when compared to PoT-high (hazard ratio (HR) ¼ 2.087, 95% CI ¼ 1.088 -4.003, P ¼ 0.024). On sub-analysis, the prognostic effect remained significant in colonic tumours (HR ¼ 2.474, 95% CI ¼ 1.132 -5.408, P ¼ 0.019) and tumour, node, metastasis stage III disease (HR ¼ 3.480, 95% CI ¼ 0.325 -9.136, P ¼ 0.007). Multivariate Cox regression analysis demonstrated that PoT was an independent prognostic marker when adjusted for age, T stage, N stage and extramural vascular invasion (P ¼ 0.017). CONCLUSION: This study suggests that a low proportion of tumour cells in colorectal cancer is related to poor cancer-specific survival. A relatively quick, inexpensive and well-established method such as point counting on diagnostic tissue sections could be used to identify a subset of patients who may benefit from adjuvant therapy.

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Who to treat with adjuvant therapy in Dukes B/stage II colorectal cancer? The need for high quality pathology

Cited by 118 publications

References 29 publications

Comparison of tumour-based (Petersen Index) and inflammation-based (Glasgow Prognostic Score) scoring systems in patients undergoing curative resection for colon cancer

Comparison of tumour-based (Petersen Index) and inflammation-based (Glasgow Prognostic Score) scoring systems in patients undergoing curative resection for colon cancer

Significant overexpression of Hsp110 gene during colorectal cancer progression

The proportion of tumour cells is an independent predictor for survival in colorectal cancer patients

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