Elevated preoperative CEA is associated with worse survival in stage I-III rectal cancer patients

Background:

The objective of this investigation was to assess whether preoperative carcinoembryonic antigen (CEA) level is an independent predictor of overall survival in rectal cancer patients.

Methods:

All patients (n=504) undergoing a resection for stage I–III rectal cancer at the Kantonsspital St Gallen were included into a database between 1991 and 2008. The impact of preoperative CEA level on overall survival was assessed using risk-adjusted Cox proportional hazard regression models and propensity score methods.

Results:

In risk-adjusted Cox proportional hazard regression analyses, preoperative CEA level (hazard ratio (HR): 1.98, 95% confidence interval (CI): 1.36–2.90, P<0.001), distance from anal verge (<5 cm: HR: 1.93, 95% CI: 1.11–3.37; P=0.039), older age (HR: 1.07, 95% CI: 1.05–1.09; P<0.001), lower body mass index (HR: 0.94, 95% CI: 0.89–0.98; P=0.006), advanced tumour stage (stage II HR: 1.41, 95% CI: 0.85–2.32; stage III HR: 2.08, 95% CI: 1.31–3.31; P=0.004), R 1 resection (HR: 5.65, 95% CI: 1.59–20.1; P=0.005) and chronic kidney disease (HR: 2.28, 95% CI: 1.03–5.04; P=0.049) were all predictors for poor overall survival.

Conclusion:

This is one of the first investigations based on a large cohort of exclusively rectal cancer patients demonstrating that preoperative CEA level is a strong predictor of decreased overall survival. Preoperative CEA should be used as a prognostic factor in the preoperative assessment of rectal cancer patients.     

Meta-analysis of immunohistochemical prognostic markers in resected pancreatic cancer

Background:

The potential prognostic value of several commonly investigated immunohistochemical markers in resected pancreatic cancer is variably reported. The objective of this study was to conduct a systematic review of literature evaluating p53, p16, smad4, bcl-2, bax, vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) expression as prognostic factors in resected pancreatic adenocarcinoma and to conduct a subsequent meta-analysis to quantify the overall prognostic effect.

Methods:

Relevant literature was identified using Medline, EMBASE and ISI Web of Science. The primary end point was overall survival assessed on univariate analysis. Only studies analysing resected pancreatic adenocarcinoma were eligible for inclusion and the summary log_e hazard ratio (logHR) and variance were pooled using an inverse variance approach. Evidence of heterogeneity was evaluated using the χ² test for heterogeneity and its impact on the meta-analysis was assessed by the I² statisic. Hazard ratios greater than one reflect adverse survival associated with positive immunostaining.

Results:

Vascular endothelial growth factor emerged as the most potentially informative prognostic marker (11 eligible studies, n=767, HR=1.51 (95% confidence interval, CI=1.18–1.92)) with no evidence of any significant publication bias (Egger''s test, P=0.269). Bcl-2 (5 eligible studies, n=314, HR=0.51 (95% CI=0.38–0.68)), bax (5 studies, n=274, HR=0.63 (95% CI=0.48–0.83)) and p16 (3 studies, n=229, HR=0.63 (95% CI=0.43–0.92)) also returned significant overall survival differences, but in smaller patient series due to a lack of evaluable literature. Neither p53 (17 studies, n=925, HR=1.22 (95% CI=0.96–1.56)), smad4 (5 studies, n=540, HR=0.88 (95% CI=0.61–1.27)) nor EGFR (4 studies, n=250, HR=1.35 (95% CI=0.80–2.27)) was found to represent significant prognostic factors when analysing the pooled patient data. There was evidence of significant heterogeneity in four of the seven study groups.

Conclusion:

These results support the case for immunohistochemical expression of VEGF representing a significant and reproducible marker of adverse prognosis in resected pancreatic cancer.     

The impact of young age on cancer-specific and non-cancer-related survival after surgery for colorectal cancer: 10-year follow-up

Background:

It has been reported that although young patients present with more advanced disease, when adjusted for stage, cancer-specific survival is not different after surgery for colorectal cancer. However, few studies have examined non-cancer survival in young patients and 10-year survival has rarely been reported. Moreover, the largest study included patients of old age as a comparator. The aim of this study was to compare cancer-specific and non-cancer-related survival at 10 years in a young age cohort and a middle age cohort in patients undergoing surgery for colorectal cancer.

Methods:

Two thousand and seventy seven patients who underwent surgery for colorectal cancer between 1991 and 1994 in 11 hospitals in Scotland were included in the study. Ten-year cancer-specific and non-cancer-related survival and the hazard ratios (HR) were calculated according to age groups (<45/45–54/55–64/65–74 years).

Results:

On follow-up, 1066 patients died of their cancer and 369 died of non-cancer-related causes. At 10 years, overall survival was 32%, cancer-specific was 45%, and non-cancer-related survival was 72%. On multivariate analysis of all factors, sex (HR 0.77, 95% CI 0.68–0.88, P<0.001), mode of presentation (HR 1.64, 95% CI 1.44–1.87, P<0.01), Dukes'' stage (HR 2.69, 95% CI 2.49–2.90, P<0.001), and specialisation (HR 1.24, 95% CI 1.04–1.44, P<0.01) were independently associated with cancer-specific survival. On multivariate analysis of all factors, age (HR 2.46, 2.04–2.97, P<0.001), sex (HR 0.56, 0.45–0.70, P<0.001), and deprivation (HR 1.16, 1.10–1.24, P<0.001) were independently associated with non-cancer-related survival.

Conclusion:

The results of this study confirm that young age does not have a negative impact on cancer-specific survival. Moreover, they show that, with 10-year follow-up, young age does not have a negative impact on non-cancer-related survival.     

High expression of tumour-associated trypsin inhibitor correlates with liver metastasis and poor prognosis in colorectal cancer

Increased expression of tumour-associated trypsin inhibitor (TATI) in tumour tissue and/or serum has been associated with poor survival in various cancer forms. Moreover, a proinvasive function of TATI has been shown in colon cancer cell lines. In this study, we have examined the prognostic significance of tumour-specific TATI expression in colorectal cancer, assessed by immunohistochemistry (IHC) on tissue microarrays (TMAs) with tumour specimens from two independent patient cohorts. Kaplan–Meier analysis and Cox proportional hazards modelling were used to estimate time to recurrence, disease-free survival and overall survival. In both cohorts, a high (>50% of tumour cells) TATI expression was an independent predictor of a significantly shorter overall survival. In cohort II, in multivariate analysis including age, gender, disease stage, differentiation grade, vascular invasion and carcinoembryonal antigen (CEA), high TATI expression was associated with a significantly decreased overall survival (HR=1.82; 95% CI=1.19–2.79) and disease-free survival (HR=1.56; 95% CI=1.05–2.32) in curatively treated patients. Moreover, there was an increased risk for liver metastasis in both cohorts that remained significant in multivariate analysis in cohort II (HR=2.85; 95% CI=1.43–5.66). In conclusion, high TATI expression is associated with liver metastasis and is an independent predictor of poor prognosis in patients with colorectal cancer.     

Prediagnosis lifestyle exposures and survival of gastric cancer patients: a cohort study from Portugal

Background:

Dietary habits and smoking are recognised as important gastric cancer determinants. However, their impact on prognosis remains poorly understood. We aimed to quantify the association between lifestyles and survival of gastric cancer patients.

Methods:

In 2001–2006, 568 patients were recruited in the two major public hospitals in the north of Portugal. Participants were inquired about smoking and dietary habits regarding the year preceding the diagnosis. The vital status of all participants, up to 2011 (maximum follow-up: 10 years), was assessed through the North Region Cancer Registry. Cox proportional hazards regression models were used to estimate adjusted (at least for age, sex and education) hazard ratios (HR) and 95% confidence intervals (95% CI).

Results:

No significant differences in gastric cancer survival were observed according to smoking status (current vs never smokers, HR=1.00, 95% CI: 0.72–1.38) or alcohol intake (current vs never consumers, HR=0.87, 95% CI: 0.61–1.25). Only a dietary pattern (high consumptions of most food groups and low vegetable soup intake) was significantly associated with a better prognosis among patients with the extent of disease classified as regional spread (HR=0.45, 95% CI: 0.22–0.93).

Conclusion:

This study shows that prediagnosis lifestyles have a small impact in the survival of gastric cancer patients.     

NT5E CpG island methylation is a favourable breast cancer biomarker

Background:

Relapse risk assessment and individual treatment recommendations remain suboptimal for breast cancer patients. In the light of existing preclinical and clinical data, we studied NT5E (5′-nucleotidase, ecto) expression and NT5E CpG island methylation in breast cancer.

Methods:

We used RT–PCR, qPCR, methylation-specific PCR and pyrosequencing to analyse NT5E in breast carcinoma cell lines and primary and breast carcinomas.

Results:

NT5E CpG island methylation was inversely associated with NT5E expression in breast carcinoma cell lines. In clinical series, patients whose primary tumours had NT5E CpG island methylation were less likely to develop metastasis (P=0.003, OR=0.34, 95% CI: 0.17–0.69). In 3/4 paired samples, NT5E was methylated in primary tumours and demethylated in CNS metastases. Patients progressing to non-visceral as compared with visceral metastases were more likely to have NT5E CpG island methylation in primary tumours (P=0.01, OR=11.8). Patients with tumours lacking detectable methylation had shorter disease-free survival (DFS) (P=0.001, HR=2.7) and overall survival (OS) (P=0.001, HR=3). The favourable prognostic value of NT5E methylation was confirmed in oestrogen receptor negative (P=0.011, HR=3.27, 95% CI: 1.31–8.12) and in triple negative cases (P=0.004; HR=6.2, 95% CI: 1.9–20). Moreover, we observed a more favourable outcome to adjuvant chemotherapy in patients whose tumours were positive for NT5E CpG island methylation: DFS (P=0.0016, HR=5.1, 95% CI: 1.8–14.37) and OS (P=0.0005, HR=7.4, 95% CI: 2.416–23.08).

Conclusion:

NT5E CpG island methylation is a promising breast cancer biomarker.     

Why do patients with radiation-induced sarcomas have a poor sarcoma-related survival?

Background:

This study aims to provide reasons for the poor sarcoma-related survival in patients with radiation-induced sarcoma (RIS).

Methods:

We performed a case–control study comparing sarcoma-related survival of 98 patients with RIS to that of 239 sporadic high-grade malignant sarcomas.

Results:

The cumulative sarcoma-related 5-year survival was 32% (95% confidence interval (CI): 22–42) for patients with RIS vs 51% (95% CI: 44–58) for controls (P<0.001). Female gender, central tumour site and incomplete surgical remission were significantly more frequent among RIS patients than in controls. In multivariate analysis incomplete surgical remission (hazard ratio (HR) 4.48, 95% CI: 3.08–6.52), metastases at presentation (HR 2.93, 95% CI: 1.95–4.41), microscopic tumour necrosis (HR 1.88, 95% CI: 1.27–2.78) and central tumour site (HR 1.71, 95% CI: 1.18–2.47) remained significant adverse prognostic factors, but not sarcoma category (RIS vs sporadic).

Conclusion:

The poor prognosis of RIS patients are not due to the previous radiotherapy per se, but related to the unfavourable factors – central tumour site, incomplete surgical remission, microscopic tumour necrosis and the presence of metastases, the two former factors overrepresented in RIS.     

The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study

Background:

The aim of this pilot retrospective study was to investigate the immunohistochemical expression of Cathepsin S (CatS) in three cohorts of colorectal cancer (CRC) patients (n=560).

Methods:

Prevalence and association with histopathological variables were assessed across all cohorts. Association with clinical outcomes was investigated in the Northern Ireland Adjuvant Chemotherapy Trial cohort (n=211), where stage II/III CRC patients were randomised between surgery-alone or surgery with adjuvant fluorouracil/folinic acid (FU/FA) treatment.

Results:

Greater than 95% of tumours had detectable CatS expression with significantly increased staining in tumours compared with matched normal colon (P>0.001). Increasing CatS was associated with reduced recurrence-free survival (RFS; P=0.03) among patients treated with surgery alone. Adjuvant FU/FA significantly improved RFS (hazard ratio (HR), 0.33; 95% CI, 0.12–0.89) and overall survival (OS; HR, 0.25; 95% CI, 0.08–0.81) among 36 patients with high CatS. Treatment did not benefit the 66 patients with low CatS, with a RFS HR of 1.34 (95% CI, 0.60–3.19) and OS HR of 1.33 (95% CI, 0.56–3.15). Interaction between CatS and treatment status was significant for RFS (P=0.02) and OS (P=0.04) in a multivariate model adjusted for known prognostic markers.

Conclusion:

These results signify that CatS may be an important prognostic biomarker and predictive of response to adjuvant FU/FA in CRC.     

Risk of second cancers after the diagnosis of Merkel cell carcinoma in Scandinavia

Background:

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumour of the skin that has been associated with a new tumour virus, the MCC polyomavirus.

Methods:

To investigate whether MCC may have a shared aetiology with other cancers, we investigated the risk of second cancers after the diagnosis of MCC using the national cancer registries in Denmark, Norway and Sweden.

Results:

The overall cancer incidence was increased among patients diagnosed with MCC compared with the general population in these countries (79 secondary cancers total, Standardized Incidence Ratio (SIR) 1.38 (95% confidence interval (CI): 1.10–1.72); 49 secondary cancer in females, SIR 1.7 (95% CI: 1.29–2.25); 30 secondary cancers in males and SIR 1.05 (95% CI: 0.73-1.5)). There were significantly increased incidence ratios for non-melanoma skin cancers (34 secondary cancers, SIR 8.35 (95% CI: 5.97–11.68)), melanoma of skin (6 secondary cancers, SIR 4.29 (95% CI: 1.93–9.56)) and laryngeal cancer (2 secondary cancers, SIR 9.51 (95% CI: 2.38–38)). The SIRs for these three cancer sites were also elevated on restricting the follow-up to cancers occurring at least one year after MCC diagnosis.

Conclusions:

Patients diagnosed with MCC are at increased risk of a second cancer, particularly, other skin cancers. Conceivable explanations include the impact of increased surveillance of the skin and shared causative factors, for example, ultraviolet light exposure or MCC polyomavirus infection.     

High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer

Background:

The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC).

Methods:

The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed.

Results:

Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P=0.0001, P=0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15–4.07; P=0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31–4.13; P=0.0038 and HR: 3.03; 95% CI: 1.67–5.48; P=0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27–3.99; P=0.0053 and HR: 2.97; 95% CI: 1.64–5.38; P=0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99–3.55; P=0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01–3.67; P=0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17–4.33; P=0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS.

Conclusion:

Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC.     

A population-based cohort study on sun habits and endometrial cancer

Background:

No large cohort study has examined the risk of endometrial cancer in relation to sun exposure.

Methods:

A population-based cohort study of 29 508 women who answered a questionnaire in 1990–92, of whom 24 098 responded to a follow-up enquiry in 2000–02. They were followed for an average of 15.5 years.

Results:

Among the 17 822 postmenopausal women included, 166 cases of endometrial cancer were diagnosed. We used a multivariate Cox regression analysis adjusting for age and other selected demographic variables to determine the risk of endometrial cancer. Women using sun beds >3 times per year reduced their hazard risk (HR) by 40% (0.6, 95% confidence interval (CI) 0.4–0.9) or by 50% when adjusting for body mass index or physical activity (HR 0.5, 95% CI 0.3–0.9), and those women who were sunbathing during summer reduced their risk by 20% (HR 0.8 95% CI 0.5–1.5) compared with women who did not expose themselves to the sun or to artificial sun (i.e., sun beds).

Conclusion:

Exposure to artificial sun by the use of sun beds >3 times per year was associated with a 40% reduction in the risk of endometrial cancer, probably by improving the vitamin D levels during winter.     

Risk of liver cancer among US male veterans with cirrhosis, 1969-1996

Background:

Liver cancer incidence rates in the United States have increased for several decades for reasons that are not entirely clear. Regardless of aetiology, cirrhosis is a strong risk factor for liver cancer. As mortality from cirrhosis has been declining in recent decades, it is possible that the risk of liver cancer among persons with cirrhosis has been affected.

Methods:

Data from the US Veterans Affairs medical records database were analysed after adjustment for attained age, race, number of hospital visits, obesity, diabetes, and chronic obstructive pulmonary disease. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated using Cox proportional hazards modelling. Survival analyses were conducted using age as the time metric and incidence of cirrhosis as a time-dependent covariate.

Results:

Among 103 257 men with incident cirrhosis, 788 liver cancers developed. The HR of liver cancer was highest among men with viral-related cirrhosis (HR=37.59, 95% CI: 22.57–62.61), lowest among men with alcohol-related cirrhosis (HR=8.20, 95% CI: 7.55–8.91) and intermediate among men with idiopathic cirrhosis (HR=10.45, 95% CI: 8.52–12.81), when compared with those without cirrhosis. Regardless of cirrhosis type, white men had higher HRs than black men. The HR of developing liver cancer increased from 6.40 (95% CI: 4.40–9.33) in 1969–1973 to 34.71 (95% CI: 23.10–52.16) in 1992–1996 for those with cirrhosis compared with those without.

Conclusion:

In conclusion, the significantly increased HR of developing liver cancer among men with cirrhosis compared with men without cirrhosis in the United States may be contributing to the increasing incidence of liver cancer.     

Prognosis and prognostic factors of patients with mesothelioma: a population-based study

Background:

It is important to regularly update survival estimates of patients with malignant mesothelioma as prognosis may vary according to epidemiologic factors and diagnostic and therapeutic management.

Methods:

We assessed overall (baseline) survival as well as related prognostic variables in a large cohort of 1353 patients with a confirmed diagnosis of malignant mesothelioma between 2005 and 2008.

Results:

About 50% of the patients were 70 years or older at diagnosis and the median latency time since start of asbestos exposure was 49 years. One year after diagnosis, 47% of the patients were alive, 20% after 2 years and 15% after 3 years. Prognostic variables independently associated with worse survival were: older age (HR=1.04 per year 95% CI (1.03–1.06)), sarcomatoid subtype (HR=2.45 95% CI (2.06–2.90)) and non-pleural localisation (HR=1.67 95% CI (1.26–2.22)).

Conclusion:

Survival of patients with malignant mesothelioma is still limited and depends highly on patient age, mesothelioma subtype and localisation. In addition, a substantial part of the patients had a long latency time between asbestos exposure and diagnosis.     

Increased risks of third primary cancers of non-breast origin among women with bilateral breast cancer

Background:

This study examined the risk of third cancer of non-breast origin (TNBC) among women with bilateral breast cancer (BBC; either synchronous or metachronous), focussing on the relation with breast cancer treatment.

Methods:

Risk was assessed, among 8752 Dutch women diagnosed with BBC between 1989 and 2008, using standardised incidence ratios (SIR) and Cox regression analyses to estimate the hazard ratio (HR) of TNBC for different treatment modalities.

Results:

Significant increased SIRs were observed for all TNBCs combined, haematological malignancies, stomach, colorectal, non-melanoma skin, lung, head and neck, endometrial, and ovarian cancer. A 10-fold increased risk was found for ovarian cancer among women younger than 50 years (SIR=10.0, 95% confidence interval (CI)=5.3–17.4). Radiotherapy was associated with increased risks of all TNBCs combined (HR=1.3; 95%CI=1.1–1.6, respectively). Endocrine therapy was associated with increased risks of all TNBCs combined (HR=1.2; 95%CI=1.0–1.5), haematological malignancies (HR=2.0; 95%CI=1.1–3.9), and head and neck cancer (HR=3.3; 95%CI=1.1–10.4). After chemotherapy decreased risks were found for all TNBCs combined (HR=0.63; 95%CI=0.5–0.87).

Conclusion:

Increased risk of TNBC could be influenced by genetic factors (ovarian cancer) or an effect of treatment (radiotherapy and endocrine therapy). More insight in the TNBC risk should further optimise and individualise treatment and surveillance protocols in (young) women with BBC.     

Incidence and survival of childhood bone cancer in northern England and the West Midlands, 1981�C2002

There is a paucity of population-based studies examining incidence and survival trends in childhood bone tumours. We used high quality data from four population-based registries in England. Incidence patterns and trends were described using Poisson regression. Survival trends were analysed using Cox regression. There were 374 cases of childhood (ages 0–14 years) bone tumours (206 osteosarcomas, 144 Ewing sarcomas, 16 chondrosarcomas, 8 other bone tumours) registered in the period 1981–2002. Overall incidence (per million person years) rates were 2.63 (95% confidence interval (CI) 2.27–2.99) for osteosarcoma, 1.90 (1.58–2.21) for Ewing sarcoma and 0.21 (0.11–0.31) for chondrosarcoma. Incidence of Ewing sarcoma declined at an average rate of 3.1% (95% CI 0.6–5.6) per annum (P=0.04), which may be due to tumour reclassification, but there was no change in osteosarcoma incidence. Survival showed marked improvement over the 20 years (1981–2000) for Ewing sarcoma (hazard ratio (HR) per annum=0.95 95% CI 0.91–0.99; P=0.02). However, no improvement was seen for osteosarcoma patients (HR per annum=1.02 95% CI 0.98–1.05; P=0.35) over this time period. Reasons for failure to improve survival including potential delays in diagnosis, accrual to trials, adherence to therapy and lack of improvement in treatment strategies all need to be considered.     

A clinical risk score to predict 3-, 5- and 10-year survival in patients undergoing surgery for Dukes B colorectal cancer

Background:

The prognosis of patients with Dukes stage B colorectal cancer is unpredictable and there is continuing interest in simply and reliably identifying patients at high risk of developing recurrence and dying of their disease. The aim of this study was to devise a clinical risk score to predict 3-, 5- and 10-year survival in patients undergoing surgery for Dukes stage B colorectal cancer.

Methods:

A total of 1350 patients who underwent surgery for Dukes stage B colorectal cancer between 1991 and 1994 in 11 hospitals in Scotland were included in the analysis.

Results:

On follow-up, 926 patients died of whom 479 died of their cancer. At 10 years, cancer-specific survival was 61% and overall survival was 38%. On multivariate analysis, age ⩾75 (hazard ratio (HR) 1.45, 95% confidence interval (CI) 1.15–1.82, P=0.001), emergency presentation (HR 1.59, 95% CI 1.27–1.99, P<0.001) and anastomotic leak (HR 2.17, 95% CI 1.24–3.78, P<0.01) were independently associated with cancer-specific survival in colon cancer. On multivariate analysis, only age ⩾75 (HR 1.58, 95% CI 1.14–2.18, P<0.01) was associated with cancer-specific survival in rectal cancer. Age, presentation and anastomotic leak hazards could be simply added to form a clinical risk score from 0 to 2 in colon cancer. In patients with Dukes B stage colon cancer, the cancer-specific survival at 5 years for patients with a cumulative score 0 was 81%, 1 was 67% and 2 was 63%. The cancer-specific survival rate at 10 years for patients with a clinical risk score of 0 was 72%, 1 was 58% and 2 was 53%.

Conclusion:

The results of this study, in a mature cohort, introduce a new simple clinical risk score for patients undergoing surgery for Dukes B colon cancer. This provides a solid foundation for the examination of the impact of additional factors and treatment on prediction of 3-, 5- and 10-year cancer-specific survival.     

The prognostic influence of tumour-infiltrating lymphocytes in cancer: a systematic review with meta-analysis

Background:

Tumour-infiltrating lymphocytes (TILs) are often found in tumours, presumably reflecting an immune response against the tumour. We carried out a systematic review and meta-analysis, aiming to establish pooled estimates for survival outcomes based on the presence of TILs in cancer.

Methods:

A Pubmed and Embase literature search was designed. Studies were included, in which the prognostic significance of intratumoural CD3+, CD4+, CD8+, and FoxP3+ lymphocytes, as well as ratios between these subsets, were determined in solid tumours.

Results:

In pooled analysis, CD3+ TILs had a positive effect on survival with a hazard ratio (HR) of 0.58 (95% confidence interval (CI) 0.43–0.78) for death, as did CD8+ TILs with a HR of 0.71 (95% CI 0.62–0.82). FoxP3+ regulatory TILs were not linked to overall survival, with a HR of 1.19 (95% CI 0.84–1.67). The CD8/FoxP3 ratio produced a more impressive HR (risk of death: HR 0.48, 95% CI 0.34–0.68), but was used in relatively few studies. Sample size and follow-up time seemed to influence study outcomes.

Conclusion:

Any future studies should be carefully designed, to prevent overestimating the effect of TILs on prognosis. In this context, ratios between TIL subsets may be more informative.     

Clinical significance of stromal apoptosis in colorectal cancer

Background:

Epithelial and stromal cells play an important role in the development of colorectal cancer (CRC). We aimed to determine the prognostic significance of both epithelial and stromal cell apoptosis in CRC.

Methods:

Total apoptosis was determined by caspase-3 activity measurements in protein homogenates of CRC specimens and adjacent normal mucosa of 211 CRC patients. Epithelial apoptosis was determined by an ELISA specific for a caspase-3-degraded cytokeratin 18 product, the M30 antigen. Stromal apoptosis was determined from the ratio between total and epithelial apoptosis.

Results:

Epithelial and stromal apoptosis, as well as total apoptosis, were significantly higher in CRC compared with corresponding adjacent normal mucosa. Low total tumour apoptosis (⩽median caspase-3 activity) was associated with a significantly worse disease recurrence (hazard ratio (HR), 95% confidence interval (95% CI): 1.77 (1.05–3.01)), independent of clinocopathological parameters. Epithelial apoptosis was not associated with clinical outcome. In contrast, low stromal apoptosis (⩽median caspase-3/M30) was found to be an independent prognostic factor for overall survival, disease-free survival and disease recurrence, with HRs (95% CI) of 1.66 (1.17–2.35), 1.62 (1.15–2.29) and 1.69 (1.01–2.85), respectively.

Interpretation:

Stromal apoptosis, in contrast to epithelial apoptosis, is an important factor with respect to survival and disease-recurrence in CRC.     

Lower treatment intensity and poorer survival in metastatic colorectal cancer patients who live alone

Background:

Socioeconomic status (SES) and social support influences cancer survival. If SES and social support affects cancer treatment has not been thoroughly explored.

Methods:

A cohort consisting of all patients who were initially diagnosed with or who developed metastatic colorectal cancer (mCRC, n=781) in three Scandinavian university hospitals from October 2003 to August 2006 was set up. Clinical and socioeconomic data were registered prospectively.

Results:

Patients living alone more often had synchronous metastases at presentation and were less often treated with combination chemotherapy than those cohabitating (HR 0.19, 95% CI 0.04–0.85, P=0.03). Surgical removal of metastases was less common in patients living alone (HR 0.29, 95% CI 0.10–0.86, P=0.02) but more common among university-educated patients (HR 2.22, 95% CI 1.10–4.49, P=0.02). Smoking, being married and having children did not influence treatment or survival. Median survival was 7.7 months in patients living alone and 11.7 months in patients living with someone (P<0.001). Living alone remained a prognostic factor for survival after correction for age and comorbidity.

Conclusion:

Patients living alone received less combination chemotherapy and less secondary surgery. Living alone is a strong independent risk factor for poor survival in mCRC.     

Antenatal maternal bereavement and childhood cancer in the offspring: a population-based cohort study in 6 million children

Background:

Prenatal stress may increase the susceptibility to childhood cancer by affecting immune responses and hormonal balance. We examined whether antenatal stress following maternal bereavement increased the risk of childhood cancer.

Methods:

All children born in Denmark from 1968 to 2007 (N=2 743 560) and in Sweden from 1973 to 2006 (N=3 400 212) were included in this study. We compared cancer risks in children born to women who lost a first-degree relative (a child, spouse, a parent, or a sibling) the year before pregnancy or during pregnancy with cancer risks in children of women who did not experience such bereavement.

Results:

A total of 9795 childhood cancer cases were observed during follow-up of 68 360 707 person years. Children born to women who lost a child or a spouse, but not those who lost other relatives, had an average 30% increased risk of any cancer (hazard ratio (HR) 1.30, 95% confidence interval (CI) 0.96–1.77). The HRs were the highest for non-Hodgkin disease (512 cases in total, HR 3.40, 95% CI 1.51–7.65), hepatic cancer (125 cases in total, HR 5.51, 95% CI 1.34–22.64), and testicular cancer (86 cases in total, HR 8.52, 95% CI 2.03–37.73).

Conclusion:

Our data suggest that severe antenatal stress following maternal bereavement, especially due to loss of a child or a spouse, is associated with an increased risk of certain childhood cancers in the offspring, such as hepatic cancer and non-Hodgkin disease, but not with childhood cancer in general.