Chemotherapy in patients with non-resectable colorectal cancer metastases to the liver: systemic or regional?

Efficacy of the-state-of-the-art modalities of systemic and regional chemo-infusion with oxalyplatin (FOLFOX) and irinotecan (FOLFIRI) (162) was compared. Objective response to the former was 40.8%, to the latter--11.9% (p = 0.0002); survival before intrasplenic relapse--9 and 5 months, respectively, (p = 0.0005); overall survival before relapse (median 7 and 4 months, respectively, (p = 0.01). The rate of survival before intrasplenic relapse in the systemic chemo-infusion group was significantly higher (median 10.5 vs. 8.1 months, respectively, (p = 0.03). No significant differences in overall survival were reported (median 15 vs. 13 months, respectively, in the latter group (p = 0.72).     

Flavonoid intake and liver cancer: a case–control study in Greece

In the context of a case–control study undertaken in Greece, we examined the role of six flavonoid classes in the etiology of hepatocellular carcinoma (HCC), by viral status, and of cholangiocarcinoma (CAC). Data and blood samples were collected between 1995 and 1998. Information about dietary intakes and covariates, including chronic infection with hepatitis B (HBV) and C (HCV) virus, were available for 250 HBV and/or HCV positive HCC cases, 83 HBV and HCV negative HCC cases, six CAC cases, and 360 hospital controls. In logistic regression models including gender, age, education, tobacco smoking, and total energy intake, there were no distinct patterns with respect to either HCC virus positive and HCC virus negative in relation to total flavonoids or any class of flavonoids, with the exception of flavones. Flavone intake, mostly derived from spinach and peppers, was inversely associated with both virus positive (P-trend, 0.049) and virus negative (P-trend, 0.084) HCC. There was also a suggestion of an inverse association of CAC with flavan-3-ols, anthocyanidins, and total flavonoids which, however, has to be taken with due caution on account of the small number of cases of this rare tumor. We conclude that flavones may be inversely associated with HCC risk, irrespective of its dominant etiology (viral or non viral).     

Management of colorectal cancer patients after resection of liver metastases: can we offer a tailored treatment?

Surgical resection remains the only option of cure for patients with colorectal liver metastases, and no patient should be precluded from surgery. There is much controversy not only regarding the most appropriate therapeutic approach in the neoadjuvant setting but also after surgery is performed. Many patients will experience early relapses but others will be long survivors. We need to establish reliable prognostic and predictive factors to offer a tailored treatment. Several prognostic factors after metastasectomy have been identified: high C-reactive protein levels, a high neutrophil-lymphocyte ratio, elevated neutrophil count and low serum albumin are related to a worst outcome. Elevated CEA and Ki 67 levels, intrahepatic and perihepatic lymph node invasion are also some of the markers related to a worst outcome. In contrast, the administration of preoperative chemotherapy has been associated with a better prognosis after hepatectomy. The administration of adjuvant chemotherapy should be done taking in consideration these factors. Regarding predictive factors, determination of ERCC1, TS, TP and DPD and UGT1 polymorphisms assessment could be considered prior to chemotherapy administration. This would avoid treatment related toxicities and increase this population quality of life.     

Biomarker-based prediction of inflammatory bowel disease-related colorectal cancer: a case–control study

Background

Regular colonoscopic surveillance for detection of dysplasia is recommended in longstanding inflammatory bowel disease (IBD), however, its sensitivity is disputed. Screening accuracy may increase by using a biomarker-based surveillance strategy.

Methods

A case-control study was performed to determine the prognostic value of DNA ploidy and p53 in IBD-related neoplasia. Cases with IBD-related colorectal cancer (CRC), detected in our surveillance program between 1985-2008, were selected and matched with two controls, for age, gender, disease characteristics, interval of follow-up, PSC, and previous surgery. Biopsies were assessed for DNA ploidy, p53, grade of inflammation and neoplasia. Progression to neoplasia was analyzed with Cox regression analysis, adjusting for potentially confounding variables.

Results

Adjusting for age, we found statistically significant Hazard ratios (HR) between development of CRC, and low grade dysplasia (HR5.5; 95%CI 2.6-11.5), abnormal DNA ploidy (DNA index (DI) 1.06-1.34, HR4.7; 95%CI 2.9-7.8 and DI>1.34, HR6.6; 95%CI 3.7-11.7) and p53 immunopositivity (HR3.0; 95%CI 1.9-4.7) over time. When adjusting for all confounders, abnormal DNA ploidy (DI 1.06-1.34, HR4.7; 95%CI 2.7-7.9 and DI>1.34, HR5.0; 95%CI 2.5-10.0) and p53 immunopositivity (HR1.7; 95%CI 1.0-3.1) remained statistically significant predictive of neoplasia.

Conclusion

In longstanding IBD, abnormal DNA ploidy and p53 immunopositivity are important risk factors of developing CRC. The yield of surveillance may potentially increase by adding these biomarkers to the routine assessment of biopsies.     

Risk factors for hepatocellular carcinoma in patients with chronic liver disease: a case–control study

The majority of data on risk factors (RFs) for hepatocellular carcinoma (HCC) comes from studies involving populations without underlying liver disease. It is important to evaluate RFs for HCC in patients with chronic liver disease since HCC rarely occurs in those without underlying liver disease. We conducted a hospital-based case-control study of 259 incident HCC cases and 781 controls by convenience sampling between 02/2001 and 12/2009 from the liver clinic at Stanford University Medical Center. The study population was 41% White, 14% Hispanic, 3% African American, 40% Asian American, and 2% other race/ethnicity. RFs were examined through medical records and an in-person questionnaire. Alcohol and tobacco use was calculated by cumulative grams of alcohol or cumulative pack(s) of cigarette consumed over one's lifetime. Diabetes mellitus (DM) was defined by random glucose level of ≥200?mg/dL. RFs were evaluated using multivariate logistic regression. Independent predictors of HCC risk, after mutual adjustment and additional control for alcohol use, etiology of liver diseases, and DM, included age >40 (OR?=?8.5 [2.6-28.3]), male gender (OR?=?3.5 [2.2-5.8]), presence of cirrhosis (OR?=?2.8 [1.6-4.9]), Asian ethnicity (OR?=?2.8 [1.8-4.6]), AFP?>?50 (OR?=?4.2 [2.6-6.8]), and cumulative lifetime tobacco use of >11,000 packs (OR?=?1.7 [1.0-2.9]). Heavy prolonged cigarette smoking, but not alcohol use, was a significant independent predictor for HCC in patients with underlying liver disease. Besides older age, male gender, presence of cirrhosis, and elevated AFP, Asian ethnicity and heavy cumulative tobacco use are strong independent predictors of HCC.     

Hepatic arterial 5-fluorouracil in patients with liver metastases of colorectal?cancer: Single-centre experience in 145 patients

Background:Hepatic arterial chemotherapy for liver metastases ofcolorectal cancer is still under discussion. Mainly because of the technicalcomplications of this mode of treatment and the lack of a survival benefit inrandomized studies. We performed an analysis of hepatic arterial5-fluorouracil (5-FU) chemotherapy in 145 consecutive patients treated at asingle institution. Patients and methods:One hundred forty-five patients withinoperable liver metastases from colorectal cancer were included. 5-FU, 1000mg/m²/day continuous infusion for five days every three weeks, wasdelivered in the hepatic artery by percutaneous catheter or arterial accessdevice. Results:The response rate was 34% for all patients,40% in patients with extrahepatic disease, and 15% in patientswith i.v. 5-FU-based pretreatment. TTP and OS for all patients were 7.5 and14.3 months, respectively. In patients with extrahepatic disease or i.v.5-FU-based pretreatment, OS was significantly shorter compared to patientswithout extrahepatic disease or 5-FU-based pretreatment (9.7 vs. 19.3 monthsand 10.1 vs. 17.4 months, respectively). forty-seven percent of patientsstopped treatment because of a complication. Complications most often seen inpatients with arterial ports were hepatic artery thrombosis (48%) anddislocation of the catheter (22%). Conclusions:The results of our analysis are in line with previousphase III studies. Extrahepatic disease and i.v. 5-FU-based pretreatment wereprognostic for reduced OS. The complication rate of hepatic arterial deliverywas worrisome, although, no negative impact on survival could be established.There is a strong need for improvement of hepatic arterial delivery methodsbefore further evaluation of hepatic arterial 5-FU will be worthwhile.     

Low serum levels of vitamin D in metastatic cancer patients: a case–control study

We aimed to elucidate whether serum VEGFR2 concentration before and after transarterial chemoembolization (TACE) can predict survival in patients with unresectable hepatocellular carcinoma (HCC). Serum VEGFR2 concentrations were serially measured in 169 patients with advanced HCC before and after TACE. We defined a decrease in the serum VEGFR2 level >10 % from the pretreatment level as response. Serum VEGFR2 concentrations decreased in 44 (26.0 %) patients at week 4. Patients who had a VEGFR2 response at week 4 had a longer median survival than those who did not have a VEGFR2 decrease (19.0 vs. 9.8 months, p < 0.001). Clinical variables associated with OS in addition to VEGFR2 response also included extrahepatic metastases (p = 0.005) and vascular invasion (p = 0.035). VEGFR2 decrease after TACE (p = 0.012) and presence of extrahepatic metastases (p = 0.02) were independently associated with OS by multivariate analysis. A serum VEGFR2 concentration decrease at 4 weeks after TACE may predict favorable overall survival in patients with advanced HCC.     

Early detection of cancer in the general population: a blinded case–control study of p53 autoantibodies in colorectal cancer

Background:

Recent reports from cancer screening trials in high-risk populations suggest that autoantibodies can be detected before clinical diagnosis. However, there is minimal data on the role of autoantibody signatures in cancer screening in the general population.

Methods:

Informative p53 peptides were identified in sera from patients with colorectal cancer using an autoantibody microarray with 15-mer overlapping peptides covering the complete p53 sequence. The selected peptides were evaluated in a blinded case–control study using stored serum from the multimodal arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening where women gave annual blood samples. Cases were postmenopausal women who developed colorectal cancer following recruitment, with 2 or more serum samples preceding diagnosis. Controls were age-matched women with no history of cancer.

Results:

The 50 640 women randomised to the multimodal group were followed up for a median of 6.8 (inter-quartile range 5.9–8.4) years. Colorectal cancer notification was received in 101 women with serial samples of whom 97 (297 samples) had given consent for secondary studies. They were matched 1 : 1 with 97 controls (296 serial samples). The four most informative peptides identified 25.8% of colorectal cancer patients with a specificity of 95%. The median lead time was 1.4 (range 0.12–3.8) years before clinical diagnosis.

Conclusion:

Our findings suggest that in the general population, autoantibody signatures are detectable during preclinical disease and may be of value in cancer screening. In colorectal cancer screening in particular, where the current need is to improve compliance, it suggests that p53 autoantibodies may contribute towards risk stratification.     

A case–control study of non-alcoholic fatty liver disease in breast cancer

Background Patients with breast cancer sometimes present with increased liver enzymes during follow-up period that may be consistent with hepatic steatosis. This effect known as non-alcoholic fatty liver disease may be associated with the malignancy itself, drugs or some other well-known risk factors that may induce steatosis. We studied the influences of primary disease and treatment on steatosis in patients with breast cancer. Materials and methods There were four groups of patients in our study. Group 1: 40 newly diagnosed, previously untreated breast cancer; Group 2: 45 cases of breast cancer treated with systemic therapy; Group 3: 40 cases of ovarian cancer; Group 4: 40 healthy women. Hepatic steatosis was evaluated by sonography by two radiologist, independently. We also evaluated major risk factors, biochemical findings, and influences of treatment on hepatic steatosis. Results We detected steatosis in 63%, 72%, 77%, and 48% of patients in groups 1, 2, 3, and 4, respectively. There was a statistically significant difference only between groups 3 and 4 (P = 0.045). However, grade 2 and 3 steatosis were more frequent in breast cancer patients (group 1 and 2), compared with mild steatosis in ovarian cancer patients and healthy women. Although a good correlation was found between tamoxifen use and chemotherapy on development of non-alcoholic fatty liver disease, no association of hepatic steatosis with transaminase levels was found, which might be of help for earlier detection of steatosis. AST/ALT ratio was found to have no impact on the rate of hepatic steatosis, contrary to the literature. Conclusion Hepatic steatosis, excluding patients with grade 1 steatosis, which may be a normal variant, were more readily detected in patients with breast cancer. This effect was aggravated by use of tamoxifen, but not the chemotherapy. Non-alcoholic fatty liver disease in patients with breast cancer may be associated with the primary tumor itself or some well-known risk factors such as obesity, hyperlipidemia, and diabetes mellitus, which needs to be explored.     

Severe hepatic sinusoidal obstruction and oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer: a real entity?

We have read with interest the study of Rubbia-Brandt et al.[1] entitled ‘Severe hepatic sinusoidal obstruction associatedwith oxaliplatin-based chemotherapy in patients with metastaticcolorectal cancer’. In this study, the investigators identifiedin the specimens from liver resection for colorectal metastases,some histological lesions of the non-tumoral liver parenchymaattributed to oxaliplatin-based chemotherapy. The results ofthis study     

Cigarette smoking and primary liver cancer: a population-based case–control study in US men

Objective Using the case–control data from the Selected Cancers Study, the authors assessed whether cigarette smoking increases the risk of primary liver cancer in the US. Methods Cases were men who were pathologically diagnosed with primary liver cancer during 1984–1988, were 31–59 years old, and lived in the areas covered by eight US cancer registries (n = 168). Controls were men without a history of primary liver cancer who were selected by random-digit telephone dialing (n = 1910). Results Relative to non-smokers, the risks of liver cancer were 1.85 (95% confidence interval (CI), 1.05–3.25) and 1.49 (95% CI, 0.83–2.68) for former and current smokers, respectively. The adjusted odds ratio (OR) estimates were 0.96, 1.43, 1.80, and 1.87 for smoking for less than 15, 15–24, 25–34 and 35 or more years, respectively (p for trend = 0.039). The OR estimates were 1.41 (95% CI, 0.74–2.68), 1.67 (95% CI, 0.93–2.98), and 1.83 (95% CI, 0.89–3.76) for less than 1, 1–2, and 2 or more packs smoked per day (p for trend = 0.068). Conclusions Cigarette smoking may be a factor that contributes somewhat to the occurrence of primary liver cancer among men in the United States, a country with low risk of liver cancer.     

Impact of neutropenia on the outcomes of critically ill patients with cancer: a matched case–control study

BackgroundThe prognostic effect of neutropenia in cancer patients admitted to intensive care units (ICUs) was addressed exclusively in cohort studies with conflicting results. Our aim was to address this question using a matched case–control study.Patients and methodsNinety-four neutropenic patients and 94 non-neutropenic controls were matched for age, cancer type, Simplified Acute Physiology Score II, Sequential Organ Failure Assessment score, and need for mechanical ventilation and vasopressors. Conditional logistic regression was used to identify factors associated with hospital mortality.ResultsThe ICU (66% versus 66%, P = 0.999) and hospital (73% versus 78%, P = 0.611) mortality rates were similar in neutropenic and non-neutropenic patients. Adjusting for the type of admission and length of hospital stay before ICU admission, the characteristics associated with increased mortality were the severity of acute disease and organ failures, compromised performance status and sepsis diagnosis. The impact of both previous chemotherapy and neutropenia on the outcomes was not significant.ConclusionsUsing a matched case–control study design, our results provide additional evidence that the presence of neutropenia is no longer associated with worse outcomes in critically ill patients with cancer. Moreover, our results also corroborate that recent exposure to chemotherapy is not associated with increased risk for death.     

Leukocyte telomere length in a population-based case–control study of ovarian cancer: a pilot study

Objectives

Telomeres are structures at chromosome ends that contribute to maintaining genomic integrity. Telomere shortening with repeated cell divisions may lead to genomic instability and carcinogenesis. Studies suggest that shorter telomeres in constitutional DNA are associated with bladder, breast, lung, and renal cancer. Ovarian cancer tissues also have shortened telomeres and increased telomerase activity, suggesting that telomere abnormalities may be related to ovarian cancer.

Methods

We investigated leukocyte telomere length in 99 women with serous ovarian adenocarcinoma and 100 age-matched cancer-free controls enrolled in a population-based case–control study.

Results

Cases tended to have shorter telomeres than controls (P _wilcoxon = 0.002). Compared to subjects with telomere lengths in the longest tertile, those in the middle and shortest tertiles showed respective age-adjusted odds ratios (95% confidence intervals) of 2.69 (1.23–5.88) and 3.39 (1.54–7.46) (P _trend = 0.002). Strongest associations were found for subjects with poorly differentiated carcinomas (OR = 4.89, 95% CI 1.93–12.34).

Conclusions

This study shows that short leukocyte telomeres are associated with serous ovarian adenocarcinoma. These findings should be confirmed in large, prospective studies.     

Breast cancer risk in women with a primary ovarian cancer—a case–control study

Register-based studies show that women with ovarian cancer are at increased risk of developing breast cancer. Primary suggested explanations are heredity factors and a common hormonal aetiology. However, clinical surveillance that is provided for cancer patients during, and after, treatment of their primary malignancies together with possible mistakes in the registering procedures could affect the risk estimates. In order to examine these factors in women registered with ovarian cancer who develop subsequent breast cancer, a case–control study was performed. Using a regional Swedish cancer registry including 5060 women registered with ovarian cancer, 89 cases of breast cancer were found. After corrections for discrepancies in the registered and recorded information, 75 cases remained, of which 72 cases were included in the study. Information concerning possible risk factors were extracted from hospital records and compared with 177 matched controls. Suggested risk factors such as parity (relative risk (RR)=1.41), late age at menopause (52–61 years; RR=1.61) and heredity for breast and/or ovarian cancer (RR=1.50) were all connected with a non-significant increased risk of subsequent breast cancer. In all, 43% of the breast cancer cases were revealed without preceding symptoms at clinical follow-up, indicating that increased clinical surveillance is a factor of importance when explaining the increased risk. The fact that only 75 (missing records included) out of the 89 registered breast cancer cases could be linked to the preceding ovarian cancer indicates that the actual risk of developing breast cancer is smaller than previously described. The clinical implications from these findings could be that, beside general screening programmes and health controls offered to women in cancer-prone families, additional mammography examinations based on the assumption of an increased risk of breast cancer are not warranted in ovarian cancer patients.     

MR imaging features associated with distant metastasis-free survival of patients with invasive breast cancer: a case–control study

Purpose

Preoperative breast magnetic resonance (MR) imaging features of primary breast cancers may have the potential to act as prognostic biomarkers by providing morphologic and kinetic features representing inter- or intra-tumor heterogeneity. Recent radiogenomic studies reveal that several radiologist-annotated image features are associated with genes or signal pathways involved in tumor progression, treatment resistance, and distant metastasis (DM). We investigate whether preoperative breast MR imaging features are associated with worse DM-free survival in patients with invasive breast cancer.

Methods

Of the 3536 patients with primary breast cancers who underwent preoperative MR imaging between 2003 and 2009, 147 patients with DM were identified and one-to-one matched with control patients (n = 147) without DM according to clinical–pathologic variables. Three radiologists independently reviewed the MR images of 294 patients, and the association of DM-free survival with MR imaging and clinical–pathologic features was assessed using Cox proportional hazard models.

Results

Of MR imaging features, rim enhancement (hazard ratio [HR], 1.83 [95% confidence interval, CI 1.29, 2.51]; p = 0.001) and peritumoral edema (HR, 1.48 [95% CI 1.03, 2.11]; p = 0.032) were the significant features associated with worse DM-free survival. The significant MR imaging features, however, were different between breast cancer subtypes and stages.

Conclusion

Preoperative breast MR imaging features of rim enhancement and peritumoral edema may be used as prognostic biomarkers that help predict DM risk in patients with breast cancer, thereby potentially enabling improved personalized treatment and monitoring strategies for individual patients.

     

Bevacizumab+chemotherapy versus chemotherapy alone in elderly patients with untreated metastatic colorectal cancer: a randomized phase II trial—PRODIGE 20 study results

BackgroundMetastatic colorectal cancer frequently occurs in elderly patients. Bevacizumab in combination with front line chemotherapy (CT) is a standard treatment but some concern raised about tolerance of bevacizumab for these patients. The purpose of PRODIGE 20 was to evaluate tolerance and efficacy of bevacizumab according to specific end points in this population.Patients and methodsPatients aged 75 years and over were randomly assigned to bevacizumab + CT (BEV) versus CT. LV5FU2, FOLFOX and FOLFIRI regimen were prescribed according to investigator’s choice. The composite co-primary end point, assessed 4 months after randomization, was based on efficacy (tumor control and absence of decrease of the Spitzer QoL index) and safety (absence of severe cardiovascular toxicities and unexpected hospitalization). For each arm, the treatment will be consider as inefficient if 20% or less of the patients met the efficacy criteria and not safe if 40% or less met the safety criteria.ResultsAbout 102 patients were randomized (51 BEV and 51 CT), median age was 80 years (range 75–91). Primary end point was met for efficacy in 50% and 58% and for safety in 61% and 71% of patients in BEV and CT, respectively. Median progression-free survival was 9.7 months in BEV and 7.8 months in CT. Median overall survival was 21.7 months in BEV and 19.8 months in CT. The 36-month overall survival rate was 27% in BEV and 10.1% in CT. Severe toxicities grade 3/4 were mainly non-hematologic toxicities (80.4% in BEV, 63.3% in CT).ConclusionBevacizumab combined with CT was safe and efficient. Both arms met the primary safety and efficacy criteria.     

Risk factors for early-onset colorectal cancer: a population-based case–control study in Ontario,Canada

Cancer Causes & Control - There has been an alarming increase in colorectal cancer (CRC) incidence among young adults aged?&lt;?50&nbsp;years, and factors driving this...     

Nutrient dietary patterns and the risk of colorectal cancer: a case–control study from Italy

Objective

The role of diet on colorectal cancer has been considered in terms of single foods and nutrients, but less frequently in terms of dietary patterns.

Methods

Data were derived from an Italian case–control study, including 1,225 subjects with cancer of the colon, 728 subjects with rectal cancer, and 4,154 hospital controls. We identified dietary patterns on a selected set of nutrients through principal component factor analysis. Odds ratios (OR) and 95% confidence intervals for both cancers were estimated using unconditional multiple logistic regression.

Results

We identified 5 major dietary patterns. Direct associations were observed between the Starch-rich pattern and both cancer of the colon (OR = 1.68) and of the rectum (OR = 1.74). Inverse relationships were found between the Vitamins and fiber pattern and rectal cancer (OR = 0.61), between the Unsaturated fats (animal source) and the Unsaturated fats (vegetable source) and cancer of the colon (OR = 0.80 and OR = 0.79, respectively). No other significant association was found.

Conclusions

The Starch-rich pattern is potentially an unfavorable indicator of risk for both colon and rectal cancer, whereas the Vitamins and fiber pattern is associated with a reduced risk of rectal cancer and the Unsaturated fats patterns with a reduced risk of colon cancer.