Perceived cognitive impairment in people with colorectal cancer who do and do not receive chemotherapy

Purpose

Cognitive symptoms are common after cancer, but poorly associated with neuropsychological results. We previously reported colorectal cancer (CRC) patients had more cognitive impairment than controls. Here, we explore relationships between cognitive symptoms and neuropsychological domains.

Methods

Subjects with CRC (N = 362) and 72 healthy controls completed neuropsychological assessments and Functional Assessment of Cancer Therapy-Cognition (FACT-COG) at baseline (pre-chemotherapy) and 6, 12, and 24 months. Associations between neuropsychological and FACT-COG scores were explored: perceived cognitive impairment (PCI), perceived cognitive ability (PCA), impact of PCI on quality of life (CogQOL).

Results

Of 362 CRC subjects, 289 had loco-regional disease and 173 received chemotherapy (CTh+). At baseline, groups did not differ on total FACT-COG, PCI, or PCA scores. All scores, except PCA, were worse at 6 months in CTh+. CRC patients not receiving chemotherapy did not differ from controls on FACT-COG domains. PCA associated weakly (r = 0.28–0.34) with attention/executive function, visual memory, and global deficit score. There was no association between PCI and neuropsychological domains. Fatigue, anxiety/depression, and poorer quality of life were associated with PCI and CogQOL (r = 0.44–0.51) in CRC patients.

Conclusions

No association was seen between total FACT-COG or PCI, and neuropsychological domains. A weak-moderate association was found between PCA and attention/executive function and visual memory.

Trial registration

The study was registered with clinicaltrials.gov (trial registration: NCT00188331).

Implications for cancer survivors

Cognitive symptoms are associated with fatigue, anxiety/depression, and poorer quality of life, and do not appear to be related to actual cognitive performance. Rates were lower than that reported in breast cancer survivors. Cognitive symptoms were greatest in those who received chemotherapy, with no significant difference between the non-chemotherapy survivors and healthy controls.

     

Change in cognitive function after chemotherapy: a prospective longitudinal study in breast cancer patients

Some breast cancer survivors experience cognitive decline following chemotherapy. We prospectively examined changes in cognitive performance among high-risk breast cancer patients who had received high-dose chemotherapy with cyclophosphamide, thiotepa, and carboplatin (CTC group; n = 28) or standard-dose chemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide (FEC group; n = 39); stage-I breast cancer patients who had received no systemic chemotherapy (no-CT group; n = 57); and healthy control subjects (n = 60). All patients underwent neuropsychologic testing before and 6 months after treatment (12-month interval); control subjects underwent repeated testing over a 6-month interval. No differences in cognitive functioning between the four groups were observed at the first assessment. More of the CTC group than the control subjects experienced a deterioration in cognitive performance over time (25% versus 6.7%; odds ratio [OR] = 5.3, 95% confidence interval [CI] = 1.3 to 21.2, P = .02). No such difference was observed for the FEC or the no-CT groups (FEC versus control: OR = 2.2, 95% CI = 0.5 to 9.1, P = .27; no-CT versus Control: OR = 2.2, 95% CI = 0.6 to 8.0; P = .21). Some cytotoxic treatment for breast cancer affects cognition in a subset of women.     

Statins and colorectal cancer risk: a longitudinal study

Purpose

Studies evaluating the association between statins and colorectal cancer (CRC) have used various methods to address bias and have reported mixed findings. We sought to assess the association in a large cohort of residents in Emilia-Romagna, Italy, using multiple methods to address different sources of confounding. We also sought to explore potential effect measure modification by sex.

Methods

We conducted a retrospective cohort study using the 2003–2010 healthcare database of Emilia-Romagna, Italy. We identified all initiators of statins; initiators of glaucoma medications served as the comparison group to account for confounding by healthy user bias. We followed patients longitudinally to identify CRC cases in hospital discharge data. We used multivariable Cox regression analyses to adjust for confounding by CRC risk factors and we conducted a sensitivity analysis using propensity score matching.

Results

After multivariable adjustment, initiators of statins had a lower incidence rate of CRC as compared to initiators of glaucoma drugs [hazard ratio (HR) 0.79; 95 % CI 0.69–0.90]. In sex-stratified analyses we observed a protective effect in men (HR 0.77; 95 % CI 0.67–0.88) but not in women (HR 0.96; 95 % CI 0.82–1.1). Results were similar in propensity score analyses.

Conclusions

After adjusting for observed risk factors, statin initiation versus glaucoma drug initiation was associated with a reduced risk of CRC in men but not in women. While this study is subject to many limitations, it corroborates a previous study that found sex differences in the association between statins and CRC.     

Clinical features of oral chemotherapy: results of a longitudinal prospective study of breast and colorectal cancer patients receiving capecitabine in the UK

BREARLEY S.G., CRAVEN O., SAUNDERS M., SWINDELL R. & MOLASSIOTIS A. (2010) European Journal of Cancer Care
Clinical features of oral chemotherapy: results of a longitudinal prospective study of breast and colorectal cancer patients receiving capecitabine in the UK The aim was to describe the clinical sequelae of patients treated with capecitabine in terms of adverse events, treatment modifications and therapy cessation throughout the treatment trajectory. A total of 1232 toxicity assessments were undertaken on colorectal and breast cancer patients receiving palliative and adjuvant treatment prior to treatment and at days 7, 14 and 21 for six cycles of chemotherapy. Most common adverse events were diarrhoea, nausea, palmar‐plantar erythrodysesthesia (PPE), fatigue and pain which were experienced by over 80% of subjects. Grades 2 and 3 adverse events were common (n= 916 and n= 113) but their development into grade 4 was uncommon (n= 2). There was a downward trend in the percentage incidence of toxicity; however, PPE increased. Almost 60% of subjects completed six cycles, or planned treatment. Some 40% of subjects commenced treatment on a dose reduction (<1250 mg/m²), and this increased to 70% at cycle 6. In total, 2.8–11.6% of subjects experienced toxicity‐related treatment deferrals. While adverse events are common with capecitabine the lack of grade 4 adverse events support the efficacy of current clinical management strategies. The deferral and dose reduction data indicate that cycles 1 and 2 are important and require careful management and clinical interventions in order to prevent high‐grade adverse events.     

Choosing chemotherapy in patients with advanced urothelial cell cancer who are unfit to receive cisplatin-based chemotherapy

Transitional cell carcinoma of the urothelial tract is the second most common cancer of the genitourinary system and the fifth most common cancer in Western countries with more than 300,000 new cases per year worldwide. Following the introduction of cisplatin-based chemotherapy, median overall survival in patients with metastatic disease has doubled, demonstrating chemotherapy as an important treatment modality in advanced or metastatic disease. Patients 'unfit' to receive cisplatin-based chemotherapy are characterized by impaired renal function, impaired performance status, and/or comorbidity that preclude the use of cisplatin. In this review we summarize the different chemotherapeutic schemes, focusing on treatment options in cisplatin 'unfit' patients.     

Many men with castrate-sensitive metastatic prostate cancer should not receive chemotherapy

Criticism of ESMO prostate cancer guidelines     

Fatigue in advanced cancer: a prospective controlled cross-sectional study

Uncontrolled studies have reported that fatigue is a common symptom among patients with advanced cancer. It is also a frequent complaint among the general population. Simply asking cancer patients whether or not they feel fatigued does not distinguish between the 'background' level of this symptom in the community and any 'excess' arising as a result of illness. The aim of this study was to determine the prevalence of fatigue among palliative care inpatients in comparison with a control group of age and sex-matched volunteers without cancer. In addition, the correlates of fatigue were investigated. The prevalence of 'severe subjective fatigue' (defined as fatigue greater than that experienced by 95% of the control group) was found to be 75%. Patients were malnourished, had diminished muscle function and were suffering from a number of physical and mental symptoms. The severity of fatigue was unrelated to age, sex, diagnosis, presence or site of metastases, anaemia, dose of opioid or steroid, any of the haematological or biochemical indices (except urea), nutritional status, voluntary muscle function, or mood. A multivariate analysis found that fatigue severity was significantly associated with pain and dypnoea scores in the patients, and with the symptoms of anxiety and depression in the controls. The authors conclude that subjective fatigue is both prevalent and severe among patients with advanced cancer. The causes of this symptom remain obscure. Further work is required in order to determine if the associations reported between fatigue and pain and between fatigue and dyspnoea are causal or coincidental.     

Clinical significance of evaluating primary lesions in patients with gastric cancer who receive chemotherapy

Background  

In Western countries, the response of gastric cancer to chemotherapy is evaluated by assessing measurable metastatic lesions (MMLs) according to the response evaluation criteria in solid tumors (RECIST). In Japan, the response of primary lesions is assessed according to local Japanese criteria. We compared the response to chemotherapy as evaluated by these two sets of criteria.     

Fatigue and relating factors in high-risk breast cancer patients treated with adjuvant standard or high-dose chemotherapy: a longitudinal study.

PURPOSE: Determine whether standard or high-dose chemotherapy leads to changes in fatigue, hemoglobin (Hb), mental health, muscle and joint pain, and menopausal status from pre- to post-treatment and to evaluate whether fatigue is associated with these factors in disease-free breast cancer patients. PATIENTS AND METHODS: Eight hundred eighty-five patients were randomly assigned between two chemotherapy regimens both followed by radiotherapy and tamoxifen. Fatigue was assessed using vitality scale (score < or = 46 defined as fatigue), poor mental health using mental health scale (score < or = 56 defined as poor mental health) both of Short-Form 36, muscle and joint pain with Rotterdam Symptom Checklist, and Hb levels were assessed before and 1, 2, and 3 years after chemotherapy. RESULTS: Fatigue was reported in 20% of 430 assessable patients (202 standard-dose, 228 high-dose) with at least a 3-year follow-up, without change over time or difference between treatment arms. Mean Hb levels were lower following high-dose chemotherapy. Only 5% of patients experienced fatigue and anemia. Mental health score was the strongest fatigue predictor at all assessment moments. Menopausal status had no effect on fatigue. Linear mixed effect models showed that the higher the Hb level (P = .0006) and mental health score (P < .0001), the less fatigue was experienced. Joint (P < .0001) and muscle pain (P = .0283) were associated with more fatigue. CONCLUSION: In 3 years after treatment, no significant differences in fatigue were found between standard and high-dose chemotherapy. Fatigue did not change over time. The strongest fatigue predictor was poor mental health.     

Adjuvant treatments do not alter the quality of life in elderly patients with colorectal cancer: a population-based study

BACKGROUND.

The current study was performed to longitudinally assess the impact of adjuvant treatments on the quality of life (QoL) of elderly colorectal cancer survivors.

METHODS.

The Burgundy Digestive Cancer Registry was used to select all patients aged ≥75 years who were diagnosed with colorectal cancer between 2003 and 2005. A total of 209 patients were asked to complete questionnaires during the first year after diagnosis: at the time of inclusion in the study (Q0), at 3 months after the initial diagnosis (Q3), at 6 months after the initial diagnosis (Q6), and at 12 months after the initial diagnosis (Q12) using the European Organization for Research and Treatment of Cancer (EORTC) QLQ‐C30. A total of 125 patients (60%) responded. Mixed model analyses of variance for repeated measurement were used to compare QoL scores according to therapeutic schemes. Interactions between time of follow‐up and treatment were tested.

RESULTS.

Patient sex, age, location of the tumor, and TNM stage of disease did not appear to differ significantly between respondents and nonrespondents. Global Health and Emotional Functioning improved for colon cancer survivors between Q0 and Q12, and were noted to improve between Q3 and Q12 for rectal cancer patients. According to French recommendations, patients who received chemotherapy for stage III colon cancer (P = .176) or radiotherapy for rectal cancer (P = .959) reported no significant changes in Global Health compared with those patients not receiving adjuvant therapies. Patients treated with chemotherapy reported better Physical Functioning than patients who did not received chemotherapy (P = .0113).

CONCLUSIONS.

To the authors' knowledge, the current study is the first to examine trends over time with regard to the influence of adjuvant treatments for colon and rectal cancers on QoL in a general aged population. Providing evidence that adjuvant chemotherapy for colon cancer has no negative impact on the QoL of elderly patients is of great significance in encouraging clinicians to treat this population. Cancer 2008. © 2008 American Cancer Society.     

A tool for predicting breast carcinoma mortality in women who do not receive adjuvant therapy

BACKGROUND: Among the several proposed risk classification schemes for predicting survival in women with breast carcinoma, one of the most commonly used is the Nottingham Prognostic Index (NPI). The goal of the current study was to use a continuous prognostic model (similar to those that have already been demonstrated to possess greater predictive accuracy than risk group-based models in other malignancies) to predict breast carcinoma mortality more accurately compared with the NPI. METHODS: A total of 519 women who had been treated with mastectomy and axillary lymph node dissection at Memorial Sloan-Kettering Cancer Center (New York, NY) between 1976 and 1979 met the following requirements for study inclusion: confirmation of the presence of invasive mammary carcinoma, no receipt of neoadjuvant or adjuvant systemic therapy, no previous history of malignancy, and negative lymph node status as assessed on routine histopathologic examination. Paraffin blocks were available for 368 of the 519 eligible patients. All available axillary lymph node tissue blocks were subjected to enhanced pathologic analysis. The competing-risk method was used to predict disease-specific death, and the accuracy of the novel prognostic model that emerged from this process was evaluated using the concordance index. Jackknife and 10-fold cross-validation predictions yielded by this new model were compared with predictions yielded by the NPI. RESULTS: Of the 348 women for whom complete data were available, 73 died of disease; the 15-year probability of breast carcinoma-related death was 20%. On the basis of these 348 cases, the authors developed a prognostic model that took patient age, disease multifocality, tumor size, tumor grade, lymphovascular invasion, and enhanced lymph node staining into account, and using competing-risks regression analysis, they found that this new model predicted disease-specific death more accurately compared with the NPI. CONCLUSIONS: The authors have developed a model for predicting breast carcinoma-specific death with improved accuracy. This tool should be useful in counseling patients with regard to their specific need for adjuvant therapy.     

High Ki67 predicts unfavourable outcomes in early breast cancer patients with a clinically clear axilla who do not receive axillary dissection or axillary radiotherapy

AimAxillary dissection is increasingly forgone in early breast cancer patients with a clinically negative axilla. The GRISO 053 randomised trial recruited 435 patients of age over 45 years, tumour ?1.4 cm and clinically negative axilla, to assess the importance of axillary radiotherapy versus no axillary radiotherapy in patients not given axillary dissection. In the present study on a subgroup GRISO cases our aim was to assess the prognostic importance of tumour biological factors after more than 10 years of follow-up.MethodsWe retrospectively assessed biological factors in a subgroup of 285 GRISO cases (145 given axillary radiotherapy; 140 not given axillary radiotherapy) with complete biologic, therapeutic and follow-up information, using multivariable Cox proportional hazards regression modelling.ResultsOnly 10-year cumulative incidence of distant metastasis was lower in the axillary radiotherapy (1%) than no axillary radiotherapy arm (7%) (p = 0.037). Irrespective of study arm, hormone receptor positivity had significantly favourable effects on 10-year disease-free survival (DFS) and overall survival. human epidermal growth factor receptor 2 (HER2)-positive and triple-negative subtypes were associated with lower 10-year DFS (60% and 76%, respectively) than luminal A (96%) and B (91%) (p = 0.001). Ten-year DFS for high (?14%) Ki67 cancers was lower than for low Ki67 cancers (p = 0.027); however, this effect was mainly confined to the no axillary radiotherapy arm.Concluding statementFor patients with clinically node-negative small breast cancer not given axillary dissection, 10-year DFS is worsened by HER2 positivity, triple-negative phenotype and high Ki67. Axillary radiotherapy counteracts the negative prognostic effect of high Ki67 in patients not receiving axillary dissection.     

Molecular subtyping of early-stage breast cancer identifies a group of patients who do not benefit from neoadjuvant chemotherapy

The aim of this study was to analyze the correlation between the pathologic complete response (pCR) rate after neoadjuvant chemotherapy and long-term outcome (distant metastases-free survival [DMFS]) in patients with early-stage breast cancer using BluePrint and MammaPrint molecular subtyping versus clinical subtyping using immunohistochemistry/fluorescence in situ hybridization (IHC/FISH) for the determination of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor-2 (HER2). Data were analyzed from 437 patients in four neoadjuvant chemotherapy trials. BluePrint and MammaPrint outcomes were determined from 44K Agilent arrays, the I-SPY 1 data portal, or Affymetrix U133A arrays. The pCR rate differed substantially among BluePrint molecular subgroups: 6 % in Luminal A-type, 10 % in Luminal B-type, 47 % in HER2-type, and 37 % in Basal-type patients. In the Luminal A-type group (n = 90; including seven HER2-positive patients and eight triple-negative patients by IHC/FISH), the 5-year DMFS rate was 93 %. The pCR rate provided no prognostic information, suggesting these patients may not benefit from chemotherapy. Forty-three of 107 (40 %) HER2-positive patients were classified as Luminal-type by BluePrint and may have lower response rates to targeted therapy. Molecular subtyping identified 90 of 435 (21 %) patients as Luminal A-type (BluePrint Luminal-type/MammaPrint Low Risk) with excellent survival. The pCR rate provided no prognostic information. Molecular subtyping can improve the stratification of patients in the neoadjuvant setting: Luminal A-type (MammaPrint Low Risk) patients have a good prognosis with excellent survival and do not seem to benefit from chemotherapy. We observed marked benefit in response and DMFS to neoadjuvant treatment in patients subtyped as HER2-type and Basal-type. BluePrint with MammaPrint molecular subtyping helps to improve prognostic estimation and the choice of therapy versus IHC/FISH.     

Magnesium wasting associated with epidermal-growth-factor receptor-targeting antibodies in colorectal cancer: a prospective study

BACKGROUND: Preliminary evidence suggests that magnesium wasting occurs in patients who are treated with epidermal-growth-factor receptor (EGFR)-targeting antibodies for colorectal cancer. The mechanism of this side-effect is unknown, and if all or a subset of patients are affected is also unclear. We aimed to assess the incidence, characteristics, and predictive factors of magnesium wasting during treatment with EGFR-targeting antibodies, and to study the pathophysiology of this phenomenon. METHODS: We measured prospectively magnesium concentrations in a cohort of 98 patients with colorectal cancer treated with EGFR-targeting antibodies with or without combined chemotherapy. The primary outcome measure was the slope of the serum magnesium concentrations over time. In 35 patients, 24-h urinary magnesium excretion was measured. In a subset of patients (n=5), an intravenous magnesium load test was done. 16 patients who had chemotherapy alone acted as controls. A clinical protocol was written before initiation of the study, but because this was a non-interventional study, the protocol was not formally registered. FINDINGS: 95 (97%) patients had decreasing serum magnesium concentrations during EGFR-targeting treatment compared with baseline measurements. The mean serum magnesium slope during EGFR-targeting treatment (with or without combined chemotherapy) was significantly lower compared with chemotherapy alone (-0.00157 mmol/L/day, SD 0.00162 [95% CI -0.00191 to -0.00123] vs 0.00014 mmol/L/day, SD -00076 [-0.00026 to 0.00055]; (t test, p < 0.0001). 24-h urine analysis and intravenous magnesium load tests showed a defect in renal magnesium reabsorption. INTERPRETATION: EGFR-inhibiting antibodies compromised the renal magnesium retention capacity, leading to hypomagnesaemia in most patients. Future studies should address the effects of exposure and target affinity. Our study suggests a pivotal role of the EGFR-signalling pathway in regulating magnesium homoeostasis.     

Cognitive function during neoadjuvant chemotherapy for breast cancer: results of a prospective, multicenter, longitudinal study

BACKGROUND: It is believed widely that chemotherapy-induced cognitive impairment occurs in a subgroup of patients with breast cancer. However, recent reports have provided no evidence that chemotherapy affects cognition. In this study, the authors questioned whether cognitive compromise in patients with breast cancer is attributable to chemotherapy. In addition, the effects of therapy-induced menopause and of the erythropoiesis-stimulating factor darbepoetin alpha on cognitive performance were assessed. METHODS: A battery of neuropsychological tests was used to assess cognitive performance in 101 patients with breast cancer before neoadjuvant chemotherapy (T1) and toward the end of neoadjuvant chemotherapy (T2) with combined epirubicin, paclitaxel, and cyclophosphamide with concomitant darbepoetin alpha. Repeated-measures multiple analyses of variance and a reliable-change approach were used for statistical analyses. RESULTS: At T1, the group means ranged below the test norms in 5 of 12 cognitive tests. At T2, multiple analyses of variance (MANOVA) indicated a significant overall improvement in the test results (P<.001). After correcting for practice effects, cognitive decline predominated in 27% of patients, whereas improvement predominated in 28% of patients. Cognitive performance was not related significantly to self-reported cognitive problems, anxiety and depression, menopause, or darbepoetin alpha administration. CONCLUSIONS: Even before chemotherapy, a subgroup of patients with breast cancer showed cognitive compromise that was unrelated to anxiety or depression. During chemotherapy, cognitive function remained stable in most patients, improved in a subgroup, and deteriorated in another subgroup. The deterioration may have been caused by side effects of chemotherapy, but it also may have been related to currently unidentified factors that cause prechemotherapy cognitive compromise. Therapy-induced menopause and darbepoetin alpha did not appear to influence cognition.     

Late anthracycline cardiotoxicity after childhood cancer: a prospective longitudinal study

BACKGROUND: The objective of the current study was to examine the risk factors for progression in severity of anthracycline-induced cardiac dysfunction, thereby providing information that is useful in refining cancer treatment regimes and guiding follow-up. METHODS: Serial echocardiograms were performed on 101 acute lymphoblastic leukemia survivors and 83 Wilms tumor survivors after a mean interval of 6.2 years and 6.7 years since last anthracycline dose, respectively, at first study, and after 10.3 years and 11.1 years, respectively, at second study. The paired data were contrasted with data from 100 normal subjects, and potential correlations with follow-up interval, cumulative dose, cancer diagnosis, gender, age at diagnosis, and growth were explored using univariate and multiple regression techniques. RESULTS: The most important predictor of worsening cardiac performance was total anthracycline dose. As a group, patients receiving < 240 mg/m(2) showed no deterioration of left ventricular end systolic stress at > 10 years from the end of treatment. CONCLUSIONS: Survivors who have received low-dose anthracycline require cardiac surveillance infrequently. In good prognosis tumors, cumulative anthracycline dose should be maintained at < 250 mg/m(2).     

Exploring and comparing the experience and coping behaviour of men and women with colorectal cancer after chemotherapy treatment: a qualitative longitudinal study

Objectives: Men have higher incidence and mortality rates for nearly all cancers. They are less likely than women to utilise cancer information services and other social support services. The aim of this study was to explore and compare the experience and coping behaviour of men and women after treatment for colorectal cancer (CRC). Methods: A longitudinal qualitative study was conducted involving 38 individuals (24 men and 14 women) with CRC. Data were generated using semi‐structured interviews at four time points over an 18‐month period, post‐diagnosis. Interviews focused on participant's experience of CRC and on how gender affected their coping. This paper reports the findings of interviews 3 and 4 which examined the participant's experience after chemotherapy. Results: Three themes emerged from the interviews (‘new normal’, living with uncertainty and support needs). Many men and women reacted similarly; however, there was some variation evident between and within sexes. The main difference was with regard to the long‐term physical side effects of the illness. Many women admitted to still experiencing side effects, whereas many men indicated that they had no problems. These men engaged in practices that aligned with their gender identity and view of masculinity. It must be noted that some men and women were still experiencing an impact. Conclusions: Recovery from the physical and psychological effects of CRC does not occur simultaneously. Healthcare professionals should be aware that not all men (or women) conform to the social stereotypes of masculinity (or femininity). Copyright © 2010 John Wiley & Sons, Ltd.     

Circulating tumour cells and outcome in non-metastatic colorectal cancer: a prospective study

Background:

Circulating tumour cells (CTC) in the blood have been accepted as a prognostic marker in patients with metastatic colorectal cancer (CRC). Only limited data exist on the prognostic impact of CTC in patients with early stage CRC using standardised detection assays. The aim of this study was to elucidate the role of CTC in patients with non-metastatic CRC.

Methods:

A total of 287 patients with potentially curable CRC were enrolled, including 239 patients with UICC stage I–III. CTC were measured in the blood using the CellSearch system preoperatively and on postoperative days 3 and 7. The complete patient group (UICC I–IV) and the non-metastatic cohort (UICC I–III) were analysed independently. Patients were followed for 28 (0–53) months. Prognostic factors for overall and progression-free survival were analysed using univariate and multivariate analyses.

Results:

CTC were detected more frequently in patients with metastatic disease. No clinicopathological variables were associated with CTC detection in non-metastatic patients. CTC detection (⩾1 CTC per 7.5 ml blood) in the blood was significantly associated with worse overall survival (49.8 vs 38.4 months; P<0.001) in the non-metastatic group (UICC I–III), as well as in the complete cohort (48.4 vs 33.6 months; P<0.001). On multivariate analysis CTC were the strongest prognostic factor in non-metastatic patients (hazard ratio (HR) 5.5; 95% confidence interval (CI) 2.3–13.6) as well as in the entire study group (HR 5.6; 95% CI 2.6–12.0).

Conclusions:

Preoperative CTC detection is a strong and independent prognostic marker in non-metastatic CRC.     

Plasma leptin and colorectal cancer risk: a prospective study in Northern Sweden

Obesity is associated with an increased risk of colorectal cancer. Circulating levels of leptin are high in obesity and strongly correlated to levels of insulin. Leptin stimulates growth of colon cancer cells. In a nested case-control study, we measured leptin levels in prediagnostic plasma from 75 men and 93 women who were diagnosed with colorectal cancer mean time 3.4 years (SD 2.4) after recruitment and among 327 control subjects. Logistic regression analyses showed increases in colorectal cancer risk in men with increasing levels of leptin, odds ratios (OR) were 1.00 (ref), 0.85 (95% C.I.=0.33-2.23), 1.04 (0.43-2.53), and 2.15 (0.89-5.22), (pfor trend=0.08). There was a distinct threshold between the third and fourth quartile of leptin, and the odds ratio for top quartile vs. three bottom quartiles was 2.28 (1.09-4.76). Adjustment for body mass index and insulin did not affect risk estimates. In separate analysis, odds ratio for top vs. bottom tertile of colon cancer was 1.96 (95% C.I.=0.72-5.29), whereas no increase was seen for rectal cancer. In women, no association between leptin and risk was seen. These data support the hypothesis that leptin is a risk marker for colorectal cancer in men, but not in women.