In colon cancer patients, obesity, sedentary lifestyle, and high dietary glycemic load have been associated with increased risk of cancer recurrence. High sugar-sweetened beverage intake has been ...associated with obesity, diabetes, and cardio-metabolic diseases, but the influence on colon cancer survival is unknown.
We assessed the association between sugar-sweetened beverage consumption on cancer recurrence and mortality in 1,011 stage III colon cancer patients who completed food frequency questionnaires as part of a U.S. National Cancer Institute-sponsored adjuvant chemotherapy trial. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazard models.
Patients consuming ≥ 2 servings of sugar-sweetened beverages per day experienced an adjusted HR for disease recurrence or mortality of 1.67 (95% CI, 1.04-2.68), compared with those consuming <2 servings per month (P(trend) = 0.02). The association of sugar-sweetened beverages on cancer recurrence or mortality appeared greater among patients who were both overweight (body mass index ≥ 2 5 kg/m(2)) and less physically active (metabolic equivalent task-hours per week <18) (HR = 2.22; 95% CI, 1.29-3.81, P(trend) = 0.0025).
Higher sugar-sweetened beverage intake was associated with a significantly increased risk of cancer recurrence and mortality in stage III colon cancer patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Since the introduction of biologic therapies for the treatment of metastatic colorectal cancer (mCRC), few studies have examined patterns of care or predictors of specific treatment approaches.
We ...assessed 4877 mCRC patients who received chemotherapy between January 2004 and March 2011 at academic, private, and community-based oncology practices subscribing to a US-wide chemotherapy order entry (system capturing disease, patient, provider, and treatment data. Multivariable analyses of these prospectively recorded characteristics were used to identify independent predictors of specific therapeutic choices. All statistical tests were two-sided.
Throughout the study period, fluoropyrimidine/oxaliplatin combination was the most commonly used first-line chemotherapy regimen, representing 71% of first-line therapy by 2007. First-line bevacizumab use averaged 51%, peaking at 55% in 2006. Of those who received first-line bevacizumab, 34% continued to receive bevacizumab in the second-line. Only 26% of patients in our cohort ever received an anti-EGFR monoclonal antibody (cetuximab = 22%; panitumumab = 6%) at some point in their treatment course. Patients treated at academic centers, with longer duration of first-line therapy, and at sites in the western United States were statistically more likely to receive an anti-EGFR antibody. Anti-EGFR antibody use fell by 18% after the US Food and Drug Administration limited its use to patients with KRAS wild-type tumors in June 2009.
Analysis of this US-wide mCRC cohort demonstrates that bevacizumab has been more consistently integrated into treatment regimens than anti-EGFR antibody therapies, particularly in first-line therapy. However, treatment choices vary substantially according to specific patient, practice, and provider characteristics.
Statin use has been examined as a potential chemopreventive strategy against colorectal cancer (CRC). Previous studies have not been able to investigate this topic with adequate follow-up time or ...disentangle the effects of statin use and total cholesterol level. We investigated prospectively this topic.
Eligible participants (100,300 women and 47,991 men) in the Nurses' Health Study and Health Professionals Follow-Up Study were followed for up to 24 years. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals.
We documented 2,924 incident CRC cases during follow-up. In fully adjusted analyses, longer duration of statin use was associated with higher risk of colon cancer (hazard ratios, the 95% confidence interval was 1.09, 0.95-1.25 for 1-5 years; 1.16, 0.99-1.36 for 6-10 years; 1.08, 0.81-1.44 for 11-15 years; 1.85, 1.30-2.61 for >15 years; vs never users, P = 0.004 for trend) rather than rectal cancer. The risk elevation was driven by proximal colon cancer (1.16, 0.98-1.38 for 1-5 years; 1.19, 0.98-1.45 for 6-10 years; 1.25, 0.89-1.74 for 11-15 years; 2.17, 1.46-3.24 for >15 years; vs never users, P = 0.001 for trend) rather than distal colon cancer. The results remained robust in analyses among participants with hypercholesterolemia or who never received screening. Total cholesterol level was not associated with CRC risk.
This study does not support benefit of statin use in CRC chemoprevention or any association between total cholesterol level and CRC risk. On the contrary, long-term statin use may be associated with increased colon cancer risk (driven by proximal colon cancer).
Background
Muscle abnormalities such as low muscle mass and low muscle radiodensity are well known risk factors for unfavourable cancer prognosis. However, little is known in regard to the degree and ...impact of longitudinal changes in muscle mass and radiodensity within the context of cancer. Here, we explore the relationship between muscle wasting and mortality in a large population‐based study of patients with non‐metastatic colorectal cancer (CRC).
Methods
A total of 1924 patients with stage I–III CRC who underwent surgical resection in the Kaiser Permanente Northern California Health System were included. Muscle mass and radiodensity were quantified using computed tomography images obtained at diagnosis and after approximately 14 months. Cox proportional‐hazards models were used to estimate hazard ratios for all‐cause mortality.
Results
The hazard ratio for all‐cause mortality among patients with the largest deterioration in muscle mass (≥2 SD; ≥11.4% loss from baseline), as compared with those who remained stable (±1 SD; 0.0 ± 5.7%) was 2.15 95% confidence interval (CI): 1.59–2.92; P < 0.001. The hazard ratio for all‐cause mortality among patients who experienced the largest deterioration in muscle radiodensity (≥2 SD; ≥20.2% loss from baseline), as compared with those who remained stable (±1 SD; 0.0 ± 10.1%) was 1.61 (95% CI: 1.20–2.15; P = 0.002).
Conclusions
In patients with stage I–III CRC, muscle wasting is a risk factor for mortality, independent of change in body mass and other body composition parameters.
Background.
Autophagy is a catabolic pathway that permits cells to recycle intracellular macromolecules, and its inhibition reduces pancreatic cancer growth in model systems. We evaluated ...hydoxychloroquine (HCQ), an inhibitor of autophagy, in patients with pancreatic cancer and analyzed pharmacodynamic markers in treated patients and mice.
Methods.
Patients with previously treated metastatic pancreatic cancer were administered HCQ at 400 mg (n = 10) or 600 mg (n = 10) twice daily. The primary endpoint was 2‐month progression‐free survival (PFS). We analyzed peripheral lymphocytes from treated mice to identify pharmacodynamic markers of autophagy inhibition that were then assessed in peripheral lymphocytes from patients.
Results.
Among 20 patients enrolled, 2 (10%) were without progressive disease at 2 months. Median PFS and overall survival were 46.5 and 69.0 days, respectively. Treatment‐related grade 3/4 adverse events were lymphopenia (n = 1) and elevated alanine aminotransferase (n = 1). Tolerability and efficacy were similar at the two dose levels. Analysis of treated murine lymphocytes suggested that LC3‐II expression by Western blot is a reliable marker for autophagy inhibition. Analysis of LC3‐II in patient lymphocytes demonstrated inconsistent autophagy inhibition.
Conclusion.
Mouse studies identified LC3‐II levels in peripheral lymphocytes as a potential pharmacodynamic marker of autophagy inhibition. In patients with previously treated metastatic pancreatic cancer, HCQ monotherapy achieved inconsistent autophagy inhibition and demonstrated negligible therapeutic efficacy.
摘要
背景. 自噬是一种分解代谢过程，使得细胞内大分子得以回收再利用，自噬抑制在模型系统研究中显示能够阻碍胰腺癌生长。我们在胰腺癌患者中评估了自噬抑制剂羟氯喹（HCQ），并在经治患者与小鼠中分析了药效动力学标记物。
方法. 入组经治的转移性胰腺癌患者，给予HCQ 400 mg（n = 10）或600 mg（n = 10），每日2次。主要终点为2个月无疾病进展生存期（PFS）。我们针对经治小鼠开展了外周血淋巴细胞分析，以识别自噬抑制的药效动力学标记物，随后在患者外周血淋巴细胞中进行评估。
结果. 共入组20例患者，2例（10%）在2个月时未出现疾病进展。中位PFS以及总生存期分别为46.5、69.0天。 治疗相关3/4级不良事件为淋巴细胞减少（n = 1），丙氨酸氨基 转移酶升高（n = 1）。两个剂量水平的耐受性和疗效相似。经治小鼠淋巴细胞分析表明，经蛋白印迹法检测的LC3‐II表达可作为自噬抑制的可靠标记物。患者淋巴细胞LC3‐II分析则显示出自噬抑制的不一致性。
结论. 小鼠研究证实，外周血淋巴细胞LC3‐II水平是自噬抑制的潜在药效动力学标记物。在经治的转移性胰腺癌患者中，HCQ单药治疗并不能普遍达到自噬抑制效果，这提示疗效甚微。Oncologist 2014; 19:637–638
Obesity is a risk factor for the development of colon cancer. However, the influence of body mass index (BMI) on the outcome of patients with established colon cancer remains uncertain. Moreover, the ...impact of change in body habitus after diagnosis has not been studied.
We conducted a prospective, observational study of 1,053 patients who had stage III colon cancer and who were enrolled on a randomized trial of adjuvant chemotherapy. Patients reported on height and weight during and 6 months after adjuvant chemotherapy. Patients were observed for cancer recurrence or death.
In this cohort of patients with stage III cancer, 35% of patients were overweight (BMI, 25 to 29.9 kg/m(2)), and 34% were obese (BMI >or= 30 kg/m(2)). Increased BMI was not significantly associated with a higher risk of colon cancer recurrence or death (P trend = .54). Compared with normal-weight patients (BMI, 21 to 24.9 kg/m(2)), the multivariate hazard ratio for disease-free survival was 1.00 (95% CI, 0.72 to 1.40) for patients with class I obesity (BMI, 30 to 34.9 kg/m(2)) and 1.24 (95% CI, 0.84 to 1.83) for those with class II to III obesity (BMI >or= 35 kg/m(2)) after analysis was adjusted for tumor-related prognostic factors, physical activity, tobacco history, performance status, age, and sex. Similarly, after analysis was controlled for BMI, weight change (either loss or gain) during the time period between ongoing adjuvant therapy and 6 months after completion of therapy did not significantly impact on cancer recurrence and/or mortality.
Neither BMI nor weight change was significantly associated with an increased risk of cancer recurrence and death in patients with colon cancer.
Although evidence suggests an inverse association between calcium intake and colorectal cancer incidence, the influence of calcium on survival after colorectal cancer diagnosis remains unclear.
We ...prospectively assessed the association of postdiagnostic calcium intake with colorectal cancer-specific and overall mortality among 1,660 nonmetastatic colorectal cancer patients within the Nurses' Health Study and the Health Professionals Follow-up Study. Patients completed a validated food frequency questionnaire between 6 months and 4 years after diagnosis and were followed up for death. Multivariable hazard ratios (HRs) and 95% confidence intervals (95% CI) were calculated using Cox proportional hazards regression.
Comparing the highest with the lowest quartile intake of postdiagnostic total calcium, the multivariable HRs were 0.56 (95% CI, 0.32-0.96;
= 0.04) for colorectal cancer-specific mortality and 0.80 (95% CI, 0.59-1.09;
= 0.11) for all-cause mortality. Postdiagnostic supplemental calcium intake was also inversely associated with colorectal cancer-specific mortality (HR, 0.67; 95% CI, 0.42-1.06;
= 0.047) and all-cause mortality (HR, 0.71; 95% CI, 0.54-0.94;
= 0.008), although these inverse associations were primarily observed in women. In addition, calcium from diet or dairy sources was associated with lower risk in men.
Higher calcium intake after the diagnosis may be associated with a lower risk of death among patients with colorectal cancer. If confirmed, these findings may provide support for the nutritional recommendations of maintaining sufficient calcium intake among colorectal cancer survivors.
The influence of a high sugar diet on colorectal cancer (CRC) survival is unclear.
Among 1463 stage I-III CRC patients from the Nurses' Health Study and Health Professionals Follow-up Study, we ...estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for CRC-specific and all-cause mortality in relation to intake of post-diagnosis sugar-sweetened beverages (SSB), artificially sweetened beverages (ASB), fruit juice, fructose and other sugars.
Over a median 8.0 years, 781 cases died (173 CRC-specific deaths). Multivariable-adjusted HRs for post-diagnosis intake and CRC-specific mortality were 1.21 (95% CI: 0.87-1.68) per 1 serving SSBs per day (serving/day) and 1.24 (95% CI: 0.95-1.63) per 20 grams fructose per day. Significant positive associations for CRC-specific mortality were primarily observed ≤5 years from diagnosis (HR per 1 serving/day of SSBs = 1.59, 95% CI: 1.06-2.38). Significant inverse associations were observed between ASBs and CRC-specific and all-cause mortality (HR for ≥5 versus <1 serving/week = 0.44, 95% CI: 0.26-0.75 and 0.70, 95% CI: 0.55-0.89, respectively).
Higher post-diagnosis intake of SSBs and sugars may be associated with higher CRC-specific mortality, but only up to 5 years from diagnosis, when more deaths were due to CRC. The inverse association between ASBs and CRC-specific mortality warrants further examination.
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