Norms of vagal nerve activity,indexed by Heart Rate Variability,in cancer patients

Recent research has begun to show the role of the activity of the vagus nerve in cancer prognosis. However, it remains unknown whether cancer severity can impair vagal nerve activity. This study combined data (N = 657) of five different cancers (colorectal, pancreas, prostate, lung and ovarian) concerning patients’ Heart Rate Variability (HRV), a vagal nerve activity index. These data were compared to HRV levels of a healthy sample in another study. In addition, we examined the moderating effects of age, gender and cancer stage on HRV. The mean HRV of the cancer patients sample was significantly lower (HRV = 22 ms) compared to the healthy sample (HRV = 50 ms) (p < 0.000001). While age and gender did not significantly affect HRV, cancer patients with advanced stages had significantly lower HRV than those with early stages (p = 0.011). A possible bi-directional relation between cancer and vagal nerve activity is discussed. These findings are of importance for prognostication since they provide researchers and clinicians with expected values of vagal nerve activity in cancer patients.     

Peri-operative blood transfusion for resected colon cancer: Practice patterns and outcomes in a population-based study

Background & objectivesLiterature suggests that peri-operative blood transfusion among patients with resected colon cancer may be associated with inferior long-term survival. The study objective was to characterize this association in our population.MethodsThis is a retrospective cohort study using the population-based Ontario Cancer Registry (2002–2008). Pathology reports were obtained for a 25% random sample of all cases and constituted the study population. Log binomial regression was used to identify factors associated with transfusion. Cox proportional hazards model explored the association between transfusion and cancer specific survival (CSS) and overall survival (OS).ResultsThe study population included 7198 patients: 18% stage I, 36% stage II, 40% stage III, and 6% stage IV. Twenty-eight percent of patients were transfused. Factors independently associated with transfusion included advanced age (p < 0.001), female sex (p < 0.001), greater comorbidity (p < 0.001), more advanced disease (p < 0.001) and open surgical resection (p < 0.001). Transfusion was associated with inferior CSS (HR 1.51, 95% CI 1.38–1.65) and OS (HR 1.52, 95% CI 1.41–1.63), after adjusting for important confounders.ConclusionsPeri-operative transfusion rates among patients with colon cancer have decreased over time. Transfusion is associated with inferior long-term CSS and OS.     

Role of serum concentration of VEGFR1 and TIMP2 on clinical outcome in primary cervical cancer: Results of a companion protocol of the randomized,NOGGO–AGO phase III adjuvant trial of simultaneous cisplatin-based radiochemotherapy vs. carboplatin and paclitaxel containing sequential radiotherapy

ObjectiveAim of the present study was to analyze the expression-profile of IGF1, IGFBP3, sICAM1, sVCAM1, MMP2, MMP9, TIMP2, VEGFA, VEGFD, VEGFC and VEGFR1 in patients with high-risk FIGO-stage Ib-IIb cervical cancer.MethodsSerum from 68 cervical cancer patients treated within a phase-III-trial with either simultaneous cisplatin radiochemotherapy or sequential systemic carboplatin and paclitaxel followed by percutaneous irradiation was analyzed by ELISA. Both target expression and correlation with important clinicopathological factors were analyzed following standard statistic procedures.ResultsAll 68 patients underwent a primary radical hysterectomy with pelvic and/or paraaortic lymphadenectomy. 85.3% of the extirpated tumors had clear surgical margins (R0). Increased levels of VEGFR1, TIMP2 and MMP2 were significantly associated with positive surgical margins (p = 0.004, p = 0.018 and p = 0.004, respectively). High concentration of MMP2 and TIMP2 correlated additionally with an advanced age at time of diagnosis (p = 0.001 and p = 0.007, respectively). For the cut-off value of 100 pg/ml, an increased VEGFR1 was significantly associated with poor overall (OS) and progression-free (PFS) survival (p = 0.017 and p = 0.015, respectively). A TIMP2 concentration of lower than 90 ng/ml was significantly associated with poorer OS and PFS (p = 0.009 and p = 0.043, respectively). In the multivariate analysis, TIMP2 expression in serum was the only independent prognostic factor for OS (p = 0.032, HR = 6.51, 95% CI = 1.17–36.01).ConclusionsExpression-profile of specific biomarkers associated with tumor invasion, cell migration and angiogenesis seems to be of prognostic value for both OS and PFS in patients undergoing surgery due to primary cervical cancer. Further analyses are warranted to allow an implementation of such markers into clinical practice.     

Association between hypermethylation of DNA repetitive elements in white blood cell DNA and pancreatic cancer

Pancreatic cancer is a leading cause of cancer-related deaths worldwide. Methylation of DNA may influence risk or be a marker of early disease. The aim of this study was to measure the association between methylation of three DNA repetitive elements in white blood cell (WBC) DNA and pancreatic cancer.DNA from WBCs of pancreatic cancer cases (n = 559) and healthy unrelated controls (n = 603) were tested for methylation of the LINE-1, Alu and Sat2 DNA repetitive elements using MethyLight quantitative PCR assays. Odds ratios (ORs) and 95% confidence intervals (95%CI) between both continuous measures of percent of methylated sample compared to a reference (PMR) or quintiles of PMR and pancreatic cancer, adjusted for age, sex, smoking, BMI, alcohol and higher education, were estimated.The PMR for each of the three markers was higher in cases than in controls, although only LINE-1 was significantly associated with pancreatic cancer (OR per log unit = 1.37, 95%CI = 1.16–1.63). The marker methylation score for all three markers combined was significantly associated with pancreatic cancer (p-trend = 0.0006). There were no associations between measures of PMR and either presence of metastases, or timing of blood collection in relation to diagnosis, surgery, chemotherapy or death (all p > 0.1).We observed an association between methylation of LINE-1 in WBC DNA and risk of pancreatic cancer. Further studies are needed to confirm this association.     

CHEK2 gene alterations in the forkhead-associated domain, 1100delC and del5395 do not modify the risk of sporadic pancreatic cancer

Checkpoint kinase 2 gene (CHEK2) alterations increase risk of several cancer types. We analyzed selected CHEK2 alterations in 270 Czech pancreatic cancer patients and in 683 healthy controls. The pancreatic cancer risk was higher in individuals who inherited rare alterations in CHEK2 region involving forkhead-associated domain other than I157T (OR = 5.14; 95% CI = 0.94–28.23) but the observed association was non-significant (p = 0.057). The most frequent I157T mutation did not alter the pancreatic cancer risk and neither the followed deletion of 5395 bp nor c.1100delC were found in any of pancreatic cases. We conclude that the I157T, other alterations in its proximity, del5395 and c.1100delC in CHEK2 do not predispose to pancreatic cancer risk in the Czech population.     

Time to diagnosis and stage of symptomatic colorectal cancer determined by three different sources of information: A population based retrospective study

BackgroundSurvival rates from colorectal cancer (CRC) are highly variable in Europe. This variability could potentially be explained by differences in healthcare system delays in diagnosis. However, even when such delays are reduced, the relationship of the diagnostic interval (time from presentation with symptoms to diagnosis) with outcome is uncertain.MethodsA total of 795 patients with CRC from 5 regions of Spain were retrospectively examined in this population-based multicenter study. Consecutive incident cases of CRC were identified from pathology services. The total diagnostic interval (TDI) was defined as the time from the first presentation with symptoms to diagnosis based on 3 different sources of information: (i) patient-recorded data (PR-TDI) by interview, (ii) hospital-recorded data (HR-TDI), and (iii) general practitioner-recorded data (GPR-TDI). Concordance correlation coefficients (CCCs) were used to estimate the agreement of 3 different TDIs. The TDIs of patients with different stages of CRC were also compared using the Kruskal-Wallis test.ResultsThe median TDI was 131 days based on patient interview data, 91 days based on HR data, and 111 days based on GPR data. Overall, the agreement of these TDIs was poor (CCC_PRvsHR = 0.399, CCC_PRvsGPR = 0.518, CCC_HRvsGPR = 0.383). Univariate analysis indicated that the TDI was greater in those with less advanced CRC for all 3 methods of calculation, but this association was only statistically significant for the HR-TDI (p = 0.021).ConclusionThere is no evidence that patients with more advanced CRC have longer TDIs. In fact, we found an inverse relationship between the TDI and CRC stage, an example of the “waiting time paradox”. This association may likely be due to the presence of unmeasured confounders as the stage when symptoms appear or the tumour aggressiveness.     

Clinical outcomes of female breast cancer according to BRCA mutation status

BackgroundTo investigate breast cancer prognosis (disease-free (DFS) and overall survival (OS)) among carriers of germline BRCA mutations (BRCAm) in Denmark.MethodsWe identified all women in Central and Northern Denmark diagnosed with breast cancer during 2004–2011. We retrieved information on germline BRCAm testing from Clinical Genetics departments and clinical/treatment characteristics from population-based medical registries. Follow-up for recurrence, new primary cancer, and mortality extended from 180 days after diagnosis until 31/12/2012. We estimated median DFS and OS and five-year cumulative incidence and incidence rates (IR/1000 person-years), and 95% confidence intervals (95% CI), for each outcome.ResultsAmong 9874 patients, 523 (5%) underwent BRCA testing—90 were BRCAm carriers, 433 were BRCA wildtype (BRCAwt). Compared with BRCAwt women, BRCAm carriers were younger, had lower stage, and ER- and HER2- tumors. Median time from diagnosis to BRCA testing was 0.91 years and 1.3 years in BRCAm and BRCAwt women; median follow-up to first event was 3.9 and 3.4 years, respectively. Five-year DFS and OS were higher in BRCAm than BRCAwt women: 88% (95%CI = 78.3–93.5) vs. 75.3% (95%CI = 70.2–79.6) and 97.8% (95%CI = 91.4–99.4) vs 92.2% (95%CI = 88.5–94.7), respectively. Five-year IRs of recurrence were 36.7/1000 person-years (95%CI = 15.8–72.2) in the BRCAm cohort vs. 58.4 (95%CI = 42.9–77.6) in the BRCAwt cohort.ConclusionsBRCAm carriers may have a better prognosis than BRCAwt women. However, limited testing conducted mainly during follow-up, yielded low numbers for precise estimations, and may be attributable to selection bias.     

Extracellular matrix metalloproteinase inducer expression has an impact on survival in human bladder cancer

Aim: Extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to promote tumor invasion and metastasis via stimulating matrix metalloproteinase synthesis in neighboring fibroblasts, to enhance angiogenesis via vascular endothelial growth factor, to induce chemoresistant tumor cells via the production of hyaluronan, and to confer resistance of cancer cells to anoikis through inhibition of Bim. The purpose of this study was to investigate the expression of EMMPRIN in human primary bladder cancer and to evaluate its prognostic value. Methods: EMMPRIN expression patterns were detected by immunohistochemistry. In order to determine its prognostic value, overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan–Meier method, and multivariate analysis was performed using the Cox proportional hazard analysis. Results: Of the 101 cases with bladder cancers, 68 (67.3%) cases were positive for EMMPRIN expression. When categorized into negative vs. positive expression, EMMPRIN was associated with the stage (p = 0.006), the grade (p = 0.002), carcinoma in situ (p = 0.01), the recurrence (p = 0.009), the progression (p = 0.009), and the death (p = 0.01) of patients with bladder cancer. Moreover, positive EMMPRIN expression clearly predicted poorer PFS (p = 0.008) and OS (p = 0.006). In the multivariate analysis, positive EMMPRIN expression was an independent prognostic factor for PFS (p = 0.03) and OS (p = 0.03). Conclusion: EMMPRIN expression was greater in bladder cancers than in the adjacent normal tissues and may be a useful prognostic marker for patients with bladder cancer.     

Cancer with Diabetes: Prevalence,Metabolic Control,and Survival in an Academic Oncology Practice

ObjectiveTo determine the prevalence of diabetes mellitus, glycemic control, and impact of diabetes on over all survival in an academic oncology practice.MethodsData on cancer patients (1999 to 2008) were retrieved from the institutional cancer registry and linked to electronic files to obtain diabetes status and hemoglobin A1c (A1C) values within the first 6 months of cancer diagnosis. Overall survival by cancer type with and without diabetes was compared using Cox regression.ResultsExcluding skin and hematologic malignancies, 15,951 cancer cases were identified. Overall diabe tes prevalence was 6.8% (n = 1,090), declining over time (P < 0.001). Diabetes was common among patients with pancreatic (9.8% [61 of 624]), colorectal (7.7% [89 of 1,151]), or bladder cancers (7.6% [68 of 899]). Patients with diabetes were older (mean age, 70 versus 66 years; P < 0.001) and more likely to be male (66.3% [723 of 1,090] versus 60.2% [8,949 of 14,858]; P < 0.001). The mean A1C among diabetic cancer patients was 6.8% and did not dif fer across cancer types (P = 0.80). Only 58.6% (331 of 565) of diabetic cancer patients had all A1C < 7.0% during the first 6 months following cancer diagnosis. Pancreatic cancer patients with coexisting diabetes had better overall survival than pancreatic cancer patients without diabetes (hazard ratio, 0.60; 95% confidence interval 0.44 to 0.80; P < 0.001). Conversely, diabetic prostate cancer patients had worse overall survival than prostate cancer patients without diabetes (hazard ratio, 1.36; 95% confidence interval 1.05 to 1.76; P = 0.02).ConclusionIn this academic oncology practice, diabetes was common, glycemic control often was subopti mal, and survival varied by cancer type. Additional study is needed to optimize glucose management and investigate mechanisms underlying age, sex, and survival differences. (Endocr Pract. 2012;18:898-905)     

Beta-blocker usage and prostate cancer survival: A nested case–control study in the UK Clinical Practice Research Datalink cohort

BackgroundRecent laboratory and epidemiological evidence suggests that beta-blockers could inhibit prostate cancer progression. Methods: We investigated the effect of beta-blockers on prostate cancer-specific mortality in a cohort of prostate cancer patients. Prostate cancer patients diagnosed between 1998 and 2006 were identified from the UK Clinical Practice Research Database and confirmed by cancer registries. Patients were followed up to 2011 with deaths identified by the Office of National Statistics. A nested case–control analysis compared patients dying from prostate cancer (cases) with up to three controls alive at the time of their death, matched by age and year of diagnosis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression. Results: Post-diagnostic beta-blocker use was identified in 25% of 1184 prostate cancer-specific deaths and 26% of 3531 matched controls. There was little evidence (P = 0.40) of a reduction in the risk of cancer-specific death in beta-blocker users compared with non-users (OR = 0.94 95% CI 0.81, 1.09). Similar results were observed after adjustments for confounders, in analyses by beta-blocker frequency, duration, type and for all-cause mortality. Conclusions: Beta-blocker usage after diagnosis was not associated with cancer-specific or all-cause mortality in prostate cancer patients in this large UK study.     

Early adulthood body mass index,cumulative smoking,and esophageal adenocarcinoma survival

BackgroundSmoking and obesity are esophageal adenocarcinoma (EAC) risk factors. However, the same risk factors may also affect biological aggressiveness and cancer outcomes. Our study evaluated the combined effects of early-adulthood obesity and cumulative smoking on the EAC survival.Patients and methodsIn two EAC cohorts, Toronto (TO; N = 235) and Boston (BO; N = 329), associations between early adulthood body mass index (EA-BMI), BMI at 1 year prior to diagnosis (BMI-1), and smoking with overall survival (OS) were assessed using Cox proportional hazard models, adjusted for relevant covariates.ResultsBoth cohorts were predominantly Caucasian (89%), male (88%), ever-smokers (73%) with locally advanced/metastatic EAC (78%), and good ECOG performance status (90%); median packyears was 34; median EA-BMI, 24; median BMI-1, 25. No relationships with survival were found with BMI-1. For smoking and EA-BMI, TO, BO, and combined TO-BO analyses showed similar associations: smoking conferred worse OS in the combined TO-BO cohort, with adjusted hazard ratios (aHR) of 1.22 (95%CI: 1.15–1.43;p < 0.0001) for each 20 pack-year increase. Likewise, EA-BMI ≥25 was associated with worse OS (EA-BMI of 25− < 30, aHR = 1.84,95%CI: 1.37–2.48; and EA-BMI > 30, aHR = 2.78, 95%CI: 1.94–3.99). Risk of death was also increased in remotely underweight patients with EA-BMI < 18.5 (aHR = 2.03,95%CI: 1.27–3.24), when compared to normal-EA-BMI (18 ≤ EA-BMI < 25).ConclusionsTwo key modifiable behaviors, elevated BMI in early adulthood and heavy cumulative smoking history are independently associated with increased mortality risk in two North American cohorts of EAC patients.     

Nasopharyngeal carcinoma in Slovenia, 1990–2003 (results of treatment with conventional two-dimensional radiotherapy)

AimTo review the treatment results and identify prognostic factors for disease control and survival in a cohort of nasopharyngeal carcinoma (NPC) patients from a non-endemic population in Slovenia, diagnosed between 1990 and 2003.BackgroundIn Caucasians, nasopharyngeal carcinoma is a rare malignant tumor. Its diagnosis and treatment are complex and have been dramatically impacted by recent technological advances.Materials and methodsIn the Cancer Registry of Slovenia database, a total of 126 patients with NPC were identified, 93 of whom were available for analysis. All patients were treated with conventional two-dimensional radiotherapy (RT) and 29.3% underwent chemotherapy (ChT).ResultsThe median follow-up time for those alive at the last follow-up examination was 74.5 months. Disease recurred locally in 17 patients, regionally in 4 patients and at distant sites in 18 patients, resulting in 5-year locoregional control (LRC), distant failure-free survival (DFFS) and disease-free survival (DFS) of 73.7%, 78.6% and 59.3%, respectively. Disease-specific survival at 5 years was 59% and overall survival (OS) was 49.7%. In a multivariate analysis, LRC was favorably affected (P < 0.05) by an undifferentiated histology (hazard ratio [HR] = 2.86), DFFS through the absence of neck metastases (HR = 0.28), DFS by younger age (HR = 0.46), and more intensive RT (expressed as the isoeffective dose, EQD_2,T; HR = 2.08). The independent prognosticator for OS was age (≤55 years vs. >55 years, HR = 0.39); in the ≤55 years subgroup, an improved OS was connected to a more intensive RT regimen of EQD_2,T ≥ 66 Gy (HR = 4.17).ConclusionsOur results confirm an independent and favorable effect from an undifferentiated histology, the absence of neck metastases, a younger patient age at diagnosis, and more intensive RT regimens for disease control and survival.     

Consumption of fruits,vegetables, and seaweeds (sea vegetables) and pancreatic cancer risk: The Ohsaki Cohort Study

Studies on the effects of consumption of fruits, vegetables, and seaweeds on the incidence of pancreatic cancer are not conclusive. We examined the association (if any) between the consumption of fruits, vegetables, and seaweeds and the risk of pancreatic cancer in Japan. Data from 32,859 participants registered in the Ohsaki National Health Insurance Cohort Study who were 40–79 years old and free of cancer at baseline were analyzed. Consumption of fruits, vegetables, and seaweeds was assessed at baseline using a self-administered food frequency questionnaire (containing 40 items). Incidences of pancreatic cancer were identified by computer linkage with the Miyagi Prefectural Cancer Registry. During 11 years of follow-up, 137 pancreatic cancers (67 men and 70 women) were identified. The hazard ratios (95% confidence interval) of pancreatic cancer risk for the highest versus the lowest tertile were 0.82 (0.40–1.68, trend P = 0.57) in men and 0.64 (0.35–1.20, trend P = 0.22) in women for total consumption of fruits, 0.89 (0.46–1.73, trend P = 0.76) in men and 0.67 (0.33–1.35, trend P = 0.23) in women for total consumption of vegetables, and 0.92 (0.46–1.84, trend P = 0.81) in men for consumption of seaweeds (results for the consumption of seaweeds in women were not analyzed because of poor reliability), respectively. Total consumption of fruits, vegetables, and seaweeds was not associated with a reduced risk of pancreatic cancer.     

Smoking and other risk factors for pancreatic cancer: A cohort study in men in Lithuania

Background: Cancer of the pancreas is a relatively rare, but highly fatal cancer worldwide. Cigarette smoking has been recognized as an important risk factor, but the relation to other potential determinants is still inconsistent. We investigated the association between different lifestyle, biological and anthropometric factors and the risk of pancreatic cancer in a prospective population-based cohort study from Kaunas, Lithuania. Methods: Our study included 7132 urban men initially free from any diagnosed cancer, followed for up to 30 years. 77 incident cases of pancreatic cancer were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HR) and corresponding 95% confidence intervals (95% CI). Results: Compared to never smokers, current smokers had a significantly increased risk of pancreatic cancer, HR was 1.79 (95% CI 1.03–3.09) after adjustment for age, body mass index, education and alcohol consumption. Among smokers, a significant association with higher smoking intensity was shown (≥20 cigarettes/day: HR = 2.60; 95% CI 1.42–4.76, P_trend = 0.046). We also observed a significantly increased risk for ≥30 pack-years of smoking (HR = 2.24; 95% CI 1.12–4.49, P_trend = 0.16) and for age at starting smoking <18 years (HR = 2.29; 95% CI 1.11–4.70, P_trend = 0.43) as compared to never smokers. Alcohol consumption, body mass index and total cholesterol level were not significantly associated with pancreatic cancer. Conclusions: Smoking significantly increases pancreatic cancer incidence and its high prevalence in Lithuania may partly explain high incidence of the disease. No convincing evidence was found that alcohol consumption, body mass index or serum cholesterol level were associated with pancreatic cancer risk, although the assessment was limited by the lack of statistical power.     

Serum pepsinogen level,atrophic gastritis and the risk of incident pancreatic cancer—A prospective cohort study

Background: Pancreatic cancer is a highly fatal disease without screening tests. Studies have suggested possible etiologic similarities between gastric and pancreatic cancers. Atrophic gastritis, a pre-malignant condition for gastric cancer, is characterized by low serum pepsinogen I (SPGI) level. We hypothesized that low SPGI level may be associated with an increased risk of pancreatic cancer and be a useful biomarker for the disease. Methods: Our analytic cohort included 20,962 participants in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) who had SPGI level measured. Of these, 1663 (7.9%) subjects had low SPGI levels (<25 μg/l) and were invited for gastroscopy which was completed in 1059 (63.7%) participants. Atrophic gastritis was histologically confirmed in 1006 (95.0%) subjects. We used Cox proportional hazards regression to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for pancreatic cancer. Results: During follow-up of up to 16.3 years (mean = 10.8 years; 226,325 person-years), 227 incident pancreatic cancers were diagnosed. The incidence rates were 9.9, 11.3, and 12.7 per 10,000 person-years of follow-up for participants with normal pepsinogen level (≥25 μg/l), low pepsinogen level and histologically confirmed atrophic gastritis, respectively. Compared to subjects with normal pepsinogen levels, there was no statistically significant increased risk of pancreatic cancer among subjects with low pepsinogen level (adjusted HR = 1.01; 95% CI: 0.63–1.62) or those with histologically confirmed atrophic gastritis (adjusted HR = 1.13; 95% CI: 0.66–1.95). Conclusions: Atrophic gastritis, serological or histological, is not associated with increased risk of pancreatic cancer. These findings do not provide any evidence for potential usefulness of SPGI for pancreatic cancer screening.     

Pretreatment hemoglobin level as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma

AimEvaluate pretreatment hemoglobin values as a prognostic factor in patients with locally advanced head and neck squamous cell carcinoma treated with concurrent chemoradiotherapy.BackgroundAnemia is one of the most prevalent laboratory abnormalities in oncological disease. It leads to a decrease in cellular oxygen supply, altering radiosensitivity of tumor cells and compromising therapeutic outcomes.Materials and MethodsRetrospective evaluation of patients with HNSCC treated with cCRT. Primary and secondary endpoint was to evaluate the correlation of Hb levels (≥12.5 g/dL or <12.5 g/dL) at the beginning of cCRT with overall survival (OS) and progression-free survival (PFS), respectively.ResultsA total of 108 patients were identified. With a median follow-up of 16.10 months median OS was 59.70 months for Hb ≥12.5 g/dL vs. 14.13 months for Hb <12.5 g/dL (p = 0.004). PFS was 12.29 months for Hb ≥12.5 g/dL and 1.68 months for Hb <12.5 g/dL (p = 0.016).ConclusionsIn this analysis, Hb ≥12.5 g/dL correlated with significantly better OS and PFS. Further studies are needed to validate these findings.     

The impact of chemokine receptor CXCR4 on breast cancer prognosis: A meta-analysis

Background: C-X-C chemokine receptor type 4 (CXCR4) has been implicated in the invasiveness and metastasis of diverse cancers. However, the published data remain controversial on the correlation between CXCR4 expression level, as well as its subcellular distribution in tumor cells, and the clinical outcome of patients with breast cancer. Methods: To identify the precise role of CXCR4 in the clinical outcome of breast cancer, we performed a meta-analysis including 15 published studies. Original data included the hazard ratios (HRs) of overall survival (OS) and disease-free survival (DFS) in breast cancer with high CXCR4 expression versus low expression. We pooled hazard ratios (HRs) with 95% confidence intervals (CIs) to estimate the hazard. Results: A total of 15 published studies (including 3104 patients) were eligible. Overall survival (OS) and disease-free survival (DFS) of breast cancer were found to be significantly related to CXCR4 expression level, with the HR being 1.65 (95%CI: 1.34–2.03; P < 0.00001) and 1.94 (95%CI: 1.42–2.65; P < 0.00001) respectively. Stratified analysis according to subcellular distribution of CXCR4 showed that high expression in whole cells, cytoplasm and nucleus could predict unfavorable OS, with the HR of 2.02 (95%CI: 1.43–2.85; P < 0.0001), 1.57 (95%CI: 1.13–2.18; P = 0.007), and 1.47 (95%CI: 1.19–1.81; P = 0.0004) respectively. As for DFS, elevated expression level of CXCR4 both in whole cells and cytoplasm predicted a poor outcome, with the HR being 2.23 (95%CI: 1.48–3.37; P = 0.0001) and 1.76 (95%CI: 1.11–2.80; P = 0.02), while high expression in the nucleus had no statistical significance, with HR 1.15 (95%CI: 0.52–2.55; P = 0.73). Conclusions: Increased CXCR4 expression, especially in whole cells and cytoplasm, may serve as a poor prognostic indicator in patients with breast cancer. Future studies are warranted to investigate the relationship between CXCR4 expression and survival of patients with breast carcinoma, which could help predict the clinical outcome and guide clinical decision-making for therapy.     

Clinical significance of serum transforming growth factor-β1 in lung cancer

Background: Transforming growth factor-β1 (TGF-β1) plays a critical role in human cancer development. Present study aimed to explore the clinical significance of serum TGF-β1 levels in patients with lung cancer and analyze the relationship between TGF-β1 and existing tumor markers for lung cancer. Methods: Serum was collected from 118 patients with lung cancer and 40 healthy volunteers. Serum TGF-β1 levels were measured by enzyme-linked immunosorbent assay (ELISA), and the association with various clinical characteristics was analyzed. The diagnostic value of TGF-β1 was assessed alone and in combination with existing tumor markers for lung cancer. Results: Serum TGF-β1 levels were significantly higher in patients with lung cancer compared to healthy volunteers [0.6 × 10⁵ (0.4 × 10⁵, 0.9 × 10⁵) pg/ml vs 0.5 × 10⁵ (0.3 × 10⁵, 0.7 × 10⁵) pg/ml, P = 0.040]. Although there was a positive correlation between serum TGF-β1 levels and advanced stages, the significant difference was not found between early stages and advanced stages (P = 0.116). The ability of serum TGF-β1 to discriminate lung cancer at a cutoff value of 79,168 pg/ml exhibited sensitivity of 30.6% and specificity of 97.5%. Serum TGF-β1 levels were correlated to cytokeratin fragment 21-1 (CYFRA21-1; R = 0.308, P = 0.020) and neuron-specific enolase (NSE; R = 0.558, P = 0.003). The diagnostic accuracy rates for the existing lung-tumor markers, as SCC, CYFRA21-1, and NSE, were increased from 20.0%, 34.6%, and 45.9% to 48.9%, 51.7%, and 54.5%, respectively by the inclusion of serum TGF-β1 levels. Conclusion: Quantification of serum TGF-β1 levels by ELISA may provide a novel complementary tool for the clinical diagnosis of lung cancer.     

Long-term risk of receiving a total hip replacement in cancer patients

Aim: To investigate whether cancer patients have an increased risk of receiving a total hip replacement compared to the standard population of Norway. Materials and methods: By linking of The Cancer Register of Norway and The Norwegian Arthroplasty Register we obtained information on cancer diagnoses (type, date of diagnosis), total hip arthroplasties and date of death for all patients living in Norway. This includes 741,901 patients categorized into three groups: 652,197 patients with at least one cancer diagnosis but no hip arthroplasties, 72,469 patients with at least one hip arthroplasty but no cancer diagnosis and 17,235 patients who have at least one cancer diagnosis and at least one hip arthroplasty. Within this latter group, 8563 individuals had been diagnosed with cancer prior to a total hip arthroplasty. Statistical methods applied in this study were Cox interval censored regression models and standardized incidence ratios (SIR). Results: Cancer patients had a slightly increased risk of receiving a total hip arthroplasty compared to the Norwegian population (SIR = 1.15 (95% CI, 1.12–1.17)). For primary tumours located cranially to the pelvic area there was no significant increase in risk for hip arthroplasty. An exception was breast cancer (SIR = 1.13 (95% CI 1.08–1.18)). Cancer located in the pelvic region (SIR = 1.20 (95% CI 1.16–1.24)), malignant lymphoma (SIR = 1.30 (95% CI 1.15–1.46)) and leukaemia (SIR = 1.17 (95% CI 1.01–1.34)) had an increased risk for receiving a total hip arthroplasty. Conclusion: Cancer survivors, mainly those with pelvic and lympho-hematological malignancies, have a small statistically significant increase in risk for receiving total hip arthroplasty.     

Acute myeloid leukemia incidence following radiation therapy for localized or locally advanced prostate adenocarcinoma

Introduction: The effect of radiation therapy on acute myeloid leukemia incidence among prostate cancer patients has not been sufficiently elucidated despite evidence that acute myeloid leukemia is a consequence of therapeutic radiation in other primary malignancies. Therefore, we investigated the effect of definitive therapy with radiation therapy (external beam radiation therapy [EBRT] or brachytherapy) on acute myeloid leukemia incidence in a population-based cohort of patients with localized or locally advanced prostate cancer. Methods: We utilized the Surveillance, Epidemiology, and End Results database to identify a cohort of men (n = 168,612) with newly diagnosed prostate adenocarcinoma between January 1988 and December 2003. Cox proportional hazard regression was used to estimate the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) of acute myeloid leukemia incidence following definitive therapy with EBRT alone, brachytherapy alone, or surgery alone compared to no definitive therapy (i.e. no EBRT, brachytherapy, or surgery). Results: The cohort yielded 184 acute myeloid leukemia cases during 1,064,820 person-years of follow-up after prostate adenocarcinoma diagnosis. Patients treated with EBRT had a higher adjusted relative risk of developing acute myeloid leukemia than patients treated with brachytherapy or surgery when each therapy group was compared to patients who were not treated with definitive therapy (EBRT: HR = 2.05, 95% CI 1.29, 3.26; brachytherapy: HR = 1.22, 95% CI 0.46, 3.22; surgery: HR = 1.24, 95% CI 0.77, 1.98). Conclusions: Our findings suggest that acute myeloid leukemia incidence is a greater concern for patients treated with EBRT than brachytherapy for localized or locally advanced prostate adenocarcinoma.