scholarly journals Genetic Variations in the PI3K/PTEN/AKT/mTOR Pathway Are Associated With Clinical Outcomes in Esophageal Cancer Patients Treated With Chemoradiotherapy

2009 ◽  
Vol 27 (6) ◽  
pp. 857-871 ◽  
Author(s):  
Michelle A.T. Hildebrandt ◽  
Hushan Yang ◽  
Mien-Chie Hung ◽  
Julie G. Izzo ◽  
Maosheng Huang ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Genetic Variations ◽  
Chemotherapeutic Agents ◽  
Response To Therapy ◽  
Nucleotide Polymorphisms ◽  
Chemotherapeutic Regimen ◽  
Risk Of Death ◽  
Increased Risk

Purpose The phosphoinositide-3-kinase (PI3K), phosphatase and tensin homolog (PTEN), v-akt murine thymoma viral oncogene homolog (AKT), and mammalian target of rapamycin (mTOR) signaling pathway has been implicated in resistance to several chemotherapeutic agents. In this retrospective study, we determined whether common genetic variations in this pathway are associated with clinical outcomes in esophageal cancer patients with adenocarcinoma or squamous cell carcinoma who have undergone chemoradiotherapy and surgery. Patients and Methods Sixteen tagging single nucleotide polymorphisms (SNPs) in PIK3CA, PTEN, AKT1, AKT2, and FRAP1 (encoding mTOR) were genotyped in these patients and analyzed for associations with response to therapy, survival, and recurrence. Results We observed an increased recurrence risk with genetic variations in AKT1 and AKT2 (hazard ratio [HR], 2.21; 95% CI, 1.06 to 4.60; and HR, 3.30; 95% CI, 1.64 to 6.66, respectively). This effect was magnified with an increasing number of AKT adverse genotypes. In contrast, a predictable protective effect by PTEN genetic variants on recurrence was evident. Survival tree analysis identified higher-order interactions that resulted in variation in recurrence-free survival from 12 to 42 months, depending on the combination of SNPs. Genetic variations in AKT1, AKT2, and FRAP1 were associated with survival. Patients homozygous for either of the FRAP1 SNPs assayed had a more than three-fold increased risk of death. Two genes—AKT2 and FRAP1—were associated with a poor treatment response, while a better response was associated with heterozygosity for AKT1:rs3803304 (odds ratio, 0.50; 95% CI, 0.25 to 0.99). Conclusion These results suggest that common genetic variations in this pathway modulate clinical outcomes in patients who undergo chemoradiotherapy. With further validation, these results may be used to build a model of individualized therapy for the selection of the optimal chemotherapeutic regimen.

XPA and XRCC3 gene polymorphisms and survival in esophageal cancer patients receiving neoadjuvant radiochemotherapy with cisplatin (CDDP), docetaxel (DTX), and 5-fluorouracil (FU)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e14571-e14571 ◽  
Author(s):  
M. Gusella ◽  
G. De Manzoni ◽  
R. Marinelli ◽  
S. Bruscagin ◽  
A. Bononi ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cancer Patients ◽  
Gene Polymorphisms ◽  
Locally Advanced ◽  
Pathological Response ◽  
Rank Test ◽  
Neoadjuvant Radiochemotherapy ◽  
Risk Of Death ◽  
Increased Risk ◽  
Xrcc3 Gene

e14571 Background: The aim of the study was to evaluate if genetic polymorphism of DNA repair genes may predict pathological response and survival in patients affected by locally advanced esophageal cancer, treated with a neoadjuvant schedule including weekly DTX (35 mg/mq) and CDDP (25mg/mq), protracted venous infusion of FU (150 mg/mq/die) and concomitant radiotherapy for 8 weeks followed by surgery. Methods: Fifty-seven patients were enrolled, aged 60±7 years old. Median follow-up was 27 months. Genomic DNA was extracted from peripheral blood lymphocytes and XPA, XPD, XRCC1, ERCC1 and XRCC3 were genotyped through RFLP analysis. Associations between gene polymorphisms and pathological response and survival were analysed through Chi square test and Log rank test respectively. Results: Thirty-two patients presented complete remission (pCR) and 10 patients microfocal residual disease (pMRD); the remaining 15 patients were considered stable or non-responders (pS-NR). The event free(EFS) and overall (OS) median survival times have not yet reached; significantly better 3-year survival rates were observed after pCR than in case of pMRD and pS-NR (EFS: 87% vs 42.8%, p=0.0004; OS: 86% vs 56%, p=0.02, respectively). No association was found between pathological response or survival with XRCC1, ERCC1 and XPD polymorphisms. On the contrary, the XPA 23AA genotype showed an increased risk of recurrence (HR=3.5; 95% CI 1.3 to 43.7, p=0.02) and death (HR=4.4, 95% CI 1.9 to 78.2, p=0.009); there was a trend for reduced risk of negative pathological response with decreasing number of allele 23A : MRD and S-NR were found in 71%, 45% and 35% cases for AA, AG and GG genotypes, respectively. The XRCC3 241MetMet variant was significantly associated with increased risk of death (HR= 6.0, 95% CI 3.0 to 40.0, p=0.008); a trend toward a higher recurrence (p=0.07) and worse response (60% vs 43%) was found. Conclusions: XPA and XRCC3 gene defective variants were significantly associated with worse outcome and could predict OS in esophageal cancer patients treated with a neo-adjuvant intensive radio-chemotherapy protocol. Founded by CARIPARO, Italy No significant financial relationships to disclose.

EFFECTS OF SMOKING ON THE DISEASE PROGNOSIS IN CANCER PATIENTS

2019 ◽  
Vol 65 (3) ◽  
pp. 321-329
Author(s):  
David Zaridze ◽  
Anush Mukeriya
Keyword(s):  
Smoking Cessation ◽  
Cancer Patients ◽  
Malignant Tumors ◽  
Scientific Data ◽  
Second Primary ◽  
Primary Tumors ◽  
Smoking Intensity ◽  
Risk Of Death ◽  
Disease Prognosis ◽  
Increased Risk

Smoking not only increases the risk of the development of malignant tumors (MT), but affects the disease prognosis, mortality and survivability of cancer patients. The link between the smoking of cancer patients and increased risk of death by all diseases and oncological causes has been established. Mortality increases with the growth of the smoking intensity, i.e. the number of cigarettes, smoked per day. Smoking is associated with the worst general and oncological survivability. The statistically trend-line between the smoking intensity and survivability was observed: each additional unit of cigarette consumption (pack/year) leads to the Overall Survival Reduction by 1% (p = 0.002). The link between smoking and the risk of developing second primary tumors has been confirmed. Smoking increases the likelihood of side effects of the antitumor therapy both drug therapy and radiation therapy and reduces the treatment efficacy. The smoking cessation leads to a significant improvement in the prognosis of a cancer patient. Scientific data on the negative effect of smoking on the prognosis of cancer patients have a major clinical importance. The treatment program for cancer patients should include science-based methods for the smoking cessation. The latter is fundamentally important, taking into account that the smoking frequency among cancer patients is much higher than in the population.

scholarly journals Cross-sectional observational study of epidemiology of COVID-19 and clinical outcomes of hospitalised patients in North West London during March and April 2020

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e044384
Author(s):  
Guduru Gopal Rao ◽  
Alexander Allen ◽  
Padmasayee Papineni ◽  
Liyang Wang ◽  
Charlotte Anderson ◽  
...  
Keyword(s):  
Mechanical Ventilation ◽  
Clinical Outcomes ◽  
Severe Infection ◽  
Older Age ◽  
Cross Sectional ◽  
North West ◽  
Icu Admission ◽  
Risk Of Death ◽  
Hospitalised Patients ◽  
Increased Risk

ObjectiveThe aim of this paper is to describe evolution, epidemiology and clinical outcomes of COVID-19 in subjects tested at or admitted to hospitals in North West London.DesignObservational cohort study.SettingLondon North West Healthcare NHS Trust (LNWH).ParticipantsPatients tested and/or admitted for COVID-19 at LNWH during March and April 2020Main outcome measuresDescriptive and analytical epidemiology of demographic and clinical outcomes (intensive care unit (ICU) admission, mechanical ventilation and mortality) of those who tested positive for COVID-19.ResultsThe outbreak began in the first week of March 2020 and reached a peak by the end of March and first week of April. In the study period, 6183 tests were performed in on 4981 people. Of the 2086 laboratory confirmed COVID-19 cases, 1901 were admitted to hospital. Older age group, men and those of black or Asian minority ethnic (BAME) group were predominantly affected (p<0.05). These groups also had more severe infection resulting in ICU admission and need for mechanical ventilation (p<0.05). However, in a multivariate analysis, only increasing age was independently associated with increased risk of death (p<0.05). Mortality rate was 26.9% in hospitalised patients.ConclusionThe findings confirm that men, BAME and older population were most commonly and severely affected groups. Only older age was independently associated with mortality.

miR-146a and miR-196a-2 genes polymorphisms and its circulating levels in lung cancer patients

2019 ◽  
Vol 166 (4) ◽  
pp. 323-329 ◽  
Author(s):  
Randa H Mohamed ◽  
Heba F Pasha ◽  
Doaa M Gad ◽  
Mostafa M Toam
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Cancer Patients ◽  
Lung Cancer Risk ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Lung Cancer Patients ◽  
Increased Risk ◽  
Increase Risk ◽  
Circulating Levels

AbstractRecently, MicroRNAs polymorphisms and their serum expression have been linked to increase risk of various cancers. The aim of this study was to elucidate the association between single nucleotide polymorphisms of miR-146a and miR-196a-2 and their serum expression and lung cancer risk. One hundred and twenty lung cancer patients and 120 health controls were included in this study. Genotyping and expression for miR-146a and miR-196a-2 were performed using polymerase chain reaction (PCR)-restriction fragment length polymorphism and quantitative real-time PCR. Individuals carrying miR-146a CG and CC genotypes had significantly increased risk for lung cancer than those carrying miR-146a GG genotype. MiR-146a expression significantly decreased in miR-146a CG and CC genotypes carriers as compared with GG genotype carriers. MiR-196a-2 CT and TT genotypes were significantly associated with increased lung cancer while the highest expression of MiR-196a-2 was detected in miR-196a-2 CC genotype carriers. Serum miR-146a was significantly decreased in lung cancer patients while serum miR-196a-2 expression was significantly increased in lung cancer patients. In conclusion, miR-146a and miR-196a-2 genes polymorphisms and their circulating levels were associated with lung cancer risk in Egyptians and may be helpful in early detection of lung cancer.

The Prevalence of Frailty in Cancer Patients and Mortality Prediction With a Novel Frailty Index Based Clinical Algorithm-A Multicenter, Prospective, Observational Study

2020 ◽  
Author(s):  
Xi Jin ◽  
Yue Ren ◽  
Li Shao ◽  
Zengqing Guo ◽  
Chang Wang ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Frailty Index ◽  
National Level ◽  
Laboratory Data ◽  
Mortality Prediction ◽  
Prediction Algorithm ◽  
Tumor Type ◽  
Risk Of Death ◽  
Increased Risk ◽  
Chinese Cancer Patients

Abstract Purpose To investigate the prediction capacity and status of frailty in Chinese cancer patients in national level, through establishing a novel prediction algorithm. Methods The percentage of frailty in different ages, provinces and tumor type groups of Chinese cancer patients were revealed. The predictioncapacity of frailty on mortality of Chinese cancer patients was analyzed by FI-LAB that is composed of routine laboratory data from accessible blood test and calculated as the ratio of abnormal factors in 22 variables. Establishment of a novel algorithm MCP(mortality of cancer patients)to predict the five-year mortality in Chinese cancer patients was accomplished and its prediction capacity was tested in the training and validation sets using ROC analysis. ResultsWe found that the increased risk of death in cancer patients can be successfully identified through FI-LAB. The univariable and multivariable Cox regression were used to evaluate the effect of frailty on death. In the 5-year follow-up, 20.6% of the 2959 participants (age = 55.8 ± 11.7 years; 43.5% female) were dead while the mean FI-LAB score in baseline was 0.23 (standard deviation = 0.13; range = 0 to 0.73).Frailty (after adjusting for gender, age, and other confounders) could be directly correlated with increased risk of death, with a hazard ratio of 12.67 (95% confidence interval CI: 7.19, 22.31) in comparison with those without frailty. In addition, MCP algorithm presented an area under the ROC (AUC) of 0.691 (95% CI: 0.659-0.684) and 0.648 (95% CI: 0.613-0.684) in the training and validation set, respectively. Conclusion Frailty is common in cancer patients and FI-LAB has high prediction capacity on mortality. The MCP algorithm is a good supplement for frailty evaluation and mortality prediction in cancer patients.

scholarly journals Preventing Venous Thromboembolism in Ambulatory Patients with Cancer: A Narrative Review

Cancers ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 612 ◽  
Author(s):  
Anne Rossel ◽  
Helia Robert-Ebadi ◽  
Christophe Marti
Keyword(s):  
Venous Thromboembolism ◽  
Cancer Patients ◽  
Absolute Risk ◽  
Narrative Review ◽  
Relative Reduction ◽  
Number Needed To Treat ◽  
Chemotherapeutic Regimen ◽  
Patients With Cancer ◽  
Increased Risk ◽  
Risk Of Cancer

Venous thromboembolism (VTE) is frequent among patients with cancer. Ambulatory cancer patients starting chemotherapy have a 5% to 10% risk of cancer associated thrombosis (CAT) within the first year after cancer diagnosis. This risk may vary according to patient characteristics, cancer location, cancer stage, or the type of chemotherapeutic regimen. Landmark studies evaluating thrombophrophylaxis with low molecular weight heparin (LMWH) for ambulatory cancer patients have shown a relative reduction in the rate of symptomatic VTE of about one half. However, the absolute risk reduction is modest among unselected patients given a rather low risk of events resulting in a number needed to treat (NNT) of 40 to 50. Moreover, this modest benefit is mitigated by a trend towards an increased risk of bleeding, and the economic and patient burden due to daily injections of LMWH. For these reasons, routine thromboprophylaxis is not recommended by expert societies. Advances in VTE risk stratification among cancer patients, and growing evidence regarding efficacy and safety of direct oral anticoagulants (DOACs) for the treatment and prevention of CAT have led to reconsider the paradigms of this risk–benefit assessment. This narrative review aims to summarize the recent evidence provided by randomized trials comparing DOACs to placebo in ambulatory cancer patients and its impact on expert recommendations and clinical practice.

scholarly journals P.064 Delays in the emergency department for stroke patients, medical complications and predictors of outcomes: the McGill experience

2016 ◽  
Vol 43 (S2) ◽  
pp. S36-S36
Author(s):  
C Legault ◽  
B Chen ◽  
L Vieira ◽  
B Lo (Montreal) ◽  
L Wadup ◽  
...  
Keyword(s):  
Emergency Department ◽  
Clinical Outcomes ◽  
Stroke Unit ◽  
Best Practice ◽  
Brain Oedema ◽  
Medical Complications ◽  
Significant Delay ◽  
Stroke Patients ◽  
Risk Of Death ◽  
Increased Risk

Background: The Canadian Stroke Best Practice recommends admission of patients to a specialised stroke unit within three hours. We aimed at assessing delays in our emergency department (ED) and correlating these with medical complications and clinical outcomes. Methods: Predictors and outcomes This is a retrospective review of patients (n=353) admitted with ischemic strokes (January 2011-March 2014). We assessed the length of stay in ED, medical complications in ED and in the stroke unit, functional status (modified Rankin Scale) at discharge and survival. Results: The median delay in ED was 13.8 hours. The rate of medical complications in the ED was 14% (most common being delirium), compared to the stroke unit with 46.7% (most common being pneumonia). Worse functional outcome was correlated with diagnosis of pneumonia (standardised β coefficient=0.2, p=0.001) and presence of brain oedema in the stroke unit (standardised β coefficient=0.2, p<0.01). Increased risk of death was correlated with brain oedema (OR=649.2, 95%CI=19-2184, p<0.01) and sepsis in the stroke unit (OR=26.8, 95%CI=2.1-339, p<0.01). Conclusions: We found a significant delay in the admission of our patients from the ED to the stroke unit, which is not in keeping with the present guidelines. Medical complications were correlated with worse outcomes. Future analyses will correlate ED delays with clinical outcomes.

scholarly journals Preterm Nutrition and Clinical Outcomes

2020 ◽  
Vol 7 ◽  
pp. 2333794X2093785
Author(s):  
Netsanet Workneh Gidi ◽  
Amha Mekasha ◽  
Assaye K. Nigussie ◽  
Robert L. Goldenberg ◽  
Elizabeth M. McClure ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Preterm Infants ◽  
Enteral Feeding ◽  
Low Income ◽  
Neonatal Intensive Care ◽  
Low Income Countries ◽  
Preterm Neonates ◽  
Risk Of Death ◽  
Increased Risk ◽  
Preterm Formula

Background. In low-income countries, preterm nutrition is often inadequately addressed. The aim of the study was to assess the patterns of feeding and associated clinical outcomes of preterm neonates admitted to neonatal intensive care units in Ethiopia. Method. This was a multicenter, prospective study. Infants’ clinical characteristics at birth, daily monitoring of feeding history, and weight measurements were collected. An outcome assessment was completed at 28 days. Result. For this analysis, 2560 infants (53% male) were eligible. The mean (SD) gestational age was 33.1 (2.2) weeks. During the hospital stay the proportion of infants on breast milk only, preterm formula, term formula, and mixed feeding was 58%, 27.4%, 1.6%, and 34.1%, respectively. Delay in enteral feeding was associated with increased risk of death (odds ratio [OR] = 1.92, 95% confidence interval [CI] = 1.33-2.78; P < .001) and (OR = 5.06, 95% CI = 3.23-7.87; P < .001) for 1 to 3 and 4 to 6 days of delay in enteral feeding, respectively, after adjusting for possible confounders. The length of delay in enteral feeding was associated with increased risk of hypoglycemia (OR = 1.2, 95% CI = 1.1-1.2; P = .005). The mortality rate was lower in hospitals providing preterm formula more often ( P = .04). Half of the infants continued losing weight at the time of discharge. Conclusion. Delayed enteral feeding significantly increases the risk of mortality before discharge and hypoglycemia in preterm infants in resource-limited settings. Ensuring adequate nutritional support of preterm infants is highly needed.

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