Cancer by Sfakianakis Alexandros: 12/16/17

Σάββατο 16 Δεκεμβρίου 2017

Circulating tumour DNA, a promising biomarker for the management of colorectal cancer

Publication date: Available online 16 December 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Shelize Khakoo, Alexandros Georgiou, Marco Gerlinger, David Cunningham, Naureen Starling
Circulating cell free tumour DNA (ctDNA) maintains the same genomic alterations that are present in the corresponding tumour, thereby allowing for quantitative and qualitative real-time evaluation in body fluids as an alternative to onerous repeat biopsies. Improvements in the sensitivity of techniques used to identify ctDNA has led to a surge of research investigating its role in the detection of: early disease, relapse, response to therapy and emerging drug resistance mechanisms. Following curative surgery, ctDNA detection is a promising marker of minimal residual disease and could better select patients for adjuvant chemotherapy. Longitudinal monitoring could help identify early relapse. In metastatic disease, ctDNA can predict response to chemotherapy prior to evidence of disease progression on imaging and investigate novel primary and acquired resistance mechanisms to targeted therapies. More experience in detecting, analysing and interpreting ctDNA within prospective trials, will better define its role for implementation into routine clinical practice.

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A SYSTEMATIC REVIEW OF THE SAFETY PROFILE OF THE DIFFERENT COMBINATIONS OF FLUOROPYRIMIDINES AND OXALIPLATIN IN THE TREATMENT OF COLORECTAL CANCER PATIENTS

Publication date: Available online 16 December 2017
Source:Critical Reviews in Oncology/Hematology
Author(s): Chiara Baratelli, Clizia Zichi, Massimo Di Maio, Maria Pia Brizzi, Cristina Sonetto, Giorgio Vittorio Scagliotti, Marco Tampellini
The available fluoropyrimidines and oxaliplatin combinations for colorectal cancer patients have different safety profiles. The aim of this systematic review was to compare their toxicities.The eligible studies were classified as: no bolus; 5-FU single bolus; 5-FU double bolus; capecitabine. We calculated the incidence of "any-grade" and "severe" toxicity for haematological and non-haematological adverse events of each group.We identified 184 treatment groups; compared to 5-FU double bolus, except for high-grade anaemia, all the groups showed reduced risk of haematological toxicities, with the most relevant advantages for single bolus regimens. Concerning non-haematological toxicities, compared to double bolus, the single bolus group showed a statistically significant reduced risk for many gastrointestinal toxicities and for pheripheral neuropathy.This is the first systematic review of the toxicity profile of different 5-FU or capecitabine and oxaliplatin regimens. Single 5-FU bolus is associated with a definitely favourable toxicity profile, both for haematological and non-haematological toxicity.

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Circulating tumour DNA, a promising biomarker for the management of colorectal cancer

A SYSTEMATIC REVIEW OF THE SAFETY PROFILE OF THE DIFFERENT COMBINATIONS OF FLUOROPYRIMIDINES AND OXALIPLATIN IN THE TREATMENT OF COLORECTAL CANCER PATIENTS

Prognostic factors affecting overall survival and local control in meningioma patients treated with radiotherapy or combined radiotherapy and surgery

Abstract

Background

Meningiomas account for 15–20% of adult primary brain neoplasms. We reviewed 142 meningioma cases treated with radiotherapy (RT) alone or combined RT and surgery to assess prognostic factors affecting overall survival (OS) and local control (LC).

Methods

Medical records were reviewed for progesterone receptor (PR) status, World Health Organization (WHO) grade, and treatment given, and we evaluated how these factors affected OS and LC. We also assessed OS and LC in patients treated with adjuvant RT versus salvage RT.

Results

From 1997 to 2014, 142 patients with meningioma were treated with RT. The median follow-up time since the completion of RT was 4.43 years. When adjusted for age at diagnosis, there was no difference in OS for surgery + RT versus RT alone, p = 0.656. Local control at 5 years was 88.2% with adjuvant RT versus 74.9% with salvage RT, p = 0.326. Five-year OS and LC were higher for grade I (OS 92.4%, LC 80.8%) versus grade II or higher meningiomas (OS 88.0%, LC 53.7%), p < 0.05. Five-year LC was 82.9% in women and 64.2% in men, p = 0.011. Local control at 5 years was 76.1% in patients with strong PR expression versus 41.7% in patients with focal or no PR expression, p = 0.029.

Conclusions

We confirm that meningioma grade is prognostic for OS and LC. Gender and PR status were prognostic with respect to LC, with significantly better LC in women and patients with strong PR expression.

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Clinicopathologic and Immunohistochemical Study of Combined Small Cell Carcinoma and Urothelial Carcinoma Molecular Subtype

Abstract

Muscle invasive bladder cancer, an aggressive disease with heterogeneous molecular profiles, has recently been subclassified into three major molecular subtypes -basal, luminal and "p53-like" urothelial carcinomas (UCas), which bear prognostic and therapeutic implication. Similar to breast cancer, basal and luminal subtype UCas are designated by basal (CK5/14) and luminal (CK20) markers. The "p53-like" subtype presents with wild-type p53 gene with upregulated p53 pathways and is implicated in chemoresistance. Urinary bladder is one of the most common primary sites of extrapulmonary small cell carcinoma (SmCC). Bladder SmCC frequently coexists with UCa; however, the relation of SmCC with specific UCa molecular subtypes has not been studied. The aim of this study is to investigate the clinicopathology and immunophenotypes of the combined SmCC and UCa molecular subtypes. A total of 22 combined SmCC and UCa cases were studied for the clinicopathology and immunohistochemical (IHC) profiles by luminal and basal cell markers as well as Her2/Neu and p53. Our results demonstrated that all the urinary bladder SmCCs were associated with high grade UCas. They were more commonly seen in older male patients with a smoking history and had a poor prognosis. Based on the reported molecular subtyping, the UCas could be immunohistochemically subclassified into luminal, basal, dual and null types, which showed different clinicopathologic and IHC features. Compared to non-SmCC associated UCa, the subtypes of UCa in the combined SmCCs and UCas were characterized by: 1) Although overall luminal type was still relatively more common in men, basal marker-expressing subtypes were significantly increased in incidence and were more common in women. 2) Her2/Neu overexpression was more commonly observed in luminal than basal cell marker-expressing UCas. 3) IHC overexpression of p53 was common in all the subtypes, with UCas and SmCCs sharing the same p53 expression pattern. Although limited by relatively a small number of cases, the results of this study will enhance our understanding of the combined SmCC and UCa entity and potentially lead to a future therapeutic management.

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Clinicopathologic and Immunohistochemical Study of Combined Small Cell Carcinoma and Urothelial Carcinoma Molecular Subtype

Abstract

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Extracellular vesicles as drivers of epithelial-mesenchymal transition and carcinogenic characteristics in normal prostate cells

ABSTRACT

There is increasing evidence that cancer dissemination and metastasis establishment may not only be due to the movement of tumor cells. Content of extracellular vesicles (EVs) secreted by tumor cells may also reflect the origin of these cells. Some molecules that constitute these EVs have already been used as targets for detection of specific tumors. However, to the best of our knowledge, EVs from biopsies and plasma have not yet been compared nor thoroughly investigated as triggers of malignant transformation and metastatic niche formation. To evaluate the role of EVs in the cellular microenvironment, we have treated the normal epithelial prostate cell lines, RWPE-1 and PNT-2, with a pool of EVs from biopsies of prostate primary tumors (bEVs), biopsies of benign prostate hyperplasia (hEVs), plasma of prostate cancer (PCa) patients (pEVs) or plasma of healthy individuals (pnEVs). Each of the four pools consisted of isolated EVs from several subjects, of which PCa patients were in different stages of cancer. Migration and proliferation profiles, cytokine release, and a panel of PCa-associated genes' expression of epithelial-mesenchymal transition in the cell lines were evaluated after 24 h incubation with EVs. When compared to the control groups, cells treated with the pool of EVs isolated from tumor biopsies and plasma of PCa patients showed greater migration and proliferation, significant alterations in gene expression, and high levels of IL-8, factors that are associated with cancer development. Specifically, isolated bEVs and pEVs may induce malignant features in non-tumor cells by activating several cellular events associated with cancer progression, suggesting that future PCa therapy may target multiple elements found in tumor-derived EVs. This article is protected by copyright. All rights reserved

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The triterpenoid corosolic acid blocks transformation and epigenetically reactivates Nrf2 in TRAMP-C1 prostate cells

Abstract

Corosolic acid (CRA) is found in various plants and has been used as a health food supplement worldwide. Although it has been reported that CRA exhibits significant anticancer activity, the effect of this compound on prostate cancer remains unknown. In this study, we investigated the effect of CRA on cellular transformation and the reactivation of nuclear factor erythroid 2-related factor 2 (Nrf2) through epigenetic regulation in TRAMP-C1 prostate cells. Specifically, we found that CRA inhibited anchorage-independent growth of prostate cancer TRAMP-C1 cells but not Nrf2 knockout prostate cancer TRAMP-C1 cells. Moreover, CRA induced mRNA and protein expression of Nrf2, heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO1). Bisulfate genomic sequencing and methylated DNA immunoprecipitation results revealed that CRA treatment decreased the level of methylation of the first five CpG sites of the Nrf2 promoter. Histone modification was analyzed using a chromatin immunoprecipitation (ChIP) assay, which revealed that CRA treatment increased the acetylation of histone H3 lysine 27 (H3K27ac) while decreasing the trimethylation of histone H3 lysine 27 (H3K27me3) in the promoter region of Nrf2. Furthermore, CRA treatment attenuated the protein expression of DNA methyltransferases (DNMTs) and histone deacetylases (HDACs). These findings indicate that CRA has a significant anticancer effect in TRAMP-C1 cells, which could be partly attributed to epigenetics including its ability to epigenetically restore the expression of Nrf2. This article is protected by copyright. All rights reserved

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Factors associated with possible complicated grief and major depressive disorders

Abstract

Objective

Complicated grief (CG) is considered a distinctive symptom from other bereavement-related mental impairments such as major depressive disorder (MDD). CG and MDD may appear independently or co-morbidly; however, the factors associated with each situation are unclear.

Methods

We conducted a nationwide cross-sectional questionnaire survey involving bereaved family members of cancer patients in 175 institutions. The following items were included in the questionnaires to assess the prevalence of CG and MDD, and the following associated factors: demographic characteristics; bereaved family depression (Patient Health Questionnaire-9) and grief status (Brief Grief Questionnaire); structure and process of care (Care Evaluation Scale); overall care satisfaction; and achievement of a good death (Good Death Inventory).

Results

A total of 9,123 questionnaires were returned. The prevalence of CG and MDD was 14% and 17%, respectively. Additionally, 58% of the possible CG participants showed co-morbid symptoms. Common factors that showed significant association with either independent or co-morbid symptoms of CG and MDD were pre=existing mental impairment; belief in the survival of the soul after physical death; unpreparedness for the death; poor physical or psychological health status; and the belief that the deceased felt themselves as a burden to others (all p <0.05). The duration of bereavement did not remain significant after multivariate analysis.

Conclusions

While there were many common factors associated with both CG and MDD independently, few participants exhibited associations to both CG and MDD. Therefore, CG and MDD can be considered as distinctive symptoms, which frequently appear co-morbidly.

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Interventions developed with the Intervention Mapping protocol in the field of cancer: a systematic review.

Abstract

Objectives

The Intervention Mapping (IM) protocol provides a structured framework to develop, implement and evaluate complex interventions. The main objective of this review was to identify and describe the content of the interventions developed in the field of cancer with the IM protocol. Secondary objectives were to assess their fidelity to the IM protocol and to review their theoretical frameworks.

Methods

Medline, Web of Science, PsycINFO, Pascal, Francis, and BDSP databases were searched. All titles and abstracts were reviewed. A standardized extraction form was developed. All included studies were reviewed by two reviewers blinded to each other.

Results

Sixteen studies were identified, and these reported 15 interventions. The objectives were to increase cancer screening participation (n=7), early consultation (n=1) and aftercare / quality of life among cancer survivors (n=7). Six reported a complete participatory planning group and seven described a complete logic model of the problem. Ten studies described a complete logic model of change. The main theoretical frameworks used were the theory of planned behaviour (n=8), the transtheoretical model (n=6), the health belief model (n=6) and the social cognitive theory (n=6). The environment was rarely integrated in the interventions (n=4). Five interventions were reported as effective.

Conclusions

Culturally relevant interventions were developed with the IM protocol that were effective to increase cancer screening and reduce social disparities, particularly when they were developed through a participative approach and integrated the environment. Stakeholders' involvement and the role of the environment were heterogeneously integrated in the interventions.

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Extracellular vesicles as drivers of epithelial-mesenchymal transition and carcinogenic characteristics in normal prostate cells

ABSTRACT

http://ift.tt/2AY2Y3t

The triterpenoid corosolic acid blocks transformation and epigenetically reactivates Nrf2 in TRAMP-C1 prostate cells

Abstract

http://ift.tt/2yL6gRI

Factors associated with possible complicated grief and major depressive disorders

Abstract

Objective

Methods

Results

Conclusions

http://ift.tt/2B11pBJ

Interventions developed with the Intervention Mapping protocol in the field of cancer: a systematic review.

Abstract

Objectives

Methods

Results

Conclusions

http://ift.tt/2yJwvIi

Predictors of adherence to exercise interventions during and after cancer treatment: a systematic review

Abstract

Objective

Exercise interventions benefit cancer patients. However, only low numbers of patients adhere to these interventions. This review aimed to identify predictors of exercise intervention adherence in patients with cancer, during and after multimodality cancer treatment.

Methods

A literature search was performed using electronic databases (Pubmed, Embase and Cochrane) to identify relevant papers published before February 1st 2017. Papers reporting randomized controlled trials, conducted in adult cancer patients who participated in an exercise intervention during and/or after multimodality cancer treatment, providing outcome of factors predicting exercise adherence were included. Papers were assessed for methodological quality by using the Physiotherapy Evidence Database scale.

Results

The search identified 720 potentially relevant papers, of which 15 fulfilled the eligibility criteria. In these 15 studies, 2,279 patients were included and 1,383 of these patients were randomized to an exercise intervention. During cancer treatment the factors predicting exercise adherence: location of the rehabilitation center, extensive exercise history, high motivation for exercise and fewer exercise limitations. After cancer treatment, factors that predicted adherence were: less extensive surgery, low alcohol consumption, high previous exercise adherence, family support, feedback by trainers and knowledge and skills of exercise. Methodological quality of the included papers was rated 'high'.

Conclusions

The most prominent predictors of adherence to exercise interventions were location of the rehabilitation center, extensive exercise history, high motivation for exercise and fewer exercise limitations. To increase the number of cancer patients that benefit, these results should be considered into the development and implementation of future exercise interventions.

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Ovarian cancer risk, ALDH2 polymorphism and alcohol drinking: Asian data from the Ovarian Cancer Association Consortium

Summary

The ALDH2 polymorphism rs671 (Glu504Lys) causes ALDH2 inactivation and adverse acetaldehyde exposure among Asians, but little is known of the association between alcohol consumption and rs671 and ovarian cancer (OvCa) in Asians. We conducted a pooled analysis of Asian ancestry participants in the Ovarian Cancer Association Consortium. We included seven case-control studies and one cohort study comprising 460 invasive OvCa cases, 37 borderline mucinous OvCa and 1,274 controls of Asian descent with information on recent alcohol consumption. The pooled odds ratios (OR) with 95% confidence intervals (CI) for OvCa risk associated with alcohol consumption, rs671 and their interaction were estimated using logistic regression models adjusted for potential confounders. No significant association was observed for daily alcohol intake with invasive OvCa (OR comparing any consumption to none =0.83; 95% CI=0.58-1.18) or with individual histotypes. A significant decreased risk was seen for carriers of one or both Lys alleles of rs671 for invasive mucinous OvCa (OR=0.44; 95% CI=0.20-0.97) and for invasive and borderline mucinous tumors combined (OR=0.48; 95% CI=0.26-0.89). No significant interaction was observed between alcohol consumption and rs671 genotypes. In conclusion, self-reported alcohol consumption at the quantities estimated was not associated with OvCa risk among Asians. Because the rs671 Lys allele causes ALDH2 inactivation leading to increased acetaldehyde exposure, the observed inverse genetic association with mucinous ovarian cancer is inferred to mean that alcohol intake may be a risk factor for this histotype. This association will require replication in a larger sample.

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MiR-155 promotes gastric cancer growth and invasion by negatively regulating Transforming Growth Factor Beta Receptor 2

Summary

Gastric cancer (GC) has a high morbidity and mortality among the common malignancies worldwide. It is essential to elucidate the molecular events of GC proliferation and invasion, which will provide new therapeutic targets for GC. The inactivation of TGFβR2 is correlates with cancer cells growth and metastasis, but the mechanisms underlying the down-regulation of TGFβR2 expression remain unknown. MicroRNAs (miRNAs) act as post-transcriptional regulators play a key role in the development of cancers. The bioinformatics analysis and luciferase reporter assay demonstrated that miR-155 directly bind the 3′-untranslated region (3′-UTR) of TGFβR2 mRNA. In this study, we found that the TGFβR2 protein levels, but not mRNA levels, were down-regulated in GC tissues, while the levels of miR-155 were significantly increased in GC tissues. We deduced miR-155 inversely correlated with TGFβR2 in GC cells. In vitro studies showed that over-expression of miR-155 in SGC7901 inhibited the expression of TGFβR2 and then promoted GC cell proliferation and migration, whereas miR-155 inhibitor showed opposite effects. In addition, the tumor suppressing function of TGFβR2 was verified by using siRNA (small interfering RNA) and TGFβR2 over-expressing plasmid respectively. The results illustrated the miR-155 promotes cell growth and migration by negatively regulating TGFβR2. Thus, miR-155-regulated TGFβR2 as a potential therapeutic target in GC.

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ADAM9 is over-expressed in human ovarian clear cell carcinomas and suppresses cisplatin-induced cell death

Abstract

ADAMs (a disintegrin and metalloproteinases) are involved in various biological events such as cell adhesion, migration and invasion, membrane protein shedding and proteolysis. However, there have been no systematic studies on the expression of ADAMs in human ovarian carcinomas. We therefore examined the mRNA expression of all the proteolytic ADAM species including ADAM8, 9, 10, 12, 15, 17, 19, 20, 21, 28, 30, 33 and ADAMDEC1 in human ovarian carcinomas, and found that prototype membrane-anchored ADAM9m, but not secreted isoform ADAM9s, is significantly over-expressed in the carcinomas than in the control non-neoplastic ovarian tissue. Among the histological sub-types of serous, endometrioid, mucinous and clear cell carcinomas, the ADAM9m expression was highest in the clear cell carcinomas. Immunohistochemistry demonstrated that all the clear cell carcinoma samples exhibit ADAM9m primarily on the carcinoma cell membrane. By immunoblotting, ADAM9m was detected mainly in an active form in the clear cell carcinoma tissues. When two clear cell carcinoma cell lines (RMG-I and TOV21G cells) with ADAM9m expression were treated with cisplatin, the viability was significantly reduced and apoptosis increased in ADAM9m knock-down cells compared with mock transfectants. In addition, treatment of the cells with neutralizing anti-ADAM9m antibody significantly decreased viability compared with non-immune IgG, whereas ADAM9m over-expression significantly increased viability compared with mock transfectants. Our data demonstrate, to the best of our knowledge, for the first time that ADAM9m is over-expressed in an activated form in human ovarian clear cell carcinomas, and suggest that ADAM9m plays a key role in the cisplatin-resistance.

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Whole exome sequencing to identify genetic markers for trastuzumab-induced cardiotoxicity

Abstract

Although trastuzumab-induced cardiotoxicity is an important determinant to limit the use of this drug, the molecular mechanism of risk for this toxicity is not well understood. To identify genetic variants determining the risk of trastuzumab-induced cardiotoxicity, we performed whole exome sequencing of germline DNA samples from 9 patients with trastuzumab-induced cardiotoxicity, and conducted a case–control association study of 2,258 genetic variants between 9 cases (with trastuzumab-induced cardiotoxicity) and general Japanese population controls registered in Human Genetic Variation Database (HGVD). The top variant which revealed the lowest P value in the screening study was rs139503277 in PHD Finger Protein 3 (P_min = 0.00012, odds ratio (OR) = 51.23). To further validate the result of screening study, we carried out a replication study of 10 variants showing P_min < 0.001 in the screening study using 234 independent patients treated with trastuzumab, including 10 cases and 224 controls (without trastuzumab-induced cardiotoxicity). In the replication study, we observed that three variants had effect in the same direction as in the screening study (rs78272919 in exon 2 of Keratin 15, rs5762940 in exon 2 of zinc and ring finger 3 and rs139944387 in exon 44 of Eyes shut homologs (EYS)). A combined result of the screening and the replication studies suggested an association of a locus on chromosome 6q12 with trastuzumab-induced cardiotoxicity (rs139944387 in EYS, combined-P_min = 0.00056, OR = 13.73). This finding provides new insights into personalized trastuzumab therapy for the patients with HER2 positive cancer.

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Modulation of the Tumor Microenvironment by Epstein-Barr virus Latent Membrane Protein-1 in Nasopharyngeal Carcinoma

Abstract

Latent membrane protein 1 (LMP1) is a primary oncogene encoded by the Epstein-Barr virus, and various portions of LMP1 are detected in nasopharyngeal carcinoma (NPC) tumor cells. LMP1 has been extensively studied since the discovery of its transforming property in 1985. LMP1 promotes cancer cell growth during NPC development and facilitates the interaction of cancer cells with surrounding stromal cells for invasion, angiogenesis, and immune modulation. LMP1 is detected in 100% of pre-invasive NPC tumors and in approximately 50% of advanced NPC tumors. Moreover, a small population of LMP1-expressing cells in advanced NPC tumor tissue is proposed to orchestrate NPC tumor tissue maintenance and development through cancer stem cells and progenitor cells. Recent studies suggest that LMP1 activity shifts according to tumor development stage, but still has a pivotal role during all stages of NPC development.

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Ovarian cancer risk, ALDH2 polymorphism and alcohol drinking: Asian data from the Ovarian Cancer Association Consortium

Summary

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MiR-155 promotes gastric cancer growth and invasion by negatively regulating Transforming Growth Factor Beta Receptor 2

Summary

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ADAM9 is over-expressed in human ovarian clear cell carcinomas and suppresses cisplatin-induced cell death

Abstract

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Whole exome sequencing to identify genetic markers for trastuzumab-induced cardiotoxicity

Abstract

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Systematic intrafraction shifts of mediastinal lymph node targets between setup imaging and radiation treatment delivery in lung cancer patients

Internal target motion results in geometrical uncertainties in lung cancer radiotherapy. In this study, we determined the intrafraction motion and baseline shifts of mediastinal lymph node (LN) targets between setup imaging and treatment delivery.

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Nomogram to predict the benefit of additional induction chemotherapy to concurrent chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma: Analysis of a multicenter, phase III randomized trial

Recent clinical trials and network meta-analysis have suggested that the addition of induction chemotherapy (IC) to concurrent chemoradiotherapy (CCRT) could improve survival in locoregionally advanced NPC (LANPC). We aimed to develop a nomogram to estimate the benefit of IC for individual patients based on the data from a multicenter, randomized, phase III trial (NCT01245959) comparing IC plus CCRT with CCRT alone.

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Reduced deep regional cerebral venous oxygen saturation in hemodialysis patients using quantitative susceptibility mapping

Abstract

Cerebral venous oxygen saturation (SvO₂) is an important indicator of brain function. There was debate about lower cerebral oxygen metabolism in hemodialysis patients and there were no reports about the changes of deep regional cerebral SvO₂ in hemodialysis patients. In this study, we aim to explore the deep regional cerebral SvO₂ from straight sinus using quantitative susceptibility mapping (QSM) and the correlation with clinical risk factors and neuropsychiatric testing_. 52 hemodialysis patients and 54 age-and gender-matched healthy controls were enrolled. QSM reconstructed from original phase data of 3.0 T susceptibility-weighted imaging was used to measure the susceptibility of straight sinus. The susceptibility was used to calculate the deep regional cerebral SvO₂ and compare with healthy individuals. Correlation analysis was performed to investigate the correlation between deep regional cerebral SvO₂, clinical risk factors and neuropsychiatric testing. The deep regional cerebral SvO₂ of hemodialysis patients (72.5 ± 3.7%) was significantly lower than healthy controls (76.0 ± 2.1%) (P < 0.001). There was no significant difference in the measured volume of interests of straight sinus between hemodialysis patients (250.92 ± 46.65) and healthy controls (249.68 ± 49.68) (P = 0.859). There were no significant correlations between the measured susceptibility and volume of interests in hemodialysis patients (P = 0.204) and healthy controls (P = 0.562), respectively. Hematocrit (r = 0.480, P < 0.001, FDR corrected), hemoglobin (r = 0.440, P < 0.001, FDR corrected), red blood cell (r = 0.446, P = 0.003, FDR corrected), dialysis duration (r = 0.505, P = 0.002, FDR corrected) and parathyroid hormone (r = −0.451, P = 0.007, FDR corrected) were risk factors for decreased deep regional cerebral SvO₂ in patients. The Mini-Mental State Examination (MMSE) scores of hemodialysis patients were significantly lower than healthy controls (P < 0.001). However, the deep regional cerebral SvO₂ did not correlate with MMSE scores (P = 0.630). In summary, the decreased deep regional cerebral SvO₂ occurred in hemodialysis patients and dialysis duration, parathyroid hormone, hematocrit, hemoglobin and red blood cell may be clinical risk factors.

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Reduced deep regional cerebral venous oxygen saturation in hemodialysis patients using quantitative susceptibility mapping

Abstract

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Genetic analysis and clinical description of Greek patients with Peutz-Jeghers syndrome: Creation of a National Registry

Publication date: January 2018
Source:Cancer Genetics, Volume 220
Author(s): Florentia Fostira, Vasiliki Mollaki, George Lypas, George Alexandrakis, Efstratios Christianakis, Maria Tzouvala, Eirini Zacharopoulou, Despoina Kalfakakou, Irene Konstantopoulou, Drakoulis Yannoukakos
Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder caused by germline mutations in the STK11 tumor suppressor gene. PJS patients face a cumulative cancer risk as high as 93% for all sites combined. The present study reports the spectrum of STK11 mutations in eight families with clinical diagnosis of PJS, summarizes the clinical characteristics of sixteen mutation carriers and launches a National Registry for PJS in Greece. STK11 loss-of-function (LoF) mutations were detected in 87.5% of index patients. Carriers presented with their first manifestation at a median age of 24.9 years, while early-onset breast cancer was the most frequent malignancy observed, highlighting the need for breast surveillance. Out of the deleterious STK11 mutations identified, two were novel: c.375_376delGT and c.676_679dupAACG, with 57.2% of these potentially occurring de novo. Using all available clinical and genetic data, the National Registry for Greek PJS was established in an attempt to better characterize the syndrome and raise awareness among patients and clinicians (available at http://ift.tt/2BkF9zV). This is the first comprehensive genetic analysis and clinical characterization of Greek PJS patients, where a high incidence of breast cancer was observed and the first attempt to centralize all data in a National Registry.

Graphical abstract

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Circulating long non-coding RNA MALAT1 expression as molecular biomarker in Egyptian patients with breast cancer

Publication date: January 2018
Source:Cancer Genetics, Volume 220
Author(s): Haidy E. Zidan, Rehab A. Karam, Omnia S. El-Seifi, Tamer M. Abd Elrahman
The abnormal contribution of long non-coding RNA (lncRNAs) expression to human tumorigenesis is still a matter of debate. Breast cancer is the most common cancer in females; it represents a terrible problem in our country. The aim of this research was to assess the role of MALAT1, as one of lncRNAs, as a potential biomarker in breast cancer. This study comprised 80 patients with breast cancer and 80 controls. MALAT1 expression was measured by RT-quantitative polymerase chain reaction (qPCR). CA15-3 was estimated using chemiluminescence immunoassay (CLIA). MALAT1 expression was significantly elevated in breast cancer cases compared to controls (P < 0.0001). By performing the ROC curve analysis, we assumed that the diagnostic sensitivity and specificity for breast cancer were 83.7% and 81.2%, respectively for MALAT1 expression and 77.5% and 82.5% respectively for CA15-3 level. Moreover, combination analysis of the 2 parameters improved the diagnostic sensitivity of CA15-3 in breast cancer. In conclusion, MALAT1 expression level was positively correlated with lymph node status, estrogen receptor (ER), tumor stage and histological grade indicating its possible prognostic value. MALAT1 expression can be used as an accurate marker for diagnosis of breast cancer, in addition it possesses a prognostic value of such disease.

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Assessment of a FBXW8 frameshift mutation, c.1312_1313delGT, in breast cancer patients and controls from Central Europe

Publication date: January 2018
Source:Cancer Genetics, Volume 220
Author(s): Jing Wang, Natalia Bogdanova, Peter Schürmann, Tjoung-Won Park-Simon, Robert Geffers, Thilo Dörk
F-box proteins participate in multiple cellular processes through ubiquitylation and subsequent degradation of target proteins, such as cyclin D1 as target of FBXW8. To investigate the spectrum of FBXW8 germ-line mutations in patients with breast cancer and healthy controls, we analyzed the whole FBXW8 coding region and flanking untranslated portions in germ-line DNA samples of 91 breast cancer patients and 277 healthy controls using next-generation amplicon sequencing. Five missense variants, one splice site variant, one frameshift variant, one synonymous variant, and one variant in the 3′-UTR were identified. Frameshift mutation FBXW8 c.1312_1313delGT was considered functionally relevant and was investigated for its potential association with breast cancer risk through subsequent genotyping in two hospital-based breast cancer case-control series from Belarus and Germany, respectively, comprising a total of 2740 breast cancer cases and 2174 controls. The mutation was found in 30 cases and 23 controls with an adjusted Odds Ratio 1.02 (95% CI 0.59–1.77; p = 0.94) in the combined analysis. There was no statistically significant difference when patients were stratified by ER status, PR status, age at diagnosis, ductal histology, contralateral status, family history or tumor grade. Altogether, our data exclude clinically actionable breast cancer risks above two-fold for the FBXW8 c.1312_1313delGT mutation, although larger studies would be needed to exclude low-penetrance associations.

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A leukemic double-hit follicular lymphoma associated with a complex variant translocation, t(8;14;18)(q24;q32;q21), involving BCL2, MYC, and IGH

Publication date: January 2018
Source:Cancer Genetics, Volume 220
Author(s): Daisuke Minakata, Kazuya Sato, Takashi Ikeda, Yumiko Toda, Shoko Ito, Kiyomi Mashima, Kento Umino, Hirofumi Nakano, Ryoko Yamasaki, Kaoru Morita, Yasufumi Kawasaki, Miyuki Sugimoto, Chihiro Yamamoto, Masahiro Ashizawa, Kaoru Hatano, Iekuni Oh, Shin-ichiro Fujiwara, Ken Ohmine, Hirotoshi Kawata, Kazuo Muroi, Ikuo Miura, Yoshinobu Kanda
Double-hit lymphoma (DHL) is defined as lymphoma with concurrent BCL2 and MYC translocations. While the most common histological subtype of DHL is diffuse large B-cell lymphoma, the present patient had leukemic follicular lymphoma (FL). A 52-year-old man was admitted to our hospital due to general fatigue and cervical and inguinal lymph node swelling. The patient was leukemic and the pathological diagnosis of the inguinal lymph node was FL grade 1. Chromosomal analysis revealed a complex karyotype including a rare three-way translocation t(8;14;18)(q24;q32;q21) involving the BCL2, MYC, and IGH genes. Based on a combination of fluorescence in situ hybridization (FISH), using BCL2, MYC and IGH, and spectral karyotyping (SKY), the karyotype was interpreted as being the result of a multistep mechanism in which the precursor B-cell gained t(14;18) in the bone marrow and acquired a translocation between der(14)t(14;18) and chromosome 8 in the germinal center, resulting in t(8;14;18). The pathological diagnosis was consistently FL, not only at presentation but even after a second relapse. The patient responded well to standard chemotherapies but relapsed after a short remission. This patient is a unique case of leukemic DH-FL with t(8;14;18) that remained in FL even at a second relapse.

http://ift.tt/2CpU4rU

ALK-TPM3 rearrangement in adult renal cell carcinoma: report of a new case showing loss of chromosome 3 and literature review

Publication date: Available online 12 December 2017
Source:Cancer Genetics
Author(s): Yohan Bodokh, Damien Ambrosetti, Valérie Kubiniek, Branwel Tibi, Matthieu Durand, Jean Amiel, Morgane Pertuit, Anne Barlier, Florence Pedeutour
Seven cases of translocation-associated renal cell carcinoma involving ALK (ALK-tRCC) were referenced in the last World Health Organization's classification (2016), in a group of emerging/provisional RCC. The first three cases were pediatric, medullary-based, associated with sickle-cell trait and showed a fusion of ALK with VCL. Thirteen cases have been further described. They displayed clinical, morphological and genomic heterogeneity. Most of them occurred in adults. None of the patients was affected by sickle-cell disease. We report a new case of ALK-tRCC in a 55-year-old woman. Genomic profile showed losses of chromosomes 3, 9 and 14, anomalies often observed in clear cell RCC. VHL mutation or morphological features suggesting a clear cell RCC were not detected. We identified an unbalanced rearrangement of ALK and TPM3. Review of the literature identified similar features in our case and previously published cases: heterogeneous solid architecture, eosinophilic cells, mucinous cytoplasmic elements, rhabdoid cells and intracytoplasmic lumina. These elements may constitute the basis of a pathological definition of ALK-tRCC. Their observation in a RCC should lead to perform molecular detection of ALK rearrangement. This may have a crucial importance for metastatic patients treatment since ALK rearrangements confer sensitivity to tyrosine kinases inhibitors such as crizotinib.

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Characterization of novel, large duplications in the MSH2 gene of three unrelated lynch syndrome patients.

Publication date: Available online 2 December 2017
Source:Cancer Genetics
Author(s): Raffaella Liccardo, Marina De Rosa, Giovanni Battista Rossi, Gabriele Rigler, Paola Izzo, Francesca Duraturo
Lynch syndrome (LS) is associated with germ-line mutations in the DNA mismatch repair (MMR) genes, mainly MLH1, MSH2, MSH6, and PMS2. Most of genetic variants in the MMR genes predisposing to LS are point mutations, small deletions and insertions but large genomic rearrangements in the MMR genes also predisposing to Lynch syndrome. In this study, we report a novel, large rearrangement of the MSH2 gene, manifested by a duplication spanning a 14,846-bps region from intron 7 through intron 9. The breakpoints of this rearrangement were characterized by sequencing. Further analysis of the breakpoints revealed that this rearrangement was a product of Alu-mediated recombination. Finally, this large duplication was identified in three unrelated patients. Breakpoint analysis revealed the same junction fragments of introns 7 and 8 in the three index cases, suggesting a recurrent duplication or, alternatively, identity of the respective alleles by descent.

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SVAtools for junction detection of genome-wide chromosomal rearrangements by mate-pair sequencing (MPseq)

Publication date: Available online 2 December 2017
Source:Cancer Genetics
Author(s): Sarah H. Johnson, James B. Smadbeck, Stephanie A. Smoley, Athanasios Gaitatzes, Stephen J. Murphy, Faye R. Harris, Travis M. Drucker, Roman M. Zenka, Beth A. Pitel, Ross A. Rowsey, Nicole L. Hoppman, Umut Aypar, William R. Sukov, Robert B. Jenkins, Andrew L. Feldman, Hutton M. Kearney, George Vasmatzis
Mate-pair sequencing (MPseq), using long-insert, paired-end genomic libraries, is a powerful next-generation sequencing-based approach for the detection of genomic structural variants. SVAtools is a set of algorithms to detect both chromosomal rearrangements and large (>10kb) copy number variants (CNVs) in genome-wide MPseq data. SVAtools can also predict gene disruptions, gene fusions, and characterize the genomic structure of complex rearrangements.To illustrate the power of SVAtools' junction detection methods to provide comprehensive molecular karyotypes, MPseq data was compared against a set of samples previously characterized by traditional cytogenetic methods. Karyotype, FISH and chromosomal microarray (CMA), performed for 29 patients in a clinical laboratory setting, collectively revealed 285 breakpoints in 87 rearrangements. The junction detection methods of SVAtools detected 87% of these breakpoints compared to 48%, 42% and 57% for karyotype, FISH and CMA respectively. Breakpoint resolution was also reported to 1 kb or less and additional genomic rearrangement complexities not appreciable by standard cytogenetic techniques were revealed. For example, 63% of CNVs detected by CMA were shown by SVAtools' junction detection to occur secondary to a rearrangement other than a simple deletion or tandem duplication. SVAtools with MPseq provides comprehensive and accurate whole-genome junction detection with improved breakpoint resolution, compared to karyotype, FISH, and CMA combined. This approach to molecular karyotyping offers considerable diagnostic potential for the simultaneous detection of both novel and recurrent genomic rearrangements in hereditary and neoplastic disorders.

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Discussion on reply to Foley et al., ‘Acute myeloid leukemia with t(14;21) involving RUNX1 and SYNE2: A novel favorable-risk translocation?’

Publication date: Available online 27 November 2017
Source:Cancer Genetics
Author(s): Gabriel N. Mannis

http://ift.tt/2BmjNlm

Reply to Foley et al., “Acute myeloid leukemia with t(14;21) involving RUNX1 and SYNE2: A novel favorable-risk translocation?”

Publication date: Available online 20 November 2017
Source:Cancer Genetics
Author(s): Marc Sorigue, Jordi Juncà

http://ift.tt/2CogsSm

Changing temporal trends in non-AIDS cancer mortality among people diagnosed with AIDS: San Francisco, California, 1996–2013

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Nancy A. Hessol, Danning Ma, Susan Scheer, Ling C. Hsu, Sandra K. Schwarcz
BackgroundAntiretroviral therapy (ART) has reduced AIDS-defining cancer (ADC) mortality, but its effect on non-AIDS-defining cancer (NADC) mortality is unclear. To help inform cancer prevention and screening, we evaluated trends in NADC mortality among people with AIDS (PWA) in the ART era.MethodsThis retrospective cohort study analyzed AIDS surveillance data, including causes of death from death certificates, for PWA in San Francisco who died in 1996–2013. Proportional mortality ratios (PMRs), and year, age, race, sex-adjusted standardized mortality ratios (SMRs) were calculated for 1996–1999, 2000–2005, and 2006–2013, corresponding to advances in ART.ResultsThe study included 5822 deceased PWA of whom 90% were male and 68% were aged 35–54 at time of death. Over time, the PMRs significantly decreased for ADCs (2.6%, 1.4%, 1.2%) and increased for NADCs (4.3%, 7.0%, 12.3%). For all years combined (1996–2013) and compared to the California population, significantly elevated SMRs were observed for these cancers: all NADCs combined (2.1), anal (58.4), Hodgkin lymphoma (10.5), liver (5.2), lung/larynx (3.0), rectal (5.2), and tongue (4.7). Over time, the SMRs for liver cancer (SMR 19.8, 11.2, 5.0) significantly decreased while the SMRs remained significantly elevated over population levels for anal (SMR 123, 48.2, 45.5), liver (SMR 19.8, 11.2, 5.0), and lung/larynx cancer (SMR 5.3, 4.7, 3.6).ConclusionA decline in ADC PMRs and increase in NADC PMRs represent a shift in the cancer burden, likely due to ART use. Moreover, given their elevated SMRs, anal, liver, and lung/larynx cancer remain targets for improved cancer prevention, screening, and treatment.

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Cancers in France in 2015 attributable to high body mass index

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Melina Arnold, Marina Touillaud, Laure Dossus, Heinz Freisling, Freddie Bray, Irène Margaritis, Valérie Deschamps, Isabelle Soerjomataram
BackgroundOverweight, as defined by high body mass index (BMI), is an established risk factor for various morbidities including cancer. Globally, its prevalence has increased markedly over the past decades. The aim of this study was to estimate the proportion and number of cancers that were attributable to high BMI in France in 2015.MethodsPopulation attributable fractions (PAFs) and numbers of cancer cases attributable to high BMI (a population mean BMI above the optimum of 22kg/m²) were estimated by age and sex, for cancer sites with convincing or probable evidence of an established causal link. Assuming a 10-year lag-period, PAFs were calculated using mean BMI estimates from a cross-sectional French population survey, and relative risk estimates from published meta-analyses.ResultsAn estimated 18,639 cancer cases diagnosed in France in 2015 were attributable to high BMI, corresponding to 5.3% of all cancer cases (6.7% in women and 4.1% in men). This included 4507 cases of postmenopausal breast and 3380 cases of colon cancer. The highest estimated PAFs were for oesophageal adenocarcinoma and corpus uteri cancer (37% and 34%, respectively).ConclusionHigh BMI is associated with a substantial number of cancer cases in France, a country with a low but increasing prevalence of overweight and obesity when compared to other European countries. Assuming that the association between high BMI and cancer is causal, these results highlight the need to prioritise the prevention of this risk factor as part of cancer control planning in France and elsewhere in Europe.

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Incidence, prevalence, mortality, disability-adjusted life years and risk factors of cancer in Australia and comparison with OECD countries, 1990–2015: findings from the Global Burden of Disease Study 2015

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Yohannes Adama Melaku, Sarah L. Appleton, Tiffany K. Gill, Felix A. Ogbo, Elizabeth Buckley, Zumin Shi, Tim Driscoll, Robert Adams, Benjamin C. Cowie, Christina Fitzmaurice
BackgroundComparative evidence on the burden, trend, and risk factors of cancer is limited. Using data from the Global Burden of Disease (GBD) study, we aimed to assess cancer burden – incidence, prevalence, mortality, disability-adjusted life years (DALYs) – and attributable risk factors for Australia between 1990 and 2015, and to compare them with those of 34 members of the Organisation for Economic Co-operation and Development (OECD).MethodsThe general GBD cancer estimation methods were used with data input from vital registration systems and cancer registries. A comparative risk assessment approach was used to estimate the population-attributable fractions due to risk factors.ResultsIn 2015 there were 198,880 (95% uncertainty interval [UI]: 183,908–217,365) estimated incident cancer cases and 47,562 (95% UI: 46,061–49,004) cancer deaths in Australia. Twenty-nine percent (95% UI: 28.2–29.8) of total deaths and 17.0% (95% UI: 15.0–19.1) of DALYs were caused by cancer in Australia in 2015. Cancers of the trachea, bronchus and lung, colon and rectum, and prostate were the most common causes of cancer deaths. Thirty-six percent (95% UI: 33.1–37.9) of all cancer deaths were attributable to behavioral risks. The age-standardized cancer incidence rate (ASIR) increased between 1990 and 2015, while the age-standardized cancer death rate (ASDR) decreased over the same period. In 2015, compared to 34 other OECD countries Australia ranked first (highest) and 24^th based on ASIR and ASDR, respectively.ConclusionThe incidence of cancer has increased over 25 years, and behavioral risks are responsible for a large proportion of cancer deaths. Scaling up of prevention (using strategies targeting cancer risk factors), early detection, and treatment of cancer is required to effectively address this growing health challenge.

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Improvement of relative survival in elderly patients with acute myeloid leukaemia emerging from population-based cancer registries in Switzerland between 2001 and 2013

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Annatina Schnegg-Kaufmann, Anita Feller, Helen Baldomero, Alicia Rovo, Markus G. Manz, Michael Gregor, Anna Efthymiou, Mario Bargetzi, Urs Hess, Olivier Spertini, Yves Chalandon, Jakob R. Passweg, Georg Stussi, Volker Arndt, Nicolas Bonadies
Acute Myeloid Leukaemia (AML) is a rare and heterogeneous haematological malignancy with increasing incidence in the elderly. We performed a population-based, observational analysis of AML cases reported to the Cantonal Cancer Registries in Switzerland. Data was aggregated by the National Institute for Epidemiology and Cancer Registration and stratified for the two time periods 2001–2007 and 2008–2013. Overall, 2351 new AML cases were registered with a stable age-standardised incidence rate (3.0 [95 CI: 2.8-3.2] per 100,000 person-years). This indicates that our observed raise of annual AML cases (+10.9%) is mainly related to demographic ageing and not to an increase of age-specific risks. The fraction of non-classifiable AML cases decreased over time (54.6% to 41.8%) but remained high in elderly patients (65–74yrs: 44%; 75–84yrs: 54.2%, 85+yrs: 59.1%), suggesting less accurate diagnostics and reporting with increasing age. 5yrs relative survival (RS) correlated with AML risk class (favorable: 61.7%-68.4%; adverse risk: 11.4%-21.9%) and age (<65yrs: 42.6–43.3%; 75–84yrs: 2.0-3.0%), but improved only modestly overall (19.2% to 23.3%). Interestingly, we identified a significant improvement of RS in patients aged 65–74yrs (5yrs: 5.2% to 13.5%; p<0.001). As surrogate for changes in management, we found an increase of allogeneic haematopoietic stem cell transplantations (1.4 to 7%) and clinical trial activities (25 to 29%) for elderly AML patients during the observation period. Our analysis indicates that recent progress made in management of elderly AML patients results in an improvement of survival on a population-based level in Switzerland and that therapeutic nihilism is not justifiable.

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Missing data and chance variation in public reporting of cancer stage at diagnosis: Cross-sectional analysis of population-based data in England

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Matthew E. Barclay, Georgios Lyratzopoulos, David C. Greenberg, Gary A. Abel
BackgroundThe percentage of cancer patients diagnosed at an early stage is reported publicly for geographically-defined populations corresponding to healthcare commissioning organisations in England, and linked to pay-for-performance targets. Given that stage is incompletely recorded, we investigated the extent to which this indicator reflects underlying organisational differences rather than differences in stage completeness and chance variation.MethodsWe used population-based data on patients diagnosed with one of ten cancer sites in 2013 (bladder, breast, colorectal, endometrial, lung, ovarian, prostate, renal, NHL, and melanoma). We assessed the degree of bias in CCG (Clinical Commissioning Group) indicators introduced by missing-is-late and complete-case specifications compared with an imputed 'gold standard'. We estimated the Spearman-Brown (organisation-level) reliability of the complete-case specification. We assessed probable misclassification rates against current pay-for-performance targets.ResultsUnder the missing-is-late approach, bias in estimated CCG percentage of tumours diagnosed at an early stage ranged from −2 to −30 percentage points, while bias under the complete-case approach ranged from −2 to +7 percentage points. Using an annual reporting period, indicators based on the least biased complete-case approach would have poor reliability, misclassifying 27/209 (13%) CCGs against a pay-for-performance target in current use; only half (53%) of CCGs apparently exceeding the target would be correctly classified in terms of their underlying performance.ConclusionsCurrent public reporting schemes for cancer stage at diagnosis in England should use a complete-case specification (i.e. the number of staged cases forming the denominator) and be based on three-year reporting periods. Early stage indicators for the studied geographies should not be used in pay-for-performance schemes.

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Nationwide analysis on the impact of socioeconomic land use factors and incidence of urothelial carcinoma

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Maximilian P. Brandt, Kilian M. Gust, Jens Mani, Stefan Vallo, Thomas Höfner, Hendrik Borgmann, Igor Tsaur, Christian Thomas, Axel Haferkamp, Eva Herrmann, Georg Bartsch
BackgroundIncidence rates for urothelial carcinoma (UC) have been reported to differ between countries within the European Union (EU). Besides occupational exposure to chemicals, other substances such as tobacco and nitrite in groundwater have been identified as risk factors for UC. We investigated if regional differences in UC incidence rates are associated with agricultural, industrial and residential land use.MethodsNewly diagnosed cases of UC between 2003 and 2010 were included. Information within 364 administrative districts of Germany from 2004 for land use factors were obtained and calculated as a proportion of the total area of the respective administrative district and as a smoothed proportion. Furthermore, information on smoking habits was included in our analysis. Kulldorff spatial clustering was used to detect different clusters. A negative binomial model was used to test the spatial association between UC incidence as a ratio of observed versus expected incidence rates, land use and smoking habits.ResultsWe identified 437,847,834 person years with 171,086 cases of UC. Cluster analysis revealed areas with higher incidence of UC than others (p=0.0002). Multivariate analysis including significant pairwise interactions showed that the environmental factors were independently associated with UC (p<0.001). The RR was 1.066 (95% CI 1.052–1.080), 1.066 (95% CI 1.042–1.089) and 1.067 (95% CI 1.045–1.093) for agricultural, industrial and residential areas, respectively, and 0.996 (95% CI 0.869–0.999) for the proportion of never smokers.ConclusionThis study displays regional differences in incidence of UC in Germany. Additionally, results suggest that socioeconomic factors based on agricultural, industrial and residential land use may be associated with UC incidence rates.

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Plasma magnesium is inversely associated with Epstein-Barr virus load in peripheral blood and Burkitt lymphoma in Uganda

Publication date: February 2018
Source:Cancer Epidemiology, Volume 52
Author(s): Ravell Juan, Isaac Otim, Hadijah Nabalende, Ismail D. Legason, Steven J. Reynolds, Martin D. Ogwang, Christopher M. Ndugwa, Vickie Marshall, Denise Whitby, James J. Goedert, Eric A. Engels, Kishor Bhatia, Michael J. Lenardo, Sam M. Mbulaiteye
BackgroundEpstein-Barr virus (EBV) causes endemic Burkitt lymphoma (eBL). EBV control was improved by magnesium (Mg²⁺) supplementation in XMEN, an X-linked genetic disease associated with Mg²⁺ deficiency, high circulating EBV levels (viral loads), and EBV-related lymphomas. We, therefore, investigated the relationship between Mg²⁺ levels and EBV levels and eBL in Uganda.MethodsPlasma Mg²⁺ was measured in 45 women with low or high circulating EBV levels, 40 pediatric eBL cases, and 79 healthy children. Mg²⁺ uptake by T-lymphocytes was evaluated in samples from healthy donors.ResultsPlasma Mg²⁺ deficiency (plasma level <1.8 mg/dl) was more likely in women with high- vs. low-EBV levels (76.0% vs. 35%; odds ratio [OR] 11.3, 95% CI 2.14–60.2), controlling for age, and in eBL cases than controls (42.0% vs. 13.9%; OR 3.61, 95% CI 1.32–9.88), controlling for sex, age group, and malaria status. Mg²⁺ uptake by T-lymphocytes was related to extracellular Mg²⁺ concentration.InterpretationPlasma Mg²⁺ deficiency is associated with high EBV levels and eBL.

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Title page / Editorial Board

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51

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Publication date: December 2017
Source:Cancer Epidemiology, Volume 51

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Frequency of whole breast irradiation (WBRT) after intraoperative radiotherapy (IORT) is strongly influenced by institutional protocol qualification criteria

Publication date: January–February 2018
Source:Reports of Practical Oncology & Radiotherapy, Volume 23, Issue 1
Author(s): Michał Falco, Bartłomiej Masojć, Marta Milchert-Leszczyńska, Andrzej Kram
BackgroundAccelerated partial breast irradiation (APBI) is a promising method of adjuvant radiotherapy for select patients. Intraoperative radiotherapy (IORT) is a form of APBI, and appropriate patient selection is important.AimThe aim of our study was to analyse the influence of our protocol on the frequency of WBRT after IORT and our protocol's correlation with the reported use of WBRT according to TARGIT guidelines. We also aimed to verify how changes in our protocol influenced the frequency of WBRT.Material and methodsBetween April 20, 2010 and May 10, 2017, we identified 207 patients irradiated with IORT for APBI.ResultsNinety-one patients (44%) met the criteria for APBI only, while 116 (56%) should have been offered additional WBRT. Retrospective analysis showed that WBRT was applied statistically significantly less frequently compared with strict protocol indications: 99 patients (47.8%) received APBI only and 108 (51.2%) underwent adjuvant WBRT (p<0.0001). Applying the TARGIT trial guidelines, 69 patients (33.4%) should have been offered WBRT (p<0.0001), which is twice the number of patients treated with WBRT in our study. Changing the protocol to less restrictive criteria would have statistically significantly decreased the number of patients (95, 46%) offered WBRT (p<0.0001).ConclusionsFollowing international guidelines, 46% of patients should receive WBRT after IORT, which is 1.5–2 times more than for the TARGIT criteria. In our analysis, a high percentage of patients (19%) did not receive WBRT after IORT despite the protocol recommendations. The chosen protocol strongly influences the frequency of adjuvant WBRT.

http://ift.tt/2j849lx

Changing temporal trends in non-AIDS cancer mortality among people diagnosed with AIDS: San Francisco, California, 1996–2013

Cancers in France in 2015 attributable to high body mass index

Incidence, prevalence, mortality, disability-adjusted life years and risk factors of cancer in Australia and comparison with OECD countries, 1990–2015: findings from the Global Burden of Disease Study 2015

Improvement of relative survival in elderly patients with acute myeloid leukaemia emerging from population-based cancer registries in Switzerland between 2001 and 2013

Missing data and chance variation in public reporting of cancer stage at diagnosis: Cross-sectional analysis of population-based data in England

Nationwide analysis on the impact of socioeconomic land use factors and incidence of urothelial carcinoma

Plasma magnesium is inversely associated with Epstein-Barr virus load in peripheral blood and Burkitt lymphoma in Uganda

Title page / Editorial Board

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51

http://ift.tt/2yJnz5C

Publication date: December 2017
Source:Cancer Epidemiology, Volume 51

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A phase II study of 2-weeks of adjuvant whole breast/chest wall and/or regional nodal radiotherapy in patients with breast cancer

Publication date: Available online 16 December 2017
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Budhi Singh Yadav, Suresh C. Sharma
BackgroundTo report results in terms of feasibility and early toxicity of hypofractionated adjuvant whole breast/chest wall and/or regional nodal radiotherapy in patients with breast cancer.Materials & methods: Between June 2013 and October 2014, 50 patients with breast cancer, post mastectomy or after breast conservation surgery (BCS) were prospectively included. The trial was approved by institutional ethics committee and registered with ClinicalTrials.gov, number XXXX. Patients were planned on simulator with two tangential fields to breast/chest wall and incident field to supraclavicular fossa. Radiotherapy dose delivered was 34Gy/10fractions /2 weeks followed by a boost of 10Gy/5fractions/1wk in cases with BCS. Acute skin toxicities were recorded during and after treatment according to RTOG acute radiation toxicity scoring criteria. The primary objective was to obtain estimates of rates of acute toxicities and cosmetic outcomes that could be used to design a subsequent phase III comparative study. Acute skin and late toxicities were recorded during and after treatment. Cosmetic outcomes were assessed before and after treatment and then on regular follow up. Cost benefit analysis was also done and compared with standard treatment of 35Gy/15fractions/3weeks.ResultsMedian follow up was 39 months (range 14-48 months). Mean age was 51 years (range 26-75). Left sided tumor was seen in 25(50%) patients. Total mastectomy with axillary clearance (TMAC) was done in 40(80%) and BCS in 10(20%) patients. Acute grade 2 and 3 skin toxicity was seen in 16(32%) and 1(2%) patients, respectively. In patients with BCS, grade 2 skin and subcutaneous toxicity was seen in 2(20%) and 1(10%) patients, respectively. Grade 2 edema was seen in 1(10%) patient. Cosmesis was excellent/good in 8(80%) and fair/poor in 2(20%) patients. On cost benefit analysis there was significant less financial burden on the patients with 2 weeks treatment. Disease free and overall survival at 3 years was 94% and 96%, respectively.ConclusionHypofractionated radiotherapy in 2 weeks appears to be feasible in patients with breast cancer and was associated with acute and late skin toxicity profiles that are similar to what has been observed with 3 weeks of treatment. The financial burden on the patient and family may be reduced with 2 weeks of treatment. Long-term follow up and a prospective comparative study is needed to strengthen these results. Hypofractionation may help radiation centers worldwide to meet the growing need for radiation in breast cancer, particularly in developing countries where resources are limited and patients have to travel for long distance for treatment.

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