Podoplanin expression in primary brain tumors induces platelet aggregation and increases risk of venous thromboembolism.

Science.gov (United States)

Riedl, Julia; Preusser, Matthias; Nazari, Pegah Mir Seyed; Posch, Florian; Panzer, Simon; Marosi, Christine; Birner, Peter; Thaler, Johannes; Brostjan, Christine; Lötsch, Daniela; Berger, Walter; Hainfellner, Johannes A; Pabinger, Ingrid; Ay, Cihan

2017-03-30

Venous thromboembolism (VTE) is common in patients with brain tumors, and underlying mechanisms are unclear. We hypothesized that podoplanin, a sialomucin-like glycoprotein, increases the risk of VTE in primary brain tumors via its ability to induce platelet aggregation. Immunohistochemical staining against podoplanin and intratumoral platelet aggregates was performed in brain tumor specimens of 213 patients (mostly high-grade gliomas [89%]) included in the Vienna Cancer and Thrombosis Study, a prospective observational cohort study of patients with newly diagnosed cancer or progressive disease aimed at identifying patients at risk of VTE. Platelet aggregation in response to primary human glioblastoma cells was investigated in vitro. During 2-year follow-up, 29 (13.6%) patients developed VTE. One-hundred fifty-one tumor specimens stained positive for podoplanin (33 high expression, 47 medium expression, 71 low expression). Patients with podoplanin-positive tumors had lower peripheral blood platelet counts ( P < .001) and higher D-dimer levels ( P < .001). Podoplanin staining intensity was associated with increasing levels of intravascular platelet aggregates in tumor specimens ( P < .001). High podoplanin expression was associated with an increased risk of VTE (hazard ratio for high vs no podoplanin expression: 5.71; 95% confidence interval, 1.52-21.26; P = 010), independent of age, sex, and tumor type. Podoplanin-positive primary glioblastoma cells induced aggregation of human platelets in vitro, which could be abrogated by an antipodoplanin antibody. In conclusion, high podoplanin expression in primary brain tumors induces platelet aggregation, correlates with hypercoagulability, and is associated with increased risk of VTE. Our data indicate novel insights into the pathogenesis of VTE in primary brain tumors. © 2017 by The American Society of Hematology.

Assessment of rigid multi-modality image registration consistency using the multiple sub-volume registration (MSR) method

International Nuclear Information System (INIS)

Ceylan, C; Heide, U A van der; Bol, G H; Lagendijk, J J W; Kotte, A N T J

2005-01-01

Registration of different imaging modalities such as CT, MRI, functional MRI (fMRI), positron (PET) and single photon (SPECT) emission tomography is used in many clinical applications. Determining the quality of any automatic registration procedure has been a challenging part because no gold standard is available to evaluate the registration. In this note we present a method, called the 'multiple sub-volume registration' (MSR) method, for assessing the consistency of a rigid registration. This is done by registering sub-images of one data set on the other data set, performing a crude non-rigid registration. By analysing the deviations (local deformations) of the sub-volume registrations from the full registration we get a measure of the consistency of the rigid registration. Registration of 15 data sets which include CT, MR and PET images for brain, head and neck, cervix, prostate and lung was performed utilizing a rigid body registration with normalized mutual information as the similarity measure. The resulting registrations were classified as good or bad by visual inspection. The resulting registrations were also classified using our MSR method. The results of our MSR method agree with the classification obtained from visual inspection for all cases (p < 0.02 based on ANOVA of the good and bad groups). The proposed method is independent of the registration algorithm and similarity measure. It can be used for multi-modality image data sets and different anatomic sites of the patient. (note)

Chromosomal imbalance in the progression of high-risk non-muscle invasive bladder cancer

International Nuclear Information System (INIS)

Zieger, Karsten; Wiuf, Carsten; Jensen, Klaus Møller-Ernst; Ørntoft, Torben Falck; Dyrskjøt, Lars

2009-01-01

Non-muscle invasive bladder neoplasms with invasion of the lamina propria (stage T1) or high grade of dysplasia are at 'high risk' of progression to life-threatening cancer. However, the individual course is difficult to predict. Chromosomal instability (CI) is associated with high tumor stage and grade, and possibly with the risk of progression. To investigate the relationship between CI and subsequent disease progression, we performed a case-control-study of 125 patients with 'high-risk' non-muscle invasive bladder neoplasms, 67 with later disease progression, and 58 with no progression. Selection criteria were conservative (non-radical) resections and full prospective clinical follow-up (> 5 years). We investigated primary lesions in 59, and recurrent lesions in 66 cases. We used Affymetrix GeneChip ® Mapping 10 K and 50 K SNP microarrays to evaluate genome wide chromosomal imbalance (loss-of-heterozygosity and DNA copy number changes) in 48 representative tumors. DNA copy number changes of 15 key instability regions were further investigated using QPCR in 101 tumors (including 25 tumors also analysed on 50 K SNP microarrays). Chromosomal instability did not predict any higher risk of subsequent progression. Stage T1 and high-grade tumors had generally more unstable genomes than tumors of lower stage and grade (mostly non-primary tumors following a 'high-risk' tumor). However, about 25% of the 'high-risk' tumors had very few alterations. This was independent of subsequent progression. Recurrent lesions represent underlying field disease. A separate analysis of these lesions did neither reflect any difference in the risk of progression. Of specific chromosomal alterations, a possible association between loss of chromosome 8p11 and the risk of progression was found. However, the predictive value was limited by the heterogeneity of the changes. Chromosomal instability (CI) was associated with 'high risk' tumors

Quality assurance in breast cancer brachytherapy: geographic miss in the interstitial boost treatment of the tumor bed.

Science.gov (United States)

Sedlmayer, F; Rahim, H B; Kogelnik, H D; Menzel, C; Merz, F; Deutschmann, H; Kranzinger, M

1996-03-15

individual dose planning with regard to high risk subvolumes within the implanted tissue.

Quality assurance in breast cancer brachytherapy: geographic miss in the interstitial boost treatment of the tumor bed

International Nuclear Information System (INIS)

Sedlmayer, Felix; Rahim, Hassan B. K.; Kogelnik, H. Dieter; Menzel, Christian; Merz, Florian; Deutschmann, Heinz; Kranzinger, Manfred

1996-01-01

afterloading techniques offer possibilities of individual dose planning with regard to high risk subvolumes within the implanted tissue

A high-risk 70-gene signature is not associated with the detection of tumor cell dissemination to the bone marrow.

Science.gov (United States)

Walter, Vincent P; Taran, Florin-Andrei; Wallwiener, Markus; Walter, Christina; Grischke, Eva-Maria; Wallwiener, Diethelm; Brucker, Sara Y; Hartkopf, Andreas D

2018-06-01

The 70-gene signature (70-GS) is a prognostic tool, grouping patients in risk groups to assess their need for adjuvant chemotherapy. Tumor cell dissemination to the bone marrow is a marker of minimal residual disease and associated with impaired survival. In this study, we aimed to evaluate whether 70-GS is associated with the presence of disseminated tumor cells (DTCs) in the bone marrow of patients with early breast cancer. In patients with hormone receptor-positive HER2-negative early breast cancer, the 70-GS was obtained and the presence of DTCs was immunohistochemically evaluated using cytokeratin staining with the A45-B/B3 antibody. 149 patients were included into the analysis. 40 (27%) had a high-risk 70-GS and 35 (23%) had detectable DTCs in their bone marrow. 9 (22%) of the 40 patients with high-risk 70-GS and 26 (24%) of the 109 patients with a low-risk 70-GS were positive for DTCs (p = 0.863). As both 70-GS and DTC detection are known prognostic factors but do not seem to correlate, a follow-up on a larger cohort is warranted to evaluate if a combination of the two is able to better stratify the relapse risk in early breast cancer patients.

Characterizing Tumor Heterogeneity With Functional Imaging and Quantifying High-Risk Tumor Volume for Early Prediction of Treatment Outcome: Cervical Cancer as a Model

International Nuclear Information System (INIS)

Mayr, Nina A.; Huang Zhibin; Wang, Jian Z.; Lo, Simon S.; Fan, Joline M.; Grecula, John C.; Sammet, Steffen; Sammet, Christina L.; Jia Guang; Zhang Jun; Knopp, Michael V.; Yuh, William T.C.

2012-01-01

Purpose: Treatment response in cancer has been monitored by measuring anatomic tumor volume (ATV) at various times without considering the inherent functional tumor heterogeneity known to critically influence ultimate treatment outcome: primary tumor control and survival. This study applied dynamic contrast-enhanced (DCE) functional MRI to characterize tumors' heterogeneous subregions with low DCE values, at risk for treatment failure, and to quantify the functional risk volume (FRV) for personalized early prediction of treatment outcome. Methods and Materials: DCE-MRI was performed in 102 stage IB 2 –IVA cervical cancer patients to assess tumor perfusion heterogeneity before and during radiation/chemotherapy. FRV represents the total volume of tumor voxels with critically low DCE signal intensity ( 20, >13, and >5 cm 3 , respectively, significantly predicted unfavorable 6-year primary tumor control (p = 0.003, 7.3 × 10 −8 , 2.0 × 10 −8 ) and disease-specific survival (p = 1.9 × 10 −4 , 2.1 × 10 −6 , 2.5 × 10 −7 , respectively). The FRVs were superior to the ATVs as early predictors of outcome, and the differentiating power of FRVs increased during treatment. Discussion: Our preliminary results suggest that functional tumor heterogeneity can be characterized by DCE-MRI to quantify FRV for predicting ultimate long-term treatment outcome. FRV is a novel functional imaging heterogeneity parameter, superior to ATV, and can be clinically translated for personalized early outcome prediction before or as early as 2–5 weeks into treatment.

Clinical implementation of AXB from AAA for breast: Plan quality and subvolume analysis.

Science.gov (United States)

Guebert, Alexandra; Conroy, Leigh; Weppler, Sarah; Alghamdi, Majed; Conway, Jessica; Harper, Lindsay; Phan, Tien; Olivotto, Ivo A; Smith, Wendy L; Quirk, Sarah

2018-04-25

Two dose calculation algorithms are available in Varian Eclipse software: Anisotropic Analytical Algorithm (AAA) and Acuros External Beam (AXB). Many Varian Eclipse-based centers have access to AXB; however, a thorough understanding of how it will affect plan characteristics and, subsequently, clinical practice is necessary prior to implementation. We characterized the difference in breast plan quality between AXB and AAA for dissemination to clinicians during implementation. Locoregional irradiation plans were created with AAA for 30 breast cancer patients with a prescription dose of 50 Gy to the breast and 45 Gy to the regional node, in 25 fractions. The internal mammary chain (IMC CTV ) nodes were covered by 80% of the breast dose. AXB, both dose-to-water and dose-to-medium reporting, was used to recalculate plans while maintaining constant monitor units. Target coverage and organ-at-risk doses were compared between the two algorithms using dose-volume parameters. An analysis to assess location-specific changes was performed by dividing the breast into nine subvolumes in the superior-inferior and left-right directions. There were minimal differences found between the AXB and AAA calculated plans. The median difference between AXB and AAA for breast CTV V 95% , was AAA for breast radiotherapy is not expected to result in changes in clinical practice for prescribing or planning breast radiotherapy. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Kinome expression profiling of human neuroblastoma tumors identifies potential drug targets for ultra high-risk patients.

Science.gov (United States)

Russo, Roberta; Cimmino, Flora; Pezone, Lucia; Manna, Francesco; Avitabile, Marianna; Langella, Concetta; Koster, Jan; Casale, Fiorina; Raia, Maddalena; Viola, Giampietro; Fischer, Matthias; Iolascon, Achille; Capasso, Mario

2017-10-01

Neuroblastoma (NBL) accounts for >7% of malignancies in patients younger than 15 years. Low- and intermediate-risk patients exhibit excellent or good prognosis after treatment, whereas for high-risk (HR) patients, the estimated 5-year survival rates is still <40%. The ability to stratify HR patients that will not respond to standard treatment strategies is critical for informed treatment decisions. In this study, we have generated a specific kinome gene signature, named Kinome-27, which is able to identify a subset of HR-NBL tumors, named ultra-HR NBL, with highly aggressive clinical behavior that not adequately respond to standard treatments. We have demonstrated that NBL cell lines expressing the same kinome signature of ultra-HR tumors (ultra-HR-like cell lines) may be selectively targeted by the use of two drugs [suberoylanilide hydroxamic acid (SAHA) and Radicicol], and that the synergic combination of these drugs is able to block the ultra-HR-like cells in G2/M phase of cell cycle. The use of our signature in clinical practice will allow identifying patients with negative outcome, which would benefit from new and more personalized treatments. Preclinical in vivo studies are needed to consolidate the SAHA and Radicicol treatment in ultra-HR NBL patients. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

High efficiency diffusion molecular retention tumor targeting.

Directory of Open Access Journals (Sweden)

Yanyan Guo

Full Text Available Here we introduce diffusion molecular retention (DMR tumor targeting, a technique that employs PEG-fluorochrome shielded probes that, after a peritumoral (PT injection, undergo slow vascular uptake and extensive interstitial diffusion, with tumor retention only through integrin molecular recognition. To demonstrate DMR, RGD (integrin binding and RAD (control probes were synthesized bearing DOTA (for (111 In(3+, a NIR fluorochrome, and 5 kDa PEG that endows probes with a protein-like volume of 25 kDa and decreases non-specific interactions. With a GFP-BT-20 breast carcinoma model, tumor targeting by the DMR or i.v. methods was assessed by surface fluorescence, biodistribution of [(111In] RGD and [(111In] RAD probes, and whole animal SPECT. After a PT injection, both probes rapidly diffused through the normal and tumor interstitium, with retention of the RGD probe due to integrin interactions. With PT injection and the [(111In] RGD probe, SPECT indicated a highly tumor specific uptake at 24 h post injection, with 352%ID/g tumor obtained by DMR (vs 4.14%ID/g by i.v.. The high efficiency molecular targeting of DMR employed low probe doses (e.g. 25 ng as RGD peptide, which minimizes toxicity risks and facilitates clinical translation. DMR applications include the delivery of fluorochromes for intraoperative tumor margin delineation, the delivery of radioisotopes (e.g. toxic, short range alpha emitters for radiotherapy, or the delivery of photosensitizers to tumors accessible to light.

Dose painting based on tumor uptake of Cu-ATSM and FDG: a comparative study

International Nuclear Information System (INIS)

Clausen, Malene Martini; Hansen, Anders Elias; Lundemann, Michael; Hollensen, Christian; Pommer, Tobias; Munck af Rosenschöld, Per; Kristensen, Annemarie Thuri; Kjær, Andreas; McEvoy, Fintan J; Engelholm, Svend Aage

2014-01-01

Hypoxia and increased glycolytic activity of tumors are associated with poor prognosis. The purpose of this study was to investigate differences in radiotherapy (RT) dose painting based on the uptake of 2-deoxy-2-[ 18 F]-fluorodeoxyglucose (FDG) and the proposed hypoxia tracer, copper(II)diacetyl-bis(N 4 )-methylsemithiocarbazone (Cu-ATSM) using spontaneous clinical canine tumor models. Positron emission tomography/computed tomography scans of five spontaneous canine sarcomas and carcinomas were obtained; FDG on day 1 and 64 Cu-ATSM on day 2 and 3 (approx. 3 and 24 hours pi.). Sub-volumes for dose escalation were defined by a threshold-based method for both tracers and five dose escalation levels were formed in each sub-volume. Volumetric modulated arc therapy plans were optimized based on the dose escalation regions for each scan for a total of three dose plans for each dog. The prescription dose for the GTV was 45 Gy (100%) and it was linearly escalated to a maximum of 150%. The correlations between dose painting plans were analyzed with construction of dose distribution density maps and quality volume histograms (QVH). Correlation between high-dose regions was investigated with Dice correlation coefficients. Comparison of dose plans revealed varying degree of correlation between cases. Some cases displayed a separation of high-dose regions in the comparison of FDG vs. 64 Cu-ATSM dose plans at both time points. Among the Dice correlation coefficients, the high dose regions showed the lowest degree of agreement, indicating potential benefit of using multiple tracers for dose painting. QVH analysis revealed that FDG-based dose painting plans adequately covered approximately 50% of the hypoxic regions. Radiotherapy plans optimized with the current approach for cut-off values and dose region definitions based on FDG, 64 Cu-ATSM 3 h and 24 h uptake in canine tumors had different localization of the regional dose escalation levels. This indicates that 64 Cu-ATSM at two

The Prognostic Role of Circulating Tumor Cells (CTC) in High-risk Non-muscle-invasive Bladder Cancer.

Science.gov (United States)

Busetto, Gian Maria; Ferro, Matteo; Del Giudice, Francesco; Antonini, Gabriele; Chung, Benjamin I; Sperduti, Isabella; Giannarelli, Diana; Lucarelli, Giuseppe; Borghesi, Marco; Musi, Gennaro; de Cobelli, Ottavio; De Berardinis, Ettore

2017-08-01

The purpose of this study was to evaluate the impact of circulating tumor cells (CTCs) as a prognostic marker in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) and assess the efficacy and reliability of 2 different CTC isolation methods. Globally, 155 patients with a pathologically confirmed diagnosis of high-risk NMIBC were included (pT1G3 with or without carcinoma in situ) and underwent transurethral resection of bladder tumor (TURB) after a blood withdrawal for CTC evaluation. A total of 101 patients (Group A) had their samples analyzed with the CellSearch automated system, and 54 (Group B) had their samples analyzed with the CELLection Dynabeads manual system. Patients were followed for 28 months, and during this interval, there were a total of 65 (41.9%) recurrences, 27 (17.4%) disease progressions, and 9 (5.8%) lymph node and/or bone metastasis. In our CTC analysis, there were 20 (19.8%) positive patients in Group A and 24 in Group B (44.4%). In our analysis, we found a strong correlation between CTC presence and time to first recurrence; in Group A, we observed an incidence of recurrence in 75% of CTC-positive patients and in Group B of 83% of CTC-positive patients. The time to progression was also strongly correlated with CTCs: 65% and 29%, respectively, of those patients who progressed in those with CTCs in Group A and B. The study demonstrates the potential role of CTCs as a prognostic marker for risk stratification in patients with NMIBC, to predict both recurrence and progression. Copyright © 2017 Elsevier Inc. All rights reserved.

Birth weight and order as risk factors for childhood central nervous system tumors.

Science.gov (United States)

MacLean, Jane; Partap, Sonia; Reynolds, Peggy; Von Behren, Julie; Fisher, Paul Graham

2010-09-01

To determine whether birth characteristics related to maternal-fetal health in utero are associated with the development of childhood central nervous system tumors. We identified, from the California Cancer Registry, 3733 children under age 15 diagnosed with childhood central nervous system tumors between 1988 and 2006 and linked these cases to their California birth certificates. Four controls per case, matched on birth date and sex, were randomly selected from the same birth files. We evaluated associations of multiple childhood CNS tumor subtypes with birth weight and birth order. Low birth weight was associated with a reduced risk of low-grade gliomas (OR=0.67; 95% CI, 0.46 to 0.97) and high birth weight was associated with increased risk of high-grade gliomas (OR=1.57; 95% CI, 1.16 to 2.12). High birth order (fourth or higher) was associated with decreased risk of low-grade gliomas (OR=0.75; 95% CI, 0.56 to 0.99) and increased risk of high-grade gliomas (OR=1.32; 95% CI, 1.01 to 1.72 for second order). Factors that drive growth in utero may increase the risk of low-grade gliomas. There may be a similar relationship in high-grade gliomas, although other factors, such as early infection, may modify this association. Additional investigation is warranted to validate and further define these findings. Copyright (c) 2010 Mosby, Inc. All rights reserved.

Nonvisible tumors on multiparametric magnetic resonance imaging does not predict low-risk prostate cancer

Directory of Open Access Journals (Sweden)

Seung Hwan Lee

2015-12-01

Conclusions: Even though cancer foci were not visualized by postbiopsy MRI, the pathological tumor volumes and extent of GS upgrading were relatively high. Therefore, nonvisible tumors by multiparametric MRI do not appear to be predictive of low-risk PCA.

Characterizing Tumor Heterogeneity With Functional Imaging and Quantifying High-Risk Tumor Volume for Early Prediction of Treatment Outcome: Cervical Cancer as a Model

Energy Technology Data Exchange (ETDEWEB)

Mayr, Nina A., E-mail: Nina.Mayr@osumc.edu [Department of Radiation Oncology, Ohio State University, Columbus, OH (United States); Huang Zhibin [Department of Radiation Oncology and Department of Physics, East Carolina University, Greenville, NC (United States); Wang, Jian Z. [Department of Radiation Oncology, Ohio State University, Columbus, OH (United States); Lo, Simon S. [Department of Radiation Oncology, Case Western Reserve University, Cleveland, OH (United States); Fan, Joline M. [Department of Molecular Biology, Stanford University, Stanford, CA (United States); Grecula, John C. [Department of Radiation Oncology, Ohio State University, Columbus, OH (United States); Sammet, Steffen [Department of Radiology, University of Chicago, Chicago, IL (United States); Department of Radiology, Ohio State University, Columbus, OH (United States); Sammet, Christina L. [Department of Radiology, University of Chicago, Chicago, IL (United States); Jia Guang; Zhang Jun; Knopp, Michael V.; Yuh, William T.C. [Department of Radiology, Ohio State University, Columbus, OH (United States)

2012-07-01

Purpose: Treatment response in cancer has been monitored by measuring anatomic tumor volume (ATV) at various times without considering the inherent functional tumor heterogeneity known to critically influence ultimate treatment outcome: primary tumor control and survival. This study applied dynamic contrast-enhanced (DCE) functional MRI to characterize tumors' heterogeneous subregions with low DCE values, at risk for treatment failure, and to quantify the functional risk volume (FRV) for personalized early prediction of treatment outcome. Methods and Materials: DCE-MRI was performed in 102 stage IB{sub 2}-IVA cervical cancer patients to assess tumor perfusion heterogeneity before and during radiation/chemotherapy. FRV represents the total volume of tumor voxels with critically low DCE signal intensity (<2.1 compared with precontrast image, determined by previous receiver operator characteristic analysis). FRVs were correlated with treatment outcome (follow-up: 0.2-9.4, mean 6.8 years) and compared with ATVs (Mann-Whitney, Kaplan-Meier, and multivariate analyses). Results: Before and during therapy at 2-2.5 and 4-5 weeks of RT, FRVs >20, >13, and >5 cm{sup 3}, respectively, significantly predicted unfavorable 6-year primary tumor control (p = 0.003, 7.3 Multiplication-Sign 10{sup -8}, 2.0 Multiplication-Sign 10{sup -8}) and disease-specific survival (p = 1.9 Multiplication-Sign 10{sup -4}, 2.1 Multiplication-Sign 10{sup -6}, 2.5 Multiplication-Sign 10{sup -7}, respectively). The FRVs were superior to the ATVs as early predictors of outcome, and the differentiating power of FRVs increased during treatment. Discussion: Our preliminary results suggest that functional tumor heterogeneity can be characterized by DCE-MRI to quantify FRV for predicting ultimate long-term treatment outcome. FRV is a novel functional imaging heterogeneity parameter, superior to ATV, and can be clinically translated for personalized early outcome prediction before or as early as 2

Donor-Cell Origin High-Risk Myelodysplastic Syndrome Synchronous with an Intracranial Meningioma-Like Tumor, 8 Years after Allogeneic Hematopoietic Stem Cell Transplantation for Chronic Lymphocytic Leukemia

Directory of Open Access Journals (Sweden)

G. Brás

2017-01-01

Full Text Available Secondary neoplasias are well known consequences of radiotherapy or chemotherapy for a primary cancer. In this report, we describe two rare secondary neoplasias occurring in the same patient: a meningioma-like intracranial tumor and high-risk myelodysplastic syndrome (MDS of donor-cells origin, both diagnosed simultaneously, 8 years after an allogeneic hematopoietic stem cell transplantation (allo-HSCT for chronic lymphocytic leukemia (CLL. Due to an engraftment failure during the first allo-HSCT of a matched related donor for CLL treatment, the salvage treatment was a second allo-HSCT. At the moment of meningioma-like tumor diagnosis, the patient was pancytopenic due to high-risk MDS, so it was decided to postpone a surgical intervention until hematological improvement. For the high-risk MDS of donor-cells origin the chosen treatment was induction with intensive chemotherapy. Due to refractory disease, the patient was treated with 5-azacitidine and donor-lymphocytes infusion with no response and, finally, a third allo-HSCT of a matched unrelated donor was performed. The patient died 6 months after the third allo-HSCT, in cytogenetic remission but without hematological recovery, due to an intracranial hemorrhage with origin in the meningioma-like tumor.

Risk factors for oligodendroglial tumors: a pooled international study

DEFF Research Database (Denmark)

McCarthy, Bridget J; Rankin, Kristin M; Aldape, Ken

2011-01-01

Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate p...

Optimal Treatment for Intermediate- and High-Risk, Nonmuscle-Invasive Bladder Cancer

Directory of Open Access Journals (Sweden)

A.P.M. van der Meijden

2006-01-01

Full Text Available According to clinical and pathological factors the prognosis of a patient with non-muscle invasive bladder tumors can be assessed. The prognosis is determined by the likelihood of recurrence(30-70% and/or progression to muscle invasive bladder cancer(1-15%.Trans urethral resection of bladder tumors remains the initial therapy but adjuvant intravesical instillations are necessary.All patients benefit from a single immediate post operative instillation with a chemotherapeutic agent and for low risk tumors this is the optimal therapy.Patients with intermediate and high risk tumors need more intravesical chemo-or immunotherapy. Chemotherapy reduces recurrences but not progression. Intravesical immunotherapy(BCG prevents or delays progression. Patients at high risk for progression may need upfront cystectomy.

Management of Skin Cancer in the High-Risk Patient.

Science.gov (United States)

Behan, James W; Sutton, Adam; Wysong, Ashley

2016-12-01

Skin cancer is the most common of human cancers and outnumbers all other types of cancer combined in the USA by over threefold. The majority of non-melanoma skin cancers are easily treated with surgery or locally destructive techniques performed under local anesthesia in the cost-effective outpatient setting. However, there is a subset of "high-risk" cases that prove challenging in terms of morbidity, mortality, adjuvant treatment required, as well as overall cost to the health care system. In our opinion, the term "high risk" when applied to skin cancer can mean one of three things: a high-risk tumor with aggressive histologic and/or clinical features with an elevated risk for local recurrence or regional/distant metastasis, a high-risk patient with the ongoing development of multiple skin cancers, and a high-risk patient based on immunosuppression. We have recently proposed classifying NMSC as a chronic disease in a certain subset of patients. Although no consensus definition exists for a chronic disease in medicine, there are three components that are present in most definitions: duration of at least 1 year, need for ongoing medical care, and functional impairment and/or alteration of activities of daily living (ADLs) and quality of life (QOL). Immunosuppression can refer to exogenous (organ or stem cell transplant patients,) or endogenous (HIV, leukemia, lymphoma, genodermatoses with DNA mismatch repair problems or other immunosuppression) causes. These patients are at risk for high-risk tumors and/or the development of multiple tumors.

Intake of high-fat diet stimulates the risk of ultraviolet radiation-induced skin tumors and malignant progression of papillomas to carcinoma in SKH-1 hairless mice

Energy Technology Data Exchange (ETDEWEB)

Vaid, Mudit; Singh, Tripti; Prasad, Ram [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Katiyar, Santosh K., E-mail: skatiyar@uab.edu [Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294 (United States); Birmingham Veterans Affairs Medical Center, Birmingham, AL 35294 (United States)

2014-01-01

Previously, we showed that administration of a high-fat diet (HF-diet) to C57BL/6 mice exacerbates their response to short-term UVB radiation-induced inflammation in the skin. To explore the effects of an HF-diet on UVB-induced tumorigenesis, we have used the SKH-1 hairless mouse model in which the mice are exposed to UVB radiation (180 mJ/cm{sup 2}) three times a week for 24 weeks. The development of UVB-induced skin tumors was rapid and the tumor multiplicity and tumor size were significantly higher (P < 0.01–0.005) in the mice fed an HF-diet than the mice fed a control-diet (C-diet). Moreover, the malignant progression of UVB-induced papillomas to carcinomas was higher in HF-diet-fed mice. On analysis of tumors and tumor-uninvolved skin samples from the tumor-bearing mice, we found that administration of an HF-diet significantly enhanced the levels of UVB-induced expression of cyclooxygenase-2 (COX-2), prostaglandin E{sub 2} (P < 0.01), and PGE{sub 2} receptors, and activation of NF-κB in the UVB-exposed skin as well as in tumors. In addition the HF-diet enhanced the expression of proinflammatory cytokines, including tumor necrosis factor-α (P < 0.01), interleukin (IL)-1β (P < 0.01) and IL-6 (P < 0.05) in the UVB-exposed skin as well as in tumors. Western blot analysis revealed that HF-diet enhanced the levels of epidermal cell proliferation, phosphatidylinositol 3-kinase and phosphorylation of Akt at Ser{sup 473} in UVB-exposed skin and skin tumors. Collectively, these data demonstrate that the regular consumption of an HF-diet increases the risk of photocarcinogenesis in mice and that this is associated with enhanced expression of inflammatory mediators in the UVB-exposed skin and tumors. - Highlights: • Consumption of high-fat diet increases UVB-induced skin tumor development in mice. • Intake of high-fat diet stimulates progression of UV-induced papilloma to carcinoma. • Intake of high-fat diet enhances inflammation in UV-exposed skin • Regular

TU-AB-BRA-11: Evaluation of Fully Automatic Volumetric GBM Segmentation in the TCGA-GBM Dataset: Prognosis and Correlation with VASARI Features

International Nuclear Information System (INIS)

Rios Velazquez, E; Meier, R; Dunn, W; Gutman, D; Alexander, B; Wiest, R; Reyes, M; Bauer, S; Aerts, H

2015-01-01

Purpose: Reproducible definition and quantification of imaging biomarkers is essential. We evaluated a fully automatic MR-based segmentation method by comparing it to manually defined sub-volumes by experienced radiologists in the TCGA-GBM dataset, in terms of sub-volume prognosis and association with VASARI features. Methods: MRI sets of 67 GBM patients were downloaded from the Cancer Imaging archive. GBM sub-compartments were defined manually and automatically using the Brain Tumor Image Analysis (BraTumIA), including necrosis, edema, contrast enhancing and non-enhancing tumor. Spearman’s correlation was used to evaluate the agreement with VASARI features. Prognostic significance was assessed using the C-index. Results: Auto-segmented sub-volumes showed high agreement with manually delineated volumes (range (r): 0.65 – 0.91). Also showed higher correlation with VASARI features (auto r = 0.35, 0.60 and 0.59; manual r = 0.29, 0.50, 0.43, for contrast-enhancing, necrosis and edema, respectively). The contrast-enhancing volume and post-contrast abnormal volume showed the highest C-index (0.73 and 0.72), comparable to manually defined volumes (p = 0.22 and p = 0.07, respectively). The non-enhancing region defined by BraTumIA showed a significantly higher prognostic value (CI = 0.71) than the edema (CI = 0.60), both of which could not be distinguished by manual delineation. Conclusion: BraTumIA tumor sub-compartments showed higher correlation with VASARI data, and equivalent performance in terms of prognosis compared to manual sub-volumes. This method can enable more reproducible definition and quantification of imaging based biomarkers and has a large potential in high-throughput medical imaging research

TU-AB-BRA-11: Evaluation of Fully Automatic Volumetric GBM Segmentation in the TCGA-GBM Dataset: Prognosis and Correlation with VASARI Features

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Rios Velazquez, E [Dana-Farber Cancer Institute | Harvard Medical School, Boston, MA (United States); Meier, R [Institute for Surgical Technology and Biomechanics, Bern, NA (Switzerland); Dunn, W; Gutman, D [Emory University School of Medicine, Atlanta, GA (United States); Alexander, B [Dana- Farber Cancer Institute, Brigham and Womens Hospital, Harvard Medic, Boston, MA (United States); Wiest, R; Reyes, M [Institute for Surgical Technology and Biomechanics, University of Bern, Bern, NA (Switzerland); Bauer, S [Institute for Surgical Technology and Biomechanics, Support Center for Adva, Bern, NA (Switzerland); Aerts, H [Dana-Farber/Brigham Womens Cancer Center, Boston, MA (United States)

2015-06-15

Purpose: Reproducible definition and quantification of imaging biomarkers is essential. We evaluated a fully automatic MR-based segmentation method by comparing it to manually defined sub-volumes by experienced radiologists in the TCGA-GBM dataset, in terms of sub-volume prognosis and association with VASARI features. Methods: MRI sets of 67 GBM patients were downloaded from the Cancer Imaging archive. GBM sub-compartments were defined manually and automatically using the Brain Tumor Image Analysis (BraTumIA), including necrosis, edema, contrast enhancing and non-enhancing tumor. Spearman’s correlation was used to evaluate the agreement with VASARI features. Prognostic significance was assessed using the C-index. Results: Auto-segmented sub-volumes showed high agreement with manually delineated volumes (range (r): 0.65 – 0.91). Also showed higher correlation with VASARI features (auto r = 0.35, 0.60 and 0.59; manual r = 0.29, 0.50, 0.43, for contrast-enhancing, necrosis and edema, respectively). The contrast-enhancing volume and post-contrast abnormal volume showed the highest C-index (0.73 and 0.72), comparable to manually defined volumes (p = 0.22 and p = 0.07, respectively). The non-enhancing region defined by BraTumIA showed a significantly higher prognostic value (CI = 0.71) than the edema (CI = 0.60), both of which could not be distinguished by manual delineation. Conclusion: BraTumIA tumor sub-compartments showed higher correlation with VASARI data, and equivalent performance in terms of prognosis compared to manual sub-volumes. This method can enable more reproducible definition and quantification of imaging based biomarkers and has a large potential in high-throughput medical imaging research.

Family history, surgery, and APC mutation are risk factors for desmoid tumors in familial adenomatous polyposis: an international cohort study

DEFF Research Database (Denmark)

Nieuwenhuis, Marry H; Lefevre, Jérémie H; Bülow, Steffen

2011-01-01

Ability to identify patients with familial adenomatous polyposis who have a high risk of developing desmoid tumors may affect decisions in clinical practice.......Ability to identify patients with familial adenomatous polyposis who have a high risk of developing desmoid tumors may affect decisions in clinical practice....

Predictive value and modeling analysis of MSCT signs in gastrointestinal stromal tumors (GISTs) to pathological risk degree.

Science.gov (United States)

Wang, J-K

2017-03-01

By analyzing MSCT (multi-slice computed tomography) signs with different risks in gastrointestinal stromal tumors, this paper aimed to discuss the predictive value and modeling analysis of MSCT signs in GISTs (gastrointestinal stromal tumor) to pathological risk degree. 100 cases of primary GISTs with abdominal and pelvic MSCT scan were involved in this study. All MSCT scan findings and enhanced findings were analyzed and compared among cases with different risk degree of pathology. Then GISTs diagnostic model was established by using support vector machine (SVM) algorithm, and its diagnostic value was evaluated as well. All lesions were solitary, among which there were 46 low-risk cases, 24 medium-risk cases and 30 high-risk cases. For all high-risk, medium-risk and low-risk GISTs, there were statistical differences in tumor growth pattern, size, shape, fat space, with or without calcification, ulcer, enhancement method and peritumoral and intratumoral vessels (pvalue at each period (plain scan, arterial phase, venous phase) (p>0.05). The apparent difference lied in plain scan, arterial phase and venous phase for each risk degree. The diagnostic accuracy of SVM diagnostic model established with 10 imaging features as indexes was 70.0%, and it was especially reliable when diagnosing GISTs of high or low risk. Preoperative analysis of MSCT features is clinically significant for its diagnosis of risk degree and prognosis; GISTs diagnostic model established on the basis of SVM possesses high diagnostic value.

High infiltration of tumor-associated macrophages in triple-negative breast cancer is associated with a higher risk of distant metastasis

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Yuan ZY

2014-08-01

Full Text Available Zhong-Yu Yuan,1–3* Rong-Zhen Luo,1,2,4,* Rou-Jun Peng,1–3 Shu-Sen Wang,1–3 Cong Xue1–3 1State Key Laboratory of Oncology in South China, 2Collaborative Innovation Center for Cancer Medicine, 3Departments of Medical Oncology, Sun Yat-Sen University Cancer Center, 4Departments of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China  *These authors contributed equally to this work Background: Triple-negative breast cancer (TNBC is associated with poor prognosis and high probability of distant metastases. Tumor microenvironments play a pivotal role in tumor metastasis. Tumor-associated macrophages (TAMs are one of the main cell components, and they are correlated with increasing metastatic risk. The aim of this study is to analyze the prognostic significance of the infiltration of TAMs in patients with TNBC. Materials and methods: Immunohistochemical staining for cluster of differentiation (CD68 (a marker for macrophages was performed on tissue microarrays of operable breast cancer among 287 patients with TNBC, and the number of infiltrating TAMs was correlated with clinicopathological parameters. Results: We found that TNBC with a large number of infiltrating TAMs had a significantly higher risk of distant metastasis, as well as lower rates of disease-free survival and overall survival than those with a smaller number of infiltrating TAMs. Multivariate analysis indicated that the number of infiltrating TAMs was a significant independent prognostic factor of disease-free survival (P=0.001 in all patients. Conclusion: Our results suggested that high infiltrating TAMs are a significantly unfavorable prognostic factor for patients with TNBC, and they could become a potentially useful prognostic marker for TNBC. Keywords: breast carcinoma, triple-negative, tumor-associated macrophages, prognosis

Residual tumor size and IGCCCG risk classification predict additional vascular procedures in patients with germ cell tumors and residual tumor resection: a multicenter analysis of the German Testicular Cancer Study Group.

Science.gov (United States)

Winter, Christian; Pfister, David; Busch, Jonas; Bingöl, Cigdem; Ranft, Ulrich; Schrader, Mark; Dieckmann, Klaus-Peter; Heidenreich, Axel; Albers, Peter

2012-02-01

Residual tumor resection (RTR) after chemotherapy in patients with advanced germ cell tumors (GCT) is an important part of the multimodal treatment. To provide a complete resection of residual tumor, additional surgical procedures are sometimes necessary. In particular, additional vascular interventions are high-risk procedures that require multidisciplinary planning and adequate resources to optimize outcome. The aim was to identify parameters that predict additional vascular procedures during RTR in GCT patients. A retrospective analysis was performed in 402 GCT patients who underwent 414 RTRs in 9 German Testicular Cancer Study Group (GTCSG) centers. Overall, 339 of 414 RTRs were evaluable with complete perioperative data sets. The RTR database was queried for additional vascular procedures (inferior vena cava [IVC] interventions, aortic prosthesis) and correlated to International Germ Cell Cancer Collaborative Group (IGCCCG) classification and residual tumor volume. In 40 RTRs, major vascular procedures (23 IVC resections with or without prosthesis, 11 partial IVC resections, and 6 aortic prostheses) were performed. In univariate analysis, the necessity of IVC intervention was significantly correlated with IGCCCG (14.1% intermediate/poor vs 4.8% good; p=0.0047) and residual tumor size (3.7% size risk features must initially be identified as high-risk patients for vascular procedures and therefore should be referred to specialized surgical centers with the ad hoc possibility of vascular interventions. Copyright © 2011 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.10--Nuclear Information sub-volume

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 28 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the tenth one, the content is about Nuclear Information sub-volume

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.8--nuclear agriculture sub-volume

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 10 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the eighth one, the content is about nuclear agriculture sub-volume

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.4--isotope separation sub-volume

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 37 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the fourth one, the content is about isotope separation sub-volume

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.6--computational physics sub-volume

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 13 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the sixth one, the content is about computational physics sub-volume

Malignancy risk prediction for primary jejunum-ileal tumors

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MARQUES Ruy Garcia

2000-01-01

Full Text Available This work is aimed at identifying factors associated with primary jejunum-ileal tumors malignancy, defining a prediction model with sensitivity, specificity and accuracy to distinguish malign from benign neoplasms. These tumors are rare, have highly unspecific presentation and, frequently, are diagnosed late. We reviewed the charts of 42 patients with primary jejunum-ileal tumors treated in the Department of General Surgery of Rio de Janeiro State University Hospital, Rio de Janeiro, RJ, Brazil, from 1969 to 1998. We performed bivariate analyses, based on chi² test, searching associations between tumors malignancy and demographic and clinical variables. Then logistic regression was employed to consider the independent effect of variables previously identified on malignancy risk. The malign tumors included 11 adenocarcinomas, 7 leiomyosarcomas, 5 carcinoids and 4 lymphomas; the benign tumors included 10 leiomyomas, 2 hamartomas, and single cases of adenoma, multiple neurilemoma and choristoma. The bivariate analyses indicated the association between malignancy and palpable abdominal mass (P = 0.003, period from signs and symptoms onset to diagnosis (P = 0.016, anemia (P = 0.020, anorexia (P = 0.003, abdominal pain (P = 0.031, weight loss (P = 0.001, nausea and vomit (P = 0.094, and intestinal obstruction (P = 0.066; no association with patients demographic characteristics were found. In the final logistic regression model, weight loss, anemia and intestinal obstruction were statistically associated with the dependent variable of interest. Based only on three variables -- weight loss, anemia and intestinal obstruction -- the model defined was able to predict primary jejunum-ileal tumors malignancy with sensitivity of 85.2%, specificity of 80.0%, and accuracy of 83.3%.

Risk Factors for Subsequent Central Nervous System Tumors in Pediatric Allogeneic Hematopoietic Cell Transplant

DEFF Research Database (Denmark)

Gabriel, Melissa; Shaw, Bronwen E; Brazauskas, Ruta

2017-01-01

Survivors of hematopoietic cell transplantation (HCT) are at risk of subsequent solid tumors, including central nervous system (CNS) tumors. The risk of CNS tumors after HCT in pediatric HCT recipients is not known. We evaluated the incidence and risk factors for CNS tumors in pediatric recipients...

Renal transplantation-related risk factors for the development of uterine adenomatoid tumors.

Science.gov (United States)

Mizutani, Teruyuki; Yamamuro, Osamu; Kato, Noriko; Hayashi, Kazumasa; Chaya, Junya; Goto, Norihiko; Tsuzuki, Toyonori

2016-08-01

•We analyzed the epidemiological factors for clinical manifestations of uterine adenomatoid tumors.•Renal transplantation with immunosuppression therapy is risk factor for the development of uterine adenomatoid tumors.•The length of time on dialysis is risk factor for the development of uterine adenomatoid tumors.

Occupational risk factors for brain tumors. A case-referent death-certificate analysis

Energy Technology Data Exchange (ETDEWEB)

Thomas, T.L.; Fontham, E.T.; Norman, S.A.; Stemhagen, A.; Hoover, R.N.

1986-04-01

Numerous studies have suggested that employment in the oil refining and chemical manufacturing industries may be associated with excess brain tumor risk. A case-referent study was undertaken to evaluate brain tumor risk by occupation and industry in three geographic areas (northern New Jersey, Philadelphia, and the Gulf Coast of Louisiana) with a heavy concentration of these industries. Seven hundred and eighteen white men dying from brain tumor at age 30 years or older were ascertained from death certificates for 1978-1981. The referents were men who died of other causes, excluding epilepsy and stroke. Usual occupation and industry were obtained from the death certificates, and the maximum likelihood estimates of the relative risk were calculated for specific industries and occupations. Small nonsignificant excess risks of brain tumors were seen among persons whose usual employment was in the petroleum refining, electrical equipment manufacturing, health services, and educational services industries. Compared with other white-collar professionals, health diagnosticians, teachers, and artists/designers had a significantly elevated brain tumor risk. Among blue-collar workers, the only group with a significantly elevated brain tumor risk was precision metal workers, who are exposed to metal dusts and fumes and substances used as coolants, lubricants, and degreasers.

High Genomic Instability Predicts Survival in Metastatic High-Risk Neuroblastoma

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Sara Stigliani

2012-09-01

Full Text Available We aimed to identify novel molecular prognostic markers to better predict relapse risk estimate for children with high-risk (HR metastatic neuroblastoma (NB. We performed genome- and/or transcriptome-wide analyses of 129 stage 4 HR NBs. Children older than 1 year of age were categorized as “short survivors” (dead of disease within 5 years from diagnosis and “long survivors” (alive with an overall survival time ≥ 5 years. We reported that patients with less than three segmental copy number aberrations in their tumor represent a molecularly defined subgroup with a high survival probability within the current HR group of patients. The complex genomic pattern is a prognostic marker independent of NB-associated chromosomal aberrations, i.e., MYCN amplification, 1p and 11q losses, and 17q gain. Integrative analysis of genomic and expression signatures demonstrated that fatal outcome is mainly associated with loss of cell cycle control and deregulation of Rho guanosine triphosphates (GTPases functioning in neuritogenesis. Tumors with MYCN amplification show a lower chromosome instability compared to MYCN single-copy NBs (P = .0008, dominated by 17q gain and 1p loss. Moreover, our results suggest that the MYCN amplification mainly drives disruption of neuronal differentiation and reduction of cell adhesion process involved in tumor invasion and metastasis. Further validation studies are warranted to establish this as a risk stratification for patients.

High FDG uptake areas on pre-radiotherapy PET/CT identify preferential sites of local relapse after chemoradiotherapy for locally advanced oesophageal cancer

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Calais, Jeremie; Lemarignier, Charles; Vera, Pierre [Henri Becquerel Cancer Center and Rouen University Hospital, Nuclear Medicine Department, Rouen (France); University of Rouen, QuantIF-LITIS (Equipe d' Accueil 4108-FR CNRS 3638), Faculty of Medicine, Rouen (France); Dubray, Bernard [University of Rouen, QuantIF-LITIS (Equipe d' Accueil 4108-FR CNRS 3638), Faculty of Medicine, Rouen (France); Centre Henri Becquerel and Rouen University Hospital, Department of Radiotherapy and Medical Physics, Rouen (France); Nkhali, Lamyaa; Thureau, Sebastien; Modzelewski, Romain; Gardin, Isabelle [Henri Becquerel Cancer Center and Rouen University Hospital, Nuclear Medicine Department, Rouen (France); University of Rouen, QuantIF-LITIS (Equipe d' Accueil 4108-FR CNRS 3638), Faculty of Medicine, Rouen (France); Centre Henri Becquerel and Rouen University Hospital, Department of Radiotherapy and Medical Physics, Rouen (France); Di Fiore, Frederic [Rouen University Hospital, Department of Gastroenterology, Rouen (France); Rouen University Hospital, Department of Oncology, Henri Becquerel Cancer Center, IRON, Rouen (France); Michel, Pierre [Rouen University Hospital, Department of Gastroenterology, Rouen (France)

2015-05-01

The high failure rates in the radiotherapy (RT) target volume suggest that patients with locally advanced oesophageal cancer (LAOC) would benefit from increased total RT doses. High 2-deoxy-2-[{sup 18}F]fluoro-D-glucose (FDG) uptake (hotspot) on pre-RT FDG positron emission tomography (PET)/CT has been reported to identify intra-tumour sites at increased risk of relapse after RT in non-small cell lung cancer and in rectal cancer. Our aim was to confirm these observations in patients with LAOC and to determine the optimal maximum standardized uptake value (SUV{sub max}) threshold to delineate smaller RT target volumes that would facilitate RT dose escalation without impaired tolerance. The study included 98 consecutive patients with LAOC treated by chemoradiotherapy (CRT). All patients underwent FDG PET/CT at initial staging and during systematic follow-up in a single institution. FDG PET/CT acquisitions were coregistered on the initial CT scan. Various subvolumes within the initial tumour (30, 40, 50, 60, 70, 80 and 90 % SUV{sub max} thresholds) and in the subsequent local recurrence (LR, 40 and 90 % SUV{sub max} thresholds) were pasted on the initial CT scan and compared[Dice, Jaccard, overlap fraction (OF), common volume/baseline volume, common volume/recurrent volume]. Thirty-five patients had LR. The initial metabolic tumour volume was significantly higher in LR tumours than in the locally controlled tumours (mean 25.4 vs 14.2 cc; p = 0.002). The subvolumes delineated on initial PET/CT with a 30-60 % SUV{sub max} threshold were in good agreement with the recurrent volume at 40 % SUV{sub max} (OF = 0.60-0.80). The subvolumes delineated on initial PET/CT with a 30-60 % SUV{sub max} threshold were in good to excellent agreement with the core volume (90 % SUV{sub max}) of the relapse (common volume/recurrent volume and OF indices 0.61-0.89). High FDG uptake on pretreatment PET/CT identifies tumour subvolumes that are at greater risk of recurrence after CRT in

Sensitivity study of voxel-based PET image comparison to image registration algorithms

Energy Technology Data Exchange (ETDEWEB)

Yip, Stephen, E-mail: syip@lroc.harvard.edu; Chen, Aileen B.; Berbeco, Ross [Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 (United States); Aerts, Hugo J. W. L. [Department of Radiation Oncology, Brigham and Women’s Hospital, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts 02115 and Department of Radiology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115 (United States)

2014-11-01

Purpose: Accurate deformable registration is essential for voxel-based comparison of sequential positron emission tomography (PET) images for proper adaptation of treatment plan and treatment response assessment. The comparison may be sensitive to the method of deformable registration as the optimal algorithm is unknown. This study investigated the impact of registration algorithm choice on therapy response evaluation. Methods: Sixteen patients with 20 lung tumors underwent a pre- and post-treatment computed tomography (CT) and 4D FDG-PET scans before and after chemoradiotherapy. All CT images were coregistered using a rigid and ten deformable registration algorithms. The resulting transformations were then applied to the respective PET images. Moreover, the tumor region defined by a physician on the registered PET images was classified into progressor, stable-disease, and responder subvolumes. Particularly, voxels with standardized uptake value (SUV) decreases >30% were classified as responder, while voxels with SUV increases >30% were progressor. All other voxels were considered stable-disease. The agreement of the subvolumes resulting from difference registration algorithms was assessed by Dice similarity index (DSI). Coefficient of variation (CV) was computed to assess variability of DSI between individual tumors. Root mean square difference (RMS{sub rigid}) of the rigidly registered CT images was used to measure the degree of tumor deformation. RMS{sub rigid} and DSI were correlated by Spearman correlation coefficient (R) to investigate the effect of tumor deformation on DSI. Results: Median DSI{sub rigid} was found to be 72%, 66%, and 80%, for progressor, stable-disease, and responder, respectively. Median DSI{sub deformable} was 63%–84%, 65%–81%, and 82%–89%. Variability of DSI was substantial and similar for both rigid and deformable algorithms with CV > 10% for all subvolumes. Tumor deformation had moderate to significant impact on DSI for progressor

Pfetin as a Risk Factor of Recurrence in Gastrointestinal Stromal Tumors

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Hajime Orita

2014-01-01

Full Text Available Background. Despite complete resection of gastrointestinal stromal tumors (GIST, recurrent and/or metastatic disease occurs, often depending on the grade of malignancy. As such, markers are needed that accurately predict patients at high risk for recurrence. Previously our group reported Pfetin as a prognostic biomarker for GIST. In order to create an approach for predicting risk of recurrence, we incorporated Pfetin expression with clinicopathological data to produce a predictive model. Object. Forty-five patients with localized primary GIST were treated with complete gross surgical resection surgically at our institution between 1995 and 2010 were included. The majority of tumors originated in the stomach (38 cases, as well as small intestine (6 cases and rectum (1 case. Method. (1 We performed retrospective analysis of the connection between Pfetin expression, clinicopathological data, and incidences of recurrence, using bivariate and multivariate analyses. (2 The reactivity of the monoclonal antibody against Pfetin was examined by immunohistochemistry. Pfetin. We have reported Pfetin, identified microarray technology, and compared between statistically different GISTs for good and poor prognoses and for prognostic marker. Results. There were 7 cases of recurrences. (1 By univariate analysis, tumor size, mitoses, exposure to abdominal cavity, and complete tumor removal predicted risk of recurrence. (2 Pfetin-negative cases were significantly related to recurrence (P = 0.002. Conclusions. This analysis demonstrates that lack of Pfetin expression is an additional predictor of recurrence in resected GIST. Further study may determine the role of this variable added to the current predictive model for selection of adjuvant therapy.

Body mass index and risk of colorectal carcinoma subtypes classified by tumor differentiation status.

Science.gov (United States)

Hanyuda, Akiko; Cao, Yin; Hamada, Tsuyoshi; Nowak, Jonathan A; Qian, Zhi Rong; Masugi, Yohei; da Silva, Annacarolina; Liu, Li; Kosumi, Keisuke; Soong, Thing Rinda; Jhun, Iny; Wu, Kana; Zhang, Xuehong; Song, Mingyang; Meyerhardt, Jeffrey A; Chan, Andrew T; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji; Nishihara, Reiko

2017-05-01

Previous studies suggest that abnormal energy balance status may dysregulate intestinal epithelial homeostasis and promote colorectal carcinogenesis, yet little is known about how host energy balance and obesity influence enterocyte differentiation during carcinogenesis. We hypothesized that the association between high body mass index (BMI) and colorectal carcinoma incidence might differ according to tumor histopathologic differentiation status. Using databases of the Nurses' Health Study and Health Professionals Follow-up Study, and duplication-method Cox proportional hazards models, we prospectively examined an association between BMI and the incidence of colorectal carcinoma subtypes classified by differentiation features. 120,813 participants were followed for 26 or 32 years and 1528 rectal and colon cancer cases with available tumor pathological data were documented. The association between BMI and colorectal cancer risk significantly differed depending on the presence or absence of poorly-differentiated foci (P heterogeneity  = 0.006). Higher BMI was associated with a higher risk of colorectal carcinoma without poorly-differentiated foci (≥30.0 vs. 18.5-22.4 kg/m 2 : multivariable-adjusted hazard ratio, 1.87; 95% confidence interval, 1.49-2.34; P trend   0.03, with the adjusted α of 0.01). High BMI was associated with risk of colorectal cancer subtype containing no poorly-differentiated focus. Our findings suggest that carcinogenic influence of excess energy balance might be stronger for tumors that retain better intestinal differentiation throughout the tumor areas.

Risk organ preservation technique in reirradiation. Injection of native type high molecular weight hyaluronate

International Nuclear Information System (INIS)

Kishi, Kazushi; Noda, Yasutaka; Tanaka, Kayo

2012-01-01

We developed a practical method of brachytherapy effective for reirradiation, using hyaluronate gel injection to separate the target to be intensively. We intended curative reirradiation with preserving organs at risk. Native-type high molecular weight hyaluronate that has an ideal biologic property to reduce inflammation via inhibitory activity to CD44 and other inflammation receptors was injected to create space during radiotherapy. Rectum, small intestines, skin, and various normal organs are effectively separated and thus eradicative re-irradiation was carried out in safe. We reviewed 55 patients who required the method. There were no complications related to the procedure. Prescribed dose to 100% of the planning target volume (PTV) was 77.93 Gy (range 54-92) equivalent at alpha/beta ratio of 3, with much higher subvolume effect, and the saving effects were enhanced at 3.35 times in the average of those without gel injection. In conclusion, the interventional brachytherapy with hyaluronate gel injection provided 3.35 times safer dose-escalated and eradicative treatment in reirradiation. (author)

CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Single Peripheral Lung Metastases

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Snider, James W.; Oermann, Eric K.; Chen, Viola; Rabin, Jennifer; Suy, Simeng; Yu, Xia [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States); Vahdat, Saloomeh [Department of Pathology, Georgetown University Hospital, Washington, DC (United States); Collins, Sean P. [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States); Banovac, Filip [Department of Radiology, Georgetown University Hospital, Washington, DC (United States); Anderson, Eric [Division of Pulmonary, Critical Care and Sleep Medicine, Georgetown University Hospital, Washington, DC (United States); Collins, Brian T., E-mail: collinsb@gunet.georgetown.edu [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States)

2012-06-29

Standard treatment for operable patients with single peripheral lung metastases is metastasectomy. We report mature CyberKnife outcomes for high-risk surgical patients with biopsy proven single peripheral lung metastases. Twenty-four patients (median age 73 years) with a mean maximum tumor diameter of 2.5 cm (range, 0.8–4.5 cm) were treated over a 6-year period extending from September 2004 to September 2010 and followed for a minimum of 1 year or until death. A mean dose of 52 Gy (range, 45–60 Gy) was delivered to the prescription isodose line in three fractions over a 3–11 day period (mean, 7 days). At a median follow-up of 20 months, the 2-year Kaplan–Meier local control and overall survival rates were 87 and 50%, respectively. CyberKnife with fiducial tracking is an effective treatment for high-risk surgical patients with single small peripheral lung metastases. Trials comparing CyberKnife with metastasectomy for operable patients are necessary to confirm equivalence.

The effects of postoperative irradiation on loco-regional tumor control and survival in patients with head and neck carcinomas by tumor subsites and relative risk factors for recurrence

International Nuclear Information System (INIS)

Schmidt-Ullrich, Rupert K.; Johnson, Christopher R.; Payne, Cheryl; Lu Jiandong; Han, Daniel

1997-01-01

Purpose/Objective: This study reports on a unique experience in the management of patients with advanced head and neck squamous cell carcinomas (HNSCC) in which, between 1982 and 1990, patients with varied risk for recurrence were either referred for immediate postoperative irradiation by one surgical group or offered radiotherapy after surgical failure by the other. We have previously demonstrated in patients with high risk for recurrence that combined surgery and postoperative radiotherapy (S/RT) resulted in improved loco-regional tumor control (LRC) and overall patient survival (OS) for the entire patient cohort. This updated and expanded analysis describes the benefit of postoperative irradiation for patients with HNSCC depending upon relative risk factors for recurrence and different subsites of primary tumors. Materials and Methods: Of 219 patients, 190 were evaluable because of tumor locations in the major subsites analyzed, i.e. oral cavity (OC), oropharynx (OP), hypopharynx (HP), and larynx (L). Depending upon the philosophy of the two surgical groups, 79 patients were treated with combined S/RT and 111 with S alone with a >90% compliance. Minimum 2-year follow-up applies to all data reported. The two patient groups were well balanced with respect to tumor stages (AJCC 1983) and other patient characteristics. Histopathological review revealed 88 cases with one risk factor for recurrence, 49 patients with positive resection margin (PRM) and 39 with extracapsular extension (ECE); an additional 22 patients presented with both risk factors and 80 patients were found to have no risk factors. S, consisting of wide local excisions or radical resections including neck dissections, and postoperative RT with doses between 50 and 70 Gy were similar for both groups. Statistical evaluations consisted of Kaplan-Meier analyses to calculate LRC and OS rates and of multivariate Cox's proportional hazard models to estimate significance of treatment effects including S vs. S

Imaging tumor hypoxia: Blood-borne delivery of imaging agents is fundamentally different in hypoxia subtypes

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Peter Vaupel

2014-03-01

Full Text Available Hypoxic tissue subvolumes are a hallmark feature of solid malignant tumors, relevant for cancer therapy and patient outcome because they increase both the intrinsic aggressiveness of tumor cells and their resistance to several commonly used anticancer strategies. Pathogenetic mechanisms leading to hypoxia are diverse, may coexist within the same tumor and are commonly grouped according to the duration of their effects. Chronic hypoxia is mainly caused by diffusion limitations resulting from enlarged intercapillary distances and adverse diffusion geometries and — to a lesser extent — by hypoxemia, compromised perfusion or long-lasting microregional flow stops. Conversely, acute hypoxia preferentially results from transient disruptions in perfusion. While each of these features of the tumor microenvironment can contribute to a critical reduction of oxygen availability, the delivery of imaging agents (as well as nutrients and anticancer agents may be compromised or remain unaffected. Thus, a critical appraisal of the effects of the various mechanisms leading to hypoxia with regard to the blood-borne delivery of imaging agents is necessary to judge their ability to correctly represent the hypoxic phenotype of solid malignancies.

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.2--uranium mining and metallurgy sub-volume

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 48 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the second one, the content is about uranium mining and metallurgy sub-volume

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.3--nuclear power sub-volume (Pt.2)

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 86 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the third one, the content is about nuclear power sub-volume (Pt.2)

Automatic block-matching registration to improve lung tumor localization during image-guided radiotherapy

Science.gov (United States)

Robertson, Scott Patrick

To improve relatively poor outcomes for locally-advanced lung cancer patients, many current efforts are dedicated to minimizing uncertainties in radiotherapy. This enables the isotoxic delivery of escalated tumor doses, leading to better local tumor control. The current dissertation specifically addresses inter-fractional uncertainties resulting from patient setup variability. An automatic block-matching registration (BMR) algorithm is implemented and evaluated for the purpose of directly localizing advanced-stage lung tumors during image-guided radiation therapy. In this algorithm, small image sub-volumes, termed "blocks", are automatically identified on the tumor surface in an initial planning computed tomography (CT) image. Each block is independently and automatically registered to daily images acquired immediately prior to each treatment fraction. To improve the accuracy and robustness of BMR, this algorithm incorporates multi-resolution pyramid registration, regularization with a median filter, and a new multiple-candidate-registrations technique. The result of block-matching is a sparse displacement vector field that models local tissue deformations near the tumor surface. The distribution of displacement vectors is aggregated to obtain the final tumor registration, corresponding to the treatment couch shift for patient setup correction. Compared to existing rigid and deformable registration algorithms, the final BMR algorithm significantly improves the overlap between target volumes from the planning CT and registered daily images. Furthermore, BMR results in the smallest treatment margins for the given study population. However, despite these improvements, large residual target localization errors were noted, indicating that purely rigid couch shifts cannot correct for all sources of inter-fractional variability. Further reductions in treatment uncertainties may require the combination of high-quality target localization and adaptive radiotherapy.

Parental smoking and risk of childhood brain tumors by functional polymorphisms in polycyclic aromatic hydrocarbon metabolism genes.

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Jessica L Barrington-Trimis

Full Text Available BACKGROUND: A recent meta-analysis suggested an association between exposure to paternal smoking during pregnancy and childhood brain tumor risk, but no studies have evaluated whether this association differs by polymorphisms in genes that metabolize tobacco-smoke chemicals. METHODS: We assessed 9 functional polymorphisms in 6 genes that affect the metabolism of polycyclic aromatic hydrocarbons (PAH to evaluate potential interactions with parental smoking during pregnancy in a population-based case-control study of childhood brain tumors. Cases (N = 202 were ≤10 years old, diagnosed from 1984-1991 and identified in three Surveillance, Epidemiology, and End Results (SEER registries in the western U.S. Controls in the same regions (N = 286 were frequency matched by age, sex, and study center. DNA for genotyping was obtained from archived newborn dried blood spots. RESULTS: We found positive interaction odds ratios (ORs for both maternal and paternal smoking during pregnancy, EPHX1 H139R, and childhood brain tumors (P(interaction = 0.02; 0.10, such that children with the high-risk (greater PAH activation genotype were at a higher risk of brain tumors relative to children with the low-risk genotype when exposed to tobacco smoke during pregnancy. A dose-response pattern for paternal smoking was observed among children with the EPHX1 H139R high-risk genotype only (OR(no exposure = 1.0; OR(≤3 hours/day = 1.32, 95% CI: 0.52-3.34; OR(>3 hours/day = 3.18, 95% CI: 0.92-11.0; P(trend = 0.07. CONCLUSION: Parental smoking during pregnancy may be a risk factor for childhood brain tumors among genetically susceptible children who more rapidly activate PAH in tobacco smoke.

Sorafenib neoadjuvant therapy in the treatment of high risk renal cell carcinoma.

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Yushi Zhang

Full Text Available To evaluate the clinical efficacy of sorafenib as preoperative neoadjuvant therapy in patients with high risk renal cell carcinoma (RCC.Clinical data of 18 patients with high risk RCC who received surgery done successfully after preoperative neoadjuvant therapy with sorafenib in Peking Union Medical College Hospital (PUMCH from April 2007 to October 2013 have been reviewed and analyzed in this study.Among the 18 patients there were 13 male and 5 female, with a median age of 54.6 years. The objective response rate (ORR of the operation on the selected patients is very high (94.4%, including 4 cases (22.2% of partial response (PR and 13 cases (72.2% of stable disease (SD. After preoperative sorafenib treatment, the average tumor size of the 18 patients decreased from 7.8 cm (ranging from 3.6 to 19.2 cm to 6.2 cm (ranging from 2.4 to 16.8 cm, and the median value of average tumor CT value decreased from 61HU to 52 HU. Among the 5 patients who had IVC tumor thrombi, the grades of tumor thrombi in 2 patients who were grade II before sorafenib treatment became grade I and grade 0 respectively, 2 patients of grade III both became grade II.Preoperative neoadjuvant therapy with sorafenib for high risk RCC patients can significantly decrease primary tumor volume as well as tumor thrombus, which could help the nephron-sparing surgery (NSS or radical nephrectomy to be done successfully.

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.7--nuclear fusion and plasma physics sub-volume

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 22 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the seventh one, the content is about nuclear fusion and plasma physics sub-volume

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.9--nuclear technology applied in industry sub-volume

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 35 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the ninth one, the content is about nuclear technology applied in industry sub-volume

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.8--radiation research and its application sub-volume

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 12 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the eighth one, the content is about radiation research and its application sub-volume

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.4--Nuclear chemistry and radiation chemistry sub-volume

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 24 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the fourth one, the content is about Nuclear chemistry and radiation chemistry sub-volume

Expression of FOXP3, CD14, and ARG1 in Neuroblastoma Tumor Tissue from High-Risk Patients Predicts Event-Free and Overall Survival

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Sara Stigliani

2015-01-01

Full Text Available The prognosis of children with metastatic neuroblastoma (NB > 18 months at diagnosis is dismal. Since the immune status of the tumor microenvironment could play a role in the history of disease, we evaluated the expression of CD45, CD14, ARG1, CD163, CD4, FOXP3, Perforin-1 (PRF1, Granzyme B (GRMB, and IL-10 mRNAs in primary tumors at diagnosis from children with metastatic NB and tested whether the transcript levels are significantly associated to event-free and overall survival (EFS and OS, resp.. Children with high expression of CD14, ARG1 and FOXP3 mRNA in their primary tumors had significantly better EFS. Elevated expression of CD14, and FOXP3 mRNA was significantly associated to better OS. CD14 mRNA expression levels significantly correlated to all markers, with the exception of CD4. Strong positive correlations were found between PRF1 and CD163, as well as between PFR1 and FOXP3. It is worth noting that the combination of high levels of CD14, FOXP3, and ARG1 mRNAs identified a small group of patients with excellent EFS and OS, whereas low levels of CD14 were sufficient to identify patients with dismal survival. Thus, the immune status of the primary tumors of high-risk NB patients may influence the natural history of this pediatric cancer.

Investigating Contingency Risk Factors of Brain Tumor in Children and Adolescents

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A Nazemi

2014-12-01

Conclusion: According to research results, several preventable and predictable factors are linked to pediatric brain tumors. Therefore, children prone to brain tumors are recommended to be examined and screened for these risk factors.

Mammographic density and risk of breast cancer by tumor characteristics: a case-control study.

Science.gov (United States)

Krishnan, Kavitha; Baglietto, Laura; Stone, Jennifer; McLean, Catriona; Southey, Melissa C; English, Dallas R; Giles, Graham G; Hopper, John L

2017-12-16

In a previous paper, we had assumed that the risk of screen-detected breast cancer mostly reflects inherent risk, and the risk of whether a breast cancer is interval versus screen-detected mostly reflects risk of masking. We found that inherent risk was predicted by body mass index (BMI) and dense area (DA) or percent dense area (PDA), but not by non-dense area (NDA). Masking, however, was best predicted by PDA but not BMI. In this study, we aimed to investigate if these associations vary by tumor characteristics and mode of detection. We conducted a case-control study nested within the Melbourne Collaborative Cohort Study of 244 screen-detected cases matched to 700 controls and 148 interval cases matched to 446 controls. DA, NDA and PDA were measured using the Cumulus software. Tumor characteristics included size, grade, lymph node involvement, and ER, PR, and HER2 status. Conditional and unconditional logistic regression were applied as appropriate to estimate the Odds per Adjusted Standard Deviation (OPERA) adjusted for age and BMI, allowing the association with BMI to be a function of age at diagnosis. For screen-detected cancer, both DA and PDA were associated to an increased risk of tumors of large size (OPERA ~ 1.6) and positive lymph node involvement (OPERA ~ 1.8); no association was observed for BMI and NDA. For risk of interval versus screen-detected breast cancer, the association with risk for any of the three mammographic measures did not vary by tumor characteristics; an association was observed for BMI for positive lymph nodes (OPERA ~ 0.6). No associations were observed for tumor grade and ER, PR and HER2 status of tumor. Both DA and PDA were predictors of inherent risk of larger breast tumors and positive nodal status, whereas for each of the three mammographic density measures the association with risk of masking did not vary by tumor characteristics. This might raise the hypothesis that the risk of breast tumours with poorer prognosis

Air pollution from traffic and risk for brain tumors

DEFF Research Database (Denmark)

Poulsen, Aslak Harbo; Sørensen, Mette; Andersen, Zorana J

2016-01-01

PURPOSE: Air pollution is an established lung carcinogen, and there is increasing evidence that air pollution also negatively affects the brain. We have previously reported an association between air pollution and risk of brain tumors in a cohort study based on only 95 cases. We set out...... to replicate that finding in a large nationwide case-control study. METHODS: We identified all 4,183 adult brain tumor cases in Denmark in the years 2000-2009 and 8,018 risk set sampled population controls matched on gender and year of birth. We extracted residential address histories and estimated mean...... residential nitrogen oxides (NOx) concentrations since 1971 with a validated dispersion model. Categorical and linear odds ratios (OR) and confidence intervals (CI) were calculated with conditional logistic regression models. RESULTS: The highest risk estimates for any brain cancer were observed among...

Genetic and modifying factors that determine the risk of brain tumors

DEFF Research Database (Denmark)

Montelli, Terezinha de Cresci Braga; Peraçoli, Maria Terezinha Serrão; Rogatto, Silvia Regina

2011-01-01

of tumor escape, CNS tumor immunology, immune defects that impair anti-tumor systemic immunity in brain tumor patients and local immuno-suppressive factors within CNS are also reviewed. New hope to treatment perspectives, as dendritic-cell-based vaccines is summarized too. Concluding, it seems well...... responses can alert immune system. However, it is necessary to clarify if individuals with both constitutional defects in immune functions and genetic instability have higher risk of developing brain tumors. Cytogenetic prospective studies and gene copy number variations analysis also must be performed...

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.7--pulse power technology and its application sub-volume

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 18 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the seventh one, the content is about pulse power technology and its application sub-volume

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.7--Nuclear electronics and nuclear detection technology sub-volume

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 57 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the seventh one, the content is about Nuclear electronics and nuclear detection technology sub-volume

Progress report on nuclear science and technology in China (Vol.3). Proceedings of academic annual meeting of China Nuclear Society in 2013, No.10--nuclear technology economy and management modernization sub-volume

International Nuclear Information System (INIS)

2014-05-01

Progress report on nuclear science and technology in China (Vol. 3) includes 18 articles which are communicated on the third national academic annual meeting of China Nuclear Society. There are 10 books totally. This is the tenth one, the content is about nuclear technology economy and management modernization sub-volume

Inflammatory potential of the diet and colorectal tumor risk in persons with Lynch syndrome

NARCIS (Netherlands)

Brouwer, Jesca G.M.; Makama, Maureen; Woudenbergh, Van Geertruida J.; Vasen, Hans F.A.; Nagengast, Fokko M.; Kleibeuker, Jan H.; Kampman, Ellen; Duijnhoven, Van Fränzel J.B.

2017-01-01

Background: Persons with Lynch syndrome (LS) have high lifetime risk of developing colorectal tumors (CRTs) because of a germline mutation in one of their mismatch repair (MMR) genes. An important process in the development of CRTs is inflammation, which has been shown to be modulated by diet.

[Risk factors of postoperative meningitis in patients with chiasm-sellar tumors].

Science.gov (United States)

Popugaev, K A; Savin, I A; Ershova, O N; Kurdyumova, N V; Tabasaransky, T F; Oshorov, A V; Kadashev, B A; Kalinin, P L; Kutin, M A

2014-01-01

Postoperative intracranial infectious complications are one of the most topical problems of neurosurgical intensive care due to theirs significant capability to impair outcomes of the main disease. To define the risk factors of postoperative meningitis in patients with chiasm-sellar tumors. 1. to define the effect of somatic and intracranial risk factors on occurrence of postoperative meningitis in patients after transsphenoidal and transcranial approaches to the tumor. 2. To define the effect of postoperative meningitis on outcomes of treatment in patients after transsphenoidal and transcranial approaches to the tumor. Somatic and intracranial risk factors of occurrence of postoperative meningitis (pneumonia, urinary tract infection, sepsis, intra-abdominal hypertension, the presence of external ventricular and lumbar drainage, monitoring of intracranial pressure, cerebrospinal fluid, and reoperation) were fixed every day. The study was conducted in the ICU of the Burdenko from October, 2010 to July, 2012. The 34 patients (19 males, 15 females) were included in the study (average age 47.5 years). The patients were divided into two groups; 17 patients each group. The group-1 included patients after transcranial approach to the tumor and the group-2 included patients after transsphenoidal approach. In the group-1 a meningitis occurred in 3 patients (17.6% +/- 9.2%, DI [-0.4 - 35.6]). In the group-2 a meningitis occurred in 7 patients (41.2% +/- 11.9) DI 95% [17.8 - 64.4]. Accumulation of cerebrospinal fluid under the skin flap authentically increased a risk of a meningitis occurrence in patients after transcranial approach to the tumor (p = 0.031). There was no defined statistical significance of other risk factors. But there was defined a trend of the increasing of meningitis occurrence in patients after transsphenoidal approach in case of lumbar drainage or reoperation. Duration of mechanical ventilation and ICU stay in patients with meningitis was authentically

Selecting breast cancer patients with T1-T2 tumors and one to three positive axillary nodes at high postmastectomy locoregional recurrence risk for adjuvant radiotherapy

International Nuclear Information System (INIS)

Truong, Pauline T.; Olivotto, Ivo A.; Kader, Hosam A.; Panades, Miguel; Speers, Caroline H.; Berthelet, Eric

2005-01-01

.8%; p 45 years with ≤25% of nodes positive, tumor location and ER status were factors that could be used to further distinguish low-risk from higher risk subsets. Conclusion: Clinical and pathologic factors can identify women with T1-T2 breast cancer and one to three positive nodes at high LRR risk after mastectomy. Age 25% of nodes positive, a medial tumor location, and ER-negative status were statistically significant independent factors associated with greater LRR, meriting consideration and discussion of PMRT. Combinations of these factors further augmented the LRR risk, warranting recommendation of PMRT to optimize locoregional control and potentially improve survival. The absence of high-risk factors identifies women who may reasonably be spared the morbidity of PMRT

The risk of liver tumors in dogs and man from radioactive aerosols

International Nuclear Information System (INIS)

Muggenburg, B.A.; Boecker, B.B.; Hahn, F.F.; Griffith, W.G.; McClellan, R.O.

1986-01-01

Life-span studies in progress using beagle dogs that inhaled relatively soluble or relatively insoluble forms of radionuclides will provide information from which we may project the risk to humans for liver cancer from inhaled radioactive material. Twenty-two liver tumors have been observed in dogs exposed to beta-emitting radionuclides, mainly 144 Ce, and one liver tumor in a dog exposed to 238 Pu. Two liver cancers were also observed in control dogs. The risk of liver cancer in dogs that inhaled beta-emitting radionuclides was calculated to be 90 liver cancers per million rads. The risk of liver cancers in dogs in our studies and in studies at the University of Utah, when compared to the incidence of liver tumors in humans exposed to Thorotrast, suggest that the risk of liver cancer from an inhaled beta-emitting radionuclide in people is about 30 liver cancers per million person-rads. 19 refs., 3 tabs

[High oncogenic risk human papillomavirus and urinary bladder cancer].

Science.gov (United States)

Loran, O B; Sinyakova, L A; Gundorova, L V; Kosov, V A; Kosova, I V; Pogodina, I E; Kolbasov, D N

2017-07-01

To determine the role of human papillomavirus (HPV) of high oncogenic risk in the development of urinary bladder cancer. 100 patients (72 men and 28 women) aged 38 to 90 years (mean age 65+/-10 years) diagnosed with bladder cancer were examined and underwent treatment. Clinical assessment was complemented by enzyme-linked immunosorbent assays for the presence of antiviral antibodies to herpes simplex virus (HSV) type 1 and type 2, cytomegalovirus (CMV), Epstein-Barr virus (EBV), urethra scraping for detecting high oncogenic risk HPV. Tumor tissue was sampled for PCR virus detection. Semi-quantitative analysis was used to evaluate the components of lymphocyte-plasmocyte and leukocyte infiltrates and cytopathic changes in tumor tissue. There were positive correlations between cytopathic cell changes (koylocytosis and intranuclear inclusions, as manifestations of HPV) and the level of antiviral antibodies, the presence of viruses in the tumor, as well as with the components of the lymphoid-plasmocyte infiltrate. Negative correlations were found between the presence of papillomatosis and the above changes. Human papillomavirus is believed to be a trigger for the initiation of a tumor in young patients with a latent infection (CMV and EBV, HSV, HPV). Cytopathic changes (kylocytosis and intranuclear inclusions) were associated with the activity and morphological features of herpes-viral infections. Their degree varied depending on the stage of the process, but not on the anaplasia degree. Papillomatosis is associated with a more favorable course of the tumor process.

Fully automatic GBM segmentation in the TCGA-GBM dataset: Prognosis and correlation with VASARI features.

Science.gov (United States)

Rios Velazquez, Emmanuel; Meier, Raphael; Dunn, William D; Alexander, Brian; Wiest, Roland; Bauer, Stefan; Gutman, David A; Reyes, Mauricio; Aerts, Hugo J W L

2015-11-18

Reproducible definition and quantification of imaging biomarkers is essential. We evaluated a fully automatic MR-based segmentation method by comparing it to manually defined sub-volumes by experienced radiologists in the TCGA-GBM dataset, in terms of sub-volume prognosis and association with VASARI features. MRI sets of 109 GBM patients were downloaded from the Cancer Imaging archive. GBM sub-compartments were defined manually and automatically using the Brain Tumor Image Analysis (BraTumIA). Spearman's correlation was used to evaluate the agreement with VASARI features. Prognostic significance was assessed using the C-index. Auto-segmented sub-volumes showed moderate to high agreement with manually delineated volumes (range (r): 0.4 - 0.86). Also, the auto and manual volumes showed similar correlation with VASARI features (auto r = 0.35, 0.43 and 0.36; manual r = 0.17, 0.67, 0.41, for contrast-enhancing, necrosis and edema, respectively). The auto-segmented contrast-enhancing volume and post-contrast abnormal volume showed the highest AUC (0.66, CI: 0.55-0.77 and 0.65, CI: 0.54-0.76), comparable to manually defined volumes (0.64, CI: 0.53-0.75 and 0.63, CI: 0.52-0.74, respectively). BraTumIA and manual tumor sub-compartments showed comparable performance in terms of prognosis and correlation with VASARI features. This method can enable more reproducible definition and quantification of imaging based biomarkers and has potential in high-throughput medical imaging research.

Pelvic inflammatory disease and risk of invasive ovarian cancer and ovarian borderline tumors

DEFF Research Database (Denmark)

Rasmussen, Christina B; Faber, Mette T; Jensen, Allan

2013-01-01

PURPOSE: The aim of the study was to examine the potential association between a history of pelvic inflammatory disease (PID) and risk of epithelial ovarian cancer or ovarian borderline tumors. METHODS: In a population-based case-control study in Denmark, we included 554 women with invasive ovarian...... cancer, 202 with ovarian borderline tumors, and 1,564 controls aged 35-79 years. The analyses were performed in multiple logistic regression models. RESULTS: We found a significantly increased risk of ovarian borderline tumors among women with a history of PID (OR = 1.50; 95% CI 1.......08-2.08) but no apparent association between PID and risk of invasive ovarian cancer (OR = 0.83; 95% CI 0.65-1.05). We found no effect of age at time of first PID or time since first PID on the risk for either condition. CONCLUSION: Our results suggest that a history of PID is associated with an increased risk of ovarian...

Radiofrequency ablation assisted by real-time virtual sonography for hepatocellular carcinoma inconspicuous under sonography and high-risk locations

Directory of Open Access Journals (Sweden)

Cheng-Han Lee

2015-08-01

Full Text Available Radiofrequency ablation (RFA is an effective and real-time targeting modality for small hepatocellular carcinomas (HCCs. However, mistargeting may occur when the target tumor is confused with cirrhotic nodules or because of the poor conspicuity of the index tumor under ultrasonography (US. Real-time virtual sonography (RVS can provide the same reconstruction computed tomography images as US images. The aim of this study is to investigate the usefulness of RVS-assisted RFA for HCCs that are inconspicuous or conspicuous under US. A total of 21 patients with 28 HCC tumors—divided into US inconspicuous and high-risk subgroup (3 tumors in 3 patients, US inconspicuous and nonhigh-risk subgroup (5 tumors in 4 patients, US conspicuous and high-risk subgroup (16 tumors in 14 patients, and US conspicuous and nonhigh-risk subgroup (4 tumors in 3 patients—underwent RVS-assisted RFA between May 2012 and June 2014 in our institution. The mean diameter of the nodules was 2.0 ± 1.1 cm. The results showed that the complete ablation rate is 87.5% (7/8 in the US undetectable group and 75% (15/20 in the US detectable group. A comparison between six tumors with incomplete ablation and 22 tumors with complete ablation showed higher alpha-fetoprotein level (mean, 1912 ng/mL vs. 112 ng/mL and larger tumor size (mean diameter, 26 mm vs. 16 mm in the incomplete ablation nodules (both p < 0.05. In conclusion, RVS-assisted RFA is useful for tumors that are difficult to detect under conventional US and may also be useful for tumors in high-risk locations because it may prevent complication induced by mistargeting.

[Dynamic investigation of nutritional risk in patients with malignant tumor during hospitalization].

Science.gov (United States)

Zhu, M W; Wei, J M; Chen, W; Yang, X; Cui, H Y; Zhu, S N; Zhang, P P; Xiong, J; Zheng, D F; Song, H J; Liang, X Y; Zhang, L; Xu, W Y; Wang, H B; Su, G Q; Feng, L J; Chen, T; Wu, Y D; Li, H; Sun, J Q; Shi, Y; Tong, B D; Zhou, S M; Wang, X Y; Huang, Y H; Zhang, B M; Xu, J; Zhang, H Y; Chang, G L; Jia, Z Y; Chen, S F; Hu, J; Zhang, X W; Wang, H; Li, Z D; Gao, Y Y; Gui, B

2018-04-10

Objective: To prospectively investigate the changes in nutritional status of patients with malignant tumors during hospitalization by using nutritional risk screening (NRS2002), and to analyze the correlation between the nutritional status and clinical outcomes . Methods: This was a prospective and parallel research done by multi-center collaboration from 34 hospitals in China from June to September 2014.Hospitalized patients with malignant tumors inthese departments (Department of Gastroenterology, respiratory medicine, oncology, general surgery, thoracic surgery and geriatrics)were investigated. Only the patients with age≥ 18 years and hospitalization time between 7-30 days were included. During hospitalization, the physical indexes of human bodywere measured, and the NRS 2002 scores, and monitored the nutritional support at the time points of admission and 24 hours before discharge were recorded.And whether there was a nutritional risk in hospitalized patients and its association with clinical outcomes were investigated. Results: A total of 2 402 patients with malignancies were enrolled in this study. Seventy fourpatients who did not complete NRS2002 were eliminated, and 2 328 patients were included. The number of the main diseases was the top five, including 587 cases of colorectal cancer, 567 cases of lung cancer, 564 cases of gastric cancer, 146 cases of esophageal cancer, and 119 cases of liver tumor. At the time of discharge, compared with admission, the BMI, body weight, grip and calf circumferences of patients with malignant tumor were significantly decreased ( P nutritional risk screening, the rate of malnutrition at admission was 11.1% (BMI =18.5, 258/2 328) and the rate of malnutrition at discharge was 10.9% (BMI =18.5, 254/2 328), there were no significant differences (χ(2)=0.019 7, P =0.888). There were 1 204 patients with nutritional risk at admission (51.7%, NRS2002 score≥3)and 1 352 patients with nutritional risk at discharge (58.1%, NRS2002

Growth hormone treatment and risk of recurrence or progression of brain tumors in children: a review.

Science.gov (United States)

Bogarin, Roberto; Steinbok, Paul

2009-03-01

Brain tumors are one of the most common types of solid neoplasm in children. As life expectancy of these patients has increased with new and improved therapies, the morbidities associated with the treatments and the tumor itself have become more important. One of the most common morbidities is growth hormone deficiency, and since recombinant growth hormone (GH) became available, its use has increased exponentially. There is concern that in the population of children with brain tumors, GH treatment might increase the risk of tumor recurrence or progression or the appearance of a second neoplasm. In the light of this ongoing concern, the current literature has been reviewed to provide an update on the risk of tumor recurrence, tumor progression, or new intracranial tumor formation when GH is used to treat GH deficiency in children, who have had or have intracranial tumors. On the basis of this review, the authors conclude that the use of GH in patients with brain tumor is safe. GH therapy is not associated with an increased risk of central nervous system tumor progression or recurrence, leukemia (de novo or relapse), or extracranial non-leukemic neoplasms.

Laparoscopic Cryoablation Of Small Renal Tumors – Does Anatomical Tumor Complexity Affect Treatment Outcome?

DEFF Research Database (Denmark)

Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Andersen, Gratien

risk in relation to nephron sparing surgery, but they may also be useful when planning cryoablation. Aim: The aim of the present study was to investigate whether patients with an anatomical complex tumor, represented by a high PADUA-score (≥10), carried a higher risk of residual unablated tumor...... compared to patients with a less anatomical complex tumor when treated with laparoscopic cryoablation. Material and methods: A retrospective review of Aarhus Cryoablation Register identified 120 patients with a single biopsy-verified pT1a renal tumor, treated with primary laparoscopic cryoablation between....... This relative risk of 2.9 (95%CI 1.1;7.6) was statistically significant (p=0.03). The mean follow-up time from treatment to diagnosis of treatment failure was 13 months (95%CI 8;18), which was not significantly different between the two groups. Conclusion: Patients with an anatomical complex tumor, represented...

Laparoscopic Cryoablation Of Small Renal Tumors – Does Anatomical Tumor Complexity Effect Treatment Outcome?

DEFF Research Database (Denmark)

Nielsen, Tommy Kjærgaard; Østraat, Øyvind; Andersen, Gratien

risk in relation to nephron sparing surgery, but they may also be useful when planning cryoablation. Aim: The aim of the present study was to investigate whether patients with an anatomical complex tumor, represented by a high PADUA-score (≥10), carried a higher risk of residual unablated tumor...... compared to patients with a less anatomical complex tumor when treated with laparoscopic cryoablation. Material and methods: A retrospective review of Aarhus Cryoablation Register identified 120 patients with a single biopsy-verified pT1a renal tumor, treated with primary laparoscopic cryoablation between....... This relative risk of 2.9 (95%CI 1.1;7.6) was statistically significant (p=0.03). The mean follow-up time from treatment to diagnosis of treatment failure was 13 months (95%CI 8;18), which was not significantly different between the two groups. Conclusion: Patients with an anatomical complex tumor, represented...

Association between traditional clinical high-risk features and gene expression profile classification in uveal melanoma.

Science.gov (United States)

Nguyen, Brandon T; Kim, Ryan S; Bretana, Maria E; Kegley, Eric; Schefler, Amy C

2018-02-01

To evaluate the association between traditional clinical high-risk features of uveal melanoma patients and gene expression profile (GEP). This was a retrospective, single-center, case series of patients with uveal melanoma. Eighty-three patients met inclusion criteria for the study. Patients were examined for the following clinical risk factors: drusen/retinal pigment epithelium (RPE) changes, vascularity on B-scan, internal reflectivity on A-scan, subretinal fluid (SRF), orange pigment, apical tumor height/thickness, and largest basal dimensions (LBD). A novel point system was created to grade the high-risk clinical features of each tumor. Further analyses were performed to assess the degree of association between GEP and each individual risk factor, total clinical risk score, vascularity, internal reflectivity, American Joint Committee on Cancer (AJCC) tumor stage classification, apical tumor height/thickness, and LBD. Of the 83 total patients, 41 were classified as GEP class 1A, 17 as class 1B, and 25 as class 2. The presence of orange pigment, SRF, low internal reflectivity and vascularity on ultrasound, and apical tumor height/thickness ≥ 2 mm were not statistically significantly associated with GEP class. Lack of drusen/RPE changes demonstrated a trend toward statistical association with GEP class 2 compared to class 1A/1B. LBD and advancing AJCC stage was statistically associated with higher GEP class. In this cohort, AJCC stage classification and LBD were the only clinical features statistically associated with GEP class. Clinicians should use caution when inferring the growth potential of melanocytic lesions solely from traditional funduscopic and ultrasonographic risk factors without GEP data.

Genomic and epigenomic analysis of high-risk prostate cancer reveals changes in hydroxymethylation and TET1.

Science.gov (United States)

Spans, Lien; Van den Broeck, Thomas; Smeets, Elien; Prekovic, Stefan; Thienpont, Bernard; Lambrechts, Diether; Karnes, R Jeffrey; Erho, Nicholas; Alshalalfa, Mohammed; Davicioni, Elai; Helsen, Christine; Gevaert, Thomas; Tosco, Lorenzo; Haustermans, Karin; Lerut, Evelyne; Joniau, Steven; Claessens, Frank

2016-04-26

The clinical heterogeneity of prostate cancer (PCa) makes it difficult to identify those patients that could benefit from more aggressive treatments. As a contribution to a better understanding of the genomic changes in the primary tumor that are associated with the development of high-risk disease, we performed exome sequencing and copy number determination of a clinically homogeneous cohort of 47 high-risk PCas. We confirmed recurrent mutations in SPOP, PTEN and TP53 among the 850 point mutations we detected. In seven cases, we discovered genomic aberrations in the TET1 (Ten-Eleven Translocation 1) gene which encodes a DNA hydroxymethylase than can modify methylated cytosines in genomic DNA and thus is linked with gene expression changes. TET1 protein levels were reduced in tumor versus non-tumor prostate tissue in 39 of 40 cases. The clinical relevance of changes in TET1 levels was demonstrated in an independent PCa cohort, in which low TET1 mRNA levels were significantly associated with worse metastases-free survival. We also demonstrate a strong reduction in hydroxymethylated DNA in tumor tissue in 27 of 41 cases. Furthermore, we report the first exploratory (h)MeDIP-Seq analyses of eight high-risk PCa samples. This reveals a large heterogeneity in hydroxymethylation changes in tumor versus non-tumor genomes which can be linked with cell polarity.

Chromosome 17 alterations identify good-risk and poor-risk tumors independently of clinical factors in medulloblastoma

Science.gov (United States)

McCabe, Martin G.; Bäcklund, L. Magnus; Leong, Hui Sun; Ichimura, Koichi; Collins, V. Peter

2011-01-01

Current risk stratification schemas for medulloblastoma, based on combinations of clinical variables and histotype, fail to accurately identify particularly good- and poor-risk tumors. Attempts have been made to improve discriminatory power by combining clinical variables with cytogenetic data. We report here a pooled analysis of all previous reports of chromosomal copy number related to survival data in medulloblastoma. We collated data from previous reports that explicitly quoted survival data and chromosomal copy number in medulloblastoma. We analyzed the relative prognostic significance of currently used clinical risk stratifiers and the chromosomal aberrations previously reported to correlate with survival. In the pooled dataset metastatic disease, incomplete tumor resection and severe anaplasia were associated with poor outcome, while young age at presentation was not prognostically significant. Of the chromosomal variables studied, isolated 17p loss and gain of 1q correlated with poor survival. Gain of 17q without associated loss of 17p showed a trend to improved outcome. The most commonly reported alteration, isodicentric chromosome 17, was not prognostically significant. Sequential multivariate models identified isolated 17p loss, isolated 17q gain, and 1q gain as independent prognostic factors. In a historical dataset, we have identified isolated 17p loss as a marker of poor outcome and 17q gain as a novel putative marker of good prognosis. Biological markers of poor-risk and good-risk tumors will be critical in stratifying treatment in future trials. Our findings should be prospectively validated independently in future clinical studies. PMID:21292688

Dietary patterns and risk of colorectal tumors: a cohort of French women of the National Education System (E3N).

Science.gov (United States)

Kesse, E; Clavel-Chapelon, F; Boutron-Ruault, M C

2006-12-01

Little is known about the dietary patterns associated with colorectal tumors along the adenoma-carcinoma sequence. Scores for dietary patterns were obtained by factor analysis in women from the French cohort of the European Prospective Investigation into Cancer and Nutrition (1993-2000). Their association with colorectal tumors was investigated in 516 adenoma cases (175 high-risk adenomas) and 4,804 polyp-free women and in 172 colorectal cancer cases and 67,312 cancer-free women. The authors identified four dietary patterns: "healthy" (vegetables, fruit, yogurt, sea products, and olive oil); "Western" (potatoes, pizzas and pies, sandwiches, sweets, cakes, cheese, cereal products, processed meat, eggs, and butter); "drinker" (sandwiches, snacks, processed meat, and alcoholic beverages); and "meat eaters" (meat, poultry, and margarine). For quartile 4 versus quartile 1, an increased risk of adenoma was observed with high scores of the Western pattern (multivariate relative risk (RR) = 1.39, 95% confidence interval: 1.00, 1.94; p(trend) = 0.03) and the drinker pattern (RR = 1.42, 95% confidence interval: 1.10, 1.83; p(trend) = 0.01). The meat-eaters pattern was positively associated with colorectal cancer risk (for quartile 4 vs. quartile 1: RR = 1.58, 95% confidence interval: 0.98, 2.53; p(trend) = 0.02). Dietary patterns that reflect a Western way of life are associated with a higher risk of colorectal tumors.

High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

DEFF Research Database (Denmark)

Egerod, Frederikke N S Lihme; Bartels, Annette; Fristrup, Niels

2009-01-01

bladder cancer. RESULTS: The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling...... than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling...

Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

Science.gov (United States)

Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

1992-07-15

Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-line mutant proteins observed in patients with Li-Fraumeni syndrome, second primary neoplasms, or familial breast cancer to block the growth of malignant cells and compared the structural properties of the mutant proteins to that of the wild-type protein. Six of seven missense mutations disrupted the growth inhibitory properties and structure of the wild-type protein. One germ-line mutation retained the features of the wild-type p53. Genetic analysis of the breast cancer family in which this mutation was observed indicated that this germ-line mutation was not associated with the development of cancer. These results demonstrate that germ-line p53 mutations observed in patients with Li-Fraumeni syndrome and with second malignancies have inactivated the p53 tumor suppressor gene. The inability of the germ-line p53 mutants to block the growth of malignant cells can explain why patients with these germ-line mutations have an increased risk for cancer. The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance.

Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

Science.gov (United States)

Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

1992-01-01

Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-line mutant proteins observed in patients with Li-Fraumeni syndrome, second primary neoplasms, or familial breast cancer to block the growth of malignant cells and compared the structural properties of the mutant proteins to that of the wild-type protein. Six of seven missense mutations disrupted the growth inhibitory properties and structure of the wild-type protein. One germ-line mutation retained the features of the wild-type p53. Genetic analysis of the breast cancer family in which this mutation was observed indicated that this germ-line mutation was not associated with the development of cancer. These results demonstrate that germ-line p53 mutations observed in patients with Li-Fraumeni syndrome and with second malignancies have inactivated the p53 tumor suppressor gene. The inability of the germ-line p53 mutants to block the growth of malignant cells can explain why patients with these germ-line mutations have an increased risk for cancer. The observation of a functionally silent germ-line mutation indicates that, before associating a germ-line tumor suppressor gene mutation with cancer risk, it is prudent to consider its functional significance. Images PMID:1631137

Risk factors for central nervous system tumors in children: New findings from a case-control study.

Directory of Open Access Journals (Sweden)

Rebeca Ramis

Full Text Available Central nervous system tumors (CNS are the most frequent solid tumor in children. Causes of CNS tumors are mainly unknown and only 5% of the cases can be explained by genetic predisposition. We studied the effects of environmental exposure on the incidence of CNS tumors in children by subtype, according to exposure to industrial and/or urban environment, exposure to crops and according to socio-economic status of the child.We carried out a population-based case-control study of CNS tumors in Spain, covering 714 incident cases collected from the Spanish Registry of Childhood Tumors (period 1996-2011 and 4284 controls, individually matched by year of birth, sex, and autonomous region of residence. We built a covariate to approximate the exposure to industrial and/or urban environment and a covariate for the exposure to crops (GCI using the coordinates of the home addresses of the children. We used the 2001 Census to obtain information about socio-economic status (SES. We fitted logistic regression models to estimate odds ratios (ORs and 95% confidence intervals (95%CIs.The results for all CNS tumors showed an excess risk (OR = 1.37; 95%CI = 1.09-1.73 for SES, i.e., children living in the least deprived areas had 37% more risk of CNS tumor than children living in the most deprived areas. For GCI, an increase of 10% in crop surface in the 1-km buffer around the residence implied an increase of 22% in the OR (OR = 1.22; 95%CI = 1.15-1.29. Children living in the intersection of industrial and urban areas could have a greater risk of CNS tumors than children who live outside these areas (OR = 1.20; 95%CI = 0.82-1.77. Living in urban areas (OR = 0.90; 95%CI = 0.65-1.24 or industrial areas (OR = 0.96; 95%CI = 0.81-1.77 did not seem to increase the risk for all CNS tumors together. By subtype, Astrocytomas, Intracranial and intraspinal embryonal tumors, and other gliomas showed similar results.Our results suggest that higher socioeconomic status and

Hypoxia imaging with [F-18] FMISO-PET in head and neck cancer: Potential for guiding intensity modulated radiation therapy in overcoming hypoxia-induced treatment resistance

International Nuclear Information System (INIS)

Hendrickson, Kristi; Phillips, Mark; Smith, Wade; Peterson, Lanell; Krohn, Kenneth; Rajendran, Joseph

2011-01-01

Background and purpose: Positron emission tomography (PET) imaging with [F-18] fluoromisonidazole (FMISO) has been validated as a hypoxic tracer . Head and neck cancer exhibits hypoxia, inducing aggressive biologic traits that impart resistance to treatment. Delivery of modestly higher radiation doses to tumors with stable areas of chronic hypoxia can improve tumor control . Advanced radiation treatment planning (RTP) and delivery techniques such as intensity modulated radiation therapy (IMRT) can deliver higher doses to a small volume without increasing morbidity. We investigated the utility of co-registered FMISO-PET and CT images to develop clinically feasible RTPs with higher tumor control probabilities (TCP). Materials and methods: FMISO-PET images were used to determine hypoxic sub-volumes for boost planning. Example plans were generated for 10 of the patients in the study who exhibited significant hypoxia. We created an IMRT plan for each patient with a simultaneous integrated boost (SIB) to the hypoxic sub-volumes. We also varied the boost for two patients. Result: A significant (mean 17%, median 15%) improvement in TCP is predicted when the modest additional boost dose to the hypoxic sub-volume is included. Conclusion: Combined FMISO-PET imaging and IMRT planning permit delivery of higher doses to hypoxic regions, increasing the predicted TCP (mean 17%) without increasing expected complications.

Rapid COJEC versus standard induction therapies for high-risk neuroblastoma

NARCIS (Netherlands)

Peinemann, Frank; Tushabe, Doreen A.; van Dalen, Elvira C.; Berthold, Frank

2015-01-01

Neuroblastoma is a rare malignant disease and mainly affects infants and very young children. The tumors mainly develop in the adrenal medullary tissue and an abdominal mass is the most common presentation. The high-risk group is characterized by metastasis and other characteristics that increase

Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study

International Nuclear Information System (INIS)

Wu, Jia; Gensheimer, Michael F.; Dong, Xinzhe; Rubin, Daniel L.; Napel, Sandy; Diehn, Maximilian; Loo, Billy W.; Li, Ruijiang

2016-01-01

Purpose: To develop an intratumor partitioning framework for identifying high-risk subregions from "1"8F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods and Materials: In this institutional review board–approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). Conclusion: We propose a robust intratumor

Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study

Energy Technology Data Exchange (ETDEWEB)

Wu, Jia; Gensheimer, Michael F.; Dong, Xinzhe [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Rubin, Daniel L. [Department of Radiology, Stanford University School of Medicine, Stanford, California (United States); Department of Medicine (Biomedical Informatics Research), Stanford University School of Medicine, Stanford, California (United States); Napel, Sandy [Department of Radiology, Stanford University School of Medicine, Stanford, California (United States); Diehn, Maximilian [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Institute for Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, California (United States); Loo, Billy W. [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States); Li, Ruijiang, E-mail: rli2@stanford.edu [Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California (United States); Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California (United States)

2016-08-01

Purpose: To develop an intratumor partitioning framework for identifying high-risk subregions from {sup 18}F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. Methods and Materials: In this institutional review board–approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Results: Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). Conclusion: We propose a robust

Fertility drug use and the risk of ovarian tumors in infertile women: a case-control study.

Science.gov (United States)

Asante, Albert; Leonard, Phoebe H; Weaver, Amy L; Goode, Ellen L; Jensen, Jani R; Stewart, Elizabeth A; Coddington, Charles C

2013-06-01

To assess the influence of infertility and fertility drugs on risk of ovarian tumors. Case-control study (Mayo Clinic Ovarian Cancer Study). Ongoing academic study of ovarian cancer. A total of 1,900 women (1,028 with ovarian tumors and 872 controls, frequency matched on age and region of residence) who had provided complete information in a self-report questionnaire about history of infertility and fertility drug use. None. Effect of infertility history, use of fertility drugs and oral contraception, and gravidity on the risk of ovarian tumor development, after controlling for potential confounders. Among women who had a history of infertility, use of fertility drugs was reported by 44 (24%) of 182 controls and 38 (17%) of 226 cases. Infertile women who used fertility drugs were not at increased risk of developing ovarian tumors compared with infertile women who did not use fertility drugs; the adjusted odds ratio was 0.64 (95% CI, 0.37, 1.11). The findings were similar when stratified by gravidity and when analyzed separately for borderline versus invasive tumors. We found no statistically significant association between fertility drug use and risk of ovarian tumors. Further larger, prospective studies are needed to confirm this observation. Published by Elsevier Inc.

Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

Directory of Open Access Journals (Sweden)

Andrei G. Vlassenko

2015-01-01

Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

Germ-line mutations of the p53 tumor suppressor gene in patients with high risk for cancer inactivate the p53 protein.

OpenAIRE

Frebourg, T; Kassel, J; Lam, K T; Gryka, M A; Barbier, N; Andersen, T I; Børresen, A L; Friend, S H

1992-01-01

Germ-line mutations in the p53 tumor suppressor gene have been observed in patients with Li-Fraumeni syndrome, brain tumors, second malignancies, and breast cancers. It is unclear whether all of these mutations have inactivated p53 and thereby provide an increased risk for cancer. Therefore, it is necessary to establish the biological significance of these germ-line mutations by the functional and structural analysis of the resulting mutant p53 proteins. We analyzed the ability of seven germ-...

FOXP3+ Tregs and B7-H1+/PD-1+ T lymphocytes co-infiltrate the tumor tissues of high-risk breast cancer patients: Implication for immunotherapy

International Nuclear Information System (INIS)

Ghebeh, Hazem; Barhoush, Eman; Tulbah, Asma; Elkum, Naser; Al-Tweigeri, Taher; Dermime, Said

2008-01-01

Recent studies have demonstrated a direct involvement of B7-H1, PD-1 and FOXP3 molecules in the immune escape of cancer. B7-H1 is an inhibitory molecule that binds to PD-1 on T lymphocytes, while FOXP3 is a marker for regulatory T cells (T regs ). We have previously demonstrated the association of B7-H1-expressing T infiltrating lymphocytes (TIL) with high-risk breast cancer patients while other studies reported the involvement of FOXP3+ T regs as a bad prognostic factor in breast tumors. Although the co-existence between the two types of cells has been demonstrated in vitro and animal models, their relative infiltration and correlation with the clinicopathological parameters of cancer patients have not been well studied. Therefore, we investigated TIL-expressing the B7-H1, PD-1, and FOXP3 molecules, in the microenvironment of human breast tumors and their possible association with the progression of the disease. Using immunohistochemistry, tumor sections from 62 breast cancer patients were co-stained for B7-H1, PD-1 and FOXP3 molecules and their expression was statistically correlated with factors known to be involved in the progression of the disease. A co-existence of B7-H1 + T lymphocytes and FOXP3 + T regs was evidenced by the highly significant correlation of these molecules (P < .0001) and their expression by different T lymphocyte subsets was clearly demonstrated. Interestingly, concomitant presence of FOXP3 + T regs , B7-H1 + and PD-1 + TIL synergistically correlated with high histological grade (III) (P < .001), estrogen receptor negative status (P = .017), and the presence of severe lymphocytic infiltration (P = .022). Accumulation of TIL-expressing such inhibitory molecules may deteriorate the immunity of high-risk breast cancer patients and this should encourage vigorous combinatorial immunotherapeutic approaches targeting T regs and B7-H1/PD-1 molecules

Mobile phone use and risk of intracranial tumors: a consistency analysis.

Science.gov (United States)

Lagorio, Susanna; Röösli, Martin

2014-02-01

A meta-analysis of studies on intracranial tumors and mobile phone use published by the end of 2012 was performed to evaluate the overall consistency of findings, assess the sensitivity of results to changes in the dataset, and try to detect the sources of between-study heterogeneity. Twenty-nine papers met our inclusion criteria. These papers reported on 47 eligible studies (17 on glioma, 15 on meningioma, 15 on acoustic neuroma), consisting of either primary investigations or pooled analyses. Five combinations of non-overlapping studies per outcome were identified. The combined relative risks (cRRs) in long-term mobile phone users (≥10 years) ranged between 0.98 (0.75-1.28) and 1.11 (0.86-1.44) for meningioma, with little heterogeneity across studies. High heterogeneity was detected across estimates of glioma and acoustic neuroma risk in long term users, with cRRs ranging between 1.19 (95% CI 0.86-1.64) and 1.40 (0.96-2.04), and from 1.14 (0.65-1.99) to 1.33 (0.65-2.73), respectively. A meta-regression of primary studies showed that the methodological differences embedded in the variable "study-group" explained most of the overall heterogeneity in results. Summary risk estimates based on heterogeneous findings should not be over-interpreted. Overall, the results of our study detract from the hypothesis that mobile phone use affects the occurrence of intracranial tumors. However, reproducibility (or lack of) is just one clue in the critical appraisal of epidemiological evidence. Based on other considerations, such as the limited knowledge currently available on risk beyond 15 years from first exposure, or following mobile phone use started in childhood, the pursuance of epidemiological surveillance is warranted. © 2013 Wiley Periodicals, Inc.

CyberKnife with Tumor Tracking: An Effective Treatment for High-Risk Surgical Patients with Stage I Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Chen, Viola J.; Oermann, Eric [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States); Vahdat, Saloomeh [Department of Pathology, Georgetown University Hospital, Washington, DC (United States); Rabin, Jennifer; Suy, Simeng; Yu, Xia; Collins, Sean P. [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States); Subramaniam, Deepa [Division of Hematology and Oncology, Georgetown University Hospital, Washington, DC (United States); Banovac, Filip [Department of Radiology, Georgetown University Hospital, Washington, DC (United States); Anderson, Eric [Division of Pulmonary, Critical Care and Sleep Medicine, Georgetown University Hospital, Washington, DC (United States); Collins, Brian T., E-mail: collinsb@gunet.georgetown.edu [Department of Radiation Medicine, Georgetown University Hospital, Washington, DC (United States)

2012-02-01

Published data suggests that wedge resection for stage I non-small cell lung cancer (NSCLC) is associated with improved overall survival compared to stereotactic body radiation therapy. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs) were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV). Treatment plans were designed using a mean of 156 pencil beams. Doses delivered to the PTV ranged from 42 to 60 Gy in three fractions. The 30 Gy isodose contour extended at least 1 cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3 month follow-up intervals. Forty patients (median age 76) with a median maximum tumor diameter of 2.6 cm (range, 1.4–5.0 cm) and a mean post-bronchodilator percent predicted forced expiratory volume in 1 s (FEV1) of 57% (range, 21–111%) were treated. A median dose of 48 Gy was delivered to the PTV over 3–13 days (median, 7 days). The 30 Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12–72 months) follow-up, the 3 year Kaplan–Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91 and 75%, respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1–2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.

Radiotherapy and androgen ablation for clinically localized high-risk prostate cancer

Energy Technology Data Exchange (ETDEWEB)

Pollack, Alan; Zagars, Gunar K; Kopplin, Susan

1995-04-30

Purpose: The response of patients with clinical stages T1-4 prostate cancer to radiotherapy is variable. A particularly poor prognostic group has been found to be comprised of those with pretreatment prostate specific antigen (PSA) levels above 30 ng/ml with any tumor grade, or PSA levels > 10 and {<=} 30 with tumors grade 3 or 4. These patients have over an 80% actuarial risk of biochemical failure 3 years after definitive external beam radiotherapy. Thus, patients with these high-risk features require more aggressive therapy. During the last 3-4 years, the policy to treat such patients with radiotherapy and androgen ablation (XRT/HORM) was instituted. A retrospective comparison was made between high-risk patients treated with radiotherapy alone (XRT) vs. XRT/HORM. Methods and Materials: Between 1987 and 1991, there were 81 high-risk patients treated with XRT. There were 38 high-risk patients treated with XRT/HORM between 1990 and 1992. The median follow-up was 37 months for the XRT group and 22 months for the XRT/HORM group. No patient had clinical, radiographic, or pathologic evidence of lymph node involvement. The median dose to the prostate was 66 Gy for the XRT group and 68 Gy for the XRT/HORM group. Results: The distributions of several potential prognostic factors were analyzed. Significant differences between the groups were observed for tumor grade, pretreatment prostatic acid phosphatase, and age. The XRT/HORM group was composed of patients with worse features, including a greater proportion of patients with grade 4 tumors, more with abnormal acid phosphatase levels, and more under 60 years of age. The actuarial incidence of a rising PSA at 3 years for the XRT group was 81% vs. 15% for the XRT/HORM group (p < 0.0001). In addition, local relapse at 3 years was 34% for the XRT group and 15% for the XRT/HORM group (p < 0.02). There was no difference between the groups in terms of survival. Cox proportional hazards analyses were performed using several

Age and Space Irradiation Modulate Tumor Progression: Implications for Carcinogenesis Risk

Data.gov (United States)

National Aeronautics and Space Administration — Age plays a major role in tumor incidence and is an important consideration when modeling the carcinogenesis process or estimating cancer risks. Epidemiological data...

Dinutuximab in the Treatment of High-Risk Neuroblastoma in Children

Directory of Open Access Journals (Sweden)

Hazal Gur

2017-06-01

Full Text Available Neuroblastoma is the most common extracranial tumor derived from neural crest cells in childhood, and treatment of high-risk neuroblastoma is a difficulty in oncology field. The discovery of new treatment strategies to treat pediatric patients with high-risk neuroblastoma is important. Dinutuximab (ch14.18; Unituxin, a chimeric human-mouse monoclonal antibody, is approved by Food and Drug Administration in 2015 to be used specifically in the treatment of high-risk neuroblastoma. It binds the disialoganglioside (GD2 antigen on the surface of neuroblastoma cells and induces lysis of GD2-expressed neuroblastoma cells via antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. To enhance its activity, it is used with a combination of granulocyte-macrophage colony-stimulating factor, interleukin 2, and 13- cis -retinoic acid. In this review, we discuss the use of dinutuximab in the treatment of high-risk neuroblastoma.

Phrenic nerve injury after radiofrequency ablation of lung tumors: retrospective evaluation of the incidence and risk factors.

Science.gov (United States)

Matsui, Yusuke; Hiraki, Takao; Gobara, Hideo; Uka, Mayu; Masaoka, Yoshihisa; Tada, Akihiro; Toyooka, Shinichi; Mitsuhashi, Toshiharu; Mimura, Hidefumi; Kanazawa, Susumu

2012-06-01

To retrospectively investigate the incidence of and risk factors for phrenic nerve injury after radiofrequency (RF) ablation of lung tumors. The study included 814 RF ablation procedures of lung tumors. To evaluate the development of phrenic nerve injury, chest radiographs obtained before and after the procedure were examined. Phrenic nerve injury was assumed to have developed if the diaphragmatic level was elevated after the procedure. To identify risk factors for phrenic nerve injury, multiple variables were compared between cases of phrenic nerve injury and randomly selected controls by using univariate analyses. Multivariate analysis was then performed to identify independent risk factors. Evaluation of phrenic nerve injury from chest radiographs was possible after 786 procedures. Evidence of phrenic nerve injury developed after 10 cases (1.3%). Univariate analysis revealed that larger tumor size (≥ 20 mm; P = .014), proximity of the phrenic nerve to the tumor (phrenic nerve injury. Multivariate analysis demonstrated that the proximity of the phrenic nerve to the tumor (phrenic nerve injury after RF ablation was 1.3%. The proximity of the phrenic nerve to the tumor was an independent risk factor for phrenic nerve injury. Copyright © 2012 SIR. Published by Elsevier Inc. All rights reserved.

Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors.

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Young Bae Choi

Full Text Available We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs. During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant, bacteremia, urinary tract infection (UTI, respiratory virus infection, and varicella zoster virus (VZV reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant, bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection. Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children.

Utility of sentinel node biopsy in patients with high-risk cutaneous squamous cell carcinoma

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Allen, J E; Stolle, L B

2015-01-01

BACKGROUND: Currently there is no consensual agreement on the standard use of Sentinel Lymph Node Biopsy (SLNB) in staging of high-risk patients. OBJECTIVE: The objective was to define the predictive value and role of SLNB combined with the different high-risk factors to determine which patients...... cm. Sensitivity, specificity and NPV for a tumor localized at a high-risk area were 72.63%, 100% and 96.74%, respectively. Specificity was 100% as was NPV for immunosuppression. CONCLUSION: SLNB has a high NPV and low false negative rate and carries a low risk of complications. SLNB may prove...

Coffee, tea, and caffeine consumption and risk of epithelial ovarian cancer and borderline ovarian tumors

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Gosvig, Camilla F; Kjaer, Susanne K; Blaakær, Jan

2015-01-01

BACKGROUND: Epidemiological studies that have investigated the association between coffee, tea and caffeine consumption and ovarian cancer risk have produced conflicting results. Furthermore, only few studies have examined the role of coffee and tea consumption separately for borderline ovarian...... tumors. By use of data from a large Danish population-based case-control study, we examined the risk of ovarian tumors associated with coffee, tea, and caffeine consumption with a particular focus on characterizing risks by tumor behavior and histology. MATERIAL AND METHODS: From 1995 through 1999, we....... RESULTS: Both coffee (OR = 0.90; 95% CI 0.84-0.97 per cup/day) and total caffeine consumption from coffee and tea combined (OR = 0.93; 95% CI 0.88-0.98 per 100 mg/day) decreased the risk of ovarian cancer. These associations were significant only for the serous and "other" subtypes of ovarian cancer...

ON THE BENEFITS AND RISKS OF PROTON THERAPY IN PEDIATRIC CRANIOPHARYNGIOMA

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Beltran, Chris; Roca, Monica; Merchant, Thomas E.

2013-01-01

Purpose Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients. Methods and Materials For this retrospective study, we acquired imaging and treatment-planning data from 14 children with craniopharyngioma (mean age, 5.1 years) irradiated with photons (54 Gy) and monitored by weekly magnetic resonance imaging (MRI) examinations during radiation therapy. Photon intensity-modulated radiation therapy (IMRT), double-scatter proton (DSP) therapy, and intensity-modulated proton therapy (IMPT) plans were created for each patient based on his or her pre-irradiation MRI. Target volumes were contoured on each weekly MRI scan for adaptive modeling. The measured differences in conformity index (CI) and normal tissue doses, including functional sub-volumes of the brain, were compared across the planning methods, as was target coverage based on changes in target volumes during treatment. Results CI and normal tissue dose values of IMPT plans were significantly better than those of the IMRT and DSP plans (p craniopharyngioma. IMPT is the most conformal method and spares the most normal tissue; however, it is highly sensitive to target volume changes, whereas the DSP method is not. PMID:21570209

Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18 months.

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Fischer, Janina; Pohl, Alexandra; Volland, Ruth; Hero, Barbara; Dübbers, Martin; Cernaianu, Grigore; Berthold, Frank; von Schweinitz, Dietrich; Simon, Thorsten

2017-08-04

Although several studies have been conducted on the role of surgery in localized neuroblastoma, the impact of surgical timing and extent of primary tumor resection on outcome in high-risk patients remains controversial. Patients from the German neuroblastoma trial NB97 with localized neuroblastoma INSS stage 1-3 age > 18 months were included for retrospective analysis. Imaging reports were reviewed by two independent physicians for Image Defined Risk Factors (IDRF). Operation notes and corresponding imaging reports were analyzed for surgical radicality. The extent of tumor resection was classified as complete resection (95-100%), gross total resection (90-95%), incomplete resection (50-90%), and biopsy (Neuroblastoma Risk Group (INRG) staging system. Survival curves were estimated according to the method of Kaplan and Meier and compared by the log-rank test. A total of 179 patients were included in this study. 77 patients underwent more than one primary tumor operation. After best surgery, 68.7% of patients achieved complete resection of the primary tumor, 16.8% gross total resection, 14.0% incomplete surgery, and 0.5% biopsy only. The cumulative complication rate was 20.3% and the surgery associated mortality rate was 1.1%. Image defined risk factors (IDRF) predicted the extent of resection. Patients with complete resection had a better local-progression-free survival (LPFS), event-free survival (EFS) and OS (overall survival) than the other groups. Subgroup analyses showed better EFS, LPFS and OS for patients with complete resection in INRG high-risk patients. Multivariable analyses revealed resection (complete vs. other), and MYCN (non-amplified vs. amplified) as independent prognostic factors for EFS, LPFS and OS. In patients with localized neuroblastoma age 18 months or older, especially in INRG high-risk patients harboring MYCN amplification, extended surgery of the primary tumor site improved local control rate and survival with an acceptable risk of

Cerebral distribution of 133Xe and blood flow measured with high purity germanium

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Reich, T.; Rusinek, H.; Youdin, M.; Clagnaz, M.

1985-01-01

Distribution of cerebral blood flow was measured with an array of 200 ultra-pure germanium radiation detectors and 133 Xe by inhalation. The array sees the head as a composite of different subvolumes and enables measurement of the concentration history of tracer every 1-10 sec in each subvolume simultaneously. Subvolume mean flows, (fm), and partition coefficients, lambda m, are derived by compartmental analysis of tissue concentration washout curves. Errors from cross talk, scalp radiation, look through, and assumed partition coefficients are eliminated. Average fm adjusted for 40 mm Hg PACO 2 in 14 cortical subvolumes (7 right, 7 left) of four normal 21-24 year old controls ranged from 50 to 60 ml/100 cc tissue/min, and lambda m ranged from 0.97 to 1.14. Average fm and lambda m in white matter was 24 ml/100 cc/min and 1.42 - 1.14 respectively. During CO 2 inhalation, right and left hemispheric fm increased 6.4% and 5.7%/mm Hg respectively, whereas white matter fm increased 2.2% and 3.4% mm Hg respectively. There was no systematic difference between front and back or dominant vs non-dominant sides. Three 73-84 year old controls had reduced fm and CO 2 reactivity in all subvolumes, lambda m was in the same range as in younger controls. Two patients with intracranial cerebrovascular disease showed excellent localization of ischemic subvolumes. One patient with asymptomatic unilateral 98% stenosis of the internal carotid artery had a similar distribution of blood flow in both hemispheres

Association of Ovarian Tumor β2-Adrenergic Receptor Status with Ovarian Cancer Risk Factors and Survival.

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Huang, Tianyi; Tworoger, Shelley S; Hecht, Jonathan L; Rice, Megan S; Sood, Anil K; Kubzansky, Laura D; Poole, Elizabeth M

2016-12-01

The β 2 -adrenergic signaling pathway mediates the effects of chronic stress on ovarian cancer progression in mouse models. The relevance of this pathway to human ovarian cancer remains unknown. We assessed tumor expression of β 2 -adrenergic receptor (ADRB2) using tissue microarrays in 237 ovarian cancer cases from the Nurses' Health Studies (NHS/NHSII). Competing risks Cox regression was used to evaluate whether associations of reproductive, hormonal, and psychosocial factors with ovarian cancer risk differed by ADRB2. We also examined the association between tumor ADRB2 expression and ovarian cancer survival. Forty-five (19%) cases were positive for ADRB2 staining. High levels of anxiety symptoms were positively associated with ADRB2-positive tumors (HR, 2.59; 95% confidence interval [CI], 1.15-5.84) but not with ADRB2-negative tumors (HR, 1.16; 95% CI, 0.81-1.66; P heterogeneity = 0.07). We observed similar results for depression. No associations were observed for job strain, caregiving stress, or widowhood for either positive or negative ADRB2 status. Lifetime ovulatory years were more strongly associated with ADRB2-positive tumors (HR per 5 years, 1.60; 95% CI, 1.15-2.21) compared with ADRB2-negative tumors (HR, 1.11; 95% CI, 0.96-1.27; P heterogeneity = 0.04). Significant heterogeneity by ADRB2 was also observed for parity (P heterogeneity = 0.01), oral contraceptive use (P heterogeneity = 0.03), and age at menopause (P heterogeneity = 0.04). Tumor expression of ADRB2 was not associated with ovarian cancer mortality (HR, 1.05; 95% CI, 0.69-1.59). Several stress- and ovulation-related factors were differentially associated with ovarian tumors responsive to β 2 -adrenergic signaling. Replication in larger studies is warranted to confirm the role of β 2 -adrenergic signaling in ovarian cancer etiology. Cancer Epidemiol Biomarkers Prev; 25(12); 1587-94. ©2016 AACR. ©2016 American Association for Cancer Research.

[Risk factors of rupture of internal carotid artery during surgical resection of carotid body tumor].

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Li, Y H; Wang, J S; Yao, C; Chang, G Q; Yin, H H; Li, S Q; Lü, W M; Hu, Z J; Wang, S M

2017-06-13

Objective: To investigate risk factors of rupture of internal carotid artery resection during carotid body tumor resection and to summarize our treatment experience. Methods: During the period from 1991 to 2016, rupture of internal carotid artery occurred in 27 patients (28 tumors) during surgical resection of carotid body tumor in the First Affiliated Hospital of Sun Yat-sen University. Their clinical and follow-up data were retrospectively collected and analyzed. For all patients underwent surgical resection during this period, Logistic regression analysis was used to investigate the risk factors of intraoperative rupture of internal carotid artery. Results: Of these 28 tumors, there were 15 (53.6%) tumors with diameter≥5 cm and 20 (71.4%) Shamblin Ⅲ tumors. Intraoperatively, shunt was applied for 8 (28.6%) cases. Thirteen (46.4%) patients underwent ligation of external carotid artery, while 2 (7.1%) patients accepted resection of cranial nerves. Direct closure/patchplasty, autologous vessels or graft reconstruction was used in 16, 10 and 2 cases, respectively. Postoperatively, stroke occurred in 4(14.3%) cases and cranial nerve deficit in 15 (53.6%) cases. During a median length of 36 (14-125) months, cranial nerve deficit persisted in 5 cases. Follow-up radiologic examination indicated 3 (10.7%) cases of targeted vessel occlusion. However, no new-onset stroke was identified. Among all patients underwent surgical resection of carotid body tumor, female ( OR =3.650, P =0.012), age≤25 years old ( OR =3.710, P =0.013) and Shamblin Ⅲ tumor ( OR =4.631, P =0.008) increase the risks of intraoperative carotid artery rupture. Conclusions: Shamblin Ⅲ tumor is the predictor of rupture of internal carotid artery. Intraoperative, properly increased blood pressure, intraoperative heparinization and use of shunt for those cases without well-compensated cranial collateral arteries are likely to decreasing the incidence of stroke.

Soy protein isolate inhibits hepatic tumor promotion in mice fed a high-fat liquid diet.

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Mercer, Kelly E; Pulliam, Casey F; Pedersen, Kim B; Hennings, Leah; Ronis, Martin Jj

2017-03-01

Alcoholic and nonalcoholic fatty liver diseases are risk factors for development of hepatocellular carcinoma, but the underlying mechanisms are poorly understood. On the other hand, ingestion of soy-containing diets may oppose the development of certain cancers. We previously reported that replacing casein with a soy protein isolate reduced tumor promotion in the livers of mice with alcoholic liver disease after feeding a high fat ethanol liquid diet following initiation with diethylnitrosamine. Feeding soy protein isolate inhibited processes that may contribute to tumor promotion including inflammation, sphingolipid signaling, and Wnt/β-catenin signaling. We have extended these studies to characterize liver tumor promotion in a model of nonalcoholic fatty liver disease produced by chronic feeding of high-fat liquid diets in the absence of ethanol. Mice treated with diethylnitrosamine on postnatal day 14 were fed a high-fat liquid diet made with casein or SPI as the sole protein source for 16 weeks in adulthood. Relative to mice fed normal chow, a high fat/casein diet led to increased tumor promotion, hepatocyte proliferation, steatosis, and inflammation. Replacing casein with soy protein isolate counteracted these effects. The high fat diets also resulted in a general increase in transcripts for Wnt/β-catenin pathway components, which may be an important mechanism, whereby hepatic tumorigenesis is promoted. However, soy protein isolate did not block Wnt signaling in this nonalcoholic fatty liver disease model. We conclude that replacing casein with soy protein isolate blocks development of steatosis, inflammation, and tumor promotion in diethylnitrosamine-treated mice fed high fat diets. Impact statement The impact of dietary components on cancer is a topic of great interest for both the general public and the scientific community. Liver cancer is currently the second leading form of cancer deaths worldwide. Our study has addressed the effect of the protein

Predicting location of recurrence using FDG, FLT, and Cu-ATSM PET in canine sinonasal tumors treated with radiotherapy

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Bradshaw, Tyler; Jeraj, Robert; Fu, Rau; Zhu, Jun; Bowen, Stephen; Forrest, Lisa

2015-01-01

Dose painting relies on the ability of functional imaging to identify resistant tumor subvolumes to be targeted for additional boosting. This work assessed the ability of FDG, FLT, and Cu-ATSM PET imaging to predict the locations of residual FDG PET in canine tumors following radiotherapy. Nineteen canines with spontaneous sinonasal tumors underwent PET/CT imaging with radiotracers FDG, FLT, and Cu-ATSM prior to hypofractionated radiotherapy. Therapy consisted of 10 fractions of 4.2 Gy to the sinonasal cavity with or without an integrated boost of 0.8 Gy to the GTV. Patients had an additional FLT PET/CT scan after fraction 2, a Cu-ATSM PET/CT scan after fraction 3, and follow-up FDG PET/CT scans after radiotherapy. Following image registration, simple and multiple linear and logistic voxel regressions were performed to assess how well pre- and mid-treatment PET imaging predicted post-treatment FDG uptake. R 2 and pseudo R 2 were used to assess the goodness of fits. For simple linear regression models, regression coefficients for all pre- and mid-treatment PET images were significantly positive across the population (P < 0.05). However, there was large variability among patients in goodness of fits: R 2 ranged from 0.00 to 0.85, with a median of 0.12. Results for logistic regression models were similar. Multiple linear regression models resulted in better fits (median R 2 = 0.31), but there was still large variability between patients in R 2 . The R 2 from regression models for different predictor variables were highly correlated across patients (R ≈ 0.8), indicating tumors that were poorly predicted with one tracer were also poorly predicted by other tracers. In conclusion, the high inter-patient variability in goodness of fits indicates that PET was able to predict locations of residual tumor in some patients, but not others. This suggests not all patients would be good candidates for dose painting based on a single biological target. (paper)

[18F]-Fluoromisonidazole Positron Emission Tomography/Computed Tomography Visualization of Tumor Hypoxia in Patients With Chordoma of the Mobile and Sacrococcygeal Spine

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Cheney, Matthew D., E-mail: mcheney@lroc.harvard.edu [Harvard Radiation Oncology Program, Boston, Massachusetts (United States); Chen, Yen-Lin [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Lim, Ruth [Department of Diagnostic Radiology, Massachusetts General Hospital, Boston, Massachusetts (United States); Winrich, Barbara K.; Grosu, Anca L.; Trofimov, Alexei V. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Depauw, Nicolas [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Centre of Medical Radiation Physics, University of Wollongong, Wollongong, NSW (Australia); Shih, Helen A. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); Schwab, Joseph H.; Hornicek, Francis J. [Department of Orthopedic Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States); DeLaney, Thomas F. [Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts (United States)

2014-12-01

Purpose: To investigate [18F]-fluoromisonidazole positron emission tomography/computed tomography (FMISO-PET/CT) detection of targetable hypoxic subvolumes (HSVs) in chordoma of the mobile or sacrococcygeal spine. Methods and Materials: A prospective, pilot study of 20 patients with primary or locally recurrent chordoma of the mobile or sacrococcygeal spine treated with proton or combined proton/photon radiation therapy (RT) with or without surgery was completed. The FMISO-PET/CT was performed before RT and after 19.8-34.2 GyRBE (relative biologic effectiveness). Gross tumor volumes were delineated and HSVs defined including voxels with standardized uptake values ≥1.4 times the muscle mean. Clinical characteristics and treatments received were compared between patients with and without HSVs. Results: The FMISO-PET/CT detected HSVs in 12 of 20 patients (60%). Baseline and interval HSV spatial concordance varied (0%-94%). Eight HSVs were sufficiently large (≥5 cm{sup 3}) to potentially allow an intensity modulated proton therapy boost. Patients with HSVs had significantly larger gross tumor volumes (median 410.0 cm{sup 3} vs 63.4 cm{sup 3}; P=.02) and were significantly more likely to have stage T2 tumors (5 of 12 vs 0 of 8; P=.04). After a median follow-up of 1.8 years (range, 0.2-4.4 years), a local recurrence has yet to be observed. Three patients developed metastatic disease, 2 with HSVs. Conclusions: Detection of targetable HSVs by FMISO-PET/CT within patients undergoing RT with or without surgery for treatment of chordoma of the mobile and sacrococcygeal spine is feasible. The study's inability to attribute interval HSV changes to treatment, rapidly changing hypoxic physiology, or imaging inconsistencies is a limitation. Further study of double-baseline FMISO-PET/CT and hypoxia-directed RT dose escalation, particularly in patients at high risk for local recurrence, is warranted.

Robust Intratumor Partitioning to Identify High-Risk Subregions in Lung Cancer: A Pilot Study.

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Wu, Jia; Gensheimer, Michael F; Dong, Xinzhe; Rubin, Daniel L; Napel, Sandy; Diehn, Maximilian; Loo, Billy W; Li, Ruijiang

2016-08-01

To develop an intratumor partitioning framework for identifying high-risk subregions from (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) and computed tomography (CT) imaging and to test whether tumor burden associated with the high-risk subregions is prognostic of outcomes in lung cancer. In this institutional review board-approved retrospective study, we analyzed the pretreatment FDG-PET and CT scans of 44 lung cancer patients treated with radiation therapy. A novel, intratumor partitioning method was developed, based on a 2-stage clustering process: first at the patient level, each tumor was over-segmented into many superpixels by k-means clustering of integrated PET and CT images; next, tumor subregions were identified by merging previously defined superpixels via population-level hierarchical clustering. The volume associated with each of the subregions was evaluated using Kaplan-Meier analysis regarding its prognostic capability in predicting overall survival (OS) and out-of-field progression (OFP). Three spatially distinct subregions were identified within each tumor that were highly robust to uncertainty in PET/CT co-registration. Among these, the volume of the most metabolically active and metabolically heterogeneous solid component of the tumor was predictive of OS and OFP on the entire cohort, with a concordance index or CI of 0.66-0.67. When restricting the analysis to patients with stage III disease (n=32), the same subregion achieved an even higher CI of 0.75 (hazard ratio 3.93, log-rank P=.002) for predicting OS, and a CI of 0.76 (hazard ratio 4.84, log-rank P=.002) for predicting OFP. In comparison, conventional imaging markers, including tumor volume, maximum standardized uptake value, and metabolic tumor volume using threshold of 50% standardized uptake value maximum, were not predictive of OS or OFP, with CI mostly below 0.60 (log-rank P>.05). We propose a robust intratumor partitioning method to identify clinically relevant, high-risk

Folic acid-decorated polyamidoamine dendrimer exhibits high tumor uptake and sustained highly localized retention in solid tumors: Its utility for local siRNA delivery.

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Xu, Leyuan; Yeudall, W Andrew; Yang, Hu

2017-07-15

The utility of folic acid (FA)-decorated polyamidoamine dendrimer G4 (G4-FA) as a vector was investigated for local delivery of siRNA. In a xenograft HN12 (or HN12-YFP) tumor mouse model of head and neck squamous cell carcinomas (HNSCC), intratumorally (i.t.) injected G4-FA exhibited high tumor uptake and sustained highly localized retention in the tumors according to near infrared (NIR) imaging assessment. siRNA against vascular endothelial growth factor A (siVEGFA) was chosen as a therapeutic modality. Compared to the nontherapeutic treatment groups (PBS solution or dendrimer complexed with nontherapeutic siRNA against green fluorescent protein (siGFP)), G4-FA/siVEGFA showed tumor inhibition effects in single-dose and two-dose regimen studies. In particular, two doses of G4-FA/siVEGFA i.t. administered eight days apart resulted in a more profound inhibition of tumor growth, accompanied with significant reduction in angiogenesis, as judged by CD31 staining and microvessel counts. Tumor size reduction in the two-dose regimen study was ascertained semi-quantitatively by live fluorescence imaging of YFP tumors and independently supported antitumor effects of G4-FA/siVEGFA. Taken together, G4-FA shows high tumor uptake and sustained retention properties, making it a suitable platform for local delivery of siRNAs to treat cancers that are readily accessible such as HNSCC. Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide and is difficult to transfect for gene therapy. We developed folate receptor (FR)-targeted polyamidoamine (PAMAM) dendrimer for enhanced delivery of genes to HNSCC and gained in-depth understanding of how gene delivery and transfection in head and neck squamous cancer cells can be enhanced via FR-targeted PAMAM dendrimers. The results we report here are encouraging and present latest advances in using dendrimers for cancer therapies, in particular for HNSCC. Our work has demonstrated that localized delivery of FR

Occupational exposure to radio frequency/microwave radiation and the risk of brain tumors

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Berg, Gabriele; Spallek, Jacob; Schüz, Joachim

2006-01-01

It is still under debate whether occupational exposure to radio frequency/microwave electromagnetic fields (RF/MW-EMF) contributes to the development of brain tumors. This analysis examined the role of occupational RF/MW-EMF exposure in the risk of glioma and meningioma. A population-based, case....... "High" exposure was defined as an occupational exposure that may exceed the RF/MW-EMF exposure limits for the general public recommended by the International Commission on Non-Ionizing Radiation Protection. Multiple conditional logistic regressions were performed separately for glioma and meningioma...

HPV and high-risk gene expression profiles predict response to chemoradiotherapy in head and neck cancer, independent of clinical factors

International Nuclear Information System (INIS)

Jong, Monique C. de; Pramana, Jimmy; Knegjens, Joost L.; Balm, Alfons J.M.; Brekel, Michiel W.M. van den; Hauptmann, Michael; Begg, Adrian C.; Rasch, Coen R.N.

2010-01-01

Purpose: The purpose of this study was to combine gene expression profiles and clinical factors to provide a better prediction model of local control after chemoradiotherapy for advanced head and neck cancer. Material and methods: Gene expression data were available for a series of 92 advanced stage head and neck cancer patients treated with primary chemoradiotherapy. The effect of the Chung high-risk and Slebos HPV expression profiles on local control was analyzed in a model with age at diagnosis, gender, tumor site, tumor volume, T-stage and N-stage and HPV profile status. Results: Among 75 patients included in the study, the only factors significantly predicting local control were tumor site (oral cavity vs. Pharynx, hazard ratio 4.2 [95% CI 1.4-12.5]), Chung gene expression status (high vs. Low risk profile, hazard ratio 4.4 [95% CI 1.5-13.3]) and HPV profile (negative vs. Positive profile, hazard ratio 6.2 [95% CI 1.7-22.5]). Conclusions: Chung high-risk expression profile and a negative HPV expression profile were significantly associated with increased risk of local recurrence after chemoradiotherapy in advanced pharynx and oral cavity tumors, independent of clinical factors.

Dietary patterns and risk of colorectal tumors: a cohort of French women of the National Education System (E3N)

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Kesse, Emmanuelle; Clavel-Chapelon, Françoise; Boutron-Ruault, Marie-Christine

2006-01-01

Little is known about the dietary patterns associated with colorectal tumors along the adenoma-carcinoma sequence. Scores for dietary patterns were obtained by factor analysis in women from the French cohort of the European Prospective Investigation into Cancer and Nutrition (1993-2000). Their association with colorectal tumors was investigated in 516 adenoma cases (175 high-risk adenomas) and 4,804 polyp-free women and in 172 colorectal cancer cases and 67,312 cancer-free women. The authors ...

Risk factor assessment in high-risk, bacillus Calmette–Guérin-treated, non-muscle-invasive bladder cancer

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Holz S

2017-09-01

Full Text Available Serge Holz,* Simone Albisinni,* Jacques Gilsoul, Michel Pirson, Véronique Duthie, Thierry Quackels, Marc Vanden Bossche, Thierry Roumeguère Department of Urology, Erasme Hospital, Université libre de Bruxelles, Belgium *These authors contributed equally to this work Objective: To assess the risk factors associated with recurrence, progression and survival in high-risk non-muscle-invasive bladder cancer (NMIBC patients treated with bacillus Calmette–Guérin (BCG and validate the European Organization for Research and Treatment of Cancer (EORTC and Spanish Urological Club for Oncological Treatment (CUETO scores.Patients and methods: We retrospectively analyzed all BCG-treated NMIBC patients from 1998 to 2012. Multiple variables were tested as risk factors for recurrence-free survival and progression-free survival (PFS. Variables included age, sex, grade, stage, tumor size, number of tumors, carcinoma in situ (CIS, recurrence status, BCG strain used, smoking status, use of re-staging transurethral resection and use of single immediate postoperative instillation. We also tested the accuracy of EORTC and CUETO scores in predicting recurrence and progression.Results: Overall, 123 patients were analyzed. Median (interquartile range follow-up was 49 months. The 5-year overall survival, cancer-specific survival, recurrence-free survival and PFS were 75.0%, 89.3%, 59.4% and 79.2%, respectively. On univariate analysis, multiple tumors (≥3, concomitant CIS and smoking influenced recurrence. Regarding progression, multiple tumors, concomitant CIS and Connaught strain (vs Tice negatively influenced PFS on univariate and multivariate analyses were independent prognostic factors. CUETO scores were accurate, with a slight overestimation, while EORTC score was not predictive of recurrence or progression.Conclusion: In this study, CIS and tumor multiplicity were unfavorable predictors of recurrence and progression in patients with NMIBC receiving BCG

Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil.

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de Paula Silva, Neimar; de Souza Reis, Rejane; Garcia Cunha, Rafael; Pinto Oliveira, Júlio Fernando; Santos, Marceli de Oliveira; Pombo-de-Oliveira, Maria S; de Camargo, Beatriz

2016-01-01

Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics. A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS) or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma). Children aged birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS) was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67-1.01)). Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma. This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes.

High-field MR imaging of spinal cord tumors

International Nuclear Information System (INIS)

Halimi, P.; Sigal, R.; Blas, C.; Doyon, D.; Hurth, M.; Bittoun, J.

1986-01-01

In 60 patients with spinal cord tumors, MR imaging was performed using a 1.5-T unit (GE Signa) and a planar surface coil, 5-mm-thick sections, and spin-echo pulse sequences (TE/TR = 25/600 and 25-100/2,000-2,500 msec). There were 32 astrocytomas, 13 ependymomas, and five hemangioblastomas. Ten patients were not operated on. Surgical follow-up was available in 35 patients. The MR imaging results were correlated with findings on CT, myelography, intraoperative US, surgery, and pathologic examination. In all cases the tumor appeared markedly inhomogeneous. Four imaging patterns corresponding to structural abnormalities were observed: low signal intensity of the tumor core on both T1- and T2-weighted images; hypointensity on T1-weighted images and hyperintensity on T2-weighted images (low-protein cyst, syrinx, edema); isointensity on T1-weighted and slight hypertensity on T2-weighted images (high-protein tumoral necrotic cyst); and high spinal intensity on both T1- and T2-weighted images (chronic hemorrhage). MR imaging contributes the most information in the diagnosis of spinal cord tumors and delineation of their extent, and consequently has a potential impact on surgical management

High-Dose, Single-Fraction Irradiation Rapidly Reduces Tumor Vasculature and Perfusion in a Xenograft Model of Neuroblastoma

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Jani, Ashish; Shaikh, Fauzia; Barton, Sunjay [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Willis, Callen [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Banerjee, Debarshi [Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); Mitchell, Jason [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Hernandez, Sonia L. [Department of Surgery, University of Chicago, Chicago, Illinois (United States); Hei, Tom [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States); Kadenhe-Chiweshe, Angela [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Yamashiro, Darrell J. [Department of Surgery, Columbia University Medical Center, New York, New York (United States); Department of Pediatrics, Columbia University Medical Center, New York, New York (United States); Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York (United States); Connolly, Eileen P., E-mail: epc2116@cumc.columbia.edu [Department of Radiation Oncology, Columbia University Medical Center, New York, New York (United States)

2016-04-01

Purpose: To characterize the effects of high-dose radiation therapy (HDRT) on neuroblastoma tumor vasculature, including the endothelial cell (EC)–pericyte interaction as a potential target for combined treatment with antiangiogenic agents. Methods and Materials: The vascular effects of radiation therapy were examined in a xenograft model of high-risk neuroblastoma. In vivo 3-dimensional contrast-enhanced ultrasonography (3D-CEUS) imaging and immunohistochemistry (IHC) were performed. Results: HDRT significantly reduced tumor blood volume 6 hours after irradiation compared with the lower doses used in conventionally fractionated radiation. There was a 63% decrease in tumor blood volume after 12-Gy radiation compared with a 24% decrease after 2 Gy. Analysis of tumor vasculature by lectin angiography showed a significant loss of small vessel ends at 6 hours. IHC revealed a significant loss of ECs at 6 and 72 hours after HDRT, with an accompanying loss of immature and mature pericytes at 72 hours. Conclusions: HDRT affects tumor vasculature in a manner not observed at lower doses. The main observation was an early reduction in tumor perfusion resulting from a reduction of small vessel ends with a corresponding loss of endothelial cells and pericytes.

Compliance with adjuvant treatment guidelines in endometrial cancer: room for improvement in high risk patients.

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Eggink, F A; Mom, C H; Boll, D; Ezendam, N P M; Kruitwagen, R F P M; Pijnenborg, J M A; van der Aa, M A; Nijman, H W

2017-08-01

Compliance of physicians with guidelines has emerged as an important indicator for quality of care. We evaluated compliance of physicians with adjuvant therapy guidelines for endometrial cancer patients in the Netherlands in a population-based cohort over a period of 10years. Data from all patients diagnosed with endometrial cancer between 2005 and 2014, without residual tumor after surgical treatment, were extracted from the Netherlands Cancer Registry (N=14,564). FIGO stage, grade, tumor type and age were used to stratify patients into risk groups. Possible changes in compliance over time and impact of compliance on survival were assessed. Patients were stratified into low/low-intermediate (52%), high-intermediate (21%) and high (20%) risk groups. Overall compliance with adjuvant therapy guidelines was 85%. Compliance was highest in patients with low/low-intermediate risk (98%, no adjuvant therapy indicated). The lowest compliance was determined in patients with high risk (61%, external beam radiotherapy with/without chemotherapy indicated). Within this group compliance decreased from 64% in 2005-2009 to 57% in 2010-2014. In high risk patients with FIGO stage III serous disease compliance was 55% (chemotherapy with/without radiotherapy indicated) and increased from 41% in 2005-2009 to 66% in 2010-2014. While compliance of physicians with adjuvant therapy guidelines is excellent in patients with low and low-intermediate risk, there is room for improvement in high risk endometrial cancer patients. Eagerly awaited results of ongoing randomized clinical trials may provide more definitive guidance regarding adjuvant therapy for high risk endometrial cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Maternal and Birth Characteristics and Childhood Embryonal Solid Tumors: A Population-Based Report from Brazil.

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Neimar de Paula Silva

Full Text Available Several maternal and birth characteristics have been reported to be associated with an increased risk of many childhood cancers. Our goal was to evaluate the risk of childhood embryonal solid tumors in relation to pre- and perinatal characteristics.A case-cohort study was performed using two population-based datasets, which were linked through R software. Tumors were classified as central nervous system (CNS or non-CNS-embryonal (retinoblastoma, neuroblastoma, renal tumors, germ cell tumors, hepatoblastoma and soft tissue sarcoma. Children aged <6 years were selected. Adjustments were made for potential confounders. Odds ratios (OR with 95% confidence intervals (CI were computed by unconditional logistic regression analysis using SPSS.Males, high maternal education level, and birth anomalies were independent risk factors. Among children diagnosed older than 24 months of age, cesarean section (CS was a significant risk factor. Five-minute Apgar ≤8 was an independent risk factor for renal tumors. A decreasing risk with increasing birth order was observed for all tumor types except for retinoblastoma. Among children with neuroblastoma, the risk decreased with increasing birth order (OR = 0.82 (95% CI 0.67-1.01. Children delivered by CS had a marginally significantly increased OR for all tumors except retinoblastoma. High maternal education level showed a significant increase in the odds for all tumors together, CNS tumors, and neuroblastoma.This evidence suggests that male gender, high maternal education level, and birth anomalies are risk factors for childhood tumors irrespective of the age at diagnosis. Cesarean section, birth order, and 5-minute Apgar score were risk factors for some tumor subtypes.

Perioperative outcomes following surgery for brain tumors: Objective assessment and risk factor evaluation

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Aliasgar V Moiyadi

2012-01-01

Full Text Available Background: Perioperative outcomes following surgery for brain tumors are an important indicator of the safety as well as efficacy of surgical intervention. Perioperative morbidity not only has implications on direct patient care, but also serves as an indicator of the quality of care provided, and enables objective documentation, for comparision in various clinical trials. We document our experience at a tertiary care referral, a dedicated neuro-oncology center in India. Materials and Methods: One hundred and ninety-six patients undergoing various surgeries for intra-axial brain tumors were analyzed. Routine microsurgical techniques and uniform antibiotic policy were used. Navigation/ intraoperative electrophysiological monitoring was not available. The endpoints assessed included immediate postoperative neurological status, neurological outcome at discharge, regional complications, systemic complications, overall morbidity, and mortality. Various risk factors assessed included clinico-epidemiological factors, tumor-related factors, and surgery-related factors. Univariate and multivariate analysis were performed. Results: Median age was 38 years. 72% had tumors larger than 4 cm. Neurological morbidity, and regional and systemic complications occurred in 16.8, 17.3, and 10.7%, respectively. Overall, major morbidity occurred in 18% and perioperative mortality rate was 3.6%. Although a few of the known risk factors were found to be significant on univariate analysis, none achieved significance on multivariate analysis. Conclusions: Our patients were younger and had larger tumors than are generally reported. Despite the unavailability of advanced intraoperative aids we could achieve acceptable levels of morbidity and mortality. Objective recording of perioperative events is crucial to document outcomes after surgery for brain tumors.

The Elastin Receptor Complex: a unique matricellular receptor with high anti-tumoral potential

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Amandine eScandolera

2016-03-01

Full Text Available Elastin, one of the longest-lived proteins, confers elasticity to tissues with high mechanical constraints. During aging or pathophysiological conditions such as cancer progression, this insoluble polymer of tropoelastin undergoes an important degradation leading to the release of bioactive elastin-derived peptides (EDP, named elastokines. EDP exhibit several biological functions able to drive tumor development by regulating cell proliferation, invasion, survival, angiogenesis, and matrix metalloproteinase expression in various tumor and stromal cells. Although several receptors have been suggested to bind elastokines (αvβ3 and αvβ5 integrins, galectin-3, their main receptor remains the Elastin Receptor Complex (ERC. This heterotrimer comprises a peripheral subunit, named Elastin Binding Protein (EBP, associated to the Protective Protein/Cathepsin A (PPCA. The latter is bound to a membrane-associated protein called Neuraminidase-1 (Neu-1. The pro-tumoral effects of elastokines have been linked to their binding onto EBP. Additionally, Neu-1 sialidase activity is essential for their signal transduction. Consistently, EDP-EBP interaction and Neu-1 activity emerge as original anti-tumoral targets. Interestingly, besides its direct involvement in cancer progression, the ERC also regulates diabetes outcome and thrombosis, an important risk factor for cancer development and a vascular process highly increased in patients suffering from cancer. In this review, we will describe ERC and elastokines involvement in cancer development suggesting that this unique receptor would be a promising therapeutic target. We will also discuss the pharmacological concepts aiming at blocking its pro-tumoral activities. Finally, its emerging role in cancer-associated complications and pathologies such as diabetes and thrombotic events will be also considered.

Age and the risk of anaplasia in magnetic resonance-nonenhancing supratentorial cerebral tumors.

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Barker, F G; Chang, S M; Huhn, S L; Davis, R L; Gutin, P H; McDermott, M W; Wilson, C B; Prados, M D

1997-09-01

It is often assumed that a cerebral lesion that is nonenhancing on a magnetic resonance imaging study with gadolinium contrast is a low grade tumor. Some physicians recommend observation rather than biopsy for such lesions. The authors prospectively evaluated the incidence of anaplastic tumor histology in a consecutive series of patients who presented to a neuro-oncology service with a nonenhancing mass of the cerebral hemisphere. During a 5-month period, the authors evaluated 31 patients who had a nonenhancing lesion in the cerebral hemisphere on initial magnetic resonance images. Thirty patients underwent stereotactic biopsy (27%) or open resection (73%). The median patient age was 36 years (range, 6-63 years). There was no mortality or permanent neurologic morbidity from surgery. Twenty-eight patients had pathologic confirmation of diagnosis while their lesions were still nonenhancing. Of these patients, 9 (32%) had Grade 3 lesions (anaplastic astrocytoma or oligoastrocytoma), 13 (43%) had Grade 2 lesions (astrocytoma, oligodendroglioma, or oligoastrocytoma), and 2 (7%) had Grade 1 lesions (dysembryoplastic neuroepithelial tumors). Two additional patients (ages 33 and 59 years) who developed enhancement within their lesions during preoperative periods of observation had glioblastomas at surgery. Logistic regression was used to relate patient age to the risk of anaplasia in a nonenhancing cerebral mass lesion. Older age predicted a significantly higher risk of anaplasia (P = 0.025). The model predicted that nonenhancing cerebral masses in patients older than 44 years were more likely to be anaplastic tumors than low grade tumors. There was no "safe" age below which low grade histology could be confidently assumed. Magnetic resonance-nonenhancing cerebral lesions may be histologically anaplastic, even in young patients. The risk of anaplasia in magnetic resonance-nonenhancing lesions increases significantly with patient age.

Choline PET based dose-painting in prostate cancer - Modelling of dose effects

International Nuclear Information System (INIS)

Niyazi, Maximilian; Bartenstein, Peter; Belka, Claus; Ganswindt, Ute

2010-01-01

Several randomized trials have documented the value of radiation dose escalation in patients with prostate cancer, especially in patients with intermediate risk profile. Up to now dose escalation is usually applied to the whole prostate. IMRT and related techniques currently allow for dose escalation in sub-volumes of the organ. However, the sensitivity of the imaging modality and the fact that small islands of cancer are often dispersed within the whole organ may limit these approaches with regard to a clear clinical benefit. In order to assess potential effects of a dose escalation in certain sub-volumes based on choline PET imaging a mathematical dose-response model was developed. Based on different assumptions for α/β, γ50, sensitivity and specificity of choline PET, the influence of the whole prostate and simultaneous integrated boost (SIB) dose on tumor control probability (TCP) was calculated. Based on the given heterogeneity of all potential variables certain representative permutations of the parameters were chosen and, subsequently, the influence on TCP was assessed. Using schedules with 74 Gy within the whole prostate and a SIB dose of 90 Gy the TCP increase ranged from 23.1% (high detection rate of choline PET, low whole prostate dose, high γ50/ASTRO definition for tumor control) to 1.4% TCP gain (low sensitivity of PET, high whole prostate dose, CN + 2 definition for tumor control) or even 0% in selected cases. The corresponding initial TCP values without integrated boost ranged from 67.3% to 100%. According to a large data set of intermediate-risk prostate cancer patients the resulting TCP gains ranged from 22.2% to 10.1% (ASTRO definition) or from 13.2% to 6.0% (CN + 2 definition). Although a simplified mathematical model was employed, the presented model allows for an estimation in how far given schedules are relevant for clinical practice. However, the benefit of a SIB based on choline PET seems less than intuitively expected. Only under the

Selection of high risk groups among prognostically favorable patients with breast cancer.

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Andersen, J A; Fischermann, K; Hou-Jensen, K; Henriksen, E; Andersen, K W; Johansen, H; Brincker, H; Mouridsen, H T; Castberg, T; Rossing, N; Rørth, M

1981-01-01

In a prospective, nationwide, decentralized breast cancer project conducted by The Danish Breast Cancer Cooperative Group (DBCG) the recurrence rate within the first year after surgery was analysed in relation to tumor anaplasia. One thousand forty-eight patients met the requirements of eligibility, i.e. tumor size less than or equal to 5 cm with negative axillary nodes, and no skin or deep invasion. The recurrence rates in tumors with anaplasia Grades I, II, and III were 4, 9, and 14%, respectively (p = 0.001). Therefore, it seems possible, prospectively, among otherwise prognostically favorable patients, to select a group with high risk of recurrence which might benefit from adjuvant systemic therapy. PMID:7247527

Epidemiological features of brain tumors

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Živković Nenad

2013-01-01

Full Text Available Brain tumors account for 1.4% of all cancers and 2.4% of all cancer-related deaths. The incidence of brain tumors varies and it is higher in developed countries of Western Europe, North America, Australia and New Zealand. In Serbia, according to data from 2009, malignant brain tumors account for 2. 2 of all tumors, and from all cancer­related deaths, 3.2% is caused by malignant brain tumors. According to recent statistical reports, an overall incidence of brain tumors for benign and malignant tumors combined is 18.71 per 100,000 persons/year. The most common benign brain tumor in adults is meningioma, which is most present in women, and the most common malignant tumor is glioblastoma, which is most present in adult men. Due to high mortality, especially in patients diagnosed with glioblastoma and significant brain tumor morbidity, there is a constant interest in understanding its etiology in order to possibly prevent tumor occurrence in future and enable more efficient treatment strategies for this fatal brain disease. Despite the continuously growing number of epidemiological studies on possible factors of tumor incidence, the etiology remains unclear. The only established environmental risk factor of gliomas is ionizing radiation exposure. Exposure to radiofrequency electromagnetic fields via cell phone use has gained a lot of attention as a potential risk factor of brain tumor development. However, studies have been inconsistent and inconclusive, so more definite results are still expected.

CyberKnife with tumor tracking: An effective alternative to wedge resection for high-risk surgical patients with stage I non-small cell lung cancer (NSCLC

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Sean eCollins

2012-02-01

Full Text Available Published data suggests that wedge resection for stage I NSCLC results in improved overall survival compared to stereotactic body radiation therapy (SBRT. We report CyberKnife outcomes for high-risk surgical patients with biopsy-proven stage I NSCLC. PET/CT imaging was completed for staging. Three-to-five gold fiducial markers were implanted in or near tumors to serve as targeting references. Gross tumor volumes (GTVs were contoured using lung windows; the margins were expanded by 5 mm to establish the planning treatment volume (PTV. Treatment plans were designed using hundreds of pencil beams. Doses delivered to the PTV ranged from 42-60 Gy in 3 fractions. The 30-Gy isodose contour extended at least 1cm from the GTV to eradicate microscopic disease. Treatments were delivered using the CyberKnife system with tumor tracking. Examination and PET/CT imaging occurred at 3-month follow-up intervals. Forty patients (median age 76 with a median maximum tumor diameter of 2.6 cm (range, 1.4-5.0 cm and a mean post-bronchodilator percent predicted forced expiratory volume in 1 second (FEV1 of 57% (range, 21 - 111% were treated. A mean dose of 50 Gy was delivered to the PTV over 3 to 13 days (median, 7 days. The 30-Gy isodose contour extended a mean 1.9 cm from the GTV. At a median 44 months (range, 12 -72 months follow-up, the 3-year Kaplan-Meier locoregional control and overall survival estimates compare favorably with contemporary wedge resection outcomes at 91% and 75% , respectively. CyberKnife is an effective treatment approach for stage I NSCLC that is similar to wedge resection, eradicating tumors with 1 to 2 cm margins in order to preserve lung function. Prospective randomized trials comparing CyberKnife with wedge resection are necessary to confirm equivalence.

Failure-probability driven dose painting

International Nuclear Information System (INIS)

Vogelius, Ivan R.; Håkansson, Katrin; Due, Anne K.; Aznar, Marianne C.; Kristensen, Claus A.; Rasmussen, Jacob; Specht, Lena; Berthelsen, Anne K.; Bentzen, Søren M.

2013-01-01

Purpose: To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study using the optimized dose prescription in 20 patients is performed.Methods: Patients treated at our center have five tumor subvolumes from the center of the tumor (PET positive volume) and out delineated. The spatial distribution of 48 failures in patients with complete clinical response after (chemo)radiation is used to derive a model for tumor control probability (TCP). The total TCP is fixed to the clinically observed 70% actuarial TCP at five years. Additionally, the authors match the distribution of failures between the five subvolumes to the observed distribution. The steepness of the dose–response is extracted from the literature and the authors assume 30% and 20% risk of subclinical involvement in the elective volumes. The result is a five-compartment dose response model matching the observed distribution of failures. The model is used to optimize the distribution of dose in individual patients, while keeping the treatment intensity constant and the maximum prescribed dose below 85 Gy.Results: The vast majority of failures occur centrally despite the small volumes of the central regions. Thus, optimizing the dose prescription yields higher doses to the central target volumes and lower doses to the elective volumes. The dose planning study shows that the modified prescription is clinically feasible. The optimized TCP is 89% (range: 82%–91%) as compared to the observed TCP of 70%.Conclusions: The observed distribution of locoregional failures was used to derive an objective, data-driven dose prescription function. The optimized dose is predicted to result in a substantial increase in local control without increasing the predicted risk of toxicity

Modeling Freedom From Progression for Standard-Risk Medulloblastoma: A Mathematical Tumor Control Model With Multiple Modes of Failure

International Nuclear Information System (INIS)

Brodin, N. Patrik; Vogelius, Ivan R.; Björk-Eriksson, Thomas; Munck af Rosenschöld, Per; Bentzen, Søren M.

2013-01-01

Purpose: As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published pattern of failure data. Methods and Materials: Outcome data for standard-risk MB published after 1990 with pattern of relapse information were used to fit a tumor control dose-response model addressing failures in both the high-dose boost volume and the elective craniospinal volume. Estimates of 5-year event-free survival from 2 large randomized MB trials were used to model the time-to-progression distribution. Uncertainty in freedom from progression (FFP) was estimated by Monte Carlo sampling over the statistical uncertainty in input data. Results: The estimated 5-year FFP (95% confidence intervals [CI]) for craniospinal doses of 15, 18, 24, and 36 Gy while maintaining 54 Gy to the posterior fossa was 77% (95% CI, 70%-81%), 78% (95% CI, 73%-81%), 79% (95% CI, 76%-82%), and 80% (95% CI, 77%-84%) respectively. The uncertainty in FFP was considerably larger for craniospinal doses below 18 Gy, reflecting the lack of data in the lower dose range. Conclusions: Estimates of tumor control and time-to-progression for standard-risk MB provides a data-driven setting for hypothesis generation or power calculations for prospective trials, taking the uncertainties into account. The presented methods can also be applied to incorporate further risk-stratification for example based on molecular biomarkers, when the necessary data become available

Risk interrelationship among multiple primary tumors

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Safi, Mohammed; Sun, Xiuhua; Wang, Lifen; Zhang, Xinwei; Song, Jicheng; Ameen, Mohammed

2018-01-01

Abstract Rationale: Along with advanced management in oncology, great progress has been recently achieved in the studies of multiple primary tumors. Several reports have studied the coexistence between lymphoma and either renal cell carcinoma (RCC) or Warthin tumor. However, the level of coexistence between these cases remains unclear due to the absence of a distinct link between them. Patient concerns: We present a unique case of multiple primary tumors (lymphoma, RCC, and Warthin tumor) in an 80-year-old man and a review of the literature on the coexistence of RCC with lymphoma and lymphoma with Warthin tumor. Diagnosis: With a history of RCC, the patient had a freely movable lump under his left ear, and the pathological report indicated Hodgkin lymphoma and Warthin tumor. Intervention: RCC and Warthin tumor of the patient were surgically treated, followed by 2 cycles (14 days per cycle) of Epirubicin 40 mg day 1, Bleomycin 8 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1. The chemotherapy protocol was then changed to Epirubicin 40 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1 for 7 cycles. Outcomes: After the last day of chemotherapy, the patient showed a complete response. Lessons: To the best of our knowledge, this paper is the first to report a case of multiple primary tumors with a complete response. For their early detection, favorable prognosis, and correlation identification, we suggest a transitive relation between these coexisting tumors. Therefore, similar studies should be conducted. PMID:29642151

Combined 18F-Fluciclovine PET/MRI Shows Potential for Detection and Characterization of High-Risk Prostate Cancer.

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Elschot, Mattijs; Selnæs, Kirsten M; Sandsmark, Elise; Krüger-Stokke, Brage; Størkersen, Øystein; Giskeødegård, Guro F; Tessem, May-Britt; Moestue, Siver A; Bertilsson, Helena; Bathen, Tone F

2018-05-01

The objective of this study was to investigate whether quantitative imaging features derived from combined 18 F-fluciclovine PET/multiparametric MRI show potential for detection and characterization of primary prostate cancer. Methods: Twenty-eight patients diagnosed with high-risk prostate cancer underwent simultaneous 18 F-fluciclovine PET/MRI before radical prostatectomy. Volumes of interest (VOIs) for prostate tumors, benign prostatic hyperplasia (BPH) nodules, prostatitis, and healthy tissue were delineated on T2-weighted images, using histology as a reference. Tumor VOIs were marked as high-grade (≥Gleason grade group 3) or not. MRI and PET features were extracted on the voxel and VOI levels. Partial least-squared discriminant analysis (PLS-DA) with double leave-one-patient-out cross-validation was performed to distinguish tumors from benign tissue (BPH, prostatitis, or healthy tissue) and high-grade tumors from other tissue (low-grade tumors or benign tissue). The performance levels of PET, MRI, and combined PET/MRI features were compared using the area under the receiver-operating-characteristic curve (AUC). Results: Voxel and VOI features were extracted from 40 tumor VOIs (26 high-grade), 36 BPH VOIs, 6 prostatitis VOIs, and 37 healthy-tissue VOIs. PET/MRI performed better than MRI and PET alone for distinguishing tumors from benign tissue (AUCs of 87%, 81%, and 83%, respectively, at the voxel level and 96%, 93%, and 93%, respectively, at the VOI level) and high-grade tumors from other tissue (AUCs of 85%, 79%, and 81%, respectively, at the voxel level and 93%, 93%, and 91%, respectively, at the VOI level). T2-weighted MRI, diffusion-weighted MRI, and PET features were the most important for classification. Conclusion: Combined 18 F-fluciclovine PET/multiparametric MRI shows potential for improving detection and characterization of high-risk prostate cancer, in comparison to MRI and PET alone. © 2018 by the Society of Nuclear Medicine and Molecular

Gastrointestinal stromal tumors, somatic mutations and candidate genetic risk variants.

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Katie M O'Brien

Full Text Available Gastrointestinal stromal tumors (GISTs are rare but treatable soft tissue sarcomas. Nearly all GISTs have somatic mutations in either the KIT or PDGFRA gene, but there are no known inherited genetic risk factors. We assessed the relationship between KIT/PDGFRA mutations and select deletions or single nucleotide polymorphisms (SNPs in 279 participants from a clinical trial of adjuvant imatinib mesylate. Given previous evidence that certain susceptibility loci and carcinogens are associated with characteristic mutations, or "signatures" in other cancers, we hypothesized that the characteristic somatic mutations in the KIT and PDGFRA genes in GIST tumors may similarly be mutational signatures that are causally linked to specific mutagens or susceptibility loci. As previous epidemiologic studies suggest environmental risk factors such as dioxin and radiation exposure may be linked to sarcomas, we chose 208 variants in 39 candidate genes related to DNA repair and dioxin metabolism or response. We calculated adjusted odds ratios (ORs and 95% confidence intervals (CIs for the association between each variant and 7 categories of tumor mutation using logistic regression. We also evaluated gene-level effects using the sequence kernel association test (SKAT. Although none of the association p-values were statistically significant after adjustment for multiple comparisons, SNPs in CYP1B1 were strongly associated with KIT exon 11 codon 557-8 deletions (OR = 1.9, 95% CI: 1.3-2.9 for rs2855658 and OR = 1.8, 95% CI: 1.2-2.7 for rs1056836 and wild type GISTs (OR = 2.7, 95% CI: 1.5-4.8 for rs1800440 and OR = 0.5, 95% CI: 0.3-0.9 for rs1056836. CYP1B1 was also associated with these mutations categories in the SKAT analysis (p = 0.002 and p = 0.003, respectively. Other potential risk variants included GSTM1, RAD23B and ERCC2. This preliminary analysis of inherited genetic risk factors for GIST offers some clues about the disease's genetic

The Very High Risk Prostate Cancer – a Contemporary Update

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Mano, Roy; Eastham, James; Yossepowitch, Ofer

2017-01-01

Background Treatment of high-risk prostate cancer has evolved considerably over the past two decades, yet patients with very high-risk features may still experience poor outcome despite aggressive therapy. We review the contemporary literature focusing on current definitions, role of modern imaging and treatment alternatives in very high-risk prostate cancer. Methods We searched the MEDLINE database for all clinical trials or practice guidelines published in English between 2000 – 2016 with the following search terms: ‘prostatic neoplasms’ (MeSH Terms) AND (‘high risk’ (keyword) OR ‘locally advanced’ (keyword) OR ‘node positive’ (keyword)). Abstracts pertaining to very high-risk prostate cancer were evaluated and 40 pertinent studies served as the basis for this review. Results The term ‘very’ high-risk prostate cancer remains ill defined. The EAU and NCCN guidelines provide the only available definitions, categorizing those with clinical stage T3-4 or minimal nodal involvement as very-high risk irrespective of PSA level or biopsy Gleason score. Modern imaging with mpMRI and PET-PSMA scans plays a role in pretreatment assessment. Local definitive therapy by external beam radiation combined with androgen deprivation is supported by several randomized clinical trials whereas the role of surgery in the very high-risk setting combined with adjuvant radiation/ androgen deprivation therapy is emerging. Growing evidence suggest neoadjuvant taxane based chemotherapy in the context of a multimodal approach may be beneficial. Conclusions Men with very high-risk tumors may benefit from local definitive treatment in the setting of a multimodal regimen, offering local control and possibly cure in well selected patients. Further studies are necessary to better characterize the ‘very’ high-risk category and determine the optimal therapy for the individual patient. PMID:27618950

Risk factors for tumors of the brain and cranial meninges in Seventh-Day Adventists.

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Mills, P K; Preston-Martin, S; Annegers, J F; Beeson, W L; Phillips, R L; Fraser, G E

1989-01-01

We studied the occurrence of tumors of the brain and cranial meninges in a cohort of 34,000 California Seventh-Day Adventists who completed a detailed life-style questionnaire in 1976 and who were followed for cancer incidence until the end of 1982. During the period of follow-up, 31 tumors were diagnosed in the cohort (21 gliomas, 10 meningiomas). Increased risk for glioma was associated with rural residence, history of a positive tuberculosis skin test and consumption of pork products; increased meningioma risk was associated with a positive reaction to a tuberculosis skin test, previous stroke, use of tranquillizers and a vegetarian life-style in childhood.

Fine-Mapping of Common Genetic Variants Associated with Colorectal Tumor Risk Identified Potential Functional Variants.

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Mengmeng Du

Full Text Available Genome-wide association studies (GWAS have identified many common single nucleotide polymorphisms (SNPs associated with colorectal cancer risk. These SNPs may tag correlated variants with biological importance. Fine-mapping around GWAS loci can facilitate detection of functional candidates and additional independent risk variants. We analyzed 11,900 cases and 14,311 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium and the Colon Cancer Family Registry. To fine-map genomic regions containing all known common risk variants, we imputed high-density genetic data from the 1000 Genomes Project. We tested single-variant associations with colorectal tumor risk for all variants spanning genomic regions 250-kb upstream or downstream of 31 GWAS-identified SNPs (index SNPs. We queried the University of California, Santa Cruz Genome Browser to examine evidence for biological function. Index SNPs did not show the strongest association signals with colorectal tumor risk in their respective genomic regions. Bioinformatics analysis of SNPs showing smaller P-values in each region revealed 21 functional candidates in 12 loci (5q31.1, 8q24, 11q13.4, 11q23, 12p13.32, 12q24.21, 14q22.2, 15q13, 18q21, 19q13.1, 20p12.3, and 20q13.33. We did not observe evidence of additional independent association signals in GWAS-identified regions. Our results support the utility of integrating data from comprehensive fine-mapping with expanding publicly available genomic databases to help clarify GWAS associations and identify functional candidates that warrant more onerous laboratory follow-up. Such efforts may aid the eventual discovery of disease-causing variant(s.

Utility of multiple rule out CT screening of high-risk atraumatic patients in an emergency department-a feasibility study

DEFF Research Database (Denmark)

Pries-Heje, Mia M; Hasselbalch, Rasmus B; Raaschou, Henriette

2018-01-01

malignant tumors in 10 (10%) cases. The mean size specific radiation dose was 15.9 mSv (± 3.1 mSv). CONCLUSION: Screening with a multi-rule out CT scan of high-risk patients in an ED is feasible and result in discovery of clinically unrecognized diagnoses and malignant tumors, but at the cost of radiation......BACKGROUND: Several large trials have evaluated the effect of CT screening based on specific symptoms, with varying outcomes. Screening of patients with CT based on their prognosis alone has not been examined before. For moderate-to-high risk patients presenting in the emergency department (ED......), the potential gain from a CT scan might outweigh the risk of radiation exposure. We hypothesized that an accelerated "multiple rule out" CT screening of moderate-to-high risk patients will detect many clinically unrecognized diagnoses that affect change in treatment. METHOD: Patients ≥ 40 years, triaged as high...

Logistic regression analysis of risk factors for postoperative recurrence of spinal tumors and analysis of prognostic factors.

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Zhang, Shanyong; Yang, Lili; Peng, Chuangang; Wu, Minfei

2018-02-01

The aim of the present study was to investigate the risk factors for postoperative recurrence of spinal tumors by logistic regression analysis and analysis of prognostic factors. In total, 77 male and 48 female patients with spinal tumor were selected in our hospital from January, 2010 to December, 2015 and divided into the benign (n=76) and malignant groups (n=49). All the patients underwent microsurgical resection of spinal tumors and were reviewed regularly 3 months after operation. The McCormick grading system was used to evaluate the postoperative spinal cord function. Data were subjected to statistical analysis. Of the 125 cases, 63 cases showed improvement after operation, 50 cases were stable, and deterioration was found in 12 cases. The improvement rate of patients with cervical spine tumor, which reached 56.3%, was the highest. Fifty-two cases of sensory disturbance, 34 cases of pain, 30 cases of inability to exercise, 26 cases of ataxia, and 12 cases of sphincter disorders were found after operation. Seventy-two cases (57.6%) underwent total resection, 18 cases (14.4%) received subtotal resection, 23 cases (18.4%) received partial resection, and 12 cases (9.6%) were only treated with biopsy/decompression. Postoperative recurrence was found in 57 cases (45.6%). The mean recurrence time of patients in the malignant group was 27.49±6.09 months, and the mean recurrence time of patients in the benign group was 40.62±4.34. The results were significantly different (Pregression analysis of total resection-related factors showed that total resection should be the preferred treatment for patients with benign tumors, thoracic and lumbosacral tumors, and lower McCormick grade, as well as patients without syringomyelia and intramedullary tumors. Logistic regression analysis of recurrence-related factors revealed that the recurrence rate was relatively higher in patients with malignant, cervical, thoracic and lumbosacral, intramedullary tumors, and higher Mc

Associations of breast cancer risk factors with tumor subtypes: a pooled analysis from the Breast Cancer Association Consortium studies

DEFF Research Database (Denmark)

Yang, Xiaohong R; Chang-Claude, Jenny; Goode, Ellen L

2011-01-01

Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors.......Previous studies have suggested that breast cancer risk factors are associated with estrogen receptor (ER) and progesterone receptor (PR) expression status of the tumors....

Proton Radiotherapy for High-Risk Pediatric Neuroblastoma: Early Outcomes and Dose Comparison

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Hattangadi, Jona A. [Harvard Radiation Oncology Program, Boston, MA (United States); Rombi, Barbara [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Provincial Agency for Proton Therapy, Trento (Italy); Yock, Torunn I.; Broussard, George [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); Friedmann, Alison M.; Huang, Mary [Department of Pediatric Hematology-Oncology, Massachusetts General Hospital, Boston, MA (United States); Chen, Yen-Lin E.; Lu, Hsiao-Ming; Kooy, Hanne [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States); MacDonald, Shannon M., E-mail: smacdonald@partners.org [Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA (United States)

2012-07-01

Purpose: To report the early outcomes for children with high-risk neuroblastoma treated with proton radiotherapy (RT) and to compare the dose distributions for intensity-modulated photon RT (IMRT), three-dimensional conformal proton RT (3D-CPT), and intensity-modulated proton RT to the postoperative tumor bed. Methods and Materials: All patients with high-risk (International Neuroblastoma Staging System Stage III or IV) neuroblastoma treated between 2005 and 2010 at our institution were included. All patients received induction chemotherapy, surgical resection of residual disease, high-dose chemotherapy with stem cell rescue, and adjuvant 3D-CPT to the primary tumor sites. The patients were followed with clinical examinations, imaging, and laboratory testing every 6 months to monitor disease control and side effects. IMRT, 3D-CPT, and intensity-modulated proton RT plans were generated and compared for a representative case of adjuvant RT to the primary tumor bed followed by a boost. Results: Nine patients were treated with 3D-CPT. The median age at diagnosis was 2 years (range 10 months to 4 years), and all patients had Stage IV disease. All patients had unfavorable histologic characteristics (poorly differentiated histologic features in 8, N-Myc amplification in 6, and 1p/11q chromosomal abnormalities in 4). The median tumor size at diagnosis was 11.4 cm (range 7-16) in maximal dimension. At a median follow-up of 38 months (range 11-70), there were no local failures. Four patients developed distant failure, and, of these, two died of disease. Acute side effects included Grade 1 skin erythema in 5 patients and Grade 2 anorexia in 2 patients. Although comparable target coverage was achieved with all three modalities, proton therapy achieved substantial normal tissue sparing compared with IMRT. Intensity-modulated proton RT allowed additional sparing of the kidneys, lungs, and heart. Conclusions: Preliminary outcomes reveal excellent local control with proton therapy

HLA-mismatched hematopoietic stem cell tranplantation for pediatric solid tumors

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Andrea Pession

2011-06-01

Full Text Available Even if the overall survival of children with cancer is significantly improved over these decades, the cure rate of high-risk pediatric solid tumors such as neuroblastoma, Ewing’s sarcoma family tumors or rhabdomiosarcoma remain challenging. Autologous hematopoietic stem cell transplantation (HSCT allows chemotherapy dose intensification beyond marrow tolerance and has become a fundamental tool in the multimodal therapeutical approach of these patients. Anyway this procedure does not allow to these children an eventfree survival approaching more than 50% at 5 years. New concepts of allogeneic HSCT and in particular HLA-mismatched HSCT for high risk solid tumors do not rely on escalation of chemo therapy intensity and tumor load reduction but rather on a graft-versus-tumor effect. We here report an experimental study design of HLA-mismatched HSCT for the treatment of pediatric solid tumors and the inherent preliminary results.

Pelvic Inflammatory Disease and the Risk of Ovarian Cancer and Borderline Ovarian Tumors: A Pooled Analysis of 13 Case-Control Studies

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Rasmussen, Christina B.; Kjaer, Susanne K.; Albieri, Vanna; Bandera, Elisa V.; Doherty, Jennifer A.; Høgdall, Estrid; Webb, Penelope M.; Jordan, Susan J.; Rossing, Mary Anne; Wicklund, Kristine G.; Goodman, Marc T.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Edwards, Robert P.; Schildkraut, Joellen M.; Berchuck, Andrew; Olson, Sara H.; Kiemeney, Lambertus A.; Massuger, Leon F. A. G.; Narod, Steven A.; Phelan, Catherine M.; Anton-Culver, Hoda; Ziogas, Argyrios; Wu, Anna H.; Pearce, Celeste L.; Risch, Harvey A.; Jensen, Allan

2017-01-01

Inflammation has been implicated in ovarian carcinogenesis. However, studies investigating the association between pelvic inflammatory disease (PID) and ovarian cancer risk are few and inconsistent. We investigated the association between PID and the risk of epithelial ovarian cancer according to tumor behavior and histotype. We pooled data from 13 case-control studies, conducted between 1989 and 2009, from the Ovarian Cancer Association Consortium (OCAC), including 9,162 women with ovarian cancers, 2,354 women with borderline tumors, and 14,736 control participants. Study-specific odds ratios were estimated and subsequently combined into a pooled odds ratio using a random-effects model. A history of PID was associated with an increased risk of borderline tumors (pooled odds ratio (pOR) = 1.32, 95% confidence interval (CI): 1.10, 1.58). Women with at least 2 episodes of PID had a 2-fold increased risk of borderline tumors (pOR = 2.14, 95% CI: 1.08, 4.24). No association was observed between PID and ovarian cancer risk overall (pOR = 0.99, 95% CI: 0.83, 1.19); however, a statistically nonsignificantly increased risk of low-grade serous tumors (pOR = 1.48, 95% CI: 0.92, 2.38) was noted. In conclusion, PID was associated with an increased risk of borderline ovarian tumors, particularly among women who had had multiple episodes of PID. Although our results indicated a histotype-specific association with PID, the association of PID with ovarian cancer risk is still somewhat uncertain and requires further investigation. PMID:27941069

High-grade ovarian cancer secreting effective exosomes in tumor angiogenesis.

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Yi, Huan; Ye, Jun; Yang, Xiao-Mei; Zhang, Li-Wen; Zhang, Zhi-Gang; Chen, Ya-Ping

2015-01-01

Ovarian cancer, the most lethal gynecological cancer, related closely to tumor stage. High-grade ovarian cancer always results in a late diagnose and high recurrence, which reduce survival within five years. Until recently, curable therapy is still under research and anti-angiogenesis proves a promising way. Tumor-derived exosomes are essential in tumor migration and metastases such as angiogenesis is enhanced by exosomes. In our study, we have made comparison between high-grade and unlikely high-grade serous ovarian cancer cells on exosomal function of endothelial cells proliferation, migration and tube formation. Exosomes derived from high-grade ovarian cancer have a profound impact on angiogenesis with comparison to unlikely high-grade ovarian cancer. Proteomic profiles revealed some potential proteins involved in exosomal function of angiogenesis such as ATF2, MTA1, ROCK1/2 and so on. Therefore, exosomes plays an influential role in angiogenesis in ovarian serous cancer and also function more effectively in high-grade ovarian cancer cells.

Nutritional status and nutritional risk in patients with neuroendocrine tumors

DEFF Research Database (Denmark)

Borre, Mette; Dam, Gitte Aarøe; Knudsen, Anne Wilkens

2018-01-01

BACKGROUND: Malnutrition is frequent among patients with malignancies and associated with impaired function, reduced quality of life and increased mortality. Few data are available in patients with neuroendocrine tumors (NET) on nutritional status, nutritional risk, and nutrition impact symptoms...... (NIS). We aimed to assess nutritional status (NS) and risk, level of function and associations with NIS in NET patients. METHODS: In a cross-sectional study of NET patients, we measured body mass index (BMI) and handgrip strength (HGS) as markers of NS and muscle function assessed by HGS....... The nutritional risk score (NRS) was determined by NRS-2002. NIS was assessed by the eating symptoms questionnaire (ESQ), and disease-related appetite questionnaire (DRAQ). RESULTS: We included 186 patients (51% women), median age 66 years. We observed low BMI (

Endocrine tumors other than thyroid tumors

International Nuclear Information System (INIS)

Takeichi, Norio; Dohi, Kiyohiko

1992-01-01

This paper discusses the tendency for the occurrence of tumors in the endocrine glands, other than the thyroid gland, in A-bomb survivors using both autopsy and clinical data. ABCC-RERF sample data using 4136 autopsy cases (1961-1977) revealed parathyroid tumors in 13 A-bomb survivors, including 3 with the associated hyperparathyroidism, with the suggestion of dose-dependent increase in the occurrence of tumors. Based on clinical data from Hiroshima University, 7 (46.7%) of 15 parathyroid tumors cases were A-bomb survivors. Data (1974-1987) from the Tumor Registry Committee (TRC) in Hiroshima Prefecture revealed that a relative risk of parathyroid tumors was 5.6 times higher in the entire group of A-bomb survivors and 16.2 times higher in the group of heavily exposed A-bomb survivors, suggesting the dose-dependent increase in their occurrence. Adrenal tumors were detected in 47 of 123 cases from the TRC data, and 15 (31.5%) of these 47 were A-bomb survivors. Particularly, 11 cases of adrenal tumors associated with Cushing syndrome included 6 A-bomb survivors (54.5%). The incidence of multiple endocrine gonadial tumors (MEGT) tended to be higher with increasing exposure doses; and the 1-9 rad group, the 10-99 rad group, and the 100 or more rad group had a risk of developing MEGT of 4.1, 5.7, and 7.1, respectively, relative to both the not-in the city group and the 0 rad group. These findings suggested that there is a correlation between A-bomb radiation and the occurrence of parathyroid tumors (including hyperparathyroidism), adrenal tumors associated with Cushing syndrome and MEGT (especially, the combined thyroid and ovarian tumors and the combined thyroid and parathyroid tumors). (N.K.)

STUDY OF POSTERIOR FOSSA TUMORS BY HIGH RESOLUTION MRI

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Sree Hari

2016-01-01

Full Text Available INTRODUCTION Magnetic Resonance Imaging (MRI is the imaging modality used for the assessment of infratentorial neoplasms. Although Computed Tomography (CT provides better demonstration of small or subtle calcifications within tumors. OBJECTIVES Study is done to assess the potential of MRI in characterisation of different tumors in posterior fossa by evaluating various unenhanced and gadolinium enhanced sequences and to compare high resolution FSE MRI sequences with routine FSE MRI sequences in diagnosing posterior fossa brain tumors. Also correlate findings on Magnetic Resonance Imaging with Pathological diagnosis. MATERIALS AND METHODS A total of 52 patients were diagnosed by CT brain as having posterior fossa brain for a year of 2 years were included in the study. In all studies MR imaging was performed with a clinical 1.5 T system (General electrical medical systems. A dedicated phased-array coil was used. RESULTS The age group ranged from 1 year to 60 years, majority were between 1 to 20 years (39%. Slight male preponderance was seen (males 29, females 23. Commonest tumor encountered in our study was vestibular schwannoma. DWI alone can differentiate different pediatric posterior fossa brain tumors. One case of pilocytic astrocytoma showed solid lesion instead of typical cystic lesion with mural nodule. One case AT-RT showed 2 lesions one in cerebrum, one in CP angle. Common feature being intra-axial lesion involving cerebellum. MRI was able to predict diagnosis in 50 of the 52 tumors. CONCLUSION Magnetic Resonance Imaging was found to be a highly sensitive imaging procedure and method of choice for posterior fossa brain tumors.

Second malignancies in high-dose areas of previous tumor radiotherapy

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Welte, Birgitta; Suhr, Peter; Bottke, Dirk; Bartkowiak, Detlef; Wiegel, Thomas [Dept. of Radiotherapy and Radiation Oncology, Univ. of Ulm (Germany); Doerr, Wolfgang [Dept. of Radiotherapy and Radiation Oncology, Radiobiology Lab., Univ. of Technology Dresden (Germany); Trott, Klaus Ruediger [UCL Cancer Centre, Univ. Coll. London (United Kingdom)

2010-03-15

Purpose: To characterize second tumors that developed in or near the high-dose areas of a previous radiotherapy, regarding their frequency, entities, latency, and dose dependence. Patients and Methods: 9,995/15,449 tumor patients of the Radiation Oncology Department in Ulm, Germany, treated between 1981 and 2003, survived at least 1 year after radiotherapy. By long-term follow-up and review of treatment documentation, 100 of them were identified who developed an independent second cancer in or near the irradiated first tumor site. Results: Major primary malignancies were breast cancer (27%), lymphoma (24%), and pelvic gynecologic tumors (17%). Main second tumors were carcinomas of the upper (18%) and lower (12%) gastrointestinal tract, head and neck tumors (10%), lymphoma (10%), breast cancer (9%), sarcoma (9%), and lung cancer (8%). Overall median second tumor latency was 7.4 years (1-42 years). For colorectal cancer it was 3.5 and for leukemia 4.3 years, but for sarcoma 11.7 and for breast cancer 17.1 years. The relatively frequent second tumors of the upper gastrointestinal tract were associated with median radiation doses of 24 Gy. By contrast, second colorectal cancer and sarcoma developed after median doses of 50 Gy. Conclusion: The 5- and 15-year probability to develop a histopathologically independent second tumor in or near the irradiated first tumor site, i.e., after intermediate or high radiation doses, was 0.5% and 2.2%, respectively. To identify potentially radiogenic second malignancies, a follow-up far beyond 5 years is mandatory. The incidence and potential dose-response relationship intermediate will be analyzed by a case-case and a case-control study of the Ulm data. (orig.)

Adult body size and physical activity in relation to risk of breast cancer according to tumor androgen receptor status.

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Zhang, Xuehong; Eliassen, A Heather; Tamimi, Rulla M; Hazra, Aditi; Beck, Andrew H; Brown, Myles; Collins, Laura C; Rosner, Bernard; Hankinson, Susan E

2015-06-01

Obesity and physical activity have been hypothesized to affect breast cancer risk partly via the androgen signaling pathway. We conducted the first study to evaluate these associations by tumor androgen receptor (AR) status. Height, weight, and physical activity were assessed using questionnaires in the Nurses' Health Study. AR, estrogen receptor (ER), and progesterone receptor (PR) status were determined using immunohistochemistry on tumor tissue and medical/pathology reports. A total of 1,701 AR(+) and 497 AR(-) cases were documented during 26 years of follow-up of 103,577 women. After adjusting for ER/PR status and other risk factors, the relative risks (RR) and 95% confidence intervals (95% CI) for every 5 kg/m(2) increase in body mass index (BMI) were 1.07 (1.01-1.13) for AR(+) and 1.16 (1.05-1.29) for AR(-) tumors (P-heterogeneity = 0.17). The RRs (95% CIs) per 5 hours of brisk walking/week were 0.87 (0.73-1.04) for AR(+) and 0.67 (0.45-0.99) for AR(-) tumors (P-heterogeneity = 0.22). Further, BMI, but not physical activity, associations differed significantly across ER/PR/AR subtypes (P-heterogeneity = 0.04 and 0.63, respectively). The RRs (95% CIs) for 5 kg/m(2) increase in BMI were 1.23 (1.04-1.45) for ER(+)PR(+)AR(-), 1.19 (1.01-1.39) for ER(-)PR(-)AR(-), 1.15 (1.08-1.23) for ER(+)PR(+)AR(+), and 0.88 (0.75-1.03) for ER(+)PR(-)AR(+) tumors. Higher BMI was associated with an increased risk of both AR(+) and AR(-) breast tumors in postmenopausal women, whereas physical activity, including brisk walking, was associated with a reduced risk of both subtypes. In addition, a significant positive association was observed between higher BMI and ER(-)PR(-)AR(-) tumors. The similar associations observed by AR status suggest that mechanisms other than androgen signaling underlie these two breast cancer risk factors. ©2015 American Association for Cancer Research.

Genetic mapping in mice identifies DMBT1 as a candidate modifier of mammary tumors and breast cancer risk

DEFF Research Database (Denmark)

Blackburn, Anneke C; Hill, Linda Z; Roberts, Amy L

2007-01-01

Low-penetrance breast cancer susceptibility alleles seem to play a significant role in breast cancer risk but are difficult to identify in human cohorts. A genetic screen of 176 N2 backcross progeny of two Trp53(+/-) strains, BALB/c and C57BL/6, which differ in their susceptibility to mammary...... tumors, identified a modifier of mammary tumor susceptibility in an approximately 25-Mb interval on mouse chromosome 7 (designated SuprMam1). Relative to heterozygotes, homozygosity for BALB/c alleles of SuprMam1 significantly decreased mammary tumor latency from 70.7 to 61.1 weeks and increased risk...

Risk Factors for Bile Duct Injury After Percutaneous Thermal Ablation of Malignant Liver Tumors: A Retrospective Case-Control Study.

Science.gov (United States)

Lin, Man-Xia; Ye, Jie-Yi; Tian, Wen-Shuo; Xu, Ming; Zhuang, Bo-Wen; Lu, Ming-De; Xie, Xiao-Yan; Kuang, Ming

2017-04-01

Bile duct injury after ablation of malignant liver tumors (MLTs) was not unusual and should be avoided. However, few studies have focused on evaluating the risk factors for intrahepatic bile duct injury. To evaluate the risk factors for intrahepatic bile duct injury after ablation of MLTs and to evaluate the minimum safe distance for ablating tumors abutting bile ducts. Sixty-five patients with intrahepatic bile duct injury after ablation of MLTs, and 65 controls were recruited. Risk factors for intrahepatic bile duct injury were analyzed. Tumor location was recorded as ≤5 mm (group A), 5-10 mm (group B), and >10 mm (group C) from the right/left main duct or segmental bile duct. Ascites history (P bile duct dilatation before ablation (P bile duct injury. Significant differences in the risk of intrahepatic bile duct injury were found between groups B and C (P = 0.000), but not between groups A and B (P = 0.751). Ascites history (P = 0.002) and tumor location (P Bile duct injury after ablation of MLTs was the result of local treatment-related factors combined with the patients' general condition. The minimum safe distance for ablation of tumor abutting a bile duct was 10 mm.

Associations between circulating carotenoids, genomic instability and the risk of high-grade prostate cancer.

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Nordström, Tobias; Van Blarigan, Erin L; Ngo, Vy; Roy, Ritu; Weinberg, Vivian; Song, Xiaoling; Simko, Jeffry; Carroll, Peter R; Chan, June M; Paris, Pamela L

2016-03-01

Carotenoids are a class of nutrients with antioxidant properties that have been purported to protect against cancer. However, the reported associations between carotenoids and prostate cancer have been heterogeneous and lacking data on interactions with nucleotide sequence variations and genomic biomarkers. To examine the associations between carotenoid levels and the risk of high-grade prostate cancer, also considering antioxidant-related genes and tumor instability. We measured plasma levels of carotenoids and genotyped 20 single nucleotide polymorphisms (SNP) in SOD1, SOD2, SOD3, XRCC1, and OGG1 among 559 men with non-metastatic prostate cancer undergoing radical prostatectomy. We performed copy number analysis in a subset of these men (n = 67) to study tumor instability assessed as Fraction of the Genome Altered (FGA). We examined associations between carotenoids, genotypes, tumor instability and risk of high-grade prostate cancer (Gleason grade ≥ 4 + 3) using logistic and linear regression. Circulating carotenoid levels were inversely associated with the risk of high-grade prostate cancer; odds ratios (OR) and 95% confidence intervals (CI) comparing highest versus lowest quartiles were: 0.34 (95% CI: 0.18-0.66) for α-carotene, 0.31 (95% CI: 0.15-0.63) for β-carotene, 0.55 (0.28-1.08) for lycopene and 0.37 (0.18-0.75) for total carotenoids. SNPs rs25489 in XRCC1, rs699473 in SOD3 and rs1052133 in OGG1 modified these associations for α-carotene, β-carotene and lycopene, respectively (P ≤ 0.05). The proportion of men with a high degree of FGA increased with Gleason Score (P carotenoids at diagnosis, particularly among men carrying specific somatic variations, were inversely associated with risk of high-grade prostate cancer. In exploratory analyses, higher lycopene level was associated with less genomic instability among men with low-grade disease which is novel and supports the hypothesis that lycopene may inhibit progression of

INTRAOPERATIVE PHOTODYNAMIC THERAPY FOR METASTATIC PERITONEAL TUMORS

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E. A. Suleimanov

2016-01-01

Full Text Available This review is devoted to the cytoreductive treatment of malignant tumors of the abdominal organs. The actuality of the issue is determined both by increase of the incidence of abdominal cancer in Russia and in majority of developed countries and by high rate diagnosis on late stages of disease. The methods of treatment of peritoneal carcinomatosis, based on possible effects on the secondary peritoneal tumors after surgical cytoreduction to reduce the risk of local recurrence and disease progression are described. These methods of additional intraoperative specific antitumor action include intraoperative radiation therapy, hyperthermic intraperitoneal chemotherapy, intraoperative photodynamic therapy characterized by differences in difficulty of performance, mechanisms of effect on tumor and healthy tissues, efficiency. Benefits, opportunities and possibilities of application of intraoperative photodynamic therapy (IOPDT for secondary peritoneal tumors are described in details, the results of a number of domestic and foreign clinical studies are shown, the successful application of intraoperative photodynamic therapy in clinical oncology, which allows reducing the risk of secondary tumor lesions of the peritoneum significantly, is demonstrated. Photodynamic therapy – a method with high efficiency and almost no side effects and complications, based on the ability of photosensitizer to accumulate selectively and retain in the high proliferative tissues. The advantages of this type of treatment of patients with peritoneal carcinomatosis are a selective effect on the peritoneal carcinomatosis and on visually detected tumor tissue, high efficiency in patients with malignant tumors of the abdominal cavity and pelvis combined with surgical cytoreduction, minimal effect on normal organs and tissues of the patient, well tolerated procedure.

Atlas-driven scan planning for high-resolution Micro-SPECT data acquisition based on multi-view photographs : A pilot study

NARCIS (Netherlands)

Baiker, M.; Vastenhouw, B.; Branderhorst, W.; Reiber, J.H.C.; Beekman, F.; Lelieveldt, B.P.F.

2009-01-01

Highly focused Micro-SPECT scanners enable the acquisition of functional small animal data with very high-resolution. To acquire a maximum of emitted photons from a specific structure of interest and at the same time minimize the required acquisition time, typically only a small subvolume of the

Atlas-driven scan planning for high-resolution micro-SPECT data acquisition based on multi-vew photographs : A pilot study

NARCIS (Netherlands)

Baiker, M.; Vastenhouw, B.; Branderhorst, S.W.; Reiber, J.H.C.; Beekman, F.J.; Lelieveld, B.P.F.

2009-01-01

Highly focused Micro-SPECT scanners enable the acquisition of functional small animal data with very high-resolution. To acquire a maximum of emitted photons from a specific structure of interest and at the same time minimize the required acquisition time, typically only a small subvolume of the

DAP1 high expression increases risk of lymph node metastases in squamous cell carcinoma of the oral cavity.

Science.gov (United States)

Santos, M; Maia, L L; Silva, C V M; Peterle, G T; Mercante, A M C; Nunes, F D; Carvalho, M B; Tajara, E H; Louro, I D; Silva-Conforti, A M A

2015-09-08

Death-associated protein 1 (DAP1) is a member of the DAP family. Its expression is associated with cell growth and normal death of the neoplastic cells, regulated by the mammalian target of the rapamycin protein. Activated DAP1 negatively regulates autophagy, which has been associated with the development and progression of several diseases, such as cancer, and with prognosis and survival of diverse tumor types. Therefore, in this study we analyzed DAP1 expression in 54 oral squamous cell carcinoma tumor samples and in 20 non-tumoral margins by immunohistochemistry. The results showed that DAP1 is more frequently expressed in tumor tissues compared with marginal non-tumoral cells. Additionally, high DAP1 expression is associated with a 4-fold increase in the risk of lymph node metastases. Our results suggest that the DAP1 protein can be used as a potential marker of lymph node metastases predisposition, helping define the best therapy for each patient to minimize risk of developing metastases.

Place of surgery in high-risk tumours of the prostate

International Nuclear Information System (INIS)

Soulie, M.; Rozet, F.; Hennequin, C.; Salomon, L.

2010-01-01

Among the different options recommended for high-risk prostate cancer, radical prostatectomy is admitted as radiotherapy, but its role is still controversial in mono-therapy and difficult to evaluate in combined treatments. The results of clinical trials combining an external radiotherapy to a long-term androgen deprivation in locally advanced tumours sustain the principle of a multidisciplinary management in high-risk prostate cancer. The impact of surgery on the risk of progression and local recurrence is important in selected patients with low grade and small tumoral volume. Clinical and histological data associated to the MRI assessment remain essential and enhance the preoperative multidisciplinary decision, especially regarding nodal and distant metastases. Radical prostatectomy with an extended pelvic lymphadenectomy can be considered as a viable alternative to radiotherapy and hormonal therapy in these patients with a long life expectancy but presenting a high risk of local progression and a low risk of metastatic disease. Morbidity of the procedure is similar to radical prostatectomy for organ-confined tumours despite more erectile dysfunction due to non-sparing radical prostatectomy in most of cases. Oncological results from recent compiled series show 10- and 15-year specific survival rates around 85 and 75%, respectively, including adjuvant or salvage treatments with radiotherapy, androgen deprivation or chemotherapy. (authors)

Radiofrequency ablation for renal tumors. Our experience

International Nuclear Information System (INIS)

Hiraoka, Kenji; Kawauchi, Akihiro; Nakamura, Terukazu; Soh, Jintetsu; Mikami, Kazuya; Miki, Tsuneharu

2009-01-01

The objective of this study was to report our results of percutaneous radiofrequency ablation (RFA) for renal tumors and to assess predictors of therapeutic efficacy. Forty patients (median age 73 years) with renal tumors were treated with RFA under local or epidural anesthesia. All of them had high surgical risk or refused radical surgery. Tumors were punctured percutaneously using the Radionics Cool-tip RF System under computed tomography or ultrasonographic guidance. Median tumor diameter was 24 mm. After RFA, contrast-enhanced computed tomography or magnetic resonance imaging was performed within 1 month. Complete response (CR) was defined as no enhancement inside the tumor. Factors related to the outcome and to renal function were assessed. Median follow up was 16 months. CR was observed in 34 cases (85.0%). A significant difference in CR rate was observed between tumors ≤30 mm and those >30 mm. Outcomes tended to be better for tumors in the mid to lower kidney, and those away from the renal hilum. Recurrence was observed in one case (2.9%), but a CR was obtained again by additional RFA. Out of a total of 77 RFA procedures, complications occurred in only three cases (3.9%), and conservative treatment was possible in all cases. Serum creatinine levels 3 months after RFA did not differ from those before RFA. Percutaneous RFA is a safe and effective treatment for small renal tumors in patients with high surgical risk or who refuse radical surgery. (author)

Magnesium intake and colorectal tumor risk: a case-control study and meta-analysis.

NARCIS (Netherlands)

Wark, P.A.; Lau, R.; Norat, T.; Kampman, E.

2012-01-01

BACKGROUND: Dietary magnesium might be related to colorectal tumor risk through the pivotal roles of magnesium in cellular metabolism, insulin resistance, and systemic inflammation. OBJECTIVE: We evaluated the hypothesis of whether higher dietary magnesium intake is associated with reduced

Magnesium intake and colorectal tumor risk : a case-control study and meta-analysis

NARCIS (Netherlands)

Wark, P.A.; Lau, R.; Norat, T.; Kampman, E.

2012-01-01

Background: Dietary magnesium might be related to colorectal tumor risk through the pivotal roles of magnesium in cellular metabolism, insulin resistance, and systemic inflammation. Objective: We evaluated the hypothesis of whether higher dietary magnesium intake is associated with reduced

Risk stratification for venous thromboembolism in patients with testicular germ cell tumors.

Directory of Open Access Journals (Sweden)

Angelika Bezan

Full Text Available Patients with testicular germ cell tumors (TGCT have an increased risk for venous thromboembolism (VTE. We identified risk factors for VTE in this patient cohort and developed a clinical risk model.In this retrospective cohort study at the Medical University of Graz we included 657 consecutive TGCT patients across all clinical stages. A predictive model for VTE was developed and externally validated in 349 TGCT patients treated at the University Hospital Zurich.Venous thromboembolic events occurred in 34 (5.2% patients in the Graz cohort. In univariable competing risk analysis, higher clinical stage (cS and a retroperitoneal lymphadenopathy (RPLN were the strongest predictors of VTE (p<0.0001. As the presence of a RPLN with more than 5cm in greatest dimension without coexisting visceral metastases is classified as cS IIC, we constructed an empirical VTE risk model with the following four categories (12-month-cumulative incidence: cS IA-B 8/463 patients (1.7%, cS IS-IIB 5/86 patients (5.9%, cS IIC 3/21 patients (14.3% and cS IIIA-C 15/70 patients (21.4%. This risk model was externally validated in the Zurich cohort (12-month-cumulative incidence: cS IA-B (0.5%, cS IS-IIB (6.0%, cS IIC (11.1% and cS IIIA-C (19.1%. Our model had a significantly higher discriminatory performance than a previously published classifier (RPLN-VTE-risk-classifier which is based on the size of RPLN alone (AUC-ROC: 0.75 vs. 0.63, p = 0.007.According to our risk stratification, TGCT patients with cS IIC and cS III disease have a very high risk of VTE and may benefit from primary thromboprophylaxis for the duration of chemotherapy.

Awake craniotomy for tumor resection.

Science.gov (United States)

Attari, Mohammadali; Salimi, Sohrab

2013-01-01

Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with left-sided body hypoesthesia since last 3 months and a 25-year-old with severe headache of 1 month duration were operated under craniotomy for brain tumors resection. An awake craniotomy was planned to allow maximum tumor intraoperative testing for resection and neurologic morbidity avoidance. The method of anesthesia should offer sufficient analgesia, hemodynamic stability, sedation, respiratory function, and also awake and cooperative patient for different neurological test. Airway management is the most important part of anesthesia during awake craniotomy. Tumor surgery with awake craniotomy is a safe technique that allows maximal resection of lesions in close relationship to eloquent cortex and has a low risk of neurological deficit.

Awake craniotomy for tumor resection

Directory of Open Access Journals (Sweden)

Mohammadali Attari

2013-01-01

Full Text Available Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with left-sided body hypoesthesia since last 3 months and a 25-year-old with severe headache of 1 month duration were operated under craniotomy for brain tumors resection. An awake craniotomy was planned to allow maximum tumor intraoperative testing for resection and neurologic morbidity avoidance. The method of anesthesia should offer sufficient analgesia, hemodynamic stability, sedation, respiratory function, and also awake and cooperative patient for different neurological test. Airway management is the most important part of anesthesia during awake craniotomy. Tumor surgery with awake craniotomy is a safe technique that allows maximal resection of lesions in close relationship to eloquent cortex and has a low risk of neurological deficit.

Association Between Inflammatory Diet Pattern and Risk of Colorectal Carcinoma Subtypes Classified by Immune Responses to Tumor.

Science.gov (United States)

Liu, Li; Nishihara, Reiko; Qian, Zhi Rong; Tabung, Fred K; Nevo, Daniel; Zhang, Xuehong; Song, Mingyang; Cao, Yin; Mima, Kosuke; Masugi, Yohei; Shi, Yan; da Silva, Annacarolina; Twombly, Tyler; Gu, Mancang; Li, Wanwan; Hamada, Tsuyoshi; Kosumi, Keisuke; Inamura, Kentaro; Nowak, Jonathan A; Drew, David A; Lochhead, Paul; Nosho, Katsuhiko; Wu, Kana; Wang, Molin; Garrett, Wendy S; Chan, Andrew T; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji

2017-12-01

Dietary patterns affect systemic and local intestinal inflammation, which have been linked to colorectal carcinogenesis. Chronic inflammation can interfere with the adaptive immune response. We investigated whether the association of a diet that promotes intestinal inflammation with risk of colorectal carcinoma was stronger for tumors with lower lymphocytic reactions than tumors with higher lymphocytic reactions. We collected data from the molecular pathological epidemiology databases of 2 prospective cohort studies: the Nurses' Health Study (since 1976) and the Health Professionals Follow-Up Study (since 1986). We used duplication-method time-varying Cox proportional cause-specific hazards regression to assess the association of empirical dietary inflammatory pattern (EDIP) score (derived from food frequency questionnaire data) with colorectal carcinoma subtype. Foods that contribute to high EDIP scores include red and processed meats, refined grains, carbonated beverages, and some vegetables; foods that contribute to low EDIP scores include beer, wine, coffee, tea, yellow and leafy vegetables, and fruit juice. Colorectal tissue samples were analyzed histologically for patterns of lymphocytic reactions (Crohn's-like lymphoid reaction, peritumoral lymphocytic reaction, intratumoral periglandular reaction, and tumor-infiltrating lymphocytes). During follow-up of 124,433 participants, we documented 1311 incident colon and rectal cancer cases with available tissue data. The association between the EDIP and colorectal cancer risk was significant (P trend  = .02), and varied with degree of peritumoral lymphocytic reaction (P heterogeneity colorectal cancer with an absent or low peritumoral lymphocytic reaction (highest vs lowest EDIP score quintile hazard ratio, 2.60; 95% confidence interval, 1.60-4.23; P trend .80). In 2 prospective cohort studies, we associated inflammatory diets with a higher risk of colorectal cancer subtype that contains little or no peritumoral

High-risk HPV is not associated with epithelial ovarian cancer in a Caucasian population

DEFF Research Database (Denmark)

Ingerslev, Kasper Hjorth; Hogdall, Estrid; Skovrider-Ruminski, Wojciech

2016-01-01

BACKGROUND: High-risk human papillomavirus (HPV) has been suspected to play a role in the carcinogenesis of epithelial ovarian cancer (EOC). However, results from previous studies are conflicting. In most of these studies, the number of tissue samples was small. The current study was therefore...... undertaken to examine the prevalence of high-risk HPV DNA in EOC in a large series of patients. METHOD: Formalin-fixed, paraffin-imbedded tumor tissue samples from 198 cases consecutively included in the Danish Pelvic Mass Study were analyzed. The material included 163 serous adenocarcinomas, 15 endometrioid...

A Phase II Study of Preradiotherapy Chemotherapy Followed by Hyperfractionated Radiotherapy for Newly Diagnosed High-Risk Medulloblastoma/Primitive Neuroectodermal Tumor: A Report From the Children's Oncology Group (CCG 9931)

International Nuclear Information System (INIS)

Allen, Jeffrey; Donahue, Bernadine; Mehta, Minesh; Miller, Douglas C.; Rorke, Lucy B.; Jakacki, Regina; Robertson, Patricia; Sposto, Richard; Holmes, Emi; Vezina, Gilbert; Muraszko, Karin; Puccetti, Diane; Prados, Michael; Chan, K.-W.

2009-01-01

Purpose: To verify feasibility and monitor progression-free survival and overall survival in children with high-risk medulloblastoma and noncerebellar primitive neuroectodermal tumors (PNETs) treated in a Phase II study with preradiotherapy chemotherapy (CHT) followed by high-dose, hyperfractionated craniospinal radiotherapy (CSRT). Methods and Materials: Eligibility criteria included age >3 years at diagnosis, medulloblastoma with either high M stage and/or >1.5 cm 2 postoperative residual disease, and all patients with noncerebellar PNET. Treatment was initiated with five alternating monthly cycles of CHT (A [cisplatin, cyclophosphamide, etoposide, and vincristine], B [carboplatin and etoposide], A, B, and A) followed by hyperfractionated CSRT (40 Gy) with a boost to the primary tumor (72 Gy) given in twice-daily 1-Gy fractions. Results: The valid study group consisted of 124 patients whose median age at diagnosis was 7.8 years. Eighty-four patients (68%) completed the entire protocol according to study guidelines (within 9 months), and the median time to complete CSRT was 1.6 months. Major reasons for failure to complete CHT included progressive disease (17%) and toxic death (2.4%). The 5-year progression-free survival and overall survival rates were 43% ± 5% and 52% ± 5%, respectively. No significant differences were detected in subset analysis related to response to CHT, site of primary tumor, postoperative residual disease, or M stage. Conclusions: The feasibility of this intensive multimodality protocol was confirmed, and response to pre-RT CHT did not impact on survival. Survival data from this protocol can not be compared with data from other studies, given the protocol design.

Chemotherapy Toxicity Risk Score for Treatment Decisions in Older Adults with Advanced Solid Tumors.

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Nishijima, Tomohiro F; Deal, Allison M; Williams, Grant R; Sanoff, Hanna K; Nyrop, Kirsten A; Muss, Hyman B

2018-05-01

The decision whether to treat older adults with advanced cancer with standard therapy (ST) or reduced therapy (RT) is complicated by heterogeneity in aging. We assessed the potential utility of the chemotherapy toxicity risk score (CTRS) [J Clin Oncol 2011;29:3457-3465] for treatment decisions in older adults. This was a prospective observational study of patients aged ≥65 years receiving first-line chemotherapy for advanced cancer for which combination chemotherapy is the standard of care. Patients were categorized as high risk (CTRS ≥10), for whom RT (dose-reduced combination or single-agent chemotherapy) is deemed appropriate, or nonhigh risk (CTRS statistic. Fifty-eight patients (median age, 71 years) were enrolled. Thirty-eight patients received ST (21 had CTRS advanced solid tumors receiving first-line chemotherapy was assessed. Little agreement was found between chemotherapy treatment decisions based on the clinical impression versus what was recommended based on the CTRS. Among patients treated with standard-dose combination chemotherapy, patients with CTRS ≥10 had a very high incidence of grade 3-4 toxicities and hospitalization, which was significantly greater than that of patients with a low CTRS (<10). These findings suggest that the addition of CTRS to the clinical impression has a potential to improve treatment decisions. © AlphaMed Press 2018.

Risk of mortality of node-negative, ER/PR/HER2 breast cancer subtypes in T1, T2, and T3 tumors.

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Parise, Carol A; Caggiano, Vincent

2017-10-01

The purpose of this study was to assess differences in breast cancer-specific mortality within tumors of the same size when breast cancer was defined using the three tumor markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). We identified 104,499 cases of node-negative primary female invasive breast cancer from the California Cancer Registry. Tumor size was categorized as T1a, T1b, T1c, T2, and T3. Breast cancer was defined using ER, PR, and HER2. Kaplan-Meier Survival analysis was conducted and Cox Regression was used to compute the adjusted risk of mortality for the ER+/PR+/HER2+, ER-/PR-/HER2- (TNBC), and ER-/PR-/HER2+ (HER2-overexpressing) subtypes when compared with the ER+/PR+/HER2-. Separate models were computed for each tumor size. Unadjusted survival analysis showed that for all tumor sizes, the ER+/PR+ subtypes regardless of HER status have better breast cancer-specific survival than ER-/PR- subtypes. Subtype was not an important factor for risk of mortality for T1a tumors. The ER+/PR+/HER2+ subtype was only a risk for mortality in T1b tumors that were unadjusted for treatment. For all other tumor sizes, the ER+/PR+/HER2+ had the same mortality as the ER+/PR+/HER2- subtype regardless of adjustment for treatment. The HER2-overexpressing subtype had a higher risk of mortality than the ER+/PR+/HER2- subtype except for T1b tumors that were adjusted for treatment. For all tumor sizes, the TNBC had higher hazard ratios than all other subtypes. T1a tumors have the same risk of mortality regardless of ER/PR/HER2 subtype, and ER and PR negativity plays a stronger role in survival than HER2 positivity for tumors of all size.

Optimization of the fractionated irradiation scheme considering physical doses to tumor and organ at risk based on dose–volume histograms

Energy Technology Data Exchange (ETDEWEB)

Sugano, Yasutaka [Graduate School of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan); Mizuta, Masahiro [Laboratory of Advanced Data Science, Information Initiative Center, Hokkaido University, Kita-11, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0811 (Japan); Takao, Seishin; Shirato, Hiroki; Sutherland, Kenneth L. [Department of Radiation Medicine, Graduate School of Medicine, Hokkaido University, Kita-15, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-8638 (Japan); Date, Hiroyuki, E-mail: date@hs.hokudai.ac.jp [Faculty of Health Sciences, Hokkaido University, Kita-12, Nishi-5, Kita-ku, Sapporo, Hokkaido 060-0812 (Japan)

2015-11-15

Purpose: Radiotherapy of solid tumors has been performed with various fractionation regimens such as multi- and hypofractionations. However, the ability to optimize the fractionation regimen considering the physical dose distribution remains insufficient. This study aims to optimize the fractionation regimen, in which the authors propose a graphical method for selecting the optimal number of fractions (n) and dose per fraction (d) based on dose–volume histograms for tumor and normal tissues of organs around the tumor. Methods: Modified linear-quadratic models were employed to estimate the radiation effects on the tumor and an organ at risk (OAR), where the repopulation of the tumor cells and the linearity of the dose-response curve in the high dose range of the surviving fraction were considered. The minimization problem for the damage effect on the OAR was solved under the constraint that the radiation effect on the tumor is fixed by a graphical method. Here, the damage effect on the OAR was estimated based on the dose–volume histogram. Results: It was found that the optimization of fractionation scheme incorporating the dose–volume histogram is possible by employing appropriate cell surviving models. The graphical method considering the repopulation of tumor cells and a rectilinear response in the high dose range enables them to derive the optimal number of fractions and dose per fraction. For example, in the treatment of prostate cancer, the optimal fractionation was suggested to lie in the range of 8–32 fractions with a daily dose of 2.2–6.3 Gy. Conclusions: It is possible to optimize the number of fractions and dose per fraction based on the physical dose distribution (i.e., dose–volume histogram) by the graphical method considering the effects on tumor and OARs around the tumor. This method may stipulate a new guideline to optimize the fractionation regimen for physics-guided fractionation.

High Stromal Carbonic Anhydrase IX Expression Is Associated With Decreased Survival in p16-Negative Head-and-Neck Tumors

International Nuclear Information System (INIS)

Brockton, Nigel; Dort, Joseph; Lau, Harold; Hao, Desiree; Brar, Sony; Klimowicz, Alexander; Petrillo, Stephanie; Diaz, Roman; Doll, Corinne; Magliocco, Anthony

2011-01-01

Purpose: Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common malignancy worldwide. Alcohol use and tobacco use are the most established risk factors; however, human papilloma virus (HPV) infection is a major risk factor for a subset of HNSCCs. Although HPV-positive tumors typically present at a more advanced stage at diagnosis, they are associated with a better prognosis. Tumor hypoxia confers poor prognosis and treatment failure, but direct tumor oxygen measurement is challenging. Endogenous markers of hypoxia (EMHs) have been proposed but have not replicated the prognostic utility of direct oxygen measurement. The expression of endogenous markers of hypoxia may be influenced by oxygen-independent factors, such as the HPV status of the tumor. Methods and Materials: Consecutive cases of locally advanced HNSCC, treated with a uniform regimen of combined radiotherapy and chemotherapy, were identified. Tissue microarrays were assembled from triplicate 0.6-mm cores of archived tumor tissue. HPV status was inferred from semiquantitative p16 immunostaining and directly measured by use of HPV-specific chromogenic in situ hybridization and polymerase chain reaction. Automated quantitative fluorescent immunohistochemistry was conducted to measure epithelial and stromal expression of carbonic anhydrase IX (CAIX) and glucose transporter 1 (GLUT1). Results: High stromal CAIX expression was associated with significantly reduced overall survival (p = 0.03) in patients with p16-negative tumors. Conclusions: This is the first study to use quantitative immunohistochemistry to examine endogenous markers of hypoxia stratified by tumor p16/HPV status. Assessment of CAIX expression in p16-negative HNSCC could identify patients with the least favorable prognosis and inform therapeutic strategies.

Radiation induction of drug resistance in RIF-1 tumors and tumor cells

International Nuclear Information System (INIS)

Hopwood, L.E.; Moulder, J.E.

1989-01-01

The RIF-1 tumor cell line contains a small number of cells (1-20 per 10(6) cells) that are resistant to various single antineoplastic drugs, including 5-fluorouracil (5FU), methotrexate (MTX), and adriamycin (ADR). For 5FU the frequency of drug resistance is lower for tumor-derived cells than for cells from cell culture; for MTX the reverse is true, and for ADR there is no difference. In vitro irradiation at 5 Gy significantly increased the frequency of drug-resistant cells for 5FU, MTX, and ADR. In vivo irradiation at 3 Gy significantly increased the frequency of drug-resistant cells for 5FU and MTX, but not for ADR. The absolute risk for in vitro induction of MTX, 5FU, and ADR resistance, and for in vivo induction of 5FU resistance, was 1-3 per 10(6) cells per Gy; but the absolute risk for in vivo induction of MTX resistance was 54 per 10(6) cells per Gy. The frequency of drug-resistant cells among individual untreated tumors was highly variable; among individual irradiated tumors the frequency of drug-resistant cells was significantly less variable. These studies provide supporting data for models of the development of tumor drug resistance, and imply that some of the drug resistance seen when chemotherapy follows radiotherapy may be due to radiation-induced drug resistance

High risk bladder cancer: current management and survival

Directory of Open Access Journals (Sweden)

Anna M. Leliveld

2011-04-01

Full Text Available PURPOSE: To evaluate the pattern of care in patients with high risk non muscle invasive bladder cancer (NMIBC in the Comprehensive Cancer Center North-Netherlands (CCCN and to assess factors associated with the choice of treatment, recurrence and progression free survival rates. MATERIALS AND METHODS: Retrospective analysis of 412 patients with newly diagnosed high risk NMIBC. Clinical, demographic and follow-up data were obtained from the CCCN Cancer Registry and a detailed medical record review. Uni and multivariate analysis was performed to identify factors related to choice of treatment and 5 year recurrence and progression free survival. RESULTS: 74/412 (18% patients with high risk NMIBC underwent a transurethral resection (TUR as single treatment. Adjuvant treatment after TUR was performed in 90.7% of the patients treated in teaching hospitals versus 71.8 % in non-teaching hospitals (p 80 years OR 0.1 p = 0.001 and treatment in non-teaching hospitals (OR 0.25; p < 0.001 were associated with less adjuvant treatment after TUR. Tumor recurrence occurred in 191/392 (49% and progression in 84 /392 (21.4% patients. The mean 5-years progression free survival was 71.6% (95% CI 65.5-76.8. CONCLUSION: In this pattern of care study in high risk NMIBC, 18% of the patients were treated with TUR as single treatment. Age and treatment in non-teaching hospitals were associated with less adjuvant treatment after TUR. None of the variables sex, age, comorbidity, hospital type, stage and year of treatment was associated with 5 year recurrence or progression rates.

Risk of Lymphoma in Patients With Inflammatory Bowel Disease Treated With Anti-Tumor Necrosis Factor Alpha Agents: A Systematic Review and Meta-analysis.

Science.gov (United States)

Yang, Chen; Huang, Junlin; Huang, Xiaowen; Huang, Shaozhuo; Cheng, Jiaxin; Liao, Weixin; Chen, Xuewen; Wang, Xueyi; Dai, Shixue

2018-05-12

The association between anti-tumor necrosis factor alpha agents and the risk of lymphoma in patients with inflammatory bowel disease has already been sufficiently reported. However, the results of these studies are inconsistent. Hence, this analysis was conducted to investigate whether anti-tumor necrosis factor alpha agents can increase the risk of lymphoma in inflammatory bowel disease patients. MEDLINE, EMBASE and the Cochrane Library were searched to identify relevant studies which evaluated the risk of lymphoma in inflammatory bowel disease patients treated with anti-tumor necrosis factor alpha agents. A random-effects meta-analysis was performed to calculate the pooled incidence rate ratios as well as risk ratios. Twelve studies comprising 285811 participants were included. The result showed that there was no significantly increased risk of lymphoma between anti-tumor necrosis factor alpha agents exposed and anti-tumor necrosis factor alpha agents unexposed groups (random effects: incidence rate ratio [IRR], 1.43 95%CI, 0.91-2.25, p= 0.116; random effects: risk ratio [RR], 0.83 95%CI, 0.47-1.48, p=0.534). However, monotherapy of anti-tumor necrosis factor alpha agents (random effects: IRR=1.65, 95%CI, 1.16-2.35; p=0.006; random effects: RR=1.00, 95%CI, 0.39-2.59; p=0.996) or combination therapy (random effects: IRR=3.36, 95%CI, 2.23-5.05; ptumor necrosis factor alpha agents in patients with inflammatory bowel disease is not associated with a higher risk of lymphoma. Combination therapy and anti-tumor necrosis factor alpha agents monotherapy can significantly increase the risk of lymphoma in patients with inflammatory bowel disease.

Outcome of pregnancy in survivors of Wilms' tumor

International Nuclear Information System (INIS)

Li, F.P.; Gimbrere, K.; Gelber, R.D.; Sallan, S.E.; Flamant, F.; Green, D.M.; Heyn, R.M.; Meadows, A.T.

1987-01-01

Outcome of pregnancy was reported by 99 patients who were cured of childhood Wilms' tumor at seven pediatric cancer centers during 1931 to 1979. These patients carried or sired 191 singleton pregnancies of at least 20 weeks in duration. Among the 114 pregnancies in women who had received abdominal radiotherapy for Wilms' tumor, an adverse outcome occurred in 34 (30%). There were 17 perinatal deaths (five in premature low-birth-weight infants) and 17 other low-birth-weight infants. Compared with white women in the United States, the irradiated women had an increased perinatal mortality rate (relative risk, 7.9) and an excess of low-birth-weight infants (relative risk, 4.0). In contrast, an adverse outcome was found in two (3%) of the 77 pregnancies in nonirradiated female patients with Wilms' tumor and wives of male patients. The high risk of adverse pregnancy outcome should be considered in the counseling and prenatal care of women who have received abdominal radiotherapy for Wilms' tumor

Tumor Classification Using High-Order Gene Expression Profiles Based on Multilinear ICA

Directory of Open Access Journals (Sweden)

Ming-gang Du

2009-01-01

Full Text Available Motivation. Independent Components Analysis (ICA maximizes the statistical independence of the representational components of a training gene expression profiles (GEP ensemble, but it cannot distinguish relations between the different factors, or different modes, and it is not available to high-order GEP Data Mining. In order to generalize ICA, we introduce Multilinear-ICA and apply it to tumor classification using high order GEP. Firstly, we introduce the basis conceptions and operations of tensor and recommend Support Vector Machine (SVM classifier and Multilinear-ICA. Secondly, the higher score genes of original high order GEP are selected by using t-statistics and tabulate tensors. Thirdly, the tensors are performed by Multilinear-ICA. Finally, the SVM is used to classify the tumor subtypes. Results. To show the validity of the proposed method, we apply it to tumor classification using high order GEP. Though we only use three datasets, the experimental results show that the method is effective and feasible. Through this survey, we hope to gain some insight into the problem of high order GEP tumor classification, in aid of further developing more effective tumor classification algorithms.

Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers

DEFF Research Database (Denmark)

Schmidt, Marjanka K; Hogervorst, Frans; van Hien, Richard R

2016-01-01

PURPOSE: CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor...... subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC. PATIENTS AND METHODS: CHEK2*1100delC genotyping was mostly done by a custom Taqman assay....... Breast cancer odds ratios (ORs) for CHEK2*1100delC carriers versus noncarriers were estimated by using logistic regression and adjusted for study (categorical) and age. Main analyses included patients with invasive breast cancer from population- and hospital-based studies. RESULTS: Proportions...

High-risk human papilloma virus (HPV) and survival in patients with esophageal carcinoma: a pilot study

International Nuclear Information System (INIS)

Dreilich, Martin; Bergqvist, Michael; Moberg, Martin; Brattström, Daniel; Gustavsson, Inger; Bergström, Stefan; Wanders, Alkwin; Hesselius, Patrik; Wagenius, Gunnar; Gyllensten, Ulf

2006-01-01

Human papilloma virus (HPV) in patients with esophageal carcinoma has previously been studied with an average detection rate of 15%, but the role of HPV in relation to survival is less clear. In cervical cancer, lung cancer and tonsil cancer HPV viral load is a predictive factor for survival and outcome of treatment. The primary aim was to study the spectrum of high-risk HPV types in esophageal tumors. Secondary, as a pilot study we investigated the association between HPV status and the survival rates. We compared both the presence and the viral load of high-risk HPV types 16, 18, 31, 33, 39, 45, 52, 58, and 67 in relation to clinical data from patients with esophageal carcinoma. Survival data and tumor samples were retrieved from 100 patients receiving treatment at the Department of Oncology, Uppsala Hospital, Uppsala, Sweden. The tumor samples were investigated for HPV viral load using real-time PCR. HPV 16 was detected in 16% of the patients; no other HPV type was detected. HPV 16 infection had no significant effect on survival (p = 0.72). Also, HPV 16 did not improve survival after treatment (radiotherapy or chemotherapy). Only HPV 16 was detected among the patients. HPV 16 in esophageal carcinoma patients did not influence survival or improve therapy response. However, given the size of the study there is a need to examine a larger cohort in order to understand in more detail the effect of high risk HPV types in esophageal carcinoma

Awake craniotomy for tumor resection

OpenAIRE

Mohammadali Attari; Sohrab Salimi

2013-01-01

Surgical treatment of brain tumors, especially those located in the eloquent areas such as anterior temporal, frontal lobes, language, memory areas, and near the motor cortex causes high risk of eloquent impairment. Awake craniotomy displays major rule for maximum resection of the tumor with minimum functional impairment of the Central Nervous System. These case reports discuss the use of awake craniotomy during the brain surgery in Alzahra Hospital, Isfahan, Iran. A 56-year-old woman with le...

Imatinib as the first and only treatment in Europe for adult patients at significant risk of relapse following gastrointestinal stromal tumor removal

Science.gov (United States)

Duffaud, F; Salas, S; Huyn, T; Deville, JL

2010-01-01

Mutations of the KIT gene are the molecular hallmark of most gastrointestinal stromal tumors (GISTs). GIST has become a model for targeted treatment of solid tumors, imatinib becoming the standard first-line treatment of these tumors in the advanced/metastatic phase. Because of the efficacy of imatinib treatment in the advanced setting, its role following resection of a primary non-metastatic GIST was investigated. The recently published phase III, double-blind, placebo-controlled, multicenter ACOSOG Z9001 study showed that adjuvant therapy is safe, and significantly improves recurrence-free survival compared to placebo when given after resection. To what extent imatinib will improve overall survival has yet to be answered. What is clear is that high-risk GIST patients definitely need adjuvant therapy, and that 1 year of imatinib is not enough for the patients who do need it. The questions of optimal duration of imatinib treatment in the adjuvant setting, adequate selection of risk patients and effect of imatinib on overall survival are currently being studied. PMID:21694845

Dosimetric benefit of DMLC tracking for conventional and sub-volume boosted prostate intensity-modulated arc radiotherapy

Science.gov (United States)

Pommer, Tobias; Falk, Marianne; Poulsen, Per R.; Keall, Paul J.; O'Brien, Ricky T.; Meidahl Petersen, Peter; Rosenschöld, Per Munck af

2013-04-01

This study investigated the dosimetric impact of uncompensated motion and motion compensation with dynamic multileaf collimator (DMLC) tracking for prostate intensity modulated arc therapy. Two treatment approaches were investigated; a conventional approach with a uniform radiation dose to the target volume and an intraprostatic lesion (IPL) boosted approach with an increased dose to a subvolume of the prostate. The impact on plan quality of optimizations with a leaf position constraint, which limited the distance between neighbouring adjacent MLC leaves, was also investigated. Deliveries were done with and without DMLC tracking on a linear acceleration with a high-resolution MLC. A cylindrical phantom containing two orthogonal diode arrays was used for dosimetry. A motion platform reproduced six patient-derived prostate motion traces, with the average displacement ranging from 1.0 to 8.9 mm during the first 75 s. A research DMLC tracking system was used for real-time motion compensation with optical monitoring for position input. The gamma index was used for evaluation, with measurements with a static phantom or the planned dose as reference, using 2% and 2 mm gamma criteria. The average pass rate with DMLC tracking was 99.9% (range 98.7-100%, measurement as reference), whereas the pass rate for untracked deliveries decreased distinctly as the average displacement increased, with an average pass rate of 61.3% (range 32.7-99.3%). Dose-volume histograms showed that DMLC tracking maintained the planned dose distributions in the presence of motion whereas traces with >3 mm average displacement caused clear plan degradation for untracked deliveries. The dose to the rectum and bladder had an evident dependence on the motion direction and amplitude for untracked deliveries, and the dose to the rectum was slightly increased for IPL boosted plans compared to conventional plans for anterior motion with large amplitude. In conclusion, optimization using a leaf position

A pilot systematic genomic comparison of recurrence risks of hepatitis B virus-associated hepatocellular carcinoma with low- and high-degree liver fibrosis.

Science.gov (United States)

Yoo, Seungyeul; Wang, Wenhui; Wang, Qin; Fiel, M Isabel; Lee, Eunjee; Hiotis, Spiros P; Zhu, Jun

2017-12-07

integrations and pathogenic mutations showed distinct patterns between low and high liver fibrosis patients with regards to tumor recurrence. The results suggest that HBV integrations and pathogenic SNPs in non-neoplastic tissues are important for tumorigenesis and different recurrence risk models are needed for patients with low and high degrees of liver fibrosis.

Tumor mutational load and immune parameters across metastatic Renal Cell Carcinoma (mRCC) risk groups

Science.gov (United States)

de Velasco, Guillermo; Miao, Diana; Voss, Martin H.; Hakimi, A. Ari; Hsieh, James J.; Tannir, Nizar M.; Tamboli, Pheroze; Appleman, Leonard J.; Rathmell, W. Kimryn; Van Allen, Eliezer M.; Choueiri, Toni K.

2016-01-01

Patients with metastatic renal cell carcinoma (mRCC) have better overall survival when treated with nivolumab, a cancer immunotherapy that targets the immune checkpoint inhibitor programmed cell death 1 (PD-1), rather than everolimus (a chemical inhibitor of mTOR and immunosuppressant). Poor-risk mRCC patients treated with nivolumab seemed to experience the greatest overall survival benefit, compared to patients with favorable or intermediate-risk, in an analysis of the CheckMate-025 trial subgroup of the Memorial Sloan Kettering Cancer Center (MSKCC) prognostic risk groups. Here we explore whether tumor mutational load and RNA expression of specific immune parameters could be segregated by prognostic MSKCC risk strata and explain the survival seen in the poor-risk group. We queried whole exome transcriptome data in RCC patients (n = 54) included in The Cancer Genome Atlas that ultimately developed metastatic disease or were diagnosed with metastatic disease at presentation and did not receive immune checkpoint inhibitors. Nonsynonymous mutational load did not differ significantly by MSKCC risk group, nor was the expression of cytolytic genes –granzyme A and perforin – or selected immune checkpoint molecules different across MSKCC risk groups. In conclusion, this analysis found that mutational load and expression of markers of an active tumor microenvironment did not correlate with MSKCC risk prognostic classification in mRCC. PMID:27538576

Treatment outcomes and late toxicities in patients with embryonal central nervous system tumors

International Nuclear Information System (INIS)

Odagiri, Kazumasa; Omura, Motoko; Hata, Masaharu; Aida, Noriko; Niwa, Tetsu; Goto, Hiroaki; Ito, Susumu; Adachi, Masanori; Yoshida, Haruyasu; Yuki, Hiroko; Inoue, Tomio

2014-01-01

Standard treatment strategies for embryonal central nervous system (CNS) tumors have not yet been established. We treated these tumors using an original chemoradiation therapy protocol; the clinical outcomes and toxicities were retrospectively evaluated. Twenty-four patients were enrolled including sixteen with medulloblastoma, four with supratentorial primitive neuroectodermal tumor (sPNET), three with atypical teratoid/rhabdoid tumor, and one with pineoblastoma. Immediately after diagnosis, all patients underwent surgery initially. They were then categorized as high- or average-risk groups independent of tumor type/pathogenesis. The average-risk group included patients who were aged ≥3 years at diagnosis, had non-metastatic disease at diagnosis (M0), and had undergone gross total resection. Other patients were categorized as the high-risk group; this group received more intensive treatment than the average-risk group, including high-dose chemotherapy with autologous stem-cell transplantation. All patients received craniospinal irradiation (CSI). The CSI dose was 23.4 Gy for M0 patients aged ≥5 years, 18 Gy for M0 patients aged <5 years, and 30–36 Gy for all patients with M + disease. The total dose to the primary tumor bed was 54 Gy. The median follow-up time was 73.5 (range, 19–118) months. The 5-year progression-free survival (PFS) and overall survival (OS) rates were 71.1 and 88.9%, respectively in the average-risk group (n = 9) and 66.7 and 71.1%, respectively in the high-risk group (n = 15). The PFS and OS rates were not significantly different between the average- and high-risk groups. In patients with medulloblastoma only, these rates were also not significantly different between the average- and high-risk groups. Three of four patients with sPNET were disease free. The height standard deviation score (SDS) was significantly decreased at the last assessment relative to that at diagnosis (P < 0.0001). The latest median height SDS was -1.6 (range, 0

Hypofractionated Image-Guided IMRT in Advanced Pancreatic Cancer With Simultaneous Integrated Boost to Infiltrated Vessels Concomitant With Capecitabine: A Phase I Study

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Passoni, Paolo, E-mail: passoni.paolo@hsr.it [Department of Radiation Oncology, San Raffaele Scientific Institute, Milan (Italy); Reni, Michele [Department of Medical Oncology, San Raffaele Scientific Institute, Milan (Italy); Cattaneo, Giovanni M. [Department of Medical Physics, San Raffaele Scientific Institute, Milan (Italy); Slim, Najla [Department of Radiation Oncology, San Raffaele Scientific Institute, Milan (Italy); Cereda, Stefano [Department of Medical Oncology, San Raffaele Scientific Institute, Milan (Italy); Balzano, Gianpaolo; Castoldi, Renato [Department of Surgery, San Raffaele Scientific Institute, Milan (Italy); Longobardi, Barbara [Department of Medical Physics, San Raffaele Scientific Institute, Milan (Italy); Bettinardi, Valentino; Gianolli, Luigi [Department of Nuclear Medicine, San Raffaele Scientific Institute, Milan (Italy); Gusmini, Simone [Department of Radiology, San Raffaele Scientific Institute, Milan (Italy); Staudacher, Carlo [Department of Surgery, San Raffaele Scientific Institute, Milan (Italy); Calandrino, Riccardo [Department of Medical Physics, San Raffaele Scientific Institute, Milan (Italy); Di Muzio, Nadia [Department of Radiation Oncology, San Raffaele Scientific Institute, Milan (Italy)

2013-12-01

Purpose: To determine the maximum tolerated radiation dose (MTD) of an integrated boost to the tumor subvolume infiltrating vessels, delivered simultaneously with radical dose to the whole tumor and concomitant capecitabine in patients with pretreated advanced pancreatic adenocarcinoma. Methods and Materials: Patients with stage III or IV pancreatic adenocarcinoma without progressive disease after induction chemotherapy were eligible. Patients underwent simulated contrast-enhanced four-dimensional computed tomography and fluorodeoxyglucose-labeled positron emission tomography. Gross tumor volume 1 (GTV1), the tumor, and GTV2, the tumor subvolume 1 cm around the infiltrated vessels, were contoured. GTVs were fused to generate Internal Target Volume (ITV)1 and ITV2. Biological tumor volume (BTV) was fused with ITV1 to create the BTV+Internal Target Volume (ITV) 1. A margin of 5/5/7 mm (7 mm in cranium-caudal) was added to BTV+ITV1 and to ITV2 to create Planning Target Volume (PTV) 1 and PTV2, respectively. Radiation therapy was delivered with tomotherapy. PTV1 received a fixed dose of 44.25 Gy in 15 fractions, and PTV2 received a dose escalation from 48 to 58 Gy as simultaneous integrated boost (SIB) in consecutive groups of at least 3 patients. Concomitant chemotherapy was capecitabine, 1250 mg/m{sup 2} daily. Dose-limiting toxicity (DLT) was defined as any treatment-related G3 nonhematological or G4 hematological toxicity occurring during the treatment or within 90 days from its completion. Results: From June 2005 to February 2010, 25 patients were enrolled. The dose escalation on the SIB was stopped at 58 Gy without reaching the MTD. One patient in the 2{sup nd} dose level (50 Gy) had a DLT: G3 acute gastric ulcer. Three patients had G3 late adverse effects associated with gastric and/or duodenal mucosal damage. All patients received the planned dose of radiation. Conclusions: A dose of 44.25 Gy in 15 fractions to the whole tumor with an SIB of 58 Gy to small

High risk of non-sentinel node metastases in a group of breast cancer patients with micrometastases in the sentinel node.

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Tvedskov, Tove Filtenborg; Jensen, Maj-Britt; Lisse, Ida Marie; Ejlertsen, Bent; Balslev, Eva; Kroman, Niels

2012-11-15

Axillary lymph node dissection (ALND) in breast cancer patients with positive sentinel nodes is under debate. We aimed to establish two models to predict non-sentinel node (NSN) metastases in patients with micrometastases or isolated tumor cells (ITC) in sentinel nodes, to guide the decision for ALND. A total of 1,577 breast cancer patients with micrometastases and 304 with ITC in sentinel nodes, treated by sentinel lymph node dissection and ALND in 2002-2008 were identified in the Danish Breast Cancer Cooperative Group database. Risk of NSN metastases was calculated according to clinicopathological variables in a logistic regression analysis. We identified tumor size, proportion of positive sentinel nodes, lymphovascular invasion, hormone receptor status and location of tumor in upper lateral quadrant of the breast as risk factors for NSN metastases in patients with micrometastases. A model based on these risk factors identified 5% of patients with a risk of NSN metastases on nearly 40%. The model was however unable to identify a subgroup of patients with a very low risk of NSN metastases. Among patients with ITC, we identified tumor size, age and proportion of positive sentinel nodes as risk factors. A model based on these risk factors identified 32% of patients with risk of NSN metastases on only 2%. Omission of ALND would be acceptable in this group of patients. In contrast, ALND may still be beneficial in the subgroup of patients with micrometastases and a high risk of NSN metastases. Copyright © 2012 UICC.

Kinome expression profiling of human neuroblastoma tumors identifies potential drug targets for ultra high-risk patients

NARCIS (Netherlands)

Russo, Roberta; Cimmino, Flora; Pezone, Lucia; Manna, Francesco; Avitabile, Marianna; Langella, Concetta; Koster, Jan; Casale, Fiorina; Raia, Maddalena; Viola, Giampietro; Fischer, Matthias; Iolascon, Achille; Capasso, Mario

2017-01-01

Neuroblastoma (NBL) accounts for >7% of malignancies in patients younger than 15 years. Low- and intermediate-risk patients exhibit excellent or good prognosis after treatment, whereas for high-risk (HR) patients, the estimated 5-year survival rates is still <40%. The ability to stratify HR patients

Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

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Plaga, Alexis; Shields, Lisa B.E. [Norton Neuroscience Institute, Louisville, KY (United States); Sun, David A.; Vitaz, Todd W. [Norton Neuroscience Institute, Louisville, KY (United States); Brain Tumor Center, Norton Healthcare, Louisville, KY (United States); Spalding, Aaron C., E-mail: acspalding1@gmail.com [Brain Tumor Center, Norton Healthcare, Louisville, KY (United States); Norton Cancer Institute, Radiation Center, Kosair Children' s Hospital, Louisville, KY (United States)

2012-10-01

Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

International Nuclear Information System (INIS)

Plaga, Alexis; Shields, Lisa B.E.; Sun, David A.; Vitaz, Todd W.; Spalding, Aaron C.

2012-01-01

Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

A single-center experience and review of the literature: 64 cases of phyllodes tumors to better understand risk factors and disease management.

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Lightner, Amy L; Shurell, Elizabeth; Dawson, Nicole; Omidvar, Yasaman; Foster, Nova

2015-03-01

Phyllodes tumors of the breast are rare fibroepithelial tumors that are characterized as benign, borderline, or malignant based on cellular characteristics such as stromal overgrowth and number of mitoses. Currently, there is a lack of consensus on risk factors and management of patients with phyllodes tumors, which has led to variation in treatment patterns as well as patient outcomes across many institutions. This study seeks to understand the clinicopathologic features, risk factors for local and metastatic recurrence, and clinical outcomes of patients with phyllodes tumors to better define optimal treatment patterns.

Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors

International Nuclear Information System (INIS)

Pape, H.; Glag, M.; Gripp, S.; Wittkamp, M.; Schmitt, G.; Laws, H.J.; Kaik, B. van; Goebel, U.; Burdach, S.; Juergens, H.

1999-01-01

Background: Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early ( [de

Complications of radiofrequency ablation for liver cancer in high-risk locations and their prevention

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ZHANG Junchao

2017-05-01

Full Text Available Radiofrequency ablation (RFA is one of the most important methods for the treatment of liver cancer and has the advantages of small trauma, simple operation, and repeatability. However, for tumors in high-risk locations within 5 mm of the first and second branches of the hepatic portal vein, near the hepatic vein, the inferior vena cava, or the gallbladder, within 5 mm of the intestinal tract, under the Glisson’s capsule, and in the diaphragm, RFA has the issues of a low complete ablation rate, a high local recurrence rate, and serious complications. This article introduces the complications of RFA for liver cancer in high-risk locations and their prevention and points out that with the promotion of individualized and standardized RFA, liver cancer in these high-risk locations is no longer a contradiction for RFA.

Pituitary tumor risk in relation to mobile phone use: A case-control study.

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Shrestha, Mithila; Raitanen, Jani; Salminen, Tiina; Lahkola, Anna; Auvinen, Anssi

2015-01-01

The number of mobile phone users has grown rapidly, which has generated mounting public concern regarding possible health hazards. This study aims to assess pituitary tumor risk, as it has rarely been investigated. A case-control study was conducted with 80 eligible cases identified from all five university hospitals in Finland and frequency-matched 240 controls from the national population register. Controls were matched to cases by age, sex, region of residence and date of interview. A detailed history of mobile phone use was obtained using a structured interview. Several indicators of mobile phone use were assessed using conditional logistic regression. A reduced odds ratio was seen among regular mobile phone users [OR 0.39, 95% confidence interval (CI) 0.21, 0.72] relative to never/non-regular users, possibly reflecting methodological limitations. Pituitary tumor risk was not increased after 10 or more years since first use (OR 0.69, 95% CI 0.25, 1.89). The risk was not increased in relation to duration, cumulative hours of use, or cumulative number of calls. The results were similar for analog and digital phones. We found no excess risk associated with self-reported short- or medium-term use of mobile phones. This is consistent with most of the published studies. However, uncertainties remained for longer duration of use, as a very small proportion of study participants reported use beyond 10 years.

Intermittent Hypoxia Is Associated With High Hypoxia Inducible Factor-1α but Not High Vascular Endothelial Growth Factor Cell Expression in Tumors of Cutaneous Melanoma Patients

Directory of Open Access Journals (Sweden)

Isaac Almendros

2018-04-01

Full Text Available Epidemiological associations linking between obstructive sleep apnea and poorer solid malignant tumor outcomes have recently emerged. Putative pathways proposed to explain that these associations have included enhanced hypoxia inducible factor (HIF-1α and vascular endothelial growth factor (VEGF cell expression in the tumor and altered immune functions via intermittent hypoxia (IH. Here, we examined relationships between HIF-1α and VEGF expression and nocturnal IH in cutaneous melanoma (CM tumor samples. Prospectively recruited patients with CM tumor samples were included and underwent overnight polygraphy. General clinical features, apnea–hypopnea index (AHI, desaturation index (DI4%, and CM characteristics were recorded. Histochemical assessments of VEGF and HIF-1α were performed, and the percentage of positive cells (0, <25, 25–50, 51–75, >75% was blindly tabulated for VEGF expression, and as 0, 0–5.9, 6.0–10.0, >10.0% for HIF-1α expression, respectively. Cases with HIF-1α expression >6% (high expression were compared with those <6%, and VEGF expression >75% of cells was compared with those with <75%. 376 patients were included. High expression of VEGF and HIF-1α were seen in 88.8 and 4.2% of samples, respectively. High expression of VEGF was only associated with increasing age. However, high expression of HIF-1α was significantly associated with age, Breslow index, AHI, and DI4%. Logistic regression showed that DI4% [OR 1.03 (95% CI: 1.01–1.06] and Breslow index [OR 1.28 (95% CI: 1.18–1.46], but not AHI, remained independently associated with the presence of high HIF-1α expression. Thus, IH emerges as an independent risk factor for higher HIF-1α expression in CM tumors and is inferentially linked to worse clinical CM prognostic indicators.

Childhood brain tumors: epidemiology, current management and future directions.

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Pollack, Ian F; Jakacki, Regina I

2011-07-26

Brain tumors are the most common solid tumors in children. With the increasingly widespread availability of MRI, the incidence of childhood brain tumors seemed to rise in the 1980s, but has subsequently remained relatively stable. However, management of brain tumors in children has evolved substantially during this time, reflecting refinements in classification of tumors, delineation of risk groups within histological subsets of tumors, and incorporation of molecular techniques to further define tumor subgroups. Although considerable progress has been made in the outcomes of certain tumors, prognosis in other childhood brain tumor types is poor. Among the tumor groups with more-favorable outcomes, attention has been focused on reducing long-term morbidity without sacrificing survival rates. Studies for high-risk groups have examined the use of intensive therapy or novel, molecularly targeted approaches to improve disease control rates. In addition to reviewing the literature and providing an overview of the complexities in diagnosing childhood brain tumors, we will discuss advances in the treatment and categorization of several tumor types in which progress has been most apparent, as well as those in which improvements have been lacking. The latest insights from molecular correlative studies that hold potential for future refinements in therapy will also be discussed.

Thick tumor capsule is a valuable risk factor for distant metastasis in follicular thyroid carcinoma.

Science.gov (United States)

Shimbashi, Wataru; Sugitani, Iwao; Kawabata, Kazuyoshi; Mitani, Hiroki; Toda, Kazuhisa; Yamada, Keiko; Sato, Yukiko

2018-02-01

While the biological behavior of follicular thyroid carcinoma (FTC) has been studied in great detail using clinical experience, few studies have investigated pre- or intraoperative factors related to the risk of distant metastasis (DM) among patients with FTC. The aim of this study was to analyze the characteristics of FTC with DM. This study retrospectively investigated 102 patients with FTC who underwent surgery between 1988 and 2013. We compared clinicopathological characteristics between FTC with and without DM. Univariate analysis revealed nodal metastasis (p=0.045), serum thyroglobulin (Tg) at initial operation (≥1000ng/ml; pthick tumor capsule (≥1mm; pthick tumor capsule (≥1mm), serum Tg at initial operation (≥1000ng/ml), and macroscopically widely invasive appearance as risk factors independently associated with development of DM. Patients with these risk factors should undergo total thyroidectomy and radioactive iodine ablation. Copyright © 2017 Elsevier B.V. All rights reserved.

Survivin Expression as a Predictive Marker for Local Control in Patients With High-Risk T1 Bladder Cancer Treated With Transurethral Resection and Radiochemotherapy

International Nuclear Information System (INIS)

Weiss, Christian; Roemer, Felix von; Capalbo, Gianni; Ott, Oliver J.; Wittlinger, Michael; Krause, Steffen F.; Sauer, Rolf; Roedel, Claus; Roedel, Franz

2009-01-01

Purpose: The objectives of this study were to investigate the expression of survivin in tumor samples from patients with high-risk T1 bladder cancer and to correlate its expression with clinicopathologic features as well as clinical outcomes after initial transurethral resection (TURBT) followed by radiotherapy (RT) or radiochemotherapy (RCT). Methods and Materials: Survivin protein expression was evaluated by immunohistochemistry on tumor specimen (n = 48) from the initial TURBT, and was correlated with clinical and histopathologic characteristics as well as with 5-year rates of local failure, tumor progression, and death from urothelial cancer after primary bladder sparring treatment with RT/RCT. Results: Survivin was not expressed in normal bladder urothelium but was overexpressed in 67% of T1 tumors. No association between survivin expression and clinicopathologic factors (age, gender, grading, multifocality, associated carcinoma in situ) could be shown. With a median follow-up of 27 months (range, 3-140 months), elevated survivin expression was significantly associated with an increased probability of local failure after TURBT and RCT/RT (p = 0.003). There was also a clear trend toward a higher risk of tumor progression (p = 0.07) and lower disease-specific survival (p = 0.10). Conclusions: High survivin expression is a marker of tumor aggressiveness and may help to identify a subgroup of patients with T1 bladder cancer at a high risk for recurrence when treated with primary organ-sparing approaches such as TURBT and RCT.

Identification of a Polyomavirus microRNA Highly Expressed in Tumors

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Chen, Chun Jung; Cox, Jennifer E.; Azarm, Kristopher; Wylie, Karen N.; Woolard, Kevin D.; Pesavento, Patricia A.; Sullivan, Christopher S.

2014-01-01

Polyomaviruses (PyVs) are associated with tumors including Merkel cell carcinoma (MCC). Several PyVs encode microRNAs (miRNAs) but to date no abundant PyV miRNAs have been reported in tumors. To better understand the function of the Merkel cell PyV (MCPyV) miRNA, we examined phylogenetically-related viruses for miRNA expression. We show that two primate PyVs and the more distantly-related raccoon PyV (RacPyV) encode miRNAs that share genomic position and partial sequence identity with MCPyV miRNAs. Unlike MCPyV miRNA in MCC, RacPyV miRNA is highly abundant in raccoon tumors. RacPyV miRNA negatively regulates reporters of early viral (T antigen) transcripts, yet robust viral miRNA expression is tolerated in tumors. We also identify raccoon miRNAs expressed in RacPyV-associated neuroglial brain tumors, including several likely oncogenic miRNAs (oncomiRs). This work describes the first PyV miRNA abundantly expressed in tumors and is consistent with a possible role for both host and viral miRNAs in RacPyV-associated tumors. PMID:25514573

Frequency and Risk Factors of Various Complications After Computed Tomography-Guided Radiofrequency Ablation of Lung Tumors

International Nuclear Information System (INIS)

Okuma, Tomohisa; Matsuoka, Toshiyuki; Yamamoto, Akira; Oyama, Yoshimasa; Toyoshima, Masami; Nakamura, Kenji; Inoue, Yuichi

2008-01-01

Objective. To retrospectively determine the frequency and risk factors of various side effects and complications after percutaneous computed tomography-guided radiofrequency (RF) ablation of lung tumors. Methods. We reviewed and analyzed records of 112 treatment sessions in 57 of our patients (45 men and 12 women) with unresectable lung tumors treated by ablation. Risk factors, including sex, age, tumor diameter, tumor location, history of surgery, presence of pulmonary emphysema, electrode gauge, array diameter, patient position, maximum power output, ablation time, and minimum impedance during ablation, were analyzed using univariate and multivariate analyses. Results. Total rates of side effects and minor and major complications occurred in 17%, 50%, and 8% of treatment sessions, respectively. Side effects, including pain during ablation (46% of sessions) and pleural effusion (13% of sessions), occurred with RF ablation. Minor complications, including pneumothorax not requiring chest tube drainage (30% of sessions), subcutaneous emphysema (16% of sessions), and hemoptysis (9% of sessions) also occurred after the procedure. Regarding major complications, three patients developed fever >38.5 deg. C; three patients developed abscesses; two patients developed pneumothorax requiring chest tube insertion; and one patient had air embolism and was discharged without neurologic deficit. Univariate and multivariate analyses suggested that a lesion located ≤1 cm of the chest wall was significantly related to pain (p < 0.01, hazard index 5.76). Risk factors for pneumothorax increased significantly with previous pulmonary surgery (p < 0.05, hazard index 6.1) and presence of emphysema (p <0.01, hazard index 13.6). Conclusion. The total complication rate for all treatment sessions was 58%, and 25% of patients did not have any complications after RF ablation. Although major complications can occur, RF ablation of lung tumors can be considered a safe and minimally invasive

BATH AND SHOWER EFFECTS IN THE RAT PAROTID GLAND EXPLAIN INCREASED RELATIVE RISK OF PAROTID GLAND DYSFUNCTION AFTER INTENSITY-MODULATED RADIOTHERAPY

NARCIS (Netherlands)

van Luijk, Peter; Faber, Hette; Schippers, Jacobus M.; Brandenburg, Sytze; Langendijk, Johannes A.; Meertens, Harm; Coppes, Robert P.

2009-01-01

Purpose: To assess in a rat model whether adding a subtolerance dose in a region adjacent to a high-dose irradiated subvolume of the parotid gland influences its response (bath-and-shower effect). Methods and Materials: Irradiation of the whole, cranial 50%, and/or the caudal 50% of the parotid

Overexpression of nuclear AR-V7 protein in primary prostate cancer is an independent negative prognostic marker in men with high-risk disease receiving adjuvant therapy.

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Chen, Xin; Bernemann, Christof; Tolkach, Yuri; Heller, Martina; Nientiedt, Cathleen; Falkenstein, Michael; Herpel, Esther; Jenzer, Maximilian; Grüllich, Carsten; Jäger, Dirk; Sültmann, Holger; Duensing, Anette; Perner, Sven; Cronauer, Marcus V; Stephan, Carsten; Debus, Jürgen; Schrader, Andres Jan; Kristiansen, Glen; Hohenfellner, Markus; Duensing, Stefan

2018-04-01

Overexpression of the androgen receptor (AR) splice variant 7 (AR-V7) has recently been reported to be associated with resistance to antihormonal therapy. Herein, we address the question whether tumor cells with AR-V7 expression can be detected at the time of radical prostatectomy, that is, before long-term hormonal manipulation and castration resistance, and what the potential prognostic impact on the biochemical recurrence (BCR)-free survival may be. An anti-AR-V7 antibody was first validated in a training set of prostate cancer specimens by a comparison of AR-V7 protein to AR-V7 mRNA expression. We then analyzed nuclear AR-V7 protein expression in the primary tumors and lymph node metastases from 163 predominantly high-risk patients (cohort I) as well as the primary tumors from patients of a second, consecutive patient cohort (n = 238, cohort II) not selected for any clinicopathological features. Staining results were correlated to patient characteristics and BCR-free patient survival. High nuclear AR-V7 protein expression was detected in approximately 30%-40% of patients in cohort I and II at the time of radical prostatectomy. High baseline expression of nuclear AR-V7 protein was associated with an unfavorable BCR-free survival in the high-risk patient cohort I but not in the unselected consecutive cohort II. Remarkably, AR-V7 was an independent negative prognostic factor in high-risk prostate cancer patients of cohort I who were selected to receive adjuvant treatment. Prostate cancer cells with high nuclear AR-V7 protein expression can be detected in a substantial proportion of tumors at the time of radical prostatectomy. The presence of AR-V7-positive tumor cells is associated with an unfavorable prognosis for BCR-free survival in a high-risk patient cohort including a subgroup of patients selected to receive adjuvant therapy, in which AR-V7 was an independent negative prognosticator. Overexpression of nuclear AR-V7 protein hence identifies a subset of tumors

Understanding PSA and its derivatives in prediction of tumor volume: Addressing health disparities in prostate cancer risk stratification.

Science.gov (United States)

Chinea, Felix M; Lyapichev, Kirill; Epstein, Jonathan I; Kwon, Deukwoo; Smith, Paul Taylor; Pollack, Alan; Cote, Richard J; Kryvenko, Oleksandr N

2017-03-28

To address health disparities in risk stratification of U.S. Hispanic/Latino men by characterizing influences of prostate weight, body mass index, and race/ethnicity on the correlation of PSA derivatives with Gleason score 6 (Grade Group 1) tumor volume in a diverse cohort. Using published PSA density and PSA mass density cutoff values, men with higher body mass indices and prostate weights were less likely to have a tumor volume PSA derivatives when predicting for tumor volume. In receiver operator characteristic analysis, area under the curve values for all PSA derivatives varied across race/ethnicity with lower optimal cutoff values for Hispanic/Latino (PSA=2.79, PSA density=0.06, PSA mass=0.37, PSA mass density=0.011) and Non-Hispanic Black (PSA=3.75, PSA density=0.07, PSA mass=0.46, PSA mass density=0.008) compared to Non-Hispanic White men (PSA=4.20, PSA density=0.11 PSA mass=0.53, PSA mass density=0.014). We retrospectively analyzed 589 patients with low-risk prostate cancer at radical prostatectomy. Pre-operative PSA, patient height, body weight, and prostate weight were used to calculate all PSA derivatives. Receiver operating characteristic curves were constructed for each PSA derivative per racial/ethnic group to establish optimal cutoff values predicting for tumor volume ≥0.5 cm3. Increasing prostate weight and body mass index negatively influence PSA derivatives for predicting tumor volume. PSA derivatives' ability to predict tumor volume varies significantly across race/ethnicity. Hispanic/Latino and Non-Hispanic Black men have lower optimal cutoff values for all PSA derivatives, which may impact risk assessment for prostate cancer.

Dietary Patterns and Risk of Colorectal Cancer: Analysis by Tumor Location and Molecular Subtypes.

Science.gov (United States)

Mehta, Raaj S; Song, Mingyang; Nishihara, Reiko; Drew, David A; Wu, Kana; Qian, Zhi Rong; Fung, Teresa T; Hamada, Tsuyoshi; Masugi, Yohei; da Silva, Annacarolina; Shi, Yan; Li, Wanwan; Gu, Mancang; Willett, Walter C; Fuchs, Charles S; Giovannucci, Edward L; Ogino, Shuji; Chan, Andrew T

2017-06-01

Western and prudent dietary patterns have been associated with higher and lower risks of colorectal cancer (CRC), respectively. However, little is known about the associations between dietary patterns and specific anatomic subsites or molecular subtypes of CRC. We used multivariable Cox proportional hazards models to examine the associations between Western and prudent dietary patterns and CRC risk in the Health Professionals Follow-up Study and Nurses' Health Study. After up to 32 years of follow-up of 137,217 men and women, we documented 3260 cases of CRC. Among individuals from whom subsite data were available, we observed 1264 proximal colon, 866 distal colon, and 670 rectal tumors. Western diet was associated with an increased incidence of CRC (P trend pattern, we observed a RR of 0.86 for overall CRC (95% CI, 0.77-0.95; P trend  = .01), with similar trends at anatomic subsites. However, the trend appeared stronger among men than women. Among 1285 cases (39%) with tissue available for molecular profiling, Western diet appeared to be more strongly associated with some CRC molecular subtypes (no mutations in KRAS [KRAS wildtype] or BRAF [BRAF wildtype], no or a low CpG island methylator phenotype, and microsatellite stability), although formal tests for heterogeneity did not produce statistically significant results. Western dietary patterns are associated with an increased risk of CRC, particularly distal colon and rectal tumors. Western dietary patterns also appear more strongly associated with tumors that are KRAS wildtype, BRAF wildtype, have no or a low CpG island methylator phenotype, and microsatellite stability. In contrast, prudent dietary patterns are associated with a lower risk of CRC that does not vary according to anatomic subsite or molecular subtype. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

High frequency of tumor cells with nuclear Egr-1 protein expression in human bladder cancer is associated with disease progression

International Nuclear Information System (INIS)

Egerod, Frederikke Lihme; Bartels, Annette; Fristrup, Niels; Borre, Michael; Ørntoft, Torben F; Oleksiewicz, Martin B; Brünner, Nils; Dyrskjøt, Lars

2009-01-01

Egr-1 (early growth response-1 transcription factor) has been proposed to be involved in invasion and metastasis processes of human bladder cancer, but Egr-1 protein expression levels in human bladder cancer have not been investigated. In the present study we investigated the expression levels of Egr-1 protein in early stages of human bladder cancer and correlated it to later progression. Expression of Egr-1 protein in human bladder cancer was examined by immunohistochemistry, on a tissue microarray constructed from tumors from 289 patients with non-muscle invasive urothelial bladder cancer. The frequency of tumor cells with nuclear Egr-1 immunolabelling correlated to bladder cancer stage, grade and to later progression to muscle-invasive bladder cancer (T2-4). Stage T1 tumors exhibited significantly higher frequencies of tumor cells with nuclear Egr-1 immunolabelling than Ta tumors (P = 0.001). Furthermore, Kaplan-Meier survival analysis showed that a high frequency of tumor cells with nuclear Egr-1 immunolabelling was significantly associated with a higher risk of progression to stage T2-4 (log-rank test, P = 0.035). Tumor cells with nuclear Egr-1 immunolabelling were found to localize at the tumor front in some of the tumor biopsies. The results from this study support a potential involvement of Egr-1 in the progression from non-muscle invasive bladder cancers to muscle invasive bladder cancer

Prenatal and Postnatal Medical Conditions and the Risk of Brain Tumors in Children and Adolescents

DEFF Research Database (Denmark)

Tettamanti, Giorgio; Shu, Xiaochen; Adel Fahmideh, Maral

2017-01-01

BACKGROUND: Previous studies have evaluated the effect of medical diagnostic radiation on brain tumors. Recent cohort studies have reported an increased risk associated with exposure to head CT scans. METHODS: Information regarding medical conditions, including prenatal and postnatal exposure...... to medical diagnostic radiation, was obtained from CEFALO, a multicenter case-control study performed in Denmark, Norway, Sweden, and Switzerland through face-to-face interview. Eligible cases of childhood and adolescent brain tumors (CABT) were ages 7 to 19 years, diagnosed between January 1, 2004...... and August 31, 2008, and living in the participating countries (n = 352). The cases were matched by age, sex, and region to 646 population-based controls. RESULTS: Prenatal exposure to medical diagnostic radiation and postnatal exposure to X-rays were not associated with CABTs. A higher risk estimate...

Awake Craniotomy for Tumor Resection: Further Optimizing Therapy of Brain Tumors.

Science.gov (United States)

Mehdorn, H Maximilian; Schwartz, Felix; Becker, Juliane

2017-01-01

In recent years more and more data have emerged linking the most radical resection to prolonged survival in patients harboring brain tumors. Since total tumor resection could increase postoperative morbidity, many methods have been suggested to reduce the risk of postoperative neurological deficits: awake craniotomy with the possibility of continuous patient-surgeon communication is one of the possibilities of finding out how radical a tumor resection can possibly be without causing permanent harm to the patient.In 1994 we started to perform awake craniotomy for glioma resection. In 2005 the use of intraoperative high-field magnetic resonance imaging (MRI) was included in the standard tumor therapy protocol. Here we review our experience in performing awake surgery for gliomas, gained in 219 patients.Patient selection by the operating surgeon and a neuropsychologist is of primary importance: the patient should feel as if they are part of the surgical team fighting against the tumor. The patient will undergo extensive neuropsychological testing, functional MRI, and fiber tractography in order to define the relationship between the tumor and the functionally relevant brain areas. Attention needs to be given at which particular time during surgery the intraoperative MRI is performed. Results from part of our series (without and with ioMRI scan) are presented.

Combined Scintigraphy and Tumor Marker Analysis Predicts Unfavorable Histopathology of Neuroblastic Tumors with High Accuracy.

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Wolfgang Peter Fendler

Full Text Available Our aim was to improve the prediction of unfavorable histopathology (UH in neuroblastic tumors through combined imaging and biochemical parameters.123I-MIBG SPECT and MRI was performed before surgical resection or biopsy in 47 consecutive pediatric patients with neuroblastic tumor. Semi-quantitative tumor-to-liver count-rate ratio (TLCRR, MRI tumor size and margins, urine catecholamine and NSE blood levels of neuron specific enolase (NSE were recorded. Accuracy of single and combined variables for prediction of UH was tested by ROC analysis with Bonferroni correction.34 of 47 patients had UH based on the International Neuroblastoma Pathology Classification (INPC. TLCRR and serum NSE both predicted UH with moderate accuracy. Optimal cut-off for TLCRR was 2.0, resulting in 68% sensitivity and 100% specificity (AUC-ROC 0.86, p < 0.001. Optimal cut-off for NSE was 25.8 ng/ml, resulting in 74% sensitivity and 85% specificity (AUC-ROC 0.81, p = 0.001. Combination of TLCRR/NSE criteria reduced false negative findings from 11/9 to only five, with improved sensitivity and specificity of 85% (AUC-ROC 0.85, p < 0.001.Strong 123I-MIBG uptake and high serum level of NSE were each predictive of UH. Combined analysis of both parameters improved the prediction of UH in patients with neuroblastic tumor. MRI parameters and urine catecholamine levels did not predict UH.

Differential diagnosis between benign and malignant soft tissue tumors utilizing ultrasound parameters.

Science.gov (United States)

Morii, Takeshi; Kishino, Tomonori; Shimamori, Naoko; Motohashi, Mitsue; Ohnishi, Hiroaki; Honya, Keita; Aoyagi, Takayuki; Tajima, Takashi; Ichimura, Shoichi

2018-01-01

Preoperative discrimination between benign and malignant soft tissue tumors is critical for the prevention of excess application of magnetic resonance imaging and biopsy as well as unplanned resection. Although ultrasound, including power Doppler imaging, is an easy, noninvasive, and cost-effective modality for screening soft tissue tumors, few studies have investigated reliable discrimination between benign and malignant soft tissue tumors. To establish a modality for discrimination between benign and malignant soft tissue tumors using ultrasound, we extracted the significant risk factors for malignancy based on ultrasound information from 40 malignant and 56 benign pathologically diagnosed soft tissue tumors and established a scoring system based on these risk factors. The maximum size, tumor margin, and vascularity evaluated using ultrasound were extracted as significant risk factors. Using the odds ratio from a multivariate regression model, a scoring system was established. Receiver operating characteristic analyses revealed a high area under the curve value (0.85), confirming the accuracy of the scoring system. Ultrasound is a useful modality for establishing the differential diagnosis between benign and malignant soft tissue tumors.

Projected Second Tumor Risk and Dose to Neurocognitive Structures After Proton Versus Photon Radiotherapy for Benign Meningioma

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Arvold, Nils D. [Harvard Radiation Oncology Program, Harvard Medical School, Boston, MA (United States); Niemierko, Andrzej; Broussard, George P.; Adams, Judith; Fullerton, Barbara; Loeffler, Jay S. [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States); Shih, Helen A., E-mail: hshih@partners.org [Department of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School, Boston, MA (United States)

2012-07-15

Purpose: To calculated projected second tumor rates and dose to organs at risk (OAR) in patients with benign intracranial meningioma (BM), according to dosimetric comparisons between proton radiotherapy (PRT) and photon radiotherapy (XRT) treatment plans. Methods and Materials: Ten patients with BM treated at Massachusetts General Hospital during 2006-2010 with PRT were replanned with XRT (intensity-modulated or three-dimensional conformal radiotherapy), optimizing dose to the tumor while sparing OAR. Total dose was 54 Gy in 1.8 Gy per fraction for all plans. We calculated equivalent uniform doses, normal tissue complication probabilities, and whole brain-based estimates of excess risk of radiation-associated intracranial second tumors. Results: Excess risk of second tumors was significantly lower among PRT compared with XRT plans (1.3 vs. 2.8 per 10,000 patients per year, p < 0.002). Mean equivalent uniform doses were lower among PRT plans for the whole brain (19.0 vs. 22.8 Gy, p < 0.0001), brainstem (23.8 vs. 35.2 Gy, p = 0.004), hippocampi (left, 13.5 vs. 25.6 Gy, p < 0.0001; right, 7.6 vs. 21.8 Gy, p = 0.001), temporal lobes (left, 25.8 vs. 34.6 Gy, p = 0.007; right, 25.8 vs. 32.9 Gy, p = 0.008), pituitary gland (29.2 vs. 37.0 Gy, p = 0.047), optic nerves (left, 28.5 vs. 33.8 Gy, p = 0.04; right, 25.1 vs. 31.1 Gy, p = 0.07), and cochleas (left, 12.2 vs. 15.8 Gy, p = 0.39; right,1.5 vs. 8.8 Gy, p = 0.01). Mean normal tissue complication probability was <1% for all structures and not significantly different between PRT and XRT plans. Conclusions: Compared with XRT, PRT for BM decreases the risk of RT-associated second tumors by half and delivers significantly lower doses to neurocognitive and critical structures of vision and hearing.

Projected Second Tumor Risk and Dose to Neurocognitive Structures After Proton Versus Photon Radiotherapy for Benign Meningioma

International Nuclear Information System (INIS)

Arvold, Nils D.; Niemierko, Andrzej; Broussard, George P.; Adams, Judith; Fullerton, Barbara; Loeffler, Jay S.; Shih, Helen A.

2012-01-01

Purpose: To calculated projected second tumor rates and dose to organs at risk (OAR) in patients with benign intracranial meningioma (BM), according to dosimetric comparisons between proton radiotherapy (PRT) and photon radiotherapy (XRT) treatment plans. Methods and Materials: Ten patients with BM treated at Massachusetts General Hospital during 2006–2010 with PRT were replanned with XRT (intensity-modulated or three-dimensional conformal radiotherapy), optimizing dose to the tumor while sparing OAR. Total dose was 54 Gy in 1.8 Gy per fraction for all plans. We calculated equivalent uniform doses, normal tissue complication probabilities, and whole brain–based estimates of excess risk of radiation-associated intracranial second tumors. Results: Excess risk of second tumors was significantly lower among PRT compared with XRT plans (1.3 vs. 2.8 per 10,000 patients per year, p < 0.002). Mean equivalent uniform doses were lower among PRT plans for the whole brain (19.0 vs. 22.8 Gy, p < 0.0001), brainstem (23.8 vs. 35.2 Gy, p = 0.004), hippocampi (left, 13.5 vs. 25.6 Gy, p < 0.0001; right, 7.6 vs. 21.8 Gy, p = 0.001), temporal lobes (left, 25.8 vs. 34.6 Gy, p = 0.007; right, 25.8 vs. 32.9 Gy, p = 0.008), pituitary gland (29.2 vs. 37.0 Gy, p = 0.047), optic nerves (left, 28.5 vs. 33.8 Gy, p = 0.04; right, 25.1 vs. 31.1 Gy, p = 0.07), and cochleas (left, 12.2 vs. 15.8 Gy, p = 0.39; right,1.5 vs. 8.8 Gy, p = 0.01). Mean normal tissue complication probability was <1% for all structures and not significantly different between PRT and XRT plans. Conclusions: Compared with XRT, PRT for BM decreases the risk of RT-associated second tumors by half and delivers significantly lower doses to neurocognitive and critical structures of vision and hearing.

Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation.

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Plaga, Alexis; Shields, Lisa B E; Sun, David A; Vitaz, Todd W; Spalding, Aaron C

2012-01-01

Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

Allele-specific deletions in mouse tumors identify Fbxw7 as germline modifier of tumor susceptibility.

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Jesus Perez-Losada

Full Text Available Genome-wide association studies (GWAS have been successful in finding associations between specific genetic variants and cancer susceptibility in human populations. These studies have identified a range of highly statistically significant associations between single nucleotide polymorphisms (SNPs and susceptibility to development of a range of human tumors. However, the effect of each SNP in isolation is very small, and all of the SNPs combined only account for a relatively minor proportion of the total genetic risk (5-10%. There is therefore a major requirement for alternative routes to the discovery of genetic risk factors for cancer. We have previously shown using mouse models that chromosomal regions harboring susceptibility genes identified by linkage analysis frequently exhibit allele-specific genetic alterations in tumors. We demonstrate here that the Fbxw7 gene, a commonly mutated gene in a wide range of mouse and human cancers, shows allele-specific deletions in mouse lymphomas and skin tumors. Lymphomas from three different F1 hybrids show 100% allele-specificity in the patterns of allelic loss. Parental alleles from 129/Sv or Spretus/Gla mice are lost in tumors from F1 hybrids with C57BL/6 animals, due to the presence of a specific non-synonymous coding sequence polymorphism at the N-terminal portion of the gene. A specific genetic test of association between this SNP and lymphoma susceptibility in interspecific backcross mice showed a significant linkage (p = 0.001, but only in animals with a functional p53 gene. These data therefore identify Fbxw7 as a p53-dependent tumor susceptibility gene. Increased p53-dependent tumor susceptibility and allele-specific losses were also seen in a mouse skin model of skin tumor development. We propose that analysis of preferential allelic imbalances in tumors may provide an efficient means of uncovering genetic variants that affect mouse and human tumor susceptibility.

Conjunctival Melanocytic Tumors-New Developments

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Hülya Gökmen Soysal

2014-09-01

Full Text Available Melanocytic lesions of the conjunctiva represent a wide spectrum of tumors that include benign, premalignant, and malignant tumors. There are many ongoing arguments about the definition, classification, and therapeutic options of the conjunctival melanocytic tumors with many different suggestions. Conjunctival nevi are the most common melanocytic tumors and their risk of malignant transformation is less than1%. Primary acquired melanosis (PAM histopathologically includes various types of lesions from increased melanin pigmentation without melanocyte proliferation to melanoma in situ and is accepted as a clinical definition, so that a new classification is recommended which is based on more objective criteria than before. Although conjunctival melanoma is seen rarely, it is associated with a high mortality rate. Management of these tumors mainly involves surgery and adjuvant topical chemotherapy, cryotherapy, and radiation therapy that help improving the survival, however, new options are being investigated related to genetic and molecular researches. (Turk J Ophthalmol 2014; 44: Supplement 15-21

Primary intracranial tumors among atomic bomb survivors and controls, Hiroshima and Nagasaki, 1961-75

International Nuclear Information System (INIS)

Seyama, Shinichi; Ishimaru, Toranosuke; Iijima, Soichi; Mori, Kazuo.

1980-02-01

An analysis was made of the relationship of radiation dose to the occurrence of primary intracranial tumors among atomic bomb survivors and nonexposed controls, Hiroshima and Nagasaki, in the fixed cohort of the Life Span Study (LSS) extended sample during the period 1961-75, or 16 to 30 years after the A-bombs. Based on various medical sources, 104 cases of primary intracranial tumors were identified among approximately 99,000 LSS extended sample members who were alive as of 1 January 1961. Of these 104 cases, 45 had manifested clinical signs of brain tumors, but, 59 cases were identified incidentally at postmortem examination. The distributions of morphologic type, age, and size of tumor were quite different for those primary intracranial tumors with and without a clinical sign of brain tumor. Glioma was the most frequent type of tumor with a clinical sign and meningioma was the most frequent type without. In relation to radiation dose the incidence rate of primary intracranial tumors with a clinical sign showed a significant excess risk for males in the high dose group who received 100 rad or more after adjustment for age at the time of the bomb (ATB). The standardized relative risk is around 5 in this group. The data also suggest that the crude relative risk of glioma is greater in the high dose group for younger ages ATB. However, there is no increased risk in females. Among the 5,012 autopsy subjects in the LSS extended sample during 1961-75, there is no relationship between radiation dose and the prevalence rate of primary intracranial tumors in those identified incidentally by autopsy. The relative risk of subclinical adenoma of the pituitary gland between high dose subjects and controls was also examined for a sample of 95 sex- and age-matched pairs using Hiroshima autopsy materials for 1961-74, but no relationship to dose was observed. (author)

High-Risk List

Science.gov (United States)

2017-01-01

economy. The World Bank has said that “corruption creates an unfavorable business environment by undermining the operation efficiency of firms and... Bank Began as ‘Ponzi Scheme,’” 11/27/2012. 64 Independent Joint Anti-Corruption Monitoring and Evaluation Committee, Unfinished Business : The Follow...HIGH RISK AREA 7: Oversight 51 HIGH-RISK AREA 8: Strategy and Planning 55 CONCLUSION HIGH RISK LIST I JANUARY 11, 2017 2 EXECUTIVE SUMMARY

WE-E-17A-05: Complementary Prognostic Value of CT and 18F-FDG PET Non-Small Cell Lung Cancer Tumor Heterogeneity Features Quantified Through Texture Analysis

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Desseroit, M; Cheze Le Rest, C; Tixier, F [CHU Poitiers Poitiers (France); INSERM LaTIM UMR 1101, Brest (France); Majdoub, M; Visvikis, D; Hatt, M [INSERM LaTIM UMR 1101, Brest (France); Guillevin, R; Perdrisot, R [CHU Poitiers Poitiers (France)

2014-06-15

Purpose: Previous studies have shown that CT or 18F-FDG PET intratumor heterogeneity features computed using texture analysis may have prognostic value in Non-Small Cell Lung Cancer (NSCLC), but have been mostly investigated separately. The purpose of this study was to evaluate the potential added value with respect to prognosis regarding the combination of non-enhanced CT and 18F-FDG PET heterogeneity textural features on primary NSCLC tumors. Methods: One hundred patients with non-metastatic NSCLC (stage I–III), treated with surgery and/or (chemo)radiotherapy, that underwent staging 18F-FDG PET/CT images, were retrospectively included. Morphological tumor volumes were semi-automatically delineated on non-enhanced CT using 3D SlicerTM. Metabolically active tumor volumes (MATV) were automatically delineated on PET using the Fuzzy Locally Adaptive Bayesian (FLAB) method. Intratumoral tissue density and FDG uptake heterogeneities were quantified using texture parameters calculated from co-occurrence, difference, and run-length matrices. In addition to these textural features, first order histogram-derived metrics were computed on the whole morphological CT tumor volume, as well as on sub-volumes corresponding to fine, medium or coarse textures determined through various levels of LoG-filtering. Association with survival regarding all extracted features was assessed using Cox regression for both univariate and multivariate analysis. Results: Several PET and CT heterogeneity features were prognostic factors of overall survival in the univariate analysis. CT histogram-derived kurtosis and uniformity, as well as Low Grey-level High Run Emphasis (LGHRE), and PET local entropy were independent prognostic factors. Combined with stage and MATV, they led to a powerful prognostic model (p<0.0001), with median survival of 49 vs. 12.6 months and a hazard ratio of 3.5. Conclusion: Intratumoral heterogeneity quantified through textural features extracted from both CT and FDG PET

Neuroblastoma: treatment outcome after incomplete resection of primary tumors.

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Moon, Suk-Bae; Park, Kwi-Won; Jung, Sung-Eun; Youn, Woong-Jae

2009-09-01

For International Neuroblastoma Staging System (INSS) stages III or IV neuroblastoma (intermediate or high risk), complete excision of the primary tumor is not always feasible. Most current studies on the treatment outcome of these patients have reported on the complete excision status. The aim of this study is to review the treatment outcome after the incomplete resection. The medical records of 37 patients that underwent incomplete resection between January 1986 and December 2005 were reviewed retrospectively. Incomplete resection was assessed by review of the operative notes and postoperative computerized tomography. Age, gender, tumor location, INSS stage, N-myc gene copy number, pre- and postoperative therapy, and treatment outcome were reviewed. The treatment outcome was evaluated according to the postoperative treatment protocol in the high-risk group. Intermediate-risk patients were treated with conventional chemotherapy, isotretinoin (ITT) and interleukin-2 (IL-2). High-risk patients were treated with peripheral blood stem cell transplantation (PBSCT), ITT, and IL-2 (N = 11). Before the introduction of PBSCT, the high-risk patients were also treated with the conventional chemotherapy (N = 19). Intermediate-risk patients (N = 5) currently have no evidence of disease (NED). For the high-risk patients (N = 32), 19 patients were treated with chemotherapy alone; 15 patients died of their disease while four patients currently have an NED status. Eight of 11 patients that underwent PBSCT are currently alive. For intermediate risk, conventional chemotherapy appears to be acceptable treatment. However, for high-risk patients, every effort should be made to control residual disease including the use of myeloablative chemotherapy, differentiating agents and immune-modulating agents.

Will parental exposure to radiation induce tumor in sibling ?

International Nuclear Information System (INIS)

Watanabe, Hiromitsu; Takahashi, Tadateru; Toyota, Kazuhiro; Ito, Akihiro

1991-01-01

There are reports of possible risk of transmission of genetic trait(s) through the germ cell in acquired cancer from parent to sibling. We have confirmed that paternal exposure to 252 Cf neutron irradiation in mice induced sperm abnormality leading to dominant lethals and liver tumors at F 1 offspring. On the other hand, C3H male mice have been known to have high incidence of spontaneous hepatic tumors and increased hepatic tumor risk in F 1 offsprings maybe caused by the genetic transmission of the hepatoma-inducible-trait amplified by 252 Cf neutron irradiation. The present paper describes that paternal exposure to X-ray or chemicals induces heritable characteristics including anomalies and tumors in some special strains of mice and rats. Some possible mechanisms of transmission of genetic trait(s) are also discussed. (author) 52 refs

The Risk of Radiation-Induced Tumors or Malignant Transformation After Single-Fraction Intracranial Radiosurgery: Results Based on a 25-Year Experience

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Pollock, Bruce E., E-mail: pollock.bruce@mayo.edu [Department of Neurological Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota (United States); Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota (United States); Link, Michael J. [Department of Neurological Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota (United States); Department of Otorhinolaryngology, Mayo Clinic College of Medicine, Rochester, Minnesota (United States); Stafford, Scott L. [Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota (United States); Parney, Ian F. [Department of Neurological Surgery, Mayo Clinic College of Medicine, Rochester, Minnesota (United States); Garces, Yolanda I.; Foote, Robert L. [Department of Radiation Oncology, Mayo Clinic College of Medicine, Rochester, Minnesota (United States)

2017-04-01

Purpose: To determine the risk of radiation-induced tumors or malignant transformation after single-fraction intracranial stereotactic radiosurgery (SRS). Methods and Materials: We performed a retrospective review of 1837 patients who received single-fraction SRS for arteriovenous malformation or benign tumor (meningioma, vestibular schwannoma, pituitary adenoma, glomus tumor) at a single center between 1990 and 2009. Patients were excluded if they refused research authorization (n=31), had a genetic predisposition to tumor development (n=84), received prior or concurrent radiation therapy (n=79), or had less than 5 years of imaging follow-up after SRS (n=501). The median imaging follow-up period for the remaining 1142 patients was 9.0 years (range, 5-24.9 years). Results: No radiation-induced tumors were identified in 11,264 patient-years of follow-up after SRS. The risk of a radiation-induced tumor developing after SRS was 0.0% at 5 years (95% confidence interval [CI], 0.0%-0.4%), 0.0% at 10 years (95% CI, 0.0%-0.9%), and 0.0% at 15 years (95% CI, 0.0%-2.8%). Malignant transformation occurred in 7 of 316 meningioma patients (2.2%) and 1 of 358 vestibular schwannoma patients (0.3%) at a median of 4.9 years (range, 2.8-13.8 years) after SRS. No cases of malignant transformation were noted in patients with pituitary adenomas (n=188) or glomus tumors (n=47). The 5-, 10-, and 15-year risk of malignant transformation was 0.5% (95% CI, 0.0%-0.9%), 0.8% (95% CI, 0.0%-1.8%), and 2.4% (95% CI, 0.0%-5.5%), respectively. Patients who underwent prior resection (hazard ratio, 14.56; 95% CI, 1.79-118.33; P=.01) and who had meningioma pathology (hazard ratio, 11.72; 95% CI, 1.44-96.15; P=.02) were at increased risk of malignant transformation. Conclusions: The risk of radiation-induced tumors or malignant transformation after SRS is very low and should not be used as a justification for choosing alternative treatment approaches (surgical resection, observation) over SRS

The Risk of Radiation-Induced Tumors or Malignant Transformation After Single-Fraction Intracranial Radiosurgery: Results Based on a 25-Year Experience

International Nuclear Information System (INIS)

Pollock, Bruce E.; Link, Michael J.; Stafford, Scott L.; Parney, Ian F.; Garces, Yolanda I.; Foote, Robert L.

2017-01-01

Purpose: To determine the risk of radiation-induced tumors or malignant transformation after single-fraction intracranial stereotactic radiosurgery (SRS). Methods and Materials: We performed a retrospective review of 1837 patients who received single-fraction SRS for arteriovenous malformation or benign tumor (meningioma, vestibular schwannoma, pituitary adenoma, glomus tumor) at a single center between 1990 and 2009. Patients were excluded if they refused research authorization (n=31), had a genetic predisposition to tumor development (n=84), received prior or concurrent radiation therapy (n=79), or had less than 5 years of imaging follow-up after SRS (n=501). The median imaging follow-up period for the remaining 1142 patients was 9.0 years (range, 5-24.9 years). Results: No radiation-induced tumors were identified in 11,264 patient-years of follow-up after SRS. The risk of a radiation-induced tumor developing after SRS was 0.0% at 5 years (95% confidence interval [CI], 0.0%-0.4%), 0.0% at 10 years (95% CI, 0.0%-0.9%), and 0.0% at 15 years (95% CI, 0.0%-2.8%). Malignant transformation occurred in 7 of 316 meningioma patients (2.2%) and 1 of 358 vestibular schwannoma patients (0.3%) at a median of 4.9 years (range, 2.8-13.8 years) after SRS. No cases of malignant transformation were noted in patients with pituitary adenomas (n=188) or glomus tumors (n=47). The 5-, 10-, and 15-year risk of malignant transformation was 0.5% (95% CI, 0.0%-0.9%), 0.8% (95% CI, 0.0%-1.8%), and 2.4% (95% CI, 0.0%-5.5%), respectively. Patients who underwent prior resection (hazard ratio, 14.56; 95% CI, 1.79-118.33; P=.01) and who had meningioma pathology (hazard ratio, 11.72; 95% CI, 1.44-96.15; P=.02) were at increased risk of malignant transformation. Conclusions: The risk of radiation-induced tumors or malignant transformation after SRS is very low and should not be used as a justification for choosing alternative treatment approaches (surgical resection, observation) over SRS

Microsatellite instability as prognostic marker in bladder tumors: a clinical significance

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Mittal RD

2005-01-01

Full Text Available Abstract Background Carcinoma of urinary bladder is one of the leading causes of death in India. Successful treatment of bladder cancer depends on the early detection & specific diagnostic approaches. In the present study, microsatellite instability (MSI has been evaluated as a prognostic marker in patients with superficial urinary bladder cancer in lower urinary tract for determining risk of recurrence. Methods A total of 44 patients with bladder tumors diagnosed with Transitional Cell Carcinomas [TCC] from lower urinary tract were selected for the study. Tumors were staged and graded according to AJCC-UICC (1997 classification and patients were followed with cystoscopy as per the protocol. Polymerase chain reaction (PCR was done to amplify microsatellite sequences at mononucleotide BAT – 26, BAT – 40, TGFβ RII, IGFIIR, hMSH3, BAX and dinucleotide D2S123, D9S283, D9S1851 and D18S58 loci in blood (control and tumor DNA. PCR products were separated on 8% denaturing polyacrylamide gel and visualized by autoradiography. Results MSI was observed in 72.7% of tumors at BAT – 26, BAT – 40, D2S123, D9S283, D9S1851 and D18S58 loci. Good association of MSI was seen with tumor stage and grade. MSI – High (instability at > 30% of loci was frequently observed in high stage (40.6% and high grade (59.4% tumors. Of 24 tumors of Ta-T1 stage with different grades, 11 (9/18 high grade and 2/6 low grade tumors recurred in the mean duration of 36 months. MSI positivity was significantly high in patients who had one or more recurrences (p = 0.02 for high grade and 0.04 for low grade tumors. Conclusions MSI may be an independent prognostic marker for assessing risk of recurrence in superficial tumors irrespective of the grade. Further studies on progression would help in stratifying the patients of T1G3 for early cystectomy vs bladder preservation protocol.

Highly-sensitive and large-dynamic diffuse optical tomography system for breast tumor detection

Science.gov (United States)

Du, Wenwen; Zhang, Limin; Yin, Guoyan; Zhang, Yanqi; Zhao, Huijuan; Gao, Feng

2018-02-01

Diffuse optical tomography (DOT) as a new functional imaging has important clinical applications in many aspects such as benign and malignant breast tumor detection, tumor staging and so on. For quantitative detection of breast tumor, a three-wavelength continuous-wave DOT prototype system combined the ultra-high sensitivity of the photon-counting detection and the measurement parallelism of the lock-in technique was developed to provide high temporal resolution, high sensitivity, large dynamic detection range and signal-to-noise ratio. Additionally, a CT-analogous scanning mode was proposed to cost-effectively increase the detection data. To evaluate the feasibility of the system, a series of assessments were conducted. The results demonstrate that the system can obtain high linearity, stability and negligible inter-wavelength crosstalk. The preliminary phantom experiments show the absorption coefficient is able to be successfully reconstructed, indicating that the system is one of the ideal platforms for optical breast tumor detection.

High Intra- and Inter-Tumoral Heterogeneity of RAS Mutations in Colorectal Cancer

Directory of Open Access Journals (Sweden)

Marion Jeantet

2016-12-01

Full Text Available Approximately 30% of patients with wild type RAS metastatic colorectal cancer are non-responders to anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR mAbs, possibly due to undetected tumoral subclones harboring RAS mutations. The aim of this study was to analyze the distribution of RAS mutations in different areas of the primary tumor, metastatic lymph nodes and distant metastasis. A retrospective cohort of 18 patients with a colorectal cancer (CRC was included in the study. Multiregion analysis was performed in 60 spatially separated tumor areas according to the pathological tumor node metastasis (pTNM staging and KRAS, NRAS and BRAF mutations were tested using pyrosequencing. In primary tumors, intra-tumoral heterogeneity for RAS mutation was found in 33% of cases. Inter-tumoral heterogeneity for RAS mutation between primary tumors and metastatic lymph nodes or distant metastasis was found in 36% of cases. Moreover, 28% of tumors had multiple RAS mutated subclones in the same tumor. A high proportion of CRCs presented intra- and/or inter-tumoral heterogeneity, which has relevant clinical implications for anti-EGFR mAbs prescription. These results suggest the need for multiple RAS testing in different parts of the same tumor and/or more sensitive techniques.

Transcription instability in high-risk neuroblastoma is associated with a global perturbation of chromatin domains.

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Zanon, Carlo; Tonini, Gian Paolo

2017-11-01

Chromosome instability has a pivotal role among the hallmarks of cancer, but its transcriptional counterpart is rarely considered a relevant factor in cell destabilization. To examine transcription instability (TIN), we first devised a metric we named TIN index and used it to evaluate TIN on a dataset containing more than 500 neuroblastoma samples. We found that metastatic tumors from high-risk (HR) patients are characterized by significantly different TIN index values compared to low/intermediate-risk patients. Our results indicate that the TIN index is a good predictor of neuroblastoma patient's outcome, and a related TIN index gene signature (TIN-signature) is also able to predict the neuroblastoma patient's outcome with high confidence. Interestingly, we find that TIN-signature genes have a strong positional association with superenhancers in neuroblastoma tumors. Finally, we show that TIN is linked to chromatin structural domains and interferes with their integrity in HR neuroblastoma patients. This novel approach to gene expression analysis broadens the perspective of genome instability investigations to include functional aspects. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model

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Maeda, Azusa [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Wouters, Bradly G. [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario (Canada); DaCosta, Ralph S., E-mail: rdacosta@uhnres.utoronto.ca [Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario (Canada); Department of Medical Biophysics, University of Toronto, Toronto, Ontario (Canada); Techna Institute, University Health Network, Toronto, Ontario (Canada)

2017-01-01

Purpose: To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. Methods and Materials: A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. Results: In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Conclusions: Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy.

Validating Bioluminescence Imaging as a High-Throughput, Quantitative Modality for Assessing Tumor Burden

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Zain Paroo

2004-04-01

Full Text Available Bioluminescence imaging (BLI is a highly sensitive tool for visualizing tumors, neoplastic development, metastatic spread, and response to therapy. Although BLI has engendered much excitement due to its apparent simplicity and ease of implementation, few rigorous studies have been presented to validate the measurements. Here, we characterize the nature of bioluminescence output from mice bearing subcutaneous luciferase-expressing tumors over a 4-week period. Following intraperitoneal or direct intratumoral administration of luciferin substrate, there was a highly dynamic kinetic profile of light emission. Although bioluminescence was subject to variability, strong correlations (r > .8, p < .001 between caliper measured tumor volumes and peak light signal, area under light signal curve and light emission at specific time points were determined. Moreover, the profile of tumor growth, as monitored with bioluminescence, closely resembled that for caliper measurements. The study shows that despite the dynamic and variable nature of bioluminescence, where appropriate experimental precautions are taken, single time point BLI may be useful for noninvasive, high-throughput, quantitative assessment of tumor burden.

Risk-adapted single or fractionated stereotactic high-precision radiotherapy in a pooled series of nonfunctioning pituitary adenomas. High local control and low toxicity

International Nuclear Information System (INIS)

Bostroem, Jan Patrick; Meyer, Almuth; Pintea, Bogdan; Gerlach, Ruediger; Surber, Gunnar; Hamm, Klaus; Lammering, Guido

2014-01-01

The purpose of this work was to evaluate a prospectively initiated two-center protocol of risk-adapted single-fraction (SRS) or fractionated radiotherapy (SRT) in patients with nonsecretory pituitary adenomas (NSA). A total of 73 NSA patients (39 men/34 women) with a median age of 62 years were prospectively included in a treatment protocol of SRS [planning target volume (PTV) 2 mm to optic pathways = low risk] or SRT (PTV ≥ 4 ccm, ≤ 2 mm to optic pathways = high risk) in two Novalis registered centers. Mean tumor volume was 7.02 ccm (range 0.58-57.29 ccm). Based on the protocol guidelines, 5 patients were treated with SRS and 68 patients with SRT. Median follow-up (FU) reached 5 years with 5-year overall survival (OS) of 90.4 % (CI 80.2-95 %) and 5-year local control and progression-free survival rates of 100 % (CI 93.3-100 %) and 90.4 % (CI 80.2-95 %), respectively. A post-SRS/SRT new visual disorder occurred in 2 patients (2.7 %), a new oculomotor nerve palsy in one pre-irradiated patient, in 3 patients (4.1 %) a pre-existing visual disorder improved. New complete hypopituitarism occurred in 4 patients (13.8 %) and in 3 patients (25 %) with pre-existing partial hypopituitarism. Pituitary function in 26 % of patients retained normal. Patients with tumor shrinkage (65.75 %) had a significantly longer FU (p = 0.0093). Multivariate analysis confirmed correlation of new hypopituitarism with duration of FU (p = 0.008) and correlation of new hypopituitarism and tumor volume (p = 0.023). No significant influence factors for occurrence of visual disorders were found. Our SRS/SRT protocol proved to be safe and successful in terms of tumor control and protection of the visual system, especially for large tumors located close to optic pathways. (orig.) [de

Specific features of Brodie’s tumors

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D. A. Denchik

2010-01-01

Full Text Available Brodie’s tumors are comparatively rare in oncological care and difficult-to-diagnose masses with an unpredictable course, predilection for recurrences, and a high probability of malignization. These tumors have a two-component structure with the predominant develop- ment of a connective tissue component that is absolute in sarcomas and, in a group of fibroepithelial tumors, combines with the parallel development of epithelial tissue.The etiology of Brodie’s tumor is unclear, so is its pathogenesis. Molecular genetic studies have shown that the carriers of germ line missence-mutation R1699W in the BRCA1 gene have an increased risk of developing malignant Brodie’s tumor, but allele losses at the D22S264 locus of the TP5 gene determine the progression of the disease. Deletion of the short-arm of chromosome 1 (1p and allelic imbalance are associated with the more aggressive course and recurrences of Brodie’s tumor.A complex clinicomorphological and molecular genetic study will help answer some questions concerning the diagnosis and treatment of Brodie’s tumors.

Maternal hormone levels and risk of cryptorchism among populations at high and low risk of testicular germ cell tumors.

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McGlynn, Katherine A; Graubard, Barry I; Nam, Jun-Mo; Stanczyk, Frank Z; Longnecker, Matthew P; Klebanoff, Mark A

2005-07-01

Cryptorchism is one of the few well-described risk factors for testicular cancer. It has been suggested that both conditions are related to increased in utero estrogen exposure. The evidence supporting the "estrogen hypothesis" has been inconsistent, however. An alternative hypothesis suggests that higher in utero androgen exposure may protect against the development of cryptorchism and testicular cancer. In order to examine both hypotheses, we studied maternal hormone levels in two populations at diverse risks of testicular cancer; Black Americans (low-risk) and White Americans (high-risk). The study population of 200 mothers of cryptorchid sons and 200 mothers of noncryptorchid sons was nested within the Collaborative Perinatal Project, a cohort study of pregnant women and their children. Third trimester serum levels of estradiol (total, free, bioavailable), estriol, testosterone (total, free, bioavailable), sex hormone-binding globulin, alpha-fetoprotein, and the ratios of estradiols to testosterones were compared between the case and control mothers. The results found no significant differences in the levels of testosterone (total, free, bioavailable), alpha-fetoprotein, sex hormone-binding globulin, or in the ratios of estrogens to androgens. Total estradiol, however, was significantly lower in the cases versus the controls (P = 0.03) among all mothers and, separately, among White mothers (P = 0.05). Similarly, estriol was significantly lower among all cases (P = 0.05) and among White cases (P = 0.05). These results do not support either the estrogen or the androgen hypothesis. Rather, lower estrogens in case mothers may indicate that a placental defect increases the risk of cryptorchism and, possibly, testicular cancer.

Indocyanine green loaded graphene oxide for high-efficient photoacoustic tumor therapy

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Baoyun Yan

2016-07-01

Full Text Available Photoacoustic therapy, using the photoacoustic effect of agents for selectively killing tumor cells, has shown promising for treating tumor. Utilization of high optical absorption probes can help to effectively improve the photoacoustic therapy efficiency. Herein, we report a novel high-absorption photoacoustic probe that is composed of indocyanine green (ICG and graphene oxide (GO, entitled GO-ICG, for photoacoustic therapy. The attached ICG with narrow absorption spectral profile has strong optical absorption in the infrared region. The absorption spectrum of the GO-ICG solution reveals that the GO-ICG particles exhibited a 10-fold higher absorbance at 780nm (its peak absorbance as compared with GO. Importantly, ICG’s fluorescence is quenched by GO via fluorescence resonance energy transfer. As a result, GO-ICG can high-efficiently convert the absorbed light energy to acoustic wave under pulsed laser irradiation. We further demonstrate that GO-ICG can produce stronger photoacoustic wave than the GO and ICG alone. Moreover, we conjugate this contrast agent with integrin αvβ3 mono-clonal antibody to molecularly target the U87-MG human glioblastoma cells for selective tumor cell killing. Finally, our results testify that the photoacoustic therapy efficiency of GO-ICG is higher than the existing photoacoustic therapy agent. Our work demonstrates that GO-ICG is a high-efficiency photoacoustic therapy agent. This novel photoacoustic probe is likely to be an available candidate for tumor therapy.

Adjuvant chemoradiotherapy instead of revision radical resection after local excision for high-risk early rectal cancer.

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Jeong, Jae-Uk; Nam, Taek-Keun; Kim, Hyeong-Rok; Shim, Hyun-Jeong; Kim, Yong-Hyub; Yoon, Mee Sun; Song, Ju-Young; Ahn, Sung-Ja; Chung, Woong-Ki

2016-09-05

After local excision of early rectal cancer, revision radical resection is recommended for patients with high-risk pathologic stage T1 (pT1) or pT2 cancer, but the revision procedure has high morbidity rates. We evaluated the efficacy of adjuvant concurrent chemoradiotherapy (CCRT) for reducing recurrence after local excision in these patients. Eighty-three patients with high-risk pT1 or pT2 rectal cancer underwent postoperative adjuvant CCRT after local excision. We defined high-risk features as pT1 having tumor size ≤3 cm, and/or resection margin (RM) ≤3 mm, and/or lymphovascular invasion (LVI), and/or non-full thickness excision such as endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD), or unknown records regarding those features, or pT2 cancer. Radiotherapy was administered with a median dose of 50.4 Gy in 1.8 Gy fraction size over 5-7 weeks. Concurrent 5-fluorouracil and leucovorin were administered for 4 days in the first and fifth weeks of radiotherapy. The median interval between local excision and radiotherapy was 34 (range, 11-104) days. Fifteen patients (18.1 %) had stage pT2 tumors, 22 (26.5 %) had RM of ≥3 mm, and 21 (25.3 %) had tumors of ≥3 cm in size. Thirteen patients (15.7 %) had LVI. Transanal excision was performed in 58 patients (69.9 %) and 25 patients (30.1 %) underwent EMR or ESD. The median follow-up was 61 months. The 5-year overall survival (OS), locoregional relapse-free survival (LRFS), and disease-free survival (DFS) rates for all patients were 94.9, 91.0, and 89.8 %, respectively. Multivariate analysis did not identify any significant factors for OS or LRFS, but the only significant factor affecting DFS was the pT stage (p = 0.027). In patients with high-risk pT1 rectal cancer, adjuvant CCRT after local excision could be an effective alternative treatment instead of revision radical resection. However, patients with pT2 stage showed inferior DFS compared to pT1.

Megavoltage external beam irradiation of craniopharyngiomas: Analysis of tumor control and morbidity

International Nuclear Information System (INIS)

Flickinger, J.C.; Lunsford, L.D.; Singer, J.; Cano, E.R.; Deutsch, M.

1990-01-01

From 1971 to 1985, 21 patients received megavoltage external beam radiation therapy at the University of Pittsburgh for control of craniopharyngioma. Minimum tumor doses prescribed to the 95% isodose volume ranged between 51.3 to 70.0 Gy. Median total dose was 60.00 Gy and median dose per fraction was 1.83 Gy. Three deaths occurred from intercurrent disease and no deaths from tumor progression. Actuarial overall survival was 89% and 82% at 5 and 10 years. Actuarial local control was 95% at 5 and 10 years. Radiation related complications included one patient with optic neuropathy, one with brain necrosis, and one that developed optic neuropathy followed by brain necrosis. The high dose group of patients who received a NSD or Neuret equivalent of greater than 60 Gy at 1.8 Gy per fraction had a significantly greater risk of radiation complications (p = .024). The actuarial risk at 5 years for optic neuropathy was 30% and brain necrosis was 12.5% in the high dose group. Tumor control in the high dose group was not shown to be significantly better. Any possible benefit in tumor control in treating patients with craniopharyngioma with doses above 60 Gy at 1.8 Gy per fraction appears to be offset by the increased risk of radiation injury

Risk of tumor transmission after thoracic allograft transplantation from adult donors with central nervous system neoplasm-A UNOS database study.

Science.gov (United States)

Hynes, Conor F; Ramakrishnan, Karthik; Alfares, Fahad A; Endicott, Kendal M; Hammond-Jack, Katrina; Zurakowski, David; Jonas, Richard A; Nath, Dilip S

2017-04-01

We analyzed the UNOS database to better define the risk of transmission of central nervous system (CNS) tumors from donors to adult recipients of thoracic organs. Data were procured from the Standard Transplant Analysis and Research dataset files. Donors with CNS tumors were identified, and recipients from these donors comprised the study group (Group I). The remaining recipients of organs from donors who did not have CNS tumors formed the control group (Group II). Incidence of recipient CNS tumors, donor-related malignancies, and overall survival were calculated and compared in addition to multivariable logistic regression. A cohort of 58 314 adult thoracic organ recipients were included, of which 337 received organs from donors who had documented CNS tumors (Group I). None of these recipients developed CNS tumors at a median follow-up of 72 months (IR: 30-130 months). Although overall mortality in terms of the percentage was higher in Group I than Group II (163/320=51% vs 22 123/52 691=42%), Kaplan-Meier curves indicate no significant difference in the time to death between the two groups (P=.92). There is little risk of transmission of the common nonaggressive CNS tumors to recipients of thoracic organs. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Modeling tumor control probability for spatially inhomogeneous risk of failure based on clinical outcome data

DEFF Research Database (Denmark)

Lühr, Armin; Löck, Steffen; Jakobi, Annika

2017-01-01

PURPOSE: Objectives of this work are (1) to derive a general clinically relevant approach to model tumor control probability (TCP) for spatially variable risk of failure and (2) to demonstrate its applicability by estimating TCP for patients planned for photon and proton irradiation. METHODS AND ...

High prevalence of early hypothalamic-pituitary damage in childhood brain tumor survivors: need for standardized follow-up programs

NARCIS (Netherlands)

Clement, Sarah C.; Meeteren, Antoinette Y. N. Schouten-van; Kremer, Leontien C. M.; van Trotsenburg, A. S. Paul; Caron, Huib N.; van Santen, Hanneke M.

2014-01-01

Childhood brain tumor survivors (CBTS) are at increased risk to develop endocrine disorders. Alerted by two cases who experienced delay in diagnosis of endocrine deficiencies within the first 5 years after brain tumor diagnosis, our aim was to investigate the current screening strategy and the

Percentage tumor necrosis following chemotherapy in neuroblastoma correlates with MYCN status but not survival.

Science.gov (United States)

Bomken, Simon; Davies, Beverley; Chong, Leeai; Cole, Michael; Wood, Katrina M; McDermott, Michael; Tweddle, Deborah A

2011-03-01

The percentage of chemotherapy-induced necrosis in primary tumors corresponds with outcome in several childhood malignancies, including high-risk metastatic diseases. In this retrospective pilot study, the authors assessed the importance of postchemotherapy necrosis in high-risk neuroblastoma with a histological and case notes review of surgically resected specimens. The authors reviewed all available histology of 31 high-risk neuroblastoma cases treated with COJEC (dose intensive etoposide and vincristine with either cyclophosphamide, cisplatin or carboplatin) or OPEC/OJEC (etoposide, vincristine and cyclophosphamide with alternating cisplatin [OPEC] or carboplatin [OJEC]) induction chemotherapy in 2 Children's Cancer & Leukaemia Group (CCLG) pediatric oncology centers. The percentage of postchemotherapy necrosis was assessed and compared with MYCN amplification status and overall survival. The median percentage of postchemotherapy tumor necrosis was 60%. MYCN status was available for 28 cases, of which 12 were amplified (43%). Survival in cases with ≥ 60% necrosis or ≥ 90% necrosis was not better than those with less necrosis, nor was percentage necrosis associated with survival using Cox regression. However, MYCN-amplified tumors showed a higher percentage of necrosis than non-MYCN-amplified tumors, 71.3% versus 37.2% (P = .006). This effect was not related to prechemotherapy necrosis and did not confer improved overall survival. Postchemotherapy tumor necrosis is higher in patients with MYCN amplification. In this study, postchemotherapy necrosis did not correlate with overall survival and should not lead to modification of postoperative treatment. However, these findings need to be confirmed in a larger prospective study of children with high-risk neuroblastoma.

Hormone therapy and ovarian borderline tumors

DEFF Research Database (Denmark)

Mørch, Lina Steinrud; Løkkegaard, Ellen; Andreasen, Anne Helms

2012-01-01

Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk.......Little is known about the influence of postmenopausal hormone therapy on the risk of ovarian borderline tumors. We aimed at assessing the influence of different hormone therapies on this risk....

Risk Factors for Postoperative Fibrinogen Deficiency after Surgical Removal of Intracranial Tumors.

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Naili Wei

Full Text Available Higher levels of fibrinogen, a critical element in hemostasis, are associated with increased postoperative survival rates, especially for patients with massive operative blood loss. Fibrinogen deficiency after surgical management of intracranial tumors may result in postoperative intracranial bleeding and severely worsen patient outcomes. However, no previous studies have systematically identified factors associated with postoperative fibrinogen deficiency. In this study, we retrospectively analyzed data from patients who underwent surgical removal of intracranial tumors in Beijing Tiantan Hospital date from 1/1/2013to12/31/2013. The present study found that patients with postoperative fibrinogen deficiency experienced more operative blood loss and a higher rate of postoperative intracranial hematoma, and they were given more blood transfusions, more plasma transfusions, and were administered larger doses of hemocoagulase compared with patients without postoperative fibrinogen deficiency. Likewise, patients with postoperative fibrinogen deficiency had poorer extended Glasgow Outcome Scale (GOSe, longer hospital stays, and greater hospital expenses than patients without postoperative fibrinogen deficiency. Further, we assessed a comprehensive set of risk factors associated with postoperative fibrinogen deficiency via multiple linear regression. We found that body mass index (BMI, the occurrence of postoperative intracranial hematoma, and administration of hemocoagulasewere positively associated with preoperative-to-postoperative plasma fibrinogen consumption; presenting with a malignant tumor was negatively associated with fibrinogen consumption. Contrary to what might be expected, intraoperative blood loss, the need for blood transfusion, and the need for plasma transfusion were not associated with plasma fibrinogen consumption. Considering our findings together, we concluded that postoperative fibrinogen deficiency is closely associated with

A transplant recipient with a mixed germ-cell ovarian tumor

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Ketata Hafed

2008-01-01

Full Text Available Immunosuppressed renal transplant recipients seem to be at significantly increased risk of developing neoplasms comparatively to nonimmunosuppressed individuals. A history of malignancy exposes the patient to a high risk for relapse after transplantation. We present a trans-plant recipient with a history of an ovarian mixed germ-cell tumor, with choriocarcinoma com-ponent, which was treated seven years prior to transplantation. After three years of follow-up, there was no evidence of tumor relapse. To our knowledge, there is no report of such case in the English literature. Regarding our case report and patients with a history of ovarian germ-cell neoplasm, waiting time before transplantation must take into consideration the stage of the tumor, its prognosis, the proportion of different tumor components, and the overall prognosis of the patient if transplantation is withheld.

Risks of Being Malignant or High Risk and Their Characteristics in Breast Lesions 20 mm or Larger After Benign Results on Ultrasonography-Guided 14-Gauge Core Needle Biopsy.

Science.gov (United States)

Moon, Hee Jung; Kim, Min Jung; Yoon, Jung Hyun; Kim, Eun-Kyung

2016-06-01

The malignancy risk, risk of being high-risk lesions after benign results on ultrasonography-guided 14-gauge core needle biopsies (US-CNBs), and their characteristics in breast lesions of 20 mm or greater were investigated. Eight hundred forty-seven breast lesions with benign results on US-CNB were classified as benign, high risk, and malignant through excision and clinical follow-up. The risks of being malignant or high risk were analyzed in all lesions, lesions 20 to 29 mm, and lesions 30 mm or greater. Their clinicopathological characteristics were evaluated. Of 847, 18 (2.1%) were malignant, 53 (6.3%) were high-risk lesions, and 776 (91.6%) were benign. Of 18 malignancies, 6 (33.3%) were malignant phyllodes tumors and 12 (66.7%) were carcinomas. In benign lesions 20 to 29 mm, risks of being malignant or high risk were 1.6% (9 of 566) and 4.4% (25 of 566). In 281 lesions 30 mm or greater, the risks of being malignant or high risk were 3.2% and 10%. The risk of being high risk in lesions 30 mm or greater was 10%, significantly higher than 4.4% of lesions 20 to 29 mm (P = 0.002). Excision can be considered in lesions measuring 20 mm or larger because of the 2.1% malignancy risk and the 6.3% risk of being high-risk lesions despite benign results on US-CNB. Excision should be considered in lesions measuring 30 mm or larger because of the 3.2% malignancy risk and the 10% risk of being high-risk lesions.

Characteristics of Metachronous Gastric Tumors after Endoscopic Submucosal Dissection for Gastric Intraepithelial Neoplasms

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Tomoyuki Boda

2014-01-01

Full Text Available Background. Recently, endoscopic submucosal dissection (ESD has become a standard treatment method for early gastric cancer and concurrent stomach preservation. However, metachronous recurrences have become a major problem. We evaluated the incidence and clinicopathologic features of and examined the risk factors for metachronous gastric tumors. Methods. A total of 357 patients who underwent ESD for gastric tumors (245 early gastric cancers and 112 adenomas and were followed up for more than 12 months without recurrence within the first 12 months were enrolled. We investigated the incidence and clinicopathologic features of metachronous tumors after ESD. We also analyzed the potential risk factors for metachronous tumors using the Kaplan-Meier method and Cox’s proportional hazards model. Results. The annual incidence of metachronous tumors after ESD was 2.4%. The median period until discovery after initial ESD was 26.0 months, and the median observation period was 52.6 months. Male patients developed metachronous tumors more frequently (P=0.04, and the hazard ratio of female to male patients was 0.36 (95% confidence interval: 0.11–0.89. Conclusions. Patients with a previous history of gastric tumors have a high risk of subsequent gastric tumor development and male patients should be carefully followed up after ESD for gastric tumor.

Gastrointestinal Stromal Tumors with Unusual Localization: Report of Three Cases with a Brief Literature Review.

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Yucel, Ahmet Fikret; Sunar, Haldun; Hut, Adnan; Kocakusak, Ahmet; Pergel, Ahmet; Barut, Gul; Dikici, Suleyman

2010-07-26

The most common tumors derived from the mesenchyme of the gastrointestinal system are stromal tumors. These tumors are typically seen in the stomach and small intestine and less frequently in the colon, rectum and esophagus and are very rarely located outside the gastrointestinal system. Cure is provided with complete surgical resection with resection borders free of tumor. Tumor size, mitotic index, localization, CD117 and CD34 negativity in immunohistochemical studies, mucosal ulceration and presence of necrosis help to predict recurrence of the illness and patient survival. In high-risk gastrointestinal stromal tumors (GISTs) there is an increased rate of recurrence and shortened survival despite complete surgical resection. Thus patients with a high-risk GIST should be given adjuvant therapy with imatinib mesylate. Sunitinib maleate is another FDA-approved agent only for cases who cannot tolerate imatinib or who are resistant to it. Herein we present three cases with GISTs in different locations of the gastrointestinal system with a review of the relevant literature.

Gastrointestinal Stromal Tumors with Unusual Localization: Report of Three Cases with a Brief Literature Review

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Ahmet Fikret Yucel

2010-07-01

Full Text Available The most common tumors derived from the mesenchyme of the gastrointestinal system are stromal tumors. These tumors are typically seen in the stomach and small intestine and less frequently in the colon, rectum and esophagus and are very rarely located outside the gastrointestinal system. Cure is provided with complete surgical resection with resection borders free of tumor. Tumor size, mitotic index, localization, CD117 and CD34 negativity in immunohistochemical studies, mucosal ulceration and presence of necrosis help to predict recurrence of the illness and patient survival. In high-risk gastrointestinal stromal tumors (GISTs there is an increased rate of recurrence and shortened survival despite complete surgical resection. Thus patients with a high-risk GIST should be given adjuvant therapy with imatinib mesylate. Sunitinib maleate is another FDA-approved agent only for cases who cannot tolerate imatinib or who are resistant to it. Herein we present three cases with GISTs in different locations of the gastrointestinal system with a review of the relevant literature.

The correlation analysis of tumor necrosis factor-alpha-308G/A polymorphism and venous thromboembolism risk: A meta-analysis.

Science.gov (United States)

Gao, Quangen; Zhang, Peijin; Wang, Wei; Ma, He; Tong, Yue; Zhang, Jing; Lu, Zhaojun

2016-10-01

Venous thromboembolism is a common complex disorder, being the resultant of gene-gene and gene-environment interactions. Tumor necrosis factor-alpha is a proinflammatory cytokine which has been implicated in venous thromboembolism risk. A promoter 308G/A polymorphism in the tumor necrosis factor-alpha gene has been suggested to modulate the risk for venous thromboembolism. However, the published findings remain inconsistent. In this study, we conducted a meta-analysis of all available data regarding this issue. Eligible studies were identified through search of Pubmed, EBSCO Medline, Web of Science, and China National Knowledge Infrastructure (CNKI, Chinese) databases up to June 2014. Pooled Odd ratios (ORs) with 95% confidence intervals were applied to estimating the strength of the genetic association in the random-effects model or fixed-effects model. A total of 10 studies involving 1999 venous thromboembolism cases and 2166 controls were included in this meta-analysis to evaluate the association between tumor necrosis factor-alpha-308G/A polymorphism and venous thromboembolism risk. Overall, no significantly increased risk venous thromboembolism was observed in all comparison models when all studies were pooled into the meta-analysis. However, in stratified analyses by ethnicity, there was a pronounced association with venous thromboembolism risk among West Asians in three genetic models (A vs. G: OR = 1.82, 95%CI = 1.13-2.94; GA vs. GG: OR = 1.82, 95%CI = 1.08-3.06; AA/GA vs. GG: OR = 1.88, 95%CI = 1.12-3.16). When stratifying by source of controls, no significant result was detected in all genetic models. This meta-analysis demonstrates that tumor necrosis factor-alpha 308G/A polymorphism may contribute to susceptibility to venous thromboembolism among West Asians. Studies are needed to ascertain these findings in larger samples and different racial groups. © The Author(s) 2015.

Functional phosphodiesterase 11A mutations may modify the risk of familial and bilateral testicular germ cell tumors

Science.gov (United States)

Horvath, Anelia; Korde, Larissa; Greene, Mark H.; Libe, Rosella; Osorio, Paulo; Faucz, Fabio Rueda; Raffin-Sanson, Marie Laure; Tsang, Kit Man; Drori-Herishanu, Limor; Patronas, Yianna; Remmers, Elaine F; Nikita, Maria-Elena; Moran, Jason; Greene, Joseph; Nesterova, Maria; Merino, Maria; Bertherat, Jerome; Stratakis, Constantine A.

2009-01-01

Inactivating germline mutations in phosphodiesterase 11A (PDE11A) have been implicated in adrenal tumor susceptibility. PDE11A is highly-expressed in endocrine steroidogenic tissues, especially the testis, and mice with inactivated Pde11a exhibit male infertility, a known testicular germ cell tumor (TGCT) risk factor. We sequenced the PDE11A gene-coding region in 95 patients with TGCT from 64 unrelated kindreds. We identified 8 non-synonymous substitutions in 20 patients from 15 families: four (R52T; F258Y; G291R; V820M) were newly-recognized, three (R804H; R867G; M878V) were functional variants previously implicated in adrenal tumor predisposition, and one (Y727C) was a known polymorphism. We compared the frequency of these variants in our patients to unrelated controls that had been screened and found negative for any endocrine diseases: only the two previously-reported variants, R804H and R867G, known to be frequent in general population, were detected in these controls. The frequency of all PDE11A-gene variants (combined) was significantly higher among patients with TGCT (P=0.0002), present in 19% of the families of our cohort. Most variants were detected in the general population, but functional studies showed that all these mutations reduced PDE activity, and that PDE11A protein expression was decreased (or absent) in TGCT samples from carriers. This is the first demonstration of a PDE gene’s involvement in TGCT, although the cAMP signaling pathway has been investigated extensively in other reproductive organs and their diseases. In conclusion, we report that PDE11A-inactivating sequence variants may modify the risk of familial and bilateral TGCT. PMID:19549888

The long-term risk of malignant astrocytic tumors after structural brain injury--a nationwide cohort study

DEFF Research Database (Denmark)

Munch, Tina Noergaard; Gørtz, Sanne; Wohlfahrt, Jan

2015-01-01

% CI: 0.49-0.90) compared with no injury. The specific long-term risks by type of injury were: traumatic brain injury RR = 0.32 (95% CI: 0.10-0.75); cerebral ischemic infarction RR = 0.69 (95% CI: 0.47-0.96); and intracerebral hemorrhage RR = 1.39 (95% CI: 0.64-2.60). CONCLUSION: We found no evidence......BACKGROUND: Neoplastic transformation of damaged astrocytes has been proposed as a possible pathological mechanism behind malignant astrocytic tumors. This study investigated the association between structural brain injuries causing reactive astrogliosis and long-term risk for malignant astrocytic...... tumors. METHODS: The cohort consisted of all individuals living in Denmark between 1978 and 2011. The personal identification number assigned to all individuals allowed retrieval of diagnoses of traumatic brain injury, cerebral ischemic infarction, and intracerebral hemorrhage from the National Patient...

Amide proton transfer imaging of high intensity focused ultrasound-treated tumor tissue

NARCIS (Netherlands)

Hectors, S.J.C.G.; Jacobs, I.; Strijkers, G.J.; Nicolay, K.

2014-01-01

Purpose: In this study, the suitability of amide proton transfer (APT) imaging as a biomarker for the characterization of high intensity focused ultrasound (HIFU)-treated tumor tissue was assessed. Methods: APT imaging was performed on tumor-bearing mice before (n=15), directly after (n=15) and at 3

Amide Proton Transfer Imaging of High Intensity Focused Ultrasound-Treated Tumor Tissue

NARCIS (Netherlands)

Hectors, Stefanie J. C. G.; Jacobs, Igor; Strijkers, Gustav J.; Nicolay, Klaas

2014-01-01

PurposeIn this study, the suitability of amide proton transfer (APT) imaging as a biomarker for the characterization of high intensity focused ultrasound (HIFU)-treated tumor tissue was assessed. MethodsAPT imaging was performed on tumor-bearing mice before (n=15), directly after (n=15) and at 3

Occurrence of mammary tumors in beagls given radium-226

International Nuclear Information System (INIS)

Bruenger, F.W.; Lloyd, R.D.; Miller, S.C.; Taylor, G.N.; Angus, W.; Huth, D.A.

1994-01-01

A total of 128 primary mammary tumors (66 of them malignant) occurred in 35 female beagles injected with 226 Ra at eight dose levels ranging from 0.2 to 440 kBq/kg body mass as young adults, while a total of 156 mammary tumors (57 of them malignant) were seen in 46 female control beagles not given any radioactivity. Sixty-three of 65 control dogs and 59 of 61 dogs given 226 Ra survived the minimum age for diagnosis of mammary tumors of 3.75 years. Based on the observed age-dependent tumor incidence rates in the controls and on the corresponding number of dog-years at risk, the total number of observed malignant tumors in the radium group was statistically greater than the number of expected malignant tumors (66 observed vs 34 expected, P < 0.005). There was no such difference for the benign tumors. Cox regression analysis indicated no increased risk for the first tumor occurrence in irradiated dogs. Cox regression analysis of the multivariate risk sets showed no significantly increased risk for the occurrence of benign tumors but a statistically higher risk of 1.66 with a confidence interval of 1.15-2.40 for the occurrence of malignant tumors. The increased risk was dependent on dose, but a dependence on the frequency of previous occurrence of mammary tumors could not be confirmed. Censoring ovariectomized dogs at time of surgery decreased the relative risks slightly but did not alter the significance. Exposure to diagnostic X rays with cumulative exposures below 0.2 Gy had no effect on tumor formation. It is unknown whether the increased risk for malignant mammary tumors was due to some initial deposition of radium in sensitive tissue, a possible irradiation of fatty mammary tissue from transient radon → polonium deposition, or a general effect of the overall radium deposition on the immune system of the dogs that lowered their resistance to formation of mammary tumors. 27 refs., 5 figs., 4 tabs

Treatment options for high-risk T1 bladder cancer. Status quo and future perspectives of radiochemotherapy

International Nuclear Information System (INIS)

Weiss, C.; Roedel, C.; Ott, O.J.; Wittlinger, M.; Fietkau, R.; Sauer, R.; Krause, S.F.

2008-01-01

Purpose: to review the standards and new developments in diagnosis and management of high-risk T1 bladder cancer with emphasis on the role of radiotherapy (RT) and radiochemotherapy (RCT). Material and methods: a systematic review of the literature on developments in diagnosis and management of high-risk T1 bladder cancer was performed. Results: first transurethral resection (TUR), as radical as safely possible, supported by fluorescence cystoscopy, shows higher detection and decreased recurrence rates. An immediate single postoperative instillation with a chemotherapeutic drug reduces the relative risk of recurrence by 40%. A second TUR is recommended to assess residual tumor. For adjuvant intravesical therapy, bacille Calmette-Guerin (BCG) demonstrated the highest efficacy. Early cystectomy should be reserved for selected patients. A recent phase III trial comparing RT versus conservative treatment in T1 G3 tumors could not show any advantage for RT. Data from Erlangen, Germany, using combined RCT in 80% of the patients, compare favorably with most of the contemporary BCG series. Conclusion: results of intravesical therapy are still unsatisfying and early cystectomy is associated with morbidity and mortality. RT alone proved not superior to other conservative treatment strategies. However, data on RCT are promising and demonstrate an alternative to intravesical therapy and radical cystectomy. (orig.)

Quantitative assessment of the influence of tumor necrosis factor alpha polymorphism with gastritis and gastric cancer risk.

Science.gov (United States)

Li, Ming; Wang, Yinping; Gu, Yahong

2014-02-01

Tumor necrosis factor alpha (TNFA) is an important molecule in inflammatory, infectious, and tumoral processes. Inflammation is one of the early phases in the development of gastric cancer (GC). Therefore, several studies have examined the association of polymorphism in TNFA with gastritis and GC risk. A functional polymorphism, -308G>A (rs1800629), which is located in the promoter of TNFA gene, has been suggested to alter the production of TNF-α and influence cancer risk. To date, a number of studies have been carried out to investigate the relationship between the polymorphism and gastritis or GC susceptibility, but the results were conflicting. To investigate this inconsistency, we performed a meta-analysis of 36 studies for TNFA -308G>A polymorphism to evaluate the effect of TNFA on genetic susceptibility for gastritis and GC. An overall random-effects per-allele odds ratio of 1.16 (95 % confidence interval 1.04-1.29, P = 0.008) was found for the polymorphism. Significant results were also observed using dominant or recessive genetic models. In the subgroup analyses by ethnicity, significant results were found in Caucasians, whereas no significant associations were found among East Asians and other ethnic populations. No associations between the polymorphism and gastritis were observed. In addition, our data indicate that TNFA is involved in GC susceptibility and confers its effect primarily in diffuse type of tumors. Besides, -308G>A polymorphism was found to be significantly associated with both cardiac and noncardiac tumors. This meta-analysis demonstrated that the TNFA -308G>A polymorphism is a risk factor for developing GC, but the associations vary in different ethnic populations.

Filter Paper-based Nucleic Acid Storage in High-throughput Solid Tumor Genotyping.

Science.gov (United States)

Stachler, Matthew; Jia, Yonghui; Sharaf, Nematullah; Wade, Jacqueline; Longtine, Janina; Garcia, Elizabeth; Sholl, Lynette M

2015-01-01

Molecular testing of tumors from formalin-fixed paraffin-embedded (FFPE) tissue blocks is central to clinical practice; however, it requires histology support and increases test turnaround time. Prospective fresh frozen tissue collection requires special handling, additional storage space, and may not be feasible for small specimens. Filter paper-based collection of tumor DNA reduces the need for histology support, requires little storage space, and preserves high-quality nucleic acid. We investigated the performance of tumor smears on filter paper in solid tumor genotyping, as compared with paired FFPE samples. Whatman FTA Micro Card (FTA preps) smears were prepared from 21 fresh tumor samples. A corresponding cytology smear was used to assess tumor cellularity and necrosis. DNA was isolated from FTA preps and FFPE core samples using automated methods and quantified using SYBR green dsDNA detection. Samples were genotyped for 471 mutations on a mass spectrophotometry-based platform (Sequenom). DNA concentrations from FTA preps and FFPE correlated for untreated carcinomas but not for mesenchymal tumors (Spearman σ=0.39 and σ=-0.1, respectively). Average DNA concentrations were lower from FTA preps as compared with FFPE, but DNA quality was higher with less fragmentation. Seventy-six percent of FTA preps and 86% of FFPE samples generated adequate DNA for genotyping. FTA preps tended to perform poorly for collection of DNA from pretreated carcinomas and mesenchymal neoplasms. Of the 16 paired DNA samples that were genotyped, 15 (94%) gave entirely concordant results. Filter paper-based sample preservation is a feasible alternative to FFPE for use in automated, high-throughput genotyping of carcinomas.

Analysis of Surgical Site Infection after Musculoskeletal Tumor Surgery: Risk Assessment Using a New Scoring System

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Satoshi Nagano

2014-01-01

Full Text Available Surgical site infection (SSI has not been extensively studied in musculoskeletal tumors (MST owing to the rarity of the disease. We analyzed incidence and risk factors of SSI in MST. SSI incidence was evaluated in consecutive 457 MST cases (benign, 310 cases and malignant, 147 cases treated at our institution. A detailed analysis of the clinical background of the patients, pre- and postoperative hematological data, and other factors that might be associated with SSI incidence was performed for malignant MST cases. SSI occurred in 0.32% and 12.2% of benign and malignant MST cases, respectively. The duration of the surgery (P=0.0002 and intraoperative blood loss (P=0.0005 was significantly more in the SSI group than in the non-SSI group. We established the musculoskeletal oncological surgery invasiveness (MOSI index by combining 4 risk factors (blood loss, operation duration, preoperative chemotherapy, and the use of artificial materials. The MOSI index (0–4 points score significantly correlated with the risk of SSI, as demonstrated by an SSI incidence of 38.5% in the group with a high score (3-4 points. The MOSI index score and laboratory data at 1 week after surgery could facilitate risk evaluation and prompt diagnosis of SSI.

The relationship between mobile phone use and risk of brain tumor: a systematic review and meta-analysis of trails in the last decade

Institute of Scientific and Technical Information of China (English)

Lige Leng

2017-01-01

The aim of the present meta-analysis was to identify whether there was a relationship between mobile phone use and risk of brain tumor.A comprehensive search strategy was developed,and studies were eliminated in a stepwise manner,based on the inclusion criteria.The current meta-analysis collected data from the 24 eligible studies to investigate the relationship between mobile phone use and risk of brain tumor,while a detailed analysis of different classification was also conducted in order to identify the risk of mobile phone use.From the results,the relationship between cell phone use and brain tumor incidence had no significant difference between men and women.Cell phone use can increase the RF energy absorbed in the brain and apoptosis genes expression level,but glioma cell line cells were not significantly affected.Most calculations of laterality show a trend of increasing risk for time since first use,cumulative duration of subscriptions,cumulative duration of calls,and cumulative number of calls.In Asian people's,cell phone use and glioma had certain relations,while has verylittle relationship with meningioma incidence.This result seems to be no racial difference.In children and teenagers,cell phone use is associated with the incidence of brain tumors.We need longer time observation to supervise longer time (＞20 years) mobile phone use whether has severe effects on incidence of brain tumor.

Multiparametric imaging of patient and tumour heterogeneity in non-small-cell lung cancer: quantification of tumour hypoxia, metabolism and perfusion

Energy Technology Data Exchange (ETDEWEB)

Elmpt, Wouter van; Zegers, Catharina M.L.; Reymen, Bart; Even, Aniek J.G.; Oellers, Michel; Troost, Esther G.C.; Lambin, Philippe [Maastricht University Medical Centre, Department of Radiation Oncology (MAASTRO), GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Dingemans, Anne-Marie C. [Maastricht University Medical Centre, Department of Pulmonology, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Wildberger, Joachim E.; Das, Marco [Maastricht University Medical Centre, Department of Radiology, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); Mottaghy, Felix M. [Maastricht University Medical Centre, Department of Nuclear Medicine, GROW - School for Oncology and Developmental Biology, Maastricht (Netherlands); University Hospital RWTH Aachen University, Department of Nuclear Medicine, Aachen (Germany)

2016-02-15

Multiple imaging techniques are nowadays available for clinical in-vivo visualization of tumour biology. FDG PET/CT identifies increased tumour metabolism, hypoxia PET visualizes tumour oxygenation and dynamic contrast-enhanced (DCE) CT characterizes vasculature and morphology. We explored the relationships among these biological features in patients with non-small-cell lung cancer (NSCLC) at both the patient level and the tumour subvolume level. A group of 14 NSCLC patients from two ongoing clinical trials (NCT01024829 and NCT01210378) were scanned using FDG PET/CT, HX4 PET/CT and DCE CT prior to chemoradiotherapy. Standardized uptake values (SUV) in the primary tumour were calculated for the FDG and hypoxia HX4 PET/CT scans. For hypoxia imaging, the hypoxic volume, fraction and tumour-to-blood ratio (TBR) were also defined. Blood flow and blood volume were obtained from DCE CT imaging. A tumour subvolume analysis was used to quantify the spatial overlap between subvolumes. At the patient level, negative correlations were observed between blood flow and the hypoxia parameters (TBR >1.2): hypoxic volume (-0.65, p = 0.014), hypoxic fraction (-0.60, p = 0.025) and TBR (-0.56, p = 0.042). At the tumour subvolume level, hypoxic and metabolically active subvolumes showed an overlap of 53 ± 36 %. Overlap between hypoxic sub-volumes and those with high blood flow and blood volume was smaller: 15 ± 17 % and 28 ± 28 %, respectively. Half of the patients showed a spatial mismatch (overlap <5 %) between increased blood flow and hypoxia. The biological imaging features defined in NSCLC tumours showed large interpatient and intratumour variability. There was overlap between hypoxic and metabolically active subvolumes in the majority of tumours, there was spatial mismatch between regions with high blood flow and those with increased hypoxia. (orig.)

Differentiation of low- and high-grade clear cell renal cell carcinoma: Tumor size versus CT perfusion parameters.

Science.gov (United States)

Chen, Chao; Kang, Qinqin; Xu, Bing; Guo, Hairuo; Wei, Qiang; Wang, Tiegong; Ye, Hui; Wu, Xinhuai

To compare the utility of tumor size and CT perfusion parameters for differentiation of low- and high-grade clear cell renal cell carcinoma (RCC). Tumor size, Equivalent blood volume (Equiv BV), permeability surface-area product (PS), blood flow (BF), and Fuhrman pathological grading of clear cell RCC were retrospectively analyzed. High-grade clear cell RCC had significantly higher tumor size and lower PS than low grade. Tumor size positively correlated with Fuhrman grade, but PS negatively did. Tumor size and PS were significantly independent indexes for differentiating high-grade from low-grade clear cell RCC. Copyright © 2017 Elsevier Inc. All rights reserved.

Treatment of unresectable hepatocellular carcinoma with use of 90Y microspheres (TheraSphere): safety, tumor response, and survival.

Science.gov (United States)

Salem, Riad; Lewandowski, Robert J; Atassi, Bassel; Gordon, Stuart C; Gates, Vanessa L; Barakat, Omar; Sergie, Ziad; Wong, Ching-Yee O; Thurston, Kenneth G

2005-12-01

To present safety and efficacy results obtained in treatment of a cohort of patients with unresectable hepatocellular carcinoma (HCC) with use of 90Y microspheres (TheraSphere). Forty-three consecutive patients with HCC were treated with 90Y microspheres over a 4-year period. Patients were treated by liver segment or lobe on one or more occasions based on tumor distribution, liver function, and vascular flow dynamics. Patients were followed for adverse events, objective tumor response, and survival. Patients were stratified into three risk groups according to method of treatment and risk stratification (group 0, segmental; group 1, lobar low-risk; group 2, lobar high-risk) and Okuda and Child-Pugh scoring systems. Based on follow-up data from 43 treated patients, 20 patients (47%) had an objective tumor response based on percent reduction in tumor size and 34 patients (79%) had a tumor response when percent reduction and/or tumor necrosis were used as a composite measure of tumor response. There was no statistical difference among the three risk groups with respect to tumor response. Survival times from date of diagnosis were different among the risk groups (P TheraSpheres) provides a safe and effective method of treatment for a broad spectrum of patients presenting with unresectable HCC. Further investigation is warranted.

Adjuvant Sunitinib in High-Risk Renal-Cell Carcinoma after Nephrectomy.

Science.gov (United States)

Ravaud, Alain; Motzer, Robert J; Pandha, Hardev S; George, Daniel J; Pantuck, Allan J; Patel, Anup; Chang, Yen-Hwa; Escudier, Bernard; Donskov, Frede; Magheli, Ahmed; Carteni, Giacomo; Laguerre, Brigitte; Tomczak, Piotr; Breza, Jan; Gerletti, Paola; Lechuga, Mariajose; Lin, Xun; Martini, Jean-Francois; Ramaswamy, Krishnan; Casey, Michelle; Staehler, Michael; Patard, Jean-Jacques

2016-12-08

Sunitinib, a vascular endothelial growth factor pathway inhibitor, is an effective treatment for metastatic renal-cell carcinoma. We sought to determine the efficacy and safety of sunitinib in patients with locoregional renal-cell carcinoma at high risk for tumor recurrence after nephrectomy. In this randomized, double-blind, phase 3 trial, we assigned 615 patients with locoregional, high-risk clear-cell renal-cell carcinoma to receive either sunitinib (50 mg per day) or placebo on a 4-weeks-on, 2-weeks-off schedule for 1 year or until disease recurrence, unacceptable toxicity, or consent withdrawal. The primary end point was disease-free survival, according to blinded independent central review. Secondary end points included investigator-assessed disease-free survival, overall survival, and safety. The median duration of disease-free survival was 6.8 years (95% confidence interval [CI], 5.8 to not reached) in the sunitinib group and 5.6 years (95% CI, 3.8 to 6.6) in the placebo group (hazard ratio, 0.76; 95% CI, 0.59 to 0.98; P=0.03). Overall survival data were not mature at the time of data cutoff. Dose reductions because of adverse events were more frequent in the sunitinib group than in the placebo group (34.3% vs. 2%), as were dose interruptions (46.4% vs. 13.2%) and discontinuations (28.1% vs. 5.6%). Grade 3 or 4 adverse events were more frequent in the sunitinib group (48.4% for grade 3 events and 12.1% for grade 4 events) than in the placebo group (15.8% and 3.6%, respectively). There was a similar incidence of serious adverse events in the two groups (21.9% for sunitinib vs. 17.1% for placebo); no deaths were attributed to toxic effects. Among patients with locoregional clear-cell renal-cell carcinoma at high risk for tumor recurrence after nephrectomy, the median duration of disease-free survival was significantly longer in the sunitinib group than in the placebo group, at a cost of a higher rate of toxic events. (Funded by Pfizer; S-TRAC Clinical

Treatment of esophageal tumors using high intensity intraluminal ultrasound: first clinical results

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Prat Frederic

2008-06-01

Full Text Available Abstract Background Esophageal tumors generally bear a poor prognosis. Radical surgery is generally the only curative method available but is not feasible in the majority of patients; palliative therapy with stent placement is generally performed. It has been demonstrated that High Intensity Ultrasound can induce rapid, complete and well-defined coagulation necrosis. Thus, for the treatment of esophageal tumors, we have designed an ultrasound applicator that uses an intraluminal approach to fill up this therapeutic gap. Methods Thermal ablation is performed with water-cooled ultrasound transducers operating at a frequency of 10 MHz. Single lesions extend from the transducer surface up to 10 mm in depth when applying an intensity of 14 W/cm2 for 10s. A lumen inside the therapy applicator provides path for an endoscopic ultrasound imaging probe operating at a frequency of 12 MHz. The mechanical rotation of the applicator around its axis enables treatment of sectorial or cylindrical volumes. This method is thus particularly suitable for esophageal tumors that may develop only on a portion of the esophageal circumference. Previous experiments were conducted from bench to in vivo studies on pig esophagi. Results Here we report clinical results obtained on four patients included in a pilot study. The treatment of esophageal tumors was performed under fluoroscopic guidance and ultrasound imaging. Objective tumor response was obtained in all cases and a complete necrosis of a tumor was obtained in one case. All patients recovered uneventfully and dysphagia improved significantly within 15 days, allowing for resuming a solid diet in three cases. Conclusion This clinical work demonstrated the efficacy of intraluminal high intensity ultrasound therapy for local tumor destruction in the esophagus.

Malignant Trigeminal Nerve Sheath Tumor and Anaplastic Astrocytoma Collision Tumor with High Proliferative Activity and Tumor Suppressor P53 Expression

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Maher Kurdi

2014-01-01

Full Text Available Background. The synchronous development of two primary brain tumors of distinct cell of origin in close proximity or in contact with each other is extremely rare. We present the first case of collision tumor with two histological distinct tumors. Case Presentation. A 54-year-old woman presented with progressive atypical left facial pain and numbness for 8 months. MRI of the brain showed left middle cranial fossa heterogeneous mass extending into the infratemporal fossa. At surgery, a distinct but intermingled intra- and extradural tumor was demonstrated which was completely removed through left orbitozygomatic-temporal craniotomy. Histopathological examination showed that the tumor had two distinct components: malignant nerve sheath tumor of the trigeminal nerve and temporal lobe anaplastic astrocytoma. Proliferative activity and expressed tumor protein 53 (TP53 gene mutations were demonstrated in both tumors. Conclusions. We describe the first case of malignant trigeminal nerve sheath tumor (MTNST and anaplastic astrocytoma in collision and discuss the possible hypothesis of this rare occurrence. We propose that MTNST, with TP53 mutation, have participated in the formation of anaplastic astrocytoma, or vice versa.

Risk-stratifying capacity of PET/CT metabolic tumor volume in stage IIIA non-small cell lung cancer

Energy Technology Data Exchange (ETDEWEB)

Finkle, Joshua H.; Jo, Stephanie Y.; Yuan, Cindy; Pu, Yonglin [University of Chicago, Department of Radiology, Chicago, IL (United States); Ferguson, Mark K. [University of Chicago, Department of Surgery, Chicago, IL (United States); Liu, Hai-Yan [First Hospital of Shanxi Medical University, Department of Nuclear Medicine, Taiyuan, Shanxi (China); Zhang, Chenpeng [Shanghai Jiao Tong University, Department of Nuclear Medicine, RenJi Hospital, School of Medicine, Shanghai (China); Zhu, Xuee [Nanjing Medical University, Department of Radiology, BenQ Medical Center, Nanjing, Jiangsu Province (China)

2017-08-15

Stage IIIA non-small cell lung cancer (NSCLC) is heterogeneous in tumor burden, and its treatment is variable. Whole-body metabolic tumor volume (MTV{sub WB}) has been shown to be an independent prognostic index for overall survival (OS). However, the potential of MTV{sub WB} to risk-stratify stage IIIA NSCLC has previously been unknown. If we can identify subgroups within the stage exhibiting significant OS differences using MTV{sub WB}, MTV{sub WB} may lead to adjustments in patients' risk profile evaluations and may, therefore, influence clinical decision making regarding treatment. We estimated the risk-stratifying capacity of MTV{sub WB} in stage IIIA by comparing OS of stratified stage IIIA with stage IIB and IIIB NSCLC. We performed a retrospective review of 330 patients with clinical stage IIB, IIIA, and IIIB NSCLC diagnosed between 2004 and 2014. The patients' clinical TNM stage, initial MTV{sub WB}, and long-term survival data were collected. Patients with TNM stage IIIA disease were stratified by MTV{sub WB}. The optimal MTV{sub WB} cutoff value for stage IIIA patients was calculated using sequential log-rank tests. Univariate and multivariate cox regression analyses and Kaplan-Meier OS analysis with log-rank tests were performed. The optimal MTV{sub WB} cut-point was 29.2 mL for the risk-stratification of stage IIIA. We identified statistically significant differences in OS between stage IIB and IIIA patients (p < 0.01), between IIIA and IIIB patients (p < 0.01), and between the stage IIIA patients with low MTV{sub WB} (below 29.2 mL) and the stage IIIA patients with high MTV{sub WB} (above 29.2 mL) (p < 0.01). There was no OS difference between the low MTV{sub WB} stage IIIA and the cohort of stage IIB patients (p = 0.485), or between the high MTV{sub WB} stage IIIA patients and the cohort of stage IIIB patients (p = 0.459). Similar risk-stratification capacity of MTV{sub WB} was observed in a large range of cutoff values from 15 to 55 mL in

Perioperative high dose rate (HDR brachytherapy in unresectable locally advanced pancreatic tumors

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Brygida Białas

2011-07-01

Full Text Available Purpose: The aim of the study was to present an original technique of catheter implantation for perioperative HDR-Ir192 brachytherapy in patients after palliative operations of unresectable locally advanced pancreatic tumors and to estimate the influence of perioperative HDR-Ir192 brachytherapy on pain relief in terminal pancreatic cancer patients. Material and methods: Eight patients with pancreatic tumors located in the head of pancreas underwent palliative operations with the use of HDR-Ir192 brachytherapy. All patients qualified for surgery reported pain of high intensity and had received narcotic painkillers prior to operation. During the last phase of the surgery, the Nucletron® catheters were implanted in patients to prepare them for later perioperative brachytherapy. Since the 6th day after surgery HDR brachytherapy was performed. Before each brachytherapy fraction the location of implants were checked using fluoroscopy. A fractional dose was 5 Gy and a total dose was 20 Gy in the area of radiation. A comparative study of two groups of patients (with and without brachytherapy with stage III pancreatic cancer according to the TNM scale was taken in consideration. Results and Conclusions: The authors claim that the modification of catheter implantation using specially designed cannula, facilitates the process of inserting the catheter into the tumor, shortens the time needed for the procedure, and reduces the risk of complications. Mean survival time was 5.7 months. In the group of performed brachytherapy, the mean survival time was 6.7 months, while in the group of no brachytherapy performed – 4.4 months. In the group of brachytherapy, only one patient increased the dose of painkillers in the last month of his life. Remaining patients took constant doses of medicines. Perioperative HDR-Ir192 brachytherapy could be considered as a practical application of adjuvant therapy for pain relief in patients with an advanced pancreatic cancer.

CXCL17 expression by tumor cells recruits CD11b+Gr1 high F4/80- cells and promotes tumor progression.

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Aya Matsui

Full Text Available BACKGROUND: Chemokines are involved in multiple aspects of pathogenesis and cellular trafficking in tumorigenesis. In this study, we report that the latest member of the C-X-C-type chemokines, CXCL17 (DMC/VCC-1, recruits immature myeloid-derived cells and enhances early tumor progression. METHODOLOGY/PRINCIPAL FINDINGS: CXCL17 was preferentially expressed in some aggressive types of gastrointestinal, breast, and lung cancer cells. CXCL17 expression did not impart NIH3T3 cells with oncogenic potential in vitro, but CXCL17-expressing NIH3T3 cells could form vasculature-rich tumors in immunodeficient mice. Our data showed that CXCL17-expressing tumor cells increased immature CD11b(+Gr1(+ myeloid-derived cells at tumor sites in mice and promoted CD31(+ tumor angiogenesis. Extensive chemotactic assays proved that CXCL17-responding cells were CD11b(+Gr1(highF4/80(- cells (≈ 90% with a neutrophil-like morphology in vitro. Although CXCL17 expression could not increase the number of CD11b(+Gr1(+ cells in tumor-burdened SCID mice or promote metastases of low metastatic colon cancer cells, the existence of CXCL17-responding myeloid-derived cells caused a striking enhancement of xenograft tumor formation. CONCLUSIONS/SIGNIFICANCE: These results suggest that aberrant expression of CXCL17 in tumor cells recruits immature myeloid-derived cells and promotes tumor progression through angiogenesis.

Presentation of the project MobiKids Communication technologies, environmental exposures and risk of brain tumors in young people

International Nuclear Information System (INIS)

Cardis, E.; Alguacil, J.; Aragones, N.; Morales, M.; Carretero, G.; Ferreras, E.; Kinci, L.; Kogevinas, M.; Pollan, M.; Solis, R.; Vriheid, M.; Zumel, A.

2011-01-01

MOBI-Kids, an international study coordinated by CREAL, Barcelona, aims to assess the possible relationship between exposure in children and adolescents to electromagnetic fields (EMF) from communication technologies (RF - and extremely low frequency - ELF) and the risk of developing a brain tumor. It also investigated the effects of other risk factors, including environmental exposures in childhood and in utero.

Renal Tumors: Technical Success and Early Clinical Experience with Radiofrequency Ablation of 18 Tumors

International Nuclear Information System (INIS)

Sabharwal, Rohan; Vladica, Philip

2006-01-01

Purpose. To evaluate the feasibility, safety, and technical efficacy of image-guided radiofrequency ablation (RFA) for the treatment of small peripheral renal tumors and to report our early results with this treatment modality. Methods. Twenty-two RFA sessions for 18 tumors were performed in 11 patients with renal tumors. Indications included coexistent morbidity, high surgical or anesthetic risk, solitary kidney, and hereditary predisposition to renal cell carcinoma. Ten patients had CT-guided percutaneous RFA performed on an outpatient basis. One patient had open intraoperative ultrasound-guided RFA. Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor. With the exception of one patient with renal insufficiency who required gadolinium-enhanced MRI, the remaining patients underwent contrast-enhanced CT for post-treatment follow-up assessment. Follow-up was performed after 2-4 weeks and then at 3, 6, 12 months, and every 12 months thereafter. Results. Fourteen (78%) of 18 tumors were successfully ablated with one session. Three of the remaining four tumors required two sessions for successful ablation. One tumor will require a third session for areas of persistent enhancement. Mean patient age was 72.82 ± 10.43 years. Mean tumor size was 1.95 ± 0.79 cm. Mean follow-up time was 10.91 months. All procedures were performed without any major complications. Conclusions. Our early experience with percutaneous image-guided radiofrequency ablation demonstrates it to be a feasible, safe, noninvasive, and effective treatment of small peripheral renal tumors

A Rare Tumor of Nasal Cavity: Glomangiopericytoma

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Aysegul Verim

2014-01-01

Full Text Available Glomangiopericytoma is a rare vascular neoplasm characterized by a pattern of prominent perivascular growth. A 72-year-old woman was admitted to our clinic complaining of nasal obstruction, frequent epistaxis, and facial pain. A reddish tumor filling the left nasal cavity was observed on endoscopy and treated with endoscopic excision. Microscopically, closely packed cells interspersed with numerous thin-walled, branching staghorn vessels were seen. Glomangiopericytoma is categorized as a borderline low malignancy tumor by WHO classification. Long-term follow-up with systemic examination is necessary due to high risk of recurrence.

Clinical effect of increasing doses of lenalidomide in high-risk myelodysplastic syndrome and acute myeloid leukemia with chromosome 5 abnormalities

DEFF Research Database (Denmark)

Möllgård, Lars; Saft, Leonie; Treppendahl, Marianne Bach

2011-01-01

Patients with chromosome 5 abnormalities and high-risk myelodysplastic syndromes or acute myeloid leukemia have a poor outcome. We hypothesized that increasing doses of lenalidomide may benefit this group of patients by inhibiting the tumor clone, as assessed by fluorescence in situ hybridization...

Miniaturized microscope for high throughput screening of tumor spheroids in microfluidic devices

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Uranga, Javier; Rodríguez-Pena, Alejandro; Gahigiro, Desiré; Ortiz-de-Solorzano, Carlos

2018-02-01

High-throughput in vitro screening of highly physiological three-dimensional cell cultures (3D-HTS) is rapidly gaining importance in preclinical studies, to study the effect of the microenvironment in tumor development, and to evaluate the efficacy of new anticancer drugs. Furthermore, it could also be envisioned the use of 3D-HTS systems in personalized anti-cancer treatment planning, based on tumor organoids or spheroids grown from tumor biopsies or isolated tumor circulating cells. Most commercial, multi-well plate based 3D-HTS systems are large, expensive, and are based on the use of multi-well plates that hardly provide a physiological environment and require the use of large amounts of biological material and reagents. In this paper we present a novel, miniaturized inverted microscope (hereinafter miniscospe), made up of low-cost, mass producible parts, that can be used to monitor the growth of living tumor cell spheroids within customized three-dimensional microfluidic platforms. Our 3D-HTS miniscope combines phase contrast imaging based on oblique back illumination technique with traditional widefield epi-fluorescence imaging, implemented using miniaturized electro-optical parts and gradient-index refraction lenses. This small (3x6x2cm), lightweight device can effectively image overtime the growth of (>200) tumor spheroids in a controlled and reproducible environment. Our miniscope can be used to acquire time-lapse images of cellular living spheroids over the course of several hours and captures their growth before and after drug treatment, to evaluate the effectiveness of the drug.

Bilateral tumors of the upper urothelium

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Đokić Milan

2006-01-01

Full Text Available Introduction: The incidence of tumors of the upper urothelium is high in our country, apart from their relation to specific regions (BEN and PBEN and their frequent bilateralism. Bilateral forms are present in significant percentage and are followed, in most cases, by renal failure, which speaks in favor of conservative surgery, if possible. Objective: The aim of the study was to present epidemiological, pathoanatomical and clinical characteristics of bilateral tumors of the upper urothelium and evaluate the Results of their treatment. Method: Our retrospective study analyzed 12 patients with bilateral tumors of the upper urothelium who were treated in the period from 1992 to 1996, according to their epidemiological, clinical, pathoanatomical and pathohistological characteristics, type of surgical treatment and relevant success. Results: In the observed period, bilateral tumors of the upper urothelium were found in 8.2% of our patients. In the group of 12 patients, 5 females and 7 males, 11 cases were from the region of Balkan Endemic Nephropathy (BEN. Renal failure was recorded in high percentage (66%. Radical surgical treatment - total nephroureterectomy was performed in 9 kidney units, and conservative operation in 15 units. Relapse significantly depended on tumor stage and grade, not on type of surgical treatment in the majority of cases. Five-year survival was 58.33%; major cause of death was associated with further evolution of tumor, recurrence and tumor dissemination, respectively, while renal failure complications were the cause of death in one case. Conclusion: The success of treatment mainly depends on tumor stage and grade and not on type of surgical Method in conservative treatment, but renal failure and its complications are an important risk factor in these patients.

A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients.

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Habel, Laurel A; Shak, Steven; Jacobs, Marlena K; Capra, Angela; Alexander, Claire; Pho, Mylan; Baker, Joffre; Walker, Michael; Watson, Drew; Hackett, James; Blick, Noelle T; Greenberg, Deborah; Fehrenbacher, Louis; Langholz, Bryan; Quesenberry, Charles P

2006-01-01

The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting. A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score. After adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7-3.9%), 10.7% (95% CI 6.3-14.9%), and 15.5% (95% CI 7.6-22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5-7.9%), 17.8% (95% CI 11.8-23.3%), and 19.9% (95% CI 14.2-25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values. In this large, population-based study of lymph

Quantification of tumor extension in prostate biopsies: importance in the identification of confined tumors

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Leite Kátia R.M.

2003-01-01

Full Text Available OBJECTIVE: To assess the importance of quantifying the adenocarcinoma in prostate biopsies when determining the tumor's final stage in patients who undergo radical prostatectomy. To identify the best methodology for obtaining such data. PATIENTS AND METHODS: Prostate biopsies from 132 patients were examined, with determination of Gleason histological grade and tumor volume in number of involved fragments, tumor extent of the fragment mostly affected by the tumor and the total percentage of tumor in the specimen. Theses parameters were statistically correlated with the neoplasia's final stage following the evaluation of radical prostatectomy specimens. RESULTS: An average of 12 and a median of 14 biopsy fragments were evaluated per patient. In the univariate analysis the Gleason histological grade, the largest tumor extent in one fragment and the total percentage of tumor in the specimen were correlated with tumor stage of the surgical specimen. In the multivariate analysis, the Gleason histological grade and the total percentage of tumor were strongly correlated with the neoplasia's final stage. The risk of the tumor not being confined was 3 for Gleason 7 tumors and 10.6 for Gleason 8 tumors or above. In cases where the tumor involved more than 60% of the specimen, the risk of non-confined disease was 4.4 times. Among 19 patients with unfavorable histological parameters, Gleason > 7 and extension greater than 60% the tumor final stage was pT3 in 95%. CONCLUSION: When associated to the Gleason histological grade, tumor quantification in prostate biopsies is an important factor for determining organ-confined disease, and among the methods, total percentage of tumor is the most informative one. Such data should be included in the pathological report and must be incorporated in future nomograms.

Folic acid functionalized surface highlights 5-methylcytosine-genomic content within circulating tumor cells

KAUST Repository

Malara, Natalia

2014-07-01

Although the detection of methylated cell free DNA represents one of the most promising approaches for relapse risk assessment in cancer patients, the low concentration of cell-free circulating DNA constitutes the biggest obstacle in the development of DNA methylation-based biomarkers from blood. This paper describes a method for the measurement of genomic methylation content directly on circulating tumor cells (CTC), which could be used to deceive the aforementioned problem. Since CTC are disease related blood-based biomarkers, they result essential to monitor tumor\\'s stadiation, therapy, and early relapsing lesions. Within surface\\'s bio-functionalization and cell\\'s isolation procedure standardization, the presented approach reveals a singular ability to detect high 5-methylcytosine CTC-subset content in the whole CTC compound, by choosing folic acid (FA) as transducer molecule. Sensitivity and specificity, calculated for FA functionalized surface (FA-surface), result respectively on about 83% and 60%. FA-surface, allowing the detection and characterization of early metastatic dissemination, provides a unique advance in the comprehension of tumors progression and dissemination confirming the presence of CTC and its association with high risk of relapse. This functionalized surface identifying and quantifying high 5-methylcytosine CTC-subset content into the patient\\'s blood lead significant progress in cancer risk assessment, also providing a novel therapeutic strategy.© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Anticonvulsant therapy in brain-tumor related epilepsy

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Fröscher Walter

2016-06-01

Full Text Available Background. The lifetime risk of patients with brain tumors to have focal epileptic seizures is 10-100%; the risk depends on different histology. Specific guidelines for drug treatment of brain tumor-related seizures have not yet been established.

Determinants of Complications and Outcome in High-Risk Squamous Cell Head-and-Neck Cancer Treated With Perioperative High-Dose Rate Brachytherapy (PHDRB)

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Martinez-Monge, Rafael, E-mail: rmartinezm@unav.es [Department of Oncology, Clinica Universitaria de Navarra, Pamplona (Spain); Pagola Divasson, Maria; Cambeiro, Mauricio; Gaztanaga, Miren; Moreno, Marta; Arbea, Leire [Department of Oncology, Clinica Universitaria de Navarra, Pamplona (Spain); Montesdeoca, Nestor [Department of Maxillofacial Surgery, Clinica Universitaria de Navarra, Pamplona (Spain); Alcalde, Juan [Department of Otolaryngology, Clinica Universitaria de Navarra, Pamplona (Spain)

2011-11-15

Purpose: To determine the impact of a set of patient, tumor, and treatment factors on toxicity and outcome in patients with head-and-neck squamous cell cancer treated with surgical resection and perioperative high-dose rate brachytherapy (PHDRB) alone (single-modality [SM] group) (n = 46) or PHDRB combined with postoperative radiation or chemoradiation (combined-modality [CM] group) (n = 57). Methods and Materials: From 2000 to 2008, 103 patients received PHDRB after complete macroscopic resection. SM patients received 32 or 40 Gy of PHDRB in 8 or 10 twice-daily treatments for R0 and R1 resections. CM patients received 16 or 24 Gy of PHDRB in 4 or 6 twice-daily treatments for R0 and R1 resections, followed by external radiation of 45 Gy in 25 fractions with or without concomitant chemotherapy. Results: Grade {>=}4 complications according to the Radiation Therapy Oncology Group were more frequent in the SM group than in the CM group (p = 0.024). Grade {>=}3 and {>=}4 complications increased with the antecedent of prior irradiation (p = 0.032 and p = 0.006, respectively) and with TV{sub 150} values of 13 mL or greater (p = 0.032 and p = 0.032, respectively). After a median follow-up of 34.8 and 60.8 months for SM and CM patients, respectively, patients with high-risk margins had a 9-year local control rate of 68.0% whereas patients with wider margins had a 9-year local control of 93.7% (p = 0.045). Patients with primary and recurrent tumors had 9-year actuarial locoregional control rates of 81.8% and 54.2%, respectively (p = 0.003). Patients with lymph-vascular space invasion (LVSI)-positive and LVSI-negative tumors had 9-year distant control rates of 62.8% and 81.6%, respectively (p = 0.034). Disease-free survival rates decreased in recurrent cases (p = 0.006) as well as in LVSI-positive patients (p = 0.035). Conclusions: The complications observed are largely attributable to the antecedent of prior irradiation but can possibly be minimized by meticulous mapping and

Use of High-Frequency Jet Ventilation for Percutaneous Tumor Ablation

Energy Technology Data Exchange (ETDEWEB)

Denys, Alban, E-mail: alban.denys@chuv.ch; Lachenal, Yann; Duran, Rafael [Lausanne University Hospital, Department of Radiology and Interventional Radiology (Switzerland); Chollet-Rivier, Madeleine [Lausanne University Hospital, Department of Anesthesiology (Switzerland); Bize, Pierre [Lausanne University Hospital, Department of Radiology and Interventional Radiology (Switzerland)

2013-05-02

PurposeTo report feasibility and potential benefits of high-frequency jet ventilation (HFJV) in tumor ablations techniques in liver, kidney, and lung lesions.MethodsThis prospective study included 51 patients (14 women, mean age 66 years) bearing 66 tumors (56 hepatic, 5 pulmonary, 5 renal tumors) with a median size of 16 ± 8.7 mm, referred for tumor ablation in an intention-to-treat fashion before preoperative anesthesiology visit. Cancellation and complications of HFJV were prospectively recorded. Anesthesia and procedure duration, as well as mean CO{sub 2} capnea, were recorded. When computed tomography guidance was used, 3D spacial coordinates of an anatomical target <2 mm in diameter on 8 slabs of 4 slices of 3.75-mm slice thickness were registered.ResultsHFJV was used in 41 of 51 patients. Of the ten patients who were not candidate for HFJV, two patients had contraindication to HFJV (severe COPD), three had lesions invisible under HFJV requiring deep inspiration apnea for tumor targeting, and five patients could not have HFJV because of unavailability of a trained anesthetic team. No specific complication or hypercapnia related to HFJV were observed despite a mean anesthetic duration of 2 h and ventilation performed in procubitus (n = 4) or lateral decubitus (n = 6). Measured internal target movement was 0.3 mm in x- and y-axis and below the slice thickness of 3.75 mm in the z-axis in 11 patients.ConclusionsHFJV is feasible in 80 % of patients allowing for near immobility of internal organs during liver, kidney, and lung tumor ablation.

Risk analysis of fatal and incidental lung tumors in wister rats after inhalation of plutonium dioxide

International Nuclear Information System (INIS)

Kai, M.; Akahane, K.; Ogiso, Y.

2000-01-01

Cancer risk analysis was done in animal studies for inhalation of plutonium dioxide. Female Wister rats were exposed to an aerosol of plutonium with AMAD of 0.4-0.5 μm and followed up until they died. We made some model analyses using their likelihood function. This approach enables us to consider temporal variation in dose-response analysis. Each rat contributes to the total likelihood depending on fatal or incidental tumors. In Weibul model analysis, the logarithm of the hazard function can be linearly modeled with the term of log (dose), log-L model, and additional term of the square of log (dose), log-LQ model. The likelihood ratio statistics gave a significantly better fit of the log-LQ model. However, if data more than 4 Gy were excluded, there was no significant difference between both models. The ratio of hazard function at 1 Gy and 0 Gy, the excess relative risk, showed 30 for total tumors. This result was much different from those in PNL data (Sanders et al.). The difference of pulmonary deposition depending upon particle size would cause different tumor incidence. Our studies indicated significant increase of occurrence of fatal lung cancer at an average dose of 0.5 Gy and thus did not suggest that a life-span effective threshold for death was about 1 Gy to the lung, which is shown in some papers. In contrast PNL, the incidence of adenoma showing the maximum at 0.5 Gy decreased with increasing lung dose from 1.5 Gy or higher, where malignant tumors such as adenocarcinomas increased. This phenomenon was analyzed with carcinogenesis models. (author)

Breast tumor segmentation in high resolution x-ray phase contrast analyzer based computed tomography.

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Brun, E; Grandl, S; Sztrókay-Gaul, A; Barbone, G; Mittone, A; Gasilov, S; Bravin, A; Coan, P

2014-11-01

Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human-guided breast tumor segmentation. This method has been applied to high-resolution images of excised human organs, each of several gigabytes. The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure's possible applications. A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists. The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high-resolution x-ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.

Pharmacokinetic Tumor Heterogeneity as a Prognostic Biomarker for Classifying Breast Cancer Recurrence Risk.

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Mahrooghy, Majid; Ashraf, Ahmed B; Daye, Dania; McDonald, Elizabeth S; Rosen, Mark; Mies, Carolyn; Feldman, Michael; Kontos, Despina

2015-06-01

Heterogeneity in cancer can affect response to therapy and patient prognosis. Histologic measures have classically been used to measure heterogeneity, although a reliable noninvasive measurement is needed both to establish baseline risk of recurrence and monitor response to treatment. Here, we propose using spatiotemporal wavelet kinetic features from dynamic contrast-enhanced magnetic resonance imaging to quantify intratumor heterogeneity in breast cancer. Tumor pixels are first partitioned into homogeneous subregions using pharmacokinetic measures. Heterogeneity wavelet kinetic (HetWave) features are then extracted from these partitions to obtain spatiotemporal patterns of the wavelet coefficients and the contrast agent uptake. The HetWave features are evaluated in terms of their prognostic value using a logistic regression classifier with genetic algorithm wrapper-based feature selection to classify breast cancer recurrence risk as determined by a validated gene expression assay. Receiver operating characteristic analysis and area under the curve (AUC) are computed to assess classifier performance using leave-one-out cross validation. The HetWave features outperform other commonly used features (AUC = 0.88 HetWave versus 0.70 standard features). The combination of HetWave and standard features further increases classifier performance (AUCs 0.94). The rate of the spatial frequency pattern over the pharmacokinetic partitions can provide valuable prognostic information. HetWave could be a powerful feature extraction approach for characterizing tumor heterogeneity, providing valuable prognostic information.

Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer

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Vinayak Muralidhar

2016-02-01

Full Text Available Purpose : Recent retrospective data suggest that brachytherapy (BT boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA 20 ng/ml. Material and methods: We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors. Results : EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258, and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270. Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022. Conclusions : Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined “favorable high-risk” category may be used to personalize therapy for men with high-risk disease.

Value of high-risk HPV-DNA testing in the triage of ASCUS.

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Silverloo, Iréne; Andrae, Bengt; Wilander, Erik

2009-01-01

OBJECTIVE. Atypical squamous cells of undetermined significance (ASCUS) cells, occurring in organized cytological screening, may be either high-risk human papillomavirus (HPV) positive or negative. To refine the assessment of women with ASCUS, a high-risk HPV-DNA test is recommended as triage in Sweden. A total of 197 consecutive women (mean age 39 years, range 21-60) with a diagnosis of ASCUS from the primary screening were selected for triage. Their cervical smears were collected and evaluated by using conventional cytological examination in combination with a high-risk HPV-DNA test (hybrid capture 2). The women were categorized into four groups: Group A, Cytology + /HPV + ; Group B, Cytology-/HPV + ; Group C, Cytology + /HPV-; and Group D, Cytology-/ HPV-. Women within Groups A-C were admitted for colposcopy and cervical biopsy. The women in Group D were considered as a low-risk group for tumor development, and were re-examined after three years in the next round of the organized screening. In women in Group A (n=58) the prevalence of histological verified CIN2-3 was 41%, in Group B (n=41) 20%, and in Group C (n=9) 0%. In Group D (n=89), repeated primary screening three years later revealed CIN2-3 in two biopsies from 74 women studied (age in women with ASCUS. It was 74% in women or =50 years. Adding a high-risk HPV test in secondary screening increased the identification of women with CIN2-3 lesions by 33% in comparison with repeat cytology (p=0.01). The clinical significance of the ASCUS diagnosis varied with age of the women.

A minimally invasive multiple marker approach allows highly efficient detection of meningioma tumors

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Meese Eckart

2006-12-01

Full Text Available Abstract Background The development of effective frameworks that permit an accurate diagnosis of tumors, especially in their early stages, remains a grand challenge in the field of bioinformatics. Our approach uses statistical learning techniques applied to multiple antigen tumor antigen markers utilizing the immune system as a very sensitive marker of molecular pathological processes. For validation purposes we choose the intracranial meningioma tumors as model system since they occur very frequently, are mostly benign, and are genetically stable. Results A total of 183 blood samples from 93 meningioma patients (WHO stages I-III and 90 healthy controls were screened for seroreactivity with a set of 57 meningioma-associated antigens. We tested several established statistical learning methods on the resulting reactivity patterns using 10-fold cross validation. The best performance was achieved by Naïve Bayes Classifiers. With this classification method, our framework, called Minimally Invasive Multiple Marker (MIMM approach, yielded a specificity of 96.2%, a sensitivity of 84.5%, and an accuracy of 90.3%, the respective area under the ROC curve was 0.957. Detailed analysis revealed that prediction performs particularly well on low-grade (WHO I tumors, consistent with our goal of early stage tumor detection. For these tumors the best classification result with a specificity of 97.5%, a sensitivity of 91.3%, an accuracy of 95.6%, and an area under the ROC curve of 0.971 was achieved using a set of 12 antigen markers only. This antigen set was detected by a subset selection method based on Mutual Information. Remarkably, our study proves that the inclusion of non-specific antigens, detected not only in tumor but also in normal sera, increases the performance significantly, since non-specific antigens contribute additional diagnostic information. Conclusion Our approach offers the possibility to screen members of risk groups as a matter of routine

Mitochondrial DNA Mutations in Epithelial Ovarian Tumor Progression

Science.gov (United States)

2007-12-01

Panici PL, Fazio VM: Mutations of D310 mitochondrial mononu- cleotide repeat in primary tumors and cytological speci- mens . Cancer Lett 2003, 190:73...BR: Detection of LOH and mitochondrial DNA alter- ations in ductal lavage and nipple aspirate fluids from high- risk patients. Breast Cancer Res

Transcriptome sequencing in prostate cancer identifies inter-tumor heterogeneity

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Janet Mendonca

2015-06-01

Full Text Available Given the dearth of gene mutations in prostate cancer, [1] ,[2] it is likely that genomic rearrangements play a significant role in the evolution of prostate cancer. However, in the search for recurrent genomic alterations, "private alterations" have received less attention. Such alterations may provide insights into the evolution, behavior, and clinical outcome of an individual tumor. In a recent report in "Genome Biology" Wyatt et al. [3] defines unique alterations in a cohort of high-risk prostate cancer patient with a lethal phenotype. Utilizing a transcriptome sequencing approach they observe high inter-tumor heterogeneity; however, the genes altered distill into three distinct cancer-relevant pathways. Their analysis reveals the presence of several non-ETS fusions, which may contribute to the phenotype of individual tumors, and have significance for disease progression.

Open Partial Nephrectomy for High-Risk Renal Masses Is Associated with Renal Pseudoaneurysms: Assessment of a Severe Procedure-Related Complication

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M. C. Kriegmair

2015-01-01

Full Text Available Objectives. A symptomatic renal pseudoaneurysm (RPA is a severe complication after open partial nephrectomy (OPN. The aim of our study was to assess incidence and risk factors for RPA formation. Furthermore, we present our management strategy. Patients and Methods. Clinical records of consecutive patients undergoing OPN were assessed for surgical outcome and postoperative complications. Renal masses were risk stratified for tumor complexity according to the PADUA score. Uni- and multivariate analysis for symptomatic RPAs were performed using the t-tests and logistic regression. Results. We identified 233 patients treated with OPN. Symptomatic RPAs were observed in 13 (5.6% patients, on average 14 (4–42 days after surgery. Uni- and multivariate analysis identified tumor complexity to be an independent predictor for symptomatic RPAs (p=0.004. There was a significant correlation between RPAs and transfusion and the duration of stay (p<0.001 and p=0.021. Symptomatic RPAs were diagnosed with CT scans and successfully treated with arterial embolization. Discussion. Symptomatic RPAs are not uncommon after OPN for high-risk renal masses. A high nephrometry score is a predictor for this severe complication and may enable a risk-stratified followup. RPAs can successfully be located by CT angiography, which enables targeted angiographic treatment.

Complications from high-dose para-aortic and pelvic irradiation for malignant genitourinary tumors

International Nuclear Information System (INIS)

Komaki, R.; Barber-Derus, S.; Glisch, C.; Lawton, C.A.; Cox, J.D.; Wilson, J.F.

1986-01-01

Between 1967 and 1982, 59 patients (33 with gynecologic malignancies and 26 with malignant tumors of the genitourinary system) received irradiation of 40 Gy or more for metastases to the para-aortic lymph nodes, in addition to pelvic irradiation. Disease in the para-aortic lymph nodes was controlled in 50 patients; the treatment failed in nine. Moderately acute side effects were seen in 25 patients, but none was severe. Late effects of irradiation were moderate in five patients and severe in three. Thirty patients are alive at 5 years. The benefits of local control and prolonged disease-free survival appear to outweigh considerably the risk of late effects from pelvic and para-aortic irradiation for advanced malignant tumors of the genitourinary system

Quantification of tumor morphology via 3D histology: application to oral cavity cancers

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Doyle, Scott; Brandwein-Gensler, Margaret; Tomaszewski, John

2016-03-01

Traditional histopathology quantifies disease through the study of glass slides, i.e. two-dimensional samples that are representative of the overall process. We hypothesize that 3D reconstruction can enhance our understanding of histopathologic interpretations. To test this hypothesis, we perform a pilot study of the risk model for oral cavity cancer (OCC), which stratifies patients into low-, intermediate-, and high-risk for locoregional disease-free survival. Classification is based on study of hematoxylin and eosin (H and E) stained tissues sampled from the resection specimens. In this model, the Worst Pattern of Invasion (WPOI) is assessed, representing specific architectural features at the interface between cancer and non-cancer tissue. Currently, assessment of WPOI is based on 2D sections of tissue, representing complex 3D structures of tumor growth. We believe that by reconstructing a 3D model of tumor growth and quantifying the tumor-host interface, we can obtain important diagnostic information that is difficult to assess in 2D. Therefore, we introduce a pilot study framework for visualizing tissue architecture and morphology in 3D from serial sections of histopathology. This framework can be used to enhance predictive models for diseases where severity is determined by 3D biological structure. In this work we utilize serial H and E-stained OCC resections obtained from 7 patients exhibiting WPOI-3 (low risk of recurrence) through WPOI-5 (high risk of recurrence). A supervised classifier automatically generates a map of tumor regions on each slide, which are then co-registered using an elastic deformation algorithm. A smooth 3D model of the tumor region is generated from the registered maps, which is suitable for quantitative tumor interface morphology feature extraction. We report our preliminary models created with this system and suggest further enhancements to traditional histology scoring mechanisms that take spatial architecture into consideration.

Postoperative Outcomes of Enucleation and Standard Resections in Patients with a Pancreatic Neuroendocrine Tumor.

Science.gov (United States)

Jilesen, Anneke P J; van Eijck, Casper H J; Busch, Olivier R C; van Gulik, Thomas M; Gouma, Dirk J; van Dijkum, Els J M Nieveen

2016-03-01

Either enucleation or more extended resection is performed to treat patients with pancreatic neuroendocrine tumor (pNET). Aim was to analyze the postoperative complications for each operation separately. Furthermore, independent risk factors for complications and incidence of pancreatic insufficiency were analyzed. Retrospective all resected patients from two academic hospitals in The Netherlands between 1992 and 2013 were included. Postoperative complications were scored by both ISGPS and Clavien-Dindo criteria. Based on tumor location, operations were compared. Independent risk factors for overall complications were identified. During long-term follow-up, pancreatic insufficiency and recurrent disease were analyzed. Tumor enucleation was performed in 60/205 patients (29%), pancreatoduodenectomy in 65/205 (31%), distal pancreatectomy in 72/205 (35%) and central pancreatectomy in 8/205 (4%) patients. Overall complications after tumor enucleation of the pancreatic head and pancreatoduodenectomy were comparable, 24/35 (69%) versus 52/65 (80%). The same was found after tumor enucleation and resection of the pancreatic tail (36 vs.58%). Number of re-interventions and readmissions were comparable between all operations. After pancreatoduodenectomy, 33/65 patients had lymph node metastasis and in patients with tumor size ≤2 cm, 55% had lymph node metastasis. Tumor in the head and BMI ≥25 kg/m(2) were independent risk factors for complications after enucleation. During follow-up, incidence of exocrine and endocrine insufficiency was significant higher after pancreatoduodenectomy (resp. 55 and 19%) compared to the tumor enucleation and distal pancreatectomy (resp. 5 and 7% vs. 8 and 13%). After tumor enucleation 19% developed recurrent disease. Since the complication rate, need for re-interventions and readmissions were comparable for all resections, tumor enucleation may be regarded as high risk. Appropriate operation should be based on tumor size, location, and

Pathogenesis and treatment of adult-type granulosa cell tumor of the ovary.

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Färkkilä, Anniina; Haltia, Ulla-Maija; Tapper, Johanna; McConechy, Melissa K; Huntsman, David G; Heikinheimo, Markku

2017-08-01

Adult-type granulosa cell tumor is a clinically and molecularly unique subtype of ovarian cancer. These tumors originate from the sex cord stromal cells of the ovary and represent 3-5% of all ovarian cancers. The majority of adult-type granulosa cell tumors are diagnosed at an early stage with an indolent prognosis. Surgery is the cornerstone for the treatment of both primary and relapsed tumor, while chemotherapy is applied only for advanced or non-resectable cases. Tumor stage is the only factor consistently associated with prognosis. However, every third of the patients relapse, typically in 4-7 years from diagnosis, leading to death in 50% of these patients. Anti-Müllerian Hormone and inhibin B are currently the most accurate circulating biomarkers. Adult-type granulosa cell tumors are molecularly characterized by a pathognomonic somatic missense point mutation 402C->G (C134W) in the transcription factor FOXL2. The FOXL2 402C->G mutation leads to increased proliferation and survival of granulosa cells, and promotes hormonal changes. Histological diagnosis of adult-type granulosa cell tumor is challenging, therefore testing for the FOXL2 mutation is crucial for differential diagnosis. Large international collaborations utilizing molecularly defined cohorts are essential to improve and validate new treatment strategies for patients with high-risk or relapsed adult-type granulosa cell tumor. Key Messages: Adult-type granulosa cell tumor is a unique ovarian cancer with an indolent, albeit unpredictable disease course. Adult-type granulosa cell tumors harbor a pathognomonic somatic missense mutation in transcription factor FOXL2. The key challenges in the treatment of patients with adult-type granulosa cell tumor lie in the identification and management of patients with high-risk or relapsed disease.

Tumors of the brain and nervous system after radiotherapy in childhood

International Nuclear Information System (INIS)

Ron, E.; Modan, B.; Boice, J.D. Jr.; Alfandary, E.; Stovall, M.; Chetrit, A.; Katz, L.

1988-01-01

We investigated the relation between radiotherapy in childhood for tinea capitis and the later development of tumors of the brain and nervous system among 10,834 patients treated between 1948 and 1960 in Israel. Benign and malignant tumors were identified from the pathology records of all Israeli hospitals and from Israeli national cancer and death registries. Doses of radiation to the neural tissue were retrospectively estimated for each patient (mean, 1.5 Gy). Sixty neural tumors developed in the patients exposed as children, and the 30-year cumulative risk (+/- SE) was 0.8 +/- 0.2 percent. The incidence of tumors was 1.8 per 10,000 persons per year. The estimated relative risk as compared with that for 10,834 matched general-population controls and 5392 siblings who had not been irradiated was 6.9 (95 percent confidence interval, 4.1 to 11.6) for all tumors and 8.4 (confidence interval, 4.8 to 14.8) when the analysis was restricted to neural tumors of the head and neck. Increased risks were apparent for meningiomas (relative risk, 9.5; n = 19), gliomas (relative risk, 2.6; n = 7), nerve-sheath tumors (relative risk, 18.8; n = 25), and other neural tumors (relative risk, 3.4; n = 9). A strong dose--response relation was found, with the relative risk approaching 20 after estimated doses of approximately 2.5 Gy. Our study confirms that radiation doses on the order of 1 to 2 Gy can significantly increase the risk of neural tumors

Laparoscopic partial nephrectomy for endophytic hilar tumors

DEFF Research Database (Denmark)

Di Pierro, G B; Tartaglia, N; Aresu, L

2014-01-01

To analyze feasibility and outcomes of laparoscopic partial nephrectomy (LPN) for endophytic hilar tumors in low-intermediate (ASA I-II) risk patients.......To analyze feasibility and outcomes of laparoscopic partial nephrectomy (LPN) for endophytic hilar tumors in low-intermediate (ASA I-II) risk patients....

Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors: A Nationwide, Multicenter Study

NARCIS (Netherlands)

Clement, S.C.; Schouten-van Meeteren, A.Y.; Boot, A.M.; Claahsen-van der Grinten, H.L.; Granzen, B.; Han, K.; Janssens, G.O.; Michiels, E.M.; Trotsenburg, A.S. van; Vandertop, W.P.; Vuurden, D.G. van; Kremer, L.C.; Caron, H.N.; Santen, H.M. van

2016-01-01

Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived >/= 2 years after diagnosis. Patients

A Case of Nongerminomatous Germ Cell Tumor of the Pineal Region: Risks and Advantages of Biopsy by Endoscopic Approach.

Science.gov (United States)

Dobran, Mauro; Nasi, Davide; Mancini, Fabrizio; Gladi, Maurizio; Scerrati, Massimo

2018-01-01

A 21-year-old male was admitted to our department with headache and drowsiness. CT scan and MRI revealed acute obstructive hydrocephalus caused by a pineal region mass. The serum and CSF levels of beta-human chorionic gonadotropin (beta-hCG) were 215 IU/L and 447 IU/L, respectively, while levels of alpha-fetoprotein (AFP) were normal. A germ cell tumor (GCT) was suspected, and the patient underwent endoscopic third ventriculostomy (ETV) with biopsy. After four days from surgery, the tumor bled with mass expansion and ETV stoma occlusion; thus, a ventriculoperitoneal shunt was positioned. After ten months, the tumor metastasized to the thorax and abdomen with progression of intracerebral tumor mass. Despite the aggressive nature of this tumor, ETV remains a valid approach for a pineal region mass, but in case of GCT, the risk of bleeding should be taken into account, during and after the surgical procedure.

A Case of Nongerminomatous Germ Cell Tumor of the Pineal Region: Risks and Advantages of Biopsy by Endoscopic Approach

Directory of Open Access Journals (Sweden)

Mauro Dobran

2018-01-01

Full Text Available A 21-year-old male was admitted to our department with headache and drowsiness. CT scan and MRI revealed acute obstructive hydrocephalus caused by a pineal region mass. The serum and CSF levels of beta-human chorionic gonadotropin (beta-hCG were 215 IU/L and 447 IU/L, respectively, while levels of alpha-fetoprotein (AFP were normal. A germ cell tumor (GCT was suspected, and the patient underwent endoscopic third ventriculostomy (ETV with biopsy. After four days from surgery, the tumor bled with mass expansion and ETV stoma occlusion; thus, a ventriculoperitoneal shunt was positioned. After ten months, the tumor metastasized to the thorax and abdomen with progression of intracerebral tumor mass. Despite the aggressive nature of this tumor, ETV remains a valid approach for a pineal region mass, but in case of GCT, the risk of bleeding should be taken into account, during and after the surgical procedure.

Neuroendocrine tumors and smoking

Directory of Open Access Journals (Sweden)

Tanja Miličević

2016-12-01

Full Text Available Neuroendocrine cells are dispersed around the body and can be found within the gastrointestinal system, lungs, larynx, thymus, thyroid, adrenal, gonads, skin and other tissues. These cells form the so-called ''diffuse neuroendocrine system'' and tumors arising from them are defined as neuroendocrine tumors (NETs. The traditional classification of NETs based on their embryonic origin includes foregut tumors (lung, thymus, stomach, pancreas and duodenum, midgut tumors (beyond the ligament of Treitz of the duodenum to the proximal transverse colon and hindgut tumors (distal colon and rectum. NETs at each site are biologically and clinically distinct from their counterparts at other sites. Symptoms in patients with early disease are often insidious in onset, leading to a delay in diagnosis. The majority of these tumors are thus diagnosed at a stage at which the only curative treatment, radical surgical intervention, is no longer an option. Due to the increasing incidence and mortality, many studies have been conducted in order to identify risk factors for the development of NETs. Still, little is known especially when it comes to preventable risk factors such as smoking. This review will focus on smoking and its contribution to the development of different subtypes of NETs.

Ultrasmall Glutathione-Protected Gold Nanoclusters as Next Generation Radiotherapy Sensitizers with High Tumor Uptake and High Renal Clearance

Science.gov (United States)

Zhang, Xiao-Dong; Luo, Zhentao; Chen, Jie; Song, Shasha; Yuan, Xun; Shen, Xiu; Wang, Hao; Sun, Yuanming; Gao, Kai; Zhang, Lianfeng; Fan, Saijun; Leong, David Tai; Guo, Meili; Xie, Jianping

2015-03-01

Radiotherapy is often the most straightforward first line cancer treatment for solid tumors. While it is highly effective against tumors, there is also collateral damage to healthy proximal tissues especially with high doses. The use of radiosensitizers is an effective way to boost the killing efficacy of radiotherapy against the tumor while drastically limiting the received dose and reducing the possible damage to normal tissues. Here, we report the design and application of a good radiosensitizer by using ultrasmall Au29-43(SG)27-37 nanoclusters (protecting shell. The GSH-coated Au29-43(SG)27-37 nanoclusters can escape the RES absorption, leading to a good tumor uptake (~8.1% ID/g at 24 h post injection). As a result, the as-designed Au nanoclusters led to a strong enhancement for radiotherapy, as well as a negligible damage to normal tissues. After the treatment, the ultrasmall Au29-43(SG)27-37 nanoclusters can be efficiently cleared by the kidney, thereby avoiding potential long-term side-effects caused by the accumulation of gold atoms in the body. Our data suggest that the ultrasmall peptide-protected Au nanoclusters are a promising radiosensitizer for cancer radiotherapy.

Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors.

Science.gov (United States)

Adalsteinsson, Viktor A; Ha, Gavin; Freeman, Samuel S; Choudhury, Atish D; Stover, Daniel G; Parsons, Heather A; Gydush, Gregory; Reed, Sarah C; Rotem, Denisse; Rhoades, Justin; Loginov, Denis; Livitz, Dimitri; Rosebrock, Daniel; Leshchiner, Ignaty; Kim, Jaegil; Stewart, Chip; Rosenberg, Mara; Francis, Joshua M; Zhang, Cheng-Zhong; Cohen, Ofir; Oh, Coyin; Ding, Huiming; Polak, Paz; Lloyd, Max; Mahmud, Sairah; Helvie, Karla; Merrill, Margaret S; Santiago, Rebecca A; O'Connor, Edward P; Jeong, Seong H; Leeson, Rachel; Barry, Rachel M; Kramkowski, Joseph F; Zhang, Zhenwei; Polacek, Laura; Lohr, Jens G; Schleicher, Molly; Lipscomb, Emily; Saltzman, Andrea; Oliver, Nelly M; Marini, Lori; Waks, Adrienne G; Harshman, Lauren C; Tolaney, Sara M; Van Allen, Eliezer M; Winer, Eric P; Lin, Nancy U; Nakabayashi, Mari; Taplin, Mary-Ellen; Johannessen, Cory M; Garraway, Levi A; Golub, Todd R; Boehm, Jesse S; Wagle, Nikhil; Getz, Gad; Love, J Christopher; Meyerson, Matthew

2017-11-06

Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing. Using whole-exome sequencing, we validate the concordance of clonal somatic mutations (88%), copy number alterations (80%), mutational signatures, and neoantigens between cfDNA and matched tumor biopsies from 41 patients with ≥10% cfDNA tumor content. In summary, we provide methods to identify patients eligible for comprehensive cfDNA profiling, revealing its applicability to many patients, and demonstrate high concordance of cfDNA and metastatic tumor whole-exome sequencing.

Dosimetry at the location of secondary tumors after radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Baas, H W; Davelaar, J J; Broerse, J J; Noordijk, E M [University Hospital, Leiden (Netherlands). Dept. of Clinical Oncology

1995-12-01

After a latency period of many years the incidence of a secondary tumor is considered a serious late effect of radiotherapy. Analysis of about 200 patients, treated by radiotherapy for Hodgkin`s disease in our hospital, shows an actuarial risk for the incidence of a secondary tumor of about 7% after 10 years. The chance of tumor induction depends on the dose at the location of the tumor and therefore a good dose estimation is mandatory. Radiotherapy was given with Co-60 in the early years and with linear accelerators thereafter, exposing the target areas to 36 - 40 Gy. For dose estimations at the penumbra and outside the beam, where tumor incidence is expected to be high, we used a.o. Monte Carlo calculations. We developed an EGS4 computer simulation for a treatment beam from a linear accelerator irradiating a mathematical phantom representing the patient geometry (GSF ADAM phantom). The isodose curves at certain energies were obtained for a water phantom and fitted quite well with measurements. In addition to Monte Carlo calculations we also used existing treatment planning systems. The dose estimations of a number of patients and the derived risk per unit of dose, which is important for both radiotherapy as well as radiation protection in general, is discussed.

The burden of chronic pain after major head and neck tumor therapy

Directory of Open Access Journals (Sweden)

Abdullah Sulieman Terkawi

2017-01-01

Conclusion: Our study highlighted the high burden of chronic pain after therapy for major head and neck tumors. We identified demographic and clinical factors that are associated with the presence of chronic pain. Further studies are required to better understand the risk factors to implement strategies to prevent, alleviate, and treat chronic pain associated with major head and neck tumor therapies.

Risk Factors for Neovascular Glaucoma After Proton Beam Therapy of Uveal Melanoma: A Detailed Analysis of Tumor and Dose–Volume Parameters

Energy Technology Data Exchange (ETDEWEB)

Mishra, Kavita K., E-mail: kmishra@radonc.ucsf.edu [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Daftari, Inder K.; Weinberg, Vivian [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Cole, Tia [The Tumori Foundation, San Francisco, California (United States); Quivey, Jeanne M.; Castro, Joseph R.; Phillips, Theodore L. [Department of Radiation Oncology, University of California, San Francisco, San Francisco, California (United States); Char, Devron H. [The Tumori Foundation, San Francisco, California (United States)

2013-10-01

Purpose: To determine neovascular glaucoma (NVG) incidence and identify contributing tumor and dosing factors in uveal melanoma patients treated with proton beam radiation therapy (PBRT). Methods and Materials: A total of 704 PBRT patients treated by a single surgeon (DHC) for uveal melanoma (1996-2010) were reviewed for NVG in our prospectively maintained database. All patients received 56 GyE in 4 fractions. Median follow-up was 58.3 months. Analyses included the Kaplan-Meier method to estimate NVG distributions, univariate log–rank tests, and Cox's proportional hazards multivariate analysis using likelihood ratio tests to identify independent risk factors of NVG among patient, tumor, and dose–volume histogram parameters. Results: The 5-year PBRT NVG rate was 12.7% (95% confidence interval [CI] 10.2%-15.9%). The 5-year rate of enucleation due to NVG was 4.9% (95% CI 3.4%-7.2%). Univariately, the NVG rate increased significantly with larger tumor diameter (P<.0001), greater height (P<.0001), higher T stage (P<.0001), and closer proximity to the disc (P=.002). Dose–volume histogram analysis revealed that if >30% of the lens or ciliary body received ≥50% dose (≥28 GyE), there was a higher probability of NVG (P<.0001 for both). Furthermore, if 100% of the disc or macula received ≥28 GyE, the NVG rate was higher (P<.0001 and P=.03, respectively). If both anterior and posterior doses were above specified cut points, NVG risk was highest (P<.0001). Multivariate analysis confirmed significant independent risk factors to include tumor height (P<.0001), age (P<.0001), %disc treated to ≥50% Dose (<100% vs 100%) (P=.0007), larger tumor diameter (P=.01), %lens treated to ≥90% Dose (0 vs >0%-30% vs >30%) (P=.01), and optic nerve length treated to ≥90% Dose (≤1 mm vs >1 mm) (P=.02). Conclusions: Our current PBRT patients experience a low rate of NVG and resultant enucleation compared with historical data. The present analysis shows that tumor height

Experimental rat lung tumor model with intrabronchial tumor cell implantation.

Science.gov (United States)

Gomes Neto, Antero; Simão, Antônio Felipe Leite; Miranda, Samuel de Paula; Mourão, Lívia Talita Cajaseiras; Bezerra, Nilfácio Prado; Almeida, Paulo Roberto Carvalho de; Ribeiro, Ronaldo de Albuquerque

2008-01-01

The objective of this study was to develop a rat lung tumor model for anticancer drug testing. Sixty-two female Wistar rats weighing 208 +/- 20 g were anesthetized intraperitoneally with 2.5% tribromoethanol (1 ml/100 g live weight), tracheotomized and intubated with an ultrafine catheter for inoculation with Walker's tumor cells. In the first step of the experiment, a technique was established for intrabronchial implantation of 10(5) to 5 x 10(5) tumor cells, and the tumor take rate was determined. The second stage consisted of determining tumor volume, correlating findings from high-resolution computed tomography (HRCT) with findings from necropsia and determining time of survival. The tumor take rate was 94.7% for implants with 4 x 10(5) tumor cells, HRCT and necropsia findings matched closely (r=0.953; p<0.0001), the median time of survival was 11 days, and surgical mortality was 4.8%. The present rat lung tumor model was shown to be feasible: the take rate was high, surgical mortality was negligible and the procedure was simple to perform and easily reproduced. HRCT was found to be a highly accurate tool for tumor diagnosis, localization and measurement and may be recommended for monitoring tumor growth in this model.

Breast tumor segmentation in high resolution x-ray phase contrast analyzer based computed tomography

Energy Technology Data Exchange (ETDEWEB)

Brun, E., E-mail: emmanuel.brun@esrf.fr [European Synchrotron Radiation Facility (ESRF), Grenoble 380000, France and Department of Physics, Ludwig-Maximilians University, Garching 85748 (Germany); Grandl, S.; Sztrókay-Gaul, A.; Gasilov, S. [Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, 81377 Munich (Germany); Barbone, G. [Department of Physics, Harvard University, Cambridge, Massachusetts 02138 (United States); Mittone, A.; Coan, P. [Department of Physics, Ludwig-Maximilians University, Garching 85748, Germany and Institute for Clinical Radiology, Ludwig-Maximilians-University Hospital Munich, 81377 Munich (Germany); Bravin, A. [European Synchrotron Radiation Facility (ESRF), Grenoble 380000 (France)

2014-11-01

Purpose: Phase contrast computed tomography has emerged as an imaging method, which is able to outperform present day clinical mammography in breast tumor visualization while maintaining an equivalent average dose. To this day, no segmentation technique takes into account the specificity of the phase contrast signal. In this study, the authors propose a new mathematical framework for human-guided breast tumor segmentation. This method has been applied to high-resolution images of excised human organs, each of several gigabytes. Methods: The authors present a segmentation procedure based on the viscous watershed transform and demonstrate the efficacy of this method on analyzer based phase contrast images. The segmentation of tumors inside two full human breasts is then shown as an example of this procedure’s possible applications. Results: A correct and precise identification of the tumor boundaries was obtained and confirmed by manual contouring performed independently by four experienced radiologists. Conclusions: The authors demonstrate that applying the watershed viscous transform allows them to perform the segmentation of tumors in high-resolution x-ray analyzer based phase contrast breast computed tomography images. Combining the additional information provided by the segmentation procedure with the already high definition of morphological details and tissue boundaries offered by phase contrast imaging techniques, will represent a valuable multistep procedure to be used in future medical diagnostic applications.

Not all risks are equal: the risk taking inventory for high-risk sports.

Science.gov (United States)

Woodman, Tim; Barlow, Matt; Bandura, Comille; Hill, Miles; Kupciw, Dominika; Macgregor, Alexandra

2013-10-01

Although high-risk sport participants are typically considered a homogenous risk-taking population, attitudes to risk within the high-risk domain can vary considerably. As no validated measure allows researchers to assess risk taking within this domain, we validated the Risk Taking Inventory (RTI) for high-risk sport across four studies. The RTI comprises seven items across two factors: deliberate risk taking and precautionary behaviors. In Study 1 (n = 341), the inventory was refined and tested via a confirmatory factor analysis used in an exploratory fashion. The subsequent three studies confirmed the RTI's good model-data fit via three further separate confirmatory factor analyses. In Study 2 (n = 518) and in Study 3 (n = 290), concurrent validity was also confirmed via associations with other related traits (sensation seeking, behavioral activation, behavioral inhibition, impulsivity, self-esteem, extraversion, and conscientiousness). In Study 4 (n = 365), predictive validity was confirmed via associations with mean accidents and mean close calls in the high-risk domain. Finally, in Study 4, the self-report version of the inventory was significantly associated with an informant version of the inventory. The measure will allow researchers and practitioners to investigate risk taking as a variable that is conceptually distinct from participation in a high-risk sport.

Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors : A Nationwide, Multicenter Study

NARCIS (Netherlands)

Clement, Sarah C; Schouten-van Meeteren, Antoinette Y N; Boot, Annemieke M; Claahsen-van der Grinten, Hedy L; Granzen, Bernd; Sen Han, K; Janssens, Geert O; Michiels, Erna M; van Trotsenburg, A S Paul; Vandertop, W Peter; van Vuurden, Dannis G; Kremer, Leontien C M; Caron, Hubert N; van Santen, Hanneke M

2016-01-01

Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients

Prevalence and Risk Factors of Early Endocrine Disorders in Childhood Brain Tumor Survivors: A Nationwide, Multicenter Study

NARCIS (Netherlands)

Clement, Sarah C.; Schouten-van Meeteren, Antoinette Y. N.; Boot, Annemieke M.; Claahsen-van der Grinten, Hedy L.; Granzen, Bernd; Sen Han, K.; Janssens, Geert O.; Michiels, Erna M.; van Trotsenburg, A. S. Paul; Vandertop, W. Peter; van Vuurden, Dannis G.; Kremer, Leontien C. M.; Caron, Hubert N.; van Santen, Hanneke M.

2016-01-01

Purpose To evaluate the prevalence of, and risk factors for, early endocrine disorders in childhood brain tumor survivors (CBTS). Patients and Methods This nationwide study cohort consisted of 718 CBTS who were diagnosed between 2002 and 2012, and who survived ≥ 2 years after diagnosis. Patients

Activity of MM-398, nanoliposomal irinotecan (nal-IRI), in Ewing's family tumor xenografts is associated with high exposure of tumor to drug and high SLFN11 expression.

Science.gov (United States)

Kang, Min H; Wang, Jing; Makena, Monish R; Lee, Joo-Sang; Paz, Nancy; Hall, Connor P; Song, Michael M; Calderon, Ruben I; Cruz, Riza E; Hindle, Ashly; Ko, Winford; Fitzgerald, Jonathan B; Drummond, Daryl C; Triche, Timothy J; Reynolds, C Patrick

2015-03-01

To determine the pharmacokinetics and the antitumor activity in pediatric cancer models of MM-398, a nanoliposomal irinotecan (nal-IRI). Mouse plasma and tissue pharmacokinetics of nal-IRI and the current clinical formulation of irinotecan were characterized. In vivo activity of irinotecan and nal-IRI was compared in xenograft models (3 each in nu/nu mice) of Ewing's sarcoma family of tumors (EFT), neuroblastoma (NB), and rhabdomyosarcoma (RMS). SLFN11 expression was assessed by Affymetrix HuEx arrays, Taqman RT-PCR, and immunoblotting. Plasma and tumor concentrations of irinotecan and SN-38 (active metabolite) were approximately 10-fold higher for nal-IRI than for irinotecan. Two doses of NAL-IRI (10 mg/kg/dose) achieved complete responses maintained for >100 days in 24 of 27 EFT-xenografted mice. Event-free survival for mice with RMS and NB was significantly shorter than for EFT. High SLFN11 expression has been reported to correlate with sensitivity to DNA damaging agents; median SLFN11 mRNA expression was >100-fold greater in both EFT cell lines and primary tumors compared with NB or RMS cell lines or primary tumors. Cytotoxicity of SN-38 inversely correlated with SLFN11 mRNA expression in 20 EFT cell lines. In pediatric solid tumor xenografts, nal-IRI demonstrated higher systemic and tumor exposures to SN-38 and improved antitumor activity compared with the current clinical formulation of irinotecan. Clinical studies of nal-IRI in pediatric solid tumors (especially EFT) and correlative studies to determine if SLFN11 expression can serve as a biomarker to predict nal-IRI clinical activity are warranted. ©2015 American Association for Cancer Research.

Unusually Located Stroke After Chemotherapy in Testicular Germ Cell Tumors

Directory of Open Access Journals (Sweden)

Braulio Alexander Martinez MD

2015-06-01

Full Text Available Testicular cancer is a type of malignancy that affects young adults and has high rates of cure; however, as any malignancy, it is associated with an increased risk of ischemic or hemorrhagic cerebrovascular disease, given the systemic tumor effects or side effects of chemotherapy, which in turn increases morbidity, functional impairment, and additional risk of early death.

HER2,TOP2A, and TIMP-1 and responsiveness to adjuvant anthracycline-containing chemotherapy in high-risk breast cancer patients

DEFF Research Database (Denmark)

Ejlertsen, Bent; Jensen, Maj-Britt; Nielsen, Kirsten V.

2010-01-01

analyzed individually. PATIENTS AND METHODS The Danish Breast Cancer Cooperative Group (DBCG) 89D trial randomly assigned 980 high-risk Danish breast cancer patients to CMF or CEF. Archival tumor tissue was analyzed TIMP-1, and HER2-negative and TIMP-1 immunoreactive tumors were classified as HT...... nonresponsive and otherwise HT responsive. Similarly, the 2T panel was constructed by combining TOP2A and TIMP-1; tumors with normal TOP2A status and TIMP-1 immunoreactivity were classified as 2T-nonresponsive and otherwise 2T-responsive. Results In total, 623 tumors were available for analysis, of which 154......(interaction) containing chemotherapy than HER2, TIMP-1, or TOP2A individually, and compared with these, 2T classifies a larger proportion of patients as sensitive to anthracyclines....

Optimal hypofractionated conformal radiotherapy for large brain metastases in patients with high risk factors: a single-institutional prospective study

International Nuclear Information System (INIS)

Inoue, Hiroshi K; Sato, Hiro; Suzuki, Yoshiyuki; Saitoh, Jun-ichi; Noda, Shin-ei; Seto, Ken-ichi; Torikai, Kota; Sakurai, Hideyuki; Nakano, Takashi

2014-01-01

A single-institutional prospective study of optimal hypofractionated conformal radiotherapy for large brain metastases with high risk factors was performed based on the risk prediction of radiation-related complications. Eighty-eight patients with large brain metastases ≥10 cm 3 in critical areas treated from January 2010 to February 2014 using the CyberKnife were evaluated. The optimal dose and number of fractions were determined based on the surrounding brain volume circumscribed with a single dose equivalent (SDE) of 14 Gy (V14) to be less than 7 cm 3 for individual lesions. Univariate and multivariate analyses were conducted. As a result of optimal treatment, 92 tumors ranging from 10 to 74.6 cm 3 (median, 16.2 cm 3 ) in volume were treated with a median prescribed isodose of 57% and a median fraction number of five. In order to compare the results according to the tumor volume, the tumors were divided into the following three groups: 1) 10–19.9 cm 3 , 2) 20–29.9 cm 3 and 3) ≥30 cm 3 . The lesions were treated with a median prescribed isodose of 57%, 56% and 55%, respectively, and the median fraction number was five in all three groups. However, all tumors ≥20 cm 3 were treated with ≥ five fractions. The median SDE of the maximum dose in the three groups was 47.2 Gy, 48.5 Gy and 46.5 Gy, respectively. Local tumor control was obtained in 90.2% of the patients, and the median survival was nine months, with a median follow-up period of seven months (range, 3-41 months). There were no significant differences in the survival rates among the three groups. Six tumors exhibited marginal recurrence 7-36 months after treatment. Ten patients developed symptomatic brain edema or recurrence of pre-existing edema, seven of whom required osmo-steroid therapy. No patients developed radiation necrosis requiring surgical resection. Our findings demonstrate that the administration of optimal hypofractionated conformal radiotherapy based on the dose-volume prediction

Diet-induced obesity promotes colon tumor development in azoxymethane-treated mice.

Directory of Open Access Journals (Sweden)

Iina Tuominen

Full Text Available Obesity is an important risk factor for colon cancer in humans, and numerous studies have shown that a high fat diet enhances colon cancer development. As both increased adiposity and high fat diet can promote tumorigenesis, we examined the effect of diet-induced obesity, without ongoing high fat diet, on colon tumor development. C57BL/6J male mice were fed regular chow or high fat diet for 8 weeks. Diets were either maintained or switched resulting in four experimental groups: regular chow (R, high fat diet (H, regular chow switched to high fat diet (RH, and high fat diet switched to regular chow (HR. Mice were then administered azoxymethane to induce colon tumors. Tumor incidence and multiplicity were dramatically smaller in the R group relative to all groups that received high fat diet at any point. The effect of obesity on colon tumors could not be explained by differences in aberrant crypt foci number. Moreover, diet did not alter colonic expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, interleukin-1β, and interferon-γ, which were measured immediately after azoxymethane treatment. Crypt apoptosis and proliferation, which were measured at the same time, were increased in the HR relative to all other groups. Our results suggest that factors associated with obesity - independently of ongoing high fat diet and obesity - promote tumor development because HR group animals had significantly more tumors than R group, and these mice were fed the same regular chow throughout the entire carcinogenic period. Moreover, there was no difference in the number of aberrant crypt foci between these groups, and thus the effect of obesity appears to be on subsequent stages of tumor development when early preneoplastic lesions transition into adenomas.

A block matching-based registration algorithm for localization of locally advanced lung tumors

Energy Technology Data Exchange (ETDEWEB)

Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D., E-mail: gdhugo@vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, Virginia, 23298 (United States)

2014-04-15

Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm{sup 3}), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0

A block matching-based registration algorithm for localization of locally advanced lung tumors

International Nuclear Information System (INIS)

Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

2014-01-01

Purpose: To implement and evaluate a block matching-based registration (BMR) algorithm for locally advanced lung tumor localization during image-guided radiotherapy. Methods: Small (1 cm 3 ), nonoverlapping image subvolumes (“blocks”) were automatically identified on the planning image to cover the tumor surface using a measure of the local intensity gradient. Blocks were independently and automatically registered to the on-treatment image using a rigid transform. To improve speed and robustness, registrations were performed iteratively from coarse to fine image resolution. At each resolution, all block displacements having a near-maximum similarity score were stored. From this list, a single displacement vector for each block was iteratively selected which maximized the consistency of displacement vectors across immediately neighboring blocks. These selected displacements were regularized using a median filter before proceeding to registrations at finer image resolutions. After evaluating all image resolutions, the global rigid transform of the on-treatment image was computed using a Procrustes analysis, providing the couch shift for patient setup correction. This algorithm was evaluated for 18 locally advanced lung cancer patients, each with 4–7 weekly on-treatment computed tomography scans having physician-delineated gross tumor volumes. Volume overlap (VO) and border displacement errors (BDE) were calculated relative to the nominal physician-identified targets to establish residual error after registration. Results: Implementation of multiresolution registration improved block matching accuracy by 39% compared to registration using only the full resolution images. By also considering multiple potential displacements per block, initial errors were reduced by 65%. Using the final implementation of the BMR algorithm, VO was significantly improved from 77% ± 21% (range: 0%–100%) in the initial bony alignment to 91% ± 8% (range: 56%–100%;p < 0.001). Left

Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

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Bo Zhang

2017-12-01

Full Text Available Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents.

Modulating the Tumor Microenvironment to Enhance Tumor Nanomedicine Delivery

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Zhang, Bo; Hu, Yu; Pang, Zhiqing

2017-01-01

Nanomedicines including liposomes, micelles, and nanoparticles based on the enhanced permeability and retention (EPR) effect have become the mainstream for tumor treatment owing to their superiority over conventional anticancer agents. Advanced design of nanomedicine including active targeting nanomedicine, tumor-responsive nanomedicine, and optimization of physicochemical properties to enable highly effective delivery of nanomedicine to tumors has further improved their therapeutic benefits. However, these strategies still could not conquer the delivery barriers of a tumor microenvironment such as heterogeneous blood flow, dense extracellular matrix, abundant stroma cells, and high interstitial fluid pressure, which severely impaired vascular transport of nanomedicines, hindered their effective extravasation, and impeded their interstitial transport to realize uniform distribution inside tumors. Therefore, modulation of tumor microenvironment has now emerged as an important strategy to improve nanomedicine delivery to tumors. Here, we review the existing strategies and approaches for tumor microenvironment modulation to improve tumor perfusion for helping more nanomedicines to reach the tumor site, to facilitate nanomedicine extravasation for enhancing transvascular transport, and to improve interstitial transport for optimizing the distribution of nanomedicines. These strategies may provide an avenue for the development of new combination chemotherapeutic regimens and reassessment of previously suboptimal agents. PMID:29311946

Prognostic factors in breast phyllodes tumors: a nomogram based on a retrospective cohort study of 404 patients.

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Zhou, Zhi-Rui; Wang, Chen-Chen; Sun, Xiang-Jie; Yang, Zhao-Zhi; Chen, Xing-Xing; Shao, Zhi-Ming; Yu, Xiao-Li; Guo, Xiao-Mao

2018-04-01

The aim of this study was to explore the independent prognostic factors related to postoperative recurrence-free survival (RFS) in patients with breast phyllodes tumors (PTBs). A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. According to histological type, patients with benign PTBs were classified as a low-risk group, while borderline and malignant PTBs were classified as a high-risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups, and a nomogram was generated to predict recurrence-free survival at 1, 3, and 5 years. Among the 404 patients, 168 (41.6%) patients had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty-five patients experienced postoperative local recurrence, including six benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low-risk group, while the surgical approach and tumor border were independent prognostic factors for RFS in the high-risk group, and patients receiving simple excision with an infiltrative tumor border had a higher recurrence rate. A nomogram developed based on clinicopathologic features and surgical approaches could predict recurrence-free survival at 1, 3, and 5 years. For high-risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, degree of stromal cell hyperplasia, and atypia can be applied for patient counseling and clinical management. The efficacy of adjuvant radiotherapy remains uncertain. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

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Barbara Banelli

Full Text Available Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months. Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

[Desmoid tumors in three patients].

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Mohos, E; Kovács, T; Brittig, F; Nagy, A

2001-12-01

Desmoids are rare tumors of the connective tissue. It develops about 1:1000 times more in patients with familial adenomatous polyposis (FAP, Gardner syndrome) compared to normal population. It has been shown in molecular genetic examinations, that different mutations of the APC gene are responsible for desmoid tumors in FAP. It means, that this disease is one of the extraintestinal manifestations of Gardner syndrome. This tumor has high recurrence rate and is growing rapidly, and as a result it is the second most common cause of death in FAP patients. That is why genetic examination for FAP patients is advised to decide if the patient has higher risk for desmoid formation. If the result of the genetic test is positive, it is advisable to try to slow the progression of polyposis with medical treatment, and so to delay the date of the colectomy because the surgical intervention--and connective tissue damage--can induce desmoid formation in these patients. At the same time it is reasonable to examine and regularly control patients with sporadic desmoid tumors searching for other manifestations of Gardner syndrome (colon, stomach and duodenum polyposis, tumor of papilla Vateri, retinopathy, etc.). Palliative surgery is not indicated in patients with inoperable intraabdominal desmoid tumors, because partial resections (R1, R2, debulking) result in further tumor progression. In these patients medical treatment (sulindac, tamoxifen), chemotherapy (doxorubicin, dacarbazin) and radiotherapy or combination of them can result tumor remission. We describe our three patients (an abdominal wall desmoid four years following Cesarean section; a desmoid tumor in the retroperitoneum and in the pelvis diagnosed three years after total colectomy; and a retroperitoneal and abdominal wall desmoid one year after total colectomy) and etiology, diagnosis and therapy of desmoid tumors are discussed.

Mena deficiency delays tumor progression and decreases metastasis in polyoma middle-T transgenic mouse mammary tumors.

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Roussos, Evanthia T; Wang, Yarong; Wyckoff, Jeffrey B; Sellers, Rani S; Wang, Weigang; Li, Jiufeng; Pollard, Jeffrey W; Gertler, Frank B; Condeelis, John S

2010-01-01

The actin binding protein Mammalian enabled (Mena), has been implicated in the metastatic progression of solid tumors in humans. Mena expression level in primary tumors is correlated with metastasis in breast, cervical, colorectal and pancreatic cancers. Cells expressing high Mena levels are part of the tumor microenvironment for metastasis (TMEM), an anatomical structure that is predictive for risk of breast cancer metastasis. Previously we have shown that forced expression of Mena adenocarcinoma cells enhances invasion and metastasis in xenograft mice. Whether Mena is required for tumor progression is still unknown. Here we report the effects of Mena deficiency on tumor progression, metastasis and on normal mammary gland development. To investigate the role of Mena in tumor progression and metastasis, Mena deficient mice were intercrossed with mice carrying a transgene expressing the polyoma middle T oncoprotein, driven by the mouse mammary tumor virus. The progeny were investigated for the effects of Mena deficiency on tumor progression via staging of primary mammary tumors and by evaluation of morbidity. Stages of metastatic progression were investigated using an in vivo invasion assay, intravital multiphoton microscopy, circulating tumor cell burden, and lung metastases. Mammary gland development was studied in whole mount mammary glands of wild type and Mena deficient mice. Mena deficiency decreased morbidity and metastatic dissemination. Loss of Mena increased mammary tumor latency but had no affect on mammary tumor burden or histologic progression to carcinoma. Elimination of Mena also significantly decreased epidermal growth factor (EGF) induced in vivo invasion, in vivo motility, intravasation and metastasis. Non-tumor bearing mice deficient for Mena also showed defects in mammary gland terminal end bud formation and branching. Deficiency of Mena decreases metastasis by slowing tumor progression and reducing tumor cell invasion and intravasation. Mena

Rheumatoid arthritis risk allele PTPRC is also associated with response to anti-tumor necrosis factor alpha therapy

NARCIS (Netherlands)

Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

2010-01-01

OBJECTIVE: Anti-tumor necrosis factor alpha (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. METHODS: A total

Chimeric antigen receptors with human scFvs preferentially induce T cell anti-tumor activity against tumors with high B7H6 expression.

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Gacerez, Albert T; Hua, Casey K; Ackerman, Margaret E; Sentman, Charles L

2018-05-01

B7H6 is emerging as a promising tumor antigen that is known to be expressed on a wide array of tumors and is reported to stimulate anti-tumor responses from the immune system. As such, B7H6 presents a good target for tumor-specific immunotherapies. B7H6-specific chimeric antigen receptors (CAR) based on a murine antibody showed successful targeting and elimination of tumors expressing B7H6. However, mouse single chain variable fragments (scFvs) have the potential to induce host anti-CAR responses that may limit efficacy, so human scFvs specific for B7H6 were selected by yeast surface display. In this study, we validate the functionality of these human scFvs when formatted into chimeric antigen receptors. The data indicate that T cells expressing these B7H6-specific human scFvs as CARs induced potent anti-tumor activity in vitro and in vivo against tumors expressing high amounts of B7H6. Importantly, these human scFv-based CARs are sensitive to changes in B7H6 expression which may potentially spare non-tumor cells that express B7H6 and provides the foundation for future clinical development.

Plasma methoxytyramine: A novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumor size, location and SDHB mutation status

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Eisenhofer, Graeme; Lenders, Jacques W.M.; Siegert, Gabriele; Bornstein, Stefan R.; Friberg, Peter; Milosevic, Dragana; Mannelli, Massimo; Linehan, W. Marston; Adams, Karen; Timmers, Henri J.; Pacak, Karel

2012-01-01

Summary Background There are currently no reliable biomarkers for malignant pheochromocytomas and paragangliomas (PPGLs). This study examined whether measurements of catecholamines and their metabolites might offer utility for this purpose. Methods Subjects included 365 patients with PPGLs, including 105 with metastases, and a reference population of 846 without the tumor. Eighteen catecholamine-related analytes were examined in relation to tumor location, size and mutations of succinate dehydrogenase subunit B (SDHB). Results Receiver-operating characteristic curves indicated that plasma methoxytyramine, the O-methylated metabolite of dopamine, provided the most accurate biomarker for discriminating patients with and without metastases. Plasma methoxytyramine was 4.7-fold higher in patients with than without metastases, a difference independent of tumor burden and the associated 1.6- to 1.8-fold higher concentrations of norepinephrine and normetanephrine. Increased plasma methoxytyramine was associated with SDHB mutations and extra-adrenal disease, but was also present in patients without SDHB mutations and metastases or those with metastases secondary to adrenal tumors. High risk of malignancy associated with SDHB mutations reflected large size and extra-adrenal locations of tumors, both independent predictors of metastatic disease. A plasma methoxytyramine above 0.2 nmol/L or a tumor diameter above 5 cm indicated increased likelihood of metastatic spread, particularly when associated with an extra-adrenal location. Interpretation Plasma methoxytyramine is a novel biomarker for metastatic PPGLs that together with SDHB mutation status, tumor size and location provide useful information to assess the likelihood of malignancy and manage affected patients. PMID:22036874

Exposure of tumor-bearing mice to extremely high-frequency electromagnetic radiation modifies the composition of fatty acids in thymocytes and tumor tissue.

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Gapeyev, Andrew B; Kulagina, Tatiana P; Aripovsky, Alexander V

2013-08-01

To test the participation of fatty acids (FA) in antitumor effects of extremely high-frequency electromagnetic radiation (EHF EMR), the changes in the FA composition in the thymus, liver, blood plasma, muscle tissue, and tumor tissue in mice with Ehrlich solid carcinoma exposed to EHF EMR were studied. Normal and tumor-bearing mice were exposed to EHF EMR with effective parameters (42.2 GHz, 0.1 mW/cm2, 20 min daily during five consecutive days beginning the first day after the inoculation of tumor cells). Fatty acid composition of various organs and tissues of mice were determined using a gas chromatography. It was shown that the exposure of normal mice to EHF EMR or tumor growth significantly increased the content of monounsaturated FA (MUFA) and decreased the content of polyunsaturated FA (PUFA) in all tissues examined. Exposure of tumor-bearing mice to EHF EMR led to the recovery of FA composition in thymocytes to the state that is typical for normal animals. In other tissues of tumor-bearing mice, the exposure to EHF EMR did not induce considerable changes that would be significantly distinguished between disturbances caused by EHF EMR exposure or tumor growth separately. In tumor tissue which is characterized by elevated level of MUFA, the exposure to EHF EMR significantly decreased the summary content of MUFA and increased the summary content of PUFA. The recovery of the FA composition in thymocytes and the modification of the FA composition in the tumor under the influence of EHF EMR on tumor-bearing animals may have crucial importance for elucidating the mechanisms of antitumor effects of the electromagnetic radiation.

On the Benefits and Risks of Proton Therapy in Pediatric Craniopharyngioma

International Nuclear Information System (INIS)

Beltran, Chris; Roca, Monica; Merchant, Thomas E.

2012-01-01

Purpose: Craniopharyngioma is a pediatric brain tumor whose volume is prone to change during radiation therapy. We compared photon- and proton-based irradiation methods to determine the effect of tumor volume change on target coverage and normal tissue irradiation in these patients. Methods and Materials: For this retrospective study, we acquired imaging and treatment-planning data from 14 children with craniopharyngioma (mean age, 5.1 years) irradiated with photons (54 Gy) and monitored by weekly magnetic resonance imaging (MRI) examinations during radiation therapy. Photon intensity-modulated radiation therapy (IMRT), double-scatter proton (DSP) therapy, and intensity-modulated proton therapy (IMPT) plans were created for each patient based on his or her pre-irradiation MRI. Target volumes were contoured on each weekly MRI scan for adaptive modeling. The measured differences in conformity index (CI) and normal tissue doses, including functional sub-volumes of the brain, were compared across the planning methods, as was target coverage based on changes in target volumes during treatment. Results: CI and normal tissue dose values of IMPT plans were significantly better than those of the IMRT and DSP plans (p 3 , and the mean increase in PTV was 11.3% over the course of treatment. The dose to 95% of the PTV was correlated with a change in the PTV; the R 2 values for all models, 0.73 (IMRT), 0.38 (DSP), and 0.62 (IMPT), were significant (p < 0.01). Conclusions: Compared with photon IMRT, proton therapy has the potential to significantly reduce whole-brain and -body irradiation in pediatric patients with craniopharyngioma. IMPT is the most conformal method and spares the most normal tissue; however, it is highly sensitive to target volume changes, whereas the DSP method is not.

Integrated analysis of oral tongue squamous cell carcinoma identifies key variants and pathways linked to risk habits, HPV, clinical parameters and tumor recurrence [version 1; referees: 2 approved

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Neeraja Krishnan

2015-11-01

Full Text Available Oral tongue squamous cell carcinomas (OTSCC are a homogeneous group of tumors characterized by aggressive behavior, early spread to lymph nodes and a higher rate of regional failure. Additionally, the incidence of OTSCC among younger population (<50yrs is on the rise; many of whom lack the typical associated risk factors of alcohol and/or tobacco exposure. We present data on single nucleotide variations (SNVs, indels, regions with loss of heterozygosity (LOH, and copy number variations (CNVs from fifty-paired oral tongue primary tumors and link the significant somatic variants with clinical parameters, epidemiological factors including human papilloma virus (HPV infection and tumor recurrence. Apart from the frequent somatic variants harbored in TP53, CASP8, RASA1, NOTCH and CDKN2A genes, significant amplifications and/or deletions were detected in chromosomes 6-9, and 11 in the tumors. Variants in CASP8 and CDKN2A were mutually exclusive. CDKN2A, PIK3CA, RASA1 and DMD variants were exclusively linked to smoking, chewing, HPV infection and tumor stage. We also performed a whole-genome gene expression study that identified matrix metalloproteases to be highly expressed in tumors and linked pathways involving arachidonic acid and NF-k-B to habits and distant metastasis, respectively. Functional knockdown studies in cell lines demonstrated the role of CASP8 in a HPV-negative OTSCC cell line. Finally, we identified a 38-gene minimal signature that predicts tumor recurrence using an ensemble machine-learning method. Taken together, this study links molecular signatures to various clinical and epidemiological factors in a homogeneous tumor population with a relatively high HPV prevalence.

Diagnosis and Management of Rectal Neuroendocrine Tumors

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Shreya Chablaney

2017-11-01

Full Text Available The incidence of rectal neuroendocrine tumors (NETs has increased by almost ten-fold over the past 30 years. There has been a heightened awareness of the malignant potential of rectal NETs. Fortunately, many rectal NETs are discovered at earlier stages due to colon cancer screening programs. Endoscopic ultrasound is useful in assessing both residual tumor burden after retrospective diagnosis and tumor characteristics to help guide subsequent management. Current guidelines suggest endoscopic resection of rectal NETs ≤10 mm as a safe therapeutic option given their low risk of metastasis. Although a number of endoscopic interventions exist, the best technique for resection has not been identified. Endoscopic submucosal dissection (ESD has high complete and en-bloc resection rates, but also an increased risk of complications including perforation. In addition, ESD is only performed at tertiary centers by experienced advanced endoscopists. Endoscopic mucosal resection has been shown to have variable complete resection rates, but modifications to the technique such as the addition of band ligation have improved outcomes. Prospective studies are needed to further compare the available endoscopic interventions, and to elucidate the most appropriate course of management of rectal NETs.

[Utility of Multiple Increased Lung Cancer Tumor Markers in Treatment of Patients with Advanced Lung Adenocarcinoma].

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Peng, Yan; Wang, Yan; Hao, Xuezhi; Li, Junling; Liu, Yutao; Wang, Hongyu

2017-10-20

Among frequently-used tumor markers in lung cancer, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125), cytokeratin 19 (CYFRA21-1) and squamous carcinoma antigen (SCC), neuron specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP) are respectively expressed highly in lung adenocarcinoma, lung squamous carcinoma and small cell lung cancer. By comparing patients with multiple increased tumor markers (group A) and patients with increase of CEA and/or CA125 (group B), this study aims to investigate the utility of multiple increased tumor markers in therapeutic evaluation and prediction of disease relapsing in patients with advanced lung adenocarcinoma. Patients with stage IV lung adenocarcinoma who receiving the first line chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed. Clinical characteristic, serum tumor markers before chemotherapy, efficacy evaluation, progression-free survival (PFS) were analyzed. Except CEA and CA125, the highest ratio of increased tumor markersin group A was CYFRA21-1 (93%), then was NSE (36%), SCC (13%) and ProGRP (12%). Patients with multiple increased tumor markers tend to have more distant metastasis (Ptumor markers have high risk of relapse, and maintenance therapy can reduce relapse risk.

The Effect of Tumor-Prostate Ratio on Biochemical Recurrence after Radical Prostatectomy

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Sung Yong Cho

2016-08-01

Full Text Available Purpose: Prostate tumor volume calculated after surgery using pathologic tissue has been shown to be an independent risk factor for biochemical recurrence. Nonetheless, prostate size varies among individuals, regardless of the presence or absence of cancer. We assumed to be lower margin positive rate in the surgical operation, when the prostate volume is larger and the tumor lesion is same. Thus, we defined the tumor-prostate ratio in the ratio of tumor volume to prostate volume. In order to compensate the prostate tumor volume, the effect of tumor-prostate ratio on biochemical recurrence was examined. Materials and Methods: This study included 251 patients who underwent open retropubic radical prostatectomy for prostate cancer in a single hospital. We analyzed the effects of tumor volume and tumor-prostate ratio, as well as the effects of known risk factors for biochemical recurrence, on the duration of disease-free survival. Results: In the univariate analysis, the risk factors that significantly impacted disease-free survival time were found to be a prostate-specific antigen level ≥10 ng/mL, a tumor volume ≥5 mL, tumor-prostate ratio ≥10%, tumor capsular invasion, lymph node invasion, positive surgical margins, and seminal vesicle invasion. In the multivariate analysis performed to evaluate the risk factors found to be significant in the univariate analysis, positive surgical margins (hazard ratio=3.066 and a tumor density ≥10% (hazard ratio=1.991 were shown to be significant risk factors for biochemical recurrence. Conclusions: Tumor-prostate ratio, rather than tumor volume, should be regarded as a significant risk factor for biochemical recurrence.

Epigenetic markers for early detection of nasopharyngeal carcinoma in a high risk population

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Haryana Sofia M

2011-05-01

Full Text Available Abstract Background Undifferentiated nasopharyngeal carcinoma (NPC is strongly related to Epstein-Barr virus (EBV infection, allowing aberrant antibodies against EBV and viral DNA load as screening tools in high risk populations. Methylation analysis in the promoter of tumor suppressor genes (TSGs may serve as a complementary marker for identifying early cases. This study determined methylation status of multiple TSGs and evaluated whether it may improve early detection. Methods Nasopharyngeal brushings were taken from 53 NPC patients, 22 high risk subjects and 25 healthy EBV carriers. Corresponding NPC paraffin tissue was included. DNA was bisulfite-modified preceding analysis by methylation-specific PCR (MSP. Ten TSGs were studied. Results NPC paraffin and brushing DNA revealed an 81.8% concordance so that MSP analysis was done using either one of both specimens. NPC samples showed methylation for individual TSGs (DAPK1 79.2%, CDH13 77.4%, DLC1 76.9%, RASSF1A 75.5%, CADM1 69.8%, p16 66.0%, WIF1 61.2%, CHFR 58.5%, RIZ1 56.6% and RASSF2A 29.2%. High risk individuals, having elevated EBV IgA and viral load, showed high frequency of methylation of CDH13, DAPK1, DLC1 and CADM1, but low frequency of methylation of p16 and WIF1 and undetectable methylation of RASSF1A, CHFR, RIZ1 and RASSF2A. Healthy subjects showed similar patterns as high risk individuals. A combination of RASSF1A and p16 gave good discrimination between NPC and non-NPC, but best results were combined analysis of five methylation markers (RASSF1A, p16, WIF1, CHFR and RIZ1 with detection rate of 98%. Conclusion Multiple marker MSP is proposed as a complementary test for NPC risk assessment in combination with EBV-based markers.

Highly Specific and Sensitive Fluorescent Nanoprobes for Image-Guided Resection of Sub-Millimeter Peritoneal Tumors.

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Colby, Aaron H; Berry, Samantha M; Moran, Ann M; Pasion, Kristine Amber; Liu, Rong; Colson, Yolonda L; Ruiz-Opazo, Nelson; Grinstaff, Mark W; Herrera, Victoria L M

2017-02-28

A current challenge in the treatment of peritoneal carcinomatosis is the inability to detect, visualize, and resect small or microscopic tumors of pancreatic, ovarian, or mesothelial origin. In these diseases, the completeness of primary tumor resection is directly correlated with patient survival, and hence, identifying small sub-millimeter tumors (i.e., disseminated disease) is critical. Thus, new imaging techniques and probes are needed to improve cytoreductive surgery and patient outcomes. Highly fluorescent rhodamine-labeled expansile nanoparticles (HFR-eNPs) are described for use as a visual aid during cytoreductive surgery of pancreatic carcinomatosis. The covalent incorporation of rhodamine into ∼30 nm eNPs increases the fluorescent signal compared to free rhodamine, thereby affording a brighter and more effective probe than would be achieved by a single rhodamine molecule. Using the intraperitoneal route of administration, HFR-eNPs localize to regions of large (∼1 cm), sub-centimeter, and sub-millimeter intraperitoneal tumor in three different animal models, including pancreatic, mesothelioma, and ovarian carcinoma. Tumoral localization of the HFR-eNPs depends on both the material property (i.e., eNP polymer) as well as the surface chemistry (anionic surfactant vs PEGylated noncharged surfactant). In a rat model of pancreatic carcinomatosis, HFR-eNP identification of tumor is validated against gold-standard histopathological analysis to reveal that HFR-eNPs possess high specificity (99%) and sensitivity (92%) for tumors, in particular, sub-centimeter and microscopic sub-millimeter tumors, with an overall accuracy of 95%. Finally, as a proof-of-concept, HFR-eNPs are used to guide the resection of pancreatic tumors in a rat model of peritoneal carcinomatosis.

Hypothalamic tumor

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... in the brain to reduce spinal fluid pressure. Risks of radiation therapy include damage to healthy brain cells when tumor cells are destroyed. Common side effects from chemotherapy include loss of appetite, nausea and vomiting, and fatigue.

Defining Survivorship Trajectories Across Patients With Solid Tumors: An Evidence-Based Approach.

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Dood, Robert L; Zhao, Yang; Armbruster, Shannon D; Coleman, Robert L; Tworoger, Shelley; Sood, Anil K; Baggerly, Keith A

2018-06-02

Survivorship involves a multidisciplinary approach to surveillance and management of comorbidities and secondary cancers, overseen by oncologists, surgeons, and primary care physicians. Optimal timing and coordination of care, however, is unclear and often based on arbitrary 5-year cutoffs. To determine high- and low-risk periods for all tumor types that could define when survivorship care might best be overseen by oncologists and when to transition to primary care physicians. In this pan-cancer, longitudinal, observational study, excess mortality hazard, calculated as an annualized mortality risk above a baseline population, was plotted over time. The time this hazard took to stabilize defined a high-risk period. The percent morality elevation above age- and sex-matched controls in the latter low-risk period was reported as a mortality gap. The US population-based Surveillance, Epidemiology, and End Results database defined the cancer population, and the US Census life tables defined controls. Incident cases of patients with cancer were separated into tumor types based on International Classification of Diseases for Oncology definitions. Population-level data on incident cancer cases was compared with the general US population. Overall mortality and cause of death were reported on observed cancer cases. A total of 2 317 185 patients (median age, 63 years; 49.8% female) with 66 primary tumor types were evaluated. High-risk surveillance period durations ranged from less than 1 year (breast, prostate, lip, ocular, and parathyroid cancers) up to 19 years (unspecified gastrointestinal cancers). The annualized mortality gap, representing the excess mortality in the stable period, ranged from a median 0.26% to 9.33% excess annual mortality (thyroid and hypopharyngeal cancer populations, respectively). Cluster analysis produced 6 risk cluster groups: group 1, with median survival of 16.2 (5th to 95th percentile range [PR], 10.7-40.2) years and median high-risk period

High Center Volume Does Not Mitigate Risk Associated with Using High Donor Risk Organs in Liver Transplantation.

Science.gov (United States)

Beal, Eliza W; Black, Sylvester M; Mumtaz, Khalid; Hayes, Don; El-Hinnawi, Ashraf; Washburn, Kenneth; Tumin, Dmitry

2017-09-01

High-risk donor allografts increase access to liver transplant, but potentially reduce patient and graft survival. It is unclear whether the risk associated with using marginal donor livers is mitigated by increasing center experience. The United Network for Organ Sharing registry was queried for adult first-time liver transplant recipients between 2/2002 and 12/2015. High donor risk was defined as donor risk index >1.9, and 1-year patient and graft survival were compared according to donor risk index in small and large centers. Multivariable Cox regression estimated the hazard ratio (HR) associated with using high-risk donor organs, according to a continuous measure of annual center volume. The analysis included 51,770 patients. In 67 small and 67 large centers, high donor risk index predicted increased mortality (p = 0.001). In multivariable analysis, high-donor risk index allografts predicted greater mortality hazard at centers performing 20 liver transplants per year (HR 1.35; 95% CI 1.22, 1.49; p donor risk index and center volume was not statistically significant (p = 0.747), confirming that the risk associated with using marginal donor livers was comparable between smaller and larger centers. Results were consistent when examining graft loss. At both small and large centers, high-risk donor allografts were associated with reduced patient and graft survival after liver transplant. Specific strategies to mitigate the risk of liver transplant involving high-risk donors are needed, in addition to accumulation of center expertise.

The genetic landscape of high-risk neuroblastoma.

Science.gov (United States)

Pugh, Trevor J; Morozova, Olena; Attiyeh, Edward F; Asgharzadeh, Shahab; Wei, Jun S; Auclair, Daniel; Carter, Scott L; Cibulskis, Kristian; Hanna, Megan; Kiezun, Adam; Kim, Jaegil; Lawrence, Michael S; Lichenstein, Lee; McKenna, Aaron; Pedamallu, Chandra Sekhar; Ramos, Alex H; Shefler, Erica; Sivachenko, Andrey; Sougnez, Carrie; Stewart, Chip; Ally, Adrian; Birol, Inanc; Chiu, Readman; Corbett, Richard D; Hirst, Martin; Jackman, Shaun D; Kamoh, Baljit; Khodabakshi, Alireza Hadj; Krzywinski, Martin; Lo, Allan; Moore, Richard A; Mungall, Karen L; Qian, Jenny; Tam, Angela; Thiessen, Nina; Zhao, Yongjun; Cole, Kristina A; Diamond, Maura; Diskin, Sharon J; Mosse, Yael P; Wood, Andrew C; Ji, Lingyun; Sposto, Richard; Badgett, Thomas; London, Wendy B; Moyer, Yvonne; Gastier-Foster, Julie M; Smith, Malcolm A; Guidry Auvil, Jaime M; Gerhard, Daniela S; Hogarty, Michael D; Jones, Steven J M; Lander, Eric S; Gabriel, Stacey B; Getz, Gad; Seeger, Robert C; Khan, Javed; Marra, Marco A; Meyerson, Matthew; Maris, John M

2013-03-01

Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 affected individuals (cases) using a combination of whole-exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per Mb (0.48 nonsilent) and notably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, and an additional 7.1% had focal deletions), MYCN (1.7%, causing a recurrent p.Pro44Leu alteration) and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1 and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies that rely on frequently altered oncogenic drivers.

The genetic landscape of high-risk neuroblastoma

Science.gov (United States)

Pugh, Trevor J.; Morozova, Olena; Attiyeh, Edward F.; Asgharzadeh, Shahab; Wei, Jun S.; Auclair, Daniel; Carter, Scott L.; Cibulskis, Kristian; Hanna, Megan; Kiezun, Adam; Kim, Jaegil; Lawrence, Michael S.; Lichenstein, Lee; McKenna, Aaron; Pedamallu, Chandra Sekhar; Ramos, Alex H.; Shefler, Erica; Sivachenko, Andrey; Sougnez, Carrie; Stewart, Chip; Ally, Adrian; Birol, Inanc; Chiu, Readman; Corbett, Richard D.; Hirst, Martin; Jackman, Shaun D.; Kamoh, Baljit; Khodabakshi, Alireza Hadj; Krzywinski, Martin; Lo, Allan; Moore, Richard A.; Mungall, Karen L.; Qian, Jenny; Tam, Angela; Thiessen, Nina; Zhao, Yongjun; Cole, Kristina A.; Diamond, Maura; Diskin, Sharon J.; Mosse, Yael P.; Wood, Andrew C.; Ji, Lingyun; Sposto, Richard; Badgett, Thomas; London, Wendy B.; Moyer, Yvonne; Gastier-Foster, Julie M.; Smith, Malcolm A.; Auvil, Jaime M. Guidry; Gerhard, Daniela S.; Hogarty, Michael D.; Jones, Steven J. M.; Lander, Eric S.; Gabriel, Stacey B.; Getz, Gad; Seeger, Robert C.; Khan, Javed; Marra, Marco A.; Meyerson, Matthew; Maris, John M.

2013-01-01

Neuroblastoma is a malignancy of the developing sympathetic nervous system that often presents with widespread metastatic disease, resulting in survival rates of less than 50%1. To determine the spectrum of somatic mutation in high-risk neuroblastoma, we studied 240 cases using a combination of whole exome, genome and transcriptome sequencing as part of the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) initiative. Here we report a low median exonic mutation frequency of 0.60 per megabase (0.48 non-silent), and remarkably few recurrently mutated genes in these tumors. Genes with significant somatic mutation frequencies included ALK (9.2% of cases), PTPN11 (2.9%), ATRX (2.5%, an additional 7.1% had focal deletions), MYCN (1.7%, a recurrent p.Pro44Leu alteration), and NRAS (0.83%). Rare, potentially pathogenic germline variants were significantly enriched in ALK, CHEK2, PINK1, and BARD1. The relative paucity of recurrent somatic mutations in neuroblastoma challenges current therapeutic strategies reliant upon frequently altered oncogenic drivers. PMID:23334666

Urinary bladder tumors among atomic bomb survivors Hiroshima and Nagasaki, 1961-1972

International Nuclear Information System (INIS)

Sanefuji, Hayato; Ishimaru, Toranosuke.

1980-03-01

A study was made of the relationship of radiation dose to the incidence of urinary bladder tumors among atomic bomb survivors and controls in the RERF Life Span Study extended sample. A total of 112 cases of urinary bladder tumors was identified among approximately 99,000 subjects in this fixed cohort during 1961-72. Morphologic diagnoses were available for 86 cases (76.8%), cystoscopy alone for 21 cases (18.7%), and only the cause of death recorded on death certificates for 5 cases (4.5%). Urothelial carcinoma (transitional cell carcinoma) is the most common type of urinary bladder tumor for which morphologic diagnoses are available. The 1961-72 incidence rate was calculated using 106 cases identified as urinary bladder tumors. Although the crude annual incidence rate in the high dose group (100 rad or more) is elevated in both cities and both sexes, all nine cases with this dose were aged 40 years or more at the time of the bomb (ATB). The standardized relative risk adjusted for city and sex for those of age 40 or more ATB in the high dose group is 1.8 in comparison with the control group and this is a suggestive statistical difference. A statistically significant elevation of risk occurs in the high dose group for urothelial carcinoma and adenocarcinoma of the urinary bladder among those aged 40 or more ATB. (author)

Actual and future strategies in interdisciplinary treatment of medulloblastomas, supratentorial PNET and intracranial germ cell tumors in childhood

International Nuclear Information System (INIS)

Kortmann, R.D.; Timmermann, B.; Bamberg, M.; Kuehl, J.; Calaminus, G.; Goebel, U.; Dieckmann, K.; Wurm, R.; Soerensen, N.; Urban, C.

2001-01-01

Methods: Systemic irradiation of neuroaxis is an essential part in the management of medulloblastoma, stPNET and intracranial germ cell tumors. The introduction of quality assurance programs in radiooncology assures a precise radiotherapy of target volumes and is a prerequisite to improve survival. Results: Hyperfractionated radiotherapy has the potential of increasing dose to tumor more safely without increasing the risk for late adverse effects. Pilot studies revealed excellent tumor control in medulloblastoma with acceptable acute toxicity and a long-term survival of up to 96%. In medulloblastoma stereotactic radiation techniques reveal an acceptable toxicity and promising results in tumor control in recurrent disease or as primary treatment. They are now part of future treatment protocols in case of persisting residual tumor. Radiotherapy alone in pure germinoma is continuously yielding high cure rates. In secreting germ cell tumors cisplatin containing chemotherapies in conjunction with radiotherapy achieve a long-term survival rate of 80% today. Especially in high risk medulloblastoma and secreting germ cell tumors chemotherapies are playing an increasingly important role in the interdisciplinary management. It can be expected that future developments of chemotherapeutic protocols and the introduction of new cytostatic substances will further improve the therapeutic outcome. (orig.) [de

[Tumors of the central nervous system].

Science.gov (United States)

Alegría-Loyola, Marco Antonio; Galnares-Olalde, Javier Andrés; Mercado, Moisés

2017-01-01

Central nervous system (CNS) tumors constitute a heterogeneous group of neoplasms that share a considerable morbidity and mortality rate. Recent advances in the underlying oncogenic mechanisms of these tumors have led to new classification systems, which, in turn, allow for a better diagnostic approach and therapeutic planning. Most of these neoplasms occur sporadically and several risk factors have been found to be associated with their development, such as exposure to ionizing radiation or electromagnetic fields and the concomitant presence of conditions like diabetes, hypertension and Parkinson's disease. A relatively minor proportion of primary CNS tumors occur in the context of hereditary syndromes. The purpose of this review is to analyze the etiopathogenesis, clinical presentation, diagnosis and therapy of CNS tumors with particular emphasis in the putative risk factors mentioned above.

Interphone study - on mobile phones and brain tumors

International Nuclear Information System (INIS)

2010-01-01

Interphone study is the largest study on mobile phone use and risk of brain tumors that have been implemented. The study does not provide reliable answers to whether there is an increased risk of brain tumors using the mobile phone, but is an important contribution. (AG)

Basal (18)F-FDG PET/CT as a predictive biomarker of tumor response for neoadjuvant therapy in breast cancer.

Science.gov (United States)

García Vicente, A M; Soriano Castrejón, A; Pruneda-González, R E; Fernández Calvo, G; Muñoz Sánchez, M M; Álvarez Cabellos, R; Espinosa Aunión, R; Relea Calatayud, F

2016-01-01

To explore the relation between tumor kinetic assessed by (18)F-FDG PET and final neoadjuvant chemotherapy (NC) response within a molecular phenotype perspective. Prospective study included 144 women with breast cancer. All patients underwent a dual-time point (18)F-FDG PET/CT previous to NC. The retention index (RI), between SUV-1 and SUV-2 was calculated. Molecular subtypes were re-grouped in low, intermediate and high-risk biological phenotypes. After NC, all residual primary tumor specimens were histopathologically classified in tumor regression grades (TRG) and response groups. The relation between SUV-1, SUV-2 and RI with the TRG and response groups was evaluated in all molecular subtypes and in accordance with the risk categories. Responder's lesions showed significant greater SUVmax compared to non-responders. The RI value did not show any significant relation with response. Attending to molecular phenotypes, statistical differences were observed with greater SUV for responders having high-risk molecular subtypes. Glycolytic tumor characteristics showed a significant correlation with NC response and dependence of risk phenotype. Copyright © 2015 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Magnetic resonance–guided interstitial high-intensity focused ultrasound for brain tumor ablation

Science.gov (United States)

MacDonell, Jacquelyn; Patel, Niravkumar; Rubino, Sebastian; Ghoshal, Goutam; Fischer, Gregory; Burdette, E. Clif; Hwang, Roy; Pilitsis, Julie G.

2018-01-01

Currently, treatment of brain tumors is limited to resection, chemotherapy, and radiotherapy. Thermal ablation has been recently explored. High-intensity focused ultrasound (HIFU) is being explored as an alternative. Specifically, the authors propose delivering HIFU internally to the tumor with an MRI-guided robotic assistant (MRgRA). The advantage of the authors’ interstitial device over external MRI-guided HIFU (MRgHIFU) is that it allows for conformal, precise ablation and concurrent tissue sampling. The authors describe their workflow for MRgRA HIFU delivery. PMID:29385926

Modeling freedom from progression for standard-risk medulloblastoma: a mathematical tumor control model with multiple modes of failure

DEFF Research Database (Denmark)

Brodin, Nils Patrik; Vogelius, Ivan R.; Bjørk-Eriksson, Thomas

2013-01-01

As pediatric medulloblastoma (MB) is a relatively rare disease, it is important to extract the maximum information from trials and cohort studies. Here, a framework was developed for modeling tumor control with multiple modes of failure and time-to-progression for standard-risk MB, using published...

Assessment of Canine Mast Cell Tumor Mortality Risk Based on Clinical, Histologic, Immunohistochemical, and Molecular Features.

Science.gov (United States)

Horta, Rodrigo S; Lavalle, Gleidice E; Monteiro, Lidianne N; Souza, Mayara C C; Cassali, Geovanni D; Araújo, Roberto B

2018-03-01

Mast cell tumor (MCT) is a frequent cutaneous neoplasm in dogs that is heterogeneous in clinical presentation and biological behavior, with a variable potential for recurrence and metastasis. Accurate prediction of clinical outcomes has been challenging. The study objective was to develop a system for classification of canine MCT according to the mortality risk based on individual assessment of clinical, histologic, immunohistochemical, and molecular features. The study included 149 dogs with a histologic diagnosis of cutaneous or subcutaneous MCT. By univariate analysis, MCT metastasis and related death was significantly associated with clinical stage ( P < .0001, r P = -0.610), history of tumor recurrence ( P < .0001, r P = -0.550), Patnaik ( P < .0001, r P = -0.380) and Kiupel grades ( P < .0001, r P = -0.500), predominant organization of neoplastic cells ( P < .0001, r P = -0.452), mitotic count ( P < .0001, r P = -0.325), Ki-67 labeling index ( P < .0001, r P = -0.414), KITr pattern ( P = .02, r P = 0.207), and c-KIT mutational status ( P < .0001, r P = -0.356). By multivariate analysis with Cox proportional hazard model, only 2 features were independent predictors of overall survival: an amendment of the World Health Organization clinical staging system (hazard ratio [95% CI]: 1.824 [1.210-4.481]; P = .01) and a history of tumor recurrence (hazard ratio [95% CI]: 9.250 [2.158-23.268]; P < .001]. From these results, we propose an amendment of the WHO staging system, a method of risk analysis, and a suggested approach to clinical and laboratory evaluation of dogs with cutaneous MCT.

Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base

Energy Technology Data Exchange (ETDEWEB)

Combs, Stephanie E.; Kessel, Kerstin; Habermehl, Daniel; Debus, Jurgen [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)], e-mail: Stephanie.Combs@med.uni-heidelberg.de; Haberer, Thomas [Heidelberger Ionenstrahl Therapiezentrum (HIT), Heidelberg (Germany); Jaekel, Oliver [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); Heidelberger Ionenstrahl Therapiezentrum (HIT), Heidelberg (Germany)

2013-10-15

To analyze clinical concepts, toxicity and treatment outcome in patients with brain and skull base tumors treated with photons and particle therapy. Material and methods: In total 260 patients with brain tumors and tumors of the skull base were treated at the Heidelberg Ion Therapy Center (HIT). Patients enrolled in and randomized within prospective clinical trials as well as bony or soft tissue tumors are not included in this analysis. Treatment was delivered as protons, carbon ions, or combinations of photons and a carbon ion boost. All patients are included in a tight follow-up program. The median follow-up time is 12 months (range 2-39 months). Results: Main histologies included meningioma (n = 107) for skull base lesions, pituitary adenomas (n = 14), low-grade gliomas (n = 51) as well as high-grade gliomas (n = 55) for brain tumors. In all patients treatment could be completed without any unexpected severe toxicities. No side effects > CTC Grade III were observed. To date, no severe late toxicities were observed, however, for endpoints such as secondary malignancies or neuro cognitive side effects follow-up time still remains too short. Local recurrences were mainly seen in the group of high-grade gliomas or atypical meningiomas; for benign skull base meningiomas, to date, no recurrences were observed during follow-up. Conclusion: The specific benefit of particle therapy will potentially reduce the risk of secondary malignancies as well as improve neuro cognitive outcome and quality of life (QOL); thus, longer follow-up will be necessary to confirm these endpoints. Indication-specific trials on meningiomas and gliomas are underway to elucidate the role of protons and carbon ions in these indications.

Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base

International Nuclear Information System (INIS)

Combs, Stephanie E.; Kessel, Kerstin; Habermehl, Daniel; Debus, Jurgen; Haberer, Thomas; Jaekel, Oliver

2013-01-01

To analyze clinical concepts, toxicity and treatment outcome in patients with brain and skull base tumors treated with photons and particle therapy. Material and methods: In total 260 patients with brain tumors and tumors of the skull base were treated at the Heidelberg Ion Therapy Center (HIT). Patients enrolled in and randomized within prospective clinical trials as well as bony or soft tissue tumors are not included in this analysis. Treatment was delivered as protons, carbon ions, or combinations of photons and a carbon ion boost. All patients are included in a tight follow-up program. The median follow-up time is 12 months (range 2-39 months). Results: Main histologies included meningioma (n = 107) for skull base lesions, pituitary adenomas (n = 14), low-grade gliomas (n = 51) as well as high-grade gliomas (n = 55) for brain tumors. In all patients treatment could be completed without any unexpected severe toxicities. No side effects > CTC Grade III were observed. To date, no severe late toxicities were observed, however, for endpoints such as secondary malignancies or neuro cognitive side effects follow-up time still remains too short. Local recurrences were mainly seen in the group of high-grade gliomas or atypical meningiomas; for benign skull base meningiomas, to date, no recurrences were observed during follow-up. Conclusion: The specific benefit of particle therapy will potentially reduce the risk of secondary malignancies as well as improve neuro cognitive outcome and quality of life (QOL); thus, longer follow-up will be necessary to confirm these endpoints. Indication-specific trials on meningiomas and gliomas are underway to elucidate the role of protons and carbon ions in these indications

Local Control With 21-Gy Radiation Therapy for High-Risk Neuroblastoma

International Nuclear Information System (INIS)

Casey, Dana L.; Kushner, Brian H.; Cheung, Nai-Kong V.; Modak, Shakeel; LaQuaglia, Michael P.; Wolden, Suzanne L.

2016-01-01

Purpose: To evaluate local control after 21-Gy radiation therapy (RT) to the primary site in patients with high-risk neuroblastoma. Methods and Materials: After receiving dose-intensive chemotherapy and gross total resection (GTR), 246 patients (aged 1.2-17.9 years, median 4.0 years) with high-risk neuroblastoma underwent RT to the primary site at Memorial Sloan Kettering from 2000 to 2014. Radiation therapy consisted of 21 Gy in twice-daily fractions of 1.5 Gy each. Local failure (LF) was correlated with biologic prognostic factors and clinical findings at the time of diagnosis and start of RT. Results: Median follow-up of surviving patients was 6.4 years. Cumulative incidence of LF was 7.1% at 2 years after RT and 9.8% at 5 years after RT. The isolated LF rate was 3.0%. Eighty-six percent of all local failures were within the RT field. Local control was worse in patients who required more than 1 surgical resection to achieve GTR (22.4% vs 8.3%, P=.01). There was also a trend toward inferior local control with MYCN-amplified tumors or serum lactate dehydrogenase ≥1500 U/L (P=.09 and P=.06, respectively). Conclusion: After intensive chemotherapy and maximal surgical debulking, hyperfractionated RT with 21 Gy in high-risk neuroblastoma results in excellent local control. Given the young patient age, concern for late effects, and local control >90%, dose reduction may be appropriate for patients without MYCN amplification who achieve GTR.

Local Control With 21-Gy Radiation Therapy for High-Risk Neuroblastoma

Energy Technology Data Exchange (ETDEWEB)

Casey, Dana L. [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Kushner, Brian H.; Cheung, Nai-Kong V.; Modak, Shakeel [Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York (United States); LaQuaglia, Michael P. [Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York (United States); Wolden, Suzanne L., E-mail: woldens@mskcc.org [Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York (United States)

2016-10-01

Purpose: To evaluate local control after 21-Gy radiation therapy (RT) to the primary site in patients with high-risk neuroblastoma. Methods and Materials: After receiving dose-intensive chemotherapy and gross total resection (GTR), 246 patients (aged 1.2-17.9 years, median 4.0 years) with high-risk neuroblastoma underwent RT to the primary site at Memorial Sloan Kettering from 2000 to 2014. Radiation therapy consisted of 21 Gy in twice-daily fractions of 1.5 Gy each. Local failure (LF) was correlated with biologic prognostic factors and clinical findings at the time of diagnosis and start of RT. Results: Median follow-up of surviving patients was 6.4 years. Cumulative incidence of LF was 7.1% at 2 years after RT and 9.8% at 5 years after RT. The isolated LF rate was 3.0%. Eighty-six percent of all local failures were within the RT field. Local control was worse in patients who required more than 1 surgical resection to achieve GTR (22.4% vs 8.3%, P=.01). There was also a trend toward inferior local control with MYCN-amplified tumors or serum lactate dehydrogenase ≥1500 U/L (P=.09 and P=.06, respectively). Conclusion: After intensive chemotherapy and maximal surgical debulking, hyperfractionated RT with 21 Gy in high-risk neuroblastoma results in excellent local control. Given the young patient age, concern for late effects, and local control >90%, dose reduction may be appropriate for patients without MYCN amplification who achieve GTR.

T1 ρ mapping for the evaluation of high intensity focused ultrasound tumor treatment

NARCIS (Netherlands)

Hectors, Stefanie J. C. G.; Moonen, Rik P. M.; Strijkers, Gustav J.; Nicolay, Klaas

2015-01-01

This study was aimed to assess the effects of High Intensity Focused Ultrasound (HIFU) thermal ablation on tumor T1ρ . In vivo T1ρ measurements of murine tumors at various spin-lock amplitudes (B1 = 0-2000 Hz) were performed before (n = 13), directly after (n = 13) and 3 days (n = 7) after HIFU

Primary Cutaneous Carcinosarcoma of the Basal Cell Subtype Should Be Treated as a High-Risk Basal Cell Carcinoma.

Science.gov (United States)

Bourgeault, Emilie; Alain, Jimmy; Gagné, Eric

2015-01-01

Cutaneous carcinosarcoma is a rare primary tumor of the skin, characterized by biphasic epithelial and mesenchymal differentiation. Due to the limited number of cases reported, there is no consensus regarding treatment and prognosis. Some authors suggest that cutaneous carcinosarcomas should be viewed as aggressive tumors, with ancillary imaging used to evaluate potential metastatic disease. Other reports demonstrate an indolent disease course, especially with epidermal-type cutaneous carcinosarcomas. We report a case of cutaneous carcinosarcoma, which we treated with electrodessication and curettage following a shave biopsy. The tumor had an epithelial component resembling a basal cell carcinoma and a fibrosarcomatous stroma. At 1-year follow-up, our patient did not show evidence of recurrence or metastasis. Our case suggests that a cutaneous carcinosarcoma with an epithelial component composed of basal cell carcinoma can be regarded as a high-risk nonmelanoma skin cancer. © The Author(s) 2015.

Prevention of bladder tumor implantion after fluorescence-guided TUR with photodynamic therapy

Science.gov (United States)

Berrahmoune, Saoussen; Bezdetnaya, Lina; de Witte, Peter; Leroux, Agnès; Dumas, Dominique; Guillemin, François; D'Hallewin, Marie Ange

2009-06-01

The prevalence of bladder cancer is very high, due to its high recurrence rate in superficial bladder cancer (30 to 85%), which is the staging of approximately 80% of the patients at first diagnosis. Risk of recurrence and progression is associated with grade, stage, presence of concomitant carcinoma in situ, size and number of lesions, as well as time to first recurrence. Recurrences can be partly attributed to new occurrences but also to residual tumors after resection. Incomplete tumor removal has been observed in 30 to 50% of TUR's, especially when dealing with T1 or poorly visible malignant or pre-malignant disease1. Fluorescence guided resection with 5 amino levulinic acid (ALA) or its hexyl ester derivative (Hexvix, has now unequivocally been demonstrated to increase detection rate and a growing number of studies indicate this has a positive impact on recurrence and progression ratesImplantation of viable tumor cells, dispersed during resection, is a third factor influencing bladder cancer recurrence. The aim of early intravesical therapy is to interfere with cell viability and thus reduce implantation risks.

Androgen receptor status is highly conserved during tumor progression of breast cancer.

Science.gov (United States)

Grogg, André; Trippel, Mafalda; Pfaltz, Katrin; Lädrach, Claudia; Droeser, Raoul A; Cihoric, Nikola; Salhia, Bodour; Zweifel, Martin; Tapia, Coya

2015-11-09

highly conserved during tumor progression and a change only occurs in a small fraction (4.1 %). Our study supports the notion that targeting AR could be effective for many BC patients and that re-testing of AR status in formerly negative or mixed type BC's is recommended.

Androgen receptor status is highly conserved during tumor progression of breast cancer

International Nuclear Information System (INIS)

Grogg, André; Trippel, Mafalda; Pfaltz, Katrin; Lädrach, Claudia; Droeser, Raoul A.; Cihoric, Nikola; Salhia, Bodour; Zweifel, Martin; Tapia, Coya

2015-01-01

With the advent of new and more efficient anti-androgen drugs targeting androgen receptor (AR) in breast cancer (BC) is becoming an increasingly important area of investigation. This would potentially be most useful in triple negative BC (TNBC), where better therapies are still needed. The assessment of AR status is generally performed on the primary tumor even if the tumor has already metastasized. Very little is known regarding discrepancies of AR status during tumor progression. To determine the prevalence of AR positivity, with emphasis on TNBCs, and to investigate AR status during tumor progression, we evaluated a large series of primary BCs and matching metastases and recurrences. AR status was performed on 356 primary BCs, 135 matching metastases, and 12 recurrences using a next-generation Tissue Microarray (ngTMA). A commercially available AR antibody was used to determine AR-status by immunohistochemistry. AR positivity was defined as any nuclear staining in tumor cells ≥1 %. AR expression was correlated with pathological tumor features of the primary tumor. Additionally, the concordance rate of AR expression between the different tumor sites was determined. AR status was positive in: 87 % (307/353) of primary tumors, 86.1 % (105/122) of metastases, and in 66.7 % (8/12) of recurrences. TNBC tested positive in 11.4 %, (4/35) of BCs. A discrepant result was seen in 4.3 % (5/117) of primary BC and matching lymph node (LN) metastases. Three AR negative primary BCs were positive in the matching LN metastasis, representing 17.6 % of all negative BCs with lymph node metastases (3/17). Two AR positive primary BCs were negative in the matching LN metastasis, representing 2.0 % of all AR positive BCs with LN metastases (2/100). No discrepancies were seen between primary BC and distant metastases or recurrence (n = 17). Most primary (87 %) and metastasized (86.1 %) BCs are AR positive including a significant fraction of TNBCs (11.4 %). Further, AR status is highly

Expression and lymphatic microvessel density in primary tumors of node-neagtive colorectal cancer patients predict disease recurrence

NARCIS (Netherlands)

Doekhie, F.S.; Morreau, H.; de Bock, G.H.; Speetjens, F.M.; Dekker-Ensink, N.G.; Putter, H.; vand e Velde, C.J.H.; Tollenaar, R.A.E.M.; Kuppen, P.J.K.; Sialyl lewis, X.

2008-01-01

Up to 30% of curatively resected colorectal cancer patients with tumor-negative lymph nodes, show disease recurrence. We assessed whether these high-risk patients can be identified by examining primary tumors for the following blood and lymphatic vasculature markers: A) sialyl Lewis X (sLeX),

A metasynthesis of risk perception in women with high risk pregnancies.

Science.gov (United States)

Lee, Suzanne; Ayers, Susan; Holden, Des

2014-04-01

risk perception in women with high risk pregnancies affects their decisions about perinatal care and is of interest to anyone involved in the care of pregnant women. This paper provides a metasynthesis of qualitative studies of risk perception in women with high risk pregnancies. a systematic search of eight electronic databases was conducted. Additional papers were obtained through searching references of identified articles. Six studies were identified that reported qualitative research into risk perception in relation to high risk pregnancy. A metasynthesis was developed to describe and interpret the studies. the synthesis resulted in the identification of five themes: determinants of risk perception; not seeing it the way others do; normality versus risk; if the infant is ok, I׳m ok; managing risk. this metasynthesis suggests women at high risk during pregnancy use multiple sources of information to determine their risk status. It shows women are aware of the risks posed by their pregnancies but do not perceive risk in the same way as healthcare professionals. They will take steps to ensure the health of themselves and their infants but these may not include following all medical recommendations. Copyright © 2013 Elsevier Ltd. All rights reserved.

Volume fractions of DCE-MRI parameter as early predictor of histologic response in soft tissue sarcoma: A feasibility study.

Science.gov (United States)

Xia, Wei; Yan, Zhuangzhi; Gao, Xin

2017-10-01

To find early predictors of histologic response in soft tissue sarcoma through volume transfer constant (K trans ) analysis based on dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). 11 Patients with soft tissue sarcoma of the lower extremity that underwent preoperative chemoradiotherapy followed by limb salvage surgery were included in this retrospective study. For each patient, DCE-MRI data sets were collected before and two weeks after therapy initiation, and histologic tumor cell necrosis rate (TCNR) was reported at surgery. The DCE-MRI volumes were aligned by registration. Then, the aligned volumes were used to obtain the K trans variation map. Accordingly, three sub-volumes (with increased, decreased or unchanged K trans ) were defined and identified, and fractions of the sub-volumes, denoted as F + , F - and F 0 , respectively, were calculated. The predictive ability of volume fractions was determined by using area under a receiver operating characteristic curve (AUC). Linear regression analysis was performed to investigate the relationship between TCNR and volume fractions. In addition, the K trans values of the sub-volumes were compared. The AUC for F - (0.896) and F 0 (0.833) were larger than that for change of tumor longest diameter ΔD (0.625) and the change of mean K trans ΔK trans ¯ (0.792). Moreover, the regression results indicated that TCNR was directly proportional to F 0 (R 2 =0.75, P=0.0003), while it was inversely proportional to F - (R 2 =0.77, P=0.0002). However, TCNR had relatively weak linear relationship with ΔK trans ¯ (R 2 =0.64, P=0.0018). Additionally, TCNR did not have linear relationship with DD (R 2 =0.16, P=0.1246). The volume fraction F - and F 0 have potential as early predictors of soft tissue sarcoma histologic response. Copyright © 2017 Elsevier B.V. All rights reserved.

Individualized risk assessment in neuroblastoma. Does the tumoral metabolic activity on 123I-MIBG SPECT predict the outcome?

International Nuclear Information System (INIS)

Rogasch, Julian M.M.; Furth, Christian; Wedel, Florian; Brenner, Winfried; Amthauer, Holger; Schatka, Imke; Hundsdoerfer, Patrick; Hofheinz, Frank; Krueger, Paul-Christian; Lode, Holger; Eggert, Angelika

2017-01-01

Risk-adapted treatment in children with neuroblastoma (NB) is based on clinical and genetic factors. This study evaluated the metabolic tumour volume (MTV) and its asphericity (ASP) in pretherapeutic 123 I-MIBG SPECT for individualized image-based prediction of outcome. This retrospective study included 23 children (11 girls, 12 boys; median age 1.8 years, range 0.3-6.8 years) with newly diagnosed NB consecutively examined with pretherapeutic 123 I-MIBG SPECT. Primary tumour MTV and ASP were defined using semiautomatic thresholds. Cox regression analysis, receiver operating characteristic analysis (cut-off determination) and Kaplan-Meier analysis with the log-rank test for event-free survival (EFS) were performed for ASP, MTV, laboratory parameters (including urinary homovanillic acid-to-creatinine ratio, HVA/C), and clinical (age, stage) and genetic factors. Predictive accuracy of the optimal multifactorial model was determined in terms of Harrell's C and likelihood ratio χ 2 . Median follow-up was 36 months (range 7-107 months; eight patients showed disease progression/relapse, four patients died). The only significant predictors of EFS in the univariate Cox regression analysis were ASP (p = 0.029; hazard ratio, HR, 1.032 for a one unit increase), MTV (p = 0.038; HR 1.012) and MYCN amplification status (p = 0.047; HR 4.67). The mean EFS in patients with high ASP (>32.0%) and low ASP were 21 and 88 months, respectively (p = 0.013), and in those with high MTV (>46.7 ml) and low MTV were 22 and 87 months, respectively (p = 0.023). A combined risk model of either high ASP and high HVA/C or high MTV and high HVA/C best predicted EFS. In this exploratory study, pretherapeutic image-derived and laboratory markers of tumoral metabolic activity in NB (ASP, MTV, urinary HVA/C) allowed the identification of children with a high and low risk of progression/relapse under current therapy. (orig.)

[Detecting high risk pregnancy].

Science.gov (United States)

Doret, Muriel; Gaucherand, Pascal

2009-12-20

Antenatal care is aiming to reduce maternal land foetal mortality and morbidity. Maternal and foetal mortality can be due to different causes. Their knowledge allows identifying pregnancy (high risk pregnancy) with factors associated with an increased risk for maternal and/or foetal mortality and serious morbidity. Identification of high risk pregnancies and initiation of appropriate treatment and/or surveillance should improve maternal and/or foetal outcome. New risk factors are continuously described thanks to improvement in antenatal care and development in biology and cytopathology, increasing complexity in identifying high risk pregnancies. Level of risk can change all over the pregnancy. Ideally, it should be evaluated prior to the pregnancy and at each antenatal visit. Clinical examination is able to screen for intra-uterin growth restriction, pre-eclampsia, threatened for preterm labour; ultrasounds help in the diagnosis of foetal morphological anomalies, foetal chromosomal anomalies, placenta praevia and abnormal foetal growth; biological exams are used to screen for pre-eclampsia, gestational diabetes, trisomy 21 (for which screening method just changed), rhesus immunisation, seroconversion for toxoplasmosis or rubeola, unknown infectious disease (syphilis, hepatitis B, VIH). During pregnancy, most of the preventive strategies have to be initiated during the first trimester or even before conception. Prevention for neural-tube defects, neonatal hypocalcemia and listeriosis should be performed for all women. On the opposite, some measures are concerning only women with risk factors such as prevention for toxoplasmosis, rhesus immunization (which recently changed), tobacco complications and pre-eclampsia and intra-uterine growth factor restriction.

Kirkwood-Buff integrals of finite systems: shape effects

Science.gov (United States)

Dawass, Noura; Krüger, Peter; Simon, Jean-Marc; Vlugt, Thijs J. H.

2018-06-01

The Kirkwood-Buff (KB) theory provides an important connection between microscopic density fluctuations in liquids and macroscopic properties. Recently, Krüger et al. derived equations for KB integrals for finite subvolumes embedded in a reservoir. Using molecular simulation of finite systems, KB integrals can be computed either from density fluctuations inside such subvolumes, or from integrals of radial distribution functions (RDFs). Here, based on the second approach, we establish a framework to compute KB integrals for subvolumes with arbitrary convex shapes. This requires a geometric function w(x) which depends on the shape of the subvolume, and the relative position inside the subvolume. We present a numerical method to compute w(x) based on Umbrella Sampling Monte Carlo (MC). We compute KB integrals of a liquid with a model RDF for subvolumes with different shapes. KB integrals approach the thermodynamic limit in the same way: for sufficiently large volumes, KB integrals are a linear function of area over volume, which is independent of the shape of the subvolume.

Aging, tumor suppression and cancer: High-wire act!

Energy Technology Data Exchange (ETDEWEB)

Campisi, Judith

2004-08-15

Evolutionary theory holds that aging is a consequence of the declining force of natural selection with age. We discuss here the evidence that among the causes of aging in complex multicellular organisms, such as mammals, is the antagonistically pleiotropic effects of the cellular responses that protect the organism from cancer. Cancer is relatively rare in young mammals, owing in large measure to the activity of tumor suppressor mechanisms. These mechanisms either protect the genome from damage and/or mutations, or they elicit cellular responses--apoptosis or senescence--that eliminate or prevent the proliferation of somatic cells at risk for neoplastic transformation.We focus here on the senescence response, reviewing its causes, regulation and effects. In addition, we describe recent data that support the idea that both senescence and apoptosis may indeed be the double-edged swords predicted by the evolutionary hypothesis of antagonistic pleiotropy--protecting organisms from cancer early in life, but promoting aging phenotypes, including late life cancer, in older organisms.

Pregnancy following Radical Resection of Solid Pseudopapillary Tumor of the Pancreas

Directory of Open Access Journals (Sweden)

James M. O’Brien

2014-01-01

Full Text Available Solid pseudopapillary tumor of the pancreas is a rare tumor seen in predominately young women and carries a low malignant potential. We discuss a patient, who presented to our high risk clinic, with a clinical history of solid pseudopapillary tumor of the pancreas, predating her pregnancy. The patient had undergone previous surgery and imaging which had excluded recurrence of disease; however, increased attention was paid to the patient during her pregnancy secondary to elevated hormonal levels of progesterone, which any residual disease would have a heightened sensitivity to. In cases of pregnant patients with a history of pancreatic tumors, a multidisciplinary approach with maternal fetal medicine, medicine, and general surgery is appropriate and can result in a healthy mother and healthy term infant.

Dielectrophoretic capture and genetic analysis of single neuroblastoma tumor cells

Directory of Open Access Journals (Sweden)

Erica L Carpenter

2014-07-01

Full Text Available Our understanding of the diversity of cells that escape the primary tumor and seed micrometastases remains rudimentary, and approaches for studying circulating and disseminated tumor cells have been limited by low throughput and sensitivity, reliance on single parameter sorting, and a focus on enumeration rather than phenotypic and genetic characterization. Here we utilize a highly sensitive microfluidic and dielectrophoretic approach for the isolation and genetic analysis of individual tumor cells. We employed fluorescence labeling to isolate 208 single cells from spiking experiments conducted with 11 cell lines, including 8 neuroblastoma cell lines, and achieved a capture sensitivity of 1 tumor cell per 106 white blood cells. Sample fixation or freezing had no detectable effect on cell capture. Point mutations were accurately detected in the whole genome amplification product of captured single tumor cells but not in negative control white blood cells. We applied this approach to capture 144 single tumor cells from 10 bone marrow samples from patients suffering from neuroblastoma. In this pediatric malignancy, high-risk patients often exhibit wide-spread hematogenous metastasis, but access to primary tumor can be difficult or impossible. Here we used flow-based sorting to pre-enrich samples with tumor involvement below 0.02%. For all patients for whom a mutation in the Anaplastic Lymphoma Kinase gene had already been detected in their primary tumor, the same mutation was detected in single cells from their marrow. These findings demonstrate a novel, non-invasive, and adaptable method for the capture and genetic analysis of single tumor cells from cancer patients.

Pharmacodynamic and pharmacokinetic neoadjuvant study of hedgehog pathway inhibitor Sonidegib (LDE-225) in men with high-risk localized prostate cancer undergoing prostatectomy.

Science.gov (United States)

Ross, Ashley E; Hughes, Robert M; Glavaris, Stephanie; Ghabili, Kamyar; He, Ping; Anders, Nicole M; Harb, Rana; Tosoian, Jeffrey J; Marchionni, Luigi; Schaeffer, Edward M; Partin, Alan W; Allaf, Mohamad E; Bivalacqua, Trinity J; Chapman, Carolyn; O'Neal, Tanya; DeMarzo, Angelo M; Hurley, Paula J; Rudek, Michelle A; Antonarakis, Emmanuel S

2017-11-28

To determine the pharmacodynamic effects of Sonidegib (LDE-225) in prostate tumor tissue from men with high-risk localized prostate cancer, by comparing pre-surgical core-biopsy specimens to tumor tissue harvested post-treatment at prostatectomy. We conducted a prospective randomized (Sonidegib vs. observation) open-label translational clinical trial in men with high-risk localized prostate cancer undergoing radical prostatectomy. The primary endpoint was the proportion of patients in each arm who achieved at least a two-fold reduction in GLI1 mRNA expression in post-treatment versus pre-treatment tumor tissue. Secondary endpoints included the effect of pre-surgical treatment with Sonidegib on disease progression following radical prostatectomy, and safety. Fourteen men were equally randomized (7 per arm) to either neoadjuvant Sonidegib or observation for 4 weeks prior to prostatectomy. Six of seven men (86%) in the Sonidegib arm (and none in the control group) achieved a GLI1 suppression of at least two-fold. In the Sonidegib arm, drug was detectable in plasma and in prostatic tissue; and median intra-patient GLI1 expression decreased by 63-fold, indicating potent suppression of Hedgehog signaling. Sonidegib was well tolerated, without any Grade 3-4 adverse events observed. Disease-free survival was comparable among the two arms (HR = 1.50, 95% CI 0.26-8.69, P = 0.65). Hedgehog pathway activity (as measured by GLI1 expression) was detectable at baseline in men with localized high-risk prostate cancer. Sonidegib penetrated into prostatic tissue and induced a >60-fold suppression of the Hedgehog pathway. The oncological benefit of Hedgehog pathway inhibition in prostate cancer remains unclear.

Testing of mechanisms of action of rituximab and clinical results in high-risk patients with aggressive CD20+ lymphoma

International Nuclear Information System (INIS)

Jezersek Novakovic, B.; Juznic Setina, T.; Vovk, M.; Kotnik, V.; Novakovic, S.

2007-01-01

Rituximab has been applied successfully in the treatment of indolent and aggressive CD20 positive B cell lymphomas, yet the exact in vivo mechanisms of its action have not been unambiguously explained. This study was therefore aimed to confirm the presumed major mechanisms of action of rituximab and concomitantly to assess the effectiveness of first-line chemo immunotherapy in high-risk patients with aggressive CD20 lymphomas. The activity of rituximab was tested in vitro on Raji and SU-DHL-4 cells using the cell proliferation assay and flow cytometry. In the clinical part of the study, 20 high-risk patients with aggressive CD 20 lymphomas were treated with R-CHOP. Only complement-mediated cytotoxicity was observed under the in vitro applied experimental conditions. Neither the direct apoptotic effect nor the antibody-dependent cell-mediated cytotoxicity was detected probably due to a too low concentration of rituximab and a too low ratio of cytotoxic lymphocytes to tumor cells. The treatment outcome in patients was excellent since complete remissions were achieved in 90% of poor-risk patients at the end of primary treatment and 80% of patients were disease-free at 18.5 months median observation period. According to our results, the complement-dependent cytotoxicity is an important mechanism of rituximab action in vitro. To achieve direct apoptosis, higher concentrations than 20 μg/ml of rituximab should be used, while for an effective antibody-dependent cell-mediated cytotoxicity, the ratio of cytotoxic lymphocytes to tumor cells should be higher than 1:1. In the high-risk patients with aggressive CD20 lymphomas, the addition of rituximab to CHOP substantially improves the therapeutic results. (author)

Incidence of liver tumors in beagles with body burdens of 239Pu or 241Am

International Nuclear Information System (INIS)

Taylor, G.N.; Mays, C.W.; Wrenn, M.E.; Shabestari, L.; Lloyd, R.D.

1986-01-01

Tetravalent 239 Pu or trivalent 241 Am in a citrate buffer, given via a single intravenous injection to beagles, induced very pronounced liver changes, usually at relatively long postinjection times. The lesions consisted of cell injury or cell necrosis which was followed by nodular hyperplasia and a significant incidence of primary liver tumors. The most frequent neoplasm was the bile duct adenoma, followed by the bile duct carcinoma. A lesser number of sarcomas were also induced, especially fibrosarcomas. The number of hepatic cell tumors was low. An abnormally high incidence of both hyperplastic nodules and primary liver tumors occurred at long postinjection times and at average doses extending down to ∼10 rads. The various nodular lesions and liver tumors frequently occurred as incidental findings in dogs dying from other causes, especially bone cancer. In comparison to bone neoplasia, the liver was a much less important target organ in the high-dose level groups, but in some of the low-dose groups, especially in the 241 Am groups, the risk of radiation-induced liver cancer was approximately equal to or exceeded the risk of skeletal tumors. However, in any projection of the risks observed in this animal model to man, one should be mindful that the beagle skeleton is approximately 25 times more sensitive to radiation-induced bone neoplasia than is the human skeleton (Mays et al., 1976) and that the radiosensitivity difference for the beagle and human liver is unknown. 41 refs., 8 figs., 5 tabs

Chemo-radiotherapy for malignant brain tumors

Energy Technology Data Exchange (ETDEWEB)

Kochi, Masato; Ushio, Yukitaka [Kumamoto Univ. (Japan). School of Medicine

2002-05-01

Malignant gliomas: Randomized clinical trials conducted in the USA showed that radiotherapy plus chemotherapy with nitrosoureas offered a long-term survival advantage to patients younger than 60 years old with malignant gliomas. Combination chemotherapy, such as procarbazine/CCNU/vincristine (PCV) must be tested further, and intra-arterial chemotherapy with nitrosoureas offered no survival advantage. Combination chemotherapy with PCV showed efficacy for patients with anaplastic oligodendroglioma and anaplastic oligoastrocytoma. Medulloblastoma: The addition of chemotherapy to radiotherapy improved the survival of patients with poor risk medulloblastoma, and may reduce the required craniospinal radiation dose in patients with good risk medulloblastoma. Primary CNS lymphoma (PCNSL): Combination of chemotherapy with high-dose MTX and radiotherapy improved survival of patients with PCNSL; however, the neurotoxicity produced by this treatment modality is a serious problem in older patients. Intracranial germ cell tumors: The addition of chemotherapy to radiotherapy may produce long term survival with good quality of life in patients with germinoma. Neoadjuvant therapy consisting of chemotherapy and radiotherapy followed by complete surgical excision improved survival of patients with intracranial nongerminomatous germ cell tumors. (author)

Chemo-radiotherapy for malignant brain tumors

International Nuclear Information System (INIS)

Kochi, Masato; Ushio, Yukitaka

2002-01-01

Malignant gliomas: Randomized clinical trials conducted in the USA showed that radiotherapy plus chemotherapy with nitrosoureas offered a long-term survival advantage to patients younger than 60 years old with malignant gliomas. Combination chemotherapy, such as procarbazine/CCNU/vincristine (PCV) must be tested further, and intra-arterial chemotherapy with nitrosoureas offered no survival advantage. Combination chemotherapy with PCV showed efficacy for patients with anaplastic oligodendroglioma and anaplastic oligoastrocytoma. Medulloblastoma: The addition of chemotherapy to radiotherapy improved the survival of patients with poor risk medulloblastoma, and may reduce the required craniospinal radiation dose in patients with good risk medulloblastoma. Primary CNS lymphoma (PCNSL): Combination of chemotherapy with high-dose MTX and radiotherapy improved survival of patients with PCNSL; however, the neurotoxicity produced by this treatment modality is a serious problem in older patients. Intracranial germ cell tumors: The addition of chemotherapy to radiotherapy may produce long term survival with good quality of life in patients with germinoma. Neoadjuvant therapy consisting of chemotherapy and radiotherapy followed by complete surgical excision improved survival of patients with intracranial nongerminomatous germ cell tumors. (author)

Folic acid functionalized surface highlights 5-methylcytosine-genomic content within circulating tumor cells

KAUST Repository

Malara, Natalia; Coluccio, Maria Laura; Limongi, Tania; Asande, Monica; Trunzo, Valentina; Cojoc, Gheorghe; Raso, Cinzia; Candeloro, Patrizio; Perozziello, Gerardo; Raimondo, Raffaella; De Vitis, Stefania; Roveda, Laura; Renne, Maria; Prati, Ubaldo; Mollace, Vincenzo; Di Fabrizio, Enzo M.

2014-01-01

Although the detection of methylated cell free DNA represents one of the most promising approaches for relapse risk assessment in cancer patients, the low concentration of cell-free circulating DNA constitutes the biggest obstacle in the development of DNA methylation-based biomarkers from blood. This paper describes a method for the measurement of genomic methylation content directly on circulating tumor cells (CTC), which could be used to deceive the aforementioned problem. Since CTC are disease related blood-based biomarkers, they result essential to monitor tumor's stadiation, therapy, and early relapsing lesions. Within surface's bio-functionalization and cell's isolation procedure standardization, the presented approach reveals a singular ability to detect high 5-methylcytosine CTC-subset content in the whole CTC compound, by choosing folic acid (FA) as transducer molecule. Sensitivity and specificity, calculated for FA functionalized surface (FA-surface), result respectively on about 83% and 60%. FA-surface, allowing the detection and characterization of early metastatic dissemination, provides a unique advance in the comprehension of tumors progression and dissemination confirming the presence of CTC and its association with high risk of relapse. This functionalized surface identifying and quantifying high 5-methylcytosine CTC-subset content into the patient's blood lead significant progress in cancer risk assessment, also providing a novel therapeutic strategy.© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tumor-reactive immune cells protect against metastatic tumor and induce immunoediting of indolent but not quiescent tumor cells.

Science.gov (United States)

Payne, Kyle K; Keim, Rebecca C; Graham, Laura; Idowu, Michael O; Wan, Wen; Wang, Xiang-Yang; Toor, Amir A; Bear, Harry D; Manjili, Masoud H

2016-09-01

Two major barriers to cancer immunotherapy include tumor-induced immune suppression mediated by myeloid-derived suppressor cells and poor immunogenicity of the tumor-expressing self-antigens. To overcome these barriers, we reprogrammed tumor-immune cell cross-talk by combined use of decitabine and adoptive immunotherapy, containing tumor-sensitized T cells and CD25(+) NKT cells. Decitabine functioned to induce the expression of highly immunogenic cancer testis antigens in the tumor, while also reducing the frequency of myeloid-derived suppressor cells and the presence of CD25(+) NKT cells rendered T cells, resistant to remaining myeloid-derived suppressor cells. This combinatorial therapy significantly prolonged survival of animals bearing metastatic tumor cells. Adoptive immunotherapy also induced tumor immunoediting, resulting in tumor escape and associated disease-related mortality. To identify a tumor target that is incapable of escape from the immune response, we used dormant tumor cells. We used Adriamycin chemotherapy or radiation therapy, which simultaneously induce tumor cell death and tumor dormancy. Resultant dormant cells became refractory to additional doses of Adriamycin or radiation therapy, but they remained sensitive to tumor-reactive immune cells. Importantly, we discovered that dormant tumor cells contained indolent cells that expressed low levels of Ki67 and quiescent cells that were Ki67 negative. Whereas the former were prone to tumor immunoediting and escape, the latter did not demonstrate immunoediting. Our results suggest that immunotherapy could be highly effective against quiescent dormant tumor cells. The challenge is to develop combinatorial therapies that could establish a quiescent type of tumor dormancy, which would be the best target for immunotherapy. © The Author(s).

Intra-Tumor Genetic Heterogeneity in Wilms Tumor: Clonal Evolution and Clinical Implications

Directory of Open Access Journals (Sweden)

George D. Cresswell

2016-07-01

Full Text Available The evolution of pediatric solid tumors is poorly understood. There is conflicting evidence of intra-tumor genetic homogeneity vs. heterogeneity (ITGH in a small number of studies in pediatric solid tumors. A number of copy number aberrations (CNA are proposed as prognostic biomarkers to stratify patients, for example 1q+ in Wilms tumor (WT; current clinical trials use only one sample per tumor to profile this genetic biomarker. We multisampled 20 WT cases and assessed genome-wide allele-specific CNA and loss of heterozygosity, and inferred tumor evolution, using Illumina CytoSNP12v2.1 arrays, a custom analysis pipeline, and the MEDICC algorithm. We found remarkable diversity of ITGH and evolutionary trajectories in WT. 1q+ is heterogeneous in the majority of tumors with this change, with variable evolutionary timing. We estimate that at least three samples per tumor are needed to detect >95% of cases with 1q+. In contrast, somatic 11p15 LOH is uniformly an early event in WT development. We find evidence of two separate tumor origins in unilateral disease with divergent histology, and in bilateral WT. We also show subclonal changes related to differential response to chemotherapy. Rational trial design to include biomarkers in risk stratification requires tumor multisampling and reliable delineation of ITGH and tumor evolution.

Parity, infertility, oral contraceptives, and hormone replacement therapy and the risk of ovarian serous borderline tumors

DEFF Research Database (Denmark)

Rasmussen, Emma L Kaderly; Hannibal, Charlotte Gerd; Dehlendorff, Christian

2017-01-01

OBJECTIVE: Few studies have examined the risk of an ovarian serous borderline tumor (SBT) associated with parity, infertility, oral contraceptives (OCs), or hormone replacement therapy (HRT), which was the study aim. METHODS: This nationwide case-control study included all women with an SBT...... diagnosis in Denmark, 1978-2002. SBTs were confirmed by centralized expert pathology review. For each case, 15 age-matched female controls were randomly selected using risk-set sampling. Cases and controls with previous cancer (except for non-melanoma skin cancer) and controls with bilateral oophorectomy...... or salpingo-oophorectomy were excluded. Conditional logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We found a strongly decreased risk of SBTs among parous women which decreased with increasing number of children (p