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FRANCHI, MATTEO. "Healthcare utilization databases as a powerful tool to generate evidence in real-world clinical practice: an application on the treatment of metastatic colorectal cancer with bevacizumab." Doctoral thesis, Università degli Studi di Milano-Bicocca, 2017. http://hdl.handle.net/10281/158183.
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L’efficacia di bevacizumab come prima linea di trattamento nel tumore del colon-retto metastatico è stata valutata attraverso diversi studi clinici controllati e randomizzati. Gli studi che valutano il valore aggiunto di bevacizumab nella pratica clinica corrente sono, però, scarsi. Tuttavia, le caratteristiche dei pazienti inclusi negli studi clinici randomizzati sono diverse rispetto a quelle dei pazienti che vengono trattati correntemente nella pratica clinica, limitandone la generalizzabilità.
I database amministrativi, al contrario, permettono il reclutamento di soggetti non selezionati rispetto ad alcune caratteristiche, come l’età, la presenza di comorbidità e il trattamento presso centri altamente specializzati, che solitamente vengono utilizzate come criteri di esclusione negli studi clinici randomizzati.
Il presente studio ha l’obiettivo di valutare l’efficacia (effectiveness) della prima linea di trattamento con bevacizumab, in aggiunta a chemioterapia (CT), nella pratica clinica corrente di pazienti con tumore del colon-retto metastatico. L’obiettivo principale è il confronto della sopravvivenza generale tra i pazienti trattati in prima linea con bevacizumab e CT, rispetto a quelli trattati solo con CT. Gli obiettivi secondari sono la valutazione delle caratteristiche dei pazienti inclusi nella coorte e la valutazione dell’associazione tra tali caratteristiche e la sopravvivenza.
I pazienti con diagnosi incidente di tumore del colon-retto metastatico nel periodo 2010-2012 sono stati selezionati dai Registri Tumori di cinque province italiane: Varese, Mantova, Cremona, Palermo e Ragusa. Per ognuno di questi pazienti sono state estratte le informazioni provenienti dai database amministrativi regionali, con l’obiettivo di ricostruirne i percorsi diagnostici e terapeutici. Tra le informazioni disponibili vi erano le prescrizioni di farmaci oncologici ad alto costo (tra cui bevacizumab), i codici relativi a diagnosi ed interventi dei ricoveri di ospedali pubblici e privati e le prestazioni sanitarie erogate in regime ambulatoriale, tra cui radioterapie e procedure diagnostiche.
Sono stati selezionati 1,118 casi incidenti di tumore del colon-retto metastatico, di cui 480 hanno soddisfatto i criteri di inclusione. Tra questi, 101 hanno ricevuto bevacizumab+CT come prima linea di trattamento e 379 hanno ricevuto solo CT. Rispetto a questi ultimi, i pazienti trattati con bevacizumab erano più giovani e più frequentemente avevano subito un intervento chirurgico prima dell’inizio del trattamento farmacologico. La sopravvivenza mediana era di 22.5 e 14.6 mesi, rispettivamente, nel gruppo di pazienti trattati con bevacizumab+CT e in quelli trattati solo con CT. Il corrispondente hazard ratio, aggiustato per una serie di covariate, era 0.82 (IC 95% 0.62-1.08). I pazienti con età meno avanzata (≤70 anni) e quelli sottoposti ad intervento chirurgico erano associati ad una sopravvivenza migliore.
Diverse analisi di sensibilità sono state effettuate per valutare la robustezza dei risultati dell’analisi principale.
Le stime di sopravvivenza ottenute sono risultate confrontabili rispetto a quelle provenienti da tre ampi studi osservazionali.
Il presente studio mostra un effetto protettivo, anche se non statisticamente significativo, dell’utilizzo di bevacizumab in aggiunta a CT nella prima linea di pazienti con tumore del colon-retto metastatico.
I database amministrativi rappresentano un potente strumento nella conduzione di studi basati sulla reale pratica clinica. Tuttavia, devono essere utilizzati con cautela, tenendo in considerazione i limiti associati al loro uso.<br>The efficacy of first-line bevacizumab added to chemotherapy (CT) in patients with metastatic colorectal cancer (mCRC) was assessed by several randomized clinical trials (RTC). However, data on the added value of bevacizumab in real-world post-marketing studies are scant. Moreover, the characteristics of patients included in RTCs are different from those of patients that physicians generally face in daily clinical practice, limiting the external validity of the results.
Healthcare utilization (HCU) databases, contrarily, allow the recruitment of unselected patients, including the elderly and those with co-morbidities, not always treated in highly specialised centres, reflecting the real clinical practice.
The present study aimed to evaluate the effectiveness of first-line bevacizumab in the Italian clinical practice of patients with mCRC. The overall survival (OS) of patients treated with first-line bevacizumab+CT was compared to the OS of patients treated with CT alone. Baseline characteristics of patients included in the cohort and the predictors of OS were also assessed.
Incident mCRC cases during the period 2010-2012 were selected from five Cancer Registries from Northern (Province of Varese, Mantova and Cremona) and Southern (Province of Palermo and Ragusa) Italy. Cases were linked to the Regional HCU databases of the five areas covered by the Cancer Registries, in order to obtain the entire pathway of health services provided by the National Health Service to each patient. The information collected from the HCU databases included the outpatient dispensations of high-cost drugs (among which bevacizumab), the diagnostic and intervention codes for admission to public or private hospitals and the outpatient services (including radiotherapies and diagnostic procedures).
A cohort of 1,118 incident mCRC cases was identified. After excluding subjects who did not meet the inclusion criteria, a final study cohort of 480 subjects was selected, of which 101 received first-line bevacizumab+CT and 379 received CT alone. As compared to patients using CT alone, those using bevacizumab+CT were younger and received a surgical intervention before starting first-line treatment. The median OS was 22.5 and 14.6 months in patients treated with or without bevacizumab, respectively (p=0.011). The corresponding adjusted hazard ratio was 0.82 (95% CI 0.62-1.08). Young ages at baseline (≤70 years) and experiencing surgery were significant protective factors.
Several sensitivity analyses were conducted, confirming the robustness of the results obtained from the main analysis.
The OS estimates were comparable to those coming from three large observational studies that assessed the OS of patients treated with first-line bevacizumab.
This study suggested a beneficial effect, even not statistically significant, of adding bevacizumab to CT in the real-world clinical practice of mCRC patients. HCU databases represented a powerful tool for conducting observational studies based on real-world data. However, they need to be handled carefully, taking into account the limitations associated to their use.
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Morris, Paul David. "Predicting survival post-liver transplantation for hepatocellular carcinoma." Thesis, The University of Sydney, 2018. http://hdl.handle.net/2123/18334.
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Hepatocellular carcinoma is the sixth most common malignancy worldwide and the third most common cause of death from cancer. In Australia, 1,778 patients were diagnosed with a primary liver cancer in 2013 with an age-standardised rate of 6.9/100,000 people. For a selected group of patients, liver transplantation represents the best chance of cure. Transplantation not only removes the disease, it also removes the abnormal liver parenchyma that provides a fertile ground for development and growth of new disease. Appropriate patient selection forms the cornerstone for any transplantation service, and organ shortages necessitate an efficient allocation of resources and careful prioritisation of the transplantation waiting list in order maximise benefit over a large patient cohort. Current allocation schemes are primarily based on tumour morphology. The goal of this thesis is to analyse pre-transplant radiological and biochemical markers in order to identify markers of poor prognosis that may be used to modify selection criteria.
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Kataoka, Yuki. "External validation of prognostic indices for overall survival of malignant pleural mesothelioma." Kyoto University, 2019. http://hdl.handle.net/2433/245296.
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Cnossen, Jitske. "Overall survival in metastatic breast cancer patients: a single-centre analysis (2000-2005)." Diss., lmu, 2011. http://nbn-resolving.de/urn:nbn:de:bvb:19-131980.
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Östman, Elin. "Trends in overall survival in Swedish patients withprimary metastatic breast cancer – 1994 to 2014." Thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2018. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-68117.
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Introduction Each year approximately 7600 individuals are diagnosed with breast cancer in Sweden, someof which with primary metastatic breast cancer (PMBC). Several new drugs for treatingmetastatic breast cancer have been introduced during the last three decades, many of whichclaims to prolong survival. Aim The aim of this study was to determine if the median overall survival (OS) had improved from1994 to 2014 in patients with PMBC in the healthcare region of Uppsala/Örebro. Material and methods Between 1994 and 2014, 871 patients were diagnosed with PMBC in the healthcare region ofUppsala/Örebro, 168 in 1994-1999, 362 in 2000-2006 and 341 in 2007-2014. The patientcharacteristics were compared with Chi2 test and the Kaplan-Meier method was used tocalculate the median survival for each group. Univariate and multivariate analyses were usedto calculate factors affecting survival. Results The estimated median OS was 12.1 months in 1994-1999, 22.0 months in 2000-2006 and 19.7months in 2007-2014. There was a statistically significant difference in median OS between1994-1999 and 2000-2006, and between 1994-1999 and 2007-2014, but no significantdifference was seen between 2000-2006 and 2007-2014. Increasing age had a negative impacton survival, whereas estrogen receptor-positivity and Grade I-II correlated with prolongedsurvival. Women who had undergone surgery of the breast tumor had longer survival thanthose who had not had surgery. Conclusion The median OS in patients with PMBC have improved from 1994-1999 to 2000-2014. Nodifference was seen between 2000-2006 and 2007-2014.
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Iyer, Sukanya Raj. "Deformation heterogeneity radiomics to predict molecular sub-types and overall survival in pediatric Medulloblastoma." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1588601774292049.
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Crawford, Alyson. "Association of Wait Times to Surgical, Medical and Radiation Therapies with Overall Survival in Ontarians with Melanoma." Thesis, Université d'Ottawa / University of Ottawa, 2015. http://hdl.handle.net/10393/33365.
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Purpose:
Assess for an association of wait times to melanoma treatment with overall survival.
Methods:
Retrospective review of Ontario patients with melanoma, with descriptive and survival analyses.
Results:
Median wait times were 43 days (interquartile range (IQR), 24-64) for wide local excision (WLE), 59 days (IQR, 41-81) for sentinel lymph node biopsy (SNB), 63 days (IQR, 43-91) for lymph node dissection (LND), 124 days (IQR, 96-150) for medical therapy, and 130 days (IQR, 89.5-157.5) for radiation therapy. In multivariate analysis, wait times to treatment were not associated with overall survival for WLE (hazard ratio (HR), 0.97; 95% confidence interval (CI), 0.87-1.08; p=0.62), SNB (HR, 0.89; 95% CI, 0.74-1.07; p=0.21), LND (HR, 0.99; 95% CI, 0.89-1.11; p=0.92), medical therapy (HR, 0.94; 95% CI, 0.80-1.10; p=0.41) or radiation therapy (HR, 0.80; 95% CI, 0.61-1.03; p=0.08).
Conclusion:
Overall survival for patients with melanoma was not associated with wait times to surgical, medical or radiation therapy.
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Belkacemi, Mohamed. "Modèles bivariés et mesures de dépendance pour les survies globale et sans progression dans les essais cliniques sur le cancer." Thesis, Montpellier 1, 2014. http://www.theses.fr/2014MON1T021.
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L'analyse de survie constitue bien souvent l'objectif principal des études cliniques en cancérologie. Les données de survie découlent d'un événement subi par les sujets de l'étude, événement qui correspond par exemple au décès pour la survie globale et à la progression tumorale pour la survie sans progression. Les méthodes non-paramétriques de Kaplan-Meier et semi-paramétriques de Cox représentent les modèles standards les plus utilisés pour modéliser ces données de survie, mais ne s'appliquent que dans le cas d'un seul événement temporel. La survie globale est considérée comme le critère clinique optimal pour juger de l'efficacité d'un traitement. La survie sans progression est un critère intermédiaire, qui représente un critère potentiel de substitution pour la survie globale. Depuis plusieurs années, un intérêt croissant s'est porté sur la validation statistique de critères intermédiaires. Cette validation passe par la mesure de la corrélation entre le critère clinique principal et le critère intermédiaire. Ainsi, une modélisation bivariée apparait intéressante afin de décrire la structure de dépendance entre les survies sans progression et globale. L'objectif de cette thèse concerne la modélisation de la structure d'association entre les survies sans progression et globale ainsi que la quantification de cette association via des mesures de dépendance. Pour cela, nous étudions en premier lieu les extensions du modèle de Cox qui peuvent traiter la dépendance statistique entre les données. Nous proposons ensuite une nouvelle modélisation paramétrique de la survie globale basée sur une distribution conditionnelle et sur les survies sans progression et post-progression. De plus, nous examinons différents modèles paramétriques de survie bivariée en termes de mesures de corrélation. Ces modèles sont fondés sur deux approches : les distributions marginales et l'indépendance conditionnelle. Enfin, nous appliquons et comparons les modèles étudiés en utilisant les données d'un essai clinique randomisé de phase III, impliquant des patients atteints de cancer du poumon non à petites cellules localement avancé<br>Analysis of survival often represents the main aim in cancer clinical studies. Survival data arise from an event experienced by the study subjects. This event corresponds for example to the death for overall survival and to tumor progression for progression-free survival. The Kaplan-Meier nonparametric estimator and the Cox semiparametric model are the most used standard methods for modeling survival data, although they are applied only in the case of unique temporal event. Overall survival is the optimal clinical endpoint for assessing the efficiency of treatment. Progression-free survival is an intermediate endpoint considered as a potential surrogate of overall survival. For the past few years, we observed an increasing focus on statistical validation of intermediate endpoints and this through measurement of the correlation between the principal clinical endpoint and the intermediate one. Thus, bivariate modeling could be of interest for describing the dependence structure between progression-free survival and overall survival. The aim of this thesis is the modeling of the structure of association between progression-free survival and overall survival as well as the quantification of this association using dependence measures. For this, we study at first extensions of Cox model able to address the topic concerning the statistical dependence between data. Next, we propose a new parametric modeling of overall survival based on two survival times : progression-free survival and post-progression survival, assumed to be linked by a conditional distribution. Moreover, we examine different parametric models for bivariate survival data concerning correlation measurement. These models are based on the marginal distributions and the conditional independence. Finally, we apply and compare these models using data from a phase III randomized clinical trial, involving patients with locally advanced non-small cell lung cancer
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Dyer, Greg Bryan. "Possible effects of HIV infection on overall survival of patients diagnosed with acute myeloid leukaemia." Diss., University of Pretoria, 2019. http://hdl.handle.net/2263/75830.
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Background
The effects of Human Immunodeficiency Virus (HIV) on the Overall Survival (OS) in patients diagnosed with Acute Myeloid Leukaemia (AML) are not well documented. All studies to date have been with small sample sizes and based on collections of case studies from different facilities with different treatment protocols, as a result it has been difficult to draw definitive conclusions.
Method
This retrospective record review of a cohort of AML patients (n=304) treated at a single site between 2000 and 2017 was conducted. Age (16-93 years), gender (Male: n=157 ; Female: n=138), ECOG PS (Eastern Co-Operative Oncology Group Performance Status), FAB (French-American-British) staging, blast count, CD4 count, HIV viral load, financial status, response to treatment as measured on bone marrow biopsy and OS were measured. The OS was compared for HIV status. Further comparisons were conducted in a sub-group where age, ECOG PS and FAB staging were controlled.
Results
210 (69.07%) were HIV negative, 31 (10.1%) were HIV positive, 63 (20.7%) had an unknown HIV status. A statistically significant difference was found between HIV negative and HIV positive groups’ OS (563 vs. 121 days ; P<0.01)(HR 2.02 ; 95% CI 1.36 - 2.99) in the main analysis. This difference was also noted when patients who were not treated for AML were excluded from the comparison (OS, 740 vs 194 days, P<0.01)(HR, 2.10 ; 95% CI 1.26-3.50). In the main analysis mean ECOG PS was better in the HIV negative population compared to the positive population (1.80 vs. 2.06). In the controlled group sub-study, where Age, ECOG PS and FAB staging were controlled, the OS between HIV positive and HIV negative patients was not statistically significant (141 days vs. 121 days) (P=0.17; 95% CI). CD4 counts ranged from 29 – 1416, with a mean CD4 of 432 on presentation. No statistically significant difference could be found between CD4 and OS (HR, 1.0 ; 95% CI 0.99-1.00), possibly due to very few patients presenting with a low CD4 count. HIV Viral Loads ranged from <100 – 106640. Similarly, no statistically significant difference was found between HIV Viral Load and OS (HR 0.99 ; 95% CI 0.99-1.00).
Conclusion
HIV has a negative impact upon the OS of patients with AML. HIV appears to impact on OS as a chronic comorbidity by affecting ECOG PS on presentation, reducing their chance of being treated as well as possibly reducing a patients’ functional reserve. This impact does not appear to be as a result of a direct interaction between the HIV and AML disease processes, as when controlling for other factors that may influence OS there is no statistically significant difference in OS between HIV positive and negative patients.<br>Dissertation (MSc (Medical Oncology))--University of Pretoria, 2019.<br>This thesis/dissertation is under embargo until September 2023.<br>Medical Oncology<br>MSc (Medical Oncology)<br>Restricted
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Cook, Victoria Tracy 1960. "The effects of temporal uncertainty resolution on the overall utility and suspense of risky monetary and survival gambles /." Thesis, McGill University, 1989. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=75966.
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We extend Kreps and Porteus' (1978, 1979a,b) temporal utility theory to include measures of suspense for gambles that vary in the timing of uncertainty resolution. Our f$ sp t$-modification (of their theory) defines overall utility and suspense in terms of two functions: a standard utility function and an iterative function whose properties determine attitude towards temporal uncertainty resolution. Suspense, which is increasing with time delay to uncertainty resolution, is defined as the "variance" of the standard utilities of the outcome streams taken about our measure of overall utility (rather than about the standard mean utility). We explore the properties of our measures and their implications for the overall utility and suspense of various key examples. Two preliminary experiments are reported which give some support for our overall utility and suspense measures, and which suggest that risk and suspense are different concepts. Iteration theory is also discussed in some detail.
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Rudaitis, Vilius. "BRCA1/2 mutation spectrum and its prognostic significance for progression-free and overall survival in advanced ovarian cancer." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2014. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2014~D_20140925_135101-34767.
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In general population 1 of 72 women develop ovarian cancer and to 1 of 95 women this disease is lethal. A great number of clinical trials have shown that the course of the disease is not dependent only on the classical prognostic indicators such as histological tumor type, tumor differentiation, stage of the disease or treatment modalities. More than two decades ago the first publications on heredity factors indicated similarity among the patients diagnosed ovarian malignancies and their first degree relatives. The first genetic autosomal dominant inheritance was determined in the high-risk cancer tumor suppressor BRCA1/2 genes. In spite of the abundant number of trials studying the BRCA1/2 genes role in breast and ovarian carcinogenesis still it is not sufficiently clear the influence of these genes for the disease prognosis. The aim of our conducted trial was to determine the BRCA1/2 genes prognostic significance for progression-free and overall survival in the event of advanced ovarian cancer. In case of advanced ovarian cancer the BRCA1/2 mutation frequency was 51,4 %. Among all determined BRCA1/2 gene mutations BRCA1 4035delA or founder mutation was most frequent. It amounted to 63.6%. Non-optimal cytoreduction (p<0,0001 ) , patients’ older age (p=0,005) and absence of BRCA1/2 mutations (p=0,049) are closely connected with a shorter PFS and OS. Only non-optimal cytoreduction was related to a shorter OS (p=0,010).<br>Bendrojoje populiacijoje 1 iš 72 moterų suserga kiaušidžių vėžiu ir 1 iš 95 moterų miršta nuo šios ligos. Tyrimų duomenys rodo, kad ligos eiga nėra priklausoma vien tik nuo klasikinių prognozinių rodiklių, tokių kaip histologinis naviko tipas, naviko diferenciacija, ligos stadija, taikytas gydymas.Prognozinių veiksnių paieška krypstą link genetinių veiksnių galinčių įtakoti ligos eigą. Literatūros duomenys apie klinikinę BRCA1/2 genų reikšmę yra kontroversiški – nuo visiškai bereikšmio iki ženkliai teigiamo poveikio ligos eigai prognoziniu požiūriu.. Mūsų tyrėjų grupės atlikto tyrimo tikslas buvo nustatyti BRCA1/2 genų mutacijų dažnį ir jų įvairovę tarp pacienčių, sergančių išplitusiu kiaušidžių vėžiu, ir įvertinti šių mutacijų įtaką berecidyviam ir bendrajam išgyvenamumui. Mes nustatėme , kad tarp pacienčių sergančių išplitusių epiteliniu kiaušidžių vėžiu buvo net 51,4 proc. BRCA 1/2 mutacijų genuose turinčių pacienčių. 98,2 proc. šių pacienčių sirgo serozine papiline adenokarcinoma. Šios histologinės formos kiaušidžių vėžio buvo ženkliai daugiau mutuotų BRCA1/2 genų pacienčių grupėje nei tarp pacienčių be mutacijų (p-0,029). Tyrimo metu nustatėme dažniausiai sutinkamą arba bendro protėvio BRCA 1 4035 delA mutaciją bei taip kad statistiškai reikšmingos įtakos sergančiųjų išplitusiu kiaušidžių vėžiu berecidyviam išgyvenamumui turi pacienčių amžius (p=0,005), BRCA1/2 genų mutacijos(p=0,049) bei operacijos apimtis (p<0,0001), o bendrajam išgyvenamumui – tik operacijos... [toliau žr. visą tekstą]
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Cnossen, Jitske Alida [Verfasser], and Volker [Akademischer Betreuer] Heinemann. "Overall survival in metastatic breast cancer patients : a single-centre analysis (2000 - 2005) / Jitske Cnossen. Betreuer: Volker Heinemann." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2011. http://d-nb.info/1015130933/34.
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Campbell, David. "CT Textural Analysis (CTTA) of Metastatic Treatment‐Resistant Pancreatic Adenocarcinoma (PDAC): Identifying Biomarkers for Genetic Instability and Overall Survival." Thesis, The University of Arizona, 2016. http://hdl.handle.net/10150/603564.
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A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.<br>Metastatic, treatment‐resistant pancreatic ductal adenocarcinoma (PDAC) is a rapidly fatal disease that typically carries a bleak prognosis. Contrast‐enhanced CT is the current standard of care tool for imaging evaluation, and repeat imaging is routinely performed in clinical trials. The availability of these imaging data render them exploitable for further analysis. CT texural analysis (CTTA), a quantitative tool for examining a region of interest on CT and generating statistical parameters based on gray‐level pixel data, is powerful technique that has been studied in other cancers and shown to correlate with features such as tumor grade, stage, and prognosis. However, the application of CTTA to PDAC has not been studied. Given the paucity of diagnostic tests to guide therapy, validated CTTA biomarkers could be immensely useful. Identifying PDAC variants that have a relative deficit in DNA repair might allow these cancers to be treated with targeted cytotoxic regimens sooner. Additionally, identifying prognostic CTTA parameters would be useful in gauging the severity of disease. We sought to perform quantitative textural analysis on CT imaging from a clinical trial cohort of patients with metastatic, treatment‐resistant PDAC. We aimed to correlate CTTA features to molecular profiling results (copy number variations obtained by array CGH) and clinical features (overall survival). Metastatic tumor sites from patients with treatment‐resistant PDAC were biopsied and molecularly profiled. Intrachromosal copy number were assessed by CGH in tumor specimens, and patients were treated based on these individual molecular profiling results. Pre‐biopsy portal‐venous phase and non‐contrast CT scans were obtained for retrospective analysis (n=15). CTTA was performed by drawing regions of interest around the primary pancreas adenocarcinoma and the normal pancreas tissue. CTTA parameters including mean positive pixels, entropy, kurtosis, and skewness were derived using the TexRAD platform at texture filtering densities of 0, 2, 3, 4, 5, and 6 pixels. CTTA values were then compared to intrachromosomal copy number variation (CNV) per tumor and overall survival (OS) post treatment using a Spearman’s rank correlation coefficient. Additional linear regression analysis was performed for positive correlations, and a Kaplan‐Meier statistic was generated for OS using median CTTA entropy. Multivariate analyses for CNV and OS were also performed. CNV were negatively correlated with the kurtosis value of the primary tumor mass using medium texture filtering (p=0.034, n=15). Linear regression revealed a significant negative correlation between kurtosis and CNV (p=0.038). Secondary analysis of the normal pancreas using coarse texture filtering revealed that increasing entropy was associated with decreased OS (p=0.0014, n=12). Using median entropy as a cutoff value (median: 4.165), median OS was greater in the entropy < 4.165 group versus the entropy > 4.165 group (179 days v 43 days; 95% CI 73.137 – 166.87; p=0.004, n=12). This exploratory study with admittedly limited sample size raises interesting questions about the use of CTTA parameters as diagnostic tools and/or biopsy adjuncts in assessing PDAC susceptibility to commercially available cytotoxics. Secondarily, entropy, a potential marker of heterogeneity and inflammation in the normal pancreas, represents an intriguing possibility for gauging prognosis.
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Young, Jonathan Richard. "A retrospective analysis of the effect of platinum hypersensitivity reactions on overall survival in patients with epithelial ovarian cancer." Thesis, Boston University, 2012. https://hdl.handle.net/2144/12692.
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Thesis (M.A.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.<br>Objective: Platinum-based compounds are frequently used as chemotherapeutic agents in the treatment of epithelial ovarian cancer. Due to the frequency of platinum hypersensitivity reactions observed among these patients, the important question arises as to how the subset of patients that experience a hypersensitivity reaction fare in terms of overall survival compared to patients that do not. In matching the prognostic factors of those patients that have experienced a platinum hypersensitivity reaction to those patients that have not, this retrospective analysis serves to investigate the relationship between platinum hypersensitivity reactions and overall survival.
Methods: This is a retrospective analysis of patient data extracted from Massachusetts General Hospital's LMR patient database. The primary end-point was overall survival for patients who experienced a platinum-induced hypersensitivity reaction. A random sample of patients with the primary diagnosis of epithelial ovarian cancer that died between the years of 2002 and 2011 and were treated with platinum-based regimen (carboplatin, cisplatin, or oxaliplatin) were included in the analysis. Patients were then classified into 2 groups, those that developed platinum hypersensitivity, and those that did not (controls). Subjects were matched on a number of prognostic factors: age ±5 years, tumor grade, tumor histology, volume of residual disease post cytoreductive surgery (optimal or sub-optimal), and number of platinum cycles received. Both the platinum allergy group and the control group were only included in the analysis if they received both primary cytoreductive surgery and a platinum-based first line of chemotherapy. Statistical analysis included matched analysis by stratified Cox's Regression and representation of Overall Survival probability curves.
Results: Thirty-one patients diagnosed from February 1992 through October 2008 were included in this analysis. The age range at the time of diagnosis was from 42.0 to 77.0 years of age, with a median age of 55.9 years. Of the thirty-one patients analyzed that had platinum hypersensitivity reactions, the tumor histologies were noted to be either serous (N=29), endometrioid (N=1), or mixed (N=1). Tumor grade ranged from the most differentiated grade 1 (N=1) to grade 3 (poorly differentiated), however the majority of the patients were grade 3 (N=29). Tumor stage ranged from IC to stage IV, with the majority of the patients being Stage IIIC (N=26). The volume of residual disease following primary cytoreductive surgery was deemed as either optimal (less than 1 cm of residual disease) or suboptimal (greater than 1 em of residual disease). Most of the patients were optimally surgically debulked (N=26). The number of total platinum cycles received ranged from 6 cycles to 28 cycles, with the median number of cycles being 15.7 for the platinum allergy patients and 12.3 for the controls. In analyzing the overall survival data, the platinum allergy group had a median overall survival period of 68.7 (95% CI: 52.30-75.47) months from their date of diagnosis. The control group had a median overall survival period of 35.3 (95% CI: 30.77-38.40) months. The Hazards Ratio (Allergic Patients to Controls) by Matched Analysis using Stratified Cox's Regression was 0.24 with (p=0.0017).
Conclusions: In this retrospective analysis, there appears to be a strong correlation between the platinum allergy patients experiencing a greater than double period of overall survival than the control group (Median ST; PA: 68.7 months, C: 35.3 months). Although the sample size in this analysis is relatively small, the correlation between a platinum hypersensitivity reaction and a significant increase in overall survival warrants further exploration.
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Wahib, Ramez [Verfasser], and Dean [Akademischer Betreuer] Bogoevski. "Overall survival after pancreatectomy with en bloc portal vein resection for macroscopically infiltrating pancreatic cancer / Ramez Wahib ; Betreuer: Dean Bogoevski." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2019. http://d-nb.info/1200101898/34.
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Wahib, Ramez Verfasser], and Dean [Akademischer Betreuer] [Bogoevski. "Overall survival after pancreatectomy with en bloc portal vein resection for macroscopically infiltrating pancreatic cancer / Ramez Wahib ; Betreuer: Dean Bogoevski." Hamburg : Staats- und Universitätsbibliothek Hamburg, 2019. http://nbn-resolving.de/urn:nbn:de:gbv:18-101193.
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Kale, Hrishikesh P. "Economic Burden of Renal Cell Carcinoma (RCC) and Treatment Patterns, Overall Survival and Healthcare Costs among Older Metastatic RCC Patients." VCU Scholars Compass, 2018. https://scholarscompass.vcu.edu/etd/5555.
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Background
Renal cell carcinoma (RCC) is the most common type of kidney cancer. Patients diagnosed with metastatic RCC (mRCC) have shorter overall survival compared to those diagnosed at earlier stages. Several targeted therapies, which cost from $7,000 - $16,000 per month have been approved since 2005 to treat mRCC. In addition, there is a growing interest in the use of cytoreductive nephrectomy (CN) with targeted therapies among mRCC patients. However, little is known regarding the economic burden of RCC and role of CN and prescribing patterns of targeted therapies among older mRCC patients.
Objectives
1) To assess the economic burden of RCC among older adults in the targeted therapy era 2) To compare the overall survival (OS) and total healthcare cost (THC) among older mRCC patients receiving CN and targeted therapy versus patients receiving targeted therapy alone 3) To describe prescribing patterns of targeted therapies and associated OS and THC among older mRCC patients.
Methods
This dissertation was conducted using the Surveillance Epidemiology and End Results (SEER) - Medicare linked data. For the first objective, the study included a prevalent cohort of RCC patients from 2013, diagnosed during 2005 - 2013 and continuously enrolled in Medicare. RCC patients were matched to non-cancer beneficiaries using propensity score matching. Generalized linear models estimated the incremental healthcare costs. Incremental total healthcare cost (THC) was multiplied by the estimated number of RCC patients on Medicare to calculate the total economic burden of RCC. For the second objective, we included patients diagnosed with mRCC between 2007-2014 and compared overall survival (OS), and THC between patients who received CN + targeted therapy and targeted therapy alone. A propensity score based inverse probability of treatment weighting (IPTW) method was used to balance the two treatment groups. A Cox proportional hazard model assessed the risk for death and a GLM compared healthcare costs between the groups. For the third objective, patients with mRCC were defined as patients who were diagnosed at stage-IV or at earlier stages but were currently using targeted therapies. Further, we restricted our sample to patients who initiated targeted therapy. We described the frequencies of the most common first and second line targeted therapies. We also described OS and THC per month for clear-cell and non-clear cell mRCC for each therapy and line of therapy.
Results
The first study included 10,392 each of RCC and control patients. The average THC associated with RCC was $7,419. The average THC was $4,584 for patients diagnosed at stage-I, $4,727 for stage-II, $9,331 for stage-III, and $31,637 for stage-IV. The annual economic burden of RCC on Medicare was estimated to be $1.5 billion. The second study included 471 mRCC patients that received CN + targeted therapy or targeted therapy alone. The median OS from the adjusted survival curves was significantly higher (p
Conclusions
The economic burden of RCC varied substantially between early stage and metastatic patients. Among mRCC patients, use of CN among targeted therapy users was associated with a higher median OS and similar monthly THC over a lifetime. Sunitinib and everolimus were the most common first and second line targeted therapies among mRCC patients. The descriptive analysis suggested that OS and THC were similar across types of targeted therapy sequences.
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MASSOBRIO, ANDREA. "EARLY HEPATIC RECURRENCE AFTER COLORECTAL CANCER LIVER METASTASES SURGERY: A SINGLE PROSPECTIVE CENTRE STUDY." Doctoral thesis, Università degli studi di Genova, 2020. http://hdl.handle.net/11567/1011221.
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Liver resection, combined with modern chemotherapy, is considered the standard treatment for patients with resectable CRLM. However, the recurrence of hepatic metastasis after liver resection remains a concern worldwide. About twenty years ago, important studies overwhelmed the historical concept that 1.0-cm margin was not an absolute requirement for a curative approach in the treatment of patients with colorectal cancer liver metastases.
This is a prospective observational study, performed at the Oncological Surgery, Hospital Policlinic San Martino, Genoa, Italy from 1st April 2014 to the 1st June 2019. Patients undergoing primary hepatic resection for colorectal liver metastasis with curative intent and having a minimum follow-up period of 6 months were included.
Several clinical, pathological, and surgical factors have been tested for correlation with early recurrence and disease-free survival (DFS) in univariate analyses with a specific focus on the impact of resection margin depth. Microscopically and in line with the histological reports, the widths were stratified as coincidental margins if the tumor was in contact with the surgical margin (0 mm); widths of less than, or equal to, 1 mm or greater than 1 mm.
During the follow up period, recurrence after liver resection was documented in 24 patients (48%). Early recurrence (within 6 months after liver resection) occurred in 11 patients (22% of the sample and 46% of the total recurrences), including 4 patients (36%) with liver-only recurrence and 7 patients (63%) with systemic recurrence (with or without liver recurrence). One-year and two-year mortality were 12% and 22%, respectively.
According to univariate analysis, no significant differences were found in early recurrence and DFS between gender, location of the primary tumor, number and size of resected liver metastases, growth pattern and KRAS wild type. Time of diagnosis of liver metastases was the only significant prognostic factor for both DFS and for early recurrence. Moreover, histological grade of primary tumor (G2:33% vs. G3:86% vs. G4:100%; p<0.040) and synchronous presentation of liver metastases (80% vs. 20%; p<0.037) were associated with shorter DFS. No significant differences were found in the early recurrence rates and DFS in R1 versus R0 patients and even between the stratification of surgical margin size. Indeed, patients with wider-margin groups showed similar trend of recurrence in comparison with the narrow-margin group. Additionally, there was a slightly significant association between the severity of postoperative complication and the occurrence of a recurrence disease (p<0.08).
In conclusion, in the present study, the lack of association between R1 status and DFS or early recurrence disease suggested that R1 margin status may be a surrogate indicator of advanced and/or more extensive disease. Even exploratory in nature, the present study suggests that the tumor biology (in term of grading and synchronous metastasis) rather than R1 resection was associated recurrence disease.
So, up to date, the preferred surgical technique should be a parenchymal-sparing non-anatomic resection using modern surgical devices to keep as much liver parenchyma as possible. Furthermore, the risk of an R1 resection should not be considered a contraindication to surgery with curative intent, as neoadjuvant chemotherapy may destroy peripheral micrometastases before liver resection, minimizing consequently the residual micro-metastatic disease.
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Kato, Ayako. "Prognostic Value of Quantitative Parameters of ¹⁸F-FDG PET/CT for Patients With Angiosarcoma." Kyoto University, 2020. http://hdl.handle.net/2433/259007.
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NERI, BENEDETTA. "Nella leucemia acuta mieloide una terapia induzione con dosi standard di citarabina è associata a una migliore qualità della risposta rispetto ad una terapia di induzione con alte dosi di citarabina." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2010. http://hdl.handle.net/2108/1293.
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La leucemia mieloide acuta (LAM) è una malattia clonale caratterizzata dalla proliferazione e dall'accumulo di cellule progenitrici mieloidi nel midollo osseo, che in ultima analisi conduce al fallimento della proliferazione ematopoietica fisiologica. L'incidenza di LAM aumenta con l'età, ed i pazienti più anziani hanno in genere dei risultati peggiori in termini di risposta al trattamento rispetto ai pazienti più giovani.La molecola Citarabina (Ara-C) è la pietra angolare della terapia di induzione e di consolidamento per la LAM. Con questo studio abbiamo voluto dimostrare come l'utilizzo in induzione di schemi di trattamento contenenti dosi standard di citarabina (SDAC) sia associato ad una migliore qualità della risposta rispetto all'utilizzo di schemi di trattamento contenenti alte dosi di citarabina (HDAC). Il nostro lavoro si pone come scopo di verificare l'impatto sulla qualità della risposta di uno schema di trattamento con SDAC versus uno contenente HDAC, quantificando la malattia minima residua (MRD), una volta ottenuta la RC. Conseguentemente all'importanza dell'ottenimento di una cosiddetta “remissione citofluorimetrica”, abbiamo valutato la DFS in relazione alla dose di citarabina ed allo stato di MRD dopo il ciclo di consolidamento ed abbiamo evidenziato che i pazienti MRD negativi che abbiano ricevuto SDAC hanno una DFS significativamente migliore rispetto ai pazienti MRD positivi ed a quelli MRD negativi che abbiano ricevuto HDAC. (p: 0.0001).
Una valutazione analoga è stata ovviamente effettuata anche per la OS: il risultato è sovrapponibile al precedente e nettamente a favore dei pazienti MRD negativi che abbiano ricevuto SDAC (p:0.0014).<br>Acute myeloid leukemia (AML) is a clonal disease characterized by the proliferation and accumulation of myeloid progenitor cells in the bone marrow, which ultimately leads to hematopoietic failure. The incidence of AML increases with age, and older patients typically have worse treatment outcomes than younger patients do.
Cytosine arabinoside (ARA-C) is the golden standard for induction and consolidation therapy in AML. With this study we want to demonstrate how the use of an induction chemotherapy schedule with Standard dose of ARA-C (SDAC) leads to a better quality of response, compared with a schedule containing High Dose of ARA-C (HDAC).
Our aim is to value the impact of the SDAC schedule on the quality of response to chemotherapy, monitoring minimal residual disease (MRD), once achieved RC. Basing on the importance of a so called “cytofluorimetric remission”, we have valued Disease Free Survival (DFS) according to ARA-C dose and to MRD status after consolidation: we found that MRD negative patients after SDAC schedule have a better DFS rate comparing to MRD positive and MRD negative patients who received HDAC schedule.(p: 0.0001).
A similar evaluation was done for Overall Survival (OS) as well :the result is similar to the previous and definitely better in MRD negative patients after SDAC schedule.(p:0.0014).
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Song, Bolin. "Dynamic Co-occurrence of Local Anisotropic Gradient Orientations (DyCoLIAGe) Descriptors from Pre-treatment Perfusion DSC-MRI to Predict Overall Survival in Glioblastoma." Case Western Reserve University School of Graduate Studies / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=case1554299860994274.
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Khaddam, Sinan M. D. "Difference in outcomes between central airway lesions requiring stents and lesions that donot in patients with NSCLC." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1553513958608363.
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Olešová, Kristína. "Klasifikace stupně gliomů v MR datech mozku." Master's thesis, Vysoké učení technické v Brně. Fakulta elektrotechniky a komunikačních technologií, 2020. http://www.nusl.cz/ntk/nusl-413113.
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This thesis deals with a classification of glioma grade in high and low aggressive tumours and overall survival prediction based on magnetic resonance imaging. Data used in this work is from BRATS challenge 2019 and each set contains information from 4 weighting sequences of MRI. Thesis is implemented in PYTHON programming language and Jupyter Notebooks environment. Software PyRadiomics is used for calculation of image features. Goal of this work is to determine best tumour region and weighting sequence for calculation of image features and consequently select set of features that are the best ones for classification of tumour grade and survival prediction. Part of thesis is dedicated to survival prediction using set of statistical tests, specifically Cox regression
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Kolokotronis, Theodoros [Verfasser], and Matthias [Akademischer Betreuer] Glanemann. "Postoperative outcome and overall survival after surgery for esophageal cancer : a retrospective, single-center experience of 320 patients encompassing 14 years / Theodoros Ioannis Fernant Kolokotronis ; Betreuer: Matthias Glanemann." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2017. http://d-nb.info/1135956847/34.
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Kolokotronis, Theodoros Ioannis Fernant [Verfasser], and Matthias [Akademischer Betreuer] Glanemann. "Postoperative outcome and overall survival after surgery for esophageal cancer : a retrospective, single-center experience of 320 patients encompassing 14 years / Theodoros Ioannis Fernant Kolokotronis ; Betreuer: Matthias Glanemann." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2017. http://d-nb.info/1135956847/34.
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Zhao, Feng. "Bootstrap variable selection and model validation for Cox's proportional hazards regression models, with applications to the identification of factors predictive of overall and post-relapse survival in advanced epithelial ovarian cancer." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0026/MQ31275.pdf.
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Mölle, Ulrike [Verfasser], Dirk [Akademischer Betreuer] Vordermark, Christoph [Akademischer Betreuer] Thomssen, and Rainer [Akademischer Betreuer] Souchon. "External beam radiotherapy for cervical cancer with Cobalt-60 in Ethiopia : adherence to therapy, adverse effects and overall survival of 1009 patients 2008-2012 / Ulrike Mölle ; Dirk Vordermark, Christoph Thomssen, Rainer Souchon." Halle, 2016. http://d-nb.info/1127579932/34.
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Morys, Beata Magdalena. "Klinische Ergebnisse von Patientinnen mit primärem und sekundärem epithelialem Ovarialkarzinom im Krankenhaus im Friedrichshain von 1992 bis 1998." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2005. http://dx.doi.org/10.18452/15163.
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Zielsetzung: Das Ovarialkarzinom ist die häufigste Krebstodesursache innerhalb der gynäkologischen Malignome. Im Rahmen dieser retrospektiven Arbeit werden die klinischen Ergebnissen von 84 Patientinnen dargestellt, die an Ovarialkarzinom erkrankten und im Krankenhaus im Friedrichshain in Berlin behandelt wurden. Das Ziel dieser Studie war die Analyse des Einflusses verschiedener Prognosefaktoren auf das Gesamtüberleben, Identifikation unabhängiger Prognosefaktoren und Erarbeitung von Prognoseregeln in Bezug auf das Gesamtüberleben sowie Beurteilung des Therapieerfolges und kritische Diskussion des second-look Verfahrens. Methodik: Zur Bestimmung der kumulierten Überlebensraten wurde die Kaplan-Meier-Methode verwendet, zur Identifikation unabhängiger Prognosefaktoren die multivariate Analyse. Als statistisch signifikant galten Ergebnisse mit einer Irrtumswahrscheinlichkeit von p < 0,05. Ergebnisse: Das mediane Alter zum Zeitpunkt der Erstdiagnose betrug 61 Jahre. Die kumulierte Fünfjahresüberlebensrate betrug 53 %. Die kumulierten Fünfjahresüberlebensraten lagen für die Stadien FIGO I, II, III bzw. IV bei 93 %, 83 %, 20 % bzw. 11 %. Seitens der Histologie handelte es sich überwiegend um serös-papilläre Karzinome. Die Rezidivrate lag bei 36 %. Der Median bis zum Auftreten eines Rezidivs betrug 11,5 Monate. Schlussfolgerungen: Eine gute Prognose ergibt sich bei geringem Alter bei Erstdiagnose, gutem Allgemeinzustand, normwertigem präoperativem Tumormarker CA 125, fehlendem Aszites bzw. möglichst geringer Aszitesmenge, hochdifferenzierten Tumoren, möglichst vollständiger Tumorentfernung und Lymphonodektomie. Als unabhängige Prognosefaktoren haben sich nur das FIGO-Stadium, Alter und Grading erwiesen. Anhand der unabhängigen Prognosefaktoren lässt sich die prognostizierte Überlebenswahrscheinlichkeit angeben.<br>Objective: Ovarian carcinoma is the most frequent reason of the cancer death among malignant gynaecological tumours. The clinical outcome of 84 patients, who had ovarian carcinoma and underwent the treatment in "The Hospital in Friedrichshain" in Berlin, is presented in this retrospective study. The objective of this study was to analyse the influence of different prognostic factors related to overall survival, to identify the independent prognostic factors, to set up prognostic rules for patients with ovarian carcinoma related to overall survival, to assess the benefit of the therapy and the critical discussion of the second-look operation. Methods: The Kaplan-Meier method was applied in order to estimate overall survival rates and multivariate analysis in order to evaluate the independent prognostic factors. The results with p < 0,05 were of statistic significance. Results: The median age at diagnosis was 61 years. The cumulated 5-year survival rate was 53 %. The cumulated 5-year survival rates for the stages FIGO I, II, III and IV were 93 %, 83 %, 20 % and 11 %, respectively. Concerning histology there were mostly serous-papillar carcinomas. The recurrence rate was 36 %. The median until the recurrence occurred was 11,5 months. Conclusions: A good prognosis is associated with lower patient age at diagnosis, good performance status, normal preoperative serum CA-125 level, absence or minimal presence of ascites, well differentiated tumours, minimal size of the residual disease after primary cytoreductive surgery and lymphadenectomy. However, on multivariate analysis, only tumour stage, patient age and tumour grade retained prognostic significance as independent prognostic factors. Due to independent prognostic factors the survival probability can be predicted.
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Gurung, P. M. S. "The tumour suppressor gene, AIMP3, sensitises bladder cancer to chemo/radiotherapy in vitro and is, with ERCC1, a predictive marker of overall survival in patients treated with radical radiotherapy for muscle-invasive disease." Thesis, University College London (University of London), 2015. http://discovery.ucl.ac.uk/1461130/.
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Bladder cancer is the second most common urological cancer after prostate cancer and is one of the leading causes of cancer mortality in most western countries. For organ-confined, muscle-invasive disease, the standard of care, in terms of definitive cure, remains radical surgery (cystectomy) with lymphadenectomy. However, survival rates remain poor following supposedly curative treatment. Radical radiotherapy and more recently, multimodality treatment incorporating chemo-radiotherapy, are alternatives which allow bladder preservation in those choosing not to undergo or are unsuitable for radical surgery. However, survival rates following radiotherapy are generally lower relative to radical cystectomy and multimodality treatments can only be offered to select cases in few institutions. Biomarkers which can accurately predict tumour response to radiotherapy or chemotherapy can aid the selection of patients who are likely to respond well to treatment options incorporating radiotherapy and/or chemotherapy, as alternatives to radical cystectomy, in the management of bladder cancer. Such a strategy would allow personalised cancer care with patients likely to benefit from treatments that they are likely to respond well to and concomitantly avoid complications arising from other treatments less likely to benefit them. This thesis investigated the novel tumour suppressor gene, AIMP3 which is involved in the DNA damage response (DDR) pathway following exposure to genotoxic insults such as irradiation and chemotherapy. The expression and cellular localisation of AIMP3 protein was characterised in a panel of bladder cancer cell lines. Expression of AIMP3 was altered by gene knockdown with siRNA transfection and survival outcomes assessed following irradiation and chemotherapy. The predictive value of AIMP3 expression in determining survival outcome of patients with muscle-invasive bladder cancer who had undergone radical radiotherapy, with or without carbogen supplementation, in the BCON trial, was assessed. Prognostic significance was evaluated by interrogating a control cohort of patients who had undergone radical cystectomy and had not had exposure to radiotherapy or either neoadjuvant or adjuvant chemotherapy. Reportedly important DDR proteins, including Mre11, p53 and ERCC1, were also interrogated in the BCON, Radical Cystectomy, Neodjuvant and LaMB trial TMA datasets. Clonogenic survival outcomes following AIMP3 knockdown were also investigated in cisplatin-sensitive (RT112) and cisplatin-resistant (RT112CP) cell lines following cisplatin exposure. Survival outcome, stratified for AIMP3 as well as ERCC1, Mre11 and p53 status, were interrogated in the Neoadjuvant set, which incorporated a cohort of patients who had undergone cisplatin-based neoadjuvant chemotherapy prior to radical treatment. This was validated in a second cohort of patients who had undergone cisplatin-based chemotherapy as part of the LaMB trial.
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Fröhner, Michael, Albrecht Scholz, Rainer Koch, Oliver W. Hakenberg, Gustavo B. Baretton, and Manfred P. Wirth. "Competing Mortality Contributes to Excess Mortality in Patients with Poor-Risk Lymph Node-Positive Prostate Cancer Treated with Radical Prostatectomy." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133747.
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Background: Factors predicting survival in men with lymph node-positive prostate cancer are still poorly defined. Patients and Methods: 193 prostate cancer patients with histopathologically proven lymph node involvement with a median follow-up of 7.3 years were studied. 94% of patients received immediate hormonal therapy. Kaplan-Meier curves were calculated to evaluate overall survival rates and compared with the log-rank test. Cumulative disease-specific and competing mortality rates were calculated by competing risk analysis and compared with the Pepe-Mori test. Cox proportional hazard models were used to determine the independent significance of predictors of all-cause mortality. Results: Age (70 years or older vs. younger), Gleason score (8–10 vs. 7 or lower) and the number of involved nodes (3 or more vs. 1–2) were identified as independent predictors of all-cause mortality. When patients with 0–1 of these risk factors were compared with those with 2–3 risk factors, all-cause (rates after 10 years 21% vs. 71%, p < 0.0001), disease-specific (12 vs. 37%, p = 0.009) and competing mortality (9 vs. 33%, p = 0.02) differed significantly. Conclusions: Some of the excess mortality in patients with poor-risk lymph node-positive prostate cancer may be attributed to increased competing mortality, possibly caused by an interaction between comorbid diseases and hormonally treated persistent or progressive prostate cancer<br>Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich
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Broggi, M. A. "FLUORESCEIN-GUIDED SURGERY FOR RESECTION OF MALIGNANT GLIOMAS." Doctoral thesis, Università degli Studi di Milano, 2014. http://hdl.handle.net/2434/233145.
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Introduction:
Fluorescein is widely used as a fluorescent tracer for many applications. Its capability to accumulate in cerebral areas with blood-brain barrier damage makes it an ideal dye for intraoperative visualization of high-grade gliomas (HGG). This study presents a new fluorescein-guided technique to remove HGG with a dedicated filter on the surgical microscope (FLUOGLIO trial).
Methods:
The FLUOGLIO study is a prospective phase II-trial to evaluate safety and obtain initial indications about efficacy of fluorescein-guided surgery for HGG.
Since September 2011, 24 patients (age range 45-74 years) were enrolled in the study. Fluorescein was intravenous injected after intubation (5-10 mg/Kg). Tumor was removed with microsurgical technique and fluorescence visualization by BLU400 or YELLOW560 filters on the Pentero microscope (Carl Zeiss, Germany). Degree of tumor resection was calculated on an early (within 72 hours of surgery) postoperative MRI.
In 11 patients, biopsies were performed at the tumor margin in order to evaluate sensitivity and specificity of fluorescein in tumor tissue identification.
The study was approved by our Ethical Committee and registered on the European Regulatory Authorities website (EudraCT No. 2011-002527-18)
Results:
Median pre-operative tumor volume was 33.1 cm3 (1.3-87.8 cm3). No adverse reaction related to the administration of fluorescein was registered. Contrast-enhanced tumor was
completely removed in 83% of the patients on early postoperative MRI. The remaining patients had a mean tumor resection of 92.6%. Median follow-up was 12 months. The biopsies at the tumor margins gave a preliminary estimation of sensitivity and specificity of fluorescein in identifying tumor tissue of 95% and 86% respectively.
Conclusion:
The presented data suggest that fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows a high-rate of complete resection of HGG at the early post-operative MRI.
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Takeda, Flavio Roberto. "Estudo comparativo dos resultados da esofagectomia transhiatal com a transtorácica por toracoscopia no adenocarcinoma da junção esôfago-gástrica." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5168/tde-09112017-103518/.
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O tratamento cirúrgico do adenocarcinoma da junção esofagogástrica (AJEG) ainda é controverso, particularmente, em relação à sobrevida e complicações pós-operatórias. Com o advento da cirurgia minimamente invasiva e toracoscopia, houve um aumento da linfadenectomia e menores complicações, entretanto seu impacto na sobrevida do AEGJ é pouco conhecido. Objetivos: Comparar a esofagectomia por via transtorácica por toracoscopia (grupo A) com esofagectomia por via transhiatal (grupo B) em pacientes com AJEG em relação a ocorrência de complicações e mortalidade; número de linfonodos ressecados, acometidos e relação ressecados e acometidos; sobrevidas global e livre de doença; e sobrevida após recidiva. Métodos: Foram selecionados 147 pacientes entre 2000 e 2016. Cento e trinta (88%) do sexo masculino, média de idade de 64 anos. Os dados epidemiológicos (idade, sexo, índice de massa corpórea, ECOG e antecedentes pessoais) foram avaliados e comparados entre os grupos. As complicações pós-operatórias (fistula cervical, quilotorax, complicações respiratórias, rouquidão e infecções cirúrgicas) foram avaliadas. O estadiamento anátomo-patológico foi avaliado pela 7a. edição AJCC, analisando os linfonodos ressecados, acometidos e a relação de ressecados e acometidos. Foram feitas análises da sobrevivência global, livre de doença, e após recidiva; além de análise multivariada de fatores relacionados à sobrevida. Resultados: Em relação aos dados epidemiológicos, o grupo A apresentava uma média de idade de 61,1 anos e grupo B, de 65,7 anos (p=0,009). Dos 54 pacientes do grupo A, 47 (87,0%) foram submetidos a tratamento neoadjuvante, contra 43 (46,3%) dos 93 pacientes do grupo B (p < 0,001). Em relação às complicações, o grupo A apresentou maior ocorrência de rouquidão e infecções cirúrgicas. Em relação à mortalidade, o grupo A apresentou dois casos (3,7%) e grupo B apresentou quatro (4,3%), sem diferença estatística. Não houve diferença estatística entre os grupos A e B quanto à localização topográfica do tumor, grau histológico, pT, pN, estádio, extensão do tumor, invasão linfática, venosa e perineural. No grupo A, a média de linfonodos ressecados foi 31,88 linfonodos e no grupo B 20,73 linfonodos (p < 0,001); entretanto a média de linfonodos acometidos no grupo A foi 3,96 linfonodos e no grupo B 4,25 linfonodos, sem diferença estatística, bem como a razão ressecados acometidos. A sobrevida global geral foi 42,3%, nos grupo A, 38,9% e no grupo B, 7,6% (p=0,298). Na análise multivariada da sobrevida global somente a invasão linfática (p=0,005), diabetes mellitus (p=0,038) e infecção cirúrgica (p=0,001) foram significantes. A sobrevida livre de doença geral foi 45,6%, no grupo A 40% e grupo B 46% (p=0,77) e, na multivariada, somente a invasão linfática (p=0,01) e o diabetes mellitus (p=0,049) foram significantes. Entretanto nos tumores com estádio até 2B a sobrevida global do grupo A foi 80,4% e do grupo B, 38,5% (p=0,001). A sobrevida após recidiva foi melhor na recidiva pulmonar, seguida pela hepática ou mediastinal e peritoneal (p=0,001). Conclusão: Ambos os métodos são seguros com taxas de morbidade e mortalidade semelhantes. A esofagectomia por toracoscopia permite uma ressecção maior do número de linfonodos. As sobrevidas globais e livres de doença são semelhantes, entretanto até o estádio 2B a esofagectomia por toracoscopia melhora a sobrevida global. Diabetes e invasão linfática interferem na sobrevida global e livre de doença<br>The surgical treatment of adenocarcinoma of the esophagogastric junction surgical treatment (AGEJ) is still controversial, particularly concerning to survival and postoperative complications. With the advent of minimally invasive surgery and thoracoscopy, there has been an increase in lymphadenectomy and less complications, however its impact on survival of AGEJ is still unknown. Objectives: To compare transthoracic thoracoscopic esophagectomy (group A) with transhiatal esophagectomy (group B) in patients with AGEJ in relation to the occurrence of complications and mortality; number of ressected lymph nodes, the positive and the ratio between the ressected and positive; overall and disease free survival; and survival after relapse. Methods: There was a selection of 147 patients from 2000 to 2016. One hundred and thirty (88%) were male, the average age was 64 years old. Epidemiological data (age, sex, body mass index, ECOG and past medical history) were analyzed and compared between the groups. Postoperative complications (cervical fistulae, chylothorax, respiratory complications, hoarseness and surgical infections) were evaluated. The anatomopathological staging was evaluated by the 7th UICC edition, analyzing the resected lymph nodes, the affected and the ratio between the resected and affected. Analysis of overall survival, disease free survival and survival after relapse were made, besides multivariate analysis of survival related factors. Results: In relation to the epidemiological data, group A presented an average age of 61.1 years, and group B of 65.7 years (p=0.009). 47 (87.0%) of the 54 patients in group A were submitted to neoadjuvant treatments, against 43 (46.3%) of the 93 patients in group B (p < 0.001). In relation to the complications, group A presented greater occurrence of hoarseness and surgical infections. In relation to mortality, group A presented 2 cases (3.7%) and group B presented 4 (4.3%), without statistical difference. There was no statistical difference between groups A and B about topographic location of the tumor, histologic grade, pT, pN, stage, tumor extension, lymphatic, venous or perineural invasion. In group A, the average number of ressected lymph nodes was 31.88 and in group B was 20.73 (p < 0.001), however the average number of affected lymph nodes was 3.96 in group A and 4.25 in group B, without statistical difference, as well as the ratio between ressected and affected lymph nodes. The general overall survival was 42.3%, in group A was 38.9% and in group B was 47.6% (p=0.298). In the multivariate analysis of overall survival only lymphatic invasion (p=0.005), diabetes mellitus (p=0.038) and surgical infection (p- 0.001) were significant. The general disease free survival was 45.6%, in group A was 40% and in group B was 46% (p=0.77) and in multivariate analysis only lymphatic invasion (p=0.01) and diabetes mellitus (p=0.049) were significant. However, in tumors with stage until 2B, group A overall survival was 80.4% and group B was 38.5% (p=0.001). Survival after relapse was better in pulmonary relapse, followed by hepatic or mediastinal and peritoneal (p=0.001). Conclusion: Both methods are safe with similar morbidity and mortality rates. Transthoracic thoracoscopic esophagectomy allows a larger ressection in the number of lymph nodes. Overall survival and disease free survival are similar, however until stage 2B thoracoscopic esophagectomy improves overall survival. Diabetes and lymphatic invasion interfere in overall and disease free survival
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Lo, Presti Caroline. "Reprogrammation métabolique dans les leucémies aigues myéloblastiques (LAM) : Impact clinique et mécanismes oncogéniques De novo adult acute myeloid leukemia patients display at diagnosis functional deregulation of redox balance correlated with molecular subtypes and overall survival." Thesis, Université Grenoble Alpes, 2020. http://www.theses.fr/2020GRALV017.
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Le métabolisme des cellules cancéreuses est fortement perturbé et dérégulé dans les cancers. Plusieurs exemples illustrent ce phénomène, notamment la reprogrammation métabolique décrite dans l’effet Warburg, les dérégulations fonctionnelles de certaines voies métaboliques telles que l’augmentation de la production de ROS dans les cellules cancéreuses, ou la mise en évidence d’oncométabolites liés à des mutations acquises telles que les mutations IDH1/2 qui entraînent la production d’un métabolite directement associé au processus leucémique dans les LAM. Afin de caractériser les reprogrammations métaboliques associées au processus leucémique, nous avons analysé par une approche HRMAS les métabolites produits par différentes lignées cellulaires leucémiques représentant différents sous types de LAM (génotype et phénotype différents). Dans ce modèle, nous avons montré que chaque type de lignée présentait un métabolisme particulier à l’état basal, témoin d’une signature métabolique différente selon la nature de la lignée. En situation de stress métabolique (culture en milieu sans sérum), toutes ces lignées développent des mécanismes d’adaptation de leur métabolisme à la carence en nutriments. En particulier, il existe une signature commune caractérisée par la surexpression de métabolites de la voie des phospholipides et de régulation du stress oxydant au bout de 24h de culture en milieu sans sérum. Grâce à ces mécanismes d’adaptation les cellules leucémiques retrouvent au bout de 48h, une viabilité supérieure à 95% et un profil métabolique quasi-identique aux conditions normales. Ces résultats montrent que les cellules leucémiques développent des mécanismes communs de survie, impliquant notamment des dérégulations du métabolisme des lipides, qui leur permettent de continuer à proliférer en situation de stress métabolique. D’autres conditions expérimentales ont été testées, notamment en condition de carence en glucose afin d’explorer la piste de la dérégulation de certains acides aminés comme l’alanine dans ces lignées. De plus, l’étude quantitative et qualitative des acides gras dans les LAM via une approche lipidomique révèle une adaptation similaire des profils lipidomiques des lignées dans les mêmes conditions de privation en sérum précédemment testées. En parallèle, dans une étude sur 54 patients au diagnostic de LAM, nous avons confirmé par l’approche HRMAS qu’il existait chez les patients LAM des différences de profil métabolique en fonction du sous-type de LAM. Nous avons également montré que ces signatures métaboliques étaient significativement corrélées aux sous-groupes pronostiques cytogénétiques, à la réponse au traitement par chimiothérapie et à la survie des patients. Nous montrons notamment que les métabolites surexprimés chez les patients de mauvais pronostic sont retrouvés surexprimés également chez les patients réfractaires au traitement. L’analyse de ces métabolites montrent le rôle particulier de plusieurs voies métaboliques dans le pronostic des LAM : i) la dérégulation de la synthèse de 2-hydroxyglutarate associée aux mutations de l’enzyme IDH1/2, ii) la dérégulation du métabolisme des phospholipides, retrouvant une surexpression de phospholipides dans les plasmas de patients de pronostic défavorable, et iii) la surexpression de la synthèse de certains acides aminés chez les patients chimiorésistants, suggérant une implication de la voie de signalisation LKB1/AMPK<br>Cells metabolism is strongly disturbed and deregulated in cancers. Several examples reflect this phenomenon, including metabolic reprogramming described in the Warburg effect, functional deregulations of particular metabolic pathways such as the increase of the ROS production in cancer cells, or the identification of oncometabolites linked to acquired mutations such as IDH1/2 mutations, which lead to the production of a metabolite directly linked to the leukemic process in AML. In order to characterize the metabolic reprogramming associated with the leukemic process, we analyzed by an HRMAS approach the metabolites produced by different leukemic cell lines representing different subtypes of AML (different genotype and phenotype). In this model, we have shown that each type of cell line exhibited a particular metabolism in the basal state, witnessing a different metabolic signature depending on the nature of the cell line. In condition of metabolic stress (culture in a serum-free environment), all these cell lines develop mechanisms to adapt their metabolism to nutrient deficiency. Particularly, there is a common signature characterized by the overexpression of metabolites of the phospholipid pathway and of regulation of oxidative stress after 24 hours of culture in a medium without serum. Thanks to these adaptation mechanisms, the leukemic cells find after 48 hours a viability higher than 95% and a metabolic profile almost identical to normal conditions. These results show that leukemic cells develop common survival mechanisms, notably involving deregulations of lipid metabolism, which allow them to continue to proliferate in condition of metabolic stress. Other experimental conditions have been tested, in particular in glucose deficiency conditions in order to explore the path of deregulation of some amino acids such as alanine in these cell lines. Moreover, the quantitative and qualitative study of fatty acids in AMLs through a lipidomic approach reveals a similar adaptation of the lipidomic profiles of the cell lines in the same serum-free conditions previously tested. In parallel, in a study on 54 patients diagnosed with AML, we confirmed by the HRMAS approach that there were differences in metabolic profile in AML patients according to the AML subtype. We also showed that these metabolic signatures were significantly correlated with cytogenetic prognostic subgroups, response to chemotherapy treatment and patient survival. We show in particular that the metabolites overexpressed in patients with poor prognosis are found overexpressed also in patients refractory to treatment. The analysis of these metabolites shows the particular role of several metabolic pathways in the prognosis of AML: i) deregulation of the synthesis of 2-hydroxyglutarate associated with mutations in the IDH1/2 enzyme, ii) deregulation of the metabolism of phospholipids, showing an overexpression of phospholipids in adverse prognosis patients plasmas, and iii) overexpression of the synthesis of some amino acids in chemoresistant patients, suggesting an involvement of the LKB1/AMPK signaling pathway
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Taubenhansl, Clara [Verfasser], and Elisabeth C. [Akademischer Betreuer] Inwald. "Guideline concordant chemotherapy in patients with hormone receptor positive and nodal positive, early breast cancer leads to better overall and metastases-free survival with limited benefit in elderly patients / Clara Taubenhansl ; Betreuer: Elisabeth C. Inwald." Regensburg : Universitätsbibliothek Regensburg, 2020. http://d-nb.info/1223198154/34.
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Fröhner, Michael, Albrecht Scholz, Rainer Koch, Oliver W. Hakenberg, Gustavo B. Baretton, and Manfred P. Wirth. "Competing Mortality Contributes to Excess Mortality in Patients with Poor-Risk Lymph Node-Positive Prostate Cancer Treated with Radical Prostatectomy." Karger, 2012. https://tud.qucosa.de/id/qucosa%3A27531.
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Background: Factors predicting survival in men with lymph node-positive prostate cancer are still poorly defined.
Patients and Methods: 193 prostate cancer patients with histopathologically proven lymph node involvement with a median follow-up of 7.3 years were studied. 94% of patients received immediate hormonal therapy. Kaplan-Meier curves were calculated to evaluate overall survival rates and compared with the log-rank test. Cumulative disease-specific and competing mortality rates were calculated by competing risk analysis and compared with the Pepe-Mori test. Cox proportional hazard models were used to determine the independent significance of predictors of all-cause mortality.
Results: Age (70 years or older vs. younger), Gleason score (8–10 vs. 7 or lower) and the number of involved nodes (3 or more vs. 1–2) were identified as independent predictors of all-cause mortality. When patients with 0–1 of these risk factors were compared with those with 2–3 risk factors, all-cause (rates after 10 years 21% vs. 71%, p < 0.0001), disease-specific (12 vs. 37%, p = 0.009) and competing mortality (9 vs. 33%, p = 0.02) differed significantly.
Conclusions: Some of the excess mortality in patients with poor-risk lymph node-positive prostate cancer may be attributed to increased competing mortality, possibly caused by an interaction between comorbid diseases and hormonally treated persistent or progressive prostate cancer.<br>Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.
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Carranza, Neira Julia Alejandra, Subauste Roxana Sofía Díaz, and Tupayachi Silvana Patricia Roig. "Quimioterapia adyuvante asociada a hormonoterapia en mujeres postmenopáusicas con cáncer de mama subtipo Luminal A en estadio temprano: análisis comparativo de la supervivencia global." Bachelor's thesis, Universidad Peruana de Ciencias Aplicadas (UPC), 2015. http://hdl.handle.net/10757/621762.
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Purpose: to evaluate if there is a difference between adjuvant chemo-endocrine therapy (QHT) and hormone therapy (HT) alone in ten years overall survival (OS) in post-menopausal women with early stage luminal A breast cancer
Methods: A non concurrent cohort study was conducted in a cancer treatment center in Peru, we measured demographic and clinical-pathologic anatomy variables. Log-rank test and a Kaplan-Meier (KM) curve were performed to evaluate ten years OS. Cox regression analysis was used and hazard ratio were reported with confidence intervals 95% (95%CI) for crude and adjusted by the significant variables in the bivariate analysis. The fullfilment of hazard proportionality was evaluated by Schoenfeld residuals method and graphic method.
Results: 65 patients received adjuvant chemo-endocrine therapy and 140 only received hormone therapy. Ten years OS was 77% for QHT and 84% for HT, this difference was not significant when using KM and log-rank; age at diagnosis (p=0,01), clinical status (p=0,02), tumor size (p=0,04), positive estrogen receptor (p=0,03), node status (p=0,012) and type of surgery (p=0,03) were statistically significant when compare with OS. When proportional hazards assumption was evaluated (SPH), only the period of time after two years of following was satisfied, cox models were created for this period of time. Crude HR for ten years OS was 1,48 (CI95%:0,65-3,39). First model adjusted HR was 1,83 (CI95%:0,64-5,30) and second model adjusted HR was 1,77 (CI95%:0,64-4,90).
Conclusions: There was no significant difference in ten years OS between both courses of treatment evaluated in post-menopausal women with luminal A breast cancer.<br>Objetivo: evaluar si existe diferencia en la supervivencia global (SG) a diez años entre la quimioterapia adyuvante asociada a hormonoterapia (QHT) frente a la hormonoterapia sola en mujeres posmenopáusicas diagnosticadas con cáncer de mama luminal A (CMLA) en estadio temprano.
Métodos: se realizó un estudio cohortes no concurrente en un centro de atención oncológica en Perú. Se incluyeron variables demográficas y clínico-patológicas. Para comparar la SG se utilizó la curva de Kaplan-Meier (KM), test de log-Rank y la regresión de Cox para estimar el Hazard Ratio (HR) con intervalos de confianza 95% (IC95%) tanto crudos como ajustados por las variables asociadas durante el análisis bivariado. Se evaluó el cumplimiento del supuesto de proporcionalidad de hazard (SPH) con el método de residuos de Schoenfeld y método gráfico. Resultados: 65 pacientes recibieron QHT y 140 sólo hormonoterapia. La SG a los diez años fue 77% y 84% para QHT y HT respectivamente, esta diferencia no fue significativa al utilizar KM y test de log-Rank; no obstante la edad (p=0,01), estadio clínico (p=0,02), tamaño tumoral (p=0,04), receptor estrogénico positivo (p=0,03), número de ganglios (p=0,012) y tipo de cirugía (p=0,03) resultaron asociadas significativamente a la supervivencia global a los diez años. Cuando se evaluó el SPH se evidenció que sólo se cumplía tras los dos años de seguimiento, por lo que se generaron modelos de Cox en éste periodo. El HR crudo a los diez años fue de 1,48 (IC95%: 0,65-3,39). En el modelo ajustado uno se observó un HR de 1,83 (IC95%: 0,64-5,30) y para el segundo modelo ajustado un HR de 1,77 (IC 95%: 0,64-4,90).
Conclusiones: no se encontró diferencia significativa en la SG a los diez años entre los esquemas terapéuticos evaluados en mujeres posmenopáusicas con CMLA.
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Santos, Heron Teixeira Andrade dos. "Avaliação da sobrevida global dos pacientes portadores de câncer de pulmão invasores da fáscia endotorácica, submetidos à ressecção extramusculoperiostal em Gaiola de Passarinho." Universidade do Estado do Rio de Janeiro, 2014. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=8398.
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O câncer de pulmão tem alto grau de letalidade. O tabagismo é considerado o principal fator de risco associado ao carcinoma de pulmão não pequenas células. O tratamento que oferece as maiores possibilidades de cura é a cirurgia. A ressecção pulmonar associada atoracectomia é a cirurgia preconizada nos tumores T3 invadindo a parede torácica. A ressecção em Gaiola de Passarinho pode ser considerada uma técnica alternativa. Foram analisados retrospectivamente, de janeiro de 1990 à dezembro de 2009, 13 pacientes portadores de câncer de pulmão aderidos a parede torácica. Eles foram submetidos à ressecção extramusculoperiostal em Gaiola de Passarinho no Hospital Universitário Pedro Ernesto. A avaliação do grau de invasão à parede torácica foi feita no pré-operatório por métodos de imagem; e sua comprovação baseada nos achados histopatológicos dos fragmentos de tecidos enviados para a biópsia de congelação, assim como nos laudos definitivos das peças ressecadas. Os pacientes com tumores de Pancoast ou que abandonaram o acompanhamento foram excluídos do estudo. A avaliação da sobrevida global foi feita a partir dos dados de seguimento pós operatório a nível ambulatorial. A análise estatística foi composta pela curva de sobrevida ou livre de eventos ajustada pelo método de Kaplan-Meier. Complicações pós operatórias, intervalo livre de doença, recidiva local, e uso de terapia complementar também foram incluídos na análise. A idade média em anos foi de 59,6. Todos os pacientes eram tabagistas. O tipo histológico mais encontrado foi o carcinoma escamoso. A média de intervalo livre de doença foi de 44,7 meses. A sobrevida global em cinco anos foi de 60% e o índice de complicações pós-operatórias foi de 69,2%. Não houve mortalidade operatória. O estágio Ib foi encontrado em 80 %. A ressecção extramusculoperiostal demonstrou ser uma alternativa segura de tratamento cirúrgico dos tumores que não invadiram efetivamente o gradil costal. Porém novos estudos tornam-se necessários. Esta dissertação pode servir de base para futuras pesquisas sobre o tratamento cirúrgico do câncer de pulmão.<br>Lung cancer has high level of lethality. Smoking is considered the main risk factor associated with non small-cell lung cancer. The treatment that offers better opportunity for cure is surgery. Lung resection with thoracectomy is the procedure performed in T3 tumours invading chest wall. The bird cage resection can be considered an alternative approach. Between january 1990 and december 2009, 13 pacients with non-small cell lung cancer invading chest wall were retrospectively analyzed. They underwent resection in bird cage in Pedro Ernesto Hospital of State of Rio de Janeiro University. Preoperative evaluation of chest wall invasion was performed with imaging methods and based on histopathological findings of tissue fragments sent for frozen biopsy, as well as the final reports of surgical specimens. Pacients with Pancoasttumours and whose abandoned treatment was excluded. Overall survival evaluation was done from follow-up outpacients. Statistics analysis was performed using cumulative survival and cumulative metastasis-free survival curves, adjusted by Kaplan-Meier method. Postoperative complications, disease-free interval, local disease recurrence and complementary therapy were also included in the study. Median age was 56,9 years. Median free-disease interval was 44,7 months. All pacients were smokers. Carcinoma squamous cell was the main histological type founded. Overall long-term survival was 60% in five years and the rate of postoperative complications was 69,2%. There was no operative mortality. Stage Ib was present in 80%. The extramusculoperiosteal in bird cage resection has demonstrated to be a safe alternative in surgical treatment of tumours that effectively doesnt violate the chest wall. However, new studies are necessary. This dissertation can be used as basis for future researches in surgical treatment of lung cancer.
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Gonçalves, Júnior Homero. "Aspectos clínico-epidemiológicos dos tumores mamários triplo negativos em uma população brasileira." Universidade Federal de Juiz de Fora (UFJF), 2018. https://repositorio.ufjf.br/jspui/handle/ufjf/7240.
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Previous issue date: 2018-07-06<br>O tratamento do câncer de mama baseia-se na classificação dos casos, em termos de estadiamento e do perfil biomolecular. Os Tumores Triplo Negativos (TTN) representam um grupo especial de neoplasias mamárias que não expressam receptores hormonais e nem o antígeno Her2. São considerados agressivos e de pior evolução, e quando estudados em particular, apresentam muita heterogeneidade. Importa saber se a caracterização dos tumores como Triplo Negativos, é suficiente para delimitar o grupo em termos de prognóstico e terapêutica. Este estudo teve como objetivo comparar os aspectos clínico-epidemiológicos dos Tumores Triplo Negativos em relação aos Não Triplo Negativos, em coorte de mulheres com câncer de mama assistidas em centros oncológicos de referência de Juiz de Fora, Minas Gerais. A sobrevida global e a sobrevida livre de doença foram calculadas pelo método de Kaplan Meier, e as curvas de sobrevida foram avaliadas pelo teste de Log-Rank, nos subgrupos Triplo Negativos e Não Triplo Negativos (NTN). Os fatores prognósticos foram comparados pelo modelo de riscos proporcionais de Cox. Os Tumores Triplo Negativos apresentaram diferenças demográficas em relação aos NTN, com acúmulo de pacientes não brancas e de baixo nível sociocultural; e ainda com aspectos de maior gravidade ao diagnóstico. A evolução também foi pior, tanto em termos de sobrevida global quanto sobrevida livre de doença dentre os TTN. Na análise univariada, os fatores: idade, cor da pele, escolaridade, tamanho do tumor e grau tumoral, estado das axilas e estadiamento, bem como taxas elevadas dos marcadores P53 e Ki 67, se mostraram associados a sobrevida livre de doença nos Tumores Não Triplo Negativos. No cálculo da sobrevida global, essas variáveis se mantiveram, exceto a idade; e foi constatado maior risco para as mulheres oriundas do serviço público de saúde, bem como o surgimento de metástases no decurso do seguimento. Para os Triplo Negativos, a análise univariada mostrou influência do estado axilar e estadiamento na sobrevida livre de doença; e os mesmos fatores acrescidos do surgimento de metástases, para a sobrevida global. Na análise multivariada a escolaridade e o estado axilar representaram risco à sobrevida livre de doença para NTN, enquanto a cor da pele e o estadiamento para a sobrevida global. Quanto aos TTN, sua evolução se mostrou ligada a dois aspectos: o comprometimento axilar para sobrevida livre de doença e global; e também a multicentricidade para a sobrevida global. Os Tumores Triplo Negativos aparentam ter biologia bem diversa dos Não Triplo Negativos, na dependência dos componentes histológicos e moleculares que portam. A classificação molecular por imunoistoquímica se mostrou capaz de identificar os dois grupos tumorais e auxiliar na orientação terapêutica.<br>Current breast cancer treatment is based on the classification of tumor stage and molecular profile. Triple-negative breast cancer (TNBC) is a specific subset of tumors characterized by the absence of hormone and HER2 receptors. Despite being usually associated with a more aggressive clinical course, there is high heterogeneity within TNBC. Therefore, it has been questioned whether current classification of TNBC is adequate enough to assess its prognosis and make therapeutic decisions. This study thus aimed to investigate to which extent TNBC profile classification was able to efficiently distinguish this tumor subtype from other subtypes of breast cancer. It was performed on a cohort of women with breast cancer treated at referral centers in Juiz de Fora, Southeastern Brazil. Overall and disease-free survival and prognostic factors were assessed and compared for TNBC and non-TNBC. Survival functions were calculated using the Kaplan-Meier method, and the log-rank test was used to compare the survival curves. Prognostic factors were analyzed by the Cox proportional hazards model. TNBC presented demographic differences compared to non-TNBC as it was more prevalent among nonwhite and less educated women. TNBC also presented at diagnosis with clinical parameters of advanced disease and had overall and disease-free survival significantly lower than non-TNBC. In univariate analysis the factors: age, color of the skin, education level, size and degree of tumor, axillary status and staging, as well as high rates of P53 e Ki 67 have been shown to be associated with disease-free survival in non-TNBC. These variables remained the same in the calculation of overall survival except for age; and it was also observed a greater risk for women from the public health service as well as the appearance of metastases during the follow-up. In multivariate analysis education level and axillary lymph node involvement presented a risk for disease-free survival while the color of skin and staging, for overall survival in non-TNBC. Regarding TNBC, its evolution was related to two aspects: axillary impairment for disease-free and global survival and multicentricity for overall survival. TNBC presents distinct biological properties compared to non-TNBC, which seems to be related to its specific histological and molecular components. The molecular classification by immunohistochemistry showed to be able to identify the two tumor groups and to support the therapeutic orientation.
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Eberst, Guillaume Nicolas. "Seconds cancers après traitement curatif d'un cancer broncho-pulmonaire." Electronic Thesis or Diss., Bourgogne Franche-Comté, 2023. http://www.theses.fr/2023UBFCE029.
Full textAbstract:
Le premier des objectifs du plan cancer 2014-2019 était de guérir plus de malades en favorisant les diagnostics plus précoces. Cet objectif laisse espérer davantage de diagnostic à des stades précoces accessibles à une résection chirurgicale. A l’heure actuelle, la chirurgie exérèse d’un cancer broncho-pulmonaire non à petites cellules (CBNPC) est le traitement offrant le plus d’espoir de guérison. Ce travail de thèse s’intéresse tout particulièrement au devenir des patients opérés.Malgré une intention curatrice, les patients opérés d’un CBNPC sont à risque de récidive du cancer opéré mais ont également un risque de second cancer, et en particulier de second cancer broncho-pulmonaire primitif (SCBP), supérieur à celui de la population générale, de l’ordre de 20% d’incidence cumulée à 10 ans. Lorsque survient une lésion pulmonaire de même diagnostic histologique que le cancer opéré, le diagnostic différentiel entre récidive du cancer opéré ou SCBP est difficile. Plusieurs définitions existent. En se basant sur l’hypothèse que les récidives sont le témoin d’une agressivité de la maladie cancéreuse, et donc le plus souvent de plus mauvais pronostic que les deuxièmes cancers, nous avons conduit dans un premier temps une revue systématique Cochrane de l’ensemble des définitions utilisées dans la littérature afin d’identifier celle qui offre la meilleure distinction pronostique, sur laquelle se baser pour le diagnostic différentiel entre récidive du cancer opéré et SCBP.Il y a quelques années, l'immunothérapie s'est imposée dans l'arsenal thérapeutique du cancer broncho-pulmonaire. D'abord utilisée en situation métastatique, l'immunothérapie est maintenant testée en situation péri-opératoire dans de nombreux essais. Cependant, en raison de la diversité des combinaisons et des stratégies thérapeutiques, qui n'ont pas toutes été comparées entre elles, une incertitude demeure quant à la meilleure thérapie péri-opératoire pour les patients opérés d'un CBNPC de stade précoce. Nous avons initié une revue systématique d’essais interventionnels avec méta-analyse en réseau selon la méthode Cochrane portant sur l'efficacité de ces traitements péri-opératoires chez les patients atteints de cancer du poumon non à petites cellules.L’étude IFCT-0302 est la seule large étude randomisée de surveillance des opérés d’un CBNPC. Elle a inclus 1775 patients. Son objectif était de comparer la survie globale de deux stratégies de surveillance : par clinique et radiographies thoraciques dans le groupe contrôle, et par clinique, radiographies thoraciques et scanners thoraco-abdominaux dans le groupe expérimental. La qualité de vie décrite par le patient (QdV) est une mesure de trois domaines de la santé perçue : physique, social et émotionnel. La QdV est impactée par une condition médicale ou son traitement. L'évidence suggère que la chirurgie du cancer du poumon a un impact significatif sur la QdV. L’objectif de notre travail a été d’évaluer l’influence du type de surveillance sur la QdV dans la population de l’étude IFCT-0302.Lorsqu’une image pulmonaire anormale est détectée, son diagnostic histologique s’obtient fréquemment par ponction transthoracique guidée par le scanner. La principale complication du geste est le pneumothorax. Les contraintes hospitalières ne permettent pas d’hospitaliser tous les patients après une ponction transthoracique. Nous avons dans ce troisième axe, travaillé à la validation d’un score prédictif de survenue d’un pneumothorax retardé après une ponction-biopsie transpariétale pulmonaire scannoguidée, afin de sélectionner les patients qui doivent être surveillés en hospitalisation conventionnelle. Ce travail a été réalisé sur une cohorte de patients du CHU de Besançon, une partie de la cohorte ayant permis d’élaborer le score, l’autre de le valider. Enfin un travail de validation externe sur une cohorte de patients de l’Hôpital Bichat – Claude Bernard a été réalisé<br>The first objective of the 2014-2019 cancer plan was to cure more patients by promoting earlier diagnosis. This objective gives hope for more diagnosis at early stages accessible to surgical resection. Currently, excisional surgery for non-small cell bronchopulmonary cancer (NSCLC) is the treatment offering the most hope for a cure. This thesis work is particularly interested in the future of operated patients.Despite a curative intention, patients operated on for NSCLC are at risk of recurrence of the operated cancer but also have a higher risk of second cancer, and in particular second primary lung cancer (SPLC), higher than that of the general population. , of the order of 20% cumulative incidence at 10 years.When a lung lesion with the same histological diagnosis as the operated cancer occurs, the differential diagnosis between recurrence of the operated cancer or SPLC is difficult. Several definitions exist. Based on the hypothesis that recurrences indicate an aggressiveness of the cancerous disease, and therefore most often have a worse prognosis than second cancers, we first conducted a Cochrane systematic review of the set of definitions used in the literature in order to identify the one which offers the best prognostic distinction, on which to base the differential diagnosis between recurrence of operated cancer and SCBP.A few years ago, immunotherapy established itself in the therapeutic arsenal for bronchopulmonary cancer. First used in the metastatic situation, immunotherapy is now tested in the perioperative situation in numerous trials. However, due to the diversity of combinations and therapeutic strategies, not all of which have been compared with each other, uncertainty remains regarding the best perioperative therapy for patients undergoing surgery for early-stage NSCLC. We initiated a systematic review of interventional trials with network meta-analysis according to the Cochrane method on the effectiveness of these perioperative treatments in patients with non-small cell lung cancer.The IFCT-0302 study is the only large randomized surveillance study of NSCLC patients. It included 1775 patients. Its objective was to compare the overall survival of two monitoring strategies: by clinic and chest x-rays in the control group, and by clinic, chest x-rays and thoraco-abdominal scans in the experimental group. Patient-described quality of life (HRQoL) is a measure of three domains of perceived health: physical, social, and emotional. QoL is impacted by a medical condition or its treatment. Evidence suggests that lung cancer surgery has a significant impact on QoL. The objective of our work was to evaluate the influence of the type of surveillance on HRQoL in the population of the IFCT-0302 study.When an abnormal lung image is detected, its histological diagnosis is frequently obtained by transthoracic puncture guided by the scanner. The main complication of the procedure is pneumothorax. Hospital constraints do not allow all patients to be hospitalized after a transthoracic puncture. In this third axis, we worked on the validation of a predictive score for the occurrence of delayed pneumothorax after a CT-guided transparietal lung biopsy, in order to select patients who must be monitored in conventional hospitalization. This work was carried out on a cohort of patients from Besançon University Hospital, one part of the cohort having made it possible to develop the score, the other to validate it. Finally, external validation work on a cohort of patients from the Bichat – Claude Bernard Hospital was carried out
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Branchoux, Sébastien. "Critères de substitution de la survie globale chez les patients atteints de cancer métastatique traités par inhibiteurs de points de contrôle immunologiques." Thesis, Bordeaux, 2020. http://www.theses.fr/2020BORD0253.
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La prise en charge du cancer au stade avancé ou métastatique a été profondément modifiée avec l’arrivée des inhibiteurs des points de contrôle immunologiques (immune-checkpoint inhibitors (ICI)). Ces anticorps monoclonaux immuno-modulateurs ont été développés pour soit déclencher une nouvelle réponse immunitaire anti-tumorale, soit réactiver une réponse existante pour lutter contre le cancer. L’espérance de vie des patients traités par ce type de thérapie est plus longue par rapport à ceux traités par les thérapies usuelles. Par conséquent, la puissance statistique requise dans un essai clinique randomisé (ECR) ayant pour objectif principal d’estimer l’effet relatif du traitement sur la survie globale (SG), critère de référence en oncologie, peut être difficile à atteindre. Dans ce contexte, il est important d’identifier et de valider des critères de substitution de la SG chez les patients traités par ICI afin notamment de permettre un accès précoce à ces traitements innovants. Nous avons tout d’abord effectué une revue systématique de la littérature des différents critères cliniques intermédiaires associés à la SG chez les patients traités par ICI. Puis, à partir des conclusions de cette revue et de la connaissance de la spécificité du mécanisme d’action des ICI, nous avons évalué les propriétés de substitution d’un nouveau critère, le « temps jusqu’à l’initiation d’un traitement systémique ultérieur » (time to next treatment (TNT)), chez les patients atteints d’un mélanome avancé ou d’un carcinome à cellules rénales avancé, à partir de modèles statistiques récemment développés pour la validation de critères de substitution. D’après les résultats de ces analyses, le TNT semble être un critère de substitution prometteur dans ces 2 populations. Nous encourageons les promoteurs d’ECR d’ICI à recueillir la date d’initiation du traitement systémique ultérieur afin de pouvoir réaliser des analyses similaires de plus grande ampleur et de confirmer ainsi nos résultats<br>Advanced cancer treatment has been recently revolutionized by the development of the immune-checkpoint inhibitors (ICI). These immunomodulatory monoclonal antibodies are designed to either elicit a novel anti-tumoral immune response or revitalize an existing one to fight against cancer. Patients with cancer are living longer due to these improved therapies. Powering a study for overall survival (OS), the gold standard primary endpoint in randomized controlled trial (RCT) of anticancer drugs is becoming increasingly challenging. Therefore, it is of importance to identify and validate novel surrogate endpoints (SE) for OS in ICI-treated patients for expediting patients’ access to innovative and potentially life extending medicines. We first systematically reviewed published studies reporting on an association between alternative endpoints and OS in ICI-treated patients. Then, based on the learnings from this systematic literature review and from the specificity of the mechanism of action of ICIs, we evaluated the surrogacy properties of an emerging intermediate endpoint in solid tumors, namely time to next treatment (TNT), in ICI-treated patients with advanced melanoma and renal cell carcinoma (aRCC), through recent innovative statistical models for the validation of SE. Based on the results of these surrogacy analyses, TNT seems a promising SE for OS in RCTs of ICI-treated patients with advanced melanoma and aRCC. We encourage sponsors of RCTs of ICI to carefully collect the date of subsequent systemic treatment, so that surrogacy analyses could consequently be performed with a larger number of RCTs in order to confirm our findings
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Afonso, Maria Eva Vaz. "Influência do status mutacional dos genes KRAS e NRAS na resposta terapêutica a anticorpos monoclonais observada em pacientes com cancro col-retal, seguidos no Hospital Espírito Santo de Évora." Master's thesis, Universidade de Évora, 2016. http://hdl.handle.net/10174/23121.
Full textAbstract:
O cancro colo-retal é uma importante causa de morbilidade e mortalidade. A fase
metastática desta patologia atinge aproximadamente 40% dos pacientes e o seu
tratamento é um desafio. A adição de cetuximab e de bevacizumab à terapêutica
contribuiu para uma significativa melhoria da sobrevivência. Contudo, a eficácia do
cetuximab parece estar limitada a tumores sem mutações nos genes KRAS e NRAS. A
escolha do tratamento mais apropriado para obtenção do máximo benefício terapêutico
é complexa e suscita muitas questões.
O objetivo deste estudo é descrever as mutações RAS em tumores colo-retais e
avaliar a resposta terapêutica em pacientes com doença metastática e tratados com
cetuximab e bevacizumab, a fim de avaliar a terapêutica mais eficaz.
Dos tumores testados, 42% apresentaram mutação no exão 2 do gene KRAS. Os
tempos de sobrevivência global foram, de uma forma geral, superiores a 24 meses,
destacando-se positivamente o esquema cetuximab/FOLFIRI com 33,8 meses; ABSTRACT:
Influence of the mutational status of KRAS and NRAS genes on the
therapeutic response of colorectal cancer – evaluation in patients treated
with monoclonal antibodies in Hospital Espírito Santo de Évora
Colorectal cancer is one of the most important causes of morbidity and mortality
worldwide. The metastatic stage of this disease will affect around 40% of patients and
its treatment is a challenge. Addition of cetuximab and bevacizumab to therapeutic has
significantly improved survival. However, cetuximab efficacy seems to be limited to
tumours with no mutation in KRAS and NRAS genes. Choosing the most appropriated
treatment to obtain the maximum therapeutic benefit is a complex issue, with numerous
questions.
This study aim is to describe RAS mutations in colorectal tumours and to assess the
therapeutic response in patients with metastatic disease and treated with cetuximab and
bevacizumab in order to identify the most efficient therapy.
From all the tumours tested, 42% had mutations in exon 2 of KRAS. Generally, the
overall survival was superior to 24 months, with special attention to the therapeutic
scheme cetuximab/FOLFIRI, which achieved 33,8 months.
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Dandoit, Mylène. "Evaluation de l'impact de la prise en charge thérapeutique sur la survie et la qualité de vie des patients atteints d'un lymphome folliculaire ou d'un lymphome B diffus à grandes cellules." Thesis, Dijon, 2014. http://www.theses.fr/2014DIJOS038/document.
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En France, les hémopathies lymphoïdes, se situant au sixième rang des cancers les plus fréquents, sontun problème majeur de santé publique. Ce travail a pour objectif d’étudier l’impact de la prise en charge thérapeutiquesur la survie et sur la qualité de vie (QdV) des patients atteints de ce type d’hémopathies. Le premierobjectif de ce travail est un état des lieux de l’épidémiologie des hémopathies lymphoïdes avec l’étudede l’évolution de l’incidence et de la survie nette en Côte d’Or entre 1980 et 2009. L’incidence, en nette augmentationdepuis 1980, semble se stabiliser depuis les années 2000 pour certaines entités, notamment pourles lymphomes folliculaires (LF) et les lymphomes B diffus à grandes cellules (LBDGC). Nous observons globalementune amélioration de la survie nette avec, toutefois, un pronostic à court et à long terme qui restedéfavorable pour certaines entités. Les LF et les LBDGC sont les premiers lymphomes à bénéficier de l’introductiondes anticorps monoclonaux dans leur prise en charge thérapeutique. Notre deuxième étude a pourobjectif demesurer l’impact du rituximab sur la survie globale des patients atteints d’un LF ou d’un LBDGC enCôte d’Or en utilisant une méthodologie basée sur le score de propension. Nos résultats confirment le bénéficesignificatif du rituximab sur la survie globale en population générale, sans critère de sélection. En vue de cesrésultats, nous avons étudié la QdV de ces patients pendant et à la suite de la prise en charge thérapeutique. LaQdV évolue différemment au cours du suivi en fonction du type de lymphome<br>In France, hematologic malignancies, which are the sixthmost common cancers, are amajor public healthproblem. This work aimed to study the impact of the therapeutic management on survival and healt-relatedquality of life (HRQoL) in patients with these hematologic malignancies. The first objective of this work is topresent an overview of the epidemiology of lymphoid malignancies with a study of changes in the incidenceand net survival in the Côte d’Or department between 1980 and 2009. The incidence, which has increased since1980, seems to have stabilized since the 2000s for some entities, including follicular lymphoma (FL) and diffuselarge B-cell lymphoma (DLBCL). Overall, we observed an improvement in net survival, with, however, a lessfavorable prognosis in the short and long-term for some entities. FL and DLBCL were the first lymphomas tobenefit from the introduction of monoclonal antibodies in their therapeutic management. Our second studyaimed to assess the impact of rituximab on overall survival in patients with FL or DLBCL in the Côte d’Or departmentusing a methodology based on the propensity score. Our results confirmed the significant benefit ofrituximab on overall survival in an unselected population of patients. In view of these results, we studied theHRQoL of these patients during and after treatment. HRQoL evolved differently during follow-up dependingon the type of lymphoma
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Deng, Qi. "Survivable Overlay Layout of IP Over WDM." Thesis, University of Hawaii at Manoa, 2002. http://hdl.handle.net/10125/6943.
Full textAbstract:
Wavelength Division Multiplexing (WDM) technology's capacity of providing very wide bandwidths in optical transport network makes it a good choice to meet the exponential growth of Internet traffic. We consider the problem of routing the Internet Protocol (IP) network over the WDM network in such a way that the IP network is still connected under physical failures. We call such a routing survivable. We formulate the survivable routing problem dealing with any single fiber cut as a Mixed Integer Linear Program (MILP), which is a modified version of the Integer Linear Program (ILP) in [1]. We route various IP networks over a number of WDM networks to show the dramatic run-time improvement of this MILP compared to the ILP in [1]. We also consider the survivable routing problem dealing with multiple link failures that are referred to as a shared risk link group. Finally, we study a scenario where we design a IP network based on a traffic matrix, and then overlay the IP network over the WDM network.<br>x, 65 leaves
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Rakotonjanahary, Ndrianjaka Josué. "Suivi à long terme des enfants traités pour gliome des voies optiques par chimiothérapie première BB-SFOP : survie à long terme - perte de la vision - outil d'interprétation des données IRMs." Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ116.
Full textAbstract:
Les gliomes des voies optiques (GVO) sont des tumeurs bénignes pouvant être observées durant l’enfance. La prise en charge des GVO a évolué durant ces dernières décennies en évitant la radiothérapie et en donnant une place plus importante à la chimiothérapie. L’IRM est un des éléments fondamentaux dans la prise en charge. Cependant, les mesures tumorales sont soumises à des importantes variabilités inter et/ou intra-observateur. Pour mieux comprendre le devenir à long terme des enfants traités par chimiothérapie initiale, le devenir des enfants traités en France pour GVO par chimiothérapie initiale BB-SFOP a été évalué. Un outil standardisé permettant des interprétations fiables et reproductibles des IRMs a été créé et validé. La survie globale de ces patients montre un plus mauvais pronostic à long terme. Certains facteurs cliniques et radiologiques sont également associés à une perte de la vision observée à long terme. Ces découvertes pourraient justifier la mise en place d’une prise en charge adaptée en fonction du niveau de risque<br>Optic Pathway Gliomas (OPG) are benign tumors that typically develop during early childhood. The management of patients varied throughout the last decades and was characterized by an emphasis on avoiding the use of radiotherapy. The role of chemotherapy in the management of OPG has increased. MRI is one of the fundamental elements of the management of these children. However, the tumor measurements are subject to inter and/or intraobserver variations. In an attempt to better understand the long-term outcomes of children treated with initial chemotherapy, long-term outcomes of OPG treated in France with up-front BB-SFOP chemotherapy were evaluated. A standardized and reproducible imaging classification for MRI that can be used as a reliable monitoring tool for patients with OPG was created and validated. The long-term outcomes of these patients showed a poorer prognosis for overall survival. Some clinical and radiological factors were associated with long-term vision loss. These findings could justify a risk-based approach to this tumor
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Bousquet, Carole. "L'articulation des compétences individuelles et collectives à la stratégie de l'entreprise." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE3081/document.
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Les mutations de l’organisation du travail, et de la place de l’Homme dans l’entreprise ont mené, au cours de trois années de recherches-interventions socio-économique au sein d’une PME, à étudier l’objet complexe et dynamique que représente l’articulation entre les compétences individuelles et collectives à la stratégie de l’entreprise. Cette recherche a pour objet l’étude d’une des composantes du potentiel humain, les compétences, dans leurs dimensions individuelles et collectives, mises en œuvre au niveau de la stratégie de l’entreprise. Elle questionne notamment la mobilisation de l’ensemble des acteurs de l’entreprise ainsi que la mise en adéquation entre des objectifs stratégiques définis et les moyens alloués à leur mise en œuvre. Après avoir mis en exergue les impacts sociaux et économiques des défauts d’articulation entre compétences et stratégie, ces résultats sont discutés et analysés au regard de la littérature. Puis, la thèse présente les outils et processus expérimentés, qui ont permis d’améliorer l’articulation entre compétences individuelles et collectives à la stratégie de l’entreprise. Mobilisant en particulier le concept d’Investissement Immatériel en Développement Qualitatif du Potentiel Humain, la thèse souligne la contribution stratégique, à la fois en termes sociaux et économiques, des ressources humaines à la mise en œuvre stratégique et à la performance globale de l’entreprise<br>The changes in the work organization, and the place of human beings in the companies led, during three years of socio-economic intervention-research within an SME, to study the complex and dynamic object that represents the articulation between the individual and collective competencies to the strategy of the company.The purpose of the thesis is to study one of the components of human potential, the competencies, in their individual and collective dimensions, implemented at the level of the company's strategy. In particular, it questions the mobilization of all the company's stakeholders as well as the alignment between the defined strategic objectives and the resources allocated to their implementation.Following an emphasis on the social and economic impacts of the lack of articulation between competencies and strategy, these results are discussed and analyzed in relation to the literature. Then, the thesis presents tools and processes experimented in order to improve this articulation between individual and collective competencies to the company's strategy.Mobilizing in particular the concept of Intangible Investment in Qualitative Development of Human Potential, the thesis highlights the strategic contribution, both in social and economic terms, of human resources to the strategic implementation and the overall performance of the company
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Rosa, Victor Domingos Lisita. "Características clínicas, morfológicas e imunofenotípicas dos Adenocarcinomas de Ampola de Vater." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/17/17154/tde-26042018-172449/.
Full textAbstract:
Introdução: O adenocarcinoma ampular é uma neoplasia maligna rara, com frequência de 1% em relação a todos os tumores gastrintestinais e, de 6 a 25% dos casos de neoplasias periampulares. Como distintos epitélios convalescem dentro da ampola de Vater, a origem histológica desses tumores ainda é uma questão desafiadora na prática clínica. As diferenças nas classificações histomorfológicas tornam difícil a avaliação e comparação dos estudos clínicos desses tumores. Por isso, a divisão histológica em dois tipos principais (intestinal e pancreatobiliar) é necessária para comparação terapêutica e prognóstica desta neoplasia. Materiais e métodos: No presente estudo foram incluídos 27 pacientes no período de 2007 a 2013 com diagnóstico de Adenocarcinoma Ampular no HCFMRP-USP. Foi realizada a avaliação histológica e imuno-histoquímica com os anticorpos CK7, CK20, CDX2, MUC1, MUC2, MUC5AC e, em seguida, avaliado a sobrevida global. Resultados: A média de sobrevida global foi de 40,26 meses. 63% eram carcinomas do tipo intestinal e 37% eram do tipo pancreatobiliar. A expressão dos marcadores CK20, MUC 2 e CDX 2 foram mais frequentes nos tumores do tipo intestinal, já os marcadores CK7, MUC 1 e MUC5AC foram expressos com maior frequência no tipo pancreatobiliar. O CDX2 é o marcador com maior sensibilidade e especificidade para o tipo intestinal quando usado de forma isolada (p<0,01). A associação de CK7 e MUC1 apresentou alta sensibilidade (80%) para o subtipo pancreatobiliar, enquanto as associações CK20 e CDX2 ou MUC2 e CDX2 apresentavam especificidade de 100% para o subtipo intestinal. A média global de sobrevida foi de 40,26 meses. Não houve interferência do tipo histológico (p=0,48), estadiamento (p=0,90) ou realização de quimioterapia (p=0.30) na sobrevida global. Conclusão: O presente estudo propõe que a utilização de um painel imuno-histoquímica composto por CDX2, CK7 e MUC1 permite a classificação com maior acurácia dos adenocarcinomas ampulares em tipo intestinal ou pancreatobiliar. Não foi possível afirmar que a realização de quimioterapia, o estadiamento patológico ou o perfil histopatológico influenciou na sobrevida global, porém o grande impacto deste estudo foi a possibilidade de classificar, a partir de um painel imuno-histoquímico reduzido, os dois subtipos histológicos usuais dos adenocarcinoma ampulares e com isso estabelecer um protocolo para direcionar melhor os pacientes.<br>Background: Ampullary carcinoma is a rare malignant neoplasm, with a frequency of 1% of all gastrointestinal tumors and represents 6 to 25% of the cases of periampullary neoplasms. As distinct epithelia convalesce within the ampulla of Vater, the histological origin of these tumors is still a challenging question in clinical practice. Differences in histomorphological classifications make difficult to evaluate and compare the clinical trials of these tumors. Therefore, the histological division into two main types (intestinal and pancreatobiliary) is necessary for therapeutic and prognostic comparison of this cancer. Methods: 27 patients were included between 2007 and 2013 with diagnosis of ampullary carcinoma from HCFMRP-USP. Histological and immunohistochemical evaluation was performed with the antibodies CK7, CK20, CDX2, MUC1, MUC2, MUC5AC and then was evaluated the overall survival. Results: The overall survival rate was 40.26 months. Sixty three percent were intestinal type carcinomas and 37% were pancreatobiliary type. Expression of the CK20, MUC 2 and CDX 2 were more frequent in intestinal tumors, whereas the CK7, MUC 1 and MUC5AC markers were expressed more frequently in the pancreatobiliary type. The immunostaining of CDX2 presented highest sensitivity and specificity for the intestinal type when used alone (p <0.01). The association of CK7 and MUC1 showed high sensitivity (80%) for the pancreatobiliary type, while CK20 and CDX2 or MUC2 and CDX2 associations had 100% specificity for the intestinal type. The overall survival rate was 40.26 months. There was no significative relation of histological type (p = 0.48), staging (p = 0.90) or chemotherapy (p = 0.30) with the overall survival. Conclusions: This study suggests that the use of an immunohistochemical panel of CDX2, CK7 and MUC1 allows the classification with higher accuracy in the intestinal or pancreatobiliary type. It was not possible to affirm that chemotherapy, pathological staging or histopathological profile influenced the overall survival, but the major impact of this study was the possibility to classify, from a reduced immunohistochemical panel, the two usual histological subtypes of ampullary adenocarcinoma and thus establish a protocol to better target patients.
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Fernandes, Margareth. ""Expressão de Zap-70 e CD38 em leucemia linfocítica crônica (LLC) e sua correlação com prognóstico"." Universidade de São Paulo, 2006. http://www.teses.usp.br/teses/disponiveis/5/5136/tde-30052006-160411/.
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Atualmente, a Leucemia Linfocítica Crônica (LLC) pode ser dividida em dois grupos: um com mutações somáticas no gene da região variável da cadeia pesada da imunoglobulina (MIgVH) e outro sem mutações (NMIgVH). Alguns estudos mostraram que a expressão de CD38 na superfície das células B de LLC pode estar correlacionada com o estado mutacional do gene VHIg, entretanto, esses controversos. Estudos recentes mostraram que a expressão da proteína tirosina quinase Zap-70 está melhor associada com o estado mutacional do gene IgVH. O objetivo deste estudo foi avaliar a expressão de Zap-70 e CD38, por citometria de fluxo, nas células CD19+ de pacientes com LLC e correlacioná-los com o estádio clínico (EC), sobrevida livre de tratamento (SLT) e sobrevida global (SG). A expressão de Zap-70 e CD38 foi avaliada, em 144 de pacientes com LLC classificados nos estádios clínicos A, B e C de acordo com os critérios de Binet: 59 (41%) do EC-A, 38 (26%) do EC-B e 47 (33%) do EC-C. Foi observada menor positividade para Zap-70 e CD38 nos pacientes do EC-A do que nos EC-B e C. Quando avaliada a SLT nos pacientes do EC-A, os casos Zap-70+ assim como os CD38+ apresentaram menor SLT. A média de SG dos pacientes Zap-70+ e CD38+ foi menor quando comparado com os Zap-70- e CD38- entretanto quando correlacionada com o EC não foi observada diferença estatisticamente significante entre a expressão desses marcadores e o EC-A, B ou C. Pela analise combinada de CD38 e Zap-70, dividimos os pacientes em dois grupos (Zap-70-/CD38- e Zap-70+ ou CD38+). Observamos que a expressão positiva desses dois marcadores estava associada ao EC, uma vez que a grande maioria dos pacientes dos estádios B (74%) e C (66%) expressam Zap-70 ou CD38. Entretanto, os pacientes do EC-A, Zap-70+ ou CD38+, apresentaram SG menor quando comparado com os Zap-70-/CD38-. Essa diferença não foi observada nos pacientes do EC-B e do EC-C. Também foi observada menor SLT nos pacientes no EC-A, Zap-70+ ou CD38+. Esses resultados sugerem que análise combinada de Zap-70 e CD38 podem ser empregadas na avaliação dos pacientes do EC-A para se acompanhar a evolução clinica desse grupo de pacientes. Porém, estudos adicionais devem ser realizados para se validar a utilização clínica desses marcadores.<br>Actually, chronic lymphocytic leukemia (CLL) can be divided in two subsets: one with somatically mutated immunoglobulin heavy-chain variable-region genes (MIgVH) and other with unmutated sequences. (UMIgVH). Some studies have shown that CD38 expression in CLL cells are correlated with IgVH mutational status. However, the value of CD38 as surrogate IgVH mutational status is controversial. Recent studies, have found that Zap-70 protein tyrosine kinase expression is strongly associated with the mutational status IgVH. The aim of this study was to evaluate the Zap-70 and CD38 expression, for flow cytometry, in CD19+ LLC cells and correlate with the Binets staging system, treatment-free survival (TFS) and a overall survival (OS). Zap-70 and CD38 was evaluated, in 144 CLL patients that was classified in A, B and C Binets staging system: 59 (41%) in stage A, 38 (26%) in B and 47 (33%) in C. We observed low Zap-70 and CD38 expression in stage A patients than in stage B and C cases. When we analyzed the TFS in stage A patients Zap-70+ and CD38+ patients showed shorter TFS than Zap-70- and CD38-. Then we observed that the OS of Zap-70+ and CD38+ patients was, also, shorter than Zap-70- and CD38- cases. However, statistical differences was not found when Zap-70 and CD38 expression was correlated with stage A, B or C Binets staging system. To understand the associated Zap-70 and CD38 expression, we divided the CLL patients in two subgroups (Zap-70-/CD38 - and Zap-70+ or CD38+). We observed that CD38+ or Zap-70+ was associated Binets staging system, once most of stage B (74%) and C (66%) patients are Zap-70+ or CD38+. However, stage A patients, Zap-70+ or CD38+, showed shorter OS than Zap-70-/CD38-. These differences were not observed in stage B and C patients. Shorter TFS was also observed in the Zap-70+ or CD38+ stage A patients. These results suggest that combined analysis of Zap-70 and CD38 can be used to evaluate stage A patients to observe the clinical evolution of the disease. Nevertheless, other studies must be carried to confirm the clinical use of these markers.
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Chen, Po-Chieh, and 陳柏傑. "Deep learning in predicting outcomes of cancer type, overall survival and disease free survival." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/r8mddv.
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碩士<br>國立中央大學<br>資訊工程學系<br>106<br>Deep neural networks (DNN) have extraordinary performances in various of fields such as sound and image processing. Recently, deep learning methods are applied in the field of biomedical engineering. In this paper, we use the RNA-sequencing data from TCGA (The Cancer Genome Atlas), which is sequenced from RNA data and generated by NGS (Next Generation Sequencing). Due to its high flux number and low background impurities, the most accurate detection of gene expression become possible.
In this paper, we have tree main directions:
1. Classification of cancer types based on RNA- sequencing data.
2. To predict the OS (Overall Survival) of lung, breast, and brain cancer.
3. To predict the DFS (Disease Free Survival) of lung, breast, and brain cancer.
In this paper, we have experimented with a number of methods of machine learning, such as Decision tree, Support Vector Machine and XGBoost (Extreme gradient boost), as well as deep learning methods, including DNN (Deep neural network), autoencoder and VAE (Variational Autoencoder). Our goal is to perform all of these methods and compare the recognition rate of each method.
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PERRONE, GABRIELE. "Identificazione di MTHFR 1298A>C come marcatore predittivo di sopravvivenza in due coorti di pazienti con carcinoma colorettale (stadio II e III) trattati con chemioterapia adiuvante a base di fluoropirimidine con o senza oxaliplatino." Doctoral thesis, 2014. http://hdl.handle.net/2158/854506.
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Adjuvant treatment based on fluoropyrimidines alone or in association with oxaliplatin improves both disease free and overall survival in stage II/III colorectal cancer. However, a certain percentage of patients do not take advantage of the treatment.
The identification of predictive genetic biomarkers may be useful in the selection of patients for chemotherapy treatment by identifying responsive patients and avoiding treatment in non-responsive patients .
The aim of this study was to compare the impact of a set of fluoropyrimidines-related polymorphisms on 5-year disease free survival in two groups of colorectal cancer patients treated with adjuvant fluoropyrimidines with or without oxaliplatin.
A set of 23 polymorphisms in 10 fluoropyrimidines-related genes in two cohorts of stage II/III fluoropyrimidines-treated colorectal cancer patients, including a total of 262 cases were analysed. A concordant effect for MTHFR-1298A>C (rs1801131) polymorphism was found. Carriers of MTHFR-1298CC genotype had a worse disease free survival in both groups (HR=3.48, 95%CI 1.01-11.96 in fluoropyrimidines alone; HR=3.13, 95%CI 1.23-7.97 in fluoropyrimidines + oxaliplatin). In the pooled group of patients MTHFR-1298CC carriers had also a worse overall survival (HR=2.01, 95%CI 0.85-4.75, adjusted P-value=0.035). We computed a clinical score related to disease free survival including MTHFR-1298A>C, disease stage, sex, and tumor location, where MTHFR-1298A>C is the most detrimental factor.
In conclusion MTHFR-1298A>C is a prognostic factor for disease free survival and overall survival in stage II/III colorectal cancer patients treated with a fluoropyrimidines-based treatment and could be used as an additional criteria for the choice of the proper adjuvant regimen.
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TAMBURRINO, DOMENICO. "Efficacy of chemopreventive agents on overall survival in patients with pancreatic ductal adenocarcinoma." Doctoral thesis, 2020. http://hdl.handle.net/11573/1353164.
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Background Previous studies on statins’ effect on survival of patients with pancreatic ductal adenocarcinoma (PDAC) report conflicting results Aims To evaluate the association between statin use and PDAC patients’ survival. Methods A systematic review and meta-analysis was performed including case-control, cohort studies and randomized controlled trials assessing the association between statin use and survival in PDAC patients. Pooled HRs with 95%CIs were calculated using random effects model; publication bias was assessed through Begg and Mazumdar test and heterogeneity by I2 value. Results 14 studies with 33,137 PDAC patients,40% under statins, were included. Statins use was associated to a reduced death risk (HR 0.871; 95%CI: 0.819;0.927; p= 0.0001) suggesting a protective effect, homogeneous for different geographic areas. This effect was significant in surgically resected patients (HR 0.50; 95%CI: 0.32;0.76; p=0.001) but not in those with advanced disease (HR 0.78; 95%CI: 0.59;1.02; p=0.07). In studies providing information on statin type, only rosuvastatin resulted associated to a reduced risk of death (HR 0.88; 95%CI: 0.81;0.96; p=0.004). Conclusions Statins use is significantly associated with a reduced risk of death in resected PDAC patients. This finding has to be considered with caution due to publication bias and the availability of only few studies for sensitivity analyses.<br>BACKGROUND Pancreatic ductal adenocarcinoma is currently the fourth leading cause of cancer-related death in the United States with a 5-year survival rate of 6.7% Surgical resection of early-stage disease remains the only opportunity for potential cure. Despite advances in therapy, pancreatic cancer continues to have a poor prognosis and up to 80–85% of patients undergoing resection experience disease recurrence In this setting cancer chemoprevention with the use of natural or synthetic substances to inhibit, retard or reverse the carcinogenesis has been recently investigated by several authors AIM To investigate the effect of chemopreventive agents on overall survival in patients with pancreatic ductal adenocarcinoma. METHODS A retrospective study has been conducted on patients treated with pancreatic resection for PDAC. Inclusion criteria were as follows: age ≥ 18 years, absence of distant metastasis at preoperative imaging, use of statin and/or metformin and/or ACE-inhibitors and/or B-Blockers and/or aspirin (chemopreventive agents). A patient was considered in therapy with the drugs above mentioned in case of assumption for at least 6 months before diagnosis. RESULTS The median follow-up time was 29 months (IQR: 19-43 months). The median DFS and DSS of the entire population was 21 months (95% CI: 17-24 months) and 34 (95% CI: 30-38) respectively. On multivariable analysis factors associated with DFS were: pT3/pT4 (HR: 2.46; p=0.001); N1 (H.R.: 1.42, p=0.08) and N2 (HR: 2.52; p<0.0001); No adjuvant treatment (HR: 2.0; p<0.0001). Moreover, Aspirin assumption maintain its protective effect on DFS at multivariate analysis (HR: 0.62; p=0.038). On multivariable analysis factors associated with DSS were: pT3/pT4 (HR: 2.55; p=0.001); N1 (H.R.: 2.61, p<0.001) N2 (HR: 4.83; p<0.001); No adjuvant treatment (HR:1.6; p<0.0001); G3 (HR: 1.57; p=0.011); ASA score >3 (HR: 1.45; p=0.025). The regular treatment with ACE-inhibitors is associated with a poor prognosis and lower survival (p=0.027) at univariate analysis ad the data is confirmed at multivariate analysis (HR: 1.65; p=0.009). DISCUSSION The present study demonstrates that the routinely assumption of metformin and/or aAspirin is associated with an increased DFS among patients with PDAC. Also among Metformin-assuming patients a clear trend to a better DFS was observed but without reaching the statistical significance.