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Meerten, Esther van. "Chemotherapy and Chemoradiotherapy Studies in Oesophageal Cancer." [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/13209.
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Witztum, Alon. "Modelling normal tissue toxicity in pancreatic chemoradiotherapy." Thesis, University of Oxford, 2018. http://ora.ox.ac.uk/objects/uuid:52a0b44b-84d4-444e-9f2a-fdbe0fc29edf.
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The relationship between radiation dose and toxicity in pancreatic chemoradiotherapy is not well understood. Clinically, excessive normal tissue toxicity is avoided by placing a constraint on the volume of the organ receiving a dose above a threshold. Dose-volume constraints lack spatial information which may be important in determining normal tissue response. Spatial dose distribution information can be found in dose-surface maps (DSMs). A dose-surface map is a 2-dimensional virtual unwrapping of the surface dose of on organ. Due to the complex geometry of the duodenum, previous methods for unwrapping tubular organs for spatial toxicity modelling are insuficient. A geometrically robust method for producing dose-surface maps, specifically for the duodenum, was created in order to characterise the spatial dose distribution. This unwrapping methodology was shown to be generalisable to simple organs such as the stomach, and extendable to more complex organs such as the bronchial tree. A graphical user interface to create dose-surface maps from organs in commercial treatment planning systems was also demonstrated. Duodenal and stomach dose-surface maps were created for patients from two pancreatic chemoradiotherapy trials, ARCII and SCALOP, treating locally-advanced pancreatic cancer (LAPC). New spatial features were extracted from dose-surface maps and their correlation with upper-gastrointestinal toxicity quantified and compared to traditional dose-volume metrics. The predictive power of some of these new metrics were found to be superior to dose-volume metrics in the stomach, but no significant correlation was found in the duodenum. Duodenal motion throughout treatment occurs both due to respiratory motion and peristalsis. On board imaging using cone-beam CT (CBCT) during individual treatment fractions shows that interfraction variability is non-systematic and cannot be predicted. While abdominal compression is able to restrict some interfraction motion, it is unable to control peristaltic changes. Accumulated duodenal dose-surface maps from these images were created to investigate the differences between the planned and delivered dose.
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Lee, W. M. Anne, and 李詠梅. "Therapeutic benefits of concurrent chemoradiotherapy for advanced nasopharyngeal carcinoma." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41290677.
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Lee, W. M. Anne. "Therapeutic benefits of concurrent chemoradiotherapy for advanced nasopharyngeal carcinoma." Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/B41290677.
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Alderdice, Matthew. "Personalised medicine in rectal cancer : understanding and predicting response to neoadjuvant chemoradiotherapy." Thesis, Queen's University Belfast, 2017. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.725327.
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Around 12-15% of patients with locally advanced rectal cancer (LARC) undergo a pathologically complete response (Tumour Regression Grade 4 - TRG4) to neoadjuvant chemoradiotherapy; the remainder exhibit a spectrum of tumour regression (TRG1-3). Understanding therapy-related genomic alterations may help us better predict response, progression-free and overall survival, and also identify both novel and repurposed treatment strategies based on the underlying biology of the disease. The Northern Ireland Biobank provided 48 formalin fixed paraffin embedded (FFPE) rectal cancer biopsies and matched resections following neoadjuvant therapy (discovery cohort). These were analysed using high-throughput gene expression microarray, DNA mutational profiling and microsatellite instability profiling. Differential gene expression analysis (analysis of variance) was performed contrasting tumour regression grades in both biopsies and resections to identify predictive and therapy related features. Real time PCR was utilised for microarray validation while immunohistochemistry (IHC) was employed to measure CD56+ cell populations in an independent (validation) cohort (n=150). A NK cell-like gene expression signature was observed following long course chemoradiotherapy in a tumour regression-dependent manner. CD56+ NK cel, populations were measured by IHC and found to be significantly higher in TRG3 patients. Furthermore, it was observed that patients positive for CD56 ceils after therapy had a better overall survival (HR=0.282, 95%C,=0.109-0.729, x2=7.854, p=.OO5). In silico drug selection using QUADrATiC analysis identified clinically relevant therapeutic FDA-approved compounds based upon the NK cell-like signature. We demonstrated that identifying an independently validated predictive signature from biopsies for LARC patients treated with LCPCRT was not possible. However, we identified a novel post-therapeutic NK-like transcription signature in patients responding to neoadjuvant chemoradiotherapy. Furthermore, CD56 positive patients had better overall survival. Therefore, harnessing an NK-like response after therapy may improve outcomes for locally advanced rectal cancer patients.
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Shyam, Sunitha. "S-phase Synchronization Promotes Chemoradiotherapy-induced Apoptosis in Prostate Cancer Cell Lines." Kent State University / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=kent1185835523.
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Fujii, Kota. "Association of Chemoradiotherapy With Thoracic Vertebral Fractures in Patients With Esophageal Cancer." Doctoral thesis, Kyoto University, 2021. http://hdl.handle.net/2433/264656.
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Chand, Manish. "The prognostic role of extramural venous invasion in post-chemoradiotherapy rectal cancer." Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/31467.
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Introduction Extramural venous invasion (EMVI) is a poor prognostic factor in rectal cancer. It is detected by magnetic resonance imaging (MRI) and histopathological analysis. Neoadjuvant chemoradiotherapy (CRT) is often given to patients with locally advanced disease however the clinical outcomes of EMVI-positive tumours following such treatment remains unknown. This thesis aimed to investigate the radiological, pathological and molecular changes which occur in EMVI-positive tumours following CRT to determine whether these changes can predict prognosis. Methods Following a systematic review (SR) of EMVI in rectal cancer, a series of studies were conducted. Patients were identified from a prospectively maintained database of primary rectal cancers who were scheduled for CRT followed by curative surgery between 2006 and 2012. Imaging and pathology samples were reviewed and tissue samples were further processed for molecular profiling using micro-RNA analytical techniques. Data were correlated with disease-free survival (DFS), recurrence rate and patterns of relapse. Results SR demonstrated that EMVI is associated with locally advanced tumours, distant disease recurrence and worse overall survival. However there is a variation in technique and definitions which makes interpretation of historical studies problematic. EMVI is an important consideration in the multidisciplinary management of rectal cancer as most clinicians use it to influence treatment decisions. MRI may allow for improved detection rates of EMVI following CRT compared with routine histopathology techniques and it is an independent prognostic factor for recurrence at 3 years. Patients with persistent EMVI following CRT have improved DFS if given adjuvant chemotherapy. Finally, EMVI-positive tumours express specific patterns of microRNA sequences. Conclusion EMVI is a poor prognostic factor following CRT. Patients with evidence of EMVI may be considered for intensive adjuvant chemotherapy and more frequent surveillance for distant disease. Unique molecular signatures may hold the key for future management strategies. These results have led to the development of the MARVEL Study.
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Fujita, Shiro. "Postoperative complications after induction chemoradiotherapy in patients with non-small-cell lung cancer." Kyoto University, 2008. http://hdl.handle.net/2433/135810.
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Tohnai, Iwai. "Chemotherapy using Intra-Arterial Infusion for Oral Cancer." Nagoya University School of Medicine, 2006. http://hdl.handle.net/2237/6962.
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Kördel, Kristin [Verfasser]. "Targeting JAK/STAT signalling for sensitization of colorectal cancer cells to chemoradiotherapy / Kristin Kördel." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2021. http://d-nb.info/123712896X/34.
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Ishikura, Satoshi. "Long-term toxicity after definitive chemoradiotherapy for squamous cell carcinoma of the thoracic esophagus." Kyoto University, 2004. http://hdl.handle.net/2433/147560.
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Bunting, David Mark. "The performance of circulating biomarkers in the prediction of response to neoadjuvant therapy in patients with oesophago-gastric cancer." Thesis, University of Plymouth, 2016. http://hdl.handle.net/10026.1/6565.
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Introduction The prognosis in oesophago-gastric cancer is poor with less than 15% patients surviving beyond 5 years after diagnosis. The addition of neoadjuvant therapy has been shown to increase survival in patients suitable for curative surgery. However, the additional gains are modest and the majority of patients do not respond sufficiently from therapy to gain any benefit. There is an urgent need to identify markers that can predict response to neoadjuvant therapy in order provide safer, more effective, individualised treatment regimes. Methods A prospective, multi-centre, collaborative study was undertaken in patients with oesophago-gastric cancer undergoing neoadjuvant therapy and potentially curative surgery. Levels of circulating biomarkers M2-Pyruvate kinase, alkaline phosphatase, CA19-9, CEA and CA 72-4 were measured in patients before and after administering the first cycle of chemotherapy. Binary logistic regression analysis was performed to assess the ability of biomarkers to predict histological response to therapy. Results 165 patients were recruited to the main study. 105 patients had complete histopathological data for analysis. There were 27 responders and 78 non-responders to neoadjuvant therapy. There were no differences in pre-therapy demographic, pathological or treatment factors between the two groups. Responders had less post-operative lymphovascular invasion (P= 0.004) and higher R0 resection rates (P=0.03). Pre-therapy M2-Pyruvate kinase levels were lower in responders compared to non-responders (P=0.037) and levels were able to predict response with each unit increase in the biomarker level being associated with a 4.1% decrease in the likelihood of response (P=0.027). M2-PK levels were not associated with any pre-operative demographic, clinical or pathological factors. Conclusions Pre-therapy dimeric M2-PK levels can predict response to neoadjuvant therapy in patients with oesophago-gastric cancer. The test could be of clinical value for 1 in every 8 patients undergoing the test.
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Nishimura, Takao. "SIX1 maintains tumor basal cells via transforming growth factor-β pathway and associates with poor prognosis in esophageal cancer." Kyoto University, 2019. http://hdl.handle.net/2433/236593.
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Väyrynen, O. (Otto). "Factors affecting aggressive oral tongue cancer invasion and development of in vitro models for chemoradiotherapy assay." Doctoral thesis, Oulun yliopisto, 2019. http://urn.fi/urn:isbn:9789526222813.
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Abstract Tumor associated macrophages (TAMs) are linked to the invasion of oral tongue squamous cell carcinoma (OTSCC). We modified THP-1 leukemia cells to M1 (inflammatory), M2 (TAM-like) and R848 (imidazoquinoline-treated) type macrophages in order to examine their interactions with OTSCC-cells (HSC-3) by using different kinds of in vitro migration and invasion models. We observed that interaction of TAM-resembling M2-type macrophages with HSC-3 cells induced invasion and migration, whereas the influence of M1 macrophages reduced them. Patient response to chemoradiotherapy is highly reliant on the characteristics such as the aggressiveness and stage of the cancer. Therefore, new methods for treatment testing are needed in order to design personalized therapies. We tested the applicability and consistency of human TME mimicking tissue methods for analyzing the effects of chemoradiation using commercial OTSCC cell lines. Based on our trials, both our human uterine leiomyoma tissue -based matrix models provide viable platforms for future in vitro chemoradiotherapy testing. Conventionally pro-tumorigenic activities of matrix metalloproteinase (MMP)9 have been linked with oral squamous cell carcinoma, but recently its tumor-suppressor role has also been revealed. Our study provides strong evidence that MMP9 also has an anti-invasive effect in OTSCC and is a potential mediator of the protective effects of arresten in tongue cancer cellsTiivistelmä Makrofageilla on yhteys kielen levyepiteelikarsinooman invaasioon eli syöpäkasvaimen tunkeutumiseen ympäröivään kudokseen. Tutkimuksessamme muokkasimme ihmisen THP-1 leukemiasoluja kemiallisesti tulehdusreittejä aktivoiviksi M1-makrofageiksi, kasvaimeen liittyvien makrofagien kaltaisiksi M2-makrofageiksi sekä imidatsokinoliini-käsitellyiksi R848-makrofageiksi. Tarkoituksenamme oli tutkia makrofagien ja kielisyöpäsolujen vuorovaikutuksia erilaisilla in vitro migraatio- ja invaasiomalleilla. Anti-inflammatoristen, syövän etenemistä edesauttavien TAM-makrofagien kaltaisiksi erilaistetut M2-tyypin makrofagit lisäsivät HSC-3 kielikarsinoomasolujen invaasiota ja migraatiota, kun taas M1-tyypin makrofagien vaikutus oli päinvastainen. Potilaan vaste kemosädehoitoon riippuu syöpäkasvaimen ominaisuuksista, kuten syöpäsolujen aggressiivisuudesta ja syövän levinneisyysasteesta. Tämän vuoksi on tarve uusille menetelmille, joiden avulla voidaan ottaa huomioon potilaan sekä syöpätyypin yksilölliset ominaisuudet hoitoa suunniteltaessa. Testasimme syöpäkasvaimen mikroympäristöä mallintavien, ihmiskudokseen perustuvien menetelmien käyttökelpoisuutta ja luotettavuutta kemosädehoidon vaikutusten arvioimiseen. Testiemme perusteella myoomakudokseen pohjautuvat menetelmät voivat auttaa kemosädehoidon vaikutusten testauksessa. Matriksin metalloproteinaasi (MMP) 9:n on pitkään uskottu olevan yksinomaan syövän etenemistä edesauttava molekyyli. Viimeaikaisissa tutkimuksissa on myös havaittu, että MMP9:llä voi olla syövältä suojaavia vaikutuksia. Tutkimme MMP9:n vaikutusta kielisyöpäsoluihin ja havaitsimme, että MMP9:llä on myös invaasiota hillitseviä vaikutuksia. Lisäksi MMP9 saattaa toimia verisuonten muodostumista estävän arresten-molekyylin syövältä suojaavien mekanismien välittäjänä
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Tamaoki, Masashi. "Multiple roles of single-minded 2 in esophageal squamous cell carcinoma and its clinical implications." Kyoto University, 2018. http://hdl.handle.net/2433/235983.
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Yano, Tomonori. "A multicenter phase II study of salvage photodynamic therapy using talaporfin sodium (ME2906) and a diode laser (PNL6405EPG) for local failure after chemoradiotherapy or radiotherapy for esophageal cancer." Kyoto University, 2017. http://hdl.handle.net/2433/228216.
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Wilson, James Matthew. "Using functional imaging to improve chemoradiotherapy outcomes in pancreatic and rectal cancer : moving towards a hypoxia targeting approach." Thesis, University of Oxford, 2015. https://ora.ox.ac.uk/objects/uuid:d55d096c-3750-4854-856f-198e64fdb0b5.
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Biologically individualised, adaptive radiotherapy requires the integration of information obtained from molecular biomarkers with functional imaging to inform high-precision radiotherapy planning. Functional imaging allows the non-invasive assessment of heterogeneity in a number of tumour physiological characteristics, including the well-documented cause of chemoradioresistance, hypoxia. Functional imaging may be useful in treatment strategy selection and biological target volume (BTV) definition for selective radiotherapy dose escalation. Studies in a number of tumour sites suggest that the response in functional imaging parameters offers more predictive and prognostic information than single time-point assessments, including heterogeneity in tumour reoxygenation in head and neck cancer. In this thesis, the role of functional imaging was investigated in two tumour types. Data from the ARC-II clinical trial in locally advanced pancreatic cancer (LAPC) was used and a new trial in rectal cancer (RHYTHM) was developed and opened. Chemoradiotherapy (CRT) outcomes in LAPC are poor, with a median overall survival of around 15 months. The benefit of definitive CRT over chemotherapy alone in LAPC is controversial despite 30% of patients with pancreatic cancer only ever having locally progressive disease. The utility of pre- and post-chemoradiotherapy 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-derived parameters in treatment strategy selection and patient prognosis was assessed. The limitations of using FDG-PET for BTV definition were explored. A method of characterising hypoxia using 18F-fluoromisonidazole (FMISO) PET was developed that demonstrated the hypoxic BTV to remain spatially consistent with time. The ability of nelfinavir to modulate hypoxia and perfusion was then assessed using dynamic FMISO-PET and perfusion computed tomography (pCT). While approximately 75% of patients with locally advanced rectal cancer can be successfully cured, the current treatment paradigm includes CRT followed by total mesorectal excision (TME) with its associated long-term morbidity. If pathological complete response (pCR) could be accurately identified on post-CRT imaging and if rates of pCR could be improved upon, organ-preserving strategies may be adopted. Current anatomical imaging techniques recognise poor treatment responses well, but under-report pCR. The ability of a CT texture feature approach to pCR prediction was investigated. Imaging, tissue and circulating biomarkers of hypoxia (FMISO-PET, pimonidazole and carbonic anhydrase IX [CAIX] immunohistochemistry of rectal cancer tissue and osteopontin) and perfusion (pCT, dynamic contrast-enhanced magnetic resonance imaging [dce-MRI], CD31 immunohistochemistry) as well as RNA sequencing of rectal cancer tissue were assessed in a clinical study to identify the best method of characterising the modulation of hypoxia and perfusion in rectal cancer during fractionated CRT. Early analyses of trial data will be discussed. Trial recruitment is ongoing.
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Castro, Rafael Amaral de [UNESP]. "Avaliação da resposta à quimiorradioterapia neoadjuvante em pacientes com adenocarcinomas retais." Universidade Estadual Paulista (UNESP), 2012. http://hdl.handle.net/11449/88140.
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castro_ra_me_botfm.pdf: 397298 bytes, checksum: bd41f7c70dc73b4d33ae31fb53337714 (MD5)Universidade Estadual Paulista (UNESP)
O câncer colorretal é o segundo câncer mais comum com 2,4 milhões de pessoas diagnosticadas. Desses casos, 27% são neoplasias retais (NR). Quimiorradioterapia neoadjuvante (QRTN) tornou-se padrão nestes casos, mas trouxe controvérsia no tratamento adjuvante. O objetivo foi avaliar o impacto da resposta patológica completa (RPC). Além disso, investigamos a influência da quimioterapia adjuvante (QADJ) após QRTN, biópsia, tempo entre QRTN e cirurgia e ausência de cirurgia após QRTN. Métodos: Entre mar/96 e Out/2010, 84 pacientes receberam QRTN, 58 foram submetidos à ressecção retal (RR). A QRTN consistiu de 5-FU em bolus, na primeira e na quinta semana das 25 sessões de radioterapia (RT) no acelerador linear (total 45 - 50 Gy). A biópsia foi feita de acordo com a opção do cirurgião após a RT. A cirurgia (excisão mesorretal total - TME), foi realizada idealmente 8 semanas após a QRTN. Aqueles não submetidos à cirurgia, também foram seguidos. Quando realizada, a QADJ consistiu de 5-FU no D1-D5 por 4 ciclos. Avaliação da sobrevida global (SG) e sobrevida livre de doença (SLD) foi realizada com uso da curva de Kaplan-Meier. Resultados: Dos 58 pacientes submetidos à cirurgia, 90% eram estágio II, 51% ocorreram no reto inferior e 66% eram ECOG 1. RPC foi obtida em 25,8% (15) dos casos. Destes, 20% (3) receberam QADJ. Pacientes sem RPC receberam QADJ em 51% dos casos (22). O tempo médio de seguimento foi de 41 meses. Tanto o SLD (p = 0,024) e SG (p = 0,0488) foram maiores em pacientes com RPC independente do uso de QADJ. Por outro lado, o uso de QADJ vs sem QADJ, independente da presença de RPC, não alterou significativamente a SLD (p = 0,74) ou SG (p = 0,32). Em pacientes com RPC, QADJ não interferiu nos desfechos (SLD, p = 0,76; SG, p = 0,73). No grupo dos pacientes sem RPC, o subgrupo com QADJ...
Colorectal cancer is the second most common cancer with 2,4 million people diagnosed. The rectal cancer (RC) is 27% of these cases. Neoadjuvant chemoradiotherapy (NCRT) has become standard but brought controversy in the adjuvant treatment. The objective was to assess the impact of Pathologic Complete Response (pCR). Furthermore, we investigated the influence of adjuvant chemotherapy (ADJC) after NCRT, biopsy and time between NCRT and surgery, and the absence of surgery after NCRT. Methods: Between mar/96 and Oct/2010, 84 patients received NCRT, and 58 patients underwent resection of the rectum. The NCRT consisted of 5- Fluorouracil (5-FU) and Leucovorin (LV) bolus in the 1st and 5th week of the 25 sessions of radiotherapy (RT) in linear accelerator (total 45 - 50 Gy). Biopsy was made according to the surgeon option after RT. Ideally surgery (Total mesorretal excision - TME) was performed after 8 weeks NCRT ends. Those not undergoing surgery, were followed too. When performed, Adjuvant Chemotherapy (ADJC) consisted of 5-FU and LV bolus on D1-D5 for 4 cycles. Evaluation of Overall Survival (O.S) and Disease-Free Survival (DFS) performed using Kaplan-Meier curve. Results: Of the 58 patients who underwent surgery, 90% were stage II, 51% occurred in the lower rectum, 66% were ECOG 1 and pCR was obtained in 25.8% (15) of patients (group 1). Of these, 20% (3) received ADJC. Patients without PCR (group 2) received ADJC in 51% of the cases (22). The mean follow-up was 41 months. Both the DFS (p = 0.024) and OS (p = 0.0488) were higher in patients with pPCR independent of the use of ADJC. Patients treated with ADJC vs without ADJC, independent of presence of pCR, did not alter DFS (p = 0.74) or OS (p = 0.32). In pCR patients, ADJC do not interfere in the outcome... (Complete abstract click electronic access below)
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Kalmbach, Sophie [Verfasser], and Martin [Akademischer Betreuer] Schuler. "Identification of novel targets for rational chemoradiotherapy strategies in non-small-cell lung cancer / Sophie Kalmbach ; Betreuer: Martin Schuler." Duisburg, 2018. http://d-nb.info/1172634084/34.
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Khan, A. A. "Study of serial markers of biological response in rectal cancer patients receiving preoperative chemoradiotherapy with or without biological agents." Thesis, University College London (University of London), 2017. http://discovery.ucl.ac.uk/1545253/.
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The key to understanding the heterogeneous behaviour of similar stage locally advance rectal cancer lies in the understanding of tumour biology. The aim of this project was to investigate the biological behaviour of rectal cancers and its alterations in response to neoadjuvant chemoradiotherapy, by studying the intrinsic radiosensitivity, pathophysiology and angiogenesis of rectal cancers. It was intended to provide information that may help risk-stratify patients for individualised treatments including optimal timing of surgery after chemoradiotherapy. Consecutive patients with locally advanced, non-metastatic rectal cancer, who were considered suitable for long-course neoadjuvant chemoradiotherapy, were prospectively recruited. Radiosensitivity was studied by investigating the timing of DNA repair analysis with single cell gel electrophoresis (comet assay). The tumour pathophysiology and angiogenesis was investigated in vivo by novel functional imaging techniques (multiparametric magnetic resonance imaging and dynamic contrast enhanced computed tomography). It is demonstrated that rectal cancer tissue consists of cells with heterogeneous radiosensitivities and functional microvascularity. Until six weeks after NCRT, the DNA repair remains inhibited with progressive devascularisation and increasing hypoxic blood volume resulting in loss of tumour cells. Thereafter, variable fractions of cancer cell may continue to perish or survive with corresponding changes in vascularity. Therefore, the period between the sixth and eleventh weeks after neoadjuvant therapy is a critical time when surviving cells from rectal cancers may develop aggressive traits with long-term consequences. Hence, biological assessment of locally advance rectal cancers after six weeks post-NCRT may help risk-stratify patients for individualised therapy.
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Oliveira, Antonio Carlos Zuliani de 1973. "Braquiterapia com alta taxa de dose e cisplatina concomitante no tratamento do carcinoma espinocelular do colo do útero estadio IIIB : comparação histórica e ensaio clínico aleatorizado = High-dose rate brachitherapy and concomittant cisplatin for the treatment of stage IIIB cervical cancer: historical comparison and an aleatorized controlled trial." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310524.
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Orientador: Luis Otavio Zanatta SarianTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Introdução: Ensaios clínicos das últimas duas décadas do século XX demonstraram a superioridade da radioterapia associada à quimioterapia na abordagem do carcinoma espinocelular do colo do útero (CEC). Contudo, tais estudos abordaram todos os estádios clínicos e para o subgrupo de mulheres com CEC estádio IIIB e os benefícios da quimioterapia não foram totalmente comprovados. Objetivos: Esta tese divide-se em dois estudos: 1) uma comparação histórica de sobrevida livre de doença (SLD), sobrevida total (ST) e toxicidade de tratamento em mulheres com CEC IIIB submetidas à braquiterapia de baixa taxa de dose (BBTD) versus braquiterapia de alta taxa de dose exclusiva (BATD) versus braquiterapia de alta taxa de dose associada à quimioterapia (BATD-QT) e 2) um ensaio clínico aleatorizado comparando esses mesmos parâmetros em mulheres submetidas à BATD versus BATD-QT. Métodos: Na comparação histórica de tratamentos, foram levantados os dados de evolução de pacientes admitidas entre 1985 e 2005 no CAISM-UNICAMP e seguidas até 2007, totalizando 230 pacientes com CEC IIIB que receberam BBTD (42 pacientes), BATD (155 pacientes) ou BATD-QT (33 pacientes). As SLD e ST das mulheres nos três grupos foram comparadas usando curvas de sobrevida tipo Kaplan-Meyer e testes de log-rank. Já o ensaio clínico aleatorizado foi realizado entre setembro de 2003 e julho de 2010. Foram incluídas no estudo 147 mulheres com CEC IIIB. Após aceitarem participar e assinarem o termo de consentimento, as mulheres foram randomizadas para BATD ou BATD-QT através de planilha de aleatorização criada pelo programa SAS e trazida ao conhecimento de pacientes e médicos através de envelopes opacos. Todas as mulheres receberam teleterapia com dose de 45Gy para a região pélvica em 25 frações, 14,4Gy de reforço no(s) paramétrio(s) comprometido(s) e BATD em quatro frações semanais de 7Gy, prescritos no ponto A. O grupo BATD-QT recebeu cisplatina concomitante semanal (40mg/m2) durante a teleterapia pélvica. O follow-up durou até janeiro de 2013, (72 pacientes do grupo com cisplatina e 75 no grupo-controle), com o seguimento médio de 54,9 meses (intervalo interquartil = 55,4 meses). Comparações de SLD e ST foram realizadas usando curvas de Kaplan-Meyer, testes de log-rank e modelos multivariados de Riscos Proporcionais de Cox, os quais englobaram características clínicas das mulheres como variáveis de controle. Resultados: Na comparação histórica, a SLD média para o grupo BATD foi de 60%, para BBTD 45% e para BATD-QT foi de 65% (p = 0,02). Já a ST foi de 65% para o grupo BATD, 49% para BBTD e a ST em dois anos para o grupo BATD-QT foi de 86% (p = 0,02). A toxicidade retal de grau II foi de 7% para o grupo que recebeu BBTD, de 4% para BATD e 7% para o grupo BATD-QT, que teve um caso de toxicidade retal grau IV. No ensaio clínico aleatorizado, mulheres alocadas no grupo BATD-QT tiveram SLD significativamente melhor (RR = 0,52, 95% CI 0,28-0,98, p = 0,04), porém não houve diferença em relação a ST (RR = 0,67, 95% CI 0,37-1,183, p = 0,16). Mulheres com Karnofsky <90 tiveram uma SLD significativamente pior (RR = 2,52, 95% CI 1,23-4,78, p = 0,01). O mesmo ocorreu para as mulheres com invasão parametrial bilateral até a parede óssea (RR = 2,93, 95% CI 1,21-7,13, p = 0,02), e a hemoglobina média durante o tratamento <10mg/dL (RR = 2,22, 95% CI 1,01-4,93, p = 0,04). A ST também foi menor em mulheres com Karnofsky <90 (RR = 2,75, 95% CI 1,29-5,87, p <0,01), e hemoglobina média durante o tratamento <10mg/dL (RR = 2,82, 95% CI 1,27-6,29, p = 0,01). Conclusões: Na revisão da série histórica, as pacientes que receberam braquiterapia de alta taxa de dose tiveram melhores SLD e ST, e as taxas de toxicidade não foram diferentes entre os três grupos. O ensaio clínico, que é o único estudo controlado randomizado comparando a BATD-QT e BATD para CEC IIIB, sugere que há um pequeno, mas significativo, benefício na SLD com a adição de cisplatina à BATD, com uma toxicidade aceitável
Abstract: Introduction: Clinical trials of the last two decades of the twentieth century demonstrated the superiority of radiotherapy combined with chemotherapy in the management of squamous cell carcinoma of the cervix (SCC). However, such studies have addressed all clinical stages and for the subgroup of women with stage IIIB SCC the benefits of chemotherapy have not been fully proven. Objectives: This thesis is divided into two studies: 1) a historical comparison of disease-free survival (DFS), overall survival (OS) and toxicity of treatment in women with SCC IIIB undergoing low-dose rate brachytherapy (LDR) brachytherapy versus high dose rate exclusive (HDR) brachytherapy versus high dose rate associated with chemotherapy (CHT) and 2) a randomized clinical trial comparing these parameters in women undergoing HDR versus CHT. Methods: In the historical comparison of treatments, data on the outcomes of patients admitted between 1985 and 2005 in CAISM-Unicamp and followed until 2007 were collected, totaling 230 patients with SCC stage IIIB who received either LDR (42 patients), HDR (155 patients) or CHT (33 patients). The DFS and OS of women in the three groups were compared using Kaplan-Meyer survival curves and the "log-rank" test. The randomized clinical trial was conducted between September 2003 and July 2010. A total of 147 with SCC stage IIIB were included. After accepting to participate and signing the consent form, women were randomized to HDR or CHT through a randomization spreadsheet created by SAS program and concealment allocation of patients through opaque envelopes. Patients of either the CHT or HDR groups received external-beam radiation (45 Gy) to the entire pelvic region in 25 fractions over a 5-week period. Compromised parametria were treated with 14.4 Gy boost. High-dose rate brachytherapy consisted of four weekly fractions of 7 Gy prescribed to point A. Patients in the CHT group also received concomitant weekly cisplatin (40mg/m2) during the pelvic external beam radiotherapy. The follow-up lasted until January 2013 (72 patients in the cisplatin group and 75 in the control group), with a mean follow-up of 54.9 months (interquartile range = 55.4 months). Comparisons of DFS and OS were performed using Kaplan-Meyer log-rank tests and multivariate models of Cox proportional hazards model, which encompassed the clinical characteristics of women as control variables. Results: In the historical comparison, the DFS for the group HDR was 60% , 45% for LDR and 65% for CHT (p = 0.02). The OS was 65% for the HDR group, 49% for LDR and 86% for CHT (p = 0.02). The Grade II rectal toxicity was 7% for LDR, 4% in HDR patients and 7% in CHT group, which had a case of rectal toxicity grade IV. In the randomized clinical trial, women in the CHT group had significantly better DFS (RR = 0.52, 95% CI from 0.28 to 0.98, p = 0.04), but there was no difference in OS (RR = 0.67, 95% CI 0.37 to 1.183, p = 0.16). Women with Karnofsky <90 had a significantly worse DFS (RR = 2.52, 95% CI 1.23 to 4.78, p = 0.01). The same was true for women with bilateral parametrial invasion to the bone wall (RR = 2.93, 95% CI 1.21 to 7.13, p = 0.02), and mean hemoglobin during treatment <10mg/dL (RR = 2.22, 95% CI 1.01 to 4.93, p = 0.04). The OS was also lower in women with Karnofsky <90 (RR = 2.75, 95% CI 1.29 to 5.87, p <0.01), and mean hemoglobin during treatment <10mg/dL (RR = 2, 82, 95% CI 1.27 to 6.29, p = 0.01). Conclusions: Patients who received HDR had better DFS and OS, and toxicity rates were not different among the three groups. The randomized trial, which is the only randomized controlled study comparing HDR and CHT for CEC IIIB, suggests that there is a small but significant DFS benefit with the addition of cisplatin to HDR, with acceptable toxicity
Doutorado
Oncologia Ginecológica e Mamária
Doutor em Ciências da Saúde
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Castro, Rafael Amaral de. "Avaliação da resposta à quimiorradioterapia neoadjuvante em pacientes com adenocarcinomas retais /." Botucatu : [s.n.], 2012. http://hdl.handle.net/11449/88140.
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Orientador: Rogério Saad-HossneBanca: Fábio Vieira Teixeira
Banca: Odair Carlito Michelin
Resumo: O câncer colorretal é o segundo câncer mais comum com 2,4 milhões de pessoas diagnosticadas. Desses casos, 27% são neoplasias retais (NR). Quimiorradioterapia neoadjuvante (QRTN) tornou-se padrão nestes casos, mas trouxe controvérsia no tratamento adjuvante. O objetivo foi avaliar o impacto da resposta patológica completa (RPC). Além disso, investigamos a influência da quimioterapia adjuvante (QADJ) após QRTN, biópsia, tempo entre QRTN e cirurgia e ausência de cirurgia após QRTN. Métodos: Entre mar/96 e Out/2010, 84 pacientes receberam QRTN, 58 foram submetidos à ressecção retal (RR). A QRTN consistiu de 5-FU em bolus, na primeira e na quinta semana das 25 sessões de radioterapia (RT) no acelerador linear (total 45 - 50 Gy). A biópsia foi feita de acordo com a opção do cirurgião após a RT. A cirurgia (excisão mesorretal total - TME), foi realizada idealmente 8 semanas após a QRTN. Aqueles não submetidos à cirurgia, também foram seguidos. Quando realizada, a QADJ consistiu de 5-FU no D1-D5 por 4 ciclos. Avaliação da sobrevida global (SG) e sobrevida livre de doença (SLD) foi realizada com uso da curva de Kaplan-Meier. Resultados: Dos 58 pacientes submetidos à cirurgia, 90% eram estágio II, 51% ocorreram no reto inferior e 66% eram ECOG 1. RPC foi obtida em 25,8% (15) dos casos. Destes, 20% (3) receberam QADJ. Pacientes sem RPC receberam QADJ em 51% dos casos (22). O tempo médio de seguimento foi de 41 meses. Tanto o SLD (p = 0,024) e SG (p = 0,0488) foram maiores em pacientes com RPC independente do uso de QADJ. Por outro lado, o uso de QADJ vs sem QADJ, independente da presença de RPC, não alterou significativamente a SLD (p = 0,74) ou SG (p = 0,32). Em pacientes com RPC, QADJ não interferiu nos desfechos (SLD, p = 0,76; SG, p = 0,73). No grupo dos pacientes sem RPC, o subgrupo com QADJ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Colorectal cancer is the second most common cancer with 2,4 million people diagnosed. The rectal cancer (RC) is 27% of these cases. Neoadjuvant chemoradiotherapy (NCRT) has become standard but brought controversy in the adjuvant treatment. The objective was to assess the impact of Pathologic Complete Response (pCR). Furthermore, we investigated the influence of adjuvant chemotherapy (ADJC) after NCRT, biopsy and time between NCRT and surgery, and the absence of surgery after NCRT. Methods: Between mar/96 and Oct/2010, 84 patients received NCRT, and 58 patients underwent resection of the rectum. The NCRT consisted of 5- Fluorouracil (5-FU) and Leucovorin (LV) bolus in the 1st and 5th week of the 25 sessions of radiotherapy (RT) in linear accelerator (total 45 - 50 Gy). Biopsy was made according to the surgeon option after RT. Ideally surgery (Total mesorretal excision - TME) was performed after 8 weeks NCRT ends. Those not undergoing surgery, were followed too. When performed, Adjuvant Chemotherapy (ADJC) consisted of 5-FU and LV bolus on D1-D5 for 4 cycles. Evaluation of Overall Survival (O.S) and Disease-Free Survival (DFS) performed using Kaplan-Meier curve. Results: Of the 58 patients who underwent surgery, 90% were stage II, 51% occurred in the lower rectum, 66% were ECOG 1 and pCR was obtained in 25.8% (15) of patients (group 1). Of these, 20% (3) received ADJC. Patients without PCR (group 2) received ADJC in 51% of the cases (22). The mean follow-up was 41 months. Both the DFS (p = 0.024) and OS (p = 0.0488) were higher in patients with pPCR independent of the use of ADJC. Patients treated with ADJC vs without ADJC, independent of presence of pCR, did not alter DFS (p = 0.74) or OS (p = 0.32). In pCR patients, ADJC do not interfere in the outcome... (Complete abstract click electronic access below)
Mestre
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Nougaret-Jung, Stéphanie. "Evaluation de la réponse thérapeutique par imagerie multiparamétrique et fonctionnelle après traitement neoadjuvant dans le cancer du rectum." Thesis, Montpellier, 2015. http://www.theses.fr/2015MONTT039.
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Le cancer colo-rectal est un problème de santé publique majeur dans les pays développés. Le cancer du rectum est défini comme une marge distale de la tumeur à moins de 15 cm de la marge anale. Sa prise en charge optimale impose une discussion entre une chirurgie mutilante emportant les sphincters ou une chirurgie conservatrice laissant en place l'appareil sphinctérien et évitant l'incontinence et la colostomie. L’Imagerie par résonance magnétique (IRM) est l’examen de référence pour le diagnostic de la tumeur initiale. Dans projet, nous avons utilisé des outils IRM modernes comme la volumétrie et l’imagerie de diffusion dans l’évaluation thérapeutique des cancers du rectum après chimioradiothérapie.Nous avons ainsi montré que la variation de volume tumoral au cours du traitement du cancer du rectum était associée à une survie sans récidive à 5 ans : les patients dont le volume tumoral diminuait d'au moins 70% au cours du traitement néoadjuvant avaient une survie à 5 ans sans récidive et un grade de régression histologique significativement plus élevée que chez les patients dont le volume diminuait de moins de 70%. En utilisant la même technique de volumétrie tumorale tridimensionnelle au cours d'un essai thérapeutique, nous avons également montré pour la première fois que la variation précoce de volume tumoral du rectum au cours du traitement néoadjuvant par chimiothérapie seule pouvait prédire le succès du traitement ultérieur par radio-chimiothérapie puis chirurgie. L'étude de la variation précoce de volume tumoral est actuellement utilisée dans un essai randomisé prospectif multicentrique dans lequel la variation de volume tumoral du rectum après radio-chimiothérapie néoadjuvante chez des patients avec tumeur avancée (T3c, T4) est le déterminant de la poursuite d'un traitement radio-chimiothérapique néoadjuvant ou le traitement chirurgical radical (essai GRECCAR4, ClinicalTrials.gov NCT01333709). Nous nous sommes ensuite intéressés à l’imagerie de diffusion et en particulier l’IVIM marqueur prédictif de réponse thérapeutique. Dans cette étude, la diffusion pure permettait d’obtenir des résultats prometteurs pour l’évaluation de la réponse au traitement néoadjuvant. Finalement, nous présenterons les perspectives de recherche concernant un type particulier de réponse, les réponses colloïdesColo-Rectal Cancer is the third most commonly diagnosed cancer in males and the second in females. Around 30% of all colorectal cancers are diagnosed in the rectum. Despite the major improvements that have been made management of rectal cancer still remains a challenge. Chemoradiotherapy (CRT) followed by surgery has been widely adopted for the management of locally advanced rectal cancers because this approach increases the probability of anal sphincter preservation, decreases the local recurrence rate and decreased the risk of colostomy. As we enter the era of personalized medicine with therapies stratified according to the risk of local or distant recurrence, imaging has become an essential tool in the preoperative decision making, to avoid both under- and overtreatment. Magnetic Resonance (MR) imaging is now an essential tool to enable the oncology team to make appropriate treatment decisions. First, we demonstrated that tumor shrinkage after preoperative chemotherapy–radiation therapy was associated with good response. Second, we demonstrated that early tumor volume decrease after induction chemotherapy before chemoradiotherapy was as well associated with good patient prognosis. Third, we demonstrated the added value of DW MR imaging for predicting tumor response using IVIM, a more sophisticated diffusion analytic approaches, which allows quantitative parameters that reflect tissue microcapillary perfusion and tissue diffusivity to be derived. In this study we demonstrated that true diffusion was associated with regression grade on pathology. Finally, we will present our perspectives especially in tumor response evaluation in patient with colloidal response
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Sowa, Terumasa. "Hypoxia-inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX expression." Kyoto University, 2017. http://hdl.handle.net/2433/226768.
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Georgi, Alexander. "Lokal fortgeschrittene Kopf-Hals-Tumoren- Eine retrospektive, monoinstitutionale Studie zur Beurteilung der postoperativen Radiochemotherapie im klinischen Alltag." Doctoral thesis, Universitätsbibliothek Leipzig, 2013. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-130129.
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Die vorliegende retrospektive Studie zur postoperativen Radiochemothera-pie bei fortgeschrittenen Kopf-Hals-Tumoren sollte die eigenen Ergebnisse mit den prospektiv-randomisierten Studien vergleichend darlegen und dabei den Nutzen einer Radiochemotherapie überprüfen. Insgesamt wurden 155 Patienten in der retrospektiven Analyse eingeschlossen. Die Überlebens- und Rezidivraten des Patientengutes konnten anlehnend zu den publizier-ten Studien reproduziert werden. Ein Vorteil der Radiochemotherapie in Bezug nehmend auf den posttherapeutischen Verlauf konnte hierbei nicht festgestellt werden. Es traten signifikant vermehrt höhergradige Akutne-benwirkungen nach Applizierung der simultanen, systemischen Therapie auf. Die Arbeit konnte zeigen, dass sich durch die Reduzierung der Gesamt-behandungszeit als auch des Intervalls zwischen Operation und Beginn der adjuvanten Therapie das Gesamtüberleben sowie die lokoregionäre Rezidiv-rate signifikant verbessern ließen. Insgesamt scheinen die Fernmetastasie-rungen und die lokoregionären Rezidive maßgebend für die immer noch un-befriedigenden Überlebensraten zu sein. Gegenstand weiterer Untersu-chungen sollte daher die Optimierung der prätherapeutischen Diagnostik sowie der adjuvanten Therapie sein.
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West, Malcolm. "The effects of neoadjuvant chemoradiotherapy and a structured exercise training programme on physical fitness and in vivo mitochrondrial function in advanced rectal cancer patients." Thesis, University of Liverpool, 2015. http://livrepository.liverpool.ac.uk/2007379/.
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Outcomes after major surgery depend partly on patients’ physiological tolerance to iatrogenic trauma. Objectively measured fitness assessments (cardiopulmonary exercise testing; CPET) show a link between poor fitness and poor surgical outcome, especially in major colorectal surgery. However evidence on fitness of surgical patients undergoing neoadjuvant chemoradiotherapy (NACRT) and/or preoperative exercise training is lacking. This thesis focuses on the physiological effects of NACRT and a preoperative structured responsive exercise training programme (SRETP) on objectively measured physical fitness using cardiopulmonary exercise testing, and the related effects on mitochondrial function using 31-phosphorus magnetic resonance spectroscopy (31P MRS) in operable advanced rectal cancer patients. First, CPET variables (oxygen uptake ( o2) at estimated lactate threshold ( L) and at peak exercise) were measured in advanced rectal cancer patients pre and post-NACRT and were followed up to 1 year postoperatively. A reduction in o2 at L and o2 at Peak exercise was observed (-1.5 and -1.4 ml.kg-1.min-1 respectively; p<0.0001), both significantly associated with in-hospital complications. This is the first direct evidence that the benefits of NACRT in tumour downsizing may be partly offset by increased perioperative risk due to a reduction in physical fitness. A SRETP was then constructed, and a feasibility and tolerability study carried out. The SRETP improved physical fitness within 6 weeks following NACRT ( o2 at L +3.3 ml.kg-1.min-1 and o2 Peak by +5.8 ml.kg-1.min-1), enough to reverse the deleterious effects of NACRT. A 98% adherence proves the SRETP both feasible and tolerable, with no adverse events encountered. Next, locally advanced rectal cancer patients were recruited to an interventional pilot study scheduled to undergo standardised NACRT and a 6-week SRETP (exercise group n=22) or a control period (n=13). A significant benefit in o2 at L of +2.12 ml.kg-1.min-1 (p<0.0001) in the exercise group was observed. This study reinforces the benefits of prehabilitation with exercise training to improve physical fitness after the deleterious effects of NACRT prior to the added insult of major surgery. Lastly, patients were randomized to the SRETP or to negative control after undergoing standardized NACRT, serial measures of whole body fitness and in vivo mitochondrial function by 31P MRS (measuring the rate constant of phosphocreatine recovery, kPCr). Significant reductions in o2 at L (-2.36 ml.kg-1.min-1) were observed with NACRT, after which the SRETP improved fitness ( o2 at L +3.85 ml.kg-1.min-1). A significant reduction in kPCr of -0.34 was found with NACRT, improved by +0.66 after SRETP. These novel, clinically relevant findings show a significant decline in fitness with NACRT in an advanced rectal cancer cohort, reversible by a tailored exercise intervention post-NACRT. Concomitant changes in muscle mitochondrial function may account for this acute loss in fitness. The improvement in mitochondrial function observed with exercise, might indicate that a structured intervention immediately after NACRT is necessary to rescue and reverse NACRT’s deleterious effect on mitochondrial function and fitness in this patient cohort.
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Brasiūnienė, Birutė. "Kasos vėžio kombinuoto gydymo įtaka ligonių gyvenimo trukmei ir gyvenimo kokybei." Doctoral thesis, Lithuanian Academic Libraries Network (LABT), 2006. http://vddb.library.lt/obj/LT-eLABa-0001:E.02~2006~D_20060130_151509-67222.
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Treatment of pancreatic cancer is an important medical problem. Most pancreatic cancer patients are diagnosed with advanced disease and their prognosis is poor. In Lithuania there were 440 new cases in year 2004. More than fifty percent of patients are diagnosed with stage IV disease [Kurtinaitis J et al., 2005].
Median survival of patients diagnosed with pancreatic cancer, depending on a stage of a disease, spread of the tumor, treatment method, functional status of a patient is from 6 to 20 months. Five-year survival is only 0–5 percent [Bramhall S et al., 1998; Oya N, 2004].
Today, pancreatic cancer is treated by combined methods: surgery combined with RT and/or chemotherapy. It is questionable if a patient diagnosed with pancreatic cancer in early stages must be treated by adjuvant treatment methods, or should patients diagnosed with unresectable cancer be treated with chemotherapy or ChRT; and what is more important for the patient: increased survival or better quality of life.
Kaunas University of Medicine Clinic (KMUC) is a suitable hospital to treat patients diagnosed with pancreatic cancer. At the Clinic of Surgery pancreatic cancer patients are treated by radical and palliative surgery; and at the Clinic of Oncology patients with pancreatic cancer are treated applying contemporary methods of RT, chemotherapy and combined treatment methods. In this thesis treatment results of patients treated for resectable and unresectable pancreatic cancer from year 1987 to year... [to full text]
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Bessa, Lucas Veloso Teixeira. "Diferença de toxicidade em pacientes portadoras de câncer de colo de útero durante o tratamento com radioterapia isolada e radioquimioterapia." Botucatu, 2018. http://hdl.handle.net/11449/154553.
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Orientador: Batista de Oliveira JuniorResumo: O câncer de colo de útero é a sétima neoplasia maligna mais frequente no mundo e segundo tipo mais incidente na população feminina brasileira. O seu tratamento envolve a cirurgia, a radioterapia (RT) e, em caso mais avançados, o uso da concomitância com quimioterapia (RQT) com ganhos de sobrevida de 15-27%, bem descritos desde o final do século 20. O objetivo deste estudo retrospectivo é avaliar a toxicidade aguda dos pacientes portadores de câncer de colo de útero fizeram RT e RQT durante o ano de 2016 no Hospital Amaral Carvalho de Jaú – SP. De 86 pacientes com idade média de 50 (variação 22-85), o braço teve 25 pacientes, e o RQT 61 pacientes. Completaram o tratamento 96% do grupo RT e 93% do grupo RQT, sendo que somente 73,41% do grupo RQT recebeu todo o tratamento como o planejado. A toxicidade aguda acometeu 73% dos pacientes, sendo 47% com somente um sintoma e 27% com dois ou mais. Somente 14,3% dos eventos foram de toxicidade grave, graus III e IV, todos do grupo RQT. A toxicidade mais frequente foi a cistite (41,8% RQT Vs 32%RT), seguido de diarreia (23% RQT Vs 16%RT) e vômitos (16% RQT Vs 8%RT). Nenhuma pausa foi registrada em decorrência de toxicidade. O tratamento de radioquimioterapia apresenta mais toxicidade aguda do que a radioterapia isolada, mas todas são reversíveis e não o contraindicam.
Mestre
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Moraes, Juliana Lopes de 1982. "Qualidade de vida do paciente com câncer avançado de laringe = revisão sistemática e metanálise de tratamento cirúrgico versus quimioradioterápico = Quality of life of patients with advanced laryngeal cancer: systematic review and meta-analysis of surgery versus chemoradiation." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312535.
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Orientador: Carlos Takahiro ChoneDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-25T13:57:24Z (GMT). No. of bitstreams: 1 Moraes_JulianaLopesde_M.pdf: 943040 bytes, checksum: 4d94adb829d86ae614ad5e737c31b7af (MD5) Previous issue date: 2014
Resumo: Objetivo: Comparar a qualidade de vida do paciente tratado cirurgicamente por câncer avançado de laringe com aquele que foi submetido a quimioradioterapia exclusivos. Método: Revisão sistemática que utilizou, para a seleção dos artigos, 06 bases de dados (PubMed, MedLine, Embase, Web of Science, Cochrane Library e Lilacs) e as palavras-chave "head and neck cancer"; "advanced laryngeal cancer"; "laryngeal neoplasm"; larynx cancer"; "quality of life"; "outcomes/functional results";"total laringectomy"; "chemoradiotherapy". Os critérios de inclusão foram estudos específicos de câncer avançado de laringe, com comparação de modalidades de tratamento e avaliação da qualidade de vida. Resultados: Foram encontrados 321 artigos. Nove artigos preencheram todos os critérios de inclusão e desses, apenas três possuíam desenho metodológico e instrumento de mensuração de qualidade de vida comparáveis entre si e foram submetidos à metanálise . Os resultados evidenciaram que 90% dos estudos são retrospectivos e não randomizados. O tempo pós-tratamento em que os questionários de qualidade de vida foram aplicados mostrou grande variabilidade (3 meses a 11 anos). Conclusão: A meta-análise dos três estudos comparativos mostraram uma melhor qualidade de vida após o tratamento para indivíduos tratados com quimioradioterapia exlcusiva. No entanto, devido a existência de poucos estudos com dados relevantes na literatura, é necessário realizar pesquisas futuras com as seguintes características: (a) estudos prospectivos e randomizados, (b) multicêntrico, com maior número de indivíduos, e (c) enfatizando o funcional sequelas que ambos os tratamentos acarretam
Abstract: Objective: To compare studies of quality of life in patients undergoing chemoradiotherapy or surgery for advanced laryngeal cancer. Method: Articles were selected for a systematic review by searching six databases (PubMed, Medline, Embase, Web of Science, Cochrane Library and Lilacs) for keywords "head and neck cancer," "advanced laryngeal cancer," "laryngeal neoplasm," "larynx cancer," "quality of life," "outcomes and functional results," "total laryngectomy" and "chemoradiotherapy." The included studies must related to advanced larynx cancer, comparisons of treatment modalities and assessment of patient quality of life in validated scales, well defined inclusion and exclusion criteria. Articles with poor methodological evaluation and duplicated results were excluded. Results: It was found 321 articles. Nine articles fitted to all inclusion criteria and of these, only three observed comparable methodological designs and standardized instruments for measuring quality of life and therefore subjected to meta-analysis. Our analysis observed that 90% of the studies were retrospective and nonrandomized. The time point post-treatment at which the quality of life questionnaires were assessed varied widely (3 months to 11 years). Conclusion: The meta-analysis of three comparable studies showed improved quality of life after treatment for subjects treated with chemoradiation alone. However, because of few studies with relevant data in literature, it is necessary to conduct future research with the following study characteristics: (a) prospective and randomized; (b) multicentric, with larger numbers of subjects; and (c) emphasizing the functional sequelae that both treatments entail
Mestrado
Ciencias Biomedicas
Mestra em Ciências Médicas
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Leitão, Glauber Moreira. "Osteopontina como marcador de resposta à radioterapia e quimioterapia em pacientes com câncer de cabeça e pescoço localmente avançado." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-12012009-162533/.
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INTRODUÇÃO: Osteopontina (OPN) é uma glicoproteína presente em tecidos e fluidos orgânicos e envolvida em vários processos patológicos que incluem inflamação, proliferação celular, invasão da matriz extracelular, progressão tumoral e metástase. Em pacientes (pts) portadores de carcinoma epidermóide de cabeça e pescoço (CECCP), OPN tem sido associada a uma maior agressividade tumoral e empregada como marcador prognóstico. Nós investigamos o valor prognóstico e preditivo da OPN sérica em pacientes portadores de CECCP tratados de forma uniforme. MÉTODOS: Estudo longitudinal prospectivo de 47 pts portadores de CECCP localmente avançado e irressecável submetidos à quimioterapia e radioterapia. OPN sérica foi determinada pelo método ELISA (kit 1 com17 pts e kit 2 com 30 pts) com coleta realizada antes e após o término do tratamento e estudada a relação entre OPN, categorizada como alta ou baixa em relação ao valor mediano, e as características clínico-patológicas, resposta ao tratamento, sobrevida global (SG) e sobrevida livre de progressão (SLP). RESULTADOS: A OPN sérica mediana dos pacientes determinada pelo kit 1 (em ng/ml) foi de 2,1 e 1,9 pré e pós-tratamento, respectivamente; no kit 2 (em ng/ml) foi de 69,5 e 87,9 pré e pós-tratamento, respectivamente. Pacientes portadores de tumores de orofaringe foram mais freqüentemente associados a baixos níveis séricos de OPN pós-tratamento, em comparação com outros sub-sítios (p=0,03). Observada tendência à associação entre os valores séricos baixos de osteopontina pós-tratamento e a resposta tratamento (p=0,06). Houve associação entre os valores elevados da osteopontina pós-tratamento e menor SLP (p=0,09, log rank), com medianas de 11,9 meses e 14,5 meses, conforme valores séricos de OPN pós-tratamento altos e baixos, respectivamente. Não houve associação dos valores séricos de OPN pré e pós-tratamento e a SG (p=0,19 e p= 0,10, respectivamente). CONCLUSÃO: Neste grupo de pacientes portadores de CECCP, sugere-se que OPN sérica baixa após a quimioradioterapia associa-se à resposta ao tratamento e melhor SLP.INTRODUCTION: Osteopontin (OPN) is a glycoprotein present in tissues and body fluids involved in several pathological processes that include inflammation, cell proliferation, invasion of the extracellular matrix, tumor progression and metastasis. In head and neck squamous cell carcinoma (HNSCC) patients, OPN has been associated with greater tumor aggressiveness and used as a prognostic marker. We investigated the prognostic and predictive value of plasma OPN in homogeneously treated (HNSCC) patients. METHODS: Longitudinal prospective study of 47 patients with locally advanced and inoperable HNSCC treated with exclusive platin based concomitant chemoradiotherapy. Plasma OPN was determined by ELISA (n=14 kit I, n=32 kit II) pre and postreatment and correlated with tumor response, overall survival (OS) and progression-free survival (PFS). RESULTS: Median OPN levels in ng/ml were 2,1 and 1,9 pre and postreatment, respectively, by kit I and 69,5 and 87,9 by kit II. Patients were categorized as OPN low or high, using the median as a cut-off point. Patients with oropharynx tumors, as compared to other subsites, were more frequently categorized as low OPN (p = 0,03). A low postreatment OPN level was associated with tumor response (p = 0,06) and a high postreatment OPN level was associated with poor PFS, 11.9 vs. 14.5 months (p=0.09, log rank). Mean OS was 16.2 and 13.7 months in low and high postreatment OPN pts, respectively (p=0.10, log rank). CONCLUSIONS: In this group of HNSCC patients, it is suggested that a low plasma OPN after chemoradiotherapy is associated with a lower response rate and a worse PFS.
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Merten, Ricarda [Verfasser], Rainer [Akademischer Betreuer] Fietkau, Rainer [Gutachter] Fietkau, and Luitpold [Gutachter] Distel. "Long-term experience of chemoradiotherapy combined with deep regional hyperthermia for organ preservation in high-risk bladder cancer (Ta, Tis, T1, T2) / Ricarda Merten ; Gutachter: Rainer Fietkau, Luitpold Distel ; Betreuer: Rainer Fietkau." Erlangen : Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU), 2020. http://d-nb.info/1209740990/34.
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Garcia, Fabyane de Oliveira Teixeira. "Identificação de microRNAs na saliva associados ao benefício a longo prazo da quimiorradioterapia em pacientes com carcinoma epidermoide de cavidade oral e orofaringe." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-06022017-105322/.
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INTRODUÇÃO: A maioria dos pacientes com CECP é diagnosticada em estágios avançados da doença, apresentando taxas de sobrevida insatisfatórias. Em carcinomas localmente avançados e irressecáveis, o tratamento padrão na rotina do ICESP é a QRT a base de cisplatina. Entretanto, cerca de dois terços desses pacientes apresentam recidiva local, à distância ou óbito em cinco anos. Entender os mecanismos de resistência a QRT e descobrir marcadores que possam indicar resposta ao tratamento continuam sendo um desafio. Os microRNAs possuem papel chave nos mecanismos de resistência a QRT, sendo possível quantificá-los em saliva. Neste estudo avaliamos a expressão de microRNAs na saliva de pacientes com CEC de cavidade oral e orofaringe e se esses microRNAs estão contidos dentro de microvesículas. MÉTODOS: Por meio de revisão da literatura e análises in sílico, selecionamos 8 microRNAs para serem avaliados: miR-15a-5p, 21-5p, 23a-3p, 125b-5p, 142-3p, 200b-3p, 296-5p e 503-5p. A expressão dos microRNAs foi determinada por PCR quantitativo na saliva livre de células de 70 pacientes portadores de CEC de cavidade oral e orofaringe localmente avançado e irressecável, em diferentes estágios da progressão da doença: antes de iniciar tratamento (G1), com falha do tratamento (G2) e livre da doença há 2 anos (G3) e em 28 voluntários sadios (G0). Microvesículas foram isolados por ultracentrifugação ou exoQuick, analisados por Microscopia Eletrônica de Transmissão (MET), Nanosight e para determinação da expressão do miR-21-5p. RESULTADOS: Os miRs-296-5p e 503-5p foram indetectáveis na maioria das amostras testadas. Quando comparamos os grupos em diferentes situações clínicas, encontramos diferença significativa na expressão do miR-21-5p (p=0.005), miR-23a-3p (p=0,026), miR-125-5p (p=0,013), miR-142-3p (p=0,033) e miR-200b-3p (p=0,031). Observou-se aumento na expressão dos miRs 21-5p (p=0,001), 23a-3p (p=0,004), 125b-5p (p=0,026) e 142-3p (p=0,005) na saliva dos pacientes em G1 em relação ao voluntários sadios (G0). O grupo G3 também apresentou maior expressão do mir-21-5p (p=0,018), 125b-5p (p=0,002) e 200b-3p (p=0,014) comparado ao G0, assim como o grupo G2 teve maior expressão do mir-15a-5p (p=0,023) e 23a-3p (p=0,017) comparado ao grupo G0. O grupo G2 apresentou menor expressão do miR-200b-3p (p= 0,019) e maior expressão do miR-15a-5p (p=0,057) em relação ao grupo G3. Além disso, os pacientes tabagistas e/ou etilistas apresentaram maior expressão relativa do miR-21-5p (p=0,001 e p=0,046, respectivamente) e os etilistas também tiveram maior expressão do miR-200b-3p (p=0,013). Com relação à resposta inicial do paciente ao tratamento avaliada pelo médico bem como, com a resposta a longo prazo (recidiva, status global e prognóstico), a expressão dos miR-15a-5p, miR-125b-5p, miR-23a-3p e miR-142-3p apresentaram associação com sobrevida livre de progressão e sobrevida global, porém não atingiram significância estatística. Microvesículas foram detectadas na saliva tanto na MET como na contagem no nanosight. A expressão do miR-21-5p foi predominantemente detectada dentro de microveículas em relação ao sobrenadante livre de vesículas. CONCLUSÕES: Alguns dos microRNAs analisados foram diferencialmente expressos entre os diferentes grupos estudados, a expressão do miR-21 foi associada ao tabagismo e etilismo e a do miR-200b com etilismo e a expressão de alguns microRNAs podem estar associadas à resposta ao tratamento e ao prognóstico dos pacientesBACKGROUND: Most patients with HNSCC are diagnosed in advanced stages of the disease, with unsatisfactory survival rates. In locally advanced and unresectable carcinoma, the standard treatment in ICESP is cisplatin based QRT. However, about two-thirds of these patients have local recurrence, distance or death within five years. Understanding the QRT resistance mechanisms and discovery of markers that may indicate benefit of treatment is a great challenge. MicroRNAs have key role in the mechanisms of QRT resistance and are detectable in saliva. In the present study we analyzed the expression of microRNAs in the saliva from oral cavity/oropharynx squamous cell carcinoma (OSCC) patients and whether these microRNAs are contained within exosomes. METHODS: Through a review of studies in the literature and by in silico analysis, we choose 8 microRNAs to be evaluated: miR-15a-5p, 21-5p, 23a-3p, 125b-5p, 142-3p, 200b-3p, 296-5p and 503-5p. The expression of microRNAs was determined by quantitative PCR in the cell-free saliva from 70 locally advanced and unresectable OSCC patients at different stages of disease progression: treatment naive (G1), after treatment failure (G2) and disease free for at least 2 years (G3) and 28 healthy volunteers (G0). Exosomes were isolated by ultracentrifugation or exoQuick, analyzed by transmission electron microscopy (MET), Nanosight quantification and by determination of the miR-21-5p expression. RESULTS: The miRs-296-5p and 503-5p were undetectable in almost all saliva samples. Significant differences was observed in the expression of miR-21-5p (p=0.005), miR-23a-3p (p=0.026), miR-125-5p (p=0.013) miR-142-3p (p=0.033) and miR-200b-3p (p=0.031) among the groups analyzed. The expression of miRs 21-5p (p=0.001), 23a-3p (p=0.004), 125b-5p (p=0.026) and 142-3p (p=0.005) were high in saliva of G1 patients as compared to heath volunteers (G0). The G3 group also showed higher expression of mir-21-5p (p=0.018), 125b-5p (p=0.002) and 200b-3p (p=0.014) and G2 presented higher expression of miR-15a-5p (p=0.023) and 23a-3p (p=0.017) as both compared to the G0. The group G2 presented lower expression of the miR-200b-3p (p=0.019) and higher expression of the miR-15a-5p (p=0.057) as compared to the G3 group. In addition, saliva from the smokers and/or drinkers patients showed high relative expression of the miR-21-5p (p=0.001 e p=0.046; respectively) compared to former drinker/smokers and drinkers also showed high expression of the miR-200b-3p (p=0.013). In relation to the initial response to treatment assessed by the physician, as well the long-term response (relapse, global status and prognosis), the expression of the miR-15a-5p, miR-125b-5p, miR-23a-3p e miR-142-3p showed association with progression-free survival and overall survival, however did not reach statistical significance. Microvesicles were detected in saliva by both MET as the count in nanosight. The expression of the miR-21-5p was predominantly detected in microvesicles in relation to the supernatant. CONCLUSIONS: Some of the microRNAs analyzed were differentially expressed between the different groups, the expression of the miR-21 was associated with smoking and drinking habits and of the miR-200b with drinking habits and the expression of some microRNAs may be associated with the treatment response and prognosis of the patients
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Tatjana, Šarčev. "Prognostički faktori u lečenju medijastinoskopski dokazanog N2 i N3 stadijuma nemikrocelularnog karcinoma bronha." Phd thesis, Univerzitet u Novom Sadu, Medicinski fakultet u Novom Sadu, 2014. https://www.cris.uns.ac.rs/record.jsf?recordId=86753&source=NDLTD&language=en.
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Karcinom bronha je danas u svetu najčešći uzrok smrti povezanih sa malignim bolestima. U XX veku je registrovan značajan porast kako incidence, tako i mortaliteta karcinoma bronha u većini zemalja. Medijana preživljavanja u svim stadijumima bolesti se značajno poboljšala poslednjih godina XX veka, ali nedovoljno u odnosu na očekivano. U najvećem broju slučajeva, bolest se otkriva u uznapredovalom stadijumu, kada je radikalno hirurško lečenje kao optimalan vid lečenja nemoguće. Određivanje stadijuma bolesti (stejdžing) je najbitniji segment u evaluaciji svakog bolesnika s karcinomom bronha. Utvrđivanje zahvaćenosti medijastinalnih limfnih čvorova karcinomom je od posebne važnosti, jer je u velikom broju slučajeva upravo nodalni status faktor koji određuje svsishodnost primene hirurškog lečenja, radioterapije i hemioterapije, a samim tim i jedan od bitnih faktora prognoze bolesnika sa nemikrocelularnim karcinomom bronha NSCLC. Bolesnici sa dokazanom zahvaćenošću N2 medijastinalnih limfnih čvorova se svrstavaju u IIIA stadijum NSCLC koji je potencijalno resektabilan, dok se bolesnici sa dokazanom zahvaćenošću N3 medijastinalnih limfnih čvorova svrstavaju u IIIB stadijum NSCLC, koji se smatra neresektabilnim. Cilj ove doktorske disertacije je bio da se utvrdi da li postoje prognostički značajni faktori za rezultat lečenja medijastinoskopski dokazanog N2 i N3 stadijuma NSCLC. Studija je bila nerandomizovana, delom retrospektivnog, a delom prospektivnog karaktera. U ispitivanje je uključeno 60 bolesnika lečenih u Institutu za plućne bolesti Vojvodine tokom 2006., 2007. i 2008. godine. Kod svih uključenih bolesnika medijastinoskopijom je dokazana propagacija NSCLC u medijastinalne limfne čvorove. U radu su analizirani sledeći faktori: pol, starost, ECOG performans status, pridružena hronična opstruktivna bolest pluća (HOBP), pridruženo kardiovaskularno oboljenje sa simtomatologijom klasifikovanom prema NYHA, T faktor, lokalizacija i broj medijastinoskopski dokazanih metastatski zahvaćenih limfnih čvorova, vrsta primenjenog lečenja (hemioradioterapija, hemioterapija, operacija), rezultat lečenja (odgovor na terapiju i preživljavanje). Univarijantnom analizom je utvrđeno da su kod bolesnika sa medijastinoskopski dokazanim N2 i N3 stadijumom NSCLC prognostički faktori koji su imali uticaj na lošije preživljavanje bili: ECOG PS 2 (p=0,00000), pridruženo kardivaskularno oboljenja sa simptomatologijom klase NYHA II (p=0,00113), zahvaćenost kontralateralnih medijastinalnih medijastinalnih limfnih čvorova (N3 stadijum) (p=0,000003), dok je uticaj zahvaćenosti više pozicija ipsilateralnih medijastinalnih limfnih čvorova (multi station N2) bio na granici statističke značajnosti (p=0,05385). Utvrđeno je da bolesnici sa N2 i N3 stadijumom NSCLC lečeni hemioradioterapijom imaju bolju stopu odgovora na primenjenu terapiju u odnosu na bolesnike lečene samo hemioterapijom (p=0,03118), kao i da operativno lečenje primenjeno kod bolesnika koji su imali dobar odgovor na sprovedenu terapiju ima statistički značajan uticaj u vidu boljeg preživljavanja (p=0,00121). Univarijantnom analizom nije utvrđen značajan uticaj sledećih faktora na preživljavanje bolesnika sa N2 i N3 stadijomom NSCLC: pol, starost, pridružena HOBP, skvamozni tip NSCLC i T faktor. Multivarijantnom analizom su kao nezavisni prognostički faktori na preživljavanje bolesnika sa N2 i N3 stadijumom NSCLC utvrđeni klinički N status (bolje preživljavanje ima N2 u odnosu na N3 stadijum) i sprovedena terapija (bolje preživljavanje ima hemioradioterapija u odnosu na hemioterapiju). Dobijeni rezultati navode nas na zaključak da su pozicija i broj zahvaćenih pozicija medijastinalnih limfnih čvorova, koji su utvrđeni medijastinoskopski, kao i sprovođenje multimodalnog lečenja ključni prognostički faktori za preživljavanje bolesnika sa N2 i N3 stadijumom NSCLC.Lung cancer is the most common cause of cancer related mortality worldwide. Increase in both incidence and mortality of lung cancer was registered throughout 20th century. The median survival in every stage of lung cancer has been improved in last years of 20th century but it is still not satisfactory. In most cases, lung cancer is diagnosed in advanced stage when surgical treatment as the optimal approach is not possible. Staging is the most important element in the evaluation of every lung cancer patient. Mediastinal lymph node involvement is crucial, because in most of the cases nodal staging is factor which determines appropriate use of surgery, radiotherapy and chemotherapy and it is one of the important factors influencing prognosis of lung cancer patients. Patients with proven involvement of ipsilateral mediastinal lymph nodes (N2 stage) are categorized in IIIA stage which is considered to be potentially resectable, and patients with proven involvement of contralateral mediastinal lymph nodes (N3 stage) are categorized in IIIB stage, which is considered to be nonresectable. The aim of this study was the determination of significant prognostic factors that have influence on treatment and survival of non-small cell lung cancer (NSCLC) patients in stage N2 and N3. Study was nonrandomized, partially retrospective and partially prospective. It included 60 patients treated at the Institute for Pulmonary Diseases of Vojvodina during 2006, 2007 and 2008. Cancer involvement of mediastinal lymph nodes was determined by mediastinoscopy in every patient. In study we analyzed following factors: gender, age, ECOG performance status, associated chronic obstructive pulmonary disease (COPD), associated cardiovascular disease with symptoms graded by NYHA classification, T status, position and number of involved mediastinal lymph nodes, applied treatment (surgery, chemoradiotherapy, chemotherapy alone), treatment result (response to treatment and survival). Prognostic factors for poorer survival on univariant analysis were ECOG PS 2 (p=0,0000), associated cardiovascular disease with symptoms NYHA II (p=0,00113) and involvement of contralateral mediastinal lymph nodes (N3 stage) (p=0,00003) while multi station N2 disease was borderline significant at level of p=0,05385. It was determined that patients treated with chemoradiotherapy achieved better response to treatment compared to patients treated with chemotherapy alone (p=0,03118). Univariant analyses did not confirm significance of gender, age, associate COPD, squamous cell lung cancer and T factor on survival. Multivariante analyses identified N status (better survival has N2 stage compared to N3 stage of NSCLC) and conducted treatment (better survival has chemoradiotherapy compared to chemotherapy alone) as independent prognostic factors. Our results suggest that position and number of cancer involved mediastinal lymph nodes position, proven by mediastinoscopy, as well as the conducted multimodality treatment are key prognostic factors which might influence the survival of patients with N2 and N3 stage of NSCLC.
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Rivelli, Thomás Giollo. "Avaliação de toxicidades tardias em pacientes com carcinoma epidermoide de cabeça e pescoço submetidos a quimiorradiação concomitante baseada em cisplatina." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5155/tde-24102018-132812/.
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Introdução: A quimiorradioterapia (QRT) concomitante baseada em cisplatina é uma opção de tratamento empregada para os pacientes com carcinoma epidermoide de cabeça e pescoço (CECCP) localmente avançado e com bom performance status, seja em caráter adjuvante ou definitivo. O ganho de sobrevida com esta modalidade de tratamento é acompanhado de aumento das toxicidades agudas em comparação com a radioterapia isolada. A ocorrência de toxicidades tardias é menos reportada na literatura e incluem xerostomia, disfagia, hipotireoidismo, ototoxicidade, fístula/necrose cutânea, dentre outras. Tais sequelas tardias podem comprometer a qualidade de vida do sobrevivente ao CECCP. Objetivos: Verificar a prevalência de toxicidades tardias em sobreviventes ao CECCP tratados com QRT baseada em cisplatina. Métodos: Estudo transversal, uni-institucional, que incluiu de forma sequencial pacientes acima de 18 anos, tratados para CECCP (sítios primários: nasofaringe, orofaringe, cavidade oral, hipofaringe e laringe) e que haviam recebido QRT adjuvante ou definitiva, baseada em cisplatina. Estes pacientes estavam em seguimento há pelo menos 2 anos, sem evidência de doença. Os pacientes realizaram audiometria, endoscopia digestiva alta (EDA), nasofibrolaringoscopia da deglutição (NFL), exames laboratoriais (toxicidade tireoidiana e renal). Os pacientes incluídos também foram examinados clinicamente e as toxicidades apresentadas foram graduadas de acordo com a escala de toxicidades tardias do RTOG/EORTC. Os sobreviventes foram ainda avaliados quanto à percepção das toxicidades através de um inventário de sintomas e responderam questionários de qualidade de vida. Resultados: De janeiro de 2014 a fevereiro de 2017, 120 pacientes assinaram o TCLE. A idade mediana dos pacientes é 59 anos (21-78), com predomínio do sexo masculino (73%) e da cor branca (58%). Antecedente de tabagismo foi referido por 80% da amostra e de etilismo por 63%. Referente ao sítio primário, a maioria dos pacientes apresenta tumor em orofaringe (42%), seguido por laringe (23%) e cavidade oral (19%). O tempo de seguimento mediano é 42 meses (24-125). Há predomínio de pacientes com doença localmente avançada, tumores T3/T4 em 75% da amostra e N+ em 72%. A dose mediana de cisplatina recebida durante a concomitância foi 300 mg/m² (100-300) e de radioterapia foi 70 Gy (60-70,4). A QRT foi oferecida em caráter adjuvante em 49% da amostra. As toxicidades mais relatadas pelos pacientes foram: xerostomia (83%), alteração na voz (74%), saliva pegajosa (73%) e disfagia (73%). Ao se graduar as toxicidades conforme escala do RTOG/EORTC, verificou-se que a maioria das toxicidades apresentadas eram de graus leves, 1 ou 2. EDA encontrou estenose faríngea em 10% dos pacientes e NFL identificou fibrose em 37% dos sobreviventes. Dos pacientes submetidos a audiometria, 42% apresentaram perda auditiva de possível causa ototóxica. Cerca de 14% dos sobreviventes apresentam clearance de creatinina estimado < 60 mL/min/1,73m². Conclusões: Toxicidades tardias foram frequentemente reportadas pelos sobreviventes ao CECCP após QRT, porém, na maioria das vezes, de intensidade leve (graus 1 ou 2). Após a QRT, um seguimento cuidadoso é essencial para diagnóstico precoce e reabilitação a essas toxicidades, a fim de preservar a funcionalidade e qualidade de vida dos pacientesBackground: Cisplatin based CRT is the standard therapy for patients with locally advanced HNSCC with good performance status either as adjuvant or as definitive treatment. The survival gain with this treatment modality is accompanied by an increase in acute toxicities in comparison with isolated radiotherapy. The occurrence of LT is less reported in the literature and includes xerostomia, dysphagia, hypothyroidism, ototoxicity, cutaneous fistula / necrosis, among others. Such late sequelae may compromise the survivor\'s quality of life. Endpoints: To verify the prevalence of late toxicities in HNSCC survivors treated with cisplatin based CRT. Methods: A cross-sectional study that sequentially included patients over 18 years of age who were previously treated for HNSCC (primary sites: nasopharynx, oropharynx, oral cavity, hypopharynx and larynx) and who had received either adjuvant or definitive cisplatin based CRT. These patients were in follow-up for at least 2 years, with no evidence of disease. The patients underwent audiometry, upper GI endoscopy, nasopharyngolaryngoscopy (NPL), laboratory tests (thyroid and kidney toxicity). The included patients were also clinically assessed for mucous membrane, skin, subcutaneous tissue, salivary gland, larynx and esophagus LT according to the RTOG/EORTC Late Radiation Morbidity Scoring Schema. All patients answered a questionnaire about their perception of LT through a symptoms inventory and also answered QoL questionnaires. Results: From January 2014 to February 2017, 120 patients signed the informed consent form. The mean age of the patients is 59 years (21-78), predominantly male (73%) and white (58%). Previous smoking habits were reported by 80% of the sample and alcohol consumption by 63%. Most common primary sites were oropharynx (42%), followed by larynx (23%) and oral cavity (19%). The median follow-up time is 42 months (24-125). There was a predominance of locally advanced disease, T3 / T4 tumors in 75% of the sample and N + in 72%. The median cisplatin dose during concomitance was 300 mg/m² (100-300) and the median radiotherapy delivered dose was 70Gy (60-70.4). CRT was delivered as an adjuvant treatment in 49% of the sample. The most frequently selfreported LT were xerostomia (83%), voice disorders (74%), sticky saliva (73%) and dysphagia (73%). Assessing the toxicities according to the RTOG / EORTC scale most of them were mild, grade 1-2. Upper GI endoscopy diagnosed stenosis in 10% of the patients and NPL identified fibrosis in 37% of the survivors. Audiometry identified ototoxic hearing loss in 42% of the sample. About 14% of the survivors present chronic kidney disease (an estimated creatinine clearance < 60 mL/min/1.73m²). Conclusion: High rates of self-reported LT were detected although most of them seem to be mild. After CRT, a close follow-up of HNSCC patients is essential for early diagnosis, treatment of these late sequelae and rehabilitation, in order to preserve QoL and functionality and to avoid lifethreatening conditions and social reclusion
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Díaz, Beveridge Roberto Pedro. "Clinical, radiological and pathological prognostic factors for local relapse, distant metastases and long-term survival in patients with locally advanced rectal cancer treated with neoadjuvant long-course oral fluoropyrimidine- and oxaliplatin-based chemoradiotherapy and total mesorectal excision: Can we move towards a more personalised approach?" Doctoral thesis, Universitat Autònoma de Barcelona, 2016. http://hdl.handle.net/10803/400285.
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Fundamentos: La radioterapia (RT) neoadyuvante previa a la cirugía, ya sea la radioterapia de duración corta (RTDC) como la radioterapia de duración larga combinada con quimioterapia (QT) basada en 5-FU (QRTLD), es usada de forma rutinaria en el manejo del cáncer de recto localmente avanzado, con beneficios consistentes en el riesgo de recidiva local. Desafortunadamente, no se han podido demostrar mejorías en la supervivencia, especialmente en los casos tratados con cirugía radical en forma de una escisión mesorectal total (EMT). El riesgo de sobretratar a algunos pacientes y los posibles efectos secundarios a largo plazo han provocado a su vez dudas sobre el manejo con RT neoadyuvante, especialmente con QRTLD, en todos los pacientes con cáncer de recto localmente avanzado independientemente de su riesgo basal de recidiva local.
Material y métodos: Revisión retrospectiva de una base prospectiva de pacientes con cáncer de recto cT3-T4 y/o cN+, tratados entre 1999 y 2014 con QRTLD basada en fluoropirimidinas orales y (en un 65%) oxaliplatino, seguido de EMT y QT adyuvante basada en 5-FU. Evaluamos factores pronóstico clínicos, radiológicos y patológicos para un mayor riesgo de recidiva local y de metástasis a distancia y una menor supervivencia libre de progresión (SLP) y supervivencia global (SG).
Resultados: 203 pacientes fueron analizados. El riesgo de progresión precoz fue bajo y la mayor parte de pacientes procedieron a cirugía; hubo una EMT satisfactoria en el 89.7%. La tasa de infraestadiaje fue del 70.4% y el porcentaje de respuestas completas patológicas fue del 14.9%. No hubo ningún beneficio con la adición de oxaliplatino a la QRTLD. La tasa de recidivas locales fue del 8.3%. Los factores de riesgo para la recidiva local y para las metástasis a distancia fueron, con un valor variable para las dos situaciones, una EMT no exitosa, la calidad insuficiente del mesorecto, una resección R2, afectación del margen circunferencial radial (MCR) y del margen distal, no infraestadiaje, tumores pobremente diferenciados, regresión tumoral moderada o mínima, invasión perineural, afectación patológica linfática y una gran carga tumoral linfática. Los factores pronóstico clásicos como el estadio ypT ó ypN tuvieron mayor importancia que la regresión tumoral patológica. En el análisis multivariante, la afectación del MCR y la invasión perineural mantuvieron la significación. La cumplimentación de la QT adyuvante fue pobre, especialmente en los pacientes ancianos; menos de la mitad recibieron la dosis completa prevista.
La SLP y SG a 5 y 10 años fue del 71.4% y 54.9% y del 75.4% y 62.4%, respectivamente. Los pacientes ancianos tuvieron una peor SLP y SG; ello estaba ligado a un aumento de las toxicidades graves no previsibles y una menor cumplimentación de la QRTLD y de la QT adyuvante. Los tumores mucinosos mostraron una respuesta muy pobre a la QRTLD. Factores significativos en el análisis multivariante para SLP y SG fueron una mayor edad, afectación del MRC, una EMT no exitosa y una gran carga tumoral linfática.
Conclusiones: El pronóstico de los pacientes con un cancer de recto está determinado por dos factores competitivos: el riesgo de recidiva local y el de las metástasis a distancia. La identificación de los pacientes con un riesgo muy bajo de recidiva local, en donde el beneficio de la RT sea escaso depende de una exquisita estadificación con RMN y de un equipo quirúrgico especializado en la EMT. Un MRC libre y una EMT exitosa son los factores más importantes; los tumores rectales bajos y la carga linfática son también importantes. La QRTLD debería ser usada en los pacientes con una fascia mesorectal afecta clínica. El papel de la QT adyuvante es controvertido, aunque la cumplimentación es pobre. La QT neoadyuvante es una opción atractiva, especialmente en los pacientes con un mayor riesgo de metástasis a distancia. Por el contrario, otras opciones menos agresivas y mejor toleradas, como la RTCD, deberían ser usadas en pacientes ancianos o frágiles.Background: Neoadjuvant radiotherapy previous to radical surgery, both as short-course radiotherapy (SCRT) and as long-course radiotherapy combined with 5-FU-based chemotherapy (LCRCT), is routinely used in the management of locally advanced rectal cancer, with consistent benefits in the reduction of the local relapse risk. Unfortunately, survival benefits have been elusive to demonstrate with this approach, especially in the setting of radical surgery in the form of total mesorectal excision (TME). Concerns about over-treating early-stage patients and of the possible long-term side effects have also cast more doubts in a blanket approach of treating all patients with neoadjuvant radiotherapy, especially with LCRT. Material and methods: Retrospective review of a prospective base of patients with cT3-T4 and/or N+ rectal cancer treated at our Institution between 1999 and 2014 with LCRCT and oral fluoropyrimidines and (in 65% of patients) oxaliplatin, followed by TME and adjuvant 5-FU-based chemotherapy. We report clinical, radiological and pathological prognostic factors for local relapse, distant metastases and long-term survival endpoints (disease-free survival (DFS) and overall survival (OS)) Results: 203 patients were analysed. The risk of early progression was small and most proceeded to surgery; a TME was done in 89.7%. The downstaging rate was 70.4% and the pathological complete response rate was 14.9%. No benefit was seen with the addition of oxaliplatin to LCRCT. Local relapse rate was 8.3%. Risk factors for local relapse and distant metastases were, to a varying degree for each situation, an unsuccessful TME, the unsatisfactory quality of the mesorectum, an R2 resection, involvement of the circumferential (CRM) and distal margins, no downstaging, poorly differentiated tumours, moderate or minimal regression, perineural invasion, pathological lymph node invasion and heavy lymph node burden. Classical pathological data such as ypT and ypN stage were better prognostic factors than tumour regression grading. In the multivariate analysis, CRM and perineural invasion retained their prognostic value. Compliance to adjuvant chemotherapy was poor, especially in elderly patients; less than half of patients received the full intended dose. 5- and 10-year DFS and OS were 71.4% and 54.9% and 75.4% and 62.4%, respectively. Elderly patients had an overall worse survival compared to younger patients; this was linked to higher unexpected toxicity and a lower compliance with LCRCT and adjuvant chemotherapy. Mucinous tumours showed a very poor response to LCRCT. Significant factors in the multivariate analysis for OS and DFS were older age, CRM involvement, an unsuccessful TME and a heavy lymph node burden. Conclusions: The prognosis of patients with locally advanced rectal cancer is determined by two competing factors: the risk of local relapse and the risk of distant metastases. The identification of patients with an extremely low risk of local relapse where radiotherapy would presumably offer little benefit is based on the premise of an exquisite imaging staging with MRI, supplemented with EUS, and a surgical team specialized in the TME procedure. A free CRM and a successful TME procedure are the most important factors; lower rectal tumours and a heavy lymph node burden are also important. In patients with invasion of the mesorectal fascia in the MRI, LCRCT should be used in order to lower the risk of a positive CRM. The role of adjuvant chemotherapy remains surprisingly undefined, although the compliance rates are poor in all published trials. Neoadjuvant chemotherapy is a possible option, especially in patients with a higher risk of distant metastases. On the other hand, other, better tolerated, options such as SCRT should be used in elderly or frail patients.
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Sundelin, Kaarina. "Head and Neck Cancer : Factors Affecting Tumour Growth." Doctoral thesis, Linköping : Univ, 2007. http://www.bibl.liu.se/liupubl/disp/disp2007/med1032s.pdf.
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中原, 理絵, and Rie Nakahara. "Treatment outcomes of definitive chemoradiotherapy for patients with hypopharyngeal cancer." Thesis, 2014. http://hdl.handle.net/2237/20391.
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陳昭如. "Nutritional state associated factors among esophageal cancer patients receiving concurrent chemoradiotherapy." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/20743818923696752602.
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碩士美和科技大學
健康照護研究所
104
This study focused on nutritional state associated factors among esophageal cancer patients receiving concurrent chemoradiotherapy. In cross-sectional survey study, purposive sampling approach, the resumption of the case at a medical center in the south of Hematology and Oncology and radiation oncology clinic; collected 96 esophageal cancer patients. The questionnaire included basic properties (contains basic information and health variables), Social Support Scale, symptom distress scale, nutrition assessment. Descriptive statistical analysis, t test, analysis of variance, Pearson product moment correlation and regression analysis statistical method analyzed data. The results affect the nutritional status of patients predictors have "symptom distress", "physical functional status", "primary caregivers", "family income", "marital status." The main symptom distress except esophageal dysphagia, "poor appetite", "tired", "pain", "oral / mucosal damage" will affect the patient's eating habits, and displays the patient in radiation therapy of acute chemotherapy, have problems eating and nutrition. Married, and the primary caregivers and psychological supporters who are spouses, relatives and friends of his family and their social support system of health care are high, and relatively good nutritional status. The results of this study will help nurses understand the nutritional status of focus of esophageal cancer care, it is recommended to assess the nutritional status of nurses in patient care process, the only timely provide appropriate care. Nursing education can help to enhance cancer care symptom distress related to the teaching and assessment of nutritional status, help improve patient nutrition and enhance treatment success rate.
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Chen, Kai-Li, and 陳凱麗. "The Lived Experience of the Women with Cervical Cancer During Concurrent Chemoradiotherapy." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/75422848290188389760.
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碩士國立臺灣大學
護理學研究所
97
Cervical cancer could be totally healed if it is diagnosed in cervical carcinoma in situ stage. However, many patients did not obtain confirmed diagnosis until the cancer proceeds to its advance stage. Concurrent chemoradiotherapy has become the standard treatment of local advance cervical cancer since 1999. The new treatment improved patient’s survival but they therefore suffer from a series of concurrent chemoradiotherapy treatment procedures which cause them enormous physical and psychological impacts. The purpose of this study was to explore lived experiences of patients receiving concurrent chemoradiotherapy treatment in a medical center in Taipei City. Qualitative research methods were used to figure out patients’ profound experiences. Seven patients receiving concurrent chemoradiotherapy treatment were recruited by using purposive sampling strategy. As an observer-as-participant, the author took care of the subjects, observed the process while patients receiving treatments, and talked to patients in order to understand their explicit and implicit experiences. All the data were densely described and analyzed inductively. Five main themes were identified as the followings: （1）complicated emotions while the cancer diagnosis became apparent; （2） strong fear of the coming battles with cancer treatments; （3） suffering from the first stage treatment; （4） experiencing the most painful stage of the treatments; and （5） ongoing fright after the treatment procedures. The staged and anguished experiences among women with cervical cancer and receiving concurrent chemoradiotherapy treatment were uncovered in this study. Implications and suggestions for health professionals were made based on the findings to improve the quality of care for their patients.
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Yang, Ching-chieh, and 楊清傑. "Clinical Significance of Tumor Regression Grading after Preoperative Chemoradiotherapy for Rectal Cancer." Thesis, 2013. http://ndltd.ncl.edu.tw/handle/00840578966320078102.
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碩士國立中山大學
生物科學系研究所
101
Preoperative chemoradiotherapy has been the standard treatment for locally advanced rectal cancer patients but there is no technique suggested to be used to predicate the outcome. Here, we use the tumor regression grading (TRG) and analyzed it with clinic-pathological parameters and survival rate. One hundred and seventy-two patients with rectal cancers were enrolled in this study from January 1998 to December 2008. All patients underwent preoperative chemoradiotherapy and curative surgery for rectal cancer (stages I-III) at our institute. TRG was retrospective reviwed on excised specimens from the patients after radical surgery. Preoperative concurrent chemoradiotherapy was given at a total dose of 45-50.4 Gy in 25 fractions over a period about 5.5 weeks, and a continuous infusion of 5-fluorouracil (300 mg/m2/day over 24 hours, 5 days per week for 5 weeks) was administered. Surgery was performed 4-6 weeks after completion of the preoperative chemoradiotherapy. Our result showed that subgroup of complete response (TRG 4), intermittent response (TRG 2-3), and minor or no response TRG (0-1) were found in 9.9%, 68.6%, and 21.5% of these resected specimens. Five-year overall survival (OS) after preoperative chemoradiotherapy and curative resection was 93% for TRG 4, 77% for grouped TRG 2-3, and 47% for grouped TRG 0-1 (P=.037). Patients with more tumor regression (4 vs. 2-3 vs. 01) also have better results for 5-year local-free (LFS), disease-free (DFS), and metastases free survival (MFS) (P = .004, P = .002, and P = .0001, respectively). But in multivariate analysis, the vascular invasion of pathologic specimens and TRG were the most important independent prognostic factors for LFS and DFS. In conclusion, higher TRG after preoperative chemoradiotherapy for rectal cancer closely contributed to better survival and local control. The TRG is considered to be a significant prognostic factor but it could not predict distant metastases.
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Edge, S. D., I. Renard, E. Pyne, Hannah Moody, R. Roy, A. W. Beavis, S. J. Archibald, C. J. Cawthorne, S. G. Maher, and I. M. Pires. "PI3K inhibition as a novel therapeutic strategy for neoadjuvant chemoradiotherapy resistant oesophageal adenocarcinoma." 2001. http://hdl.handle.net/10454/18357.
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NoNeoadjuvant chemoradiotherapy (neo-CRT) prior to surgery is the standard of care for oesophageal adenocarcinoma (OAC) patients. Unfortunately, most patients fail to respond to treatment. MiR-187 was previously shown to be downregulated in neo-CRT non-responders, whist in vitro miR-187 overexpression enhanced radiosensitivity and upregulated PTEN. This study evaluates the role of miR-187 and downstream PI3K signalling in radiation response in OAC. The effect of miR-187 overexpression on downstream PI3K signalling was evaluated in OAC cell lines by qPCR and Western blotting. PTEN expression was analysed in OAC pre-treatment biopsies of neo-CRT responders and non-responders. Pharmacological inhibition of PI3K using GDC-0941 was evaluated in combination with radiotherapy in two-dimensional and three-dimensional OAC models in vitro and as a single agent in vivo. Radiation response in vitro was assessed via clonogenic assay. PTEN expression was significantly decreased in neo-CRT non-responders. MiR-187 overexpression significantly upregulated PTEN expression and inhibited downstream PI3K signalling in vitro. GDC-0941 significantly reduced viability and enhanced radiation response in vitro and led to tumour growth inhibition as a single agent in vivo. Targeting of PI3K signalling is a promising therapeutic strategy for OAC patients who have repressed miR-187 expression and do not respond to conventional neo-CRT. This is the first study evaluating the effect of PI3K inhibition on radiosensitivity in OAC, with a particular focus on patients that do not respond to neo-CRT. We have shown for the first time that targeting of PI3K signalling is a promising alternative therapeutic strategy for OAC patients who do not respond to conventional neo-CRT.
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Edge, S. D., I. Renard, E. Pyne, Hannah L. Moody, R. Roy, A. W. Beavis, S. J. Archibald, C. J. Cawthorne, S. G. Maher, and I. M. Pires. "PI3K inhibition as a novel therapeutic strategy for neoadjuvant chemoradiotherapy resistant oesophageal adenocarcinoma." 2020. http://hdl.handle.net/10454/18357.
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NoNeoadjuvant chemoradiotherapy (neo-CRT) prior to surgery is the standard of care for oesophageal adenocarcinoma (OAC) patients. Unfortunately, most patients fail to respond to treatment. MiR-187 was previously shown to be downregulated in neo-CRT non-responders, whist in vitro miR-187 overexpression enhanced radiosensitivity and upregulated PTEN. This study evaluates the role of miR-187 and downstream PI3K signalling in radiation response in OAC. The effect of miR-187 overexpression on downstream PI3K signalling was evaluated in OAC cell lines by qPCR and Western blotting. PTEN expression was analysed in OAC pre-treatment biopsies of neo-CRT responders and non-responders. Pharmacological inhibition of PI3K using GDC-0941 was evaluated in combination with radiotherapy in two-dimensional and three-dimensional OAC models in vitro and as a single agent in vivo. Radiation response in vitro was assessed via clonogenic assay. PTEN expression was significantly decreased in neo-CRT non-responders. MiR-187 overexpression significantly upregulated PTEN expression and inhibited downstream PI3K signalling in vitro. GDC-0941 significantly reduced viability and enhanced radiation response in vitro and led to tumour growth inhibition as a single agent in vivo. Targeting of PI3K signalling is a promising therapeutic strategy for OAC patients who have repressed miR-187 expression and do not respond to conventional neo-CRT. This is the first study evaluating the effect of PI3K inhibition on radiosensitivity in OAC, with a particular focus on patients that do not respond to neo-CRT. We have shown for the first time that targeting of PI3K signalling is a promising alternative therapeutic strategy for OAC patients who do not respond to conventional neo-CRT.
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Andrade, Teresa do Rosário Richardson Rebello de. "Response of Rectal Cancer Patients to Long Course Neoadjuvant Chemoradiotherapy: Retrospective Cohort Study." Master's thesis, 2017. https://hdl.handle.net/10216/104163.
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Andrade, Teresa do Rosário Richardson Rebello de. "Response of Rectal Cancer Patients to Long Course Neoadjuvant Chemoradiotherapy: Retrospective Cohort Study." Dissertação, 2017. https://hdl.handle.net/10216/104163.
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Lo, Chuan Wei, and 羅全位. "Pre-treatment Risk Factors Assessment for Outcomes in Hypopharyngeal Carcinoma Patients with Concurrent Chemoradiotherapy." Thesis, 2008. http://ndltd.ncl.edu.tw/handle/5v4ry3.
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碩士長庚大學
醫學物理暨影像科學研究所
96
Purpose: To assess pre-treatment risk factors for survival in hypopharyngeal Carcinoma Patients treated with concurrent chemoradiotherapy (CCRT). Materials and Methods: We retrospectively analyzed data of primary stage M0 hypopharyngeal cancer patients who receiving concurrent chemoradiotherapy from May 2004 to May 2006. Excluding those with synchronous 2nd primary cancer or incomplete chart record, 30 patients were enrolled. To calculate SUV and TLG were performed using P-MOD. All of them received [18F] FDG PET before treatment. Actuarial overall survival (OS), recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) were calculated by Kaplan-Meier method. The Cox’s proportional hazards model was used for cluster analysis. Results: The 2-year OS, RFS, and DMFS were 59.03%, 47.27%, and 84.86%, respectively. Univariate analysis showed that Gross tumor volume (GTV)>465 (p = 0.0136), mean standardized uptake value (SUVmean)>6.4 (p = 0.0163), and total lesion glycolysis (TLG) (p < 0.0001) were significant risk factors for 2-year OS. No risk factors were related to RFS or DMFS. Cox’s proportional hazards model analysis showed that patients with 2 or 1 risk factors had 29-fold or 10-fold rate of death within 2 years. Conclusions: TLG is an important prognostic factor for primary hypopharyngeal cancer patients treated with CCRT. This “imaging biomarker” should be considered in further clinical study for hypopharyngeal cancer. Treatment strategy may be modified to radical surgery plus adjuvant therapy for patients with 2 risk factors.
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Yang, Kai-Lin, and 楊凱琳. "In vitro study of hyperthermia and its clinical application in combination with concurrent chemoradiotherapy." Thesis, 2018. http://ndltd.ncl.edu.tw/handle/2zfnj8.
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博士國立陽明大學
生物醫學影像暨放射科學系
106
The biologic properties of hyperthermia (HT) make it an important modality for cancer treatment, including its complementary role for radiotherapy, its radiosensitizing potential and immune-stimulating effects against tumor cells. Clinical evidence of tumor regression following heat treatments looked very promising, although controversial results existed. The key point may be adequate techniques, which can achieve uniform or selective heating. Radiofrequency-induced hyperthermia treatments for cancer include conventional capacitive coupling hyperthermia (cCHT) and modulated electro-hyperthermia (mEHT). The heating mechanism and the working power were different between the two hyperthermia methods, so we hypothesized that the different hyperthermia methods might cause different biological effects. In this study, we directly compared these methods with regard to in vitro cytotoxicity and mechanisms of action under isothermal conditions. Hepatoma (HepG2) cells were exposed to HT treatment (42°C for 30 min) using mEHT, cCHT or a water bath. Apoptotic cells were evaluated by Annexin-V assay and cell cycle analysis. Apoptotic pathway was evaluated by caspase-3, 8, 9 expression. Adhesion molecule expression, heat shock protein (HSP) release and calreticulin generation were also evaluated and compared. mEHT produced a much higher apoptosis rate (43.1% ± 5.8%) than cCHT (10.0% ± 0.6%), the water bath (8.4% ± 1.7%) or a 37°C control (6.6% ± 1.1%). The apoptosis-inducing effect of mEHT at 42°C was similar to that achieved with a water bath at 46°C. mEHT also increased expression of caspase-3, 8 and 9. All three hyperthermia methods increased intracellular heat shock protein 70 (Hsp70) levels, but only mEHT greatly increased the release of Hsp70 from cells. Calreticulin and E-cadherin levels in the cell membrane also increased after mEHT treatment, but not after cCHT or water bath. In conclusion, mEHT induces apoptosis more efficiently than cCHT or water bath, based on isothermal conditions. The finding suggested that mEHT may carry more significant non-thermal effect. For-example, these results suggested that mEHT seemed to selectively deposit energy on the cell membrane and may be a useful treatment modality that targets cancer cell membranes. In addition, the immunostimulatory effect with mEHT may be stronger due to higher levels of calreticulin expression and Hsp release. Concurrent chemoradiotherapy (CCRT) is one of the main treatment for various kinds of cancer. However, only CCRT may not be effective enough for some cancer conditions, or the doses of CCRT may be limited by normal tissue tolerance. Therefore, incorporation with other treatment modalities would be considered, such as surgery or hyperthermia. This is so-called multimodality cancer treatment. However, surgical excision is not suitable for many cancer patients, and in the situation we suggest that incorporation of immunotherapy or other immune-stimulating strategy such as hyperthermia should be evaluated. Hyperthermia can sensitize radiotherapy and may avoid toxicity caused by conventional high-dose CCRT. Further considering potential immune-stimulating effect from hyperthermia, perhaps the story of further studies in low-dose CCRT combining hyperthermia may be encouraging. We evaluate the efficacy and safety of low-dose CCRT combined with hyperthermia firstly in recurrent head and neck (HN) cancer. Despite aggressive efforts to cure HN cancer, a substantial proportion of patients with HN cancer will experience relapse or metastatic disease. Locoregional recurrence remains a serious problem. Only selected patients with a locoregional recurrence can be salvaged by surgery, such as those with limited invasion, good performance status, and no contraindication for surgery. When patients present with unresectable recurrent disease or are unable to undergo surgery, alternative nonsurgical treatments ranging from chemotherapy (ChT) alone to re-irradiation (re-RT) with or without ChT are recommended. The prognosis of recurrent HN cancer is poor, with a median overall survival of only 6 to 12 months. Immunotherapy using immune checkpoint inhibitor was approved for recurrent/metastatic HN cancer, but is very expensive. Hyperthermia can sensitize chemo-radiotherapy with the support of some early clinical studies in various cancers and can also serve as an immune-stimulating strategy with bench evidence. An important randomized phase III study also demonstrate that addition of regional hyperthermia to chemotherapy, followed by surgery with or without radiotherapy, improved local-regional tumor control in localized high-risk soft tissue sarcoma. Another small study in Japan showed that hyperthermia plus CCRT using superselective intra-arterial infusion with docetaxel and cisplatin provided good pathological response and locoregional control rates in primary advanced oral cancer patients with N3 metastatic lymph nodes. Hyperthermia combined with CCRT may have its role in the management of recurrent HN cancer. We hypothesized that the treatment response of low-dose CCRT combined with hyperthermia would be good, and conducted a single-arm phase II clinical trial which aimed at investigating the safety and efficacy of adding hyperthermia to salvage concurrent chemoradiotherapy (CCRT) for recurrent head and neck cancer. An interim analysis was conducted and reported. Patients with recurrent head and neck cancer, age of 20-85 years and unfitness for surgical excision were enrolled. Twenty-one eligible patients receiving hyperthermia during salvage CCRT per protocol were evaluated in this interim analysis. The treatment protocol included radiotherapy (RT) 10Gy/2 fractions in 2 weeks followed by 40Gy/20 fractions in 4 weeks (totaling 50Gy/22 fractions); hyperthermia for 40 minutes within 2 hours after RT, with maximum temperature of 42±0.5°C, once a week since the 1st week of RT, for 6 times; concurrent chemotherapy with cisplatin 20mg/m2 and docetaxel 10-12mg/m2 per week, for 6 weeks. Overall response rate, survival curves and toxicities were analyzed. Of all 21 patients, median age was 58 years (range, 37 to 73 years), 86% were male, 100% had ECOG performance status <2, and 100% previously received radiotherapy for their primary head and neck cancer. Overall response rate was 76% (complete response: 62%; partial response: 14%; stable disease: 14%; progressive disease: 10%). After a median follow-up of 14.8 months, median overall survival (OS) was 23.9 months, median progression-free survival (PFS) was 18.5 months, and median time to progression (TTP) was not reached. One-year rates of local-regional failure and distant metastasis were 33.4% and 11.6%, respectively. Among all patients, acute mucositis was grade 0-1 in 86%, grade 2 in 14%, and grade 3-5 in 0%; acute dermatitis was grade 0-1 in 90%, grade 2 in 10%, and grade 3-5 in 0%; grade 3-4 leucopenia, anemia and thrombocytopenia were 14%, 19% and 19%, respectively. Osteoradionecrosis was noted in 6 patients. No grade 5 toxicity was observed. In conclusion, for recurrent head and neck cancer, adding hyperthermia to salvage CCRT was very effective as compared to historical outcomes of re-irradiation cases. Treatment-related toxicities were tolerable. Continuing studies on hyperthermia is warranted.
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CHEN, YING-JUNG, and 陳盈蓉. "The effect of nutritional counseling model on oral cancer patients receiving post operative concurrent chemoradiotherapy." Thesis, 2016. http://ndltd.ncl.edu.tw/handle/55454597939310936933.
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碩士輔仁大學
營養科學系碩士班
104
Introduction: Eating betel nuts, smoking and drinking were the majority of carcinogenic factors so that oral cancer occurred mostly in men in Taiwan. Patients had a high weight loss and lower quality of life because of tumor location, cancer stage, treatment toxicity and side effects. Study suggested that nutrition intervention should be administered before the start of cancer therapy. In Taiwan, 30% adults had a deficiency of vitamin B2, so the status of vitamin B2 would be monitored in those patients. Objectives: The aim of the study was to improve the nutritional status of patients with oral cancer and reduce the percentages of body weight loss through personalized nutrition counseling. Design: This was a random, control trail. We randomly assigned 60 patients within 20-70 years old with postoperative oral cancer receiving concurrent chemoradiotherapy (CCRT) into two groups. Treatment group (T group) (n=30) had personalized nutrition counseling (1 time/week) until 1 month after treatment and control group (C group) (n=30) only got one nutritional education manual and was taken care by CGMF during treatment. The nutritional status would be assessed by Patient-Generated Subjective Global Assessment (PG-SGA), body composition, blood biochemical, physical activities questionnaire and 24-hour food intake at 4 timings: before treatment (T0), ending treatment (T1), treatment after 1 month (T2) and 3 months (T3) in two group. The side effects and compliance were also be observed. Results: No significant difference in baseline was observed between groups. There was no significant different in body weight loss and dietary intake between C group and T group during the period of time. However, vitamin D intake was higher than C group. No significant differences in PG-SGA, blood biochemical and vitamin B2 were observed between groups at 4 timings. Conclusion: The effect of personal nutritional counseling in patients with oral cancer improves dietary intake after CCRT. Nutritional counseling should be given after CCRT.
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Fang, Chih Hao, and 方志豪. "The Study of Treatment with Traditional Chinese Medicine for Chemoradiotherapy-induced Thrombocytopenia in Animal Model." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/87479517552164365532.
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碩士長庚大學
生物醫學研究所
99
Chemoradiotherapy-induced thrombocytopenia is happened in many cancer patients after treating chemotherapy multiple times. To date, platelet transfusion remains the most important treatment in clinical circumstances. But it may cause platelet alloimmunization by variation in HLA molecules. In past two decades, although many cytokines involving in megakaryocyte development have been candidates in Chemoradiotherapy-induced thrombocytopenia treatment, no cytokines can be well use in clinical practice. Traditional Chinese medicines (TCMs) may have a great potential to promote blood circulation, but whether it can be a treatment in Chemoradiotherapy-induced thrombocytopenia is not clear. In our clinical study, we treated cancer patients who received multiple times chemotherapy with many different TCMs and found it can increase peripheral platelet numbers. We fed the myelosuppressed mice with usual recommended clinical dose of aqueous extract of KL and HU, but no significant difference in number of peripheral platelets was found. Next, we tried another drug delivery system, using intraperitoneal injection (i.p) instead of feed. The results showed HU extract can increase peripheral platelet number at 7 day after chemotherapy. At 14 day after chemotherapy, i.p HU extract mice had higher platelet number than other TCMs and negative group. In addition, i.p HU extract mice had more nuclear cells in bone marrow environment. Importantly, platelet number of i.p HU extract mice could recover to normal range at 21 day after chemotherapy. We will use in vitro assay to confirm carboplatin-damaged BM cell could differentiate into CD41+ cell after treated with HU and KL+HU. And we using fetal liver derived megakaryocyte show more proplatelet formation after treated HU extract. Taken toge ther, our study will support TCMs can be a candidate in chemoradiotherapy-induced thrombocytopenia treatment.
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Chen, Shun Ting, and 陳舜鼎. "DangGui BuXue Tang Sensitizes Colorectal Cancer Cells to Chemoradiotherapy in vitro and in vivo Model." Thesis, 2017. http://ndltd.ncl.edu.tw/handle/2469ah.
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博士長庚大學
臨床醫學研究所中醫組
105
Chemotherapy is an important treatment modality for colon cancer, and concurrent chemoradiation therapy (CCRT) is the preferred treatment route for patients with stage II and III rectal cancer. The induction of autophagic cell death is an important process in the development of anticancer therapeutics. We examined how could DangGui BuXue Tang (DBT), a traditional Chinese herbal extract, against colorectal cancer (CRC) and its autophagy-related mechanism in sensitizing colorectal cancer cells for anticancer treatments. The polysaccharide-depleted fraction of DBT (DBT-PD) contains greater amounts of astragaloside IV and ferulic acid than the original formula does. Treatment of the murine colon carcinoma cell line (CT26) with DBT-PD inhibited cell growth, whereas treatment with comparable amounts of purified astragaloside IV and ferulic acid showed no significant effect. Concurrent treatment with DBT-PD increases the growth inhibitory effect of 5-fluorouracil up to 4.39-fold. DBT-PD enhances the effect of radiation therapy (RT) with a sensitizer enhancement ratio (SER) of up to 1.3 fold. It also increases the therapeutic effect of CCRT on CT26 cells. Cells treated with DBP-PD showed ultrastructural changes characteristic of autophagy, including multiple cytoplasmic vacuoles with double-layered membranes, vacuoles containing remnants of degraded organelles, marked swelling and vacuolization of mitochondria, and autolysosome-like vacuoles. In the tumor specimen, the expression of microtubule-associated proteins 1A/1B light chain 3B (LC3B) was upregulated by DBT-PD and DBT. In vitro experiments for mechanism clarification demonstrated that DBT-PD could induce autophagic death in CT26 cells accompanied by LC3B lipidation, downregulation of phospho-p70s6k, and upregulation of Atg7. RNA interference of Atg7, but not Atg5, partially reversed the effect of DBT-PD on LC3B lipidation and expression of phospho-p70s6k and Atg7. The changes in ultrastructural morphology and LC3B expression induced by DBT-PD were also partially blocked by the knockdown of Atg7 mRNA. We conclude that DBT-PD induces autophagy-associated cell death in CT26 cells through the upregulation of Atg7 and modulation of the mTOR/p70s6k signaling pathway, and may have the potential as the chemotherapy or radiotherapy sensitizer in colorectal cancer treatment.