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Academic literature on the topic 'Prostate – Cancer – Radiotherapy'

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Published: 4 June 2021
Last updated: 10 March 2023

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Journal articles on the topic "Prostate – Cancer – Radiotherapy"

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Catton, Charles N., Himu Lukka, and Jarad Martin. "Prostate Cancer Radiotherapy: An Evolving Paradigm." Journal of Clinical Oncology 36, no. 29 (October 10, 2018): 2909–13. http://dx.doi.org/10.1200/jco.2018.79.3257.

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The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A urologist referred a 69-year-old man for a radiotherapy opinion regarding a recently diagnosed adenocarcinoma of the prostate. Annual serum prostate-specific antigen (PSA) testing over 7 years demonstrated a rise in PSA from 1.36 ng/mL to 5.8 ng/mL, prompting a transrectal ultrasound that revealed a heterogeneous 37-mL gland containing no visualized hypoechoic nodules. Biopsy disclosed a Gleason score 3+4 (grade group 2) adenocarcinoma of the prostate. The synoptic report stated that six of 14 cores and 17% of the tissue were involved, with the greatest core involvement being 80% at the right apex. Perineural invasion was present without lymphovascular invasion. Disease was present bilaterally at the base, midgland, and apex.His medical history was significant only for treated peptic ulcer disease and he was taking no medication. His International Prostate Symptom Score was six of 35, and he reported being sexually active with good erectile function. There was no family history of prostate cancer. He is retired. Digital rectal examination revealed moderate benign prostatic hypertrophy with no suspicious nodules. A staging computerized tomography (CT) scan of the abdomen and pelvis and a whole-body bone scan ordered by his referring urologist reported no evidence of metastatic disease. The patient had discussed surgical options with his urologist and now wished to consider radiotherapy approaches.
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Park, Won. "Radiotherapy for prostate cancer." Journal of the Korean Medical Association 58, no. 1 (2015): 21. http://dx.doi.org/10.5124/jkma.2015.58.1.21.

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3

Khoo, V. "Radiotherapy of prostate cancer." European Journal of Cancer 47 (September 2011): S298—S301. http://dx.doi.org/10.1016/s0959-8049(11)70178-2.

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4

Nash, GF, KJ Turner, T. Hickish, J. Smith, M. Chand, and BJ Moran. "Interactions in the aetiology, presentation and management of synchronous and metachronous adenocarcinoma of the prostate and rectum." Annals of The Royal College of Surgeons of England 94, no. 7 (October 2012): 456–62. http://dx.doi.org/10.1308/003588412x13373405384611.

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Adenocarcinoma of the prostate and rectum are common male pelvic cancers and may present synchronously or metachronously and, due to their anatomic proximity. The treatment of rectal or prostate cancer (in particular surgery and/or radiotherapy) may alter the presentation, incidence and management should a metachronous tumour develop. This review focuses on the interaction between prostatic and rectal cancer diagnosis and management. We have restricted the scope of this large topic to general considerations, management of rectal cancer after prostate cancer treatment and vice versa, management of synchronous disease and cancer follow-up issues.
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Stanić, Jelena, Vesna Stanković, and Marina Nikitović. "Radiation toxicity in prostate cancer patients." Medicinski podmladak 72, no. 2 (2021): 26–33. http://dx.doi.org/10.5937/mp72-32377.

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Prostate cancer (PC) is the most frequent male tumor, accounting for about one-third of all cancers in men. Since survival is often favorable regardless of therapy, treatment decisions may depend on therapy-specific health outcomes. The majority of men initially diagnosed with localized PC ultimately die with, rather than of, their disease. As a result, men who are diagnosed will live many years with the treatment's sequelae. The major therapeutic strategies include radical prostatectomy or external beam radiotherapy. Radiotherapy is one of the curative treatment options. The tumor dose-response relationship has been studied and is widely accepted. The unsatisfactory local control with doses < 70 Gy led to dose escalation using highly precise radiotherapy techniques - three-dimensional conformal radiotherapy and intensity-modulated radiotherapy enabling the delivery of high radiation doses up to 74 - 78 Gy. Bowel, rectal and urinary toxicities are the principal limiting factors in delivering a high dose. Acute symptoms include a change in bowel habits, urgency, and fecal incontinence. The most commonly reported late toxicities were chronic diarrhea, proctitis, or rectal bleeding. Several factors have been associated with increased gastrointestinal toxicity such as larger bowel volume receiving high doses, the patient's age, diabetes, and concomitant use of androgen deprivation therapy. Bladder damage resulting from acute radiation toxicity is manifested as radiation cystitis (frequent urination and dysuric disorders). Smoking, previous abdominopelvic surgeries and the use of diuretics significantly affect the occurrence of acute genitourinary toxicity grade ≥ 2. Risk factors for the development of late genitourinary complications are higher radiation dose, previous urinary problems, transurethral interventions, and acute genitourinary complications. It is essential to strike a balance between the therapeutic benefits and radiotherapy side effects. Severe late complications significantly reduce the quality of life (QOL) of PC survivors. Early detection and proper evaluation of complications are especially important in increasing the patient's QOL.
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Ulys, Albertas, Alvydas Vėželis, Andrius Ivanauskas, and Marius Snicorius. "Treatment methods of prostate cancer recurrence after radiotherapy. Current treatment alternatives and our clinical experience." Lietuvos chirurgija 12, no. 3 (January 1, 2013): 138–43. http://dx.doi.org/10.15388/lietchirur.2013.3.1840.

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Background / objectiveProstate cancer is the most common cancer among men of Lithuania. Every year about 3000 new cases of prostate cancer are diagnosed in our country. Many patients receive radiotherapy as primary treatment. Unfortunately, after several years some of the patients are diagnosed with prostate cancer recurrence. These cases are more challenging and require to apply salvage treatment methods. The aim of this article is to present our clinical experience and discuss the main features, advantages and disadvantages of the treatment methods.Patients and methodsRetrospective analysis of 10 salvage prostate cancer recurrence treatment cases was completed. All patients previously received radiotherapy as primary treatment. 5 patients received salvage high- dose brachiterapy (group 1) and other 5- salvage cryotherapy (group 2). Prostate cancer recurrences were diagnosed by multiparametric MRI and ultrasound guided transrectal or transperineal biopsies.ResultsAverage patient age was 64,2±7,9 years in group 1 and 68±3,1 years in group 2. None of the patients had prostate cancer progression to lymph nodes (N) or metastases (M) on initial diagnosis or before salvage treatment. No intraoperative complications were observed. Average time between radiotherapy and salvage therapy in both groups was 88,9±30,1 months. In both groups 1 patient suffered from salvage treatment failure- prostate cancer progression was observed.ConclusionsCurrently there is no perfect treatment method for recurrent prostate cancer. Every situation requires universal aproach. Our initial experience shows that salvage cryotherapy and brachiterapy can be a viable alternative for patients with disease progression after radiotherapy.Key words: prostate cancer, prostate cancer recurrence, salvage treatment.Prostatos vėžio recidyvų po spindulinės terapijos gydymo metodaiŠiuolaikinėje medicinoje naudojami metodai ir mūsų klinikinė patirtis Įvadas / tikslasLietuvoje kasmet nustatoma apie 3000 naujų prostatos vėžio atvejų. Daugeliui pacientų taikomas spindulinis gydymas. Deja, praėjus keletui metų, kai kuriems pacientams diagnozuojamas prostatos vėžio recidyvavimas. Šiuo metu yra daug gydymometodų, bet dažnai iškyla problemų pasirenkant optimalų. Šio straipsnio tikslas – pasidalinti mūsų klinikine patirtimi bei apžvelgti prostatos vėžio recidyvų po spindulinės terapijos gydymo alternatyvas.Pacientai ir metodaiRetrospektyviai buvo išanalizuota dešimt pacientų, kuriems po pirminio gydymo radioterapija buvo diagnozuotas prostatos vėžio recidyvavimas. 5 pacientai buvo gydomi didelių dozių brachiterapija (1 grupė), o likusiems 5 buvo skirta krioterapija(2 grupė). Prostatos vėžio recidyvai diagnozuoti multiparametriniu kontroliuojant MRT ir ultragarsu atliktomis transrektalinėmis ir transperinealinėmis prostatos biopsijomis.RezultataiPirmoje grupėje vidutinis pacientų amžius buvo 64,2±7,9 metų, o antroje grupėje 68±3,1. Nė vienam pacientui nebuvo nustatytas prostatos vėžio išplitimas į limfmazgius (N) ar metastazavimas (M). Intraoperacinių komplikacijų nepasitaikė. Vidutiniškaitarp pirminės radioterapijos ir gelbstinčio prostatos vėžio recidyvavimo gydymo praėjo 88,9±30,1 mėnesio. Gelbstintis prostatos vėžio recidyvavimo gydymas buvo nesėkmingas dviem atvejais – po vieną atvejį abiejose grupėse.IšvadosŠiuo metu nėra tobulo gydymo tų pacientų, kuriems prostatos vėžys recidyvavo po spindulinio gydymo. Tokiais atvejais reikalingi unikalūs sprendimai. Mūsų nedidelė pirmoji patirtis rodo, jog gelbstinčioji krioterapija ir brachiterapija – tinkami metodaigydyti pacientams, kuriems recidyvavo prostatos vėžys po spindulinės terapijos.Reikšminiai žodžiai: prostatos vėžys, prostatos vėžio recidyvai, gelbstintis gydymas.
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Chua, Melvin, Erle Holgersen, Veronica Sabelnykova, Adriana Salcedo, Alice Meng, Michael Fraser, Theodorus Van Der Kwast, Paul Christopher Boutros, and Robert G. Bristow. "Genomic architecture of radioresistant prostate cancer." Journal of Clinical Oncology 35, no. 6_suppl (February 20, 2017): 26. http://dx.doi.org/10.1200/jco.2017.35.6_suppl.26.

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26 Background: Spatial intra-tumoral heterogeneity of prostate cancer is secondary to genomic diversity and multi-clonality. These unique features potentially promote resistance to treatment. Here, we investigated if clonal selection or adaptation of new clones dominates in prostate cancer at the time of recurrence following radiotherapy. Methods: We identified 11 patients with biopsy-proven multifocal recurrent prostate cancer following radiotherapy. Copy number aberration (CNA) profiling was performed on 33 anatomically distinct tumor foci with 11 matched-normals. 4 cases had matched pre-radiotherapy tumors for CNA profiling to assess for clonality. We evaluated for recurrent gene amplifications and deletions, and determined genomic instability by percent genome aberration (PGA). We also compared these genomic indices against 373 sporadic prostate cancers from the Canadian Prostate Cancer Gene Network. Results: We observed large intra- and inter-patient variation (p <0.001, one-way ANOVA) in PGA scores among the radioresistant tumors. Interestingly, although total CNA counts did not differ between the radioresistant and sporadic cohorts (median = 40, radioresistant vs 33, sporadic, p = 0.20], there was a trend for increased genomic instability in the radioresistant cohort (median PGA = 8.8 vs 4.9, p = 0.059). Spatial resolution of gene-level CNAs revealed the acquisition of CNAs that were both common and non-recurrent in the multi-focal radioresistant tumors, thus suggesting a common clonal origin, with subsequent divergent evolution. Importantly, we observed a mixture of CNAs, including known prognostic genes in prostate cancer, namely NKX3-1, PTEN, TP53, CDKN1B, and CDH1,that was shared between pre-treatment and radioresistant tumors, favoring clonal selection. We also discovered a novel deleted region on Chr3p, consisting of RAD18 and FANCD2, which was uniquely present in the radioresistant tumors. Conclusions: Our novel observations in a small cohort of radioresistant prostate cancers favor the model of clonal selection, as opposed to new-onset tumors. These results support the discovery of biomarkers a priori, and targeted treatment of these radioresistant clones to improve the therapeutic ratio of precision radiotherapy.
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Ghadjar, Pirus, Stefan Höcht, and Thomas Wiegel. "Postoperative radiotherapy in prostate cancer." Lancet 397, no. 10285 (May 2021): 1623. http://dx.doi.org/10.1016/s0140-6736(21)00273-7.

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Ohri, Nitin, Xinglei Shen, Robert B. Den, Adam P. Dicker, Edouard J. Trabulsi, and Timothy N. Showalter. "Salvage radiotherapy for prostate cancer." Cancer Biology & Therapy 13, no. 14 (December 6, 2012): 1449–53. http://dx.doi.org/10.4161/cbt.22006.

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Brenner, David J., and Eric J. Hall. "Hypofractionation in prostate cancer radiotherapy." Translational Cancer Research 7, S6 (July 2018): S632—S639. http://dx.doi.org/10.21037/tcr.2018.01.30.

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Dissertations / Theses on the topic "Prostate – Cancer – Radiotherapy"

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Rios, Patiño Richard. "Statistical modeling of bladder motion and deformation in prostate cancer radiotherapy." Thesis, Rennes 1, 2017. http://www.theses.fr/2017REN1S116/document.

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Le cancer de la prostate est le cancer le plus fréquent chez les hommes dans la plupart des pays développés. C'est le cancer le plus fréquent chez les hommes en France (73.609 cas en 2014) et en Colombie (9564 cas en 2014). En outre, c'est la troisième cause de décès par cancer chez les hommes dans les deux pays (9,3 % en France et 7,1 % en Colombie en 2014). L'une des techniques de traitement est la radiothérapie externe, qui consiste à délivrer un rayonnement ionisant à une cible clinique, à savoir la prostate et les vésicules séminales. En raison des variations anatomiques au cours du traitement, qui consiste en environ 40 fractions de rayonnement délivrant une dose totale allant de 70 à 80Gy, des marges de sécurité sont définies autour de la cible tumorale lors de la planification du traitement. Ceci entraîne des portions d'organes sains voisins de la prostate - la vessie et le rectum - à être inclus dans le volume cible, pouvant conduire à des événements indésirables affectant les fonctions urinaires (hématurie et cystite, entre autres) ou rectale (saignement rectal, incontinence fécale, Etc.). La vessie présente les plus grandes variations de forme entre fractions de traitement, provoquées par des changements continus de volume. Ces variations de forme introduisent des incertitudes géométriques qui rendent difficile l'évaluation de la dose réellement délivrée à la vessie pendant le traitement. Ces incertitudes limitent la possibilité de modéliser une relation dose-volume pour la toxicité génito-urinaire tardive (GU). Le projet QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) a déclaré que la relation dose-réponse pour la toxicité gastro-intestinale tardive (GI) était loin d'être établie. Les variables dosimétriques obtenues à partir de la tomodensitométrie de planification peuvent être faiblement représentative de la dose effectivement administrée. En conséquence, il est crucial de quantifier les incertitudes produites par les variations inter-fraction de la vessie afin de déterminer les facteurs dosimétriques qui affectent les complications GU tardives. Le but de cette thèse était donc de caractériser et de prédire les incertitudes produites par les variations géométriques de la vessie entre les fractions de traitement, en utilisant uniquement la tomodensitométrie de planification comme information d'entrée. En pratique clinique, une seule tomodensitométrie est disponible au moment de la planification du traitement pour un patient typique, alors que des images supplémentaires peuvent être acquises en cours de traitement. Dans cette thèse une approche population a été utilisée pour obtenir suffisamment de données pour apprendre les directions les plus importantes du mouvement et de la déformation de la vessie en utilisant l'analyse en composante principales (ACP). Comme dans les travaux de référence, ces directions ont ensuite été utilisées pour développer des modèles basés population pour prédire et quantifier les incertitudes géométriques de la vessie. Cependant, nous avons utilisé une analyse longitudinale afin de caractériser correctement la variance du patient et les modes spécifiques du patient à partir de la population. Nous avons proposé d'utiliser un modèle à effets mixtes (ME) et une ACP hiérarchique pour séparer la variabilité intra et inter-patients afin de contrôler les effets de cohorte confondus. Finalement, nous avons présenté des modèles sur l'APC comme un outil pour quantifier des incertitudes de la dose produit par le mouvement et déformation de la vessie entre fractions
Prostate cancer is the most common cancer amongst the male population in most developed countries. It is the most common cancer amongst the male population in France (73.609 cases in 2014) and in Colombia (9564 cases in 2014). It is also the third most common cause of cancer deaths in males in both countries (9.3% and 7.1% in France and in Colombia in 2014, respectively). One of the standard treatment methods is external radiotherapy, which involves delivering ionizing radiation to a clinical target, namely the prostate and seminal vesicles. Due to the uncertain location of organs during treatment, which involves around forty (40) radiation fractions delivering a total dose ranging from 70 to 80Gy, safety margins are defined around the tumor target upon treatment planning. This leads to portions of healthy organs neighboring the prostate or organs at risk — the bladder and rectum — to be included in the target volume, potentially resulting in adverse events affecting patients’ urinary (hematuria and cystitis, among others) or rectal (rectal bleeding, fecal incontinence, etc.) functions. The bladder is notorious for presenting the largest inter-fraction shape variations during treatment, caused by continuous changes in volume. These variations in shape introduce geometric uncertainties that render assessment of the actual dose delivered to the bladder during treatment difficult, thereby leading to dose uncertainties that limit the possibility of modeling dose-volume response for late genitourinary (GU) toxicity. The Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) project has stated that a similar dose-response to that of late gastrointestinal (GI) toxicity is far from being established. The dosimetric variables obtained from the planning CT prove to be very poor surrogates for the real delivered dose. As a result, it appears crucial to quantify uncertainties produced by inter-fraction bladder variations in order to determine dosimetric factors that affect late GU complications. The aim of this thesis was thus to characterize and predict uncertainties produced by geometric variations of the bladder between fractions, using solely the planning CT as input information. In clinical practice, a single CT scan is only available for a typical patient during the treatment planning while on-treatment CTs/CBCTs are seldom available. In this thesis, we thereby used a population approach to obtain enough data to learn the most important directions of bladder motion and deformation using principal components analysis (PCA). As in groundwork, these directions were then used to develop population-based models in order to predict and quantify geometrical uncertainties of the bladder. However, we use a longitudinal analysis in order to properly characterize both patient-specific variance and modes from the population. We proposed to use mixed-effects (ME) models and hierarchical PCA to separate intra and inter-patient variability to control confounding cohort effects. . Subsequently, we presented PCA models as a tool to quantify dose uncertainties produced by bladder motion and deformation between fractions
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Knight, Kellie Ann. "Daily Image Guided Radiation Therapy for Prostate Cancer: An assessment of treatment plan reproducibility." Thesis, The University of Sydney, 2006. http://hdl.handle.net/2123/1628.

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It is well documented that for prostate cancer patients undergoing radiation therapy there is a correlation between target volume displacement and changes in bladder and rectal volumes. However, these studies have used a methodology that has captured only a subset of all treatment positions. This research used daily Computer Tomography (CT) imaging to comprehensively assess organ volumes, organ motion and their effect on dose, something that has never been performed previously, thus adding considerably to the understanding of the topic. Daily CT images were obtained using a Siemens Primus Linear Accelerator equipped with an in-room Somatom CT unit in the accelerator suite, marketed as ‘Primatom’, to accurately position the patient prior to treatment delivery. The internal structures of interest were contoured on the planning workstation by the investigator. The daily volume and location of the organs were derived from the computer to assess and analyse internal organ motion. The planned dose distribution was then imported onto the treatment CT datasets and used to compare the planned dose to i) the actual isocentre, where the isocentre was actually placed for that fraction, ii) the uncorrected isocentre, by un-doing any on-line corrections performed by the treatment staff prior to treatment delivery, and iii) the future isocentre, by placing the isocentre relative to internal organ motion on a daily basis. The results of this study did not confirm a statistically significant decrease in rectum volumes over time (hypothesis 1), however large fluctuations in bladder volume were confirmed (hypothesis 2). Internal organ motion for the rectum and bladder was demonstrated to be related to organ filling. Ideal planning volumes for these organs have been reported to minimise systematic and random uncertainty in the treatment volumes. An observed decrease in prostate volume over time, a systematic uncertainty in the location of the prostate at the time of the planning CT scan and a significant relationship between prostate centre of volume and rectum and bladder volumes has resulted in a recommendation that patients should be re-scanned during treatment to ensure appropriate clinical target volume coverage. A significant relationship between rectal and bladder volumes and the dose delivered to these organs was found (hypothesis 3). The dose delivered to the planning target volume was not related to the rectal or bladder volumes, although it was related to the motion of these organs. Despite these results only minimal effects on the dose delivered to any of the three isocentres occurred, indicating that the planned dose was accurately delivered using the methodology presented here (hypothesis 4). However the results do indicate that the patient preparation instructions need to be improved if margins are to be reduced in the future. It is unrealistic to assume that Image Guided Radiation Therapy will ever become routine practice due to infrastructure costs and time limitations. This research will inform radiation therapy centres of the variables associated with prostate cancer treatment on a daily basis, something that has never before been realistically achievable. As a result centres will be able to devise protocols to improve treatment outcomes.
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Knight, Kellie Ann. "Daily Image Guided Radiation Therapy for Prostate Cancer: An assessment of treatment plan reproducibility." University of Sydney, 2006. http://hdl.handle.net/2123/1628.

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Doctor of Health Science
It is well documented that for prostate cancer patients undergoing radiation therapy there is a correlation between target volume displacement and changes in bladder and rectal volumes. However, these studies have used a methodology that has captured only a subset of all treatment positions. This research used daily Computer Tomography (CT) imaging to comprehensively assess organ volumes, organ motion and their effect on dose, something that has never been performed previously, thus adding considerably to the understanding of the topic. Daily CT images were obtained using a Siemens Primus Linear Accelerator equipped with an in-room Somatom CT unit in the accelerator suite, marketed as ‘Primatom’, to accurately position the patient prior to treatment delivery. The internal structures of interest were contoured on the planning workstation by the investigator. The daily volume and location of the organs were derived from the computer to assess and analyse internal organ motion. The planned dose distribution was then imported onto the treatment CT datasets and used to compare the planned dose to i) the actual isocentre, where the isocentre was actually placed for that fraction, ii) the uncorrected isocentre, by un-doing any on-line corrections performed by the treatment staff prior to treatment delivery, and iii) the future isocentre, by placing the isocentre relative to internal organ motion on a daily basis. The results of this study did not confirm a statistically significant decrease in rectum volumes over time (hypothesis 1), however large fluctuations in bladder volume were confirmed (hypothesis 2). Internal organ motion for the rectum and bladder was demonstrated to be related to organ filling. Ideal planning volumes for these organs have been reported to minimise systematic and random uncertainty in the treatment volumes. An observed decrease in prostate volume over time, a systematic uncertainty in the location of the prostate at the time of the planning CT scan and a significant relationship between prostate centre of volume and rectum and bladder volumes has resulted in a recommendation that patients should be re-scanned during treatment to ensure appropriate clinical target volume coverage. A significant relationship between rectal and bladder volumes and the dose delivered to these organs was found (hypothesis 3). The dose delivered to the planning target volume was not related to the rectal or bladder volumes, although it was related to the motion of these organs. Despite these results only minimal effects on the dose delivered to any of the three isocentres occurred, indicating that the planned dose was accurately delivered using the methodology presented here (hypothesis 4). However the results do indicate that the patient preparation instructions need to be improved if margins are to be reduced in the future. It is unrealistic to assume that Image Guided Radiation Therapy will ever become routine practice due to infrastructure costs and time limitations. This research will inform radiation therapy centres of the variables associated with prostate cancer treatment on a daily basis, something that has never before been realistically achievable. As a result centres will be able to devise protocols to improve treatment outcomes.
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Cheng, Kun. "Deformable models for adaptive radiotherapy planning." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/22893.

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Radiotherapy is the most widely used treatment for cancer, with 4 out of 10 cancer patients receiving radiotherapy as part of their treatment. The delineation of gross tumour volume (GTV) is crucial in the treatment of radiotherapy. An automatic contouring system would be beneficial in radiotherapy planning in order to generate objective, accurate and reproducible GTV contours. Image guided radiotherapy (IGRT) acquires patient images just before treatment delivery to allow any necessary positional correction. Consequently, real-time contouring system provides an opportunity to adopt radiotherapy on the treatment day. In this thesis, freely deformable models (FDM) and shape constrained deformable models (SCDMs) were used to automatically delineate the GTV for brain cancer and prostate cancer. Level set method (LSM) is a typical FDM which was used to contour glioma on brain MRI. A series of low level image segmentation methodologies are cascaded to form a case-wise fully automatic initialisation pipeline for the level set function. Dice similarity coefficients (DSCs) were used to evaluate the contours. Results shown a good agreement between clinical contours and LSM contours, in 93% of cases the DSCs was found to be between 60% and 80%. The second significant contribution is a novel development to the active shape model (ASM), a profile feature was selected from pre-computed texture features by minimising the Mahalanobis distance (MD) to obtain the most distinct feature for each landmark, instead of conventional image intensity. A new group-wise registration scheme was applied to solve the correspondence definition within the training data. This ASM model was used to delineated prostate GTV on CT. DSCs for this case was found between 0.75 and 0.91 with the mean DSC 0.81. The last contribution is a fully automatic active appearance model (AAM) which captures image appearance near the GTV boundary. The image appearance of inner GTV was discarded to spare the potential disruption caused by brachytherapy seeds or gold markers. This model outperforms conventional AAM at the prostate base and apex region by involving surround organs. The overall mean DSC for this case is 0.85.
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Ospina, Arango Juan David. "Predictive models for side effects following radiotherapy for prostate cancer." Thesis, Rennes 1, 2014. http://www.theses.fr/2014REN1S046/document.

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La radiothérapie externe (EBRT en anglais pour External Beam Radiotherapy) est l'un des traitements référence du cancer de prostate. Les objectifs de la radiothérapie sont, premièrement, de délivrer une haute dose de radiations dans la cible tumorale (prostate et vésicules séminales) afin d'assurer un contrôle local de la maladie et, deuxièmement, d'épargner les organes à risque voisins (principalement le rectum et la vessie) afin de limiter les effets secondaires. Des modèles de probabilité de complication des tissus sains (NTCP en anglais pour Normal Tissue Complication Probability) sont nécessaires pour estimer sur les risques de présenter des effets secondaires au traitement. Dans le contexte de la radiothérapie externe, les objectifs de cette thèse étaient d'identifier des paramètres prédictifs de complications rectales et vésicales secondaires au traitement; de développer de nouveaux modèles NTCP permettant l'intégration de paramètres dosimétriques et de paramètres propres aux patients; de comparer les capacités prédictives de ces nouveaux modèles à celles des modèles classiques et de développer de nouvelles méthodologies d'identification de motifs de dose corrélés à l'apparition de complications. Une importante base de données de patients traités par radiothérapie conformationnelle, construite à partir de plusieurs études cliniques prospectives françaises, a été utilisée pour ces travaux. Dans un premier temps, la fréquence des symptômes gastro-Intestinaux et génito-Urinaires a été décrite par une estimation non paramétrique de Kaplan-Meier. Des prédicteurs de complications gastro-Intestinales et génito-Urinaires ont été identifiés via une autre approche classique : la régression logistique. Les modèles de régression logistique ont ensuite été utilisés dans la construction de nomogrammes, outils graphiques permettant aux cliniciens d'évaluer rapidement le risque de complication associé à un traitement et d'informer les patients. Nous avons proposé l'utilisation de la méthode d'apprentissage de machine des forêts aléatoires (RF en anglais pour Random Forests) pour estimer le risque de complications. Les performances de ce modèle incluant des paramètres cliniques et patients, surpassent celles des modèle NTCP de Lyman-Kutcher-Burman (LKB) et de la régression logistique. Enfin, la dose 3D a été étudiée. Une méthode de décomposition en valeurs populationnelles (PVD en anglais pour Population Value Decomposition) en 2D a été généralisée au cas tensoriel et appliquée à l'analyse d'image 3D. L'application de cette méthode à une analyse de population a été menée afin d'extraire un motif de dose corrélée à l'apparition de complication après EBRT. Nous avons également développé un modèle non paramétrique d'effets mixtes spatio-Temporels pour l'analyse de population d'images tridimensionnelles afin d'identifier une région anatomique dans laquelle la dose pourrait être corrélée à l'apparition d'effets secondaires
External beam radiotherapy (EBRT) is one of the cornerstones of prostate cancer treatment. The objectives of radiotherapy are, firstly, to deliver a high dose of radiation to the tumor (prostate and seminal vesicles) in order to achieve a maximal local control and, secondly, to spare the neighboring organs (mainly the rectum and the bladder) to avoid normal tissue complications. Normal tissue complication probability (NTCP) models are then needed to assess the feasibility of the treatment and inform the patient about the risk of side effects, to derive dose-Volume constraints and to compare different treatments. In the context of EBRT, the objectives of this thesis were to find predictors of bladder and rectal complications following treatment; to develop new NTCP models that allow for the integration of both dosimetric and patient parameters; to compare the predictive capabilities of these new models to the classic NTCP models and to develop new methodologies to identify dose patterns correlated to normal complications following EBRT for prostate cancer treatment. A large cohort of patient treated by conformal EBRT for prostate caner under several prospective French clinical trials was used for the study. In a first step, the incidence of the main genitourinary and gastrointestinal symptoms have been described. With another classical approach, namely logistic regression, some predictors of genitourinary and gastrointestinal complications were identified. The logistic regression models were then graphically represented to obtain nomograms, a graphical tool that enables clinicians to rapidly assess the complication risks associated with a treatment and to inform patients. This information can be used by patients and clinicians to select a treatment among several options (e.g. EBRT or radical prostatectomy). In a second step, we proposed the use of random forest, a machine-Learning technique, to predict the risk of complications following EBRT for prostate cancer. The superiority of the random forest NTCP, assessed by the area under the curve (AUC) of the receiving operative characteristic (ROC) curve, was established. In a third step, the 3D dose distribution was studied. A 2D population value decomposition (PVD) technique was extended to a tensorial framework to be applied on 3D volume image analysis. Using this tensorial PVD, a population analysis was carried out to find a pattern of dose possibly correlated to a normal tissue complication following EBRT. Also in the context of 3D image population analysis, a spatio-Temporal nonparametric mixed-Effects model was developed. This model was applied to find an anatomical region where the dose could be correlated to a normal tissue complication following EBRT
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Foo, Kerwyn Yi Min. "Methodological uncertainties in radiotherapy dose-effect analysis." Thesis, University of Sydney, 2020. https://hdl.handle.net/2123/24421.

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Cancer and normal tissues in patient populations exhibit variability in biological response to the same dose of radiation. Sources of this variability include: • Inherent biological factors of patient, tumour or tissue • Metrics to measure, classify or declare biological outcomes • Volumetric (prescription of target or avoidance regions) • Dosimetric and delivery Dosimetric and delivery variation is easily measured and has relatively little impact on variation of outcome in modelling studies. Volumetric variation contributes greatly to uncertainty, dependent on human judgement by oncologists. However, analysis methodology is generally overlooked as a source of variation in reported dose-effect results and is the subject of investigation in this thesis. Dosimetric and clinical data from clinical trials and prospective cohort studies have been used to illustrate the contribution of analysis methodology to variation in dose-effect relationships using evidence from prostate cancer radiation therapy. The primary data source is the Trans-Tasman Radiation Oncology Group clinical trial 03.04 “RADAR”, which investigated dose escalation in external beam radiotherapy for prostate cancer. Systematic review of the medical physics literature shows that prostate cancer radiotherapy toxicity reporting does not fully account for fractionation, which biases and causes unreported variation in dose-effect results. The toxicity-dose-volume-effect relationship is shown to depend on the anatomical subsite delineated and the type/grade of toxicity outcome chosen. Multivariate regression of multiple dose factors is not reliable due to multicollinearity of these factors. Heterogeneity in method of analysis is an important and overlooked component of variability in reported results of dose effect relationships in radiotherapy studies. Harmonisation of analysis or correction for this heterogeneity will reduce uncertainties to allow better modelling of biological effects in the molecular oncology era.
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Rimmer, Yvonne Louise. "The Implementation and Optimisation of Image-Guided Radiotherapy in Prostate Cancer." Thesis, University of East Anglia, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.521025.

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Khoo, Vincent. "A study of conformal radiotherapy methods for brain and prostate cancer." Thesis, Institute of Cancer Research (University Of London), 2000. http://publications.icr.ac.uk/9718/.

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State-of-the-art radiotherapy involves a technology chain that includes 3D tumour imaging, 3D treatment planning, treatment delivery using conformal or intensity modulated techniques, and treatment verification. This thesis evaluates some of the recent imaging and planning developments to assess their role in optimisation of the technology chain for brain and prostate cancer. I focused on two major links in this technology chain. The 'imaging' link compared the use of MRI and CT in localising target volumes. An image registration protocol was developed to combine CT and MRI images in the brain. For the localisation of skull base meningiomas, MRI was found to provide contrasting information to CT. A composite target volume derived from both CT and MR information provided the most appropriate volume. For prostate radiotherapy, four MRI sequences were compared to CT. All MRI sequences provided improved localisation of relevant radiotherapy volumes-of-interest especially for the prostatic apex and rectum. The 'treatment planning' link investigated the impact of intra-fraction prostate motion for prostate planning margins, the creation of planning margins, the optimisation of beam orientations for prostate radiotherapy, and the utility of IMRT methods for brain tumours. Cine MR demonstrated a significant relationship between moderate rectal distension and increased rectal activity resulting in prostate motion. Mean prostate motion was < 5mm and lasted < 5% of a7 minute period indicating that the current 10mm prostate planning margin was adequate. The use of a 3D margin-growing method allowed the planning target margin to be accurately realised in all spatial orientations and avoided problems associated with 2D margin growing methods. A variety of co-planar arrangements using 3-, 4-, and 6-fields were evaluated for conformal prostate radiotherapy. Standard prostate plans could be optimised by proper consideration of beam orientations. A 3-field plan with gantry angles of 0", 90', 270' Provided the best rectal sparing for both prostate alone and prostate plus seminal vesicles volumes. Using this 3-field plan, dose escalation may be achieved with a smaller increase in predicted late rectal complications than with other 3-, 4-, or 6-field plans. An IMRT tomotherapy method was compared with conformal radiotherapy for convex shaped brain tumours to assess its potential for improved dose conformation. This IMRT method provided slightly improved PTV coverage but also higher OARs doses. However, these OARs doses remained within acceptable clinical limits. This IMRT tomotherapy method did not provide significant planning improvement compared to current conformal radiotherapy technique.
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Murray, Louise Janet. "Optimising treatment outcomes using Stereotactic Body Radiotherapy (SBRT) for prostate cancer." Thesis, University of Leeds, 2014. http://etheses.whiterose.ac.uk/8666/.

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Aims: to optimise linear accelerator-based prostate stereotactic ablative radiotherapy (SABR) through planning studies, tumour control probability (TCP) and normal tissue complication probability (NTCP) calculations and radiation-induced second primary cancer (RISPC) risk assessment. Methods: A planning study was performed to develop a class solution for prostate SABR. A second planning study delivered boosts to dominant intra-prostatic lesions (DILs) and TCP and NTCP were calculated. A third planning study compared prostate SABR planning using flattened and flattening filter free (FFF) beams. A systematic review examined RISPC risk following prostate radiotherapy. A final study estimated RISPC risks following prostate SABR in comparison to other contemporary radiation techniques. Results: Prostate SABR was optimal using a single anterior arc which resulted in highly conformal plans, lower rectal doses and improved delivery times and monitor unit requirements for most patients. Boosting DILs resulted in small TCP increases, but the benefit was offset by increases in NTCP. SABR to the whole prostate without DIL boosting resulted in high TCP and low NTCP. Plans using flattened and FFF beams were dosimetrically similar but FFF resulted in reduced delivery times. Clinical evidence, largely based on older radiation techniques, suggests that prostate radiotherapy increases RISPC risk. Clinical evidence concerning risk following modern techniques is too immature to draw firm conclusions. The final study demonstrated that SABR techniques resulted in lower estimated RISPC risks in all organs compared to conventionally fractionated techniques, while FFF techniques reduced RISPC risks in out-of-field organs. Conclusions: Linear accelerator-based prostate SABR delivered with a single partial arc is optimal and high levels of TCP and low levels of NTCP are predicted from whole prostate SABR. FFF allows faster treatment delivery. Second malignancy risk is lower using SABR, particularly with FFF, compared to conventionally fractionated techniques. Phase III trials are required to investigate prostate SABR in practice.
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Wirth, Manfred P., and Michael Fröhner. "Adjuvant Hormonal Treatment for Prostate Cancer: The Bicalutamide Early Prostate Cancer Program." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-133551.

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Adjuvant hormonal therapy has been demonstrated to be able to delay disease progression in nonmetastatic prostate cancer. To date, however, a favorable impact on survival has only been demonstrated in lymph-node-positive disease and in external-beam radiotherapy series with locally advanced and probably mainly micrometastatic tumors. The Bicalutamide Early Prostate Cancer Program is the largest study under way to define the role of adjuvant treatment in early prostate cancer and identify subgroups of patients likely to benefit from immediate hormonal therapy. At the time of the most recently published analysis, the risk of objective clinical progression was significantly reduced in the bicalutamide arm (hazards ratio 0.58, 95% confidence interval 0.51–0.66, p < 0.0001). However, further maturation of data is needed to see whether this difference will lead to a survival advantage
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Books on the topic "Prostate – Cancer – Radiotherapy"

1

Carlo, Greco, and Zelefsky Michael, eds. Radiotherapy of prostate cancer. Australia: Harwood Academic, 2000.

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Geinitz, Hans, Mack Roach III, and Nicholas van As, eds. Radiotherapy in Prostate Cancer. Berlin, Heidelberg: Springer Berlin Heidelberg, 2015. http://dx.doi.org/10.1007/978-3-642-37099-1.

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Vijayakumar, Srinivasan. Prostate cancer. New York: Demos Medical, 2011.

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Innovative radiotherapy techniques for prostate cancer. Bremen: UNI-MED-Verl., 2012.

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Chen, Allen. Prostate cancer. New York: Demos Medical, 2011.

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V, D'Amico Anthony, and Hanks Gerald E, eds. Advances in the radiotherapeutic management of carcinoma of the prostate. New York: Chapman & Hall, 1998.

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Wallner, Kent. Prostate cancer : a non-surgical perspective. Canaan, N.Y: SmartMedicine Press, 1996.

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1955-, Klein Eric A., ed. Management of prostate cancer. 2nd ed. Totowa, N.J: Humana Press, 2004.

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1955-, Klein Eric A., ed. Management of prostate cancer. 2nd ed. Totowa, N.J: Humana Press, 2004.

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K, Valicenti Richard, Dicker Adam P, and Jaffray David A, eds. Prostate cancer: Image-guided radiation therapy. New York, USA: Informa Healthcare, 2008.

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Book chapters on the topic "Prostate – Cancer – Radiotherapy"

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Tsuji, Hiroshi, Hitoshi Ishikawa, and Takuma Nomiya. "Prostate Cancer." In Carbon-Ion Radiotherapy, 231–39. Tokyo: Springer Japan, 2013. http://dx.doi.org/10.1007/978-4-431-54457-9_27.

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Henderson, Daniel R., and Nicholas van As. "Prostate Cancer." In PET/CT in Radiotherapy Planning, 63–66. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-54744-2_11.

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Donnelly, Ann E., and Robert Den. "Radiotherapy for Prostate Cancer." In Chemotherapy and Immunotherapy in Urologic Oncology, 55–75. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-52021-2_6.

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Perna, Carla, Jennifer Uribe, Santiago Uribe-Lewis, and Stephen E. M. Langley. "Salvage Radiotherapy." In Salvage Therapy for Prostate Cancer, 115–20. Cham: Springer International Publishing, 2020. http://dx.doi.org/10.1007/978-3-030-57181-8_10.

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Kübler, Hubert, Tobias Maurer, Thomas Horn, and Jürgen E. Gschwend. "Salvage Prostatectomy After Radiotherapy." In Radiotherapy in Prostate Cancer, 253–59. Berlin, Heidelberg: Springer Berlin Heidelberg, 2014. http://dx.doi.org/10.1007/174_2013_950.

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Mason, Malcolm. "IMRT, Hypofractionated Radiotherapy and Stereotactic Radiotherapy: Technique, Indications, and Results." In Management of Prostate Cancer, 203–16. Cham: Springer International Publishing, 2017. http://dx.doi.org/10.1007/978-3-319-42769-0_14.

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Tendulkar, Rahul, and Kevin Stephans. "Contemporary External Beam Radiotherapy." In Management of Prostate Cancer, 243–61. Totowa, NJ: Humana Press, 2012. http://dx.doi.org/10.1007/978-1-60761-259-9_15.

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Arcangeli, Giorgio, Stefano Arcangeli, and Lidia Strigari. "Hypofractionation and Stereotactic Treatment: Clinical Data." In Radiotherapy in Prostate Cancer, 163–72. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/174_2013_871.

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Langsenlehner, Tanja. "Biochemical Recurrence: A Valuable Endpoint?" In Radiotherapy in Prostate Cancer, 55–64. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/174_2013_904.

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Roach III, Mack. "Prophylactic Treatment of the Pelvic Lymphatics in Patients with High-Risk Prostate Cancer: Pro Radiation." In Radiotherapy in Prostate Cancer, 123–29. Berlin, Heidelberg: Springer Berlin Heidelberg, 2013. http://dx.doi.org/10.1007/174_2013_906.

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Conference papers on the topic "Prostate – Cancer – Radiotherapy"

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Demeshko, P. D., A. N. Batyan, and E. V. Hancharova. "METHODS FOR EVALUATING LONG-TERM RESULTS OF RADIOTHERAPY FOR CANCER WITH HIGH AND LOW PROLIFERATION POTENTIAL." In SAKHAROV READINGS 2021: ENVIRONMENTAL PROBLEMS OF THE XXI CENTURY. International Sakharov Environmental Institute, 2021. http://dx.doi.org/10.46646/sakh-2021-1-249-252.

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The quality of radiation treatment for oncological diseases can be influenced by a large number of factors. Among them, the breaks that occur during the course of radiotherapy play an important role. Split courses of radiotherapy are used in the practice of radiation treatment of head and neck cancer, as well as prostate cancer. Breaks between the stages of the course of radiotherapy lasting 1-2 weeks are carried out in elderly, debilitated patients or in the presence of radiation reactions of 3-4 degrees. Before the start of radiotherapy, a set of measures is taken to prevent radiation reactions. This can affect the fact that the course of radiotherapy will be carried out without interruption. Using Cox regression, it is proposed to evaluate the effect of interruptions in the course of radiotherapy on the outcome of treatment for head and neck tumors, as well as the prostate tumors taking into account the observation period.
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Ospina, J. D., A. Fargeas, G. Drean, A. Simon, O. Acosta, and R. de Crevoisier. "Recent advancements in toxicity prediction following prostate cancer radiotherapy." In 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC). IEEE, 2015. http://dx.doi.org/10.1109/embc.2015.7319571.

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Azuddin, A. Yusof, I. Abdul Rahman, N. J. Siah, F. Mohamed, M. Saadc, and F. Ismail. "Radiation-induced complications in prostate cancer patients treated with radiotherapy." In THE 2014 UKM FST POSTGRADUATE COLLOQUIUM: Proceedings of the Universiti Kebangsaan Malaysia, Faculty of Science and Technology 2014 Postgraduate Colloquium. AIP Publishing LLC, 2014. http://dx.doi.org/10.1063/1.4895181.

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Reddy, Joseph A., Melissa Nelson, LeCun Xu, Elaine Westrick, Marilynn Vetzel, Leroy Wheeler, Albert Felten, Hari Santhapuram, Iontcho Vlahov, and Christopher P. Leamon. "Abstract 852: Specificity of PSMA-617 radiotherapy for prostate cancer." In Proceedings: AACR Annual Meeting 2018; April 14-18, 2018; Chicago, IL. American Association for Cancer Research, 2018. http://dx.doi.org/10.1158/1538-7445.am2018-852.

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Bruens, Serena T., Chiara Milanese, Nicole Verkaik, Pier Mastroberardino, Akos Gyenis, Jiang Chang, Kasper Derks, et al. "Abstract 1657: Mapping mechanisms of radiotherapy resistance in prostate cancer." In Proceedings: AACR 107th Annual Meeting 2016; April 16-20, 2016; New Orleans, LA. American Association for Cancer Research, 2016. http://dx.doi.org/10.1158/1538-7445.am2016-1657.

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Acharya, Suryakanta. "Abstract PO-213: Financial implication of prostate cancer hypofractionated radiotherapy." In Abstracts: AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; October 6-8, 2021. American Association for Cancer Research, 2022. http://dx.doi.org/10.1158/1538-7755.disp21-po-213.

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Krishnan, Karthik, and Rex Cheung. "Evaluation of the accuracy of deformable registration of prostate MRI for targeted prostate cancer radiotherapy." In SPIE Medical Imaging, edited by Josien P. W. Pluim and Benoit M. Dawant. SPIE, 2009. http://dx.doi.org/10.1117/12.811697.

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Skalski, Andrzej, Tomasz Zieliński, Paweł Kukołowicz, and Piotr Kędzierawski. "Computed tomography-based radiotherapy planning on the example of prostate cancer." In the 4th International Symposium. New York, New York, USA: ACM Press, 2011. http://dx.doi.org/10.1145/2093698.2093840.

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Gandhi, Vanita, Kuthpady Shrinivas, and Sarah Needleman. "37 Virtual reality: enhancing the prostate cancer patient’s experience of radiotherapy." In Leadership in Healthcare conference, 14th to 16th November 2018, Birmingham, UK. BMJ Publishing Group Ltd, 2018. http://dx.doi.org/10.1136/leader-2018-fmlm.37.

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Chua, Melvin L. K., Erle Holgersen, Veronica Sabelnykova, Adriana Salcedo, Alice Meng, Michael Fraser, Theodorus van der Kwast, Paul C. Boutros, and Robert G. Bristow. "Abstract 5860: Genomic architecture of prostate cancer at recurrence following radiotherapy." In Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC. American Association for Cancer Research, 2017. http://dx.doi.org/10.1158/1538-7445.am2017-5860.

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Reports on the topic "Prostate – Cancer – Radiotherapy"

1

Buchsbaum, Donald J. Genetic Radiotherapy of Prostate Cancer. Fort Belvoir, VA: Defense Technical Information Center, December 2003. http://dx.doi.org/10.21236/ada422767.

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Li, Chuan-Yuan. Enhancement of Prostate Cancer Radiotherapy by Immunogenetherapy. Fort Belvoir, VA: Defense Technical Information Center, February 2004. http://dx.doi.org/10.21236/ada424647.

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Silvia S. Jurisson, PhD. Rhodium-105 Bombesin Analogs for Prostate Cancer Radiotherapy. Office of Scientific and Technical Information (OSTI), December 2005. http://dx.doi.org/10.2172/951630.

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Rogers, Buck E. Enhanced Peptide Radiotherapy of Prostate Cancer Using Targeted Adenoviral Vectors. Fort Belvoir, VA: Defense Technical Information Center, June 2004. http://dx.doi.org/10.21236/ada428235.

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Chen, Lili. MR Imaging Based Treatment Planning for Radiotherapy of Prostate Cancer. Fort Belvoir, VA: Defense Technical Information Center, February 2005. http://dx.doi.org/10.21236/ada435143.

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Park, Jong Y. Genetic and Epigenetic Biomarkers for Recurrent Prostate Cancer After Radiotherapy. Fort Belvoir, VA: Defense Technical Information Center, May 2014. http://dx.doi.org/10.21236/ada609389.

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Park, Jong. Genetic and Epigenetic Biomarkers for Recurrent Prostate Cancer After Radiotherapy. Fort Belvoir, VA: Defense Technical Information Center, May 2013. http://dx.doi.org/10.21236/ada581491.

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Rogers, Buck E. Enhanced Peptide Radiotherapy of Prostate Cancer Using Targeted Adenoviral Vectors. Fort Belvoir, VA: Defense Technical Information Center, June 2003. http://dx.doi.org/10.21236/ada420846.

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Chen, Lili. MR Imaging Based Treatment Planning for Radiotherapy of Prostate Cancer. Fort Belvoir, VA: Defense Technical Information Center, February 2007. http://dx.doi.org/10.21236/ada468037.

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Fenton, Bruce M. Potentiation of Prostate Cancer Radiotherapy Using Antiangiogenic and Antitumor Therapies. Fort Belvoir, VA: Defense Technical Information Center, October 2007. http://dx.doi.org/10.21236/ada478113.

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