Thesis--University of Copenhagen. / Resumé in Danish. Bibliography: p. [171]-184.

Thesis (M.S. in Physics)--Naval Postgraduate School, March 2010. / Thesis Advisor(s): Rodeback, G. W. "January 1962." Description based on title screen as viewed on June 2, 2010. DTIC Descriptor(s): Research Reactors, Hafnium, Half Life, Pneumatic Equipment, Measuring Instruments, Reactor Cores, Shielding, Detection, Gamma Emission, Computer Programming, Radioactive Isotopes, Radioactive Decay, Mixtures, Scintillation Counters, Isotopes, Least Squares Method. DTIC Identifier(s): AGN-201 Reactors, Fortran. Includes bibliographical references (p. 25). Also available in print.

Thesis (Ph. D.)--University of Bombay, 1969. / Includes bibliographical references (leaves 91-100).

Thesis--University of Copenhagen. / Resumé in Danish. Bibliography: p. [171]-184.

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The use of the radioisotope 14C in polymer chemistry has been reviewed, showing how it has been used to investigate the mechanistic aspects of free radical polymerizations, and the use of polymers in other scientific disciplines such as environmental, physical, chemical and medical sciences. An overview of the application of fluorescent spectroscopy to polymer chemistry is also reported. It covers the fundamentals of fluorescence chemistry, its application and the potential problems of the use of fluorescent labels in polymer chemistry. The application of radioisotopes to atom transfer radical polymerisation (ATRP) to investigate the fate of initiators used in the ATRP of 2-hydroxypropyl methacrylate (2- HPMA) is also reported. By using 14C radiolabelled initiators, radio thin layer chromatography (Radio TLC) and the liquid scintillation counting of fractions, collected from gel permeation chromatography (GPC), the fate of the initiating species where monitored during the polymerization of samples of 14C poly(2-HPMA), with degrees of polymerization of 10, 25 and 50 was assessed. GPC and Radio TLC, data showed that there was an under-utilisation of the initiator, 16% clearly observable at high monomer conversion (>97%), which could result in the initiation of new chains at monomer conversions of >90% and as late as 300 minutes after the polymerisation had started. These results contradict ATRP theory which states all initiator is consumed immediately at the commencement of the polymerization. 14C poly(2-HPMA) was also used to determine the efficiencies of the polymer purification methods, flash chromatography and precipitation. Although repeated precipitation increased fractionation, it was shown to be superior to flash chromatography in removing residual unreacted or terminated initiator. Finally, the possible effects of fluorescent labels on adsorption of low molecular weight 14C poly(DEAEMA) onto real surfaces (filter paper, photo graphic paper and hair) from aqueous solutions at pH=2 were investigated. Three low molecular weight samples of 14C poly(DEAEMA) were prepared by ATRP using 14C labelled initiators synthesized from alcohols of increasing hydrophobicity i.e. methyl, benzyl and 9-hydroxyfluorene (fluorescent label). The levels of adsorption were determined using phosphor imaging, oxidation of organic samples and liquid scintillation counting. Results indicated that differences in the chemistry of the polymer end groups can affect adsorption of the 14C poly(DEAEMA) and polymer assembly at the air/water interface. There was greater adsorption of polymers with a fluorescent end group. The increasing deposition was attributed to the increasing hydrophobicity of the polymer end group. Moreover, the controlled placement of one fluorescent label per polymer chain can influence the polymer’s properties, prompting the question, is the use of fluorescent groups to assess polymer behaviour and properties viable?

INTRODUÇÃO: Braquiterapia de alta taxa de dose (BATD) para o câncer de próstata pode ser uma boa opção para escalonamento de dose, como um reforço de dose, associada à radioterapia externa, principalmente se não há disponibilidade de radioterapia tridimensional conformada ou tecnologia mais avançada. OBJETIVOS: Neste trabalho, analisaram-se os resultados e as toxicidades de um reforço de dose com BATD prévio à radioterapia externa convencional ou tridimensional conformada em pacientes portadores de câncer localizado da próstata. Fatores prognósticos relacionados à sobrevida livre de doença, além de toxicidade do tratamento também foram estudados. MÉTODOS: Estudo retrospectivo de 403 pacientes com adenocarcinoma localizado da próstata tratados entre dezembro de 2000 e março de 2004, que receberam 3 esquemas de fracionamento distintos de BATD de acordo com o seu grupo de risco: três frações de 5,5 a 6 Gy, 6 a 6,5 Gy ou 6,5 a 7 Gy, para baixo, médio ou alto risco, respectivamente, em um único implante, no decorrer de 24h de internação. A radioterapia externa convencional ou conformada compreendeu dose de 45 Gy na próstata e vesículas seminais. Foram realizadas análises uni e multivariada para avaliação dos fatores prognósticos relacionados à sobrevida livre de falha bioquímica e toxicidades. RESULTADOS: A idade mediana dos pacientes foi de 68 anos, com PSA médio de 9g/ml, peso prostático médio de 35 cc. Grau histológico de Gleason igual a 6 ocorreu em 43% dos casos, estádio menor do que T2c em 97%, presença de nódulo prostático em 49%; 11% dos pacientes apresentaram história de ressecção transuretral e 16% obstrução urinária prévias. No grupo de baixo risco foram classificados 36.1% dos pacientes, 42.8% no grupo de risco intermediário e 21.1% foram considerados de alto risco. Hormonioterapia neoadjuvante por até 6 meses foi utilizada em 64% dos casos e teleterapia conformada em 19%. O seguimento médio foi de 50 meses (mediano de 48,4 meses), variando de 24 a 113 meses. Nove (2,2%) pacientes não responderam ao tratamento e 4,5% evoluíram a óbito por neoplasia prostática em um tempo médio de 22 meses. Falha bioquímica, tanto pelo critério ASTRO, quanto PHOENIX ocorreu em 9,6% dos pacientes. Entretanto, o tempo médio para falha foi de 13 meses pelo critério ASTRO e 26 meses pelo PHOENIX. O único fator preditivo de falha bioquímica pela análise multivariada por ambos os critérios ASTRO e PHOENIX foi a presença de nódulos prostáticos, mas pacientes com menos de 60 anos apresentaram maior chance de falha apenas pela definição de PHOENIX. Toxicidades urinárias agudas como retenção e hematúria ocorreram em 2,8% e 1,3% dos casos, respectivamente; sendo 23,7% grau 1, 15,1% grau 2 e 2% grau 3. Estenose uretral tardia foi observada em 8,5% dos pacientes e as toxicidades urinárias tardias foram grau 1 em 8,8%, grau 2 em 3,9%, grau 3, em 7,7% e grau 4, em 0,3% dos casos. Toxicidade urinária aguda foi relacionada a obstrução urinária prévia e maior dose de braquiterapia na uretra. Estenose uretral tardia também foi relacionada à maior dose uretral pela braquiterapia e com maior idade. Toxicidade retal precoce ocorreu como grau 1 em 14,8% dos pacientes; como grau 2, em 10,5%; e como grau 3, em 1,3%. Toxicidade retal tardia ocorreu como grau 1 em 3,4% dos pacientes; como grau 2, em 1,5%; como grau 3, em 0,3%; e como grau 4, em 0,3%. O risco para toxicidades retais agudas e tardias foi maior quando teleterapia conformada foi utilizada. Foi observada dor na glande em 4,9% dos pacientes e 71% apresentaram disfunção erétil tardiamente. O uso de Sildenafil foi eficiente em 59%. Pacientes mais velhos, ou com uma ou mais comorbidades, comprometimento prévio da ereção, ou que receberam radioterapia externa conformada apresentaram maior incidência de disfunção erétil. CONCLUSÕES: a associação de BATD como um reforço de dose para teleterapia mostrou ser um método viável e seguro apresentando boa eficácia e toxicidade aceitável. Os fatores relacionados à sobrevida e toxicidade podem colaborar na melhor seleção e tratamento de pacientes com câncer de próstata localizado. / INTRODUCTION: high dose-rate brachytherapy (HDR) for prostate cancer may be a nice treatment option for dose escalation as a boost, when associated to external beam irradiation, mainly if 3D conformal or more advanced technology is not available. PURPOSE: this study analyzes the results and toxicities of HDR brachytherapy boost prior to external beam radiotherapy with 2D or 3D conformal irradiation in patients with localized prostate cancer. Prognostic factors associated to overall and disease-free survival, as well as to treatment related toxicity were also studied. METHODS: A retrospective study of 403 patients with localized prostate adenocarcinoma treated between December 2000 and March 2004 was performed. According to the risk group, three fractions of HDR brachytherapy were delivered in the course of 24 hours, with a single implant: 5.5 to 6 Gy per fraction for low risk, 6 to 6.5 Gy per fraction for intermediate risk, and 6.5 to 7 Gy per fraction for high risk patients. The interval between fractions was of at least 6 hours. Conventional 2D or 3D conformal external beam irradiation was delivered to the prostate and seminal vesicles with 25 fractions of 1.8Gy (45Gy), about 2 weeks after brachytherapy. Multivariate analysis was done to evaluate unfavorable prognostic factors for biochemical failure free survival (BFFS). RESULTS: Patients presented a median age of 68 years, mean PSA of 9g/ml, and average prostate weight of 35 cc. Gleason score was equal to 6 in 43% of the cases, and 97% of the cases were at a stage lower than T2c. Prostate nodules were present in 49% of the patients; prior history of transurethral resection or urinary obstruction was present in 11% and 16% of the patients, respectively. There were 36.1% patients in the low risk group, 42.8% in the intermediate, and 21.1% in the high risk groups, respectively. Up to six months of neoadjuvant hormone therapy was used in 64% of the cases. External beam radiation was delivered with 3D conformal radiation in 19% of patients. The mean follow-up was 50 months ranging from 24 to 113 months (median 48,4 months). Nine patients (2.2%) did not respond to treatment. Death from prostate cancer occurred in 4.5% of the cases in a mean period of 22 months. Biochemical failure occurred in 9.6% according to both ASTRO and Phoenix consensus criteria. However, the mean time to relapse was 13 months using the ASTRO criteria and 26 months with the Phoenix definition. The five-year BFFS using the ASTRO criteria was 94.3%, 86.9% and 86.6% for the low, intermediate and high risk groups, respectively. Using the Phoenix criteria, 92.4%, 88.0% and 85.3% for the low, intermediate and high risk groups, respectively (p = 0.109). The only feature predicting biochemical failure (BF) in the multivariate analysis by both ASTRO and Phoenix criteria was the presence of prostate nodules, but patients younger than 60 years presented higher chance of BF using Phoenix criteria only. Acute urinary toxicities as urinary retention and hematúria occurred respectively in 2.8% and 1.3% of the patients. They presented as grade 1 in 23.7%, grade 2 in 15.1% and grade 3 in 2%. Late urethral stenosis was observed in 8.5% and late urinary toxicity was grade 1 in 8.8% of the patients, grade 2 in 3.9%, grade 3 in 7.7% and grade 4 in 0.3%. Acute urinary toxicity was related to previous urinary obstruction and higher brachytherapy dose to the urethra. Late urethral stenosis was related to older age and higher brachytherapy dose. Grade 1 early rectal toxicity occurred in 14.8% of the patients, grade 2 in 10.5% and grade 3 in 1.3%. Late rectal toxicity occurred as grade 1 in 3.4% of patients, as grade 2 in 1.5%, grade 3 in 0.3% and grade 4 in 0.3%. The risk of acute and late rectal toxicity was higher when 3D conformal irradiation was used. Glans pain was observed in 4.9% of the patients. Late sexual impotence occurred in 71% of cases. Sildenafil was effective in 59%. Sexual impotence presented a higher incidence in older patients with one or two co-morbidities, previous sexual impairment, or 3D conformal irradiation. CONCLUSIONS: the association of HDR brachytherapy as a boost for external beam irradiation seems to be a feasible and safe procedure, with good efficacy and acceptable toxicity. Factors related to survival and toxicity can help to better select and manage patients with localized prostate carcinoma.

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