Po radikalaus gydymo 20–50 proc. pacientų, kuriems nustatytas galvos–kaklo srities vėžys lokoregioninis atkrytis nustatomas per pirmus dvejus metus. Literatūroje paskelbtų tyrimų rezultatai taikant pakartotinę nuotolinę spindulinę terapiją dėl galvos-kaklo vėžio atkryčio prasti: 2-jų metų bendras išgyvenimas siekė 15,2–40 proc., vėlyvųjų 3-4 laipsnio komplikacijų dažnis buvo 1,4–47 proc., 5 laipsnio - 7,6 proc. Retrospektyvinių ir II fazės tyrimų rezultatai naudojant didelės dozės galios brachiterapiją galvos-kaklo srities vėžio atkryčiui gydyti: 2-jų metų bendras išgyvenimas siekė 19–63 proc., vėlyvųjų 3-4 laipsnio komplikacijų dažnis buvo 4–22,2 proc. Tyrimų metu skirtos 3–4 Gy frakcijos iki 30–40 Gy suminės dozės. Iki šiol neatlikti tyrimai lyginantys nuotolinės spindulinės terapijos ir didelės dozės galios brachiterapijos gydymo veiksmingumą ir saugumą. Šioje disertacijoje palyginti skirtingi spindulinio gydymo metodai gydant galvos-kaklo srities vėžio atkrytį: kontrolinei grupei taikytas nuotolinis konforminis spindulinis gydymas (25 frakcijos po 2 Gy, suminė dozė 50 Gy), tiriamajai grupei - hipofrakcionuota didelės dozės galios brachiterapija skiriant naują frakcionavimo režimą – po 2,5 Gy per frakciją po dvi frakcijas per dieną, iki 30 Gy suminės dozės. Toks frakcionavimo režimas pasirinktas siekiant sumažinti spindulinių reakcijų dažnį ir sunkumo laipsnį, o suminė dozė yra biologiškai ekvivalentiška suminėms dozėms, kurios buvo naudotos ankstesniuose tyrimuose. / After radical treatment of head and neck cancer 20–50% of patients are diagnosed with the locoregional recurrence during first two years. In the literature the results of studies, using reirradiation by three-dimensional radiotherapy for head and neck cancer recurrence, according to a 2-year overall survival and toxicity, are poor: overall survival reached 15.2–40%, the grade 3 - 4 toxicity reached 1.4–47% and grade 5 - 7.6%. The results of phase II and retrospective studies using the high-dose-rate brachytherapy for treatment of head and neck cancer relapse were: 2-year overall survival was 19–63%; grade 3 - 4 late toxicity 4–22.2%. In these studies 3–4 Gy per fraction up to 30–40 Gy total dose were administered. So far, the randomized study, comparing the high-dose-rate brachytherapy with the three-dimensional radiotherapy, treating head and neck cancer relapse, hasn’t been conducted. We compared different radiotherapy methods: three-dimensional conformal radiotherapy was administered to the control group (25 fractions of 2 Gy, total dose of 50 Gy); the hypofractionated high-dose-rate brachytherapy was administered to the experimental group, while applying a new regime of fractionation: 2.5 Gy per fraction, two fractions per day, up to 30 Gy total dose. Such fractionation regimen was selected in order to reduce the rate and grade of toxicity, while the total dose is biologically equivalent to the total doses, which have been used in previous studies.

Recently a powerful electron accelerator, 50 MeV race-track microtron, has been taken into clinical use. This gives the opportunity to treat patients with higher x-ray and electron energies than before. Furthermore, treatments can be performed were the entire fractional dose can be delivered in parts of a second. The relative biological effectiveness (RBE) of high energy photons (up to 50 MV) was studied in vitro and in vivo. Oxygen enhancement ratio (OER) of 50 MV photons and RBE of 50 MeV electrons were investigated in vitro. Single-fraction experiments, in vitro, using V-79 Chinese hamster fibroblasts showed an RBE for 50 MV x-rays of approximately 1.1 at surviving fraction 0.01, with reference to the response to 4 MV x- rays. No significant difference in OER could be demonstrated. Fractionation experiments were carried out to establish the RBE at the clinically relevant dose level, 2 Gy. The RBE calculated for the 2 Gy/fraction experiments was 1.17. The RBEs for 20 MV x-rays and 50 MeV electrons were equal to one. In order to investigate the validity of these results, the jejunal crypt microcolony assay in mice was used to determine the RBE of 50 MV x-rays. The RBE for 50 MV x-rays in this case was estimated to be 1.06 at crypt surviving fraction 0.1. Photonuclear processes are proposed as one possible explanation to the higher RBE for 50 MV x-rays. Several studies of biological response to ionizing radiation of high absorbed dose rates have been performed, often with conflicting results. With the aim of investigating whether a difference in effect between irradiation at high dose rates and at conventional dose rates could be verified, pulsed 50 MeV electrons from a clinical accelerator were used for experiments with ultra high dose rates (mean dose rate: 3.8 x 10^ Gy/s) in comparison to conventional (mean dose rate: 9.6 x 10"^ Gy/s). V-79 cells were irradiated in vitro under both oxic and anoxic conditions. No significant difference in relative biological effectiveness (RBE) or oxygen enhancement ratio (OER) was observed for ultra high dose rates compared to conventional dose rates. A central issue in clinical radiobiological research is the prediction of responses to different radiation qualities. The choice of cell survival and dose response model greatly influences the results. In this context the relationship between theory and model is emphasized. Generally, the interpretations of experimental data are dependent on the model. Cell survival models are systematized with respect to their relations to radiobiological theories of cell kill. The growing knowledge of biological, physical, and chemical mechanisms is reflected in the formulation of new models. This study shows that recent modelling has been more oriented towards the stochastic fluctuations connected to radiation energy deposition. This implies that the traditional cell survival models ought to be complemented by models of stochastic energy deposition processes at the intracellular level. / <p>S. 1-44: sammanfattning, s. 47-130: 5 uppsatser</p> / digitalisering@umu

Submitted by SBI Biblioteca Digital (sbi.bibliotecadigital@puc-campinas.edu.br) on 2018-02-07T13:06:22Z No. of bitstreams: 1 ANA CAROLINA MASSAROTTO.pdf: 924874 bytes, checksum: 09a1ac55208a09df27e003db121d89d6 (MD5) / Made available in DSpace on 2018-02-07T13:06:22Z (GMT). No. of bitstreams: 1 ANA CAROLINA MASSAROTTO.pdf: 924874 bytes, checksum: 09a1ac55208a09df27e003db121d89d6 (MD5) Previous issue date: 2017-12-15 / Breast cancer is the second most common type of cancer in the world, and the most common among women, affecting men who account for 1% of all cases of the disease. The risk factors of the disease are related to age, endocrine / reproductive history, behavioral / environmental factors, and genetic / hereditary factors. The prognosis of the disease depends on its extension (staging), with greater curative potential when diagnosed at baseline.Among the types of treatment of breast cancer stand out surgery, radiotherapy, chemotherapy, hormone therapy and biological therapy. It is highlighted in the radiotherapy modality, Brachytherapy, which is the application of radiation in a more precise and localized way in the tumor. In this work we will focus on high-grade interstitial brachytherapy dose rate, partial and accelerated breast irradiation (IPAM), which has been shown to have better esthetic results, lower risk of injury from radiation from healthy adjacent tissues, shorter duration of treatment, and low recurrence rates. This is a retrospective, longitudinal, descriptive, analytical study, with a review of medical records of patients diagnosed with breast cancer, stages 0-I-II, between the years 2004 and 2013 who received IPAM using brachytherapy after conservative surgery of the breast at the Radium Institute of Campinas, Campinas-SP, Brazil.This work aims to report and evaluate the viability, acute and chronic toxicity, aesthetic aspects, efficacy and factors related to the use of Partial and Accelerated Breast Irradiation with high dose rate brachytherapy for patients with early stage of breast cancer. In addition to assessing recurrence rates and local control of the disease. / O c?ncer de mama ? o segundo tipo de c?ncer mais comum no mundo,e o mais frequente entre as mulheres, acometendo tamb?m homens que representam 1% do total de casos da doen?a. Os fatores de risco da doen?a est?o relacionados com idade, fatores end?crinos/hist?ria reprodutiva, fatores comportamentais/ambientais e fatores gen?ticos/heredit?rios. O progn?stico da doen?a depende da sua extens?o (estadiamento), com maior potencial curativo quando diagnosticada no in?cio. Entre os tipos de tratamento do c?ncer de mama destacam-se a cirurgia, radioterapia , quimioterapia, hormonioterapia e terapia biol?gica. Apresenta destaque na modalidade radioter?pica, a Braquiterapia, que trata-se da aplica??o de radia??o de forma mais precisa e localizada no tumor. Neste trabalho teremos como enfoque a braquiterapia intersticial de alta taxa de dose, irradia??o parcial e acelerada da mama (IPAM), que vem apresentando melhores resultados est?ticos, menor risco de les?o pela radia??o de tecidos adjacentes saud?veis, menor dura??o do tratamento, e baixas taxas de recorr?ncia. Trata-se de um estudo retrospectivo, longitudinal, descritivo, anal?tico, com revis?o de prontu?rios de pacientes com diagn?stico de c?ncer de mama, est?dios 0-I-II , entre os anos de 2004 e 2013 que receberam IPAM utilizando braquiterapia ap?s a cirurgia conservadora da mama no Instituto do Radium de Campinas, Campinas-SP, Brasil. Tal trabalho objetiva relatar e avaliar a viabilidade, toxicidade aguda e cr?nica, aspectos est?ticos, efic?cia e fatores relacionados com utiliza??o de Irradia??o Parcial e Acelerada da Mama com braquiterapia de alta taxa de dose para pacientes com est?dio inicial de c?ncer de mama. Al?m de avaliar as taxas de recorr?ncia e controle local da doen?a.

Submitted by SBI Biblioteca Digital (sbi.bibliotecadigital@puc-campinas.edu.br) on 2018-02-15T12:50:05Z No. of bitstreams: 1 VANDERLEI JOSE JUNIOR.pdf: 1351825 bytes, checksum: 599d050ec951a6a8e7497a0cea5d2e17 (MD5) / Made available in DSpace on 2018-02-15T12:50:05Z (GMT). No. of bitstreams: 1 VANDERLEI JOSE JUNIOR.pdf: 1351825 bytes, checksum: 599d050ec951a6a8e7497a0cea5d2e17 (MD5) Previous issue date: 2017-12-15 / Introduction: Prostate cancer is one of the most prevalent diseases in the male population, occupying the second position among malignant neoplasms. There are several therapeutic options for the treatment of localized prostate cancer, ranging from conservative behaviors to interventional treatments such as radical prostatectomy or external radiotherapy, associated or not with brachytherapy. Objective: To identify the factors that can predict biochemical recurrence and to evaluate treatment toxicity. METHOD: This is a retrospective and longitudinal study of 162 patients diagnosed with prostate cancer treated with conformational external radiotherapy associated with high dose rate brachytherapy (BTATD) between 2005 and 2014. The database was used of the Radium ? Campinas Oncology Institute, collected prospectively. Results: The mean follow-up time was 57 months. No grade 3 late toxicity was observed in the gastrointestinal tract, with only 1 patient (0.6%) genitourinary tract. The only categorical variable that presented statistical significance for biochemical relapse was the Nadir PSA <1 ng / ml (p = 0.018). The biochemical recurrence rate found was 96.3%, based on the Phoenix criteria (PSA nadir + 2 ng / ml). Conclusions: This study demonstrated that in the treatment of localized prostate cancer, the association of external radiotherapy with BATD is a safe therapeutic option, with a low degree 3 late toxicity and a biochemical recurrence of only 3.7% (with HF = 95 %). / Introdu??o: O c?ncer de pr?stata ? uma das doen?as mais prevalentes na popula??o masculina, ocupando a segunda posi??o entre as neoplasias malignas. H? v?rias op??es terap?uticas para o tratamento do c?ncer de pr?stata localizado, podendo variar de condutas conservadoras ? tratamentos intervencionistas como a prostatectomia radical ou a radioterapia externa, associada ou n?o ? braquiterapia. Objetivo: Identificar os fatores que possam predizer recidiva bioqu?mica e avaliar a toxicidade do tratamento. M?todo: Tratase de um estudo retrospectivo e longitudinal, com 162 pacientes diagnosticados com c?ncer de pr?stata, tratados com radioterapia externa conformacional associada ? braquiterapia de alta taxa de dose (BATD), entre 2005 e 2014. Utilizou-se o banco de dados do Radium - Instituto de Oncologia de Campinas, coletados prospectivamente. Resultados: O tempo m?dio de seguimento foi de 57 meses. N?o foi observada toxicidade tardia grau 3 no trato gastrointestinal, sendo apenas 1 paciente (0,6%) trato genitourin?rio. A ?nica vari?vel categ?rica que apresentou signific?ncia estat?stica para recidiva bioqu?mica foi o PSA Nadir <1 ng/ ml (p = 0,018). A taxa de recidiva bioqu?mica encontrada foi de 96,3%, baseando-se nos crit?rios de Phoenix (PSA nadir + 2 ng/ml). Conclus?es: Esse estudo demonstrou que, no tratamento de c?ncer de pr?stata localizado, a associa??o de radioterapia externa com BATD ? uma op??o terap?utica segura, com baixa taxa de toxicidade tardia grau 3 e recidiva bioqu?mica de apenas 3,7% (com I.C = 95%).