No description available.

Recently, there has been an increase in the number of proton beam therapy (PBT) centers operating worldwide. For certain cases, proton beams have been shown to provide dosimetric and radiobiological advantages when used for cancer treatment, compared to the regular photon-beam based treatments. Under ideal circumstances, the dose given to the tissues surrounding a target can be reduced with PBT. The risk for side effects following treatment is then expected to decrease. Until present, mainly stationary targets, e.g. targets in the brain, have been treated with PBT. There is currently a growing interest to treat also target volumes in other parts of the body with PBT. However, there are sources of uncertainties, which must be more carefully considered when PBT is used, especially for PBT carried out with scanned proton beams. PBT is more sensitive to anatomical changes, e.g. organ motion or a variable gas content in the intestines, which requires that special precautions are taken prior to treating new tumour sites. In photon beam radiotherapy (RT) of moving targets, the main consequence of organ motion is the loss of sharpness of the dose gradients (dose smearing). When scanned proton beams are used, dose deformation caused by the fluctuations in the proton beam range, due to varying tissue heterogeneities (e.g., the ribs moving in and out of the beam path) and the so-called interplay effect, can be expected to impact the dose distributions in addition to the dose smearing. The dosimetric uncertainties, if not accounted for, may cause the planned and accurately calculated dose distribution to be distorted, compromising the main goal of RT of achieving the maximal local disease control while accepting certain risks for normal tissue complications. Currently there is a lack of clinical follow-up data regarding the outcome of PBT for different tumour sites, in particular for extra-cranial tumour sites in moving organs. On the other hand, the use of photon beams for this kind of cancer treatment is well-stablished. A treatment planning comparison between RT carried out with photons and with protons may provide guidelines for when PBT could be more suitable. New clinical applications of particle beams in cancer therapy can also be transferred from photon-beam treatments, for which there is a vast clinical experience. The evaluation of the different uncertainties influencing RT of different tumour sites carried out with photon- and with proton-beams, will hopefully create an understanding for the feasibility of treating cancers with scanned proton beams instead of photon beams. The comparison of two distinct RT modalities is normally performed by studying the dosimetric values obtained from the dose volume histograms (DVH). However, in dosimetric evaluations, the outcome of the treatments in terms of local disease control and healthy tissue toxicity are not estimated. In this regard, radiobiological models can be an indispensable tool for the prediction of the outcome of cancer treatments performed with different types of ionising radiation. In this thesis, different factors that should be taken into consideration in PBT, for treatments influenced by organ motion and density heterogeneities, were studied and their importance quantified. This thesis consists of three published articles (Articles I, II and III). In these reports, the dosimetric and biological evaluations of photon-beam and scanned proton-beam RT were performed and the results obtained were compared. The studies were made for two tumour sites influenced by organ motion and density changes, gastric cancer (GC) and liver metastases. For the GC cases, the impact of changes in tissue density, resulting from variable gas content (which can be observed inter-fractionally), was also studied. In this thesis, both conventional fractionations (implemented in the planning for GC treatments) and hypofractionated regimens (implemented in the planning for the liver metastases cases) were considered. In this work, it was found that proton therapy provided the possibility to reduce the irradiations of the normal tissue located near the target volumes, compared to photon beam RT. However, the effects of density changes were found to be more pronounced in the plans for PBT. Furthermore, with proton beams, the reduction of the integral dose given to the OARs resulted in reduced risks of treatment-induced secondary malignancies.

This report from Groote Schuur therefore sets out to review cases of postradiation sarcomas, including malignant mixed mullerian tumors (MMMT), presenting to the Radiation Oncology Departments of Groote Schuur Hospital and the affiliated hospitals (Frere Hospital, East London and Provincial Hospital, Port Elizabeth) or known to have occurred in patients initially treated in these hospitals. It aims [1] to establish the features of the initial malignancy as well as the latent period for the development of postradiation sarcoma, the type of postradiation tumor and the outcome of the disease; [2] to establish as accurately as possible dose levels at which the postradiation tumors have developed; and [3] to briefly describe possible risk factors such as a genetic predisposition to the development of malignancy, repeated courses of radiotherapy, surgery as part of the treatment of the initial tumor, and chemotherapy. Questions regarding the genesis of postradiation sarcomas cannot be answered by a review of 20 cases, even when combined with an analysis of literature. This review aims to add relevant information to the body of data from which the final answers may come. In view of the late diagnosis often made in cases of postradiation sarcoma (25, 94) the review also aims to heighten awareness of the condition so that it may be more often reported at a curable stage.

No description available.

Thesis--University of Oklahoma. / Bibliography: leaves 115-119.

Thesis--University of Oklahoma. / Bibliography: leaves 90-92.

<b>Background:</b> Systemic chemotherapy and radiotherapy play an important role in the treatment of colorectal cancer. Tumour perfusion and oxygenation is known to influence radiosensitivity and chemosensitivity. In this thesis, I propose that the evaluation of changes in tumour perfusion using perfusion CT (pCT) and dynamic contrast-enhanced (Dce) MRI can guide the rational sequencing of drugs and radiation. <b>Methods:</b> Dce-MRI and pCT scans were incorporated into a clinical trial of hypofractionated pelvic radiotherapy and nelfinavir in 10 patients with rectal cancer. Toxicity and tissue biomarkers (tumour cell density, microvessel density, CAIX, HIF1-alpha, phospho-Akt and phospho-PRAS40) were evaluated. pCT liver scans were incorporated into an imaging study in patients with colorectal liver metastases randomised to receive either oxaliplatin/ 5FU chemotherapy or oxaliplatin/ 5FU chemotherapy plus selective internal radiotherapy. <b>Results:</b> After 7 days of nelfinavir concurrent with hypo-fractionated pelvic radiotherapy, there was a mean 42&percnt; increase in median K^trans (P=0.03, paired t test) on Dce-MRI and a median 30&percnt; increase in mean blood flow on pCT (P=0.028, Wilcoxon Rank Sum), although no statistically significant changes in perfusion parameters were demonstrated after 7 days of nelfinavir prior to radiotherapy. The feasibility of evaluating tumour cell density in rectal biopsies before and after radiotherapy and a radiosensitising drug as an early endpoint of response was demonstrated. In patients with colorectal liver metastases who received oxaliplatin and modified de Gramont chemotherapy alone, after 4 cycles of chemotherapy, a 28&percnt; decrease in the mean hepatic arterial fraction was observed (P=0.018, paired t test). Between pCT scans 2 days before SIRT and 39-47 days following SIRT and continued 2-weekly chemotherapy, there was a mean 62&percnt; (P=0.009) reduction in Blood Flow and 61&percnt; (P=0.006) reduction in Blood Volume (paired t test). <b>Conclusions</b> This research does not support the hypothesis that nelfinavir before radiotherapy improves blood flow to human rectal cancer. Increases in rectal tumour perfusion during radiotherapy and concurrent nelfinavir are likely to be primarily explained by the acute biological effects of radiation. Four or more cycles of oxaliplatin and modified de Gramont chemotherapy may result in changes in tumour perfusion of colorectal liver metastases which would be detrimental to subsequent radiotherapy. Selective internal radiotherapy resulted in substantial reductions in tumour perfusion 39-47 days after the treatment. Perfusion imaging can be used to detect changes in tumour perfusion in response to radiotherapy and systemic therapy which have implications for the sequencing of therapies.

Quando uma mulher grávida é submetida à radioterapia mamária, o feto pode ser gravemente afetado pela dose periférica. Com o objetivo de verificar essa dose, um objeto simulador humanóide foi irradiado na mama esquerda. O phantom é um manequim adaptado, com alguns materiais (de densidades próximas a da água) dentro e fora do mesmo. A irradiação foi feita usando feixes de raios X de energia de 6 MeV, provenientes de um acelerador linear “Clinac 600C”. Durante as irradiações, foi empregada uma blindagem, constituída de blocos e placas de chumbo, em torno da região abdominal do manequim. Além disso, foram utilizados dois tipos de filtros: físico, com angulação de 30o, e dinâmico. Através de uma câmara de ionização cilíndrica posicionada na região fetal do simulador, verificou-se que, ao final do tratamento mamário, a dose de radiação periférica atinge valores entre 3,90 e 48,67 cGy quando se irradia com o filtro físico, e entre 1,75 e 13,78 cGy para o filtro dinâmico; ambos com a blindagem. Através dos dados obtidos, conclui-se que a implantação do filtro físico incrementa a dose periférica devido ao aumento da intensidade da radiação de fuga e ao espalhamento causado pelo material atenuador. Além disso, a blindagem empregada não foi suficiente para bloquear toda radiação secundária: Ao se empregar o filtro em cunha, segundo a literatura, as doses podem ser capazes de induzir o retardo mental e o câncer durante a vida pós-nascimento. Já com o filtro dinâmico esses riscos são reduzidos drasticamente, chegando a ser ínfimos. / When a pregnant woman is submitted to breast radiotherapy, the fetus may be seriously affected by the peripheral dose. In order to verify that dose, a humanoid phantom, was irradiated at the left breast. The phantom is an adapted manikin, with some materials (densities close to water) inside and outside of it. The irradiation was done using a 6 MeV x-ray beam energy from a linear accelerator “Clinac 600C”. During the irradiation, a shield around the abdominal area of the manikin, consisting of blocks and slabs of lead was used. In addition, two types of filters were used: a physical, with 30o angulation, and an enhanced dynamic one. Through a cylindrical ionization chamber, positioned in the simulator ́s fetal region, it was found that, at the end of the breast treatment, the peripheral doses reach values between 3.90 and 48.67 cGy, when the physical wedge was used. With the application of the enhanced dynamic wedge, the values were between 1.75 and 13.78 cGy. According to the obtained data, the physical wedge can increase the peripheral dose due to the larger background radiation intensity and to the scattering caused by the attenuator material. In addition, the shielding couldn ́t block all the secondary radiation, which, according to the literature, can be able to induce mental retardation and cancer during postnatal life. However, the induction to these effects is negligible, when the type of wedge was changed.

Quando uma mulher grávida é submetida à radioterapia mamária, o feto pode ser gravemente afetado pela dose periférica. Com o objetivo de verificar essa dose, um objeto simulador humanóide foi irradiado na mama esquerda. O phantom é um manequim adaptado, com alguns materiais (de densidades próximas a da água) dentro e fora do mesmo. A irradiação foi feita usando feixes de raios X de energia de 6 MeV, provenientes de um acelerador linear “Clinac 600C”. Durante as irradiações, foi empregada uma blindagem, constituída de blocos e placas de chumbo, em torno da região abdominal do manequim. Além disso, foram utilizados dois tipos de filtros: físico, com angulação de 30o, e dinâmico. Através de uma câmara de ionização cilíndrica posicionada na região fetal do simulador, verificou-se que, ao final do tratamento mamário, a dose de radiação periférica atinge valores entre 3,90 e 48,67 cGy quando se irradia com o filtro físico, e entre 1,75 e 13,78 cGy para o filtro dinâmico; ambos com a blindagem. Através dos dados obtidos, conclui-se que a implantação do filtro físico incrementa a dose periférica devido ao aumento da intensidade da radiação de fuga e ao espalhamento causado pelo material atenuador. Além disso, a blindagem empregada não foi suficiente para bloquear toda radiação secundária: Ao se empregar o filtro em cunha, segundo a literatura, as doses podem ser capazes de induzir o retardo mental e o câncer durante a vida pós-nascimento. Já com o filtro dinâmico esses riscos são reduzidos drasticamente, chegando a ser ínfimos. / When a pregnant woman is submitted to breast radiotherapy, the fetus may be seriously affected by the peripheral dose. In order to verify that dose, a humanoid phantom, was irradiated at the left breast. The phantom is an adapted manikin, with some materials (densities close to water) inside and outside of it. The irradiation was done using a 6 MeV x-ray beam energy from a linear accelerator “Clinac 600C”. During the irradiation, a shield around the abdominal area of the manikin, consisting of blocks and slabs of lead was used. In addition, two types of filters were used: a physical, with 30o angulation, and an enhanced dynamic one. Through a cylindrical ionization chamber, positioned in the simulator ́s fetal region, it was found that, at the end of the breast treatment, the peripheral doses reach values between 3.90 and 48.67 cGy, when the physical wedge was used. With the application of the enhanced dynamic wedge, the values were between 1.75 and 13.78 cGy. According to the obtained data, the physical wedge can increase the peripheral dose due to the larger background radiation intensity and to the scattering caused by the attenuator material. In addition, the shielding couldn ́t block all the secondary radiation, which, according to the literature, can be able to induce mental retardation and cancer during postnatal life. However, the induction to these effects is negligible, when the type of wedge was changed.

PURPOSE:To assess if intensity-modulated radiotherapy (IMRT) can possibly lead to improved local control and lower incidence of vision impairment/blindness in comparison to non-IMRT techniques when treating sinonasal malignancies / what is the most optimal dose constraints for the optic pathway / and the impact of different IMRT strategies on optic pathway sparing in this setting.METHODS AND MATERIALS:A literature search in the PubMed databases was conducted in July, 2012.RESULTS:Clinical studies on IMRT and 2D/3D (2 dimensional/3 dimensional) RT for sinonasal malignancies suggest improved local control and lower incidence of severe vision impairment with IMRT in comparison to non-IMRT techniques. As observed in the non-IMRT studies, blindness due to disease progression may occur despite a lack of severe toxicity possibly due to the difficulty of controlling locally very advanced disease with a dose less than or equal to] 70Gy. Concurrent chemotherapy's influence on the the risk of severe optic toxicity after radiotherapy is unclear. A maximum dose of less than or equal to] 54Gy with conventional fractionation to the optic pathway may decrease the risk of blindness. Increased magnitude of intensity modulation through increasing the number of segments, beams, and using a combination of coplanar and non-coplanar arrangements may help increase dose conformality and optic pathway sparing when IMRT is used.CONCLUSION:IMRT optimized with appropriate strategies may be the treatment of choice for the most optimal local control and optic pathway sparing when treating sinonasal malignancy.