Intensity modulated radiotherapy (IMRT) can potentially increase the dose delivered to liver tumours while sparing normal tissues from dose. More complex IMRT, with more modulation of the radiation beam is more susceptible to geometric and dosimetric uncertainties than simpler radiotherapy plans. Simple breath-hold liver IMRT using few radiation beam segments (<30) was investigated in 27 patients to determine the quality of treatment in terms of tumour dose coverage and normal tissue sparing as compared to index IMRT using >30 segments. In all 27 plans number of segments was reduced to <30 without compromising tumour coverage or normal tissue dose constraints, at the expense of dose conformity. Delivered tumour and normal tissue dose did not differ statistically between IMRT plans when accounting for treatment residual geometric error. This research supports considering the use of simple IMRT for treatment of liver cancer, except when loss of dose conformation is undesirable (i.e. very high doses).

Intensity Modulated Radiation Therapy (IMRT) is a modern radiotherapy treatment technique used to obtain highly conformal dose distributions. The delivery of IMRT is commonly achieved through the use of a multileaf collimator (MLC). One of the hindrances at present to the widespread use of IMRT is the increased time required for its planning, delivery and verification. In this thesis one particular method of MLC based IMRT, known as Static Multileaf Collimator based IMRT (SMLC-IMRT), has been studied along with methods for improving it???s delivery efficiency. The properties of an MLC commonly used in SMLC-IMRT have been characterised. The potential ramifications of these properties on the dosimetric accuracy of the delivered IMRT field were also investigated. An Interactive Leaf Sequencing (ILS) program was developed that allowed for the manipulation and processing of intensity maps using a variety of methods. The objective of each method was to improve the delivery efficiency whilst maintaining the dosimetric quality of the IMRT treatment. The different methods investigated were collimator angle optimisation, filtration, and intensity level optimisation. The collimator was optimised by identifying the angle at which the minimum monitor unit???s (MU???s) were required when using a sliding-window delivery method. A Savitzky-Golay filter was applied to random intensity maps and suitable filtration parameters identified for filtering clinical IMRT fields, and the intensity levels were optimised based on a deviation threshold. The deviation threshold identified the acceptable level of difference tolerable between the original and modified intensity map. Several IMRT cases were investigated and the impact of each the methods on MU???s, segments and dose distribution observed. As the complexity of IMRT fields increases the dosimetric impact of the MLC properties increases. Complex SMLC-IMRT fields require longer delivery times due to the increased number of MU???s and segments. Collimator optimisation was shown to be a fast and effective means of improving delivery efficiency with negligible dosimetric change to the optimised plan. Modifying intensity maps by applying a filter and optimising the intensity levels did reduce the complexity and improve the delivery efficiency, but also required a dosimetric compromise of the optimised plan.

Intensity modulated radiotherapy (IMRT) can potentially increase the dose delivered to liver tumours while sparing normal tissues from dose. More complex IMRT, with more modulation of the radiation beam is more susceptible to geometric and dosimetric uncertainties than simpler radiotherapy plans. Simple breath-hold liver IMRT using few radiation beam segments (<30) was investigated in 27 patients to determine the quality of treatment in terms of tumour dose coverage and normal tissue sparing as compared to index IMRT using >30 segments. In all 27 plans number of segments was reduced to <30 without compromising tumour coverage or normal tissue dose constraints, at the expense of dose conformity. Delivered tumour and normal tissue dose did not differ statistically between IMRT plans when accounting for treatment residual geometric error. This research supports considering the use of simple IMRT for treatment of liver cancer, except when loss of dose conformation is undesirable (i.e. very high doses).

Intensity Modulated Radiation Therapy (IMRT) is a modern radiotherapy treatment technique used to obtain highly conformal dose distributions. The delivery of IMRT is commonly achieved through the use of a multileaf collimator (MLC). One of the hindrances at present to the widespread use of IMRT is the increased time required for its planning, delivery and verification. In this thesis one particular method of MLC based IMRT, known as Static Multileaf Collimator based IMRT (SMLC-IMRT), has been studied along with methods for improving it???s delivery efficiency. The properties of an MLC commonly used in SMLC-IMRT have been characterised. The potential ramifications of these properties on the dosimetric accuracy of the delivered IMRT field were also investigated. An Interactive Leaf Sequencing (ILS) program was developed that allowed for the manipulation and processing of intensity maps using a variety of methods. The objective of each method was to improve the delivery efficiency whilst maintaining the dosimetric quality of the IMRT treatment. The different methods investigated were collimator angle optimisation, filtration, and intensity level optimisation. The collimator was optimised by identifying the angle at which the minimum monitor unit???s (MU???s) were required when using a sliding-window delivery method. A Savitzky-Golay filter was applied to random intensity maps and suitable filtration parameters identified for filtering clinical IMRT fields, and the intensity levels were optimised based on a deviation threshold. The deviation threshold identified the acceptable level of difference tolerable between the original and modified intensity map. Several IMRT cases were investigated and the impact of each the methods on MU???s, segments and dose distribution observed. As the complexity of IMRT fields increases the dosimetric impact of the MLC properties increases. Complex SMLC-IMRT fields require longer delivery times due to the increased number of MU???s and segments. Collimator optimisation was shown to be a fast and effective means of improving delivery efficiency with negligible dosimetric change to the optimised plan. Modifying intensity maps by applying a filter and optimising the intensity levels did reduce the complexity and improve the delivery efficiency, but also required a dosimetric compromise of the optimised plan.

Thesis (M.S.)--University of Toledo, 2009. / "In partial fulfillment of the requirements for the degree of Master of Science in Biomedical Sciences." Title from title page of PDF document. Bibliography: p. 34-35.

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.

INTRODUÇÃO: A combinação de radioterapia e altas doses de cisplatina no tratamento do meduloblastoma tem se mostrado causa de importante ototoxicidade. Com a introdução da técnica de intensidade modulada do feixe (IMRT), tornou-se possível diminuir a dose média de radiação no aparelho auditivo. OBJETIVOS: O objetivo é determinar se com a radioterapia com reforço de dose com IMRT, é possível atingir índices menores de perda auditiva e se há um limite de dose no ouvido para a mesma. Analisar também se o volume de ouvido contornado durante o planejamento inverso influencia o resultado. MÉTODO: Quarenta e um pacientes com meduloblastoma (idade mediana, 10 anos) com audição normal ao início da radioterapia com IMRT foram avaliados retrospectivamente. O último seguimento e a última audiometria realizada após o término da radioterapia foram considerados. A função auditiva foi graduada em uma escala de 0 a 4 de acordo com os critérios de toxicidade do Pediatric Oncology Group (POG). As doses mínima, máxima, média e mediana recebidas pelo aparelho auditivo, bem como o volume contornado no planejamento do IMRT foram correlacionados com o grau de função auditiva. Foi realizada análise univariada e multivariada dos dados. RESULTADOS: O seguimento mediano foi de 41 meses (12,8 a 71) para avaliação audiométrica e 44 meses (14-72) para a sobrevida global. As doses medianas mínima, máxima, média e mediana recebidas pelo aparelho auditivo foram respectivamente de: 3785 (589,4 a 4758,2), 4832,5 (3724 a 5447,9), 4366,5 (2808,5 a 5097,3) e 4360,5 (2878 a 5031,1). Sete pacientes (17%) apresentaram perda auditiva graus 3 e 4. A análise univariada entre as variáveis não mostrou diferença com significância estatística, exceto para a dose de cisplatina (P < 0,03). Na análise multivariada com regressão logística, a dose mediana no aparelho auditivo foi um fator significativo para a perda auditiva graus 3 e 4 (P < 0,01), ao passo que a dose cumulativa de cisplatina apresentou tendência à perda graus 3 e 4 (P = 0,075). Não houve correlação entre o volume contornado no planejamento a perda auditiva. Perda auditiva graus 3 e 4 foi incomum com dose mediana no aparelho auditivo menor que 42 Gy (P = 0,063) e dose cumulativa de cisplatina abaixo de 375 mg/m² (P < 0,01). Nenhum paciente que recebeu carboplatina em substituição à cisplatina apresentou perda auditiva grave. Não houve associação, com significância estatística, entre as variáveis analisadas e a ototoxicidade, quando estes pacientes foram excluídos da análise. Quatro pacientes morreram e dois apresentaram recidiva no momento do estudo, levando a uma sobrevida global de 90% e uma sobrevida livre de doença de 85% em 44 meses. CONCLUSÕES: Os resultados mostram que o tratamento com IMRT leva a uma baixa taxa de perda auditiva grave, mesmo com um seguimento maior, o que é consistente com outros estudos. Acreditamos ser seguro contornar somente a cóclea e que uma dose mediana para a mesma deve ser mantida abaixo de 42 Gy. A quimioterapia com cisplatina continua a ter um papel importante no tratamento, no entanto a dose cumulativa não deve exceder 375 mg/m². A sobrevida foi impressionante neste estudo, uma vez que 21 (51,2%) foram classificados como alto risco / INTRODUCTION: The combination of radiation therapy and cisplatin chemotherapy for the treatment of medulloblastoma is a known cause of important ototoxicity. With the introduction of intensity-modulated radiation therapy (IMRT), it became possible to deliver less radiation to the auditory apparatus. PURPOSE: To determine if boost radiotherapy with IMRT can achieve a lower rate of hearing loss and if theres a cutoff dose for it. Also, to analyze whether the auditory apparatus volume contoured in inverse planning influences the outcome. METHODS: Forty-one pediatric medulloblastoma patients (median age, 10 years) with normal hearing at the time of radiation with IMRT were retrospectively evaluated. The last audiogram and follow-up from the completion of radiation were considered. Hearing function was graded on a scale 0 to 4 according to Pediatric Oncology groups toxicity criteria. Minimum, maximum, mean and median doses to the inner ear and its volume contoured in IMRT planning, as well the cisplatin dose were recorded and correlated with hearing function. Univariate and multivariate data analysis were performed. RESULTS: The median follow-up was 41 months (range 12.8-71.0 months) for audiometric evaluation and 44 months (range 14-72 months) for survival. Median doses for minimum, maximum, mean and median in the inner ear were respectively: 3785 (range, 589.4 to 4758.2), 4832.5 (range 3724 to 5447.9), 4366.5 (range 2808.5 to 5097,3) and 4360,5 (range 2878 to 5031,1). Seven patients (17%) have experienced Grade 3 or 4 hearing loss. Univariate analysis showed no difference among the variables with statistical significance, except for cisplatin dose (P < 0.03). In multivariate analysis with logistic regression, median dose in inner ear was a significant factor for hearing loss grade 3 or 4 (P < 0,01), meanwhile cisplatin dose had a trend to hearing loss grade 3 or 4 (P = 0.075). There was no relationship between the auditory apparatus volume contoured in planning and hearing loss. Grade 3 or 4 hearing loss were uncommon with median dose to the inner ear bellow 42 Gy (P = 0.063) and cisplatin dose less than 375 mg/m² (P < 0.01). None of the patients who received carboplatin in lieu of cisplatin had severe hearing loss. There was no statistically significant association between ototoxicity and the variables, when these patients were excluded from the analysis. Four patients died and two have recurred at the time of the study with a 90% overall survival rate and 85% disease free survival in 44 months. CONCLUSIONS: Our findings shows that IMRT treatment leads to a low rate of serious hearing loss even with a longer follow-up, which is consistent with others trials. We believe that is safe to contour only the cochlea and that a median dose to it should be kept below 42Gy. Cisplatin chemotherapy continues to have an important role in treatment, however doses should not exceed 375 mg/m². Survival rates were impressing in this trial given the fact that 21 (51.2%) patients were classified as high risk

INTRODUÇÃO: A combinação de radioterapia e altas doses de cisplatina no tratamento do meduloblastoma tem se mostrado causa de importante ototoxicidade. Com a introdução da técnica de intensidade modulada do feixe (IMRT), tornou-se possível diminuir a dose média de radiação no aparelho auditivo. OBJETIVOS: O objetivo é determinar se com a radioterapia com reforço de dose com IMRT, é possível atingir índices menores de perda auditiva e se há um limite de dose no ouvido para a mesma. Analisar também se o volume de ouvido contornado durante o planejamento inverso influencia o resultado. MÉTODO: Quarenta e um pacientes com meduloblastoma (idade mediana, 10 anos) com audição normal ao início da radioterapia com IMRT foram avaliados retrospectivamente. O último seguimento e a última audiometria realizada após o término da radioterapia foram considerados. A função auditiva foi graduada em uma escala de 0 a 4 de acordo com os critérios de toxicidade do Pediatric Oncology Group (POG). As doses mínima, máxima, média e mediana recebidas pelo aparelho auditivo, bem como o volume contornado no planejamento do IMRT foram correlacionados com o grau de função auditiva. Foi realizada análise univariada e multivariada dos dados. RESULTADOS: O seguimento mediano foi de 41 meses (12,8 a 71) para avaliação audiométrica e 44 meses (14-72) para a sobrevida global. As doses medianas mínima, máxima, média e mediana recebidas pelo aparelho auditivo foram respectivamente de: 3785 (589,4 a 4758,2), 4832,5 (3724 a 5447,9), 4366,5 (2808,5 a 5097,3) e 4360,5 (2878 a 5031,1). Sete pacientes (17%) apresentaram perda auditiva graus 3 e 4. A análise univariada entre as variáveis não mostrou diferença com significância estatística, exceto para a dose de cisplatina (P < 0,03). Na análise multivariada com regressão logística, a dose mediana no aparelho auditivo foi um fator significativo para a perda auditiva graus 3 e 4 (P < 0,01), ao passo que a dose cumulativa de cisplatina apresentou tendência à perda graus 3 e 4 (P = 0,075). Não houve correlação entre o volume contornado no planejamento a perda auditiva. Perda auditiva graus 3 e 4 foi incomum com dose mediana no aparelho auditivo menor que 42 Gy (P = 0,063) e dose cumulativa de cisplatina abaixo de 375 mg/m² (P < 0,01). Nenhum paciente que recebeu carboplatina em substituição à cisplatina apresentou perda auditiva grave. Não houve associação, com significância estatística, entre as variáveis analisadas e a ototoxicidade, quando estes pacientes foram excluídos da análise. Quatro pacientes morreram e dois apresentaram recidiva no momento do estudo, levando a uma sobrevida global de 90% e uma sobrevida livre de doença de 85% em 44 meses. CONCLUSÕES: Os resultados mostram que o tratamento com IMRT leva a uma baixa taxa de perda auditiva grave, mesmo com um seguimento maior, o que é consistente com outros estudos. Acreditamos ser seguro contornar somente a cóclea e que uma dose mediana para a mesma deve ser mantida abaixo de 42 Gy. A quimioterapia com cisplatina continua a ter um papel importante no tratamento, no entanto a dose cumulativa não deve exceder 375 mg/m². A sobrevida foi impressionante neste estudo, uma vez que 21 (51,2%) foram classificados como alto risco / INTRODUCTION: The combination of radiation therapy and cisplatin chemotherapy for the treatment of medulloblastoma is a known cause of important ototoxicity. With the introduction of intensity-modulated radiation therapy (IMRT), it became possible to deliver less radiation to the auditory apparatus. PURPOSE: To determine if boost radiotherapy with IMRT can achieve a lower rate of hearing loss and if theres a cutoff dose for it. Also, to analyze whether the auditory apparatus volume contoured in inverse planning influences the outcome. METHODS: Forty-one pediatric medulloblastoma patients (median age, 10 years) with normal hearing at the time of radiation with IMRT were retrospectively evaluated. The last audiogram and follow-up from the completion of radiation were considered. Hearing function was graded on a scale 0 to 4 according to Pediatric Oncology groups toxicity criteria. Minimum, maximum, mean and median doses to the inner ear and its volume contoured in IMRT planning, as well the cisplatin dose were recorded and correlated with hearing function. Univariate and multivariate data analysis were performed. RESULTS: The median follow-up was 41 months (range 12.8-71.0 months) for audiometric evaluation and 44 months (range 14-72 months) for survival. Median doses for minimum, maximum, mean and median in the inner ear were respectively: 3785 (range, 589.4 to 4758.2), 4832.5 (range 3724 to 5447.9), 4366.5 (range 2808.5 to 5097,3) and 4360,5 (range 2878 to 5031,1). Seven patients (17%) have experienced Grade 3 or 4 hearing loss. Univariate analysis showed no difference among the variables with statistical significance, except for cisplatin dose (P < 0.03). In multivariate analysis with logistic regression, median dose in inner ear was a significant factor for hearing loss grade 3 or 4 (P < 0,01), meanwhile cisplatin dose had a trend to hearing loss grade 3 or 4 (P = 0.075). There was no relationship between the auditory apparatus volume contoured in planning and hearing loss. Grade 3 or 4 hearing loss were uncommon with median dose to the inner ear bellow 42 Gy (P = 0.063) and cisplatin dose less than 375 mg/m² (P < 0.01). None of the patients who received carboplatin in lieu of cisplatin had severe hearing loss. There was no statistically significant association between ototoxicity and the variables, when these patients were excluded from the analysis. Four patients died and two have recurred at the time of the study with a 90% overall survival rate and 85% disease free survival in 44 months. CONCLUSIONS: Our findings shows that IMRT treatment leads to a low rate of serious hearing loss even with a longer follow-up, which is consistent with others trials. We believe that is safe to contour only the cochlea and that a median dose to it should be kept below 42Gy. Cisplatin chemotherapy continues to have an important role in treatment, however doses should not exceed 375 mg/m². Survival rates were impressing in this trial given the fact that 21 (51.2%) patients were classified as high risk

Cervix cancer affects women of all ages and causes significant morbidity and mortality. Locally advanced disease is curable with radiotherapy (RT) in about 50% of patients, although often at the expense of serious side effects. In order to improve the therapeutic ratio of tumour control versus normal tissue toxicity, conformal intensity-modulated radiotherapy (IMRT) is being investigated. However, inter- and intra-fractional motion of cervix cancer can contribute to both geographical miss of the target and overdosing of surrounding normal tissues, particularly in the setting of conformal IMRT with steep dose gradients. Defining the target volume accurately and understanding the dose consequence of these complex intra-pelvic organ dynamics during external beam radiotherapy forms the essential foundations for future treatment optimization and adaptation. This in turn will lead to improvements in tumour control and disease-free survival while minimising treatment toxicity.

Cervix cancer affects women of all ages and causes significant morbidity and mortality. Locally advanced disease is curable with radiotherapy (RT) in about 50% of patients, although often at the expense of serious side effects. In order to improve the therapeutic ratio of tumour control versus normal tissue toxicity, conformal intensity-modulated radiotherapy (IMRT) is being investigated. However, inter- and intra-fractional motion of cervix cancer can contribute to both geographical miss of the target and overdosing of surrounding normal tissues, particularly in the setting of conformal IMRT with steep dose gradients. Defining the target volume accurately and understanding the dose consequence of these complex intra-pelvic organ dynamics during external beam radiotherapy forms the essential foundations for future treatment optimization and adaptation. This in turn will lead to improvements in tumour control and disease-free survival while minimising treatment toxicity.