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1.
Radiat Oncol ; 15(1): 129, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32471500

RESUMO

BACKGROUND: The targeting accuracy of proton therapy (PT) for moving soft-tissue tumours is expected to greatly improve by real-time magnetic resonance imaging (MRI) guidance. The integration of MRI and PT at the treatment isocenter would offer the opportunity of combining the unparalleled soft-tissue contrast and real-time imaging capabilities of MRI with the most conformal dose distribution and best dose steering capability provided by modern PT. However, hybrid systems for MR-integrated PT (MRiPT) have not been realized so far due to a number of hitherto open technological challenges. In recent years, various research groups have started addressing these challenges and exploring the technical feasibility and clinical potential of MRiPT. The aim of this contribution is to review the different aspects of MRiPT, to report on the status quo and to identify important future research topics. METHODS: Four aspects currently under study and their future directions are discussed: modelling and experimental investigations of electromagnetic interactions between the MRI and PT systems, integration of MRiPT workflows in clinical facilities, proton dose calculation algorithms in magnetic fields, and MRI-only based proton treatment planning approaches. CONCLUSIONS: Although MRiPT is still in its infancy, significant progress on all four aspects has been made, showing promising results that justify further efforts for research and development to be undertaken. First non-clinical research solutions have recently been realized and are being thoroughly characterized. The prospect that first prototype MRiPT systems for clinical use will likely exist within the next 5 to 10 years seems realistic, but requires significant work to be performed by collaborative efforts of research groups and industrial partners.

2.
Med Phys ; 2018 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-30007067

RESUMO

PURPOSE: Hypofractionated radiotherapy of prostate cancer is gaining clinical acceptance given its potential increase in therapeutic ratio and evidence for noninferiority and lack of added late toxicities compared to conventional fractionation. However, concerns have been raised that smaller number of fractions might lead to larger dosimetric influence by interfractional motion. We aim to compare the effect of these variations on hypofractionated pencil beam scanning (PBS) proton therapy and volumetric modulated arc therapy (VMAT) for localized prostate cancer. METHODS: Weekly CT images were acquired for 6 patients participating in a randomized clinical trial. PBS plans featuring bilateral (BL) and a combination of lateral and anterior-oblique beams (AOL), and VMAT plans were created. All patients were treated to a conventional 79.2 Gy total dose in 44 fractions. For this study, hypofractionated dose to the prostate gland was 51.6 Gy in 12 fractions or 36.25 Gy in 5 fractions, and 32.8, and 23.1 Gy to proximal seminal vesicles, respectively. Patients were simulated with endorectal balloons to aid gland immobilization. Three fiducial markers were implanted for setup guidance. All plans were recomputed on the weekly CT images after aligning with the simulation CT. The entire set of 9 CT images was used for dose recalculation for 12-fraction and only 5 used for the 5-fraction case. Adaptive range adjustments were applied to anterior-oblique beams assuming clinical availability of in vivo range verification. Fractional doses were summed using deformable dose accumulation to approximate the delivered dose. Biologically equivalent dose to 2 Gy(EQD2) was calculated assuming α/ß of 1.5 Gy for prostate and 3 Gy for bladder and rectum. RESULTS: The median delivered prostate D98 was 0.13/0.14/0.13 Gy(EQD2) smaller than planned for PBS-BL, 0.13/0.27/0.17 Gy(EQD2) for PBS-AOL and 0.59/0.66/0.59 Gy(EQD2) for VMAT, for 44/12/5 fractions, respectively. The largest D98 reduction was 1.5 and 3.5 Gy(EQD2) for CTV1 and CTV2, respectively. Target dose degradation was comparable for all fractionation schemes within each modality. The maximum increase in rectum D2 was 0.98 Gy(EQD2) for a 5-fraction PBS case. CONCLUSIONS: The robustness of PBS and VMAT were comparable for all patients for the studied fractionations. The delivered target dose generally remained within clinical tolerance and the deviations were relatively minor for both fractionation schemes. The delivered OAR dose stayed in compliance with the RTOG hypofractionation constraints for all cases.

3.
Acta Oncol ; 56(4): 575-581, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28075206

RESUMO

AIM: Anterior-oblique (AO) proton beams can form an attractive option for prostate patients receiving external beam radiotherapy (EBRT) as they avoid the femoral heads. For a cohort with hydrogel prostate-rectum spacers, we asked whether it was possible to generate AO proton plans robust to end-of-range elevations in linear energy transfer (LET) and modeled relative biological effectiveness (RBE). Additionally we considered how rectal spacers influenced planned dose distributions for AO and standard bilateral (SB) proton beams versus intensity-modulated radiotherapy (IMRT). MATERIAL AND METHODS: We studied three treatment strategies for 10 patients with rectal spacers: (A) AO proton beams, (B) SB proton beams and (C) IMRT. For strategy (A) dose and LET distributions were simulated (using the TOPAS Monte Carlo platform) and the McNamara model was used to calculate proton RBE as a function of LET, dose per fraction, and photon α/ß. All calculations were performed on pretreatment scans: inter- and intra-fractional changes in anatomy/set-up were not considered. RESULTS: For 9/10 patients, rectal spacers enabled generation of AO proton plans robust to modeled RBE elevations: rectal dose constraints were fulfilled even when the variable RBE model was applied with a conservative α/ß = 2 Gy. Amongst a subset of patients the proton rectal doses for the planning target volume plans were remarkably low: for 2/10 SB plans and 4/10 AO plans, ≤10% of the rectum received ≥20 Gy. AO proton plans delivered integral doses a factor of approximately three lower than IMRT and spared the femoral heads almost entirely. CONCLUSION: Typically, rectal spacers enabled the generation of anterior beam proton plans that appeared robust to modeled variation in RBE. However, further analysis of day-to-day robustness would be required prior to a clinical implementation of AO proton beams. Such beams offer almost complete femoral head sparing, but their broader value relative to IMRT and SB protons remains unclear.


Assuntos
Neoplasias da Próstata/radioterapia , Terapia com Prótons/instrumentação , Planejamento da Radioterapia Assistida por Computador/métodos , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato , Masculino , Órgãos em Risco , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Reto , Eficiência Biológica Relativa
4.
Int J Radiat Oncol Biol Phys ; 95(1): 190-8, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-27084640

RESUMO

PURPOSE: This study aimed to assess the clinical impact of spot size and the addition of apertures and range compensators on the treatment quality of pencil beam scanning (PBS) proton therapy and to define when PBS could improve on passive scattering proton therapy (PSPT). METHODS AND MATERIALS: The patient cohort included 14 pediatric patients treated with PSPT. Six PBS plans were created and optimized for each patient using 3 spot sizes (∼12-, 5.4-, and 2.5-mm median sigma at isocenter for 90- to 230-MeV range) and adding apertures and compensators to plans with the 2 larger spots. Conformity and homogeneity indices, dose-volume histogram parameters, equivalent uniform dose (EUD), normal tissue complication probability (NTCP), and integral dose were quantified and compared with the respective PSPT plans. RESULTS: The results clearly indicated that PBS with the largest spots does not necessarily offer a dosimetric or clinical advantage over PSPT. With comparable target coverage, the mean dose (Dmean) to healthy organs was on average 6.3% larger than PSPT when using this spot size. However, adding apertures to plans with large spots improved the treatment quality by decreasing the average Dmean and EUD by up to 8.6% and 3.2% of the prescribed dose, respectively. Decreasing the spot size further improved all plans, lowering the average Dmean and EUD by up to 11.6% and 10.9% compared with PSPT, respectively, and eliminated the need for beam-shaping devices. The NTCP decreased with spot size and addition of apertures, with maximum reduction of 5.4% relative to PSPT. CONCLUSIONS: The added benefit of using PBS strongly depends on the delivery configurations. Facilities limited to large spot sizes (>∼8 mm median sigma at isocenter) are recommended to use apertures to reduce treatment-related toxicities, at least for complex and/or small tumors.


Assuntos
Neoplasias/radioterapia , Órgãos em Risco/efeitos da radiação , Terapia com Prótons/métodos , Lesões por Radiação/prevenção & controle , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias do Sistema Nervoso Central/radioterapia , Criança , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Distribuição Normal , Tratamentos com Preservação do Órgão/instrumentação , Tratamentos com Preservação do Órgão/métodos , Neoplasias Pélvicas/radioterapia , Terapia com Prótons/instrumentação , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/instrumentação , Neoplasias Torácicas/radioterapia
5.
Int J Radiat Oncol Biol Phys ; 95(1): 454-64, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-27084660

RESUMO

PURPOSE: For prostate treatments, robust evidence regarding the superiority of either intensity modulated radiation therapy (IMRT) or proton therapy is currently lacking. In this study we investigated the circumstances under which proton therapy should be expected to outperform IMRT, particularly the proton beam orientations and relative biological effectiveness (RBE) assumptions. METHODS AND MATERIALS: For 8 patients, 4 treatment planning strategies were considered: (A) IMRT; (B) passively scattered standard bilateral (SB) proton beams; (C) passively scattered anterior oblique (AO) proton beams, and (D) AO intensity modulated proton therapy (IMPT). For modalities (B)-(D) the dose and linear energy transfer (LET) distributions were simulated using the TOPAS Monte Carlo platform and RBE was calculated according to 3 different models. RESULTS: Assuming a fixed RBE of 1.1, our implementation of IMRT outperformed SB proton therapy across most normal tissue metrics. For the scattered AO proton plans, application of the variable RBE models resulted in substantial hotspots in rectal RBE weighted dose. For AO IMPT, it was typically not possible to find a plan that simultaneously met the tumor and rectal constraints for both fixed and variable RBE models. CONCLUSION: If either a fixed RBE of 1.1 or a variable RBE model could be validated in vivo, then it would always be possible to use AO IMPT to dose-boost the prostate and improve normal tissue sparing relative to IMRT. For a cohort without rectum spacer gels, this study (1) underlines the importance of resolving the question of proton RBE within the framework of an IMRT versus proton debate for the prostate and (2) highlights that without further LET/RBE model validation, great care must be taken if AO proton fields are to be considered for prostate treatments.


Assuntos
Órgãos em Risco/efeitos da radiação , Neoplasias da Próstata/radioterapia , Terapia com Prótons/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Reto/efeitos da radiação , Eficiência Biológica Relativa , Humanos , Transferência Linear de Energia , Masculino , Método de Monte Carlo , Tratamentos com Preservação do Órgão/métodos , Pênis/efeitos da radiação , Próteses e Implantes , Terapia com Prótons/efeitos adversos , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/efeitos adversos , Bexiga Urinária/efeitos da radiação
6.
Int J Radiat Oncol Biol Phys ; 95(1): 444-53, 2016 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-26907917

RESUMO

PURPOSE: To quantify and compare the impact of interfractional setup and anatomic variations on proton therapy (PT) and intensity modulated radiation therapy (IMRT) for prostate cancer. METHODS AND MATERIALS: Twenty patients with low-risk or intermediate-risk prostate cancer randomized to receive passive-scattering PT (n=10) and IMRT (n=10) were selected. For both modalities, clinical treatment plans included 50.4 Gy(RBE) to prostate and proximal seminal vesicles, and prostate-only boost to 79.2 Gy(RBE) in 1.8 Gy(RBE) per fraction. Implanted fiducials were used for prostate localization and endorectal balloons were used for immobilization. Patients in PT and IMRT arms received weekly computed tomography (CT) and cone beam CT (CBCT) scans, respectively. The planned dose was recalculated on each weekly image, scaled, and mapped onto the planning CT using deformable registration. The resulting accumulated dose distribution over the entire treatment course was compared with the planned dose using dose-volume histogram (DVH) and γ analysis. RESULTS: The target conformity index remained acceptable after accumulation. The largest decrease in the average prostate D98 was 2.2 and 0.7 Gy for PT and IMRT, respectively. On average, the mean dose to bladder increased by 3.26 ± 7.51 Gy and 1.97 ± 6.84 Gy for PT and IMRT, respectively. These values were 0.74 ± 2.37 and 0.56 ± 1.90 for rectum. Differences between changes in DVH indices were not statistically significant between modalities. All volume indices remained within the protocol tolerances after accumulation. The average pass rate for the γ analysis, assuming tolerances of 3 mm and 3%, for clinical target volume, bladder, rectum, and whole patient for PT/IMRT were 100/100, 92.6/99, 99.2/100, and 97.2/99.4, respectively. CONCLUSION: The differences in target coverage and organs at risk dose deviations for PT and IMRT were not statistically significant under the guidelines of this protocol.


Assuntos
Órgãos em Risco/efeitos da radiação , Neoplasias da Próstata/radioterapia , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Fracionamento da Dose de Radiação , Marcadores Fiduciais , Humanos , Masculino , Pessoa de Meia-Idade , Movimento , Tamanho do Órgão/efeitos da radiação , Estudos Prospectivos , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia , Radiografia , Reto/efeitos da radiação , Eficiência Biológica Relativa , Glândulas Seminais/efeitos da radiação , Estatísticas não Paramétricas , Bexiga Urinária/efeitos da radiação
7.
Phys Med Biol ; 61(1): 12-22, 2016 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-26605679

RESUMO

The purpose of this study was to compare the radiation-induced second cancer risks for in-field and out-of-field organs and tissues for pencil beam scanning (PBS) and passive scattering proton therapy (PPT) and assess the impact of adding patient-specific apertures to sharpen the penumbra in pencil beam scanning for pediatric brain tumor patients. Five proton therapy plans were created for each of three pediatric patients using PPT as well as PBS with two spot sizes (average sigma of ~17 mm and ~8 mm at isocenter) and choice of patient-specific apertures. The lifetime attributable second malignancy risks for both in-field and out-of-field tissues and organs were compared among five delivery techniques. The risk for in-field tissues was calculated using the organ equivalent dose, which is determined by the dose volume histogram. For out-of-field organs, the organ-specific dose equivalent from secondary neutrons was calculated using Monte Carlo and anthropomorphic pediatric phantoms. We find that either for small spot size PBS or for large spot size PBS, a patient-specific aperture reduces the in-field cancer risk to values lower than that for PPT. The reduction for large spot sizes (on average 43%) is larger than for small spot sizes (on average 21%). For out-of-field organs, the risk varies only marginally by employing a patient-specific aperture (on average from -2% to 16% with increasing distance from the tumor), but is still one to two orders of magnitude lower than that for PPT. In conclusion, when pencil beam spot sizes are large, the addition of apertures to sharpen the penumbra decreases the in-field radiation-induced secondary cancer risk. There is a slight increase in out-of-field cancer risk as a result of neutron scatter from the aperture, but this risk is by far outweighed by the in-field risk benefit from using an aperture with a large PBS spot size. In general, the risk for developing a second malignancy in out-of-field organs for PBS remains much lower compared to PPT even if apertures are being applied.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Induzidas por Radiação/prevenção & controle , Modelagem Computacional Específica para o Paciente , Terapia com Prótons/efeitos adversos , Planejamento da Radioterapia Assistida por Computador/métodos , Adolescente , Pré-Escolar , Feminino , Humanos , Lactente , Masculino
8.
Phys Med Biol ; 61(2): 683-95, 2016 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-26716718

RESUMO

The goal of this work was to determine the scattered photon dose and secondary neutron dose and resulting risk for the sensitive fetus from photon and proton radiotherapy when treating a brain tumor during pregnancy. Anthropomorphic pregnancy phantoms with three stages (3-, 6-, 9-month) based on ICRP reference parameters were implemented in Monte Carlo platform TOPAS, to evaluate the scattered dose and secondary neutron dose and dose equivalent. To evaluate the dose equivalent, dose averaged quality factors were considered for neutrons. This study compared three treatment modalities: passive scattering and pencil beam scanning proton therapy (PPT and PBS) and 6-MV 3D conformal photon therapy. The results show that, for 3D conformal photon therapy, the scattered photon dose equivalent to the fetal body increases from 0.011 to 0.030 mSv per treatment Gy with increasing stage of gestation. For PBS, the neutron dose equivalent to the fetal body was significantly lower, i.e. increasing from 1.5 × 10(-3) to 2.5 × 10(-3) mSv per treatment Gy with increasing stage of gestation. For PPT, the neutron dose equivalent of the fetus decreases from 0.17 to 0.13 mSv per treatment Gy with the growing fetus. The ratios of dose equivalents to the fetus for a 52.2 Gy(RBE) course of radiation therapy to a typical CT scan of the mother's head ranged from 3.4-4.4 for PBS, 30-41 for 3D conformal photon therapy and 180-500 for PPT, respectively. The attained dose to a fetus from the three modalities is far lower than the thresholds of malformation, severe mental retardation and lethal death. The childhood cancer excessive absolute risk was estimated using a linear no-threshold dose-response relationship. The risk would be 1.0 (95% CI: 0.6, 1.6) and 0.1 (95% CI: -0.01, 0.52) in 10(5) for the 9-month fetus for PBS with a prescribed dose of 52.2 Gy(RBE). The increased risks for PPT and photon therapy are about two and one orders of magnitude larger than that for PBS, respectively. We can conclude that a pregnant woman with a brain tumor could be treated with pencil beam scanning with acceptable risks to the fetus.


Assuntos
Neoplasias Encefálicas/radioterapia , Feto/efeitos da radiação , Terapia com Prótons/efeitos adversos , Radioterapia Conformacional/efeitos adversos , Feminino , Humanos , Imagens de Fantasmas , Fótons/efeitos adversos , Fótons/uso terapêutico , Gravidez , Prótons/efeitos adversos
9.
Int J Radiat Oncol Biol Phys ; 92(5): 1157-1164, 2015 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-26025779

RESUMO

PURPOSE: To assess the impact of approximations in current analytical dose calculation methods (ADCs) on tumor control probability (TCP) in proton therapy. METHODS: Dose distributions planned with ADC were compared with delivered dose distributions as determined by Monte Carlo simulations. A total of 50 patients were investigated in this analysis with 10 patients per site for 5 treatment sites (head and neck, lung, breast, prostate, liver). Differences were evaluated using dosimetric indices based on a dose-volume histogram analysis, a γ-index analysis, and estimations of TCP. RESULTS: We found that ADC overestimated the target doses on average by 1% to 2% for all patients considered. The mean dose, D95, D50, and D02 (the dose value covering 95%, 50% and 2% of the target volume, respectively) were predicted within 5% of the delivered dose. The γ-index passing rate for target volumes was above 96% for a 3%/3 mm criterion. Differences in TCP were up to 2%, 2.5%, 6%, 6.5%, and 11% for liver and breast, prostate, head and neck, and lung patients, respectively. Differences in normal tissue complication probabilities for bladder and anterior rectum of prostate patients were less than 3%. CONCLUSION: Our results indicate that current dose calculation algorithms lead to underdosage of the target by as much as 5%, resulting in differences in TCP of up to 11%. To ensure full target coverage, advanced dose calculation methods like Monte Carlo simulations may be necessary in proton therapy. Monte Carlo simulations may also be required to avoid biases resulting from systematic discrepancies in calculated dose distributions for clinical trials comparing proton therapy with conventional radiation therapy.


Assuntos
Algoritmos , Método de Monte Carlo , Neoplasias/radioterapia , Terapia com Prótons/estatística & dados numéricos , Dosagem Radioterapêutica , Neoplasias da Mama/radioterapia , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Neoplasias Hepáticas/radioterapia , Neoplasias Pulmonares/radioterapia , Masculino , Órgãos em Risco/efeitos da radiação , Probabilidade , Neoplasias da Próstata/radioterapia , Radiometria/métodos , Reto/efeitos da radiação , Incerteza , Bexiga Urinária/efeitos da radiação
10.
Radiother Oncol ; 113(1): 77-83, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25443861

RESUMO

BACKGROUND: Pediatric rhabdomyosarcoma (RMS) is highly curable, however, cure may come with significant radiation related toxicity in developing tissues. Proton therapy (PT) can spare excess dose to normal structures, potentially reducing the incidence of adverse effects. METHODS: Between 2005 and 2012, 54 patients were enrolled on a prospective multi-institutional phase II trial using PT in pediatric RMS. As part of the protocol, intensity modulated radiation therapy (IMRT) plans were generated for comparison with clinical PT plans. RESULTS: Target coverage was comparable between PT and IMRT plans with a mean CTV V95 of 100% for both modalities (p=0.82). However, mean integral dose was 1.8 times higher for IMRT (range 1.0-4.9). By site, mean integral dose for IMRT was 1.8 times higher for H&N (p<0.01) and GU (p=0.02), 2.0 times higher for trunk/extremity (p<0.01), and 3.5 times higher for orbit (p<0.01) compared to PT. Significant sparing was seen with PT in 26 of 30 critical structures assessed for orbital, head and neck, pelvic, and trunk/extremity patients. CONCLUSIONS: Proton radiation lowers integral dose and improves normal tissue sparing when compared to IMRT for pediatric RMS. Correlation with clinical outcomes is necessary once mature long-term toxicity data are available.


Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Neoplasias Pélvicas/radioterapia , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Rabdomiossarcoma/radioterapia , Neoplasias Torácicas/radioterapia , Criança , Feminino , Humanos , Masculino , Tratamentos com Preservação do Órgão/métodos , Estudos Prospectivos , Radiometria , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos
11.
Phys Med Biol ; 59(12): 2883-99, 2014 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-24828559

RESUMO

The incidence of second malignant tumors is a clinically observed adverse late effect of radiation therapy, especially in organs close to the treatment site, receiving medium to high doses (>2.5 Gy). For pediatric patients, choosing the least toxic radiation modality is of utmost importance, due to their high radiosensitivity and small size. This study aims to evaluate the risk of second cancer incidence in the vicinity of the primary radiation field, for pediatric patients with brain/head and neck tumors and compare four treatment modalities: passive scattering and pencil beam scanning proton therapy (PPT and PBS), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). For a cohort of six pediatric patients originally treated with PPT, additional PBS, IMRT and VMAT plans were created. Dose distributions from these plans were used to calculate the excess absolute risk (EAR) and lifetime attributable risk (LAR) for developing a second tumor in soft tissue and skull. A widely used risk assessment formalism was employed and compared with a linear model based on recent clinical findings. In general, LAR was found to range between 0.01%-2.8% for PPT/PBS and 0.04%-4.9% for IMRT/VMAT. PBS was associated with the lowest risk for most patients using carcinoma and sarcoma models, whereas IMRT and VMAT risks were comparable and the highest among all modalities. The LAR for IMRT/VMAT relative to PPT ranged from 1.3-4.6 for soft tissue and from 3.5-9.5 for skull. Larger absolute LAR was observed for younger patients and using linear risk models. The number of fields used in proton therapy and IMRT had minimal effect on the risk. When planning treatments and deciding on the treatment modality, the probability of second cancer incidence should be carefully examined and weighed against the possibility of developing acute side effects for each patient individually.


Assuntos
Neoplasias Encefálicas/radioterapia , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/etiologia , Radioterapia de Intensidade Modulada/efeitos adversos , Criança , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Masculino , Órgãos em Risco/efeitos da radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Medição de Risco
12.
Phys Med Biol ; 57(19): 6047-61, 2012 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-22968191

RESUMO

There is clinical evidence that second malignancies in radiation therapy occur mainly within the beam path, i.e. in the medium or high-dose region. The purpose of this study was to assess the risk for developing a radiation-induced tumor within the treated volume and to compare this risk for proton therapy and intensity-modulated photon therapy (IMRT). Instead of using data for specific patients we have created a representative scenario. Fully contoured age- and gender-specific whole body phantoms (4 year and 14 year old) were uploaded into a treatment planning system and tumor volumes were contoured based on patients treated for optic glioma and vertebral body Ewing's sarcoma. Treatment plans for IMRT and proton therapy treatments were generated. Lifetime attributable risks (LARs) for developing a second malignancy were calculated using a risk model considering cell kill, mutation, repopulation, as well as inhomogeneous organ doses. For standard fractionation schemes, the LAR for developing a second malignancy from radiation therapy alone was found to be up to 2.7% for a 4 year old optic glioma patient treated with IMRT considering a soft-tissue carcinoma risk model only. Sarcoma risks were found to be below 1% in all cases. For a 14 year old, risks were found to be about a factor of 2 lower. For Ewing's sarcoma cases the risks based on a sarcoma model were typically higher than the carcinoma risks, i.e. LAR up to 1.3% for soft-tissue sarcoma. In all cases, the risk from proton therapy turned out to be lower by at least a factor of 2 and up to a factor of 10. This is mainly due to lower total energy deposited in the patient when using proton beams. However, the comparison of a three-field and four-field proton plan also shows that the distribution of the dose, i.e. the particular treatment plan, plays a role. When using different fractionation schemes, the estimated risks roughly scale with the total dose difference in%. In conclusion, proton therapy can significantly reduce the risk for developing an in-field second malignancy. The risk depends on treatment planning parameters, i.e. an analysis based on our formalism could be applied within treatment planning programs to guide treatment plans for pediatric patients.


Assuntos
Neoplasias Induzidas por Radiação/etiologia , Órgãos em Risco/efeitos da radiação , Terapia com Prótons/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Adolescente , Pré-Escolar , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Glioma do Nervo Óptico/radioterapia , Planejamento da Radioterapia Assistida por Computador , Medição de Risco , Sarcoma de Ewing/radioterapia , Espalhamento de Radiação
13.
Radiother Oncol ; 103(1): 12-7, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22391053

RESUMO

PURPOSE: Given concerns of excess malignancies following adjuvant radiation for seminoma, we evaluated photon and proton beam therapy (PBT) treatment plans to assess dose distributions to organs at risk and model rates of second cancers. MATERIALS AND METHODS: Ten stage I seminoma patients who were treated with conventional para-aortic AP-PA photon radiation to 25.5 Gy at Massachusetts General Hospital had PBT plans generated (AP-PA, PA alone). Dose differences to critical organs were examined. Risks of second primary malignancies were calculated. RESULTS: PBT plans were superior to photons in limiting dose to organs at risk. PBT decreased dose by 46% (8.2 Gy) and 64% (10.2 Gy) to the stomach and large bowel, respectively (p<0.01). Notably, PBT was found to avert 300 excess second cancers among 10,000 men treated at a median age of 39 and surviving to 75 (p<0.01). CONCLUSIONS: In this study, the use of protons provided a favorable dose distribution with an ability to limit unnecessary exposure to critical normal structures in the treatment of early-stage seminoma. It is expected that this will translate into decreased acute toxicity and reduced risk of second cancers, for which prospective studies are warranted.


Assuntos
Fótons/uso terapêutico , Terapia com Prótons , Planejamento da Radioterapia Assistida por Computador , Seminoma/radioterapia , Neoplasias Testiculares/radioterapia , Adulto , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Induzidas por Radiação , Fótons/efeitos adversos , Prótons/efeitos adversos , Dosagem Radioterapêutica , Radioterapia Adjuvante , Estudos Retrospectivos , Fatores de Risco , Seminoma/patologia
14.
Phys Med Biol ; 57(5): 1159-72, 2012 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-22330133

RESUMO

Traditionally, dose in proton radiotherapy is prescribed as Gy(RBE) by scaling up the physical dose by 10%. The relative biological effectiveness (RBE) of protons is considered to vary with dose-averaged linear energy transfer (LET(d)), dose (d) and (α/ß)(x). The increase of RBE with depth causes a shift of the falloff of the beam, i.e. a change of the beam range. The magnitude of this shift will depend on dose and (α/ß)(x). The aim of this project was to quantify the dependence of the range shift on these parameters. Three double-scattered beams of different ranges incident on a computational phantom consisting of different regions of interest (ROIs) were used. Each ROI was assigned with (α/ß)(x) values between 0.5 and 20 Gy. The distribution of LET(d) within each ROI was obtained from a Monte Carlo simulation. The LET(d) distribution depends on the beam energy and thus its nominal range. The RBE values within the ROIs were calculated for doses between 1 and 15 Gy using an in-house developed biophysical model. Dose-volume histograms of the RBE-weighted doses were extracted for each ROI for a 'fixed RBE' (RBE = 1.1) and a 'variable RBE' (RBE = f (d, α/ß, LET(d))), and the percentage difference in range was obtained from the difference of the percentage volumes at the distal 80% of the dose. Range differences in normal tissue ((α/ß)(x) = 3 Gy) of the order of 3-2 mm were obtained, respectively, for a shallow (physical range 4.8 cm) and a deep (physical range 12.8 cm) beam, when a dose of 1 Gy normalized to the mid-SOBP was delivered. As the dose increased to 15 Gy, the variable RBE decreases below 1.1 which induces ranges of about 1 mm shorter than those obtained with an RBE of 1.1. The shift in the range of an SOBP when comparing biological dose distributions obtained with a fixed or a variable RBE was quantified as a function of dose, (α/ß)(x) and physical range (as a surrogate of the initial beam energy). The shift increases with the physical range but decreases with increasing dose or (α/ß)(x). The results of our study allow a quantitative consideration of RBE-caused range uncertainties as a function of treatment site and dose in treatment planning.


Assuntos
Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia/métodos , Encéfalo/patologia , Simulação por Computador , Relação Dose-Resposta à Radiação , Humanos , Transferência Linear de Energia , Modelos Estatísticos , Método de Monte Carlo , Imagens de Fantasmas , Prótons , Eficiência Biológica Relativa , Incerteza
15.
Phys Med Biol ; 57(2): 499-515, 2012 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-22217682

RESUMO

Secondary neutron fluence created during proton therapy can be a significant source of radiation exposure in organs distant from the treatment site, especially in pediatric patients. Various published studies have used computational phantoms to estimate neutron equivalent doses in proton therapy. In these simulations, whole-body patient representations were applied considering either generic whole-body phantoms or generic age- and gender-dependent phantoms. No studies to date have reported using patient-specific geometry information. The purpose of this study was to estimate the effects of patient­phantom matching when using computational pediatric phantoms. To achieve this goal, three sets of phantoms, including different ages and genders, were compared to the patients' whole-body CT. These sets consisted of pediatric age specific reference, age-adjusted reference and anatomically sculpted phantoms. The neutron equivalent dose for a subset of out-of-field organs was calculated using the GEANT4 Monte Carlo toolkit, where proton fields were used to irradiate the cranium and the spine of all phantoms and the CT-segmented patient models. The maximum neutron equivalent dose per treatment absorbed dose was calculated and found to be on the order of 0 to 5 mSv Gy(-1). The relative dose difference between each phantom and their respective CT-segmented patient model for most organs showed a dependence on how close the phantom and patient heights were matched. The weight matching was found to have much smaller impact on the dose accuracy except for very heavy patients. Analysis of relative dose difference with respect to height difference suggested that phantom sculpting has a positive effect in terms of dose accuracy as long as the patient is close to the 50th percentile height and weight. Otherwise, the benefit of sculpting was masked by inherent uncertainties, i.e. variations in organ shapes, sizes and locations.Other sources of uncertainty included errors associated with beam positioning, neutron weighting factor definition and organ segmentation. This work demonstrated the importance of hybrid phantom height matching for more accurate organ dose calculation in proton therapy and the potential limitations of reference phantoms released by regulatory bodies for radiation therapy applications.


Assuntos
Neoplasias Induzidas por Radiação/etiologia , Nêutrons/efeitos adversos , Órgãos em Risco/efeitos da radiação , Imagens de Fantasmas , Terapia com Prótons , Prótons/efeitos adversos , Radiometria/instrumentação , Adolescente , Adulto , Estatura , Peso Corporal , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Medição de Risco
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