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1.
Med Phys ; 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32557747

RESUMO

PURPOSE: Linear energy transfer (LET)-guided methods have been applied to intensity-modulated proton therapy (IMPT) to improve its biological effect. However, using LET as a surrogate for biological effect ignores the topological relationship of the scanning spot to different structures of interest. In this study, we developed an optimization method that takes advantage of the continuing increase in LET beyond the physical dose Bragg peak. This method avoids placing high biological-effect values in critical structures and increases biological effect in the tumor area without compromising target coverage. METHODS: We selected the cases of two patients with brain tumors and two patients with head and neck tumors who had been treated with proton therapy at our institution. Three plans were created for each case: a plan based on conventional dose-based optimization (DoseOpt), one based on LET-incorporating optimization (LETOpt), and one based on the proposed distal-edge avoidance-guided optimization method (DEAOpt). In DEAOpt, an L1 -norm sparsity term, in which the penalty of each scanning spot was set according to the topological relationship between the organ positions and the location of the peak scaled LET-weighted dose (c LETxD) was added to a conventional dose-based optimization objective function. All plans were normalized to give the same target dose coverage. Dose (assuming a constant relative biological effectiveness value of 1.1, as in clinical practice), biological effect (c LETxD), and computing time consumption were evaluated and compared among the three optimization approaches for each patient case. RESULTS: For all four cases, all three optimization methods generated comparable dose coverage in both target and critical structures. The LETOpt plans and DEAOpt plans reduced biological-effect hot spots in critical structures and increased biological effect in the target volumes to a similar extent. For the target, the c LETxD98% and c LETxD2% in the DEAOpt plans were on average 7.2% and 11.74% higher than in the the DoseOpt plans, respectively. For the brainstem, the c LETxDmean in the DEAOpt plans was on average 33.38% lower than in the DoseOpt plans. In addtion, the DEAOpt method saved 30.37% of the computation cost over the LETOpt method. CONCLUSIONS: DEAOpt is an alternative IMPT optimization approach that correlates the location of scanning spots with biological effect distribution. IMPT could benefit from the use of DEAOpt because this method not only delivers comparable biological effects to LETOpt plans, but also is faster.

2.
Pediatr Blood Cancer ; 67(8): e28373, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32453481

RESUMO

BACKGROUND: As treatment modalities for medulloblastoma have developed and overall survival (OS) has improved, there are relatively limited data on the impact of long-term effects such as risk of second primary tumors (SPT). To address the knowledge gap, we analyzed factors associated with the risk of SPT and OS by treatment modality for medulloblastoma. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER)-18 database for patients diagnosed with medulloblastoma in 1973-2014. Patients were then grouped by age, gender, race, geographic region, histology, adjuvant treatment (no radiation [RT] and no chemotherapy [CT], RT and CT, RT alone, or CT alone), era of diagnosis (1973-1994 or 1995-2014), and survival time. Cumulative incidence, factors associated with SPT and OS were analyzed. RESULTS: Of 2271 patients, 146 developed SPT, of which 42 were benign. The incidence of SPT was 3.1% and 4.9% at 10 and 15 years, respectively. The incidence of SPT was 3.1% with RT + CT versus 3.7% with RT alone at 10 years. The most common site for an SPT was the central nervous system. Female gender (P = 0.01) and longer OS of ≥21 years (P < 0.01) were associated with higher risk of SPT. RT + CT led to better OS than RT only (66.1% and 61.4% vs 55.6% and 49.7% at 10 and 15 years) (P < 0.01). CONCLUSIONS: Medulloblastoma patients have a relatively low risk of SPT at 10 years with treatment. Use of RT + CT led to better OS with no statistical difference in SPT compared with the RT alone.

3.
Br J Radiol ; : 20190949, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32464080

RESUMO

OBJECTIVES: The relative biological effectiveness (RBE) of X-rays and γ radiation increases substantially with decreasing beam energy. This trend affects the efficacy of medical applications of this type of radiation. This study was designed to develop a model based on a survey of experimental data that can reliably predict this trend. METHODS: In our model, parameters α and ß of a cell survival curve are simple functions of the frequency-average linear energy transfer (LF) of delta electrons. The choice of these functions was guided by a microdosimetry-based model. We calculated LF by using an innovative algorithm in which LF is associated with only those electrons that reach a sensitive-to-radiation volume (SV) within the cell. We determined model parameters by fitting the model to 139 measured (α,ß) pairs. RESULTS: We tested nine versions of the model. The best agreement was achieved with [Formula: see text] and ß being linear functions of [Formula: see text] .The estimated SV diameter was 0.1-1 µm. We also found that α, ß, and the α/ß ratio increased with increasing [Formula: see text] . CONCLUSIONS: By combining an innovative method for calculating [Formula: see text] with a microdosimetric model, we developed a model that is consistent with extensive experimental data involving photon energies from 0.27 keV to 1.25 MeV. ADVANCES IN KNOWLEDGE: We have developed a photon RBE model applicable to an energy range from ultra-soft X-rays to megaelectron volt γ radiation, including high-dose levels where the RBE cannot be calculated as the ratio of α values. In this model, the ionization density represented by [Formula: see text] determines the RBE for a given photon spectrum.

5.
Med Phys ; 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32249429

RESUMO

INTRODUCTION: To revisit the formulation of the mean chord length in microdosimetry and replace it by the particle mean free path appropriate for modelings in radiobiology. METHODS: We perform a collision-by-collision followed by event-by-event Geant4 Monte Carlo simulation and calculate double-averaged stepping length, 〈〈l〉〉, for a range of target sizes from mm down to µm and depth in water. We consider 〈〈l〉〉 to represent the particle mean free path. RESULTS: We show that 〈〈l〉〉 continuously drops as a function of depth and asymptotically saturates to a minimum value in low energies, where it exhibits a universal scaling behavior, independent of particle nominal beam energy. We correlate 〈〈l〉〉 to linear density of DNA damage, complexities of initial lethal lesions and illustrate a relative difference between predictive RBEs in model calculations using mean chord length vs the proposed mean free path. We demonstrate consistency between rapid increase in RBE within and beyond the Bragg peak and 〈〈l〉〉, a decreasing function of depth. DISCUSSION AND CONCLUSION: An interplay between localities in imparted energy at nanometer scale and subsequent physio-chemical processes, causalities and pathways in DNA damage requires substitution of geometrical chord length of cell nuclei by mean-free path of proton and charged particles to account for a mean distance among sequential collisions in DNA materials. To this end, the event averaging over cell volume in the current microdosimetry formalism must be superseded by the collision averaging scored within the volume. The former, is fundamentally a global attribute of the cell nuclei surfaces and boundaries and is characterized by their membrane diameters, hence such global indices are not appropriate to quantitatively represent the radiobiological strength of the particles and their RBE variabilities that is associated with the sensitivities to local structure of the collisions and their spatio-temporal collective patterns in DNA materials.

6.
J Clin Oncol ; 38(10): 1019-1029, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32058845

RESUMO

PURPOSE: Radiation dose to the neuroregenerative zone of the hippocampus has been found to be associated with cognitive toxicity. Hippocampal avoidance (HA) using intensity-modulated radiotherapy during whole-brain radiotherapy (WBRT) is hypothesized to preserve cognition. METHODS: This phase III trial enrolled adult patients with brain metastases to HA-WBRT plus memantine or WBRT plus memantine. The primary end point was time to cognitive function failure, defined as decline using the reliable change index on at least one of the cognitive tests. Secondary end points included overall survival (OS), intracranial progression-free survival (PFS), toxicity, and patient-reported symptom burden. RESULTS: Between July 2015 and March 2018, 518 patients were randomly assigned. Median follow-up for alive patients was 7.9 months. Risk of cognitive failure was significantly lower after HA-WBRT plus memantine versus WBRT plus memantine (adjusted hazard ratio, 0.74; 95% CI, 0.58 to 0.95; P = .02). This difference was attributable to less deterioration in executive function at 4 months (23.3% v 40.4%; P = .01) and learning and memory at 6 months (11.5% v 24.7% [P = .049] and 16.4% v 33.3% [P = .02], respectively). Treatment arms did not differ significantly in OS, intracranial PFS, or toxicity. At 6 months, using all data, patients who received HA-WBRT plus memantine reported less fatigue (P = .04), less difficulty with remembering things (P = .01), and less difficulty with speaking (P = .049) and using imputed data, less interference of neurologic symptoms in daily activities (P = .008) and fewer cognitive symptoms (P = .01). CONCLUSION: HA-WBRT plus memantine better preserves cognitive function and patient-reported symptoms, with no difference in intracranial PFS and OS, and should be considered a standard of care for patients with good performance status who plan to receive WBRT for brain metastases with no metastases in the HA region.

7.
Sci Rep ; 10(1): 3199, 2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32081928

RESUMO

In current treatment plans of intensity-modulated proton therapy, high-energy beams are usually assigned larger weights than low-energy beams. Using this form of beam delivery strategy cannot effectively use the biological advantages of low-energy and high-linear energy transfer (LET) protons present within the Bragg peak. However, the planning optimizer can be adjusted to alter the intensity of each beamlet, thus maintaining an identical target dose while increasing the weights of low-energy beams to elevate the LET therein. The objective of this study was to experimentally validate the enhanced biological effects using a novel beam delivery strategy with elevated LET. We used Monte Carlo and optimization algorithms to generate two different intensity-modulation patterns, namely to form a downslope and a flat dose field in the target. We spatially mapped the biological effects using high-content automated assays by employing an upgraded biophysical system with improved accuracy and precision of collected data. In vitro results in cancer cells show that using two opposed downslope fields results in a more biologically effective dose, which may have the clinical potential to increase the therapeutic index of proton therapy.

8.
Med Phys ; 47(4): 2005-2012, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31955444

RESUMO

PURPOSE: To develop a first principle and multiscale model for normal tissue complication probability (NTCP) as a function of dose and LET for proton and in general for particle therapy with a goal of incorporating nanoscale radio-chemical to macroscale cell biological pathways, spanning from initial DNA damage to tissue late effects. METHODS: The method is a combination of analytical and multiscale computational steps including (a) derivation of functional dependencies of NTCP on DNA-driven cell lethality in nanometer and mapping to dose and LET in millimeter, and (b) three-dimensional-surface fitting to Monte Carlo data set generated based on postradiation image change and gathered for a cohort of 14 pediatric patients treated by scanning beam of protons for ependymoma. We categorize voxel-based dose and LET associated with development of necrosis in NTCP. RESULT: Our model fits well the clinical data, generated for postradiation tissue toxicity and necrosis. The fitting procedure results in extraction of in vivo radio-biological α-ß indices and their numerical values. DISCUSSION AND CONCLUSION: The NTCP model, explored in this work, allows to correlate the tissue toxicities to DNA initial damage, cell lethality and the properties and qualities of radiation, dose, and LET.

9.
J Clin Oncol ; 38(5): 454-461, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31774710

RESUMO

PURPOSE: Proton radiotherapy (PRT) may lessen the neuropsychological risk traditionally associated with cranial radiotherapy for the treatment of pediatric brain tumors by reducing the dose to normal tissue compared with that of photon radiotherapy (XRT). We examined the change in intellectual scores over time in patients with pediatric medulloblastoma treated with craniospinal PRT versus XRT. METHODS: Intelligence test scores were obtained for a sample of pediatric patients treated between 2007 and 2018 on the same medulloblastoma protocols that differed only in radiotherapy modality (PRT v XRT). Growth curve analyses compared change in scores over time since diagnosis between groups. RESULTS: Longitudinal intelligence data from 79 patients (37 PRT, 42 XRT) were examined. Groups were similar on most demographic/clinical variables, including sex (67.1% male), age at diagnosis (mean, 8.6 years), craniospinal irradiation dose (median, 23.4 Gy), length of follow-up (mean, 4.3 years), and parental education (mean, 14.3 years). Boost dose (P < .001) and boost margin (P = .001) differed between groups. Adjusting for covariates, the PRT group exhibited superior long-term outcomes in global intelligence quotient (IQ), perceptual reasoning, and working memory compared with the XRT group (all P < .05). The XRT group exhibited a significant decline in global IQ, working memory, and processing speed (all P < .05). The PRT group exhibited stable scores over time in all domains with the exception of processing speed (P = .003). CONCLUSION: To our knowledge, this is the first study to compare intellectual trajectories between pediatric patients treated for medulloblastoma with PRT versus those treated with XRT on comparable, contemporary protocols. PRT was associated with more favorable intellectual outcomes in most domains compared with XRT, although processing speed emerged as a vulnerable domain for both groups. This study provides the strongest evidence to date of an intellectual sparing advantage with PRT in the treatment of pediatric medulloblastoma.

10.
Pediatr Blood Cancer ; 67(2): e28064, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31736188

RESUMO

BACKGROUND: Cranial radiotherapy (RT) is associated with risk for cognitive and adaptive dysfunction. Proton RT (PRT) is a technique hypothesized to spare cognition by reducing exposure to nontarget brain tissue. However, little is known regarding functional outcomes in survivors of pediatric brain tumor (BT) treated with PRT. The present study examined the relationship between cognitive and adaptive outcomes in pediatric BT survivors post-PRT. METHODS: Survivors treated with either focal (n = 33) or craniospinal irradiation (CSI; n = 37) PRT completed neurocognitive evaluations approximately 5 years post-treatment. Results of intelligence testing and ratings of adaptive functioning are reported. Mediation models examined the relationship among radiation field, cognition, and adaptive functioning. RESULTS: The PRT CSI group demonstrated worse cognitive outcomes than the PRT Focal group across each cognitive index (Cohen's d = 0.56-0.70). Parent ratings of adaptive functioning were also worse in the PRT CSI group than the PRT Focal group (Global Adaptive Composite, d = 0.53; conceptual skills, d = 0.67). Cognitive performance fully mediated the relationship between radiation field and adaptive outcomes, while controlling for group differences in tumor histology and RT dose. CONCLUSIONS: Focal PRT survivors demonstrated generally positive outcomes with weaknesses in processing speed and aspects of adaptive functioning. CSI exposure was associated with more consistently poor cognitive and adaptive outcomes. The increased risk for adaptive dysfunction in the PRT CSI group appeared due to the effects of CSI on cognition. Efforts to reduce the volume of tissue exposure to RT remain important.


Assuntos
Atividades Cotidianas , Adaptação Psicológica , Neoplasias Encefálicas/radioterapia , Cognição/fisiologia , Radiação Cranioespinal/métodos , Terapia com Prótons/métodos , Sobreviventes/psicologia , Adolescente , Adulto , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/psicologia , Criança , Pré-Escolar , Cognição/efeitos da radiação , Estudos de Coortes , Feminino , Seguimentos , Humanos , Masculino , Prognóstico , Qualidade de Vida , Ajustamento Social , Adulto Jovem
11.
Pediatr Blood Cancer ; 67(4): e28135, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31886612

RESUMO

BACKGROUND: Research on neurodevelopmental outcome in survivors of pediatric brain tumor (BT) is often based on the assumption of normal development up to the onset of overt symptoms. We sought to verify the "normalcy assumption" and to investigate corollary issues including challenges inherent to the measurement of premorbid neurobehavioral functioning. PROCEDURE: The Brain Radiation Investigative Study Consortium (BRISC) is a prospective longitudinal multisite study of 58 children diagnosed with BT. Premorbid functioning was assessed via retrospective parent report on standardized rating scales and detailed questionnaires. Findings were examined for the sample as a whole and in patients grouped by tumor histology (embryonal and non-embryonal). RESULTS: Mean age at diagnosis was 9.84 years (range, 3-16). The overall sample showed low proportions of pre/postnatal risk factors and delays in development. The proportion of children with clinically significant premorbid attention (18%) problems based on the BASC-2 exceeded expectation of that in healthy children (6.68%). Similar findings were obtained for somatization (18%) and anxiety (14%). Delays in talking were significantly more common in children with embryonal than non-embryonal tumors (P = 0.02). The non-embryonal tumor group had significantly higher overall rates of premorbid psychosocial problems than the embryonal tumor group (P < 0.001). CONCLUSIONS: We describe a rigorous approach to estimating premorbid developmental status in pediatric BT. The findings suggest mixed support for the "normalcy assumption" and highlight the complexity of this concept and need for further investigation. Our results also suggest the need for further study of potential premorbid correlates with tumor histology.


Assuntos
Neoplasias Encefálicas/complicações , Transtornos do Comportamento Infantil/complicações , Deficiências do Desenvolvimento/complicações , Adolescente , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco
12.
Neurooncol Adv ; 1(1): vdz012, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31608330

RESUMO

Background: Cranial radiotherapy (CRT) is an important part of brain tumor treatment, and although highly effective, survivors suffer from long-term cognitive side effects. In this study we aim to establish late-term imaging markers of CRT-induced brain injury and identify functional markers indicative of cognitive performance. Specifically, we aim to identify changes in executive function, brain metabolism, and neuronal organization. Methods: Male Sprague Dawley rats were fractionally irradiated at 28 days of age to a total dose of 30 Gy to establish a radiation-induced brain injury model. Animals were trained at 3 months after CRT using the 5-choice serial reaction time task. At 12 months after CRT, animals were evaluated for cognitive and imaging changes, which included positron emission tomography (PET) and magnetic resonance imaging (MRI). Results: Cognitive deficit with signs of neuroinflammation were found at 12 months after CRT in irradiated animals. CRT resulted in significant volumetric changes in 38% of brain regions as well as overall decrease in brain volume and reduced gray matter volume. PET imaging showed higher brain glucose uptake in CRT animals. Using MRI, irradiated brains had an overall decrease in fractional anisotropy, lower global efficiency, increased transitivity, and altered regional connectivity. Cognitive measurements were found to be significantly correlated with six image features that included myelin integrity and local organization of the neural network. Conclusions: These results demonstrate that CRT leads to late-term morphological changes, reorganization of neural connections, and metabolic dysfunction. The correlation between imaging markers and cognitive deficits can be used to assess late-term side effects of brain tumor treatment and evaluate efficacy of new interventions.

13.
Phys Med Biol ; 64(21): 215018, 2019 11 04.
Artigo em Inglês | MEDLINE | ID: mdl-31553958

RESUMO

The purpose of this study was to generate physical data needed for microdosimetry-based models of proton RBE. Our focus was on the frequency and dose average lineal energies, y  F and y  D . We report data for proton energies from 0.1 to 100 MeV, for spherical volumes 2-103 nm in diameter. These data were calculated using Geant4-DNA Monte Carlo software. The physics implemented in Geant4-DNA has been extensively tested for this type of calculations but data on y  F and y  D for protons generated with this code have been very limited. An innovative aspect of our study is that we introduced a straightforward procedure for calculation of y  F and y  D for polyenergetic beams and presented the data in a format that simplifies these calculations. We compared our data with previous studies that used different Monte Carlo codes and with experimental data.


Assuntos
Método de Monte Carlo , Terapia com Prótons/métodos , Algoritmos , Radiometria , Planejamento da Radioterapia Assistida por Computador , Software
14.
Int J Radiat Oncol Biol Phys ; 105(5): 1119-1125, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31425731

RESUMO

PURPOSE: This study seeks to identify biological factors that may yield a therapeutic advantage of proton therapy versus photon therapy. Specifically, we address the role of nonhomologous end-joining (NHEJ) and homologous recombination (HR) in the survival of cells in response to clinical photon and proton beams. METHODS AND MATERIALS: We irradiated HT1080, M059K (DNA-PKcs+/+), and HCC1937 human cancer cell lines and their isogenic counterparts HT1080-shDNA-PKcs, HT1080-shRAD51IND, M059J (DNA-PKcs-/-), and HCC1937-BRCA1 (BRCA1 complemented) to assess cell clonogenic survival and γ-H2AX radiation-induced foci. Cells were irradiated with either clinically relevant photons or 1 of 3 proton linear energy transfer (LET) values. RESULTS: Our results indicate that NHEJ deficiency is more important in dictating cell survival than proton LET. Cells with disrupted HR through BRCA1 mutation showed increased radiosensitivity only for high-LET protons whereas RAD51 depletion showed increased radiosensitivity for both photons and protons. DNA double strand breaks, assessed by γ-H2AX radiation-induced foci, showed greater numbers after 24 hours in cells exposed to higher LET protons. We also observed that NHEJ-deficient cells were unable to repair the vast majority of double strand breaks after 24 hours. CONCLUSIONS: BRCA1 mutation significantly sensitizes cells to protons, but not photons. Loss of NHEJ renders cells hypersensitive to radiation, whereas the relative importance of HR increases with LET across several cell lines. This may be attributable to the more clustered damage induced by higher LET protons, which are harder to repair through NHEJ. This highlights the importance of tumor biology in dictating treatment modality and suggests BRCA1 as a potential biomarker for proton therapy response. Our data also support the use of pharmacologic inhibitors of DNA repair to enhance the sensitivity to different radiation types, although this raises issues for normal tissue toxicity.


Assuntos
Morte Celular/genética , Reparo do DNA por Junção de Extremidades/fisiologia , Genes BRCA1 , Recombinação Homóloga/fisiologia , Transferência Linear de Energia , Fótons , Prótons , Proteínas de Ligação ao Cálcio/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Sobrevivência Celular/efeitos da radiação , Quebras de DNA de Cadeia Dupla , Inativação Gênica , Histonas/análise , Humanos , Mutação , Rad51 Recombinase/genética , Tolerância a Radiação/genética , Tolerância a Radiação/efeitos da radiação , Fatores de Tempo
15.
Pediatr Blood Cancer ; 66(11): e27952, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31397065

RESUMO

PURPOSE/OBJECTIVE(S): Bladder and prostate are unfavorable sites for rhabdomyosarcoma (B/P-RMS), and represent a challenging location for radiotherapy. MATERIALS/METHODS: Nineteen patients with B/P-RMS were enrolled on a prospective registry protocol (2008-2017) and treated with chemotherapy, proton beam therapy (PBT), and surgical resection (n = 8; 42%). Emphasis was given to treatment technique, disease-related outcomes, and toxicity associated with PBT. RESULTS: The majority of patients had bladder RMS (74%) of embryonal histology (95%), Group III (68%), and intermediate-risk disease by Children's Oncology Group (COG) risk stratification (89%). Seven patients (37%) had primary tumors >5 cm in size. All patients were treated according to COG protocols. With a median follow-up of 66.2 months, 5-year overall survival (OS) and progression-free survival (PFS) were 76%. Four patients (21%) experienced disease relapse, all presenting with local failure. The 5-year local control (LC) rate was 76%. Tumor size predicted LC, with 5-year LC for patients with >5 cm tumors being 43% versus 100% for those with ≤5 cm tumors (P = .006). Univariate analysis demonstrated an effect of tumor size on OS (tumor >5 cm, hazard ratio [HR] 17.7, P = .049) and PFS (HR 17.7, P = .049). Acute grade 2 toxicity was observed in two patients (11%, transient proctitis). Late grade 2+ toxicity was observed in three patients (16%; n = 1 grade 2 skeletal deformity; n = 3 transient grade 2 urinary incontinence; one patient experienced both). CONCLUSIONS: PBT for B/P-RMS affords promising disease-related outcomes with an acceptable toxicity profile. Higher local failure rates were observed for larger tumors, supporting dose-escalation components of ongoing RMS clinical trials.


Assuntos
Neoplasias da Próstata/radioterapia , Terapia com Prótons , Rabdomiossarcoma Embrionário/radioterapia , Neoplasias da Bexiga Urinária/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Pré-Escolar , Terapia Combinada , Cistectomia , Feminino , Seguimentos , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Estadiamento de Neoplasias , Proctite/etiologia , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Prostatectomia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/cirurgia , Terapia com Prótons/efeitos adversos , Terapia com Prótons/métodos , Lesões por Radiação/etiologia , Sistema de Registros , Rabdomiossarcoma Alveolar/tratamento farmacológico , Rabdomiossarcoma Alveolar/patologia , Rabdomiossarcoma Alveolar/radioterapia , Rabdomiossarcoma Alveolar/cirurgia , Rabdomiossarcoma Embrionário/tratamento farmacológico , Rabdomiossarcoma Embrionário/patologia , Rabdomiossarcoma Embrionário/cirurgia , Risco , Carga Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , Incontinência Urinária/etiologia
18.
Pediatr Blood Cancer ; 66(8): e27786, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31050179

RESUMO

PURPOSE: Proton therapy is currently used in the management of pediatric tumors to decrease late toxicities. However, one of the criticisms of proton therapy is the limited data regarding efficacy on disease control. The purpose of this study was to examine local and distant control rates after proton therapy for neuroblastoma. METHODS AND MATERIALS: Eighteen patients with high-risk (n = 16) and locally recurrent neuroblastoma (n = 2) were treated with curative intent and received proton therapy to the primary site and up to three post-induction MIBG-avid metastatic sites. Primary sites (n = 18) were treated to 21-36 Gy (relative biological effectiveness [RBE]), and metastatic sites (n = 16) were treated to 21-24 Gy (RBE). Local control and survival rates were calculated using the Kaplan-Meier method. RESULTS: With a median follow-up of 60.2 months, two- and five-year local control rates at the irradiated primary site were 94% and 87%, respectively. No failures at irradiated distant metastatic sites were observed. The five-year progression-free survival (PFS) was 64%, and the five-year overall survival (OS) was 94%. The extent of surgical resection was not associated with local control, PFS, or OS. No radiation-related nephropathy or hepatopathy was reported. CONCLUSIONS: Excellent local control was achieved using proton therapy to the primary and post-induction MIBG-positive distant sites. The predominant site of failure is progression in post-induction non-MIBG-avid distant sites. Although proton therapy provides high rates of local control with acceptable toxicity for neuroblastoma, further advances in systemic therapy are needed for the improved control of systemic disease.


Assuntos
Recidiva Local de Neoplasia/radioterapia , Neoplasia Residual/radioterapia , Neuroblastoma/radioterapia , Terapia com Prótons/métodos , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/patologia , Neoplasia Residual/patologia , Neuroblastoma/patologia , Estudos Prospectivos , Eficiência Biológica Relativa , Resultado do Tratamento
19.
Pediatr Blood Cancer ; 66(9): e27800, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31134755

RESUMO

BACKGROUND: Survivors of pediatric brain tumor are at risk for adaptive difficulties. The present study examined adaptive functioning in a multiethnic sample of survivors accounting for socioeconomic status, and whether demographic, diagnostic, and/or treatment-related variables predict adaptive outcomes. METHOD: Participants included a multiethnic sample of survivors (58 Caucasian, 34 Hispanic, and 22 other non-Caucasian; M age = 14.05 years, SD = 4.33) who were approximately seven years post-treatment. Parents rated adaptive functioning and provided demographic information. Diagnostic and treatment-related information was abstracted from the electronic medical record. RESULTS: Parent ratings of adaptive functioning were similar across Caucasian, Hispanic, and other non-Caucasian survivors covarying for family income and primary caregiver education, both of which served as proxies for socioeconomic status. All ethnic groups were rated lower than the normative mean in overall adaptive functioning as well as the specific domains of conceptual, social, and practical skills. Demographic, diagnostic, and treatment-related variables were differentially associated with adaptive functioning in survivors of pediatric brain tumor, though socioeconomic status emerged as a strong significant predictor of adaptive functioning domains. CONCLUSIONS: Adaptive outcomes do not differ as a function of ethnicity after accounting for primary caregiver education and family income. Racial and ethnic minorities may be at increased risk for poorer outcomes given their overrepresentation at lower income levels. Assessing demographic and treatment-related variables early on may be helpful in identifying children likely to develop adaptive difficulties.


Assuntos
Neoplasias Encefálicas/etnologia , Sobreviventes de Câncer , Grupo com Ancestrais do Continente Europeu , Hispano-Americanos , Classe Social , Adolescente , Adulto , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/terapia , Criança , Pré-Escolar , Feminino , Humanos , Masculino
20.
Adv Radiat Oncol ; 4(2): 362-366, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31011682

RESUMO

Purpose: This study aimed to report on the safety, feasibility, and workflow of using magnetic resonance imaging (MRI) simulation, while immobilized in the treatment position, for radiation therapy treatment planning in the pediatric population. Methods and Materials: Between May and December 2017, 10 pediatric patients completed both MRI and computed tomography imaging simulation in treatment immobilization for radiation therapy planning for central nervous system disease. We report our initial institutional experience and workflow of the use of MRI simulation in immobilization for treatment planning in this population. Results: Ten pediatric patients successfully underwent MRI and computed tomography imaging simulation for CNS disease. Two patients required anesthesia for sedation during the simulations. From our initial experience, MRI simulation was tolerated by all 10 pediatric patients without any safety or clinical issues, including those who required anesthesia. Conclusions: Our initial experience supports the use of MRI simulation for radiation treatment planning in the pediatric population, with and without anesthetic sedation, as a safe and feasible image-guidance tool. This is particularly useful in the treatment of pediatric patients because MRI simulation enables superior, soft-tissue, anatomic imaging for a more robust delineation of organs at risk and target volumes without increasing radiation exposure.

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