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1.
Neuro Oncol ; 2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32514542

RESUMO

BACKGROUND: Treatment for pediatric ependymoma includes surgical resection followed by local radiotherapy. Proton radiotherapy (PRT) enables superior sparing of critical structures compared to photons, with potential to reduce late effects. We report mature outcomes, patterns of failure, and predictors of outcomes in patients treated with PRT. METHODS: 150 patients (<22 years) with grade II/III ependymoma were treated with PRT between 1/2001 and 1/2019 at Massachusetts General Hospital. Demographic, tumor, and treatment-related characteristics were analyzed. Event free survival (EFS), overall survival (OS), and local control (LC) were assessed. RESULTS: Median follow-up was 6.5 years. EFS, OS, and LC for the intracranial cohort (n=145) at 7 years were 63.4%, 82.6%, and 76.1%. 51 patients recurred: 26 (51.0%) local failures, 19 (37.3%) distant failures, and 6 (11.8%) synchronous failures. 116 patients (77.3%) underwent gross total resection (GTR), 5 (3.3%) underwent near total resection (NTR), and 29 (19.3%) underwent subtotal resection (STR). EFS for the intracranial cohort at 7 years for GTR/NTR and STR was 70.3% and 35.2%. With multivariate analysis, the effect of tumor excision persisted after controlling for tumor location. There was no adverse effect on disease control if surgery to RT interval was within 9 weeks of GTR/NTR. CONCLUSION: PRT is effective and safe in pediatric ependymoma. Similar to previous studies, GTR/NTR was the most important prognostic factor. Intervals up to 9 weeks from surgery to PRT did not compromise disease outcomes. There was no LC benefit between patients treated with >54 GyRBE vs ≤54 GyRBE.

2.
Int J Radiat Oncol Biol Phys ; 107(3): 449-454, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32240774

RESUMO

PURPOSE: A prospective trial of proton therapy for breast cancer revealed an increased rib fracture rate of 7%, which is higher than the expected rate based on the literature on photon therapies. We aim to evaluate the hypothesis that the increased relative biological effectiveness (RBE) at the distal edge of proton beams is the cause. METHODS AND MATERIALS: We combined the cohort from the prospective clinical trial and a retrospective cohort from a database. Monte Carlo simulations were performed to recalculate the physical dose and dose-averaged linear energy transfer (LETd). The first 10 ribs and fracture areas in patients with fractures were contoured and deformably registered. The LETd-weighted dose was used as a surrogate for biological effectiveness and compared with the conventional fixed RBE of 1.1. Dose to 0.5 cm3 of the ribs (D0.5) was selected to analyze the dose-response relationship using logistic regression. We chose an alpha/beta ratio of 3 to calculate the biological effective dose in Gy3(RBE). RESULTS: Thirteen of 203 patients in the cohorts exhibited a total of 25 fractures. The LETd in fractured areas is increased (6.1 ± 2.0 keV/µm, mean ± standard deviation), suggesting possible end-of-range radiobiological effects with increased RBE. The D0.5 of the fractured ribs is 80.3 ± 9.4 Gy3(RBE) with a generic factor of 1.1 and is relatively low compared with historical photon results. On the other hand, the D0.5 of the fractured ribs is 100.0 ± 12.5 Gy3(RBE) using the LETd-based model with a dose-response curve that is more consistent with historical photon data. CONCLUSIONS: The increased rib fracture rate seen in our trial is probably associated with the increased LETd and RBE at the distal edge of proton beams. This phenomenon warrants further investigation and possible integration of LETd into treatment planning and optimization in proton therapy.

3.
Technol Cancer Res Treat ; 19: 1533033820920650, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32329413

RESUMO

BACKGROUND: Lower-dose cone-beam computed tomography protocols for image-guided radiotherapy may permit target localization while minimizing radiation exposure. We prospectively evaluated a lower-dose cone-beam protocol for central nervous system image-guided radiotherapy across a multinational pediatrics consortium. METHODS: Seven institutions prospectively employed a lower-dose cone-beam computed tomography central nervous system protocol (weighted average dose 0.7 mGy) for patients ≤21 years. Treatment table shifts between setup with surface lasers versus cone-beam computed tomography were used to approximate setup accuracy, and vector magnitudes for these shifts were calculated. Setup group mean, interpatient, interinstitution, and random error were estimated, and clinical factors were compared by mixed linear modeling. RESULTS: Among 96 patients, with 2179 pretreatment cone-beam computed tomography acquisitions, median age was 9 years (1-20). Setup parameters were 3.13, 3.02, 1.64, and 1.48 mm for vector magnitude group mean, interpatient, interinstitution, and random error, respectively. On multivariable analysis, there were no significant differences in mean vector magnitude by age, gender, performance status, target location, extent of resection, chemotherapy, or steroid or anesthesia use. Providers rated >99% of images as adequate or better for target localization. CONCLUSIONS: A lower-dose cone-beam computed tomography protocol demonstrated table shift vector magnitude that approximate clinical target volume/planning target volume expansions used in central nervous system radiotherapy. There were no significant clinical predictors of setup accuracy identified, supporting use of this lower-dose cone-beam computed tomography protocol across a diverse pediatric population with brain tumors.

4.
Neuro Oncol ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32064512

RESUMO

BACKGROUND: The purpose of this analysis is to report long-term health related quality of life (HRQoL) among brain tumor survivors treated with proton therapy (PRT) at a very young age. METHODS: Fifty-nine children < 4 years old received PRT between 2000-2011. Forty families participated. HRQoL was assessed by child self report (CSR, age ≥ 5) and parent proxy report (PPR, age 2+) using the PedsQL Core. RESULTS: The median age was 2.5 years (range 0.3-3.8) at PRT and 9.1 years (5.5-18) at last follow-up. The most common diagnoses were ependymoma (n=22), and medulloblastoma (n=7). Median follow-up is 6.7 years (3-15.4). Follow-up mean CSR and PPR scores were: total core (78.4 and 72.9); physical (82.9 and 75.2), psychosocial (76.0 and 71.6) emotional (74.4 and 70.7), social (81.2 and 75.1), school (72.4 and 69.9). Parent-reported HRQoL fell within a previously defined range for healthy children in 37.5% of patients, and for children with severe health conditions in 45% of patients. PPR HRQoL was stable from baseline to last follow-up among all domains except for the social functioning. History of gastrostomy-tube was significantly associated with poorer CSR and PPR HRQoL on multivariable analysis. Ninety-percent of children functioned in a regular classroom; 14(36%) used a classroom aid, 9(23%) used an outside tutor, and 18(46%) had an individualized education plan. CONCLUSION: Long-term HRQoL among brain tumor survivors treated with proton therapy at a very young age is variable with over a third achieving HRQoL levels commensurate with healthy children.

5.
BMJ Open ; 9(10): e025556, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31619413

RESUMO

INTRODUCTION: A broad range of stakeholders have called for randomised evidence on the potential clinical benefits and harms of proton therapy, a type of radiation therapy, for patients with breast cancer. Radiation therapy is an important component of curative treatment, reducing cancer recurrence and extending survival. Compared with photon therapy, the international treatment standard, proton therapy reduces incidental radiation to the heart. Our overall objective is to evaluate whether the differences between proton and photon therapy cardiac radiation dose distributions lead to meaningful reductions in cardiac morbidity and mortality after treatment for breast cancer. METHODS: We are conducting a large scale, multicentre pragmatic randomised clinical trial for patients with breast cancer who will be followed longitudinally for cardiovascular morbidity and mortality, health-related quality of life and cancer control outcomes. A total of 1278 patients with non-metastatic breast cancer will be randomly allocated to receive either photon or proton therapy. The primary outcomes are major cardiovascular events, defined as myocardial infarction, coronary revascularisation, cardiovascular death or hospitalisation for unstable angina, heart failure, valvular disease, arrhythmia or pericardial disease. Secondary endpoints are urgent or unanticipated outpatient or emergency room visits for heart failure, arrhythmia, valvular disease or pericardial disease. The Radiotherapy Comparative Effectiveness (RadComp) Clinical Events Centre will conduct centralised, blinded adjudication of primary outcome events. ETHICS AND DISSEMINATION: The RadComp trial has been approved by the institutional review boards of all participating sites. Recruitment began in February 2016. Current version of the protocol is A3, dated 08 November 2018. Dissemination plans include presentations at scientific conferences, scientific publications, stakeholder engagement efforts and presentation to the public via lay media outlets. TRIAL REGISTRATION NUMBER: NCT02603341.

7.
J Clin Oncol ; 37(30): 2778-2785, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31449469

RESUMO

PURPOSE: To evaluate the safety and efficacy of proton beam radiation therapy (RT) for patients with breast cancer who require regional nodal irradiation. METHODS: Patients with nonmetastatic breast cancer who required postoperative RT to the breast/chest wall and regional lymphatics and who were considered suboptimal candidates for conventional RT were eligible. The primary end point was the incidence of grade 3 or higher radiation pneumonitis (RP) or any grade 4 toxicity within 3 months of RT. Secondary end points were 5-year locoregional failure, overall survival, and acute and late toxicities per Common Terminology Criteria for Adverse Events (version 4.0). Strain echocardiography and cardiac biomarkers were obtained before and after RT to assess early cardiac changes. RESULTS: Seventy patients completed RT between 2011 and 2016. Median follow-up was 55 months (range, 17 to 82 months). Of 69 evaluable patients, median age was 45 years (range, 24 to 70 years). Sixty-three patients (91%) had left-sided breast cancer, two had bilateral breast cancer, and five had right-sided breast cancer. Sixty-five (94%) had stage II to III breast cancer. Sixty-eight (99%) received systemic chemotherapy. Fifty (72%) underwent immediate reconstruction. Median dose to the chest wall/breast was 49.7 Gy (relative biological effectiveness) and to the internal mammary nodes, 48.8 Gy (relative biological effectiveness), which indicates comprehensive coverage. Among 62 surviving patients, the 5-year rates for locoregional failure and overall survival were 1.5% and 91%, respectively. One patient developed grade 2 RP, and none developed grade 3 RP. No grade 4 toxicities occurred. The unplanned surgical re-intervention rate at 5 years was 33%. No significant changes in echocardiography or cardiac biomarkers after RT were found. CONCLUSION: Proton beam RT for breast cancer has low toxicity rates and similar rates of disease control compared with historical data of conventional RT. No early cardiac changes were observed, which paves the way for randomized studies to compare proton beam RT with standard RT.

9.
J Appl Clin Med Phys ; 20(4): 45-50, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30945803

RESUMO

PURPOSE: Patients undergoing external beam accelerated partial breast irradiation (APBI) receive permanent tattoos to aid with daily setup alignment and verification. With the advent of three-dimensional (3D) body surface imaging and two-dimensional (2D) x-ray imaging-based matching to surgical clips, tattoos may not be necessary to ensure setup accuracy. We compared the accuracy of conventional tattoo-based setups to a patient setup without tattoos. MATERIALS/METHODS: Twenty consecutive patients receiving APBI at our institution from July 10, 2017 to February 13, 2018 were identified. All patients received tattoos per standard of care. Ten patients underwent setup using tattoos for initial positioning followed by surface imaging and 2D matching of surgical clips. The other ten patients underwent positioning using surface imaging followed by 2D matching without reference to tattoos. Overall setup time and orthogonal x-ray-based shifts after surface imaging per fraction were recorded. Shift data were used to calculate systematic and random error. RESULTS: Among ten patients in the "no tattoo" group, the average setup time per fraction was 6.83 min vs 8.03 min in the tattoo cohort (P < 0.01). Mean 3D vector shifts for patients in the "no tattoo" group were 4.6 vs 5.9 mm in the "tattoo" cohort (P = NS). Mean systematic errors in the "no tattoo" group were: 1.2 mm (1.5 mm SD) superior/inferior, 0.5 mm (1.6 mm SD) right/left, and 2.3 mm (1.9 mm SD) anterior/posterior directions. Mean systematic errors in the "tattoo" group were: 0.8 mm (2.2 mm SD) superior/inferior, 0.3 mm (2.5 mm SD) right/left, and 1.4 mm (4.4 mm SD) anterior/posterior directions. The random errors in the "no tattoo" group ranged from 0.6 to 0.7 mm vs 1.2 to 1.7 mm in the "tattoo" group. CONCLUSIONS: Using both surface imaging and 2D matching to surgical clips provides excellent accuracy in APBI patient alignment and setup verification with reduced setup time relative to the tattoo cohort. Skin-based tattoos may no longer be warranted for patients receiving external beam APBI.


Assuntos
Neoplasias da Mama/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Erros de Configuração em Radioterapia/prevenção & controle , Tatuagem , Estudos de Viabilidade , Feminino , Humanos , Dosagem Radioterapêutica
10.
Radiother Oncol ; 134: 25-29, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31005220

RESUMO

PURPOSE: Consistent follow-up and data collection are necessary to identify long-term benefits/detriments of proton radiotherapy. Obtaining comprehensive clinical follow-up can be difficult and time-intensive for proton centers. Here we evaluate what factors affect maximum follow-up time among MGH Pediatric Proton Consortium Registry (PPCR) participants. PATIENTS AND METHODS: Enrollment in the PPCR was offered to any patient <22 years receiving protons. Patients were excluded from analysis if they were taken off study due to death or withdrawal. Distance from MGH was calculated by the great-circle formula. We utilized both univariate and multivariate analyses to determine risk factors associated with follow-up time. RESULTS: 333 PPCR patients enrolled between 10/2012 and 03/2017 were included. Median follow-up was 2.4 years (<1-5.5), and median distance away from the proton center was 256.4 km (<1.6-16,949.6). Distance from MGH significantly predicted follow-up time: patients living outside the Boston Metropolitan Statistical Area, >121 km from the proton center, had average follow-up that was 0.53 years less compared to those living within 121 km (p = 0.0002). Loss in average follow-up was also associated with Medicaid insurance, treatment delay due to insurance, and non-White race. Those co-enrolled on a proton trial or seen at a facility had significantly increased follow-up by almost one year (p < 0.0001). CONCLUSION: Patients living further from treating proton center have shorter follow-up durations. Increased distance from treating centers may adversely affect clinical outcomes research. Enhanced sharing of medical information among care providers and improved collection methods are needed to effectively evaluate the benefits of proton therapy.


Assuntos
Acesso aos Serviços de Saúde/estatística & dados numéricos , Neoplasias/radioterapia , Terapia com Prótons/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Estudos Multicêntricos como Assunto , Sistema de Registros , Fatores de Risco , Estados Unidos , Adulto Jovem
12.
J Clin Oncol ; 36(28): 2854-2862, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30118397

RESUMO

PURPOSE: There are sparse data defining the dose response of radiation therapy (RT) to the hypothalamus and pituitary in pediatric and young adult patients with brain tumors. We examined the correlation between RT dose to these structures and development of endocrine dysfunction in this population. MATERIALS AND METHODS: Dosimetric and clinical data were collected from children and young adults (< 26 years of age) with brain tumors treated with proton RT on three prospective studies (2003 to 2016). Deficiencies of growth hormone (GH), thyroid hormone, adrenocorticotropic hormone, and gonadotropins were determined clinically and serologically. Incidence of deficiency was estimated using the Kaplan-Meier method. Multivariate models were constructed accounting for radiation dose and age. RESULTS: Of 222 patients in the study, 189 were evaluable by actuarial analysis, with a median follow-up of 4.4 years (range, 0.1 to 13.3 years), with 31 patients (14%) excluded from actuarial analysis for having baseline hormone deficiency and two patients (0.9%) because of lack of follow-up. One hundred thirty patients (68.8%) with medulloblastoma were treated with craniospinal irradiation (CSI) and boost; most of the remaining patients (n = 56) received involved field RT, most commonly for ependymoma (13.8%; n = 26) and low-grade glioma (7.4%; n = 14). The 4-year actuarial rate of any hormone deficiency, growth hormone, thyroid hormone, adrenocorticotropic hormone, and gonadotropin deficiencies were 48.8%, 37.4%, 20.5%, 6.9%, and 4.1%, respectively. Age at start of RT, time interval since treatment, and median dose to the combined hypothalamus and pituitary were correlated with increased incidence of deficiency. CONCLUSION: Median hypothalamic and pituitary radiation dose, younger age, and longer follow-up time were associated with increased rates of endocrinopathy in children and young adults treated with radiotherapy for brain tumors.


Assuntos
Neoplasias Encefálicas/radioterapia , Irradiação Craniana/efeitos adversos , Hipotálamo/efeitos da radiação , Hipófise/efeitos da radiação , Terapia com Prótons/efeitos adversos , Lesões por Radiação/epidemiologia , Adolescente , Criança , Pré-Escolar , Ensaios Clínicos Fase II como Assunto , Irradiação Craniana/métodos , Doenças do Sistema Endócrino/epidemiologia , Doenças do Sistema Endócrino/etiologia , Feminino , Humanos , Masculino , Adulto Jovem
13.
Int J Radiat Oncol Biol Phys ; 101(4): 809-819, 2018 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-29976493

RESUMO

PURPOSE: Clinical practice assumes a fixed proton relative biological effectiveness (RBE) of 1.1, but in vitro experiments demonstrate higher RBEs at the distal edge of the proton spread-out Bragg peak, that is, in a region that falls within the lung for chest-wall patients. We performed retrospective qualitative and quantitative analyses of lung-density changes-indicative of asymptomatic fibrosis-for chest-wall patients treated with protons or photons. Our null hypothesis was that, assuming a fixed RBE of 1.1, these changes would be the same for the 2 cohorts, supporting current RBE practice. Our alternative hypothesis was that radiographic abnormalities would be greater for the proton cohort, suggesting an RBE > 1.1. METHODS AND MATERIALS: We analyzed follow-up computed tomography (CT) scans for 20 proton and photon patients. All were prescribed 50.4 Gy (RBE) in 28 fractions, assuming a fixed RBE of 1.1 for protons and 1 for photons. Deformable registrations enabled us to calculate density changes in the normal lung, specifically (1) median Hounsfield unit (HU) values among posttreatment CT scans and (2) changes in median HU values between pretreatment and posttreatment CT scans, both as a function of grays (RBE). In addition, qualitative abnormality grading was performed by a radiologist. RESULTS: Proton patients exhibited higher values of HU/Gy (RBE) (endpoint 1) and ΔHU/Gy (RBE) (endpoint 2): P = .049 and P = .00019, respectively, were obtained (likelihood ratio tests of full linear mixed-effects models against models without "modality"). Furthermore, qualitative radiologic scoring indicated a significant difference between the cohorts (Wilcoxon P = .018; median score, 3 of 9 for protons and 1.5 of 9 for photons). CONCLUSIONS: Our data support the hypothesis that the proton RBE for lung-density changes exceeds 1.1. This RBE elevation could be attributable to (1) the late, normal tissue endpoint that we consider or (2) end-of-range proton linear energy transfer elevation-or a combination of the two. Regardless, our results suggest that variations in proton RBE prove important in vivo as well as in vitro.


Assuntos
Doenças Assintomáticas , Pulmão/efeitos da radiação , Fótons/efeitos adversos , Terapia com Prótons/efeitos adversos , Fibrose Pulmonar/diagnóstico por imagem , Eficiência Biológica Relativa , Adulto , Idoso , Humanos , Pulmão/diagnóstico por imagem , Pessoa de Meia-Idade , Fótons/uso terapêutico , Radioterapia Conformacional/métodos , Estudos Retrospectivos , Parede Torácica , Tomografia Computadorizada por Raios X
14.
Radiother Oncol ; 128(1): 44-55, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29937209

RESUMO

Radiotherapy plays an important role in the management of childhood cancer, with the primary aim of achieving the highest likelihood of cure with the lowest risk of radiation-induced morbidity. Proton therapy (PT) provides an undisputable advantage by reducing the radiation 'bath' dose delivered to non-target structures/volume while optimally covering the tumor with tumoricidal dose. This treatment modality comes, however, with an additional costs compared to conventional radiotherapy that could put substantial financial pressure to the health care systems with societal implications. In this review we assess the data available to the oncology community of PT delivered to children with cancer, discuss on the urgency to develop high-quality data. Additionally, we look at the advantage of combining systemic agents with protons and look at the cost-effectiveness data published so far.


Assuntos
Neoplasias/radioterapia , Terapia com Prótons/economia , Criança , Consenso , Análise Custo-Benefício , Humanos , Dosagem Radioterapêutica
15.
Cancer ; 124(16): 3390-3400, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29905942

RESUMO

BACKGROUND: To the authors' knowledge, health-related quality of life (HRQOL) outcomes are not well described in patients with medulloblastoma. The use of proton radiotherapy (RT) may translate into an improved HRQOL. In the current study, the authors report long-term HRQOL in patients with proton-treated pediatric medulloblastoma. METHODS: The current study was a prospective cohort HRQOL study of patients with medulloblastoma who were treated with proton RT and enrolled between August 5, 2002, and October 8, 2015. Both child report and parent-proxy report Pediatric Quality of Life Inventory (PedsQL) surveys were collected at baseline during RT and annually thereafter (score range on surveys of 0-100, with higher scores indicating better HRQOL). Patients were dichotomized by clinical/treatment variables and subgroups were compared. Mixed-model analysis was performed to determine the longitudinal trajectory of PedsQL scores. The Student t test was used to compare long-term HRQOL measures with published means from a healthy child population. RESULTS: Survey data were evaluable for 116 patients with a median follow-up of 5 years (range, 1-10.6 years); the median age at the time of diagnosis was 7.6 years (range, 2.1-18.1 years). At baseline, children reported a total core score (TCS) of 65.9, which increased by 1.8 points annually (P<.001); parents reported a TCS of 59.1, which increased by 2.0 points annually. Posterior fossa syndrome adversely affected baseline scores, but these scores significantly improved with time. At the time of last follow-up, children reported a TCS of 76.3, which was 3.3 points lower than that of healthy children (P = .09); parents reported a TCS of 69, which was 11.9 points lower than that of parents of healthy children (P<.001). Increased follow-up time from diagnosis correlated with improved HRQOL scores. CONCLUSIONS: HRQOL scores appear to increase over time after treatment in children treated with proton RT for medulloblastoma but remain lower compared with those of parent-proxy reports as well as published means from a healthy normative sample of children. Additional follow-up may translate into continued improvements in HRQOL. Cancer 2018. © 2018 American Cancer Society.


Assuntos
Meduloblastoma/epidemiologia , Meduloblastoma/radioterapia , Pediatria , Terapia com Prótons/efeitos adversos , Adolescente , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Meduloblastoma/patologia , Pais , Qualidade de Vida , Inquéritos e Questionários , Adulto Jovem
16.
Int J Radiat Oncol Biol Phys ; 101(3): 541-549, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29893273

RESUMO

PURPOSE: While cranial irradiation is often essential to attain a cure for pediatric brain tumors, it is associated with adverse neurocognitive outcomes, primarily manifested as declines in full-scale IQ (FSIQ). This decline results primarily from a decline in processing speed, a component of FSIQ. However, estimated IQ (EIQ) is frequently used in research and clinical settings but does not incorporate processing speed. We hypothesized that EIQ systematically underestimates neurocognitive sequelae in irradiated pediatric brain tumor survivors. METHODS AND MATERIALS: We treated 185 pediatric brain tumor patients with proton radiation therapy. All patients had at least 1 neuropsychological evaluation at baseline and/or 1 or more follow-up evaluations with sufficient data to calculate both FSIQ and EIQ. The Wechsler Intelligence Scales were used to calculate FSIQ and EIQ for each patient, and mixed linear models were used to assess disparities between FSIQ and EIQ. RESULTS: At baseline, EIQ was 2.2 points (95% confidence interval 1.2-3.2 points) higher on average than FSIQ (P < .001). The median follow-up period was 26 months. The disparity between EIQ and FSIQ persisted and worsened over time (P = .012), with FSIQ losing on average 0.4 points/year (95% confidence interval 0.01-0.8 points/year) relative to EIQ. The disparity at baseline varied with sex and age. CONCLUSIONS: EIQ systematically underestimates the neurocognitive sequelae of children treated with cranial radiation therapy. FSIQ is much more likely than EIQ to identify neurocognitive deficits, allowing for appropriate interventions, as well as academic services and accommodations. Thus, EIQ should have a very limited role in both clinical and research settings for this population.


Assuntos
Neoplasias Encefálicas/fisiopatologia , Neoplasias Encefálicas/radioterapia , Cognição/efeitos da radiação , Irradiação Craniana/efeitos adversos , Escalas de Wechsler , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Sobreviventes , Adulto Jovem
17.
Pediatr Blood Cancer ; 65(7): e27046, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29630784

RESUMO

Proton therapy is a form of particle therapy with physical properties that provide a superior dose distribution compared to photons. The ability to spare healthy, developing tissues from low dose radiation with proton therapy is well known. The capability to decrease radiation exposure for children has been lauded as an important advance in pediatric cancer care, particularly for central nervous system (CNS) tumors. Favorable clinical outcomes have been reported and justify the increased cost and burden of this therapy. In this review, we summarize the current literature for proton therapy for pediatric CNS malignancies, with a focus on clinical outcomes to date.


Assuntos
Neoplasias do Sistema Nervoso Central/radioterapia , Terapia com Prótons/métodos , Resultado do Tratamento , Criança , Humanos , Terapia com Prótons/efeitos adversos
18.
Cancer ; 124(10): 2238-2245, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29499085

RESUMO

BACKGROUND: Radiotherapy (RT) in the pediatric brain tumor population causes late neurocognitive effects. In the current study, the authors investigated associations between clinical and dosimetric risk factors and memory outcomes in a cohort of patients treated with proton radiotherapy (PRT). METHODS: A total of 70 patients (median age at PRT, 12.1 years [range, 5.0-22.5 years]) who were treated with PRT were identified with baseline and follow-up evaluations of visual and verbal memory (Children's Memory Scale and the third edition of the Wechsler Memory Scale). Whole-brain as well as bilateral hippocampal and temporal lobe contours were delineated for the calculation of dosimetric indices. Multivariate analyses were performed to assess associations of score changes over time with clinical factors and dosimetric indices. RESULTS: The median neurocognitive follow-up was 3.0 years (range, 1.1-11.4 years). For the entire cohort, delayed and immediate verbal memory scaled scores demonstrated small declines. The mean decline for delayed verbal memory scores was 0.6 (P = .01), and that for immediate verbal memory scores was 0.5 (P = .06). Immediate and delayed visual memory scores were not found to change significantly (+0.1 and -0.3, respectively; P>.30). A higher left hippocampal V20GyE (percentage of the volume of a particular anatomical region receiving at least a 20 gray equivalent) was correlated with a score decline in all 4 measures. Female sex was found to be predictive of lower delayed verbal memory follow-up scores (P = .035). CONCLUSIONS: Only delayed verbal memory scores were found to have declined statistically significantly at follow-up after PRT, reflecting some weakness in verbal memory retrieval. Given a correlation of left hippocampal dosimetry and memory outcomes after PRT, left hippocampal-sparing PRT plans may assist patients with pediatric brain tumors in preserving memory-retrieval abilities. Cancer 2018;124:2238-45. © 2018 American Cancer Society.


Assuntos
Neoplasias Encefálicas/radioterapia , Sobreviventes de Câncer/estatística & dados numéricos , Hipocampo/efeitos da radiação , Transtornos da Memória/diagnóstico , Terapia com Prótons/efeitos adversos , Adolescente , Adulto , Criança , Pré-Escolar , Cognição/fisiologia , Cognição/efeitos da radiação , Feminino , Seguimentos , Hipocampo/fisiopatologia , Humanos , Masculino , Memória/fisiologia , Memória/efeitos da radiação , Transtornos da Memória/etiologia , Transtornos da Memória/fisiopatologia , Testes Neuropsicológicos , Tratamentos com Preservação do Órgão/efeitos adversos , Tratamentos com Preservação do Órgão/métodos , Órgãos em Risco/fisiopatologia , Órgãos em Risco/efeitos da radiação , Terapia com Prótons/métodos , Radiometria , Planejamento da Radioterapia Assistida por Computador/métodos , Resultado do Tratamento , Adulto Jovem
19.
Int J Radiat Oncol Biol Phys ; 100(3): 719-729, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29413284

RESUMO

PURPOSE: Proton radiation therapy is commonly used in young children with brain tumors for its potential to reduce late effects. However, some proton series report higher rates of brainstem injury (0%-16%) than most photon series (2.2%-8.6%). We report the incidence of brainstem injury and a risk factor analysis in pediatric patients with posterior fossa primary tumors treated with proton radiation therapy at our institution. METHODS AND MATERIALS: The study included 216 consecutive patients treated between 2000 and 2015. Dosimetry was available for all but 4 patients. Grade 2 to 5 late brainstem toxicity was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The histologies include medulloblastoma (n=154, 71.3%), ependymoma (n=56, 25.9%), and atypical teratoid rhabdoid tumor (n=6, 2.8%). The median age at irradiation was 6.6 years (range, 0.5-23.1 years); median dose, 54 gray relative biological effectiveness (Gy RBE) (range, 46.8-59.4 Gy RBE); and median follow-up period, 4.2 years (range, 0.1-15.3 years) among 198 survivors. Of the patients, 83.3% received chemotherapy; 70.4% achieved gross total resection. The crude rate of injury was 2.3% in all patients, 1.9% in those with medulloblastoma, 3.6% in those with ependymoma, and 0% in those with atypical teratoid rhabdoid tumor. The 5-year cumulative incidence of injury was 2.0% (95% confidence interval, 0.7%-4.8%). The median brainstem dose (minimum dose received by 50% of brainstem) in the whole cohort was 53.6 Gy RBE (range, 16.5-56.8 Gy RBE); maximum point dose within the brainstem (Dmax), 55.2 Gy RBE (range, 48.4-60.5 Gy RBE); and mean dose, 50.4 Gy RBE (range, 21.1-56.7 Gy RBE). In the 5 patients with injury, the median minimum dose received by 50% of the brainstem was 54.6 Gy RBE (range, 50.2-55.1 Gy RBE); Dmax, 56.2 Gy RBE (range, 55.0-57.1 Gy RBE); mean dose, 51.3 Gy RBE (range, 45.4-54.4 Gy RBE); and median volume of the brainstem receiving ≥55 Gy RBE (V55), 27.4% (range, 0%-59.4%). Of the 5 patients with injury, 4 had a brainstem Dmax in the highest quartile (≥55.8 Gy RBE, P = .016) and a V55 in the highest tertile (>6.0%) of the cohort distribution (P = .047). Of the 5 patients with injury, 3 were aged >6 years (age range, 4.1-22.8 years), and 4 of 5 patients received chemotherapy and achieved gross total resection. CONCLUSIONS: The incidence of injury in pediatric patients with posterior fossa tumors is consistent with previous reports in the photon setting. Our data suggest that when Dmax and V55 are kept <55.8 Gy RBE and ≤6.0%, respectively, the 5-year rate of radiation brainstem injury would be <2%.


Assuntos
Tronco Encefálico/efeitos da radiação , Neoplasias Infratentoriais/radioterapia , Terapia com Prótons/efeitos adversos , Lesões por Radiação/epidemiologia , Adolescente , Criança , Pré-Escolar , Intervalos de Confiança , Ependimoma/tratamento farmacológico , Ependimoma/mortalidade , Ependimoma/radioterapia , Feminino , Seguimentos , Humanos , Incidência , Lactente , Neoplasias Infratentoriais/tratamento farmacológico , Neoplasias Infratentoriais/mortalidade , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/mortalidade , Meduloblastoma/radioterapia , Intervalo Livre de Progressão , Lesões por Radiação/mortalidade , Lesões por Radiação/patologia , Dosagem Radioterapêutica , Eficiência Biológica Relativa , Tumor Rabdoide/tratamento farmacológico , Tumor Rabdoide/mortalidade , Tumor Rabdoide/radioterapia , Medição de Risco , Teratoma/tratamento farmacológico , Teratoma/mortalidade , Teratoma/radioterapia , Adulto Jovem
20.
J Neurooncol ; 137(1): 119-126, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29214403

RESUMO

Radiation therapy (RT) is integral in the treatment of pediatric brain tumors; however, photon RT (XRT) often results in intellectual decline, executive functioning (EF) deficits, academic underachievement/failure, and lower health-related quality of life (HRQoL). Proton RT (PRT) provides more targeted therapy, minimizing damage to the developing brain, yet few studies have examined its neuropsychological effects. This study investigated the role of EF in academic skills and HRQoL in a sample of children treated with PRT. A mediation model was proposed in which academic skills mediated relations between aspects of EF and school-based HRQoL (sHRQoL). Sixty-five children (x̅age = 12.4; 43.9% male) treated with PRT completed follow-up neuropsychological testing as part of routine care. Measures included assessment of intellectual functioning, EF, attention, and academic skills (reading, math, spelling). Parents reported on children's EF and attention problems. sHRQoL was assessed via child self-report. Children who underwent PRT demonstrated relatively intact intelligence, academics, attention, EF, and sHRQoL, but were at risk for reduced processing speed. Poorer working memory and processing speed were related to lower sHRQoL. Better EF and faster processing speed were associated with better academic skills, which were linked to higher sHRQoL. Better working memory was associated with better math performance, which was linked to higher sHRQoL; this relationship did not hold for reading or spelling. Results highlight the importance of EF skills in academic performance and sHRQoL, and the need for routine screening of EF deficits and proactive supports. Supports may include cognitive rehabilitation and in-class accommodations. Overall, results compare favorably to XRT outcomes reported in the literature.


Assuntos
Neoplasias Encefálicas/psicologia , Neoplasias Encefálicas/radioterapia , Função Executiva , Terapia com Prótons/efeitos adversos , Qualidade de Vida , Sucesso Acadêmico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Memória de Curto Prazo , Testes Neuropsicológicos , Resultado do Tratamento
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