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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.
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.

4.
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
5.
Adv Radiat Oncol ; 3(4): 478-483, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30370345

RESUMO

There is currently much interest in identifying and mitigating gender inequity within medicine, the greater workforce and society as a whole. We provide an evidence-based review of current and historical trends in gender diversity in the RO physician workforce and identify potential barriers to diversity and inclusion in training, professional development, and career advancement. Next, we move to actionable items, addressing methods to mitigate bias, harassment, and other impediments to professional productivity and characterizing leadership lessons and imperatives for departmental, institutional, and organizational leaders.

6.
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
7.
Int J Radiat Oncol Biol Phys ; 102(2): 391-398, 2018 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-30108004

RESUMO

PURPOSE: Radiation therapy is integral in treatment of pediatric brain tumors, but it is associated with negative long-term sequelae. Proton beam radiation therapy (PRT), which enables better focusing of radiation on tumors, may entail fewer sequelae. This prospective study examined cognitive and adaptive functioning in children and young adults treated with PRT. METHODS AND MATERIALS: A total of 155 patients were assessed using age-appropriate measures for cognitive and adaptive functioning at start of or during PRT (baseline) and at follow-up. Mean age at baseline was 8.9 years; mean follow-up interval was 3.6 years. Diagnoses included medulloblastoma, craniopharyngioma, ependymoma, glial tumors, germ cell tumors, and others. The sample was divided by age at baseline (<6 years [N = 57, or 37%] and ≥6 years [N = 98, or 63%]) and by PRT field (craniospinal irradiation [CSI; 39%] and focal irradiation [61%]). RESULTS: Scores for mean intelligence quotient (IQ) and adaptive functioning skills were in the average range at baseline and follow-up. Overall, mean IQ scores declined from 105.4 to 102.5 (P = .005); however, only the younger CSI group showed significant decline. Patients receiving CSI, regardless of age, appeared particularly vulnerable in IQ, processing speed, and working memory. Adaptive skills were stable across the 4 age-by-treatment field groups. CONCLUSIONS: At a mean of 3.6 years after PRT, IQ declined slightly for the group, largely because of significant IQ decline in younger patients treated with CSI. No significant change was seen in patients <6 years treated with focal PRT or in older patients. Adaptive skills remained stable across age and treatment type.


Assuntos
Neoplasias Encefálicas/radioterapia , Cognição/efeitos da radiação , Radiação Cranioespinal/efeitos adversos , Inteligência/efeitos da radiação , Terapia com Prótons/efeitos adversos , Adaptação Fisiológica , Adolescente , Fatores Etários , Análise de Variância , Criança , Pré-Escolar , Cognição/fisiologia , Craniofaringioma/radioterapia , Radiação Cranioespinal/métodos , Ependimoma/radioterapia , Feminino , Glioma/radioterapia , Humanos , Lactente , Inteligência/fisiologia , Masculino , Meduloblastoma/radioterapia , Neoplasias Embrionárias de Células Germinativas/radioterapia , Estudos Prospectivos , Terapia com Prótons/métodos , Adulto Jovem
8.
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
9.
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
10.
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
11.
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
12.
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
13.
Adv Radiat Oncol ; 2(1): 44-52, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28607957

RESUMO

PURPOSE: Proton radiotherapy (PRT) is used in the treatment of retinoblastoma (RB) and has the potential to minimize exposure of normal tissue to radiation and thus decrease risk of toxicity and second malignancies. However, comprehensive analyses of long-term patient outcomes are not available. METHODS: RB patients treated with PRT at our institution between 1986 and 2012 were invited to return for participation in a study designed to assess long-term outcomes. Enrolled patients underwent comprehensive analysis including oncologic, ophthalmic, endocrine, cephalometric, and quality of life (QOL) assessments. RESULTS: A total of 12 patients were enrolled in this study, and the average length of follow-up among enrolled patients was 12.9 years (range 4.8-22.2 years). All enrolled patients had bilateral disease, and the disease and visual outcomes for enrolled patients were similar to outcomes for all RB patients treated with PRT over the same time period at our institution. Endocrine evaluation revealed no growth abnormalities or hormonal deficiencies across the cohort. Based on MRI and external cephalometry, PRT was associated with less facial hypoplasia than enucleation. Patient and parent-proxy QOL assessments revealed that RB treatment did not appear to severely impact long-term QOL. CONCLUSIONS: In addition to providing an opportunity for long-term disease control and functional eye preservation, PRT does not appear to be associated with unexpected late visual, endocrine, or QOL effects in this cohort.

14.
Int J Radiat Oncol Biol Phys ; 98(1): 37-46, 2017 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-28587051

RESUMO

PURPOSE: At present, proton craniospinal irradiation (CSI) for growing children is delivered to the whole vertebral body (WVB) to avoid asymmetric growth. We aimed to demonstrate the feasibility and potential clinical benefit of delivering vertebral body sparing (VBS) versus WVB CSI with passively scattered (PS) and intensity modulated proton therapy (IMPT) in growing children treated for medulloblastoma. METHODS AND MATERIALS: Five plans were generated for medulloblastoma patients, who had been previously treated with CSI PS proton radiation therapy: (1) single posteroanterior (PA) PS field covering the WVB (PS-PA-WVB); (2) single PA PS field that included only the thecal sac in the target volume (PS-PA-VBS); (3) single PA IMPT field covering the WVB (IMPT-PA-WVB); (4) single PA IMPT field, target volume including thecal sac only (IMPT-PA-VBS); and (5) 2 posterior-oblique (-35°, +35°) IMPT fields, with the target volume including the thecal sac only (IMPT2F-VBS). For all cases, 23.4 Gy (relative biologic effectiveness [RBE]) was prescribed to 95% of the spinal canal. The dose, linear energy transfer, and variable-RBE-weighted dose distributions were calculated for all plans using the tool for particle simulation, version 2, Monte Carlo system. RESULTS: IMPT VBS techniques efficiently spared the anterior vertebral bodies (AVBs), even when accounting for potential higher variable RBE predicted by linear energy transfer distributions. Assuming an RBE of 1.1, the V10 Gy(RBE) decreased from 100% for the WVB techniques to 59.5% to 76.8% for the cervical, 29.9% to 34.6% for the thoracic, and 20.6% to 25.1% for the lumbar AVBs, and the V20 Gy(RBE) decreased from 99.0% to 17.8% to 20.0% for the cervical, 7.2% to 7.6% for the thoracic, and 4.0% to 4.6% for the lumbar AVBs when IMPT VBS techniques were applied. The corresponding percentages for the PS VBS technique were higher. CONCLUSIONS: Advanced proton techniques can sufficiently reduce the dose to the vertebral body and allow for vertebral column growth for children with central nervous system tumors requiring CSI. This was true even when considering variable RBE values. A clinical trial is planned for VBS to the thoracic and lumbosacral spine in growing children.


Assuntos
Neoplasias Cerebelares/radioterapia , Radiação Cranioespinal/métodos , Meduloblastoma/radioterapia , Tratamentos com Preservação do Órgão/métodos , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Espalhamento de Radiação , Coluna Vertebral/crescimento & desenvolvimento , Fatores Etários , Criança , Esôfago/diagnóstico por imagem , Estudos de Viabilidade , Lâmina de Crescimento , Humanos , Intestino Delgado/diagnóstico por imagem , Rim/diagnóstico por imagem , Transferência Linear de Energia , Fígado/diagnóstico por imagem , Método de Monte Carlo , Órgãos em Risco/diagnóstico por imagem , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Eficiência Biológica Relativa , Coluna Vertebral/diagnóstico por imagem , Glândula Tireoide/diagnóstico por imagem
15.
Acad Med ; 92(8): 1160-1167, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28030418

RESUMO

PURPOSE: Academic faculty experience barriers to career development and promotion. In 1996, Harvard Medical School (HMS) initiated an intramural junior faculty fellowship to address these obstacles. The authors sought to understand whether receiving a fellowship was associated with more rapid academic promotion and retention. METHOD: Junior faculty fellowship recipients and all other instructor and assistant professors at HMS between 1996 and 2011 were identified. Using propensity score modeling, the authors created a matched comparison group for the fellowship recipients based on educational background, training, academic rank, department, hospital affiliation, and demographics. Time to promotion and time to leaving were assessed by Kaplan-Meier curves. RESULTS: A total of 622 junior faculty received fellowships. Faculty who received fellowships while instructors (n = 480) had shorter times to promotion to assistant professor (P < .0001) and longer retention times (P < .0001) than matched controls. There were no significant differences in time to promotion for assistant professors who received fellowships (n = 142) compared with matched controls, but assistant professor fellowship recipients were significantly more likely to remain longer on the faculty (P = .0005). Women instructors advanced more quickly than matched controls, while male instructors' rates of promotions did not differ. CONCLUSIONS: Fellowships to support junior faculty were associated with shorter times to promotion for instructors and more sustained faculty retention for both instructors and assistant professors. This suggests that relatively small amounts of funding early in faculty careers can play a critical role in supporting academic advancement and retention.


Assuntos
Centros Médicos Acadêmicos/economia , Mobilidade Ocupacional , Comportamento do Consumidor/economia , Docentes de Medicina/economia , Docentes de Medicina/normas , Bolsas de Estudo/economia , Faculdades de Medicina/economia , Centros Médicos Acadêmicos/normas , Adulto , Distinções e Prêmios , Boston , Comportamento do Consumidor/estatística & dados numéricos , Docentes de Medicina/estatística & dados numéricos , Bolsas de Estudo/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reorganização de Recursos Humanos/estatística & dados numéricos , Faculdades de Medicina/normas , Fatores Sexuais , Fatores Socioeconômicos , Estudantes de Medicina/psicologia , Estudantes de Medicina/estatística & dados numéricos , Fatores de Tempo
18.
Lancet Oncol ; 17(3): 287-98, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26830377

RESUMO

BACKGROUND: Compared with traditional photon radiotherapy, proton radiotherapy irradiates less normal tissue and might improve health outcomes associated with photon radiotherapy by reducing toxic effects to normal tissue. We did a trial to assess late complications, acute side-effects, and survival associated with proton radiotherapy in children with medulloblastoma. METHODS: In this non-randomised, open-label, single-centre, phase 2 trial, we enrolled patients aged 3-21 years who had medulloblastoma. Patients had craniospinal irradiation of 18-36 Gy radiobiological equivalents (GyRBE) delivered at 1·8 GyRBE per fraction followed by a boost dose. The primary outcome was cumulative incidence of ototoxicity at 3 years, graded with the Pediatric Oncology Group ototoxicity scale (0-4), in the intention-to-treat population. Secondary outcomes were neuroendocrine toxic effects and neurocognitive toxic effects, assessed by intention-to-treat. This study is registered at ClinicalTrials.gov, number NCT00105560. FINDINGS: We enrolled 59 patients from May 20, 2003, to Dec 10, 2009: 39 with standard-risk disease, six with intermediate-risk disease, and 14 with high-risk disease. 59 patients received chemotherapy. Median follow-up of survivors was 7·0 years (IQR 5·2-8·6). All patients received the intended doses of proton radiotherapy. The median craniospinal irradiation dose was 23·4 GyRBE (IQR 23·4-27·0) and median boost dose was 54·0 GyRBE (IQR 54·0-54·0). Four (9%) of 45 evaluable patients had grade 3-4 ototoxicity according to Pediatric Oncology Group ototoxicity scale in both ears at follow-up, and three (7%) of 45 patients developed grade 3-4 ototoxicity in one ear, although one later reverted to grade 2. The cumulative incidence of grade 3-4 hearing loss at 3 years was 12% (95% CI 4-25). At 5 years, it was 16% (95% CI 6-29). Pediatric Oncology Group hearing ototoxicity score at a follow-up of 5·0 years (IQR 2·9-6·4) was the same as at baseline or improved by 1 point in 34 (35%) of 98 ears, worsened by 1 point in 21 (21%), worsened by 2 points in 35 (36%), worsened by 3 points in six (6%), and worsened by 4 points in two (2%). Full Scale Intelligence Quotient decreased by 1·5 points (95% CI 0·9-2·1) per year after median follow-up up of 5·2 years (IQR 2·6-6·4), driven by decrements in processing speed and verbal comprehension index. Perceptual reasoning index and working memory did not change significantly. Cumulative incidence of any neuroendocrine deficit at 5 years was 55% (95% CI 41-67), with growth hormone deficit being most common. We recorded no cardiac, pulmonary, or gastrointestinal late toxic effects. 3-year progression-free survival was 83% (95% CI 71-90) for all patients. In post-hoc analyses, 5-year progression-free survival was 80% (95% CI 67-88) and 5-year overall survival was 83% (95% CI 70-90). INTERPRETATION: Proton radiotherapy resulted in acceptable toxicity and had similar survival outcomes to those noted with conventional radiotherapy, suggesting that the use of the treatment may be an alternative to photon-based treatments. FUNDING: US National Cancer Institute and Massachusetts General Hospital.


Assuntos
Neoplasias Cerebelares/diagnóstico , Neoplasias Cerebelares/radioterapia , Meduloblastoma/diagnóstico , Meduloblastoma/radioterapia , Terapia com Prótons , Adolescente , Fatores Etários , Neoplasias Cerebelares/mortalidade , Criança , Pré-Escolar , Intervalos de Confiança , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Imagem por Ressonância Magnética/métodos , Masculino , Meduloblastoma/mortalidade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Dosagem Radioterapêutica , Medição de Risco , Fatores Sexuais , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
Int J Radiat Oncol Biol Phys ; 94(1): 133-138, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26700707

RESUMO

PURPOSE: The purpose of this study was to compare long-term disease control and overall survival between children treated with proton and photon radiation therapy (RT) for standard-risk medulloblastoma. METHODS AND MATERIALS: This multi-institution cohort study includes 88 children treated with chemotherapy and proton (n=45) or photon (n=43) RT between 2000 and 2009. Overall survival (OS), recurrence-free survival (RFS), and patterns of failure were compared between the 2 cohorts. RESULTS: Median (range) age was 6 years old at diagnosis (3-21 years) for proton patients versus 8 years (3-19 years) for photon patients (P=.011). Cohorts were similar with respect to sex, histology, extent of surgical resection, craniospinal irradiation (CSI) RT dose, total RT dose, whether the RT boost was delivered to the posterior fossa (PF) or tumor bed (TB), time from surgery to RT start, or total duration of RT. RT consisted of a median (range) CSI dose of 23.4 Gy (18-27 Gy) and a boost of 30.6 Gy (27-37.8 Gy). Median follow-up time is 6.2 years (95% confidence interval [CI]: 5.1-6.6 years) for proton patients versus 7.0 years (95% CI: 5.8-8.9 years) for photon patients. There was no significant difference in RFS or OS between patients treated with proton versus photon RT; 6-year RFS was 78.8% versus 76.5% (P=.948) and 6-year OS was 82.0% versus 87.6%, respectively (P=.285). On multivariate analysis, there was a trend for longer RFS with females (P=.058) and higher CSI dose (P=.096) and for longer OS with females (P=.093). Patterns of failure were similar between the 2 cohorts (P=.908). CONCLUSIONS: Disease control with proton and photon radiation therapy appears equivalent for standard risk medulloblastoma.


Assuntos
Neoplasias Cerebelares/radioterapia , Meduloblastoma/radioterapia , Fótons/uso terapêutico , Terapia com Prótons/métodos , Adolescente , Análise de Variância , Neoplasias Cerebelares/tratamento farmacológico , Neoplasias Cerebelares/mortalidade , Neoplasias Cerebelares/patologia , Criança , Pré-Escolar , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Meduloblastoma/tratamento farmacológico , Meduloblastoma/mortalidade , Meduloblastoma/patologia , Recidiva Local de Neoplasia , Terapia com Prótons/mortalidade , Fatores Sexuais , Falha de Tratamento , Adulto Jovem
20.
Neuro Oncol ; 18(6): 881-7, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26688075

RESUMO

BACKGROUND: Endocrine dysfunction is a common sequela of craniospinal irradiation (CSI). Dosimetric data suggest that proton radiotherapy (PRT) may reduce radiation-associated endocrine dysfunction but clinical data are limited. METHODS: Seventy-seven children were treated with chemotherapy and proton (n = 40) or photon (n = 37) radiation between 2000 and 2009 with ≥3 years of endocrine screening. The incidence of multiple endocrinopathies among the proton and photon cohorts is compared. Multivariable analysis and propensity score adjusted analysis are performed to estimate the effect of radiotherapy type while adjusting for other variables. RESULTS: The median age at diagnosis was 6.2 and 8.3 years for the proton and photon cohorts, respectively (P = .010). Cohorts were similar with respect to gender, histology, CSI dose, and total radiotherapy dose and whether the radiotherapy boost was delivered to the posterior fossa or tumor bed. The median follow-up time was 5.8 years for proton patients and 7.0 years for photon patients (P = .010). PRT was associated with a reduced risk of hypothyroidism (23% vs 69%, P < .001), sex hormone deficiency (3% vs 19%, P = .025), requirement for any endocrine replacement therapy (55% vs 78%, P = .030), and a greater height standard deviation score (mean (± SD) -1.19 (± 1.22) vs -2 (± 1.35), P = .020) on both univariate and multivariate and propensity score adjusted analysis. There was no significant difference in the incidence of growth hormone deficiency (53% vs 57%), adrenal insufficiency (5% vs 8%), or precocious puberty (18% vs 16%). CONCLUSIONS: Proton radiotherapy may reduce the risk of some, but not all, radiation-associated late endocrine abnormalities.


Assuntos
Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/radioterapia , Radiação Cranioespinal , Sistema Endócrino/efeitos da radiação , Meduloblastoma/metabolismo , Meduloblastoma/radioterapia , Adulto , Neoplasias Cerebelares/patologia , Radiação Cranioespinal/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia com Prótons/métodos , Radiação Ionizante , Dosagem Radioterapêutica , Adulto Jovem
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