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1.
Pediatr Blood Cancer ; : e28080, 2019 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-31736243

RESUMO

PURPOSE: Despite the dosimetric advantages of proton therapy, little data exist on patients who receive proton therapy for Ewing sarcoma of the cranium and skull base. This study reports local disease control and toxicity in such patients. MATERIALS/METHODS: We reviewed 25 patients (≤21 years old) with nonmetastatic Ewing sarcoma of the cranium and skull base treated between 2008 and 2018. Treatment toxicity was graded per the Common Terminology Criteria for Adverse Events v4.0. The Kaplan-Meier product limit method provided estimates of disease control and survival. RESULTS: Median patient age was 5.9 years (range, 1-21.7). Tumor subsites included the skull base (48%), non-skull-base calvarial bones (28%), paranasal sinuses (20%), and nasal cavity (4%). All patients underwent multiagent alkylator- and anthracycline-based chemotherapy; 16% underwent gross total resection (GTR) before radiation. Clinical target volume (CTV) 1 received 45 GyRBE and CTV2 received 50.4 GyRBE following GTR or 54-55.8 GyRBE following biopsy or subtotal resection. Median follow-up was 3.7 years (range, 0.26-8.3); no patients were lost. The 4-year local control, disease-free survival, and overall survival rates were 96%, 86%, and 92%, respectively. Two patients experienced in-field recurrences. One patient experienced bilateral conductive hearing loss requiring aids, two patients developed intracranial vasculopathy, and 6 patients required hormone replacement therapy for neuroendocrine deficits. None developed a secondary malignancy. CONCLUSION: Proton therapy is associated with a favorable therapeutic ratio in children with large Ewing tumors of the cranium and skull base. Despite its high conformality, we observed excellent local control and no marginal recurrences. Treatment dosimetry predicts limited long-term neurocognitive and neuroendocrine side effects.

2.
Pediatr Blood Cancer ; 66(12): e27990, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31524334

RESUMO

PURPOSE: In children treated for nasopharyngeal carcinoma, proton therapy and postchemotherapy target volumes can reduce the radiation dose to developing tissue in the brain and the skull base region. We analyzed outcomes in children with nasopharyngeal carcinoma treated with induction chemotherapy followed by moderate-dose proton therapy. METHODS/MATERIALS: Seventeen patients with nonmetastatic nonkeratinizing undifferentiated/poorly differentiated nasopharyngeal carcinoma underwent double-scattered proton therapy between 2011 and 2017. Median age was 15.3 years (range, 7-21). The American Joint Committee on Cancer T and N stage distribution included the following: T1, one patient; T2, five patients; T3, two patients; and T4, nine patients; and N1, six patients; N2, nine patients; and N3, two patients. Median radiation dose to the primary target volume and enlarged lymph nodes was 61.2 Gy (range, 59.4-61.2). Uninvolved cervical nodes received 45 Gy (range, 45-46.8). All radiation was delivered at 1.8 Gy/fraction daily using sequential plans. In 11 patients, photon-based intensity-modulated radiotherapy was used for elective neck irradiation to optimize dose homogeneity and improve target conformity. All patients received induction chemotherapy; all but one received concurrent chemotherapy. Five received adjuvant beta-interferon therapy. RESULTS: Median follow-up was 3.0 years (range, 1.6-7.9). No patients were lost to follow-up. Overall survival, progression-free survival, and local control rates were 100%. Fifteen patients developed mucositis requiring enteral feeding (n = 14) or total parenteral nutrition (n = 1) during radiotherapy. Serious late side effects included cataract (n = 1), esophageal stenosis requiring dilation (n = 1), sensorineural hearing loss requiring aids (n = 1), and hormone deficiency (n = 5, including three with isolated hypothyroidism). CONCLUSION: Following induction chemotherapy, moderate-dose proton therapy can potentially reduce toxicity in the brain and skull base region without compromising disease control. However, further follow-up is needed to fully characterize and evaluate any reduction in long-term complications.

3.
Int J Radiat Oncol Biol Phys ; 104(1): 149-156, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30684665

RESUMO

PURPOSE: Dosimetric studies show that proton therapy can reduce the low/intermediate radiation dose to uninvolved tissue in children with low-grade glioma (LGG). For this reason, LGG is the fourth most common pediatric tumor treated with proton therapy, yet clinical outcome data on efficacy and toxicity are limited. METHODS AND MATERIALS: We reviewed the medical records of 174 children (≤21 years old) with nonmetastatic LGG enrolled on a prospective protocol and treated with proton therapy between 2007 and 2017. We assessed clinical outcomes and toxicity and analyzed patient, tumor, and treatment-related variables. RESULTS: The median age was 10.2 years (range, 2-21). Fifty-eight percent of tumors were World Health Organization grade 1 and 30% were grade 2; 12% were diagnosed on imaging characteristics alone. The most common histology was pilocytic astrocytoma (47%). The most common tumor subsites were diencephalon/optic pathway (52%), caudal brainstem (16%), and cerebellum (13%). Forty-two percent received chemotherapy before radiation therapy. The median follow-up was 4.4 years. The 5-year actuarial rates of local control, progression-free survival, and overall survival were 85% (95% confidence interval [CI], 78%-90%), 84% (95% CI, 77%-89%), and 92% (95% CI, 85%-95%), respectively. On univariate analysis, brainstem/spinal cord tumor location (62% vs 90% elsewhere) and dose <54 GyRBE (67% vs 91% for 54 GyRBE) were associated with inferior local control (P < .01 for both). Twenty-two patients (12.6%) experienced acute nausea or vomiting requiring ondansetron; 2 patients (1.1%) required corticosteroids. Serious toxicities (4% of patients) included brainstem necrosis requiring corticosteroids (n = 2), symptomatic vasculopathy (n = 2), radiation retinopathy (n = 1), epilepsy (n = 1), and death from radiation-induced high-grade glioma (n = 1). Thirty-nine patients (22%) developed new-onset central hormone deficiency. Pseudoprogression was observed in 32.1%. CONCLUSIONS: Compared with modern photon series, proton therapy reduces the radiation dose to developing brain tissue, diminishing acute toxicities without compromising disease control.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Terapia com Prótons , Adolescente , Corticosteroides/uso terapêutico , Análise de Variância , Astrocitoma/tratamento farmacológico , Astrocitoma/mortalidade , Astrocitoma/patologia , Astrocitoma/radioterapia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Criança , Pré-Escolar , Intervalos de Confiança , Feminino , Glioma/tratamento farmacológico , Glioma/mortalidade , Glioma/patologia , Humanos , Masculino , Intervalo Livre de Progressão , Estudos Prospectivos , Terapia com Prótons/efeitos adversos , Lesões por Radiação/tratamento farmacológico , Dosagem Radioterapêutica , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
4.
Pediatr Blood Cancer ; 65(6): e26997, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29380526

RESUMO

BACKGROUND: Although dosimetric comparisons demonstrate the advantage of proton therapy (PT) over conventional radiotherapy for nongerminomatous germ cell tumors (NGGCT), clinical outcome data for this rare tumor are lacking. We sought to evaluate outcomes for children with NGGCT treated with PT. METHODS: Between 2007 and 2016, 14 children (median age 11, range, 5-19 years) with nonmetastatic NGGCT were treated with PT after induction chemotherapy. Most (8/14) were mixed germ cell. Five of 14 patients had complete resection of their primary tumor before radiation. Off study, eight patients received 36 Gy (RBE [relative biological effectiveness]) craniospinal irradiation (CSI). On study, two patients received 30.6 Gy (RBE) whole-ventricle irradiation and four received focal radiation alone. All patients received a total dose of 54 Gy (RBE) to the tumor/tumor bed. RESULTS: At a median follow-up of 2.8 years, all patients were alive with no local recurrences. Three-year progression-free survival was 86%. Both metastatic recurrences occurred in patients treated with focal radiation alone; one with an immature teratoma developed an isolated spinal recurrence 5 months after treatment. Another with a mixed germ cell tumor developed a multifocal ventricular and shunt tract recurrence 7 months after treatment. Serious toxicity was minimal, including cataracts and hormone deficiency, and limited to children who received CSI. CONCLUSION: Early outcomes in children treated for NGGCT suggest the high conformality of PT does not compromise disease control and yields low toxicity. This pattern of failure data adds to growing evidence suggesting chemotherapy followed by focal radiotherapy alone is inadequate in controlling localized NGGCT.

5.
Acta Oncol ; 57(5): 644-648, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29239262

RESUMO

BACKGROUND: Proton therapy can reduce the low and intermediate radiation dose to uninvolved brain tissue in children with intracranial ependymomas, which may improve functional outcomes and reduce second malignancies in survivors. Accordingly, ependymoma has become the most common pediatric tumor treated with proton therapy, yet data on efficacy and toxicity are limited. MATERIAL AND METHODS: Between June 2007 and February 2017, 179 children (≤21 years old) with nonmetastatic grade II/III intracranial ependymoma received proton therapy at our institution. Median age, 3.5 years (range, 0.7-21); 58% were male. Most (66%) tumors were in the posterior fossa and classified as WHO grade III (67%). 27% underwent multiple operations to maximize the extent of resection; ultimately 85% had a gross total or near total tumor resection before radiotherapy. 33% received preradiation chemotherapy. Median radiation dose in children ≤3 years old, 54 Gy(RBE). Most (>90%) children over 3 years old received 59.4 Gy(RBE). Patient and treatment variables were assessed for correlation with disease control. RESULTS: Median follow-up, 3.2 years. 3-year local control, progression-free survival, and overall survival rates were 85%, 76%, and 90%, respectively. First site of progression was local, metastatic, or simultaneous in 14, 17 and 6 patients, respectively. On multivariate analysis, subtotal resection was associated with inferior local control (67% vs. 88%; p ≤ .01) and progression-free survival (59% vs. 79%; p < .05). Male sex was associated with inferior progression-free (67% vs. 87%; p< .05) and overall survival (84% vs. 99%; p < .01). The 3-year CTCAE grade 2 + brainstem toxicity rate was 5.5% (95% CI: 2.9-10.2), including 1 grade 5 toxicity. CONCLUSIONS: This series of proton therapy for pediatric intracranial ependymoma demonstrates disease control comparable to photon series without unexpected toxicity. Subtotal resection and male sex were associated with inferior disease control. Additional follow-up to quantify the expected reductions in late toxicity with proton therapy is ongoing.


Assuntos
Neoplasias Encefálicas/radioterapia , Ependimoma/radioterapia , Terapia com Prótons/métodos , Adolescente , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/cirurgia , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Ependimoma/mortalidade , Ependimoma/cirurgia , Feminino , Humanos , Lactente , Estimativa de Kaplan-Meier , Masculino , Procedimentos Neurocirúrgicos , Terapia com Prótons/efeitos adversos , Terapia com Prótons/mortalidade , Resultado do Tratamento , Adulto Jovem
6.
Pediatr Blood Cancer ; 64(12)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28544746

RESUMO

BACKGROUND: International, multidisciplinary care of children with central nervous system (CNS) tumors presents unique challenges. The aim of this study is to report patient outcomes of U.K. children referred for proton therapy to a North American facility. METHODS: From 2008 to 2016, 166 U.K. children with approved CNS tumors were treated with proton therapy at a single academic medical center in the United States. Median age was 7 years (range, 1-19). Median follow-up was 2.6 years. RESULTS: The 3-year actuarial overall survival (OS) and local control (LC) rates were 96% and 91%, respectively, for the overall group, 92% and 85% for the ependymoma subgroup (n = 57), 95% and 88% for the low-grade glioma subgroup (n = 54), and 100% and 100%, respectively, for the craniopharyngioma subgroup (n = 45). Cyst expansion was observed in 13 patients, including one case resulting in visual impairment. Serious side effects included new-onset seizures in three patients (1.8%), symptomatic vasculopathy in three patients (1.8%), and symptomatic brainstem necrosis in one patient (0.6%). CONCLUSIONS: In this cohort of British children referred overseas for proton therapy, disease control does not appear compromised, toxicity is acceptable, and improvement in long-term function is anticipated in survivors owing to the reduced brain exposure afforded by proton therapy.


Assuntos
Neoplasias Encefálicas/radioterapia , Terapia com Prótons , Adolescente , Neoplasias Encefálicas/mortalidade , Criança , Pré-Escolar , Craniofaringioma/radioterapia , Ependimoma/radioterapia , Feminino , Seguimentos , Glioma/radioterapia , Humanos , Lactente , Masculino , Resultado do Tratamento , Reino Unido , Adulto Jovem
7.
Pediatr Blood Cancer ; 61(2): 281-5, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24019241

RESUMO

BACKGROUND: To determine feasibility and safety of proactive enteral tube feeding (ETF) in pediatric oncology patients. METHODS: Pediatric patients with newly diagnosed brain tumors, myeloid leukemia or high-risk solid tumors were eligible. Subjects agreeing to start ETF before cycle 2 chemotherapy were considered proactive participants (PPs). Those who declined could enroll as chart collection receiving nutritional standard of care. Nutritional status was assessed using standard anthropometric measurements. Episodes of infection and toxicity related to ETF were documented from diagnosis to end of therapy. A descriptive comparison between PPs and controls was conducted. RESULTS: One hundred four eligible patients were identified; 69 enrolled (20 PPs and 49 controls). At diagnosis, 17% of all subjects were underweight and 26% overweight. Barriers to enrollment included physician, subject and/or family refusal, and inability to initiate ETF prior to cycle 2 of chemotherapy. Toxicity of ETF was minimal, but higher percentage of subjects in the proactive group had episodes of infection than controls. Thirty-nine percent of controls eventually started ETF and were twice as likely to receive parenteral nutrition. PPs experienced less weight loss at ETF initiation than controls receiving ETF and were the only group to demonstrate improved nutritional status at end of study. CONCLUSIONS: Proactive ETF is feasible in children with cancer and results in improved nutritional status at end of therapy. Episodes of infection in this study are concerning; therefore, a larger randomized trial is required to further delineate infectious risks and toxicities that may be mitigated by improved nutritional status.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Nutrição Enteral , Intubação Gastrointestinal , Neoplasias/tratamento farmacológico , Neoplasias/reabilitação , Estado Nutricional , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Lactente , Masculino , Projetos Piloto , Prognóstico , Adulto Jovem
8.
Biol Blood Marrow Transplant ; 18(1): 84-91, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21689773

RESUMO

The Children's Oncology Group conducted a multicenter Phase III trial for chronic graft-versus-host disease (cGVHD). The double-blind, placebo-controlled, randomized study evaluated hydroxychloroquine added to standard therapy for children with newly diagnosed cGVHD. The study also used a novel grading and response scoring system and evaluated clinical laboratory correlates of cGVHD. The primary endpoint was complete response (CR) after 9 months of therapy. Fifty-four patients (27 on each arm) were enrolled before closure because of slow accrual. The CR rate was 28% in the hydroxychloroquine arm versus 33% in the placebo arm (odds ratio [OR] = 0.77, 95% confidence interval [CI]: 0.20-2.93, P = .75) for 42 evaluable patients. For 41 patients with severity assessment at enrollment, 20 (49%) were severe and 18 (44%) moderate according to the National Institutes of Health Consensus Conference global scoring system. The CR rate was 15% for severe cGVHD and 44% for moderate cGVHD (OR = 0.24, 95% CI: 0.05-1.06, P = .07). Although the study could not resolve the primary question, it provided important information for future cGVHD study design in this population.


Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Método Duplo-Cego , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Humanos , Lactente , Masculino , Resultado do Tratamento , Adulto Jovem
9.
J Pediatr Hematol Oncol ; 28(4): 210-5, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16679917

RESUMO

BACKGROUND: Relapsed acute lymphoblastic leukemia (ALL) in children is associated with a poor outcome, especially for those patients whose relapse occurs during the first 36 months after diagnosis. The best therapy for these patients is not known. This study was designed to evaluate the feasibility of enrolling children with recurrent ALL in a standardized treatment protocol that included receipt of a hematopoietic stem cell transplant (HSCT). PROCEDURE: Eligible patients with a bone marrow relapse of non-T, non-B ALL underwent a common induction and consolidation followed by receipt of either an allogeneic HSCT from a human leukocyte antigen (HLA)-identical sibling or an autologous HSCT purged with B-4 blocked ricin. A common conditioning regimen was used for all patients. RESULTS: Twenty-eight patients from eight institutions were enrolled. Fourteen patients did not receive a transplant during the study, because of toxicity (4), relapse (1), inadequate purging (1), and parental or physician preference for an alternative donor transplant (8). Six patients received allogeneic HSCTs. Five of them have remained in remission for a median of 78 months. Eight patients received autologous HSCTs purged with B4-blocked ricin. Four have remained in remission for a median of 94 months. Of the nine patients who received alternative donor transplants, only two remain in remission. CONCLUSION: We conclude that well designed and controlled prospective studies are necessary to define the role of HSCTs in children with recurrent ALL. In order to be successful, such studies must have the full support of participating centers. Autologous HSC transplantation may have a role in the treatment of relapsed ALL, but further studies are needed.


Assuntos
Medula Óssea/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante de Células-Tronco , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Projetos Piloto , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Recidiva , Resultado do Tratamento
10.
J Clin Oncol ; 22(18): 3798-804, 2004 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-15365077

RESUMO

PURPOSE: To determine prognostic factors correlated with outcomes after autologous hematopoietic stem-cell transplantation (HSCT) in children with acute myeloid leukemia (AML). PATIENTS AND METHODS: We studied 219 children who received autologous HSCT for AML in first complete remission (CR) and 73 children in second CR and who were reported to the Autologous Blood and Marrow Transplant Registry. Among 29 of 73 patients who underwent transplantation in second CR, duration of first CR was > or = 12 months. RESULTS: Three-year cumulative incidences of relapse were 37% (95% CI, 31% to 44%), 60% (95% CI, 41% to 74%), and 36% (95% CI, 20% to 53%) for children in first CR, second CR after a short (< 12 months) first CR, and second CR after a long (> or = 12 months) first CR, respectively. Corresponding 3-year probabilities of leukemia-free survival were 54% (95% CI, 47% to 60%), 23% (95% CI, 10% to 39%), and 60% (95% CI, 42% to 75%). In multivariate analyses, risks of relapse, mortality, and treatment failure (relapse or death, inverse of leukemia-free survival) were higher for patients in second CR after a short first CR than for the other two groups. Transplant-related mortality, treatment failure, and overall mortality rates were higher in older (> 10 years) children. CONCLUSION: Duration of first CR seems to be the most important determinant of outcome. Results in children who experience treatment failure with conventional chemotherapy support the use of autologous transplantation as salvage therapy if such patients achieve a subsequent CR.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide/terapia , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Leucemia Mieloide/patologia , Masculino , Mortalidade , Prognóstico , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
11.
J Pediatr Hematol Oncol ; 24(9): 710-3, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12468909

RESUMO

PURPOSE: This study was undertaken to determine if central venous catheter (CVC)-related infection in children with cancer could be prevented by monthly flushing of the catheter with urokinase. PATIENTS AND METHODS: Between August 1994 and July 1998, 103 patients with cancer were randomized at the time of subcutaneous CVC placement to receive monthly flushing of their catheters with either 5000 IU of urokinase-heparin or heparin alone. Patients subsequently had blood cultures taken from their CVCs during an episode of fever. RESULTS: Seventy-four of the 103 patients (72%) enrolled in the study received at least 6 catheter flushes: 40 with urokinase-heparin and 34 with heparin. The median number of flushes was 9.5 in the urokinase-heparin group and 10.2 in the heparin-only group (P = 0.62). There were 5 positive blood cultures in the urokinase-heparin group and seven in patients receiving heparin alone (P = 0.27). Staphylococcus epidermidis was isolated from the blood of 3 patients receiving urokinase-heparin and 6 in those receiving heparin alone (P = 0.17). CONCLUSION: Prophylactic monthly catheter flushes with 5000 IU urokinase did not significantly decrease the number of documented bacteremic events in children with cancer who have CVCs.


Assuntos
Bacteriemia/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Heparina/uso terapêutico , Ativadores de Plasminogênio/uso terapêutico , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico , Adolescente , Adulto , Anticoagulantes/uso terapêutico , Criança , Pré-Escolar , Método Duplo-Cego , Feminino , Humanos , Lactente , Leucemia/tratamento farmacológico , Linfoma/tratamento farmacológico , Masculino , Neoplasias/tratamento farmacológico
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