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1.
Pediatr Blood Cancer ; : e28299, 2020 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-32743983

RESUMO

This report provides a summary of the global burden of childhood cancer morbidity and mortality, which disproportionately affects low- and middle-income countries as well as low- and middle-income communities within high-income countries. We review past successes and current challenges to improving clinical pediatric radiotherapy, education, and research in these regions. The Pediatric Radiation Oncology Society Taskforce in Low- and Middle-Income Countries recently outlined specific aims: (a) to increase access and quality of radiotherapy for children and adolescents afflicted with cancer; (b) to enumerate, engage, and educate a global community of providers of childhood and adolescent radiotherapy; and (c) to create evidence establishing the outcomes of setting-specific treatment standards of care when first-world standards are not achievable. This report will improve awareness of these disparities and promote attempts to correct them.

2.
Phys Med Biol ; 2020 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-32580177

RESUMO

To study radiotherapy-related adverse effects, detailed dose information (3D distribution) is needed for accurate dose-effect modeling. For childhood cancer survivors who underwent radiotherapy in the pre-CT era, only 2D radiographs were acquired, thus 3D dose distributions must be reconstructed from limited information. State-of-the-art methods achieve this by using 3D surrogate anatomies. These can however lack personalization and lead to coarse reconstructions. We present and validate a surrogate-free dose reconstruction method based on Machine Learning (ML). Abdominal planning CTs (n=142) of recently-treated childhood cancer patients were gathered, their organs at risk were segmented, and 300 artificial Wilms' tumor plans were sampled automatically. Each artificial plan was automatically emulated on the 142 CTs, resulting in 42,600 3D dose distributions from which dose-volume metrics were derived. Anatomical features were extracted from digitally reconstructed radiographs simulated from the CTs to resemble historical radiographs. Further, patient and radiotherapy plan features typically available from historical treatment records were collected. An evolutionary ML algorithm was then used to link features to dose-volume metrics. Besides 5-fold cross validation, a further evaluation was done on an independent dataset of five CTs each associated with two clinical plans. Cross-validation resulted in mean absolute errors ≤0.6 Gy for organs completely inside or outside the field. For organs positioned at the edge of the field, mean absolute errors ≤1.7 Gy for Dmean, ≤2.9 Gy for D2cc, and ≤13% for V5Gyand V10Gy, were obtained, without systematic bias. Similar results were found for the independent dataset. To conclude, we proposed a novel organ dose reconstruction method that uses ML models to predict dose-volume metric values given patient and plan features. Our approach is not only accurate, but also efficient, as the setup of a surrogate is no longer needed.

3.
Pediatr Blood Cancer ; : e28395, 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32386126

RESUMO

Children with medulloblastoma, atypical teratoid rhabdoid tumor (ATRT), and ependymoma are treated with a multidisciplinary approach including surgery, radiotherapy, and chemotherapy. Lower doses of craniospinal irradiation and tumor bed boost together with chemotherapy are the current standard of care for average-risk medulloblastoma in the Children's Oncology Group (COG). The International Society of Pediatric Oncology (SIOP) is examining the role of hyperfractionated craniospinal irradiation and chemotherapy in high-risk patients. The recent stratification of medulloblastoma into specific molecular risk groups has prompted both COG and SIOP to reexamine the role of these modalities in these different risk groups to maximize cure rates and minimize long-term complications. Proton therapy has shown lower rates of neurocognitive and endocrine complications compared with photons. Ependymomas are treated with maximal surgical resection and adjuvant radiation therapy. The role of chemotherapy in ependymoma is currently being studied in both COG and SIOP. Likewise, for ATRT the role of different high-dose chemotherapy regimens together with local radiation therapy in infants, or craniospinal radiation in older children, is the current focus of research.

4.
Radiother Oncol ; 148: 216-222, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32342872

RESUMO

OBJECTIVE: To derive evidence-based recommendations for the optimal utilisation of resources during unexpected shortage of radiotherapy capacity. METHODS AND MATERIALS: We have undertaken a rapid review of published literature on the role of radiotherapy in the multimodality treatment of paediatric cancers governing the European practise of paediatric radiotherapy. The derived data has been discussed with expert paediatric radiation oncologists to derive a hierarchy of recommendations. RESULTS: The general recommendations to mitigate the potential detriment of an unexpected shortage of radiotherapy facilities include: (1) maintain current standards of care as long as possible (2) refer to another specialist paediatric radiotherapy department with similar level of expertise (3) prioritise use of existing radiotherapy resources to treat patients with tumours where radiotherapy has the most effect on clinical outcome (4) use chemotherapy to defer the start of radiotherapy where timing of radiotherapy is not expected to be detrimental (5) active surveillance for low-grade tumours if appropriate and (6) consider iso-effective hypofractionated radiotherapy regimens only for selected patients with predicted poor prognosis. The effectiveness of radiotherapy and recommendations for prioritisation of its use for common and challenging paediatric tumours are discussed. CONCLUSION: This review provides evidence-based treatment recommendations during unexpected shortage of paediatric radiotherapy facilities. It has wider applications for the optimal utilisation of facilities, to improve clinical outcome in low- and middle-income countries, where limited resources continue to be a challenge.


Assuntos
Betacoronavirus , Infecções por Coronavirus/prevenção & controle , Neoplasias/radioterapia , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Criança , Terapia Combinada , Guias como Assunto , Humanos , Radioterapia (Especialidade)
5.
Br J Haematol ; 189(6): 1093-1106, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32030738

RESUMO

Population-based studies that assess long-term patterns of incidence, major aspects of treatment and survival are virtually lacking for Hodgkin lymphoma (HL) at a younger age. This study assessed the progress made for young patients with HL (<25 years at diagnosis) in the Netherlands during 1990-2015. Patient and tumour characteristics were extracted from the population-based Netherlands Cancer Registry. Time trends in incidence and mortality rates were evaluated with average annual percentage change (AAPC) analyses. Stage at diagnosis, initial treatments and site of treatment were studied in relation to observed overall survival (OS). A total of 2619 patients with HL were diagnosed between 1990 and 2015. Incidence rates increased for 18-24-year-old patients (AAPC + 1%, P = 0·01) only. Treatment regimens changed into less radiotherapy and more 'chemotherapy only', different for age group and stage. Patients aged 15-17 years were increasingly treated at a paediatric oncology centre. The 5-year OS for children was already high in the early 1990s (93%). For patients aged 15-17 and 18-24 years the 5-year OS improved from 84% and 90% in 1990-1994 to 96% and 97% in 2010-2015, respectively. Survival for patients aged 15-17 years was not affected by site of treatment. Our present data demonstrate that significant progress in HL treatment has been made in the Netherlands since 1990.

6.
J Neurooncol ; 147(2): 417-425, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32088813

RESUMO

INTRODUCTION: Childhood, adolescent and young adult (CAYA) cancer survivors treated with cranial radiotherapy are at risk for developing subsequent meningiomas. There is insufficient evidence concerning the benefits and harms of screening for subsequent meningiomas, and uncertainty about the most appropriate clinical management of asymptomatic meningiomas. Data describing current clinical decision-making is essential to formulate surveillance recommendations. METHODS: We created an online survey to identify the current international clinical practice regarding screening for and management of subsequent asymptomatic meningiomas among CAYA cancer survivors. Fifty-nine physicians from North America and Europe with expertise relevant to meningiomas were invited to participate. RESULTS: Thirty-four physicians (58%) completed the survey. The reported number of CAYA cancer survivors that physicians are willing to screen to detect one meningioma varied widely from 0 to 750 (median 50). Physicians expressed concerns regarding harms from MRI screening, including risks of unnecessary interventions (n = 25, 73%) and overdiagnosis (n = 19, 56%). Growth pattern (n = 33, 97%), location (n = 31, 91%) and size (n = 29, 85%) were endorsed as the most important factors influencing the decision to treat asymptomatic meningiomas. A challenging location (n = 14, 52%), indolent tumor growth pattern (n = 13, 48%), and absence of symptoms (n = 12, 44%) were endorsed as the main reasons to monitor without intervention. CONCLUSIONS: There is international variation in opinions and clinical practice regarding screening for subsequent asymptomatic meningiomas among at risk CAYA cancer survivors. Decision-making regarding interventions of asymptomatic meningiomas are largely driven by clinical characteristics. These valuable insights into current clinical practice will inform surveillance guidelines for CAYA cancer survivors.

7.
Pediatr Blood Cancer ; 67(2): e28039, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31625685

RESUMO

BACKGROUND: As a significant proportion of relapses occurred in the tumor bed or abdomen on patients with the fifth National Wilms Tumor Study stage I anaplastic Wilms tumor (WT), flank radiotherapy was added for stage I anaplastic WT in the subsequent study of the Children's Oncology Group (AREN0321). Preliminary results revealed reduction of relapse rate and improved survival. In cases treated with preoperative chemotherapy, such as in International Society of Pediatric Oncology (SIOP), the value of radiotherapy has never been studied. The aim of this observational study is to describe the pattern of recurrence and survival of patients with stage I diffuse anaplastic WT (DAWT) after induction chemotherapy. METHODS: Retrospective data analysis of the pattern of relapse and survival of all patients with stage I DAWT were included in recent SIOP, L'Associazone Italiana Ematologica Oncologia Pediatrica (AIEOP), Japan Wilms Tumor Study Group (JWiTS), United Kingdom Children's Cancer Study Group (UKCCSG) renal tumor registries. Postoperative treatment consisted of actinomycin D, vincristine, and doxorubicin for 28 weeks without local irradiation. RESULTS: One hundred nine cases with stage I DAWT were identified, of which 95 cases received preoperative chemotherapy. Of these, seven patients underwent preoperative true-cut biopsy. Sixteen of the 95 patients relapsed (17%), six locally, four at distant site, and six combined, and all treated according to SIOP 2001 relapse protocol, which resulted in a 5-year overall survival of 93%. CONCLUSION: Despite 13% locoregional relapse rate, an excellent rescue rate was achieved after salvage treatment, in patients with stage I DAWT whose first-line treatment comprised three-drug chemotherapy (including doxorubicin), without flank irradiation. Therefore, we continue not to advocate the use of radiotherapy in first-line treatment after preoperative chemotherapy in stage I DAWT in the next SIOP protocol.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Renais/mortalidade , Tumor de Wilms/mortalidade , Pré-Escolar , Ensaios Clínicos como Assunto , Terapia Combinada , Dactinomicina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Humanos , Lactente , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Masculino , Prognóstico , Estudos Prospectivos , Radioterapia , Estudos Retrospectivos , Taxa de Sobrevida , Vincristina/administração & dosagem , Tumor de Wilms/patologia , Tumor de Wilms/terapia
8.
J Neurooncol ; 145(1): 177-184, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31522324

RESUMO

INTRODUCTION: Diffuse intrinsic pontine glioma (DIPG) is a rare clinically, neuro-radiologically, and molecularly defined malignancy of the brainstem with a median overall survival of approximately 11 months. Our aim is to evaluate the current tendency for its treatment in Europe in order to develop (inter)national consensus guidelines. METHODS: Healthcare professionals specialized in DIPG were asked to fill in an online survey with questions regarding usual treatment strategies at diagnosis and at disease progression in their countries and/or their centers, respectively. RESULTS: Seventy-four healthcare professionals responded to the survey, of which 87.8% were pediatric oncologists. Only 13.5% of the respondents biopsy all of their patients, 41.9% biopsy their patients infrequently. More than half of the respondents (54.1%) treated their patients with radiotherapy only at diagnosis, whereas 44.6% preferred radiotherapy combined with chemotherapy. When the disease progresses, treatment strategies became even more diverse, and the tendency for no treatment increased from 1.4% at diagnosis to 77.0% after second progression. 36.5% of the healthcare professionals treat children younger than 3 years differently than older children at diagnosis. This percentage decreased, when the disease progresses. Most of the participants (51.4%) included less than 25% of their patients in clinical trials. CONCLUSION: This survey demonstrates a large heterogeneity of treatment regimens, especially at disease progression. We emphasize the need for international consensus guidelines for the treatment of DIPG, possible by more collaborative clinical trials.


Assuntos
Neoplasias do Tronco Encefálico/diagnóstico , Neoplasias do Tronco Encefálico/terapia , Glioma Pontino Intrínseco Difuso/diagnóstico , Glioma Pontino Intrínseco Difuso/terapia , Biópsia , Terapia Combinada , Progressão da Doença , Humanos , Prognóstico
9.
Acta Oncol ; 58(12): 1740-1744, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31526171

RESUMO

Background: The SIOPE-Brain Tumor Group recently published a guideline on craniospinal target volume delineation for highly conformal radiotherapy. In order to spare critical structures like e.g., the lens or cochlea, highly conformal techniques can underdose the cerebrospinal fluid (CSF) in the dural reflections around cranial and sacral nerves. The purpose of this study is to generate evidence for CSF extension within the dural sheaths of the cranial and sacral nerves in order to improve accuracy in target volume delineation.Material and methods: Ten healthy volunteers, age 21 till 41 years, underwent an MRI-scan of the skull-base and sacral plexus. To evaluate CSF extension, cT2-weighted images with fat suppression, low signal to noise ratio and little to no motion-related artifacts were used. Two observers measured the extension of CSF from the inner table of the skull for the cranial nerves, and outside the spinal canal for the sacral nerves.Results: CSF extension (mean distance [95% CI]) was visible within the dural sheaths surrounding the majority of the cranial nerves: optic nerve (40 mm [38-42]), trigeminal nerve (16 mm [15-19]), facial-vestibulocochlear nerve (11 mm [11-12]), glossopharyngeal-vagus-accessory nerve (7 mm [7-9]) and hypoglossal nerve (8 mm [7-9]). No CSF was observed outside the spinal canal at sacral level. No significant difference between both observers was measured.Conclusion: This study generates evidence for significant CSF extension outside the inner table of the skull. Despite the vicinity of the lens and cochlea, we therefore recommend the inclusion of both optic nerves and internal auditory canals in the clinical target volume for craniospinal irradiation when using highly conformal delivery techniques.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Líquido Cefalorraquidiano/diagnóstico por imagem , Nervos Cranianos/diagnóstico por imagem , Radiação Cranioespinal/métodos , Plexo Lombossacral/diagnóstico por imagem , Imagem por Ressonância Magnética Intervencionista/métodos , Adulto , Neoplasias Encefálicas/radioterapia , Feminino , Voluntários Saudáveis , Humanos , Masculino , Variações Dependentes do Observador , Canal Vertebral/diagnóstico por imagem , Adulto Jovem
10.
Radiother Oncol ; 138: 158-165, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31302390

RESUMO

BACKGROUND AND PURPOSE: To evaluate the dosimetric sparing and robustness against inter-fraction anatomical changes between photon and proton dose distributions for children with abdominal tumors. MATERIAL AND METHODS: Volumetric modulated arc therapy (VMAT) and intensity-modulated pencil beam scanning (PBS) proton dose distributions were calculated for 20 abdominal pediatric cases (average 3, range 1-8 years). VMAT plans were based on a full-arc while PBS plans on 2-3 posterior-oblique irradiation fields. Plans were robustly optimized on a patient-specific internal target volume (ITV) using a uniform 5 mm set-up uncertainty. Additionally, for the PBS plans a ± 3% proton range uncertainty was accounted for. Fractional dose re-calculations were performed using the planning computed tomography (CT) deformably registered to the daily cone-beam CT (CBCT) images. Fractional doses were accumulated rigidly. Planned and CBCT accumulated VMAT and PBS dose distributions were compared using dose-volume histogram (DVH) parameters. RESULTS: Significant better sparing of the organs at risk with a maximum reduction in the mean dose of 40% was achieved with PBS. Mean ITV DVH parameters differences between planned and CBCT accumulated dose distributions were smaller than 0.5% for both VMAT and PBS. However, the ITV coverage (V95% > 99%) was not reached for one patient for the accumulated VMAT dose distribution. CONCLUSIONS: For pediatric patients with abdominal tumors, improved dosimetric sparing was obtained with PBS compared to VMAT. In addition, PBS delivered by posterior-oblique irradiation fields demonstrated to be robust against anatomical inter-fraction changes. Compared to PBS, daily anatomical changes proved to affect the target coverage of VMAT dose distributions to a higher extent.


Assuntos
Neoplasias Abdominais/radioterapia , Terapia com Prótons/métodos , Radioterapia de Intensidade Modulada/métodos , Neoplasias Abdominais/diagnóstico por imagem , Neoplasias Abdominais/patologia , Criança , Pré-Escolar , Tomografia Computadorizada de Feixe Cônico , Humanos , Lactente , Dosagem Radioterapêutica
12.
Eur J Cancer ; 114: 47-54, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31059973

RESUMO

Disparities in survival and long-term side-effects from paediatric cancer are observed across European Society for Paediatric Oncology (SIOPE)-affiliated countries. The Joint Action on Rare Cancers (JARC) is a project supported by the European Union and member states aiming to formulate recommendations on rare cancers, including paediatric malignancies, to reduce inequalities and to improve health outcomes. Most paediatric cancers are treated by a combination of systemic agents, surgery and/or radiotherapy. Radiotherapy for children is becoming increasingly complex because of the growing availability of new modalities and techniques and the evolution in molecular biology. These added challenges have the potential to enhance disparities in survival and side-effects between countries, but also among centres in the same country. To tackle radiotherapy-related inequalities, representatives of SIOPE, European SocieTy for Radiotherapy and Oncology, Paediatric Radiation Oncology Society and Childhood Cancer International-Europe defined 'standard' and 'optional' levels to deliver Good Clinical Practice-compliant treatment in paediatric radiation oncology with a focus on patient-related care, education and training. In addition, more than 250 paediatric radiotherapy centres across the SIOPE-affiliated countries have been mapped. For a better understanding of resources in paediatric radiotherapy, JARC representatives are working on an online survey for paediatric radiation oncologists of each centre in SIOPE-affiliated countries. The outcome of this survey will give an insight into the strengths and weaknesses of paediatric radiotherapy across SIOPE-affiliated countries and can be relevant for European Reference Networks in terms of collaboration pathways and referrals in paediatric radiotherapy.

13.
Eur J Cancer ; 114: 36-46, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31035085

RESUMO

AIM: The aim of the study is to analyse radiotherapy quality assurance (RTQA) processes in the treatment of paediatric central nervous system (CNS) tumours across Europe. METHODS: The RTQA aspects of major past and current European trials for paediatric CNS tumours were reviewed based on study protocols and publications. A survey among radiation oncologists and paediatric oncologists about the practices of RTQA in paediatric CNS tumours across European countries was also performed. RESULTS: Several (inter)national initiatives to implement RTQA are being developed across Europe, with an apparent paradigm shift from retrospective to prospective RTQA. Experts from 21 of 29 contacted countries responded to the survey. National consensus guidelines for paediatric CNS tumours are available in 10 of 21 countries. Twenty-one of 33 experts believe that the level of involvement of paediatric radiation oncologists in the meetings and activities of the national paediatric oncology societies is adequate. Central storage of radiotherapy data is available in France, Germany and Denmark. RTQA programmes for paediatric brain tumours are available in 7 countries. Twelve of 21 experts believe that there is a well-established national referral network for the radiation treatment of paediatric patients in their respective countries. CONCLUSION: As a result of the review and survey, the following measures are proposed: (1) developing international RT guidelines for paediatric CNS tumours, (2) improving the collaboration between paediatric oncologists and paediatric radiation oncologists, (3) building a central storage system for RT data, (4) implementing international prospective RTQA platforms and (5) promoting European referral networks to reduce inequality.

14.
JAMA Oncol ; 5(5): 671-680, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30920605

RESUMO

Importance: Survivors of childhood cancer (CCSs) face risk of developing subsequent tumors. Solid benign tumors may be cancer precursors; benign tumors and cancers may share etiologic factors. However, comprehensive data on the risk for solid benign tumors are lacking. Objective: To quantify the incidence of and treatment-related risk factors for histologically confirmed solid nonskin benign tumors among CCSs. Design, Setting, and Participants: This record linkage study involves the Dutch Childhood Oncology Group-Long-Term Effects After Childhood Cancer (DCOG-LATER) cohort of 6165 individuals diagnosed with childhood cancer at younger than 18 years from January 1, 1963, through December 31, 2001, in 7 Dutch pediatric centers and who survived at least 5 years after the diagnosis. Study groups eligible for record linkage from 1990 onward included 5843 CCSs (94.8%) and 883 siblings. Benign tumors were identified from the population-based Dutch histopathology and cytopathology registry (PALGA). Follow-up was completed on May 1, 2015. Data were analyzed from January 1, 1990, through May 1, 2015. Main Outcomes and Measures: Cumulative incidence of any subsequent benign tumor for cohort strata and multivariable Cox proportional hazards regression models (hazard ratios [HRs]) were used to evaluate potential risk factors for 8 major benign tumor subtypes. Results: Of the 5843 eligible CCSs (55.9% male), 542 (9.3%) developed a histologically confirmed subsequent benign tumor after a median follow-up of 22.7 years (range, 5.0-52.2 years). Among women, abdominopelvic radiotherapy inferred dose-dependent increased risks for uterine leiomyoma (n = 43) for doses of less than 20 Gy (HR, 1.9; 95% CI, 0.5-7.0), 20 to less than 30 Gy (HR, 3.4; 95% CI, 1.1-10.4), and at least 30 Gy (HR, 5.4; 95% CI, 2.4-12.4) compared with no abdominopelvic radiotherapy (P = .002 for trend). High-dose radiotherapy to the trunk was not associated with breast fibroadenoma (n = 45). Of 23 osseous and/or chondromatous neoplasms, 16 occurred among leukemia survivors, including 11 after total body irradiation (HR, 37.4; 95% CI, 14.8-94.7). Nerve sheath tumors (n = 55) were associated with radiotherapy (HR at 31 years of age, 2.9; 95% CI, 1.5-5.5) and a crude indicator of neurofibromatosis type 1 or 2 status (HR, 5.6; 95% CI, 2.3-13.7). Subsequent risk for benign tumors was higher than the risks for subsequent nonskin solid malignant neoplasms and for benign tumors among siblings. Conclusions and Relevance: This record linkage study uses a unique resource for valid and complete outcome assessment and shows that CCSs have an approximately 2-fold risk of developing subsequent benign tumors compared with siblings. Site-specific new findings, including for uterine leiomyoma, osteochondroma, and nervous system tumors, are important to enable early diagnosis; this information will be the first step for future surveillance guidelines that include some benign tumors in CCSs and will provide leads for in-depth etiologic studies.


Assuntos
Sobreviventes de Câncer/estatística & dados numéricos , Neoplasias/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Neoplasias/patologia , Países Baixos/epidemiologia , Radioterapia/efeitos adversos , Sistema de Registros , Fatores de Risco , Adulto Jovem
15.
Lancet Oncol ; 20(3): e155-e166, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30842059

RESUMO

Inhomogeneities in radiotherapy dose distributions covering the vertebrae in children can produce long-term spinal problems, including kyphosis, lordosis, scoliosis, and hypoplasia. In the published literature, many often interrelated variables have been reported to affect the extent of potential radiotherapy damage to the spine. Articles published in the 2D and 3D radiotherapy era instructed radiation oncologists to avoid dose inhomogeneity over growing vertebrae. However, in the present era of highly conformal radiotherapy, steep dose gradients over at-risk structures can be generated and thus less harm is caused to patients. In this report, paediatric radiation oncologists from leading centres in 11 European countries have produced recommendations on how to approach dose coverage for target volumes that are adjacent to vertebrae to minimise the risk of long-term spinal problems. Based on available information, it is advised that homogeneous vertebral radiotherapy doses should be delivered in children who have not yet finished the pubertal growth spurt. If dose fall-off within vertebrae cannot be avoided, acceptable dose gradients for different age groups are detailed here. Vertebral delineation should include all primary ossification centres and growth plates, and therefore include at least the vertebral body and arch. For partial spinal radiotherapy, the number of irradiated vertebrae should be restricted as much as achievable, particularly at the thoracic level in young children (<6 years old). There is a need for multicentre research on vertebral radiotherapy dose distributions for children, but until more valid data become available, these recommendations can provide a basis for daily practice for radiation oncologists who have patients that require vertebral radiotherapy.

16.
Phys Med Biol ; 64(5): 055010, 2019 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-30669135

RESUMO

The purpose of this study was to develop a method enabling synthetic computed tomography (sCT) generation of the whole abdomen using magnetic resonance imaging (MRI) scans of pediatric patients with abdominal tumors. The proposed method relies on an automatic atlas-based segmentation of bone and lungs followed by an MRI intensity to synthetic Hounsfield unit conversion. Separate conversion algorithms were used for bone, lungs and soft-tissue. Rigidly registered CT and T2-weighted MR images of 30 patients in treatment position and with the same field of view were used for the evaluation of the atlas and the conversion algorithms. The dose calculation accuracy of the generated sCTs was verified for volumetric modulated arc therapy (VMAT) and pencil beam scanning (PBS). VMAT and PBS plans were robust optimized on an internal target volume (ITV) against a patient set-up uncertainty of 5 mm. Average differences between CT and sCT dose calculations for the ITV V 95% were 0.5% (min 0.0%; max 5.0%) and 0.0% (min -0.1%; max 0.1%) for VMAT and PBS dose distributions, respectively. Average differences for the mean dose to the organs at risk were <0.2% (min -0.6%; max 1.2%) and <0.2% (min -2.0%; max 2.6%) for VMAT and PBS dose distributions, respectively. Results show that MRI-only photon and proton dose calculations are feasible for children with abdominal tumors.


Assuntos
Neoplasias Abdominais/diagnóstico por imagem , Neoplasias Abdominais/radioterapia , Imagem por Ressonância Magnética , Fótons/uso terapêutico , Prótons , Doses de Radiação , Planejamento da Radioterapia Assistida por Computador/métodos , Algoritmos , Criança , Estudos de Viabilidade , Humanos , Masculino , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada
17.
Acta Oncol ; 58(1): 57-65, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30474448

RESUMO

BACKGROUND AND PURPOSE: Patients with low-grade glioma (LGG) have a prolonged survival expectancy due to better discriminative tumor classification and multimodal treatment. Consequently, long-term treatment toxicity gains importance. Contemporary radiotherapy techniques such as intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), tomotherapy (TOMO) and intensity-modulated proton therapy (IMPT) enable high-dose irradiation of the target but they differ regarding delivered dose to organs at risk (OARs). The aim of this comparative in silico study was to determine these dosimetric differences in delivered doses. MATERIAL AND METHODS: Imaging datasets of 25 LGG patients having undergone postoperative radiotherapy were included. For each of these patients, in silico treatment plans to a total dose of 50.4 Gy to the target volume were generated for the four treatment modalities investigated (i.e., IMRT, VMAT, TOMO, IMPT). Resulting treatment plans were analyzed regarding dose to target and surrounding OARs comparing IMRT, TOMO and IMPT to VMAT. RESULTS: In total, 100 treatment plans (four per patient) were analyzed. Compared to VMAT, the IMPT mean dose (Dmean) for nine out of 10 (90%) OARs was statistically significantly (p < .02) reduced, for TOMO this was true in 3/10 (30%) patients and for 1/10 (10%) patients for IMRT. IMPT was the prime modality reducing dose to the OARs followed by TOMO. DISCUSSION: The low dose volume to the majority of OARs was significantly reduced when using IMPT compared to VMAT. Whether this will lead to a significant reduction in neurocognitive decline and improved quality of life is to be determined in carefully designed future clinical trials.


Assuntos
Neoplasias Encefálicas/radioterapia , Glioma/radioterapia , Órgãos em Risco/efeitos da radiação , Terapia com Prótons/métodos , Humanos , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada
18.
Neuro Oncol ; 21(3): 392-403, 2019 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-30099534

RESUMO

BACKGROUND: Pediatric cranial radiotherapy (CrRT) markedly increases risk of meningiomas. We studied meningioma risk factors with emphasis on independent and joint effects of CrRT dose, exposed cranial volume, exposure age, and chemotherapy. METHODS: The Dutch Cancer Oncology Group-Long-Term Effects after Childhood Cancer (DCOG-LATER) cohort includes 5-year childhood cancer survivors (CCSs) whose cancers were diagnosed in 1963-2001. Histologically confirmed benign meningiomas were identified from the population-based Dutch Pathology Registry (PALGA; 1990-2015). We calculated cumulative meningioma incidence and used multivariable Cox regression and linear excess relative risk (ERR) modeling. RESULTS: Among 5843 CCSs (median follow-up: 23.3 y, range: 5.0-52.2 y), 97 developed a benign meningioma, including 80 after full- and 14 after partial-volume CrRT. Compared with CrRT doses of 1-19 Gy, no CrRT was associated with a low meningioma risk (hazard ratio [HR] = 0.04, 95% CI: 0.01-0.15), while increased risks were observed for CrRT doses of 20-39 Gy (HR = 1.66, 95% CI: 0.83-3.33) and 40+ Gy (HR = 2.81, 95% CI: 1.30-6.08). CCSs whose cancers were diagnosed before age 5 versus 10-17 years showed significantly increased risks (HR = 2.38, 95% CI: 1.39-4.07). In this dose-adjusted model, volume was not significantly associated with increased risk (HR full vs partial = 1.66, 95% CI: 0.86-3.22). Overall, the ERR/Gy was 0.30 (95% CI: 0.03-unknown). Dose effects did not vary significantly according to exposure age or CrRT volume. Cumulative incidence after any CrRT was 12.4% (95% CI: 9.8%-15.2%) 40 years after primary cancer diagnosis. Among chemotherapy agents (including methotrexate and cisplatin), only carboplatin (HR = 3.55, 95% CI: 1.62-7.78) appeared associated with meningioma risk. However, we saw no carboplatin dose-response and all 9 exposed cases had high-dose CrRT. CONCLUSION: After CrRT 1 in 8 survivors developed late meningioma by age 40 years, associated with radiation dose and exposure age, relevant for future treatment protocols and awareness among survivors and physicians.


Assuntos
Sobreviventes de Câncer , Irradiação Craniana , Neoplasias Meníngeas/epidemiologia , Meningioma/epidemiologia , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias/terapia , Doses de Radiação , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Países Baixos/epidemiologia , Órgãos em Risco , Modelos de Riscos Proporcionais , Risco , Adulto Jovem
19.
Endocr Connect ; 7(12): 1322-1332, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30400062

RESUMO

Objective: The incidence of cranial radiotherapy (cRT)-induced central hypothyroidism (TSHD) in childhood brain tumor survivors (CBTS) is reported to be low. However, TSHD may be more frequent than currently suspected, as its diagnosis is challenging due to broad reference ranges for free thyroxine (FT4) concentrations. TSHD is more likely to be present when FT4 levels progressively decline over time. Therefore, we determined the incidence and latency time of TSHD and changes of FT4 levels over time in irradiated CBTS. Design: Nationwide, 10-year retrospective study of irradiated CBTS. Methods: TSHD was defined as 'diagnosed' when FT4 concentrations were below the reference range with low, normal or mildly elevated thyrotropin levels, and as 'presumed' when FT4 declined ≥ 20% within the reference range. Longitudinal FT4 concentrations over time were determined in growth hormone deficient (GHD) CBTS with and without diagnosed TSHD from cRT to last follow-up (paired t-test). Results: Of 207 included CBTS, the 5-year cumulative incidence of diagnosed TSHD was 20.3%, which occurred in 50% (25/50) of CBTS with GHD by 3.4 years (range, 0.9-9.7) after cRT. Presumed TSHD was present in 20 additional CBTS. The median FT4 decline in GH-deficient CBTS was 41.3% (P < 0.01) to diagnosis of TSHD and 12.4% (P = 0.02) in GH-deficient CBTS without diagnosed TSHD. Conclusions: FT4 concentrations in CBTS significantly decline over time after cRT, also in those not diagnosed with TSHD, suggesting that TSHD occurs more frequently and earlier than currently reported. The clinical relevance of cRT-induced FT4 decline over time should be investigated in future studies.

20.
Lancet Oncol ; 19(8): e419-e428, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30102236

RESUMO

Paediatric CNS tumours are the most common cause of childhood cancer-related morbidity and mortality, and improvements in their diagnosis and treatment are needed. New genetic and epigenetic information about paediatric CNS tumours is transforming the field dramatically. For most paediatric CNS tumour entities, subgroups with distinct biological characteristics have been identified, and these characteristics are increasingly used to facilitate accurate diagnoses and therapeutic recommendations. Future treatments will be further tailored to specific molecular subtypes of disease, specific tumour predisposition syndromes, and other biological criteria. Successful biomaterial collection is a key requirement for the application of contemporary methodologies for the validation of candidate prognostic factors, the discovery of new biomarkers, the establishment of appropriate preclinical research models for targeted agents, a quicker clinical implementation of precision medicine, and for other therapeutic uses (eg, for immunotherapies). However, deficits in organisational structures and interdisciplinary cooperation are impeding the collection of high-quality biomaterial from CNS tumours in most centres. Practical, legal, and ethical guidelines for consent, storage, material transfer, biobanking, data sharing, and funding should be established by research consortia and local institutions to allow optimal collection of primary and subsequent tumour tissue, body fluids, and normal tissue. Procedures for the collection and storage of biomaterials and related data should be implemented according to the individual and organisational structures of the local institutions.


Assuntos
Bancos de Espécimes Biológicos/normas , Biomarcadores Tumorais , Neoplasias do Sistema Nervoso Central , Oncologia/normas , Pesquisa Médica Translacional/métodos , Bancos de Espécimes Biológicos/ética , Bancos de Espécimes Biológicos/organização & administração , Criança , Feminino , Humanos , Masculino , Oncologia/organização & administração , Oncologia/tendências , Pesquisa Médica Translacional/organização & administração , Pesquisa Médica Translacional/normas
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