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BACKGROUND AND PURPOSE: During head-and-neck (H&N) radiotherapy, the parotid glands (PGs) may be overdosed; thus, a tool is required to monitor the delivered dose. This study aimed to assess the dose accuracy of a patient-specific density assignment method (DAM) for dose calculation to monitor the dose to PGs during treatment. PATIENTS AND METHODS: Forty patients with H&N cancer received an intensity modulated radiation therapy (IMRT), among whom 15 had weekly CTs. Dose distributions were calculated either on the CTs (CTref), on one-class CTs (1C-CT, water), or on three-class CTs (3C-CT, water-air-bone). The inter- and intra-patient DAM uncertainties were evaluated by the difference between doses calculated on CTref and 1C-CTs or 3C-CTs. PG mean dose (Dmean) and spinal cord maximum dose (D2%) were considered. The cumulated dose to the PGs was estimated by the mean Dmean of the weekly CTs. RESULTS: The mean (maximum) inter-patient DAM dose uncertainties for the PGs (in cGy) were 23 (75) using 1C-CTs and 12 (50) using 3C-CTs (pâ¯≤ 0.001). For the spinal cord, these uncertainties were 118 (245) and 15 (67; pâ¯≤ 0.001). The mean (maximum) DAM dose uncertainty between cumulated doses calculated on CTs and 3C-CTs was 7 cGy (45 cGy) for the PGs. Considering the difference between the planned and cumulated doses, 53% of the ipsilateral and 80% of the contralateral PGs were overdosed by +3.6â¯Gy (up to 8.2â¯Gy) and +1.9â¯Gy (up to 5.2â¯Gy), respectively. CONCLUSION: The uncertainty of the three-class DAM appears to be clinically non-significant (<0.5â¯Gy) compared with the PG overdose (up to 8.2â¯Gy). This DAM could therefore be used to monitor PG doses and trigger replanning.
Assuntos
Neoplasias Orofaríngeas/radioterapia , Glândula Parótida/efeitos da radiação , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/patologia , Glândula Parótida/diagnóstico por imagem , Radiometria , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , IncertezaRESUMO
INTRODUCTION: Large anatomical variations can be observed during the treatment course intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC), leading to potential dose variations. Adaptive radiotherapy (ART) uses one or several replanning sessions to correct these variations and thus optimize the delivered dose distribution to the daily anatomy of the patient. This review, which is focused on ART in the HNC, aims to identify the various strategies of ART and to estimate the dosimetric and clinical benefits of these strategies. MATERIAL AND METHODS: We performed an electronic search of articles published in PubMed/MEDLINE and Science Direct from January 2005 to December 2016. Among a total of 134 articles assessed for eligibility, 29 articles were ultimately retained for the review. Eighteen studies evaluated dosimetric variations without ART, and 11 studies reported the benefits of ART. RESULTS: Eight in silico studies tested a number of replanning sessions, ranging from 1 to 6, aiming primarily to reduce the dose to the parotid glands. The optimal timing for replanning appears to be early during the first two weeks of treatment. Compared to standard IMRT, ART decreases the mean dose to the parotid gland from 0.6 to 6 Gy and the maximum dose to the spinal cord from 0.1 to 4 Gy while improving target coverage and homogeneity in most studies. Only five studies reported the clinical results of ART, and three of those studies included a non-randomized comparison with standard IMRT. These studies suggest a benefit of ART in regard to decreasing xerostomia, increasing quality of life, and increasing local control. Patients with the largest early anatomical and dose variations are the best candidates for ART. CONCLUSION: ART may decrease toxicity and improve local control for locally advanced HNC. However, randomized trials are necessary to demonstrate the benefit of ART before using the technique in routine practice.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Órgãos em Risco , Glândula Parótida/efeitos da radiação , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada , Medula Espinal/efeitos da radiaçãoRESUMO
The aims of this multicentre retrospective study were to identify prognostic or therapeutic factors impacting on overall survival in patients with gliosarcoma. The analysis included all patients treated for gliosarcoma between 1998 and 2014 in seven French academic centres. Seventy-five patients with a median age of 60 years (range from 23 to 79 years) were treated with a combination of surgery (n = 66), radiotherapy (adjuvant for 64 patients and exclusive for 8 patients) and temozolomide based chemotherapy (n = 58). Median follow-up was 12 months (range from 2 to 71 months). Two-year overall survival (OS) and disease free survival rates were 12 % (95 % CI 4-20 %) and 2 % (95 % CI 0-6 %), respectively. The median OS was 13 months. Treatment at recurrence consisted of chemotherapy (n = 38) (bevazicumab for 18 patients, repeat temozolomide for 10 patients), salvage surgery (n = 8) and radiochemotherapy (n = 1). In univariate analysis, younger age, higher total dose of radiotherapy, longer time to recurrence and treatment at recurrence significantly increased OS. In multivariate analysis, high total dose of radiotherapy (HR = 0.97, p = 0.007) and treatment at recurrence (HR = 0.28, p < 0.001) were favourable prognostic factors of OS. Radiotherapy at a minimum dose of 54 Gy and salvage treatment increased OS of gliosarcoma. Unlike glioblastoma, in our analysis, TMZ based chemotherapy was not associated with an improvement in OS compared to patients who received radiation therapy only.
Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Gliossarcoma/diagnóstico , Gliossarcoma/terapia , Adulto , Idoso , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/epidemiologia , Terapia Combinada , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Intervalo Livre de Doença , Feminino , Gliossarcoma/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Radioterapia , Estudos Retrospectivos , Terapia de Salvação , Temozolomida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Fabry disease (FD) is a genetic disorder resulting from deficiency of the lysosomal enzyme α-galactosidase A (α-Gal A) which leads to globotriaosylceramide (GL-3) accumulation in multiple tissues. We report on the safety and pharmacodynamics of migalastat hydrochloride, an investigational pharmacological chaperone given orally every other day (QOD) to females with FD. METHODS: This was an open-label, uncontrolled, Phase 2 study of 12 weeks with extension to 48 weeks in nine females with FD. Doses of 50mg, 150 mg and 250 mg were given QOD. At multiple time points, α-Gal A activity and GL-3 levels were quantified in blood cells, kidney and skin. GL-3 levels were also evaluated through skin and renal histology. Each individual GLA mutation was retrospectively categorized as being amenable or not to migalastat HCl based on an in vitro α-Gal A transfection assay developed in human embryonic kidney (HEK)-293 cells. RESULTS: Migalastat HCl was generally well tolerated. Patients with amenable mutations seem to demonstrate greater pharmacodynamic response to migalastat HCl compared to patients with non-amenable mutations. The greatest declines in urine GL-3 were observed in the three patients with amenable GLA mutations that were treated with 150 or 250 mg migalastat HCl QOD. Additionally, these three patients all demonstrated decreases in GL-3 inclusions in kidney peri-tubular capillaries. CONCLUSIONS: Migalastat HCl is a candidate oral pharmacological chaperone that provides a potential novel genotype-specific treatment for FD. Treatment resulted in GL-3 substrate decrease in female patients with amenable GLA mutations. Phase 3 studies are ongoing.
Assuntos
1-Desoxinojirimicina/análogos & derivados , Inibidores Enzimáticos/administração & dosagem , Doença de Fabry/tratamento farmacológico , Doença de Fabry/genética , alfa-Galactosidase/antagonistas & inibidores , 1-Desoxinojirimicina/administração & dosagem , Adulto , Inibidores Enzimáticos/efeitos adversos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Doença de Fabry/metabolismo , Doença de Fabry/patologia , Feminino , Células HEK293 , Humanos , Rim/efeitos dos fármacos , Rim/enzimologia , Pessoa de Meia-Idade , Mutação , Pele/efeitos dos fármacos , Pele/enzimologia , Transfecção , alfa-Galactosidase/metabolismoAssuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Relação Dose-Resposta à Radiação , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/radioterapia , Medicina de Precisão/métodos , Dosagem Radioterapêutica , Carga Tumoral/efeitos da radiaçãoRESUMO
Radiotherapy for locally advanced head and neck cancer classically include large prophylactic node volume. However, the use of these large volumes can be responsible for significant toxicity. Furthermore, the disappointing results of radioimmunotherapy combinations in head and neck tumors raise concerns about radiotherapy's potential negative impact on the immune response when large lymph node volumes are treated. Besides, in other tumor locations, such as lung cancers, the volumes of elective irradiation have been considerably reduced, with the same local control as before. This opinion piece reviews the current state of radiation volumes in head and neck cancers, the rationale for these volumes, the potential impact of radiotherapy on immune response, and the volume changes that would improve the efficacy of radioimmunotherapy combinations.
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Neoplasias de Cabeça e Pescoço , Procedimentos de Cirurgia Plástica , Radioterapia (Especialidade) , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Imunidade , Linfonodos/patologiaRESUMO
AIMS: Hypofractionated stereotactic radiotherapy (HSRT) to the cavity after surgical resection of brain metastases improves local control. Most reported cohorts include few patients with melanoma, a population known to have high rates of recurrence and neurological death. We aimed to assess outcomes in patients with melanoma brain metastases who received HSRT after surgery at two Australian institutions. MATERIALS AND METHODS: A retrospective analysis was carried out including patients treated between January 2012 and May 2020. HSRT was recommended for patients with melanoma brain metastases at high risk of local recurrence after surgery. Treatment was delivered using appropriately commissioned linear accelerators. Routine follow-up included surveillance magnetic resonance imaging brain every 3 months for at least 2 years. Primary outcomes were overall survival, local control, incidence of radiological radionecrosis and symptomatic radionecrosis. RESULTS: There were 63 cavities identified in 57 patients. The most common HSRT dose prescriptions were 24 Gy in three fractions and 27.5 Gy in five fractions. The median follow-up was 32 months in survivors. Local control was 90% at 1 year, 83% at 2 years and 76% at 3 years. Subtotal brain metastases resection (hazard ratio 12.5; 95% confidence interval 1.4-111; P = 0.0238) was associated with more local recurrence. Overall survival was 64% at 1 year, 45% at 2 years and 40% at 3 years. There were 10 radiological radionecrosis events (16% of cavities) during the study period, with 5% at 1 year and 8% at 2 years after HSRT. The median time to onset of radiological radionecrosis was 21 months (range 6-56). Of these events, three became symptomatic (5%) during the study period at a median time to onset of 26 months (range 21-32). CONCLUSION: Cavity HSRT is associated with high rates of local control in patients with melanoma brain metastases. Subtotal resection strongly predicts for local recurrence after HSRT. Symptomatic radionecrosis occurred in 5% of cavities but increased to 8% of longer-term survivors.
Assuntos
Neoplasias Encefálicas , Melanoma , Lesões por Radiação , Radiocirurgia , Austrália/epidemiologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Humanos , Melanoma/radioterapia , Melanoma/cirurgia , Lesões por Radiação/etiologia , Radiocirurgia/efeitos adversos , Radiocirurgia/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Myelodysplastic Syndrome (MDS) with isolated deletion 5q is associated with a low risk to leukemic evolution and long overall survival (OS); it comprises 3%-4.5% of MDS cases in Latin America classified according to the World Health Organization 2008. This study aims to describe clinical, laboratory and the outcome of patients according to the newest World Health Organization 2016 proposal. METHODS: We retrospectively reviewed patients from four Brazilian (BR) and four Argentinean (AR) centers diagnosed between 1999 and 2019. RESULTS: The 58 patients (16-AR and 42-BR) presented a median age of 67 (IQR 61-75) years old, women predominance (70.7%) and transfusion dependency (62.5%) at diagnosis. Median hemoglobin level was 8.1g/dL, 27.5% and 44.4% presented thrombocytosis and neutropenia, respectively. Bone marrow (BM) was predominantly hypercellular (43.1%) with 66% showing dysplasia >1 lineage and 37.9% with >2% of blasts. Deletion 5q was mostly isolated (79.3%) and a variety of abnormalities were observed in remaining cases. Most patients were treated with erythropoietin-stimulating agents (ESA), 18 with lenalidomide and 15 with thalidomide. Median follow-up was 7.6 years, with a median OS of 3.5 years and an 8-years leukemic evolution rate of 18.4%. Multivariate analysis showed that age >75 years (HR 2.19), ECOG ≥2 (HR 5.76), BM blasts >2% (HR 2.92) and lenalidomide treatment (HR 0.25) independently influenced the OS. CONCLUSION: Older age, worse performance status and higher percentage of blasts, that can be easily assessed, were associated to a worse prognosis. Also, our results corroborate the protective influence of lenalidomide in terms of OS in this South American series.
Assuntos
Cromossomos Humanos Par 5/genética , Lenalidomida/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Fatores Etários , Idoso , Deleção Cromossômica , Feminino , Humanos , Lenalidomida/farmacologia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Resultado do TratamentoRESUMO
Prion diseases or spongiform encephalopathies are a family of rare neurodegenerative diseases characterized by long incubation periods associated with slow, irreversible and invariably fatal evolution. In humans, they are classified as sporadic, acquired and hereditary or genetic. Diagnosing sporadic "Creutzfeldt-Jakob Disease" (sCJD) is a real challenge for the intensive care physician, given the variability in its clinical presentation and its low incidence. The cases of two patients admitted to the Intensive Care Unit are presented. After ruling out other diseases, they were diagnosed with sCJD with a likelihood level according to the World Health Organization Classification. Clinical and laboratory diagnostic aspects of the disease were analyzed, highlighting the utility of 14-3-3 protein identification in the cerebrospinal fluid.
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Síndrome de Creutzfeldt-Jakob/diagnóstico , Idoso , Cuidados Críticos , Feminino , HumanosRESUMO
OBJECTIVES: The duration of stereotactic body radiotherapy (SBRT) for early-stage non-small cell lung cancer (NSCLC) may affect patient outcomes. We aimed to determine the impact of a continuous versus discontinuous SBRT schedule on local control (LC) and overall survival (OS) in NSCLC patients. MATERIALS AND METHODS: Consecutive NSCLC stage I patients (475) treated with SBRT in four centers were retrospectively analyzed. The delivered dose ranged from 48 to 75â¯Gy in 3-10 fractions. Based on the ratio between the treatment duration (TD) and number of fractions (n), patients were divided into two groups: continuous schedule (CS) (TDâ¯≤â¯1.6n; 239 patients) and discontinuous schedule (DS) (TDâ¯>â¯1.6n; 236 patients). LC and OS were compared using Cox regression analyses after propensity score matching (216 pairs). RESULTS: The median follow-up period was 41 months. Multivariate analysis showed that the DS (hazard ratio (HR): 0.42; 95 % confidence interval (CI): 0.22-0.78) and number of fractions (HR: 1.24; 95 % CI: 1.07-1.43) were significantly associated with LC. The DS (HR: 0.67; 95 % CI: 0.51-0.89), age (HR: 1.02; 95 % CI: 1-1.03), WHO performance status (HR: 2.27; 95 % CI: 1.39-3.7), and T stage (HR: 1.4; 95 % CI: 1.03-1.87) were significantly associated with OS. The 3-year LC and OS were 92 % and 64 % and 81 % and 53 % for DS and CS treatments, respectively (pâ¯<â¯0.01). Cox analysis confirmed that the discontinuous SBRT schedule significantly increased LC and OS. CONCLUSION: DS is associated with significantly improved LC and OS in early-stage NSCLC patients treated with SBRT.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Carcinoma de Pequenas Células do Pulmão , Carcinoma Pulmonar de Células não Pequenas/patologia , Humanos , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: A Benchmark Case (BC) was performed as part of the quality assurance process of the randomized phase 2 GORTEC 2014-14 OMET study, testing the possibility of multisite stereotactic radiation therapy (SBRT) alone in oligometastatic head and neck squamous cell carcinoma (HNSCC) as an alternative to systemic treatment and SBRT. MATERIAL AND METHODS: Compliance of the investigating centers with the prescription, delineation, planning and evaluation recommendations available in the research protocol was assessed. In addition, classical dosimetric analysis was supplemented by quantitative geometric analysis using conformation indices. RESULTS: Twenty centers participated in the BC analysis. Among them, four major deviations (MaD) were reported in two centers. Two (10%) centers in MaD had omitted the satellite tumor nodule and secondarily validated after revision. Their respective DICE indexes were 0.37 and 0 and use of extracranial SBRT devices suboptimal There were significant residual heterogeneities between participating centers, including those with a similar SBRT equipment, with impact of plan quality using standard indicators and geometric indices. CONCLUSION: A priori QA using a BC conditioning the participation of the clinical investigation centers showed deviations from good SBRT practice and led to the exclusion of one out of the twenty participating centers. The majority of centers have demonstrated rigorous compliance with the research protocol. The use of quality indexes adds a complementary approach to improve assessment of plan quality.
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Benchmarking , Neoplasias de Cabeça e Pescoço/radioterapia , Radiocirurgia/normas , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia , França , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Metástase Neoplásica/radioterapia , Órgãos em Risco , Neoplasias Faríngeas/patologia , Neoplasias Faríngeas/radioterapia , Garantia da Qualidade dos Cuidados de Saúde , Radiometria , Radiocirurgia/instrumentação , Radiocirurgia/métodos , Dosagem Radioterapêutica , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundárioRESUMO
The 2-5A system contributes to the antiviral effect of interferons through the synthesis of 2-5A and its activation of the ribonuclease, RNase L. RNase L degrades viral and cellular RNA after activation by unique, 2'-5' phosphodiester-linked, oligoadenylates [2-5A, (pp)p5' A2'(P5'A2')]n, n >=2. Because both the 2-5A system and apoptosis can serve as viral defense mechanisms and RNA degradation occurs during both processes, we investigated the potential role of RNase L in apoptosis. Overexpression of human RNase L by an inducible promoter in NIH3T3 fibroblasts decreased cell viability and triggered apoptosis. Activation of endogenous RNase L, specifically with 2-5A or with dsRNA, induced apoptosis. Inhibition of RNase L with a dominant negative mutant suppressed poly (I).poly (C)-induced apoptosis in interferon-primed fibroblasts. Moreover, inhibition of RNase L suppressed apoptosis induced by poliovirus. Thus, increased RNase L levels induced apoptosis and inhibition of RNase L activity blocked viral-induced apoptosis. Apoptosis may be one of the antiviral mechanisms regulated by the 2-5A system.
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Nucleotídeos de Adenina/metabolismo , Apoptose/fisiologia , Interferons/fisiologia , Oligorribonucleotídeos/metabolismo , Interferência Viral/fisiologia , Células 3T3 , Animais , Fragmentação do DNA , Endorribonucleases/antagonistas & inibidores , Endorribonucleases/genética , Endorribonucleases/metabolismo , Humanos , Camundongos , Poliovirus/patogenicidade , RNA de Cadeia Dupla/metabolismo , TransfecçãoRESUMO
BACKGROUND: The internal target volume (ITV) approach and the mid-ventilation (MidV) concept are the two main respiratory motion-management strategies under free breathing. The purpose of this work was to compare the actual in-treatment target coverage during volumetric modulated arctherapy (VMAT) delivered through both ITV-based and MidV-based planning target volume (PTV) and to provide knowledge in choosing the optimal PTV for stereotactic body radiotherapy (SBRT) for lung lesions. METHODS AND MATERIALS: Thirty-two lung cancer patients treated by a VMAT technique were included in the study. For each fraction, the mean time-weighted position of the target was localized by using a 4-dimensional cone-beam CT (4D-CBCT)-based image guidance procedure. The respiratory-correlated location of the gross tumor volume (GTV) during treatment delivery was determined for each fraction by using in-treatment 4D-CBCT images acquired concurrently with VMAT delivery (4D-CBCTin-treat). The GTV was delineated from each of the ten respiratory phase-sorted 4D-CBCTin-treat datasets for each fraction. We defined target coverage as the average percentage of the GTV included within the PTV during the patient's breathing cycle averaged over the treatment course. Target coverage and PTVs were reported for a MidV-based PTV (PTVMidV) using dose-probabilistic margins and three ITV-based PTVs using isotropic margins of 5 mm (PTVITV + 5mm), 4 mm (PTVITV + 4mm) and 3 mm (PTVITV + 3mm). The in-treatment baseline displacements and target motion amplitudes were reported to evaluate the impact of both parameters on target coverage. RESULTS: Overall, 100 4D-CBCTin-treat images were analyzed. The mean target coverage was 98.6, 99.6, 98.9 and 97.2% for PTVMidV, PTVITV + 5mm, PTVITV + 4mm and PTVITV + 3mm, respectively. All the PTV margins led to a target coverage per treatment higher than 95% in at least 90% of the evaluated cases. Compared to PTVITV + 5mm, PTVMidV, PTVITV + 4mm and PTVITV + 3mm had mean PTV reductions of 16, 19 and 33%, respectively. CONCLUSION: When implementing VMAT with 4D-CBCT-based image guidance, an ITV-based approach with a tighter margin than the commonly used 5 mm margin remains an alternative to the MidV-based approach for reducing healthy tissue exposure in lung SBRT. Compared to PTVMidV, PTVITV + 3mm significantly reduced the PTV while still maintaining an adequate in-treatment target coverage.
Assuntos
Tomografia Computadorizada de Feixe Cônico/métodos , Tomografia Computadorizada Quadridimensional/métodos , Neoplasias Pulmonares/radioterapia , Radiocirurgia/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Humanos , Neoplasias Pulmonares/patologiaRESUMO
Adaptive radiotherapy (ART) corresponds to various replanning strategies aiming to correct for anatomical variations occurring during the course of radiotherapy. The goal of the article was to report the rational, feasibility and benefit of using PET and/or MRI to guide this ART strategy in various tumor localizations. The anatomical modifications defined by scanner taking into account tumour mobility and volume variation are not always sufficient to optimise treatment. The contribution of functional imaging by PET or the precision of soft tissue by MRI makes it possible to consider optimized ART. Today, the most important data for both PET and MRI are for lung, head and neck, cervical and prostate cancers. PET and MRI guided ART appears feasible and safe, however in a very limited clinical experience. Phase I/II studies should be therefore performed, before proposing cost-effectiveness comparisons in randomized trials and before using the approach in routine practice.
Assuntos
Imageamento por Ressonância Magnética , Neoplasias/radioterapia , Tomografia por Emissão de Pósitrons , Radioterapia Guiada por Imagem/métodos , Estudos de Viabilidade , Feminino , Neoplasias de Cabeça e Pescoço/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Neoplasias da Próstata/radioterapia , Neoplasias do Colo do Útero/radioterapiaRESUMO
PURPOSE: To guide parotid gland (PG) sparing at the dose planning step, a specific model based on overlap between PTV and organ at risk (Moore et al.) was developed and evaluated for VMAT in head-and-neck (H&N) cancer radiotherapy. MATERIALS AND METHODS: One hundred and sixty patients treated for locally advanced H&N cancer were included. A model optimization was first performed (20 patients) before a model evaluation (110 patients). Thirty cases were planned with and without the model to quantify the PG dose sparing. The inter-operator variability was evaluated on one case, planned by 12 operators with and without the model. The endpoints were PG mean dose (Dmean), PTV homogeneity and number of monitor units (MU). RESULTS: The PG Dmean predicted by the model was reached in 89% of cases. Using the model significantly reduced the PG Dmean: -6.1±4.3Gy. Plans with the model showed lower PTV dose homogeneity and more MUs (+10.5% on average). For the inter-operator variability, PG dose volume histograms without the optimized model were significantly different compared to those with the model; the Dmean standard deviation for the ipsilateral PG decreased from 2.2Gy to 1.2Gy. For the contralateral PG, this value decreased from 2.9Gy to 0.8Gy. CONCLUSION: During the H&N inverse planning, the optimized model guides to the lowest PG achievable mean dose, allowing a significant PG mean dose reduction of -6.1Gy. Integrating this method at the treatment-planning step significantly reduced the inter-patient and inter-operator variabilities.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Órgãos em Risco , Glândula Parótida , Dosagem Radioterapêutica , Radioterapia de Intensidade Modulada/métodos , Carcinoma de Células Escamosas/radioterapia , Humanos , Glândula Parótida/efeitos da radiação , Planejamento da Radioterapia Assistida por Computador/métodosRESUMO
PURPOSE: In context of head-and-neck radiotherapy, this study aims to compare MR image quality according to diagnostic (DIAG) and radiotherapy (RT) setups; and to optimise an MRI-protocol (including 3D T1 and T2-weighted sequences) for dose-planning (based on pseudo-CT generation). MATERIALS AND METHODS: To compare DIAG and RT setups, signal-to-noise-ratio (SNR) and percentage-image-uniformity (PIU) were computed on T1 images of phantoms and volunteers. Influence of the sample conductivity on SNR was quantified using homemade phantoms. To obtain reliable T1 and T2 images for RT-planning, an experimental design was performed on volunteers by using SNR, contrast-to-noise-ratio (CNR) and mean-opinion-score (MOS). Further, pseudo-CTs were generated from 8 patients T2 images with a state-of-art deep-learning method. These pseudo-CTs were evaluated by mean-absolute-error (MAE) and mean-error (ME). RESULTS: SNR was higher for DIAG-setup compared to RT-setup (SNR-ratio=1.3). A clear influence of the conductivity on SNR was observed. PIU was higher for DIAG-setup (38.8%) compared to RT-setup (33.5%). Regarding the protocol optimisation, SNR, CNR, and MOS were 20.6, 6.16, and 3.91 for the optimal T1 sequence. For the optimal T2 sequence, SNR, CNR and MOS were 25.6, 44.46 and 4.0. In the whole head-and-neck area, the mean MAE and ME of the pseudo-CTs were 82.8 and -3.9 HU. CONCLUSION: We quantified the image quality decrease induces by using an RT-setup for head-and-neck radiotherapy. To compensate this decrease, an MRI protocol was optimised by using an experimental design. This protocol of 15minutes provides accurate images which could be used for MRI-dose-planning in clinical practice.
Assuntos
Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/radioterapia , Imageamento por Ressonância Magnética/métodos , Posicionamento do Paciente/métodos , Planejamento da Radioterapia Assistida por Computador/métodos , Razão Sinal-Ruído , Desenho de Equipamento , Voluntários Saudáveis , Humanos , Posicionamento do Paciente/normas , Imagens de Fantasmas , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador/instrumentação , Fatores de TempoRESUMO
Multicenter studies are needed to demonstrate the clinical potential value of radiomics as a prognostic tool. However, variability in scanner models, acquisition protocols and reconstruction settings are unavoidable and radiomic features are notoriously sensitive to these factors, which hinders pooling them in a statistical analysis. A statistical harmonization method called ComBat was developed to deal with the "batch effect" in gene expression microarray data and was used in radiomics studies to deal with the "center-effect". Our goal was to evaluate modifications in ComBat allowing for more flexibility in choosing a reference and improving robustness of the estimation. Two modified ComBat versions were evaluated: M-ComBat allows to transform all features distributions to a chosen reference, instead of the overall mean, providing more flexibility. B-ComBat adds bootstrap and Monte Carlo for improved robustness in the estimation. BM-ComBat combines both modifications. The four versions were compared regarding their ability to harmonize features in a multicenter context in two different clinical datasets. The first contains 119 locally advanced cervical cancer patients from 3 centers, with magnetic resonance imaging and positron emission tomography imaging. In that case ComBat was applied with 3 labels corresponding to each center. The second one contains 98 locally advanced laryngeal cancer patients from 5 centers with contrast-enhanced computed tomography. In that specific case, because imaging settings were highly heterogeneous even within each of the five centers, unsupervised clustering was used to determine two labels for applying ComBat. The impact of each harmonization was evaluated through three different machine learning pipelines for the modelling step in predicting the clinical outcomes, across two performance metrics (balanced accuracy and Matthews correlation coefficient). Before harmonization, almost all radiomic features had significantly different distributions between labels. These differences were successfully removed with all ComBat versions. The predictive ability of the radiomic models was always improved with harmonization and the improved ComBat provided the best results. This was observed consistently in both datasets, through all machine learning pipelines and performance metrics. The proposed modifications allow for more flexibility and robustness in the estimation. They also slightly but consistently improve the predictive power of resulting radiomic models.
Assuntos
Neoplasias Laríngeas/diagnóstico por imagem , Interpretação de Imagem Radiográfica Assistida por Computador/métodos , Neoplasias do Colo do Útero/diagnóstico por imagem , Feminino , Humanos , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Estudos Multicêntricos como Assunto , Tomografia por Emissão de Pósitrons , PrognósticoRESUMO
Head and neck cancers comprise a variety of tumours depending on the sub-site, for which target volumes and the prescribed doses need to be individualized according to each patient's history and presentation. This article aims at describing the main factors involved in decision-making regarding dose and volume, as well as ongoing research. Contouring and treatment guidelines, use of altered fractionation, major prognostic factors, the role of Human papillomavirus and of functional imaging will be presented and discussed.
Assuntos
Neoplasias de Cabeça e Pescoço/radioterapia , Medicina de Precisão , Dosagem Radioterapêutica , Fracionamento da Dose de Radiação , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/virologia , Humanos , Neoplasias Orofaríngeas/diagnóstico por imagem , Neoplasias Orofaríngeas/radioterapia , Neoplasias Orofaríngeas/virologia , Papillomaviridae , Tomografia por Emissão de Pósitrons , Guias de Prática Clínica como Assunto , PrognósticoRESUMO
Adaptive radiotherapy (ART) is a complexe image-guided radiotherapy modality that comprises multiple planning to account for anatomical variations occurring during irradiation. Schematically, two strategies of RTA can be distinguished and combined according to tumor locations. One or more replanning can be proposed to correct systematic variations such as tumor shrinkage. A library of treatment plans with day-to-day plan selection from cone-beam CT imaging can also be proposed to correct random variations such as uterine motion or bladder/rectum volume changes. Because of strong anatomical variations occurring during irradiation, RTA appears therefore particularly justified in head and neck, lung, bladder, cervical and rectum and pancreas tumors, and to a lesser extent for prostate tumors and other digestive tumors. For these tumor locations, ART provides a fairly clear dosimetric benefit but a clinical benefit not yet formally demonstrated. ART cannot be proposed in a routine practice but must be evaluated medico-economically in the context of prospective trials. A rigorous quality control must be associated.
Assuntos
Neoplasias/diagnóstico por imagem , Neoplasias/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia Guiada por Imagem/métodos , Radioterapia de Intensidade Modulada/métodos , Feminino , Neoplasias Gastrointestinais/radioterapia , Humanos , Neoplasias Pulmonares/radioterapia , Masculino , Neoplasias Otorrinolaringológicas/radioterapia , Neoplasias da Próstata/radioterapia , Neoplasias da Bexiga Urinária/radioterapia , Neoplasias do Colo do Útero/radioterapiaRESUMO
BACKGROUND: Overall, 40% of patients with a locally advanced head and neck cancer (LAHNC) treated by chemoradiotherapy (CRT) present local recurrence within 2 years after the treatment. The aims of this study were to characterize voxel-wise the sub-regions where tumor recurrence appear and to predict their location from pre-treatment 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images. MATERIALS AND METHODS: Twenty-six patients with local failure after treatment were included in this study. Local recurrence volume was identified by co-registering pre-treatment and recurrent PET/CT images using a customized rigid registration algorithm. A large set of voxel-wise features were extracted from pre-treatment PET to train a random forest model allowing to predict local recurrence at the voxel level. RESULTS: Out of 26 expert-assessed registrations, 15 provided enough accuracy to identify recurrence volumes and were included for further analysis. Recurrence volume represented on average 23% of the initial tumor volume. The MTV with a threshold of 50% of SUVmax plus a 3D margin of 10 mm covered on average 89.8% of the recurrence and 96.9% of the initial tumor. SUV and MTV alone were not sufficient to identify the area of recurrence. Using a random forest model, 15 parameters, combining radiomics and spatial location, were identified, allowing to predict the recurrence sub-regions with a median area under the receiver operating curve of 0.71 (range 0.14-0.91). CONCLUSION: As opposed to regional comparisons which do not bring enough evidence for accurate prediction of recurrence volume, a voxel-wise analysis of FDG-uptake features suggested a potential to predict recurrence with enough accuracy to consider tailoring CRT by dose escalation within likely radioresistant regions.