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BACKGROUND: Thoracic radiation intensification is debated in patients with stage III non-small-cell lung cancer (NSCLC). We aimed to assess the activity and safety of a boost radiotherapy dose up to 74 Gy in a functional sub-volume given according to on-treatment [18F]fluorodeoxyglucose ([18F]FDG)-PET results. METHODS: In this multicentre, randomised, controlled non-comparative phase 2 trial, we recruited patients aged 18 years or older with inoperable stage III NSCLC without EGFR mutation or ALK rearrangement with an Eastern Cooperative Oncology Group performance status of 0-1, and who were affiliated with or a beneficiary of a social benefit system, with evaluable tumour or node lesions, preserved lung function, and who were amenable to curative-intent radiochemotherapy. Patients were randomly allocated using a central interactive web-response system in a non-masked method (1:1; minimisation method used [random factor of 0·8]; stratified by radiotherapy technique [intensity-modulated radiotherapy vs three-dimensional conformal radiotherapy] and by centre at which patients were treated) either to the experimental adaptive radiotherapy group A, in which only patients with positive residual metabolism on [18F]FDG-PET at 42 Gy received a boost radiotherapy (up to 74 Gy in 33 fractions), with all other patients receiving standard radiotherapy dosing (66 Gy in 33 fractions over 6·5 weeks), or to the standard radiotherapy group B (66 Gy in 33 fractions) over 6·5 weeks. All patients received two cycles of induction platinum-based chemotherapy cycles (paclitaxel 175 mg/m2 intravenously once every 3 weeks and carboplatin area under the curve [AUC]=6 once every 3 weeks, or cisplatin 80 mg/m2 intravenously once every 3 weeks and vinorelbine 30 mg/m2 intravenously on day 1 and 60 mg/m2 orally [or 30 mg/m2 intravenously] on day 8 once every 3 weeks). Then they concomitantly received radiochemotherapy with platinum-based chemotherapy (three cycles for 8 weeks, with once per week paclitaxel 40 mg/m2 intravenously and carboplatin AUC=2 or cisplatin 80 mg/m2 intravenously and vinorelbine 20 mg/m2 intravenously on day 1 and 40 mg/m2 orally (or 20 mg/m2 intravenously) on day 8 in 21-day cycles). The primary endpoint was the 15-month local control rate in the eligible patients who received at least one dose of concomitant radiochemotherapy. This RTEP7-IFCT-1402 trial is registered with ClinicalTrials.gov (NCT02473133), and is ongoing. FINDINGS: From Nov 12, 2015, to July 7, 2021, we randomly assigned 158 patients (47 [30%] women and 111 [70%] men) to either the boosted radiotherapy group A (81 [51%]) or to the standard radiotherapy group B (77 [49%)]. In group A, 80 (99%) patients received induction chemotherapy and 68 (84%) received radiochemotherapy, of whom 48 (71%) with residual uptake on [18F]FDG-PET after 42 Gy received a radiotherapy boost. In group B, all 77 patients received induction chemotherapy and 73 (95%) received radiochemotherapy. At the final analysis, the median follow-up for eligible patients who received radiochemotherapy (n=140) was 45·1 months (95% CI 39·3-48·3). The 15-month local control rate was 77·6% (95% CI 67·6-87·6%) in group A and 71·2% (95% CI 60·8-81·6%) in group B. Acute (within 90 days from radiochemotherapy initiation) grade 3-4 adverse events were observed in 20 (29%) of 68 patients in group A and 33 (45%) of 73 patients in group B, including serious adverse events in five (7%) patients in group A and ten (14%) patients in group B. The most common grade 3-4 adverse events were febrile neutropenia (seven [10%] of 68 in group A vs 16 [22%] of 73 in group B), and anaemia (five [7%] vs nine [12%]). In the acute phase, two deaths (3%) occurred in group B (one due to a septic shock related to chemotherapy, and the other due to haemotypsia not related to study treatment), and no deaths occurred in group A. After 90 days, one additional treatment-unrelated death occurred in group A and two deaths events occurred in group B (one radiation pneumonitis and one pneumonia unrelated to treatment). INTERPRETATION: A thoracic radiotherapy boost, based on interim [18F]FDG-PET, led to a meaningful local control rate with no difference in adverse events between the two groups in organs at risk, in contrast with previous attempts at thoracic radiation intensification, warranting a randomised phase 3 evaluation of such [18F]FDG-PET-guided radiotherapy dose adaptation in patients with stage III NSCLC. FUNDING: Programme Hospitalier de Recherche Clinique National 2014.
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BACKGROUND: PET-CT with 18F-FDG or other radiopharmaceuticals is a recommended tool to help the delineation of lung cancers candidate to radiotherapy. The motion artifacts caused by respiratory movements are reduced by 4D acquisitions. We introduced an extended reconstruction algorithm (multiple reconstruct register and average [multi-RRA]) which requires much shorter acquisition times than standard 4D PET-CT. Our aim was to evaluate the interest on multi-RRA images as an alternative of 3D and 4D PET-CT for the delineation of lung lesion. METHODS: PET acquisitions synchronized to the respiratory signal were obtained in 18 patients with mobile lung tumors. We compared the tumor volumes delineated on Multi-RRA images to 3D and 4D PET-CT, considering the 4D CT as a reference. The tumor volumes were delineated and compared with topologic similarity indexes (Dice, Jaccard and overlap). RESULTS: Twenty tumors were delineated. The volumes delineated with multi-RRA and 4D PET were not significantly different (mean difference of 0.2±0.7 mL). Comparison by pairs (Tukey-Kramer test) showed that 3D-PET volumes were significantly smaller than 4D-PET and multi-RRA volumes (P<0.001). Topologic similarity indexes with 4D-PET were slightly statistically higher with multi-RRA than with 3D-PET (Dice and Jaccard) or 4D-CT (Dice, Jaccard and Overlap). CONCLUSIONS: The tumor volumes delineated on multi-RRA are similar to the volumes obtained with 4D PET, with shorter acquisition time.
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Neoplasias Pulmonares , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fluordesoxiglucose F18 , Tomografia Computadorizada Quadridimensional/métodos , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/radioterapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Tomografia por Emissão de Pósitrons/métodosRESUMO
The purpose of this study was to evaluate the positioning uncertainties of two PET/CT-MR imaging setups, C1 and C2. Because the PET/CT data were acquired on the same hybrid device with automatic image registration, experiments were conducted using CT-MRI data. In C1, a transfer table was used, which allowed the patient to move from one imager to another while maintaining the same position. In C2, the patient stood up and was positioned in the same radiotherapy treatment position on each imager. The two setups provided a set of PET/CT and MR images. The accuracy of the registration software was evaluated on the CT-MRI data of one patient using known translations and rotations of MRI data. The uncertainties on the two setups were estimated using a phantom and a cohort of 30 patients. The accuracy of the positioning uncertainties was evaluated using descriptive statistics and a t-test to determine whether the mean shift significantly deviated from zero (p < 0.05) for each setup. The maximum registration errors were less than 0.97 mm and 0.6° for CT-MRI registration. On the phantom, the mean total uncertainties were less than 2.74 mm and 1.68° for C1 and 1.53 mm and 0.33° for C2. For C1, the t-test showed that the displacements along the z-axis did not significantly deviate from zero (p = 0.093). For C2, significant deviations from zero were present for anterior-posterior and superior-inferior displacements. The mean total uncertainties were less than 4 mm and 0.42° for C1 and less than 1.39 mm and 0.27° for C2 in the patients. Furthermore, the t-test showed significant deviations from zero for C1 on the anterior-posterior and roll sides. For C2, there was a significant deviation from zero for the left-right displacements.This study shows that transfer tables require careful evaluation before use in radiotherapy.
Assuntos
Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tomografia Computadorizada por Raios X , Humanos , Imageamento por Ressonância Magnética/métodos , Posicionamento do Paciente/métodos , Imagens de Fantasmas , Planejamento da Radioterapia Assistida por Computador/métodos , Tomografia Computadorizada por Raios X/métodosRESUMO
PURPOSE: It has been suggested that FDG PET has predictive value for the prognosis of treated oesophageal carcinoma. However, the studies reported in the literature have shown discordant results. The aim of this study was to determine whether pretherapy quantitative metabolic parameters correlate with patient outcomes. METHODS: Included in the study were 67 patients with a histological diagnosis of oesophageal squamous cell carcinoma. Each patient underwent (18)F-FDG PET (4.5 MBq/kg) before chemoradiotherapy. Quantitative analysis was performed using the following parameters: age, weight loss, location, N stage, OMS performance status, MTVp and MTVp' (metabolic tumour volume determined by two different physicians), MTV40% (volume for a threshold of 40 % of SUVmax), MTVa (volume automatically determined with a contrast-based adaptive threshold method), SUVmax, SUVmean and TLG (total lesion glycolysis). RESULTS: MTVp and MTV40% were highly correlated (Pearson's index 0.92). SUVmeanp and SUVmean40% were also correlated (Pearson's index 0.86), as were TLGp and TLG40% (Pearson's index 0.98). Similarly, the parameters obtained with the adaptive threshold method (MTVa, SUVmeana and TLGa) were correlated with those obtained manually (MTVp, SUVmeanp and TLGp). The manual metabolic tumour volume determination (MTVp and MTVp') was reproducible. Multivariate analysis for disease-free survival (DFS) showed that a larger MTVp was associated with a shorter DFS (p = 0.004) and that a higher SUVmax was associated with a longer DFS (p = 0.02). Multivariate analysis for overall survival (OS) showed that a larger MTVp was associated with a shorter OS (p = 0.01) and that a tumour in the distal oesophagus was associated with a longer OS (p = 0.005). The associations among the other parameters were not statistically significant. CONCLUSION: Metabolic tumour volume is a major prognostic factor for DFS and OS in patients with oesophageal squamous cell carcinoma. Higher SUVmax values were paradoxically associated with longer survival. The location of the tumour also appeared to affect prognosis.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carga Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/terapia , Quimiorradioterapia , Intervalo Livre de Doença , Neoplasias Esofágicas/diagnóstico por imagem , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas do Esôfago , Feminino , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Estudos RetrospectivosRESUMO
Tumor hypoxia is a complex and evolving phenomenon both in time and space. Molecular imaging allows to approach these variations, but the tracers used have their own limitations. PET imaging has the disadvantage of low resolution and must take into account molecular biodistribution, but has the advantage of high targeting accuracy. The relationship between the signal in MRI imaging and oxygen is complex but hopefully it would lead to the detection of truly oxygen-depleted tissue. Different ways of imaging hypoxia are discussed in this review, with nuclear medicine tracers such as [18F]-FMISO, [18F]-FAZA, or [64Cu]-ATSM but also with MRI techniques such as perfusion imaging, diffusion MRI or oxygen-enhanced MRI. Hypoxia is a pejorative factor regarding aggressiveness, tumor dissemination and resistance to treatments. Therefore, having accurate tools is particularly important.
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Intratumoral hypoxia is associated with a poor prognosis and poor response to treatment in head and neck cancers. Its identification would allow for increasing the radiation dose to hypoxic tumor subvolumes. 18F-FMISO PET imaging is the gold standard; however, quantitative multiparametric MRI could show the presence of intratumoral hypoxia. Thus, 16 patients were prospectively included and underwent 18F-FDG PET/CT, 18F-FMISO PET/CT, and multiparametric quantitative MRI (DCE, diffusion and relaxometry T1 and T2 techniques) in the same position before treatment. PET and MRI sub-volumes were segmented and classified as hypoxic or non-hypoxic volumes to compare quantitative MRI parameters between normoxic and hypoxic volumes. In total, 13 patients had hypoxic lesions. The Dice, Jaccard, and overlap fraction similarity indices were 0.43, 0.28, and 0.71, respectively, between the FDG PET and MRI-measured lesion volumes, showing that the FDG PET tumor volume is partially contained within the MRI tumor volume. The results showed significant differences in the parameters of SUV in FDG and FMISO PET between patients with and without measurable hypoxic lesions. The quantitative MRI parameters of ADC, T1 max mapping and T2 max mapping were different between hypoxic and normoxic subvolumes. Quantitative MRI, based on free water diffusion and T1 and T2 mapping, seems to be able to identify intra-tumoral hypoxic sub-volumes for additional radiotherapy doses.
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The evaluation of tumor follow-up according to RECIST 1.1 has become essential in clinical practice given its role in therapeutic decision making. At the same time, radiologists are facing an increase in activity while facing a shortage. Radiographic technologists could contribute to the follow-up of these measures, but no studies have evaluated their ability to perform them. Ninety breast cancer patients were performed three CT follow-ups between September 2017 and August 2021. 270 follow-up treatment CT scans were analyzed including 445 target lesions. The rate of agreement of classifications RECIST 1.1 between five technologists and radiologists yielded moderate (k value between 0.47 and 0.52) and substantial (k value = 0.62 and k = 0.67) agreement values. 112 CT were classified as progressive disease (PD) by the radiologists, and 414 new lesions were identified. The analysis showed a percentage of strict agreement of progressive disease classification between reader-technologists and radiologists ranging from substantial to almost perfect agreement (range 73-97%). Analysis of intra-observer agreement was strong at almost perfect (k > 0.78) for 3 technologists. These results are encouraging regarding the ability of selected technologists to perform measurements according to RECIST 1.1 criteria by CT scan with good identification of disease progression.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Critérios de Avaliação de Resposta em Tumores Sólidos , Projetos Piloto , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X/métodos , Variações Dependentes do Observador , Estudos RetrospectivosRESUMO
Tetrodotoxin is one of the most potent neurotoxins in the aquatic world. This review of published and unpublished reports aims to describe the poisoning cases that have occurred in mainland France and overseas territories. Six articles were included, with 13 poisoning events, individuals or collective (number (n) = 53 patients). Moreover, 13 unpublished poisoning events from toxicovigilance networks were found (n = 17). All cases happened in overseas territories: French Guyana (n = 7), New Caledonia (n = 11), Reunion (n = 35) and French Polynesia (n = 17). The median age was 36 years. The most frequent signs were neurological (81.8%), digestive (54.5%) and general (52.3%). Three cases of dysgueusia and nine cases of urogenital discomfort were observed in French Polynesia. Twelve severe cases were reported, including seven deaths. Only three events (11.5%) were documented by a tetrodotoxin assay. Two families of fish accounted for 91.6% of the poisonings: 33.3% due to the Diodontidae family and 58.3% to the Tetraodontidae family. Although rare, information and collection campaigns on tetrodotoxin poisoning are, therefore, essential.
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Ciguatera , Síndromes Neurotóxicas , Tetraodontiformes , Animais , França , Humanos , Tetrodotoxina/toxicidadeRESUMO
Purpose: We aimed to evaluate the accuracy of T 1 and T 2 mappings derived from a multispectral pulse sequence (magnetic resonance image compilation, MAGiC®) on 1.5-T MRI and with conventional sequences [gradient echo with variable flip angle (GRE-VFA) and multi-echo spin echo (ME-SE)] compared to the reference values for the purpose of radiotherapy treatment planning. Methods: The accuracy of T 1 and T 2 measurements was evaluated with 2 coils [head and neck unit (HNU) and BODY coils] on phantoms using descriptive statistics and Bland-Altman analysis. The reproducibility and repeatability of T 1 and T 2 measurements were performed on 15 sessions with the HNU coil. The T 1 and T 2 synthetic sequences obtained by both methods were evaluated according to quality assurance (QA) requirements for radiotherapy. T 1 and T 2 in vivo measurements of the brain or prostate tissues of two groups of five subjects were also compared. Results: The phantom results showed good agreement (mean bias, 8.4%) between the two measurement methods for T 1 values between 490 and 2,385 ms and T 2 values between 25 and 400 ms. MAGiC® gave discordant results for T 1 values below 220 ms (bias with the reference values, from 38% to 1,620%). T 2 measurements were accurately estimated below 400 ms (mean bias, 8.5%) by both methods. The QA assessments are in agreement with the recommendations of imaging for contouring purposes for radiotherapy planning. On patient data of the brain and prostate, the measurements of T 1 and T 2 by the two quantitative MRI (qMRI) methods were comparable (max difference, <7%). Conclusion: This study shows that the accuracy, reproducibility, and repeatability of the multispectral pulse sequence (MAGiC®) were compatible with its use for radiotherapy treatment planning in a range of values corresponding to soft tissues. Even validated for brain imaging, MAGiC® could potentially be used for prostate qMRI.
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Hypoxic areas are typically resistant to treatment. However, the fluorine-18-fluoroazomycin-arabinoside (FAZA) and fluorine 18 misonidazole (FMISO) tracers have never been compared in non small cell lung cancer (NSCLC). This study compares the capability of 18F-FAZA PET/CT with that of 18F-FMISO PET/CT for detecting hypoxic tumour regions in early and locally advanced NSCLC patients. We prospectively evaluated patients who underwent preoperative PET scans before surgery for localised NSCLC (i.e., fluorodeoxyglucose (FDG)-PET, FMISO-PET, and FAZA-PET). The PET data of the three tracers were compared with each other and then compared to immunohistochemical analysis (GLUT-1, CAIX, LDH-5, and HIF1-Alpha) after tumour resection. Overall, 19 patients with a mean age of 68.2 ± 8 years were included. There were 18 lesions with significant uptake (i.e., SUVmax >1.4) for the F-MISO and 17 for FAZA. The mean SUVmax was 3 (±1.4) with a mean volume of 25.8 cc (±25.8) for FMISO and 2.2 (±0.7) with a mean volume of 13.06 cc (±13.76) for FAZA. The SUVmax of F-MISO was greater than that of FAZA (p = 0.0003). The SUVmax of F-MISO shows a good correlation with that of FAZA at 0.86 (0.66-0.94). Immunohistochemical results are not correlated to hypoxia PET regardless of the staining. The two tracers show a good correlation with hypoxia, with FMISO being superior to FAZA. FMISO, therefore, remains the reference tracer for defining hypoxic volumes.
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Computed tomography (CT) has revolutionized external radiotherapy by making it possible to visualize and segment the tumors and the organs at risk in a three-dimensional way. However, if CT is a now a standard, it presents some limitations, notably concerning tumor characterization and delineation. Its association with functional and anatomical images, that are positron emission tomography (PET) and magnetic resonance imaging (MRI), surpasses its limits. This association can be in the form of a trimodality PET/CT/MRI. The objective of this mini-review is to describe the process of performing this PET/CT/MRI trimodality for radiotherapy and its potential clinical applications. Trimodality can be performed in two ways, either a PET/MRI fused to a planning CT (possibly with a pseudo-CT generated from the MRI for the planning), or a PET/CT fused to an MRI and then registered to a planning CT (possibly the CT of PET/CT if calibrated for radiotherapy). These examinations should be performed in the treatment position, and in the second case, a patient transfer system can be used between the PET/CT and MRI to limit movement. If trimodality requires adapted equipment, notably compatible MRI equipment with high-performance dedicated coils, it allows the advantages of the three techniques to be combined with a synergistic effect while limiting their disadvantages when carried out separately. Trimodality is already possible in clinical routine and can have a high clinical impact and good inter-observer agreement, notably for head and neck cancers, brain tumor, prostate cancer, cervical cancer.
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PURPOSE: To determine the impact of the Bayesian penalized likelihood (BPL) reconstruction algorithm in comparison to OSEM on hypoxia PET/CT images of NSCLC using 18F-MIZO and 18F-FAZA. MATERIALS AND METHODS: Images of low-contrasted (SBR = 3) micro-spheres of Jaszczak phantom were acquired. Twenty patients with lung neoplasia were included. Each patient benefitted from 18F-MISO and/or 18F-FAZA PET/CT exams, reconstructed with OSEM and BPL. Lesion was considered as hypoxic if the lesion SUVmax > 1.4. A blind evaluation of lesion detectability and image quality was performed on a set of 78 randomized BPL and OSEM images by 10 nuclear physicians. SUVmax, SUVmean, and hypoxic volumes using 3 thresholding approaches were measured and compared for each reconstruction. RESULTS: The phantom and patient datasets showed a significant increase of quantitative parameters using BPL compared to OSEM but had no impact on detectability. The optimal beta parameter determined by the phantom analysis was ß350. Regarding patient data, there was no clear trend of image quality improvement using BPL. There was no correlation between SUVmax increase with BPL and either SUV or hypoxic volume from the initial OSEM reconstruction. Hypoxic volume obtained by a SUV > 1.4 thresholding was not impacted by the BPL reconstruction parameter. CONCLUSION: BPL allows a significant increase in quantitative parameters and contrast without significantly improving the lesion detectability or image quality. The variation in hypoxic volume by BPL depends on the method used but SUV > 1.4 thresholding seems to be the more robust method, not impacted by the reconstruction method (BPL or OSEM). TRIAL REGISTRATION: ClinicalTrials.gov, NCT02490696. Registered 1 June 2015.
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INTRODUCTION: The purpose of our present study was to assess the prognostic impact of FDG PET-CT after induction chemotherapy for patients with inoperable non-small-cell lung cancer (NSCLC). MATERIAL AND METHODS: This retrospective study included 50 patients with inoperable stage II/III NSCLC from January 2012 to July 2015. They were treated for curative intent with induction chemotherapy, followed by concomitant chemoradiation therapy or sequential radiation therapy. FDG PET-CT scans were acquired at initial staging (PET1) and after the last cycle of induction therapy (PET2). Five parameters were evaluated on both scans: SUVmax, SUVpeak, SUVmean, TLG, MTV, and their respective deltas. The prognostic value of each parameter for overall survival (OS) and progression-free survival (PFS) was evaluated with Cox proportional-hazards regression models. RESULTS: Median follow-up was 19 months. PET1 parameters, clinical and histopathological data were not predictive of the outcome. TLG2 and ΔTLG were prognostic factors for OS. TLG2 was the only prognostic factor for PFS. For OS, log-rank test showed that there was a better prognosis for patients with TLG2< 69g (HR = 7.1, 95%CI 2.8-18, p = 0.002) and for patients with ΔTLG< -81% after induction therapy (HR = 3.8, 95%CI 1.5-9.6, p = 0.02). After 2 years, the survival rate was 89% for the patients with low TLG2 vs 52% for the others. We also evaluated a composite parameter considering both MTV2 and ΔSUVmax. Patients with MTV2> 23cc and ΔSUVmax> -55% had significantly shorter OS than the other patients (HR = 5.7, 95%CI 2.1-15.4, p< 0.01). CONCLUSION: Post-induction FDG PET might be an added value to assess the patients' prognosis in inoperable stage II/III NSCLC. TLG, ΔTLG as well as the association of MTV and ΔSUVmax seemed to be valuable parameters, more accurate than clinical, pathological or pretherapeutic imaging data.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/diagnóstico por imagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Feminino , Fluordesoxiglucose F18/administração & dosagem , Raios gama/uso terapêutico , Humanos , Quimioterapia de Indução/métodos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Estadiamento de Neoplasias , Pemetrexede/uso terapêutico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Compostos Radiofarmacêuticos/administração & dosagem , Indução de Remissão , Estudos Retrospectivos , Taxoides/uso terapêutico , Carga Tumoral/efeitos dos fármacos , Vinorelbina/uso terapêutico , GencitabinaRESUMO
BACKGROUND: In FDG-PET, SUV images are hampered by large potential biases. Our aim was to develop an alternative method (ParaPET) to generate 3D kinetic parametric FDG-PET images easy to perform in clinical oncology. METHODS: The key points of our method are the use of a new error model of PET measurement extracted from a late dynamic PET acquisition of 15 min, centered over the lesion and an image-derived input function (IDIF). The 15-min acquisition is reconstructed to obtain five images of FDG mean activity concentration and images of its variance to model errors of PET measurement. Our approach is carried out on each voxel to derive 3D kinetic parameter images. ParaPET was evaluated and compared to Patlak analysis as a reference. Hunter and Barbolosi methods (Barbolosi-Bl: with blood samples or Barbolosi-Im: with IDIF) were also investigated and compared to Patlak. Our evaluation was carried on Ki index, the net influx rate and its maximum value in the lesion (Ki,max). RESULTS: This parameter was obtained from 41 non-small cell lung cancer lesions associated with 4 to 5 blood samples per patient, required for the Patlak analysis. Compare to Patlak, the median relative difference and associated range (median; [min;max]) in Ki,max estimates were not statistically significant (Wilcoxon test) for ParaPET (- 3.0%; [- 31.9%; 47.3%]; p = 0.08) but statistically significant for Barbolosi-Bl (- 8.0%; [- 30.8%; 53.7%]; p = 0.001), Barbolosi-Im (- 7.9%; [- 38.4%; 30.6%]; p = 0.007) or Hunter (32.8%; [- 14.6%; 132.2%]; p < 10- 5). In the Bland-Altman plots, the ratios between the four methods and Patlak are not dependent of the Ki magnitude, except for Hunter. The 95% limits of agreement are comparable for ParaPET (34.7%), Barbolosi-Bl (30.1%) and Barbolosi-Im (30.8%), lower to Hunter (81.1%). In the 25 lesions imaged before and during the radio-chemotherapy, the decrease in the FDG uptake (ΔSUVmax or ΔKi,max) is statistically more important (p < 0.02, Wilcoxon one-tailed test) when estimated from the Ki images than from the SUV images (additional median variation of - 2.3% [- 52.6%; + 19.1%] for ΔKi,max compared to ΔSUVmax). CONCLUSION: None of the four methodologies is yet ready to replace the Patlak approach, and further improvements are still required. Nevertheless, ParaPET remains a promising approach, offering a non-invasive alternative to methods based on multiple blood samples and only requiring a late PET acquisition. It allows deriving Ki values, highly correlated and presenting the lowest relative bias with Patlak estimates, in comparison to the other methods we evaluated. Moreover, ParaPET gives access to quantitative information at the pixel level, which needs to be evaluated in the perspective of radiomic and tumour response. TRIAL REGISTRATION: NCT 02821936 ; May 2016.
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PURPOSE: In oncology, texture features extracted from positron emission tomography with 18-fluorodeoxyglucose images (FDG-PET) are of increasing interest for predictive and prognostic studies, leading to several tens of features per tumor. To select the best features, the use of a random forest (RF) classifier was investigated. METHODS: Sixty-five patients with an esophageal cancer treated with a combined chemo-radiation therapy were retrospectively included. All patients underwent a pretreatment whole-body FDG-PET. The patients were followed for 3 years after the end of the treatment. The response assessment was performed 1 month after the end of the therapy. Patients were classified as complete responders and non-complete responders. Sixty-one features were extracted from medical records and PET images. First, Spearman's analysis was performed to eliminate correlated features. Then, the best predictive and prognostic subsets of features were selected using a RF algorithm. These results were compared to those obtained by a Mann-Whitney U test (predictive study) and a univariate Kaplan-Meier analysis (prognostic study). RESULTS: Among the 61 initial features, 28 were not correlated. From these 28 features, the best subset of complementary features found using the RF classifier to predict response was composed of 2 features: metabolic tumor volume (MTV) and homogeneity from the co-occurrence matrix. The corresponding predictive value (AUC = 0.836 ± 0.105, Se = 82 ± 9%, Sp = 91 ± 12%) was higher than the best predictive results found using the Mann-Whitney test: busyness from the gray level difference matrix (P < 0.0001, AUC = 0.810, Se = 66%, Sp = 88%). The best prognostic subset found using RF was composed of 3 features: MTV and 2 clinical features (WHO status and nutritional risk index) (AUC = 0.822 ± 0.059, Se = 79 ± 9%, Sp = 95 ± 6%), while no feature was significantly prognostic according to the Kaplan-Meier analysis. CONCLUSIONS: The RF classifier can improve predictive and prognostic values compared to the Mann-Whitney U test and the univariate Kaplan-Meier survival analysis when applied to several tens of features in a limited patient database.
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Neoplasias Esofágicas/diagnóstico por imagem , Fluordesoxiglucose F18/química , Tomografia por Emissão de Pósitrons , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Área Sob a Curva , Quimiorradioterapia , Intervalo Livre de Doença , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Curva ROC , Compostos Radiofarmacêuticos/química , Estudos Retrospectivos , Resultado do TratamentoRESUMO
PURPOSE: Various segmentation methods for 18F-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography/computed tomography (PET/CT) images were correlated with pathological volume in breast cancer patients as a model of small mobile tumours. METHODS: Thirty women with T2-T3/M0 breast invasive ductal carcinoma (IDC) were included prospectively. A FDG-PET/CT was acquired 4 ± 3d before surgery in prone and supine positions, with/without respiratory gating. The segmentation methods were as follows: manual (Vm), relative (Vt%) and adaptive (Va) standard uptake value (SUV) threshold and semi-automatic on CT (Vct). Pathological volumes (Vpath) were measured for 26 lesions. RESULTS: The mean (±SD) Vpath was 4.1 ± 2.9 mL, and the lesion displacements were 3.9 ± 2.8 mm (median value: 3 mm). The delineated VOIs did not vary with the acquisition position nor with respiration, regardless of the segmentation method. The Vm, Va, Vct and Vt% methods, except Vt30%, were correlated with Vpath (0.5Assuntos
Neoplasias da Mama/diagnóstico
, Carcinoma Ductal de Mama/diagnóstico
, Fluordesoxiglucose F18
, Tomografia por Emissão de Pósitrons/métodos
, Compostos Radiofarmacêuticos
, Tomografia Computadorizada por Raios X/métodos
, Adulto
, Idoso
, Idoso de 80 Anos ou mais
, Mama/diagnóstico por imagem
, Mama/patologia
, Neoplasias da Mama/patologia
, Carcinoma Ductal de Mama/patologia
, Feminino
, Humanos
, Mamografia/métodos
, Pessoa de Meia-Idade
, Imagem Multimodal/métodos
, Estudos Prospectivos
, Carga Tumoral
RESUMO
OBJECTIVES: To test the influence of media injection in PET/CT on the functional or gross tumour volume measurement. PATIENTS AND METHODS: Thirty-three patients (56 ± 19 years) with non-Hodgkin's lymphoma (n=22) or Hodgkin's disease (n=11) were prospectively studied at staging. PET/CTs were performed 60 min after injection of FDG. Iopamiron 300 (Iopamidol, 1.5cc/kg) was injected immediately after, followed 50s later by a second craniocaudal CT (CT+). PET images were successively reconstructed using the unenhanced CT (PET-) and the CT+ (PET+) for attenuation correction using iterative reconstruction (4 iterations, 8 subsets, 5mm post-filtering). The SUVmax, SUVmean, SUVpeak and functional tumoural volume were measured in tumoural lymphadenopathies or malignant tissues (n=56 VOIs) using 5 3D-thresholding methods on PET- and PET+ images: absolute SUV value of 2.5; 40% of SUVmax, and 3 adaptative thresholding methods (Vauclin, Black and Schaefer methods). RESULTS: The SUVmean and the volume measurement were significantly different (p<0.001) for the five segmentation methods for PET- (p<0.001) and PET+ (p<0.001). The SUVmax, SUVmean and SUVpeak increased significantly in PET+ compared to PET- (2-5%). The SUVpeak was not significantly different for the five segmentation methods. The functional volume measurements were significantly different between PET- and PET+ only for the 2.5 segmentation method (+3%; p=0.001), but not for the 40%, Vauclin, Black and Schaefer methods. CONCLUSION: The functional volume could be measured in PET/CT when CT was performed with enhanced media. Caution should be taken when using the volume delineation method. Volume delineation methods using absolute threshold may artefactually increase the functional volume when enhanced CT is used for attenuation correction. The delineation volume using the relative or adaptative method should be preferred when contrast media are used for PET/CT.