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.
BackgroundConcomitant chemo-radiotherapy is the reference treatment for non-resectable locally-advanced Non-Small Cell Lung Cancer (NSCLC). Increasing radiotherapy total dose in the whole tumour volume has been shown to be deleterious. Functional imaging with positron emission tomography (PET/CT) offers the potential to identify smaller and biologically meaningful target volumes that could be irradiated with larger doses without compromising Organs At Risk (OAR) tolerance. This study investigated four scenarios, based on 18FDG and 18F-miso PET/CT, to delineate the target volumes and derive radiotherapy plans delivering up to 74Gy.MethodTwenty-one NSCLC patients, selected from a prospective phase II trial, had 18FDG- and 18F-miso PET/CT before the start of radiotherapy and 18FDG PET/CT during the radiotherapy (42Gy). The plans were based planned on a standard plan delivering 66 Gy (plan 1) and on three different boost strategies to deliver 74Gy total dose in pre-treatment 18FDG hotspot (70% of SUVmax) (plan 2), pre-treatment 18F-miso target (SUVmax > 1.4) (plan 3) and per-treatment 18FDG residual (40% of SUVmax). (plan 4).ResultsThe mean target volumes were 4.8 cc (± 1.1) for 18FDG hotspot, 38.9 cc (± 14.5) for 18F-miso and 36.0 cc (± 10.1) for per-treatment 18FDG. In standard plan (66 Gy), the mean dose covering 95% of the PTV (D95%) were 66.5 (± 0.33), 66.1 (± 0.32) and 66.1 (± 0.32) Gy for 18FDG hotspot, 18F-miso and per-treatment 18FDG. In scenario 2, the mean D95% was 72.5 (± 0.25) Gy in 18FDG hotspot versus 67.9 (± 0.49) and 67.9 Gy (± 0.52) in 18F-miso and per-treatment 18FDG, respectively. In scenario 3, the mean D95% was 72.2 (± 0.27) Gy to 18F-miso versus 70.4 (± 0.74) and 69.5Gy (± 0.74) for 18FDG hotspot and per-treatment 18FDG, respectively. In scenario 4, the mean D95% was 73.1 (± 0.3) Gy to 18FDG per-treatment versus 71.9 (± 0.61) and 69.8 (± 0.61) Gy for 18FDG hotspot and 18F-miso, respectively. The dose/volume constraints to OARs were matched in all scenarios.ConclusionEscalated doses can be selectively planned in NSCLC target volumes delineated on 18FDG and 18F-miso PET/CT functional images. The most relevant strategy should be investigated in clinical trials.Trial registration(RTEP5, NCT01576796, registered 15 june 2012)
IntroductionThe 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 methodsThis 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.ResultsMedian 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).ConclusionPost-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.
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 β350. 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
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.
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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