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.

Concomitant 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. Twenty-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). The 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. Escalated 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. (RTEP5, NCT01576796 , registered 15 june 2012)

Background: PET/CT image quality is directly influenced by the F-18-FDG injected activity. The higher the injected activity, the less noise in the reconstructed images but the more radioactive staff exposition. A new FDA cleared software has been introduced to obtain clinical PET images, acquired at 25% of the count statistics considering US practices. Our aim is to determine the limits of a deep learning based denoising algorithm (SubtlePET) applied to statistically reduced PET raw data from 3 different last generation PET scanners in comparison to the regular acquisition in phantom and patients, considering the European guidelines for radiotracer injection activities. Images of low and high contrasted (SBR = 2 and 5) spheres of the IEC phantom and high contrast (SBR = 5) of micro-spheres of Jaszczak phantom were acquired on 3 different PET devices. 110 patients with different pathologies were included. The data was acquired in list-mode and retrospectively reconstructed with the regular acquisition count statistic (PET100), 50% reduction in counts (PET50) and 66% reduction in counts (PET33). These count reduced images were post-processed with SubtlePET to obtain PET50 + SP and PET33 + SP images. Patient image quality was scored by 2 senior nuclear physicians. Peak-signal-to-Noise and Structural similarity metrics were computed to compare the low count images to regular acquisition (PET100). Results: SubtlePET reliably denoised the images and maintained the SUV_max values in PET50 + SP. SubtlePET enhanced images (PET33 + SP) had slightly increased noise compared to PET100 and could lead to a potential loss of information in terms of lesion detectability. Regarding the patient datasets, the PET100 and PET50 + SP were qualitatively comparable. The SubtlePET algorithm was able to correctly recover the SUV_max values of the lesions and maintain a noise level equivalent to full-time images. Conclusion: Based on our results, SubtlePET is adapted in clinical practice for half-time or half-dose acquisitions based on European recommended injected dose of 3 MBq/kg without diagnostic confidence loss.

To propose an easily applicable segmentation method (perPET-RT) for delineation of tumour volume during radiotherapy on interim fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in patients with non-small cell lung cancer (NSCLC). Sixty-seven patients (51 primary tumours, 60 lymph nodes), from 4 prospective studies, underwent an FDG PET/CT scan during the fifth week of radiation therapy, using different generations of PET/CT. Per-therapeutic PET/CT scans were delineated in consensus by two experienced physicians leading to the gold standard threshold to be applied. The mathematical expression of Thopt, the optimal threshold to be applied as a function of the maximum standard uptake value (SUVmax), was determined. The performance of this method (perPET-RT) was assessed by computing the DICE similarity coefficient (DSC) and was compared with 8 fixed threshold values and 3 adaptive thresholding methods. Thopt verified the following expression: Thopt = A.ln(1/SUVmax) + B where A and B were 2 constants. A and B were independent from the generation of PET/CT, but depended on the type of lesions (primary lung tumours vs. lymph nodes). PerPET-RT showed good to very good agreement in comparison to the gold standard. The mean and standard deviation of DSC value was 0.81 ± 0.13 for lung lesions and 0.78 ± 0.15 for lymph nodes. PerPET-RT showed a significant better agreement than the other segmentation methods (p < 0.001), except for one of the adaptive thresholding method ADT (p = 0.11). On the database used, perPET-RT has proven its reliability and accuracy for tumour delineation on per-therapeutic FDG PET/CT using only SUVmax measurement. This method may be used to delineate tumour volume for dose-escalation planning. NCT01261598 , NCT01261585 , NCT01576796 .

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 SUV_max > 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. SUV_max, SUV_mean, 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 SUV_max 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

The objective of this study is to investigate the feasibility and the additional interest of a parametric imaging (PI) method to monitor the early tumour metabolic response in a prospective series of oesophageal cancer patients who underwent positron emission tomography with fluoro-2-deoxy-d-glucose (FDG-PET/CT) before and during curative-intent chemo-radiotherapy. Fifty-seven patients with squamous cell carcinoma (SCC) of the oesophagus prospectively underwent FDG-PET/CT before chemo-radiotherapy (CRT) (PET₁) and at 21 ± 3 days after the beginning of CRT (PET₂). The outcome was assessed at 3 months and 1 year after the completion of CRT (clinical examination, CT scan or FDG-PET/CT, biopsy). For each patient, PET₁ and PET₂ were registered using CT images. The 2 PET image sets were subtracted, so the voxels with significant changes in FDG uptake were identified. A model-based analysis of this graph was used to identify the tumour voxels in which significant changes occurred between the two scans and yielded indices characterising these changes (green and red clusters). Quantitative parameters were compared with clinical outcome at 3 months and at 1 year. The baseline tumour FDG uptake decreased significantly at PET₂ (p < 0.0001). The tumour volume significantly decreased between PET₁ and PET₂ (p < 0.02). The initial functional volume of the lesion (TV₁) was significantly lower (p < 0.02) in patients in clinical response (CR) at 3 months and 1 year. The volume of the lesion during the treatment (TV₂) was significantly lower in patients identified as in CR at 3 months (p < 0.03), but did not predict the outcome at 1 year. Multivariate analyses of outcome at 3 months showed that the risk of failure/death increased with younger age (p = 0.001), larger metabolic volume on PET₁ (p = 0.009) and larger volume with decreased FDG uptake (p = 0.047). As for outcome at 1 year, the risk of failure/death increased with younger age (p = 0.006), nodal involvement (p = 0.08) and larger volumes with increased uptake (p = 0.03). A parametric method to assess tumour response on serial FDG-PET performed during chemo-radiotherapy was evaluated. Early metabolic changes, i.e. variations in FDG uptake, provided additional prognostic information in multivariate analyses ClinicalTrials.gov NCT 00934505. Current Controlled Trials ISRCTN7824458