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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., (Copyright © 2020. Published by Elsevier Masson SAS.)

Multimodal imaging has become a standard for planning radiation therapy via magnetic resonance imaging (MRI) or positron emission tomography (PET) in many cancers. However, its use is now old, and its impact has not been much discussed in light of technological improvements in imaging and advances in radiotherapy. However, in 20 years, the exclusive functional imaging has been replaced by hybrid imaging (functional and anatomical) with successive improvements (flight time, detector modifications, digitisation, etc.) have enabled us to go from centimetric resolution to the current 3 to 4mm resolution. This article will specifically review PET technology, its latest advances and the potential impact on radiotherapy, particularly head and neck cancers., (Copyright © 2020. Published by Elsevier Masson SAS.)

Computed tomography (CT) in the treatment position is currently indispensable for planning radiation therapy. Other imaging modalities, such as magnetic resonance imaging (MRI) and positron emission-tomography (PET), can be used to improve the definition of the tumour and/or healthy tissue but also to provide functional data of the target volume. Accurate image registration is essential for treatment planning, so MRI and PET scans should be registered at the planning CT scan. Hybrid PET/MRI scans with a hard plane can be used but pose the problem of the absence of CT scans. Finally, techniques for moving the patient on a rigid air-cushioned table allow PET/CT/MRI scans to be performed in the treatment position while limiting the patient's movements exist. At the same time, the advent of MRI-linear accelerator systems allows to redefine image-guided radiotherapy and to propose treatments with daily recalculation of the dose. The place of PET during treatment remains more confidential and currently only in research and prototype status. The same development of imaging during radiotherapy is underway in proton therapy., (Copyright © 2020 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Background: 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 18 FDG and 18 F-miso PET/CT, to delineate the target volumes and derive radiotherapy plans delivering up to 74Gy., Method: Twenty-one NSCLC patients, selected from a prospective phase II trial, had 18 FDG- and 18 F-miso PET/CT before the start of radiotherapy and 18 FDG 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 18 FDG hotspot (70% of SUV max ) (plan 2), pre-treatment 18 F-miso target (SUV max  > 1.4) (plan 3) and per-treatment 18 FDG residual (40% of SUV max ). (plan 4)., Results: The mean target volumes were 4.8 cc (± 1.1) for 18 FDG hotspot, 38.9 cc (± 14.5) for 18 F-miso and 36.0 cc (± 10.1) for per-treatment 18 FDG. 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 18 FDG hotspot, 18 F-miso and per-treatment 18 FDG. In scenario 2, the mean D95% was 72.5 (± 0.25) Gy in 18 FDG hotspot versus 67.9 (± 0.49) and 67.9 Gy (± 0.52) in 18 F-miso and per-treatment 18 FDG, respectively. In scenario 3, the mean D95% was 72.2 (± 0.27) Gy to 18 F-miso versus 70.4 (± 0.74) and 69.5Gy (± 0.74) for 18 FDG hotspot and per-treatment 18 FDG, respectively. In scenario 4, the mean D95% was 73.1 (± 0.3) Gy to 18 FDG per-treatment versus 71.9 (± 0.61) and 69.8 (± 0.61) Gy for 18 FDG hotspot and 18 F-miso, respectively. The dose/volume constraints to OARs were matched in all scenarios., Conclusion: Escalated doses can be selectively planned in NSCLC target volumes delineated on 18 FDG and 18 F-miso PET/CT functional images. The most relevant strategy should be investigated in clinical trials., Trial Registration: (RTEP5, NCT01576796 , registered 15 june 2012).

Functional imaging with positron emission tomography (PET) is interesting to optimize radiotherapy planning, and probably to perform dose redistribution in many cancers. However, in 2015, fluorodeoxyglucose (FDG)-PET is validated only for therapy planning for lung cancer. The interest of dose painting, PET in non-lung cancers, the interest of other tracers (even PET hypoxia tracers), DW-MRI, and PET-MR for radiotherapy needs to be demonstrated in prospective multicentric phase III studies on large series of patients., (Copyright © 2015. Published by Elsevier SAS.)

Background: A planning study investigated whether reduced target volumes defined on FDG-PET/CT during radiotherapy allow total dose escalation without compromising normal tissue tolerance in patients with esophageal cancer., Material and Methods: Ten patients with esophageal squamous cell carcinoma (SCC), candidate to curative-intent concomitant chemo-radiotherapy (CRT), had FDG-PET/CT performed in treatment position, before and during (Day 21) radiotherapy (RT). Four planning scenarios were investigated: 1) 50 Gy total dose with target volumes defined on pre-RT FDG-PET/CT; 2) 50 Gy with boost target volume defined on FDG-PET/CT during RT; 3) 66 Gy with target volumes from pre-RT FDG-PET/CT; and 4) 66 Gy with boost target volume from during-RT FDG-PET/CT., Results: The median metabolic target volume decreased from 12.9 cm3 (minimum 3.7-maximum 44.8) to 5.0 cm3 (1.7-13.5) (p=0.01) between pre- and during-RCT FDG-PET/CT. The median PTV66 was smaller on during-RT than on baseline FDG-PET/CT [108 cm3 (62.5-194) vs. 156 cm3 (68.8-251), p=0.02]. When total dose was set to 50 Gy, planning on during-RT FDG-PET/CT was associated with a marginal reduction in normal tissues irradiation. When total dose was increased to 66 Gy, planning on during-RT PET yielded significantly lower doses to the spinal cord [Dmax=44.1Gy (40.8-44.9) vs. 44.7Gy (41.5-45.0), p=0.007] and reduced lung exposure [V20Gy=23.2% (17.3-27) vs. 26.8% (19.7-30.2), p=0.006]., Conclusion: This planning study suggests that adaptive RT based on target volume reduction assessed on FDG-PET/CT during treatment could facilitate dose escalation up to 66 Gy in patients with esophageal SCC.

Purpose: The high failure rates in the radiotherapy (RT) target volume suggest that patients with locally advanced oesophageal cancer (LAOC) would benefit from increased total RT doses. High 2-deoxy-2-[(18)F]fluoro-D-glucose (FDG) uptake (hotspot) on pre-RT FDG positron emission tomography (PET)/CT has been reported to identify intra-tumour sites at increased risk of relapse after RT in non-small cell lung cancer and in rectal cancer. Our aim was to confirm these observations in patients with LAOC and to determine the optimal maximum standardized uptake value (SUVmax) threshold to delineate smaller RT target volumes that would facilitate RT dose escalation without impaired tolerance., Methods: The study included 98 consecutive patients with LAOC treated by chemoradiotherapy (CRT). All patients underwent FDG PET/CT at initial staging and during systematic follow-up in a single institution. FDG PET/CT acquisitions were coregistered on the initial CT scan. Various subvolumes within the initial tumour (30, 40, 50, 60, 70, 80 and 90% SUVmax thresholds) and in the subsequent local recurrence (LR, 40 and 90% SUVmax thresholds) were pasted on the initial CT scan and compared[Dice, Jaccard, overlap fraction (OF), common volume/baseline volume, common volume/recurrent volume]., Results: Thirty-five patients had LR. The initial metabolic tumour volume was significantly higher in LR tumours than in the locally controlled tumours (mean 25.4 vs 14.2 cc; p = 0.002). The subvolumes delineated on initial PET/CT with a 30-60% SUVmax threshold were in good agreement with the recurrent volume at 40% SUVmax (OF = 0.60-0.80). The subvolumes delineated on initial PET/CT with a 30-60% SUVmax threshold were in good to excellent agreement with the core volume (90% SUVmax) of the relapse (common volume/recurrent volume and OF indices 0.61-0.89)., Conclusion: High FDG uptake on pretreatment PET/CT identifies tumour subvolumes that are at greater risk of recurrence after CRT in patients with LAOC. We propose a 60% SUVmax threshold to delineate high FDG uptake areas on initial PET/CT as reduced target volumes for RT dose escalation.

Unlabelled: The high rates of failure in the radiotherapy target volume suggest that patients with stage II or III non-small cell lung cancer (NSCLC) should receive an increased total dose of radiotherapy. Areas of high (18)F-FDG uptake on preradiotherapy (18)F-FDG PET/CT have been reported to identify intratumor subvolumes at high risk of relapse after radiotherapy. We wanted to confirm these observations on a cohort of patients included in 3 sequential prospective studies. Our aim was to assess an appropriate threshold (percentage of maximum standardized uptake value [SUVmax]) to delineate subvolumes on staging (18)F-FDG PET/CT scans assuming that a smaller target volume would facilitate isotoxic radiotherapy dose escalation., Methods: Thirty-nine patients with inoperable stage II or III NSCLC, treated with chemoradiation or with radiotherapy alone, were extracted from 3 prospective studies (ClinicalTrials.gov identifiers NCT01261585, NCT01261598, and RECF0645). All patients underwent (18)F-FDG PET/CT at initial staging, before radiotherapy, during radiotherapy, and during systematic follow-up in a single institution. All (18)F-FDG PET/CT acquisitions were coregistered on the initial scan. Various subvolumes in the initial acquisition (30%, 40%, 50%, 60%, 70%, 80%, and 90% SUVmax thresholds) and in the 3 subsequent acquisitions (40% and 90% SUVmax thresholds) were pasted on the initial scan and compared., Results: Seventeen patients had a local relapse. The SUVmax measured during radiotherapy was significantly higher in locally relapsed tumors than in locally controlled tumors (mean, 6.8 vs. 4.6; P = 0.02). The subvolumes delineated on initial PET/CT scans with 70%-90% SUVmax thresholds were in good agreement with the recurrent volume at a 40% SUVmax threshold (common volume/baseline volume, 0.60-0.80). The subvolumes delineated on initial PET/CT scans with 30%-60% SUVmax thresholds were in good to excellent agreement with the core volume of the relapse (90% SUVmax threshold) (common volume/recurrent volume and overlap fraction indices, 0.60-0.93). The agreement was moderate (>0.51) when a 70% SUVmax threshold was used to delineate on initial PET/CT scans., Conclusion: High (18)F-FDG uptake areas on pretreatment PET/CT scans identify tumor subvolumes at greater risk of relapse in patients with NSCLC treated by concomitant chemoradiation. We propose a 70% SUVmax threshold to delineate areas of high (18)F-FDG uptake on initial PET/CT scans as the target volumes for potential radiotherapy dose escalation., (© 2015 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

A segmentation algorithm based on the random walk (RW) method, called 3D-LARW, has been developed to delineate small tumors or tumors with a heterogeneous distribution of FDG on PET images. Based on the original algorithm of RW [1], we propose an improved approach using new parameters depending on the Euclidean distance between two adjacent voxels instead of a fixed one and integrating probability densities of labels into the system of linear equations used in the RW. These improvements were evaluated and compared with the original RW method, a thresholding with a fixed value (40% of the maximum in the lesion), an adaptive thresholding algorithm on uniform spheres filled with FDG and FLAB method, on simulated heterogeneous spheres and on clinical data (14 patients). On these three different data, 3D-LARW has shown better segmentation results than the original RW algorithm and the three other methods. As expected, these improvements are more pronounced for the segmentation of small or tumors having heterogeneous FDG uptake., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Purpose: To assess prospectively the prognostic value of FDG PET/CT during curative-intent radiotherapy (RT) with or without concomitant chemotherapy in patients with non-small-cell lung cancer (NSCLC)., Methods: Patients with histological proof of invasive localized NSCLC and evaluable tumour, and who were candidates for curative-intent radiochemotherapy (RCT) or RT were preincluded after providing written informed consent. Definitive inclusion was conditional upon significant FDG uptake before RT (PET₁). All included patients had a FDG PET/CT scan during RT (PET₂, mean dose 43 Gy) and were evaluated by FDG PET/CT at 3 months and 1 year after RT. The main endpoint was death (from whatever cause) or tumour progression at 1 year., Results: Of 77 patients preincluded, 52 were evaluable. Among the evaluable patients, 77% received RT with induction chemotherapy and 73% RT with concomitant chemotherapy. At 1 year, 40 patients (77 %) had died or had tumour progression. No statistically significant association was found between stage (IIIB vs. other), histology (squamous cell carcinoma vs. other), induction or concomitant chemotherapy, and death/tumour progression at 1 year. The SUVmax in the PET2 scan was the single variable predictive of death or tumour progression at 1 year (odds ratio 1.97, 95% CI 1.25 - 3.09, p = 0.003) in multivariate analysis. The area under the receiver operating characteristic curve was 0.85 (95% CI 0.73 - 0.94, p < 10(-4)). A SUVmax value of 5.3 in the PET₂ scan yielded a sensitivity of 70% and a specificity of 92% for predicting tumour progression or death at 1 year., Conclusion: This prospective multicentre study demonstrated the prognostic value in terms of disease-free survival of SUVmax assessed during the 5th week of curative-intent RT or RCT in NSCLC patients (NCT01261598; RTEP2 study).

Unlabelled: As the preparation phase of a multicenter clinical trial using (18)F-fluoro-2-deoxy-d-glucose ((18)F-FDG), (18)F-fluoromisonidazole ((18)F-FMISO), and 3'-deoxy-3'-(18)F-fluorothymidine ((18)F-FLT) in non-small cell lung cancer (NSCLC) patients, we investigated whether 18 nuclear medicine centers would score tracer uptake intensity similarly and define hypoxic and proliferative volumes for 1 patient and we compared different segmentation methods., Methods: Ten (18)F-FDG, ten (18)F-FMISO, and ten (18)F-FLT PET/CT examinations were performed before and during curative-intent radiotherapy in 5 patients with NSCLC. The gold standards for uptake intensity and volume delineation were defined by experts. The between-center agreement (18 nuclear medicine departments connected with a dedicated network, SFMN-net [French Society of Nuclear Medicine]) in the scoring of uptake intensity (5-level scale, then divided into 2 levels: 0, normal; 1, abnormal) was quantified by κ-coefficients (κ). The volumes defined by different physicians were compared by overlap and κ. The uptake areas were delineated with 22 different methods of segmentation, based on fixed or adaptive thresholds of standardized uptake value (SUV)., Results: For uptake intensity, the κ values between centers were, respectively, 0.59 for (18)F-FDG, 0.43 for (18)F-FMISO, and 0.44 for (18)F-FLT using the 5-level scale; the values were 0.81 for (18)F-FDG and 0.77 for both (18)F-FMISO and (18)F-FLT using the 2-level scale. The mean overlap and mean κ between observers were 0.13 and 0.19, respectively, for (18)F-FMISO and 0.2 and 0.3, respectively, for (18)F-FLT. The segmentation methods yielded significantly different volumes for (18)F-FMISO and (18)F-FLT (P < 0.001). In comparison with physicians, the best method found was 1.5 × maximum SUV (SUVmax) of the aorta for (18)F-FMISO and 1.3 × SUVmax of the muscle for (18)F-FLT. The methods using the SUV of 1.4 and the method using 1.5 × the SUVmax of the aorta could be used for (18)F-FMISO and (18)F-FLT. Moreover, for (18)F-FLT, 2 other methods (adaptive threshold based on 1.5 or 1.6 × muscle SUVmax) could be used., Conclusion: The reproducibility of the visual analyses of (18)F-FMISO and (18)F-FLT PET/CT images was demonstrated using a 2-level scale across 18 centers, but the interobserver agreement was low for the (18)F-FMISO and (18)F-FLT volume measurements. Our data support the use of a fixed threshold (1.4) or an adaptive threshold using the aorta background to delineate the volume of increased (18)F-FMISO or (18)F-FLT uptake. With respect to the low tumor-on-background ratio of these tracers, we suggest the use of a fixed threshold (1.4).

The recent advances in medical imaging have profoundly altered the radiotherapy of non-small cell lung cancers (NSCLC). A meta-analysis has confirmed the superiority of FDG PET-CT over CT for initial staging. FDG PET-CT improves the reproducibility of target volume delineation, especially close to the mediastinum or in the presence of atelectasia. Although not formally validated by a randomized trial, the reduction of the mediastinal target volume, by restricting the irradiation to FDG-avid nodes, is widely accepted. The optimal method of delineation still remains to be defined. The role of FDG PET-CT in monitoring tumor response during radiotherapy is under investigation, potentially opening the way to adapting the treatment modalities to tumor radiation sensitivity. Other tracers, such as F-miso (hypoxia), are also under clinical investigation. To avoid excessive delays, the integration of PET-CT in routine practice requires quick access to the imaging equipment, technical support (fusion and image processing) and multidisciplinary delineation of target volumes., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)