Transport, health and climate change: Deciding on the optimal policy

Transport generates many externalities, some related to atmospheric pollution. In this paper, we focus on two: greenhouse gases, and local pollution. In the search for optimal transport policies, these two externalities have usually been analysed separately. Here, we study them jointly, in a sequential decision-making model. Our model allows for the irreversibility of the policies undertaken, as well as the possibility of a progressive reduction of uncertainties with the arrival of information. We find that when both sources of externalities are analysed jointly, structural measures enabling private transport requirements to be reduced are identified as being more advantageous economically than technological measures to reduce emissions of pollutants. We illustrate the usefulness of a joint analysis of externalities with two examples: tax measures on cars and housing policy.climate change; model of decision-making under uncertainty; irreversibilities; transport policy

Transport, health and global warming: Deciding on the optimal policy

International audienceTransport generates many externalities, some related to atmospheric pollution. In this paper, we focus on two: greenhouse gases, and local pollution. In the search for optimal transport policies, these two externalities have usually been analysed separately. Here, we study them jointly, in a sequential decision-making model. Our model allows for the irreversibility of the policies undertaken, as well as the possibility of a progressive reduction of uncertainties with the arrival of information. We find that when both sources of externalities are analysed jointly, structural measures enabling private transport requirements to be reduced are identified as being more advantageous economically than technological measures to reduce emissions of pollutants. We illustrate the usefulness of a joint analysis of externalities with two examples: tax measures on cars and housing policy

Transport, health and global warming: Deciding on the optimal policy

Transport generates many externalities, some related to atmospheric pollution. In this paper, we focus on two: greenhouse gases, and local pollution. In the search for optimal transport policies, these two externalities have usually been analysed separately. Here, we study them jointly, in a sequential decision-making model. Our model allows for the irreversibility of the policies undertaken, as well as the possibility of a progressive reduction of uncertainties with the arrival of information. We find that when both sources of externalities are analysed jointly, structural measures enabling private transport requirements to be reduced are identified as being more advantageous economically than technological measures to reduce emissions of pollutants. We illustrate the usefulness of a joint analysis of externalities with two examples: tax measures on cars and housing policy.

Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients : a cohort study

Background: Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. Methods: The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. Results: The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend Conclusions: Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.Peer reviewe

Marie Juliette Vergnaud-Bouvier

Vergnaud Claire, Vergnaud Anne, Vergnaud Laure. Marie Juliette Vergnaud-Bouvier. In: Diplômées, n°278-279, 2021. 100 ans de parcours. pp. 278-281

Dosimétrie pour les thérapies par radionucléides 177Lu et 90Y par imagerie et simulations Monte Carlo

In nuclear medicine, targeted radionuclide therapy (TRT) involves intravenous injection of a radiopharmaceutical that specifically binds to tumour cells through a selected vector based on the type of receptors overexpressed. This treatment has proven effective for neuroendocrine tumours (NETs) and metastatic castration-resistant prostate cancer. However, treatment plans are standardised despite studies showing variations in absorbed doses (energy absorbed per unit mass) among different patients’ organs at risk and tumours. To personalise these treatments, it is necessary to estimate absorbed doses and compare them with treatment toxicities and efficacy. During the radioactive decay of certain radioisotopes such as 177Lu, gamma photons are emitted and can be detected using a gamma camera. A SPECT acquisition is typically performed to determine the 3D biodistribution of the radiopharmaceutical at a given time point, which is necessary for estimating absorbed doses in the regions of interest. In this thesis, we focused on the quantitative and dosimetric aspects of 177Lu and 90Y therapies using acquired SPECT images. In TRT, dosimetry for 177Lu requires monitoring the biodistribution of the radiopharmaceutical over time, which involves multiple post-injection SPECT acquisitions. However, clinical constraints often limit the availability of desired acquisition times and numbers. Therefore, the primary objective of the first contribution was to provide a dosimetric workflow that can adapt to the available number of acquisitions for 177Lu-DOTATATE therapies in NETs. Several simplified dosimetry methods were proposed and evaluated against a reference method based on three post-injection acquisitions. Selective Internal Radiation Therapy (SIRT) is a local treatment for liver lesions where 90Y microspheres are injected into the intrahepatic artery to destroy the tumours. This treatment is simulated using an injection of 99mTc combined with albumin macroaggregates. A SPECT acquisition is then performed before being reconstructed to predict absorbed doses and adjust the activity to be injected. During the SPECT acquisition, respiratory motion can impact the acquisition but is not necessarily corrected during reconstruction. The second contribution assessed the dosimetric impact of correcting for respiratory motion in the reconstruction by comparing dose and activity estimates for injection. Finally, more recently, CZT gamma cameras have allowed for reduced acquisition times while maintaining image quality. However, they do not always enable the acquisition of high-energy photons (>200 keV) and therefore, the recommended energy peak for 177Lu dosimetry. In a third contribution, a feasibility study of quantification with 177Lu (energy peak at 113 keV) was conducted using phantoms, and optimal reconstruction parameters were provided. These parameters were then used in a preliminary dosimetric study on patients treated with 177Lu-PSMA.En médecine nucléaire, la radiothérapie interne vectorisée (RIV) consiste à injecter par intraveineuse un radiopharmaceutique qui va venir se fixer aux cellules tumorales grâce à un vecteur sélectionné selon le type de récepteurs sur-exprimés par ces dernières. Bien qu’efficace, les plans de traitement de ces thérapies sont standardisés alors que des études ont montrées que les doses absorbées (énergie absorbée par unité de masse) par les organes à risque et les tumeurs diffèrent d’un patient à un autre. Afin de pouvoir les personnaliser, il est donc nécessaire d’estimer les doses absorbées et de les corréler aux toxicités et à l’efficacité du traitement. Lors de la désintégration du 177Lu, des photons gamma sont émis et sont détectés à l’aide d’une gamma caméra. Une acquisition TEMP est réalisée afin de connaître la biodistribution 3D du radiopharmaceutique à un instant donné qui est nécessaire pour l’estimation des doses absorbées par les régions d’intérêt. Dans cette thèse, nous nous sommes intéressés aux aspects quantitatifs et dosimétriques des thérapies au 177Lu et à l’90Y à partir des images TEMP. En RIV, la dosimétrie au 177Lu requière un suivi de la biodistribution du radiopharmaceutique au cours du temps et donc, des acquisitions TEMP post-injection multiples. Cependant, les contraintes cliniques limitent les temps et le nombre d’acquisitions souhaitables. Dans la première contribution, un workflow dosimétrique s’adaptant au nombre d’acquisitions disponibles pour les thérapies au 177Lu-DOTATATE a été proposé comprenant des méthodes de dosimétrie simplifiées qui ont été évaluées par rapport à une méthode de référence (trois acquisitions). La radiothérapie interne sélective (RIS) est un traitement local des lésions hépatiques dans lequel des microsphères d’90Y sont injectées dans l’artère intrahépatique pour détruire les tumeurs. Ce traitement est simulé à l’aide d’une injection de 99mTc associé à des macroaggrégats d’albumine. Une acquisition TEMP est ensuite réalisée puis l’image est reconstruite afin de prédire les doses absorbées et d’adapter l’activité à injecter pour la thérapie. Pendant l’acquisition TEMP, les mouvements respiratoires peuvent impacter l’acquisition mais ne sont pas forcément corrigés au cours de la reconstruction. La seconde contribution a permis d’évaluer l’impact dosimétrique de la correction du mouvement respiratoire dans la reconstruction en comparant les estimations de doses et d’activité à injecter. Récemment, les gamma caméras CZT ont permis de réduire les durées d’acquisition tout en conservant la qualité de l’image. Cependant, elles ne permettent pas toujours d’acquérir les photons de hautes énergies (>200 keV). Dans une troisième contribution, une étude de faisabilité de la quantification au 177Lu (113 keV) a été réalisée sur fantômes et des paramètres de reconstruction optimaux ont été fournis. Ils ont ensuite été utilisés lors d’une étude dosimétrique préliminaire sur patients traités au 177Lu-PSMA

Transport, health and climate change: Deciding on the optimal policy

Transport generates many externalities, some related to atmospheric pollution. In this paper, we focus on two: greenhouse gases, and local pollution. In the search for optimal transport policies, these two externalities have usually been analysed separately. Here, we study them jointly, in a sequential decision-making model. Our model allows for the irreversibility of the policies undertaken, as well as the possibility of a progressive reduction of uncertainties with the arrival of information. We find that when both sources of externalities are analysed jointly, structural measures enabling private transport requirements to be reduced are identified as being more advantageous economically than technological measures to reduce emissions of pollutants. We illustrate the usefulness of a joint analysis of externalities with two examples: tax measures on cars and housing policy

Patient-specific dosimetric workflow with a reduced number of time-points for 177Lu treatments

International audienceAim/Introduction: Patients with unresectable neuroendocrine tumors can be treated by internal radiation therapy administrating 7.4 GBq of Lu177-labeled somatostatin analog. Image-based absorbed dose estimation to organs requires several time-points acquisitions but their number is limited by clinical and logistical constraints. The goal of this work was to propose an adaptive dosimetric workflow for estimating absorbed doses from a reduced number of acquisitionacquisitionMaterials and Methods: Thirteen patients with neuroendocrine tumors received four injections of 7.4 GBq of 177Lu-DOTATATE except one patient because of haematological toxicity. Three SPECT/CT acquisitions were performed after the first cycle at 1h, 24h and 96h or 144h and a single acquisition after three latter cycles at 24h for estimating absorbed doses by kidneys, liver and intrahepatic tumors, spleen and bone marrow. Monte Carlo simulations were used to estimate dose rates for each acquisition to take into account self- and cross- doses. These dose rates were then integrated at the organ level (ODR). Time dose rate curves (TDC) were fitted with a tri-exponential function to respect the patients' physiology. For cycles with less than three acquisitions, three methods were proposed and evaluated. If the acquisition at 24h of cycle 1 was missing, the ODR was approximated by the next first ODR at 24h scaled according to the injected activities at each cycle. When only one acquisition was available, two cases were distinguished. Absorbed doses were estimated from the TDC of a previous cycle for the samepatient scaled to the ODR available. Otherwise, TDC of other patients were scaled to the ODR and their integrals were averaged to obtain absorbed doses as proposed by Jackson and al. (1) with time activity curvesResults: Estimated errors when the ODR at 24h was replaced was inferior to 15.9% except for one patient. With only one acquisition, the lowest error was obtained for acquisitions at 96h or 144h with two methods: less than 11% for liver and spleen and less than 20% for kidneys. Thesemethods are being tested for bone marrow dose estimation. Absorbed doses estimated with this workflow were: 2⼟.50.9 Gy (left kidney), 2.7⼟1.2 Gy (right kidney), 2.8⼟1.7 Gy (liver) and 3.4⼟1.6 Gy (spleen) all cycles taken together. Conclusion: The proposed workflow allows the estimation of organ doses from a reduced number of acquisitions for patients treated with 177Lu. References: (1) Jackson and al. JNM 202

Patient-specific dosimetry adapted to variable number of SPECT/CT time-points per cycle for 177^{177}Lu-DOTATATE therapy

International audienceBackground: The number of SPECT/CT time-points is important for accurate patient dose estimation in peptide receptor radionuclide therapy. However, it may be limited by the patient's health and logistical reasons. Here, an image-based dosimetric workflow adapted to the number of SPECT/CT acquisitions available throughout the treatment cycles was proposed, taking into account patient-specific pharmacokinetics and usable in clinic for all organs at risk.Methods: Thirteen patients with neuroendocrine tumors were treated with four injections of 7.4 GBq of 177 Lu-DOTATATE. Three SPECT/CT images were acquired during the first cycle (1H, 24H and 96H or 144H post-injection) and a single acquisition (24H) for following cycles. Absorbed doses were estimated for kidneys (LK and RK), liver (L), spleen (S), and three surrogates of bone marrow (L2 to L4, L1 to L5 and T9 to L5) that were compared. 3D dose rate distributions were computed with Monte Carlo simulations. Voxel dose rates were averaged at the organ level. The obtained Time Dose-Rate Curves (TDRC) were fitted with a tri-exponential model and time-integrated. This method modeled patient-specific uptake and clearance phases observed at cycle 1. Obtained fitting parameters were reused for the following cycles, scaled to the measure organ dose rate at 24H. An alternative methodology was proposed when some acquisitions were missing based on population average TDRC (named STP-Inter). Seven other patients with three SPECT/CT acquisitions at cycles 1 and 4 were included to estimate the uncertainty of the proposed methods.Results: Absorbed doses (in Gy) per cycle available were: 3.1 ± 1.1 (LK), 3.4 ± 1.5 (RK), 4.5 ± 2.8 (L), 4.6 ± 1.8 (S), 0.3 ± 0.2 (bone marrow). There was a significant difference between bone marrow surrogates (L2 to L4 and L1 to L5, Wilcoxon's test: p value < 0.05), and while depicting very doses, all three surrogates were significantly different than dose in background (p value < 0.01). At cycle 1, if the acquisition at 24H is missing and approximated, medians of percentages of dose difference (PDD) compared to the initial tri-exponential function were inferior to 3.3% for all organs. For cycles with one acquisition, the median errors were smaller with a late time-point. For STP-Inter, medians of PDD were inferior to 7.7% for all volumes, but it was shown to depend on the homogeneity of TDRC