Mechanically-Assisted and Non-Invasive Ventilation can improve the motion management strategies while treating thoracic or upper abdominal tumours with protontherapy

Objectives: Protontherapy of mobile tumours faces many uncertainties given their breathing-related motion, but also the proton range variations within the crossed tissues and the interplay effect that can unpredictively distort the dose distribution. Mechanically-assisted non-invasive ventilation (MANIV) could stabilize breathing with the volume-controlled (VC) mode, reduce amplitude with the shallow-controlled mode (SH) or prolong breath-hold with the slow-controlled mode (SL). Patient’s tolerance and tumour motion reproducibility were evaluated in this trial. Material and methods: In lung, liver and breast cancer patients, the tumour motion was assessed with MANIV and compared to spontaneous breathing (SP)(Figure1). All the patients underwent 2 dynamic MRI sessions with each breathing mode. Tolerance was assessed through oxymetric analyses and questionnaires. The tumour/nipple motion was tracked and analysed within each MRI and between MRI (intra- and inter-session reproducibility). Results: Twenty patients (49-83 years old) were included (Table 1). They all tolerated MANIV very well. The breath rate (BR) was always more stable in VC/SH than in SP. With SH, the motion amplitude was reduced of 0.6mm to 9mm proportionally to the BR increase (1.5 to 3.4-fold increase). With SL, the breath-holds were as stable as in SP in terms of range within a same plateau (0.9mm) or position between plateaus (0.2mm). Breath-holds in SL lasted on average 16,7sec. Conclusion: MANIV and its different ventilation modes offers exciting perspectives for motion management in protontherapy. MANIV may thus be proposed in clinical practice for different dedicated applications (reduced margins with SH, breath-hold with SL, gating with VC or SL)

Réduction des variations respiro-induites pendant et entre les fractions : le potentiel de la ventilation mécanique orientée vers les stratégies de mitigation du mouvement pour l’irradiation des tumeurs thoraciques ou abdominales -

Introduction et but de l’étude: La gestion de la variabilité intra- et inter-fraction respiro-induite des tumeurs thoraciques ou abdominales reste sub-optimale malgré les stratégies de mitigation du mouvement respiratoire. Par cette étude, nous voulons démontrer l’avantage de la ventilation mécanique et non-invasive (MANIV) en radiothérapie, et son innocuité pour les patients. Matériel et méthode : Une première cohorte A incluait des patients avec des tumeurs pulmonaires ou hépatiques. Ces patients, non-anesthésiés, étaient ventilés avec le mode volume-contrôlé VC (impose un volume courant (Vt) et une fréquence respiratoire (FR)), et le mode Shallow-contrôlé SH (vise à réduire l’amplitude du mouvement en accélérant la FR et diminuant proportionnellement le Vt). La cohorte B incluait des patientes adressés pour irradiation du sein gauche. Elles étaient ventilées en mode Slow-contrôlé SL, qui produisait des inspirations bloquées par un jeu de pression. Deux séances de 6 minutes en IRM évaluaient en intra- et inter-fraction le mouvement interne de la tumeur/du sein. Résultats et statistiques (valeurs médianes): Vingt-deux patients ont été inclus dans cette étude (49-83 ans). Dans la cohorte A, comparativement à la respiration libre, la variation de la FR était diminuée de 35% en VC et 45% en SH (p<0,001). En passant de VC à SH, la FR était doublée et l’amplitude réduite de 38,2%/6,1mm (p≤0,001). Dans la cohorte B, les plateaux inspiratoires duraient 16,7 sec et étaient aussi stables qu’en spontané (écart de 0,7mm entre le début et la fin des plateaux en spontané, contre 0,8mm en SL, p=0,98), tout comme les positions entre plateaux (différence de 7,2 mm en spontané contre 7,3mm en SL, p=0,15). Conclusion : MANIV peut être proposée à un large éventail de patients et peut faciliter les différentes stratégies de mitigation du mouvement afin de réduire les marges, régulariser le mouvement ou faciliter les techniques de tracking ou gating

Non-invasive ventilation techniques to serve respiratory-related motion management strategies in radiotherapy

Radiotherapy of tumours a↵ected by breathing motion still entails geometrical accuracy issues. Breathing moves lung, upper abdominal, or breast tumours along a trajectory that must be considered for irradiation. Motion mitiga- tion strategies were therefore introduced, either including the tumour motion within a margin or synchronising the beam to the breathing. However, breath- ing changes continuously with the patient physiological condition, leading to unexpected changes in tumour motion amplitude and tumour mean position. These changes are not properly considered by the motion mitigation strategies and may induce target under-dosages or synchronisation errors between the tu- mour and beam motions, both harmful for the patient outcomes. To overcome these geometrical uncertainties, mechanically assisted and non-invasive ventila- tion techniques, which constrain and modulate breathing, may be the missing support to optimise the accuracy and eciency of the motion mitigation strate- gies. In this thesis, we investigated the safety and tolerance of such techniques and assessed their e↵ects on breathing and tumour motion.(MED - Sciences médicales) -- UCL, 202

Virtual reality animations, a new strategy to reduce patients’ anxiety induced by radiotherapy

PURPOSE OR OBJECTIVE : Patients facing medical and technological interventions such as radiotherapy, mechanically-assisted and non-invasive ventilation (MANIV), or MRI can experience a high level of anxiety and discomfort in addition of the stressful background linked to cancer. This can lead to negative impacts on their mental status but also have deleterious consequences during radiation treatments (difficulties in positioning, movements during irradiation, impaired breathing) and thus also impact the treatment efficacy. Virtual reality and hypnosis are stress management strategies that showed encouraging results in different medical fields. The efficacy on anxiety of a dedicated hypnotising Virtual Reality Animation (VRA) commercialised by Oncomfort® was evaluated in patients included in a trial assessing MANIV. This trial aimed to demonstrate the safety and the efficacy of MANIV to stabilize and modulate the breathing pattern without any sedation. Patients were therefore connected to a mechanical ventilator and asked to give up control on their breathing. They could thus experience anxiety. [...

Added value of mechanical ventilation in the treatment of moving tumors with photon and proton therapies

Breathing-related motion is a well-known and significant source of geometrical uncertainties in radiotherapy planning and delivery. For this reason, several respiratory-synchronized techniques have been proposed to mitigate the motion, such as 4D (robust) optimization, respiratory gating or tracking. However, all these techniques face the same issue: the motion model derived from the planning 4D-CT does not necessarily represent the actual motion at the time of treatment, because the depth and pattern of spontaneous breathing are known to vary markedly over time [...

Implications of the Organ-Specific Immune Environment for Immune Priming Effect of Radiotherapy in Metastatic Setting

With the development of immune checkpoint inhibitors (ICIs), the tumour immune microenvironment (TIME) has been increasingly considered to improve cancer management. The TIME of metastatic lesions is strongly influenced by the underlying immune contexture of the organ in which they are located. The metastatic location itself appears to be an important prognostic factor in predicting outcomes after ICI treatment in cancer patients. Patients with liver metastases are less likely to respond to ICIs than patients with metastases in other organs, likely due to variations in the metastatic TIME. Combining additional treatment modalities is an option to overcome this resistance. Radiotherapy (RT) and ICIs have been investigated together as an option to treat various metastatic cancers. RT can induce a local and systemic immune reaction, which can promote the patient’s response to ICIs. Here, we review the differential impact of the TIME according to metastatic location. We also explore how RT-induced TIME modifications could be modulated to improve outcomes of RT-ICI combinations

Continuous real time 3D motion reproduction using dynamic MRI and precomputed 4DCT deformation fields

Radiotherapy of mobile tumors requires specific imaging tools and models to reduce the impact of motion on the treatment. Online continuous nonionizing imaging has become possible with the recent development of magnetic resonance imaging devices combined with linear accelerators. This opens the way to new guided treatment methods based on the real‐time tracking of anatomical motion. In such devices, 2D fast MR‐images are well‐suited to capture and predict the real‐time motion of the tumor. To be used effectively in an adaptive radiotherapy, these MR images have to be combined with X‐ray images such as CT, which are necessary to compute the irradiation dose deposition. We therefore developed a method combining both image modalities to track the motion on MR images and reproduce the tracked motion on a sequence of 3DCT images in real‐time. It uses manually placed navigators to track organ interfaces in the image, making it possible to select anatomical object borders that are visible on both MRI and CT modalities and giving the operator precise control of the motion tracking quality. Precomputed deformation fields extracted from the 4DCT acquired in the planning phase are then used to deform existing 3DCT images to match the tracked object position, creating a new set of 3DCT images encompassing irregularities in the breathing pattern for the complete duration of the MRI acquisition. The final continuous reconstructed 4DCT image sequence reproduces the motion captured by the MRI sequence with high precision (difference below 2 mm)

Continuous real time 3D motion reproduction using dynamic MRI and precomputed 4DCT deformation fields

Radiotherapy of mobile tumors requires specific imaging tools and models to reduce the impact of motion on the treatment. Online continuous nonionizing imaging has become possible with the recent development of magnetic resonance imaging devices combined with linear accelerators. This opens the way to new guided treatment methods based on the real‐time tracking of anatomical motion. In such devices, 2D fast MR‐images are well‐suited to capture and predict the real‐time motion of the tumor. To be used effectively in an adaptive radiotherapy, these MR images have to be combined with X‐ray images such as CT, which are necessary to compute the irradiation dose deposition. We therefore developed a method combining both image modalities to track the motion on MR images and reproduce the tracked motion on a sequence of 3DCT images in real‐time. It uses manually placed navigators to track organ interfaces in the image, making it possible to select anatomical object borders that are visible on both MRI and CT modalities and giving the operator precise control of the motion tracking quality. Precomputed deformation fields extracted from the 4DCT acquired in the planning phase are then used to deform existing 3DCT images to match the tracked object position, creating a new set of 3DCT images encompassing irregularities in the breathing pattern for the complete duration of the MRI acquisition. The final continuous reconstructed 4DCT image sequence reproduces the motion captured by the MRI sequence with high precision (difference below 2 mm)

Mechanically-assisted and non-invasive ventilation for radiation therapy: A safe technique to regularize and modulate internal tumour motion

BACKGROUND AND PURPOSE: Current motion mitigation strategies, like margins, gating, and tracking, deal with geometrical uncertainties in the tumour position, induced by breathing during radiotherapy (RT). However, they often overlook motion variability in amplitude, respiratory rate, or baseline position, when breathing spontaneously. Consequently, this may negatively affect the delivered dose conformality in comparison to the plan. We previously demonstrated on volunteers that 3 different modes of mechanically-assisted and non-invasive ventilation (MANIV) may reduce variability in breathing motion. The volume-controlled mode (VC) constraints the amplitude and respiratory rate (RR) in physiologic condition. The shallow-controlled mode (SH), derived from VC, increases the RR and decreases amplitude. The slow-controlled mode (SL) induces repeated breath holds with constrained ventilation pressure. In this study, we compared these mechanical ventilation modes to spontaneous breathing or breath hold and assessed their tolerance and effects on internal tumour motion in patients receiving RT. MATERIAL AND METHODS: The VC and SH modes were evaluated in ten patients with lung or liver cancers (cohort A). The SL mode was evaluated in 12 left breast cancer patients (cohort B). After a training and simulation session, the patients underwent 2 MRI sessions to analyze the internal motion of breast and tumour. RESULTS: MANIV was well tolerated, without any adverse events or oxymetric changes, even in patients with respiratory comorbidities. In cohort A, when compared to spontaneous breathing (SP), VC reduced significantly inter-session variations of the tumour motion amplitude (p = 0.01), as well as intra- and inter-session variations of the RR (p < 0.05). As to SH, the RR increased, while its variations within and across sessions decreased when compared to SP (p < 0.001). SH reduced the median amplitude of the tumour motion by 6.1 mm or 38.2% (p ≤ 0.01) compared to VC. In cohort B, breast position stability over the end-inspiratory plateaus obtained spontaneously or with SL remained similar. Median duration of the plateaus in SL was 16.6 s. CONCLUSION: MANIV is a safe and well tolerated ventilation technique for patients receiving radiotherapy. MANIV could thus make current motion mitigation strategies less critical and more robust. Clinical implementation might be considered, provided the ventilation mode is carefully selected with respect to the treatment indication and patient individualities

Breathing modulation in patients treated for mobile tumours: moving forward to clinical integration

PURPOSE OR OBJECTIVE : We previously demonstrated that mechanically-assisted and non-invasive ventilation (MANIV) can be used safely without sedation on healthy volunteers. MANIV can be used to regularise the breathing pattern by constraining the breathing rate (BR) and the tidal volume (Volume-controlled ventilation mode – VC). Breathing modulation can also be achieved by the shallow-controlled mode (SH) which reduces the breathing amplitude proportionally to the BR increase while the Slow-controlled mode (SL) mimics repeated end-inspiratory breath-holds. To allow the clinical integration of MANIV in radiotherapy, patients’ tolerance and the intra- and inter-session reproducibility of the breathing-related tumour motion were thus evaluated. [...