One-year mortality and causes of death after stereotactic radiation therapy for refractory ventricular arrhythmias: A systematic review and pooled analysis.

Patients treated with cardiac stereotactic body radiation therapy (radioablation) for refractory ventricular arrhythmias are patients with advanced structural heart disease and significant comorbidities. However, data regarding 1-year mortality after the procedure are scarce. This systematic review and pooled analysis aimed at determining 1-year mortality after cardiac radioablation for refractory ventricular arrhythmias and investigating leading causes of death in this population. MEDLINE/EMBASE databases were searched up to January 2023 for studies including patients undergoing cardiac radioablation for the treatment of refractory ventricular arrhythmias. Quality of included trials was assessed using the NIH Tool for Case Series Studies (PROSPERO CRD42022379713). A total of 1,151 references were retrieved and evaluated for relevance. Data were extracted from 16 studies, with a total of 157 patients undergoing cardiac radioablation for refractory ventricular arrhythmias. Pooled 1-year mortality was 32 % (95 %CI: 23-41), with almost half of the deaths occurring within three months after treatment. Among the 157 patients, 46 died within the year following cardiac radioablation. Worsening heart failure appeared to be the leading cause of death (52 %), although non-cardiac mortality remained substantial (41 %) in this population. Age≥70yo was associated with a significantly higher 12-month all-cause mortality (p<0.022). Neither target volume size nor radiotherapy device appeared to be associated with 1-year mortality (p = 0.465 and p = 0.199, respectively). About one-third of patients undergoing cardiac stereotactic body radiation therapy for refractory ventricular arrhythmias die within the first year after the procedure. Worsening heart failure appears to be the leading cause of death in this population.

Multimodal fusion workflow for target delineation in cardiac radioablation of ventricular tachycardia.

BACKGROUND: Cardiac radioablation (CR) is an innovative treatment to ablate cardiac arrythmia sources by radiation therapy. CR target delineation is a challenging task requiring the exploitation of highly different imaging modalities, including cardiac electro-anatomical mapping (EAM). PURPOSE: In this work, a data integration process is proposed to alleviate the tediousness of CR target delineation by generating a fused representation of the heart, including all the information of interest resulting from the analysis and registration of electro-anatomical data, PET scan and planning computed tomography (CT) scan. The proposed process was evaluated by cardiologists during delineation trials. METHODS: The data processing pipeline was composed of the following steps. The cardiac structures of interest were segmented from cardiac CT scans using a deep learning method. The EAM data was registered to the cardiac CT scan using a point cloud based registration method. The PET scan was registered using rigid image registration. The EAM and PET information, as well as the myocardium thickness, were projected on the surface of the 3D mesh of the left ventricle. The target was identified by delineating a path on this surface that was further projected to the thickness of the myocardium to create the target volume. This process was evaluated by comparison with a standard slice-by-slice delineation with mental EAM registration. Four cardiologists delineated targets for three patients using both methods. The variability of target volumes, and the ease of use of the proposed method, were evaluated. RESULTS: All cardiologists reported being more confident and efficient using the proposed method. The inter-clinician variability in delineated target volume was systematically lower with the proposed method (average dice score of 0.62 vs. 0.32 with a classical method). Delineation times were also improved. CONCLUSIONS: A data integration process was proposed and evaluated to fuse images of interest for CR target delineation. It effectively reduces the tediousness of CR target delineation, while improving inter-clinician agreement on target volumes. This study is still to be confirmed by including more clinicians and patient data to the experiments.

Cardiac stereotactic radiation therapy for refractory ventricular arrhythmias in patients with left ventricular assist devices.

Left ventricular assist device (LVAD) implantation is an established treatment for patients with advanced heart failure refractory to medical therapy. However, the incidence of ventricular arrhythmias (VAs) is high in this population, both in the acute and delayed phases after implantation. About one-third of patients implanted with an LVAD will experience sustained VAs, predisposing these patients to worse outcomes and complicating patient management. The combination of pre-existing myocardial substrate and complex electrical remodeling after LVAD implantation account for the high incidence of VAs observed in this population. LVAD patients presenting VAs refractory to antiarrhythmic therapy and catheter ablation procedures are not rare. In such patients, treatment options are extremely limited. Stereotactic body radiation therapy (SBRT) is a technique that delivers precise and high doses of radiation to highly defined targets, reducing exposure to adjacent normal tissue. Cardiac SBRT has recently emerged as a promising alternative with a growing number of case series reporting the effectiveness of the technique in reducing the VA burden in patients with arrhythmias refractory to conventional therapies. The safety profile of cardiac SBRT also appears favorable, even though the current clinical experience remains limited. The use of cardiac SBRT for the treatment of refractory VAs in patients implanted with an LVAD are even more scarce. This review summarizes the clinical experience of cardiac SBRT in LVAD patients and describes technical considerations related to the implementation of the SBRT procedure in the presence of an LVAD.

Monte Carlo-based software for 3D personalized dose calculations in image-guided radiotherapy.

BACKGROUND AND PURPOSE: Image-guided radiotherapy (IGRT) involves frequent in-room imaging sessions contributing to additional patient irradiation. The present work provided patient-specific dosimetric data related to different imaging protocols and anatomical sites. MATERIAL AND METHODS: We developed a Monte Carlo based software able to calculate 3D personalized dose distributions for five imaging devices delivering kV-CBCT (Elekta and Varian linacs), MV-CT (Tomotherapy machines) and 2D-kV stereoscopic images from BrainLab and Accuray. Our study reported the dose distributions calculated for pelvis, head and neck and breast cases based on dose volume histograms for several organs at risk. RESULTS: 2D-kV imaging provided the minimum dose with less than 1 mGy per image pair. For a single kV-CBCT and MV-CT, median dose to organs were respectively around 30 mGy and 15 mGy for the pelvis, around 7 mGy and 10 mGy for the head and neck and around 5 mGy and 15 mGy for the breast. While MV-CT dose varied sparsely with tissues, dose from kV imaging was around 1.7 times higher in bones than in soft tissue. Daily kV-CBCT along 40 sessions of prostate radiotherapy delivered up to 3.5 Gy to the femoral heads. The dose level for head and neck and breast appeared to be lower than 0.4 Gy for every organ in case of a daily imaging session. CONCLUSIONS: This study showed the dosimetric impact of IGRT procedures. Acquisition parameters should therefore be chosen wisely depending on the clinical purposes and tailored to morphology. Indeed, imaging dose could be reduced up to a factor 10 with optimized protocols.

Cardiac radioablation for ventricular tachycardia: Which approach for incorporating cardiorespiratory motions into the planning target volume?

PURPOSE: To evaluate different approaches for generating a cardiorespiratory ITV for cardiac radioablation. METHODS: Four patients with ventricular tachycardia were included in this study. For each patient, cardiac-gated and respiration-correlated 4D-CT scans were acquired. The cardiorespiratory ITV was defined using registrations of the cardiac and respiratory 4D-CT images. Five different approaches, which differed in the number of incorporated cardiac phases (1, 2, 10, or 1 with a fixed 3 mm margin (FM) expansion) and respiratory phases (2 or 10), were evaluated. For each approach, a VMAT treatment plan was simulated. Target coverage (TC) and spill were evaluated geometrically and dosimetrically for each approach. RESULTS: When employing one cardiac phase, the TC did not exceed 85%. Using the two extreme phases of the cardiac and respiratory cycles resulted in a geometric TC < 88% for two patients, with a dosimetric TC of 83% for one patient. An acceptable TC for all patients (geometric TC > 89%, dosimetric TC > 92%) was only achieved when combining 10 respiratory phases with either 2 or 10 cardiac phases or a single cardiac phase with FM. The use of a single cardiac phase with FM combined with 10 respiratory phases lead to a mean geometric and dosimetric spill of 43% and 35%, respectively. CONCLUSION: For cardiac radioablation, the use of two extreme cardiac phases combined with 10 respiratory phases is a robust approach to generate a cardiorespiratory ITV. The use of a single cardiac phase with or without fixed margin expansion is not recommended based on this study.

Cardiac stereotactic ablative radiotherapy for refractory ventricular arrhythmias: A radical alternative? A narrative review of rationale and cardiological aspects.

Ventricular arrhythmias are serious life-threatening cardiac disorders. Despite many technological improvements, a non-negligible number of patients present refractory ventricular tachycardias, resistant to a catheter ablation procedure, placing these patients in a therapeutic impasse. Recently, a cardiac stereotactic radioablative technique has been developed to treat patients with refractory ventricular arrhythmias, as a bail out strategy. This new therapeutic option historically brings together two fields of expertise unknown to each other, pointing out the necessity of an optimal partnership between cardiologists and radiation oncologists. As described in this narrative review, the understanding of cardiological aspects of the technique for radiation oncologists and treatment technical aspects comprehension for cardiologists represent a major challenge for the application and the future development of this promising treatment.

Optimized radiotherapy to improve clinical outcomes for locally advanced lung cancer.

BACKGROUND: We aimed to evaluate the toxicity, loco-regional control (LRC) and overall survival (OS) associated with accelerated intensity-modulated radiotherapy (IMRT) for locally advanced lung cancer. METHODS: Seventy-three patients were consecutively treated with IMRT from November 2011 to August 2016. A total dose of 66 Gy was delivered using two different schedules of radiotherapy: simultaneous modulated accelerated radiotherapy (SMART) (30 × 2.2 Gy, across 6 weeks) with or without chemotherapy, or moderate hypofractionated radiotherapy (HRT) (24 × 2.75 Gy, across 4 weeks) in patients unfit to receive concomitant chemotherapy. Data on esophageal and pulmonary toxicities, LRC and OS were prospectively collected. RESULTS: The median follow-up duration was 44 months. Severe pneumonitis and esophagitis (grade 3-4) were observed in 7% and 1% of patients respectively, with only one case of grade 4 (pneumonitis). Overall, the 1-year and 2-year LRCs were 76% [95 confidence interval (CI)%: 66-87%] and 62% [95 CI%: 49-77%] respectively. The 1 and 2-year OS rates were 72% [95% CI: 63-83%] and 54% [95 CI%: 43-68%] respectively. None parameters were correlated with LRC or OS. In particular, no difference was observed between patients treated with SMART and H-RT (p = 0.26 and 0.6 respectively), with a 1-year LRC of 74% [95 CI%: 62-86%] for SMART and 91% [95 CI%: 74-100%] for H-RT. No significant differences were observed in the toxicity rates associated with each of the RT schedules. CONCLUSIONS: Accelerated IMRT for locally advanced lung cancer is associated with low toxicities and high LRC. Moderate hypofractionated RT, by decreasing the total treatment time, may be promising in improving clinical outcomes.

Simultaneously modulated accelerated radiation therapy reduces severe oesophageal toxicity in concomitant chemoradiotherapy of locally advanced non-small-cell lung cancer.

OBJECTIVE: The aim of this study was to evaluate the potential of simultaneously modulated accelerated radiation therapy (SMART) to reduce the incidence of severe acute oesophagitis in the treatment of unresectable locally advanced non-small-cell lung cancer (LANSCLC). METHODS: 21 patients were treated with SMART and concomitant platinum-based chemotherapy. The prescribed doses were limited to 54 Gy at 1.8 Gy per day to the zones of presumed microscopic extent while simultaneously maintaining doses of 66 Gy at 2.2 Gy per day to the macroscopic disease. The whole treatment was delivered over 30 fractions and 6 weeks. Dosimetric parameters of SMART and the standard technique of irradiation [intensity-modulated radiation therapy (IMRT)] were compared. Acute toxicity was prospectively recorded. RESULTS: The highest grade of oesophagitis was 62% (13 patients) grade 1, 33% (7 patients) grade 2 and 5% (1 patient) grade 3. Three (14%) patients experienced acute grade 2 pneumonitis. There was no grade 4 oesophageal or pulmonary toxicity. Doses to the organs at risk were significantly reduced in SMART compared with IMRT [oesophagus: V50Gy, 28.5 Gy vs 39.9 Gy (p = 0.003); V60Gy, 7.1 Gy vs 30.7 Gy (p = 0.003); lung: V20Gy, 27.4 Gy vs 30.1 Gy (p = 0,002); heart: V40Gy, 7.3 Gy vs 10.7 Gy (p = 0.006); spine: Dmax, 42.4 Gy vs 46.4 Gy (p = 0.003)]. With a median follow-up of 18 months (6-33 months), the 1-year local control rate was 70% and the disease-free survival rate was 47%. CONCLUSION: SMART reduces the incidence of severe oesophagitis and improves the whole dosimetric predictors of toxicity for the lung, heart and spine. ADVANCES IN KNOWLEDGE: Our study shows that SMART optimizes the therapeutic ratio in the treatment of LANSCLC, opening a window for dose intensification.