Adaptive MR-Guided Stereotactic Radiotherapy is Beneficial for Ablative Treatment of Lung Tumors in High-Risk Locations

PurposeTo explore the benefit of adaptive magnetic resonance-guided stereotactic body radiotherapy (MRgSBRT) for treatment of lung tumors in different locations with a focus on ultracentral lung tumors (ULT).Patients & MethodsA prospective cohort of 21 patients with 23 primary and secondary lung tumors was analyzed. Tumors were located peripherally (N = 10), centrally (N = 2) and ultracentrally (N = 11, planning target volume (PTV) overlap with proximal bronchi, esophagus and/or pulmonary artery). All patients received MRgSBRT with gated dose delivery and risk-adapted fractionation. Before each fraction, the baseline plan was recalculated on the anatomy of the day (predicted plan). Plan adaptation was performed in 154/165 fractions (93.3%). Comparison of dose characteristics between predicted and adapted plans employed descriptive statistics and Bayesian linear multilevel models. The posterior distributions resulting from the Bayesian models are presented by the mean together with the corresponding 95% compatibility interval (CI).ResultsPlan adaptation decreased the proportion of fractions with violated planning objectives from 94% (predicted plans) to 17% (adapted plans). In most cases, inadequate PTV coverage was remedied (predicted: 86%, adapted: 13%), corresponding to a moderate increase of PTV coverage (mean +6.3%, 95% CI: [5.3–7.4%]) and biologically effective PTV doses (BED10) (BEDmin: +9.0 Gy [6.7–11.3 Gy], BEDmean: +1.4 Gy [0.8–2.1 Gy]). This benefit was smaller in larger tumors (−0.1%/10 cm³ PTV [−0.2 to −0.02%/10 cm³ PTV]) and ULT (−2.0% [−3.1 to −0.9%]). Occurrence of exceeded maximum doses inside the PTV (predicted: 21%, adapted: 4%) and violations of OAR constraints (predicted: 12%, adapted: 1%, OR: 0.14 [0.04–0.44]) was effectively reduced. OAR constraint violations almost exclusively occurred if the PTV had touched the corresponding OAR in the baseline plan (18/19, 95%).ConclusionAdaptive MRgSBRT is highly recommendable for ablative treatment of lung tumors whose PTV initially contacts a sensitive OAR, such as ULT. Here, plan adaptation protects the OAR while maintaining best-possible PTV coverage.

Evaluation of silicon strip detectors in transmission mode for online beam monitoring in microbeam radiation therapy at the Australian Synchrotron

Successful transition of synchrotron-based microbeam radiation therapy (MRT) from pre-clinical animal studies to human trials is dependent upon ensuring that there are sufficient and adequate measures in place for quality assurance purposes. Transmission detectors provide researchers and clinicians with a real-time quality assurance and beam-monitoring instrument to ensure safe and accurate dose delivery. In this work, the effect of transmission detectors of different thicknesses (10 and 375 µm) upon the photon energy spectra and dose deposition of spatially fractionated synchrotron radiation is quantified experimentally and by means of a dedicated Geant4 simulation study. The simulation and experimental results confirm that the presence of the 375 µm thick transmission detector results in an approximately 1–6% decrease in broad-beam and microbeam peak dose. The capability to account for the reduction in dose and change to the peak-to-valley dose ratio justifies the use of transmission detectors as thick as 375 µm in MRT provided that treatment planning systems are able to account for their presence. The simulation and experimental results confirm that the presence of the 10 µm thick transmission detector shows a negligible impact (<0.5%) on the photon energy spectra, dose delivery and microbeam structure for both broad-beam and microbeam cases. Whilst the use of 375 µm thick detectors would certainly be appropriate, based upon the idea of best practice the authors recommend that 10 µm thick transmission detectors of this sort be utilized as a real-time quality assurance and beam-monitoring tool during MRT.

646 Acute peri-myocarditis following COVID-19 Pfizer-Biontech vaccine second dose delivery in a male teenager: the good prognosis and unusual ECG

Aims Myocarditis due to COVID-19 mRNA vaccine is an uncommon side effect and the cases seem to have occurred predominantly in young adults under 30 years old. The estimated incidence is 12.6 cases per one million second dose m-RNA vaccine delivery. Methods and results A 17-years-old male was admitted at our department after 18 days COVID-19 Pfizer-BioNtech vaccine second dose delivery with persistent chest pain without respiratory symptoms and, ST-elevation and PR-depression in V3–V6 at the ECG on 3 August 2021. He had no history of heart disease. Physical examination didn’t show anything relevant except for mildly tachycardic heart sounds. In addition blood test showed increase in C-reactive protein, cardiac troponin and N-terminal-pro-B-type natriuretic peptide. An echocardiography showed widespread hypokinesia with reduced left ventricular ejection fraction and highly echogenic pericardium. During the first day cardiac magnetic resonance (CMR) was performed, which showed mild diffuse myocardial oedema on T2-weighted images and T2 mapping and two thin areas of delayed enhancement with non-ischaemic pattern in the lateral wall with involvement of the pericardial sheets confirming peri-myocarditis diagnosis. After 24 h, the ECG showed spread and deep T-waves with QTc prolongation. We performed multiple ECG during the days after to assess morphology changes and QTc. The patient has been asymptomatic for all the hospitalization and on day 7 was performed an echocardiography which describe a full recovery in terms of kinesia and left ventricular ejection fraction. He was discharged asymptomatic with ‘better’ but still negative T-waves and QTc normalization. Two months after discharge CMR was repeated and showed normal left ventricular function without myocardial oedema and pericardial involvement, but with persistent the areas of delayed enhancement with non-ischaemic pattern in the lateral wall. Conclusions In this case report we describe an uncommon COVID-19 m-RNA Vaccine side effect. The first issue is the timing of presentation. On 19 July 2021, AIFA stated that myocarditis is a very uncommon side effect and it usually presents within 14 days after 2nd dose delivery. Our patient was admitted at our department after that time period, probably because we reported the ending part of the myocarditis presented with symptoms of pericarditis; indeed we didn’t report the cardiac troponin plateau but only the descending cardiac troponin wave and we attend a very quick recovery. The second issue in the unique ECG with a very quick evolution (Tako-Tsubo morphology like) which could be characteristic of this kind of Myocarditis. Third, the good progress of the inflammation and quick recovery. Surely is a serious side effect but it’s still less frequent and with better prognosis than COVID-19 Myocarditis. European Medicines Agency (EMA) and Centers for Disease Control and Prevention (CDC) recently stated authorized COVID-19 vaccines advantages are still above risks in all age groups beyond 12 y/o. Why is myocarditis a side effect, Why are adolescent males affected the most and Why is the onset after second dose of m-RNA vaccine are questions still unanswered.

Metallic Nanoparticles: A Useful Prompt Gamma Emitter for Range Monitoring in Proton Therapy?

In clinical practice, dose delivery in proton therapy treatment is affected by uncertainties related to the range of the beam in the patient, which requires medical physicists to introduce safety margins on the penetration depth of the beam. Although this ensures an irradiation of the entire clinical target volume with the prescribed dose, these safety margins also lead to the exposure of nearby healthy tissues and a subsequent risk of side effects. Therefore, non-invasive techniques that allow for margin reduction through online monitoring of prompt gammas emitted along the proton tracks in the patient are currently under development. This study provides the proof-of-concept of metal-based nanoparticles, injected into the tumor, as a prompt gamma enhancer, helping in the beam range verification. It identifies the limitations of this application, suggesting a low feasibility in a realistic clinical scenario but opens some avenues for improvement.

Beyond the MAA-Y90 Paradigm: The Evolution of Radioembolization Dosimetry Approaches and Scout Particles

Radioembolization is a well-established treatment for primary and metastatic liver cancer. There is increasing interest in personalized treatment planning supported by dosimetry, as it provides an opportunity to optimize dose delivery to tumor and minimize nontarget deposition, which demonstrably increases the efficacy and safety of this therapy. However, the optimal dosimetry procedure in the radioembolization setting is still evolving; existing data are limited as few trials have prospectively tailored dose based on personalized planning and predominantly semi-empirical methods are used for dose calculation. Since the pretreatment or “scout” procedure forms the basis of dosimetry calculations, an accurate and reliable technique is essential. 99mTc-MAA SPECT constitutes the current accepted standard for pretreatment imaging; however, inconsistent patterns in published data raise the question whether this is the optimal agent. Alternative particles are now being introduced to the market, and early indications suggest use of an identical scout and treatment particle may be superior to the current standard. This review will undertake an evaluation of the increasingly refined dosimetric methods driving radioembolization practices, and a horizon scanning exercise identifying alternative scout particle solutions. Together these constitute a compelling vision for future treatment planning methods that prioritize individualized care.