Current practices and perspectives on the integration of contrast agents in MRI-guided radiation therapy clinical practice: A worldwide survey

Aims: The introduction of on-line magnetic resonance image-guided radiotherapy (MRIgRT) has led to an improvement in the therapeutic workflow of radiotherapy treatments thanks to the better visualization of therapy volumes assured by the higher soft tissue contrast. Magnetic Resonance contrast agents (MRCA) could improve the target delineation in on-line MRIgRT planning as well as reduce inter-observer variability and enable innovative treatment optimization protocols. The aim of this survey is to investigate the utilization of MRCA among centres that clinically implemented on-line MRIgRT technology. Methods: In September 2021, we conducted an online survey consisting of a sixteen-question questionnaire that was distributed to the all the hospitals around the world equipped with MR Linacs. The questionnaire was developed by two Italian 0.35 T and 1.5 T MR-Linac centres and was validated by four other collaborating centres, using a Delphi consensus methodology. Results: The survey was distributed to 52 centres and 43 centres completed it (82.7%). Among these centres, 23 institutions (53.5%) used the 0.35T MR-Linac system, while the remaining 20 (46.5%) used the 1.5T MR-Linac system.According to results obtained, 25 (58%) of the centres implemented the use of MRCA for on-line MRIgRT. Gadoxetate (Eovist®; Primovist®) was reported to be the most used MRCA (80%) and liver the most common site of application (58%). Over 70% of responders agreed/strongly agreed to the need for international guidelines. Conclusions: The use of MRCA in clinical practice presents several pitfalls and future research will be necessary to understand the actual advantage derived from the use of MRCA in clinical practice, their toxicity profiles and better define the need of formulating guidelines for standardising the use of MRCA in MRIgRT workflow

Unsolved Issues in Thymic Epithelial Tumour Stage Classification: The Role of Tumour Dimension

According to the different classifications now in use, thymic tumours are staged by the extent of local invasiveness, and tumour size is not included as a major determinant for the T category. The aim of this double-site retrospective study is to analyse the correlation between tumour dimension and overall survival (OS) in patients who underwent surgical treatment. From January 2000 to December 2020, patients with thymic epithelial tumours who underwent surgical resection were included in this study. Data from a total of 332 patients were analysed. Five- and ten-year overall survival (5–10 YOS) was 89.26% and 87.08%, respectively, while five- and ten-year disease-free survival (DFS) was 88.12% and 84.2%, respectively. Univariate analysis showed a significant correlation between male sex (p-value 0.02), older age (p-value p-value p-value 0.03) and increase in the number of infiltrated organs (p-value 0.02) with an increase in tumour dimension. Tumour dimension alone was not effective in the prediction of DFS and OS, both when considered as a continuous variable and when considered with a cut-off of 3 and 5 cm. However, with multivariate analysis, it was effective in predicting OS in the aforementioned conditions (p-value < 0.01). Moreover, multivariate analysis was also used in the thymoma and Masaoka I subgroups. In our experience, the role of tumour dimension as a descriptor of the T parameter of the TNM (Tumor Node Metastasis) staging system seemed to be useful in improving this system

MOREOVER: multiomics MR-guided radiotherapy optimization in locally advanced rectal cancer

Abstract Background Complete response prediction in locally advanced rectal cancer (LARC) patients is generally focused on the radiomics analysis of staging MRI. Until now, omics information extracted from gut microbiota and circulating tumor DNA (ctDNA) have not been integrated in composite biomarkers-based models, thereby omitting valuable information from the decision-making process. In this study, we aim to integrate radiomics with gut microbiota and ctDNA-based genomics tracking during neoadjuvant chemoradiotherapy (nCRT). Methods The main hypothesis of the MOREOVER study is that the incorporation of composite biomarkers with radiomics-based models used in the THUNDER-2 trial will improve the pathological complete response (pCR) predictive power of such models, paving the way for more accurate and comprehensive personalized treatment approaches. This is due to the inclusion of actionable omics variables that may disclose previously unknown correlations with radiomics. Aims of this study are: - to generate longitudinal microbiome data linked to disease resistance to nCRT and postulate future therapeutic strategies in terms of both type of treatment and timing, such as fecal microbiota transplant in non-responding patients. - to describe the genomics pattern and ctDNA data evolution throughout the nCRT treatment in order to support the prediction outcome and identify new risk-category stratification agents. - to mine and combine collected data through integrated multi-omics approaches (radiomics, metagenomics, metabolomics, metatranscriptomics, human genomics, ctDNA) in order to increase the performance of the radiomics-based response predictive model for LARC patients undergoing nCRT on MR-Linac. Experimental design The objective of the MOREOVER project is to enrich the phase II THUNDER-2 trial (NCT04815694) with gut microbiota and ctDNA omics information, by exploring the possibility to enhance predictive performance of the developed model. Longitudinal ctDNA genomics, microbiome and genomics data will be analyzed on 7 timepoints: prior to nCRT, during nCRT on a weekly basis and prior to surgery. Specific modelling will be performed for data harvested, according to the TRIPOD statements. Discussion We expect to find differences in fecal microbiome, ctDNA and radiomics profiles between the two groups of patients (pCR and not pCR). In addition, we expect to find a variability in the stability of the considered omics features over time. The identified profiles will be inserted into dedicated modelling solutions to set up a multiomics decision support system able to achieve personalized treatments

Clinical Stage III NSCLC Patients Treated with Neoadjuvant Therapy and Surgery: The Prognostic Role of Nodal Characteristics

BACKGROUND: The aim of this study is to analyze the prognostic factors in patients that underwent induction therapy and surgery for clinical stage III NSCLC. METHODS: Clinical and pathological characteristics of stage III NSCLC patients for N2 involvement that underwent neoadjuvant treatment (NAD) and surgery from 1/01/1998 to 31/12/2017 were collected and retrospectively analyzed. Tumor characteristics, yClinical, yPathological stage and lymph node characteristics were correlated to Overall Survival (OS). RESULTS: The analysis was conducted on 180 patients. Five-year OS (5YOS) was 50.9%. Univariable analysis results revealed old age (p = 0.003), clinical N2 post-NAD (p = 0.01), pneumonectomy (0.005), persistent pathological N2 (p = 0.039, HR 1.9, 95% CI 1.09-2.68) and adjuvant therapy absence (p = 0.049) as significant negative prognostic factors. Multivariable analysis confirmed pN0N1 (p = 0.02, HR 0.29, 95% CI 0.13-0.62) as a favorable independent prognostic factor and adjuvant therapy absence (p = 0.012, HR 2.61, 95% CI 1.23-5.50) as a negative prognostic factor. Patients with persistent N2 presented a 5YOS of 35.3% vs. 55.8% in pN0N1 patients. Regarding lymph node parameters, the lymph node ratio (NR) significantly correlated with OS: 5YOS of 67.6% in patients with NR &lt; 50% vs. 29.5% in NR &gt; 50% (p = 0.029). CONCLUSION: Clinical response aided the stratification of prognosis in patients that underwent multimodal treatment for stage III NSCLC. Adjuvant therapy seemed to be an important option in these patients, while node ratio was a strong prognosticator in patients with persistent nodal involvement