Magnetic Resonance Imaging Guided Radiation Therapy for Splenomegaly: Clinical Experiences and Technical Tips.

Purpose: Splenomegaly is a common manifestation in chronic lymphoid and myeloid malignancies. Although splenectomy is the preferred treatment for symptomatic splenomegaly, it carries significant risks. Radiation therapy (RT) has traditionally been considered a palliative option. This study explores the use of magnetic resonance guided radiation therapy(MRgRT) for splenic irradiation (SI) in patients with myelofibrosis (MFI) and myelodysplastic/myeloproliferative neoplasms (MDS/MPN). Methods: This single-center retrospective analysis includes patients with MFI and MDS/MPN who underwent MRgRT SI between 2018 and 2022. Ten 1 Gy fractions were delivered to the planning target volume (spleen + 3/5mm margin). An adaptive online/offline strategy has been used to reduce the dose to healthy organs. Dosimetric data and clinical outcomes, including pain relief, gastrointestinal symptoms, and hematological values, were assessed. Results: Twelve patients completed SI without interruption, with supportive transfusions as needed for cytopenias. Pain and gastrointestinal symptom relief was observed in most cases. The mean percentage reduction in spleen volume was 53.61%, with an average craniocaudal extension reduction of 77.78%. Twenty-nine (24.2%) of 120 fractions were online adapted, and 14 (11.7%) were replanned offline. Nonhematological toxicities were not reported. At a median follow-up of 12.9 months, 6 patients died, whereas 9 patients underwent hematopoietic cell transplantation, with 6 of them surviving. Conclusion: This study demonstrates MRgRT SI feasibility in MFI and MDS/MPN patients, offering symptom relief and significant spleen volume reduction. Real-time setup verification and adaptive planning allowed for tailored treatment with reduced margins, minimizing healthy tissue exposure. Larger prospective studies with longer follow-ups are needed to further validate its efficacy and safety.

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

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.

Uterus motion analysis for radiotherapy planning optimization. The innovative contribution of on-board hybrid MR imaging.

Introduction: Organ motion (OM) and volumetric changes pose challenges in radiotherapy (RT) for locally advanced cervical cancer (LACC). Magnetic Resonance-guided Radiotherapy (MRgRT) combines improved MRI contrast with adaptive RT plans for daily anatomical changes. Our goal was to analyze cervico-uterine structure (CUS) changes during RT to develop strategies for managing OM. Materials and methods: LACC patients received chemoradiation by MRIdian system with a simultaneous integrated boost (SIB) protocol. Prescription doses of 55-50.6 Gy at PTV1 and 45-39.6 Gy at PTV2 were given in 22 and 25 fractions. Daily MRI scans were co-registered with planning scans and CUS changes were assessed.Six PTVs were created by adding 0.5, 0.7, 1, 1.3, 1.5, and 2 cm margins to the CUS, based on the simulation MRI. Adequate margins were determined to include 95 % of the CUSs throughout the entire treatment in 95 % of patients. Results: Analysis of 15 LACC patients and 372 MR scans showed a 31 % median CUS volume decrease. Asymmetric margins of 2 cm cranially, 0.5 cm caudally, 1.5 cm posteriorly, 2 cm anteriorly, and 1.5 cm on both sides were optimal for PTV, adapting to CUS variations. Post-14th fraction, smaller margins of 0.7 cm cranially, 0.5 cm caudally, 1.3 cm posteriorly, 1.3 cm anteriorly, and 1.3 cm on both sides sufficed. Conclusion: CUS mobility varies during RT, suggesting reduced PTV margins after the third week. MRgRT with adaptive strategies optimizes dose delivery, emphasizing the importance of streamlined IGRT with reduced PTV margins using a tailored MRgRT workflow with hybrid MRI-guided systems.

Impact of body composition parameters on radiation therapy compliance in locally advanced rectal cancer: A retrospective observational analysis.

Background: The impact of body composition and sarcopenia in locally advanced rectal cancer (LARC) is still unclear, even several studies have been published on this issue. Our study aims to analyze the impact of sarcopenia on neoadjuvant chemoradiotherapy (nCRT) tolerance and survival outcomes. Methods: This is a retrospective, monocentric study where LARC patients treated between 2010 and 2020 were enrolled. A single slice, from the pre-therapy simulation computed tomography (CT) scan, was used to perform the body composition analysis with dedicated software. The primary endpoint was the impact of body composition on radiotherapy (RT) interruption secondarily on overall survival (OS), disease-free survival (DFS), and local control (LC). Results: The study included 628 LARC patients (40.9 % female, mean age 63.4 years): 24 % had low skeletal muscle index (SMI), 30 % had low muscle density (MD) and 17 (10.3 % of obese) were sarcopenic obese. Higher BMI (OR 2.38, 95 % CI 1.36-4.01) and lower SMI (0.73, 95 % CI 0.55-0.94) resulted as independent predictors of RT interruption. Sarcopenic obesity (HR 2.83, 95 % CI 1.24-6.45) was related to worse OS, while MD (0.96, 95 % CI 0.93-0.98), and higher SMI (0.97, 95 % CI 0.95-0.99) were related to better OS; a lower MD remained also associated even in adjusted multivariable analysis (0.96, 95 % CI0.93-0.98). Moreover, higher visceral adipose tissue (VAT) resulted associated with worse DFS (1.02, 95 % CI 1.01-1.03), while higher SMI was related to better Local Control (0.96, 95 % CI 0.93-0.99). Conclusions: Body composition analysis, particularly of muscle and fat masses, may be a useful tool for better management of LARC patients undergoing RT. Increased collaboration between radiation oncologists and clinical nutritionists is advisable, to enable early nutritional support of LARC.

Impact of bias field correction on 0.35 T pelvic MR images: evaluation on generative adversarial network-based OARs' auto-segmentation and visual grading assessment.

Purpose: Magnetic resonance imaging (MRI)-guided radiotherapy enables adaptive treatment plans based on daily anatomical changes and accurate organ visualization. However, the bias field artifact can compromise image quality, affecting diagnostic accuracy and quantitative analyses. This study aims to assess the impact of bias field correction on 0.35 T pelvis MRIs by evaluating clinical anatomy visualization and generative adversarial network (GAN) auto-segmentation performance. Materials and methods: 3D simulation MRIs from 60 prostate cancer patients treated on MR-Linac (0.35 T) were collected and preprocessed with the N4ITK algorithm for bias field correction. A 3D GAN architecture was trained, validated, and tested on 40, 10, and 10 patients, respectively, to auto-segment the organs at risk (OARs) rectum and bladder. The GAN was trained and evaluated either with the original or the bias-corrected MRIs. The Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (HD95th) were computed for the segmented volumes of each patient. The Wilcoxon signed-rank test assessed the statistical difference of the metrics within OARs, both with and without bias field correction. Five radiation oncologists blindly scored 22 randomly chosen patients in terms of overall image quality and visibility of boundaries (prostate, rectum, bladder, seminal vesicles) of the original and bias-corrected MRIs. Bennett's S score and Fleiss' kappa were used to assess the pairwise interrater agreement and the interrater agreement among all the observers, respectively. Results: In the test set, the GAN trained and evaluated on original and bias-corrected MRIs showed DSC/HD95th of 0.92/5.63 mm and 0.92/5.91 mm for the bladder and 0.84/10.61 mm and 0.83/9.71 mm for the rectum. No statistical differences in the distribution of the evaluation metrics were found neither for the bladder (DSC: p = 0.07; HD95th: p = 0.35) nor for the rectum (DSC: p = 0.32; HD95th: p = 0.63). From the clinical visual grading assessment, the bias-corrected MRI resulted mostly in either no change or an improvement of the image quality and visualization of the organs' boundaries compared with the original MRI. Conclusion: The bias field correction did not improve the anatomy visualization from a clinical point of view and the OARs' auto-segmentation outputs generated by the GAN.

REPeated mAgnetic resonance Image-guided stereotactic body Radiotherapy (MRIg-reSBRT) for oligometastatic patients: REPAIR, a mono-institutional retrospective study.

BACKGROUND: Oligo-progression or further recurrence is an open issue in the multi-integrated management of oligometastatic disease (OMD). Re-irradiation with stereotactic body radiotherapy (re-SBRT) technique could represent a valuable treatment option to improve OMD clinical outcomes. MRI-guided allows real-time visualization of the target volumes and online adaptive radiotherapy (oART). The aim of this retrospective study is to evaluate the efficacy and toxicity profile of MRI-guided repeated SBRT (MRIg-reSBRT) in the OMD setting and propose a re-SBRT classification. METHODS: We retrospectively analyzed patients (pts) with recurrent liver metastases or abdominal metastatic lesions between 1 and 5 centimeters from liver candidate to MRIg-reSBRT showing geometric overlap between the different SBRT courses and assessing whether they were in field (type 1) or not (type 2). RESULTS: Eighteen pts completed MRIg-reSBRT course for 25 metastatic hepatic/perihepatic lesions from July 2019 to January 2020. A total of 20 SBRT courses: 15 Type 1 re-SBRT (75%) and 5 Type 2 re-SBRT (25%) was delivered. Mean interval between the first SBRT and MRIg-reSBRT was 8,6 months. Mean prescribed dose for the first treatment was 43 Gy (range 24-50 Gy, mean BEDα/ß10=93), while 41 Gy (range 16-50 Gy, mean BEDα/ß10=92) for MRIg-reSBRT. Average liver dose was 3,9 Gy (range 1-10 Gy) and 3,7 Gy (range 1,6-8 Gy) for the first SBRT and MRIg-reSBRT, respectively. No acute or late toxicities were reported at a median follow-up of 10,7 months. The 1-year OS and PFS was 73,08% and 50%, respectively. Overall Clinical Benefit was 54%. CONCLUSIONS: MRIg-reSBRT could be considered an effective and safe option in the multi-integrated treatment of OMD.

Impact of data transfer between treatment planning systems on dosimetric parameters.

PURPOSE: In radiotherapy it is often necessary to transfer a patient's DICOM (Digital Imaging and COmmunications in Medicine) dataset from one system to another for re-treatment, plan-summation or registration purposes. The aim of the study is to evaluate effects of dataset transfer between treatment planning systems. MATERIALS AND METHODS: Twenty-five patients treated in a 0.35T MR-Linac (MRidian, ViewRay) for locally-advanced pancreatic cancer were enrolled. For each patient, a nominal dose distribution was optimized on the planning MRI. Each plan was daily re-optimized if needed to match the anatomy and exported from MRIdian-TPS (ViewRay Inc.) to Eclipse-TPS (Siemens-Varian). A comparison between the two TPSs was performed considering the PTV and OARs volumes (cc), as well as dose coverages and clinical constraints. RESULTS: From the twenty-five enrolled patients, 139 plans were included in the data comparison. The median values of percentage PTV volume variation are 10.8 % for each fraction, while percentage differences of PTV coverage have a mean value of -1.4 %. The median values of the percentage OARs volume variation are 16.0 %, 7.0 %, 10.4 % and 8.5 % for duodenum, stomach, small and large bowel, respectively. The percentage variations of the dose constraints are 41.0 %, 52.7 % and 49.8 % for duodenum, stomach and small bowel, respectively. CONCLUSIONS: This study has demonstrated a non-negligible variation in size and dosimetric parameters when datasets are transferred between TPSs. Such variations should be clinically considered. Investigations are focused on DICOM structure algorithm employed by the TPSs during the transfer to understand the cause of such variations.

High-tailored Anal Canal Radiotherapy (HIT-ART): Outcomes of a 10-Year Single Center Clinical Experience.

BACKGROUND/AIM: The current standard for anal cancer treatment is essentially a 'one size fits all' approach where the dose of radiotherapy is similar whether the tumor is very small or very large. Trials are ongoing to evaluate dose de-escalation or escalation in localized disease depending on tumor size. The aim of the study was to assess results of a personalized approach involving dose stratification by stage and boost dose adjusted according to tumor early response. PATIENTS AND METHODS: We retrospectively reviewed squamous cell anal cancer (SCAC) patients treated between 2011 and 2021 by long-course intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy (CT); a sequential boost could be administered by IMRT or interventional radiotherapy (IRT) to obtain a total equivalent dose in 2 Gy (EQD2) of 54-60 Gy. RESULTS: We analyzed 110 patients (61% T3-4 stage, 71% node-positive). A total of 68.2% of patients received a sequential boost, mainly by IRT; median total EQD2 to primary site was 59.3 Gy. Acute ≥G3 toxicity rate was 36.4%. Median follow-up (FUP) was 35.4 months. A total of 83% of patients achieved clinical complete response (cCR); locoregional recurrence (LRR) occurred in 20.9% and distant metastases in 6.4% of cases. A total of 12.7% patients underwent salvage surgery. A total of 25.5% of patients reported ≥G2 and 4.5% ≥G3 late toxicity. The estimated 3-year overall survival, disease-free survival and colostomy-free survival were 92%, 72% and 84% respectively; 3-year-LRR was 22%. Nodal stage was associated with poorer cCR probability and higher LRR (p<0.05). CONCLUSION: Our results on a large cohort of patients with locally advanced SCAC and long FUP time confirmed the efficacy of IMRT; high local control and manageable toxicity also suggest IRT as a promising method in treatment personalization.

Radiomics-enhanced early regression index for predicting treatment response in rectal cancer: a multi-institutional 0.35 T MRI-guided radiotherapy study.

PURPOSE: The accurate prediction of treatment response in locally advanced rectal cancer (LARC) patients undergoing MRI-guided radiotherapy (MRIgRT) is essential for optimising treatment strategies. This multi-institutional study aimed to investigate the potential of radiomics in enhancing the predictive power of a known radiobiological parameter (Early Regression Index, ERITCP) to evaluate treatment response in LARC patients treated with MRIgRT. METHODS: Patients from three international sites were included and divided into training and validation sets. 0.35 T T2*/T1-weighted MR images were acquired during simulation and at each treatment fraction. The biologically effective dose (BED) conversion was used to account for different radiotherapy schemes: gross tumour volume was delineated on the MR images corresponding to specific BED levels and radiomic features were then extracted. Multiple logistic regression models were calculated, combining ERITCP with other radiomic features. The predictive performance of the different models was evaluated on both training and validation sets by calculating the receiver operating characteristic (ROC) curves. RESULTS: A total of 91 patients was enrolled: 58 were used as training, 33 as validation. Overall, pCR was observed in 25 cases. The model showing the highest performance was obtained combining ERITCP at BED = 26 Gy with a radiomic feature (10th percentile of grey level histogram, 10GLH) calculated at BED = 40 Gy. The area under ROC curve (AUC) of this combined model was 0.98 for training set and 0.92 for validation set, significantly higher (p = 0.04) than the AUC value obtained using ERITCP alone (0.94 in training and 0.89 in validation set). CONCLUSION: The integration of the radiomic analysis with ERITCP improves the pCR prediction in LARC patients, offering more precise predictive models to further personalise 0.35 T MRIgRT treatments of LARC patients.

Rectal Sparing Approach after preoperative Radio- and/or Chemo-therapy (ReSARCh): a prospective, multicenter, observational study.

BACKGROUND: Rectal-sparing approaches for patients with rectal cancer who achieved a complete or major response following neoadjuvant therapy constitute a paradigm of a potential shift in the management of patients with rectal cancer; however, their role remains controversial. The aim of this study was to investigate the feasibility of rectal-sparing approaches to preserve the rectum without impairing the outcomes. METHODS: This prospective, multicenter, observational study investigated the outcomes of patients with clinical stage II-III mid-low rectal adenocarcinoma treated with any neoadjuvant therapy, and either transanal local excision or watch-and-wait approach, based on tumor response (major or complete) and patient/surgeon choice. The primary endpoint of the study was rectum preservation at a minimum follow-up of 2 years. Secondary endpoints were overall, disease-free, local and distant recurrence-free, and stoma-free survival at 3 years. RESULTS: Of the 178 patients enrolled in 16 centers, 112 (62.9%) were managed with local excision and 66 (37.1%) with watch-and-wait. At a median (interquartile range) follow-up of 36.1 (30.6-45.6) months, the rectum was preserved in 144 (80.9%) patients. The 3-year rectum-sparing, overall survival, disease-free survival, local recurrence-free survival, and distant recurrence-free survival was 80.6% (95% CI 73.9-85.8), 97.6% (95% CI 93.6-99.1), 90.0% (95% CI 84.3-93.7), 94.7% (95% CI 90.1-97.2), and 94.6% (95% CI 89.9-97.2), respectively. The 3-year stoma-free survival was 95.0% (95% CI 89.5-97.6). The 3-year regrowth-free survival in the watch-and-wait group was 71.8% (95% CI 59.9-81.2). CONCLUSIONS: In rectal cancer patients with major or complete clinical response after neoadjuvant therapy, the rectum can be preserved in about 80% of cases, without compromising the outcomes.

Auto-segmentation of pelvic organs at risk on 0.35T MRI using 2D and 3D Generative Adversarial Network models.

PURPOSE: Manual recontouring of targets and Organs At Risk (OARs) is a time-consuming and operator-dependent task. We explored the potential of Generative Adversarial Networks (GAN) to auto-segment the rectum, bladder and femoral heads on 0.35T MRIs to accelerate the online MRI-guided-Radiotherapy (MRIgRT) workflow. METHODS: 3D planning MRIs from 60 prostate cancer patients treated with 0.35T MR-Linac were collected. A 3D GAN architecture and its equivalent 2D version were trained, validated and tested on 40, 10 and 10 patients respectively. The volumetric Dice Similarity Coefficient (DSC) and 95th percentile Hausdorff Distance (HD95th) were computed against expert drawn ground-truth delineations. The networks were also validated on an independent external dataset of 16 patients. RESULTS: In the internal test set, the 3D and 2D GANs showed DSC/HD95th of 0.83/9.72 mm and 0.81/10.65 mm for the rectum, 0.92/5.91 mm and 0.85/15.72 mm for the bladder, and 0.94/3.62 mm and 0.90/9.49 mm for the femoral heads. In the external test set, the performance was 0.74/31.13 mm and 0.72/25.07 mm for the rectum, 0.92/9.46 mm and 0.88/11.28 mm for the bladder, and 0.89/7.00 mm and 0.88/10.06 mm for the femoral heads. The 3D and 2D GANs required on average 1.44 s and 6.59 s respectively to generate the OARs' volumetric segmentation for a single patient. CONCLUSIONS: The proposed 3D GAN auto-segments pelvic OARs with high accuracy on 0.35T, in both the internal and the external test sets, outperforming its 2D equivalent in both segmentation robustness and volume generation time.

Magnetic resonance imaging for assessment of rectal cancer nodes after chemoradiotherapy: A single center experience.

BACKGROUND: Accurate nodal restaging is becoming clinically more important in patients with locally advanced rectal cancer (LARC) with the emergence of organ-preserving treatment after a good response to neoadjuvant chemoradiotherapy (nCRT). PURPOSE: To evaluate the accuracy of MRI in identifying negative N status (ypN0 patients) in LARC after nCRT. MATERIAL AND METHODS: 191 patients with LARC underwent MRI before and 6-8 weeks after nCRT and subsequent total mesorectal excision. Short-axis diameter of mesorectal lymph nodes was evaluated on the high resolution T2-weighted images to compare MRI restaging with histopathology.. RESULTS: 146 and 45 patients had a negative N status (ypN0) and positive N status (ypN + ), respectively. On restaging MRI, the 70 % reduction in size of the largest node was associated with an area under the curve (AUC) of 0.818 to predict ypN0 stage, with a sensitivity of 93.3 % and a negative predictive value (NPV) of 95.4 %. No nodes were observed in 38 pts (37 pts ypN0 and 1 patient ypN + ), with sensitivity and NPV of nodes disappearance for ypN0 stage of 93.3 % and 92.5 % respectively. A 2.2 mm cut-off in short-axis diameter was associated with an AUC of 0.83 for the prediction of ypN0 nodal stage, with sensitivity and NPV of 79,5% and 91.1 % respectively. CONCLUSION: A reduction in size of 70 % of the largest limph-node on MRI at rectal cancer restaging has high sensitivity and NPV for prediction of ypN0 stage after nCRT. The high NPV of node disappearance and of a ≤ 2.2 mm short-axis diameter is confirmed.

Evaluation of clinical parallel workflow in online adaptive MR-guided Radiotherapy: A detailed assessment of treatment session times.

Introduction: Advancements in MRI-guided radiotherapy (MRgRT) enable clinical parallel workflows (CPW) for online adaptive planning (oART), allowing medical physicists (MPs), physicians (MDs), and radiation therapists (RTTs) to perform their tasks simultaneously. This study evaluates the impact of this upgrade on the total treatment time by analyzing each step of the current 0.35T-MRgRT workflow. Methods: The time process of the workflow steps for 254 treatment fractions in 0.35 MRgRT was examined. Patients have been grouped based on disease site, breathing modality (BM) (BHI or FB), and fractionation (stereotactic body RT [SBRT] or standard fractionated long course [LC]). The time spent for the following workflow steps in Adaptive Treatment (ADP) was analyzed: Patient Setup Time (PSt), MRI Acquisition and Matching (MRt), MR Re-contouring Time (RCt), Re-Planning Time (RPt), Treatment Delivery Time (TDt). Also analyzed was the timing of treatments that followed a Simple workflow (SMP), without the online re-planning (PSt + MRt + TDt.). Results: The time analysis revealed that the ADP workflow (median: 34 min) is significantly (p < 0.05) longer than the SMP workflow (19 min). The time required for ADP treatments is significantly influenced by TDt, constituting 40 % of the total time. The oART steps (RCt + RPt) took 11 min (median), representing 27 % of the entire procedure. Overall, 79.2 % of oART fractions were completed in less than 45 min, and 30.6 % were completed in less than 30 min. Conclusion: This preliminary analysis, along with the comparative assessment against existing literature, underscores the potential of CPW to diminish the overall treatment duration in MRgRT-oART. Additionally, it suggests the potential for CPW to promote a more integrated multidisciplinary approach in the execution of oART.

Rectal Cancer MRI Guided Radiotherapy: A Practical Review for the Physician.

MR-guided radiotherapy is a treatment approach that combines the advantages of magnetic resonance imaging (MRI) with the precision of radiation therapy. This practical review provides an overview of the current state-of-the-art of MR-guided radiotherapy for rectal cancer, including its technical aspects, clinical outcomes, and existing limitations. Even though some studies have demonstrated the feasibility and safety of this treatment modality, challenges remain in terms of patient selection, treatment planning optimization, and long-term follow-up. Despite these issues, MR-guided radiotherapy shows promise as a potentially valuable rectal cancer treatment approach.

Motion and dosimetric criteria for selecting gating technique for apical lung lesions in magnetic resonance guided radiotherapy.

Introduction: Patients treatment compliance increases during free-breathing (FB) treatment, taking generally less time and fatigue with respect to deep inspiration breath-hold (DIBH). This study quantifies the gross target volume (GTV) motion on cine-MRI of apical lung lesions undergoing a SBRT in a MR-Linac and supports the patient specific treatment gating pre-selection. Material and methods: A total of 12 patients were retrospectively enrolled in this study. During simulation and treatment fractions, sagittal 0.35 T cine-MRI allows real-time GTV motion tracking. Cine-MRI has been exported, and an in-house developed MATLAB script performed image segmentation for measuring GTV centroid position on cine-MRI frames. Motion measurements were performed during the deep inspiration phase of DIBH patient and during all the session for FB patient. Treatment plans of FB patients were reoptimized using the same cost function, choosing the 3 mm GTV-PTV margin used for DIBH patients instead of the original 5 mm margin, comparing GTV and OARs DVH for the different TP. Results: GTV centroid motion is <2.2 mm in the antero-posterior and cranio-caudal direction in DIBH. For FB patients, GTV motion is lower than 1.7 mm, and motion during the treatment was always in agreement with the one measured during the simulation. No differences have been observed in GTV coverage between the TP with 3-mm and 5-mm margins. Using a 3-mm margin, the mean reduction in the chest wall and trachea-bronchus Dmax was 2.5 Gy and 3.0 Gy, respectively, and a reduction of 1.0 Gy, 0.6 Gy, and 2.3% in Dmax, Dmean, and V5Gy, respectively, of the homolateral lung and 1.7 Gy in the contralateral lung Dmax. Discussions: Cine-MRI allows to select FB lung patients when GTV motion is <2 mm. The use of narrower PTV margins reduces OARs dose and maintains target coverage.

Preoperative Intensified Chemoradiation with Intensity-Modulated Radiotherapy and Simultaneous Integrated Boost Combined with Capecitabine in Locally Advanced Rectal Cancer: Long-Term Outcomes of a Real-Life Multicenter Study.

BACKGROUND: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. PATIENTS AND METHODS: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m2 twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. RESULTS: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3-4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3-77.4) and 85.9% (95% CI: 80.2-90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0-13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5-26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3-5 were significantly associated with worse PFS, OS and metastasis-free survival. CONCLUSIONS: Preoperative IMRT-SIB with the moderate dose intensification of 52.5-57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest.

Why we should care about gas pockets in online adaptive MRgRT: a dosimetric evaluation.

Introduction: Contouring of gas pockets is a time consuming step in the workflow of adaptive radiotherapy. We would like to better understand which gas pockets electronic densitiy should be used and the dosimetric impact on adaptive MRgRT treatment. Materials and methods: 21 CT scans of patients undergoing SBRT were retrospectively evaluated. Anatomical structures were contoured: Gross Tumour Volume (GTV), stomach (ST), small bowel (SB), large bowel (LB), gas pockets (GAS) and gas in each organ respectively STG, SBG, LBG. Average HU in GAS was converted in RED, the obtained value has been named as Gastrointestinal Gas RED (GIGED). Differences of average HU in GAS, STG, SBG and LBG were computed. Three treatment plans were calculated editing the GAS volume RED that was overwritten with: air RED (0.0012), water RED (1.000), GIGED, generating respectively APLAN, WPLAN and the GPLAN. 2-D dose distributions were analyzed by gamma analysis. Parameter called active gas volume (AGV) was calculated as the intersection of GAS with the isodose of 5% of prescription dose. Results: Average HU value contained in GAS results to be equal to -620. No significative difference was noted between the average HU of gas in different organ at risk. Value of Gamma Passing Rate (GPR) anticorrelates with the AGV for each plan comparison and the threshold value for GPR to fall below 90% is 41, 60 and 139 cc for WPLANvsAPLAN, GPLANvsAPLAN and WPLANvsGPLAN respectively. Discussions: GIGED is the right RED for Gastrointestinal Gas. Novel AGV is a useful parameter to evaluate the effect of gas pocket on dose distribution.

Modern Techniques in Re-Irradiation for Locally Recurrent Rectal Cancer: A Systematic Review.

BACKGROUND: Radiotherapy (RT) plays an important role in the treatment of patients with previously irradiated locally recurrent rectal cancer (LRRC). Over the years, numerous technologies and different types of RT have emerged. The aim of our systematic literature review was to determine whether the new techniques have led to improvements in both outcomes and toxicities. METHODS: A computerized search was performed by MEDLINE and the Cochrane database. The studies reported data from patients treated with carbon ion radiotherapy (CIRT), intensity-modulated photon radiotherapy (IMRT), and stereotactic radiotherapy (SBRT). RESULTS: Seven publications of the 126 titles/abstracts that emerged from our search met the inclusion criteria and presented outcomes of 230 patients. OS was reported with rates of 90.0% and 73.0% at 1 and 2 years, respectively; LC was 89.0% and 71.6% at 1 and 2 years after re-RT, respectively. Toxicity data vary widely, with emphasis on acute and chronic gastrointestinal and urogenital toxicity, even with modern techniques. CONCLUSION: data on toxicity and outcomes of re-RT for LRRC with new technologies are promising compared with 3D techniques. Comparative studies are needed to define the best technique, also in relation to the site of recurrence.