Magnetic resonance guided SBRT reirradiation in locally recurrent prostate cancer: a multicentric retrospective analysis.

AIMS: Reirradiation of prostate cancer (PC) local recurrences represents an emerging challenge for current radiotherapy. In this context, stereotactic body radiation therapy (SBRT) allows the delivery of high doses, with curative intent. Magnetic Resonance guided Radiation Therapy (MRgRT) has shown promising results in terms of safety, feasibility and efficacy of delivering SBRT thanks to the enhanced soft tissue contrast and the online adaptive workflow. This multicentric retrospective analysis evaluates the feasibility and efficacy of PC reirradiation, using a 0.35 T hybrid MR delivery unit. METHODS: Patients affected by local recurrences of PC and treated in five institutions between 2019 and 2022 were retrospectively collected. All patients had undergone previous Radiation Therapy (RT) in definitive or adjuvant setting. Re-treatment MRgSBRT was delivered with a total dose ranging from 25 to 40 Gy in 5 fractions. Toxicity according to CTCAE v 5.0 and treatment response were assessed at the end of the treatment and at follow-up. RESULTS: Eighteen patients were included in this analysis. All patients had previously undergone external beam radiation therapy (EBRT) up to a total dose of 59.36 to 80 Gy. Median cumulative biologically effective dose (BED) of SBRT re-treatment was 213,3 Gy (103,1-560), considering an α/ß of 1.5. Complete response was achieved in 4 patients (22.2%). No grade ≥ 2 acute genitourinary (GU) toxicity events were recorded, while gastrointestinal (GI) acute toxicity events occurred in 4 patients (22.2%). CONCLUSION: The low rates of acute toxicity of this experience encourages considering MRgSBRT a feasibile therapeutic approach for the treatment of clinically relapsed PC. Accurate gating of target volumes, the online adaptive planning workflow and the high definition of MRI treatment images allow delivering high doses to the PTV while efficiently sparing organs at risk (OARs).

Management of single pulmonary metastases from colorectal cancer: State of the art.

Colorectal cancer (CRC) is one of the most common causes of death from cancer. Lung seeding occurs in approximately 10% of patients surgically treated for primary CRC with radical intent: the lung is the most common site of metastases after the liver. While surgical treatment of liver metastases is widely accepted to affect long-term outcomes, more controversial and not standardized is the therapy for CRC patients developing lung metastases. Experience suggests the potential curative role of pulmonary metastasectomy, especially in oligometastatic disease. However, the optimal strategy of care and the definition of prognostic factors after treatment still need to be defined. This review focused on the uncommon scenario of single pulmonary metastases from CRC. We explored pertinent literature and provide an overview of the epidemiology, clinical characteristics and imaging of single pulmonary metastases from CRC. Additionally, we identified the best available evidence for overall management. In particular, we analyzed the role and results of locoregional approaches (surgery, radiotherapy or ablative procedures) and their integration with systemic therapy.

The Role of Simultaneous Integrated Boost in Locally Advanced Rectal Cancer Patients with Positive Lateral Pelvic Lymph Nodes.

Aims: Between 11 to 14% of patients with locally advanced rectal cancer (LARC) have positive lateral pelvic lymph nodes (LPLN) at diagnosis, related to a worse prognosis with a 5-year survival rate between 30 to 40%. The best treatment choice for this group of patients is still a challenge. The optimal radiotherapy (RT) dose for LPLN patients has been investigated. Methods: We retrospectively collected data from LARC patients with LPLN at the primary staging MRI, treated in our center from March 2003 to December 2020. Patients underwent a neoadjuvant concomitant chemo-radiotherapy (CRT) treatment on the primary tumor (T), mesorectum, and pelvic nodes, associated with a fluoride-based chemotherapy. The total reached dose was 45 Gy at 1.8 Gy/fr on the elective sites and 55 Gy at 2.2 Gy/fr on the disease and mesorectum. Patients were divided in two groups based on whether they received a simultaneous integrated RT boost on the LPLN or not. Overall Survival (OS), Disease Free Survival (DFS), Metastasis Free Survival (MFS), and Local Control (LC) were evaluated in the whole group and then compared between the two groups. Results: A total of 176 patients were evaluated: 82 were included in the RT boost group and 94 in the non-RT boost group. The median follow-up period was 57.8 months. All the clinical endpoint (OS, DFS, MFS, LC), resulted were affected by the simultaneous integrated boost on LPLN with a survival rate of 84.7%, 79.5%, 84.1%, and 92%, respectively, in the entire population. From the comparison of the two groups, there was a statistical significance towards the RT boost group with a p < 0.006, 0.030, 0.042, 0.026, respectively. Conclusions: Concomitant radiotherapy boost on positive LPLN has shown to be beneficial on the survival outcomes (OS, DFS, MFR, and LC) in patients with LARC and LPLN. This analysis demonstrates that a higher dose of radiotherapy on positive pelvic lymph nodes led not only to a higher local control but also to a better survival rate. These results, if validated by future prospective studies, can bring a valid alternative to the surgery dissection without the important side effects and permanent disabilities observed during the years.

Modern Management of Esophageal Cancer: Radio-Oncology in Neoadjuvancy, Adjuvancy and Palliation.

The modern management of esophageal cancer is crucially based on a multidisciplinary and multimodal approach. Radiotherapy is involved in neoadjuvant and adjuvant settings; moreover, it includes radical and palliative treatment intention (with a focus on the use of a stent and its potential integration with radiotherapy). In this review, the above-mentioned settings and approaches will be described. Referring to available international guidelines, the background evidence bases will be reviewed, and the ongoing, more relevant trials will be outlined. Target definitions and radiotherapy doses to administer will be mentioned. Peculiar applications such as brachytherapy (interventional radiation oncology), and data regarding innovative approaches including MRI-guided-RT and radiomic analysis will be reported. A focus on the avoidance of surgery for major clinical responses (particularly for SCC) is detailed.

Efficacy of low-dose radiotherapy (2 Gy × 2) in the treatment of marginal zone and mucosa-associated lymphoid tissue lymphomas.

OBJECTIVES: To investigate the efficacy of a schedule of low-dose radiotherapy (LDRT) with 4 Gy (2 Gy x 2) in a cohort of unselected MALT or MZL patients. METHODS: We retrospectively collected all patients receiving LDRT, either for cure or palliation, for a stage I-IV histologically proven MALT or MZL between 2016 and 2020. Response to LDRT was evaluated with the Lugano criteria. Local control (LC), distant relapse-free survival (DRFS), progression-free survival (PFS) and overall survival (OS) were stratified for treatment intent (curative vs palliative) and estimated by the Kaplan-Meier product-limit. RESULTS: Among 45 consecutively enrolled patients with a median age of 68 years (range 22-86), 26 (58%) were female. Thirty-one patients (69%) with a stage I-II disease received LDRT as first line therapy and with a curative intent. Overall response rate was 93%, with no significant difference among curative and palliative intent. With a median follow-up of 18 months, LC, DRFS, PFS and OS at 2 years were 93, 92, 76 and 91%, respectively, in the overall population. Patients receiving curative LDRT had a better PFS at 2 years (85% vs 54%, p < 0.01) compared to patients receiving palliative treatment. LDRT was well tolerated in all patients, without any significant acute or chronic side-effect. CONCLUSIONS: LDRT is effective and well tolerated in patients affected with MALT or nodal MZL, achieving high response rates and durable remission at 2 years. ADVANCES IN KNOWLEDGE: This study shows the efficacy of LDRT in the treatment of MALT and MZL.

Delta radiomics for rectal cancer response prediction using low field magnetic resonance guided radiotherapy: an external validation.

INTRODUCTION: A recent study performed on 16 locally advanced rectal cancer (LARC) patients treated using magnetic resonance guided radiotherapy (MRgRT) has identified two delta radiomics features as predictors of clinical complete response (cCR) after neoadjuvant radio-chemotherapy (nCRT). This study aims to validate these features (ΔLleast and Δglnu) on an external larger dataset, expanding the analysis also for pathological complete response (pCR) prediction. METHODS: A total of 43 LARC patients were enrolled: Gross Tumour Volume (GTV) was delineated on T2/T1* MR images acquired during MRgRT and the two delta features were calculated. Receiver Operating Characteristic (ROC) curve analysis was performed on the 16 cases of the original study and the best cut-off value was identified. The performance of ΔLleast and Δglnu was evaluated at the best cut-off value. RESULTS: On the original dataset of 16 patients, ΔLleast reported an AUC of 0.81 for cCR and 0.93 for pCR, while Δglnu 0.72 and 0.54 respectively. The best cut-off values of ΔLleast was 0.73 for both outcomes, while Δglnu reported 0.54 for cCR and 0.93 for pCR. At the external validation, ΔLleast showed an accuracy of 81% for cCR and 79% for pCR, while Δglnu reported 63% for cCR and 40% for pCR. CONCLUSION: The accuracy of ΔLleast in predicting cCR and pCR is significantly higher than those obtained considering Δglnu, but inferior if compared with other image-based biomarker, such as the early-regression index. Studies with larger cohorts of patients are recommended to further investigate the role of delta radiomic features in MRgRT.

Adoption of Expansion Margins to Reduce the Dose Received by the Coronary Arteries and the Risk of Cardiovascular Events in Lymphoma Patients.

PURPOSE: Mediastinal radiation therapy (RT) in patients with lymphoma implies involuntary coronary artery (CA) exposure, resulting in an increased risk of coronary artery disease (CAD). Accurate delineation of CAs may spare them from higher RT doses. However, heart motion affects the estimation of the dose received by CAs. An expansion margin (planning organ at risk volume [PRV]), encompassing the nearby area where CAs displace, may compensate for these uncertainties, reducing CA dose and CAD risk. Our study aimed to evaluate if a planning process optimized on CA-specific PRVs, rather than just on CAs, could provide any dosimetric or clinical benefit. METHODS AND MATERIALS: Forty patients receiving RT for mediastinal lymphomas were included. We contoured left main trunk, left anterior descending, left circumflex, and right coronary arteries. An isotropic PRV was then applied to all CAs, in accordance with literature data. A comparison was then performed by optimizing treatment plans either on CAs or on PRVs, to detect any difference in CA sparing in terms of maximum (Dmax), median (Dmed), and mean (Dmean) dose. We then investigated, through risk modeling, if any dosimetric benefit obtained with the PRV-related optimization process could translate to a lower risk of ischemic complications. RESULTS: Plan optimization on PRVs demonstrated a significant dose reduction (range, 7%-9%) in Dmax, Dmed, and Dmean for the whole coronary tree, and even higher dose reductions when vessels were located 5- to 20-mm from PTV (range, 13%-15%), especially for left main trunk and left circumflex (range, 16%-21%). This translated to a mean risk reduction of developing CAD of 12% (P < .01), which increased to 17% when CAs were located 5- to 20-mm from PTV. CONCLUSIONS: Integration of CA-related PRVs in the optimization process reduces the dose received by CAs and translates to a meaningful prevention of CAD risk in patients with lymphoma treated with mediastinal RT.

Bone Marrow-Sparing IMRT in Anal Cancer Patients Undergoing Concurrent Chemo-Radiation: Results of the First Phase of a Prospective Phase II Trial.

PURPOSE: to investigate the role of selective avoidance of hematopoietically active BM within the pelvis, as defined with 18FDG-PET, employing a targeted IMRT approach, to reduce acute hematologic toxicity (HT) profile in anal cancer patients undergoing concurrent chemo-radiation. METHODS: a one-armed two-stage Simon's design was selected to test the hypothesis that BM-sparing approach would improve by 20% the rate of G0-G2 (vs. G3-G4) HT, from 42% of RTOG 0529 historical data to 62% (α = 0.05 and the ß = 0.20). At the first stage, among 21 enrolled patients, at least 9 should report G0-G2 acute HT to further proceed with the trial. We employed 18FDG-PET to identify active BM within the pelvis. Acute HT was assessed via weekly blood counts and scored as per the Common Toxicity Criteria for Adverse Effects version 4.0. RESULTS: from December 2017 to October 2019, 21 patients were enrolled. Maximum observed acute HT comprised 9% rate of ≥G3 leukopenia and 5% rate of ≥G3 neutropenia and anemia. Overall, only 4 out of 21 treated patients (19%) experienced ≥G3 acute HT. Conversely, 17 patients (81%) experienced G0-G2 events, way above the threshold set by the trial design. CONCLUSION: 18FDG-PET-guided BM-sparing IMRT was able to reduce acute HT in anal cancer patients treated with concomitant chemo-radiation. These results prompted us to conclude the second part of this prospective phase II trial.

A deep learning approach to generate synthetic CT in low field MR-guided adaptive radiotherapy for abdominal and pelvic cases.

PURPOSE: Artificial intelligence (AI) can play a significant role in Magnetic Resonance guided Radiotherapy (MRgRT), especially to speed up the online adaptive workflow. The aim of this study is to set up a Deep Learning (DL) approach able to generate synthetic computed tomography (sCT) images from low field MR images in pelvis and abdomen. METHODS: A conditional Generative Adversarial Network (cGAN) was used for sCT generation: a total of 120 patients treated on pelvic and abdominal sites were enrolled and divided in training (80) and test sets (40). Intensity modulated radiotherapy (IMRT) treatment plans were calculated on sCT and original CT and then compared in terms of gamma analysis and differences in Dose Volume Histogram (DVH). The two one-sided test for paired samples (TOST-P) was used to evaluate the equivalence among different DVH parameters calculated for target and organs at risks (OAR) on CT and sCT images. RESULTS: Using a CPU architecture, the mean time required by the neural network to generate a synthetic CT was 175 ± 43 seconds (s) for pelvic cases and 110 ± 40 s for abdominal ones. Mean gamma passing rates for the three tolerance criteria analysed (1%/1 mm, 2%/2 mm and 3%/3 mm) were respectively 90.8 ± 4.5%, 98.7 ± 1.1% and 99.8 ± 0.2% for abdominal cases; 89.3 ± 4.8%, 99.0 ± 0.7% and 99.9 ± 0.2% for pelvic ones, while equivalence within 1% was observed among the DVH indicators. CONCLUSION: This study demonstrated that sCT generation using a DL approach is feasible for low field MR images in pelvis and abdomen, allowing a reliable calculation of IMRT plans in MRgRT.

Quantitative analysis of MRI-guided radiotherapy treatment process time for tumor real-time gating efficiency.

PURPOSE: Magnetic Resonance-guided radiotherapy (MRgRT) systems allow continuous monitoring of therapy volumes during treatment delivery and personalized respiratory gating approaches. Treatment length may therefore be significantly affected by patient's compliance and breathing control. We quantitatively analyzed treatment process time efficiency (TE ) using data obtained from real-world patient treatment logs to optimize MRgRT delivery settings. METHODS: Data corresponding to the first 100 patients treated with a low T hybrid MRI-Linac system, both in free breathing (FB) and in breath hold inspiration (BHI) were collected. TE has been computed as the percentage difference of the actual single fraction's total treatment time and the predicted treatment process time, as computed by the TPS during plan optimization. Differences between the scheduled and actual treatment room occupancy time were also evaluated. Finally, possible correlations with planning, delivery and clinical parameters with TE were also investigated. RESULTS: Nine hundred and nineteen treatment fractions were evaluated. TE difference between BHI and FB patients' groups was statistically significant and the mean TE were 42.4%, and -0.5% respectively. No correlation was found with TE for BHI and FB groups. Planning, delivering and clinical parameters classified BHI and FB groups, but no correlation with TE was found. CONCLUSION: The use of BHI gating technique can increase the treatment process time significantly. BHI technique could be not always an adequate delivery technique to optimize the treatment process time. Further gating techniques should be considered to improve the use of MRgRT.

Inclusion of heart substructures in the optimization process of volumetric modulated arc therapy techniques may reduce the risk of heart disease in Hodgkin's lymphoma patients.

BACKGROUND AND PURPOSE: Radiotherapy is an effective treatment for Hodgkin's lymphoma (HL), but increases the risk of long term complications as cardiac events and second cancers. This study aimed to reduce the risk of cardiovascular events through an optimization of the dose distribution on heart substructures in mediastinal HL patients with the adoption of different volumetric modulated arc therapy (VMAT) techniques, while maintaining the same risk of second cancer induction on lungs and breasts. MATERIALS AND METHODS: Thirty patients (15 males and 15 females, 15 bulky lesions) treated between 2012 and 2017 at our institution were selected. Disease extent was mediastinum plus neck (n = 10), mediastinum plus unilateral axilla (n = 10) and mediastinum alone (n = 10). Lungs, breasts, whole heart and sub-structures (coronary arteries, valves and chambers) were contoured as organs at risk and included in the optimization process. A "first-generation" multi-arc butterfly VMAT (B-VMAT) planning solution was compared to a full-arc butterfly VMAT (FaB-VMAT) approach, consisting of a full arc plus a non-coplanar arc. Lifetime attributable risk (LAR) of second breast and lung cancer and relative risk (RR) of coronary artery disease (CAD) and chronic heart failure (CHF) were estimated. RESULTS: FaB-VMAT resulted in lower mean dose to whole heart (7.6 vs 6.9 Gy, p = 0.003), all coronary arteries (16.1 vs 13.5 Gy, p < 0.001), left ventricle (4.2 vs 3.4 Gy, p = 0.007) and in lower V20Gy to the lungs (15% vs 14%, p = 0.008). A significant lower RR for CAD and CHF was observed for FaB-VMAT. The risk of second breast and lung cancer was comparable between the two solutions, with the exception of female patients with mediastinal bulky involvement, where B-VMAT resulted in lower mean dose (2.8 vs 3.5 Gy, p = 0.03) and V4Gy (22% vs 16%, 0.04) to breasts, with a significant reduction in LAR (p = 0.03). CONCLUSIONS: FaB-VMAT significantly decreased the RR for CAD and CHF compared to B-VMAT, with almost the same overall risk of lung and breast cancer induction. These results are influenced by the different anatomical presentations, supporting the need for an individualized approach.

Plan optimization for mediastinal radiotherapy: Estimation of coronary arteries motion with ECG-gated cardiac imaging and creation of compensatory expansion margins.

BACKGROUND AND PURPOSE: Inadvertent heart and coronary arteries (CA) irradiation may increase the risk of coronary artery disease (CAD) in patients receiving thoracic irradiation. To date, the entity of cardiac-related CA displacement and the possible margins to be used for planning organs at risk volume (PRV) have been poorly described. Aim of this study was to quantify CA displacement and to estimate PRV through the use of ECG-gated computed tomography (CT) scans. MATERIAL AND METHODS: Eight patients received an ECG-gated intravenous contrast enhanced CT for non-cancer related reasons. Nine data sets were reconstructed over the entire R-R cycle with a dedicated retrospective algorithm and the following structures were delineated: Left main trunk (LM), left anterior descending (LAD), left circumflex (CX) and right coronary artery (RCA). CA displacements across the different cardiac phases were evaluated in left-right (X), cranio-caudal (Y) and anteroposterior (Z) directions using the McKenzie-van Herk formula (1.3 * Σ + 0.5 * σ). RESULTS: The following CA displacements were found in X, Y and Z coordinates: 3.6, 2.7 and 2.7 mm for LMT, respectively; 2.6, 5.0 and 6.8 mm for LAD, respectively; 3.5, 4.5 and 3.7 mm for CX, respectively; 3.6, 4.6 and 6.9 mm for RCA, respectively. Based on the mean displacements, we created a PRV of 3 mm for LM, 4 mm for CX and 5 mm for LAD and RCA. CONCLUSION: CA showed relevant displacements over the heart cycle, suggesting the need for a specific PRV margin to accurately estimate the dose received by these structures and optimize the planning process.