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.

Background and Aims: Stereotactic arrhythmia radioablation (STAR) is increasingly used for refractory ventricular tachycardia (VT), yet prospective multicentre outcome data remain limited. Here, the planned interim analysis of the prospective Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) registry is reported. Methods: STOPSTORM is a European prospective, international, multicentre registry of patients treated with STAR. The primary efficacy endpoint was the change in sustained VT episode burden comparing the 6 months before versus the 6 months after STAR. The primary safety endpoint was the occurrence of serious adverse events (SAEs) adjudicated as possibly or probably treatment-related. Overall survival was assessed using time-to-event methods. Results: Across 28 centres, 193 patients were included (mean age 68±9 years; 88% male; 53% non-ischaemic cardiomyopathy). Median follow-up was 19 months. Among 107 evaluable patients with ≥6-month follow-up, the median VT episode burden was reduced by 80% after STAR. Among patients surviving ≥6 months, 72% were free from implantable cardioverter-defibrillator (ICD) shock. In the full cohort, 12 SAEs were adjudicated as possibly or probably treatment-related, including pericardial effusion, coronary events, and early post-treatment ventricular arrhythmia. Overall survival probability was 77% at 12 months. Conclusions: In the largest prospective multicentre cohort reported to date, STAR was associated with a substantial reduction in VT burden and ICD shocks, with a low frequency of possibly or probably treatment-related SAEs.

Long-term cancer survivors are at high risk of developing cardiac complications from the treatments, both systemic agents and thoracic irradiation, received to cure the primary tumor. Modern advances, particularly in the field of radiotherapy, aim to reduce the risk of cardiovascular disease. Also, new diagnostic tools increasingly improve their efficacy in early detection of the preclinical treatment-induced cardiac damage. In this review, we summarize the mechanisms of radiotherapy- and chemotherapy-induced cardiac injury, the available clinical data, the strategies to mitigate cardiac exposure with modern radiotherapy and the current diagnostic tools for an early detection and prompt management of these complications in long-term cancer survivors.

Local ablative therapy (LAT), intended as stereotactic ablative radiotherapy or stereotactic radiosurgery, is a well-recognized effective treatment for selected patients with oligometastatic NSCLC. Current clinical evidence supports LAT alone or in combination with systemic therapies. Our retrospective mono-institutional study aims to assess the role of LAT with a peculiar focus on the largest series of non-oncogene addicted oligometastatic NSCLC patients to date. We included in this analysis all patients with the mentioned disease characteristics who underwent LAT for intracranial and/or extracranial metastases between 2011 and 2020. The main endpoints were local control (LC), progression free survival (PFS) and overall survival (OS) in the whole population and after stratification for prognostic factors. We identified a series of 245 consecutive patients (314 lesions), included in this analysis (median age 69 years). In 77% of patients, a single metastasis was treated with LAT and intracranial involvement was the most frequent indication (53% of patients) in our series. The overall response rate (ORR) after LAT was 95%. In case of disease progression, 66 patients underwent new local treatments with curative intent. With a median follow-up of 18 months, median PFS was 13 months (1-year PFS 50%) and median OS was 32 months (1-year OS 75%). The median LC was not reached (1-year LC 89%). The presence of brain metastases was the only factor that negatively affected all clinical endpoints, with a 1-year LC, PFS and OS of 82%, 29% and 62% respectively, compared to 95%, 73% and 91%, respectively, for patients without BMs (p < 0.001 for each endpoint). At the multivariate analysis, mediastinal nodal involvement at baseline (p = 0.049), ECOG PS = 1 (p = 0.011), intracranial disease involvement (p = 0.001), administration of chemotherapy in combination with LAT (p = 0.020), and no delivery of further local treatment for progression or delivery of focal treatment for intracranial progression (p < 0.001) were related to a poorer OS. In our retrospective series, which is to our knowledge the largest to date, LAT showed encouraging results and confirmed the safety and effectiveness of focal treatments in non-oncogene addicted oligometastatic NSCLC patients.

This study explored Continuous Positive Airway Pressure (CPAP) as an alternative to breath-holding (DIBH) techniques by comparing it with free-breathing (FB) in mediastinal lymphoma patients treated with optimized volumetric arc therapy (VMAT). Patients underwent computed tomography (CT) simulation in both FB and CPAP (18 cm H2O). The amount of residual respiratory motion with CPAP was assessed using 4D-CT in 27 patients. Lungs, breasts, heart, and cardiac structures were contoured and included in VMAT optimization. Maximum and mean doses were compared for all organs, and CPAP was used if beneficial. Risks of coronary artery disease (CAD) and chronic heart failure (CHF) were estimated via excess relative risk (ERR). The study included 58 patients (22 males, 36 females; mean age 29 years) with Hodgkin (45) or large B-cell lymphoma (13). The median prescribed dose was 30 Gy (range 30-40 Gy). CPAP was well tolerated by all patients. Only nine patients (16%) had no dosimetric benefit from CPAP and were treated in FB. CPAP increased mean lung volume by 1.6 L (4460 vs 2810 cc, p < 0.01) minimized respiratory motion in patients assessed with 4D-CT (mean residual excursion: 388 cc), and significantly reduced lung V20 (10% vs 12.7%, p < 0.01) and V5 (38.2% vs 42.7%, p < 0.01). Moreover, CPAP decreased the intersection of the whole heart with planning target volume (27.9 to 20.9 cc, p < 0.01), which resulted in lower mean doses to the heart (5.3 vs 6.1 Gy, p < 0.01), coronary arteries (7.6 vs 9.5 Gy, p < 0.01), and left ventricle (2.8 vs 3.5 Gy, p < 0.01). CAD and CHF risks significantly reduced with CPAP (p < 0.01). CPAP significantly reduced radiation doses to lungs and heart, was well tolerated and easy to implement and to use also in department with high patients workload, representing a valid and reproducible alternative to DIBH in mediastinal lymphoma radiotherapy.

Unresectable locally advanced non-small cell lung cancer (LA-NSCLC) remains a therapeutic challenge, despite the paradigm shift established by the PACIFIC trial (concurrent chemoradiation followed by Durvalumab consolidation). A substantial number of patients still experience disease progression and significant toxicity. This narrative review explores innovative radiation therapy (RT) strategies and their integration with systemic therapy. Key innovations analyzed include: 1. Systemic Therapy Intensification: Induction chemo-immunotherapy or novel multi-agent consolidation regimens show promise, but managing increased toxicity remains critical. The integration of DNA damage response inhibitors with RT is also being actively explored to maximize radiosensitization. 2. RT Dose and Volume Modulation: Recent data suggests that dose escalation via highly conformal hypofractionation or stereotactic ablative body radiotherapy (SABR) may enhance efficacy, particularly when combined with immunotherapy. Conversely, risk-adapted de-escalation of dose or volumes is studied to reduce immunosuppression and treatment-related toxicity, allowing more patients, including the elderly and frail, to complete consolidation. 3. Organ-at-Risk (OAR) Sparing: Advanced techniques like intensity-modulated radiation therapy (IMRT), adaptive RT (ART), and proton beam therapy (PBT) are crucial for minimizing dose to OARs and new substructures, such as specific cardiac subregions and lymphoid tissues. This OAR sparing is strongly correlated with improved OS and reduced immunosuppression. In conclusion, this narrative review focuses on the future of LA-NSCLC treatment, which is moving toward personalized, precision RT, embracing both intensification and thoughtful de-escalation, supported by synergistic systemic agents, to maximize curative potential and minimize toxicity.