Background: Possible advantages of magnetic resonance (MR)-guided radiation therapy (MRgRT) for the treatment of brain tumors include improved definition of treatment volumes and organs at risk (OARs) that could allow margin reductions, resulting in limited dose to the OARs and/or dose escalation to target volumes. Recently, hybrid systems integrating a linear accelerator and an magnetic resonance imaging (MRI) scan (MRI-linacs, MRL) have been introduced, that could potentially lead to a fully MRI-based treatment workflow. Methods: We performed a systematic review of the published literature regarding the adoption of MRL for the treatment of primary or secondary brain tumors (last update November 3, 2022), retrieving a total of 2487 records; after a selection based on title and abstracts, the full text of 74 articles was analyzed, finally resulting in the 52 papers included in this review. Results and discussion: Several solutions have been implemented to achieve a paradigm shift from CT-based radiotherapy to MRgRT, such as the management of geometric integrity and the definition of synthetic CT models that estimate electron density. Multiple sequences have been optimized to acquire images with adequate quality with on-board MR scanner in limited times. Various sophisticated algorithms have been developed to compensate the impact of magnetic field on dose distribution and calculate daily adaptive plans in a few minutes with satisfactory dosimetric parameters for the treatment of primary brain tumors and cerebral metastases. Dosimetric studies and preliminary clinical experiences demonstrated the feasibility of treating brain lesions with MRL. Conclusions: The adoption of an MRI-only workflow is feasible and could offer several advantages for the treatment of brain tumors, including superior image quality for lesions and OARs and the possibility to adapt the treatment plan on the basis of daily MRI. The growing body of clinical data will clarify the potential benefit in terms of toxicity and response to treatment.

Background and purpose: Although chemotherapy, biological agents, and radiotherapy (RT) are cornerstones of the treatment of multiple myeloma (MM), the literature regarding the possible interactions of concurrent systemic treatment (CST) and RT is limited, and the optimal RT dose is still unclear. Materials and methods: We retrospectively analyzed the records of patients who underwent RT for MM at our institution from 1 January 2005 to 30 June 2020. The data of 312 patients and 577 lesions (treated in 411 accesses) were retrieved. Results: Most of the treated lesions involved the vertebrae (60%) or extremities (18.9%). Radiotherapy was completed in 96.6% of the accesses and, although biologically effective doses assuming an α/β ratio of 10 (BED 10) > 38 Gy and CST were significantly associated with higher rates of toxicity, the safety profile was excellent, with side effects grade ≥2 reported only for 4.1% of the accesses; CST and BED 10 had no impact on the toxicity at one and three months. Radiotherapy resulted in significant improvements in performance status and in a pain control rate of 87.4% at the end of treatment, which further increased to 96.9% at three months and remained at 94% at six months. The radiological response rate at six months (data available for 181 lesions) was 79%, with only 4.4% of lesions in progression. Progression was significantly more frequent in the lesions treated without CST or BED 10 < 15 Gy, while concurrent biological therapy resulted in significantly lower rates of progression. Conclusion: Radiotherapy resulted in optimal pain control rates and fair toxicity, regardless of BED 10 and CST; the treatments with higher BED 10 and CST (remarkably biological agents) improved the already excellent radiological disease control.

Introduction and Aim: Stage III Non-Small Cell Lung Cancer (NSCLC) has a poor prognosis, with median survival ranging from 9 to 34 months. The PACIFIC trial demonstrated that durvalumab after platinum-based chemoradiotherapy (CRT) improves overall survival (OS) and progression-free survival (PFS). This review evaluates real-world evidence (RWE) on durvalumab’s efficacy and safety, focusing on patient characteristics, prognostic factors, treatment protocols, and outcomes beyond progression. Materials and Methods: A literature search of PubMed, Embase, and Google Scholar identified 49 observational studies published from January 2017 to August 2024 on unresectable stage III NSCLC. Clinical trials, early-stage disease, and alternative treatments were excluded. Results: Compared to the PACIFIC trial, real-world patients were older, had poorer ECOG performance (≥2), and more comorbidities like COPD. Despite this, durvalumab provided consistent survival benefits. Positive prognostic factors included non-squamous histology, high PD-L1 expression, and timely durvalumab initiation (≤42 days post-CRT). Most radiotherapy regimens mirrored PACIFIC (54–66 Gy). Concomitant CRT was used in 90% of cases, with sequential CRT for frail patients. Chemotherapy regimens varied. Immune-mediated pneumonitis was a major adverse event, with incidence rates between 15% and 100%. Severe cases led to treatment discontinuation, impacting survival. Treatment beyond progression remains uncertain, with limited benefits from immunotherapy rechallenge. Conclusions: RWE supports durvalumab’s efficacy, emphasizing the need for personalized treatment strategies and further research to improve long-term outcomes.

The use of immunotherapy (IOT) in treating non-small-cell lung cancer (NSCLC) has revolutionized care standards. However, full compliance with neoadjuvant, perioperative, and adjuvant treatment protocols remains a challenge. This study aims to evaluate compliance rates with IOT-based protocols in neoadjuvant, adjuvant, and perioperative settings. A systematic review and meta-analysis were conducted on prospective clinical trials involving preoperative, perioperative, and postoperative IOT protocols in resectable NSCLC up to December 2024. Primary outcomes included compliance with medical treatment (e.g., omission of therapy rate, incomplete therapy rate, and omission of surgery rate), surgical outcomes (R0 resection rate), and post-treatment severe adverse events (AEs). A total of 30 studies, with 10,493 patients, were included. In the neoadjuvant settings, 26 studies (16 neoadjuvant; 10 perioperative) investigated IOT alone or in combination with chemotherapy. Almost all patients received at least one therapy administration, while 11.3 % experienced incomplete cycles. Surgery was not performed in 16.1 % of cases, and an R0 resection was achieved in 80.5 % of patients. Grade ≥ 3 AEs were observed in 67.7 % of patients. In the adjuvant setting, 14 studies evaluated IOT (4 adjuvant; 10 perioperative). Complete omission of adjuvant therapy occurred in 9,6 % of patients, while 34,6 % required a discontinuation or cycle reduction. Grade ≥ 3 were AEs observed in 19.0 % of patients. Overall protocol compliance was superior in neoadjuvant protocols (effect size: 0.78 [IC 95 %: 0.70-0.85]) compared to adjuvant protocols (effect size: 0.61 [IC 95 %: 0.53-0.69]) and perioperative protocols (effect size: 0.49 [IC 95 %: 0.43-0.55]). However, perioperative protocols showed similar compliance and Grade ≥ 3 AE rates compared to preoperative and postoperative protocols. Compliance with treatment protocols in NSCLC remains a critical factor, particularly for radical surgery candidates. This study represents a landmark effort in synthesizing comprehensive data on compliance with immunotherapy protocols in resectable NSCLC. Improving protocol compliance through tailored strategies and multidisciplinary coordination is essential to maximize the therapeutic potential of immunotherapy in resectable NSCLC and enhance patient outcomes.

MR-linac could offer several advantages for radical radiochemotherapy (RCHT) in oropharyngeal squamous cell carcinoma (OPSCC) patients. Currently, only a few case series have been published and no comparison with other techniques have been performed. Data of 34 consecutive patients treated from September 2022 to May 2024 at a single Institution with RCHT on Unity® MR-linac for OPSCC with daily adaptive radiotherapy (RT) according to the adapt-to-shape (ATS) workflow were prospectively analyzed. A comparative cohort of 34 patients with similar characteristics treated with helical treatment on Radixact® was retrieved. Characteristics were well balanced across the two groups. Maximal toxicity grade ≥2 rate was borderline higher at RT end in MRI-linac group (p 0.049), but lower one month after RT (76.5 % vs 91.2 %; p = 0.257).Non-significantly lower rates of grade ≥2 xerostomia and dysgeusia were reported in Unity® group one and three months after RT. Higher rates of hospitalizations were reported in Radixact group at 20 fractions and at RT end (64.1 % vs 35.3 %; p = 0.015). Mean Karnofsky performance status (KPS) was higher in Unity group three months after RT (87.67 vs 83.87; p = 0.038).After a median follow up of 361.5 days, local complete response was reported for 93.6 % of patients treated with Unity® and 96.8 % of patients treated with Radixact®. Results of this analysis support the feasibility of an ATS MR-linac workflow for RCHT in OPSCC. Compared with tomotherapy, treatment with Unity® resulted in significantly lower rates of hospitalization and higher KPS three months after RT. Grade 2 xerostomia and dysgeusia rates were non-significantly lower in Unity group. Optimal results in terms of local control were reported for both techniques.