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Background: Definitive local therapy with stereotactic ablative radiation therapy (SABR) for ultracentral lung lesions is associated with a high risk of toxicity, including treatment related death. Stereotactic MR-guided adaptive radiation therapy (SMART) can overcome many of the challenges associated with SABR treatment of ultracentral lesions., Methods: We retrospectively identified 14 consecutive patients who received SMART to ultracentral lung lesions from 10/2019 to 01/2021. Patients had a median distance from the proximal bronchial tree (PBT) of 0.38 cm. Tumors were most often lung primary (64.3%) and HILUS group A (85.7%). A structure-specific rigid registration approach was used for cumulative dose analysis. Kaplan-Meier log-rank analysis was used for clinical outcome data and the Wilcoxon Signed Rank test was used for dosimetric data., Results: Here we show that SMART dosimetric improvements in favor of delivered plans over predicted non-adapted plans for PBT, with improvements in proximal bronchial tree DMax of 5.7 Gy (p = 0.002) and gross tumor 100% prescription coverage of 7.3% (p = 0.002). The mean estimated follow-up is 17.2 months and 2-year local control and local failure free survival rates are 92.9% and 85.7%, respectively. There are no grade ≥ 3 toxicities., Conclusions: SMART has dosimetric advantages and excellent clinical outcomes for ultracentral lung tumors. Daily plan adaptation reliably improves target coverage while simultaneously reducing doses to the proximal airways. These results further characterize the therapeutic window improvements for SMART. Structure-specific rigid dose accumulation dosimetric analysis provides insights that elucidate the dosimetric advantages of SMART more so than per fractional analysis alone., (© 2024. The Author(s).)

Stereotactic body radiotherapy (SBRT) is an effective radiation therapy technique that has allowed for shorter treatment courses, as compared to conventionally dosed radiation therapy. As its name implies, SBRT relies on daily image guidance to ensure that each fraction targets a tumor, instead of healthy tissue. Magnetic resonance imaging (MRI) offers improved soft-tissue visualization, allowing for better tumor and normal tissue delineation. MR-guided RT (MRgRT) has traditionally been defined by the use of offline MRI to aid in defining the RT volumes during the initial planning stages in order to ensure accurate tumor targeting while sparing critical normal tissues. However, the ViewRay MRIdian and Elekta Unity have improved upon and revolutionized the MRgRT by creating a combined MRI and linear accelerator (MRL), allowing MRgRT to incorporate online MRI in RT. MRL-based MR-guided SBRT (MRgSBRT) represents a novel solution to deliver higher doses to larger volumes of gross disease, regardless of the proximity of at-risk organs due to the (1) superior soft-tissue visualization for patient positioning, (2) real-time continuous intrafraction assessment of internal structures, and (3) daily online adaptive replanning. Stereotactic MR-guided adaptive radiation therapy (SMART) has enabled the safe delivery of ablative doses to tumors adjacent to radiosensitive tissues throughout the body. Although it is still a relatively new RT technique, SMART has demonstrated significant opportunities to improve disease control and reduce toxicity. In this review, we included the current clinical applications and the active prospective trials related to SMART. We highlighted the most impactful clinical studies at various tumor sites. In addition, we explored how MRL-based multiparametric MRI could potentially synergize with SMART to significantly change the current treatment paradigm and to improve personalized cancer care.

Introduction: High-dose total body irradiation (TBI) is often part of myeloablative conditioning in acute leukemia. Modern volumetric modulated arc therapy (VMAT)-based plans employ arcs to the inferior-most portion of the body that can be simulated in a head-first position and use 2D planning for the inferior body which can result in heterogeneous doses. Here, we describe our institution's unique protocol for delivering high-dose TBI entirely with VMAT and retrospectively compare dosimetric outcomes with helical tomotherapy (HT) plans. Additionally, we describe our method of oropharyngeal mucosal sparing that was implemented after fatal mucositis occurred in two patients. Methods: Thirty-one patients were simulated and treated in head-first (HFS) and feet-first (FFS) orientations. Patients were treated with VMAT (n = 26) or HT (n = 5). In VMAT plans, to synchronize doses between the orientations, images were deformably registered and the HFS dose was transferred to the FFS plan and used as a background dose when optimizing plans. Six to eight isocenters with two arcs per isocenter were generated. HT was delivered with an established technique. Patients were treated to 13.2 Gy over eight twice daily fractions. Dosimetric outcomes and toxicities were retrospectively compared. Results: Prescription dose and organ at risk (OAR) constraints were met for all patients. Lower lung doses were achieved with VMAT relative to HT plans (7.4 vs 7.7 Gy, P  = .009). Statistically significant improvement in mucositis was not achieved after adopting a mucosal-sparing technique, however lower doses to the oropharyngeal mucosal were achieved (6.9 vs 14.1 Gy, P  = .009), and no further mucositis-related deaths occurred. Conclusions: This full-body VMAT method of TBI achieves dose goals, eliminates risk of heterogenous doses within the femur, and demonstrates that selective OAR sparing with the purpose of reducing TBI-related morbidity and mortality is possible at any institution with a VMAT-capable linear accelerator.

Background: The systemic immune-inflammation index (SII) correlates with patient survival in various types of solid malignancies, including non-small cell lung cancer (NSCLC). However, limited information is available on the prognostic implication and disease-specific survival of SII in patients undergoing definitive chemoradiation therapy (CRT) for stage III NSCLC., Methods: We retrospectively reviewed 125 patients who underwent curative intent CRT for stage III NSCLC with sufficient laboratory assessment from 2010-2019. SII was calculated at the time of diagnosis as platelet count × neutrophil count/lymphocyte count. Chi-squared analysis was used to compare categorical variables. A Kaplan-Meier analysis was performed to estimate progression-free survival (PFS), disease specific survival (DSS), and overall survival (OS) rates, with Cox regression used to determine absolute hazards., Results: At a median follow-up of 19.7 months, 5-year OS, DSS, and PFS rates were 22.6%, 30.9%, and 13.4%, respectively. A low SII (<1,266) at diagnosis was independently associated with an improved OS (HR: 0.399, 95%, CI: 0.247-0.644, P<0.001), DSS (HR: 0.383, 95%, CI: 0.228-0.645, P<0.001), and PFS (HR: 0.616, 95%, CI: 0.407-0.932, P=0.022). We did not detect an association between SII and freedom from recurrence (FFR), freedom from locoregional recurrence (FFLRR), or freedom from distant recurrence (FFDR). NSAID (1,483.4 vs. 2,302.9, P=0.038) and statin usage (1,443.9 vs. 2,201.7, P=0.046) were associated with a lower SII while COPD exacerbations (2,699.7 vs. 1,573.7, P=0.032) and antibiotic prescriptions (2,384.6 vs. 1,347.9, P=0.009) were associated with an elevated SII. These factors were not independently associated with improved survival outcomes., Conclusions: Low SII scores were independently associated with improved OS, DSS, and PFS rates in patients with stage III NSCLC undergoing definitive CRT. NSAIDs and statin usage may be associated with lower SII at diagnosis of NSCLC. This study suggests that SII may be an effective prognostic indicator of patient mortality. Further investigation of the therapeutic potential of these agents in patients with an elevated SII in this setting may be warranted., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-6710). The authors have no conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)