Structure-specific rigid dose accumulation dosimetric analysis of ablative stereotactic MRI-guided adaptive radiation therapy in ultracentral lung lesions.

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.

Stereotactic MR-guided Adaptive Radiation Therapy (SMART) is a type of radiation therapy for cancer. With SMART, treatment can be adapted based on daily changes in the body seen via imaging. SMART can safely deliver radiation to lung tumors near the center of the body which are risky to treat, due to potential damage to nearby organs. We looked at 14 patients who received SMART to determine how much changing the radiation plan each day improved our ability to safely deliver high doses. We found that SMART not only improved our ability to cover the entirety of the tumor with the dose originally intended, but also reduced dose to nearby organs. Treatment resulted in excellent control of the tumor with few side effects. SMART shows promise for safer and more effective treatment for lung tumors in this part of the body.

Thirty-day mortality as a metric for palliative radiotherapy in pediatric patients.

PURPOSE OF REVIEW: Thirty-day mortality (30DM) is an emerging consideration for determining whether terminally ill adult patients may benefit from palliative radiotherapy (RT). However, the efficacy and ethics of delivering palliative RT at the end of life (EOL) in children are seldom discussed and not well-established. RECENT FINDINGS: Palliative RT is perhaps underutilized among patients ≤21 years old with rates as low as 11%. While effective when delivered early, clinical benefit decreases when administered within the last 30 days of life. Pediatric 30DM rates vary widely between institutions (0.7-30%), highlighting the need for standardized practices. Accurate prognosis estimation remains challenging and prognostic models specific to palliative pediatric patients are limited. Discordance between provider and patient/parent perceptions of prognosis further complicates decision-making. SUMMARY: RT offers effective symptom control in pediatric patients when administered early. However, delivering RT within the last 30 days of life may provide limited clinical benefit and hinder optimal EOL planning and care. Early referral for palliative RT, preferably with fewer fractions (five or fewer), along with multidisciplinary supportive care, optimizes the likelihood of maintaining patients' quality of life. Prognosis estimation remains difficult, and improving patient and family understanding is crucial. Further research is needed to refine prognostic models and enhance patient-centered care.

Palliative whole brain radiation therapy: an international state of practice.

BACKGROUND: Improvements in radiation delivery and systemic therapies have resulted in few remaining indications for palliative whole brain radiation therapy (WBRT). Most centers preferentially use stereotactic radiotherapy (SRT) and reserve WBRT for those with >15 lesions, leptomeningeal presentation, rapidly progressive disease, or limited estimated survival. Despite regional differences among preferred dose, fractionation, and treatment technique, we predict survival post-WBRT will remain poor-indicating appropriate application of WBRT in this era of SRT and improved systemic therapies. METHODS: A multi-center, international retrospective analysis of patients receiving WBRT in 2022 was performed. Primary end point was survival after WBRT. De-identified data were analyzed centrally. Patients receiving WBRT as part of a curative regimen, prophylactically, or as bridging therapy were excluded. The collected data consisted of patient parameters including prescription dose and fractionation, use of neurocognitive sparing techniques and survival after WBRT. Survival was calculated via the Kaplan-Meier method. RESULTS: Of 29,943 international RT prescriptions written at ten participating centers in 2022, 462 (1.5%) were for palliative WBRT. Participating centers were in the United States (n=138), the United Kingdom (n=111), Hong Kong (n=72), Italy (n=49), Belgium (n=45), Germany (n=27), Ghana (n=15), and Cyprus (n=5). Twenty-six different dose regimens were used. The most common prescriptions were for 3,000 cGy over 10 fractions (45.0%) and 2,000 cGy over 5 fractions (43.5%) with significant regional preferences (P<0.001). Prior SRT was delivered in 32 patients (6.7%), hippocampal avoidance (HA) was used in 44 patients (9.5%), and memantine was prescribed in 93 patients (20.1%). Survival ranged from 0 days to still surviving at 402 days post-treatment. The global median overall survival (OS) was 84 days after WBRT [95% confidence interval (CI): 68.0-104.0]. Actuarial survival at 7 days, 1 month, 3 months, and 6 months were 95%, 78%, 48%, and 32%, respectively. Twenty-seven patients (5.8%) were unable to complete their prescribed WBRT. CONCLUSIONS: This moment-in-time analysis confirms that patients with poor expected survival are being appropriately selected for WBRT-illustrating the dwindling indications for WBRT-and demonstrates the variance in global practice. Since poor survival precludes patients from deriving benefit, memantine and HA are best suited in carefully selected cases.

Feasibility and Toxicity of Full-Body Volumetric Modulated Arc Therapy Technique for High-Dose Total Body Irradiation.

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.

Stereotactic Magnetic Resonance-Guided Adaptive and Non-Adaptive Radiotherapy on Combination MR-Linear Accelerators: Current Practice and Future Directions.

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.

Systemic inflammation is associated with inferior disease control and survival in stage III non-small cell lung cancer.

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.

Impact of statin use on overall and time to biochemical failure following radical prostatectomy or radiation therapy.

OBJECTIVES: To assess the impact of statin use on overall and time to biochemical failure following primary treatment of localized prostate cancer (PCa). SUBJECTS/PATIENTS AND METHODS: 1581 patients undergoing radical prostatectomy (RP) or radiation therapy (RT) for primary treatment of PCa between July 2007 and January 2020 were evaluated for statin use, demographic/oncologic characteristics, and biochemical outcomes. Rate of biochemical failure (BF) was assessed overall and at 1, 3, and 5 years; time to BF was estimated with Kaplan-Meier. Logistic and linear regression were used to control for treatment modality and disease characteristics. RESULTS: The average age was 63.0 ± 7.5 years and median pre-treatment PSA was 6.55 (IQR 4.94). 1473 (93.2%) and 108 (6.8%) underwent RP and RT, respectively. RP patients were younger, had lower pre-PSA, lower BMI, and lower risk disease. At 3.4 ± 2.7 years follow-up, 323 (20.4%) experienced BF. When stratified by statin use, BF overall and within 1, 3, and 5 years were not different. Time to BF, was lower in patients using statins (1.8 ± 1.9 years vs. 2.4 ± 2.6 years; p = 0.016). These results persisted in multivariate analysis, wherein statin use was not associated with BF but was associated with a shorter time to BF. CONCLUSION: Overall, statin use was not associated with a reduced risk of BF in RP or RT patients. However, for patients with BF, statin use was associated with a decreased time to BF. Future investigations are warranted to further elucidate the impact of statin use on PCa recurrence.

Protective Effects of Metformin Against Biochemical Failure Following Radical Prostatectomy or Radiation Therapy in Localized Prostate Cancer.

OBJECTIVE: To assess the impact of metformin on biochemical failure (BF) in localized prostate cancers (PC) treated with radical prostatectomy or radiation therapy. MATERIALS AND METHODS: About 1449 patients undergoing radical prostatectomy (n = 1338, 92.3%) or radiation therapy (n = 108, 7.5%) for localized PC between July 2007 and January 2020 were evaluated for metformin use, demographic/oncologic characteristics, and biochemical outcomes. Androgen deprivation therapy was utilized per NCCN guidelines. BF rates were assessed overall and at 1, 3, and 5 years. Time to BF was estimated via Kaplan-Meier; logistic regression and Cox proportionate hazards models were generated to adjust for significant differences. RESULTS: Of 1449 patients, 148 (10.2%) utilized metformin at time of diagnosis, while 1,301 (89.8%) did not. Patients on metformin were significantly older, had higher body mass indexes, and more aggressive disease (Gleason score >7). At a mean ± SD follow-up of 3.6 ± 2.6 years, patients on metformin were less likely to experience BF at later timepoints; however, univariate analysis showed no differences at 1, 3, and 5 years. In multivariate analysis, patients on metformin were significantly less likely to experience BF at 5 years and overall in both treatment groups. In Cox regression, metformin was independently associated with a 40% relative risk reduction in BF. CONCLUSION: In multivariate analysis, metformin use was associated with a significant risk reduction in BF overall and at 5 years following primary treatment; this trend was not witnessed in univariate analysis. This suggests the need for future investigations of metformin's role in disease-free survival in men with localized PC.

Expansion of Two-dimension Electrospun Nanofiber Mats into Three-dimension Scaffolds.

Electrospinning has been the preferred technology in producing a synthetic, functional scaffold due to the biomimicry to extracellular matrix and the ease control of composition, structure, and diameter of fibers. However, despite these advantages, traditional electrospun nanofiber scaffolds come with limitations including disorganized nanofiber orientation, low porosity, small pore size, and mainly two-dimensional mats. As such, there is a great need for developing a new process for fabricating electrospun nanofiber scaffolds that can overcome the above limitations. Herein, a novel and simple method is outlined. A traditional 2D nanofiber mat is transformed into a 3D scaffold with desired thickness, gap distance, porosity, and nanotopographic cues to allow for cell seeding and proliferation through the depressurization of subcritical CO2 fluid. In addition to providing a scaffold for tissue regeneration to occur, this method also provides the opportunity to encapsulate bioactive molecules such as antimicrobial peptides for local drug delivery. The CO2 expanded nanofiber scaffolds hold great potential in tissue regeneration, wound healing, 3D tissue modeling, and topical drug delivery.