Radiation Oncology Associates

BackgroundBrepocitinib is a first-in-class, oral, selective TYK2–JAK1 inhibitor that blocks cytokine signaling, which has been implicated in dermatomyositis.MethodsIn this phase 3, double-blind, randomized, placebo-controlled trial, adults with dermatomyositis were assigned in a 1:1:1 ratio to receive once-daily oral brepocitinib at a dose of 30 mg, brepocitinib at a dose of 15 mg, or placebo for 52 weeks. Standard therapies were continued, and glucocorticoids were tapered. The primary end point was the Total Improvement Score, a validated composite myositis index (with scores ranging from 0 to 100 and higher scores indicating greater improvement) at week 52. Key secondary end points, including skin disease activity, glucocorticoid tapering, and physical function, were tested in a multiplicity-controlled sequence.ResultsA total of 241 patients underwent randomization: 81 to receive brepocitinib 30 mg, 81 to receive brepocitinib 15 mg, and 79 to receive placebo. At week 52, the mean Total Improvement Score was 46.5, 37.5, and 31.2, respectively (difference with brepocitinib 30 mg vs. placebo, 15.3; 95% confidence interval [CI], 6.7 to 24.0; P<0.001; difference with brepocitinib 15 mg vs. placebo, 6.3; 95% CI, −2.4 to 14.9). Brepocitinib 30 mg was superior to placebo across all nine key secondary end points, including skin disease activity, systemic glucocorticoid tapering, and functional disability, with improvements observed as early as week 4. Serious infections were more frequent in the brepocitinib 30-mg group than in the placebo group (10% vs. 1%). No deaths occurred during the trial.ConclusionsIn adults with dermatomyositis that was resistant to previous therapy, the use of brepocitinib at a dose of 30 mg (but not at a dose of 15 mg) resulted in significant benefits with respect to a composite myositis index, skin disease severity, glucocorticoid tapering, and functional disability. (Funded by Priovant Therapeutics; ClinicalTrials.gov number, NCT05437263.)

This study aimed to identify sociodemographic predictors of stereotactic body radiotherapy (SBRT) use and assess temporal trends in first-line SBRT use among patients with spinal metastatic renal cell carcinoma (mRCC) in relation to National Comprehensive Cancer Network guidelines. Using the PearlDiver Database, adults with spinal mRCC were identified. The database includes patients from 2010 to 2023. Patients with documented first-line radiotherapy were grouped as either receiving SBRT or conventional external beam radiation therapy (EBRT). Cohorts were compared using the χ2 tests for categorical variables and independent-samples t tests for continuous variables (P<0.05). Utilization trends were examined before versus after guideline implementation in 2019, and predictors of SBRT utilization were evaluated using multivariate logistic regression. Of 86,482 patients with spinal metastatic RCC, 10,988 met the inclusion criteria (SBRT=453; EBRT=10,535). Cohorts differed significantly by age, sex, insurance coverage, and US region. After multivariate analysis, younger age, male sex, commercial insurance, and Midwest or Northeast residence were associated with higher odds of receiving first-line SBRT (P<0.05). SBRT use decreased after 2019, while EBRT use exceeded SBRT in every study year. From 2010 to 2023, EBRT remained the predominant first-line radiotherapy for spinal mRCC. Higher commercial insurance rates among SBRT recipients and regional variability in SBRT use suggest that payer mechanisms and institutional variation may influence first-line SBRT use. Policy alignment with contemporary evidence and expansion of SBRT infrastructure may enhance patient access.

We present UCL-MetIsoLib, a publicly accessible high-resolution tandem mass spectrometry (HRMS/MS) library developed for HILIC-based, ion-pairing-free, isomer-resolved metabolomics using a bioinert UHPLC system and the Acquity Premier BEH Amide column. The platform integrates two complementary methods operating under distinct chromatographic conditions (pH 3.5, ESI+; pH 11.0, ESI-), enabling broad metabolic coverage. A total of 334 metabolites are annotated in the library structure, with thiol derivatization incorporated into the extraction protocol to mitigate redox-driven artifacts. Metabolite identification is supported by 245 authentic reference standards and curated according to MSI Level 1 and Level 2 criteria. Validation followed FDA guidelines for bioanalytical method validation across five biological matrices─urine, plasma, tissues, cells, and patient-derived colorectal organoids. The method demonstrated high precision (<15% RSD intra/inter-day) and recovery (85-115% across all QC levels). To demonstrate biological applicability, UCL-MetIsoLib was applied to a case study comparing healthy and colorectal cancer-derived organoids. The method enabled confident annotation of metabolite isomers, including key glycolytic intermediates such as DHAP and GA3P, as well as sugar phosphates from the glycolysis and pentose phosphate pathways. Metabolic alterations were observed in tumor organoids, including accumulation of nucleotide derivatives and shifts in central carbon metabolism. The library is constantly under expansion and is freely available in its latest version at: https://github.com/kserafimov10/UCLMetIsoLib.

Results of breast conserving therapy with adjuvant radiation therapy (RT) may be impacted by RT effects on breast symmetry, ptosis, and volume. This investigation sought to quantify these effects on breast volume in the setting of oncoplastic reduction mammaplasty performed at the time of lumpectomy. A single-center, retrospective review included women who underwent bilateral oncoplastic reduction mammaplasty simultaneous with lumpectomy (2017 to 2021). Breast volumes were calculated using mammograms 1, 2, and 3 years after RT. Paired t tests compared volumes of irradiated to nonirradiated breasts each year. Multivariable regression explored effects of other variables on volume changes. Thirty-two patients completed 2 years of mammograms, and 28 completed 3 years. At year 1, an irradiated breast comprised approximately 93% of the volume of its nonirradiated counterpart, decreasing approximately 5% (95% CI, 0.4% to 11%; P = 0.04), to 88% of volume at year 2. Comparing years 1 and 3, an irradiated breast comprised 84% of the volume of its nonirradiated counterpart, a 9% volume loss (95% CI, 2.5% to 15%; P = 0.008). Comparing baseline to year 3, multivariable regression demonstrated increasing age was protective against greater volume differences, with a 0.70% increase in volume retained per year of age (95% CI, 0.12% to 1.28%; P = 0.02). Findings demonstrate significant volume discrepancies between irradiated and contralateral nonirradiated breasts over a 3-year period following oncoplastic reduction/RT. Volume difference increased over time, highlighting the long-term impact of RT and need for continuing interventions to address asymmetry. These results may guide preoperative planning and patient counseling regarding long-term results.

SMARCB1-deficient sinonasal carcinoma (SDSC) is a recently recognized rare malignancy. Despite growing awareness, SDSC remains susceptible to misdiagnosis owing to its rarity and overlapping features with diverse mimics. A retrospective review of the clinical and pathologic features of 32 SDSC including 4 SMARCB-1 deficient adenocarcinoma (SDAC) cases was performed. The patients were aged 19 to 76 years with a male predominance. Most tumors arose in the naso-ethmoid (75%), and advanced stage (93.6%), with frequent multi-sinus (90.5%) involvement. Histologically, tumors exhibited diverse morphologies, including basaloid (50%), rhabdoid (25%), and undifferentiated (12.5%) types. SDAC cases showed glandular differentiation with intraluminal and stromal mucin. Empty vacuoles (62.5%), pagetoid spread (31.3%), eosinophilic-granular bodies (18.8%), hyaline globules (15.2%), and florid glomeruloid neovascularization (15.6%) were additional findings. Yolk sac-like areas were encountered in 18.6%. Immunohistochemically, tumors were defined by a complete loss of SMARCB1 (100%); a variable reactivity for p40 (65.6%), synaptophysin (13.6%), glypican3 (6.1%), and CD34 (6.1%) was present. Notably, >90% of our patients had different initial diagnoses before referral. Lymph node metastasis, locoregional recurrence, and distant metastasis were seen in 23.3%, 24.1%, and 27.6% patients, respectively; 37.9% died of disease. In conclusion, SDSCs are rare and aggressive sinonasal malignancies that display a wide histologic spectrum including glandular differentiation. This study expands on the morphologic spectrum of SDSC by analyzing a large cohort of 32 cases, adding comprehensive clinical, histopathologic, and immunohistochemical data, and highlighting features to improve diagnostic accuracy. The emergence of targeted therapies, such as EZH2 inhibitors, further underscores the importance of accurate diagnosis.