Improving responses to neoadjuvant therapy for patients with locally advanced rectal cancer has the potential to improve organ preservation and disease-free survival. Knowing which patients may need therapeutic escalation or de-escalation from standard-of-care treatment remains an area of investigation. We previously reported the primary and secondary endpoints of our single-arm study combining transforming growth factor beta receptor inhibitor, Galunisertib, with neoadjuvant chemoradiation in patients with locally advanced rectal cancer. Here we analyze RNA sequencing data obtained from tissue biopsies at baseline and after 2 weeks of galunisertib. Differences in expression of genes associated with MYC, inflammation, and epithelial-to-mesenchymal transition were observed between complete responders (CR) and <CR, with galunisertib upregulating MYC pathway expression in CR. Radiosensitivity and TGFβ response scores demonstrated limited ability to predict for response to galunisertib + chemoradiation. Typically treatment-resistant consensus molecular subtype 4 (CMS4), characterized by TGFβ expression, and metabolic subtype (CMS3) were associated with response to galunisertib + chemoradiation. Differences in correlations between RNA based measures of cell composition and immunohistologic quantification of infiltrates and extracted MRI parameters were observed for CIBERSORT, MCPcounter, and xCell methodologies. Based on these data, we hypothesize that the stromal radioresistant phenotype driven by TGFβ can be overcome by the addition of galunisertib to chemoradiation in rectal cancer.
BACKGROUND:There is a paucity of literature to guide the surgical management of the simultaneous presentation of a diastematomyelia, two hemicords, and a unilateral bar unsegmented vertebra, a form of formation failure. OBSERVATIONS:An 11-year-old female presented with acute-onset back pain, urinary incontinence, and lower extremity numbness. Evaluation revealed T7 diastematomyelia with a tethered cord and a right-sided T6-11 nonsegmented unilateral bar, resulting in thoracolumbar levoscoliosis (maximal Cobb angle of 49°). Initial surgical decompression and spinal cord detethering were performed, including a T7 laminectomy. A bony septation attached to the lamina and projecting through the dura mater and cord was removed and the cord was detethered. The patient subsequently regained neurological function. Eight months later, repeat scoliosis radiographic imaging showed progression to a maximal Cobb angle of 58.4°. The patient then underwent a second-stage T2-L3 posterior lateral fixation and fusion with a pedicle screw-rod construction. The postoperative curve magnitude was 25.2°. Five years following operation, she required no revision surgery and remained neurologically intact. LESSONS:The authors present a successful surgical correction of concomitant diastematomyelia and a unilateral bar and unsegmented butterfly vertebra in a pediatric patient. While the curve magnitude at presentation warranted surgical correction, neurological deficits necessitated urgent decompression before stabilization. https://thejns.org/doi/10.3171/CASE25315.
Purpose/Objective(s) Dose-escalated stereotactic ablative radiotherapy (SAbR) for localized pancreatic cancer may improve outcomes but is limited by concern for gastrointestinal toxicity. In a prior phase Ib/II study (NCT03340974), a selective superoxide dismutase mimetic demonstrated favorable safety and preliminary signals of enhanced disease control when combined with dose escalated SAbR. GRECO-2 (NCT04698915) was designed to evaluate the survival impact of adding rucosopasem to SAbR in localized pancreatic cancer. Materials/Methods GRECO-2 is an international, multicenter, randomized, double-blind, placebo-controlled phase II trial of SAbR (50 Gy in 5 fractions) ± rucosopasem in borderline resectable or locally advanced pancreatic cancer. Patients without progression after 4 months (m) of multiagent chemotherapy were randomized 1:1 to receive SAbR with rucosopasem (100 mg IV before each fraction) or placebo. The primary endpoint was overall survival. Secondary endpoints included progression-free survival, locoregional control, and time to metastasis, and acute grade ≥3 toxicity. Results The trial enrolled 177 of 220 planned patients across 30 centers in November of 2023 prior to closure for futility after an early review. Following generation of a PI consortium across centers we conducted a single data update in 2026. Of the 177 patients enrolled we collected long term follow up data for vital status from 114 patients with median follow up of 13m revealing a median survival from randomization of 15m for placebo and 12m in the rucosopasm arm (log rank p=0.088). Median survival was 20 and 19m from diagnosis (log rank p=0.113). The two-year overall survival of the whole group was 34%. We were able to collect local and distant recurrence data from 92 patients with a median follow up of 15m from randomization. The median local failure was not reached, and the 12 and 18m local failure free survival was no different between groups at 84.5% and 74.7% respectively. The 6, 12 and 18m distant failure free survival for 92 of the patients was 75.5%, 56.8% and 38.9%. Conclusion In this incomplete review of outcomes, the addition of rucosopasem to dose-escalated SAbR across a diversity of centers and treatment approaches did not improve survival or disease control in localized pancreatic cancer. Durable local control was observed following SAbR, with median local failure-free survival not reached, whereas distant progression remained frequent, underscoring the need for more effective systemic therapies to complement aggressive local treatment.
Hinchey grade III (H3) and IV (H4) diverticulitis represent the operative spectrum of complicated diverticular disease, yet consensus on optimal management remains limited. We aimed to define current practice patterns and factors influencing operative decision-making to inform on future trials. We conducted a cross-sectional survey of surgeons regarding management of H3/H4 diverticulitis. Respondents were provided clinical scenarios and asked to identify preferred operative approaches and provide free-text rationale. Surgeon demographics, training, and institutional characteristics were collected. Descriptive statistics, thematic analysis, and multivariable regression were performed. A total of 104 attending surgeons responded. Most practiced at academic centers (71.2
