Citations

Abstract AI-powered pathology foundation models provide general-purpose representations of histopathological images by encoding image tiles into numerical embeddings. However, these embeddings are not directly interpretable in biological or clinical terms and must be translated into biologically meaningful features, such as cell-type composition or gene expression, to enable downstream clinical applications. To bridge this gap, we developed STpath, a framework that integrates histopathology image embeddings derived from existing pathology foundation models with matched, spatially resolved transcriptomics data. STpath consists of cancer-specific XGBoost models trained to infer cell-type compositions and gene expression from histopathology image tiles. We evaluated STpath in colorectal and breast cancer datasets and showed that it provides accurate estimates of the composition of major cell types and the expression of a subset of genes, with further performance gains achieved by combining embeddings from multiple foundation models. Finally, we demonstrated that STpath inferred features that can be used in downstream studies to evaluate their associations with clinical outcomes.

Abstract There is a growing number of cancer survivors given improvement in early cancer diagnosis, therapeutics, and supportive care strategies. Cognitive impairment is among the most common and clinically significant symptoms managed by cancer survivors, which negatively impacts quality of life, functional and occupational status for patients and their care partners. Cancer-related cognitive impairment is often multifactorial—impacted by patient and cancer-specific factors. For systemic (non-CNS) malignancies, cognitive impairment has been identified in up to 75%, depending on cohort, which persists in up to 35% of patients in the years following initial treatment. The most common areas of impairment include memory and processing speed, and executive function. These adverse effects of cancer treatment have been reported after chemotherapy, hormone therapy, targeted therapy, and immunotherapy. This review will summarize existing knowledge regarding the nature and pattern of cognitive changes, mechanisms and risk factors underlying these changes, and biomarkers to support identification of this adverse consequence of cancer therapies.

Purpose: The anatomic position of the appendix may influence both the clinical presentation and diagnostic imaging accuracy in pediatric appendicitis, but its impact remains uncertain. This study aimed to determine the prevalence of retrocecal appendicitis in children and to evaluate whether appendix positioning affects ultrasound diagnostic performance or clinical outcomes. Methods: This was a retrospective cohort study including all children 0 to 18 years of age who presented to the Mayo Clinic Rochester Emergency Department between 2018 and 2023 and were diagnosed with appendicitis during their evaluation or subsequent hospitalization. Appendix location was determined by imaging or surgical documentation. Demographics, symptoms, signs, and complication rates were collected for patients with retrocecal appendicitis (RCA) and non-retrocecal appendicitis (NRCA). Results: Four hundred seven patients were included with 12.5% having RCA. Ultrasound was obtained in 92% of patients with RCA versus 82% of NRCA (rate difference: 10%, 95% CI: 2%-19%, P =0.018). In patients who received ultrasound imaging, findings were equivocal or falsely negative in 53% of RCA patients versus 30% of NRCA patients (RD = 24%, 9%-39%; P =0.003). Computed tomography (CT) was obtained in 51% of RCA patients versus 29% of NRCA (RD = 22%, 8%-37%; P =0.003) and was equivocal or falsely negative at similar rates in RCA (12%) and NRCA (13%; P =0.88). Clinically, there were no differences in diarrhea, emesis, location of abdominal pain, or white blood cell counts between RCA and NRCA. Rates of perforation, abscess formation, hospitalization longer than 7 days, and repeat hospitalizations were also similar. Conclusions: Retrocecal appendicitis is a common anatomic variant in children that presents with similar clinical features and outcomes compared with non-retrocecal appendicitis. However, its retrocecal position reduces the diagnostic sensitivity of limited abdominal ultrasound, often necessitating additional imaging with computed tomography. Despite these diagnostic challenges, retrocecal positioning is not associated with a worsened clinical course.

Abstract Purpose Although the Woven EndoBridge (WEB) device is increasingly used for the treatment of wide-neck intracranial aneurysms, including in the acute rupture setting, comparative evidence assessing the impact of rupture status remains limited. This study compared angiographic, safety, and clinical outcomes between ruptured and unruptured intracranial aneurysms treated with WEB. Methods We conducted a retrospective analysis of prospectively collected data from the multicenter cohort registry WorldWideWEB, including consecutive adult patients with intracranial aneurysms treated with the WEB. Patients were stratified into groups of ruptured and unruptured aneurysms. Propensity score matching was used to balance baseline characteristics between both groups. Retreatment rate was the primary outcome. Secondary outcomes included mRS, safety events (thromboembolic complications) and angiographic outcomes (periprocedurally and last follow-up). Results Among 1,220 patients, 342 (28.0%) presented with ruptured aneurysms. There was no significant difference in the rate of thromboembolic complications between groups (11.8% vs 5.9%, p = 0.056). At follow-up, adequate occlusion was lower (82.2% vs 93.3%, p < 0.002) and functional outcomes were worse (mRS ≥2 in 34.1% vs 21.9%, p = 0.012) among patients with ruptured aneurysms. Periprocedural adequate occlusion (53.3% vs 53.8%, p>0.9) and retreatment rates (11.8% vs 7.1%, p = 0.14) did not differ between groups after matching. Conclusion Ruptured aneurysms demonstrated expected inferior follow-up functional and angiographic outcomes when compared with unruptured aneurysms, but no difference in retreatment rate and procedural safety. These findings support WEB as a safe and effective treatment option for appropriately selected ruptured intracranial aneurysms in routine clinical practice.

Invasive lobular breast carcinoma (ILC), the most common special histological subtype of breast cancer, is characterized by nearly universal expression of estrogen receptor alpha (ER) and unique sites of metastases, neither of which is fully recapitulated by genetically engineered mouse models. Using reporter-labeled ILC mouse xenografts, herein we used mammary fat pad, tail vein and intracardiac orthotopic growth to analyze spontaneous and experimental metastasis and gene expression. We observed ER-positive primary tumors with single-file histology and collagen deposition, and spontaneous metastasis from the mammary fat pad to bones, ovaries, and brain including the leptomeninges, thereby closely mirroring the growth and metastatic spread of human ILC. Brain metastases showed strong ER staining, confirmed by sequencing analyses which identified estrogen signaling as top activated pathway, and the lesions exhibited robust response to endocrine therapy. In summary, we report endocrine responsive mammary fat pad, tail vein and intracardiac xenografts that faithfully demonstrate unique ILC features and can serve as invaluable pre-clinical translational platforms for validating candidate ILC genetic drivers and testing novel therapeutics.

Abstract Radiotherapy is an established treatment for low-grade primary cutaneous B-cell lymphoma. Recommendations on its use differ internationally, which prompted our group to conduct this analysis. Twenty-two institutions participated in this international study. Patient eligibility required a diagnosis of limited (T1/T2) primary cutaneous marginal zone or follicle center lymphoma treated with radiotherapy between 1995 and 2023. Data were collected retrospectively until February 2024 within the framework of the International Lymphoma Radiation Oncology Group. Overall, 535 patients were analyzed. Predominant locations were the head (40%) and trunk (36%). Radiotherapy had a median dose of 24 Gy in fractions of 2 Gy. Complete responses were observed in 91% at a median time of 3.6 months following radiotherapy. There was no statistically significant difference between treatments ≤4 Gy and &gt;4 Gy for complete or overall response rates (P = .077 and P = .056, respectively). However, there was an inferior duration of local control with ≤4 Gy (5-year local control 73% ± 12% vs 96% ± 2%; P&lt; .001). Radiation dose was the main prognostic factor in the univariate and multivariable Cox analysis; however, higher doses did not translate into an overall survival benefit. Toxicities rarely exceeded grade 2 but were more frequent in the &gt;4 Gy group. Radiotherapy remains an effective treatment option for indolent skin lymphoma with low toxicity. High response rates are observed with low doses of ≤4 Gy. In comparison to conventional doses, these treatments have a shorter duration of local control but a favorable toxicity profile.

Abstract Background S0221 investigated weekly vs every 2 weeks dosing of doxorubicin (A) and cyclophosphamide (C) followed by paclitaxel in patients with high-risk early breast cancer. After an interim analysis, random assignment to the 2 AC arms was stopped for futility, and the trial was modified to study only the paclitaxel schedules. Methods Between December 2003 and November 2010, a total of 2716 patients were randomly assigned in a 2 × 2 factorial design to 15 weeks of weekly A and daily C vs 6 cycles of every 2 weeks AC; and weekly paclitaxel for 12 weeks vs 6 cycles of every 2 weeks paclitaxel. Between January 2011 and January 2012, an additional 578 patients were assigned to 4 cycles of every 2 weeks AC and randomly assigned to weekly vs every 2 weeks paclitaxel. Updated survival was assessed using log-rank tests and Cox regression models. We compared outcomes by breast cancer subtype as well. Results At a median follow-up of 12.1 years, there were no statistically significant differences among the 4 treatment arms in disease-free survival (DFS) (P = .91) or overall survival (P = .34) in the original protocol. Among the 578 patients assigned AC for 4 cycles and randomly assigned to paclitaxel weekly vs every 2 weeks paclitaxel, there were no overall differences in DFS (P = .32) or overall survival (P = .42). Conclusion As there were no statistically significant outcome differences in DFS or overall survival between the studied schedules of AC and paclitaxel with extended follow-up in the original or revised protocol, either paclitaxel schedule may be recommended, with selection based on toxicity, cost, or patient preference.

Bruton tyrosine kinase inhibitors (BTKis) and BCL2 inhibitor (BCL2i)–containing regimens significantly improve survival outcomes in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Results from randomized clinical trials have demonstrated that time-limited treatment with BCL2i-containing regimens resulted in higher rates of undetectable measurable residual disease (uMRD) than BTKi monotherapy or chemoimmunotherapy (CIT). Pirtobrutinib (a noncovalent BTKi) and lisocabtagene maraleucel (CD19-directed CAR T-cell therapy) are newer options for relapsed or refractory disease after prior therapy with BTKi and BCL2i-contining regimens. Histologic transformation of CLL/SLL to diffuse large B-cell lymphoma (Richter transformation) is associated with a poor prognosis. Molecular analysis to determine whether there is clonal relationship between CLL/SLL and transformed diffuse large B-cell lymphoma is useful to select an appropriate treatment option. These NCCN Guideline Insights highlight significant updates to the NCCN Guidelines for the treatment of CLL/SLL and Richter transformation.