Baseline cytomolecular features and measurable residual disease (MRD) dynamics are both strongly prognostic in acute lymphoblastic leukemia (ALL). Whether early MRD response can overcome the adverse prognosis of high-risk (HR) cytomolecular features is largely unknown. We retrospectively identified 161 patients with newly diagnosed B-cell ALL who underwent MRD assessment with next-generation sequencing (NGS) for IG/TR rearrangements (sensitivity: 1 × 10^-6). Early NGS MRD negativity (i.e. after 1 cycle of induction) was achieved in 33% of patients. Rates of NGS MRD negativity were similar in patients with standard-risk (SR) and HR cytomolecular features. Patients who achieved early NGS MRD negativity had the best outcomes (2-year relapse-free survival (RFS): 94% versus 66% if MRD-positive; P = 0.03). None of the 26 patients with early NGS MRD negativity subsequently relapsed. Early NGS MRD response also identified patients with HR Philadelphia-chromosome (Ph)-negative ALL with low risk of relapse and excellent long-term survival (2-year RFS: 100%); in contrast, the 2-year RFS was 38% for patients with HR ALL who remained MRD-positive after induction (P = 0.01). Outcomes remained poor for HR patients who achieved NGS MRD negativity at later timepoints. In a landmark analysis, allogeneic stem cell transplant (alloSCT) improved outcomes of patients with HR Ph-negative ALL who remained MRD-positive after induction (2-year RFS 80% versus 0% if no alloSCT; P = 0.009). In patients with B-cell ALL, achievement of early NGS MRD negativity is associated with durable remissions, regardless of baseline cytomolecular features. AlloSCT may improve outcomes of patients with HR ALL with suboptimal early MRD dynamics.

The present study examined factors preventing the achievement of pentafecta in patients who have already met trifecta criteria following robot-assisted partial nephrectomy (RAPN).

A retrospective observational study was conducted on 103 patients who underwent RAPN for localized renal tumors at Keio University Hospital between 2019 and 2023. Clinical characteristics, surgical parameters, and postoperative renal function were analyzed. Multivariate logistic regression analyses were performed to identify independent predictors of trifecta and pentafecta achievement.

The achievement rates for trifecta and pentafecta were 88% and 27%, respectively. Independent predictors of trifecta achievement were tumor size ≤ 20 mm (OR = 5.496, p = 0.039) and estimated blood loss ≤ 50 cc (OR = 7.983, p = 0.011). Significant predictors of pentafecta achievement were age ≤ 63 years (OR = 3.753, p = 0.026) and tumor exophyticity ≥ 50% (OR = 4.054, p = 0.018). Independent predictors of pentafecta failure despite trifecta achievement were age > 63 years (OR = 0.223, 95% CI: 1.347-14.904, p = 0.014) and tumor exophyticity < 50% (OR = 0.205, 95% CI: 1.474-16.159, p = 0.009). The pentafecta failure rate was 95% in patients who achieved trifecta but had both risk factors, namely, older age and embedded tumors.

Older age and tumor exophyticity < 50% are significant predictors of pentafecta failure despite achieving trifecta. The consideration of these factors may help refine surgical planning and postoperative management.

Late-stage breast cancer contributes to a growing number of deaths in sub-Saharan Africa (SSA) but few studies examine scalable early detection strategies. Following small-scale pilots, in 2020 Rwanda launched an adapted Women's Cancer Early Detection Programme (WCEDP), integrating clinical breast exam (CBE) for symptomatic patients with cervical cancer screening. A WCEDP-specific electronic health record (EHR) was developed to facilitate patient tracking.

We used the RE-AIM implementation science framework to retrospectively evaluate implementation of breast cancer early detection within the WCEDP over 12 months in the first three scale-up districts (population: 2 009 888), using routinely-collected electronic and paper data from 15 health centres and 3 hospitals. We examined the WCEDP's Reach in the target population, Effectiveness linking patients to care, Adoption by facilities and fidelity to the Implementation protocol.

Regarding Reach, average weekly health centre visits for CBE increased from 18 to 33 post-WCEDP launch; of 1688 women receiving CBE through the WCEDP, 12.0% were ≥50 years. Regarding effectiveness, among 383 women referred to district or referral hospitals, 157 (40.9%) had no documented referral facility visit. Of those seen at a referral facility, median days from health centre to district hospital visit and from district to referral hospital visit were 6 (IQR 1.8-14.8) and 8 (IQR 5.0-40.5) respectively. Among the 36 patients receiving biopsy, 72.2% were biopsied within 60 days of initial presentation. In terms of adoption, 79 clinicians were trained in cancer early detection, with 69.6% remaining at WCEDP facilities after 3 years. Regarding implementation fidelity, WCEDP clinics were held 52.6% of weeks. EHR data quality was inconsistent, with half of patients seen at district hospitals for breast care lacking EHR documentation.

Breast cancer early detection services can be implemented in resource-constrained SSA health facilities. Integration with cervical cancer screening may be a promising strategy. However, investing in data systems is critical to support programme evaluation and high-quality care.

Lymphoma is a haematologic malignancy affecting cells of the immune system. With numerous treatment options available, clinicians and patients frequently face difficulty in selecting the most appropriate therapy. Patient-reported Outcome (PRO) offers valuable patients' insight that may support treatment differentiation. A PRO measure (PROM) is a questionnaire or survey measuring a PRO. Despite many efforts to guide the selection of PROMs in clinical trials, choosing the appropriate ones remains a challenge. This study aims to develop a pragmatic paradigm for selecting PROMs in clinical trials involving adult patients with lymphoma through the collaboration and communication between clinical investigators involved in trials and Health Economics and Outcomes Research (HEOR) scientists specialised in research methodologies.

A rapid review was conducted to identify existing PROMs for adult patients with lymphoma in clinical trials and guidelines supporting PROM selection.

PubMed, Google Scholar and websites for regulatory and health technology assessment (HTA) bodies in eight countries of interest were searched from 2009 to July 2024.

Publications with PROMs were identified for adult patients in lymphoma trials. The most relevant guidelines supporting the development of the pragmatic paradigm were selected.

The initial search and data extraction were conducted by one author. All authors participated in an in-depth review process.

We categorise 31 applicable PROMs for lymphoma into four distinct groups, streamlining the PROM selection process to facilitate effective communication among clinical investigators, HEOR scientists, patients and others. Additionally, a five-step pragmatic paradigm is developed for identifying appropriate PROM(s).

The pragmatic paradigm presents a practical approach for selecting PROM(s) in lymphoma clinical trials. An appropriate PROM should conceptually align with the treatment goals and be acceptable to regulatory and HTA bodies. Thus, lymphoma clinical trials can generate more patient-focused data, contributing to improving patients' quality of life and advancing lymphoma care.

BACKGROUND Schwannomas are benign tumors of Schwann cell origin, and their intraosseous presentation in the infraorbital region is exceptionally rare. We report a case in which computed tomography (CT) revealed an expansile lesion in this location, subsequently diagnosed as a cellular schwannoma. This report underscores the importance of histological analysis in the differential diagnosis of infraorbital lesions, particularly to distinguish schwannoma from entities such as neurofibroma. CASE REPORT Our patient was a 31-year-old man with right infraorbital facial pain, described as an "electric shock" sensation, radiating to the maxillary region, with gradual clinical progression over 2 years. It was also observed that his right eyeball became protruded and displaced upward, leading to vertical diplopia. Clinical and neurological examination revealed facial asymmetry, mild upward divergent strabismus, right exophthalmos, and allodynia during tactile stimulation of the right maxillary region. Craniofacial CT and magnetic resonance imaging (MRI) revealed a circumscribed 2.5×3 cm mass occupying the floor of the orbital cavity and invading the maxillary sinus. Histopathological analysis showed organized neoplastic cells and strong expression of the S-100 protein, as well as immunostaining for the Ki-67 protein, indicating proliferative activity. The final diagnosis was cellular schwannoma. CONCLUSIONS This case highlights the importance of differential diagnosis in rare lesions of the infraorbital region and the need for histological analysis to avoid misdiagnosis and surgically preserve functional nerves.

Bortezomib (BTZ) containing regimens induces significant antitumor response in multiple myeloma (MM) and are considered as the first-line treatment. However, resistance is still one of the unsolved problems. This study aims to explore the mechanism underlying BTZ resistance in MM.

The gene expression profile (GEP) data of the GEO dataset GSE9782 was analyzed. All cases were divided into BTZ sensitive and resistant arms. Differentially expressed genes (DEGs) and later the hub genes between the two groups were screened. The key hub gene NPM1 was inhibited by shRNA and small molecule inhibitor, proliferation, apoptosis and expression of CXCR4 in myeloma cells were assayed.

NPM1 was a dismal survival prognostic factor in MM, and MM patients with high NPM1 expression achieved significantly lower response rate to BTZ-containing regimens. In vitro, qRT-PCR revealed that NPM1 expression in the BTZ-resistant MM cell line KM3/BTZ (also known as KB) was significantly higher than its parental cell line KM3 cells. Knockdown of NPM1 and treatment with the NPM1 inhibitor NSC348884 both restored the sensitivity of KB cells to BTZ. Further analysis revealed that inhibition of NPM1 down-regulated CXCR4 expression at both transcriptional and translational level.

In conclusion, NPM1 might causes BTZ resistance via up-regulating CXCR4 expression in MM and could be served as both a new prognostic biomarker and a promising therapeutic target.

Lung squamous cell carcinoma (LUSC) remains an aggressive malignancy with limited therapeutic options and poor prognosis. Understanding the molecular drivers of LUSC pathogenesis is crucial for developing novel interventions. This study investigates the functional significance and mechanistic basis of long non-coding RNA LINC00885 in LUSC progression. We employed integrated methodologies including bioinformatic analysis, clinical specimen validation, in vitro functional assays (EdU incorporation, colony formation, Transwell migration/invasion), molecular profiling (qPCR, immunoblotting, northern blot, fluorescence in situ hybridization, subcellular fractionation), mechanistic investigations (chromatin isolation by RNA purification, luciferase reporter assays), and in vivo xenograft modeling. LINC00885 was significantly upregulated in LUSC clinical tissues and cell lines. Genetic depletion of LINC00885 suppressed malignant phenotypes including cellular proliferation, migration, invasion, and epithelial-mesenchymal transition. Mechanistically, LINC00885 directly bound and repressed tumor-suppressive miR-654-3p, which targeted stem-loop binding protein (SLBP). LINC00885 activated PI3K/Akt signaling through SLBP upregulation, and either SLBP overexpression or miR-654-3p depletion rescued the tumor-suppressive effects of LINC00885 knockdown. Xenograft models confirmed LINC00885 silencing significantly inhibited tumor growth in vivo. LINC00885 promotes LUSC progression via the miR-654-3p/SLBP/PI3K/Akt signaling axis.

Pancreatic cancer is an extremely aggressive and lethal malignant cancer; almost half of the patients have distant metastasis when first diagnosed, and many challenges arise during treatment. Lymph node metastasis is a vital indicator of disease progression in pancreatic cancer and directly influences patient prognosis and survival rate. The cancer cells invade the lymphatics, promote the growth of lymphatics, propagate to lymph nodes, and finally settle down in lymph nodes. Aiming at this process, treatment modalities involving surgery, targeted therapy, and nanodelivery of chemotherapy are tested regarding their efficacy in both local tumor management and lymph node metastasis. As lymph node metastasis presents a poor prognosis and higher recurrence rate, precise assessment of lymph node metastasis is imperative for clinical management in pancreatic ductal adenocarcinoma. Precise evaluation of lymph node metastasis will not only help in formulating personalized treatment but also provide more accurate prognostic information to the patients. This review aims at synthesizing current knowledge of the molecular mechanisms, treatment options, clinical implications, and evaluation techniques regarding lymph node metastasis in pancreatic cancer, hence allowing a focused perspective for clinicians and researchers in striving for more effective management strategies against lymph node metastasis of pancreatic cancer.

Triple-negative breast cancer (TNBC) is notorious for its rapid progression, tendency to metastasize, high recurrence rates, dismal outcomes, and limited treatment options, underscoring the urgent need to uncover new biomarkers and molecular pathways to enhance diagnosis, prognosis, and therapeutic strategies. Metabolic reprogramming continues to play a role throughout the life cycle of cancer, evolving and adapting. In this study, we aimed to identify specific genes associated with metabolic reprogramming in TNBC, which can potentially become unique biomarkers of this cancer. TNBC datasets retrieved from the Gene Expression Omnibus were employed to pinpoint genes exhibiting altered expression linked to tumor metabolic reprogramming. Key genes were accurately screened through machine learning algorithms, and then externally verified using the TBNC dataset based on the Cancer Genome Atlas database. Finally, immunohistochemical methods were used to clinically confirm the differential expression and trends of these key genes. Our analysis accurately identified four genes-CLEC7A, IRS1, RSPO3, and ALB-that are closely correlated with the metabolic reprogramming characteristics of cancer, and could be regarded as innovative biomarkers for TNBC. This opens a new avenue for further investigation into the mechanisms of metabolic reprogramming in TNBC and new treatment strategies.

Cell-to-cell communication through ligand-receptor (LR) interactions can fundamentally shape the tumor microenvironment and immune responses, but the full spectrum of these interactions in anti-PD-1 therapy remains unexplored. We developed a predictive model for anti-PD-1 therapy responses incorporating 2,705 LR pairs across 121 melanoma samples. Using a random forest classifier, our model achieved robust accuracy in the training and test datasets as well as in two independent external validation cohorts. Feature importance analysis revealed nine key LR pairs with substantial predictive power, including both known immune checkpoint molecules and novel interaction pairs. The genes comprising these top-ranking pairs were significantly enriched in tumor-related pathways, particularly MAPK and PI3K/AKT signaling pathways. Importantly, our systematic LR profiling approach identified previously uncharacterized ligand-receptor interactions that may represent alternative therapeutic targets beyond the established PD-1/PD-L1 axis. These findings demonstrate the clinical utility of integrated LR expression analysis for predicting anti-PD-1 therapy responses and reveal potential novel biomarkers and combination therapy targets that could expand treatment options for immunotherapy-resistant patients.