Cancers

BackgroundLeptomeningeal disease (LMD) is a serious complication of metastatic breast cancer (MBC) with poor survival. This single-institution retrospective study compares overall survival (OS) among MBC patients with LMD based on CSF parameters (glucose, protein, and WBC count) MethodologyMBC patients who were diagnosed with LMD between 2010-2023 at Wilmot Cancer Institute were screened for eligibility. Only those with available data on CSF glucose, protein, and WBC count were included. OS was...

BackgroundThe management of residual axillary disease after neoadjuvant therapy (NAT) remains controversial, as current recommendations often treat ypN1 breast cancer as a homogeneous entity despite potential prognostic heterogeneity. Evidence supporting uniform axillary surgical strategies across different levels of residual nodal burden is limited. We investigated whether survival associations related to axillary surgical evaluation differ according to residual nodal burden in ypN1 disease, us...

Background and ObjectivePatients with upper urinary tract urothelial carcinoma (UTUC) undergoing radical surgery are at high risk of developing intravesical recurrences (IVR). The biology of IVR after surgery for UTUC is poorly understood, and urine markers to replace cystoscopic surveillance of the bladder are lacking. Here, we characterized the genomic landscape of UTUC and paired IVR to discover therapeutic targets and identify diagnostic markers for IVR. MethodsWe performed targeted next-ge...

Background & AimsPerihilar cholangiocarcinoma is an aggressive malignancy with clinical heterogeneity and poor long-term outcomes after resection. Current prognostic assessment relies mainly on anatomical staging and pathological features, which incompletely capture the entire postoperative risk. We aimed to determine whether integrative analysis of clinical, surgical, pathological and tumor genomic data could improve time-resolved, individualized recurrence-risk prediction after curative-intent...

PurposePrognosis in metastatic non-seminomatous germ cell tumors (mNSGCT) is currently guided by the IGCCCG classification, which incorporates tumor markers, organs involved with metastatic disease, and primary site but not histologic subtype. We aimed to evaluate whether specific histological components provide additional prognostic information in a large international mNSGCT cohort. Patient and MethodsWe analyzed clinical, pathologic, and outcome data from 662 patients with mNSGCT across mult...

Gastrointestinal (GI) polyposis is a major risk factor for colorectal cancer (CRC) and a defining feature of hereditary polyposis syndromes such as familial adenomatous polyposis (FAP). Therapy-associated polyposis (TAP), however, is a rare and incompletely characterized condition that develops decades after treatment for childhood or young adult cancers (CYAC), most often following abdominopelvic radiation or exposure to alkylating agents. As long-term CYAC survival improves, the burden of late...

IntroductionThe precise determination of diagnostic cut-off points is essential for the development of multimarker panels in oncology. In previous work on pulmonary nodules, it was observed that the standard two-parameter logistic fit could be insufficient for biomarkers with asymmetric distributions. Furthermore, the calculation of empirical cut-off points based on graphical visualization presented limitations in precision and reproducibility. ObjectiveThis study presents a methodological adva...

BackgroundTumor-associated macrophages (TAMs) display context-dependent functional polarization, but whether their prognostic impact is consistent across tumor types remains unclear. MethodsWe analyzed RNA-sequencing and clinical data from The Cancer Genome Atlas (TCGA) lung adenocarcinoma (LUAD; n=648), lung squamous carcinoma (LUSC; n=623), and melanoma (SKCM; n=466). Cox proportional hazards models adjusted for age and AJCC stage evaluated per-standard deviation (SD) expression of TAM marker...

BackgroundPancreatic ductal adenocarcinoma is one of the most aggressive and lethal malignancies of the gastrointestinal tract. The poor prognosis is largely attributed to late-stage diagnosis, pronounced tumor heterogeneity, and limited therapeutic efficacy. These challenges underscore the urgent need for the identification of robust molecular biomarkers and novel therapeutic targets. MethodsGene expression data from a total of 146 pancreatic tissue samples, comprising 72 normal and 74 tumor s...

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by profound molecular heterogeneity and inconsistent responses to gemcitabine-based therapy. Although KRAS mutations are nearly ubiquitous, the broader RTK-RAS and MAPK signaling networks, and their association with therapeutic response, remain insufficiently characterized. We performed an integrative clinical-genomic study of 184 PDAC tumors, stratified by age at diagnosis and gemcitabine exposure, systematically...

POLE sequencing for somatic mutations (POLEmut) guides adjuvant therapy in endometrial cancer (EC), but cost and infrastructural considerations lead to limited uptake. Omission of POLE testing leads to unnecessary exposure to radiotherapy and/or chemotherapy. We developed POLARIX, a multiple instance deep learning model with attention pooling, which predicts POLE mutation status from routine hematoxylin and eosin whole-slide images (WSIs). Trained on 2,238 cases from eleven EC cohorts, POLARIX s...

Immunotherapy with immune checkpoint inhibitors and immunotherapy combined with chemotherapy have represented promising treatments for NSCLC patients leading to prolonged survival. However, the majority of patients with advanced NSCLC have a poor prognosis. The identification and development of biomarkers for stratifying responders and non responders to immune checkpoint inhibitors contribute to unravel the mechanism of immune checkpoint pathway and the immune tumor interaction underlying the re...

BackgroundGastric cancer is one of the most common malignancies worldwide and is associated with poor prognosis, placing a considerable burden on public health. Overall treatment outcomes remain unsatisfactory, and accurate lymph node staging is essential for optimizing therapeutic strategies and improving survival. This study aimed to compare the prognostic value of different lymph node staging systems in patients with gastric adenocarcinoma and to provide a more refined prognostic assessment t...

BackgroundAlthough DCIS has a relatively low recurrence rate, many patients still receive adjuvant radiotherapy or endocrine therapy, raising concerns about overtreatment. Reliable biomarkers are therefore needed to predict an individual patients risk and guide treatment decisions. Recent studies suggest that the composition of the tumour-associated stroma (TAS) affects progression and outcome, highlighting TAS-derived biomarkers as promising candidates for further investigation. MethodsWe trai...

Recurrence scores based on a 21-gene assay are clinically useful for predicting prognosis and chemotherapy benefit in postmenopausal node-positive breast cancer patients, but its performance in premenopausal patients is inconsistent. Here, we evaluated Ataraxis Breast RISK (ATX), an AI test that predicts recurrence risk, and compared it with the genomic assay. ATX identified high risk patients misclassified as low risk by the genomic assay and therefore may refine selection of patients for adjuv...

IntroductionDespite advancements in non-small cell lung cancer (NSCLC) management through the use of molecular biomarkers, the recently introduced 9th edition of the TNM staging system remains based exclusively on anatomic descriptors, with no consistently demonstrated improvement in risk stratification for early-stage disease. This study explores the integration of a molecular prognostic classifier into the conventional TNM staging system. MethodsWe analyzed 502 patients with stage I-III lung ...

AO_SCPLOWBSTRACTC_SCPLOWLung cancer is characterized by profound intratumoral and inter-patient heterogeneity, spanning histological subtypes, molecular landscapes, and the tumor microenvironment. While multi-omics integration is essential for capturing this complexity, leveraging these data to explicitly define survival-associated subpopulations remains a significant challenge. In this study, we developed NeuroMDAVIS-FS, an unsupervised deep learning framework designed to stratify lung cancer p...

Clear cell renal cell carcinoma (ccRCC) is the leading cause of kidney cancer-related death, but how the tumor microenvironment shapes patient survival is not completely understood. Here, we describe the characterization of ccRCC tumor ecosystems from 498 patients using imaging mass cytometry with a focus on tumor, myeloid, and T cell landscapes. Data from more than 3 million single cells is analyzed using machine-learning to identify key ecosystem features that outperform basic clinical data fo...

Cancer heterogeneity is traditionally attributed to multiple parallel signaling pathways. This belief is challenged here by proposing the ER/PR axis as the dominant pathway underlying the full spectrum of breast cancer. Absolutely quantitated ER, PR, Her2 and Ki67 protein levels were accumulated over 8 years from 1652 specimens collected non-selectively and measured with Quantitative Dot Blot (QDB) method over time. Cox analysis showed ER and Ki67 as independent adverse prognostic factors while ...

PurposeThis study evaluated the safety and effectiveness of an intraoral light-emitting diode (LED)-based photobiomodulation (PBM) device to reduce the incidence and severity of oral mucositis (OM) from intensity modulated radiation therapy (IMRT) for head and neck cancer (HNC). MethodsThis randomized, double-blind, sham-controlled trial enrolled patients with HNC undergoing high-dose IMRT over 6-8 weeks, with or without concurrent chemotherapy. Participants received daily 10-minute PBM or sham...