Cancers

Ovarian cancer is the deadliest of gynecological cancers and surgery is often necessary for a final diagnosis. Benign cases could be managed more conservatively, avoiding the risks and complications associated with surgery, if accurate diagnostic biomarkers existed. Underlying differences between circulating protein biomarkers and tumor gene expression also restricts interpretation and prioritization of potential biomarkers for diagnosis and potential drug targets. Here, high-throughput affinity...

BackgroundInflammatory breast cancer (IBC) is a rare and highly aggressive form of breast cancer with an increased propensity to metastasize to distant organs including the brain. Higher serum levels of the calcium-binding proteins S100A8/A9, particularly of S100A9, have emerged as a clinically and biologically significant factor in aggressive breast cancers that are associated with poorer prognosis, tumor progression, and resistance to therapy. However, its contribution in IBC specifically rema...

BackgroundOlder age and comorbidities complicate initial therapy in non-small-cell lung cancer (NSCLC), as platinum ineligibility has not been systematically characterized. MethodsAll 2592 patients presenting with metastatic NSCLC between 2018-2023 at Thoraxklinik Heidelberg were analyzed. ECOG status (PS), comorbidities, molecular testing, therapy, toxicities, and outcomes were verified from individual patient records. ResultsAmong 1306 patients with PD-L1 0-49%, systemic therapy was initiate...

BackgroundLung cancer remains the deadliest malignancy. Although PD-1/PD-L1 immune checkpoint inhibitors have improved survival, their benefit is limited by persistent immune resistance. Identifying systemic regulators of tumor immune microenvironment may enhance therapeutic efficacy. We previously showed that RBC-derived miR-93-5p promotes PTEN loss and PI3K-AKT activation. This study examined whether RBC-derived miR-93-5p is associated with immune checkpoint activity and features of T-cell exh...

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...

Structured AbstractO_ST_ABSPurpose/ObjectivesC_ST_ABSThe role of postmastectomy radiotherapy (PMRT) in patients with pathologic N1 (pN1) breast cancer, including triple-negative breast cancer (TNBC), remains controversial in the era of modern systemic therapy. We evaluated the association between PMRT and recurrence-free survival (RFS) and overall survival (OS) and identified prognostic factors in a contemporary single-institution pN1 cohort. Materials/MethodsWe retrospectively reviewed female ...

Between 10 and 20% of cervical cancers are adenocarcinomas with poorer five-year survival and higher recurrence. To identify somatic alterations driving cervical cancer, we performed whole-exome sequencing of 308 subjects with invasive disease from Guatemala and Venezuela. Consistent with other studies, there is a higher rate of TP53 mutations in adenocarcinomas versus squamous cell carcinomas (SCC), especially in HPV-negative tumors. We identified a higher rate of mutations and deletions (23%) ...

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...

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high mortality rates, often exhibiting resistance to conventional treatments such as radiotherapy (RT) or a combination of chemotherapy and radiotherapy (CRT). The nerve growth factor receptor (NGFR, also known as p75NTR or CD271) is a well-established cancer stem cell marker in melanoma, where it has been linked to resistance to multiple therapies. In HNSCC, NGFR has been reported as a poor prognostic marker, with it...

Head and neck cancer (HNC) is highly prevalent in South-Asia, driven by additional region-specific exposures such as chewing tobacco and betel nut. Despite therapeutic advances, five-year survival rate remains around 50-60%, underscoring urgent need to identify novel therapeutic targets and improve disease-free survival. This study was designed to identify both somatic and germline drivers contributing to HNC pathogenesis. Through whole-exome sequencing of 103 patients, we detected mutations in ...

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...

Pediatric solid high-risk malignancies mostly lack established molecular biomarkers for early detection, minimal residual disease assessment, or treatment monitoring. Challenges include small patient numbers, limited sample volumes, low tumor mutational burden, and few recurrent alterations. Within the prospective multicenter pediatric precision oncology program INFORM, we collected liquid biopsies from 130 pediatric patients and optimized cfDNA isolation and analysis. Whole-genome, whole-exome,...

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...

BackgroundLiver transplantation (LT) offers a curative option for early-stage hepatocellular carcinoma (HCC). Its role in intrahepatic cholangiocarcinoma (ICC) remains controversial, with limited comparative evidence on long-term outcomes, especially for early-stage disease. MethodsThis retrospective population-based study utilized the SEER database (2004-2015). Patients with AJCC 6th edition Stage I HCC or ICC who underwent LT were included. Cancer-specific survival (CSS) and overall survival ...

Examining LncRNA-driven cancer biology, our study represents the first comprehensive investigation of the LncRNA CDKN2B-AS1 across multiple cancer types, revealing its genetic basis for cancer susceptibility, and associations with thromboembolic risks and immunological dynamics. Stratification across hematological and non-hematological cancers revealed predominant prevalence rates of the CDKN2B-AS1 C-allele, notably higher in solid tumor malignancies, peaking at 86.8% in colorectal carcinoma (CR...

Importance: Recurrence rates for locally advanced HPV-independent (HPV-) head and neck squamous cell carcinoma (HNSCC) are high. Circulating tumor DNA (ctDNA)-based minimal residual disease (MRD) assays have shown promise to improve management and surveillance in several tumor types, but their clinical utility in HPV- HNSCC remains understudied. Objective: To evaluate the performance of a tumor-informed ctDNA-based MRD assay (PredicineBEACON) in patients with newly diagnosed, locally advanced H...

BackgroundHER2-positive (HER2+) cancers are associated with aggressive tumor development but also high response rates to targeted blockade treatments of the HER-2/neu signaling pathway leading to improved clinical outcome for the patient. Current clinical analysis of the HER2 status primarily relies on solid tumor biopsies low-suitable for continuous real-time monitoring needed for possible adjustment of the treatment, while serum tests targeting blood-circulating HER-2/neu fragments often show ...

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...

ObjectiveTumor transformation is accompanied by widespread methylation changes, in the form of cytosine modifications, in transposable elements (TEs). The purpose of this study was to investigate whether changes in methylation and hydroxymethylation in the form of 5mC and 5hmC within transposable elements in circulating cell-free DNA (cfDNA) can serve as predictive markers of ovarian malignancy. MethodsHealthy women as well as women undergoing surgery for various benign, borderline, or malignan...

BackgroundInflammatory responses and nutritional status are critical determinants of colorectal cancer (CRC) progression and clinical outcomes. This study aimed to evaluate the prognostic value of a novel albumin-neutrophil composite grading (ANPG) system and to develop a nomogram for predicting overall survival (OS) in CRC patients following curative resection. MethodsA retrospective analysis was conducted on 660 consecutive patients with primary CRC who underwent R0 resection between December...