Cancers

Background/Objectives This study aimed to evaluate whether very early interim 18F-fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) after a single cycle of first-line chemotherapy predicts long-term survival outcome in patients with diffuse large B-cell lymphoma (DLBCL). Methods A total of 51 patients (31 males and 20 females; mean age 55 years) had four FDG PET/CT studies, at baseline and after one, three, and six cycles of chemotherapy (PET0, PET1, PET3, and PET6). Visually and quantitatively assessed PET parameters were analyzed for associations with long-term survival. Results The estimated 10-year progression-free survival (PFS) and overall survival (OS) was 48% and 61%, respectively. During a median follow-up of 63 months (range 9–134), 17 patients (33%) exhibited disease progression and 15 (29%) died. On PET1, all but one showed decreased FDG uptake, and all showed decreased metabolic tumor volume. None of the PET1 or PET3 parameters were associated with survival. The PET6 parameters retained independent predictive value for OS after adjustment for the International Prognostic Index. Negative PET6 was associated with longer PFS (mean 99 vs. 50 mo, p = 0.04) and OS (mean 107 vs. 57 mo, p = 0.02). Con-clusions The FDG PET/CT parameters obtained after a single cycle of chemotherapy were not associated with long-term survival in DLBCL, while negative end-of-therapy FDG PET/CT was associated with longer PFS and OS. Tumor regression very early into first-line chemotherapy was not as clinically relevant as the presence of viable tumor on FDG PET/CT at the end of therapy for predicting long-term outcomes.

Background: Implant-based breast reconstruction (IBBR) following conservative mastectomy is the most common approach for women undergoing breast cancer surgery. The aim of this study was to compare the oncological outcomes of conservative mastectomy combined with prepectoral IBBR to the subpectoral technique. Methods: The clinical and demographic data of consecutive breast cancer patients who underwent conservative mastectomy with either prepectoral or subpectoral IBBR between January 2018 and December 2023 were retrospectively analyzed. The primary outcome was the impact of conservative mastectomy with prepectoral IBBR on local recurrence-free survival (LRFS). Secondary outcomes included distant disease-free survival (DDFS) and overall survival (OS). Results: A total of 842 women (with a median age of 46 years and a range of 20–79 years) were included in the study. Of these, 648 patients (77.0%) underwent prepectoral IBBR, while 194 (23.0%) received subpectoral IBBR. The median follow-up was 32 months (3–74). Locoregional relapse occurred in 19 patients (2.9%) in the prepectoral group and 14 (7.2%) in the subpectoral group. Distant metastases were observed in 21 (3.2%) patients in the prepectoral group and 11 (5.7%) in the subpectoral group. Deaths were reported in eight patients (1.2%) in the prepectoral group and five (2.6%) in the subpectoral group. There were no statistically significant differences between the two groups in terms of the LRFS, DDFS, and OS (p = 0.676; p = 0.994; p = 0.940, respectively). Conclusions: Our study indicates that conservative mastectomy combined with prepectoral IBBR produces similar results to those of the subpectoral approach, with no significant differences in LRFS, DDFS, and OS.

Background/Objectives: This study evaluates the impact of clinical, pathological, and treatment-related factors on breast cancer recurrence and overall survival following neoadjuvant chemotherapy and surgery. Patients and Method: A total of 298 patients treated at Diakoneo Diak Klinikum, Schwäbisch Hall, Germany (2010–2021) were analyzed. Key variables included hormone receptor status, molecular subtypes, tumor grade, treatment protocols, and metastatic disease at diagnosis. Results: Recurrence was strongly associated with metastatic disease (p < 0.001) but not with hormone receptor status or molecular subtypes. Platinum/taxane-based chemotherapy was linked to a lower recurrence risk (p = 0.05) compared to anthracycline-based regimens. Patients with recurrence had significantly lower overall survival (27.91% vs. 8.24%, p < 0.001). Logistic regression suggested a trend toward increased recurrence in ER-positive and PR-negative patients, though not statistically significant. These findings emphasize the importance of personalized treatment strategies and highlight the need for future studies incorporating genomic data and residual disease analysis to refine recurrence risk prediction and therapy selection.

Introduction: Liquid biopsies provide a less-invasive option to tissue biopsies for the early diagnosis, prognosis, and tailored therapy of colorectal cancer (CRC). CRC is a major cause of cancer-related death, and early identification is essential for improving patient outcomes. Review: Conventional diagnostic techniques, including colonoscopy and tissue biopsy, may be enhanced by liquid biopsies that examine circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), extracellular vesicles (EVs), and other indicators present in body fluids. These markers provide significant insights into tumor biology, heterogeneity, and therapeutic response. CTCs detected in early-stage CRC have prognostic significance for disease recurrence and survival, while ctDNA investigation may uncover genetic mutations, epigenetic alterations, and tumor development. The identification of ctDNA in minimal residual disease (MRD) postsurgery correlates with an elevated risk of recurrence and unfavorable prognosis, underscoring its use in assessing treatment effectiveness. Furthermore, non-coding RNAs (ncRNAs) contained inside EVs provide potential prospective biomarkers and therapeutic targets, facilitating diagnosis and treatment assessment. Notwithstanding the potential of liquid biopsies, obstacles persist in assay standardization, sensitivity enhancement, and the management of tumor heterogeneity. Additional extensive research is required to determine their function in clinical practice. Conclusion: Overall, liquid biopsies serve as a potential instrument for real-time monitoring, evaluating therapy responses, and directing individualized therapeutic strategies in CRC patients.

Background/Objectives: Non-small cell lung cancer (NSCLC) patients without gene driver mutations receive anti-PD1 treatments either as monotherapy or in combination with chemotherapy based on PD-L1 expression in tumor tissue. Anti-PD1 antibodies target various immune system components, perturbing the balance between immune cells and soluble factors. In this study, we identified the immune signatures of NSCLC patients associated with different clinical outcomes through network analysis. Methods: Twenty-seven metastatic NSCLC patients were assessed at baseline for the levels of circulating CD137+ T cells (total, CD4+, and CD8+) via cytofluorimetry, along with 14 soluble checkpoints and 20 cytokines through Luminex analysis. Hierarchical clustering and connectivity heatmaps were executed, analyzing the response to therapy (R vs. NR), performance status (PS = 0 vs. PS > 0), and overall survival (OS < 3 months vs. OS > 3 months). Results: The clustering of immune checkpoints revealed three groups with a significant differential proportion of six checkpoints between patients with PS = 0 and PS > 0 (p < 0.0001). Furthermore, significant pairwise correlations among immune factors evaluated in R were compared to the lack of significant correlations among the same immune factors in NR patients and vice versa. These comparisons were conducted for patients with PS = 0 vs. PS > 0 and OS < 3 months vs. OS > 3 months. The results indicated that NR with PS > 0 and OS ≤ 3 months exhibited an inflammatory-specific signature compared to the contrasting clinical conditions characterized by a checkpoint molecule-based network (p < 0.05). Conclusions: Identifying various connectivity immune profiles linked to response to therapy, PS, and survival in NSCLC patients represents significant findings that can optimize therapeutic choices.

Purpose: Existing T3 subclassifications for upper tract urothelial cancer (UTUC) are limited by heterogeneity and a primary focus on renal pelvis tumors. Our study aimed to propose a novel pT3 subclassification system specifically tailored to pT3 UTUC patients. Materials and Methods: This study analyzed 120 pT3 UTUC cases from a Taiwanese multicenter registry, using a standardized pathology report and a single pathologist for evaluation. Results: Univariate analysis revealed survival differences based on existing subclassifications. Multivariate analysis identified concurrent fat and parenchyma invasion as an independent predictor of worse overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Conclusions: This study proposes a novel pT3 subclassification incorporating fat and parenchyma invasion, applicable to all UTUC sites. This subclassification may improve risk stratification, guide treatment decisions, and ultimately enhance patient outcomes.

Background: Cervical cancer, primarily driven by persistent high-risk human papillomavirus (HPV) infections, remains a significant global health challenge. Systemic inflammatory markers, such as neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), and lymphocyte/monocyte ratio (LMR), may reflect disease progression. This study examines the association between these markers and p16 positivity in cervical intraepithelial neoplasia (CIN) cases. Methods: This retrospective analysis included 395 patients undergoing LEEP conization. Data on HPV status, p16 immunostaining, and hematological parameters were collected. Statistical analyses, including Mann–Whitney U and chi-square tests, assessed relationships between markers and outcomes, with significance set at p < 0.05. Results: Elevated NLR was significantly associated with p16 positivity (p = 0.011) and HPV DNA positivity (p = 0.04). HPV-positive individuals showed higher mean NLR (2.15) compared to HPV-negative individuals (1.61). Receiver operating characteristic (ROC) analysis demonstrated moderate diagnostic accuracy for NLR (AUC = 0.610), highlighting its potential as a biomarker. No significant associations were observed for PLR or LMR with p16 positivity. These findings suggest systemic inflammation, indicated by NLR, contributes to HPV persistence and CIN progression. Conclusions: NLR is a valuable prognostic biomarker for HPV-related cervical disease, correlating with both p16 and HPV DNA positivity. Incorporating hematological and immunohistochemical markers may enhance personalized cervical cancer management.

Background/Objectives: The oncofetal membrane protein Claudin 6 (CLDN6) is an attractive target for T cell-based therapies. There is a lack of detailed analyses on the age-dependent expression of CLDN6 in normal tissues is lacking, which limits the expansion of CLDN6 CAR-T cell clinical trials to pediatric populations. Methods: We analyzed CLDN6 expression in extracranial solid tumors and normal tissues of children using RNA-sequencing data from over 500 pediatric solid tumor samples, qRT-PCR and immunohistochemistry (IHC) in more than 100 fresh-frozen tumor samples and, approximately, 250 formalin-fixed paraffin-embedded (FFPE) samples. We examined normal tissue expression via qRT-PCR in 32 different infant tissues and via IHC in roughly 290 tissues from donors across four age groups, as well as in fetal autopsy samples. Results: In fetal tissues, we detected CLDN6 expression primarily in the epithelial cells of several organs, including the skin, lungs, kidneys, intestinal tract, and pancreas, but not in undifferentiated blastemal cells. Postnatally, we found CLDN6-positive epithelial progenitors only during the first few weeks of life. In older-age groups, isolated clusters of CLDN6-positive progenitors were present, but in scarce quantities. In tumor tissues, we found strong and homogeneous CLDN6 expression in desmoplastic small round cell tumors and germ cell tumors. Wilms tumors demonstrated heterogeneous CLDN6 expression, notably absent in the blastemal component. Conclusions: These findings highlight an organ-specific presence of CLDN6-positive epithelial precursors that largely disappear in terminally differentiated epithelia within weeks after birth. Therefore, our data support CLDN6 as a viable therapeutic target in pediatric patients and justify their inclusion in basket studies for anti-CLDN6-based therapies.

Among the 152,810 estimated new cases of adenocarcinoma of the colon (COAD) and the rectum (READ) in 2024, the rates of colorectal cancer (CRC) are increasing in young adults (age < 55 years) […]

Background/Objectives: Accurate non-invasive tests to improve early detection and diagnosis of lung cancer are urgently needed. However, no regulatory-approved blood tests are available for this purpose. We aimed to improve pulmonary nodule classification to identify malignant nodules in a high-prevalence patient group. Methods: This study involved 806 participants with undiagnosed nodules larger than 5 mm, focusing on assessing nucleosome levels and histone modifications (H3.1 and H3K27Me3) in circulating blood. Nodules were classified as malignant or benign. For model development, the data were randomly divided into training (n = 483) and validation (n = 121) datasets. The model’s performance was then evaluated using a separate testing dataset (n = 202). Results: Among the patients, 755 (93.7%) had a tissue diagnosis. The overall malignancy rate was 80.4%. For all datasets, the areas under curves were as follows: training, 0.74; validation, 0.86; and test, 0.79 (accuracy range: 0.80–0.88). Sensitivity showed consistent results across all datasets (0.91, 0.95, and 0.93, respectively), whereas specificity ranged from 0.37 to 0.64. For smaller nodules (5–10 mm), the model recorded accuracy values of 0.76, 0.88, and 0.85. The sensitivity values of 0.91, 1.00, and 0.94 further highlight the robust diagnostic capability of the model. The performance of the model across the reporting and data system (RADS) categories demonstrated consistent accuracy. Conclusions: Our epigenetic biomarker panel detected non-small-cell lung cancer early in a high-risk patient group with high sensitivity and accuracy. The epigenetic biomarker model was particularly effective in identifying high-risk lung nodules, including small, part-solid, and non-solid nodules, and provided further evidence for validation.