Cancer diagnosis & prognosis最新文献

Background/aim: Platinum-based adjuvant chemotherapy (AC) is recommended for invasive upper tract urothelial carcinoma (UTUC); however, many patients are ineligible for cisplatin due to renal impairment following radical nephroureterectomy (RNU). The optimal perioperative chemotherapy (PC) strategy for RNU remains unclear. This study focused on the impact of PC on renal function.

Patients and methods: We retrospectively evaluated patients with clinical T2-4N0M0 UTUC who underwent RNU at our institution between 2018 and 2024. Patients were stratified into three groups: AC, neoadjuvant chemotherapy (NAC), and no-PC. New baseline estimated glomerular filtration rate (NB-eGFR) was defined as the eGFR at one-month post-treatment. Longitudinal eGFR changes from NB-eGFR were assessed, and the incidence of a 20% decline in eGFR from NB-eGFR was examined.

Results: A total of 27 patients were included: eight (30%) received NAC, five (19%) received AC, and 14 (51%) received no-PC. No patient received both NAC and AC. The mean NB-eGFR for the AC, NAC, and no-PC groups was 47.7, 42.3, and 40.7 ml/min/1.73 m², respectively. Over a median follow-up of 29 months, three patients (two in the NAC group and one in the no-PC group) developed a 20% decline in eGFR from NB-eGFR. Annual changes in eGFR were +1.0, -1.5, and -0.8 ml/min/1.73 m²/year, with no significant differences among groups.

Conclusion: Although the sample size was limited, this study suggests that PC does not significantly impair long-term renal function. Both AC and NAC appear to be viable treatment options for patients with invasive UTUC.

Background/aim: Advanced osteosarcomas tend to have poor prognosis with limited therapeutic options beyond first-line therapy. This retrospective, multi-institutional study aimed to evaluate the association between histological response to chemotherapy and survival outcomes, as well as the influence of sex, tumor size, location, and other factors in a Greek cohort.

Patients and methods: We retrospectively studied the predictive value of distant metastasis, percentage of necrosis, and grade of tumor in 77 cases of sarcoma treated in 8 medical centers in Greece between 2004 and 2022. Median follow up time from the time of diagnosis was 27 months. Statistical analysis was performed using a two-sided significance level of p=0.05.

Results: Our analysis revealed that short bones were affected significantly more frequently in older [median age=43 years, interquartile range (IQR)=30-50] than younger patients (median age=26 years, IQR=18-40). Distant metastasis was significantly associated with shorter overall survival [OS; HR=3.7, 95% confidence interval (CI)=1.5-9.16, p=0.01]. In addition, we found that 90% or greater tumor necrosis was significantly associated with longer disease-free survival (DFS; HR=0.09, 95% CI=0.01-0.09, p=0.003) but not with OS (HR=0.62, 95% CI=0.24-1.58, p=0.3). Male sex was associated with shorter DFS (HR=5.61, 95% CI=2.12-14.9), p<0.001). Grade or bone affected (long vs. short) were not significantly associated with survival.

Conclusion: Osteosarcoma patients with 90% or more tumor necrosis were found to have survival advantage. Differences in DFS between sexes highlight the need for tailored treatment approaches and further exploration of biological underpinnings.

Background/aim: Pancreatic cancer is a highly aggressive disease, with limited prognostic tools available for risk stratification. This study aimed to evaluate the prognostic significance of nine tissue biomarkers and develop a biomarker-based risk score for predicting patient survival.

Patients and methods: Tumor samples from 141 resected patients with pancreatic cancer were analyzed with tissue microarrays and immunohistochemistry to assess the expression levels of CA 19-9, CA 50, CA 242, CA 724, GDF15, MMP7, MUC2, TFF1, and THBS2. A Lasso-Cox regression model was used to develop a prognostic risk score and the performance of the risk score was assessed using Kaplan-Meier survival analysis and receiver operating characteristic (ROC) curves.

Results: Among the nine biomarkers, CA19-9, CA50, CA242, CA724, and THBS2 were identified as significant predictors of survival in univariable analyses. A prognostic model was constructed and included CA19-9, CA724, THBS2, tumor location, resection margin status, grade, and American Joint Committee on Cancer stage. The prognostic risk score effectively stratified patients into high- and low-risk groups, demonstrating a significant difference in median survival (14.8 vs. 36.0 months) and 5-year survival (5.9% vs. 26.0%) (p<0.001). The model achieved good predictive performance for long-term survival with an AUC of 0.704.

Conclusion: This study identifies several tissue biomarkers associated with survival and introduces an integrative risk model to stratify pancreatic cancer patients by outcomes. The model shows good discriminatory ability and may provide a basis for more personalized risk assessment and treatment planning, although additional validation is required.

Background/aim: Plasmacytomas are neoplastic proliferations of plasma cells, usually presenting as solitary lesions distinct from multiple myeloma (MM). Solitary plasmacytomas in the oral cavity and head and neck are very rare, with limited data on clinical course and treatment response.

Case report: A 78-year-old woman presented with a solitary plasmacytoma on the palate. Imaging ruled out bone or systemic involvement. Pathology showed positivity for CD138, lambda light chain, CD79a, MUM1, Ki-67 (10-15%), and amyloid deposits. Although the patient received definitive radiation therapy (50 Gy/25 fractions), residual disease remained. At the patient's request, six cycles of systemic chemotherapy with daratumumab, lenalidomide, and dexamethasone (DRd) were administered, leading to further shrinkage without complete response.

Conclusion: This rare case of solitary plasmacytoma showed residual disease post definitive radiotherapy. In those residual tumors, close long-term monitoring is crucial.

Background/aim: Immune checkpoint inhibitors (ICIs) have been shown to be effective in various cancer subtypes and their use in clinical practice has become widespread in recent years. However, discussions on their effectiveness in geriatric patients and in cases of malnutrition are still ongoing. The aim of the study was to evaluate the association of geriatric nutritional index (GNRI) detected malnutrition risk with progression-free survival (PFS) and immune related adverse events (irAEs) in geriatric solid tumor patients treated with ICIs.

Patients and methods: The study was conducted retrospectively and included patients with metastatic solid tumors who received second- or third-line immunotherapy between 2018 and 2024 at the Dr. Abdurrahman Yurtaslan, Ankara Oncology Education and Research Hospital and Etlik City Hospital. The GNRI score of the patients at the start of immunotherapy was calculated, and the relationship between the GNRI score and PFS and irAEs was evaluated.

Results: No significant association was found between sex (p=0.28), comorbidity (p=0.34), polypharmacy (p=0.09), antibiotic (p=0.24) use and PFS. A significant association was found between ECOG PS (p<0.05) and GNRI (p=0.012) and PFS. In multivariate analysis, ECOG PS [hazard ratio (HR)=1.5, 95% confidence interval (CI)=1.0-2.2, p=0.036] and GNRI (HR=0.6, 95% CI=0.4-0.9, p=0.033) were statistically significant. The incidence of irAEs was statistically higher in patients with GNRI <98 (p=0.019).

Conclusion: Geriatric solid tumor patients are not fully represented in prospective clinical drug trials. Prospective studies are needed in which only geriatric patients are included, treatment efficacy and toxicity are assessed stepwise according to nutritional status, and malnutrition is treated to increase treatment efficacy and reduce toxicity.

Background/aim: Neo-lymphangiogenesis induces lymphatic invasion of cancer cells, significantly increasing the metastatic potential of breast carcinomas (BCs). Among the molecules that are implicated in lymphangiogenesis, podoplanin (PDPN, gene locus: 1p36.21) - a transmembrane receptor glycoprotein - is expressed exclusively in lymphatic vessels. The current study explored the impact of PDPN-dependent mean lymphatic micro-vessel density (mLMVD) in invasive ductal (inDBC) and invasive lobular breast adenocarcinomas (inLBC).

Materials and methods: A set of thirty (n=30) paraffin-embedded invasive BC tissue sections (22 inDBCs and 8 inLBCs, respectively) were analyzed by applying a combination of immunocytochemistry (IHC) and digital image analysis (DIA) assays.

Results: High and moderate mLMVD rates (defined by the mean number of lymphatic domains with emboli in five optical fields under 400X magnification) were detected in 5/30 (16.6%) and 6/30 (20%) cases (total 11/30 (36.6%), respectively. In these cases, PDPN demonstrated strong cytoplasmic/membranous staining intensity. The remaining 19 cases (63.4%) demonstrated low levels of mLMVD. mLMVD was significantly correlated with the stage of the examined malignancies (p=0.019), whereas a marginal association with the grade of differentiation was identified (p=0.042). No significant correlation was observed with histological subtype (p=0.234) or tumor size (p=0.085).

Conclusion: Neo-lymphangiogenesis in BCs is a critical histological feature in the progression of the malignancy and is correlated with an aggressive phenotype (advanced stage). PDPN expression in lymphatic micro vessels is a reliable biomarker for evaluating lymphangiogenic activity in BCs, independently of their histotype, especially when assessed with precise DIA techniques.

Background/aim: Immune checkpoint inhibitors (ICIs) have improved survival in metastatic renal cell carcinoma (mRCC), with nivolumab (NIVO) plus ipilimumab (IPI) showing benefits in intermediate- and poor-risk patients. Despite first-line efficacy, progression is common, requiring second-line therapies. Tyrosine kinase inhibitors (TKIs) are commonly administered after ICIs; however, the relationship between progression-free survival (PFS) in first- and second-line settings is not well defined. This study examined the correlation of PFS in patients with mRCC treated with ICIs followed by TKIs.

Patients and methods: This retrospective multicenter study analyzed 66 patients with mRCC who received NIVO + IPI as first-line therapy and subsequent TKIs between September 2018 and February 2023. Patients were stratified according to the International Metastatic RCC Database Consortium (IMDC) risk classification.

Results: Median PFS for second-line TKIs was 6.9 months, and overall survival was 17.7 months. While no significant correlation was observed between first- and second-line PFS in the overall cohort or the IMDC intermediate-risk subgroup, a significant positive correlation was found in the poor-risk group (Spearman's rho=0.677, p=0.002).

Conclusion: Treatment outcomes in poor-risk patients may exhibit a predictable response pattern across therapy lines, potentially informing personalized treatment strategies.

Background/aim: Tumor treatments remain unsatisfactory, as many patients continue to die despite therapy. There is an urgent need for novel drug targets, particularly for rare tumors. In this study, we sought to identify genes with prognostic significance for survival in patients with phaeochromocytoma or paraganglioma. We also examined whether these genes are relevant in other tumor entities.

Patients and methods: We mined the TCGA-based KM Plotter and studied 186 risk genes for phaeochromocytoma and paraganglioma.

Results: Using Kaplan-Meier statistics, we performed 3,163 calculations based on 7,489 tumor biopsies and identified a 2-gene signature for phaeochromocytoma/paraganglioma (AQP4, FAM84H). Since the 186 risk genes are not exclusively related to the development of phaeochromocytoma/paraganglioma alone, we also investigated their prognostic relevance in 17 other tumor types. A clustered 12-gene signature has been found common in four other tumor entities (liver hepatocellular carcinoma, renal clear cell carcinoma, renal papillary cell carcinoma, lung adenocarcinoma). This signature consisted of BUB1, BUB1B, CDK1, CENPA, CKAP2L, IQGAP3, MKI67, NDC80, PBK, RRM2, TOP2A, and TTK.

Conclusion: Our analysis provides a basis for the development of a novel prognostic test to predict the survival time of patients.

Background/aim: Identification of cancer biomarkers for early detection is required. However, little is known about which candidate cell signaling pathway markers can be identified and which pathways may serve as therapeutic targets. We focused on the disulfidptosis among numerous signaling pathways, because it is a mechanism that causes cell death and is associated with iron-dependent cell death or ferroptosis, the tricarboxylic acid cycle, energy metabolism, and glucose uptake. The aim of the study was to detect the disulfidptosis-linked gene signatures associated with stage-specific makers and prognosis.

Materials and methods: We examined the expression of 106 related genes in 324 patients with prostate cancer for disulfidptosis, a type of cell death triggered by disulfide stress resulting in disulfide bond-induced collapse of the cytoskeleton.

Results: The expression levels of UBASH3B, ANP32E, PRC1, ACTB, SPG20, and DBN1 increased with cancer progression. Of these, UBASH3B, PRC1, and ANP32E were strongly expressed in cases with Gleason score ≥8. Conversely, the expression levels of MYH13, FLNC, GLUD1, SAMM50, CHCHD3, and CAPZB decreased. Of these, GLUD1, CAPZB, and SAMM50 were decreased in cases with Gleason score ≥8. In addition, UBASH3B, ANP32E, PRC1, DBN1, FLNC, and GLUD1 enabled the estimation of biochemical recurrence (BCR)-free survival. In particular, the prognostic formula comprising ZHX2, SMPD4, and CHD4 using the Lasso-Cox regression model properly distinguished the BCR-free survival curves, indicating that these genes could be signatures for disulfidptosis.

Conclusion: Decoding disulfidptosis-related data in the transcriptome would provide crucial clues for finding novel approaches to personalized cancer medicine in prostate cancer.

Background/aim: The platelet-to-lymphocyte ratio (PLR), a systemic inflammatory biomarker, has been linked to treatment response in breast cancer (BC). However, its prognostic value in triple-negative breast cancer (TNBC) remains unclear. This meta-analysis evaluated the association between PLR and survival outcomes in patients with TNBC.

Materials and methods: This study was registered on PROSPERO in January 2024 under protocol number CRD42024506786. Databases searched were PubMed, Embase and Cochrane Library in December 2024. Hazard ratios (HRs) with 95% confidence intervals (CIs) were pooled to evaluate the association between PLR and overall (OS), progression-free (PFS), and disease-free (DFS) survival. Heterogeneity was assessed using I² statistics.

Results: Six studies with 819 patients with TNBC were included. PLR cut-off values were reported in five studies, determined either from previous research or receiver operating characteristic curves. A high PLR was not significantly associated with OS (HR=1.35, 95% CI=0.99-1.84; p=0.06; I²=43%). However, after excluding a high-risk bias study, high PLR was associated with reduced OS (HR=1.55, 95% CI=1.21-2.00; p=0.006; I²=0%). PLR was not significantly associated with PFS (HR=1.73, 95% CI=0.69-4.33; p=0.24; I²=79%) but was significantly associated with lower DFS (HR=1.69, 95% CI=1.25-2.28; p=0.0006; I²=0%).

Conclusion: While PLR was not significantly associated with OS or PFS, it correlated with DFS in TNBC: These findings suggest that PLR may have prognostic value, but further large-scale studies are needed to establish its clinical utility and optimal cut-off values.