Journal of Cancer Research and Clinical Oncology最新文献

Purpose: The COVID-19 pandemic was associated with severe disruptions in healthcare worldwide. Cancer patients are at particular risk of adverse consequences from delays in diagnosis and treatment. To evaluate the available data on the impact of the pandemic on cancer diagnoses, oncological care and patient well-being in Germany, the German Society for Epidemiology (DGEpi) in collaboration with the Epidemiological Cancer Registry of Lower Saxony invited to a workshop on "COVID & Cancer" (held on 26-27 October 2023 in Hanover, Germany). This report provides a summary of the scientific presentations, highlights methodological challenges, and recognises essential evidence gaps.

Methods: Twelve studies addressing various aspects in relation to cancer diagnoses, oncological care and patient well-being during the COVID-19 pandemic in Germany and two talks sharing experiences from the UK and the Netherlands were presented at the workshop.

Results and conclusions: Results from German cancer registries consistently showed lower number of incident cancer diagnoses among adults during the first months of the pandemic compared to the respective months of the years before the pandemic. Data from the cancer registries of Baden-Württemberg and Lower Saxony found especially for breast cancer a notable drop (by approximately one third) in the numbers of diagnoses during the first restriction period (April-May 2020), during which the nationwide mammography screening programme in Germany was temporarily suspended. Overall, the extent and ways, in which the pandemic had adversely affected cancer diagnoses, oncological care and created service backlogs, is still not adequately understood. The long-term consequences are yet to be determined.

The Nod-Like Receptor (NLR) family pyrin domain containing 3 (NLRP3) inflammasome plays a role in regulating inflammatory signaling and is a well-established contributor to pyroptotic cell death. It has been investigated extensively in cancer but there remains limited evidence of its role within ovarian cancer (OC). Bioinformatic investigation of gene expression data has highlighted that higher expression of NLRP3 and genes associated with the NLRP3 complex appear to be positively correlated with OC and may also have prognostic significance. However, heterogeneity exists within the results and experimental data is limited and contradictory. If the NLRP3 inflammasome is to be exploited as a therapeutic target, further laboratory-based investigation is required to determine its role in cancer. Furthermore, its relationship with clinically important characteristics such as histopathological subtype may be of key significance in developing targeted therapies towards specific cohorts of patients.

Purpose: Highly complex tumor microenvironment makes hepatocellular carcinoma (HCC) as one of the most malignant tumors worldwide. The role of cellular senescence in HCC has been gradually recognized. The present study aimed to comprehensively elucidate the senescence-related features of HCC in single-cell and spatial dimension.

Methods: Single-cell RNA sequencing (scRNA-Seq) data was used to clarify the heterogeneity of senescence-related genes (SRGs) among multiple cell types within HCC. Spatial transcriptome RNA sequencing (stRNA-Seq) data was used for depicting SRGs features in spatial dimension. A prognostic model based on SRGs was constructed by using of bulk sequencing (bulk-Seq) data of HCC. The cell-cell interaction of senescent endothelial cells (ECs) in tumor microenvironment was analyzed. Then, the role of senescent ECs was verified through in vitro and in vivo experiments.

Results: The level of senescence demonstrated substantial heterogeneity among different cell types within tumor microenvironment of HCC, where ECs exhibited the most prominent senescent phenotype. Senescent ECs activated specific regulatory pathways through communicating with other cell types, with a potential impact on tumor progression. Spatial analysis revealed senescent ECs mainly located in the core region of HCC. The interaction of senescent ECs and immune cells implicated their role in tumor progression and immunotherapeutic response. In addition, CDKN2A was identified as an independent risk factor for HCC prognosis by constructing a prognostic model. Patients with high risk displayed an even worse outcome. The experimental verification indicated senescence of ECs determined by CDKN2A exhibited a secretory phenotype. Furthermore, senescent ECs with CDKN2A overexpression promote the proliferation and migration of HCC.

Conclusion: The present study recognizes the critical effect of senescent ECs defined by CDKN2A in the promotion of tumor progression, which sheds new light on the investigation of ECs senescence in HCC.

Purpose: In the treatment of hepatocellular carcinoma (HCC) with transarterial radioembolization (TARE), identifying reliable biomarkers for predicting survival outcomes remains a critical challenge. We aimed to address this gap by investigating the significance of serum cytokines associated with inflammation as potential biomarkers for the selection of patients for TARE.

Methods: Our retrospective study involved 161 patients diagnosed with HCC who underwent Y90 radioembolization at our medical center between 2010 and 2020. Serum samples from a subset of 78 patients were retrospectively analyzed to determine the concentrations of pro-inflammatory cytokines. The results from the prospective SORAMIC trial were used for independent validation.

Results: With a median overall survival of 36 weeks (range 4-436), our study showed the strongest correlation between 12-week survival and IL-8 levels before treatment (p < 0.001), while other relevant interleukins, interferon-α2, INF-γ, TNF-α and MCP-1 were not associated with survival. IL-8 levels below the cut-off of 190 pg/mL were significantly associated with increased 12-week and 24-week survival, with hazard ratios of 19.01 (95% CI: 2.29-157.89) and 2.57 (95% CI: 1.05-6.31), respectively (p = 0.006 and p = 0.039, respectively). In the adjusted multivariate analysis, the 190 pg/mL cut-off for IL-8 remained independently associated with 12- (p = 0.011) and 24-week survival (p = 0.039). Similarly, the SORAMIC population showed a strong association between IL-8 levels and 36-week survival (p = 0.03).

Conclusion: Our study emphasizes the pivotal role of IL-8 as a valuable parameter, demonstrating its potential for predicting treatment outcomes and assessing liver function in patients with HCC undergoing TARE. The robustness of these findings warrants further validation.

Purpose: Renal and hematological toxicity are side effects and dose-limiting factors of Peptide Receptor Radionuclide Therapy (PRRT). We aimed to assess the changes in renal and hematological function and associations with survival in neuroendocrine tumor (NET) patients treated with PRRT.

Methods: A retrospective cohort of 448 NET patients treated with either ¹⁷⁷Lu-DOTATATE or ⁹⁰Y-DOTATOC were followed for changes of renal and hematological function. Renal function was assessed by monitoring changes in serum creatinine, blood urea nitrogen and estimated glomerular filtration rate. Hematological function was determined by examining changes in white blood cell counts (WBC), platelet counts, and hemoglobin levels over time. Piecewise linear mixed effect models were applied to model the longitudinal repeated measurements of renal and hematological function. Overall survival (OS) and progression-free survival (PFS) were modelled using Cox proportional hazard regressions.

Results: Of the 448 PRRT treated patients, 335 received ¹⁷⁷Lu-DOTATATE (74.78%) and 113 were treated with ⁹⁰Y-DOTATOC (25.22%). Comparing patients treated with ¹⁷⁷Lu-DOTATATE to those treated with ⁹⁰Y-DOTATOC, renal function did not differ significantly prior to, during or after PRRT. Compared with patients treated with ⁹⁰Y-DOTATOC, significantly decreased indicators of hematological function were observed in those treated with ¹⁷⁷Lu-DOTATATE prior to and during PRRT treatment (WBC: estimate, -0.10, 95% CI, -0.15 to -0.05; P < 0.001; platelet count: estimate, -2.53, 95% CI, -3.83 to -1.24; P < 0.001), and no significant recovery was observed in hematological function post PRRT. Individuals who received ¹⁷⁷Lu-DOTATATE tended to have a longer PFS (hazard ratio, 0.47, 95%CI: 0.28-0.79, P = 0.004) compared with ⁹⁰Y-DOTATOC, but there was no difference in OS.

Conclusion: There was no significant renal, but minor hematological toxicity, in patients treated with ¹⁷⁷Lu-DOTATATE compared with ⁹⁰Y-DOTATOC. Compared to ⁹⁰Y-DOTATOC, ¹⁷⁷Lu-DOTATATE appears to enhance PFS, but not OS. Treatment with ¹⁷⁷Lu-DOTATATE may necessitate follow-up for hematological toxicity irrespective of other therapies prior to PRRT.

Objective: To investigate the value of ¹⁸F-FDG PET/CT-based intratumoral and peritumoral radiomics in predicting the efficacy of neoadjuvant chemotherapy (NAC) for breast cancer.

Methods: 190 patients who met the inclusion and exclusion criteria from 2017 to 2022 were studied. Features were extracted from the PET/CT intratumoral and peritumoral regions, feature selection was performed through the correlation analysis, t-tests, and least absolute shrinkage and selection operator regression (LASSO). Four classifiers, support vector machine (SVM), k-nearest neighbor (KNN), logistic regression (LR), and naive bayes (NB) were used to build the prediction models. The receiver operating characteristic (ROC) curves were plotted to measure the predictive performance of the models. Concurrent stratified analysis was conducted to establish subtype-specific features for each molecular subtype.

Results: Compared to intratumoral features alone, intratumoral + peritumoral features achieved higher AUC values in each classifier. The SVM model constructed with intratumoral + peritumoral features achieved the highest AUC values in both the train and test set (train set: 0.95 and test set: 0.83). Subtype-specific features improve performance in predicting the efficacy of NAC (luminal group: 0.90; HER2 + group: 0.86; triple negative group: 0.92).

Conclusion: Intratumoral and peritumoral radiomics models based on ¹⁸F-FDG PET/CT can reliably forecast the efficacy of NAC, thereby assisting clinical decision-making.

Background: The hyperintensity area surrounding the residual cavity on postoperative fluid-attenuated inversion recovery (FLAIR) image is a potential site for glioblastoma (GBM) recurrence. This study aimed to develop a nomogram using quantitative metrics from subregions of this area, prior to chemoradiotherapy (CRT), to predict early GBM recurrence.

Methods: Adult patients with GBM diagnosed between October 2018 and October 2022 were retrospectively analyzed. Quantitative metrics, including the mean, maximum, minimum, median values, and standard deviation of FLAIR signal intensity (SI) (measured using 3D-Slicer software), were extracted from the following subregions surrounding the residual cavity on post-contrast T1-weighted (CE-T1WI)-FLAIR fusion images: the enhancing region (ER), non-enhancing region (NER), and combined ER + NER. Independent prognostic factors were identified using Cox regression and least absolute shrinkage and selection operator (LASSO) analyses and were incorporated into the prediction nomogram model. The model's performance was evaluated using the C-index, calibration curves, and decision curves.

Results: A total of 129 adult GBM patients were enrolled and randomly assigned to a training (n = 90) and a validation cohorts (n = 39) in a 7:3 ratio. Sixty-nine patients experienced postoperative recurrence. Cox regression analysis identified subventricular zone involvement, the median FLAIR intensity in the ER, the rFLAIR (relative FLAIR intensity compared to the contralateral normal region) of ER + NER, and corpus callosum involvement as independent prognostic factors. For predicting recurrence within 1 year after surgery, the nomogram model had a C-index of 0.733 in the training cohort and 0.746 in the validation cohort. Based on the nomogram score, post-operative GBM patients could be stratified into high- and low-risk for recurrence.

Conclusions: Nomogram models which based on quantitative metrics from FLAIR hyperintensity subregions may serve as potential markers for assessing GBM recurrence risk. This approach could enhance clinical decision-making and provide an alternative method for recurrence estimation in GBM patients.

Purpose: Despite the development of novel drugs and the widespread use of hematopoietic cell transplantation, the prognosis of patients (pts) with multiple myeloma and extramedullary involvement (soft-tissue plasmacytoma, STP) is rather unfavorable.

Methods: A retrospective analysis of 120 pts with STP treated between 2007 and 2022 was performed. The effects of demographic and clinical characteristics on treatment response, progression-free survival (PFS), and overall survival (OS) were evaluated.

Results: The rate of serological response to first-line STP treatment (at least partial remission) was 67%, and the rate of imaging response was 59%. With a median follow-up of 84.2 months, the median PFS was 10.5 months (primary STP: 20.2 months; secondary STP: 5.8 months), and the median OS was 24.5 months (primary STP: 34.5 months; secondary STP: 12.4 months). Based on the multivariate regression analysis, secondary STP (HR_PFS 2.75; HR_OS 2.63) and organ involvement (HR_PFS 1.45; HR_OS 1.68) were found to be negative prognostic factors of both PFS and OS. In a prognostic model, pts with at least one of these factors had a significantly worse PFS (HR_PFS 3.31) and OS (HR_OS 3.45) than those with none risk factor.

Conclusion: In pts with STP, risk-adapted treatment strategies including immunotherapies and cell therapies are urgently required.

Purpose: To investigate the clinical significance and functional role of SIGLEC1-positive cells in non-small cell lungcancer (NSCLC) patients, focusing on their prognostic impact and therapeutic response.

Methods: A multicenter retrospective cohort analysis was conducted, integrating data from multiple sources. Weanalyzed SIGLEC1 expression in NSCLC tissues, clinicopathological features, overall survival outcomes,chemotherapy responsiveness, and sensitivity to targeted therapies. We also developed a prognostic model basedon SIGLEC1 expression and clinical variables.

Results: SIGLEC1 expression was significantly downregulated in NSCLC tissues, and the density of SIGLEC1-positivecells was inversely correlated with various clinicopathological features. Notably, patients with high infiltration ofSIGLEC1-positive cells exhibited significantly better overall survival outcomes. Furthermore, elevated SIGLEC1expression was associated with improved responsiveness to chemotherapy and demonstrated distinct patterns ofsensitivity to targeted therapies. A robust prognostic model was developed by integrating SIGLEC1 expression andclinical variables.

Conclusions: This study highlighted the downregulation of SIGLEC1 in NSCLC tissues and its significant associationwith patient prognosis and therapeutic response. The findings suggested that SIGLEC1 played a critical role inmodulating the tumor immune microenvironment and has potential as both a prognostic biomarker and therapeutictarget in NSCLC.

Purpose: Tumor recurrence after radiofrequency ablation (RFA) affects the survival rate of patients and limits its clinical application. Tumor recurrence around the ablation area may be related to the thermal injury of hepatocytes (HCs) around the tumor, but the specific mechanism is still unclear.

Methods: A liver cancer thermal injury mouse model was established via RFA in the C57BL/6 mice. Primary HCs and Kupffer cells (KCs) were isolated and cultured to assess their sensitivity to thermal injury via the MTT assay. Flow cytometry was used to assess macrophage polarization. Furthermore, Western blotting and co-immunoprecipitation (co-IP) were utilized to evaluate the protein expression of intracellular signaling pathway. Finally, Transwell and wound healing assays was conducted to evaluate the invasion potential of liver cancer cells.

Results: Our findings revealed that RFA-induced liver thermal injury promoted the upregulation and secretion of HMGB1 in HCs. HMGB1 had a protective effect on HCs thermal injury, potentially mediated through autophagy regulation. Heat-injured HCs release HMGB1, which activates the TREM1/JAK2/STAT3 signaling pathway in KCs, thus fostering an immunosuppressive tumor microenvironment (TME). Moreover, HMGB1 secretion by heat-injured HCs exacerbates the migration and invasion of HCC cells by influencing macrophage polarization.

Conclusion: RFA-induced thermal injury triggers HMGB1 release from HCs, driving macrophage M2 polarization and increasing the invasion ability of liver cancer cells. These findings reveal a potential therapeutic target for combating liver cancer recurrence following thermal ablation.