Frontiers in Oncology
Latest articles in this journal
Frontiers in Oncology, Volume 13; https://doi.org/10.3389/fonc.2023.1077780
Background: The C-X-C motif chemokine ligand-9 (CXCL9) is related to the progression of multiple neoplasms. Yet, its biological functions in uterine corpus endometrioid carcinoma (UCEC) remain shrouded in confusion. Here, we assessed the prognostic significance and potential mechanism of CXCL9 in UCEC.Methods: Firstly, bioinformatics analysis of the public cancer database, including the Cancer Genome Atlas / the Genotype-Tissue Expression project (TCGA+ GTEx, n=552) and Gene Expression Omnibus (GEO): GSE63678 (n=7), were utilized for the CXCL9 expression-related analysis in UCEC. Then, the survival analysis of TCGA-UCEC was performed. Futher, the gene set enrichment analysis (GSEA) was carried out to reveal the potential molecular signaling pathway in UCEC associated with CXCL9 expression. Moreover, the immunohistochemistry (IHC) assay of our validation cohort (n=124) from human specimens were used to demonstrate the latent significance of CXCL9 in UCEC.Results: The bioinformatics analysis suggested that CXCL9 expression was significantly upregulated in UCEC patients; and hyper-expression of CXCL9 was related to prolonged survival. the GSEA enrichment analysis showed various immune response-related pathways, including T/NK cell, lymphocyte activation, cytokine-cytokine receptor interaction network, and chemokine signaling pathway, mediated by CXCL9. In addition, the cytotoxic molecules (IFNG, SLAMF7, JCHAIN, NKG7, GBP5, LYZ, GZMA, GZMB, and TNF3F9) and the immunosuppressive genes (including PD-L1) were positively related to the expression of CXCL9. Further, the IHC assay indicated that the CXCL9 protein expression was mainly located in intertumoral and significantly upregulated in the UCEC patients; UCEC with high intertumoral CXCL9 cell abundance harbored an improved prognosis; a higher ratio of anti-tumor immune cells (CD4+, CD8+, and CD56+ cell) and PD-L1 was found in UCEC with CXCL9 high expression.Conclusion: Overexpressed CXCL9 correlates with antitumor immunity and is predictive of a favorable prognosis in UCEC. It hinted that CXCL9 may serve as an independent prognostic biomarker or therapeutic target in UCEC patients, which augmented anti-tumor immune effects to furnish survival benefits.
Frontiers in Oncology, Volume 13; https://doi.org/10.3389/fonc.2023.1125637
Purpose: To develop and assess a deep convolutional neural network (DCNN) model for the automatic detection of bone metastases from lung cancer on computed tomography (CT)Methods: In this retrospective study, CT scans acquired from a single institution from June 2012 to May 2022 were included. In total, 126 patients were assigned to a training cohort (n = 76), a validation cohort (n = 12), and a testing cohort (n = 38). We trained and developed a DCNN model based on positive scans with bone metastases and negative scans without bone metastases to detect and segment the bone metastases of lung cancer on CT. We evaluated the clinical efficacy of the DCNN model in an observer study with five board-certified radiologists and three junior radiologists. The receiver operator characteristic curve was used to assess the sensitivity and false positives of the detection performance; the intersection-over-union and dice coefficient were used to evaluate the segmentation performance of predicted lung cancer bone metastases.Results: The DCNN model achieved a detection sensitivity of 0.894, with 5.24 average false positives per case, and a segmentation dice coefficient of 0.856 in the testing cohort. Through the radiologists-DCNN model collaboration, the detection accuracy of the three junior radiologists improved from 0.617 to 0.879 and the sensitivity from 0.680 to 0.902. Furthermore, the mean interpretation time per case of the junior radiologists was reduced by 228 s (p = 0.045).Conclusions: The proposed DCNN model for automatic lung cancer bone metastases detection can improve diagnostic efficiency and reduce the diagnosis time and workload of junior radiologists.
Frontiers in Oncology, Volume 13; https://doi.org/10.3389/fonc.2023.1109978
Population-based cancer registries are responsible for collecting incidence and survival data on all reportable neoplasms within a defined geographical area. During the last decades, the role of cancer registries has evolved beyond monitoring epidemiological indicators, as they are expanding their activities to studies on cancer aetiology, prevention, and quality of care. This expansion relies also on the collection of additional clinical data, such as stage at diagnosis and cancer treatment. While the collection of data on stage, according to international reference classification, is consolidated almost everywhere, data collection on treatment is still very heterogeneous in Europe. This article combines data from a literature review and conference proceedings together with data from 125 European cancer registries contributing to the 2015 ENCR-JRC data call to provide an overview of the status of using and reporting treatment data in population-based cancer registries. The literature review shows that there is an increase in published data on cancer treatment by population-based cancer registries over the years. In addition, the review indicates that treatment data are most often collected for breast cancer, the most frequent cancer in women in Europe, followed by colorectal, prostate and lung cancers, which are also more common. Treatment data are increasingly being reported by cancer registries, though further improvements are required to ensure their complete and harmonised collection. Sufficient financial and human resources are needed to collect and analyse treatment data. Clear registration guidelines are to be made available to increase the availability of real-world treatment data in a harmonised way across Europe.
Frontiers in Oncology, Volume 13; https://doi.org/10.3389/fonc.2023.1051641
Background: Nicotinamide adenine dinucleotide (NAD+) metabolism is involved in a series of cancer pathogenesis processes, and is considered a promising therapeutic target for cancer treatment. However, a comprehensive analysis of NAD+ metabolism events on immune regulation and cancer survival has not yet been conducted. Here, we constructed a prognostic NAD+ metabolism-related gene signature (NMRGS) associated with immune checkpoint inhibitor (ICI) efficacy in glioma.Methods: 40 NAD+ metabolism-related genes (NMRGs) were obtained from the Reactome database and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Glioma cases with transcriptome data and clinical information were obtained from Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). NMRGS was constructed based on the calculated risk score using univariate analysis, Kaplan–Meier analysis, multivariate Cox regression, and nomogram. This NMRGS was verified in training (CGGA693) and validation (TCGA and CGGA325) cohorts. The immune characteristics, mutation profile, and response to ICI therapy were subsequently analyzed for different NMRGS subgroups.Results: Six NAD+ metabolism-related genes, including CD38, nicotinamide adenine dinucleotide kinase (NADK), nicotinate phosphoribosyltransferase (NAPRT), nicotinamide/nicotinic acid mononucleotide adenylyltransferase 3 (NMNAT3), poly(ADP-Ribose) polymerase family member 6 (PARP6), and poly(ADP-Ribose) polymerase family member 9 (PARP9), were ultimately used to construct a comprehensive risk model for glioma patients. Patients in the NMRGS-high group showed a poorer survival outcome than those in the NMRGS-low group. The area under curve (AUC) indicated that NMRGS has good potential in glioma prognostic prediction. A nomogram with improved accuracy was established based on independent prognostic factors (NMRGS score, 1p19q codeletion status, and WHO grade). Furthermore, patients in the NMRGS-high group showed a more immunosuppressive microenvironment, higher tumor mutation burden (TMB), higher human leucocyte antigen (HLA) expression and a more therapeutic response to ICI therapy.Conclusions: This study constructed a prognostic NAD+ metabolism-related signature associated with the immune landscape in glioma, which can be used for guiding individualized ICI therapy.
Frontiers in Oncology, Volume 13; https://doi.org/10.3389/fonc.2023.1095637
Introduction: Diffusion-weighted imaging (DWI) with parallel reconstruction may suffer from a mismatch between the coil calibration scan and imaging scan due to motions, especially for abdominal imaging.Methods: This study aimed to construct an iterative multichannel generative adversarial network (iMCGAN)-based framework for simultaneous sensitivity map estimation and calibration-free image reconstruction. The study included 106 healthy volunteers and 10 patients with tumors.Results: The performance of iMCGAN was evaluated in healthy participants and patients and compared with the SAKE, ALOHA-net, and DeepcomplexMRI reconstructions. The peak signal-to-noise ratio (PSNR), structural similarity index measure (SSIM), root mean squared error (RMSE), and histograms of apparent diffusion coefficient (ADC) maps were calculated for assessing image qualities. The proposed iMCGAN outperformed the other methods in terms of the PSNR (iMCGAN: 41.82 ± 2.14; SAKE: 17.38 ± 1.78; ALOHA-net: 20.43 ± 2.11 and DeepcomplexMRI: 39.78 ± 2.78) for b = 800 DWI with an acceleration factor of 4. Besides, the ghosting artifacts in the SENSE due to the mismatch between the DW image and the sensitivity maps were avoided using the iMCGAN model.Discussion: The current model iteratively refined the sensitivity maps and the reconstructed images without additional acquisitions. Thus, the quality of the reconstructed image was improved, and the aliasing artifact was alleviated when motions occurred during the imaging procedure.
Frontiers in Oncology, Volume 13; https://doi.org/10.3389/fonc.2023.1107171
Clonality assessment using the unique rearrangements of immunoglobulin (IG) and T-cell receptor (TR) genes in lymphocytes is a widely applied supplementary test for the diagnosis of B-cell and T-cell lymphoma. To enable a more sensitive detection and a more precise comparison of clones compared with conventional clonality analysis based on fragment analysis, the EuroClonality NGS Working Group developed and validated a next-generation sequencing (NGS)-based clonality assay for detection of the IG heavy and kappa light chain and TR gene rearrangements for formalin-fixed and paraffin-embedded tissues. We outline the features and advantages of NGS-based clonality detection and discuss potential applications for NGS-based clonality testing in pathology, including site specific lymphoproliferations, immunodeficiency and autoimmune disease and primary and relapsed lymphomas. Also, we briefly discuss the role of T-cell repertoire of reactive lymphocytic infiltrations in solid tumors and B-lymphoma.
Frontiers in Oncology, Volume 13; https://doi.org/10.3389/fonc.2023.1096027
Objective: The study aimed to evaluate the non-cancer-specific death risk and identify the risk factors affecting the non-cancer-specific survival (NCSS) in patients with primary central nervous system lymphoma (PCNSL).Methods: This multi-center cohort study included 2497 patients with PCNSL in the Surveillance, Epidemiology and End Results (SEER) database from 2007 to 2016, with a mean follow-up of 4.54 years. The non-cancer-specific death risk in patients with PCNSL and primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) was evaluated using the proportion of deaths, standardized mortality ratio (SMR), and absolute excess risk (AER). Univariate and multivariate competing risk regression models were utilized to identify the risk factors of NCSS.Results: PCNSL was the most frequent cause of death in PCNSL patients (75.03%). Non-cancer-specific causes constituted a non-negligible portion of death (20.61%). Compared with the general population, PCNSL patients had higher risks of death from cardiovascular disease (CVD) (SMR, 2.55; AER, 77.29), Alzheimer’s disease (SMR, 2.71; AER, 8.79), respiratory disease (SMR, 2.12; AER, 15.63), and other non-cancer-specific diseases (SMR, 4.12; AER, 83.12). Male sex, Black race, earlier year of diagnosis (2007–2011), being unmarried, and a lack of chemotherapy were risk factors for NCSS in patients with PCNSL and PCNS-DLBCL (all P < 0.05).Conclusion: Non-cancer-specific causes were important competing causes of death in PCNSL patients. More attention is recommended to non-cancer-specific causes of death in the management of PCNSL patients.
Frontiers in Oncology, Volume 13; https://doi.org/10.3389/fonc.2023.1010561
Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by uncontrolled activation of the immune system. HLH is a reactive mononuclear phagocytic response that occurs in association with a constellation of conditions such as malignancies and infections. The clinical diagnosis of HLH remains challenging because HLH can present with symptoms that significantly overlap with other causes of cytopenia, such as sepsis, autoimmune diseases, hematological cancers, and multiorgan failure. A 50-year-old man went to the emergency room (ER) for hyperchromic urine, melena, gingivorrhagia, and spontaneous abdominal wall hematomas. The first blood tests showed severe thrombocytopenia, alteration of the INR, and consumption of fibrinogen, and therefore, a diagnosis of disseminated intravascular coagulation (DIC) was made. A bone marrow aspirate showed numerous images of hemophagocytosis. With the suspicion of immune-mediated cytopenia, oral etoposide, intravenous immunoglobulin, and intravenous methylprednisolone were administered. Then, a diagnosis of gastric carcinoma was performed with a lymph node biopsy and gastroscopy. On the 30th day, the patient was transferred to the oncology ward of another hospital. On admission, he had serious piastrinopenia, anemia, hypertriglyceridemia, and hyperferritinemia. He was supported with a platelet transfusion and underwent a bone biopsy that showed a picture compatible with myelophthisis from diffuse medullary localization of a carcinoma of gastric origin. A diagnosis of HLH secondary to solid neoplasm was formulated. The patient started chemotherapy with oxaliplatin, calcium levofolinate, 5-fluorouracil bolus, 5-fluorouracil for 48 h (mFOLFOX6), and methylprednisolone. Six days after the third cycle of mFOLFOX6, the patient was discharged with the stabilization of his piastrinopenia condition. The patient continued chemotherapy with an improvement in his clinical conditions and normalization of hematological values. After 12 cycles of mFOLFOX, it was decided to start maintenance chemotherapy with capecitabine but, unfortunately, after only one cycle, HLH reappeared. The oncologist has to keep in mind the existence of HLH when there is an unusual clinical presentation of cancer, such as cytopenia affecting ≥2 lineages and alterations of ferritin and triglycerides other than fibrinogen and coagulation. Increased attention and additional research as well as a close collaboration with hematologists are needed to benefit patients with solid tumors complicated by HLH.
Frontiers in Oncology, Volume 13; https://doi.org/10.3389/fonc.2023.1082789
Introduction: Acute lymphoblastic leukemia (ALL) and lymphomas affect both pediatric and adult populations, therefore, they might be treated by pediatric or adult centers.It has been proven that the prognosis among adolescents and young adults (AYA) is poorer than among children, which remains a subject of research. Many factors are suspected to affect the diagnostic and treatment processes in adolescents and young adults, one of them being the organization of the healthcare system.The aimof the studywas to compare the time intervals between different events on disease trajectory in pediatric and AYA groups suffering from ALL and lymphomas.Methods: We collected data on 81 patients diagnosed with ALL (50 children and 31 AYAs) and 100 patients diagnosed with lymphomas (50 children and 50 AYAs). Statistical analysis was performed in order to compare the groups.Results: The results confirmed the hypothesis that the duration of the diagnostic process differs significantly between groups. For patients with ALL, the analyzed time intervals were significantly shorter in the pediatric group than in the AYA group: first contact with a GP - admission to Hematology Department (2 vs. 5 days; pvalue= 0.004), first contact with a GP - treatment (6 vs. 12 days, p-value=0.001), diagnosis - treatment (1 vs. 3 days, p-value=0.003). In the case of patients suffering from lymphomas, the results were similar. The analyzed time intervals were significantly shorter in the pediatric group than in the AYA group: first contact with a GP- diagnosis (21 vs. 40.5 days, p-value<0.0001), first contact with a GP - treatment (27 vs. 65 days, p-value<0.0001). Trend analysis showed that the longer patients had presented symptoms before contacting the primary care physician, the longer they waited for the beginning of treatment both in ALL and lymphomas groups (p-values=0.0129 and 0.0038 respectively).Discussion: As the diagnostic and treatment processes are longer for AYA patients, actions must be undertaken in order to ensure equality and improve the healthcare system in Poland and possibly other countries.
Frontiers in Oncology, Volume 13; https://doi.org/10.3389/fonc.2023.1044327
Background: Several randomized controlled trials (RCTs) have confirmed the favorable clinical benefit of pembrolizumab in advanced non-small cell lung cancer (NSCLC). However, considering the strict inclusion and exclusion criteria in clinical research, there are certain differences between patients in the real-world, it is unclear whether the findings of clinical trials are fully representative of the treatment efficacy in patients who will eventually use it. Therefore, to further comprehensively assess the efficacy and safety of pembrolizumab in NSCLC, we conducted a systematic review and meta-analysis based on the latest RCTs and real-world studies (RWSs).Methods: We systematically searched PubMed, Embase, The Cochrane Library, The Web of Science, and clinical trials.gov as of December 2021. RCTs and RWSs of patients receiving pembrolizumab monotherapy or in combination with chemotherapy for advanced NSCLC were included.Results: The meta-analysis ultimately included 11 RCTs and 26 RWSs with a total of 10,695 patients. The primary outcomes of this study were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), serious adverse events (SAEs), the incidence of severe pneumonia reactions, and drug-related mortality. Direct meta-analysis results showed that in RCTs, pembrolizumab in combination with chemotherapy was superior to chemotherapy in terms of OS (HR=0.60, 95%CI:0.50-0.73), PFS (HR=0.47, 95%CI:0.38-0.58) and ORR (OR=3.22, 95%CI:2.57-4.03); pembrolizumab monotherapy was superior to chemotherapy in terms of OS (HR=0.73, 95%CI:0.66-0.80) and ORR (OR=1.90, 95%CI:1.17-3.09), but comparable to chemotherapy in terms of PFS (HR=0.83, 95%CI:0.66-1.04). The ORR values in retrospective single-arm studies were 45% (40%-51%).Conclusion: In RCTs, pembrolizumab monotherapy or in combination with chemotherapy is more effective and safer than chemotherapy for advanced NSCLC. In RWSs, ECOG PS 0-1 was shown to correlate with PFS and OS for patients with NSCLC.