Metastasis Group Research Articles

Differences in tissue-associated bacteria between metastatic and non-metastatic colorectal cancer.

Accumulated evidence indicates that the intestinal microbiota plays crucial roles in the initiation and progression of colorectal cancer (CRC). However, the effects of the tissue-associated microbiota on CRC metastasis are poorly defined. The aim of this study was to explore the differences in bacteria between metastatic and non-metastatic CRC tissues and identify potential bacterial species that associate with CRC metastasis. 16S rDNA amplicon high-throughput sequencing was used to test the intestinal tissue-associated microbiota in patients with metastatic CRC (n = 48) and non-metastatic CRC (n = 44). The microbial diversity and differential species were analysed by standard microbiological methods, and then the differential bacteria were confirmed by qPCR. Receiver operating characteristic (ROC) curves were plotted to evaluate the ability of the differential bacteria in predicting the metastasis of CRC. In addition, the microbial compositions of tumor-adjacent tissues from the metastatic and non-metastatic CRC groups were analysed. The α- or β-diversity of microbial community between the metastatic and non-metastatic CRC groups did not exhibit significant differences. However, some bacterial abundances between two groups showed significant differences. At the phylum level, Bacteroidota and Desulfobacterota were significantly higher in the metastatic group than in the non-metastatic group, while Proteobacteria was significantly decreased in the metastatic group. At the genus level, Bacteroides (mainly composed of Bacteroides fragilis and Bacteroides uniformis) was significantly higher in the metastatic group than in the non-metastatic group, while Streptococcus and Escherichia-Shigella were significantly decreased. The ROC curves of the selected bacteria showed area under the curve (AUC) values ranging from 0.598 to 0.69; when CEA and the selected bacteria were combined, the AUC values increased from 0.678 to 0.705. In addition, the bacterial composition of tumor-adjacent tissues from the metastatic and non-metastatic CRC groups were also different, and the differential bacteria were consistent with those between metastatic and non-metastatic CRC tumor tissues. The bacterial composition of tumor and tumor adjacent tissue from the metastatic CRC group was different from that of the non-metastatic CRC group; in particular, Bacteroides was increased, and Streptococcus was decreased. These findings are helpful to further reveal the mechanism of CRC metastasis and provide new ideas for the clinical diagnosis and treatment of CRC metastasis.

Atezolizumab plus cabozantinib versus cabozantinib monotherapy for patients with renal cell carcinoma after progression with previous immune checkpoint inhibitor treatment (CONTACT-03): a multicentre, randomised, open-label, phase 3 trial

Immune checkpoint inhibitors are the standard of care for first-line treatment of patients with metastatic renal cell carcinoma, yet optimised treatment of patients whose disease progresses after these therapies is unknown. The aim of this study was to determine whether adding atezolizumab to cabozantinib delayed disease progression and prolonged survival in patients with disease progression on or after previous immune checkpoint inhibitor treatment. CONTACT-03 was a multicentre, randomised, open-label, phase 3 trial, done in 135 study sites in 15 countries in Asia, Europe, North America, and South America. Patients aged 18 years or older with locally advanced or metastatic renal cell carcinoma whose disease had progressed with immune checkpoint inhibitors were randomly assigned (1:1) to receive atezolizumab (1200 mg intravenously every 3 weeks) plus cabozantinib (60 mg orally once daily) or cabozantinib alone. Randomisation was done through an interactive voice-response or web-response system in permuted blocks (block size four) and stratified by International Metastatic Renal Cell Carcinoma Database Consortium risk group, line of previous immune checkpoint inhibitor therapy, and renal cell carcinoma histology. The two primary endpoints were progression-free survival per blinded independent central review and overall survival. The primary endpoints were assessed in the intention-to-treat population and safety was assessed in all patients who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov, NCT04338269, and is closed to further accrual. From July 28, 2020, to Dec 27, 2021, 692 patients were screened for eligibility, 522 of whom were assigned to receive atezolizumab-cabozantinib (263 patients) or cabozantinib (259 patients). 401 (77%) patients were male and 121 (23%) patients were female. At data cutoff (Jan 3, 2023), median follow-up was 15·2 months (IQR 10·7-19·3). 171 (65%) patients receiving atezolizumab-cabozantinib and 166 (64%) patients receiving cabozantinib had disease progression per central review or died. Median progression-free survival was 10·6 months (95% CI 9·8-12·3) with atezolizumab-cabozantinib and 10·8 months (10·0-12·5) with cabozantinib (hazard ratio [HR] for disease progression or death 1·03 [95% CI 0·83-1·28]; p=0·78). 89 (34%) patients in the atezolizumab-cabozantinib group and 87 (34%) in the cabozantinib group died. Median overall survival was 25·7 months (95% CI 21·5-not evaluable) with atezolizumab-cabozantinib and was not evaluable (21·1-not evaluable) with cabozantinib (HR for death 0·94 [95% CI 0·70-1·27]; p=0·69). Serious adverse events occurred in 126 (48%) of 262 patients treated with atezolizumab-cabozantinib and 84 (33%) of 256 patients treated with cabozantinib; adverse events leading to death occurred in 17 (6%) patients in the atezolizumab-cabozantinib group and nine (4%) in the cabozantinib group. The addition of atezolizumab to cabozantinib did not improve clinical outcomes and led to increased toxicity. These results should discourage sequential use of immune checkpoint inhibitors in patients with renal cell carcinoma outside of clinical trials. F Hoffmann-La Roche and Exelixis.

Diagnosis of SPECT/CT bone imaging combined with two serum examinations in patients with bone metastases from pulmonary cancer.

To study the clinical diagnostic value of SPECT/CT bone imaging combined with two serum examinations in patients with bone metastases from pulmonary cancer. The clinical data of 120 patients consistent with pulmonary cancer admitted to the First Affiliated Hospitalof Hebei North University from March 2019 to December 2019 were selected for retrospective analysis, and they were divided into the bone metastasis group (n = 58) and non-bone metastasis group (n = 62) according to comprehensive evaluation result of X-ray, CT, MRI and clinical follow-up. The CT values of patients were obtained by SPECT/CT bone imaging to compare serum levels of ALP (alkaline phosphatase belongs to phosphoric monoester hydrolases, as a specific phosphatase, mainly in body tissues and body fluid) and BAP (bone alkaline phosphatase is formed by different modification and processing of alkaline phosphatase, and is mainly released by osteoblasts) and CT values of patients in both groups, using receiver operating characteristic (ROC) curve to evaluate the diagnostic efficacy of single detection and combined detection. SPECT/CT bone imaging in patients with bone metastasis from pulmonary cancer showed abnormal radioactive accumulation in spine, pelvis and bilateral ribs. Serum ALP, BAP and CT values in bone metastasis group were overtly higher than the non-bone metastasis group (P < 0.001). Logistic regression analysis showed that serum ALP, BAP and CT value were independent risk factors for bone metastasis from pulmonary cancer. The AUC value and Youden index of combined diagnosis were higher than those of single diagnosis. SPECT/CT bone imaging combined with serum detection of ALP and BAP in patients with pulmonary cancer is helpful for early diagnosis of bone metastasis, which provides more basis for the formulation and selection of clinical treatment options.

Abstract 37: Exploring the Impact of Metastatic Breast Cancer Support Group in Nigeria

Abstract Purpose: Over 70% of breast cancer patients in Nigeria present metastatic/advanced breast cancer (MBC). An estimated 90% of breast cancer deaths are a result of metastatic disease, either at diagnosis or recurrence. MBC is associated with a severe burden to the patient, family, healthcare delivery system and society at large. Women living with MBC face many challenges ranging from poor access to MBC information, untreated pain, frequent breakdown of radiotherapy machines and absence of peer support. Methods: In this research, we set up the first metastatic breast cancer support group in Abuja. The group meet once every month on a face-to-face basis and also uses WhatsApp group for regular meaningful engagement. We explored the impact of the group on the patient’s quality of life (QoL) using a focused group discussion (FGD). Eighteen (18) patients participated in the two sessions of FGD. We also conducted a follow-up semi-structured interview with 8 MBC patients. Results: Many of the patients report that the support group provides a culture of love and strength over their death anxiety, especially meeting other patients who have lived with MBC longer. They also report having found peer support on the online WhatsApp group. Citation Format: Runcie C.W. Chidebe, Mary-Gloria A. Orji, Theodora Zitta-Nwosu, Khadijat Banwo-Fatai, Agha A. Agha, Darlingtina K. Esiaka, Tochukwu C. Orjiakor. Exploring the Impact of Metastatic Breast Cancer Support Group in Nigeria [abstract]. In: Proceedings of the 11th Annual Symposium on Global Cancer Research; Closing the Research-to-Implementation Gap; 2023 Apr 4-6. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(6_Suppl):Abstract nr 37.

Sequential learning for pan-tumor detection of metastatic disease progression.

e13591 Background: Detection of progression of patients with early stage cancer is a challenge for real world data from electronic health records (EHR). Temporal patterns common to patients’ data can detect patients with metastatic progression. A deep learning approach on longitudinal patient records of cancer lab testing, visit diagnosis codes, and cancer treatments was used to identify metastatic status. Methods: ICD-10-CM diagnosis codes, clinical lab values specific to cancer testing, and antineoplastic treatments were evaluated from longitudinal data of 128,614 patients who did not progress and 5,884 who did develop metastasis, across 47 tumor types in the Syapse Learning Health Network. Patients metastatic at diagnosis were excluded. Data were included beginning at the time of primary cancer diagnosis and ended for all surviving patients at an established administrative cutoff date. In the metastatic group, visits after the progression event were included but censored if they contained diagnosis codes specifically for secondary malignant neoplasms. A binary classification was developed using a multi-headed attention transformer in order to determine metastatic status. Patient history was sequentially aggregated to visit-level embeddings across their longitudinal record. Categorical layers were used for antineoplastics and diagnosis codes. Linear layers were used to embed lab values, as well as for visit intervals from primary cancer date and administrative cutoff date. All embeddings were used as feature inputs for the classifier. Pre-training random sampling of the non-metastatic population was applied to establish equally-weighted labels in a 80:10:10 split for training, validation, and testing sets; to account for the smaller population of patients who progressed to metastatic status. Results: This classification approach achieved 0.86 PR-AUC, 0.79 ROC-AUC, and 0.75 F1. This performance is comparable to published models trained for single tumor cohort prediction. With our censoring constraints, these model results are robust in the absence of routine signals of metastasis in the EHR, such as staging reports and diagnosis coding for distant metastases. Conclusions: This method generalizes, across multiple cancer types, an accurate classification of metastatic progression from patient visit history. This work is immediately useful for real world evidence data analysis complementing patients with metastases already captured in hospital registries. Using sequential deep learning with EHR data classes, this approach may be used to forecast metastatic progression for early intervention.

Biomarker analysis of phase II pembrolizumab maintenance treatment after chemotherapy response in patients with HER2-negative inflammatory breast cancer and triple-negative breast cancer.

1105 Background: Accumulating toxicities make indefinite chemotherapy unfeasible for many patients with metastatic/recurrent HER2-negative inflammatory breast cancer (IBC) or triple-negative breast cancer (TNBC). We conducted a single-arm phase II trial of pembrolizumab monotherapy to determine the efficacy of maintenance immunotherapy in patients with metastatic HER2-negative aggressive breast cancer and to identify biomarkers correlated with disease control. Methods: The study enrolled patients who had a complete response, partial response, or stable disease after a minimum of 3 cycles of chemotherapy for metastatic TNBC/IBC regardless of PD-L1 expression between 2015 and 2022. Pembrolizumab was administered at 200 mg every 3 weeks until disease progression, intolerable toxicity, or 2 years of exposure to the drug. The primary endpoint was the 4-month disease control rate (DCR), and the secondary endpoint was progression-free survival (PFS). Correlative studies were performed to determine associations between clinical response, and immune profiling consisting of T-cell clonality, immunophenotyping, and dendritic cell (DC) function with blood collected at baseline and after 2 cycles of pembrolizumab treatment. Results: Of 43 treated patients, 11 had metastatic IBC and 32 had TNBC. The median number of prior lines of chemotherapy for metastatic disease was 1. During a median follow-up of 11.4 months, 33 patients had progressive disease and 25 were deceased. The 4-month DCR was 58.1% (95% CI: 43.4%-72.9%) and the median PFS was 4.8 months (95% CI: 3.0-7.1 months). The median PFS of the metastatic IBC group (2.2 months) and TNBC group (4.8 months) did not differ significantly ( p = .12). Thirty-one patients discontinued treatment due to progressive disease rather than toxicity. Observed toxicities were consistent with the known profile of pembrolizumab. Correlative blood studies showed availability of PD-1 on CD8 T cells decreased on therapy. T-cell exhaustion markers 2B4, CTLA4, and TIM3 decreased in patients who had therapeutic benefit, while LAG3 increased in patients without benefit. During therapy, ex vivo cytokine synthesis (IL-6/IL-12/TNFα) by DCs was superior in patients who benefited from therapy and increased from pretreatment samples. High T-cell clonality at baseline predicted response to immunotherapy (10.4 vs 3.6 months, p = .04). Additionally, patients exhibiting the greatest clinical benefit also had a significant increase in T-cell clonality over the course of therapy (20% vs 5.9% mean increase, p = .04). Conclusions: Increased T-cell clonality and DC activity, along with reductions in T-cell exhaustion, were associated with prolonged disease control following pembrolizumab maintenance therapy, achieving acceptable disease control with manageable toxicity. Clinical trial information: NCT02411656 .

Differential Performances in Lesions and Radiotracer of 18F-FDG PET/CT between Multiple Myeloma and Unknown Osteolytic Metastasis.

The aim of the study was to investigate the differential performances in lesions and 18F-FDG radiotracer distribution detected by PET/CT between multiple myeloma and unknown osteolytic metastasis. A retrospective study was performed on 18F-FDG PET/CT imaging of 63 patients with multiple bone destructions without extraosseous primary malignant tumors. By pathological diagnosis, 20 patients were confirmed to have multiple myeloma and 43 patients to have unknown osteolytic metastasis. The whole body was categorized into 8 sites: skull, spine, ribs, pelvis, sternum, clavicle, scapula and limb bone. The length of lesion cross-sections, cortical bone damage, SUVmax and radiotracer distribution were comprehensively compared to differentiate these two diseases. The cross-section lengths and SUVmax of the lesions in 5 sites (e.g., skull, spine, ribs, pelvis, and limb bone) were significantly shorter and lower in the multiple myeloma group than those of the unknown osteolytic metastasis group (P < 0.05). The 18F-FDG was more uniformly distributed in the lesion sites of the skull, spine, ribs, pelvis, scapula, and limb bone in the multiple myeloma group (P < 0.05). In the spine and rib lesion sites, the multiple myeloma group was more likely to show noncortical bone damage than the unknown osteolytic metastasis group (P < 0.05). Differential observations in lesions and 18F-FDG distribution between multiple myeloma and unknown osteolytic metastasis were detected by comprehensively comparing the length of lesion cross-sections, cortical bone damage, SUVmax, and the distribution of radiotracer on18F-FDG PET/CT imaging.

Effects of stereotactic body radiotherapy for clinical outcomes of patients with liver metastasis and hepatocellular carcinoma: A retrospective study.

This retrospective clinical study described the treatment efficacy and safety of stereotactic body radiotherapy (SBRT) for patients of hepatocellular carcinoma (HCC) and liver metastasis tumors. The therapeutic effect and prognosis of patients with liver cancer treated with stereotactic body radiation therapy (SBRT) at the Fudan University Shanghai Cancer Center (Shanghai, China) between July 2011 and December 2020 were retrospectively analyzed. Overall survival (OS), local control (LC) rates and progression-free survival (PFS) were evaluated using Kaplan-Meier analysis and the log-rank test. Local progression was defined as tumor growth after SBRT on dynamic computed tomography follow-up. Treatment-related toxicities were assessed according to the Common Terminology Criteria for Adverse Events version 4. A total of 36 patients with liver cancer were enrolled in the present study. The prescribed dosages (14 Gy in 3 fractions or 16 Gy in 3 fractions) were applied for SBRT treatments. The median follow-up time was 21.4 months. The median OS time was 20.4 [95% confidence interval (CI): 6.6-34.2] months, and the 2-year OS rates for the total population, HCC group and liver metastasis group were 47.5, 73.3 and 34.2%, respectively. The median PFS time was 17.3 (95% CI: 11.8-22.8) months and the 2-year PFS rates for the total population, HCC group and liver metastasis group were 36.3, 44.0 and 31.4%, respectively. The 2-year LC rates for the total population, HCC group and liver metastasis group were 83.4, 85.7 and 81.6%, respectively. The most common grade IV toxicity for the HCC group was liver function impairment (15.4%), followed by thrombocytopenia (7.7%). There were no grade III/IV radiation pneumonia or digestive discomfort. The present study aimed to explore a safe, effective and non-invasive treatment method for liver tumors. At the same time, the innovation of the present study is to find a safe and effective prescription dose of SBRT in the absence of consensus on guidelines.

Difüzyon Ağırlıklı Manyetik Rezonans Görüntülemede Hepatoselüler Karsinom ve Karaciğer Metastazı Ayırımında Hedef İşaretinin ve Görünür Difüzyon Katsayısı Ölçümlerinin Tanısal Değeri

Objective: The aim of our study is to investigate probable differences between the incidence of target sign detected by diffusion-weighted magnetic resonance imaging (DWI) and apparent diffusion coefficient (ADC) values between metastases and hepatocellular carcinomas (HCC).&#x0D; Materials and Methods: A total of 155 lesions obtained from 57 (female/male: 18/39) patients were included in the study. Dimensions of lesions, the appearance of lesions detected by DWI, minimum ADC (ADCmin) values, and average ADC (ADCav) values were evaluated with 1.5 Tesla MRI using b= 0 and b = 1000 s/mm2 values. Differences between metastases and HCC were investigated in terms of defined parameters. Also, ROC (receiver operating curve) analysis was used to evaluate the performance of ADCmin and ADCav parameters in distinguishing metastases from HCC.&#x0D; Results: Of the lesions, 131 were metastases, while 24 were HCC. The image showing centrally hypointense, periphery hyperintense signal in DWI defined as target sign. Target sign detected in 72 metastatic lesions (55%) and 6 HCC lesions (25%) with DWI, and the rate of target sign detection was higher in the metastatic group compared with HCC (p

Integrating analysis of proteome profile and drug screening identifies therapeutic potential of MET pathway for the treatment of malignant peripheral nerve sheath tumor

ABSTRACT Background Malignant peripheral nerve sheath tumor (MPNST) is an aggressive sarcoma with a poor prognosis that requires novel therapeutic agents. Proteome information is useful for identifying new therapeutic candidates because it directly reflects the biological phenotype. Additionally, in vitro drug screening is an effective tool to identify candidate drugs for common cancers. Hence, we attempted to identify novel therapeutic candidates for MPNST by integrating proteomic analysis and drug screening. Methods We performed comprehensive proteomic analysis on 23 MPNST tumor samples using liquid chromatography – tandem mass spectrometry to identify therapeutic targets. We also conducted drug screening of six MPNST cell lines using 214 drugs. Results Proteomic analysis revealed that the MET and IGF pathways were significantly enriched in the local recurrence/distant metastasis group of MPNST, whereas drug screening revealed that 24 drugs showed remarkable antitumor effects on the MPNST cell lines. By integrating the results of these two approaches, MET inhibitors, crizotinib and foretinib, were identified as novel therapeutic candidates for the treatment of MPNST. Conclusions We successfully identified novel therapeutic candidates for the treatment of MPNST, namely crizotinib and foretinib, which target the MET pathway. We hope that these candidate drugs will contribute to the treatment of MPNST.

Relationship of Inflammatory Parameters and Nutritional Status in Cancer Patients.

Chronic inflammation and cytokine storm can cause uncontrolled events in cancer. Pro-inflammatory molecules released by malignant cells send signals to the brain, liver, and neuroendocrine cells, interfering with appetite and promoting anorexia. Malnutrition in cancer patients is associated with increased treatment toxicity, reduced physical efficiency, and decreased survival. Therefore, early recognition of malnutrition could improve quality of life, treatment compliance, and survival. The aim of the study was to explore the relationship between inflammatory parameters with disease stage and nutritional status in patients with solid cancers. We screened 77 consecutive patients from 3 clinical Institutions in Sicily, Italy, with solid tumors who were either in follow-up after curative treatment or being treated for metastatic disease using the Mini Nutritional Assessment (MNA) questionnaire. Inflammatory parameters, including interleukin 6 (IL6), C-reactive protein (CRP), β2-microglobulin, ferritin, and transferrin were evaluated. A statistically significant difference was found in mean values of IL6, CRP, β2-microglobulin, ferritin, and transferrin between patients without evidence of disease and metastatic patients. Among the metastatic group, there was a significant difference in mean values of these inflammatory parameters between patients with malnutrition and those with normal nutritional status. The difference in average IL6, CRP, β2-microglobulin, and ferritin between patients at risk of malnutrition and those with normal nutritional status was also significant. However, the difference between patients at risk of malnutrition and those with malnutrition was not significant. IL6, CRP, transferrin, ferritin, and β2-microglobulin are functional inflammatory parameters that indicate risk of malnutrition and support the MNA screening test to identify patients with solid tumors who require nutritional support.

Identification of RAC1 in promoting brain metastasis of lung adenocarcinoma using single-cell transcriptome sequencing

This study aims to give a new perspective to the biomarkers in the lung adenocarcinoma (LUAD) brain metastasis, pathways involved and potential therapeutics. We performed a comprehensive single-cell level transcriptomic analysis on one LUAD patient with circulating tumor cells (CTCs), primary tumor tissue and metastatic tumor tissue using scRNA-seq approach to identify metastasis related biomarkers. Further scRNA-seq were performed on 7 patients to validate the cancer metastatic hallmark. with single cells collected from either metastatic or primary LUAD tissues. Pathological and functional studies were also performed to evidence the critical role of RAC1 in the LUAD metastasis. Hallmark gene was verified based on immunohistochemistry staining, cytological experiment, survival information from The Cancer Genome Atlas (TCGA), and staining results from Human Protein Atlas (HPA) databases. PCA analysis revealed that CTCs were in the intermediate place between the metastatic group and primary group. In the unsupervised clustering analysis CTCs were closer to one of the metastatic tumor cells, implying heterogeneity of the metastatic tumor and origin of the CTCs were from metastatic site. Transitional phase related gene analysis identified RAC1 was enriched in metastatic tumor tissue (MTT) preferred gene set functioning as regulated cell death and apoptosis as well as promoted macromolecule organization. Compared with normal tissue, expression levels of RAC1 increased significantly in LUAD tissue based on HPA database. High expression of RAC1 predicts worse prognosis and higher-risk. EMT analysis identified the propensity of mesenchymal state in primary cells while epithelial signals were higher in the metastatic site. Functional clustering and pathway analyses suggested genes in RAC1 highly expressed cells played critical roles in adhesion, ECM and VEGF signaling pathways. Inhibition of RAC1 attenuates the proliferation, invasiveness and migration ability of lung cancer cells. Besides, through MRI T2WI results, we proved that RAC1 can promote brain metastasis in the RAC1-overexpressed H1975 cell burden nude mouse model. RAC1 and its mechanisms might promote drug design against LUAD brain metastasis.

COPS3 inhibition promotes cell proliferation blockage and anoikis via regulating PFKFB3 in osteosarcoma cancer cells

As a key component of the COP9 signalosome complex, which participates in a variety of physiological processes, COPS3 is intimately related to multiple cancers. It promotes cell proliferation, progression and metastasis in several cancer cells. However, whether COPS3 participates in regulating anoikis, a specific kind of apoptosis and functions as an essential modulator of cell metastasis, has not yet been studied. Here, we found COPS3 is highly expressed in several cancers especially in osteosarcoma (OS). Overexpression of COPS3 promoted cell proliferation, cell viability and migration/invasion in both control cells and oxaliplatin (Oxa) treated cells. On the contrary, knockdown of COPS3 further enhanced the cytotoxicity of Oxa. Utilizing bioinformatics analysis, we found that COPS3 was higher expressed in the metastatic group, and associated with the extra-cellular matrix (ECM) receptor interaction pathway, which involve in regulating anoikis. In an anoikis model, COPS3 expression varied and genetic modification of COPS3 influenced the cell death enhanced by Oxa. PFKFB3, an essential modulator of glycolysis, was found to interact with COPS3. Inhibition of PFKFB3 promoted apoptosis and anoikis enhanced by Oxa, and COPS3 overexpression failed to rescue this cell death. On the contrary, in the COPS3 knockdown cells, overexpression of PFKFB3 recovered the anoikis resistance, indicating COPS3 function upstream of PFKFB3. In summary, our results elucidated that COPS3 modulated anoikis via affecting PFKFB3 in OS cancer cells.

Correlation analysis of lung mucosa-colonizing bacteria with clinical features reveals metastasis-associated bacterial community structure in non-small cell lung cancer patients

BackgroundMicrobes colonizing lower airways can regulate the host immune profile and consequently participate in lung disease. Increasing evidence indicate that individual microbes promote lung cancer progression and are involved in metastasis incidence. To date, however, no study has revealed the community structure of lung bacteria in metastatic non-small cell lung cancer (NSCLC) patients.MethodsWe prospectively enrolled 50 healthy subjects and 57 NSCLC patients. All healthy subjects and NSCLC patients underwent bronchoscope procedures for brush specimen collection. The 16 S ribosomal RNA gene was sequenced to characterize the community structure of lung mucosa-colonizing bacteria. The peripheral blood of NSCLC patients was also measured for leukocytes and cancer markers.ResultsThe lung bacteria of healthy subjects and NSCLC patients were divided into four communities. All community 2 members showed increased abundance in NSCLC patients compared with healthy subjects, and most community 2 members showed increased abundance in the metastatic NSCLC patients compared with the non-metastatic group. These bacteria were significantly and positively correlated with eosinophils, neutrophils and monocytes in the metastatic NSCLC group. In addition, the correlation between lung bacteria and cancer markers differed between the metastatic and non-metastatic NSCLC patients. Furthermore, bronchoalveolar lavage fluid from lung adenocarcinoma patients directly promoted NSCLC cell migration.ConclusionsThe community structure of lung mucosa-colonizing bacteria was relatively stable, but changed from the healthy population to NSCLC patients, especially the metastatic group. This distinct community structure and specific correlation with immune cells and cancer markers could help to distinguish NSCLC patients with or without metastasis.

GSTM1, GSTP1, p53 as some probable predictors of prognosis in primary and metastatic epithelial ovarian cancer

Objectives: Ovarian carcinomas are responsible for the death of more women than all other gynecologic malignancies in the Western world. Ovarian carcinomas are detected in an advanced stage of the disease in approximately 80% of the patients. Glutathione S-transferases (GSTs) are an important family involved in the detoxification of several xenobiotics. Thus, this mechanism protects tissues from the harmful effects of oxidative stress and chemical-induced damages. The expression of them may contribute to the characteristics of ovarian carcinoma as they can metabolise both exogenous and endogenous compounds, which are implicated in the development of ovarian cancer. Therefore, our aim was to determine the expressions of GST Mu 1 (GSTM1), GST Pi 1 (GSTP1), and also p53, which is a tumor suppressor gene, in benign and malign ovarian tumors and metastasis tissues. Methods: A total of the 99 patients with ovarian tumor enrolled in the study. Thirty-one of the tissues was benign tumor, 17 was malign tumor and 51 was metastasis. The immunohistochemical GSTM1, GSTP1, and p53 staining characteristics of these tissues were investigated. Results: The highest GSTM1, GSTP1, and p53 expression was noted in the malignant group followed by the metastasis group. GSTP1 expression was significantly higher in malignant tissues than benign ones (p = 0.015). No statistically significant difference was observed in the level of GSTM1 expression between groups (p = 0.524). p53 expression was significantly higher in the metastasis and malignant tissues than the benign ones (p &amp;lt; 0.001). Conclusions: The higher expressions of GSTP1 and p53 in malignant and metastasis tissues than benign ones indicate that these expressions could be important biomarkers in ovarian cancer development and progression. Further studies with more cases are required to confirm the results of our present study.

Diagnostic accuracy of f18-fluorodeoxyglucose positron emission tomography-computed tomography in the evaluation of carcinoma of unknown primary: A single-center study

Background: The term carcinoma of unknown primary (CUP) is not a single disease entity that it can be explicated as the recognition of metastasized tumor, in which the primary origin of the malignancy from an organ or site remains occult. The term refers to a clinical disorder that revolves around and represents a diversified metastatic tumor group, for whom the diagnostic investigations are unable to pinpoint the primary site of the tumor, comprising extensive radiological techniques, invasive endoscopic procedures, and histopathology, many which fail to diagnose the primary site. Aims and Objectives: The study was conducted to ascertain the diagnostic accuracy of fluorine-18 labeled fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT) in the evaluation of CUP. The secondary objective of the study was to identify rate of the primary malignancies localized on 18F-FDG PET-CT that presents as CUP in local settings. Materials and Methods: The prospective and cross-sectional study included patients with CUP who underwent 18F-FDG PET-CT scans between October 2021 and February 2022. The primary site localized on 18F-FDG PET-CT was confirmed through biopsy and histology. False-negative and false-positive patients were ascertained through biopsy and/or follow-up of 6 months. Results: Of a total of 63 patients, 57.1% were male, while 42.9% were female with a mean age of 56.27 years. The overall detection rate of primary tumor (PT) site on 18F-FDG PET-CT was 88.8%. Abnormal sites and indicative of primary malignant tumor were correctly detected in 79.36% that were truly positive proven on biopsy. False-negative rate of scan was 4.76%, though malignancy was proven through other investigations or follow-up, while 6.36% had true negative and 9.52% showed false-positive results on the scan. In this study, the calculated diagnostic accuracy of 18F-FDG PET-CT identified as 85.7%, sensitivity 94%, specificity 40%, positive predictive value 89.2%, and negative predictive value 57.1%. Conclusion: 18F-FDG PET-CT demonstrated high sensitivity and diagnostic accuracy ascertaining the PT site in patients with CUP in our study population.

Options of locoregional therapy for primary foci of breast cancer influence the rate of nonregional lymph node metastasis in N2-N3 status patients: a SEER database analysis.

We aim to use the SEER database to discuss the effect of various surgical methods of primary foci and other influencing factors on the nonregional lymph node (NRLN) metastasis in invasive ductal carcinoma (IDC) patients. Clinical information of IDC patients used in this study was obtained from the SEER database. The statistical analyses used included a multivariate logistic regression model, the chi-squared test, log-rank test and propensity score matching (PSM). 243,533 patients were included in the analysis. 94.3% of NRLN patients had a high N positivity (N3) but an equal distribution in T status. The proportion of operation type, especially BCM and MRM, differed significantly between the N0-N1 and N2-N3 groups in the NRLN metastasis group and nonmetastasis group. Age > 80years, positive PR, modified radical mastectomy (MRM)/radical mastectomy (RM) and radiotherapy for primary tumor were shown to be protective factors for NRLN metastasis, and higher N positivity was the most significant risk factors. N2-N3 patients receiving MRM had a lower metastasis to NRLN than those receiving BCM (1.4% vs 3.7%, P < 0.001), while this relevance was not discovered in N0-N1 patients. In N2-N3 patients, a better OS was observed in MRM group than BCM group (P < 0.001). MRM exerted a protective effect on NRLN metastasis compared to BCM in N2-N3 patients but not N0-N1 patients. This implies the need for more consideration when choosing the operation methods of primary foci in patients with high N positivity.

Extended follow-up from JAVELIN Renal 101: subgroup analysis of avelumab plus axitinib versus sunitinib by the International Metastatic Renal Cell Carcinoma Database Consortium risk group in patients with advanced renal cell carcinoma

We report updated data for avelumab plus axitinib versus sunitinib in patients with advanced renal cell carcinoma from the third interim analysis of the phase III JAVELIN Renal 101 trial. Progression-free survival (PFS), objective response rate (ORR), and duration of response per investigator assessment (RECIST version 1.1) and overall survival (OS) were evaluated in the overall population and in International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups; safety was also assessed. Overall, median OS [95% confidence interval (CI)] was not reached [42.2 months-not estimable (NE)] with avelumab plus axitinib versus 37.8 months (31.4-NE) with sunitinib [hazard ratio (HR) 0.79, 95% CI 0.643-0.969; one-sided P= 0.0116], and median PFS (95% CI) was 13.9 months (11.1-16.6 months) versus 8.5 months (8.2-9.7 months), respectively (HR 0.67, 95% CI 0.568-0.785; one-sided P < 0.0001). In patients with IMDC favorable-, intermediate-, poor-, or intermediate plus poor-risk disease, respectively, HRs (95% CI) for OS with avelumab plus axitinib versus sunitinib were 0.66 (0.356-1.223), 0.84 (0.649-1.084), 0.60 (0.399-0.912), and 0.79 (0.636-0.983), and HRs (95% CIs) for PFS were 0.71 (0.490-1.016), 0.71 (0.578-0.866), 0.45 (0.304-0.678), and 0.66 (0.550-0.787), respectively. ORRs, complete response rates, and durations of response favored avelumab plus axitinib overall and across all risk groups. In the avelumab plus axitinib arm, 81.1% had a grade ≥3 treatment-emergent adverse event (TEAE), and incidences of TEAEs and immune-related AEs were highest <6 months after randomization. Avelumab plus axitinib continues to show improved efficacy versus sunitinib and a tolerable safety profile overall and across IMDC risk groups. The OS trend favors avelumab plus axitinib versus sunitinib, but data remain immature; follow-up is ongoing. ClinicalTrials.govNCT02684006; https://clinicaltrials.gov/ct2/show/NCT02684006.

Prognostic value of lymph node features in patients diagnosed with stage IIIC endometrial adenocancer.

Our study investigated the lymph node (LN) features most affecting survival in endometrial adenocancer (EAC) patients with LN involvement. This retrospective study was based on a review of the records of patients diagnosed with EAC, who underwent hysterectomy and systematic retroperitoneal lymphadenectomy at the gynecologic oncology clinics of three centers between January 2009 and January 2019. A total of 120 stage IIIC endometrioid-type EAC patients were included in the study. The patients were divided into small (<10 mm) and large (≥10 mm) groups according to the size of the largest metastatic LN. Patients were divided into single and multiple metastasis groups according to the number of metastatic LNs. The patients were divided into pelvic and paraaortic groups according to the location of the metastatic LNs. The effects of prognostic factors on disease-free survival (DFS) and overall survival (OS) were evaluated by Cox regression analysis. Large-sized metastatic LNs were an independent prognostic factor for DFS (hazard ratio [HR] = 5.4, 95% confidence interval [CI]: 1.-26.2; P = 0.035) and OS (HR = 9.0, 95% CI: 1.1-68.0; P = 0.033). The number (P = 0.093 for DFS, P = 0.911 for OS) and location (P = 0.217 for DFS, P = 0.124 for OS) of metastatic LNs were not independent prognostic factors for DFS or OS. Large-sized metastatic LNs were an independent prognostic factor for survival in patients with stage IIIC EAC. Larger prospective studies including similar patient populations are required to verify these findings.

Sarcoidosis or sarcoid-like reaction with mediastinal lymphadenopathy in patients after breast cancer surgery

BackgroundPatients with breast cancer present with lymphadenopathy involving non-caseating epithelioid cell granulomas in the mediastinum or axilla, referred to as sarcoidosis or sarcoid-like reactions (SLRs). However, sarcoidosis/SLRs prevalence and clinical presentation remain unclear. This study aimed to determine the frequency and clinical presentation of sarcoidosis/SLRs among postoperative patients with breast cancer. MethodsAmong all patients who underwent surgery for early-stage breast cancer at St. Luke's International Hospital in Japan between 2010 and 2021, those who subsequently developed enlarged mediastinal lymph nodes and underwent bronchoscopy for suspected breast cancer recurrence were included. Patients were classified into sarcoidosis/SLR or metastatic breast cancer groups, and the clinical characteristics were compared. ResultsA total of 9,559 patients underwent breast cancer surgery; bronchoscopy was performed to diagnose enlarged mediastinal lymph nodes in 29 cases. Breast cancer recurrence was observed in 20 patients. Eight women with a median age of 49 years (range 38–75) and a median time from surgery to diagnosis of 4.0 years (range 0.2–10.8) were diagnosed with sarcoidosis/SLRs. Four of the eight patients underwent mammoplasty with silicone breast implants (SBIs), and two experienced postoperative recurrences of breast cancer before or after lymphadenopathy, which was considered inciting factors for SLRs. The remaining two cases could have developed sarcoidosis after breast cancer surgery with no underlying causes for SLR. ConclusionsPostoperative sarcoidosis/SLRs rarely occur in patients with breast cancer. An adjuvant action of SBI likely contributed to the progression of SLRs; few cases exhibited a causal relationship with breast cancer recurrence.