scholarly journals How Mathematical Modeling Could Contribute to the Quantification of Metastatic Tumor Burden Under Therapy: Insights in Immunotherapeutic Treatment of Non-Small Cell Lung Cancer

2020 ◽  
Author(s):  
Pirmin Schlicke ◽  
Christina Kuttler ◽  
Christian Schumann
Keyword(s):  
Metastatic Tumor ◽  
Clinical History ◽  
Primary Diagnosis ◽  
Tumor Burden ◽  
Primary Tumors ◽  
Prognostic Features ◽  
Therapeutic Decisions ◽  
Platinum Based Chemotherapy ◽  
The Individual ◽  
The Mathematical Model

Abstract Background: Cancer is one of the leading death causes globally with about 8.2 million deaths per year and an increase in numbers in recent years. About 90% of cancer deaths do not occur due to primary tumors but due to metastases, of which most are not clinically identifiable because of their relatively small size at primary diagnosis and limited technical possibilities. However, therapeutic decisions are formed depending on the existence of metastases and their properties. Therefore non-identified metastases might have huge influence in the treatment outcome. The quantification of clinically visible and invisible metastases is important for the choice of an optimal treatment of the individual patient as it could clarify the burden of non-identifiable tumors as well as the future behavior of the cancerous disease. Results: The mathematical model presented in this study gives insights in how this could be achieved, taking into account different treatment possibilities and therefore being able to compare therapy schedules for individual patients with different clinical parameters. The framework was tested on three patients with NSCLC, one of the deadliest types of cancer worldwide, and clinical history including platinum-based chemotherapy and PD-L1-targeted immunotherapy. Results yield promising insights into the framework to establish methods to quantify effects of different therapy methods and prognostic features for individual patients already at stage of primary diagnosis.

scholarly journals How Mathematical Modeling Could Contribute to the Quantification of Metastatic Tumor Burden Under Therapy: Insights in Immunotherapeutic Treatment of Non-Small Cell Lung Cancer

2020 ◽  
Author(s):  
Pirmin Schlicke ◽  
Christina Kuttler ◽  
Christian Schumann
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Primary Diagnosis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Prognostic Features ◽  
Therapeutic Decisions ◽  
Platinum Based Chemotherapy

Abstract Background: Cancer is one of the leading death causes globally with about 8.2 million deaths per year and an increase in numbers in recent years. About 90% of cancer deaths do not occur due to primary tumors but due to metastases, of which most are not clinically identifiable because of their relatively small size at primary diagnosis and limited technical possibilities. However, therapeutic decisions are formed depending on the existence of metastases and their properties. Therefore non-identified metastases might have huge influence in the treatment outcome. The quantification of clinically visible and invisible metastases is important for the choice of an optimal treatment of the individual patient as it could clarify the burden of non identifiable tumors as well as the future behavior of the cancerous disease. Results: The mathematical model presented in this study gives insights in how this could be achieved, taking into account different treatment possibilities and therefore being able to compare therapy schedules for individual patients with different clinical parameters. The framework was tested on three patients with non-small cell lung cancer, one of the deadliest types of cancer worldwide, and clinical history including platinum-based chemotherapy and PD-L1-targeted immunotherapy. Results yield promising insights into the framework to establish methods to quantify effects of different therapy methods and prognostic features for individual patients already at stage of primary diagnosis.

scholarly journals How mathematical modeling could contribute to the quantification of metastatic tumor burden under therapy: insights in immunotherapeutic treatment of non-small cell lung cancer

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Pirmin Schlicke ◽  
Christina Kuttler ◽  
Christian Schumann
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Primary Diagnosis ◽  
Small Cell ◽  
Small Cell Lung ◽  
Primary Tumors ◽  
Prognostic Features ◽  
Therapeutic Decisions ◽  
Platinum Based Chemotherapy

Abstract Background Cancer is one of the leading death causes globally with about 8.2 million deaths per year and an increase in numbers in recent years. About 90% of cancer deaths do not occur due to primary tumors but due to metastases, of which most are not clinically identifiable because of their relatively small size at primary diagnosis and limited technical possibilities. However, therapeutic decisions are formed depending on the existence of metastases and their properties. Therefore non-identified metastases might have huge influence in the treatment outcome. The quantification of clinically visible and invisible metastases is important for the choice of an optimal treatment of the individual patient as it could clarify the burden of non-identifiable tumors as well as the future behavior of the cancerous disease. Results The mathematical model presented in this study gives insights in how this could be achieved, taking into account different treatment possibilities and therefore being able to compare therapy schedules for individual patients with different clinical parameters. The framework was tested on three patients with non-small cell lung cancer, one of the deadliest types of cancer worldwide, and clinical history including platinum-based chemotherapy and PD-L1-targeted immunotherapy. Results yield promising insights into the framework to establish methods to quantify effects of different therapy methods and prognostic features for individual patients already at stage of primary diagnosis.

scholarly journals Multiple Synchronous Squamous Cell Cancers of the Skin and Esophagus: Differential Management of Primary Versus Secondary Tumor

2020 ◽  
pp. 1-3
Author(s):  
Didier Mutter ◽  
Cristians Gonzalez ◽  
Silvana Perretta ◽  
Bernard Dallemagne ◽  
Antonio D’Urso ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Squamous Cell ◽  
Metastatic Tumor ◽  
Skin Tumor ◽  
Primary Tumors ◽  
Positron Emission Tomography Scanner ◽  
Secondary Tumor ◽  
Squamous Cell Esophageal Cancer ◽  
Positron Emission ◽  
Therapeutic Decisions

Multiple primary tumors are uncommon in patients with squamous cell esophageal cancer. Conventional imaging methods have limitations in detecting those tumors. Although 18-F-fluoro-deoxyglucose-positron emission tomography scanner increases the detection of multiple synchronous tumors in patients with other malignancies, its contribution in patients with squamous cell esophageal cancer has not been assessed as it is not systematically performed. The detection of synchronous skin squamous cell tumors in patients with squamous cell esophageal cancer presents a challenge for making diagnostic and therapeutic decisions. A metastatic tumor leads to palliative management, whereas the diagnosis of a primary skin tumor requires curative treatment of both squamous cell tumors. Pathological evaluation appears crucial in the decision.

scholarly journals Low Concordance Between T-Cell Densities in Matched Primary Tumors and Liver Metastases in Microsatellite Stable Colorectal Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Vegar Johansen Dagenborg ◽  
Serena Elizabeth Marshall ◽  
Krzysztof Grzyb ◽  
Åsmund Avdem Fretland ◽  
Marius Lund-Iversen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
T Cell ◽  
Liver Metastases ◽  
Predictive Biomarkers ◽  
Metastatic Tumor ◽  
Primary Tumors ◽  
Individual Level ◽  
Cell Densities ◽  
The Individual

BackgroundThe subtype, density and location of tumor infiltrating T-cells are being explored as prognostic and predictive biomarkers in primary colorectal cancer (pCRC) and colorectal liver metastases (CLM). Very limited data exist comparing findings in pCRC and matched CLM.Patients and methodsFifty-eight patients with available pCRC and matched CLM (57/58 microsatellite stable) were included in this OSLO-COMET substudy. In immunohistochemically stained sections, total (Ttot), helper (TH), cytotoxic (CTL), and regulatory (Treg) T-cells were manually counted in hotspots from the invasive margin (IM), intratumor (IT), and tumor adjacent regions to determine T-cell densities.ResultsA striking accumulation of T-cells was found in IM of both pCRC and CLM with much lower densities in the IT region, exemplified by Ttot of 2838 versus 340 cells/mm2, respectively, in CLM. The correlation at the individual level between T-cell densities in pCRC and corresponding CLM was poor for all regions and T-cell subtypes; for instance, the correlation coefficient (R2) for IM Ttot was 0.07. The IT TH : CTL and Treg : TH ratios were 2.94 and 0.44, respectively, in pCRC, and 1.84 and 0.24, respectively, in CLM.ConclusionThe observed accumulation of T-cells in the IM regions of pCRC and CLM with low penetration to the IT regions, combined with high TH : CTL and Treg : TH ratios, point to the presence of an immune suppressive microenvironment. T-cell densities of CLM differed markedly from the matched pCRC, indicating that to evaluate T-cell biomarkers in metastasis, the commonly available pCRC cannot serve as a surrogate for the metastatic tumor.

Rab11 family-interacting protein 4, RAB11FIP4, is a differentially expressed gene in brain metastatic human breast cancer.

2021 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Differentially Expressed Gene ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Interacting Protein ◽  
Primary Tumors ◽  
Free Survival ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes for the discovery of genes associated with brain metastasis in humans with metastatic breast cancer. We found that Rab11 family-interacting protein 4, encoded by RAB11FIP4, was among the genes whose expression was most different in the brain metastases of patients with metastatic breast cancer as compared to primary tumors of the breast. RAB11FIP4 mRNA was present at increased quantities in brain metastatic tissues as compared to primary tumors of the breast. Importantly, expression of RAB11FIP4 in primary tumors was significantly correlated with patient recurrence-free survival and distant metastasis-free survival. Modulation of RAB11FIP4 expression may be relevant to the biology by which tumor cells metastasize from the breast to the brain in humans with metastatic breast cancer.

Imaging Features of Primary Tumors of the Hand

2020 ◽  
Vol 16 ◽  
Author(s):  
Filippo Boriani ◽  
Edoardo Raposio ◽  
Costantino Errani
Keyword(s):  
Soft Tissue ◽  
Soft Tissues ◽  
Epithelioid Sarcoma ◽  
Case Series ◽  
Malignant Neoplasm ◽  
Benign Tumors ◽  
Imaging Features ◽  
Primary Tumors ◽  
Therapeutic Decisions ◽  
Tumors Of The Hand

: Musculoskeletal tumors of the hand are a rare entity and are divided into skeletal and soft tissue tumors. Either category comprises benign and malignant or even intermediate tumors. Basic radiology allows an optimal resolution of bone and related soft tissue areas, ultrasound and more sophisticated radiologic tools such as scintigraphy, CT and MRI allow a more accurate evaluation of tumor extent. Enchondroma is the most common benign tumor affecting bone, whereas chondrosarcoma is the most commonly represented malignant neoplasm localized to hand bones. In the soft tissues ganglions are the most common benign tumors and epithelioid sarcoma is the most frequently represented malignant tumor targeting hand soft tissues. The knowledge regarding diagnostic and therapeutic management of these tumors is often deriving from small case series, retrospective studies or even case reports. Evidences from prospective studies or controlled trials are limited and for this lack of clear and supported evidences data from the medical literature on the topic are controversial, in terms of demographics, clinical presentation, diagnosis prognosis and therapy.The correct recognition of the specific subtype and extension of the tumor through first line and second line radiology is essential for the surgeon, in order to effectively direct the therapeutic decisions.

A cross-sectional survey among physicians on Internet use for epilepsy-related information (Preprint)

2019 ◽  
Author(s):  
Francesco Brigo ◽  
Simona Lattanzi ◽  
Giorgia Giussani ◽  
Laura Tassi ◽  
Nicola Pietrafusa ◽  
...  
Keyword(s):  
Internet Use ◽  
The Internet ◽  
Online Information ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Related Information ◽  
Internet Users ◽  
Therapeutic Decisions ◽  
The Individual ◽  
The Web

BACKGROUND The Internet has become one of the most important sources of health information, accessed daily by an ever-growing number of both patients and physicians, seeking medical advice and clinical guidance. A deeper insight into the current use of the Web as source of information on epilepsy would help in clarifying the individual attitude towards this medium by Internet users. OBJECTIVE We investigated views towards the Internet in a sample of Italian healthcare specialists involved in epilepsy field, to explore factors which explained the influence of information found on the internet. METHODS This study was a self-administered survey conducted in a group of members of the Italian Chapter of the International League Against Epilepsy (ILAE) in January 2018. RESULTS 184 questionnaires were analyzed. 97.8% of responders reported to seek online information on epilepsy. The Internet was most frequently searched to obtain new information (69.9%) or to confirm a diagnostic or therapeutic decision (37.3%). The influence of consulting the Internet on clinical practice was associated with registration to social network(s) (OR: 2.94; 95%CI: 1.28-6.76; p=0.011), higher frequency of Internet use (OR: 3.66; 95%CI: 1.56-9.21; p=0.006) and higher confidence in reliability of online information (OR: 2.61; 95%CI: 1.09-6.26; p=0.031). No association was found with age, sex, years in epilepsy practice or easiness to find online information. CONCLUSIONS Internet is frequently used among healthcare professionals involved in the epilepsy to obtain information about this disease. The attitude of being influenced by the Internet for diagnostic and/or therapeutic decisions in epilepsy is independent on age and years of experience in epilepsy, and probably reflects an individual approach towards the Web.

scholarly journals MMP-7 Serum and Tissue Levels Are Associated with Poor Survival in Platinum-Treated Bladder Cancer Patients

Diagnostics ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 48
Author(s):  
Tibor Szarvas ◽  
Michèle J. Hoffmann ◽  
Csilla Olah ◽  
Eszter Szekely ◽  
Andras Kiss ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Checkpoint Inhibitors ◽  
Serum Concentrations ◽  
Serum Samples ◽  
Poor Overall Survival ◽  
Platinum Sensitivity ◽  
Therapeutic Decisions ◽  
Platinum Based Chemotherapy

Chemotherapy resistance is a main cause of therapeutic failure and death in bladder cancer. With the approval of immune checkpoint inhibitors, prediction of platinum treatment became of great clinical importance. Matrix metalloproteinase-7 (MMP-7) was shown to be involved in cisplatin resistance. Therefore, tissue and circulating MMP-7 levels were evaluated in 124 bladder cancer patients who received postoperative platinum-based chemotherapy. Tissue MMP-7 levels were analyzed by immunohistochemistry in 72 formalin-fixed, paraffin-embedded chemo-naïve tumor samples, while MMP-7 serum concentrations were determined in 132 serum samples of an independent cohort of 52 patients. MMP-7 tissue and serum levels were correlated with clinicopathological and follow-up data. MMP-7 gene expression was determined by RT-qPCR in 20 urothelial cancer cell lines and two non-malignant urothelial cell lines. MMP-7 was overexpressed in RT-112 and T-24 cells by stable transfection, to assess its functional involvement in platinum sensitivity. High MMP-7 tissue expression and pretreatment serum concentrations were independently associated with poor overall survival (tissue HR = 2.296, 95%CI = 1.235–4.268 and p = 0.009; serum HR = 2.743, 95%CI = 1.258–5.984 and p = 0.011). Therefore, MMP-7 tissue and serum analysis may help to optimize therapeutic decisions. Stable overexpression in RT-112 and T-24 cells did not affect platinum sensitivity.

Arterial Thrombosis in Cancer Patients: An Update

2021 ◽  
Author(s):  
Massimo Franchini ◽  
Antonella Tufano ◽  
Aniello Casoria ◽  
Antonio Coppola
Keyword(s):  
Cancer Patients ◽  
Arterial Thrombosis ◽  
Cardiovascular Events ◽  
Tumor Burden ◽  
Vascular Events ◽  
Time Period ◽  
Treatment Considerations ◽  
Arterial Thromboembolic Events ◽  
The Individual ◽  
Patients Experience

AbstractCancer is associated with an increased incidence of both venous thromboembolism (VTE) and arterial thrombosis (cardiovascular events and ischemic stroke). Cancer-associated arterial thrombotic events are less well studied than VTE, but increasingly recognized, particularly in specific malignancies and in association with specific anticancer therapies. The pathogenesis of arterial thrombotic events in cancer is complex and involves generation of tumor-associated procoagulant factors and a variety of alterations in platelet function as well as in the coagulation and fibrinolytic systems, and endothelial injury and dysfunction, that combine to produce hypercoagulability. The multifactorial interaction between this prothrombotic state, the individual cardiovascular risk, advanced age and presence of comorbidities, and the specific neoplasm characteristics and therapy, may induce the vascular events. Recent studies based on population databases and prospective or retrospective analyses with prolonged follow-up highlight that cancer patients experience an increased (approximately 1.5–2-fold) risk of both cerebrovascular and cardiovascular events compared with noncancer individuals, which peaks in the time period of the diagnosis of cancer but may persist for years. Beyond the type of cancer, the risk reflects the tumor burden, being higher in advanced stages and metastatic cancers. The occurrence of arterial thromboembolic events is also associated with increased overall mortality. We here present an update of the pathophysiology, risk factors, clinical evidence, and treatment considerations on cancer-associated arterial thrombosis, in the light of the need for specific multidisciplinary prevention and surveillance strategies in this setting, in the frame of cardio-oncology approaches.

scholarly journals AKT1 is differentially expressed in primary tumors and brain metastases in humans with breast cancer.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Metastatic Breast ◽  
Metastatic Tumor ◽  
Clinical Problem ◽  
Central Nervous System Metastasis ◽  
Human Breast ◽  
Primary Tumors ◽  
Breast Tissues ◽  
The Brain

Metastasis to the brain is a clinical problem in patients with breast cancer (1-3). We mined published microarray data (4, 5) to compare primary and metastatic tumor transcriptomes to discover genes associated with brain metastasis in patients with metastatic breast cancer. We report here the differential expression of the protein kinase AKT1 in the primary tumors and brain metastases of humans with breast cancer. AKT1 mRNA was present at significantly increased quantities in brain metastatic tissues as compared to primary tumors of the breast. These data combined suggest that up-regulation of AKT1 is a conserved event, both during transformation of breast tissues and progression to central nervous system metastasis and further point to potential importance of AKT1 modulation during progression of human breast cancer.

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