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En un secadero túnel, con aire introducido por presión y con circulación cíclica, se consiguen las mayores ventajas prácticas. Se reduce el peligro de la condensación de humedad, evitándose, por consiguiente, el reblandecimiento de los ladrillos y la formación de grietas durante el secado.

Soil conditioners to fertilize, improve soil structure and support the phytostabilization of trace metal elements (TMEs) are being used more and more frequently. One of the options are agrosinters - slow-release ceramic fertilizers consisting mainly of SiO 2 , CaO, P 2 O 5 and K 2 O, with an alkaline pH and high impact strength. The effect of two different agrosinters, A1 and A2, on the growth and physiological condition of Brassica napus grown in uncontaminated and Pb-, Cd- and Zn-contaminated soil was investigated in a pot experiment. In vivo data were collected using an infrared gas analyzer, a fluorimeter, a pigment content meter and a thermal camera. Elemental composition of the biomass was also investigated. The tested agrosinters promote biomass yield and have an effect on improving leaf chlorophyll content, phenomenological energy fluxes and plant gas exchange. The effect of the agrosinters on the plants was dose- and amendment-specific. An immobilization effect was observed not only in the soil but also in the plants. A reduction in the Cd (22%) and Zn (40%) content in the biomass was measured. All this was related to the effect of increasing the available form of P (50%), K (300%) and Ca (50%) in the soil, which improves soil fertility and reduces the bioavailable forms of the studied TMEs, due to the increase in soil pH and/or the complexation of these with phosphate compounds. The multidimensional analysis of A2 agrosinter shows the most positive effects on plant conditions, indicating that fly ash as a mixed substrate benefits the plants., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lung cancer treatment and detection can be improved by the identification of new biomarkers. Novel approaches in investigating circular RNAs (circRNAs) as biomarkers have yielded promising results. A circRNA molecule circHIPK3 was found to be widely expressed in non-small-cell lung cancer (NSCLC) cells, where it plays a crucial role in lung cancer tumorigenesis. CircHIPK3 promotes lung cancer progression by sponging oncosuppressive miRNAs such as miR-124, miR-381-3p, miR-149, and miR-107, which results in increased cell proliferation, migration, and resistance to therapies. Inhibiting circHIPK3 has been demonstrated to suppress tumour growth and induce apoptosis, which suggests its potential use in the development of new lung cancer treatment strategies targeting circHIPK3-related pathways. As a biomarker, circHIPK3 shows promise for early detection and monitoring of lung cancer. CircHIPK3 increased expression levels in lung cancer cells, and its potential link to metastasis risk highlights its clinical relevance. Given the promising preliminary findings, more clinical trials are needed to validate circHIPK3 efficacy as a biomarker. Moreover, future research should determine if the mechanisms discovered in NSCLC apply to small cell lung cancer (SCLC) to investigate circHIPK3-targeted therapies for SCLC.

Hepatocellular carcinoma is one of the most common cancers worldwide. Despite progress in treatment, recurrence after radical treatment is common, and the prognosis remains poor for patients with advanced disease. Therefore, there is a need to identify prognostic and predictive factors for the response to therapy or more intensive surveillance or treatment. Because the tumor microenvironment plays a crucial role in the development of cancer and metastasis, it is a crucial need to understand processes that are involved in carcinogenesis. Within the microenvironment, several immune cells with different roles are present. One of the most important of these is tumor-associated macrophages. These cells may exert either antitumor or protumor roles. Several studies have suggested that tumor-associated macrophages can be used as prognostic markers. Furthermore, they may be involved in resistance to immunotherapy or systemic treatment. As they play an important role in cancer development, tumor-associated macrophages are also a good target for therapy. In this review, we briefly summarize recent progress on knowledge regarding the basic molecular characteristics, impact on prognosis and potential clinical implications of tumor-associated macrophages in hepatocellular carcinoma., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Chronic Kidney Disease (CKD) and cancer constitute two major public health burdens and are on the rise. Moreover, the number of patients affected simultaneously by both conditions is growing. Potential nephrotoxic effect of cancer therapies is particularly important for patients with CKD, as they are also affected by several comorbidities. Therefore, administering the right therapy at the right dose for patients with decreased kidney function can represent a daunting challenge. We review in detail the renal toxicities of anti-cancer therapies i.e. conventional chemotherapy, targeted therapy, immune checkpoint inhibitors, and radioligand therapies, issue recommendations for patient monitoring along with guidance on when to withdraw treatment and suggest dosage guidelines for select agents in advanced stage CKD. Various electrolytes disturbances can occur as the result of the administration of anti-cancer agents in the patient with decreased kidney function. These patients are prone to developing hyponatremia, hyperkalemia, and other metabolic abnormalities because of a decreased GFR. Therefore, all electrolytes, minerals and acid base status should be checked at baseline and before each administration of chemotherapeutic agents. Moreover, studies on patients on kidney replacement therapy (KRT) are very limited and only single cases or small case series are published. Therefore, clinical therapeutical decisions in cancer patients with decreased function should be made by multidisciplinary teams constituted of medical oncologists, nephrologists, and other specialists. Onconephrology is an evolving and expanding subspecialty. It is crucial to consider anticancer drug treatment in these patients and offer them a chance to be treated effectively., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Non-small-cell lung cancer (NSCLC) poses a challenge due to its heterogeneity, necessitating precise histopathological subtyping and prognostication for optimal treatment decision-making. Molecular markers emerge as a potential solution, overcoming the limitations of conventional methods and supporting the diagnostic-therapeutic interventions. In this study, we validated the expression of six genes ( MIR205HG , KRT5 , KRT6A , KRT6C , SERPINB5 , and DSG3 ), previously identified within a 53-gene signature developed by our team, utilizing gene expression microarray technology. Real-time PCR on 140 thoroughly characterized early-stage NSCLC samples revealed substantial upregulation of all six genes in squamous cell carcinoma (SCC) compared to adenocarcinoma (ADC), regardless of clinical factors. The decision boundaries of the logistic regression model demonstrated effective separation of the relative expression levels between SCC and ADC for most genes, excluding KRT6C . Logistic regression and gradient boosting decision tree classifiers, incorporating all six validated genes, exhibited notable performance (AUC: 0.8930 and 0.8909, respectively) in distinguishing NSCLC subtypes. Nevertheless, our investigation revealed that the gene expression profiles failed to yield predictive value regarding the progression of early-stage NSCLC. Our molecular diagnostic models manifest the potential for an exhaustive molecular characterization of NSCLC, subsequently informing personalized treatment decisions and elevating the standards of clinical management and prognosis for patients.

KRAS G12C mutation is prevalent in ~4% of colorectal cancer (CRC) and is associated with poor prognosis. Divarasib, a KRAS G12C inhibitor, has shown modest activity as a single agent in KRAS G12C-positive CRC at 400 mg. Epidermal growth factor receptor has been recognized as a major upstream activator of RAS-MAPK signaling, a proposed key mechanism of resistance to KRAS G12C inhibition in CRC. Here, we report on divarasib plus cetuximab (epidermal growth factor receptor inhibitor) in patients with KRAS G12C-positive CRC (n = 29) from arm C of an ongoing phase 1b trial. The primary objective was to evaluate safety. Secondary objectives included preliminary antitumor activity. The safety profile of this combination was consistent with those of single-agent divarasib and cetuximab. Treatment-related adverse events led to divarasib dose reductions in four patients (13.8%); there were no treatment withdrawals. The objective response rate was 62.5% (95% confidence interval: 40.6%, 81.2%) in KRAS G12C inhibitor-naive patients (n = 24). The median duration of response was 6.9 months. The median progression-free survival was 8.1 months (95% confidence interval: 5.5, 12.3). As an exploratory objective, we observed a decline in KRAS G12C variant allele frequency associated with response and identified acquired genomic alterations at disease progression that may be associated with resistance. The manageable safety profile and encouraging antitumor activity of divarasib plus cetuximab support the further investigation of this combination in KRAS G12C-positive CRC.ClinicalTrials.gov identifier: NCT04449874., (© 2023. Crown.)

Introduction: A tumor microenvironment plays an important role in bladder cancer development and in treatment response., Purpose: The aim of the study was to assess how the components of the microenvironment affect tumor recurrence and to find the potential biomarkers for immunotherapy in NMIBC., Methods: The study group consisted of 55 patients with primary NMIBC. Immunohistochemistry was performed on sections of primary papillary urothelial carcinoma of the bladder. Cox proportional hazard multiple regression analysis was performed to characterize tumors with the highest probability of an unfavorable outcome., Results: Multivariate analysis confirmed that the CD4 ( p = 0.001), CD20 ( p = 0.008) and PD-L1 expressed on tumor cells ( p = 0.01) were independently associated with the risk of recurrence of bladder cancer. Patients with weak CD4 + cell infiltration (<4.6%) and severe CD20 + infiltration (>10%) belong to the group with a lower risk of recurrence. The cancer in this group also frequently recurs after 12 months ( p = 0.0005)., Conclusions: The evaluation of CD4 + and CD20 + cells in the tumor microenvironment, in addition to PD-L1 on tumor cells, facilitates the determination of a group of patients with a low risk of recurrence.

Neuroendocrine neoplasms (NENs) are a heterogenous and recurrent group of malignancies originating from neuroendocrine secretory cells diffused on all parts of the human body. Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) account for most NENs. Considering the abundance of possible origins, locations, and tumor specifications, there is still no consensus about optimal treatment options for these neoplasms. In light of the escalating immunotherapeutic approaches, it is crucial to define indications for such therapy in GEP-NETs. Bearing in mind the significance of pathophysiological mechanisms and tumor microenvironment (TME) impact on carcinogenesis, defining TME structure and correlation with the immune system in GEP-NETs appears essential. This paper aimed to assess the characterization of the tumor immune microenvironment for a better understanding of the possible therapeutic options in GEP-NETS. The authors performed a systematic review, extracting papers from the PubMed, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Among 3800 articles identified through database searching, 292 were assessed for eligibility. Ultimately, 28 articles were included in the qualitative synthesis. This paper sums up the research on the immune cell infiltrates, immune checkpoint expression, cytokine profile, neoangiogenesis, and microbiome in the TME of GEP-NETs.

Non-small cell lung cancer is the predominant form of lung cancer and is associated with a poor prognosis. MiRNAs implicated in cancer initiation and progression can be easily detected in liquid biopsy samples and have the potential to serve as non-invasive biomarkers. In this study, we employed next-generation sequencing to globally profile miRNAs in serum samples from 71 early-stage NSCLC patients and 47 non-cancerous pulmonary condition patients. Preliminary analysis of differentially expressed miRNAs revealed 28 upregulated miRNAs in NSCLC compared to the control group. Functional enrichment analyses unveiled their involvement in NSCLC signaling pathways. Subsequently, we developed a gradient-boosting decision tree classifier based on 2588 miRNAs, which demonstrated high accuracy (0.837), sensitivity (0.806), and specificity (0.859) in effectively distinguishing NSCLC from non-cancerous individuals. Shapley Additive exPlanations analysis improved the model metrics by identifying the top 15 miRNAs with the strongest discriminatory value, yielding an AUC of 0.96 ± 0.04, accuracy of 0.896, sensitivity of 0.884, and specificity of 0.903. Our study establishes the potential utility of a non-invasive serum miRNA signature as a supportive tool for early detection of NSCLC while also shedding light on dysregulated miRNAs in NSCLC biology. For enhanced credibility and understanding, further validation in an independent cohort of patients is warranted.

Non-small cell lung cancer (NSCLC) encompasses distinct histopathological subtypes, namely adenocarcinoma (AC) and squamous cell lung carcinoma (SCC), which require precise differentiation for effective treatment strategies. In this study, we present a novel molecular diagnostic model that integrates tissue-specific expression profiles of microRNAs (miRNAs) obtained through next-generation sequencing (NGS) to discriminate between AC and SCC subtypes of NSCLC. This approach offers a more comprehensive and precise molecular characterization compared to conventional methods such as histopathology or immunohistochemistry. Firstly, we identified 31 miRNAs with significant differential expression between AC and SCC cases. Subsequently, we constructed a 17-miRNA signature through rigorous multistep analyses, including LASSO/elastic net regression. The signature includes both upregulated miRNAs (hsa-miR-326, hsa-miR-450a-5p, hsa-miR-1287-5p, hsa-miR-556-5p, hsa-miR-542-3p, hsa-miR-30b-5p, hsa-miR-4728-3p, hsa-miR-450a-1-3p, hsa-miR-375, hsa-miR-147b, hsa-miR-7705, and hsa-miR-653-3p) and downregulated miRNAs (hsa-miR-944, hsa-miR-205-5p, hsa-miR-205-3p, hsa-miR-149-5p, and hsa-miR-6510-3p). To assess the discriminative capability of the 17-miRNA signature, we performed receiver operating characteristic (ROC) curve analysis, which demonstrated an impressive area under the curve (AUC) value of 0.994. Our findings highlight the exceptional diagnostic performance of the miRNA signature as a stratifying biomarker for distinguishing between AC and SCC subtypes in lung cancer. The developed molecular diagnostic model holds promise for providing a more accurate and comprehensive molecular characterization of NSCLC, thereby guiding personalized treatment decisions and improving clinical management and prognosis for patients.

Bladder cancer (BC) can be divided into two subgroups depending on invasion of the muscular layer: non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Its aggressiveness is associated, inter alia, with genetic aberrations like losses of 1p, 6q, 9p, 9q and 13q; gain of 5p; or alterations in the p53 and p16 pathways. Moreover, there are reported metabolic disturbances connected with poor diagnosis-for example, enhanced aerobic glycolysis, gluconeogenesis or haem catabolism.Currently, the primary way of treatment method is transurethral resection of the bladder tumour (TURBT) with adjuvant Bacillus Calmette-Guérin (BCG) therapy for NMIBC or radical cystectomy for MIBC combined with chemotherapy or immunotherapy. However, intravesical BCG immunotherapy and immune checkpoint inhibitors are not efficient in every case, so appropriate biomarkers are needed in order to select the proper treatment options. It seems that the success of immunotherapy depends mainly on the tumour microenvironment (TME), which reflects the molecular disturbances in the tumour. TME consists of specific conditions like hypoxia or local acidosis and different populations of immune cells including tumour-infiltrating lymphocytes, natural killer cells, neutrophils and B lymphocytes, which are responsible for shaping the response against tumour neoantigens and crucial pathways like the PD-L1/PD-1 axis.In this review, we summarise holistically the impact of the immune system, genetic alterations and metabolic changes that are key factors in immunotherapy success. These findings should enable better understanding of the TME complexity in case of NMIBC and causes of failures of current therapies., (© 2023. The Author(s).)

Drought is a serious threat worldwide and has a significant impact on agricultural production and soil health. It can pose an even greater threat when it involves land contaminated with trace metal element (TMEs). To prevent desertification, such land should be properly managed and growing Miscanthus for energy or raw material purposes could be a solution. The effects of drought and TMEs were studied in a pot experiment on three different Miscanthus hybrids (conventional Miscanthus × giganteus, TV1 and GNT10) considering growth parameters, photosynthetic parameters and elemental composition of roots, rhizomes and shoots. GNT10 was characterised by the weakest gas exchange among the hybrids, which was compensated by the highest number of leaves and biomass. The strongest correlations between the studied parameters were found for TV1, which might indicate a high sensitivity to TME stress. For M × g and GNT10, the main mechanisms for coping with stress seem to be biomass management through number of shoots and leaves and gas exchange. The main factor determining the extent of accumulation of TMEs was the amount of water applied in the experimental treatment, which was related to the location of the plant in the aniso-isohydric continuum. GNT10 was the most resistant plant to combined stress, while it responded similarly to TV1 when drought and trace metal elements were applied separately., (© 2023. The Author(s).)

Nature-based solutions are promising for climate adaptation and environmental management in urban areas, but urban conditions are stressful for vegetation. In particular, the interaction of drought and high temperatures may be detrimental. Guiding plant selection for urban greening with native species requires a far better knowledge of plant adaptations and stress acclimation. We tested the physiological responses of four candidate calcareous grassland species for green roofs and walls to the combined effects of drought and high temperatures under controlled conditions. The tested species proved relatively resistant to stress despite different strategies to protect the photosynthetic apparatus, maintain water balance, and repair damages. Based on the physiological responses, we rank the species in descending order of resistance to the stress factors tested: Trifolium medium > Festuca ovina > Carex flacca > Potentilla reptans , but all four can serve as potential candidates for green walls and roofs. Physiological stress screening of plant species for use on green roofs and walls supplements the habitat template approach to provide a stronger and wider base for prioritizations.

Climate change and man-made pollution can have a negative impact on the establishment of Miscanthus plants in the field. This is particularly important because biomass can be produced on marginal land without conflicting with food crops. The establishment success depends on the hybrid chosen, the cultivation method, the climatic conditions, and the concentration of pollutants in the soil. There are several ways to increase the survival rate of the plants during the first growing season and after the first winter. One of them is the application of biochar and photodegradable plastic mulch, which can provide a solution for soils polluted with trace elements (TMEs). The aim of this study was to investigate the application of plastic mulch and biochar separately and in combination at the planting stage for two Miscanthus hybrids planted by the rhizome method (TV1) and seedling plugs (GNT43) on soils contaminated with trace metal elements (Pb, Cd, Zn). TV1 seems unsuitable for TME-contaminated field cultivation, as the survival rate was <60% in most treatments studied. The selected treatments did not increase the survival rate. Furthermore, the application of plastic mulch in combination with biochar resulted in a significant reduction of this parameter, regardless of the hybrid studied. The applied agrotechnology did not influence the TME accumulation in the aboveground plant parts in TV1, while Pb and Cd in GNT43 showed significantly higher values in all treatments. Contrary to expectations, biochar and plastic mulch applied separately and together neither increased survival nor reduced the accumulation of toxic TMEs during establishment on soil contaminated with TMEs and after the first growing season.

Hepatocellular carcinoma (HCC) is one of the most common types of cancer diagnosed worldwide. After a decade of stagnation, several novel compounds have recently been shown to be effective in the treatment of HCC. Since immunotherapy is associated with important clinical benefits in some, but not all patients, it is essential to identify reliable predictive biomarkers. As the complex interplay between hepatocytes and immune cells is highly dependent on the tumor microenvironment, the tumor microenviroment has been suggested to be an important factor associated with the response to therapy and is currently being extensively investigated. Within this network, several important factors should be highlighted. Most of the cells are hepatocytes, but fibroblasts, endothelial cells, and immune cells are also present. Tumor-infiltrating leukocytes include several populations of cells and each of them plays a role in forming the tumor environment. Some of these cells may have antitumor effects, whereas others may be associated with the progression of the disease. The most important subsets include tumor-associated macrophages, tumor-associated neutrophils, and lymphocytes. These groups are described in the present review. The immune response is controlled by immune checkpoint molecules. One of the most important molecules involved in this checkpoint process seems to be the programmed death-1 (PD-1) receptor, which typically is induced on activated T cells, natural killer (NK) cells, B cells, and antigen-presenting cells. On the other hand, programmed death ligand 1 (PD-L1) is expressed by tumor cells, hepatocytes and hepatic stellate cells, and Kupffer cells or liver sinusoidal cells. Complex interactions between ligands and receptors are dependent on the signals from the microenvironment leading to either cancer development or apoptosis. Evidence from several studies indicates that patients with higher expression levels of PD-L1 on tumor cells or immune cells are more likely to achieve beneficial results from treatment with checkpoint blockers. This review focuses on the basic information regarding the microenvironment and its components, particularly on immune system involvement., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Gryziak et al.)

This document - "Polish Consensus on Gastric Cancer Diagnosis and Treatment - Update 2022" - represents an expert consensus following a year's worth of dedicated effort by a team of specialists throughout 2021, put forward in a conference in December 2021 in Krakow, and finalized below for publication in 2022. The effective date of this document is June 14th 2022. The work that went into updating this consensus was made under auspices of the Polish Society of Surgical Oncology and the Association of Polish Surgeons.

Malignancy is the second cause of death in the dialyzed population. However, data on the prevalence of cancer are very scarce. Kidney transplantation improves quality of life, prolongs survival, and is cost-effective but bears some serious complications including malignancy. Therefore, active screening for cancer is of utmost importance. The aim of this study was to assess the prevalence of malignancy in dialyzed patients in relation to status on the on the waiting list and type of dialysis. This cross-sectional study was conducted in 108 hemodialyzed patients (mean age 65 years, 47 women) and 47 peritoneally dialyzed patients (mean age 51 years, 25 women). Among the population studied, 20 patients were actively waitlisted, including 14 peritoneal dialysis patients. Patients who had been active on the cadaver kidney waiting list and not listed did not differ in regard to sex, dialysis vintage, and causes of end-stage renal failure, but were significantly younger. Among hemodialysis patients, 24 of them had a history of malignancy and 10 in the peritoneal dialysis population. The most common were renal cell carcinoma in 6, breast cancer in 4, lung cancer in 3, prostate cancer in 3, hepatocellular cancer in 2, colorectal cancer in 2, esophageal cancer in 2, and others 14. In waitlisted patients, only 2 hemodialysis patients had a history of malignancy. Waitlisted patients represent a very selected and healthier dialyzed population. Malignancy has become a more common comorbidity in dialyzed patients, which may have important clinical implication regarding therapy. Guidelines for cancer screening in potential transplant recipients should be developed, as nowadays there are scarcity of data in this matter., (Copyright © 2022 Elsevier Inc. All rights reserved.)

The tumor microenvironment is the space between healthy tissues and cancer cells, created by the extracellular matrix, blood vessels, infiltrating cells such as immune cells, and cancer-associated fibroblasts. These components constantly interact and influence each other, enabling cancer cells to survive and develop in the host organism. Accumulated intermediate metabolites favoring dysregulation and compensatory responses in the cell, called oncometabolites, provide a method of communication between cells and might also play a role in cancer growth. Here, we describe the changes in metabolic pathways that lead to accumulation of intermediate metabolites: lactate, glutamate, fumarate, and succinate in the tumor and their impact on the tumor microenvironment. These oncometabolites are not only waste products, but also link all types of cells involved in tumor survival and progression. Oncometabolites play a particularly important role in neoangiogenesis and in the infiltration of immune cells in cancer. Oncometabolites are also associated with a disrupted DNA damage response and make the tumor microenvironment more favorable for cell migration. The knowledge summarized in this article will allow for a better understanding of associations between therapeutic targets and oncometabolites, as well as the direct effects of these particles on the formation of the tumor microenvironment. In the future, targeting oncometabolites could improve treatment standards or represent a novel method for fighting cancer.

COVID-19 has become the biggest public health problem and one of the most important causes of death in many countries in the world. SARS-CoV-2 infection is most likely to be fatal in elderly patients with concomitant diseases. In this article we present two cases of asymptomatic SARS-CoV-2-positive patients suffering from cancer who were treated with chemotherapy. The first case, a patient with primary mediastinal B-cell lymphoma, shows that confirmed SARS-CoV-2 infection does not have to be a contraindication to chemotherapy. We describe the course of disease and discuss doubts related to the choice of chemotherapy regimen. The second patient was a male with metastatic sigmoid cancer treated with FOLFOX4 as first-line palliative chemotherapy. This case draws attention to asymptomatic SARS-CoV-2 carriers who underwent chemotherapy. Our patient was safely treated with chemotherapy without long break caused by viral infection. It should be remembered that there are asymptomatic carriers among cancer patients and that they may spread infection to others. On the other hand, delaying chemotherapy can cause rapid disease progression and reduce overall survival of our patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest., (Copyright © 2021 Woźniak, Sachs, Boguradzki, Basak and Stec.)

According to data provided by WHO (World Health Organization), hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths worldwide. Since the approval of sorafenib in 2008, several trials have assessed other particles for the treatment of HCC, but few have proven to be effective. ESMO (European Society for Medical Oncology) guidelines have been changed several times recently. This systematic review aims to describe both successful and failed trials of systemic treatments for HCC. Methods: We examined randomized, phase III trials of first- and second-line treatments in adults, identifying 23 fully-published trials and 2 reported as abstracts. The latest advances in immunotherapy were also briefly discussed. Conclusions: The landscape of HCC treatment has changed significantly in recent years. Several small molecule inhibitors currently form the core of HCC treatment; however, immunotherapy is now emerging as a promising treatment option., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Life-threatening diseases have a negative impact on emotional well-being and psychosocial functioning. This study aimed to assess the relationship between the level of anxiety caused by a neoplasm and the threat of coronavirus infection among patients with cancer actively treated with systemic therapy during the COVID-19 pandemic. Additionally, we searched for clinical factors associated with a higher level of anxiety., Methods: In this multicentre, prospective, non-interventional study conducted in Poland, we enrolled 306 actively treated patients with cancer and collected their clinical data, including age, gender, cancer type and treatment intention. The fear/anxiety of SARS-CoV-2 were rated in Fear of COVID-19 Scale (SRA-FCV-19S) and Numerical Anxiety Scale (SRA-NAS). The fear and anxiety associated with cancer (CRA) were rated with the NAS (CRA-NAS)., Results: The mean level of SRA-FCV-19S was 18.5±7.44, which was correlated with the SRA-NAS (r=0.741, p<0.001). SRA-FCV-19S was significantly higher in women versus men (20.18±7.56 vs 16.54±6.83; p<0.001) and was tumour type-dependent (p=0.037), with the highest anxiety observed in patients with breast cancer (17.63±8.75). In the multivariate analysis, only the female gender was significantly associated with higher SRA. CRA-NAS was higher in women versus men (7.07±2.99 vs 5.47±3.01; p<0.001), in patients treated with curative versus palliative intention (7.14±3.06 vs 5.99±3.06; p=0.01) and in individuals aged ≤65 years versus >65 years (6.73±2.96 vs 5.66±3.24; p=0.007)., Conclusions: For an actively treated patient with cancer, cancer remains the main life-threatening disease during the COVID-19 pandemic. The need for more attentive psychological care should be provided especially to female patients, patients with breast cancer, those under 65 years of age and treated with curative intention, as these factors are associated with a higher level of anxiety., Competing Interests: Competing interests: None declared., (© Author (s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ on behalf of the European Society for Medical Oncology.)

Introduction: After transurethral resection of a bladder tumor, patients frequently have a recurrence of the disease, thereby requiring adjuvant therapy., Purpose: The study aimed to determine the prognostic value of expression levels of p53, Ki-67, and survivin, and to develop a new prognostic model for patients with non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of a bladder tumor., Methods: The study group consisted of 101 patients with primary NMIBC. Univariate followed by multivariate Cox proportional hazard regression analysis was performed to obtain a model including the smallest possible number of descriptive variables with the highest statistical significance and impact on risk., Results: The RECINT model (RECurrence In Not Treated) including factors independently associated with cancer recurrence (tumor size [HR 1.148; p = 0.034], intensity of the color reaction for p53 [HR 1.716; p = 0.008], Ki-67 [HR 3.001; p = 0.022], and survivin [HR 1.461; p = 0.021]) adequately stratified recurrence free-survival (R 2  = 0.341, p < 0.001) in patients with primary NMIBC. Patients with the lowest RECINT score (0-6) had the lowest probability of cancer recurrence (1- and 5-year recurrence of 16%) in comparison with other groups (p < 0.001)., Conclusions: The RECINT model may be useful for stratifying the risk of recurrence in patients with non-muscle-invasive bladder cancer and may allow for identification of those who may benefit the most from adjuvant BCG immunotherapy.

The aim of the study was to determine the prognostic value of expression levels of biomarkers selected on the basis of the literature: p53, Ki-67, survivin, β-catenin, E-cadherin and N-cadherin in patients with non-muscle invasive bladder cancer. Immunohistochemistry was performed on sections of primary papillary carcinoma of the bladder removed during transurethral resection of the tumor in 134 patients. The expression of β-catenin and E-cadherin was found in all analyzed cases and N-cadherin expression was demonstrated in 3.73% of the tissues examined. The expression of the p53 protein was confirmed in 96.27% of tissues examined. The expression of the Ki-67 protein was demonstrated in all analyzed cases. Survivin expression was found in 95.52% of the study group. Multivariate analysis confirmed the relationship between the recurrence-free survival (RFS) and the intensity of the nuclear reaction for p53 (HR 1417, 95% CI 1.001-2.007, p = 0.049) and survivin (HR 1.451; 95% CI 1.078-1.955; p = 0.014), the expression level of the Ki-67 protein expressed by the TS index (HR 1.146, 95% CI 1.116-1.823, p = 0.005) and the use of adjuvant BCG therapy (HR 0.218, 95% CI 0.097-0.489, p = 0.0002). The evaluation of Ki-67 expression and the intensity of nuclear staining for survivin and p53 may provide additional information that will allow more accurate stratification of the risk of NMIBC recurrence after TURBT.

Microbiome (microbiota) is a community of all microorganisms inhabiting a specific site of the body, including pathogens, which distinguishes it from the physiological microflora. Intestinal dysbiosis plays a key role in the development of colorectal cancer. In the process of carcinogenesis, inflammation, immune response, and toxic metabolites play a significant role. Specific species of bacteria might affect the risk of colorectal cancer and growth of tumor already present. Assessment of changes in the intestinal microbiome during the development and progression of colorectal cancer might create a simple diagnostic tool, a useful biomarker, or might influence treatment strategies in colorectal cancer patients. Analysis of the gut microbiome provides the potential to develop noninvasive diagnostic tests that would be useful as new protective markers of colorectal cancer, prognostic markers in already present colorectal cancer, and predictive markers of response to treatment, especially immunotherapy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: We conducted a study to validate the influence of the systemic immune-inflammation index (SII) on overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) and to verify whether the implementation of the SII in place of neutrophil and platelet counts within the International Metastatic Renal Cell Carcinoma Consortium (IMDC) model might increase its prognostic accuracy., Patients and Methods: We retrospectively analyzed consecutive patients with mRCC, who were treated with first-line tyrosine kinase inhibitors from 2008 to 2016 in two major oncology centres in Poland. We stratified patients into low SII (< 730) and high SII (≥ 730) groups according to a recent literature report. We used multivariable Cox proportional hazards regressions (CPHRs) to assess the impact of the SII on OS and concordance, global 'goodness-of-fit', calibration and reclassification measures to quantify a potential prognostic benefit from the modification of the IMDC model., Results: Overall, 502 patients (294 with low and 208 with high SII) were included. Median OS was 36.7 months [95% confidence interval (CI) 30.4-41.5 months] and 17.0 months (95% CI 12.5-19.6 months) in the low and high SII groups, respectively. The SII status was significant in CPHRs with the hazard ratio ranging from 1.38 to 1.68. All prognostic accuracy measures favored the SII-modified-IMDC model over the original IMDC model., Conclusions: Using an external dataset, we showed that high SII was an independent factor for poor OS. The addition of the SII to the IMDC model in place of neutrophil and platelet counts increased the model's prognostic performance.

Background: The aim of the present study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of the WNT/β-catenin pathway., Patients and Methods: In a prospective, single-arm, phase II study, patients with mRCC received everolimus (10 mg/d) in a 30-day cycle. We performed a prospectively planned evaluation of the potential biomarkers of the WNT/β-catenin pathway., Results: The serum level of soluble E-cadherin (sE-cadherin) in patients with RCC was significantly greater than that in the controls (71.62 ± 22.28 pg/mL vs. 54.26 ± 10.317 pg/mL; P = .0069). After 2 cycles of everolimus therapy, we observed a significance increase in sE-cadherin (from 71.81 ± 21.18 pg/mL to 77.50 ± 28.212 pg/mL; P = .0151). The Dickkopf-1 protein levels in the study and control groups were not significantly different (P = .2135). The favorable independent predictors for everolimus therapy were normal lactate dehydrogenase level before treatment (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.28-0.98; P = .0443) and low sE-cadherin level (HR, 0.54; 95% CI, 0.29-0.98; P = .0422). On multivariate analysis, we observed that worse overall survival was seen in patients with a lower regression coefficient of sE-cadherin after 2 cycles of treatment (HR, 2.60; 95% CI, 1.23-5.52; P = .0128), an increased corrected calcium level (HR, 3.09; 95% CI, 1.21-7.88; P = .0180), and an increased lactate dehydrogenase level before treatment (HR, 1.98; 95% CI, 1.02-3.83; P = .0426)., Conclusion: WNT/β-catenin component expression in patients with mRCC had no effect on progression-free survival or overall survival. However, we found that the sE-cadherin level might interact with response to everolimus therapy, although confirmation in future studies is needed., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Inflammation plays a crucial role in cancer development. In this study, we evaluate the prognostic values of systemic inflammation markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) for the progression-free survival and overall survival in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors., Materials and Methods: PubMed and the Cochrane Library databases were searched for published studies on the effect of NLR, PLR, and CRP in patients with metastatic renal cell carcinoma treated with tyrosine kinase inhibitors., Results: In the meta-analysis, NLR (hazard ratio [HR], 2.01; 95% confidence interval [CI], 1.27-3.18; P = .003) and PLR (HR, 6.96; 95% CI, 5.04-9.62; P < .001) had a significant influence on progression-free survival, whereas all considered proinflammatory markers had a significant impact on overall survival: NLR (HR, 2.14; 95% CI, 1.67-2.73; P < .001), PLR (HR, 14.67; 95% CI, 11.10-19.57; P < .001), and CRP (HR, 1.96; 95% CI, 1.26-3.05; P = .003)., Conclusions: Inflammation markers such as NLR, PLR, and CRP are predictors of clinical outcome and could provide additional information to individualize treatment., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

In order to facilitate long-term treatment decisions, we aimed to define biomarkers defining the probability of receiving second-line (SL) targeted therapy (TT) in patients with metastatic renal cell carcinoma (mRCC) based on their characteristics present at first-line TT initiation. We analysed 152 consecutive mRCC patients treated and used multivariable binominal logistic regression to identify factors contributing to the probability of receiving SL TT. Final model was assessed with bias-corrected indices (Nagelkerke's R 2 and area under receiver operating characteristic curve [AUC]) and two bootstrap procedures were used for internal validation. Factors associated with the probability of SL TT eligibility were the presence of brain metastases (odds ratio [OR] 0.084, 95% confidence interval [CI] 0.010-0.707), number of metastatic sites (OR 0.740, 95% CI 0.575-0.953 per each site), platelet count (OR 0.971, 95% CI 0.947-0.997, per 10 4 /ml), lactate dehydrogenase level (OR 0.952, 95% CI 0.910-0.997 per 10 units/l), and albumin concentration (OR 1.924, 95% CI 1.057-3.503 per 1 g/dl). We developed on-line calculator that enables practicing clinicians to estimate SL treatment probability ( http://www.r-calc.com ).

Purpose: The study investigated whether a replacement of neutrophil count and platelet count by neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) within the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model would improve its prognostic accuracy., Materials and Methods: This retrospective analysis included consecutive patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors. The IMDC and modified-IMDC models were compared using: concordance index (CI), bias-corrected concordance index (BCCI), calibration plots, the Grønnesby and Borgan test, Bayesian Information Criterion (BIC), generalized R 2 , Integrated Discrimination Improvement (IDI), and continuous Net Reclassification Index (cNRI) for individual risk factors and the three risk groups., Results: Three hundred and twenty-one patients were eligible for analyses. The modified-IMDC model with NLR value of 3.6 and PLR value of 157 was selected for comparison with the IMDC model. Both models were well calibrated. All other measures favoured the modified-IMDC model over the IMDC model (CI, 0.706 vs. 0.677; BCCI, 0.699 vs. 0.671; BIC, 2,176.2 vs. 2,190.7; generalized R 2 , 0.238 vs. 0.202; IDI, 0.044; cNRI, 0.279 for individual risk factors; and CI, 0.669 vs. 0.641; BCCI, 0.669 vs. 0.641; BIC, 2,183.2 vs. 2,198.1; generalized R 2 , 0.163 vs. 0.123; IDI, 0.045; cNRI, 0.165 for the three risk groups)., Conclusion: Incorporation of NLR and PLR in place of neutrophil count and platelet count improved prognostic accuracy of the IMDC model. These findings require external validation before introducing into clinical practice.

Aim: The study aimed to define the true impact of pancreatic metastases (PM) from renal cell carcinoma on overall survival (OS) in patients treated with first-line tyrosine kinase inhibitors., Patients and Methods: Overall, 321 consecutive patients were analysed. The influence of PM on OS was assessed using the Kaplan-Meier estimator and the log-rank test (unadjusted and adjusted) and two multivariabe Cox proportional hazards regressions (CPHR)., Results: Thirty-four patients (10%) had PM and 287 (90%) had sites of metastasis other than the pancreas; the median OS was 46.1 and 23.1 months, respectively (unadjusted log-rank p=0.020; adjusted log-rank p=0.544). The PM status was an insignificant factor for OS in both CPHR (hazard ratio(HR)=0.84, p=0.603, and HR=0.66, p=0.098)., Conclusion: The presence of PM was not an independent prognostic factor, but was rather an indicator of an indolent course of the disease., (Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Renal cell carcinoma (RCC) is one of the most common kidney malignancies. An upgraded comprehension of the molecular biology implicated in the development of cancer has stimulated an increase in research and development of innovative antitumor therapies. The aim of the study was to analyze the medical literature for hypertension and renal toxicities as the adverse events of the vascular endothelial growth factor (VEGF) signaling pathway inhibitor (anti-VEGF) therapy. Relevant studies were identified in PubMed and ClinicalTrials.gov databases. Eligible studies were phase III and IV prospective clinical trials, meta-analyses and retrospective studies that had described events of hypertension or nephrotoxicity for patients who received anti-VEGF therapy. A total of 48 studies were included in the systematic review. The incidence of any grade hypertension ranged from 17% to 49.6%. Proteinuria and increased creatinine levels were ascertained in 8% to 73% and 5% to 65.6% of patients, respectively. These adverse events are most often mild in severity but may sometimes lead to treatment discontinuation. Nephrotoxicity and hypertension are related to multiple mechanisms; however, one of the main disturbances in those patients is VEGF inhibition. There is a significant risk of developing hypertension and renal dysfunction among patients receiving anti-VEGF treatment; however, there is also some evidence that these side effects may be used as biomarkers of response to antiangiogenic agents., Competing Interests: The authors declare no conflict of interest.

Background: The present study investigated the various features that might influence the overall survival (OS) of patients with metastatic renal cell carcinoma (RCC) treated with first-line tyrosine kinase inhibitors (TKIs)., Patients and Methods: A retrospective analysis was performed of consecutive patients with metastatic RCC, in whom treatment with a first-line TKI was initiated from January 2010 to December 2014, at the Department of Oncology, Military Institute of Medicine (Warsaw, Poland). Cox proportional hazards regression was used to construct a prognostic model that included independent factors for OS. We validated the model using 2 bootstrap procedures and calculation of the bias-corrected concordance index., Results: Of the 266 patients included in the study, 201, 45, and 20 received sunitinib, pazopanib, and sorafenib, respectively. The median OS for the whole cohort was 24.8 months (95% confidence interval, 20.2-29.4 months). Six factors were independently associated with poor survival: Eastern Cooperative Oncology Group performance status > 0 (P < .0001), Fuhrman grade 3 to 4 (P < .0001), hemoglobin less than the lower limit of normal (P < .0001), lactate dehydrogenase greater than the upper limit of normal (P = .0011), neutrophil-to-lymphocyte ratio ≥ 4 (P < .0001), and > 2 metastatic sites (P = .0012). The bias-corrected concordance index was 0.751., Conclusion: Fuhrman grade and neutrophil-to-lymphocyte ratio are potential factors that affect the survival of patients with metastatic RCC treated with first-line TKIs. The presented prognostic model demonstrated satisfactory performance but requires external validation with a larger data set., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We evaluated the influence of serum cystatin C (CysC) with respect to other glomerular filtration rate (GFR) markers on the treatment effect of everolimus in a phase II study in patients with metastatic renal cell carcinoma (mRCC)., Materials and Methods: Outcomes were from the study's primary analysis. GFR was calculated according to CKD-EPI-sCr equation, CKD-EPI-CysC equation and CKD-EPI-sCr-CysC equation, Modification of Diet in Renal Disease (MDRD) equation and Cockcroft-Gault (CG) equation, serum levels of creatinine (sCr) and CysC before the treatment., Results: We observed in 56 patients analysed patients high correlation (R Spearman from ±0.69 to ±1.00; P < 0.0001) between CysC level and GFR markers: sCr, CKD-EPI-sCr, CKD-EPI-CysC, CKD-EPI-sCr-CysC, MDRD, GFR (CG) before everolimus therapy. We observed that the adverse independent predictors for everolimus therapy were increased CysC level [HR: 2.85 (95 % CI 1.34-6.05), P = 0.0065], histologic grade G1/2 [HR: 3.38 (95 % CI 1.59-7.20), P = 0.0016] and increased LDH level [HR: 5.59 (95 % CI 2.52-12.40), P < 0.0001]. Worse OS was seen in multivariate analysis in patients with increased cystatin C level before treatment [HR: 2.60 (1.03-2.60), P = 0.0428], increased corrected calcium level [HR: 2.78 (95 % CI 1.03-7.54), P = 0.0441] and increased LDH level before treatment [HR: 2.34 (95 % CI 1.11-4.97), P = 0.0262]., Conclusion: Increased serum CysC level in contrast to other studied GFR markers had predictive significance in patients with mRCC.

Metastasis is a process consisting of cells spreading from the primary site of the cancer to distant parts of the body. Our understanding of this spread is limited and molecular mechanisms causing particular characteristics of metastasis are still unknown. There is some evidence that primary renal cell carcinoma (RCC) and metastases of RCC exhibit molecular differences that may effect on the biological characteristics of the tumor. Some authors have detected differences in clear cell and nonclear cell component between these 2 groups of tumors. Investigators have also determined that primary RCC and metastases of RCC diverge in their range of renal-specific markers and other protein expression, gene expression pattern, and microRNA expression. There are also certain proteins that are variously expressed in primary RCCs and their metastases and have effect on clinical outcome, e.g., endothelin receptor type B, phos-S6, and CD44. However, further studies are needed on large cohorts of patients to identify differences representing promising targets for prognostic purposes predicting disease-free survival and the metastatic burden of a patient as well as their suitability as potential therapeutic targets. To sum up, in this review we have attempted to summarize studies connected with differences between primary RCC and its metastases and their influence on the biological characteristics of renal cancer., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Colorectal cancer (CRC) is one of the most common cancers worldwide, with ~700,000 mortalities occurring due to CRC in 2012. The treatment options are effective in a small percentage of patients, and it is important to identify specific biomarkers in order to determine patients for whom the available therapies will be beneficial. It has been hypothesised that the PIK3CA gene mutation may affect the response to therapy of patients with metastatic CRC. In the present study, primary tumour specimens were collected from 156 patients with CRC who were treated in the Military Institute of Medicine in Warsaw (Warsaw, Poland). Codons 12 and 13 of exon 1 of KRAS , exons 11 and 15 of BRAF and exons 9 and 20 of PIK3CA were analysed for mutation using direct sequencing. The prognostic value of each mutation and the clinical and pathological variables of these tumours were estimated. The results revealed that PIK3CA mutations were present in 15 patients (9.6%), of whom seven (46.7%) possessed mutations in codon 9 and eight (53.3%) possessed mutations in codon 20. Mutation in the PIK3CA gene was detected in six patients with KRAS gene mutations, which accounted for 40% of PIK3CA -mutated tumours, and in one patient with BRAF mutations, which accounted for 6.6% of PIK3CA -mutated tumours. No significant differences were identified between the overall survival (OS) rates of patients with PIK3CA mutations (median OS, 56.7 months) and those with wild-type PIK3CA genes (median OS, 47.6 months) (P=0.1270). Univariate analysis identified that the following prognostic factors affected the OS rate in the current patient cohort: Gender, female patients survived for 57.5 months compared with 39.3 months for male patients (P=0.0111); and lymph node involvement grade, as survival of patients without lymph node metastases was 61.4 months compared with 45.4 months in patients presenting with metastases (P=0.0122). The findings of the present analysis indicate that PIK3CA mutation status is not a prognostic factor in CRC patients. In addition, no statistically significant association exists between tumours with PIK3CA mutations and clinical or pathological factors.

Due to its high incidence and poor prognosis, gastric cancer is an important health problem worldwide. The only possible curative treatment is to remove the primary tumor at an early stage of the disease. However, at diagnosis, most patients have unresectable or metastatic disease. Relapse in patients after primary surgery is frequent. In these patients, the aim of treatment is to extend the duration of survival and to improve quality of life and this accomplished by systemic therapies. Regimens containing fluoropyrimidine and platinum agents, in combination with trastuzumab in patients with overexpression of human epidermal growth factor receptor 2 (HER2), are recommended as the first-line treatment. Unfortunately, all patients develop progressive disease, but at least half of them are eligible for further treatment. This article presents current possibilities and near-future developments of chemotherapy and molecular targeted-therapy in patients with advanced gastric cancer after failure of prior regimens containing fluoropyrimidine and platinum., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Background: The aim of this study was to search for predictive and prognostic factors in patients with metastatic renal cell carcinoma (mRCC) treated with everolimus among the components of PI3K/AKT/mTOR pathway., Patients and Methods: In a prospective, one-arm, phase II study, patients with mRCC received everolimus (10 mg/day) using a 30-day cycle. A prospectively planned evaluation of potential biomarkers of PI3K/AKT/mTOR pathway., Results: The median age of the 58 patients enrolled into the study was 60 years (range 41-78 years). In multivariate analysis, it was found that the adverse independent predictors for everolimus therapy were histological grade G1/2 {hazard ratio (HR): 2.68 [95% confidence interval (CI) 1.29-5.58, P = 0.0082]}, increased lactate dehydrogenase (LDH) level before treatment [HR: 2.55 (95% CI 1.30-4.99, P = 0.0064)] and the PIK3CA gene variant rs6443624 (HR: AC + AA versus CC = 2.08, 95% CI 1 11-3.89, P = 0.0254). In multivariate analysis, it was observed that the adverse independent prognostic factors were: elevated corrected calcium level [HR: 4.17 (95% CI 1.66-10.51; P = 0.0024)] and the PIK3CA gene variant rs6443624 [HR: AC + AA versus CC = 1.97 (95% CI 1.02-3.79; P = 0.0421)]., Conclusions: The PI3KCA gene polymorphism, LDH, and histologic grade can predict the effects of everolimus treatment. The corrected calcium level and the PIK3CA gene variant rs6443624 may be independent prognostic factors. Further investigation is needed to confirm and validate these findings prospectively in other RCC trials., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

In oncology, a rational approach to identify patients who are likely to benefit from therapy, already before initiation of treatment, is urgently required. Excision repair cross-complementation group 1 enzyme (ERCC1) has been proposed as a molecular predictor of clinical resistance to platinum-based chemotherapy. Other data suggest Tau protein expression as a predictor of clinical outcome in cancer patients treated with paclitaxel-based chemotherapy as low tau expression may render microtubules more vulnerable to paclitaxel. Therefore, the combination of ERCC1 and Tau may be a valuable predictor of sensitivity to platinum/paclitaxel treatment. The primary aim of the study was to investigate whether ERCC1 and Tau protein expression correlates with patient outcome in newly diagnosed epithelial ovarian cancer (EOC) patients. Formalin-fixed, paraffin-embedded tissue sections from 227 newly diagnosed EOC patients were used for immunohistochemical staining for ERCC1 and Tau proteins. All patients received standard first-line combination platinum and paclitaxel chemotherapy. The patients were divided in a training set of 84 patients and an independent validation cohort of 143 patients. Neither ERCC1 nor Tau expression was associated with clinical response or platinum resistance in both the training and validation sets. Patients with ERCC1-positive tumors had significantly shortened progression-free and overall survival compared to patients with ERCC1-negative tumors, p<0.00001 and p=0.0006. In multivariate analysis ERCC1 also proved as an independent predictor of PFS and OS with HR of 3.86 and 1.98, respectively but the data could not be confirmed in the validation set. Tau expression was not associated with PFS or OS in this study. ERCC1 and Tau might serve as biomarkers of DNA repair and for paclitaxel sensitivity but the present study could not validate ERCC1 or Tau protein expression in tumors as pre-treatment tools to predict sensitivity to first-line platinum/paclitaxel chemotherapy.

Background: Standard treatment for patients with unresectable colorectal cancer metastases includes chemotherapy regimens based on irinotecan, oxaliplatin, fluoropyrimidines, anti-vascular endothelial growth factor therapy, and anti-EGFR. Additional therapeutic options are needed for patients with good performance status who have disease progression during or after standard therapies., Methods: A nonrandomized phase II study was modeled as a two-stage Chen design. Eligible patients had a diagnosis of metastatic colorectal cancer (mCRC) with progression after prior cytotoxic regimens based on oxaliplatin and irinotecan. Treatment consisted of mitomycin C in combination with high-dose 5-fluorouracil (5-FU) and folinic acid (the MLF regimen; mitomycin C as an intravenous bolus of 6 mg/m² i.v. on days 1 and 22 every 7 weeks; folinic acid at 250 mg/m² in combination with 5-FU at 2,600 mg/m² as a continuous intravenous infusion (24 hours) weekly for 6 of every 7 weeks., Results: The median age of the 74 eligible patients was 62 years (range: 47-79 years). In these heavily pretreated patients with mCRC, the MLF regimen was the fourth or fifth line in more than 60% of the patients. Two patients (3.2%) achieved a partial response, and 33 (53.2%) achieved a best response of stable disease, defined as neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease. Median progression-free survival was 4.9 months. The median overall survival was 9.7 months. The most common nonhematologic side effects included mucositis (24.4% for all grades, and 9.5% with grade 3/4), diarrhea (15.0% for all grades, 13.6% with grade 3/4), fatigue (44.7% for all grades, 13.6% with grade 3/4), nausea (12.3% for all grades, 6.8% with grade 3/4), and peripheral neuropathy (17.6% for all grades, 2.7% with grade 3/4). Among the most frequent hematological toxicities were neutropenia (27.1% for all grades, 14.9% with grade 3/4), thrombocytopenia (18.9% for all grades, 8.1% with grade 3/4), and anemia (13.6% for all grades, 4.1% with grade 3/4). Dose reductions due to adverse events were necessary in 29 of 74 patients (37.6%), and discontinuation of therapy due to toxicity was necessary for 14 of 74 patients (18.2%)., Conclusion: Our study shows the MLF regimen can be administered safely to patients with heavily pretreated mCRC. Median progression-free and overall survival compares favorably with other options used or approved in this setting. A randomized trial in this setting should be considered.

Background: Overexpression of epidermal growth factor receptor (EGFR) is found in many types of neoplasms. The aim of the study was to evaluate EGFR expression in colorectal cancer (CRC) specimens and to determine whether EGFR expression correlates with clinicopathological data and overall survival., Patients and Methods: Tissue specimens from 181 consecutive CRC patients treated at the Military Institute of Medicine in 2006-2010 were collected and examined for EGFR expression, by immunohistochemistry staining. The staining intensity and percentage of cells with membranous EGFR expression were scored and then grouped according to the parameters of the Allred Scoring system. Cutoff values were subjected to further statistical analysis. Univariate tests and a multivariate Cox proportional hazards model were used in data analysis., Results: EGFR was overexpressed in 96 of 181 CRC specimens (53%). EGFR expression was not correlated with other clinicopathological variables. On univariate analysis, overexpression of EGFR, determined by PS (percentage score) (>3) and total score (sum of PS and intensity score) (>4), was associated with poor overall survival. On multivariate analysis, EGFR overexpression (PS > 3) was an independent adverse prognostic factor (hazard ratio [HR] 1.62; 95% confidence interval [CI]: 1.03-2.53). Elevated carcinoembryonic antigen (CEA) serum concentration before treatment, performance status (Word Health Organization [WHO]-2), and tumor localized in colon and liver metastases were also independent unfavorable prognostic factors., Conclusion: EGFR overexpression (PS > 3) in a CRC patient population was an independent adverse prognostic factor. Implementation of the Allred Scoring system criteria into clinical practice might facilitate treatment decisions in CRC patients.

Background: The aim of the study was to evaluate predictive and prognostic significance of microtubule-associated protein Tau in epithelial ovarian cancer (EOC) patients treated with paclitaxel and platinum-based chemotherapy., Methods: 74 patients with EOC (stage I-IV) who underwent cytoreductive surgery followed by standard paclitaxel/platinum chemotherapy were included in the retrospective analysis. Their formalin-fixed, paraffin-embedded tissue specimens were immunohistochemically stained for Tau protein, using semi-quantitative DAKO test. Tau expression was acknowledged as negative (0 and 1+) or positive (2+ and 3+). The correlation between Tau expression, progression free survival (PFS) and overall survival (OS) was evaluated. Statistical analysis included Kaplan-Meyer estimator, long rank test, Mann Whitney test and Cox proportional hazards model., Results: 25.7% (19/74) and 74.3% (55/74) of the patients were classified as Tau-negative and Tau-positive, respectively. Median PFS was 28.7 months for Tau-negative group and 15.9 months for Tau-positive group (p = 0.0355). In the univariate analysis 3-year OS in Tau-negative and Tau-positive groups was 80.2% and 52.4%, respectively (p = 0.0198). Low expression of protein Tau was associated with better OS, whereas an advanced stage at diagnosis, suboptimal surgery, serous histological type and resistance to first line chemotherapy were each correlated with worse OS (p <0,05). In multivariate analysis only resistance to first line chemotherapy remained significant (HR 22.59; 95% CI, 8.71-58.55; p <0.0001)., Conclusions: Negative tau protein seems to be both good prognostic factor and a predictor of response to paclitaxel/platinum-based chemotherapy in EOC patients.