Validating a generic cancer consumer quality index in eight European countries, patient reported experiences and the influence of cultural differences.

BACKGROUND: Taking patient centeredness into account is important in healthcare. The European Cancer Consumer Quality Index (ECCQI) is a validated tool for international benchmarking of patient experiences and satisfaction. This study aimed to further validate the ECCQI in larger and more uniform groups of high volume tumours such as breast and prostate cancer. A second objective was the verification of the influence of cultural factors of the country to determine its possible use in international benchmarking. METHODS: Data from two survey studies in eight European countries were combined. Socio-demographic correlations were analysed with Kruskall-Wallis and Mann-Whitney tests. Cronbach's alpha was calculated to validate internal consistency. Influences of masculinity (MAS), power distance (PD) and uncertainty avoidance (UA) were determined by linear regression analysis in a general model and subgroup models. RESULTS: A total of 1322 surveys were included in the analysis (1093 breast- and 348 prostate cancer patients). Cronbach's alpha was good (α ≥ 0.7) or acceptable (0.5 ≤ α ≤ 0.7) in 8 out of 9 questionnaire categories, except in the category 'Safety' (α = 0.305). Overall ECCQI scores ranged from 22.1 to 25.1 between countries on a 1-35 scale (categories had a 1-4 scale). In certain subcategories such as 'Organisation' (range 2.2 vs 3.0) and 'Supervision & Support' (range 3.0 vs 3.8) a large difference was observed between countries. Differences in 'Overall opinion' were however small: mean scores of 3.7 vs 3.9, whereas median scores were all the maximum of 4.0. Power distance was positively associated with higher patient satisfaction scores whereas Uncertainty avoidance was negatively associated with these scores. Masculinity was only associated with patient satisfaction scores in lower educated patients. We found the highest impact of culture on overall scores in Hungary and Portugal and the lowest in Romania. CONCLUSIONS: The ECCQI shows high internal consistency in all categories except 'Safety'. Especially in separate categories and overall ECCQI scores the questionnaire showed discriminative value. This study showed a positive correlation of power distance and a negative correlation for uncertainty avoidance in some countries. When using the ECCQI for international benchmarking these two dimensions of culture should be taken into account.

[Current Recommendations for the Prevention and Treatment of Venous Thromboembolism in Cancer Patients]. / Aktuální doporucení pro prevenci a terapii venózní trombembolické nemoci u onkologicky nemocných.

About 20% of patients suffer from venous thromboembolism (VTE) during oncology disease. Active cancer, along with cancer therapy, increases the risk of VTE, especially in the first 6 months after diagnosis. Most often VTE accompanies haematological malignancies and CNS tumours, and gastrointestinal, breast, lung, ovary and uterine cancer. The presence of distant metastases, together with the implantation of a central venous catheter, increases the risk even more. A cancer patient also has a 2-5× higher risk of recurrence of VTE during anticoagulant therapy than patients without a malignancy, as well as a 2-6× higher risk of serious bleeding. Thromboembolic disease is also an independent prognostic factor for death in patients with malignant tumours. Management of VTE is a part of everyday oncological practice, and oncologists should be aware of the basic recommendations regarding individual medical procedures and the clinical situations that may occur in cancer patients. They should also be able to adequately treat VTE when it occurs. It is necessary to consider some specificity during prophylaxis, diagnostics and treatment of venous thromboembolism in cancer care. The International Initiative on Thrombosis and Cancer (ITAC-CME) has created a mobile application based on international guidelines for the prevention and treatment of venous thromboembolism. It is a simple schematic algorithm for making decisions, and it helps in choosing the best therapeutic strategy and supports the judicious and appropriate use of anticoagulants for prophylaxis and treatment of VTE in cancer patients. This text contains a summary of the recommendations applicable in routine clinical practice.Key words: venous thromboembolism - cancer - central venous catheter thrombosis - guidelines This work was supported by Czech Ministry of Health - RVO (MMCI, 00209805). The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 1. 8. 2016Accepted: 26. 10. 2016.

[Anticoagulation and Thrombembolism During Bevacizumab Treatment--To Be Careful or Fearful?]. / Antikoagulacní lécba a trombembolizmus pri lécbe bevacizumabem--opatrnost, ci obavy?

Inhibition of angiogenesis is a valid approach in today's medicine. Besides oncology, it is used in ophthalmology, as well. In oncology, angiogenesis inhibition has become a routine and accessible method. A combination of angiogenesis inhibition and other therapies, including anticoagulation and antiaggregation is common in many cases. Bevacizumab is the most used antiangiogenic agent and has been in use for the longest period of time. A concomitant administration of angiogenesis inhibitors and anticoagulation may be feared by oncologists. From the available literature it is obvious that concomitant administration of bevacizumab and anticoagulation is safe. Also, use of antiaggregation and bevacizumab is safe. The risk of venous and arterial thromboembolism is real during the treatment with bevacizumab. Therefore, concomitant anticoagulation is not only possible but also may be desirable.

[Metachronous lung metastases of mammary carcinoma, or dual malignancy? a surgeons and oncologists point of view case report]. / Metachronní plicní metastázy mamárního karcinomu nebo duplexní malignita? Pohled chirurga a onkologa kazuistika.

Synchronous and metachronous metastases significantly diminish the possibility of remission from cancer. Therefore, therapy needs to be highly effective and strictly individualised. The authors present a case report of a female patient after radical mastectomy due to breast cancer with incidental detection of peripheral lung carcinoid. The aim of the case report is to inform about current trends in primary lung carcinoid therapy through a surgeons and oncologists point of view.

Treatment of tobacco dependence in cancer patients - Recommendations of the Section of Supportive Treatment and Care and the Section of Preventive Oncology of the Czech Cancer Society of the Czech Medical Association of J. E. Purkyne, Working Group for t .

Smoking is a significant risk factor for the development of many cancers. In addition, after a cancer dia-gnosis, it also has an adverse effect on survival, the course and effectiveness of cancer treatment and quality of life, and increases the likelihood of a number of other complications. Treating tobacco dependence reduces the risk of their occurrence or the extent of their consequences. A working group of authors from professional groups (the Section of Supportive Treatment and Care and the Section of Preventive Oncology of the Czech Society of Oncology of the Czech Medical Association of J. E. Purkyne, the Society for the Treatment of Tobacco Dependence, Czech Nurses Association, Working Group for the Prevention and Treatment of Tobacco Dependence of the Czech Medical Association J. E. P. and the Society for Treatment of Tobacco Dependence) prepared a simple basic scheme of intervention in contact with smokers in routine practice based on recommendations of professional societies, outcomes of studies, scientific literature and proven practice. A smoke-free environment, the importance of zero exposure to tobacco smoke, smoking cessation recommendations for smokers, relapse prevention for ex-smokers and the offer of tobacco dependence treatment should be a natural part of cancer care at least in the form of a brief DIK (abbreviation for "question - intervention - contact" in the Czech language) intervention. It is important to record smoking status, including exposure to second-hand smoke, in all patients, and to empathically repeat interventions in smokers (active and passive), including relapse prevention. This ap-proach contributes to abstinence in cancer patients and thus to higher efficacy of cancer treatment, longer survival and reduction of other risks.

Barriers and supportive factors in engaging cancer patients in physical activity programmes - a literature review.

BACKGROUND: Regardless of cancer type or stage of treatment, physical activity (PA) has been shown to reduce the risk of cancer recurrence and death. It is associated with a range of positive effects on patients' physical and psychological well-being, particularly in the areas of aerobic fitness, fatigue, mental health and perceived overall quality of life. However, in current oncology practice, the combination of its indication with treatment is still relatively rare. At the same time, cancer patients' participation in regular physical activity is usually very low. However, as PA is an effective method to support cancer treatment and plays an important role in prevention, it is necessary to find effective strategies to involve patients more widely in physical activities. To this end, physical activity programmes organised directly by facilities providing comprehensive cancer care appear to be very suitable. PURPOSE: This literature review maps the main barriers and facilitators to cancer patients' participation in physical activity programmes. In particular, economic factors related to health policy, reflected in the availability of this type of supportive care for patients, the level of health literacy, the organization of PA programs, health care providers - both physicians and health care workers, social support and intrapsychic influences on the part of patients play a major role. Since the implementation of physical activity programmes into the existing cancer care system is a rather challenging process, the paper also deals with the possibilities of using the Health Belief Model. In the given context, this model allows the prediction and identification of barriers and supportive factors to patients' involvement in PA programs in order to maximize their effectiveness and adapt them to the needs of patients and, at the same time, to the capabilities of a specific medical facility.

Clinical impact of PAI 1 4G/5G gene polymorphism in colorectal carcinoma patients.

Plasminogen activator ihnibitor (PAI 1) belongs to the plasminogen activator system, which is part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumors. Its plasma level is normally low but 4G/4G homozygotes have higher concentrations of PAI 1. This genotype may be associated with worse prognosis and proximal location of colorectal cancer than 5G/5G homozygotes. In our prospective evaluation we examined plasma level PAI 1 (using photometric microplate method ELISA) pre-surgery and, subsequently, 6-8 weeks later, from 80 patients. For the PAI 1 rs1799889 -675 4G/5G polymorphism test the PCR amplification was used.Analysis of collected data was confirmed that significantly higher plasma levels of PAI 1 were found in patients before starting therapy, which decreased (p=0.004) after initiation of treatment. Patients with higher plasma level PAI 1 before (p=0.013) and after therapy (p=0.004) had significantly shorter survival. We found no relationship between polymorphisms of PAI 1 (-675 4G/5G) in relation to stage, survival or tumor location. PAI 1 is useful as a negative marker of prognosis and could be advantageous when planning adjuvant treatment of patients with colorectal carcinoma. Although opinions on the importance of polymorphisms of PAI 1 in relation to the prognosis are not uniform, it does seem that their role in the prognosis of patients with colorectal cancer is not essential.

[The current approach to the treatment of the patients with metastatic colorectal cancer]. / Soucasný prístup k lécbe pacientu s metastatickým kolorektálním karcinomem.

Colorectal cancer is one of the most common malignant tumors. Despite the constant promotion of prevention remains around 20- 30% of cases dia-gnosed in the metastatic stage and approximately 50- 60% of patients developed the late dissemination. In 80- 90% of them we can find already unresectable metastases. Although surgical treatment is basic modality of therapy, with using mo-dern targeted therapy in combination with chemotherapy we can achieve longterm complete remission in the cases of advanced tumor and we can significantly prolonged the life of patients with this disease now. About 40- 50% patients in advanced stages who underwent metastasectomy survives 5-years and 10year survival rate is up to 25%. When administered systemic treatment median overall survival in these cases reaches around 24 months.

[Malignant melanoma treated with radical chemotherapy, resemblance histology of melanoma to soft tissue sarcomas, case report]. / Maligní melanom lécený intenzivní chemoterapií, podobnost histologického obrazu maligního melanomu a nádoru mekkých tkání, kazuistika pacientky.

BACKGROUND: Malignant melanoma is considered to be highly resistant to chemotherapy, radiotherapy, hormonotherapy and standard immunotherapy (interleukin 2, interferon alpha). Radical surgery in the early stages of the disease is still the most efficient method. Since the development of immunotherapy and targeted therapy, the role of palliative chemotherapy for advanced disease may be changing. CASE: A case report regarding 44-year-old woman with extensive tumor of the pectoral wall with contralateral axillary lymphadenopathy is presented. On the basis of imaging methods, histology and immunohistochemistry, the tumor was defined as a sarcoma. Due to PAX7-FKHR fusion gene positivity, rhabdomyosarcoma was the most probable classification. The patient was treated with radical chemotherapy including iphosphamide, vincristine, actinomycin D and doxorubicin with the effect of partial regression of the tumor. This enabled radical surgery of the chest wall tumor. Pathology proved 70% necrosis of the tumor. A contralateral axillary dissection was performed with a finding of two lymph nodes infiltrated with melanoma. The immunohistochemistry markers S100, HMB-45 and Melan A were positive. This resulted in a reclassification of the chest wall tumor to malignant melanoma. The following PET/CT scan was negative. A massive progression of the disease occurred after 5 months. B-RAF mutation leads to a plan of targeted therapy with vemurafenib. CONCLUSION: The case demonstrates the limits of the sensitivity and specificity of immunohistochemical markers of melanoma and the ability of this tumor to imitate various tumors including soft tissue sarcomas. A rare -PAX7-FKHR fusion gene positivity considered specific for rhabdomyosarcoma was found. An extraordinary response to radical chemotherapy with surgical resection led to an improvement of the quality of life and to a prolonged survival comparable with the effect of new targeted treatment for malignant melanoma.

[Significance of urokinase and its inhibitors in the invasiveness and metastasing of malignant tumors]. / Význam urokinázy a jejích inhibitoru pro invazi a metastazování zhoubných nádoru

Fibrinolysis is process, which leads to the degradation of fibrin to fibrin monomers. Fibrinolysis helps to regulate hemostasis and prevents the creation of inappropriately large thrombus, which could reduce blood flow to the bloodstream. The main enzyme involved in fibrinolysis is plasmin. Tissue plasminogen activator (tPA) and urokinase (uPA) are agents converting plasminogen into active plasmin, together with urokinase receptor (uPAR) and urokinase inhibitors (PAI 1, PAI 2, PAI 3 and protease nexin) form plasminogen activator system (PAS) which is among others also part of the metastatic cascade and significantly contributes to invasive growth and angiogenesis of malignant tumours. In contrast to tPA that is fundamental in fibrinolysis, uPA plays an essential role in tissue degradation as part of physiological and pathological processes. uPAR is a GPI (glycosylphosphatidylinositol)-anchored protein. The binding of uPA to uPAR results in activation of protein tyrosine kinase, protein kinase C and MAP kinase. At the same time, direct signalling pathway via Jak/STAT cascade utilising signalling transduction of Scr-like protein tyrosine kinase have also been described. uPAR expression is regulated by many growth factors, e.g. EGF, FGF-2 and HGF. It seems that individual PAS factors are involved in the process of rendering malignant tumors invasive. To what degree this influence is essential to specific malignancies, should be answered by further research. In the article the authors present a summary of findings about the interaction of fibrinolysis and tumor process, especially on the effects of urokinase and other activators and their inhibitors in metastasis of malignant tumors. The text contains information on the factors theirs introduction into practice is still the subject of numerous discussions, but in the future, individual PAS factors could play an important role in planning treatment strategies and also could become targets of targeted therapy.

Changes of serum protein N-glycosylation in cancer.

BACKGROUND: Glycosylation is a posttranslational modification responsible for many bio-logical processes including protein-protein interactions, cell signaling or cell cycle regulation. Changes in glycosylation of serum proteins reflects the status of tissues and cells in the organism and therefore can be used as markers for dia-gnosis of cancer, its progression and determination of its subtypes. N-glycan profiling is often used for characterization of N-glycosylation changes. It is based on the measurements of N-glycans released from the serum proteins. Beside the N-glycan profiling, glycoproteomic approach is emerging as it preserves the information about glycan composition, original protein, and its glycosylation sites. PURPOSE: This review covers existing works describing the changes in serum protein N-glycosylation in various cancer types. Attention was paid to both the glycomic and glycoproteomic approaches. The last part of the review shortly presents the analytical methods used for these analyses.

Acupuncture from the perspective of evidence-based medicine - options of clinical use based on National Comprehensive Cancer Network (NCCN) guidelines.

BACKGROUND: Acupuncture is one of the oldest therapeutic methods. The traditional view of acupuncture is represented by influencing energy pathways through stimulation of specific points. The original meridian theory, which works with the assumption of normalization of the flowing energy Qi in the organism is, with increasing evidence, supplemented with information about the bio-logical impact of the use of acupuncture from the perspective of Western medicine. Specific stimulation of particular points on the body leads to the activation of hypothalamus and pituitary gland through neurotransmitters, resulting in a wide range of systemic effects. Stimulation of nerves in the muscle, which then trans-mits a signal to the spinal cord, midbrain, and hypothalamic-pituitary system, releases neurotransmitters, endogenous opioid peptides, or hormones. Stimulation of acupuncture points changes the levels of proinflammatory cytokines, including IL-1-beta, IL-6, IL-17, and TNF-alpha. Currently, according to the National Comprehensive Cancer Network (NCCN) guidelines, the following symptoms are indicated for acupuncture treatment: pain including neuropathic pain, arthralgia, and myalgia, especially in the aromatase inhibitors therapy, nausea, and vomiting, fatigue, vasomotor symptoms in women and vasomotor symptoms in men caused by androgen deprivation therapy. Acupuncture seems to be an effective and safe treatment method for many of the cancer symptoms or the side effects of cancer treatment, but, like any other treatment method, it has its indications and contraindications. PURPOSE: This work aims to provide a comprehensive overview of the use of acupuncture in defined indications, according to current international guidelines. Thus, the therapeutic possibilities of symptomatic treatment of cancer and therapy of adverse events of oncological treatment can be extended.

Clinical significance of the plasminogen activator system in relation to grade of tumor and treatment response in colorectal carcinoma patients.

Urokinase (uPA) plays an essential role in the activation of plasminogen to plasmin, and together with its receptor (uPAR), tissue activator (tPA) and urokinase inhibitors (PAI 1, PAI 2, PAI 3 and protease nexin) forms the plasminogen activator system (PAS), a component of metastatic cascade importantly contributing to the invasive growth and angiogenesis of malignant tumours. In our project we examined the expression of uPA, uPAR, PAI 1 and PAI 2 in tumor tissue and we also studied the plasma levels of PAI 1 before and after the initiation of therapy in patients with colorectal carcinoma in relationship to grade of tumor and the treatment response. In our prospective evaluation we included 80 patients treated for adenocarcinoma of the colon and rectum. Analysis of collected data revealed statistically significant evidence of a relationship between the level of PAI 1 in plasma before treatment and grade of the tumor, which increases with tumor grade (p=0.025). We demonstrated that there exists a statistically significant relationship between the expression of PAI 2 (p<0.001) and uPAR (p=0.031) and grade of tumor. We also confirmed a statistically significant relationship between soluble levels of PAI 1 before treatment and therapeutic response (p=0.021). In our group of patients the expression of uPA, uPAR, PAI 1 and 2 in tumor tissue in relation to response to treatment was also assessed. Our results suggest that the greater expression of these parameters in tumor tissue is linked to a worse response to therapy. In conclusion, PAS factors help as a prognostic indicators and could also act as a predictive factor in colorectal carcinoma.

[Plasminogen activator system and its clinical significance in patients with a malignant disease]. / Plazminogen aktivátor systém a jeho klinický význam u pacientu s nádorovým onemocnením.

Urokinase (uPA) plays an essential role in the activation of plasminogen to plasmin, a serine protease participating in the activation of matrixmetaloproteinases, latent elastases, growth factors and cytokines involved in the degradation of extracellular matrix elements. Together with its receptor (uPAR), tissue activator (tPA) and urokinase inhibitors (PAI-1, PAI-2, PAI-3 and protease nexin), it forms the plasminogen activator system (PAS), a component of metastatic cascade importantly contributing to the invasive growth and angiogenesis of malignant tumours. Plasminogen activator inhibitor 1 inhibits uPA-dependent invasiveness of some cancer cell lines. The vitronectin-PAI-1 complex inhibits migration of smooth muscle cells by binding alpha(v)beta3 integrin to vitronectin. PAI-1 or its deficiency interferes with signalling pathways such as PI3K/Akt and JAK/STAT and it is included in the processes of maintaining the integrity of the endothelial cells and thereby regulation of cell death. PAI-1 affects apoptosis by reducing cell adhesion and functioning of intracellular signalling pathways. The individual components of PAS undoubtedly play an important role in angiogenesis and metastasising of malignant tumours. In the near future, results of published studies with various types of cancer could be reflected in diagnostic and therapeutic algorithms and, at the same time, could serve as the goal for targeted therapies.

Anisocoria as a side effect of paclitaxel treatment.

BACKGROUND: Paclitaxel is one of the most common cytostatics used in oncology; it is part of the therapeutic protocols of many malignancies. One of its most common side effects is peripheral neuropathy. This symptomatology often leads to a reduction in the dose intensity of chemotherapeutic drugs or to early discontinuation of the treatment. CASE: In our case report, we describe a rare case of paclitaxel-induced anisocoria in a young woman with breast cancer. CONCLUSION: Ocular side effects related to taxanes are rare, with an estimated frequency of about 1%. In addition to relatively frequent obstruction of the nasolacrimal duct, the cystoid macular edema or ischemic retinopathy have been reported. However, in most cases paclitaxel-induced ocular side effects, there is no need to reduce or discontinue therapy. However, the collaboration of an oncologist with an experienced and trained ophthalmologist is essential.

Bile duct malignancies.

Bile duct malignancies include intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), gall bladder carcinoma (GC) and carcinoma of Vater's ampulla (ampulloma). Bile duct neoplasms are rare tumours with overall poor prognosis. The overall incidence affects up to 12.5 per 100,000 persons in the Czech Republic. The mortality rate has risen recently to 9.5 per 100,000 persons. The incidence and mortality have been remarkably stable over the past 3 decades. The survival rate of patients with these tumours is poor, usually not exceeding 12 months. The diagnostic process is complex, uneasy and usually late. Most cases are diagnosed when unresectable, and palliative treatment is the main approach of medical care for these tumours. The treatment remains very challenging. New approaches have not brought much improvement in this field. Standards of palliative care are lacking and quality of life assessments are surprisingly not common. From the scarce data it seems, however, that multimodal individually tailored treatment can prolong patients'survival and improve the health-related quality of life. The care in specialized centres offers methods of surgery, interventional radiology, clinical oncology and high quality supportive care. These methods are discussed in the article in greater detail. Improvements in this field can be sought in new diagnostic methods and new procedures in surgery and interventional radiology. Understanding the tumour biology on the molecular level could shift the strategy to a more successful one, resulting in more cured patients. Further improvements in palliative care can be sought by defining new targets and new drug development. The lack of patients with bile duct neoplasms has been the limiting factor for any improvements. A new design of larger randomized international multicentric clinical trials with prompt data sharing could help to overcome this major problem. Defining standards of palliative care is a necessity. Addressing health-related quality of life could help to assess the real benefit of palliative treatment.

Do polymorphisms and haplotypes of mismatch repair genes modulate risk of sporadic colorectal cancer?

The Czech Republic presents one of the highest incidences of colorectal cancer in the world. We genotyped 10 single nucleotide polymorphisms in five DNA mismatch repair genes in 614 colorectal cancer cases and 614 matched controls from this country. The carriers of T-allele of the hMSH6-556G>T polymorphism were at increased risk of colorectal cancer (OR 1.29; 95% CI 1.02-1.62). The stratification of data showed that risk associated with the polymorphism was confined to rectal cancer (OR 1.42; 95% CI 1.03-1.95). The A-allele of the Ex1-145G>A polymorphism in the hMSH6 gene was associated with a decreased risk of colorectal cancer (OR 0.76; 95% CI 0.60-0.98). The C-allele of the IVS4-101G>C polymorphism in hMSH6 was associated with an increased risk of colon cancer (OR 1.34; 95% CI 1.03-1.74). The carriers of the variant allele for the polymorphism IVS9-1406C>T in hMLH1 exhibited a decreased risk of rectal cancer (OR 0.71; 95% CI 0.51-0.98). We observed a differential distribution of haplotypes based on three hMSH6 polymorphisms (-556G>T-Ex1-145G>A-IVS4-101G>C) in the cases and controls (global P=0.02). The TAG haplotype was associated with a decreased risk of colorectal cancer (OR 0.74; 95% CI 0.59-0.92), whereas the most frequent haplotype GGG was associated with increased risk of rectal cancer (OR 1.32; 95% CI 1.05-1.65). However, multiple hypotheses testing diminishes a statistical significance of above associations. Our data suggest a limited role for the investigated individual variants in mismatch repair genes for the susceptibility to the disease. The haplotypes covering hMSH6 gene may, however, be involved in risk modulation in this population.

[Systemic and paraneoplastic manifestations of malignant diseases]. / Systémové a paraneoplastické projevy maligních onemocnení.

Timely diagnosis of malignant diseases largely depends on attention being given to early symptoms and on timely start of an extensive diagnostic process. Only this way can a tumour be diagnosed in its initial stage, and better effect of therapy can be achieved. The following overview provides a list of systemic (paraneoplastic - distant) manifestations of a tumour, and of symptoms related to local tumour expansion. The objective of the overview is to draw attention to all early symptoms of malignant diseases in patients, and to contribute to timely diagnosis and treatment.

MicroRNAs as outcome predictors in patients with metastatic colorectal cancer treated with bevacizumab in combination with FOLFOX.

Bevacizumab is a humanized anti-vascular endothelial growth factor monoclonal antibody, used in combination with a oxaliplatin-based chemotherapy in the treatment of metastatic colorectal cancer (mCRC). The aim of the present study was to identify microRNA (miRNA)-based predictive biomarkers of therapy response in order to avoid unnecessary and costly therapy to non-responding patients. High-throughput miRNA microarray profiling (Affymetrix miRNA array) was performed on a discovery cohort of patients with mCRC. The discovery cohort was (n=20) divided into either responding (n=10) or non-responding (n=10) groups of bevacizumab/5-flourouracil, leucovorin, oxaliplatin (FOLFOX) treatment according to Response Evaluation Criteria in Solid Tumors criteria. Validation of candidate miRNAs was performed on an independent cohort of 41 patients with mCRC using quantitative reverse transcription polymerase chain reaction. Normalized data were subjected to receiver operating characteristic and Kaplan-Meier analyses. In total, 67 miRNAs were identified to be differentially expressed when miRNA expression was compared between responding and non-responding patients to bevacizumab/FOLFOX treatment (P<0.05). A total of 7 miRNAs were chosen for independent validation, which confirmed significantly higher expression of miR-92b-3p, miR-3156-5p, miR-10a-5p and miR-125a-5p (P<0.005) in tumor tissue of responding patients compared with non-reponding patients. Using the combination of miRNAs, the present study identified responders to the therapy with sensitivity 82% and specificity 64% (area under the curve = 0.8015). In conclusion, 4 predictive miRNAs associated with progression-free survival (PFS) were identified in patients with mCRC treated with bevacizumab/FOLFOX. Following further independent validations, detection of these miRNA may enable identification of patients with mCRC who may potentially benefit from the therapy.