Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma.

Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.

Insights into the therapeutic outcomes of trimetazidine/doxorubicin combination in Ehrlich solid-phase carcinoma mouse tumor model.

One of the key features of cancer is metabolic reprogramming that can be exploited to sensitize cancer cells to chemotherapy. Trimetazidine (TMZ) is a metabolic anti-ischemic drug that blocks the activity of long-chain 3-ketoacyl CoA thiolase leading to the inhibition of fatty acid oxidation. AIMS: The objective of the current investigation was to evaluate the idea that TMZ could synergize the antitumor activity of doxorubicin (DOX). MAIN METHODS: The hypothesis was examined in vitro using the human breast cancer cell lines MCF-7 and MDA-MB231. In addition, the in vivo experiments were conducted using the Ehrlich solid phase carcinoma model. KEY FINDINGS: In vitro cytotoxicity experiments demonstrated that TMZ improved the potency of DOX in MCF-7 cell lines in a synergistic manner. In vivo testing confirmed that DOX/TMZ combination exhibits synergistic effect at both DOX/TMZ 1:10 and 1:5 ratios, where DOX was administered at one tenth and one fifth of its original dose, respectively. The co-treatment (1:5 ratio) significantly reduced tumor Nicotinamide adenine dinucleotide (NAD)+/NADH ratio (6.1-fold) and Adenosine triphosphate (ATP) levels (61 %) with concurrent activation of AMP-activated protein kinase (AMPK) (2.2-fold) and peroxisome proliferator-activated receptor-gamma coactivator (PGC)1-α (5.5-fold) protein expression versus control. The same treatment decreased the nuclear levels of NF-κB (p65) (57.5 %) and induced tumor apoptosis as evidenced by elevated Bax/Bcl-2 ratio (6.8-fold) along with active caspase-3 levels (6.6-fold) against control. SIGNIFICANCE: The current investigation constitutes a proof-of-concept study that provided preclinical evidence for the anticancer activity of DOX/TMZ combination and warrants further investigation for repurposing TMZ in DOX protocols.

Optimizing treatment selection and sequencing decisions for first-line maintenance therapy of newly diagnosed advanced ovarian cancer.

The incidence and mortality rates of ovarian cancer are increasing globally. Ovarian cancer is diagnosed at an advanced stage in 80% of women. After standard, platinum-based, front-line chemotherapy, poly (ADP-ribose) polymerase (PARP) inhibitors and antiangiogenic agents are successfully employed as maintenance strategies for newly diagnosed, advanced ovarian cancer patients. Landmark clinical studies, including SOLO-1, PAOLA-1, PRIMA, and VELIA, have provided crucial insights on optimizing first-line maintenance treatment using PARP inhibitors. A group of ovarian cancer experts, primarily from low- and middle-income countries, met in September 2019 to discuss new developments for the first-line treatment of ovarian cancer and its implications. Key implications of the evolving clinical data included: (1) olaparib or niraparib maintenance therapy appears to be the preferred choice for patients with BRCA1/2 mutations; hence, BRCA testing is beneficial in identifying these patients; (2) niraparib monotherapy and olaparib in combination with bevacizumab have demonstrated significant benefit in progression-free survival (PFS) in homologous recombination deficiency (HRD)-positive patients; (3) bevacizumab, niraparib alone, or observation can be an alternative for HRD-negative patients; (4) further data is warranted to explore the role of PARP inhibitors in treating HRD-negative, ovarian cancer patients to confirm findings of the exploratory analysis of PRIMA; (5) PARP inhibitors may be beneficial for stage IV ovarian cancer patients with inoperable disease and patients with prior neoadjuvant chemotherapy; and (6) there is an urgent need to increase awareness in both clinicians and patients on BRCA and HRD testing for optimizing treatment decision-making and improving clinical outcomes in newly diagnosed, advanced ovarian cancer patients. In clinical medicine, the limited availability of family history (FH) information and the complexity of FH criteria has hampered the implementation of BRCA testing. Moreover, many cancer patients with BRCA mutations are not tested because they do not meet the criteria for FH. Consequently, BRCA testing in many high income countries, including the US and Australia, is underused and used inappropriately, which has resulted in the loss of valuable opportunities for better cancer management and cancer prevention.

Identifying SARS-CoV-2 Lineage Mutation Hallmarks and Correlating Them With Clinical Outcomes in Egypt: A Pilot Study.

The SARS-CoV-2 pandemic has led to over 4.9 million deaths as of October 2021. One of the main challenges of creating vaccines, treatment, or diagnostic tools for the virus is its mutations and emerging variants. A couple of variants were declared as more virulent and infectious than others. Some approaches were used as nomenclature for SARS-CoV-2 variants and lineages. One of the most used is the Pangolin nomenclature. In our study, we enrolled 35 confirmed SARS-CoV-2 patients and sequenced the viral RNA in their samples. We also aimed to highlight the hallmark mutations in the most frequent lineage. We identified a seven-mutation signature for the SARS-CoV-2 C36 lineage, detected in 56 countries and an emerging lineage in Egypt. In addition, we identified one mutation which was highly negatively correlated with the lineage. On the other hand, we found no significant correlation between our clinical outcomes and the C36 lineage. In conclusion, the C36 lineage is an emerging SARS-CoV-2 variant that needs more investigation regarding its clinical outcomes compared to other strains. Our study paves the way for easier diagnosis of variants of concern using mutation signatures.

Impact of circ-0000221 in the Pathogenesis of Hepatocellular via Modulation of miR-661-PTPN11 mRNA Axis.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death in Egypt. A deep understanding of the molecular events occurring in HCC can facilitate the development of novel diagnostic and/or therapeutic approaches. In the present study, we describe a novel axis of hsa-circ-0000221-miR-661-PTPN11 mRNA proposed by in silico and in vitro analysis and its role in HCC pathogenesis. We observe a reduction in the expression levels of hsa-circ-0000221 and PTPN11 mRNA in HCC patients' sera tested compared with control subjects. The reduction occurs with a concomitant increase in the expression of miR-661. Furthermore, the introduction of exogenous hsa-circ-0000221 into Hep-G2 or SNU449 cell lines results in detectable decrease in cellular viability and an increase in apoptotic manifestations that is associated with G1 accumulation and CCDN1 overexpression. Altogether, these findings indicate the tumor-suppressive role of hsa-circ-0000221 in HCC, which acts through miR-661 inhibition, along with a subsequent PTPN11 mRNA increase, where PTPN11 is known to inhibit cell proliferation in many forms of cancer. Our study encourages further investigation of the role of circRNAs in cancer and their potential use as molecular biomarkers.

In Silico Identification and Clinical Validation of a Novel Long Non-Coding RNA/mRNA/miRNA Molecular Network for Potential Biomarkers for Discriminating SARS CoV-2 Infection Severity.

(1) Background: The coronavirus (COVID-19) pandemic is still a major global health problem, despite the development of several vaccines and diagnostic assays. Moreover, the broad symptoms, from none to severe pneumonia, and the various responses to vaccines and the assays, make infection control challenging. Therefore, there is an urgent need to develop non-invasive biomarkers to quickly determine the infection severity. Circulating RNAs have been proven to be potential biomarkers for a variety of diseases, including infectious ones. This study aimed to develop a genetic network related to cytokines, with clinical validation for early infection severity prediction. (2) Methods: Extensive analyses of in silico data have established a novel IL11RA molecular network (IL11RNA mRNA, LncRNAs RP11-773H22.4 and hsa-miR-4257). We used different databases to confirm its validity. The differential expression within the retrieved network was clinically validated using quantitative RT-PCR, along with routine assessment diagnostic markers (CRP, LDH, D-dimmer, procalcitonin, Ferritin), in100 infected subjects (mild and severe cases) and 100 healthy volunteers. (3) Results: IL11RNA mRNA and LncRNA RP11-773H22.4, and the IL11RA protein, were significantly upregulated, and there was concomitant downregulation of hsa-miR-4257, in infected patients, compared to the healthy controls, in concordance with the infection severity. (4) Conclusion: The in-silico data and clinical validation led to the identification of a potential RNA/protein signature network for novel predictive biomarkers, which is in agreement with ferritin and procalcitonin for determination of COVID-19 severity.

ABHD4-Regulating RNA Panel: Novel Biomarkers in Acute Coronary Syndrome Diagnosis.

BACKGROUND: Acute coronary syndrome (ACS) is a major cause of death all over the world. STEMI represents a type of myocardial infarction with acute ST elevation. We aimed to assess the predictive power of potential RNA panel expression in acute coronary syndrome. METHOD: We used in silico data analysis to retrieve RNAs related to glycerophospholipid metabolism dysregulation and specific to ACS that results in the selection of Alpha/Beta hydrolase fold domain4 (ABHD4) mRNA and its epigenetic regulators (Foxf1 adjacent noncoding developmental regulatory RNA (FENDRR) lncRNA, miRNA-221, and miRNA-197). We assessed the expression of the serum RNA panel in 68 patients with ACS, 21 patients with chest pain due to non-cardiac causes, and 21 healthy volunteers by quantitative real-time polymerase chain reaction. RESULTS: The study data showed significant down regulation in the expression of the serum levels of FENDRR lncRNA and miRNA-221-3p by 120-fold and 22-fold in Unstable angina (UA) in comparison with healthy volunteers, and by 8.6-fold and 2-fold in ST segment elevation myocardial infarction (STEMI) patients versus UA; concomitant upregulation in the expression of ABHD4 mRNA and miRNA-197-5p by 444-fold and 10-fold in UA compared with healthy volunteers, and by 1.54-fold and 4.5-fold in STEMI versus unstable angina. Performance characteristics analysis showed that the ABHD4-regulating RNA panel were potential biomarkers for prediction of ACS. Moreover, there was a significant association between the 2 miRNAs and ABHD4 mRNA and the regulating FENDRR lncRNA. CONCLUSION: Collectively, ABHD4 mRNA regulating RNA panel based on putative interactions seems to be novel non-invasive biomarkers that could detect ACS early and stratify severity of the condition that could improve health outcome.

Association between Interferon-Lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 Variant Polymorphisms with the Course and Outcome of SARS-CoV-2 Patients.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection provides a critical host-immunological challenge. AIM: We explore the effect of host-genetic variation in interferon-lambda-3 rs12979860, Tolloid Like-1 (TLL1) rs17047200 and Discoidin domain receptor 1(DDR1) rs4618569 on host response to respiratory viral infections and disease severity that may probe the mechanistic approach of allelic variation in virus-induced inflammatory responses. METHODS: 141 COVID-19 positive patients and 100 healthy controls were tested for interferon-lambda-3 rs12979860, TLL1 rs17047200 and DDR1 rs4618569 polymorphism by TaqMan probe-based genotyping. Different genotypes were assessed regarding the COVID-19 severity and prognosis. RESULTS: There were statistically significant differences between the studied cases and control group with regard to the presence of comorbidities, total leucocytic count, lymphocytic count, CRP, serum LDH, ferritin and D-dimer (p < 0.01). The CC genotype of rs12979860 cytokine, the AA genotype of TLL1 rs17047200 and the AA genotype of the rs4618569 variant of DDR1 showed a higher incidence of COVID-19 compared to the others. There were significant differences between the rs4618569 variant of DDR and the outcome of the disease, with the highest mortality in AG genotype 29 (60.4%) in comparison to 16 (33.3%) and 3 (6.2%) in the AA and GG genotypes, respectively (p = 0.007*), suggesting that the A allele is associated with a poor outcome in the disease. CONCLUSION: Among people who carry C and A alleles of SNPs IFN-λ rs12979860 and TLL1 rs17047200, respectively, the AG genotype of the DDR1 rs4618569 variant is correlated with a COVID-19 poor outcome. In those patients, the use of anti-IFN-λ 3, TLL1 and DDR1 therapy may be promising for personalized translational clinical practice.

Breast-Gynaecological & Immuno-Oncology International Cancer Conference (BGICC) Consensus and Recommendations for the Management of Triple-Negative Breast Cancer.

Background: The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. Methods: A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when ≥75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. Results and conclusion: These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.

Breast-Gynaecological & Immuno-Oncology International Cancer Conference (BGICC) Consensus and Recommendations for the Management of Triple-Negative Breast Cancer

The management of patients with triple-negative breast cancer (TNBC) is challenging with several controversies and unmet needs. During the 12th Breast-Gynaecological & Immuno-oncology International Cancer Conference (BGICC) Egypt, 2020, a panel of 35 breast cancer experts from 13 countries voted on consensus guidelines for the clinical management of TNBC. The consensus was subsequently updated based on the most recent data evolved lately. Methods: A consensus conference approach adapted from the American Society of Clinical Oncology (ASCO) was utilized. The panellists voted anonymously on each question, and a consensus was achieved when ≥75% of voters selected an answer. The final consensus was later circulated to the panellists for critical revision of important intellectual content. Results and conclusion: These recommendations represent the available clinical evidence and expert opinion when evidence is scarce. The percentage of the consensus votes, levels of evidence and grades of recommendation are presented for each statement. The consensus covered all the aspects of TNBC management starting from defining TNBC to the management of metastatic disease and highlighted the rapidly evolving landscape in this field. Consensus was reached in 70% of the statements (35/50). In addition, areas of warranted research were identified to guide future prospective clinical trials.

Safety and efficacy of favipiravir versus hydroxychloroquine in management of COVID-19: A randomised controlled trial.

Favipiravir is considered a potential treatment for COVID-19 due its efficacy against different viral infections. We aimed to explore the safety and efficacy of favipiravir in treatment of COVID-19 mild and moderate cases. It was randomized-controlled open-label interventional phase 3 clinical trial [NCT04349241]. 100 patients were recruited from 18th April till 18th May. 50 patients received favipiravir 3200 mg at day 1 followed by 600 mg twice (day 2-day 10). 50 patients received hydroxychloroquine 800 mg at day 1 followed by 200 mg twice (day 2-10) and oral oseltamivir 75 mg/12 h/day for 10 days. Patients were enrolled from Ain Shams University Hospital and Assiut University Hospital. Both arms were comparable as regards demographic characteristics and comorbidities. The average onset of SARS-CoV-2 PCR negativity was 8.1 and 8.3 days in HCQ-arm and favipiravir-arm respectively. 55.1% of those on HCQ-arm turned PCR negative at/or before 7th day from diagnosis compared to 48% in favipiravir-arm (p = 0.7). 4 patients in FVP arm developed transient transaminitis on the other hand heartburn and nausea were reported in about 20 patients in HCQ-arm. Only one patient in HCQ-arm died after developing acute myocarditis resulted in acute heart failure. Favipiravir is a safe effective alternative for hydroxychloroquine in mild or moderate COVID-19 infected patients.

Insulin-like growth factor 1/Child-Turcotte-Pugh composite score as a predictor of treatment outcomes in patients with advanced hepatocellular carcinoma treated with sorafenib.

BACKGROUND: Sorafenib was the first systemic therapy approved for the treatment of Child-Turcotte-Pugh (CTP) class A patients with advanced hepatocellular carcinoma (HCC). However, there are no biomarkers to predict survival and treatment outcomes and guide HCC systemic therapy. Type 1 insulin-like growth factor (IGF-1)/CTP composite score has emerged as a potential hepatic reserve assessment tool. Our study investigated the association of the IGF/CTP score with overall survival (OS) and progression-free survival (PFS) of HCC patients treated with sorafenib. MATERIALS AND METHODS: In this prospective study, patients with HCC were treated with sorafenib and followed up until progression/death. We calculated the IGF/CTP score and used the Kaplan-Meier method and log-rank test to estimate and compare the time-to-event outcomes between patient subgroups. RESULTS: 171 patients were included, 116 of whom were CTP class A. Median PFS for IGF/CTP score AA and AB patients were 6.88 and 4.28 months, respectively (p = 0.1359). Median OS for IGF/CTP score AA and AB patients were 14.54 and 7.60 months, respectively (p = 0.1378). The PFS and OS was superior in AA patients, but the difference was not significant, likely due to the sample size. However, there was a significant difference in early OS and PFS curves between AA and AB (p = 0.0383 and p = 0.0099), respectively. CONCLUSIONS: In CTP class A patients, IGF/CTP score B was associated with shorter PFS and OS, however, study was underpowered to reach statistical significance. If validated in larger cohorts, IGF/CTP score may serve as stratification tool in clinical trials, a hepatic reserve assessment tool for HCC outcomes prediction and to assist in therapy decisions.

The first BGICC consensus and recommendations for breast cancer awareness, early detection and risk reduction in low- and middle-income countries and the MENA region.

In low-middle income countries (LMICs) and the Middle East and North Africa (MENA) region, there is an unmet need to establish and improve breast cancer (BC) awareness, early diagnosis and risk reduction programs. During the 12th Breast, Gynecological & Immuno-oncology International Cancer Conference - Egypt 2020, 26 experts from 7 countries worldwide voted to establish the first consensus for BC awareness, early detection and risk reduction in LMICs/MENA region. The panel advised that there is an extreme necessity for a well-developed BC data registries and prospective clinical studies that address alternative modalities/modified BC screening programs in areas of limited resources. The most important recommendations of the panel were: (a) BC awareness campaigns should be promoted to public and all adult age groups; (b) early detection programs should combine geographically distributed mammographic facilities with clinical breast examination (CBE); (c) breast awareness should be encouraged; and (d) intensive surveillance and chemoprevention strategies should be fostered for high-risk women. The panel defined some areas for future clinical research, which included the role of CBE and breast self-examination as an alternative to radiological screening in areas of limited resources, the interval and methodology of BC surveillance in women with increased risk of BC and the use of low dose tamoxifen in BC risk reduction. In LMICs/MENA region, BC awareness and early detection campaigns should take into consideration the specific disease criteria and the socioeconomic status of the target population. The statements with no consensus reached should serve as potential catalyst for future clinical research.

Clinical recommendations in the management of advanced prostate cancer: International Gastrointestinal, Liver and Uro-oncology (IGILUC 2019) experts.

PURPOSE: Advancements in the diagnosis and treatment of prostate cancer (PC) have rapidly progressed through the past years. Various factors should be taken into account while treating individual patients to ensure optimal and careful decision making. The purpose of this consensus review is to summarize the current practice patterns when managing patients with advanced prostate cancer (APC) as there is still a lack of or very limited evidence on its clinical management in some areas. METHODS: Pre-defined questions were shared with experts prior to the consensus session that took place in Cairo, Egypt in April 2019 during the 8th International gastrointestinal, liver and uro-oncology conference (IGILUC). Voting was based mainly on the expert opinions of the panel after a thorough discussion and review of available evidence from guidelines or best evidence available concerning the topic at hand. RESULTS: A strong consensus or unanimity was reached on 47% of the proposed questions. Notably, the panelists reached consensus on several topics based on high-level expert opinion. These findings contribute in several ways to our understanding of the management of PC and provide a basis for future recommendations. There was also a lack of consensus on other several topics, which suggests the need for further supporting data addressing these knowledge gaps. CONCLUSION: This review offers a thorough understanding of APC practice and offers insight on the various opinions shared amongst experts in the field that can serve as guidance regionally and deepens our understanding of disease management globally.

Impact of Integrating Insulin-Like Growth Factor 1 Levels into Model for End-Stage Liver Disease Score for Survival Prediction in Hepatocellular Carcinoma Patients.

BACKGROUND: Liver reserve affects survival in hepatocellular carcinoma (HCC). Model for End-Stage Liver Disease (MELD) score is used to predict overall survival (OS) and to prioritize HCC patients on the transplantation waiting list, but more accurate models are needed. We hypothesized that integrating insulin-like growth factor 1 (IGF-1) levels into MELD score (MELD-IGF-1) improves OS prediction as compared to MELD. METHODS: We measured plasma IGF-1 levels in training (n = 310) and validation (n = 155) HCC cohorts and created MELD-IGF-1 score. Cox models were used to determine the association of MELD and MELD-IGF-1 with OS. Harrell's c-index was used to compare the predictive capacity. RESULTS: IGF-1 was significantly associated with OS in both cohorts. Patients with an IGF-1 level of ≤26 ng/mL in the training cohort and in the validation cohorts had significantly higher hazard ratios than patients with the same MELD but IGF-1 >26 ng/mL. In both cohorts, MELD-IGF-1 scores had higher c-indices (0.60 and 0.66) than MELD scores (0.58 and 0.60) (p < 0.001 in both cohorts). Overall, 26% of training and 52.9% of validation cohort patients were reclassified into different risk groups by MELD-IGF-1 (p < 0.001). CONCLUSIONS: After independent validation, the MELD-IGF-1 could be used to risk-stratify patients in clinical trials and for priority assignment for patients on liver transplantation waiting list.

Implementation of breast cancer continuum of care in low- and middle-income countries during the COVID-19 pandemic.

Breast cancer is the most common malignancy among women worldwide. The current COVID-19 pandemic represents an unprecedented challenge leading to care disruption, which is more severe in low- and middle-income countries (LMIC) due to existing economic obstacles. This review presents the global perspective and preparedness plans for breast cancer continuum of care amid the COVID-19 outbreak and discusses challenges faced by LMIC in implementing these strategies. Prioritization and triage of breast cancer patients in a multidisciplinary team setting are of paramount importance. Deescalation of systemic and radiation therapy can be utilized safely in selected clinical scenarios. The presence of a framework and resource-adapted recommendations exploiting available evidence-based data with judicious personalized use of current resources is essential for breast cancer care in LMIC during the COVID-19 pandemic.

MicroRNA-21 as a predictor and prognostic factor for trastuzumab therapy in human epidermal growth factor receptor 2-positive metastatic breast cancer.

Breast cancer is the second most common cancer diagnosed worldwide. Human epidermal growth factor receptor 2 (HER2)-positive breast cancer represents about 20% to 30% of all breast cancers. Trastuzumab is used in the treatment of HER2-positive breast cancer. MicroRNA-21 (miR-21) is an oncomiR that acts by inhibiting many tumor-suppressor genes. We analyzed the relative expression levels of serum miR-21 in 20 HER2-positive metastatic breast cancer patients before and after 3 months of treatment with trastuzumab. miR-21 levels decreased with a high significant difference after trastuzumab therapy (P = 0.001). Although miR-21 expression levels were lower in responders than in nonresponders, the difference was not statistically significant ( P = 0.6). Our results demonstrated a significant negative correlation between its basal expression, expression levels after treatment, and time to progression ( P = 0.03 and 0.01, respectively). These results make miR-21 a potential prognostic factor for HER2-positive metastatic breast cancer patients. Additionally, it can be an interesting potential target in therapy using antisense oligonucleotides for miR-21.

All-oral combination of vinorelbine and capecitabine as first-line treatment in HER2/Neu-negative metastatic breast cancer.

PURPOSE: To evaluate the efficacy and safety of an all-oral vinorelbine and capecitabine combination therapy in anthracycline- ± taxane-pretreated HER2/Neu-negative metastatic breast cancer (MBC). METHODS: A phase 2 trial including women >18 years with HER2/Neu-negative MBC previously exposed to anthracycline- ± taxane-based chemotherapy in the adjuvant or neoadjuvant setting. Enrolled patients received oral vinorelbine 60 mg/m(2) on days 1 and 8 and oral capecitabine 1,000 mg/m(2) twice daily on days 1-14 on a 3 weekly schedule. Patients with progressive disease after 3 cycles discontinued the study, while the remaining patients continued treatment for a maximum of 6 cycles. RESULTS: From January 2007 to March 2011, 30 patients were enrolled in this study (median age 47 years). In the 28 evaluable patients, the overall response rate was 57.1 % (95 % CI 30-67 %), including 3 complete (10.7 %) and 13 partial (46.4 %) responses. Six (21.4 %) patients suffered from disease progression. With a median follow-up time of 13 months, the median time to disease progression was 8.6 months (95 % CI 6.2-10.6 months) and the median survival time was 27.2 months. Treatment-related adverse events were manageable, and no World Health Organization grade 4 toxicities were noted. Neutropenia observed in 6 (21.4 %) patients was the main grade 3 toxicity. Grade 3 nausea and vomiting were reported in 2 (7.1 %) and 3 (10.7 %) patients, respectively. Two (7.1 %) patients developed grade 3 hand and foot syndrome. CONCLUSION: These results show that the combination of oral vinorelbine and capecitabine is an effective and well-tolerated first-line regimen for HER2/Neu-negative MBC patients pretreated with anthracyclines ± taxanes.

Treatment of diffuse pigmented villonodular synovitis of the knee with combined surgical and radiosynovectomy.

Treatment of extensive diffuse pigmented villonodular synovitis (PVNS) of large joints by isolated surgical resection is unsatisfactory, with high rates of local recurrence. Post-synovectomy adjuvant treatment with external beam radiation therapy or intra-articular injection of radioactive material as yttrium-90 ((90)Y) yielded better results. Between January 2005 and January 2007, 12 patients (eight men and four women aged 19-49 years) with extensive diffuse PVNS of the knee were treated. All patients had an adjuvant post-operative external beam radiation therapy (2,600-3,000 cGy) conventionally fractionated 200 cGy/fraction, five fractions/week, 6-8 weeks after surgery. Mean follow-up time was 27 months (range from 20 to 36 months). All patients were followed up using clinical assessment, magnetic resonance imaging, and plain X-ray. In all patients, neither evidence of disease recurrence nor progression of bone or articular destruction was noted. No complications were noticed after surgery or after post-operative external beam radiation therapy. A combination of debulking surgery using anterior and posterior approach with adjuvant post-operative external beam radiation therapy for extensive diffuse PVNS of the knee joint is a reliable treatment method, with good results in regard to the incidence of local recurrence and functional outcome.