Background: Malignant pleural mesothelioma is a fatal and aggressive disease; most patients present with advanced stages. Mesothelioma have one of the highest circulating serum VEGF levels of any solid tumor which is considered as a poor prognostic factor in this disease. Macrophage migration inhibitory factor (MIF) and its receptor CD74 found to be associated with angiogenic activity. Role of MIF has not been shown yet in MPM. This study targets the correlation between expression of VEGF and CD74 (on stored retrospective 44 paraffin embedded mesothelioma specimens) and tumor response to chemotherapy Gemcitabine and platinum combination. The study also figures out the prognostic impact of VEGF and CD74 on the progression free survival (PFS) and overall survival (OS) of the studied patients. Methods: Immunohistochemical staining for VEGF scored from 0 to 3 represent the percentage of cytoplasmic positively stained cells in the tumor. The CD74 expression was recorded in the tumor and the stroma semiquantitatively using the histoscore method with the final score resulting from the percentage of tumor cells staining positively multiplied by the staining intensity grade. Both CD74 and VEGF immunohistochemical markers were furtherly categorized in the statistical analyses as none (0)/low (1) vs medium (2)/high expression (3). Results: Combined med/high expression of CD74-TS and VEGF are significantly associated with poor response to gemcitabine and cisplatin chemotherapy (P = 0.03). VEGF expression level did not correlate with PFS (P = 0.09) while high CD74 (T) (P = 0.001) and (S) (P = 0.006) expression significantly impair PFS. Med/high VEGF expression is significantly associated with shorter OS (P = 0.025) whereas, med/high expression of CD74-TS yield a highly significant shorter OS. (P = 0.001). Conclusions: High expression of VEGF and CD74 T&S are inversely correlated with OS and response to chemotherapy with gemcitabine and cisplatin in Egyptian mesothelioma patients. Legal entity responsible for the study: Clinical Oncology Department Ethical Committe Funding: Has not received any funding Disclosure: All authors have declared no conflicts of interest.
Cochrane, and MEDLINE (via PubMed). No language restrictions were applied. Two researchers independently reviewed studies using the Cochrane methodology for systematic reviews. Outcomes of interest included progression-free survival (PFS), Disease free survival (DFS), overall survival (OS), overall response rate (ORR), and safety. Results: A total of 105 potentially relevant studies were screened. Five clinical trials involving 7768 patients with HER2 positive Breast cancer were included. Overall 1892 patients were received Trastuzumab. The combination of Trastuzumab with Pertuzumab plus Docetaxel significantly prolonged progression-free survival, with no increase in cardiac toxic effects when used as first-line treatment for HER2positive metastatic breast cancer. The addition of 1 year of adjuvant trastuzumab significantly improved disease-free and overall survival among women with HER2positive breast cancer. The addition of trastuzumab to paclitaxel after doxorubicin and cyclophosphamide in early-stage HER2-positive breast cancer results in a substantial and durable improvement in survival as a result of a sustained marked reduction in cancer recurrence. Adjuvant trastuzumab improves RFS of patients treated with TX-CEX or T-CEF. Very few patients had cardiac failure. ConClusions: Trastuzumab is an important treatment option for patients with HER2 positive Breast cancer. Trastuzumab improved overall survival and progression-free survival in HER2-positive women with metastatic breast cancer. Provides good survival benefit with minimal adverse events. However, the results have to be interpreted cautiously due to limited number of trials available.
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