Epirubicin, cisplatin plus ifosfamide versus standard chemotherapeutic regimens for advanced/unresectable primary thoracic sarcomas.

PURPOSE: Thoracic sarcomas are rare malignancies, with limited data for unresectable/advanced scenarios. Our goal is to provide insights of a three-drug chemotherapy regimen improving patient survival compared to standard regimens. METHODS: Retrospective cohort analysis of patients diagnosed with unresectable/advanced primary thoracic sarcoma divided between primary pulmonary sarcomas (PPS) and chest wall sarcomas (CWS) comparing chemotherapeutical regimens efficacy. Not true soft tissue sarcomas (STS) for PPS were excluded from the analysis. Univariate and multivariate analysis performed via Cox-regression model. Progression-free survival (PFS) and overall survival (OS) analysis via Kaplan-Meier with hazard ratio (HR) obtained via Mantel-Haenszel or log rank. RESULTS: 157 total cases were included, from which 50 cases were PPS and 107 cases CWS. For PPS, 4 cases were excluded from the analysis as they were not true STS. The most common histology was undifferentiated sarcomas, 63% of cases were treated with E/C/I and 37% with another regimen. The E/C/I regimen demonstrated a benefit for both OS (p = 0.020) and PFS (p = 0.010) when compared to any other regimen as well as when compared to non-platinum regimens (p = 0.016 and p = 0.001). Regarding CWS, the most common histology was synovial and undifferentiated sarcomas, 55.1% were treated with E/C/I and 44.9% treated with another regimen. The E/C/I regimen did not demonstrate a benefit for OS or PFS compared to any other regimen, neither when compared to other non-platinum regimens. However, a benefit was observed in favor of E/C/I when compared to other platinum regimens in both OS (p = 0.049) and PFS (0.015). Both analyses for PPS and CWS demonstrated a benefit in favor of cisplatin therapies compared to carboplatin in both OS and PFS. CONCLUSION: This study demonstrates that platinum therapy alone does not work, and that cisplatin must be the agent of choice and it's used in combination could increase treatment response. The E/C/I regimen demonstrated a in PPS but not for CWS, this is due do their rarity of PPS and that no standard treatment is established yet. The regimen proposed here could represent a possible new standard of treatment for PPS as long as it is validated in a prospective study.

Human skin biomarkers relationship to response to treatment with tyrosine kinase inhibitors in advanced EGFR-mutated lung adenocarcinoma.

BACKGROUND: A relationship between the EGFR signaling pathway expression in skin and the use of targeted cancer therapies has been previously demonstrated. Consistent evidence to support the use of skin biopsies as a surrogate for therapeutic evaluation is needed. The purpose of this study was to establish the relationship between the expression of EGFR signaling pathway markers in skin samples from EGFR-mutated metastatic lung adenocarcinoma patients and their response to tyrosine kinase inhibitors. METHODS: This was a prospective single blind analysis of 35 skin biopsies from 31 patients with confirmed advanced EGFR-mutated lung adenocarcinoma. Immunohistochemistry was performed: EGFR, p27, Ki67, STAT3 and MAPK, as well as H&E histopathological analysis, in order to determine their treatment response to tyrosine kinase inhibitors. RESULTS: EGFR, Ki67, STAT3, stratum corneum thickness (number of layers and millimeters) from skin samples had a statistical correlation with an adequate treatment response (P = 0.025, 0.015, 0.017, 0.041, 0.039 respectively). EGFR, p27 and number of layers of the stratum corneum were related to a better median progression-free survival (P = 0.025 and P = 0.030). CONCLUSIONS: The relationship between EGFR pathway inhibition in the skin and oncological outcomes obtained explains the parallel biological effects of tyrosine kinase inhibitors. We hope that our work incites future research to help validate and assess the use of these markers as potential prognostic and predictive factors.

Expression of estrogen receptor beta (ERß) and its prognostic value in pleural mesothelioma.

BACKGROUND: Overexpression of estrogen receptors in malignant pleural mesothelioma has shown an independent relation with a better prognosis of survival, and the use of selective estrogen receptor beta (ERß) agonists increases the susceptibility to antitumor treatment. METHODS: This was a retrospective single center study that analyzed the response of malignant pleural mesothelioma with an expression of ERß to first-line chemotherapy. The study included patients with pleural mesothelioma pathologically confirmed between 2013 and 2016 at the National Institute for Respiratory Disease (INER), who underwent an immunohistochemistry assay for ERß (mouse monoclonal antibody PPG5/10). The primary endpoint was the response to chemotherapy based on RECIST 1.1 according to the ERß expression; secondary outcomes were the overall survival (OS) and progression-free survival (PFS). RESULTS: We included 22 patients, regarding the expression of ERß, 17 (77.2%) patients had high or moderate degree, while 5 (22.7%) had low degree or null expression. The response to treatment as by RECIST 1.1, 12 (54.5%) had partial response, 5 (22.7%) had stable disease, and 3 (13.6%) had progression. None of the patients had a complete response. Of those who had a partial response, 9 (75%) had a high or moderate degree of ERß expression in tumor cells, and 3 (25%) had a low or null degree of expression. CONCLUSIONS: High and moderate expression of ERß group with advanced clinical stage malignant pleural mesothelioma was associated with a tendency of higher OS and better response to chemotherapy treatment resulting in longer PFS although statistical significance was not achieved.