P1.14-21 Circulating Biomarkers in Thymic Epithelial Tumors

Abstract

MAVS pathway by direct administration into the tumor. We performed the phase I dose escalation safety/tolerability and preliminary efficacy study of intra-tumoral and subcutaneous administration of HVJ-E in patients suffering from chemotherapy-resistant malignant pleural mesothelioma. Method: We performed the dose upward titration clinical study for checking the safety, drug tolerance, and preliminary efficacy of the intra-tumoral and subsequent subcutaneous administration of HVJ-E. We administrated HVJ-E to the patients 4 times per 2 weeks (the first was intra-tumoral, and residual 3 times were subcutaneous injection), and then washed out the drug from the body for 2 weeks. This cycle was repeated 2 times. We observed the patients for 8 weeks, and evaluated them by CTCAE, modified RECIST, and PERCIST. Result: Three patients were enrolled as a low-dose group, and three patients were enrolled as a high-dose group. There was no discontinuation of the administration due to the severe adverse events. Results; The mean disease duration from confirmed diagnosis to this trial was 2.27 years (0.6-4.5 years). We defined the primary endpoint as an assessment of dose limiting toxicity related with HVJ-E. Neither serious adverse events (SAE) nor DLT were observed during the observation period.The following symptoms were observed. Fever (83.3%), and the local symptoms at injection site, for example, rubor, swelling, or induration (100%) were observed, but the local relapse of mesothelioma at the injection site was not observed. It was confirmed that the intra-tumoral and subcutaneous administration of HVJ-E was safe for chemotherapyresistant pleural mesothelioma patients, because these AEs were transient and slight. The efficacy as a secondary endpoint was evaluated with modified RECIST, and PERCIST. DCR of low dose level cohort was 0% (0/3), because of PD, meanwhile, high dose level cohort indicated 100% (3/3). Consequently, the DCR of all cases who had treated with HVJ-E was 50% (3/6) by mRECIST, meanwhile, the DCR evaluated by PERCIST was 100%. Conclusion: It was suggested that HVJ-E was useful for disease control of advanced pleural mesothelioma patients without severe adverse events. Now we do the next step trial for malignant pleural mesothelioma and melanoma with high dose of HVJ-E.

Thymic epithelial tumors: Do we know all the prognostic factors?

“…in the analysis of 90 patients diagnosed with stage III or IV thymic cancer (LDH 190 U/L – relative risk of death 2.7; P = 0.004) 28 and Valdivia et al . who showed a very clear tendency for increase of LDH activity among patients with stage IV thymic carcinomas, according to the Masaoka classification 10 . The studies involving patients with other cancers of the chest area also confirmed the prognostic value of increased LDH activity 29,30 …”

“…Additionally, resection radicality, clinical stage and histological type are, together with the initial tumor size, the risk factors for disease recurrence after surgery 9 . There have also been reports of the prognostic value of the so‐called circulating biomarkers (C Reactive Protein – CRP and lactate dehydrogenase – LDH), 10 as well as the importance of the neutrophil‐to‐lymphocyte ratio (NLR) 11 for survival and prognosis.…”