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P2.04-026 Expression Patterns of PD-L1 in Esophageal Adenocarcinomas: Comparison between Primary Tumors and Metastases
S1012
day 1, 4 and 7, was administrated in group B. Group C was administrated with combined therapy of Endostar and Cisplatin. Results: A total of 317 patients were included in full analysis set (FAS), and 275 patients were included in per-protocol set (PPS). There were 298 cases and 273 cases qualified for evaluation on drug efficacy in FAS and PPS respectively. There was a significant difference in ORR among three groups (P＜0.05), and ORR was higher in Group C than that in Groups A and B (P＜0.05 or P＜ 0.01). Patients without intracavitary treatment history, with hydrothorax, female, without systemic chemotherapy, with initial treatment on effusion, with sufficient drainage, with hemorrhagic effusion and without diagnosis of gastric carcinoma had better outcome in ORR after treatment (P＜0.05 or P＜0.01). In those with hemorrhagic effusion, the ORRs in Groups A and C were significantly higher than that of Group C (P＜0.01). The median TTP was 68.869 d, 44.951 d, 69.030 d in Groups A, B and C, respectively, with a significant difference (P＜ 0.01), and was shorter in Group B than that in Groups A and C (P＜0.05 or P＜0.01). The proportion of patients with improved QOL and KPS in Group A was higher than that in Groups B and C after third and sixth administration, respectively (P＜0.05 or P＜0.01). The incidence of adverse reactions was lower in Group A than that in Group B (P＜0.01), but no significant difference was shown between Groups B and C (P＞0.05). Conclusion: Intra-pleural injection of Endostar is potentially effective in treatment of patients with malignant hydrothorax and ascites, especially those with hemorrhagic effusion. It shows a synergistic effect with Cisplatin in improving the clinical efficacy, TTP and QOL, but without increasing the risk of adverse reactions. Keywords: Recombinant human endostatin, Malignant hydrothorax, Malignant ascites, Endostar
P2.04-026 Expression Patterns of PD-L1 in Esophageal Adenocarcinomas: Comparison between Primary Tumors and Metastases Topic: Esophageal Cancer and Other Malignancies Bastian Dislich,1 Alexandra Stein,1 Jose Galvan,1 Sabina Berezowska,1 Christian Seiler,2 Dino Kroell,2 Rupert Langer1 1Institute of Pathology, University of Bern, Bern/Switzerland, 2Department of Visceral Surgery and Medicine, Bern University Hospital, Bern/Switzerland
Journal of Thoracic Oncology
Vol. 12 No. 1S
Background: Immune checkpoint inhibition through PD-L1 (Programmed death-ligand 1) is a powerful therapeutic option for many solid tumors, potentially including esophageal adenocarcinomas (EAC). Immunohistochemical expression analysis of PD-L1 may be helpful for guiding therapeutic decisions, but testing may be influenced by heterogeneous staining patterns within tumors and expression changes during metastatic course. Methods: We investigated PD-L1 expression in EAC using tissue microarrays from 116 primary resected tumors, corresponding lymph nodes (n¼56) and distant metastases (n¼18). PD-L1 expression was analyzed using two different antibodies (SP142 and E1LN3), together with intratumoral CD3+ and CD8+ T-lymphocyte (TIL) counts. In addition, preoperative biopsies and full slide sections from a subset of tumors (n¼24) were investigated. Results: PD-L1 expression was first scored as 0%, >0<1%, 1%, 5%, 50% positive membranous staining of tumor cells and of tumor associated inflammatory infiltrates and/or stroma cells. There was a significant correlation between the results of full slide sections and 12 cores/tumor containing TMAs (p¼0.001), but not with the corresponding biopsies. For further analysis, PD-L1 positivity was defined as >1% positive staining for tumor cells and/or inflammatory and stroma cells according to the majority of current drug trails. We observed a very good concordance between the two antibodies for overall staining (p<0.001; concordance rate 89.5%). SP142 appeared slightly superior in terms of a more homogenous staining pattern. PD-L1 expression in tumor cells was detected by SP142 in 3 cases (2.6%) of primary EAC, whereas expression in the inflammatory and stromal cells was observed in 35 cases (30.2%). PD-L1 positive tumors had higher CD3+ and CD8+ TIL counts (p<0.001 and p¼0.001) but no other distinct pathological or clinical features. Of note, there was no significant correlation between tumoral PD-L1 expression in primary tumors and lymph node and distant metastases. Conclusion: EAC show tumoral PD-L1expression only a minority of cases, whereas PD-L1 positivity in the inflammatory and stromal cells can be detected in a significant subset of cases. For the determination of PD-L1 status, it should be taken into account that PD-L1 expression in metastases may differ from primary tumors. Moreover, investigation of superficial small biopsies may produce false staining results, which, however, may be more likely be due to fixation artifacts or vicinity to ulceration than to intratumoral heterogeneity. Keywords: Esophagus, PD-L1, Cancer, Immunohistochemistry
day 1, 4 and 7, was administrated in group B. Group C was administrated with combined therapy of Endostar and Cisplatin. Results: A total of 317 patients were included in full analysis set (FAS), and 275 patients were included in per-protocol set (PPS). There were 298 cases and 273 cases qualified for evaluation on drug efficacy in FAS and PPS respectively. There was a significant difference in ORR among three groups (P＜0.05), and ORR was higher in Group C than that in Groups A and B (P＜0.05 or P＜ 0.01). Patients without intracavitary treatment history, with hydrothorax, female, without systemic chemotherapy, with initial treatment on effusion, with sufficient drainage, with hemorrhagic effusion and without diagnosis of gastric carcinoma had better outcome in ORR after treatment (P＜0.05 or P＜0.01). In those with hemorrhagic effusion, the ORRs in Groups A and C were significantly higher than that of Group C (P＜0.01). The median TTP was 68.869 d, 44.951 d, 69.030 d in Groups A, B and C, respectively, with a significant difference (P＜ 0.01), and was shorter in Group B than that in Groups A and C (P＜0.05 or P＜0.01). The proportion of patients with improved QOL and KPS in Group A was higher than that in Groups B and C after third and sixth administration, respectively (P＜0.05 or P＜0.01). The incidence of adverse reactions was lower in Group A than that in Group B (P＜0.01), but no significant difference was shown between Groups B and C (P＞0.05). Conclusion: Intra-pleural injection of Endostar is potentially effective in treatment of patients with malignant hydrothorax and ascites, especially those with hemorrhagic effusion. It shows a synergistic effect with Cisplatin in improving the clinical efficacy, TTP and QOL, but without increasing the risk of adverse reactions. Keywords: Recombinant human endostatin, Malignant hydrothorax, Malignant ascites, Endostar
P2.04-026 Expression Patterns of PD-L1 in Esophageal Adenocarcinomas: Comparison between Primary Tumors and Metastases Topic: Esophageal Cancer and Other Malignancies Bastian Dislich,1 Alexandra Stein,1 Jose Galvan,1 Sabina Berezowska,1 Christian Seiler,2 Dino Kroell,2 Rupert Langer1 1Institute of Pathology, University of Bern, Bern/Switzerland, 2Department of Visceral Surgery and Medicine, Bern University Hospital, Bern/Switzerland
Journal of Thoracic Oncology
Vol. 12 No. 1S
Background: Immune checkpoint inhibition through PD-L1 (Programmed death-ligand 1) is a powerful therapeutic option for many solid tumors, potentially including esophageal adenocarcinomas (EAC). Immunohistochemical expression analysis of PD-L1 may be helpful for guiding therapeutic decisions, but testing may be influenced by heterogeneous staining patterns within tumors and expression changes during metastatic course. Methods: We investigated PD-L1 expression in EAC using tissue microarrays from 116 primary resected tumors, corresponding lymph nodes (n¼56) and distant metastases (n¼18). PD-L1 expression was analyzed using two different antibodies (SP142 and E1LN3), together with intratumoral CD3+ and CD8+ T-lymphocyte (TIL) counts. In addition, preoperative biopsies and full slide sections from a subset of tumors (n¼24) were investigated. Results: PD-L1 expression was first scored as 0%, >0<1%, 1%, 5%, 50% positive membranous staining of tumor cells and of tumor associated inflammatory infiltrates and/or stroma cells. There was a significant correlation between the results of full slide sections and 12 cores/tumor containing TMAs (p¼0.001), but not with the corresponding biopsies. For further analysis, PD-L1 positivity was defined as >1% positive staining for tumor cells and/or inflammatory and stroma cells according to the majority of current drug trails. We observed a very good concordance between the two antibodies for overall staining (p<0.001; concordance rate 89.5%). SP142 appeared slightly superior in terms of a more homogenous staining pattern. PD-L1 expression in tumor cells was detected by SP142 in 3 cases (2.6%) of primary EAC, whereas expression in the inflammatory and stromal cells was observed in 35 cases (30.2%). PD-L1 positive tumors had higher CD3+ and CD8+ TIL counts (p<0.001 and p¼0.001) but no other distinct pathological or clinical features. Of note, there was no significant correlation between tumoral PD-L1 expression in primary tumors and lymph node and distant metastases. Conclusion: EAC show tumoral PD-L1expression only a minority of cases, whereas PD-L1 positivity in the inflammatory and stromal cells can be detected in a significant subset of cases. For the determination of PD-L1 status, it should be taken into account that PD-L1 expression in metastases may differ from primary tumors. Moreover, investigation of superficial small biopsies may produce false staining results, which, however, may be more likely be due to fixation artifacts or vicinity to ulceration than to intratumoral heterogeneity. Keywords: Esophagus, PD-L1, Cancer, Immunohistochemistry