Prognosis and tumor biology of pancreatic cancer patients with isolated lung metastases: translational results from the German multicenter AIO-YMO-PAK-0515 study

• Published in: ESMO open Vol. 7; no. 1; p. 100388
• Main Authors: Kruger, S.F., Lohneis, A., Abendroth, A., Berger, A.W., Ettrich, T.J., Waidmann, O., Kapp, M., Steiner, B., Kumbrink, J., Reischer, A., Haas, M., Westphalen, C.B., Zhang, D., Miller-Phillips, L., Burger, P.J., Kobold, S., Werner, J., Subklewe, M., von Bergwelt-Baildon, M., Kunzmann, V., Seufferlein, T., Siveke, J.T., Sinn, M., Heinemann, V., Ormanns, S., Boeck, S.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-02-2022; Elsevier
• Subjects: Biology; chemotherapy; gene expression; Humans; lung metastasis; Lung Neoplasms - genetics; Neoplasm Recurrence, Local; Original Research; pancreatic cancer; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - pathology; Prognosis; Retrospective Studies; lung metastasis; pancreatic cancer; chemotherapy; prognosis; gene expression
• ISSN: 2059-7029; 2059-7029
• DOI: 10.1016/j.esmoop.2022.100388

Pulmonary metastasis (M1-PUL) as first site of dissemination in pancreatic ductal adenocarcinoma (PDAC) is a rare event and may define a distinct biological subgroup.
Arbeitsgemeinschaft Internistische Onkologie-Young Medical Oncologists-Pankreas-0515 study (AIO-YMO-PAK-0515) was a retrospective German multicenter study investigating clinical and molecular characteristics of M1-PUL PDAC patients; 115 M1-PUL PDAC patients from 7 participating centers were included. Clinical characteristics and potential prognostic factors were defined within the M1-PUL cohort. Archival tumor samples were analyzed for Her2/neu, HNF1A and KRT81 expression. Additionally, messenger RNA (mRNA) expression analysis (using a 770-gene immune profiling panel) was carried out in the M1-PUL and in a control cohort (M1-ANY).
Median overall survival in the entire M1-PUL cohort was 20 months; the most favorable prognosis (median survival: 28 months) was observed in the subgroup of 66 PDAC patients with metachronous lung metastases after previous curative-intent surgery. The number of metastatic lesions, uni- or bilateral lung involvement as well as metastasectomy were identified as potential prognostic factors. Her2/neu expression and PDAC subtyping (by HNF1A and KRT81) did not differ between the M1-PUL and the M1-ANY cohort. mRNA expression analysis revealed significant differentially expressed genes between both cohorts: CD63 and LAMP1 were among the top 20 differentially expressed genes and were identified as potential mediators of organotropism and favorable survival outcome of M1-PUL patients.
M1-PUL represents a clinically favorable cohort in PDAC patients. Site of relapse might already be predetermined at the time of surgery and could potentially be predicted by gene expression profiling.
•The retrospective multicenter AIO-YMO-PAK-0515 study defines M1-PUL as a clinically favorable subgroup in PDAC.•The number of metastatic lesions, bilateral lung involvement and surgical metastasectomy may serve as prognostic factors.•Immune-related gene expression differs between patients with isolated pulmonary relapse versus other sites of relapse.