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Multicenter Study
. 2022 Feb;7(1):100388.
doi: 10.1016/j.esmoop.2022.100388. Epub 2022 Feb 2.

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

S F Kruger  1 , A Lohneis  2 , A Abendroth  3 , A W Berger  4 , T J Ettrich  4 , O Waidmann  5 , M Kapp  6 , B Steiner  7 , J Kumbrink  8 , A Reischer  9 , M Haas  9 , C B Westphalen  10 , D Zhang  9 , L Miller-Phillips  9 , P J Burger  9 , S Kobold  11 , J Werner  12 , M Subklewe  10 , M von Bergwelt-Baildon  10 , V Kunzmann  6 , T Seufferlein  4 , J T Siveke  3 , M Sinn  13 , V Heinemann  10 , S Ormanns  14 , S Boeck  10
Affiliations
Multicenter Study

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

S F Kruger et al. ESMO Open. 2022 Feb.

Abstract

Background: 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.

Patients and methods: 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).

Results: 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.

Conclusion: 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.

Keywords: chemotherapy; gene expression; lung metastasis; pancreatic cancer; prognosis.

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Conflict of interest statement

Disclosure CBW received personal and speakers’ fees, reimbursement for travel and accommodation and honoraria for participation in advisory boards from Bayer, BMS, Celgene, GSK, Ipsen, MedScape, Merck, MSD, Rafael Pharmaceuticals, RedHill, Roche, Servier, Shire/Baxalta, SirTex and Taiho and scientific grant support from Roche. JK received honoraria and reimbursement for travel and accommodation for participation in advisory boards and speaker’s bureau from AstraZeneca, Novartis, Quality Initiative in Pathology (QuIP) and Roche Pharma. OW received personal and speakers’ fees, reimbursement for travel and accommodation and honoraria for participation in advisory boards from Abbvie, Amgen, Bayer, BMS, Celgene, Eisai, Incyte, Ipsen, Merck Serono, MSD, Novartis, Roche, Servier and Shire. SFK is a full-time employee of MSD Sharp & Dohme GmbH; his work on this manuscript was carried out independently from his position at MSD: until 31 December 2020 as a full-time employee at LMU Munich (clinician scientist and medical oncologist at LMU) and from 1 January 2021 as a guest researcher and lecturer at LMU Munich. The remaining authors have declared no conflicts of interest.

Figures

Figure 1
Figure 1
Results of the mRNA expression analysis of 770 genes using the nCounter® PanCancer Immune Profiling Panel. nCounter analysis was successfully carried out on tumor samples from 56 resected PDAC patients (27 patients from the M1-PUL and 29 patients from the M1-ANY cohort). (A) Heatmap of mRNA expression with automated clustering according to M1-PUL versus M1-ANY cohorts. (B) Differentially expressed genes depicted as a volcano plot. (C) Networks of gene products form the top 20 differentially expressed genes visualized by using the STRING database. Adj., adjusted; M1-PUL, pulmonary metastasis; M1-ANY, any metastases excluding lung-only involvement; mRNA, messenger RNA; PDAC, pancreatic ductal adenocarcinoma.
See this image and copyright information in PMC

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