PMID- 38012155
OWN - NLM
STAT- MEDLINE
DCOM- 20231129
LR  - 20231220
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 13
IP  - 1
DP  - 2023 Nov 27
TI  - Combination of tumor asphericity and an extracellular matrix-related prognostic 
      gene signature in non-small cell lung cancer patients.
PG  - 20840
LID - 10.1038/s41598-023-46405-4 [doi]
LID - 20840
AB  - One important aim of precision oncology is a personalized treatment of patients. 
      This can be achieved by various biomarkers, especially imaging parameters and 
      gene expression signatures are commonly used. So far, combination approaches are 
      sparse. The aim of the study was to independently validate the prognostic value 
      of the novel positron emission tomography (PET) parameter tumor asphericity (ASP) 
      in non small cell lung cancer (NSCLC) patients and to investigate associations 
      between published gene expression profiles and ASP. This was a retrospective 
      evaluation of PET imaging and gene expression data from three public databases 
      and two institutional datasets. The whole cohort comprised 253 NSCLC patients, 
      all treated with curative intent surgery. Clinical parameters, standard PET 
      parameters and ASP were evaluated in all patients. Additional gene expression 
      data were available for 120 patients. Univariate Cox regression and Kaplan-Meier 
      analysis was performed for the primary endpoint progression-free survival (PFS) 
      and additional endpoints. Furthermore, multivariate cox regression testing was 
      performed including clinically significant parameters, ASP, and the extracellular 
      matrix-related prognostic gene signature (EPPI). In the whole cohort, a 
      significant association with PFS was observed for ASP (p < 0.001) and EPPI 
      (p = 0.012). Upon multivariate testing, EPPI remained significantly associated 
      with PFS (p = 0.018) in the subgroup of patients with additional gene expression 
      data, while ASP was significantly associated with PFS in the whole cohort 
      (p = 0.012). In stage II patients, ASP was significantly associated with PFS 
      (p = 0.009), and a previously published cutoff value for ASP (19.5%) was 
      successfully validated (p = 0.008). In patients with additional gene expression 
      data, EPPI showed a significant association with PFS, too (p = 0.033). The 
      exploratory combination of ASP and EPPI showed that the combinatory approach has 
      potential to further improve patient stratification compared to the use of only 
      one parameter. We report the first successful validation of EPPI and ASP in stage 
      II NSCLC patients. The combination of both parameters seems to be a very 
      promising approach for improvement of risk stratification in a group of patients 
      with urgent need for a more personalized treatment approach.
CI  - (c) 2023. The Author(s).
FAU - Zschaeck, Sebastian
AU  - Zschaeck S
AD  - Department of Radiation Oncology, Charite-Universitatsmedizin Berlin, Corporate 
      Member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin 
      Institute of Health, Berlin, Germany.
AD  - Berlin Institute of Health (BIH), 10178, Berlin, Germany.
FAU - Klinger, Bertram
AU  - Klinger B
AD  - Berlin Institute of Health (BIH), 10178, Berlin, Germany.
AD  - Computational Modelling in Medicine, Instiute of Pathology, Charite 
      Universitatsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany.
AD  - German Cancer Consortium (DKTK), Partner Site Berlin, Berlin, Germany.
FAU - van den Hoff, Jorg
AU  - van den Hoff J
AD  - Helmholtz-Zentrum Dresden-Rossendorf, PET Center, Institute of 
      Radiopharmaceutical Cancer Research, Dresden, Germany.
FAU - Cegla, Paulina
AU  - Cegla P
AD  - Department of Nuclear Medicine, Greater Poland Cancer Centre, Poznan, Poland.
FAU - Apostolova, Ivayla
AU  - Apostolova I
AD  - Department for Diagnostic and Interventional Radiology and Nuclear Medicine, 
      University Hospital Hamburg-Eppendorf, Hamburg, Germany.
AD  - Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, Otto 
      Von Guericke University, Magdeburg, Germany.
FAU - Kreissl, Michael C
AU  - Kreissl MC
AD  - Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, Otto 
      Von Guericke University, Magdeburg, Germany.
FAU - Cholewinski, Witold
AU  - Cholewinski W
AD  - Department of Nuclear Medicine, Greater Poland Cancer Centre, Poznan, Poland.
FAU - Kukuk, Emily
AU  - Kukuk E
AD  - Department of Radiation Oncology, Charite-Universitatsmedizin Berlin, Corporate 
      Member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin 
      Institute of Health, Berlin, Germany.
FAU - Strobel, Helen
AU  - Strobel H
AD  - Department of Radiation Oncology, Charite-Universitatsmedizin Berlin, Corporate 
      Member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin 
      Institute of Health, Berlin, Germany.
FAU - Amthauer, Holger
AU  - Amthauer H
AD  - Division of Nuclear Medicine, Department of Radiology and Nuclear Medicine, Otto 
      Von Guericke University, Magdeburg, Germany.
AD  - Department of Nuclear Medicine, Charite-Universitatsmedizin Berlin, Corporate 
      Member of Freie Universitat Berlin and Humboldt-Universitat zu Berlin, 
      Augustenburger Platz 1, 13353, Berlin, Germany.
FAU - Bluthgen, Nils
AU  - Bluthgen N
AD  - Berlin Institute of Health (BIH), 10178, Berlin, Germany.
AD  - Computational Modelling in Medicine, Instiute of Pathology, Charite 
      Universitatsmedizin Berlin, Chariteplatz 1, 10117, Berlin, Germany.
AD  - German Cancer Consortium (DKTK), Partner Site Berlin, Berlin, Germany.
FAU - Zips, Daniel
AU  - Zips D
AD  - Department of Radiation Oncology, Charite-Universitatsmedizin Berlin, Corporate 
      Member of Freie Universitat Berlin, Humboldt-Universitat zu Berlin, and Berlin 
      Institute of Health, Berlin, Germany.
AD  - German Cancer Consortium (DKTK), Partner Site Berlin, Berlin, Germany.
FAU - Hofheinz, Frank
AU  - Hofheinz F
AD  - Helmholtz-Zentrum Dresden-Rossendorf, PET Center, Institute of 
      Radiopharmaceutical Cancer Research, Dresden, Germany. f.hofheinz@hzdr.de.
LA  - eng
PT  - Journal Article
DEP - 20231127
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Non-Small-Cell Lung/pathology
MH  - Prognosis
MH  - *Lung Neoplasms/pathology
MH  - Retrospective Studies
MH  - Fluorodeoxyglucose F18/metabolism
MH  - Tomography, X-Ray Computed
MH  - Precision Medicine
MH  - Positron Emission Tomography Computed Tomography
PMC - PMC10681996
COIS- Holger Amthauer declares research grants, travel grants, and lecture fees from 
      Sirtex Medical Europe; Dr. Amthauer confirms that none of the above funding 
      sources were involved in the preparation of this paper. All other authors have 
      nothing to disclose.
EDAT- 2023/11/28 00:42
MHDA- 2023/11/29 06:42
PMCR- 2023/11/27
CRDT- 2023/11/27 23:20
PHST- 2023/08/10 00:00 [received]
PHST- 2023/10/31 00:00 [accepted]
PHST- 2023/11/29 06:42 [medline]
PHST- 2023/11/28 00:42 [pubmed]
PHST- 2023/11/27 23:20 [entrez]
PHST- 2023/11/27 00:00 [pmc-release]
AID - 10.1038/s41598-023-46405-4 [pii]
AID - 46405 [pii]
AID - 10.1038/s41598-023-46405-4 [doi]
PST - epublish
SO  - Sci Rep. 2023 Nov 27;13(1):20840. doi: 10.1038/s41598-023-46405-4.