PMID- 36175621
OWN - NLM
STAT- MEDLINE
DCOM- 20221124
LR  - 20230301
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Print)
IS  - 0007-0920 (Linking)
VI  - 127
IP  - 11
DP  - 2022 Nov
TI  - Longitudinal liquid biopsy anticipates hyperprogression and early death in 
      advanced non-small cell lung cancer patients treated with immune checkpoint 
      inhibitors.
PG  - 2034-2042
LID - 10.1038/s41416-022-01978-1 [doi]
AB  - BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionised treatment of 
      advanced non-small cell lung cancer (aNSCLC), but a proportion of patients had no 
      clinical benefit and even experienced detrimental effects. This study aims to 
      characterise patients experiencing hyperprogression (HPD) and early death (ED) by 
      longitudinal liquid biopsy. METHODS: aNSCLC receiving ICIs were prospectively 
      enrolled. Plasma was collected at baseline (T1) and after 3/4 weeks of treatment, 
      according to the treatment schedule (T2). Cell-free DNA (cfDNA) was quantified 
      and analysed by NGS. cfDNA quantification and variant allele fraction (VAF) of 
      tumour-associated genetic alterations were evaluated for their potential impact 
      on outcome. The genetic alteration with the highest VAF (maxVAF) at baseline was 
      considered as a reference. RESULTS: From March 2017 to August 2019, 171 patients 
      were enrolled. Five cases matched criteria for HPD and 31 ED were recorded; one 
      overlapped. Quantification of cfDNA at T2 and its absolute and relative variation 
      (T2-T1) were significantly associated with the risk of ED (P = 0.012, P = 0.005, 
      P = 0.009). MaxVAF relative change (T2-T1/T1) was significantly associated with 
      the risk of HPD (P = 0.02). After identifying optimal cut-off values, a two-step 
      risk assessment model was proposed. DISCUSSION: Liquid biopsy performed early 
      during treatment has the potential to identify patients at high risk of ED and 
      HPD.
CI  - (c) 2022. The Author(s).
FAU - Zulato, Elisabetta
AU  - Zulato E
AD  - Basic and Translational Oncology Unit, Istituto Oncologico Veneto IOV IRCCS, 
      Padova, Italy.
FAU - Del Bianco, Paola
AU  - Del Bianco P
AD  - Clinical Research Unit, Istituto Oncologico Veneto IOV IRCCS, Padova, Italy.
FAU - Nardo, Giorgia
AU  - Nardo G
AD  - Basic and Translational Oncology Unit, Istituto Oncologico Veneto IOV IRCCS, 
      Padova, Italy.
FAU - Attili, Ilaria
AU  - Attili I
AD  - Department of Surgery, Oncology and Gastroeneterology, Universita degli Studi di 
      Padova, Padova, Italy.
FAU - Pavan, Alberto
AU  - Pavan A
AD  - Department of Surgery, Oncology and Gastroeneterology, Universita degli Studi di 
      Padova, Padova, Italy.
FAU - Boscolo Bragadin, Andrea
AU  - Boscolo Bragadin A
AD  - Immunology and Molecular Oncology Diagnostics Unit, Istituto Oncologico Veneto 
      IOV IRCCS, Padova, Italy.
FAU - Marra, Ludovica
AU  - Marra L
AD  - Immunology and Molecular Oncology Diagnostics Unit, Istituto Oncologico Veneto 
      IOV IRCCS, Padova, Italy.
FAU - Pasello, Giulia
AU  - Pasello G
AD  - Department of Surgery, Oncology and Gastroeneterology, Universita degli Studi di 
      Padova, Padova, Italy.
AD  - Medical Oncology 2, Istituto Oncologico Veneto IOV IRCSS, Padova, Italy.
FAU - Fassan, Matteo
AU  - Fassan M
AD  - Surgical Pathology Unit, Department of Medicine, Universita degli Studi di 
      Padova, Padova, Italy.
FAU - Calabrese, Fiorella
AU  - Calabrese F
AD  - Surgical Pathology Unit, Department of Medicine, Universita degli Studi di 
      Padova, Padova, Italy.
FAU - Guarneri, Valentina
AU  - Guarneri V
AD  - Department of Surgery, Oncology and Gastroeneterology, Universita degli Studi di 
      Padova, Padova, Italy.
AD  - Medical Oncology 2, Istituto Oncologico Veneto IOV IRCSS, Padova, Italy.
FAU - Conte, Pier Franco
AU  - Conte PF
AD  - Department of Surgery, Oncology and Gastroeneterology, Universita degli Studi di 
      Padova, Padova, Italy.
AD  - Medical Oncology 2, Istituto Oncologico Veneto IOV IRCSS, Padova, Italy.
FAU - Indraccolo, Stefano
AU  - Indraccolo S
AUID- ORCID: 0000-0002-4810-7136
AD  - Basic and Translational Oncology Unit, Istituto Oncologico Veneto IOV IRCCS, 
      Padova, Italy.
AD  - Department of Surgery, Oncology and Gastroeneterology, Universita degli Studi di 
      Padova, Padova, Italy.
FAU - Bonanno, Laura
AU  - Bonanno L
AUID- ORCID: 0000-0001-5218-4970
AD  - Medical Oncology 2, Istituto Oncologico Veneto IOV IRCSS, Padova, Italy. 
      laura.bonanno@iov.veneto.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220929
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 0 (Cell-Free Nucleic Acids)
SB  - IM
MH  - Humans
MH  - *Carcinoma, Non-Small-Cell Lung/drug therapy/genetics/pathology
MH  - Immune Checkpoint Inhibitors/adverse effects
MH  - *Lung Neoplasms/drug therapy/genetics/pathology
MH  - Liquid Biopsy
MH  - Disease Progression
MH  - *Cell-Free Nucleic Acids/genetics
PMC - PMC9681746
COIS- The authors declare no competing interests.
EDAT- 2022/09/30 06:00
MHDA- 2022/11/25 06:00
PMCR- 2022/09/29
CRDT- 2022/09/29 23:34
PHST- 2022/02/24 00:00 [received]
PHST- 2022/08/31 00:00 [accepted]
PHST- 2022/08/24 00:00 [revised]
PHST- 2022/09/30 06:00 [pubmed]
PHST- 2022/11/25 06:00 [medline]
PHST- 2022/09/29 23:34 [entrez]
PHST- 2022/09/29 00:00 [pmc-release]
AID - 10.1038/s41416-022-01978-1 [pii]
AID - 1978 [pii]
AID - 10.1038/s41416-022-01978-1 [doi]
PST - ppublish
SO  - Br J Cancer. 2022 Nov;127(11):2034-2042. doi: 10.1038/s41416-022-01978-1. Epub 
      2022 Sep 29.