Incidence and Clinical Impact of Inflammatory Fluorodeoxyglucose Positron Emission Tomography Uptake After Neoadjuvant Pembrolizumab in Patients with Organ-confined Bladder Cancer Undergoing Radical Cystectomy.


Journal

European urology focus
ISSN: 2405-4569
Titre abrégé: Eur Urol Focus
Pays: Netherlands
ID NLM: 101665661

Informations de publication

Date de publication:
Sep 2021
Historique:
received: 27 08 2020
revised: 28 09 2020
accepted: 12 10 2020
pubmed: 12 11 2020
medline: 14 4 2022
entrez: 11 11 2020
Statut: ppublish

Résumé

Data regarding the incidence and prognostic impact of immune-related imaging changes, assessed by To evaluate the role of PET/CT to visualize the immune-related adverse events (irAEs) following pembrolizumab. From February 2017 to August 2019, in 103 patients with nonmetastatic, clinical T2-4aN0M0 bladder cancer, PET/CT scan was performed before and after neoadjuvant pembrolizumab (N = 206 scans), before radical cystectomy. PET/CT before and after neoadjuvant pembrolizumab, before radical cystectomy. We analyzed the occurrence of irAEs, evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, against the development of inflammatory FDG uptake described at PET/CT (irAEs + PET/CT). Logistic regression analyses evaluated the association between irAEs + PET/CT and the pathological response to pembrolizumab. Kaplan-Meier curves tested their association with progression-free survival (PFS) after pembrolizumab and radical cystectomy. Forty patients (39%) developed irAEs + PET/CT in several target organs. The most frequent target organs were the thyroid (N = 18), stomach (N = 14), mediastinal lymph nodes (N = 9), and lung (N = 5). These changes were clinically evident in 18 (45%) and were not associated with the pathological response, neither in terms of complete response (ypT0N0, p = 0.07) nor as downstaging to ypT≤1N0 disease (p = 0.1), although ypT0N0 responses were numerically more frequent in patients with irAEs+ PET/CT (47.5% vs 32%). Furthermore, irAE+ PET/CT events were associated with longer, not statistically significant, 24-mo PFS: 88.3% versus 76.5% (p = 0.5). Our results warrant further validation in larger datasets. We presented unique surrogate data of PET/CT that could help improve our understanding of nonclinically evident effects of ICI administration, especially in patients at the early disease stage. We evaluated the utility of PET/CT to visualize the occurrence of inflammatory changes after pembrolizumab in patients with localized bladder cancer without metastases. After immunotherapy, 39% of the patients developed

Sections du résumé

BACKGROUND BACKGROUND
Data regarding the incidence and prognostic impact of immune-related imaging changes, assessed by
OBJECTIVE OBJECTIVE
To evaluate the role of PET/CT to visualize the immune-related adverse events (irAEs) following pembrolizumab.
DESIGN, SETTING, AND PARTICIPANTS METHODS
From February 2017 to August 2019, in 103 patients with nonmetastatic, clinical T2-4aN0M0 bladder cancer, PET/CT scan was performed before and after neoadjuvant pembrolizumab (N = 206 scans), before radical cystectomy.
INTERVENTION METHODS
PET/CT before and after neoadjuvant pembrolizumab, before radical cystectomy.
OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS METHODS
We analyzed the occurrence of irAEs, evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, against the development of inflammatory FDG uptake described at PET/CT (irAEs + PET/CT). Logistic regression analyses evaluated the association between irAEs + PET/CT and the pathological response to pembrolizumab. Kaplan-Meier curves tested their association with progression-free survival (PFS) after pembrolizumab and radical cystectomy.
RESULTS AND LIMITATIONS CONCLUSIONS
Forty patients (39%) developed irAEs + PET/CT in several target organs. The most frequent target organs were the thyroid (N = 18), stomach (N = 14), mediastinal lymph nodes (N = 9), and lung (N = 5). These changes were clinically evident in 18 (45%) and were not associated with the pathological response, neither in terms of complete response (ypT0N0, p = 0.07) nor as downstaging to ypT≤1N0 disease (p = 0.1), although ypT0N0 responses were numerically more frequent in patients with irAEs+ PET/CT (47.5% vs 32%). Furthermore, irAE+ PET/CT events were associated with longer, not statistically significant, 24-mo PFS: 88.3% versus 76.5% (p = 0.5). Our results warrant further validation in larger datasets.
CONCLUSIONS CONCLUSIONS
We presented unique surrogate data of PET/CT that could help improve our understanding of nonclinically evident effects of ICI administration, especially in patients at the early disease stage.
PATIENT SUMMARY RESULTS
We evaluated the utility of PET/CT to visualize the occurrence of inflammatory changes after pembrolizumab in patients with localized bladder cancer without metastases. After immunotherapy, 39% of the patients developed

Identifiants

pubmed: 33172772
pii: S2405-4569(20)30287-X
doi: 10.1016/j.euf.2020.10.003
pii:
doi:

Substances chimiques

Antibodies, Monoclonal, Humanized 0
Fluorodeoxyglucose F18 0Z5B2CJX4D
pembrolizumab DPT0O3T46P

Banques de données

ClinicalTrials.gov
['NCT02736266']

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1092-1099

Informations de copyright

Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Auteurs

Laura Marandino (L)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Antonella Capozza (A)

Department of Nuclear Medicine-PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Marco Bandini (M)

Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy.

Daniele Raggi (D)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Elena Farè (E)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Filippo Pederzoli (F)

Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy.

Andrea Gallina (A)

Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy.

Umberto Capitanio (U)

Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy.

Marco Bianchi (M)

Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy.

Giorgio Gandaglia (G)

Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy.

Nicola Fossati (N)

Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy.

Maurizio Colecchia (M)

Department of Pathology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Patrizia Giannatempo (P)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Gianluca Serafini (G)

Department of Nuclear Medicine-PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Barbara Padovano (B)

Department of Nuclear Medicine-PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Andrea Salonia (A)

Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Alberto Briganti (A)

Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Francesco Montorsi (F)

Urological Research Institute (URI), Unit of Urology, IRCCS Ospedale San Raffaele, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy.

Alessandra Alessi (A)

Department of Nuclear Medicine-PET Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Andrea Necchi (A)

Department of Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy. Electronic address: andrea.necchi@istitutotumori.mi.it.

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Classifications MeSH