Systematic endoscopic staging of mediastinum to guide radiotherapy planning in patients with locally advanced non-small-cell lung cancer (SEISMIC): an international, multicentre, single-arm, clinical trial.

Journal

The Lancet. Respiratory medicine
ISSN: 2213-2619
Titre abrégé: Lancet Respir Med
Pays: England
ID NLM: 101605555

Informations de publication

Date de publication:
11 Mar 2024
Historique:
received: 05 09 2023
revised: 22 12 2023
accepted: 16 01 2024
medline: 16 3 2024
pubmed: 16 3 2024
entrez: 15 3 2024
Statut: aheadofprint

Résumé

Systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) improves accuracy of staging in patients with early-stage non-small-cell lung cancer (NSCLC). However, patients with locally advanced NSCLC commonly undergo only selective lymph node sampling. This study aimed to determine the proportion of patients with locally advanced NSCLC in whom systematic endoscopic mediastinal staging identified PET-occult lymph node metastases, and to describe the consequences of PET-occult disease on radiotherapy planning. This prospective, international, multicentre, single-arm, international study was conducted at seven tertiary lung cancer centres in four countries (Australia, Canada, the Netherlands, and the USA). Patients aged 18 years or older with suspected or known locally advanced NSCLC underwent systematic endoscopic mediastinal lymph node staging before combination chemoradiotherapy or high-dose palliative radiotherapy. The primary endpoint was the proportion of participants with PET-occult mediastinal lymph node metastases shown following systematic endoscopic staging. The study was prospectively registered with Australian New Zealand Clinical Trials Registry, ACTRN12617000333314. From Jan 30, 2018, to March 23, 2022, 155 patients underwent systematic endoscopic mediastinal lymph node staging and were eligible for analysis. 58 (37%) of patients were female and 97 (63%) were male. Discrepancy in extent of mediastinal disease identified by PET and EBUS-TBNA was observed in 57 (37% [95% CI 29-44]) patients. PET-occult lymph node metastases were identified in 18 (12% [7-17]) participants, including 16 (13% [7-19]) of 123 participants with clinical stage IIIA or cN2 NSCLC. Contralateral PET-occult N3 disease was identified in nine (7% [2-12]) of 128 participants staged cN0, cN1, or cN2. Identification of PET-occult disease resulted in clinically significant changes to treatment in all 18 patients. In silico dosimetry studies showed the median volume of PET-occult lymph nodes receiving the prescription dose of 60 Gy was only 10·1% (IQR 0·1-52·3). No serious adverse events following endoscopic staging were reported. Our findings suggests that systematic endoscopic mediastinal staging in patients with locally advanced or unresectable NSCLC is more accurate than PET alone in defining extent of mediastinal involvement. Standard guideline-recommended PET-based radiotherapy planning results in suboptimal tumour coverage. Our findings indicate that systematic endoscopic staging should be routinely performed in patients with locally advanced NSCLC being considered for radiotherapy to accurately inform radiation planning and treatment decision making in patients with locally advanced NSCLC. None.

Sections du résumé

BACKGROUND BACKGROUND
Systematic mediastinal lymph node staging by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) improves accuracy of staging in patients with early-stage non-small-cell lung cancer (NSCLC). However, patients with locally advanced NSCLC commonly undergo only selective lymph node sampling. This study aimed to determine the proportion of patients with locally advanced NSCLC in whom systematic endoscopic mediastinal staging identified PET-occult lymph node metastases, and to describe the consequences of PET-occult disease on radiotherapy planning.
METHODS METHODS
This prospective, international, multicentre, single-arm, international study was conducted at seven tertiary lung cancer centres in four countries (Australia, Canada, the Netherlands, and the USA). Patients aged 18 years or older with suspected or known locally advanced NSCLC underwent systematic endoscopic mediastinal lymph node staging before combination chemoradiotherapy or high-dose palliative radiotherapy. The primary endpoint was the proportion of participants with PET-occult mediastinal lymph node metastases shown following systematic endoscopic staging. The study was prospectively registered with Australian New Zealand Clinical Trials Registry, ACTRN12617000333314.
FINDINGS RESULTS
From Jan 30, 2018, to March 23, 2022, 155 patients underwent systematic endoscopic mediastinal lymph node staging and were eligible for analysis. 58 (37%) of patients were female and 97 (63%) were male. Discrepancy in extent of mediastinal disease identified by PET and EBUS-TBNA was observed in 57 (37% [95% CI 29-44]) patients. PET-occult lymph node metastases were identified in 18 (12% [7-17]) participants, including 16 (13% [7-19]) of 123 participants with clinical stage IIIA or cN2 NSCLC. Contralateral PET-occult N3 disease was identified in nine (7% [2-12]) of 128 participants staged cN0, cN1, or cN2. Identification of PET-occult disease resulted in clinically significant changes to treatment in all 18 patients. In silico dosimetry studies showed the median volume of PET-occult lymph nodes receiving the prescription dose of 60 Gy was only 10·1% (IQR 0·1-52·3). No serious adverse events following endoscopic staging were reported.
INTERPRETATION CONCLUSIONS
Our findings suggests that systematic endoscopic mediastinal staging in patients with locally advanced or unresectable NSCLC is more accurate than PET alone in defining extent of mediastinal involvement. Standard guideline-recommended PET-based radiotherapy planning results in suboptimal tumour coverage. Our findings indicate that systematic endoscopic staging should be routinely performed in patients with locally advanced NSCLC being considered for radiotherapy to accurately inform radiation planning and treatment decision making in patients with locally advanced NSCLC.
FUNDING BACKGROUND
None.

Identifiants

DOI: 10.1016/S2213-2600(24)00010-9 PMID: 38490228
pubmed: 38490228
pii: S2213-2600(24)00010-9
doi: 10.1016/S2213-2600(24)00010-9
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2024 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests We declare no competing interests.

Auteurs

Daniel P Steinfort (DP)

Department of Respiratory and Sleep Medicine, Royal Melbourne Hospital, Melbourne, VIC, Australia; Faculty of Medicine, Dentistry, and Health Sciences, University of Melbourne, Melbourne, VIC, Australia. Electronic address: daniel.steinfort@mh.org.au.

Gargi Kothari (G)

The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Neil Wallace (N)

The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Nicholas Hardcastle (N)

The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia; Centre for Medical Radiation Physics, University of Wollongong, Wollongong, NSW, Australia.

Kanishka Rangamuwa (K)

Department of Respiratory and Sleep Medicine, Royal Melbourne Hospital, Melbourne, VIC, Australia; Faculty of Medicine, Dentistry, and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.

Edith M T Dieleman (EMT)

Department of Radiation Oncology, Amsterdam UMC location AMC, Amsterdam, Netherlands.

Percy Lee (P)

Department of Radiation Oncology, City of Hope National Medical Center, Los Angeles, CA, USA.

Peixuan Li (P)

Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.

Julie A Simpson (JA)

Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia.

Shaun Yo (S)

Department of Lung and Sleep, Monash Health, Melbourne, VIC, Australia.

Farzad Bashirdazeh (F)

Department of Thoracic Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Phan Nguyen (P)

Department of Thoracic Medicine, Royal Adelaide Hospital, Adelaide, SA, Australia.

Barton R Jennings (BR)

Department of Lung and Sleep, Monash Health, Melbourne, VIC, Australia.

David Fielding (D)

Department of Thoracic Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.

Laurence Crombag (L)

Department of Pulmonology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, Netherlands.

Louis B Irving (LB)

Department of Respiratory and Sleep Medicine, Royal Melbourne Hospital, Melbourne, VIC, Australia; Faculty of Medicine, Dentistry, and Health Sciences, University of Melbourne, Melbourne, VIC, Australia.

Kazuhiro Yasufuku (K)

Division of Thoracic Surgery, Toronto General Hospital, Toronto, ON, Canada.

Jouke T Annema (JT)

Department of Pulmonology, Amsterdam University Medical Centres, University of Amsterdam, Amsterdam, Netherlands.

David E Ost (DE)

Department of Pulmonary Medicine, MD Anderson Cancer Center, The University of Texas, Houston, TX, USA.

Shankar Siva (S)

The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC, Australia; Division of Radiation Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC, Australia.

Classifications MeSH