TUMEURS NEUROENDOCRINES BRONCHO-PULMONAIRES · 2020. 1. 27. · D, Granone PL, Righi L, Rusca M,...
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TUMEURS NEUROENDOCRINES BRONCHO-PULMONAIRES
Patrice RAY
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OMS 2004 ensemble de tumeurs pulmonaires très hétérogènes au pronostic très
différent
Carcinomes de bas grade et de grade intermédiare
• CARCINOIDES TYPIQUES(TC)
• CARCINOIDES ATYPIQUES (AT)
Carcinomes de haut grade
• NEUROENDOCRINES A GRANDES CELLULES (NEG)
• NEUROENDOCRINES A PETITES CELLULES (NEP)
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On ne traitera pas les CPC
• Prise ne charge le plus souvent de stades métastatiques
• RCP de pneumologie
• Exceptionnellement chirurgicaux
• Parent pauvre des essais cliniques
• Ttt par polychimiothérapie
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Tumeurs neuroendocrines à grandes cellules
• Considéré dans le pool des CBNPC et pris en charge comme tel en RCP pneumologique
• Ttt standardisé calqué sur celui du CBNPC
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Cellules NE bronchopulmonaires
• Cellules de Kultchisky
• Capteurs pour le système neuro-végétatif
– Contrôle ventilation et perfusion
– Mécano et chémorécepteurs
– Métabolisent L DOPA, 5 hydroxytryptophane
– Rôle dans le développement de l’arbre bronchique
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Neuroendocrine tumor epidemiology
Cancer Volume 113, Issue 10, pages 2655-2664, 13 OCT 2008 DOI: 10.1002/cncr.23883 http://onlinelibrary.wiley.com/doi/10.1002/cncr.23883/full#fig1
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Epidémiologie
• Tumeurs rares
• Incidence: 0,2 à 2/100000 pour les carcinoides
• Augmentation régulière
• Découverte entre 40 et 60 ans
• KC du poumon le plus fréquent chez le jeune
• TC/AC: 8/1
• Carcinoides: 2% des tumeurs pulmonaires
• Lien avec le tabac
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Classification anatomo pathologique
WHO
2004
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Grading the neuroendocrine tumors of the lung: an evidence-based proposal.
Rindi G, Klersy C, Inzani F, Fellegara G, Ampollini L, Ardizzoni A, Campanini N, Carbognani P, De Pas TM, Galetta D, Granone PL, Righi L, Rusca M, Spaggiari L, Tiseo M, Viale G, Volante M, Papotti M, Pelosi G.
Endocr Relat Cancer. 2013 Dec 16;21(1):1-16. doi: 10.1530/ERC-13-0246. Print 2014 Feb.
399 malades opérés suivis pendant au moins un an, 21 variables
Différences de survie maximale (Cox)
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Figure 2 Kaplan–Meier survival curves for lung neuroendocrine tumors.
G Rindi et al. Endocr Relat Cancer 2014;21:1-16
© 2014 Society for Endocrinology
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Grading parameters with cutoff definitions based on present cohort findings
grade MITOSES Ki 67% NECROSE %
G 1 2 <4 no
G 2 2-47 4-25 <10
G 3 >47 >25 >10
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Figure 5 Kaplan–Meier survival curves for lung neuroendocrine tumors overall, by the new grading system inclusive of the three variables Ki67, mitosis, and necrosis as from Table 5
(n=348): 95% CIs are shown.
G Rindi et al. Endocr Relat Cancer 2014;21:1-16
© 2014 Society for Endocrinology
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Immunomarquages
CHROMOGRANIN A
SYNAPTOPHYSIN
CD56
Permettent la confirmation NE sur petites biopsies
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Classification WHO 2015
Introduction de la DIPNECH: diffuse idiopathic Pulmonary Neuroendocrine cell hyperplasia
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Neuroendocrine cell hyperplasia in children with idiopathic interstitial
pneumonia Nagehan Emiralioglu, Diclehan Orhan, Nural Kiper, Güzin Cinel, Ebru Yalçin, Deniz Dogru Ersöz, Ugur
Özçelik DOI: 10.1183/13993003.congress-2015.PA3848 Published 1 September 2015
Conclusion: We have found markedly increased numbers of NE cells with bombesin-like immunoreactivity in the lung biopsies of patients with idiopathic IP.However, the significance of PNEC hyperplasia and the mechanisms involved are unknown.This study is the first and may also provide insight to the potential role of NE cells in ILD other than NEHI.
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The IASLC Lung Cancer Staging Project: Proposals for the Inclusion of Broncho-Pulmonary Carcinoid
Tumors in the Forthcoming (Seventh) Edition of the TNM Classification for Lung Cancer William D. Travis, MD, Dorothy J. Giroux, MS, Kari Chansky, MS, John Crowley, PhD, Hisao Asamura, MD, Elisabeth Brambilla, MD,
PhD, James Jett, MD, Catherine Kennedy, Ramon Rami-Porta, MD, Valerie W. Rusch, MD, Peter Goldstraw, MB, FRCS
Journal of Thoracic Oncology
Volume 3, Issue 11, Pages 1213-1223 (November 2008)
DOI: 10.1097/JTO.0b013e31818b06e3
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Manifestations Cliniques
Dépendent du site de la lésion: centrale ou périphérique, toux, hémoptysie, infections
Sd sécrétoire: 1% au dg, 5%dans le suivi
diarrhées flush bronchospasme
Sd de Cushing 6%
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Algorithm for diagnosis of pulmonary neuroendocrine tumor.
M. E. Caplin et al. Ann Oncol 2015;26:1604-1620
© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected]
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Forme centrale: atélectasie
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Octréoscan
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Formes centrales: faut il faire des
biopsies bronchiques?
Risque hémorragique (0,3% de décès)
Risque d’erreur sur petites biopsies
entre CA et CT
entre carcinoide et CPC et épidermoide
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Nodule pulmonaire
• Lésion ronde, non spiculée
• Lentement évolutive si surveillance pour les nodules entre 5 et 10mm
• PET scan
• Ponction sous ctrl TDM ou chirurgie d’emblée (mais dans ce cas, bilan d’extension classique)
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Algorithm for diagnosis of pulmonary neuroendocrine tumor.
M. E. Caplin et al. Ann Oncol 2015;26:1604-1620
© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected]
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SCINTIGRAPHIES
PET scan
• Caméra 3 dimensions
• Seuil de détection 8mm
• Bonne spécificité
• Mauvaise sensibilité
• Détection N2: Se 35%
OCTREOSCAN
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TEP Gallium DOTA
• Caméra 3 dimension
• Seuil de détection 8mm
• Indépendant du sd sécrétoire
• Bonnes Sensibilité et spécificité
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TEP/DOTATATE
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Algorithm for diagnosis of pulmonary neuroendocrine tumor.
M. E. Caplin et al. Ann Oncol 2015;26:1604-1620
© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected]
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TTT des formes localisées T1-T4,
N0-N2 M0 • Chirurgie: lobectomie, pneumonectomie, segmentectomie, resection
anastomose pour les tumeurs centrales, curage ganglionnaire
• Rôle des chirurgies sous lobaires?
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TTT des formes localisées T1-T4,
N0-N2 M0
TTT post opératoire: généralement non en
Europe, mais recommandé aux USA chimio RT
Pour les formes non opérables: radiofréquence, RT stéréotaxique, endoscopique
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Multidisciplinary management of advanced lung
neuroendocrine tumors. Jour Thor disease April 2015
Filosso PL1, Ferolla P1,
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Traitement des formes avancées
• Stratégie de ttt se rapprochant des formes digestives
• 25% des cas
• Sd sécrétoire:
Rare, 10 % des cas
Métatastases hépatiques
atypiques
Ttt habituels, analogues somatostatines
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Traitement des formes avancées carcinoïdes typiques peu agressifs
• Surveillance
• Ttt locaux:
Chirurgie
Radiothérapie…
• Analogues de la somatostatine:
études Promid et Clarinet sphère digestive
Peu de données dans le poumon: cohorte de l’IGR 18 malades, PFS 17 mois (50 mois CT)
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Traitement des formes avancées: atypiques, formes agressives
• Contrôler le sd sécrétoire: analogues de la somatostatine, protocoles identiques avec les tumeurs digestives
• Analogues même si tumeurs non sécrétantes (PROMID et CLARINET)
• Effet prédictif de la diminution du taux de chromogranine A
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Date of download: 3/26/2016
Copyright © American College of Chest Physicians. All rights reserved.
From: Everolimus Plus Octreotide Long-Acting Repeatable in Patients With Advanced Lung Neuroendocrine
Tumors: Analysis of the Phase 3, Randomized, Placebo-Controlled RADIANT-2 Study
Chest. 2013;143(4):955-962. doi:10.1378/chest.12-1108
Progression-free survival in patients with primary lung neuroendocrine tumors (NETs). P value is obtained from the one-sided log-
rank test. HR is obtained from unadjusted Cox model. A, Central radiology review. B, Local investigator review. E + O = everolimus
plus octreotide; HR = hazard ratio; LAR = long-acting repeatable; P + O = placebo plus octreotide.
Figure Legend:
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Everolimus for the treatment of advanced, non-functional neuroendocrine
tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study (31% de tumeurs pulmonaires)
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Lung: SSA may be considered first-line therapy:
ENETS 2016
= ?
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Multicenter 3-arm trial to evaluate the efficacy and safety of
Pasireotide LAR or Everolimus alone or in combination in patients with well differentiated neuroendocrine carcinoma
of the lung and thymus -LUNA Trial
• PARISEOTIDE (analogue sst 1,2,3,5)
• EVEROLIMUS
• EVEROLIMUS ET PARISEOTIDE
• 3 BRAS, 120 MALADES, PHASE 2
• OP: nbr de malades non en progression à 1 an
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MTC PPGL Lung Ileum Pancreas
Somatostatin
Analogues
- - Expert
Consensus
Approved Approved
LAN 120
Chemotherapy - Expert
Consensus
Expert
Consensus
- Approved
PRRT - Approved Expert
Consensus
Approved ?
Lutathera
Expert
Consensus
Everolimus - Approved Approved Approved
TKI Approved
Vandetanib
Cabozantinib
Expert
Consensus
- - Approved
Sunitinib
NET : approvals or expert consensus
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MERCI