Download PDF
CC BY-NC-ND 4.0 · Pneumologie 2025; 79(01): 16-24
DOI: 10.1055/a-2465-4830
Konsensuspapier

Neoadjuvante Therapie des resektablen, nicht-kleinzelligen Lungenkarzinoms

Neoadjuvant therapy for resectable non-small cell lung cancer
Katrin Welcker
1   Klinik für Thoraxchirurgie, Kliniken Maria Hilf GmbH, Mönchengladbach, Deutschland (Ringgold ID: RIN39678)
,
Danny Jonigk
2   Institut für Pathologie, Universitätsklinikum Aachen, Aachen, Deutschland (Ringgold ID: RIN39058)
,
Cornelia Kropf-Sanchen
3   Sektion Pneumologie, Universitätsklinikum Ulm Klinik für Innere Medizin II, Ulm, Deutschland (Ringgold ID: RIN216560)
,
Amanda Tufman
4   Medizinische Klinik V, LMU Faculty of Medicine, München, Deutschland (Ringgold ID: RIN54187)
,
Andreas Draube
5   Klinik für Hämatologie und Onkologie, Innere Medizin IV, St. Vinzenz Hospital, Köln, Deutschland (Ringgold ID: RIN558389)
,
Albrecht Stenzinger
6   Molekularpathologisches Zentrum, UniversitätsKlinikum Heidelberg Pathologisches Institut, Heidelberg, Deutschland (Ringgold ID: RIN155995)
,
Mohamed Zaatar
7   Klinik für Thoraxchirurgie (Thoraxzentrum), Evangelische Lungenklinik Berlin, Berlin, Deutschland (Ringgold ID: RIN89525)
,
Michael Thomas
8   Thorakale Onkologie, Thoraxklinik am Universitätsklinikum Heidelberg, Heidelberg, Deutschland (Ringgold ID: RIN14996)
› Author Affiliations
› Further Information
Also available at
   Permissions and Reprints

Zusammenfassung

Die Behandlungsaussichten beim nicht-kleinzelligen Lungenkarzinom (NSCLC) haben sich durch die Integration von Immuncheckpoint-Inhibitoren in multimodale Therapiekonzepte deutlich erweitert. Aktuell rücken kombinierte, Immuncheckpoint-Inhibitor-basierte Therapiekonzepte auch in frühe, resektable Stadien des NSCLC vor. Die neoadjuvante und perioperative Chemoimmuntherapie eröffnet einen vielversprechenden neuen präoperativen Behandlungsansatz, impliziert aber auch einige neue Fragen und Herausforderungen. Mit den erweiterten perioperativen Therapiemöglichkeiten und der Aussicht auf eine weitere mögliche Verbesserung der Rezidivfreiheit nach Tumorresektion verschiebt sich damit auch die Notwendigkeit, therapierelevante Befunde zur Bildgebung, molekularen und histopathologischen Diagnostik frühzeitig und umfassend zu erheben, weiter nach vorne: Alle Patienten mit Lungenkarzinom sollen unabhängig von der Therapieintention in einem interdisziplinären Tumorboard mit thoraxonkologischer Schwerpunktexpertise vorgestellt werden. Dies ist regelhaft in zertifizierten Lungenkrebszentren gegeben.

Ein standardisiertes Vorgehen trägt zur optimierten prätherapeutischen Diagnostik bei und erleichtert die Abstimmung für das bestmögliche multimodale Vorgehen im interdisziplinären Tumorboard. Bei zentral gelegenen resektablen Tumoren erhöhen sich durch die neoadjuvante Behandlung z.B. die Aussichten auf ein möglichst parenchymsparendes Vorgehen. Einige Fragestellungen lassen sich noch nicht abschließend beantworten. Die perioperative Systemtherapie mit molekular-zielgerichteten und Immuncheckpoint-Inhibitoren ist Gegenstand zahlreicher laufender Studien. Die erhebliche Dynamik bei den Neuzulassungen und die Entwicklung perioperativer Therapiekonzepte macht eine kontinuierliche Anpassung der diagnostischen Algorithmen und Standards erforderlich. Die Integration in die prächirurgische Standardroutine macht eine zügige Einordnung der relevanten Befunde sowie enge Abstimmung zwischen den diagnostischen und interventionellen Fachdisziplinen unerlässlich.

Abstract

Treatment perspectives for non-small cell lung cancer (NSCLC) have been significantly expanded by the integration of immune checkpoint inhibitors into multimodal therapy concepts. Currently, combined, immune checkpoint-inhibitor-based therapy concepts are also advancing into early, resectable stages of NSCLC. Neoadjuvant and perioperative chemoimmunotherapy opened up a promising new preoperative treatment approach, but also raises some new questions and challenges. With the expanded perioperative treatment options and the perspective on a further improvement in the absence of recurrence after tumor resection, there is push towards comprehensively collecting therapy-relevant findings for imaging, molecular and histopathological diagnostics at an early stage. All patients with lung carcinoma, regardless of the therapy intention, should be presented to an interdisciplinary tumor board with thoracic oncological expertise. This is regularly given in certified lung cancer centers.

A standardized procedure contributes to optimized pre-therapeutic diagnostics and facilitates coordination for the best possible multimodal approach in the interdisciplinary tumor board. In the case of centrally located resectable tumors, for example, neoadjuvant treatment increases the chances of a procedure that is as parenchymal sparing as possible. Some questions cannot yet be answered conclusively. Perioperative systemic therapy with molecular-targeted and immune checkpoint inhibitors is the subject of numerous ongoing studies. The considerable dynamics in newly approved therapies and the development of perioperative therapy concepts require continuous adaptation of diagnostic algorithms and standards. Integration into standard pre-surgical routine makes rapid classification of the relevant findings as well as close coordination between the diagnostic and interventional disciplines essential.

Schlüsselwörter

neoadjuvant - kombinierte Chemoimmuntherapie - multimodal - interdiszipliniäres Tumorboard - Chirurgie - Regressionsgrading

Keywords

neoadjuvant - combined chemo immunotherapy - multimodal - interdisciplinary tumor board - surgery - regression gradient


Publication History

Received: 11 June 2024

Accepted after revision: 25 October 2024

Article published online:
06 December 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

 

  • Literatur

  • 1 Liang Y, Wakelee HA. Adjuvant chemotherapy of completely resected early stage non-small cell lung cancer (NSCLC). Transl Lung Cancer Res 2013; 2: 403-410
    CrossrefPubMedSearch in Google Scholar
  • 2 Taylor MD, Nagji AS, Bhamidipati CM. et al. Tumor recurrence after complete resection for non-small cell lung cancer. Ann Thorac Surg 2012; 93: 1813-1820
    CrossrefPubMedSearch in Google Scholar
  • 3 NSCLC Meta-analysis Collaborative Group. Preoperative chemotherapy for non-small-cell lung cancer: a systematic review and meta-analysis of individual participant data. Lancet 2014; 383: 1561-1571
    CrossrefPubMedSearch in Google Scholar
  • 4 Forde P, Spicer J, Lu S. et al. Neoadjuvant Nivolumab plus Chemotherapy in Resectable Lung Cancer. N Engl J Med 2022; 386: 1973-1985
    CrossrefPubMedSearch in Google Scholar
  • 5 Provencio Pulla M, Forde PM, Spicer J. et al. Neoadjuvant nivolumab plus chemotherapy in the phase 3 CheckMate 816 study: 3-year results by tumor PD-L1 expression. Annals of Oncology 2023; 34 (Suppl. 2) S1254-S1335
    CrossrefPubMedSearch in Google Scholar
  • 6 ESMO: EMA Recommends Extension of Indications for Nivolumab (09.06.2023). Accessed August 01, 2023 at: https://www.esmo.org/oncology-news/ema-recommends-extension-of-indications-for-nivolumab2
    PubMed
  • 7 Spicer JD. et al. Overall survival in the KEYNOTE-671 study of perioperative pembrolizumab for early-stage non-small-cell lung cancer (NSCLC). Annals of Oncology 2023; 34 (Suppl. 2) S1297-S1298
    CrossrefPubMedSearch in Google Scholar
  • 8 Wakelee H, Liberman M, Kato T. et al. Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer. N Engl J Med 2023; 389: 491-503
    CrossrefPubMedSearch in Google Scholar
  • 9 Pillay B, Wootten AC, Crowe H. et al. The impact of multidisciplinary team meetings on patient assessment, management and outcomes in oncology settings: A systematic review of the literature. Cancer Treat Rev 2016; 42: 56-72
    CrossrefPubMedSearch in Google Scholar
  • 10 Friedman EL, Kruklitis RJ, Patson DM. et al. Effectiveness of a thoracic multidisciplinary clinic in the treatment of stage III non-small-cell lung cancer. J Multidiscip Healthc 2016; 9: 267-274
    CrossrefPubMedSearch in Google Scholar
  • 11 Stone E, Rankin N, Kerr S. et al. Does presentation at multidisciplinary team meetings improve lung cancer survival? Findings from a consecutive cohort study. Lung Cancer 2018; 124: 199-204
    CrossrefPubMedSearch in Google Scholar
  • 12 Leitlinienprogramm Onkologie | S3-Leitlinie Lungenkarzinom: Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms. AWMF-Registernummer: 020-007OL, Version 3.0 – März. 2024
    PubMedSearch in Google Scholar
  • 13 Onkopedia-Leitlinie „Lungenkarzinom, nicht-kleinzellig (NSCLC)”, Stand: August. 2023
    PubMedSearch in Google Scholar
  • 14 Brunelli A, Kim AW, Berger KI. et al. Physiologic evaluation of the patient with lung cancer being considered for resectional surgery: Diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2013; 143 (Suppl. 5) e166S-e190
    CrossrefPubMedSearch in Google Scholar
  • 15 Daly ME, Singh N, Ismaila N. et al. Management of Stage III Non-Small-Cell Lung Cancer: ASCO Guideline. J Clin Oncol 2021; 40: 1356-1384
    CrossrefPubMedSearch in Google Scholar
  • 16 NICE guideline: Lung cancer: diagnosis and management (last updated: 26 July 2023). www.nice.org.uk/guidance/ng122
    PubMed
  • 17 Ofiara LM, Navasakulopong A, Beaudoni S. et al. Optimizing tissue sampling for the diagnosis, subtyping, and molecular analysis of lung cancer. Front Oncol 2014; 4: 1-7
    CrossrefPubMedSearch in Google Scholar
  • 18 Solomon BJ. et al. ALINA: efficacy and safety of adjuvant alectinib versus chemotherapy in patients with early-stage ALK+ non-small cell lung cancer (NSCLC). Annals of Oncology 2023; 34 (Suppl. 2) S1295-S1296
    CrossrefPubMedSearch in Google Scholar
  • 19 Pennell NA, Mutebi A, Zhou ZY. et al. Economic Impact of Next-Generation Sequencing Versus Single-Gene Testing to Detect Genomic Alterations in Metastatic Non-Small-Cell Lung Cancer Using a Decision Analytic Model. JCO Precis Oncol 2019; 4: 1-9
    CrossrefPubMedSearch in Google Scholar
  • 20 Sheffield B, Eaton K, Emond B. et al. Cost Savings of Expedited Care with Upfront Next-Generation Sequencing Testing versus Single-Gene Testing among Patients with Metastatic Non-Small Cell Lung Cancer Based on Current Canadian Practices. Curr Oncol 2023; 30: 2348-2365
    CrossrefPubMedSearch in Google Scholar
  • 21 Schildhaus HU. Der prädiktive Wert der PD-L1-Diagnostik. Pathologe 2018; 39: 498-519
    CrossrefPubMedSearch in Google Scholar
  • 22 Scheel AH, Dietel M, Heukamp LC. et al. Predictive PD-L1 immunohistochemistry for non-small cell lung cancer: Current state of the art and experiences of the first German harmonization study. Pathologe 2016; 37: 557-567
    CrossrefPubMedSearch in Google Scholar
  • 23 Scheel AH, Baenfer G, Baretton G. et al. Interlaboratory concordance of PD-L1 immunohistochemistry for non-small-cell lung cancer. Histopathology 2018; 72: 449-459
    CrossrefPubMedSearch in Google Scholar
  • 24 Hirsch FR, McElhinny A, Stanforth D. et al. PD-L1 immunohistochemistry assays for lung cancer: Results from phase 1 of the blueprint PD-L1 IHC assay comparison project. J Thorac Oncol 2018; 12: 208-222
    CrossrefPubMedSearch in Google Scholar
  • 25 Lardinois D, De Leyn P, Van Schil P. et al. ESTS guidelines for intraoperative lymph node staging in non-small cell lung cancer. Eur J Cardiothorac Surg 2006; 30: 787-792
    CrossrefPubMedSearch in Google Scholar
  • 26 Heymach JV, Harpole D, Mitsudomi T. et al. AEGEAN: A phase 3 trial of neoadjuvant durvalumab + chemotherapy followed by adjuvant durvalumab in patients with resectable NSCLC. Cancer Res 2023; 83 Abstract CT005
    CrossrefPubMedSearch in Google Scholar
  • 27 Cascone T, Awad MM, Spicer JD. et al. CheckMate 77T: Phase III study comparing neoadjuvant nivolumab (NIVO) plus chemotherapy (chemo) vs neoadjuvant placebo plus chemo followed by surgery and adjuvant NIVO or placebo for previously untreated, resectable stage II–IIIb NSCLC. Annals of Oncology 2023; 34 (Suppl. 2) S1295
    CrossrefPubMedSearch in Google Scholar
  • 28 Dornington JS. Surgical Insights Are Essential to Integration of Immune Therapy in Resectable NSCLC. JTO Clin Res Rep 2021; 2: 100240
    PubMedSearch in Google Scholar
  • 29 Travis WD, Dacic S, Wistuba I. et al. IASLC Multidisciplinary Recommendations for Pathologic Assessment of Lung Cancer Resection Specimens After Neoadjuvant Therapy. J Thorac Oncol 2020; 15: 709-740
    CrossrefPubMedSearch in Google Scholar
  • 30 Junker K. Therapieinduzierte Tumorregression und Regressionsgrading bei Lungenkarzinomen. Der Pathologe 2014; 35: 574-577
    CrossrefPubMedSearch in Google Scholar
  • 31 Yoshida Y, Nitadori JI, Shinozaki-Ushiku A. et al. Micropapillary histological subtype in lung adenocarcinoma of 2cm or less: impact on recurrence and clinical predictors. Gen Thorac Cardiovasc Surg 2017; 65: 273-279
    CrossrefPubMedSearch in Google Scholar