Zentralbl Chir 2016; 141(03): 323-329
DOI: 10.1055/s-0042-101558
Originalarbeit – Thoraxchirurgie
Georg Thieme Verlag KG Stuttgart · New York

Neoadjuvante Radiochemotherapie gefolgt von kurativer Resektion im fortgeschrittenen Stadium IIIA/IIIB eines nicht kleinzelligen Lungenkarzinoms: prognostische Faktoren und Ergebnisse

Neoadjuvant Radiochemotherapy Followed by Curative Resection in Patients with Advanced Non-Small Cell Lung Cancer in Stage IIIA/IIIB: Prognostic Factors and Results
W. Schreiner
1   Chirurgische Klinik, Thoraxchirurgische Abteilung, Universitätsklinikum der Friedrich-Alexander-Universität, Erlangen-Nürnberg, Deutschland
,
W. Dudek
1   Chirurgische Klinik, Thoraxchirurgische Abteilung, Universitätsklinikum der Friedrich-Alexander-Universität, Erlangen-Nürnberg, Deutschland
,
S. Lettmaier
2   Strahlenklinik, Universitätsklinikum der Friedrich-Alexander-Universität, Erlangen-Nürnberg, Deutschland
,
S. Gavrychenkova
1   Chirurgische Klinik, Thoraxchirurgische Abteilung, Universitätsklinikum der Friedrich-Alexander-Universität, Erlangen-Nürnberg, Deutschland
,
R. Rieker
3   Pathologisches Institut, Universitätsklinikum der Friedrich-Alexander-Universität, Erlangen-Nürnberg, Deutschland
,
R. Fietkau
2   Strahlenklinik, Universitätsklinikum der Friedrich-Alexander-Universität, Erlangen-Nürnberg, Deutschland
,
H. Sirbu
1   Chirurgische Klinik, Thoraxchirurgische Abteilung, Universitätsklinikum der Friedrich-Alexander-Universität, Erlangen-Nürnberg, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
01 April 2016 (online)

Zusammenfassung

Die Rolle der nachgeschalteten Lungenresektion nach neo-adjuvanter Radiochemotherapie (RCT) bei Patienten mit einem lokal fortgeschrittenen nicht kleinzelligen Lungenkarzinom (NSCLC) ist nicht eindeutig definiert. Ziel unserer Studie war das postoperative Überleben zu untersuchen und wichtige Prognosefaktoren zu identifizieren. Im Zeitraum von Februar 2008 bis Februar 2015 wurde bei 46 Patienten mit einem lokal fortgeschrittenen NSCLC (IIIA/IIIB) eine kurative Lungenresektion nach neo-adjuvanter RCT durchgeführt. Die retrospektive Datenanalyse erfasste die präoperative Regression, die perioperative Mortalität, das postoperative Überleben, die pathohistologische Remission, das Rezidivverhalten sowie mehrere prognostische Faktoren. Eine neo-adjuvante RCT mit einer medianen Strahlendosis von 50,4 [45–60] Gy wurde bei 44 (96 %) Patienten durchgeführt. Eine partielle und/oder komplette klinische Remission war in 32 (70 %) Fällen festzustellen. Eine R0-Resektion war bei 44 (96 %) Patienten möglich. Die 30-Tage-Letalität war 4 %. Die perioperative Morbidität war bei 17 (37 %) Patienten festzustellen. Das allgemeine und tumorfreie 5-Jahres-Überleben war 47 % bzw. 45 % [im Median 58 Monate]. Das 5-Jahres-Gesamtüberleben war in der „Responder“-Gruppe mit 64 % signifikant höher als in der „Non-Responder“-Gruppe 24 % (p = 0.038). Die Prognose im Stadium des lokal fortgeschrittenen NSCLC (IIIA/IIIB) wird durch eine trimodale Therapie verbessert. Die pathohistologisch vollständige Tumorremission bleibt ein wichtiger prognostischer Faktor. Eine Differenzierung in „Responder“ und „Non-Responder“ nach neo-adjuvanter RCT hat möglicherweise eine therapeutische Konsequenz.

Abstract

The role of surgical lung resection following neo-adjuvant radio-chemotherapy (RCT) in patients with locally advanced non-small cell lung cancer (NSCLC) is yet not clearly defined. The aim of our study was to analyze the postoperative survival and to identify relevant prognostic factors. 46 patients underwent curative resections after neo-adjuvant RCT for locally advanced NSCLC (IIIA/IIIB) between February 2008 and February 2015. A retrospective data analysis regarding preoperative regression status, perioperative mortality, postoperative survival, patho-histological remission, relapse pattern and other prognostic factors was performed. A neo-adjuvant RCT with a median radiation dose of 50.4 [range, 45–60] Gy was performed in 44 (96 %) patients. Partial and/or complete regression was observed in 32 (70 %) patients. R0-resection was achieved in 44 (96 %) patients. The 30-day mortality was 4 % and the perioperative morbidity was 37 %. The overall and progression free 5-year survival rate was 47 % and respectively 45 % [in median 58 months]. The 5-year survival rate of 64 % in the “responder”-group was significantly better when compared with 24 % in the “non-responder”-group (p = 0.038). The tri-modality therapy improved the prognosis in patients with locally advanced NSCLC (stage IIIA/IIIB). The complete patho-histological remission is an important prognostic factor for better long term survival. Dividing the patients in “responder” and “non-responder” after neo-adjuvant RCT may have large therapeutically consequences in the future.

 
  • Literatur

  • 1 Eberhardt W, De Ruysscher D, Weder W et al. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer. Ann Oncol 2015; 26: 1573-1588
  • 2 Vandenbroucke E, De Ryck F, Surmont V et al. What is the role for surgery in patients with stage III non-small cell lung cancer?. Curr Opin Pulm Med 2009; 15: 295-302
  • 3 Van Meerbeeck J. The controversial role of surgery in stage III NSCLC. Lancet Oncol 2008; 9: 607-608
  • 4 Patel V, Shrager J. Which patients with Stage III non-small cell lung cancer should undergo surgical resection?. Oncologist 2005; 10: 335-344
  • 5 Tsao AS, Roth JA, Herbst RS. Surgery: Future directions in multimodality therapy for NSCLC. Nat Rev Clin Oncol 2010; 7: 10-12
  • 6 Cerfolio R, Maniscalco L, Bryant A. The treatment of patients with stage IIIA non-small cell lung cancer from N2 disease: who returns to the surgical arena and who survives. Ann Thorac Surg 2008; 86: 912-920
  • 7 Eisenhauer E, Therasse P, Bogaerts J et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45: 228-247
  • 8 Junker K, Müller K, Abker S et al. Zelluläre Veränderungen nicht-kleinzelliger Lungenkarzinome nach neoadjuvanter Therapie. Pathologe 2004; 25: 193-201
  • 9 Junker K. Therapieinduzierte Tumorregression und Regressionsgrading bei Lungenkarzinomen. Pathologe 2014; 35: 574-577
  • 10 Lococo F, Cesario A, Margaritora S et al. Long-term results in patients with pathological complete response after induction radiochemotherapy followed by surgery for locally advanced non-small-cell lung cancer. Eur J Cardiothorac Surg 2013; 43: e71-e81
  • 11 Albain K, Swann R, Rusch V et al. Radiotherapy plus chemotherapy with and without surgical resection for stage III non-small-cell lung cancer: a phase III randomized controlled trial. Lancet 2009; 374: 379-386
  • 12 Eberhardt W, Gauler T, LePechoux C et al. 10-year long-term survival (LTS) of induction chemotherapy with three cycles cisplatin/paclitaxel followed by concurrent chemoradiation cisplatin/etoposide/45 Gy (1.5 Gy bid) plus surgery in locally advanced non-small-cell lung cancer (NSCLC) – a multicenter phase-II trial (CISTAXOL). Lung Cancer 2013; 82: 83-89
  • 13 Darling G, Li F, Patsios D et al. Neoadjuvant chemoraditation and surgery improves survival outcomes compared with definitive chemoradiation in the treatment of stage IIIA N2 non-small-cell lung cancer. Eur J Cardiothorac Surg 2015; 48: 684-690
  • 14 Kim AW, Liptay MJ, Bonomi P et al. Neo-adjuvant chemoradiation for clinically advanced non-small cell lung cancer: an analysis of 233 patients. Ann Thorac Surg 2011; 92: 233-243
  • 15 Trodella L, Granone P, Valente S et al. Neoadjuvant concurrent radiochemotherapy in locally advanced (IIIA-IIIB) non-small-cell lung cancer: long-term results according to downstaging. Ann Oncol 2004; 15: 389-398
  • 16 Uy K, Darling G, Xu W et al. Improved results of induction chemoradiation before surgical intervention for selected patients with stage IIIA N2 non-small cell lung cancer. J Thorac Cardiovasc Surg 2007; 134: 188-193
  • 17 Stupp R, Mayer M, Kann R et al. Neoadjuvant chemotherapy and radiotherapy followed by surgery in selected patients with stage IIIB non-small-cell lung cancer: a multicenter phase II trial. Lancet Oncol 2009; 10: 785-793
  • 18 Isobe K, Hata Y, Sakaguchi S et al. Pathological response and prognosis of stage III non-small cell lung cancer patients treated with induction chemoradiation. Asia Pac J Clin Oncol 2012; 8: 260-266
  • 19 Friedel G, Buddach W, Dippon J et al. Phase II Trial of a trimodality regimen for stage III non-small-cell cancer using chemotherapy as induction treatment with concurrent hyperfractionated chemoradiation with carboplatin and paclitaxel followed by subsequent resection: a single-center study. J Clin Oncol 2010; 28: 942-948
  • 20 Pataer A, Kalhor N, Correa A et al. Histopathologic response criteria predict survival of patients with resected lung cancer after neoadjuvant chemotherapy. J Thorac Oncol 2012; 7: 825-832
  • 21 Shumway D, Corbin K, Salga R et al. Pathologic response rates following definitive dose image-guided chemoradiotherapy and resection for locally advanced non-small cell lung cancer. Lung Cancer 2011; 74: 446-450
  • 22 Pourel N, Santelmo N, Naafa N et al. Concurent cisplatin/etoposide plus 3D-conformal radiotherapy followed by surgery for stage IIB (superior sulcus T3N0)/III non-small cell lung cancer yields a high rate of pathological complete response. Eur J Cardiothorac Surg 2008; 33: 829-836
  • 23 Thomas M, Rübe C, Hoffknecht P et al. Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomized trial in stage III non-small-cell lung cancer. Lancet Oncol 2008; 9: 636-648
  • 24 Paul S, Mirza F, Port J et al. Survival of patients with clinical stage IIIA non-small cell lung cancer after induction therapy: age, mediastinal downstaging, and extent of pulmonary resection as independent predictors. J Thorac Cardiovasc Surg 2011; 141: 48-58
  • 25 Steger V, Walker T, Mustafi M et al. Surgery on unfavourable persistent N2–N3 non-small-cell lung cancer after trimodal therapy: do the results justify the risk?. Interact Cardiovasc Thorac Surg 2012; 15: 948-953
  • 26 Toyooka S, Kiura K, Shien K et al. Induction chemoradiotherapy is superior to induction chemotherapy for survival of non-small-cell lung cancer patients with pathological mediastinal lymph node metastasis. Interact Cardiovasc Thorac Surg 2012; 15: 954-960
  • 27 Pöttgen C, Levgrun S, Theegarten D et al. Value of 18 F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography in non-small-cell cancer for prediction of pathologic response and time to relapse after neo-adjuvant chemoradiotherapy. Clin Cancer Res 2006; 12: 97-106
  • 28 Poettgen C, Theergarten D, Eberhardt W et al. Correlation of PET/CT findings and histopathology after neoadjuvant therapy in non-small cell lung cancer. Oncology 2007; 73: 316-323
  • 29 Pöttgen C, Stuschke M, Graupner B et al. Prognostic model for long-term survival of locally advanced non-small-cell lung cancer patients after neoadjuvant radiochemotherapy and resection integrating clinical and histopathologic factors. BMC Cancer 2015; 15: 363
  • 30 Massard G, Kessler R, Wihlm J. Improved selection of winners: a working hypothesis for neo-adjuvant chemotherapy. Ann Thorac Surg 1998; 66: 300-301