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.
BACKGROUND
Outcome of consecutive patients with locally advanced non-small cell lung cancer and histopathologically proven mediastional lymph node metastases treated with induction chemotherapy, neoadjuvant radiochemotherapy and thoracotomy at the West German Cancer Center between 08/2000 and 06/2012 was analysed. A clinico-pathological prognostic model for survival was built including partial or complete response according to computed tomography imaging (CT) as clinical parameters as well as pathologic complete remission (pCR) and mediastinal nodal clearance (MNC) as histopathologic factors.


METHODS
Proportional hazard analysis (PHA) and recursive partitioning analysis (RPA) were used to identify prognostic factors for survival. Long-term survival was defined as survival ≥ 36 months.


RESULTS
A total of 157 patients were treated, median follow-up was 97 months. Among these patients, pCR and MNC were observed in 41 and 85 patients, respectively. Overall survival was 56 ± 4% and 36 ± 4% at 24 and 60 months, respectively. Sensitivities of pCR and MNC to detect long-term survivors were 38% and 61%, specificities were 84% and 52%, respectively. Multivariable survival analysis revealed pCR, cN3 category, and gender, as prognostic factors at a level of α < 0.05. Considering only preoperative available parameters, CT response became significant. Classifying patients with a predicted hazard above the median as high risk group and the remaining as low risk patients yielded better separation of the survival curves by the inclusion of histopathologic factors than by preoperative factors alone (p < 0.0001, log rank test). Using RPA, pCR was identified as the top prognostic factor above clinical factors (p = 0.0006). No long term survivors were observed in patients with cT3-4 cN3 tumors without pCR.


CONCLUSIONS
pCR is the dominant histopathologic response parameter and improves prognostic classifiers, based on clinical parameters. The validated prognostic model can be used to estimate individual prognosis and forms a basis for patient selection for treatment intensification.
Department of Radiotherapy, West German Cancer Center, University of Duisburg-Essen, Essen, Germany. christoph.poettgen@uk-essen.de.
Christoph
C
Pöttgen
Department of Radiotherapy, West German Cancer Center, University of Duisburg-Essen, Essen, Germany. martin.stuschke@uk-essen.de.|German Cancer Consortium (DKTK), Heidelberg, Germany. martin.stuschke@uk-essen.de.
Martin
M
Stuschke
Department of Radiotherapy, West German Cancer Center, University of Duisburg-Essen, Essen, Germany. brittgraupner@googlemail.com.
Britta
B
Graupner
Institute of Pathology and Neuropathology, West German Cancer Center, University of Duisburg-Essen, Essen, Germany. dirk.theegarten@uk-essen.de.
Dirk
D
Theegarten
Department of Medical Oncology, West German Cancer Center, University of Duisburg-Essen, Essen, Germany. thomas.gauler@uk-essen.de.
Thomas
T
Gauler
Institute of Cell Biology (Cancer Research), University of Duisburg-Essen, Essen, Germany. verena.jendrossek@uni-due.de.
Verena
V
Jendrossek
Division of Interventional Pneumology, Ruhrlandklinik,West German Lung Center, University of Duisburg-Essen, Essen, Germany. lutz.freitag@ruhrlandklinik.uk-essen.de.
Lutz
L
Freitag
Department of Radiotherapy, West German Cancer Center, University of Duisburg-Essen, Essen, Germany. jehad.abu-jawad@uk-essen.de.
Jehad Abu
JA
Jawad
Department of Radiotherapy, West German Cancer Center, University of Duisburg-Essen, Essen, Germany. eleni.gkika@uk-essen.de.
Eleni
E
Gkika
Institute of Pathology and Neuropathology, West German Cancer Center, University of Duisburg-Essen, Essen, Germany. jeremias.wohlschlaeger@uk-essen.de.
Jeremias
J
Wohlschlaeger
Division of Thoracic Surgery and Thoracic Endoscopy, Ruhrlandklinik, West German Lung Center, University of Duisburg-Essen, Essen, Germany. stefan.welter@ruhrlandklinik.uk-essen.de.
Stefan
S
Welter
Department of Medical Oncology, West German Cancer Center, University of Duisburg-Essen, Essen, Germany. matthias.hoiczyk@uk-essen.de.
Matthias
M
Hoiczyk
Department of Medical Oncology, West German Cancer Center, University of Duisburg-Essen, Essen, Germany. martin.schuler@uk-essen.de.|Division of Thoracic Oncology, Ruhrlandklinik, West German Lung Center, University of Duisburg-Essen, Essen, Germany. martin.schuler@uk-essen.de.|German Cancer Consortium (DKTK), Heidelberg, Germany. martin.schuler@uk-essen.de.
Martin
M
Schuler
Division of Thoracic Surgery and Thoracic Endoscopy, Ruhrlandklinik, West German Lung Center, University of Duisburg-Essen, Essen, Germany. georgios.stamatis@ruhrlandklinik.uk-essen.de.
Georgios
G
Stamatis
Department of Medical Oncology, West German Cancer Center, University of Duisburg-Essen, Essen, Germany. wilfried.eberhardt@uni-essen.de.|Division of Thoracic Surgery and Thoracic Endoscopy, Ruhrlandklinik, West German Lung Center, University of Duisburg-Essen, Essen, Germany. wilfried.eberhardt@uni-essen.de.
Wilfried
W
Eberhardt
D000328:Adult; D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology* / Q000628:therapy*; D059186:Chemoradiotherapy, Adjuvant; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000379:methods; D011379:Prognosis; D016016:Proportional Hazards Models; D012307:Risk Factors; D016019:Survival Analysis; D013908:Thoracotomy; D016896:Treatment Outcome