Histopathologic response criteria predict survival of patients with resected lung cancer after neoadjuvant chemotherapy

Apar Pataer, Neda Kalhor, Arlene M Correa, Maria Gabriela Raso, Jeremy J Erasmus, Edward S Kim, Carmen Behrens, J Jack Lee, Jack A Roth, David J Stewart, Ara A Vaporciyan, Ignacio I Wistuba, Stephen G Swisher, University of Texas M. D. Anderson Lung Cancer Collaborative Research Group, John Heymach, Lauren Byers, Joseph Chang, George Blumenschein, James D Cox, Wayne Hofstetter, Bingliang Fang, Frank Fossella, Bonnie Glisson, Waun Ki Hong, Kathryn Gold, Faye Johnson, Merrill S Kies, Zhongxing Liao, Steven Lin, Scott Lippmann, Ritsuko Komaki, Michael O' Reilly, Vali Papadimitrakopoulou, Katherine Pisters, David Rice, Pierre Saintigny, Anne Tsao, Garrett L Walsh, James Welsh, William N William Jr, Apar Pataer, Neda Kalhor, Arlene M Correa, Maria Gabriela Raso, Jeremy J Erasmus, Edward S Kim, Carmen Behrens, J Jack Lee, Jack A Roth, David J Stewart, Ara A Vaporciyan, Ignacio I Wistuba, Stephen G Swisher, University of Texas M. D. Anderson Lung Cancer Collaborative Research Group, John Heymach, Lauren Byers, Joseph Chang, George Blumenschein, James D Cox, Wayne Hofstetter, Bingliang Fang, Frank Fossella, Bonnie Glisson, Waun Ki Hong, Kathryn Gold, Faye Johnson, Merrill S Kies, Zhongxing Liao, Steven Lin, Scott Lippmann, Ritsuko Komaki, Michael O' Reilly, Vali Papadimitrakopoulou, Katherine Pisters, David Rice, Pierre Saintigny, Anne Tsao, Garrett L Walsh, James Welsh, William N William Jr

Abstract

Introduction: We evaluated the ability of histopathologic response criteria to predict overall survival (OS) and disease-free survival (DFS) in patients with surgically resected non-small cell lung cancer (NSCLC) treated with or without neoadjuvant chemotherapy.

Methods: Tissue specimens from 358 patients with NSCLC were evaluated by pathologists blinded to the patient treatment and outcome. The surgical specimens were reviewed for various histopathologic features in the tumor including percentage of residual viable tumor cells, necrosis, and fibrosis. The relationship between the histopathologic findings and OS was assessed.

Results: The percentage of residual viable tumor cells and surgical pathologic stage were associated with OS and DFS in 192 patients with NSCLC receiving neoadjuvant chemotherapy in multivariate analysis (p = 0.005 and p = 0.01, respectively). There was no association of OS or DFS with percentage of viable tumor cells in 166 patients with NSCLC who did not receive neoadjuvant chemotherapy (p = 0.31 and p = 0.45, respectively). Long-term OS and DFS were significantly prolonged in patients who had ≤10% viable tumor compared with patients with >10% viable tumor cells (5 years OS, 85% versus 40%, p < 0.0001 and 5 years DFS, 78% versus 35%, p < 0.001).

Conclusion: The percentages of residual viable tumor cells predict OS and DFS in patients with resected NSCLC after neoadjuvant chemotherapy even when controlled for pathologic stage. Histopathologic assessment of resected specimens after neoadjuvant chemotherapy could potentially have a role in addition to pathologic stage in assessing prognosis, chemotherapy response, and the need for additional adjuvant therapies.

Conflict of interest statement

Disclosure: The authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Schematic diagram of histologic evaluation of lung cancer tissue resected from patients treated with neoadjuvant chemotherapy.
FIGURE 2
FIGURE 2
Pathologic response to neoadjuvant chemotherapy for lung cancer. Representative examples of the histopathology of tumors associated with extensive response to treatment (A, C) or no response to treatment (B, D). Arrows indicate viable tumor cells (C, D). Original magnification: ×40 (pictures) and ×200 (insets).
FIGURE 3
FIGURE 3
Kaplan-Meier estimates of overall survival (A, C) and disease-free survival (B, D) based on pathologic stages (A, B) and percentage of viable tumor cells (C, D). A, The overall survival was significantly longer in patients with stages 0, IA, and IB than in patients with pathologic stage II, III, or IV. B, The disease-free survival was significantly longer in patients with stages 0, IA, and IB than in patients with pathologic stage II, III, or IV. C, The overall survival was significantly longer in patients with ≤10% viable tumor cells than in patients with >10% viable tumor cells. D, The disease-free survival was significantly longer in patients with ≤10% viable tumor cells than in patients with >10% viable tumor cells.

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