Induction Chemotherapy versus Chemoradiotherapy for Stage III Non-small Cell Lung Cancer

Reviewer: Nathan Jones DO
Abramson Cancer Center of the University of Pennsylvania
Last Modified: September 23, 2008

Presenter: Kristin Higgins
Presenter's Affiliation: Duke University, North Carolina
Type of Session: Scientific

Background

  • Stage IIIa non-small cell lung cancer with N2 disease represents a heterogenous group of patients ranging from microscopic lymph node involvement on staging mediastinoscopy to bulky mediastinal disease on initial staging
  • The optimal treatment for these patients remains controversial
  • As surgery alone has shown poor outcomes, pre-operative treatment appears to be more efficacious
  • There is no consensus of the superiority of chemotherapy alone versus chemoradiation in the neoadjuvant setting
  • This study sets out to compare these two approaches and to identify subgroups that may benefit from the more aggressive chemoradiation approach

Materials and Methods

  • Retrospective analysis of 101 patients treated at Duke from 1995-2006
  • All patients with pathologically demonstrated N2 disease
  • All patients underwent induction therapy consisting of chemotherapy alone or chemoradiation, in anticipation of definitive surgery
  • Multivariate analysis was performed to assess the effect of various factors on overall survival, disease-free survival and local control
  • Kaplan-Meier curves were utilized to compare local control, disease-free survival, and overall survival

Results

  • 101 patients were included in the analysis, with approximately 2/3 receiving chemoradiation
  • 3-year overall survival was 40% for all patients, with no significant difference between those receiving chemotherapy alone or chemoradiation
  • Pathologic complete response (CR) rate was 65% vs 35%, favoring those receiving chemoradiation
  • Post-operative mortality was 5% in both groups
  • There was a trend towards those patients receiving chemoradiation being more likely to ultimately undergo resection (84% vs 69% of those receiving chemotherapy alone, p=0.1)
  • All patients receiving neoadjuvant therapy were included in the analysis, regardless of whether or not surgery was ultimately performed
  • Bronchopleural fistula occurred in 7% of chemoradiation patients vs 0% of chemotherapy patients, but this did not reach statistical significance (p=0.27)
  • Multivariate analysis demonstrated that pathologic CR was significantly associated with local control and disease-free survival, but not overall survival
  • 3-year overall survival for macroscopic vs microscopic N2 disease was 48% vs 32% (p=0.2)
  • Overall survival curves among patients with lymph nodes ≥ 1cm appeared to separate favoring chemoradiation, but did not reach statistical significance (p=0.22), while among patients with lymph nodes < 1cm, the trend was in favor of chemotherapy (p=0.12)

Author's Conclusions

  • These data demonstrate no clinically significant difference in outcomes for patients with stage IIIa N2 non-small cell lung cancer based on pre-operative treatment
  • No subgroup was identified which would benefit from the combined modality approach
  • Pre-operative chemoradiation did appear to offer improved pathologic CR rate, which correlated with disease-free survival and local control, but not overall survival

Clinical/Scientific Implications

  • Optimal treatment of stage III non-small cell lung cancer remains controversial
  • EORTC 08941 demonstrated similar 5-year overall survival for patients treated with neoadjuvant chemotherapy and randomized to surgery versus definitive radiation therapy, with the suggestion that forgoing surgery results in decreased morbidity
  • These data are limited by the retrospective nature of the study, uneven sized arms, and the great potential for treatment bias between the two groups
  • Additional data are necessary before one can support the practice of categorical omission of radiation in the neoadjuvant setting for stage IIIa NSCLC patients

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