Chest
Volume 120, Issue 5, November 2001, Pages 1584-1591
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Clinical Investigations
LUNG CANCER
Grading of Tumor Regression in Non-small Cell Lung Cancer: Morphology and Prognosis

https://doi.org/10.1378/chest.120.5.1584Get rights and content

Objective

Different types of multimodality therapy, including chemoradiotherapy and surgery, increasingly are being used for the treatment of patients with locally advanced non-small cell lung cancer (NSCLC; stages IIIA and IIIB). In this context, the applicability of a morphologic regression grading and its prognostic value were investigated.

Patients and methods

In a multicenter phase II trial, 54 patients with locally advanced NSCLC received neoadjuvant bimodality treatment (ie, two cycles of ifosfamide, carboplatin, and etoposide, followed by twice-daily radiation up to 45 Gy with simultaneous administration of carboplatin and vindesine). Forty patients underwent resections. Using the corresponding resection specimens of the primary and regional lymph nodes, the following regression grading was established: grade I, no regression or only spontaneous tumor regression; grade II, morphologic evidence of therapy-induced tumor regression with at least 10% (grade IIa) or< 10% (grade IIb) vital tumor tissue; and grade III, complete tumor regression with no evidence of vital tumor tissue. Regression grading then was correlated with the survival time.

Results

Three tumors were classified as regression grade I, 10 were classified as regression grade IIa, 20 were classified as regression grade IIb, and 7 were classified as regression grade III. Patients with tumors of regression grades IIb or III showed significantly longer survival times than those with tumors of regression grades I or IIa (median survival time, 36 vs 14 months, respectively; 3-year survival rate, 52% vs 9%, respectively; p = 0.02). These survival times were also compared for patients who had undergone complete resection (median survival time, not reached vs 23 months, respectively; 3-year survival rate, 56% vs 11%, respectively; p = 0.03). The presurgical clinical response after patients had received neoadjuvant multimodality therapy had no predictive value in assessing the extent of therapy-induced tumor regression in the resection specimen.

Conclusions

After neoadjuvant therapy of patients with NSCLC, the proposed tumor regression grading was of predictive value for long-term survival. Beyond the achievement of complete tumor resection (R0), a therapy-induced tumor regression of < 10% of vital tumor tissue is pivotal for superior long-term outcomes.

Section snippets

Eligibility Criteria

The study was approved by the ethical committee of the University of Mu¨nster, Germany.

From April 1992 to September 1995, patients with NSCLC stage IIIA (tumor stage T1–3N2M0) with histologically confirmed N2 status or stage IIIB (tumor stage T4N1–3M0/T1–4N3M0) were enrolled in the study. Patients with involvement of the supraclavicular lymph nodes or who had positive test results for pleural effusion were not eligible. Further requirements were a favorable medical condition (Eastern

Results

From April 1992 to September 1995, 54 patients (5 women and 49 men) with a median age of 57 years (age range, 37 to 69 years) were enrolled in the study. Twenty-five patients had stage IIIA disease, and 29 patients had stage IIIB disease. Histology identified 36 tumors as squamous cell carcinomas and 18 tumors as adenocarcinomas (Table 1). In 40 patients in the study population, surgery was performed after the completion of induction therapy. Of the remaining 14 patients, 3 were technically

Discussion

In a phase II study, 54 patients with locally advanced NSCLC (stages IIIA and IIIB) were treated with neoadjuvant chemotherapy followed by radiochemotherapy. In 40 of these patients, surgery was performed.10 Comparing the population analyzed here with 50 patients with previously untreated NSCLCs, we were able to show that spontaneous and therapy-induced tumor regression can be distinguished with high certainty.5 Several morphologic changes that were due to neoadjuvant chemoradiotherapy were

Acknowledgment

The authors thank Professor W. Bo¨cker (Mu¨nster, Germany), Professor K.-F. Bu¨rrig (Hildesheim, Germany), Dr. W.-P. Kunze (Hemer, Germany), and Professor W. Lang (Hannover, Germany) for their kind support in contributing biopsy and resection specimens to this study, and Dr. A. Heinecke (Mu¨nster, Germany) for his support in statistical analysis. This article is dedicated to Professor Dr. K.-M. Mu¨ller (Bochum, Germany) on the occasion of his 60th birthday.

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    This research was supported by the North Rhine Westfalian Cancer Society, Du¨sseldorf, Germany.

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