Study Validates Prognostic Role of Tumor Lymphocytic Infiltration in Resectable Non–Small Cell Lung Cancer

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Lymphocytic infiltration was associated with histology—10% in squamous cell carcinoma and approximately 4% in adenocarcinoma and other histologic types of NSCLC

The benefit from platinum-based adjuvant chemotherapy in non–small cell lung cancer (NSCLC) was demonstrated in four randomized trials (International Adjuvant Lung Cancer Trial [IALT], Canadian JBR.10 trial, Cancer and Leukemia Group B [­CALGB] 9633 trial, and Adjuvant Navelbine International Trialist Association [ANITA] trial).1-4 Central histopathologic review by one or two specialized pathologists on 1,587 NSCLC cases showed the following histology distribution: 624 adenocarcinoma, 727 squamous cell carcinomas, and 236 other types of NSCLC.

Concurrently with histology, the LACE-Bio team assessed the presence of lymphocytic infiltration, which has been shown as a borderline favorable prognostic factor on overall survival in the IALT study. Therefore, the LACE-Bio group performed a validation of the results concerning the prognostic role of lymphocytic infiltration on the ANITA, JBR.10, and CALGB 9633 trials.

The study was presented by ­Elisabeth Brambilla, MD, PhD, of Grenoble University Hospital, Grenoble, France, at the 3rd European Lung Cancer Conference.5

Prognostic Role of Lymphocytic Infiltration

The study authors considered lymphocytic infiltration to be intense, mimicking lymph node lymphocytic density, or not intense (null, mild, or moderate). A logistic model, stratified on trial, was used to study the correlation of lymphocytic infiltration with other covariables. Since there was no evidence of a different prognostic role in the chemotherapy and control arms in the IALT study, the prognostic values were studied for validation in all patients with adjustment for the treatment arm. Prognostic analyses were performed with Cox models stratified by studies and adjusted for treatment, sex, age, performance status, type of surgery, stage, and histology.

Among 804 analyzed patients, 763 were valuable for lymphocytic infiltration assessment. Intense lymphocytic infiltration was observed in 6% of patients in the validation set, compared to 11% in the IALT study. Lymphocytic infiltration was associated with histology—10% in squamous cell carcinoma and approximately 4% in adenocarcinoma and other histologic types of NSCLC (P =.001). No correlation was found with the other covariates. Intense lymphocytic infiltration was correlated with longer overall survival (P =.01) and disease-free survival (P = .0005) without heterogeneity among trials.

The authors concluded that the results are consistent across all trials in the validation set. Intense lymphocytic infiltration, found in only a minority of tumors, was validated as a favorable prognostic factor for survival in patients with resectable NSCLC. ■

Disclosure: This research was made possible by unrestricted grants from the Ligue Nationale Contre le Cancer (France) and Sanofi-Aventis.


1. Arriagada R, Durant A, Pignon JP, et al: Long-term results of the International Adjuvant Lung Cancer Trial evaluating adjuvant Cisplatin-based chemotherapy in resected lung cancer. J Clin Oncol 28:35-42, 2010.

2. Butts CA, Ding K, Seymour L, et al: Randomized phase III trial of vinorelbine plus cisplatin compared with observation in completely resected stage IB and II non-small-cell lung cancer: Updated survival analysis of JBR.10. J Clin Oncol 28:29-34, 2010.

3. Strauss GM, Herndon JE 2nd, Maddaus MA, et al: Adjuvant paclitaxel plus carboplatin compared with observation in stage IB non-small-cell lung cancer. J Clin Oncol 26:5043-5051, 2008.

4. Douillard JY, Rosell R, De Lena M, et al: Adjuvant vinorelbine plus cisplatin versus observation in patients with completely resected stage IB-IIIA non-small-cell lung cancer. Lancet Oncol 7:719-727, 2006.

5. Brambilla E, Domerg C, Lantuejoul S, et al: LACE-BIO: Validation of the prognostic role of tumour lymphocyte infiltration in resectable non-small cell lung cancer. 3rd European Lung Cancer Conference, Abstract 77O. Presented April 20, 2012.