Occult metastases in lymph nodes predict survival in resectable non-small-cell lung cancer

Report of the ACOSOG Z0040 trial

Valerie W. Rusch, Debra Hawes, Paul A. Decker, Sue Ellen Martin, Andrea Abati, Rodney J. Landreneau, G. Alexander Patterson, Richard I. Inculet, David R. Jones, Richard A. Malthaner, Robbin G. Cohen, Karla Ballman, Joe B. Putnam, Richard J Cote

Research output: Contribution to journalArticle

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Abstract

Purpose: The survival of patients with non-small-cell lung cancer (NSCLC), even when resectable, remains poor. Several small studies suggest that occult metastases (OMs) in pleura, bone marrow (BM), or lymph nodes (LNs) are present in early-stage NSCLC and are associated with a poor outcome. We investigated the prevalence of OMs in resectable NSCLC and their relationship with survival. Patients and Methods: Eligible patients had previously untreated, potentially resectable NSCLC. Saline lavage of the pleural space, performed before and after pulmonary resection, was examined cytologically. Rib BM and all histologically negative LNs (N0) were examined for OM, diagnosed by cytokeratin immunohistochemistry (IHC). Survival probabilities were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazards regression model were used to compare survival of groups of patients. P < .05 was considered significant. Results: From July 1999 to March 2004, 1,047 eligible patients (538 men and 509 women; median age, 67.2 years) were entered onto the study, of whom 50% had adenocarcinoma and 66% had stage I NSCLC. Pleural lavage was cytologically positive in only 29 patients. OMs were identified in 66 (8.0%) of 821 BM specimens and 130 (22.4%) of 580 LN specimens. In univariate and multivariable analyses OMs in LN but not BM were associated with significantly worse disease-free survival (hazard ratio [HR], 1.50; P = .031) and overall survival (HR, 1.58; P = .009). Conclusion: In early-stage NSCLC, LN OMs detected by IHC identify patients with a worse prognosis. Future clinical trials should test the role of IHC in identifying patients for adjuvant therapy.

Original languageEnglish
Pages (from-to)4313-4319
Number of pages7
JournalJournal of Clinical Oncology
Volume29
Issue number32
DOIs
StatePublished - Nov 10 2011

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Non-Small Cell Lung Carcinoma
Lymph Nodes
Neoplasm Metastasis
Survival
Bone Marrow
Therapeutic Irrigation
Immunohistochemistry
Pleura
Ribs
Keratins
Proportional Hazards Models
Disease-Free Survival
Adenocarcinoma
Clinical Trials
Lung

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Occult metastases in lymph nodes predict survival in resectable non-small-cell lung cancer : Report of the ACOSOG Z0040 trial. / Rusch, Valerie W.; Hawes, Debra; Decker, Paul A.; Martin, Sue Ellen; Abati, Andrea; Landreneau, Rodney J.; Patterson, G. Alexander; Inculet, Richard I.; Jones, David R.; Malthaner, Richard A.; Cohen, Robbin G.; Ballman, Karla; Putnam, Joe B.; Cote, Richard J.

In: Journal of Clinical Oncology, Vol. 29, No. 32, 10.11.2011, p. 4313-4319.

Research output: Contribution to journalArticle

Rusch, VW, Hawes, D, Decker, PA, Martin, SE, Abati, A, Landreneau, RJ, Patterson, GA, Inculet, RI, Jones, DR, Malthaner, RA, Cohen, RG, Ballman, K, Putnam, JB & Cote, RJ 2011, 'Occult metastases in lymph nodes predict survival in resectable non-small-cell lung cancer: Report of the ACOSOG Z0040 trial', Journal of Clinical Oncology, vol. 29, no. 32, pp. 4313-4319. https://doi.org/10.1200/JCO.2011.35.2500
Rusch, Valerie W. ; Hawes, Debra ; Decker, Paul A. ; Martin, Sue Ellen ; Abati, Andrea ; Landreneau, Rodney J. ; Patterson, G. Alexander ; Inculet, Richard I. ; Jones, David R. ; Malthaner, Richard A. ; Cohen, Robbin G. ; Ballman, Karla ; Putnam, Joe B. ; Cote, Richard J. / Occult metastases in lymph nodes predict survival in resectable non-small-cell lung cancer : Report of the ACOSOG Z0040 trial. In: Journal of Clinical Oncology. 2011 ; Vol. 29, No. 32. pp. 4313-4319.
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abstract = "Purpose: The survival of patients with non-small-cell lung cancer (NSCLC), even when resectable, remains poor. Several small studies suggest that occult metastases (OMs) in pleura, bone marrow (BM), or lymph nodes (LNs) are present in early-stage NSCLC and are associated with a poor outcome. We investigated the prevalence of OMs in resectable NSCLC and their relationship with survival. Patients and Methods: Eligible patients had previously untreated, potentially resectable NSCLC. Saline lavage of the pleural space, performed before and after pulmonary resection, was examined cytologically. Rib BM and all histologically negative LNs (N0) were examined for OM, diagnosed by cytokeratin immunohistochemistry (IHC). Survival probabilities were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazards regression model were used to compare survival of groups of patients. P < .05 was considered significant. Results: From July 1999 to March 2004, 1,047 eligible patients (538 men and 509 women; median age, 67.2 years) were entered onto the study, of whom 50{\%} had adenocarcinoma and 66{\%} had stage I NSCLC. Pleural lavage was cytologically positive in only 29 patients. OMs were identified in 66 (8.0{\%}) of 821 BM specimens and 130 (22.4{\%}) of 580 LN specimens. In univariate and multivariable analyses OMs in LN but not BM were associated with significantly worse disease-free survival (hazard ratio [HR], 1.50; P = .031) and overall survival (HR, 1.58; P = .009). Conclusion: In early-stage NSCLC, LN OMs detected by IHC identify patients with a worse prognosis. Future clinical trials should test the role of IHC in identifying patients for adjuvant therapy.",
author = "Rusch, {Valerie W.} and Debra Hawes and Decker, {Paul A.} and Martin, {Sue Ellen} and Andrea Abati and Landreneau, {Rodney J.} and Patterson, {G. Alexander} and Inculet, {Richard I.} and Jones, {David R.} and Malthaner, {Richard A.} and Cohen, {Robbin G.} and Karla Ballman and Putnam, {Joe B.} and Cote, {Richard J}",
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AU - Rusch, Valerie W.

AU - Hawes, Debra

AU - Decker, Paul A.

AU - Martin, Sue Ellen

AU - Abati, Andrea

AU - Landreneau, Rodney J.

AU - Patterson, G. Alexander

AU - Inculet, Richard I.

AU - Jones, David R.

AU - Malthaner, Richard A.

AU - Cohen, Robbin G.

AU - Ballman, Karla

AU - Putnam, Joe B.

AU - Cote, Richard J

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N2 - Purpose: The survival of patients with non-small-cell lung cancer (NSCLC), even when resectable, remains poor. Several small studies suggest that occult metastases (OMs) in pleura, bone marrow (BM), or lymph nodes (LNs) are present in early-stage NSCLC and are associated with a poor outcome. We investigated the prevalence of OMs in resectable NSCLC and their relationship with survival. Patients and Methods: Eligible patients had previously untreated, potentially resectable NSCLC. Saline lavage of the pleural space, performed before and after pulmonary resection, was examined cytologically. Rib BM and all histologically negative LNs (N0) were examined for OM, diagnosed by cytokeratin immunohistochemistry (IHC). Survival probabilities were estimated using the Kaplan-Meier method. The log-rank test and Cox proportional hazards regression model were used to compare survival of groups of patients. P < .05 was considered significant. Results: From July 1999 to March 2004, 1,047 eligible patients (538 men and 509 women; median age, 67.2 years) were entered onto the study, of whom 50% had adenocarcinoma and 66% had stage I NSCLC. Pleural lavage was cytologically positive in only 29 patients. OMs were identified in 66 (8.0%) of 821 BM specimens and 130 (22.4%) of 580 LN specimens. In univariate and multivariable analyses OMs in LN but not BM were associated with significantly worse disease-free survival (hazard ratio [HR], 1.50; P = .031) and overall survival (HR, 1.58; P = .009). Conclusion: In early-stage NSCLC, LN OMs detected by IHC identify patients with a worse prognosis. Future clinical trials should test the role of IHC in identifying patients for adjuvant therapy.

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