Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients

Clinical implications

David J. Kwiatkowski, David H. Harpole, John Godleski, James E. Herndon, Dar-Bin Shieh, William Richards, Rwamon Blanco, Hong Ji Xu, Gary M. Strauss, David J. Sugarbaker

Research output: Contribution to journalArticle

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Abstract

Purpose: To retrospectively construct a comprehensive multivariate model of cancer recurrence and to design o molecular pathologic substaging system in stage I non-small-cell lung cancer (NSCLC). Methods: All patients with stage I NSCLC reacted at Brigham and Women's Hospital (Boston, MA) between 1984 and 1992 with adequate clinical follow-up were studied. The importance of three demographic characteristics, surgical extent, 11 pathologic features, and seven molecular factors on cancer-free survival was examined. Results: Two hundred forty-four patients were studied, with 25 noncancer deaths and 80 patients with recurrent disease. Significant univariate predictors (P < .05) of cancer recurrence were age older than 60 years, male sex, wedge rejection, World Health Organization (WHO) adenocarcinoma subtype solid tumor with mucin, lymphatic invasion, and p53 expression. Multivariate analysis identified nine independent predictors of recurrence: solid tumor with mucin, a wedge resection, tumor diameter of 4 cm or greater, lymphatic invasion, age older than 60 years, male sex, p53 expression, K-ras codon 12 mutation, and absence of H-ras p21 expression. Multivariate cancer-free survival (CFS) analysis in the 180 patients who underwent lobectomy or pneumonectomy led to the elimination of sex and age, which left six independent factors. Conclusion: Lobectomy or pneumonectomy should be performed in stage I NSCLC. Using the six independent factors far recurrent disease, we propose a pathologic molecular substaging system. Patients with two factors or less are graded Ia, with a 5-year CFS rate of 87; those with three factors are graded lb, with a 5-year CFS rate of 58%; and those with four factors or more are graded Ic, with a 5-year CFS rate of 21%.

Original languageEnglish
Pages (from-to)2468-2477
Number of pages10
JournalJournal of Clinical Oncology
Volume16
Issue number7
DOIs
Publication statusPublished - 1998 Jan 1

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Non-Small Cell Lung Carcinoma
Neoplasms
Survival Rate
Pneumonectomy
Mucins
Recurrence
Proto-Oncogene Proteins p21(ras)
Survival Analysis
Codon
Adenocarcinoma
Multivariate Analysis
Demography
Mutation
Survival

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Kwiatkowski, D. J., Harpole, D. H., Godleski, J., Herndon, J. E., Shieh, D-B., Richards, W., ... Sugarbaker, D. J. (1998). Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: Clinical implications. Journal of Clinical Oncology, 16(7), 2468-2477. https://doi.org/10.1200/JCO.1998.16.7.2468
Kwiatkowski, David J. ; Harpole, David H. ; Godleski, John ; Herndon, James E. ; Shieh, Dar-Bin ; Richards, William ; Blanco, Rwamon ; Xu, Hong Ji ; Strauss, Gary M. ; Sugarbaker, David J. / Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients : Clinical implications. In: Journal of Clinical Oncology. 1998 ; Vol. 16, No. 7. pp. 2468-2477.
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abstract = "Purpose: To retrospectively construct a comprehensive multivariate model of cancer recurrence and to design o molecular pathologic substaging system in stage I non-small-cell lung cancer (NSCLC). Methods: All patients with stage I NSCLC reacted at Brigham and Women's Hospital (Boston, MA) between 1984 and 1992 with adequate clinical follow-up were studied. The importance of three demographic characteristics, surgical extent, 11 pathologic features, and seven molecular factors on cancer-free survival was examined. Results: Two hundred forty-four patients were studied, with 25 noncancer deaths and 80 patients with recurrent disease. Significant univariate predictors (P < .05) of cancer recurrence were age older than 60 years, male sex, wedge rejection, World Health Organization (WHO) adenocarcinoma subtype solid tumor with mucin, lymphatic invasion, and p53 expression. Multivariate analysis identified nine independent predictors of recurrence: solid tumor with mucin, a wedge resection, tumor diameter of 4 cm or greater, lymphatic invasion, age older than 60 years, male sex, p53 expression, K-ras codon 12 mutation, and absence of H-ras p21 expression. Multivariate cancer-free survival (CFS) analysis in the 180 patients who underwent lobectomy or pneumonectomy led to the elimination of sex and age, which left six independent factors. Conclusion: Lobectomy or pneumonectomy should be performed in stage I NSCLC. Using the six independent factors far recurrent disease, we propose a pathologic molecular substaging system. Patients with two factors or less are graded Ia, with a 5-year CFS rate of 87; those with three factors are graded lb, with a 5-year CFS rate of 58{\%}; and those with four factors or more are graded Ic, with a 5-year CFS rate of 21{\%}.",
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Kwiatkowski, DJ, Harpole, DH, Godleski, J, Herndon, JE, Shieh, D-B, Richards, W, Blanco, R, Xu, HJ, Strauss, GM & Sugarbaker, DJ 1998, 'Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients: Clinical implications', Journal of Clinical Oncology, vol. 16, no. 7, pp. 2468-2477. https://doi.org/10.1200/JCO.1998.16.7.2468

Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients : Clinical implications. / Kwiatkowski, David J.; Harpole, David H.; Godleski, John; Herndon, James E.; Shieh, Dar-Bin; Richards, William; Blanco, Rwamon; Xu, Hong Ji; Strauss, Gary M.; Sugarbaker, David J.

In: Journal of Clinical Oncology, Vol. 16, No. 7, 01.01.1998, p. 2468-2477.

Research output: Contribution to journalArticle

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T1 - Molecular pathologic substaging in 244 stage I non-small-cell lung cancer patients

T2 - Clinical implications

AU - Kwiatkowski, David J.

AU - Harpole, David H.

AU - Godleski, John

AU - Herndon, James E.

AU - Shieh, Dar-Bin

AU - Richards, William

AU - Blanco, Rwamon

AU - Xu, Hong Ji

AU - Strauss, Gary M.

AU - Sugarbaker, David J.

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N2 - Purpose: To retrospectively construct a comprehensive multivariate model of cancer recurrence and to design o molecular pathologic substaging system in stage I non-small-cell lung cancer (NSCLC). Methods: All patients with stage I NSCLC reacted at Brigham and Women's Hospital (Boston, MA) between 1984 and 1992 with adequate clinical follow-up were studied. The importance of three demographic characteristics, surgical extent, 11 pathologic features, and seven molecular factors on cancer-free survival was examined. Results: Two hundred forty-four patients were studied, with 25 noncancer deaths and 80 patients with recurrent disease. Significant univariate predictors (P < .05) of cancer recurrence were age older than 60 years, male sex, wedge rejection, World Health Organization (WHO) adenocarcinoma subtype solid tumor with mucin, lymphatic invasion, and p53 expression. Multivariate analysis identified nine independent predictors of recurrence: solid tumor with mucin, a wedge resection, tumor diameter of 4 cm or greater, lymphatic invasion, age older than 60 years, male sex, p53 expression, K-ras codon 12 mutation, and absence of H-ras p21 expression. Multivariate cancer-free survival (CFS) analysis in the 180 patients who underwent lobectomy or pneumonectomy led to the elimination of sex and age, which left six independent factors. Conclusion: Lobectomy or pneumonectomy should be performed in stage I NSCLC. Using the six independent factors far recurrent disease, we propose a pathologic molecular substaging system. Patients with two factors or less are graded Ia, with a 5-year CFS rate of 87; those with three factors are graded lb, with a 5-year CFS rate of 58%; and those with four factors or more are graded Ic, with a 5-year CFS rate of 21%.

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