Tumor Necrosis as a Prognostic Factor for Stage IA Non-Small Cell Lung Cancer

doi:10.1016/j.athoracsur.2010.12.028

The Annals of Thoracic Surgery

Volume 91, Issue 6, June 2011, Pages 1668-1673

https://doi.org/10.1016/j.athoracsur.2010.12.028 Get rights and content

Background

In stage IA non-small cell lung cancer (NSCLC), lobectomy and mediastinal lymph node dissection is considered the standard treatment. However, 20% to 30% of patients have cancer recurrences. The purpose of this study was to determine the patterns and risk factors for recurrence in patients with stage IA NSCLC.

Methods

We retrospectively reviewed the medical records of 201 patients who had confirmed stage IA NSCLC by lobectomy and complete lymph node dissection.

Results

There were 131 male patients with a mean age of 60.68 ± 9.26 years. The median follow-up period was 41.4 months. Recurrences were reported in 16 patients. One hundred fourteen and 87 patients were T1a (≤2 cm) and T1b (>2 cm to ≤3 cm), respectively. The pathologic results were as follows: adenocarcinomas and bronchioloalveolar carcinomas (n = 134); squamous cell carcinomas (n = 57); and other diagnoses (n = 10). Tumor necrosis and lymphatic invasion were significant adverse risk factors for recurrence based on univariate analysis. Multivariate analysis showed that tumor necrosis was the only significant risk factor to predict cancer recurrence (hazard ratio, 4.336; p = 0.032). The 5-year overall survival was 94.8% for necrosis-negative patients and 86.2% for necrosis-positive patients (p = 0.04). The 5-year disease-free survival was 92.1% for necrosis-negative patients and 78.9% for necrosis-positive patients (p = 0.016).

Conclusions

Tumor necrosis was shown to be an adverse risk factor for survival and recurrence in patients with stage IA NSCLC. Thus, close observation and individualized adjuvant therapy might be helpful for patients with stage IA NSCLC with tumor necrosis.

Section snippets

Patients

This retrospective study was approved by the institutional review board of the hospital (IRB No. NCCNCS-10-401). Two hundred one patients who were confirmed to have pathologic stage IA NSCLC after lobectomy and complete lymph node dissection between May 2001 and November 2007 were enrolled. We retrospectively reviewed the medical records and pathologic data. Chest computed tomography, positron emission tomography, bronchoscopy, and pulmonary function testing were performed preoperatively.

General Characteristics and Pathologic Reports

Among 201 patients, there were 131 male (65.2%) and 70 female patients (34.8%) with a mean age of 60.68 ± 9.26 years. The median follow-up period was 41.4 months (range, 1.7 to 95.7 months). One hundred fourteen and 87 patients were reported to have T1a (≤2 cm) and T1b (>2 cm to ≤3 cm), respectively. The mean number of dissected lymph nodes was 33.75 ± 11.38. The pathologic results were as follows: adenocarcinomas and bronchioloalveolar carcinomas (n = 134); squamous cell carcinomas (n = 57);

Comment

This study demonstrates that tumor necrosis correlates with poor outcomes in patients with surgically resected stage IA NSCLC. Several studies have reported that tumor necrosis is related to poor outcome in patients with NSCLC, and this result is correlated with previous studies [12, 13, 14]. However, this study is the largest study that has specifically performed a survival analysis involving patients with stage IA lung cancer and tumor necrosis. Swinson and colleagues [12] reported that tumor

References (24)

H. Asamura et al.
A Japanese Lung Cancer Registry study: prognosis of 13,010 resected lung cancers
J Thorac Oncol
(2008)
J.L. Port et al.
Tumor size predicts survival within stage IA non-small cell lung cancer
Chest
(2003)
M.Y. Chang et al.
Factors predicting poor survival after resection of stage IA non-small cell lung cancer
J Thorac Cardiovasc Surg
(2007)
I.G. Duarte et al.
Angiogenesis as a predictor of survival after surgical resection for stage I non-small-cell lung cancer
J Thorac Cardiovasc Surg
(1998)
V. Rigau et al.
Blood vessel invasion in resected non small cell lung carcinomas is predictive of metastatic occurrence
Lung Cancer
(2002)
A. Sayar et al.
Nonanatomic prognostic factors in resected nonsmall cell lung carcinoma: the importance of perineural invasion as a new prognostic marker
Ann Thorac Surg
(2004)
N. Martini et al.
Incidence of local recurrence and second primary tumors in resected stage I lung cancer
J Thorac Cardiovasc Surg
(1995)
D.E. Swinson et al.
Tumour necrosis is an independent prognostic marker in non-small cell lung cancer: correlation with biological variables
Lung Cancer
(2002)
A.K. Eerola et al.
Accelerated apoptosis and low bcl-2 expression associated with neuroendocrine differentiation predict shortened survival in operated large cell carcinoma of the lung
Pathol Oncol Res
(1999)
S. Lindskog
Structure and mechanism of carbonic anhydrase
Pharmacol Ther
(1997)

A. Ochiai et al.

c-erbB-2 gene product associates with catenins in human cancer cells

Biochem Biophys Res Commun

(1994)

R. Rami-Porta et al.

The IASLC Lung Cancer Staging Project: proposals for the revision of the T descriptors in the forthcoming (seventh) edition of the TNM classification for lung cancer

J Thorac Oncol

(2007)

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Citation Excerpt :
The latter included pulmonary disease [18,19], diabetes, coronary disease, heart failure, stroke and chronic kidney disease. Tumour characteristics included preoperative concentration of the carcinoembryonic antigen [20] and pathologic findings (tumour differentiation, microscopic necrosis, lymphovascular invasion, and perineural invasion) [21–23]. The tumour–node–metastasis (TNM) stage was measured using the American Joint Committee on Cancer staging system [24].
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Cox regression analyses were used to estimate the recurrence and survival in patients with NSCLC disease stages I through III who were transfused for a haemoglobin level less than 8.0 g/dL within seven days after surgical resection. Inverse probability of treatment weighting (IPTW) was used to balance covariates in the sequential cohort of patients receiving an incremental amount of blood. We applied restricted cubic spline functions to characterise dose-response effects of transfusion amount on recurrence and mortality.
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Original articleGeneral thoracicTumor Necrosis as a Prognostic Factor for Stage IA Non-Small Cell Lung Cancer

Background

Methods

Results

Conclusions

Section snippets

Patients

General Characteristics and Pathologic Reports

Comment

J Thorac Oncol

Chest

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Lung Cancer

Ann Thorac Surg

J Thorac Cardiovasc Surg

Lung Cancer

Pathol Oncol Res

Pharmacol Ther

Biochem Biophys Res Commun

J Thorac Oncol

Original article
General thoracic
Tumor Necrosis as a Prognostic Factor for Stage IA Non-Small Cell Lung Cancer