Prognostic value of the histological subtype in completely resected non-small cell lung cancer
http://www.100md.com
《血管的通路杂志》
Department of Thoracic Oncology, National Kyushu Cancer Center, 3-1-1, Notame, Minami-ku, Fukuoka, 811-1395, Japan
Abstract
Non-small cell lung cancer (NSCLC), which includes several different histological subtypes, is usually treated by the same strategy. However, the biological behavior of each cell type appears to be different. We retrospectively reviewed the clinical records of 1119 consecutive NSCLC patients who underwent a complete resection, in order to investigate whether a histological cell type is a powerful prognostic factor. The overall 5- and 10-year survivals of the patients with adenocarcinoma (AD), squamous cell carcinoma (SQ), large cell carcinoma (LA), and adenosquamous cell carcinoma (AS) were 54.2 and 40.2%, 51.6 and 30.3%, 40.9 and 18.7%, and 35.1 and 30.1%, respectively. The AD patients had a significantly better survival than the non-AD patients in Stage I (P=0.0004), whereas the SQ patients had a better survival than the non-SQ patients in Stage II (P=0.018). A multivariate survival analysis indicated the AD patients to have a significantly better survival than the SQ patients in Stage IA (P=0.04), while the SQ patients had a better survival than the AD patients in Stage II (P=0.03). These above observations suggest that the prognosis after complete resection is different between adenocarcinoma and squamous cell carcinoma in Stage IA and II.
Key Words: Non-small cell lung cancer; Adenocarcinoma; Squamous cell carcinoma; Prognosis
1. Introduction
Non-small cell lung cancer (NSCLC) comprises several different histological subtypes; including adenocarcinoma, squamous cell carcinoma, large cell carcinoma, adenosquamous carcinoma and others. They are usually considered to belong to the same category and are treated by the same strategy, because they have been reported to have similar results based on ordinary treatment courses. However, the biological aspects of different cell types seem to be different, and they actually show different clinical courses in some cases. Although the survival of patients with completely resected NSCLC is well known to be closely correlated to the pathological stage of the disease [1,2], the prognostic significance of different histological cell types in this setting is still controversial [3]. Some papers have demonstrated no significant survival advantages for any histological tumor type in pathological Stage I, while other groups have shown a survival advantage for patients with squamous cell carcinomas compared to adenocarcinomas [3]. In 1995, Ichinose and colleagues from our institution reported favorable outcomes of patients with squamous cell carcinomas with Stage II disease but not with Stage I [4]. In the present paper, we investigated whether the histological subtype is a powerful prognostic factor of Japanese patients with completely resected NSCLC at each pathological stage, in order to better understand the clinical behavior of each cell type and thereby better manage patients with NSCLC.
2. Patients and methods
From 1972 to 1999, 1235 patients with NSCLC underwent surgery as their initial treatment at our institution. Among them, we retrospectively reviewed the clinical records of 1119 patients who were pathologically confirmed to have a complete resection. The histological analysis of the tumor was based on the World Health Organization classification for cell types. The pathological stage of these patients was determined based on the TNM classification of the Union Internationale Contre le Cancer (UICC). Any patients who had been subjected to either pre-operative chemotherapy or radiotherapy were excluded. Generally, the patients were reexamined once every 3 months for 5 years, and thereafter at 6-month intervals after the operation. The evaluations included a physical examination and chest roentgenograms at each visit and computed tomography of the chest, magnetic resonance imaging of the brain and a bone scan. The overall follow-up time ranged from 1.6 to 120 months, with a median follow-up of 84.7 months.
The survival curves for each histological subtype were estimated according to the Kaplan–Meier method and then were compared by the log-rank test. The terminal event was death from any cause. A univariate survival analysis was carried out using the Cox proportional hazards model. In a multivariate survival analysis, the variables including age, gender and procedure were further analyzed in a stepwise manner. Statistical difference was considered to be significant if the P-value was below 0.05. All data were analyzed using Abacus Concepts, Survival Tools for StatView (Abacus Concepts, Inc., Berkeley, CA, USA).
3. Results
Six hundred and sixteen patients had adenocarcinoma (AD), 385 had squamous cell carcinoma (SQ), 55 had large cell carcinoma (LA), 37 had adeno-squamous cell carcinoma (AS), and 26 had other cell types. The patients consisted of 782 men and 337 women. The median age of the patients was 62.9 years, with a range from 24 to 90 years. A complete surgical resection consisted of 881 lobectomies, 75 bilobectomies, 144 pneumonectomies and 19 segmentectomies. The details of the clinicopathological characteristics for all patients are summarized in Table 1. Forty-four percent of the AD patients were female, where only 9.4% of the SQ patients were female. AD had a large number of Stage IA disease (32.1%), and a pneumonectomy was selected more frequently in SQ (23.6%) than for other tumors.
The overall 5- and 10-year survival rates of all patients were 52.2 and 35.1%, respectively. The 5- and 10-year survivals of the patients with AD, SQ, LA, and AS were 54.2 and 40.2%, 51.6 and 30.3%, 40.9 and 18.7%, and 35.1 and 30.1%, respectively. We divided the patients into each pathological stage and then investigated the possible prognostic factors at each stage (Table 2). Regarding the histological cell types, AD patients showed a significantly better survival than the non-AD patients in Stage I (P=0.0004), while the SQ patients showed a significantly better survival than the non-SQ patients in Stage II (P=0.018). No significant difference was shown in Stage III disease. The survival curves of the patients with each histological cell type were demonstrated for each stage in Fig. 1.
We next investigated the survival difference between AD patients and SQ patients, because the above results were mainly due to the difference of these major two cell types. In particular, Stage I patients were divided into two sub-stages (Stage IA and IB), for which the survival curves are shown in Fig. 2A. The survival curves of patients with both cell types in Stage IB were almost the same. As a result, we focused further analyses on both Stage IA and II. A multivariate survival analysis showed that AD patients have a significantly better survival than SQ patients in Stage IA (P=0.04), while the opposite result was observed in Stage II (P=0.03) (Table 3). We then analyzed the time trends of survival for the Stage IA patients (Fig. 2B). The survival of the patients with Stage IA, AD who underwent surgery during the late period (from 1990 to 1999) was significantly better than for those who underwent surgery during the early period (from 1972 to 1989) whereas no improvement was shown in the SQ patients. Table 4 shows the tumor size of Stage IA adenocarcinoma to be significantly smaller in the late period than in the early period (P=0.0006), whereas no difference in age, gender or surgical procedures was observed.
4. Discussion
To evaluate and classify the NSCLC patients according to the prognosis is an important procedure for planning optimal treatments protocols. Although a variety of factors have been reported to influence the patients survival in such homogenous entities as NSCLC, the TNM staging classification has consistently been reported to be closely correlated to the survival in patients who underwent a surgical resection [1,2]. A number of studies have also investigated the prognostic significance of different histological cell types in surgically resected NSCLC. However, the findings still remain controversial [3,5]. Since the distribution of patients in different stages greatly affects the overall survivals of each cell type, we compared them after stratification according to each pathological stage.
Regarding Stage I disease, past studies from Western countries showed that squamous cell carcinoma had a better prognosis than other cell types [3,6], whereas recent studies have shown no difference among the different cell types in this stage [4,7]. More recent studies have reported a survival advantage of adenocarcinoma patients in Stage I [2,8]. The present study also showed the patients with Stage I adenocarcinoma to have a better survival, and that the improved survival of Stage IA adenocarcinoma in the last decade affected the prognostic advantage in this early Stage (Fig. 2B). In comparisons between the patients with adenocarcinoma and squamous cell carcinoma, adenocarcinoma of Stage IA had a significantly better survival than squamous cell carcinoma of the same stage. In the 1990s, the incidence of adenocarcinoma was reported to be increasing while that of squamous cell carcinoma was decreasing in both Western and Asian countries [9]. Yoshino and colleagues demonstrated that the increasing population of female patients with adenocarcinoma was an important factor for the improved survival of surgically resected patients [10]. The recent spread of the computed tomography (CT) for screening has now made it possible to detect early-stage lung cancers, which cannot be detected by conventional chest X-rays [11]. In this study, a significant difference between the early and late periods was only shown in the tumor size (Table 4), thus suggesting that the improved technology in detecting small carcinoma at an earlier stage might have affected the improved survival of Stage IA adenocarcinoma. Bronchioloalveolar carcinoma was included with adenocarcinoma and an increased number of such non-invasive tumors may possibly influence the improvement of survival.
In Stage II diseases, many studies have shown no significant association between the survival and cell type. However, some studies have shown a survival advantage in squamous cell type [4,12,13], and the present study was consistent with them. Martini and colleagues mentioned that local recurrence was more frequent in patients with squamous carcinoma than adenocarcinoma (34 vs. 13%) whereas distant metastases were more common in adenocarcinoma (87 vs. 64%) [13]. It is possible that the wide-spread tendency of adenocarcinoma might result in an unsuccessful disease control even after a surgical resection in this stage.
Stage III disease also did not show any significant association between the survival and cell type in many past reports [14], although a better prognosis of squamous cell type has been mentioned in a few studies [4,15]. The current study showed no significant difference in the survival among the four cell types; however, the survival curves of adenocarcinoma and squamous carcinoma crossed in the early postoperative period. Though the meaning of this crossing is unclear, it may also be due to the biological difference of the two cell types; namely, squamous carcinoma is more likely to rapidly grow at a local site, while adenocarcinoma is likely to spread to a distant site. In the present study, local recurrence was more frequently found in Stage III patients with squamous carcinoma than in those with adenocarcinoma (36 vs. 19%) for the first recurrent site, whereas distant metastases were more common in adenocarcinoma (81 vs. 64%) (P=0.04). It is possible that the early deaths in squamous carcinoma patients were thus due to a failure to control local disease, while the late deaths in adenocarcinoma patients represented a failure to control distant metastasis.
In conclusion, our observations suggest that, in Stage IA, patients with adenocarcinoma may have a better prognosis after complete resection than squamous cell carcinoma, whereas patients with squamous cell carcinoma may have a better prognosis than adenocarcinoma in Stage II. Different treatment strategies, which best suit each histological subtype in each stage, should thus be considered for resectable NSCLC in order to increase the overall survival of resectable NSCLC.
Acknowledgements
We thank Dr. Brian T. Quinn for critical comments on the manuscript, and Ms. Yumiko Oshima for her help in preparing the manuscript.
References
Buccheri G, Ferrigno D. Prognostic value of stage grouping and TNM descriptors in lung cancer. Chest 2000; 117:1247–1255.
Naruke T, Tsuchiya R, Kondo H, Asamura H. Prognosis and survival after resection for bronchogenic carcinoma based on the 1997 TNM-staging classification: the Japanese experience. Ann Thorac Surg 2001; 71:1759–1764.
Nesbitt JC, Putnam JB Jr, Walsh GL, Roth JA, Mountain CF. Survival in early-stage non-small cell lung cancer. Ann Thorac Surg 1995; 60:466–472.
Ichinose Y, Yano T, Asoh H, Yokoyama H, Yoshino I, Katsuda Y. Prognostic factors obtained by a pathologic examination in completely resected non-small-cell lung cancer. An analysis in each pathologic stage. J Thorac Cardiovasc Surg 1995; 110:601–605.
Charloux A, Hedelin G, Dietemann A, Ifoundza T, Roeslin N, Pauli G, Quoix E. Prognostic value of histology in patients with non-small cell lung cancer. Lung Cancer 1997; 17:123–134.
Gail MH, Eagan RT, Feld R, Ginsberg R, Goodell B, Hill L, Holmes EC, Lukeman JM, Mountain CF, Oldham RK, et al. Prognostic factors in patients with resected Stage I non-small cell lung cancer. A report from the Lung Cancer Study Group. Cancer 1984; 54:1802–1813.
Padilla J, Calvo V, Penalver JC, Sales G, Morcillo A. Surgical results and prognostic factors in early non-small cell lung cancer. Ann Thorac Surg 1997; 63:324–326.
Suzuki K, Nagai K, Yoshida J, Moriyama E, Nishimura M, Takahashi K, Nishiwaki Y. Prognostic factors in clinical Stage I non-small cell lung cancer. Ann Thorac Surg 1999; 67:927–932.
Charloux A, Quoix E, Wolkove N, Small D, Pauli G, Kreisman H. The increasing incidence of lung adenocarcinoma: reality or artefact A review of the epidemiology of lung adenocarcinoma. Int J Epidemiol 1997; 26:14–23.
Yoshino I, Baba H, Fukuyama S, Kameyama T, Shikada Y, Tomiyasu M, Suemitsu R. A time trend of profile and surgical results in 1123 patients with non-small cell lung cancer. Surgery 2002; 131:S242–248.
Altorki N, Kent M, Pasmantier M. Detection of early-stage lung cancer: computed tomographic scan or chest radiograph. J Thorac Cardiovasc Surg 2001; 121:1053–1057.
Khan OA, Fitzgerald JJ, Field ML, Soomro I, Beggs FD, Morgan WE, Duffy JP. Histological determinants of survival in completely resected T1-2N1M0 nonsmall cell cancer of the lung. Ann Thorac Surg 2004; 77:1173–1178.
Martini N, Burt ME, Bains MS, McCormack PM, Rusch VW, Ginsberg RJ. Survival after resection of Stage II non-small cell lung cancer. Ann Thorac Surg 1992; 54:460–465. discussion 466.
Vansteenkiste JF, De Leyn PR, Deneffe GJ, Stalpaert G, Nackaerts KL, Lerut TE, Demedts MG. Survival and prognostic factors in resected N2 non-small cell lung cancer: a study of 140 cases. Leuven Lung Cancer Group. Ann Thorac Surg 1997; 63:1441–1450.
Inoue M, Sawabata N, Takeda S, Ohta M, Ohno Y, Maeda H. Results of surgical intervention for p-Stage IIIA (N2) non-small cell lung cancer: acceptable prognosis predicted by complete resection in patients with single N2 disease with primary tumor in the upper lobe. J Thorac CardioVasc Surg 2004; 127:1100–1106.(Tatsuro Okamoto, Riichiro)
Abstract
Non-small cell lung cancer (NSCLC), which includes several different histological subtypes, is usually treated by the same strategy. However, the biological behavior of each cell type appears to be different. We retrospectively reviewed the clinical records of 1119 consecutive NSCLC patients who underwent a complete resection, in order to investigate whether a histological cell type is a powerful prognostic factor. The overall 5- and 10-year survivals of the patients with adenocarcinoma (AD), squamous cell carcinoma (SQ), large cell carcinoma (LA), and adenosquamous cell carcinoma (AS) were 54.2 and 40.2%, 51.6 and 30.3%, 40.9 and 18.7%, and 35.1 and 30.1%, respectively. The AD patients had a significantly better survival than the non-AD patients in Stage I (P=0.0004), whereas the SQ patients had a better survival than the non-SQ patients in Stage II (P=0.018). A multivariate survival analysis indicated the AD patients to have a significantly better survival than the SQ patients in Stage IA (P=0.04), while the SQ patients had a better survival than the AD patients in Stage II (P=0.03). These above observations suggest that the prognosis after complete resection is different between adenocarcinoma and squamous cell carcinoma in Stage IA and II.
Key Words: Non-small cell lung cancer; Adenocarcinoma; Squamous cell carcinoma; Prognosis
1. Introduction
Non-small cell lung cancer (NSCLC) comprises several different histological subtypes; including adenocarcinoma, squamous cell carcinoma, large cell carcinoma, adenosquamous carcinoma and others. They are usually considered to belong to the same category and are treated by the same strategy, because they have been reported to have similar results based on ordinary treatment courses. However, the biological aspects of different cell types seem to be different, and they actually show different clinical courses in some cases. Although the survival of patients with completely resected NSCLC is well known to be closely correlated to the pathological stage of the disease [1,2], the prognostic significance of different histological cell types in this setting is still controversial [3]. Some papers have demonstrated no significant survival advantages for any histological tumor type in pathological Stage I, while other groups have shown a survival advantage for patients with squamous cell carcinomas compared to adenocarcinomas [3]. In 1995, Ichinose and colleagues from our institution reported favorable outcomes of patients with squamous cell carcinomas with Stage II disease but not with Stage I [4]. In the present paper, we investigated whether the histological subtype is a powerful prognostic factor of Japanese patients with completely resected NSCLC at each pathological stage, in order to better understand the clinical behavior of each cell type and thereby better manage patients with NSCLC.
2. Patients and methods
From 1972 to 1999, 1235 patients with NSCLC underwent surgery as their initial treatment at our institution. Among them, we retrospectively reviewed the clinical records of 1119 patients who were pathologically confirmed to have a complete resection. The histological analysis of the tumor was based on the World Health Organization classification for cell types. The pathological stage of these patients was determined based on the TNM classification of the Union Internationale Contre le Cancer (UICC). Any patients who had been subjected to either pre-operative chemotherapy or radiotherapy were excluded. Generally, the patients were reexamined once every 3 months for 5 years, and thereafter at 6-month intervals after the operation. The evaluations included a physical examination and chest roentgenograms at each visit and computed tomography of the chest, magnetic resonance imaging of the brain and a bone scan. The overall follow-up time ranged from 1.6 to 120 months, with a median follow-up of 84.7 months.
The survival curves for each histological subtype were estimated according to the Kaplan–Meier method and then were compared by the log-rank test. The terminal event was death from any cause. A univariate survival analysis was carried out using the Cox proportional hazards model. In a multivariate survival analysis, the variables including age, gender and procedure were further analyzed in a stepwise manner. Statistical difference was considered to be significant if the P-value was below 0.05. All data were analyzed using Abacus Concepts, Survival Tools for StatView (Abacus Concepts, Inc., Berkeley, CA, USA).
3. Results
Six hundred and sixteen patients had adenocarcinoma (AD), 385 had squamous cell carcinoma (SQ), 55 had large cell carcinoma (LA), 37 had adeno-squamous cell carcinoma (AS), and 26 had other cell types. The patients consisted of 782 men and 337 women. The median age of the patients was 62.9 years, with a range from 24 to 90 years. A complete surgical resection consisted of 881 lobectomies, 75 bilobectomies, 144 pneumonectomies and 19 segmentectomies. The details of the clinicopathological characteristics for all patients are summarized in Table 1. Forty-four percent of the AD patients were female, where only 9.4% of the SQ patients were female. AD had a large number of Stage IA disease (32.1%), and a pneumonectomy was selected more frequently in SQ (23.6%) than for other tumors.
The overall 5- and 10-year survival rates of all patients were 52.2 and 35.1%, respectively. The 5- and 10-year survivals of the patients with AD, SQ, LA, and AS were 54.2 and 40.2%, 51.6 and 30.3%, 40.9 and 18.7%, and 35.1 and 30.1%, respectively. We divided the patients into each pathological stage and then investigated the possible prognostic factors at each stage (Table 2). Regarding the histological cell types, AD patients showed a significantly better survival than the non-AD patients in Stage I (P=0.0004), while the SQ patients showed a significantly better survival than the non-SQ patients in Stage II (P=0.018). No significant difference was shown in Stage III disease. The survival curves of the patients with each histological cell type were demonstrated for each stage in Fig. 1.
We next investigated the survival difference between AD patients and SQ patients, because the above results were mainly due to the difference of these major two cell types. In particular, Stage I patients were divided into two sub-stages (Stage IA and IB), for which the survival curves are shown in Fig. 2A. The survival curves of patients with both cell types in Stage IB were almost the same. As a result, we focused further analyses on both Stage IA and II. A multivariate survival analysis showed that AD patients have a significantly better survival than SQ patients in Stage IA (P=0.04), while the opposite result was observed in Stage II (P=0.03) (Table 3). We then analyzed the time trends of survival for the Stage IA patients (Fig. 2B). The survival of the patients with Stage IA, AD who underwent surgery during the late period (from 1990 to 1999) was significantly better than for those who underwent surgery during the early period (from 1972 to 1989) whereas no improvement was shown in the SQ patients. Table 4 shows the tumor size of Stage IA adenocarcinoma to be significantly smaller in the late period than in the early period (P=0.0006), whereas no difference in age, gender or surgical procedures was observed.
4. Discussion
To evaluate and classify the NSCLC patients according to the prognosis is an important procedure for planning optimal treatments protocols. Although a variety of factors have been reported to influence the patients survival in such homogenous entities as NSCLC, the TNM staging classification has consistently been reported to be closely correlated to the survival in patients who underwent a surgical resection [1,2]. A number of studies have also investigated the prognostic significance of different histological cell types in surgically resected NSCLC. However, the findings still remain controversial [3,5]. Since the distribution of patients in different stages greatly affects the overall survivals of each cell type, we compared them after stratification according to each pathological stage.
Regarding Stage I disease, past studies from Western countries showed that squamous cell carcinoma had a better prognosis than other cell types [3,6], whereas recent studies have shown no difference among the different cell types in this stage [4,7]. More recent studies have reported a survival advantage of adenocarcinoma patients in Stage I [2,8]. The present study also showed the patients with Stage I adenocarcinoma to have a better survival, and that the improved survival of Stage IA adenocarcinoma in the last decade affected the prognostic advantage in this early Stage (Fig. 2B). In comparisons between the patients with adenocarcinoma and squamous cell carcinoma, adenocarcinoma of Stage IA had a significantly better survival than squamous cell carcinoma of the same stage. In the 1990s, the incidence of adenocarcinoma was reported to be increasing while that of squamous cell carcinoma was decreasing in both Western and Asian countries [9]. Yoshino and colleagues demonstrated that the increasing population of female patients with adenocarcinoma was an important factor for the improved survival of surgically resected patients [10]. The recent spread of the computed tomography (CT) for screening has now made it possible to detect early-stage lung cancers, which cannot be detected by conventional chest X-rays [11]. In this study, a significant difference between the early and late periods was only shown in the tumor size (Table 4), thus suggesting that the improved technology in detecting small carcinoma at an earlier stage might have affected the improved survival of Stage IA adenocarcinoma. Bronchioloalveolar carcinoma was included with adenocarcinoma and an increased number of such non-invasive tumors may possibly influence the improvement of survival.
In Stage II diseases, many studies have shown no significant association between the survival and cell type. However, some studies have shown a survival advantage in squamous cell type [4,12,13], and the present study was consistent with them. Martini and colleagues mentioned that local recurrence was more frequent in patients with squamous carcinoma than adenocarcinoma (34 vs. 13%) whereas distant metastases were more common in adenocarcinoma (87 vs. 64%) [13]. It is possible that the wide-spread tendency of adenocarcinoma might result in an unsuccessful disease control even after a surgical resection in this stage.
Stage III disease also did not show any significant association between the survival and cell type in many past reports [14], although a better prognosis of squamous cell type has been mentioned in a few studies [4,15]. The current study showed no significant difference in the survival among the four cell types; however, the survival curves of adenocarcinoma and squamous carcinoma crossed in the early postoperative period. Though the meaning of this crossing is unclear, it may also be due to the biological difference of the two cell types; namely, squamous carcinoma is more likely to rapidly grow at a local site, while adenocarcinoma is likely to spread to a distant site. In the present study, local recurrence was more frequently found in Stage III patients with squamous carcinoma than in those with adenocarcinoma (36 vs. 19%) for the first recurrent site, whereas distant metastases were more common in adenocarcinoma (81 vs. 64%) (P=0.04). It is possible that the early deaths in squamous carcinoma patients were thus due to a failure to control local disease, while the late deaths in adenocarcinoma patients represented a failure to control distant metastasis.
In conclusion, our observations suggest that, in Stage IA, patients with adenocarcinoma may have a better prognosis after complete resection than squamous cell carcinoma, whereas patients with squamous cell carcinoma may have a better prognosis than adenocarcinoma in Stage II. Different treatment strategies, which best suit each histological subtype in each stage, should thus be considered for resectable NSCLC in order to increase the overall survival of resectable NSCLC.
Acknowledgements
We thank Dr. Brian T. Quinn for critical comments on the manuscript, and Ms. Yumiko Oshima for her help in preparing the manuscript.
References
Buccheri G, Ferrigno D. Prognostic value of stage grouping and TNM descriptors in lung cancer. Chest 2000; 117:1247–1255.
Naruke T, Tsuchiya R, Kondo H, Asamura H. Prognosis and survival after resection for bronchogenic carcinoma based on the 1997 TNM-staging classification: the Japanese experience. Ann Thorac Surg 2001; 71:1759–1764.
Nesbitt JC, Putnam JB Jr, Walsh GL, Roth JA, Mountain CF. Survival in early-stage non-small cell lung cancer. Ann Thorac Surg 1995; 60:466–472.
Ichinose Y, Yano T, Asoh H, Yokoyama H, Yoshino I, Katsuda Y. Prognostic factors obtained by a pathologic examination in completely resected non-small-cell lung cancer. An analysis in each pathologic stage. J Thorac Cardiovasc Surg 1995; 110:601–605.
Charloux A, Hedelin G, Dietemann A, Ifoundza T, Roeslin N, Pauli G, Quoix E. Prognostic value of histology in patients with non-small cell lung cancer. Lung Cancer 1997; 17:123–134.
Gail MH, Eagan RT, Feld R, Ginsberg R, Goodell B, Hill L, Holmes EC, Lukeman JM, Mountain CF, Oldham RK, et al. Prognostic factors in patients with resected Stage I non-small cell lung cancer. A report from the Lung Cancer Study Group. Cancer 1984; 54:1802–1813.
Padilla J, Calvo V, Penalver JC, Sales G, Morcillo A. Surgical results and prognostic factors in early non-small cell lung cancer. Ann Thorac Surg 1997; 63:324–326.
Suzuki K, Nagai K, Yoshida J, Moriyama E, Nishimura M, Takahashi K, Nishiwaki Y. Prognostic factors in clinical Stage I non-small cell lung cancer. Ann Thorac Surg 1999; 67:927–932.
Charloux A, Quoix E, Wolkove N, Small D, Pauli G, Kreisman H. The increasing incidence of lung adenocarcinoma: reality or artefact A review of the epidemiology of lung adenocarcinoma. Int J Epidemiol 1997; 26:14–23.
Yoshino I, Baba H, Fukuyama S, Kameyama T, Shikada Y, Tomiyasu M, Suemitsu R. A time trend of profile and surgical results in 1123 patients with non-small cell lung cancer. Surgery 2002; 131:S242–248.
Altorki N, Kent M, Pasmantier M. Detection of early-stage lung cancer: computed tomographic scan or chest radiograph. J Thorac Cardiovasc Surg 2001; 121:1053–1057.
Khan OA, Fitzgerald JJ, Field ML, Soomro I, Beggs FD, Morgan WE, Duffy JP. Histological determinants of survival in completely resected T1-2N1M0 nonsmall cell cancer of the lung. Ann Thorac Surg 2004; 77:1173–1178.
Martini N, Burt ME, Bains MS, McCormack PM, Rusch VW, Ginsberg RJ. Survival after resection of Stage II non-small cell lung cancer. Ann Thorac Surg 1992; 54:460–465. discussion 466.
Vansteenkiste JF, De Leyn PR, Deneffe GJ, Stalpaert G, Nackaerts KL, Lerut TE, Demedts MG. Survival and prognostic factors in resected N2 non-small cell lung cancer: a study of 140 cases. Leuven Lung Cancer Group. Ann Thorac Surg 1997; 63:1441–1450.
Inoue M, Sawabata N, Takeda S, Ohta M, Ohno Y, Maeda H. Results of surgical intervention for p-Stage IIIA (N2) non-small cell lung cancer: acceptable prognosis predicted by complete resection in patients with single N2 disease with primary tumor in the upper lobe. J Thorac CardioVasc Surg 2004; 127:1100–1106.(Tatsuro Okamoto, Riichiro)