Literature DB >> 31462928

RNSCLC-PRSP software to predict the prognostic risk and survival in patients with resected T1-3N0-2 M0 non-small cell lung cancer.

Yunkui Zhang1,2, YaoChen Li3, Rongsheng Zhang2, Yujie Zhang2, Haitao Ma1.   

Abstract

BACKGROUND: The clinical outcomes of patients with resected T1-3N0-2M0 non-small cell lung cancer (NSCLC) with the same tumor-node-metastasis (TNM) stage are diverse. Although other prognostic factors and prognostic prediction tools have been reported in many published studies, a convenient, accurate and specific prognostic prediction software for clinicians has not been developed. The purpose of our research was to develop this type of software that can analyze subdivided T and N staging and additional factors to predict prognostic risk and the corresponding mean and median survival time and 1-5-year survival rates of patients with resected T1-3N0-2M0 NSCLC.
RESULTS: Using a Cox proportional hazard regression model, we determined the independent prognostic factors and obtained a prognostic index (PI) eq. PI = ∑βixi.=0.379X1-0.403X2-0.267X51-0.167X61-0.298X62 + 0.460X71 + 0.617X72-0.344X81-0.105X91-0.243X92 + 0.305X101 + 0.508X102 + 0.754X103 + 0.143X111 + 0.170X112 + 0.434X113-0.327X122-0.247X123 + 0.517X133 + 0.340X134 + 0.457X143 + 0.419X144 + 0.407X145. Using the PI equation, we determined the PI value of every patient. According to the quantile of the PI value, patients were divided into three risk groups: low-, intermediate-, and high-risk groups with significantly different survival rates. Meanwhile, we obtained the mean and median survival times and 1-5-year survival rates of the three groups. We developed the RNSCLC-PRSP software which is freely available on the web at http://www.rnsclcpps.com with all major browsers supported to determine the prognostic risk and associated survival of patients with resected T1-3N0-2 M0 non-small cell lung cancer.
CONCLUSIONS: After prognostic factor analysis, prognostic risk grouping and corresponding survival assessment, we developed a novel software program. It is practical and convenient for clinicians to evaluate the prognostic risk and corresponding survival of patients with resected T1-3N0-2M0 NSCLC. Additionally, it has guiding significance for clinicians to make decisions about complementary treatment for patients.

Entities:  

Keywords:  Prognostic index; Prognostic risk prediction; Resected non-small cell lung cancer; Software; Survival prediction

Year:  2019        PMID: 31462928      PMCID: PMC6708148          DOI: 10.1186/s13040-019-0205-0

Source DB:  PubMed          Journal:  BioData Min        ISSN: 1756-0381            Impact factor:   2.522


Background

Lung cancer is the first leading cause of cancer death among men and the second leading cause of cancer death for women worldwide [1]. At present, the eighth edition of non-small cell lung cancer (NSCLC) tumor-node-metastasis (TNM) staging system developed and validated by the International Association for the Staging of Lung Cancer (IASLC) project is considered to be the most significant prognostic predictor and the main guider of postoperative supplementary treatment [2]. The following factors were incorporated into the IASLC system: histological grade, gender, age, and performance status. No molecular prognostic factors are used in the clinic because of the lack of cross-validation, Even the new biomarker programmed cell death protein 1 ligand (PD-L1) is a predictive marker of good response to immunotherapy drugs but poor prognostic indicator of survival [3]. However, clinicians know that the outcomes are diverse among resected NSCLC patients with the same TNM stage and other similar clinical features. Some die early after surgical treatment, while some remain alive, even living longer than expected. Therefore, for clinicians, subgroups of T and N staging and other more clinicopathological features should be considered in prognostic risk and survival prediction. Recently, there have been many studies on the prognostic factors for patients with resected NSCLC [4-7]. Prognostic factors can be divided into clinical factors, tumor-related factors and treatment-related factors. TNM stage, gender, age, number of examined regional lymph nodes (NELNs), number of positive regional lymph nodes (NPLNs), surgery type, histological grade, histology, and marital status have been reported to be prognostic factors for patients with resected NSCLC [8-22]. There have been few studies on T and N staging subgroups as prognostic factors. Meanwhile, some prognostic prediction tools, such as prognostic nomograms, scores, and survival models for patients with resected NSCLC, have been reported in many published studies [23-27]. Unfortunately, for clinicians who are busy in clinical work, it is inconvenient to use the TNM stage system and tools for which the results were inaccurate and vague. Therefore, we aimed to develop software that can conveniently, specifically, accurately predict the prognostic risk and survival of patients with T1-3N0–2M0 NSCLC. In the process of building the model, T and N staging subgroups and other more clinical features were analyzed as prognostic factors.

Implementation

We collected information on patients from the Surveillance, Epidemiology, and End Results (SEER) database, which provides cancer statistics for U.S. patients. In this study, 6886 patients were obtained. Eligibility criteria included the following: [1] histological diagnosis of NSCLC; [2] suffering from only single primary NSCLC in their lifetime and had NSCLC between 2004 and 2014; [3] received resection only; [4] had definitive surgical information; [5] survival time equal to or greater than one month; and [6] ≥20 years old. Moreover, the following criteria were used to exclude patients from the study: [1] M1 stage or without definitive information on M stage; [2] without definitive information on primary site, laterality or histological grade; [3] with T4>7 and without definitive information on tumor size; [4] with T4 Inv, T4 Ipsi Nod and without definitive information on tumor extension; [5] with N3 stage or without definitive information on N stage; [6] without definitive information on the number of examined and positive regional lymph nodes; [7] unknown marital status and race. Figure 1 shows the flow chart of the process used to screen patients according to the inclusion and exclusion criteria. Clinicopathological characteristics and follow-up information were collected, as shown in Table 1, including gender, age, laterality, race, N stage, NELNs, NPLNs, surgery type, primary site, histological grade, histology, marital status, tumor extension, tumor size, survival months and status.
Fig. 1

According to the inclusion and exclusion criteria, the flow chart of screening patients. a NSCLC: non-small cell lung cancer. b According to the eighth edition of American Joint Committee on Cancer (AJCC)/ Union for International Cancer Control (UICC) stage classification for NSCLC

Table 1

The clinicopathological characteristics of patients with resected T1-3N0 − 2 M0 NSCLC

CharacteristicsNumber of patients
All patients6886 (100%)
Gender
 Male3363 (48.8%)
 Female3523 (51.2%)
Age
 ≤652964 (43.0%)
 > 653922 (57.0%)
Laterality
 Right3958 (57.5%)
 Left2928 (42.5%)
Race
 White5770 (83.8%)
 Black589 (8.6%)
 Others527 (7.6%)
N stage a
 N04578 (66.5%)
 N11228 (17.8%)
 N21080 (15.7%)
NELNs
 N ≤ 62495 (36.2%)
 6<N ≤ 122272 (33.0%)
 N>122119 (30.8%)
NPLNs
 N = 04658 (67.6%)
 1 ≤ N ≤ 31623 (23.6%)
 N ≥ 4605 (8.8%)
Surgery type
 SLET599 (8.7%)
 LET5748 (83.5%)
 PET539 (7.8%)
Primary site
 UL4125 (60.0%)
 ML414 (6.0%)
 LL2213 (32.1%)
 Others134 (1.9%)
Histological grade
 I816 (11.9%)
 II3158 (45.9%)
 III2766 (40.2%)
 IV146 (2.0%)
Histology
 AC3013 (43.8%)
 S1629 (23.7%)
 ASC206 (3.0%)
 BAA220 (3.2%)
 Others1818 (26.3%)
Marital status
 Single (never married)801 (11.6%)
 Married4115 (59.8%)
 Divorced854 (12.4%)
 Widowed1017 (14.8%)
 Others99 (1.4%)
Tumor extension a
 T1a ss729 (10.6%)
 T2 Visc PI4078 (59.2%)
 T2 Centr1366 (19.8%)
 T3 Inv68 (1.0%)
 T3 Satell645 (9.4%)
Tumor size a
 T1a ≤ 1(T ≤ 1)193 (2.8%)
 T1b>1–2(1<T ≤ 2)1573 (22.8%)
 T1c>2–3(2<T ≤ 3)1932 (28.1%)
 T2a>3–4(3<T ≤ 4)1449 (21.0%)
 T2b>4–5(4<T ≤ 5)865 (12.6%)
 T3>5–7(5<T ≤ 7)874 (12.7%)
Survival status
 Dead2443 (35.5%)
 Alive4443 (64.5%)

Abbreviations: NELNs Number of examined regional lymph nodes, NPLNs Number of positive regional lymph nodes, SLET sublobectomy, LET Lobectomy, PET Pneumonectomy, UL Upper lobe, ML Middle lobe, LL Lower lobe, I Well differentiated, II Moderately differentiated, III Poorly differentiated, IV Undifferentiated, AC Adenocarcinoma, S Squamous carcinoma, ASC Adenosquamous carcinoma, BAA Bronchioalveolar adenocarcinoma

a According to the eighth edition of the AJCC/UICC stage classification for NSCLC

According to the inclusion and exclusion criteria, the flow chart of screening patients. a NSCLC: non-small cell lung cancer. b According to the eighth edition of American Joint Committee on Cancer (AJCC)/ Union for International Cancer Control (UICC) stage classification for NSCLC The clinicopathological characteristics of patients with resected T1-3N0 − 2 M0 NSCLC Abbreviations: NELNs Number of examined regional lymph nodes, NPLNs Number of positive regional lymph nodes, SLET sublobectomy, LET Lobectomy, PET Pneumonectomy, UL Upper lobe, ML Middle lobe, LL Lower lobe, I Well differentiated, II Moderately differentiated, III Poorly differentiated, IV Undifferentiated, AC Adenocarcinoma, S Squamous carcinoma, ASC Adenosquamous carcinoma, BAA Bronchioalveolar adenocarcinoma a According to the eighth edition of the AJCC/UICC stage classification for NSCLC First, In this data set, approximately 70% of patients were randomly assigned to the training set (resulting in 4821 patients), while the remaining patients comprised the test set (resulting in 2065 patients). The training set was used to build the model, and the test set was used to verify the model. Second, based on the training set, the Cox proportional hazard regression model was used to identify independent prognostic factors and their model coefficients. Third, we obtained a prognostic index (PI) equation, which is the value of each independent prognostic factor and the sum of the corresponding regression coefficient product. Fourth, according to the quantile of the PI value, patients were divided into three risk groups: the low-, intermediary-, and high-risk groups with significantly different survival rates according to Kaplan-Meier analysis and log-rank test. Meanwhile, we obtained the mean and median survival times and 1–5-year survival rates of the three risk groups. We used a test set to verify the model. Finally, we developed a software program named RNSCLC-PRSP to predict the prognostic risk and survival of patients with resected T1-3N0–2M0 non-small cell lung cancer by selecting their clinicopathological features. The software is freely available on the web at http://www.rnsclcpps.com with all major browsers supported. Clinicians register and log in and then they select the clinicopathological characteristics of patients, and the prognostic risk and survival outcome are predicted. We used SPSS (version 16.0) software (Inc, Chicago, IL, USA) for all statistical calculations, and P<0.05 was considered to be significant. Meanwhile, the tree model analysis method was also used to rank the importance of each variable for prediction,

Results

Univariate analysis of prognostic factors

Variables codes and assignment methods of clinicopathological characteristics are provided in the Additional file 1: Table S1. After the univariate analysis, the result of which are presented in Table 2, gender, age, N stage, NELNs, NPLNs, surgery type, primary site, histological grade, histology, marital status, tumor extension, and tumor size were significant prognostic factors (P<0.05).
Table 2

Univariate analysis of the Cox proportional hazard regression model of resected T1-3N0 − 2 M0 NSCLC

FactorsVariatesbSERR95%CI P
GenderX10.3630.0491.4381.307~1.582< 0.001
AgeX2−0.3540.0500.7020.637~0.774< 0.001
LateralityX3− 0.0090.0490.9910.900~1.0910.858
Race (as dummy variables)X4
 Others1.0
 WhiteX410.1590.1021.1720.961~1.4300.118
 BlackX420.1720.1301.1880.920~1.5320.186
N stage a (as dummy variables)X5
 N0X50−0.8580.0600.4240.377~0.477< 0.001
 N1X51−0.2200.0710.8030.699~0.9220.002
NELNs (as dummy variables)X6
 N ≤ 61.0
 6<N ≤ 12X61−0.1210.0580.8860.790~0.9930.038
 N>12X62−0.0460.0590.9560.852~1.0720.438
NPLNs (as dummy variables)X7
 N = 01.0
 1 ≤ N ≤ 3X710.6980.0542.0091.808~2.234< 0.001
 N ≥ 4X720.8620.0742.3672.046~2.739< 0.001
Surgery type (as dummy variables)X8
 SLET1.0
 LETX81−0.2420.0860.7850.664~0.9290.005
 PETX820.0880.1091.0920.882~1.3530.420
Primary site (as dummy variables)X9
 OthersX90−0.2390.1600.7880.576~1.0780.136
 ULX91−0.1140.0520.8920.806~0.9870.028
 MLX92−0.2730.1140.7610.609~0.9520.017
Histological grade (as dummy variables)X10
 I1.0
 IIX1010.5510.0961.7361.437~2.097< 0.001
 IIIX1020.8340.0952.3011.909~2.775< 0.001
 IVX1030.9980.1612.7121.977~3.722< 0.001
Histology (as dummy variables)X11
 Others1.0
 ACX1110.1970.0631.2171.076~1.3770.002
 SX1120.3790.0681.4621.280~1.669< 0.001
 ASCX1130.5880.1341.8011.385~2.342< 0.001
 BAAX114−0.3040.1560.7380.543~1.0020.051
Marital status (as dummy variables)X12
 OthersX120−0.0570.2160.9450.618~1.4440.793
 Single (never married)X121−0.2580.0920.7730.645~0.9260.005
 MarriedX122−0.2860.0660.7510.660~0.855< 0.001
 DivorcedX123−0.2900.0900.7490.627~0.8940.001
Tumor extensiona (as dummy variables)X13
 T1a ss1.0
 T2 Visc PIX1310.1140.0821.1210.954~1.3170.166
 T2 CentrX1320.3530.0851.4241.206~1.680< 0.001
 T3 InvX1330.8090.1962.2471.529~3.300< 0.001
 T3 SatellX1340.5140.0921.6721.395~2.002< 0.001
Tumor sizea (as dummy variables)X14
 T1a ≤ 1(T ≤ 1)1.0
 T1b>1–2(1<T ≤ 2)X1410.0160.1721.0160.725~1.4250.927
 T1c>2–3(2<T ≤ 3)X1420.3610.1691.4341.030~1.9970.033
 T2a>3–4(3<T ≤ 4)X1430.5840.1701.7931.286~2.5010.001
 T2b>4–5(4<T ≤ 5)X1440.5850.1741.7941.276~2.5230.001
 T3>5–7(5<T ≤ 7)X1450.6640.1741.9431.382~2.732< 0.001

Abbreviations: B Regression coefficient, SE Standard error, RR Relative risk, CI Confidence interval, NELNs Number of examined regional lymph nodes, NPLNs Number of positive regional lymph nodes, SLET Sublobectomy, LET Lobectomy, PET Pneumonectomy, UL Upper lobe, ML Middle lobe, LL Lower lobe, I Well differentiated, II Moderately differentiated, III Poorly differentiated, IV Undifferentiated, AC Adenocarcinoma, S Squamous carcinoma, ASC Adenosquamous carcinoma, BAA Bronchioalveolar adenocarcinoma

a According to the eighth edition AJCC/UICC stage classification for NSCLC.

Univariate analysis of the Cox proportional hazard regression model of resected T1-3N0 − 2 M0 NSCLC Abbreviations: B Regression coefficient, SE Standard error, RR Relative risk, CI Confidence interval, NELNs Number of examined regional lymph nodes, NPLNs Number of positive regional lymph nodes, SLET Sublobectomy, LET Lobectomy, PET Pneumonectomy, UL Upper lobe, ML Middle lobe, LL Lower lobe, I Well differentiated, II Moderately differentiated, III Poorly differentiated, IV Undifferentiated, AC Adenocarcinoma, S Squamous carcinoma, ASC Adenosquamous carcinoma, BAA Bronchioalveolar adenocarcinoma a According to the eighth edition AJCC/UICC stage classification for NSCLC.

Multivariate analysis of prognostic factors

By multivariate analysis of prognostic factors, the results of which are shown in Table 3, gender, age, N1 stage, NELNs (612), NPLN (1 ≤ N ≤ 3, N ≥ 4), lobectomy (LET), primary site (UL, ML), histological grade (II, III, IV), histology (AC, S, ASC), marital status (married, divorced), tumor extension (T3 Inv, T3 Satell), and tumor size (T2a>3–4(34–5(45–7(5
Table 3

Multivariate analysis of the Cox proportional hazard regression model of resected T1-3N0 − 2 M0 NSCLC

FactorsVariatesbSERR95%CI P
GenderX10.3790.0531.4601.317~1.620< 0.001
AgeX2−0.4030.0540.6680.601~0.743< 0.001
N stage0.001
 N0X50−0.3720.1950.6890.470~1.0100.056
 N1X51−0.2670.0750.7660.661~0.886< 0.001
NELNs< 0.001
 6<N ≤ 12X61−0.1670.0600.8460.751~0.9520.006
 N>12X62−0.2980.0640.7420.655~0.841< 0.001
NPLNs0.003
 1 ≤ N ≤ 3X710.4600.1971.5831.077~2.3280.019
 N ≥ 4X720.6170.2031.8541.245~2.7620.002
Surgery type0.001
 LETX81−0.3440.0900.7090.595~0.845< 0.001
 PETX82−0.2450.1270.7830.611~1.0030.053
Primary site0.035
 OthersX90−0.3080.1720.7350.525~1.0290.073
 ULX91−0.1050.0530.9000.811~0.9990.047
 MLX92−0.2430.1160.7840.625~0.9830.035
Histological grade< 0.001
 IIX1010.3050.1001.3561.114~1.6510.002
 IIIX1020.5080.1011.6631.364~2.027< 0.001
 IVX1030.7540.1672.1261.532~2.950< 0.001
Histology0.011
 ACX1110.1430.0661.1531.013~1.3130.031
 SX1120.1700.0731.1861.028~1.3680.019
 ASCX1130.4340.1371.5441.181~2.0190.001
 BAAX114−0.0300.1600.9700.709~1.3280.851
Marital status< 0.001
 OthersX1200.0160.2211.0160.659~1.5660.944
 Single (never married)X121−0.1330.0980.8750.723~1.0600.172
 MarriedX122−0.3270.0710.7210.628~0.829< 0.001
 DivorcedX123−0.2470.0940.7810.650~0.9380.008
Tumor extensiona< 0.001
 T2 Visc PIX131−0.1150.0870.8920.752~1.0560.185
 T2 CentrX1320.0250.0921.0250.856~1.2290.786
 T3 InvX1330.5170.2041.6781.125~2.5000.011
 T3 SatellX1340.3400.0951.4051.167~1.692< 0.001
Tumor sizea< 0.001
 T1b>1–2(1<T ≤ 2)X1410.0250.1741.0250.729~1.4420.886
 T1c>2–3(2<T ≤ 3)X1420.2600.1711.2971.927~1.8150.129
 T2a>3–4(3<T ≤ 4)X1430.4570.1741.5801.122~2.2230.009
 T2b>4–5(4<T ≤ 5)X1440.4190.1791.5201.069~2.1610.020
 T3>5–7(5<T ≤ 7)X1450.4070.1801.5021.055~2.1400.024

Abbreviations: b Regression coefficient, SE Standard error, RR Relative risk, CI Confidence interval, NELNs Number of examined regional lymph nodes, NPLNs Number of positive regional lymph nodes, LET Lobectomy, PET Pneumonectomy, UL Upper lobe, ML Middle lobe, II Moderately differentiated, III Poorly differentiated, IV Undifferentiated, AC Adenocarcinoma, S Squamous carcinoma, ASC Adenosquamous carcinoma, BAA Bronchioalveolar adenocarcinoma

a According to the eighth edition AJCC/UICC stage classification for NSCLC

Multivariate analysis of the Cox proportional hazard regression model of resected T1-3N0 − 2 M0 NSCLC Abbreviations: b Regression coefficient, SE Standard error, RR Relative risk, CI Confidence interval, NELNs Number of examined regional lymph nodes, NPLNs Number of positive regional lymph nodes, LET Lobectomy, PET Pneumonectomy, UL Upper lobe, ML Middle lobe, II Moderately differentiated, III Poorly differentiated, IV Undifferentiated, AC Adenocarcinoma, S Squamous carcinoma, ASC Adenosquamous carcinoma, BAA Bronchioalveolar adenocarcinoma a According to the eighth edition AJCC/UICC stage classification for NSCLC

The tree model analysis

The tree model analysis method was used to rank the importance of each variable for prediction. The results are shown in Table 4. The third column is standardized importance. The first 12 variables were selected into the model, which was consistent with the Cox regression results.
Table 4

The importance of each variable for prediction

VariableImportanceStandard importance
Tumor extension0.045100.0%
N stage0.01635.5%
NPLNs0.01533.1%
Histology0.00715.4%
Surgery type0.00714.9%
Age0.00511.5%
Gender0.00510.6%
Histological grade0.0049.8%
Primary site0.0024.9%
Marital status0.0023.6%
NELNs0.0012.8%
Tumor size0.0012.2%
Race0.0011.4%
Laterality0.0001.0%

Abbreviations: NPLNs Number of positive regional lymph nodes, NELNs Number of examined regional lymph nodes, CRT Classification regression tree

Method: CRT

Y: survival status

a According to the eighth edition AJCC/UICC stage classification for NSCLC

The importance of each variable for prediction Abbreviations: NPLNs Number of positive regional lymph nodes, NELNs Number of examined regional lymph nodes, CRT Classification regression tree Method: CRT Y: survival status a According to the eighth edition AJCC/UICC stage classification for NSCLC

Prognostic risk model construction and software development

Using the Cox proportional hazard regression model, we obtained the PI equation, PI = ∑βixi. =0.379X1–0.403X2–0.267X51–0.167X61–0.298X62 + 0.460X71 + 0.617X72–0.344X81–0.105X91–0.243X92 + 0.305X101 + 0.508X102 + 0.754X103 + 0.143X111 + 0.170X112 + 0.434X113–0.327X122–0.247X123 + 0.517X133 + 0.340X134 + 0.457X143 + 0.419X144 + 0.407X145. Using the PI equation, we obtained the PI value of every patient. As shown in Table 5, we obtained PI ranges for the training and test sets. According to the quantile of the PI value, we divided patients in the training and test sets into three risk groups. The three risk groups were divided based on the PI values as follow: 0~50%, 50~90%, and 90 + %. The quantiles are divided into low-, intermediary-, and high-risk groups. We obtained three risk groups and their corresponding mean and median survival times and 1–5-year survival rates of the training and test sets (Tables 6 and 7, respectively). Using K-M curves and log-rank tests, we found that, from the low-, intermediate- and high-risk groups, the survival rates of the training and test sets were worse stepwise (P<0.001) (Fig. 2). Through the test set verification, the model effect is good.
Table 5

PI ranges of the training and test sets

PI-trainPI-test
20%−0.37−0.35
40%−0.03− 0.05
50%0.110.09
60%0.260.23
80%0.580.55
90%0.790.78
Table 6

(training-set) Three risk groups and their corresponding mean and median survival times and 1–5-year survival rates

GroupsPI rangesSurvival time (months)Survival rates (%)
MeanMedian1 year2 year3 year4 year5 year
Low riskPI≤0.1190.16115.094.187.079.073.568.2
Intermediate risk0.11<PI<0.7963.8647.083.969.358.949.143.8
High riskPI≥0.7942.9324.068.649.741.632.626.8
Table 7

(test-set) Three risk groups and their corresponding mean and median survival times and 1–5-years survival rates

GroupsPI rangesSurvival time (months)Survival rates (%)
MeanMedian1 year2 year3 year4 year5 year
Low riskPI≤0.0986.80105.0093.886.278.472.168.7
Intermediate risk0.09<PI<0.7863.0951.0084.569.960.051.245.9
High riskPI≥0.7840.5522.0070.647.333.926.825.1
Fig. 2

Kaplan-Meier survival curve of PI ranges

PI ranges of the training and test sets (training-set) Three risk groups and their corresponding mean and median survival times and 1–5-year survival rates (test-set) Three risk groups and their corresponding mean and median survival times and 1–5-years survival rates Kaplan-Meier survival curve of PI ranges We developed a software named RNSCLC-PRSP to predict the prognostic risk and survival of patients with resected T1-3N0–2M0 NSCLC.

Discussion

We have invented a novel tool to predict the prognosis of patients with resected T1-3N0–2M0 NSCLC. We determined the independent risk factors and obtained prognostic risk models and risk groups and their corresponding survival times. This paper highlights that comprehensive and further refined analysis that is capable with the incorporation of clinical pathological factors to predict prognosis of resected T1-3N0–2M0 NSCLC. To access the program, clinicians can enter the url http://www.rnsclcpps.com in a browse to reach the login screen of the software. At the bottom of interface is a brief introduction of the software and an explanation of the relevant abbreviations. Above the interface is the login box. New users can click the button of register on the login box to register. After successful registration, users can click the button to return to the login, enter the username and password, click the button to login and enter the software interface. The first line of interface is titled Prognostic risk and survival prediction software RNSCLC-PRSP for resected T1-3N0–2M0 NSCLC (according to the eighth edition AJCC/UICC stage classification). Operational tips (notes) are located under the title, under the note is an explanation of the relevant abbreviations, and there are alternative options located under the abbreviations. According to the note and explanation of abbreviations, clinicians first need to determine the clinicopathological characteristics of patients. Taking a resected T1-3N0–2M0 (according to the eighth edition of AJCC/UICC stage classification) non-small cell lung cancer patient as an example, the clinicopathological characteristics of a representative patient were gender (man), age (≤65), N stage (N0), NELNs (N>12) ,NPLNs (N ≥ 4) ,surgery type (LET) ,primary site (UL) ,histological grade (III) ,histology (S) ,marital status (married) ,tumor extension (T3 Inv) ,tumor size (T2b>4–5(4 The RNSCLC-PRSP software we have developed is based on the actual needs of clinicians predicting the prognosis of patients with resected NSCLC. Clinicians are very busy in clinical work; meanwhile, the prognosis of resected NSCLC patients is affected by many factors. There is no more time for clinicians to evaluate every factor to obtain a more accurate prognosis. We provide quantitative and relative analysis software, and clinicians can conveniently and swiftly get every patient’s prognostic risk and survival calculated accurately just by choosing some of the clinicopathological features. The RNSCLC-PRSP software would be gladly accepted by clinicians. At present, there have been no relative prognostic predictive software programs for resected T1-3N0–2M0 NSCLC. Pilotto S et al. developed clinicopathological prognostic nomograms for resected squamous cell lung cancer, Based on clinicopathological factors including age, T descriptor (according to the seventh edition of the TNM classification), lymph node status, and grading in the model. Every patient was assigned a prognostic score [28]. Francesco Guerrera et al. designed a prognostic model predicting 5-year survival after surgical resection for stage I non-small cell lung cancer based on clinical, pathological and surgical covariates [25]. Compared to the above two tools, our software analysis includes more clinicopathological features and more detail for more patients with resected non-small cell lung cancer and our novel software is more convenient and practical for clinicians. Although we have established predictive software using relative prognostic factors, we may need to analyze more clinicopathological factors to improve the software. Thus, further research will be conducted. The potential valuable prognostic prediction factors such as smoking status, performance status, comorbidity, molecular biological factors, biochemical and biomarker test results, lung function, tumor vascular or lymphatic invasion, surgical method (minimally invasive or open), and surgery margins, were not able to be determined or researched in more recent database. However, with the expansion of databases, further research will be carried out, and our software can be updated and improved to provide better service.

Conclusions

Using the SEER database and the Cox proportional hazard model, we identified the independent prognostic factors and corresponding PI value of patients with resected T1-3N0–2M0 NSCLC. According to different PI ranges, three prognostic risk groups (the low-, intermediate-, high-risk groups) were determined, and their corresponding survival times were obtained. We developed the RNSCLC-PRSP software for clinicians to conveniently and practically predict the prognosis of patients with resected T1-3N0–2M0 NSCLC to guide further treatment. We have shown that the software we have developed opens a new predictive method in this field.

Availability and requirements

Project name: My bioinformatics project. Project home page: http://www.rnsclcpps.com Operating system(s): Platform independent. Programming language: Java. Other requirements: no. License: no. Any restrictions to use by non-academics: no. Table S1. Variable codes and assignment methods of Cox proportional hazard regression model analysis of resected T1-3N0-2 M0 NSCLC. (DOCX 22 kb)
  28 in total

1.  Exploring Stage I non-small-cell lung cancer: development of a prognostic model predicting 5-year survival after surgical resection†.

Authors:  Francesco Guerrera; Luca Errico; Andrea Evangelista; Pier Luigi Filosso; Enrico Ruffini; Elena Lisi; Giulia Bora; Elena Asteggiano; Stefania Olivetti; Paolo Lausi; Francesco Ardissone; Alberto Oliaro
Journal:  Eur J Cardiothorac Surg       Date:  2014-11-12       Impact factor: 4.191

2.  Predictors of post-recurrence survival in patients with non-small-cell lung cancer initially completely resected.

Authors:  Yusuke Takahashi; Hirotoshi Horio; Tai Hato; Masahiko Harada; Noriyuki Matsutani; Masafumi Kawamura
Journal:  Interact Cardiovasc Thorac Surg       Date:  2015-04-15

3.  Long-term survival after non-small cell lung cancer surgery: development and validation of a prognostic model with a preoperative and postoperative mode.

Authors:  Ozcan Birim; A Pieter Kappetein; Marco Waleboer; John P A Puvimanasinghe; Marinus J C Eijkemans; Ewout W Steyerberg; Michel I M Versteegh; Ad J J C Bogers
Journal:  J Thorac Cardiovasc Surg       Date:  2006-09       Impact factor: 5.209

4.  Composite anatomical-clinical-molecular prognostic model in non-small cell lung cancer.

Authors:  A López-Encuentra; F López-Ríos; E Conde; R García-Luján; A Suárez-Gauthier; N Mañes; G Renedo; J L Duque-Medina; E García-Lagarto; R Rami-Porta; G González-Pont; J Astudillo-Pombo; J L Maté-Sanz; J Freixinet; T Romero-Saavedra; M Sánchez-Céspedes; A Gómez de la Camara
Journal:  Eur Respir J       Date:  2010-09-03       Impact factor: 16.671

5.  Prognostic nomogram to predict survival after surgery for synchronous multiple lung cancers in multiple lobes.

Authors:  Tawee Tanvetyanon; David J Finley; Thomas Fabian; Marc Riquet; Luca Voltolini; Celalettin Kocaturk; Ayesha Bryant; Lary Robinson
Journal:  J Thorac Oncol       Date:  2015-02       Impact factor: 15.609

6.  Significance of the number of positive lymph nodes in resected non-small cell lung cancer.

Authors:  Takayuki Fukui; Shoichi Mori; Kohei Yokoi; Tetsuya Mitsudomi
Journal:  J Thorac Oncol       Date:  2006-02       Impact factor: 15.609

7.  Validation of the 7th TNM classification for non-small cell lung cancer: a retrospective analysis on prognostic implications for operated node-negative cases.

Authors:  Per Bergman; Daniel Brodin; Rolf Lewensohn; Luigi de Petris
Journal:  Acta Oncol       Date:  2012-12-07       Impact factor: 4.089

8.  Gender Differences in Long-Term Survival after Surgery for Non-Small Cell Lung Cancer.

Authors:  Yukihiro Yoshida; Tomonori Murayama; Yasunori Sato; Yoshio Suzuki; Haruhisa Saito; Yukihiro Nomura
Journal:  Thorac Cardiovasc Surg       Date:  2015-09-14       Impact factor: 1.827

Review 9.  Lung Cancer Statistics.

Authors:  Lindsey A Torre; Rebecca L Siegel; Ahmedin Jemal
Journal:  Adv Exp Med Biol       Date:  2016       Impact factor: 2.622

Review 10.  A review of 250 ten-year survivors after pneumonectomy for non-small-cell lung cancer.

Authors:  Marc Riquet; Pierre Mordant; Ciprian Pricopi; Antoine Legras; Christophe Foucault; Antoine Dujon; Alex Arame; Françoise Le Pimpec-Barthes
Journal:  Eur J Cardiothorac Surg       Date:  2013-10-16       Impact factor: 4.191

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