| Literature DB >> 31462928 |
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.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
Fig. 1According 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
| Characteristics | Number of patients |
|---|---|
| All patients | 6886 (100%) |
| Gender | |
| Male | 3363 (48.8%) |
| Female | 3523 (51.2%) |
| Age | |
| ≤65 | 2964 (43.0%) |
| > 65 | 3922 (57.0%) |
| Laterality | |
| Right | 3958 (57.5%) |
| Left | 2928 (42.5%) |
| Race | |
| White | 5770 (83.8%) |
| Black | 589 (8.6%) |
| Others | 527 (7.6%) |
| N stage a | |
| N0 | 4578 (66.5%) |
| N1 | 1228 (17.8%) |
| N2 | 1080 (15.7%) |
| NELNs | |
| N ≤ 6 | 2495 (36.2%) |
| 6<N ≤ 12 | 2272 (33.0%) |
| N>12 | 2119 (30.8%) |
| NPLNs | |
| N = 0 | 4658 (67.6%) |
| 1 ≤ N ≤ 3 | 1623 (23.6%) |
| N ≥ 4 | 605 (8.8%) |
| Surgery type | |
| SLET | 599 (8.7%) |
| LET | 5748 (83.5%) |
| PET | 539 (7.8%) |
| Primary site | |
| UL | 4125 (60.0%) |
| ML | 414 (6.0%) |
| LL | 2213 (32.1%) |
| Others | 134 (1.9%) |
| Histological grade | |
| I | 816 (11.9%) |
| II | 3158 (45.9%) |
| III | 2766 (40.2%) |
| IV | 146 (2.0%) |
| Histology | |
| AC | 3013 (43.8%) |
| S | 1629 (23.7%) |
| ASC | 206 (3.0%) |
| BAA | 220 (3.2%) |
| Others | 1818 (26.3%) |
| Marital status | |
| Single (never married) | 801 (11.6%) |
| Married | 4115 (59.8%) |
| Divorced | 854 (12.4%) |
| Widowed | 1017 (14.8%) |
| Others | 99 (1.4%) |
| Tumor extension a | |
| T1a ss | 729 (10.6%) |
| T2 Visc PI | 4078 (59.2%) |
| T2 Centr | 1366 (19.8%) |
| T3 Inv | 68 (1.0%) |
| T3 Satell | 645 (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 | |
| Dead | 2443 (35.5%) |
| Alive | 4443 (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
Univariate analysis of the Cox proportional hazard regression model of resected T1-3N0 − 2 M0 NSCLC
| Factors | Variates | b | SE | RR | 95%CI |
|
|---|---|---|---|---|---|---|
| Gender | X1 | 0.363 | 0.049 | 1.438 | 1.307~1.582 | < 0.001 |
| Age | X2 | −0.354 | 0.050 | 0.702 | 0.637~0.774 | < 0.001 |
| Laterality | X3 | − 0.009 | 0.049 | 0.991 | 0.900~1.091 | 0.858 |
| Race (as dummy variables) | X4 | |||||
| Others | 1.0 | |||||
| White | X41 | 0.159 | 0.102 | 1.172 | 0.961~1.430 | 0.118 |
| Black | X42 | 0.172 | 0.130 | 1.188 | 0.920~1.532 | 0.186 |
| N stage a (as dummy variables) | X5 | |||||
| N0 | X50 | −0.858 | 0.060 | 0.424 | 0.377~0.477 | < 0.001 |
| N1 | X51 | −0.220 | 0.071 | 0.803 | 0.699~0.922 | 0.002 |
| NELNs (as dummy variables) | X6 | |||||
| N ≤ 6 | 1.0 | |||||
| 6<N ≤ 12 | X61 | −0.121 | 0.058 | 0.886 | 0.790~0.993 | 0.038 |
| N>12 | X62 | −0.046 | 0.059 | 0.956 | 0.852~1.072 | 0.438 |
| NPLNs (as dummy variables) | X7 | |||||
| N = 0 | 1.0 | |||||
| 1 ≤ N ≤ 3 | X71 | 0.698 | 0.054 | 2.009 | 1.808~2.234 | < 0.001 |
| N ≥ 4 | X72 | 0.862 | 0.074 | 2.367 | 2.046~2.739 | < 0.001 |
| Surgery type (as dummy variables) | X8 | |||||
| SLET | 1.0 | |||||
| LET | X81 | −0.242 | 0.086 | 0.785 | 0.664~0.929 | 0.005 |
| PET | X82 | 0.088 | 0.109 | 1.092 | 0.882~1.353 | 0.420 |
| Primary site (as dummy variables) | X9 | |||||
| Others | X90 | −0.239 | 0.160 | 0.788 | 0.576~1.078 | 0.136 |
| UL | X91 | −0.114 | 0.052 | 0.892 | 0.806~0.987 | 0.028 |
| ML | X92 | −0.273 | 0.114 | 0.761 | 0.609~0.952 | 0.017 |
| Histological grade (as dummy variables) | X10 | |||||
| I | 1.0 | |||||
| II | X101 | 0.551 | 0.096 | 1.736 | 1.437~2.097 | < 0.001 |
| III | X102 | 0.834 | 0.095 | 2.301 | 1.909~2.775 | < 0.001 |
| IV | X103 | 0.998 | 0.161 | 2.712 | 1.977~3.722 | < 0.001 |
| Histology (as dummy variables) | X11 | |||||
| Others | 1.0 | |||||
| AC | X111 | 0.197 | 0.063 | 1.217 | 1.076~1.377 | 0.002 |
| S | X112 | 0.379 | 0.068 | 1.462 | 1.280~1.669 | < 0.001 |
| ASC | X113 | 0.588 | 0.134 | 1.801 | 1.385~2.342 | < 0.001 |
| BAA | X114 | −0.304 | 0.156 | 0.738 | 0.543~1.002 | 0.051 |
| Marital status (as dummy variables) | X12 | |||||
| Others | X120 | −0.057 | 0.216 | 0.945 | 0.618~1.444 | 0.793 |
| Single (never married) | X121 | −0.258 | 0.092 | 0.773 | 0.645~0.926 | 0.005 |
| Married | X122 | −0.286 | 0.066 | 0.751 | 0.660~0.855 | < 0.001 |
| Divorced | X123 | −0.290 | 0.090 | 0.749 | 0.627~0.894 | 0.001 |
| Tumor extensiona (as dummy variables) | X13 | |||||
| T1a ss | 1.0 | |||||
| T2 Visc PI | X131 | 0.114 | 0.082 | 1.121 | 0.954~1.317 | 0.166 |
| T2 Centr | X132 | 0.353 | 0.085 | 1.424 | 1.206~1.680 | < 0.001 |
| T3 Inv | X133 | 0.809 | 0.196 | 2.247 | 1.529~3.300 | < 0.001 |
| T3 Satell | X134 | 0.514 | 0.092 | 1.672 | 1.395~2.002 | < 0.001 |
| Tumor sizea (as dummy variables) | X14 | |||||
| T1a ≤ 1(T ≤ 1) | 1.0 | |||||
| T1b>1–2(1<T ≤ 2) | X141 | 0.016 | 0.172 | 1.016 | 0.725~1.425 | 0.927 |
| T1c>2–3(2<T ≤ 3) | X142 | 0.361 | 0.169 | 1.434 | 1.030~1.997 | 0.033 |
| T2a>3–4(3<T ≤ 4) | X143 | 0.584 | 0.170 | 1.793 | 1.286~2.501 | 0.001 |
| T2b>4–5(4<T ≤ 5) | X144 | 0.585 | 0.174 | 1.794 | 1.276~2.523 | 0.001 |
| T3>5–7(5<T ≤ 7) | X145 | 0.664 | 0.174 | 1.943 | 1.382~2.732 | < 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.
Multivariate analysis of the Cox proportional hazard regression model of resected T1-3N0 − 2 M0 NSCLC
| Factors | Variates | b | SE | RR | 95%CI |
|
|---|---|---|---|---|---|---|
| Gender | X1 | 0.379 | 0.053 | 1.460 | 1.317~1.620 | < 0.001 |
| Age | X2 | −0.403 | 0.054 | 0.668 | 0.601~0.743 | < 0.001 |
| N stage | 0.001 | |||||
| N0 | X50 | −0.372 | 0.195 | 0.689 | 0.470~1.010 | 0.056 |
| N1 | X51 | −0.267 | 0.075 | 0.766 | 0.661~0.886 | < 0.001 |
| NELNs | < 0.001 | |||||
| 6<N ≤ 12 | X61 | −0.167 | 0.060 | 0.846 | 0.751~0.952 | 0.006 |
| N>12 | X62 | −0.298 | 0.064 | 0.742 | 0.655~0.841 | < 0.001 |
| NPLNs | 0.003 | |||||
| 1 ≤ N ≤ 3 | X71 | 0.460 | 0.197 | 1.583 | 1.077~2.328 | 0.019 |
| N ≥ 4 | X72 | 0.617 | 0.203 | 1.854 | 1.245~2.762 | 0.002 |
| Surgery type | 0.001 | |||||
| LET | X81 | −0.344 | 0.090 | 0.709 | 0.595~0.845 | < 0.001 |
| PET | X82 | −0.245 | 0.127 | 0.783 | 0.611~1.003 | 0.053 |
| Primary site | 0.035 | |||||
| Others | X90 | −0.308 | 0.172 | 0.735 | 0.525~1.029 | 0.073 |
| UL | X91 | −0.105 | 0.053 | 0.900 | 0.811~0.999 | 0.047 |
| ML | X92 | −0.243 | 0.116 | 0.784 | 0.625~0.983 | 0.035 |
| Histological grade | < 0.001 | |||||
| II | X101 | 0.305 | 0.100 | 1.356 | 1.114~1.651 | 0.002 |
| III | X102 | 0.508 | 0.101 | 1.663 | 1.364~2.027 | < 0.001 |
| IV | X103 | 0.754 | 0.167 | 2.126 | 1.532~2.950 | < 0.001 |
| Histology | 0.011 | |||||
| AC | X111 | 0.143 | 0.066 | 1.153 | 1.013~1.313 | 0.031 |
| S | X112 | 0.170 | 0.073 | 1.186 | 1.028~1.368 | 0.019 |
| ASC | X113 | 0.434 | 0.137 | 1.544 | 1.181~2.019 | 0.001 |
| BAA | X114 | −0.030 | 0.160 | 0.970 | 0.709~1.328 | 0.851 |
| Marital status | < 0.001 | |||||
| Others | X120 | 0.016 | 0.221 | 1.016 | 0.659~1.566 | 0.944 |
| Single (never married) | X121 | −0.133 | 0.098 | 0.875 | 0.723~1.060 | 0.172 |
| Married | X122 | −0.327 | 0.071 | 0.721 | 0.628~0.829 | < 0.001 |
| Divorced | X123 | −0.247 | 0.094 | 0.781 | 0.650~0.938 | 0.008 |
| Tumor extensiona | < 0.001 | |||||
| T2 Visc PI | X131 | −0.115 | 0.087 | 0.892 | 0.752~1.056 | 0.185 |
| T2 Centr | X132 | 0.025 | 0.092 | 1.025 | 0.856~1.229 | 0.786 |
| T3 Inv | X133 | 0.517 | 0.204 | 1.678 | 1.125~2.500 | 0.011 |
| T3 Satell | X134 | 0.340 | 0.095 | 1.405 | 1.167~1.692 | < 0.001 |
| Tumor sizea | < 0.001 | |||||
| T1b>1–2(1<T ≤ 2) | X141 | 0.025 | 0.174 | 1.025 | 0.729~1.442 | 0.886 |
| T1c>2–3(2<T ≤ 3) | X142 | 0.260 | 0.171 | 1.297 | 1.927~1.815 | 0.129 |
| T2a>3–4(3<T ≤ 4) | X143 | 0.457 | 0.174 | 1.580 | 1.122~2.223 | 0.009 |
| T2b>4–5(4<T ≤ 5) | X144 | 0.419 | 0.179 | 1.520 | 1.069~2.161 | 0.020 |
| T3>5–7(5<T ≤ 7) | X145 | 0.407 | 0.180 | 1.502 | 1.055~2.140 | 0.024 |
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
The importance of each variable for prediction
| Variable | Importance | Standard importance |
|---|---|---|
| Tumor extension | 0.045 | 100.0% |
| N stage | 0.016 | 35.5% |
| NPLNs | 0.015 | 33.1% |
| Histology | 0.007 | 15.4% |
| Surgery type | 0.007 | 14.9% |
| Age | 0.005 | 11.5% |
| Gender | 0.005 | 10.6% |
| Histological grade | 0.004 | 9.8% |
| Primary site | 0.002 | 4.9% |
| Marital status | 0.002 | 3.6% |
| NELNs | 0.001 | 2.8% |
| Tumor size | 0.001 | 2.2% |
| Race | 0.001 | 1.4% |
| Laterality | 0.000 | 1.0% |
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
PI ranges of the training and test sets
| PI-train | PI-test | |
|---|---|---|
| 20% | −0.37 | −0.35 |
| 40% | −0.03 | − 0.05 |
| 50% | 0.11 | 0.09 |
| 60% | 0.26 | 0.23 |
| 80% | 0.58 | 0.55 |
| 90% | 0.79 | 0.78 |
(training-set) Three risk groups and their corresponding mean and median survival times and 1–5-year survival rates
| Groups | PI ranges | Survival time (months) | Survival rates (%) | |||||
|---|---|---|---|---|---|---|---|---|
| Mean | Median | 1 year | 2 year | 3 year | 4 year | 5 year | ||
| Low risk | PI≤0.11 | 90.16 | 115.0 | 94.1 | 87.0 | 79.0 | 73.5 | 68.2 |
| Intermediate risk | 0.11<PI<0.79 | 63.86 | 47.0 | 83.9 | 69.3 | 58.9 | 49.1 | 43.8 |
| High risk | PI≥0.79 | 42.93 | 24.0 | 68.6 | 49.7 | 41.6 | 32.6 | 26.8 |
(test-set) Three risk groups and their corresponding mean and median survival times and 1–5-years survival rates
| Groups | PI ranges | Survival time (months) | Survival rates (%) | |||||
|---|---|---|---|---|---|---|---|---|
| Mean | Median | 1 year | 2 year | 3 year | 4 year | 5 year | ||
| Low risk | PI≤0.09 | 86.80 | 105.00 | 93.8 | 86.2 | 78.4 | 72.1 | 68.7 |
| Intermediate risk | 0.09<PI<0.78 | 63.09 | 51.00 | 84.5 | 69.9 | 60.0 | 51.2 | 45.9 |
| High risk | PI≥0.78 | 40.55 | 22.00 | 70.6 | 47.3 | 33.9 | 26.8 | 25.1 |
Fig. 2Kaplan-Meier survival curve of PI ranges