Heterogeneity of Synchronous Lung Metastasis Calls for Risk Stratification and Prognostic Classification: Evidence from a Population-Based Database
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Eligible Patients
2.2. Tumor Classification and Statistical Analyses
3. Results
3.1. Prevalence of Lung Metastasis
3.2. Survival Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Categories | No. of Cases | Prevalence a | Ratio | Distribution c | Survival d | ||
---|---|---|---|---|---|---|---|
All | Metastasis | sLM | sLM | sLM/Metastasis b | |||
All | 1,672,265 | 194,012 | 55,193 | 3.30% (3.27–3.33%) | 28.45% | 100.00% | 7 (2–22) |
Brain | 27,485 | 209 | 17 | 0.06% (0.03–0.09%) | 8.13% | 0.03% | 9 (3–23) |
Head and neck | 74,897 | 3079 | 1574 | 2.10% (2.00–2.20%) | 51.12% | 2.85% | 8 (3–20) |
Thyroid | 78,003 | 1574 | 996 | 1.28% (1.20–1.36%) | 63.28% | 1.80% | 11 (2–79) |
Pathology | |||||||
Solitary | 45,450 | 782 | 516 | 1.14% (1.04–1.23%) *** | 65.98% | 0.93% | 9 (2–70) *** |
Multifocal | 30,707 | 514 | 309 | 1.01% (0.89–1.12%) | 60.12% | 0.56% | 45 (6–NA) |
Unknown | 1846 | 278 | 171 | 9.26% (7.94–10.59%) | 61.51% | 0.31% | 4 (1–13) |
All breast | 358,649 | 18,819 | 5972 | 1.67% (1.62–1.71%) | 31.73% | 10.82% | 20 (5–47) |
Molecular subtype | |||||||
Her2−/HR+ | 15,831 | 1564 | 575 | 3.63% (3.34–3.92%) *** | 36.76% | 1.04% | 20 (4–52) *** |
Her2+/HR+ | 37,204 | 2905 | 907 | 2.44% (2.28–2.59%) | 31.22% | 1.64% | 32 (10–NA) |
Her2+/HR− | 245,301 | 9878 | 2794 | 1.14% (1.10–1.18%) | 28.29% | 5.06% | 27 (8–52) |
Triple negative | 37,359 | 2303 | 944 | 2.53% (2.37–2.69%) | 40.99% | 1.71% | 10 (3–19) |
Unknown | 22,954 | 2169 | 752 | 3.28% (3.05–3.51%) | 34.67% | 1.36% | 8 (1–30) |
BR grade | |||||||
Low | 82,105 | 1245 | 302 | 0.37% (0.33–0.41%) *** | 24.26% | 0.55% | 34 (10–65) *** |
Medium | 140,840 | 5221 | 1474 | 1.05% (0.99–1.10%) | 28.23% | 2.67% | 28 (10–61) |
High | 95,779 | 5413 | 1949 | 2.03% (1.95–2.12%) | 36.01% | 3.53% | 18 (5–43) |
Unknown | 39,925 | 6940 | 2247 | 5.63% (5.40–5.85%) | 32.38% | 4.07% | 15 (2–40) |
Main bronchus | 10,878 | 6848 | 1853 | 17.03% (16.33–17.74%) | 27.06% | 3.36% | 3 (1–10) |
Oesophagus | 20,068 | 6576 | 1976 | 9.85% (9.43–10.26%) | 30.05% | 3.58% | 4 (1–10) |
Stomach | 31,825 | 11,559 | 1756 | 5.52% (5.27–5.77%) | 15.19% | 3.18% | 3 (1–9) |
Liver e | 26,267 | 5793 | 2245 | 8.55% (8.21–8.88%) | 38.75% | 4.07% | 2 (1–6) |
AFP level | |||||||
Elevated | 11,959 | 2598 | 1034 | 8.65% (8.14–9.15%) *** | 39.80% | 1.87% | 2 (1–5) *** |
Normal | 6713 | 1191 | 445 | 6.63% (6.03–7.22%) | 37.36% | 0.81% | 3 (1–8) |
Borderline | 59 | 10 | 2 | NA | 20.00% | 0.00% | 8 (8–8) |
Unknown | 7536 | 1324 | 494 | 6.56% (6.00–7.11%) | 37.31% | 0.90% | 2 (1–8) |
Fibrosis grade | |||||||
None to moderate | 1923 | 277 | 101 | 5.25% (4.26–6.25%) *** | 36.46% | 0.18% | 4 (2–9) *** |
Severe or cirrhotic | 4178 | 524 | 186 | 4.45% (3.83–5.08%) | 35.50% | 0.34% | 2 (0–6) |
Unknown | 20,166 | 4992 | 1958 | 9.71% (9.30–10.12%) | 39.22% | 3.55% | 2 (1–6) |
Extrahepatic biliary tract | 14,238 | 4727 | 876 | 6.15% (5.76–6.55%) | 18.53% | 1.59% | 3 (1–8) |
Pancreas | 52,442 | 26,544 | 5682 | 10.83% (10.57–11.10%) | 21.41% | 10.29% | 3 (1–7) |
Tumor site | |||||||
Head of pancreas | 25,958 | 9343 | 1766 | 6.80% (6.50–7.11%) *** | 18.90% | 3.20% | 3 (1–9) *** |
Body of pancreas | 7272 | 4215 | 919 | 12.64% (11.87–13.40%) | 21.80% | 1.67% | 3 (1–9) |
Tail of pancreas | 8186 | 5663 | 1240 | 15.15% (14.37–15.92%) | 21.90% | 2.25% | 2 (1–6) |
Unspecified pancreas | 11,026 | 7323 | 1757 | 15.94% (15.25–16.62%) | 23.99% | 3.18% | 2 (1–6) |
Small intestine | 9628 | 2584 | 239 | 2.48% (2.17–2.79%) | 9.25% | 0.43% | 8 (2–22) |
Colon & rectum | 186,539 | 37,739 | 9645 | 5.17% (5.07–5.27%) | 25.56% | 17.48% | 11 (3–25) |
Tumor site | |||||||
Right colon | 72,383 | 13,857 | 2777 | 3.84% (3.70–3.98%) *** | 20.04% | 5.03% | 8 (2–21) *** |
Left colon | 64,014 | 13,773 | 3370 | 5.26% (5.09–5.44%) | 24.47% | 6.11% | 13 (3–28) |
Unspecified colon | 4727 | 2549 | 746 | 15.78% (14.74–16.82%) | 29.27% | 1.35% | 3 (1–12) |
Rectum | 45,415 | 7560 | 2752 | 6.06% (5.84–6.28%) | 36.40% | 4.99% | 15 (5–29) |
CEA level | |||||||
CEA elevated | 51,520 | 21,670 | 5987 | 11.62% (11.34–11.90%) *** | 27.63% | 10.85% | 11 (3–24) *** |
CEA normal | 54,991 | 4642 | 840 | 1.53% (1.43–1.63%) | 18.10% | 1.52% | 20 (7–38) |
CEA borderline | 547 | 69 | 11 | 2.01% (0.83–3.19%) | 15.94% | 0.02% | 11 (3–27) |
CEA unknown | 38,692 | 1546 | 178 | 0.46% (0.39–0.53%) | 11.51% | 0.32% | 14 (4–50) |
Perineural Invasion | |||||||
Yes | 16,415 | 5333 | 944 | 5.75% (5.39–6.11%) *** | 17.70% | 1.71% | 18 (6–34) *** |
No | 124,544 | 15,576 | 3332 | 2.68% (2.59–2.76%) | 21.39% | 6.04% | 15 (5–31) |
Unknown | 45,580 | 16,830 | 5369 | 11.78% (11.48–12.08%) | 31.90% | 9.73% | 8 (2–21) |
Anus | 9405 | 695 | 183 | 1.95% (1.67–2.22%) | 26.33% | 0.33% | 11 (5–23) |
Other GI | 8611 | 3222 | 680 | 7.90% (7.33–8.47%) | 21.10% | 1.23% | 2 (0–7) |
Kidney | 69,605 | 9564 | 5823 | 8.37% (8.16–8.57%) | 60.88% | 10.55% | 8 (2–22) |
Fuhrman grade | |||||||
I | 6144 | 131 | 81 | 1.32% (1.03–1.60%) *** | 61.83% | 0.15% | 12 (4–61) *** |
II | 28,826 | 906 | 511 | 1.77% (1.62–1.93%) | 56.40% | 0.93% | 20 (7–44) |
III | 16,496 | 1624 | 956 | 5.80% (5.44–6.15%) | 58.87% | 1.73% | 17 (6–40) |
IV | 4832 | 1569 | 1010 | 20.90% (19.76–22.05%) | 64.37% | 1.83% | 11 (5–29) |
Unknown | 13,307 | 5334 | 3265 | 24.54% (23.80–25.27%) | 61.21% | 5.92% | 4 (2–12) |
Bladder | 41,668 | 3348 | 1215 | 2.92% (2.75–3.08%) | 36.29% | 2.20% | 4 (1–11) |
Pathological grade | |||||||
Low | 3231 | 61 | 27 | 0.84% (0.52–1.15%) *** | 44.26% | 0.05% | 4 (2–15) *** |
High | 32,596 | 2322 | 813 | 2.49% (2.32–2.66%) | 35.01% | 1.47% | 4 (2–11) |
Unknown | 5841 | 965 | 375 | 6.42% (5.79–7.05%) | 38.86% | 0.68% | 3 (1–9) |
Prostate | 309,918 | 15,735 | 1339 | 0.43% (0.41–0.46%) | 8.51% | 2.43% | 22 (8–63) |
PSA level | |||||||
1st quantile | 67,653 | 588 | 81 | 0.12% (0.09–0.15%) *** | 13.78% | 0.15% | 11 (5–32) *** |
2nd quantile | 64,654 | 317 | 28 | 0.04% (0.03–0.06%) | 8.83% | 0.05% | 14 (6–42) |
3rd quantile | 64,571 | 685 | 46 | 0.07% (0.05–0.09%) | 6.72% | 0.08% | 22 (11–NA) |
4th quantile | 64,103 | 5332 | 373 | 0.58% (0.52–0.64%) | 7.00% | 0.68% | 27 (9–72) |
Unknown | 48,937 | 8813 | 811 | 1.66% (1.54–1.77%) | 9.20% | 1.47% | 20 (9–53) |
Testis | 15,881 | 1791 | 1129 | 7.11% (6.71–7.51%) | 63.04% | 2.05% | NA (20–NA) |
Other GU | 8718 | 1152 | 529 | 6.07% (5.57–6.57%) | 45.92% | 0.96% | 5 (2–12) |
Ovary | 29,789 | 7790 | 1696 | 5.69% (5.43–5.96%) | 21.77% | 3.07% | 16 (2–36) |
CA125 level | |||||||
Elevated | 20,383 | 6164 | 1343 | 6.59% (6.25–6.93%) *** | 21.79% | 2.43% | 18 (3–37) *** |
Normal | 2761 | 176 | 29 | 1.05% (0.67–1.43%) | 16.48% | 0.05% | 12 (4–25) |
Borderline | 36 | 4 | 0 | NA | 0.00% | 0.00% | NA |
Unknown | 6609 | 1446 | 324 | 4.90% (4.38–5.42%) | 22.41% | 0.59% | 7 (1–27) |
Uterus | 73,342 | 4206 | 1232 | 1.68% (1.59–1.77%) | 29.29% | 2.23% | 8 (2–22) |
Cervix | 20,658 | 2712 | 844 | 4.09% (3.82–4.36%) | 31.12% | 1.53% | 7 (3–17) |
Other GYN | 10,514 | 1355 | 457 | 4.35% (3.96–4.74%) | 33.73% | 0.83% | 5 (1–23) |
Bone tumor | 5079 | 863 | 609 | 11.99% (11.10–12.88%) | 70.57% | 1.10% | 19 (8–NA) |
STS | 25,093 | 3537 | 2181 | 8.69% (8.34–9.04%) | 61.66% | 3.95% | 8 (2–23) |
Skin Melanoma | 107,287 | 2256 | 1065 | 0.99% (0.93–1.05%) | 47.21% | 1.93% | 6 (2–20) |
Ulceration | |||||||
Yes | 13,441 | 619 | 268 | 1.99% (1.76–2.23%) *** | 43.30% | 0.49% | 7 (3–22) *** |
No | 89,168 | 567 | 235 | 0.26% (0.23–0.30%) | 41.45% | 0.43% | 11 (4–39) |
Unknown | 4678 | 1070 | 562 | 12.01% (11.08–12.95%) | 52.52% | 1.02% | 4 (1–13) |
Non-skin melanoma | 3084 | 247 | 106 | 3.44% (2.79–4.08%) | 42.91% | 0.19% | 6 (3–14) |
Skin cancer | 5345 | 203 | 37 | 0.69% (0.47–0.91%) | 18.23% | 0.07% | 9 (6–18) |
Embryonal tumors | 4281 | 877 | 334 | 7.80% (7.00–8.61%) | 38.08% | 0.61% | NA (19–NA) |
All other | 33,068 | 8408 | 2903 | 8.78% (8.47–9.08%) | 34.53% | 5.26% | 5 (1–20) |
Categories | Number of Cases | Prevalence a | Ratio | Distribution c | Survival d | ||
---|---|---|---|---|---|---|---|
All | Metastasis | sLM | sLM | sLM/Metastasis b | |||
Year of diagnosis | |||||||
2010 | 232,553 | 25,223 | 6776 | 2.91% (2.85–2.98%) *** | 26.86% | 12.28% | 7 (2–22) *** |
2011 | 236,568 | 25,572 | 7144 | 3.02% (2.95–3.09%) | 27.94% | 12.94% | 7 (2–22) |
2012 | 234,008 | 26,323 | 7504 | 3.21% (3.14–3.28%) | 28.51% | 13.60% | 7 (2–21) |
2013 | 234,946 | 27,393 | 7878 | 3.35% (3.28–3.43%) | 28.76% | 14.27% | 7 (2–23) |
2014 | 238,679 | 28,404 | 8172 | 3.42% (3.35–3.50%) | 28.77% | 14.81% | 7 (2–23) |
2015 | 245,850 | 29,658 | 8544 | 3.48% (3.40–3.55%) | 28.81% | 15.48% | 7 (2–22) |
2016 | 249,661 | 31,439 | 9175 | 3.67% (3.60–3.75%) | 29.18% | 16.62% | 8 (2–NA) |
Sex | |||||||
Female | 873,620 | 94,869 | 27,642 | 3.16% (3.13–3.20%) *** | 29.14% | 50.08% | 8 (2–25) *** |
Male | 798,645 | 99,143 | 27,551 | 3.45% (3.41–3.49%) | 27.79% | 49.92% | 7 (2–20) |
Race | |||||||
Caucasian | 1,323,660 | 149,175 | 42,188 | 3.19% (3.16–3.22%) *** | 28.28% | 76.44% | 7 (2–23) *** |
African American | 187,441 | 27,368 | 7687 | 4.10% (4.01–4.19%) | 28.09% | 13.93% | 7 (2–20) |
Other | 132,299 | 16,772 | 5138 | 3.88% (3.78–3.99%) | 30.63% | 9.31% | 8 (2–24) |
Unknown | 28,865 | 697 | 180 | 0.62% (0.53–0.71%) | 25.82% | 0.33% | 14 (4–NA) |
Age group | |||||||
0–18 | 13,939 | 1873 | 926 | 6.64% (6.23–7.06%) *** | 49.44% | 1.68% | NA (17–NA) *** |
19–40 | 115,626 | 9374 | 3311 | 2.86% (2.77–2.96%) | 35.32% | 6.00% | 21 (7–NA) |
41–60 | 597,058 | 63,954 | 17,863 | 2.99% (2.95–3.04%) | 27.93% | 32.36% | 9 (3–26) |
61–80 | 794,720 | 96,147 | 26,863 | 3.38% (3.34–3.42%) | 27.94% | 48.67% | 6 (1–19) |
81+ | 150,922 | 22,664 | 6230 | 4.13% (4.03–4.23%) | 27.49% | 11.29% | 3 (1–10) |
T stage | |||||||
T1 | 715,832 | 20,927 | 5618 | 0.78% (0.76–0.81%) *** | 26.85% | 10.18% | 9 (2–27) *** |
T2 | 403,599 | 30,559 | 8392 | 2.08% (2.04–2.12%) | 27.46% | 15.20% | 9 (2–29) |
T3 | 285,021 | 48,304 | 12,631 | 4.43% (4.36–4.51%) | 26.15% | 22.89% | 11 (3–29) |
T4 | 110,768 | 39,789 | 11,325 | 10.22% (10.05–10.40%) | 28.46% | 20.52% | 7 (2–20) |
Unknown | 157,045 | 54,433 | 17,227 | 10.97% (10.81–11.12%) | 31.65% | 31.21% | 4 (1–15) |
N stage | |||||||
N0 | 1,184,206 | 72,679 | 19,196 | 1.62% (1.60–1.64%) *** | 26.41% | 34.78% | 8 (2–25) *** |
N1 | 255,900 | 59,633 | 17,193 | 6.72% (6.62–6.82%) | 28.83% | 31.15% | 8 (2–23) |
N2 | 90,865 | 21,136 | 5313 | 5.85% (5.69–6.00%) | 25.14% | 9.63% | 9 (2–24) |
N3 | 23,729 | 7065 | 2173 | 9.16% (8.79–9.52%) | 30.76% | 3.94% | 10 (3–30) |
Unknown | 117,565 | 33,499 | 11,318 | 9.63% (9.46–9.80%) | 33.79% | 20.51% | 4 (1–15) |
Insurance status | |||||||
Insured | 1,540,367 | 181,774 | 51,501 | 3.34% (3.32–3.37%) *** | 28.33% | 93.31% | 7 (2–23) ns |
Uninsured | 42,868 | 8546 | 2663 | 6.21% (5.98–6.44%) | 31.16% | 4.82% | 6 (1–21) |
Unknown | 89,030 | 3692 | 1029 | 1.16% (1.09–1.23%) | 27.87% | 1.86% | 5 (1–22) |
Marital status | |||||||
Married | 911,531 | 97,059 | 26,141 | 2.87% (2.83–2.90%) *** | 26.93% | 47.36% | 8 (2–23) *** |
Unmarried | 610,219 | 87,716 | 26,503 | 4.34% (4.29–4.39%) | 30.21% | 48.02% | 6 (2–21) |
Unknown | 150,515 | 9237 | 2549 | 1.69% (1.63–1.76%) | 27.60% | 4.62% | 7 (2–23) |
County-level income | |||||||
1st quantile | 80,355 | 10,542 | 2900 | 3.61% (3.48–3.74%) *** | 27.51% | 5.25% | 6 (2–19) *** |
2nd quantile | 162,810 | 20,689 | 5917 | 3.63% (3.54–3.73%) | 28.60% | 10.72% | 6 (2–20) |
3rd quantile | 223,745 | 26,546 | 7504 | 3.35% (3.28–3.43%) | 28.27% | 13.60% | 7 (2–21) |
4th quantile | 1,203,286 | 135,898 | 38,754 | 3.22% (3.19–3.25%) | 28.52% | 70.22% | 8 (2–23) |
Unknown | 2069 | 337 | 118 | 5.70% (4.70–6.70%) | 35.01% | 0.21% | 5 (1–13) |
County-level education | |||||||
1st quantile | 58,086 | 7592 | 2078 | 3.58% (3.43–3.73%) *** | 27.37% | 3.76% | 6 (2–18) *** |
2nd quantile | 125,184 | 15,693 | 4524 | 3.61% (3.51–3.72%) | 28.83% | 8.20% | 6 (2–20) |
3rd quantile | 301,780 | 36,451 | 10,382 | 3.44% (3.38–3.51%) | 28.48% | 18.81% | 7 (2–20) |
4th quantile | 1,185,146 | 133,939 | 38,091 | 3.21% (3.18–3.25%) | 28.44% | 69.01% | 8 (2–24) |
Unknown | 2069 | 337 | 118 | 5.70% (4.70–6.70%) | 35.01% | 0.21% | 5 (1–13) |
Residence | |||||||
Metro | 1,489,707 | 171,907 | 48,948 | 3.29% (3.26–3.31%) *** | 28.47% | 88.69% | 7 (2–23) *** |
Urban | 159,003 | 19,010 | 5346 | 3.36% (3.27–3.45%) | 28.12% | 9.69% | 7 (2–20) |
Rural | 23,351 | 3086 | 898 | 3.85% (3.60–4.09%) | 29.10% | 1.63% | 6 (2–17) |
Unknown | 204 | 9 | 1 | NA | 11.11% | 0.00% | 73 (73–73) |
Categories | OR | 95% CI | p-Value | Categories | OR | 95% CI | p-Value |
---|---|---|---|---|---|---|---|
Sex | Liver metastasis | ||||||
Female | Reference | Yes | Reference | ||||
Male | 1.01 | (0.98–1.03) | ns | No | 0.16 | (0.16–0.17) | *** |
Race | Unknown | 0.83 | (0.75–0.92) | *** | |||
Caucasian | Reference | NA | 0.71 | (0.45–1.14) | ns | ||
African American | 1.17 | (1.14–1.21) | *** | Insurance | |||
Other | 1.15 | (1.11–1.19) | *** | Insured | Reference | ||
Unknown | 0.46 | (0.39–0.53) | *** | Uninsured | 1.27 | (1.21–1.33) | *** |
Age group | Unknown | 0.68 | (0.64–0.74) | *** | |||
0–18 | Reference | Marital status | |||||
19–40 | 0.70 | (0.63–0.77) | *** | Married | Reference | ||
41–60 | 0.82 | (0.74–0.90) | *** | Unmarried | 1.18 | (1.16–1.20) | *** |
61–80 | 1.01 | (0.92–1.12) | ns | Unknown | 0.90 | (0.86–0.95) | *** |
81+ | 1.10 | (0.99–1.21) | ns | County-level income | |||
T stage | 1st quantile | Reference | |||||
T1 | Reference | 2nd quantile | 1.02 | (0.96–1.08) | ns | ||
T2 | 2.37 | (2.28–2.46) | *** | 3rd quantile | 0.99 | (0.93–1.04) | ns |
T3 | 3.10 | (2.99–3.21) | *** | 4th quantile | 0.98 | (0.93–1.04) | ns |
T4 | 5.80 | (5.58–6.03) | *** | Unknown | NA | NA | NA |
TX | 5.43 | (5.22–5.64) | *** | County-level education | |||
N stage | 1st quantile | Reference | |||||
N0 | Reference | 2nd quantile | 1.03 | (0.96–1.10) | ns | ||
N1 | 2.20 | (2.14–2.25) | *** | 3rd quantile | 1.02 | (0.95–1.08) | ns |
N2 | 1.84 | (1.77–1.92) | *** | 4th quantile | 0.99 | (0.93–1.06) | ns |
N3 | 2.74 | (2.59–2.91) | *** | Unknown | 1.32 | (1.05–1.67) | * |
NX | 1.71 | (1.65–1.77) | *** | Residence | |||
Bone metastasis | Metro | Reference | |||||
Yes | Reference | Urban | 0.99 | (0.95–1.03) | ns | ||
No | 0.17 | (0.17–0.18) | *** | Rural | 1.06 | (0.97–1.16) | ns |
Unknown | 0.53 | (0.48–0.60) | *** | Unknown | 0.34 | (0.05–2.50) | ns |
NA | 0.73 | (0.29–1.85) | ns | ||||
Brain metastasis | |||||||
Yes | Reference | ||||||
No | 0.17 | (0.16–0.18) | *** | ||||
Unknown | 0.44 | (0.39–0.49) | *** | ||||
NA | 0.65 | (0.26–1.64) | ns |
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Wang, S.; Chen, L.; Feng, Y.; Swinnen, J.V.; Jonscher, C.; Van Ongeval, C.; Ni, Y. Heterogeneity of Synchronous Lung Metastasis Calls for Risk Stratification and Prognostic Classification: Evidence from a Population-Based Database. Cancers 2022, 14, 1608. https://doi.org/10.3390/cancers14071608
Wang S, Chen L, Feng Y, Swinnen JV, Jonscher C, Van Ongeval C, Ni Y. Heterogeneity of Synchronous Lung Metastasis Calls for Risk Stratification and Prognostic Classification: Evidence from a Population-Based Database. Cancers. 2022; 14(7):1608. https://doi.org/10.3390/cancers14071608
Chicago/Turabian StyleWang, Shuncong, Lei Chen, Yuanbo Feng, Johan V. Swinnen, Charles Jonscher, Chantal Van Ongeval, and Yicheng Ni. 2022. "Heterogeneity of Synchronous Lung Metastasis Calls for Risk Stratification and Prognostic Classification: Evidence from a Population-Based Database" Cancers 14, no. 7: 1608. https://doi.org/10.3390/cancers14071608