Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia
Abstract
:1. Introduction
2. Materials and Methods
3. Results
3.1. Baseline Characteristics of Patient Population with WD GEP-NEN
3.2. Overall Survival and Progression-Free Survival at 5 and 10 Years according to the Presence of Metabolic Syndrome
3.3. Median Overall Survival and Progression-Free Survival of Patients with WD GEP-NEN according to the Presence of MetS
3.4. Influence of Tumor Pathological Features on Patient Outcomes
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Dasari, A.; Shen, C.; Halperin, D.; Zhao, B.; Zhou, S.; Xu, Y.; Shih, T.; Yao, J.C. Trends in the Incidence, Prevalence, and Survival Outcomes in Patients With Neuroendocrine Tumors in the United States. JAMA Oncol. 2017, 3, 1335–1342. [Google Scholar] [CrossRef] [PubMed]
- NCD Countdown Collaborators. NCD Countdown 2030: Worldwide trends in non-communicable disease mortality and progress towards Sustainable Development Goal target 3.4. Lancet 2018, 392, 1072–1088. [Google Scholar] [CrossRef] [Green Version]
- Islami, F.; Goding Sauer, A.; Miller, K.D.; Siegel, R.L.; Fedewa, S.A.; Jacobs, E.J.; McCullough, M.L.; Patel, A.V.; Ma, J.; Soerjomataram, I.; et al. Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States. CA Cancer J. Clin. 2018, 68, 31–54. [Google Scholar] [CrossRef] [PubMed]
- Wu, S.; Zhu, W.; Thompson, P.; Hannun, Y.A. Evaluating intrinsic and non-intrinsic cancer risk factors. Nat. Commun. 2018, 9, 3490. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cao, Z.; Xu, C.; Yang, H.; Li, S.; Wang, Y. The role of healthy lifestyle in cancer incidence and temporal transitions to cardiometabolic disease. Cardio Oncol. 2021, 3, 663–674. [Google Scholar] [CrossRef]
- Arnold, M.; Pandeya, N.; Byrnes, G.; Renehan, P.A.G.; Stevens, G.A.; Ezzati, P.M.; Ferlay, J.; Miranda, J.J.; Romieu, I.; Dikshit, R.; et al. Global burden of cancer attributable to high body-mass index in 2012: A population-based study. Lancet Oncol. 2015, 16, 36–46. [Google Scholar] [CrossRef]
- Avgerinos, K.I.; Spyrou, N.; Mantzoros, C.S.; Dalamaga, M. Obesity and cancer risk: Emerging biological mechanisms and perspectives. Metabolism 2019, 92, 121–135. [Google Scholar] [CrossRef]
- Bhaskaran, K.; Douglas, I.; Forbes, H.; dos-Santos-Silva, I.; Leon, D.A.; Smeeth, L. Body-mass index and risk of 22 specific cancers: A population-based cohort study of 5.24 million UK adults. Lancet 2014, 384, 755–765. [Google Scholar] [CrossRef] [Green Version]
- Garg, S.K.; Maurer, H.; Reed, K.; Selagamsetty, R. Diabetes and cancer: Two diseases with obesity as a common risk factor. Diabetes Obes. Metab. 2014, 16, 97–110. [Google Scholar] [CrossRef]
- Esposito, K.; Chiodini, P.; Colao, A.; Lenzi, A.; Giugliano, D. Metabolic syndrome and risk of cancer: A systematic review and meta-analysis. Diabetes Care 2012, 35, 2402–2411. [Google Scholar] [CrossRef]
- Calle, E.E.; Rodriguez, C.; Walker-Thurmond, K.; Thun, M.J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N. Engl. J. Med. 2003, 348, 1625–1638. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gong, Z.; Agalliu, I.; Lin, D.W.; Stanford, J.L.; Kristal, A.R. Obesity is associated with increased risks of prostate cancer metastasis and death after initial cancer diagnosis in middle-aged men. Cancer 2007, 109, 1192–1202. [Google Scholar] [CrossRef] [PubMed]
- Hu, D.; Zhang, M.; Zhang, H.; Xia, Y.; Lin, J.; Zheng, X.; Peng, F.; Niu, W. Prediction of Metabolic Syndrome for the Survival of Patients With Digestive Tract Cancer: A Meta-Analysis. Front. Oncol. 2019, 9, 281. [Google Scholar] [CrossRef] [PubMed]
- Watanabe, J.; Kakehi, E.; Kotani, K.; Kayaba, K.; Nakamura, Y.; Ishikawa, S. Metabolic syndrome is a risk factor for cancer mortality in the general Japanese population: The Jichi Medical School Cohort Study. Diabetol. Metab. Syndr. 2019, 11, 3. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- You, J.; Liu, W.Y.; Zhu, G.Q.; Wang, O.C.; Ma, R.M.; Huang, G.Q.; Shi, K.Q.; Guo, G.L.; Braddock, M.; Zheng, M.H. Metabolic syndrome contributes to an increased recurrence risk of non-metastatic colorectal cancer. Oncotarget 2015, 6, 19880–19890. [Google Scholar] [CrossRef] [Green Version]
- Balentine, C.J.; Enriquez, J.; Fisher, W.; Hodges, S.; Bansal, V.; Sansgiry, S.; Petersen, N.J.; Berger, D.H. Intra-abdominal fat predicts survival in pancreatic cancer. J. Gastrointest. Surg. 2010, 14, 1832–1837. [Google Scholar] [CrossRef]
- Santos, A.P.; Santos, A.C.; Castro, C.; Raposo, L.; Pereira, S.S.; Torres, I.; Henrique, R.; Cardoso, H.; Monteiro, M.P. Visceral Obesity and Metabolic Syndrome Are Associated with Well-Differentiated Gastroenteropancreatic Neuroendocrine Tumors. Cancers 2018, 10, 293. [Google Scholar] [CrossRef] [Green Version]
- Heetfeld, M.; Chougnet, C.N.; Olsen, I.H.; Rinke, A.; Borbath, I.; Crespo, G.; Barriuso, J.; Pavel, M.; O’Toole, D.; Walter, T.; et al. Characteristics and treatment of patients with G3 gastroenteropancreatic neuroendocrine neoplasms. Endocr. Relat. Cancer 2015, 22, 657–664. [Google Scholar] [CrossRef] [Green Version]
- O’Toole, D.; Kianmanesh, R.; Caplin, M. ENETS 2016 Consensus Guidelines for the Management of Patients with Digestive Neuroendocrine Tumors: An Update. Neuroendocrinology 2016, 103, 117–118. [Google Scholar] [CrossRef]
- O’Toole, D.; Salazar, R.; Falconi, M.; Kaltsas, G.; Couvelard, A.; de Herder, W.W.; Hyrdel, R.; Nikou, G.; Krenning, E.; Vullierme, M.P.; et al. Rare functioning pancreatic endocrine tumors. Neuroendocrinology 2006, 84, 189–195. [Google Scholar] [CrossRef]
- Borrell, L.N.; Samuel, L. Body mass index categories and mortality risk in US adults: The effect of overweight and obesity on advancing death. Am. J. Public Health 2014, 104, 512–519. [Google Scholar] [CrossRef] [PubMed]
- American Diabetes, A. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010, 33 (Suppl. S1), S62–S69. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Alberti, K.G.; Eckel, R.H.; Grundy, S.M.; Zimmet, P.Z.; Cleeman, J.I.; Donato, K.A.; Fruchart, J.C.; James, W.P.; Loria, C.M.; Smith, S.C., Jr.; et al. Harmonizing the metabolic syndrome: A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation 2009, 120, 1640–1645. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pearson-Stuttard, J.; Zhou, B.; Kontis, V.; Bentham, J.; Gunter, M.J.; Ezzati, M. Worldwide burden of cancer attributable to diabetes and high body-mass index: A comparative risk assessment. Lancet Diabetes Endocrinol. 2018, 6, e6–e15. [Google Scholar] [CrossRef]
- Uzunlulu, M.; Telci Caklili, O.; Oguz, A. Association between Metabolic Syndrome and Cancer. Ann. Nutr. Metab. 2016, 68, 173–179. [Google Scholar] [CrossRef] [PubMed]
- Barberio, A.M.; Alareeki, A.; Viner, B.; Pader, J.; Vena, J.E.; Arora, P.; Friedenreich, C.M.; Brenner, D.R. Central body fatness is a stronger predictor of cancer risk than overall body size. Nat. Commun. 2019, 10, 383. [Google Scholar] [CrossRef] [Green Version]
- Santos, A.P.; Castro, C.; Antunes, L.; Henrique, R.; Cardoso, M.H.; Monteiro, M.P. Disseminated Well-Differentiated Gastro-Entero-Pancreatic Tumors Are Associated with Metabolic Syndrome. J. Clin. Med. 2019, 8, 1479. [Google Scholar] [CrossRef] [Green Version]
- Leoncini, E.; Carioli, G.; La Vecchia, C.; Boccia, S.; Rindi, G. Risk factors for neuroendocrine neoplasms: A systematic review and meta-analysis. Ann. Oncol. 2016, 27, 68–81. [Google Scholar] [CrossRef] [Green Version]
- Barrea, L.; Muscogiuri, G.; Pugliese, G.; Modica, R.; Laudisio, D.; Aprano, S.; Faggiano, A.; Colao, A.; Savastano, S. Chronotype: What role in the context of gastroenteropancreatic neuroendocrine tumors? J. Transl. Med. 2021, 19, 324. [Google Scholar] [CrossRef]
- Pischon, T.; Boeing, H.; Hoffmann, K.; Bergmann, M.; Schulze, M.B.; Overvad, K.; van der Schouw, Y.T.; Spencer, E.; Moons, K.G.; Tjonneland, A.; et al. General and abdominal adiposity and risk of death in Europe. N. Engl. J. Med. 2008, 359, 2105–2120. [Google Scholar] [CrossRef]
- Pape, U.F.; Berndt, U.; Muller-Nordhorn, J.; Bohmig, M.; Roll, S.; Koch, M.; Willich, S.N.; Wiedenmann, B. Prognostic factors of long-term outcome in gastroenteropancreatic neuroendocrine tumours. Endocr. Relat. Cancer 2008, 15, 1083–1097. [Google Scholar] [CrossRef] [PubMed]
- Cai, W.; Tan, Y.; Ge, W.; Ding, K.; Hu, H. Pattern and risk factors for distant metastases in gastrointestinal neuroendocrine neoplasms: A population-based study. Cancer Med. 2018, 7, 2699–2709. [Google Scholar] [CrossRef] [PubMed]
- Huang, P.Y.; Tsai, K.L.; Liang, C.M.; Tai, W.C.; Rau, K.M.; Wu, K.L.; Huang, C.C.; Chuah, S.K. Prognostic factors of patients with gastroenteropancreatic neuroendocrine neoplasms. Kaohsiung J. Med. Sci. 2018, 34, 650–656. [Google Scholar] [CrossRef] [PubMed]
- Pulvirenti, A.; Pea, A.; Chang, D.K.; Jamieson, N.B. Clinical and Molecular Risk Factors for Recurrence Following Radical Surgery of Well-Differentiated Pancreatic Neuroendocrine Tumors. Front. Med. 2020, 7, 385. [Google Scholar] [CrossRef] [PubMed]
- Xu, Z.; Wang, L.; Dai, S.; Chen, M.; Li, F.; Sun, J.; Luo, F. Epidemiologic Trends of and Factors Associated With Overall Survival for Patients With Gastroenteropancreatic Neuroendocrine Tumors in the United States. JAMA Netw. Open 2021, 4, e2124750. [Google Scholar] [CrossRef] [PubMed]
- Pusceddu, S.; Vernieri, C.; Di Maio, M.; Prinzi, N.; Torchio, M.; Corti, F.; Coppa, J.; Buzzoni, R.; Di Bartolomeo, M.; Milione, M. Impact of Diabetes and Metformin Use on Enteropancreatic Neuroendocrine Tumors: Post Hoc Analysis of the CLARINET Study. Cancers 2022, 14, 69. [Google Scholar] [CrossRef]
- Lei, Y.; Yi, Y.; Liu, Y.; Liu, X.; Keller, E.T.; Qian, C.-N.; Zhang, J.; Lu, Y. Metformin targets multiple signaling pathways in cancer. Chin. J. Cancer 2017, 36, 17. [Google Scholar] [CrossRef] [Green Version]
- Vlotides, G.; Tanyeri, A.; Spampatti, M.; Zitzmann, K.; Chourdakis, M.; Spöttl, G.; Maurer, J.; Nölting, S.; Göke, B.; Auernhammer, C.J. Anticancer effects of metformin on neuroendocrine tumor cells in vitro. Hormones 2014, 13, 498–508. [Google Scholar] [CrossRef]
- Pusceddu, S.; Buzzoni, R.; Vernieri, C.; Concas, L.; Marceglia, S.; Giacomelli, L.; Milione, M.; Leuzzi, L.; Femia, D.; Formisano, B. Metformin with everolimus and octreotide in pancreatic neuroendocrine tumor patients with diabetes. Future Oncol. 2016, 12, 1251–1260. [Google Scholar] [CrossRef]
- Herrera-Martínez, A.D.; Pedraza-Arevalo, S.; L-López, F.; Gahete, M.D.; Gálvez-Moreno, M.A.; Castaño, J.P.; Luque, R.M. Type 2 diabetes in neuroendocrine tumors: Are biguanides and statins part of the solution? J. Clin. Endocrinol. Metab. 2019, 104, 57–73. [Google Scholar] [CrossRef]
- Vernieri, C.; Pusceddu, S.; de Braud, F. Impact of metformin on systemic metabolism and survival of patients with advanced pancreatic neuroendocrine tumors. Front. Oncol. 2019, 9, 902. [Google Scholar] [CrossRef] [PubMed]
- Pusceddu, S.; Vernieri, C.; Di Maio, M.; Marconcini, R.; Spada, F.; Massironi, S.; Ibrahim, T.; Brizzi, M.P.; Campana, D.; Faggiano, A.; et al. Metformin Use Is Associated With Longer Progression-Free Survival of Patients With Diabetes and Pancreatic Neuroendocrine Tumors Receiving Everolimus and/or Somatostatin Analogues. Gastroenterology 2018, 155, 479–489.e477. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Martin, M.; Marais, R. Metformin: A diabetes drug for cancer, or a cancer drug for diabetics? J. Clin. Oncol. 2012, 30, 2698–2700. [Google Scholar] [CrossRef] [PubMed]
- Ni, K.; Yang, J.Y.; Baeg, K.; Leiter, A.C.; Mhango, G.; Gallagher, E.J.; Wisnivesky, J.P.; Kim, M.K. Association between somatostatin analogues and diabetes mellitus in gastroenteropancreatic neuroendocrine tumor patients: A Surveillance, Epidemiology, and End Results-Medicare analysis of 5235 patients. Cancer Rep. 2021, 4, e1387. [Google Scholar] [CrossRef] [PubMed]
- Vernieri, C.; Pusceddu, S.; Fucà, G.; Indelicato, P.; Centonze, G.; Castagnoli, L.; Ferrari, E.; Ajazi, A.; Pupa, S.; Casola, S.; et al. Impact of systemic and tumor lipid metabolism on everolimus efficacy in advanced pancreatic neuroendocrine tumors (pNETs). Int. J. Cancer 2019, 144, 1704–1712. [Google Scholar] [CrossRef] [PubMed]
- Pereira, S.S.; Pereira, R.; Santos, A.P.; Costa, M.M.; Morais, T.; Sampaio, P.; Machado, B.; Afonso, L.P.; Henrique, R.; Monteiro, M.P. Higher IL-6 peri-tumoural expression is associated with gastro-intestinal neuroendocrine tumour progression. Pathology 2019, 51, 593–599. [Google Scholar] [CrossRef] [PubMed]
- Nölting, S.; Maurer, J.; Spöttl, G.; Aristizabal Prada, E.T.; Reuther, C.; Young, K.; Korbonits, M.; Göke, B.; Grossman, A.; Auernhammer, C.J. Additive Anti-Tumor Effects of Lovastatin and Everolimus In Vitro through Simultaneous Inhibition of Signaling Pathways. PLoS ONE 2015, 10, e0143830. [Google Scholar] [CrossRef]
WD GEP-NEN | All Patients (n = 81) | Without MetS (n = 33) | With MetS (n = 48) | p-Value |
---|---|---|---|---|
Gender (Male) | 41 (50.6%) | 14 (42.4%) | 27 (56.2%) | 0.262 |
Age at Diagnosis (years) | 60 (29–86) | 53 (29–74) | 63 (39–86) | 0.002 |
Weight (kg) | 71.2 (44.5–107.0) | 67 (45.0–94.0) | 75.0 (44.5–107.0) | 0.005 |
BMI (kg/m2) | 26.4 (20.1–36.9) | 24.2 (20.1–36.3) | 27.7 (20.5–36.9) | 0.006 |
WC (cm) | 96.0 (60.0–120.0) | 87.0 (60.0–114.0) | 100.0 (73.0–120.0) | <0.001 |
SBP (mmHg) | 131.5 (98.0–214.0) | 129.0 (98.0–152.0) | 136.0 (104.0–214.0) | 0.039 |
DBP (mmHg) | 75.5 (46.0–116.0) | 74.0 (47.0–95.0) | 77.0 (46.0–116.0) | 0.331 |
Total Cholesterol (mg/dL) | 186.5 (107.0–333.0) | 186.0 (109.0–288.0) | 186.5 (107.0–333.0) | 0.694 |
Calculated LDL-c (mg/dL) | 103.6 (36.8–195.8) | 104.9 (62.0–195.8) | 102.3 (36.8–185.4) | 0.93 |
HDL-c (mg/dL) | 49.0 (21.0–92.0) | 53.0 (31.0–92.0) | 48.0 (21.0–69.0) | 0.025 |
Triglycerides (mg/dL) | 121.0 (4.0–627.0) | 96.0 (48.0–254.0) | 142.0 (59.0–627.0) | 0.002 |
FPG (mg/dL) | 101.0 (72.0–285.0) | 91.0 (79.0–126.0) | 110.0 (72.0–285.0) | <0.001 |
BMI Classification | ||||
Normal weight | 32 (39.5%) | 21 (63.6%) | 11 (22.9%) | 0.001 |
Overweight | 33 (40.7%) | 6 (18.2%) | 27 (56.2%) | |
Obesity | 15 (18.5%) | 6 (18.2%) | 9 (18.8%) | |
Unknown | 1 (1.2%) | 0 (0.0%) | 1 (2.1%) | |
Family History of T2D | 28 (34.6%) | 12 (36.4%) | 16 (33.3%) | 0.802 |
T2D Classification (n = 81) | ||||
Euglycemia | 46 (56.8%) | 26 (78.8%) | 20 (41.7%) | 0.002 |
FGA | 16 (19.8%) | 2 (6.1%) | 14 (29.2%) | |
T2D | 19 (23.5%) | 5 (15.2%) | 14 (29.2%) | |
MetS | 48 (59.3%) | 0 (0.0%) | 48.0 (100%) | |
MetS-WC | 37 (45.7%) | 7 (21.2%) | 30 (62.5%) | <0.001 |
MetS-Hypertension | 55 (67.9%) | 12 (36.4%) | 43 (89.6%) | <0.001 |
MetS-TG | 32 (39.5%) | 5 (15.2%) | 27 (56.2%) | <0.001 |
MetS-HDL-c | 46 (56.8%) | 10 (30.3%) | 36 (75.0%) | <0.001 |
MetS-FPG | 46 (56.8%) | 8 (24.2%) | 38 (79.2%) | <0.001 |
Primary Tumor Site | ||||
GI-NEN | 66 (81.5%) | 27 (81.8%) | 39 (81.2%) | 1 |
pNEN | 14 (17.3%) | 6 (18.2%) | 8 (16.7%) | |
Unknown | 1 (1.2%) | 0 (0.0%) | 1 (2.1%) | |
Hormonal Syndrome | ||||
Functioning * | 49 (60.5%) | 16 (48.5%) | 33 (68.8%) | 0.202 |
Non-Functioning | 24 (29.6%) | 12 (36.4%) | 12 (25.0%) | |
Unknown | 8 (9.9%) | 5 (15.2%) | 3 (6.2%) | |
2010 WHO Grading # | ||||
NETG1 | 48 (59.3%) | 17 (51.5%) | 31 (64.6%) | 0.241 |
NETG2 | 30 (37.0%) | 15 (45.5%) | 15 (31.2%) | |
Unknown | 3 (3.7%) | 1 (3.0%) | 2 (4.2%) | |
Stage | ||||
Locoregional Disease | 26 (32.1%) | 15 (45.5%) | 11 (22.9%) | 0.052 |
Metastatic Disease » | 55 (67.9%) | 18 (54.5%) | 37 (77.1%) | |
First Treatment | ||||
Somatostatin Analogues | 13 (16.0%) | 0 (0.0%) | 13 (27.1%) | 0.001 |
Surgery | 63 (77.8%) | 31 (93.9%) | 32 (66.7%) | |
TAE | 3 (3.7%) | 1 (3.0%) | 2 (4.2%) | |
Endoscopic Therapy | 2 (2.5%) | 1 (3.0%) | 1 (2.1%) | |
Hypertension Treatment | 41 (78.9%) | 8 (72.7%) | 33 (80.5%) | 0.669 |
Dyslipidemia Treatment Statins | 25 (53.2%) | 4 (36.4%) | 21 (58.3%) | 0.373 |
Fibrates | 1(2.1%) | 0 (0.0%) | 1 (2.8%) | |
T2D Treatment | 0.2 | |||
Metformin ϒ | 7 (38.9%) | 0 (0.0%) | 7 (50%) | |
Sulphonilurea | 2 (11.1%) | 1 (25.0%) | 1 (7.1%) | |
Other | 3 (16.7%) | 1 (25%) | 2 (14.3%) | |
Patient Outcomes | ||||
Alive | 58 (71.6%) | 23 (69.7%) | 35 (72.9%) | 0.954 |
Death attributed to NEN | 18 (22.2%) | 8 (24.2%) | 10 (20.8%) | |
Death due to other causes | 4 (4.9%) | 2 (6.1%) | 2 (4.2%) | |
Lost to Follow-up | 1 (1.2%) | 0 (0.0%) | 1 (2.1%) | |
OS follow-up (months) | 95.0 (16.8–262.5) | 101.7 (16.8–206.8) | 84.7 (17.3–262.5) | 0.204 |
PFS follow-up (months) | 50.6 (4.9–206.8) | 50.6 (4.9–206.8) | 50.7 (5.5–189.1) | 0.966 |
Characteristics | Years | OS | PFS | ||
---|---|---|---|---|---|
% | 95% CI | % | 95% CI | ||
Metabolic syndrome | |||||
No | 5 | 90.9 | 74.4–97.0 | 40 | 21.3–58.1 |
10 | 76.4 | 53.6–89.0 | 24.4 | 9.0–43.7 | |
Yes | 5 | 87.1 | 73.6–94.0 | 45.9 | 30.8–59.8 |
10 | 72.5 | 55.3–84.0 | 18.1 | 7.0–33.5 | |
Metabolic syndrome—Waist circumference | |||||
No | 5 | 90.9 | 74.4–97.0 | 48.3 | 29.5–64.8 |
10 | 76.4 | 53.6–89.0 | 25.7 | 10.4–44.2 | |
Yes | 5 | 87.1 | 73.6–94.0 | 41.5 | 24.6–57.7 |
10 | 72.5 | 55.3–84.0 | 17.6 | 6.6–32.9 | |
Metabolic syndrome—Hypertension | |||||
No | 5 | 92.3 | 72.6–98.0 | 42.9 | 21.9–62.3 |
10 | 86.9 | 64.0–95.7 | 32.1 | 13.7–52.3 | |
Yes | 5 | 87 | 74.6–93.6 | 44.2 | 29.9–57.6 |
10 | 66.5 | 48.9–79.2 | 15.5 | 5.7–29.7 | |
Metabolic syndrome—High Triglycerides | |||||
No | 5 | 89.7 | 77.1–95.6 | 47.3 | 31.3–61.8 |
10 | 72 | 54.4–83.8 | 25.1 | 11.9–40.7 | |
Yes | 5 | 87.1 | 69.2–95.0 | 38.3 | 21.1–55.2 |
10 | 77.2 | 55.1–89.4 | 13.4 | 2.8–32.3 | |
Metabolic syndrome—Low HDL–c | |||||
No | 5 | 91.4 | 75.7–97.2 | 41.4 | 23.7–58.3 |
10 | 77.7 | 56.0–89.6 | 30.7 | 13.9–49.3 | |
Yes | 5 | 86.6 | 72.6–93.8 | 45.3 | 29.6–59.9 |
10 | 70.7 | 52.2–83.1 | 15.1 | 5.4–29.5 | |
Metabolic syndrome—Fasting plasma glucose | |||||
No | 5 | 91.4 | 75.7–97.2 | 51.7 | 31.7–68.5 |
10 | 77.1 | 54.2–89.5 | 27.9 | 11.6–47.0 | |
Yes | 5 | 86.5 | 72.5–93.7 | 38.3 | 23.8–52.7 |
10 | 71.3 | 53.5–83.2 | 15.5 | 5.1–30.9 |
Characteristics | Overall Survival | Progression-Free Survival | ||||
---|---|---|---|---|---|---|
Univariable | Univariable | Multivariable | ||||
HR | 95% CI | HR | 95% CI | HR | 95% CI | |
Gender | ||||||
Male | 1 | 1 | ||||
Female | 0.89 | 0.38–2.06 | 0.79 | 0.46–1.36 | ||
Age at Diagnosis (years) | 1.02 | 0.97–1.06 | 0.99 | 0.97–1.02 | ||
Primary Tumor Site | ||||||
GI-NEN | 1 | 1 | ||||
pNEN | 1.67 | 0.61–4.60 | 1.76 | 0.90–3.43 | ||
Hormonal Syndrome | ||||||
Non-Functioning | 1 | 1 | ||||
Functioning | 1.14 | 0.46–2.85 | 1.2 | 0.66–2.20 | ||
2010 WHO Grading | ||||||
NETG1 | 1 | 1 | 1 | |||
NETG2 | 3.84 | 1.41–10.50 | 2.34 | 1.30–4.22 | 2.17 | 1.15–4.11 |
Stage | ||||||
Locoregional Disease | 1 | 1 | ||||
Metastatic Disease | 3.6 | 0.84–15.51 | 3.11 | 1.33–7.30 | ||
BMI category | ||||||
Normal weight | 1 | 1 | ||||
Overweight | 0.8 | 0.30–2.11 | 1.2 | 0.65–2.24 | ||
Obesity | 1.29 | 0.43–3.85 | 1.27 | 0.59–2.72 | ||
Diabetes Classification | ||||||
Euglycemia | 1 | 1 | ||||
FGA | 1.26 | 0.44–3.58 | 1.23 | 0.62.2.43 | ||
T2D | 0.58 | 0.19–1.81 | 1.26 | 0.66–2.42 | ||
Weight | 1.02 | 0.99–1.05 | 1.02 | 0.99–1.04 | ||
BMI | 0.99 | 0.89–1.11 | 1.02 | 0.95–1.09 | ||
Waist Circumference | 1.01 | 0.97–1.06 | 1.03 | 1.01–1.06 | 1.03 | 1.01–1.06 |
Systolic Blood Pressure | 1 | 0.98–1.02 | 1.01 | 0.99–1.02 | ||
Diastolic Blood Pressure | 1.03 | 0.99–1.07 | 1.02 | 0.99–1.04 | ||
HDL-c | 0.97 | 0.94–1.01 | 0.99 | 0.97–1.02 | ||
Triglycerides | 0.99 | 0.98–1.01 | 1 | 0.99–1.01 | ||
Fasting Plasma Glucose | 0.99 | 0.97–1.01 | 1.02 | 0.99–1.03 | ||
Metabolic Syndrome | ||||||
No | 1 | 1 | ||||
Yes | 1.01 | 0.43–2.35 | 1.03 | 0.59–1.83 | ||
MetS-WC | ||||||
No | 1 | 1 | ||||
Yes | 1.15 | 0.45–2.93 | 1.39 | 0.78–2.49 | ||
MetS-Hypertension | ||||||
No | 1 | 1 | ||||
Yes | 2 | 0.73–5.48 | 1.18 | 0.65–2.15 | ||
MetS-HDL-c | ||||||
No | 1 | 1 | ||||
Yes | 1.04 | 0.43–2.48 | 1.28 | 0.73–2.25 | ||
MetS-TG | ||||||
No | 1 | 1 | ||||
Yes | 1 | 0.39–2.52 | 1.21 | 0.70–2.09 | ||
MetS-FPG | ||||||
No | 1 | 1 | ||||
Yes | 1.2 | 0.51–2.81 | 1.47 | 0.83–2.60 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Santos, A.P.; Rodrigues, J.; Henrique, R.; Cardoso, M.H.; Monteiro, M.P. Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia. J. Clin. Med. 2022, 11, 6026. https://doi.org/10.3390/jcm11206026
Santos AP, Rodrigues J, Henrique R, Cardoso MH, Monteiro MP. Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia. Journal of Clinical Medicine. 2022; 11(20):6026. https://doi.org/10.3390/jcm11206026
Chicago/Turabian StyleSantos, Ana P., Jessica Rodrigues, Rui Henrique, M. Helena Cardoso, and Mariana P. Monteiro. 2022. "Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia" Journal of Clinical Medicine 11, no. 20: 6026. https://doi.org/10.3390/jcm11206026
APA StyleSantos, A. P., Rodrigues, J., Henrique, R., Cardoso, M. H., & Monteiro, M. P. (2022). Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia. Journal of Clinical Medicine, 11(20), 6026. https://doi.org/10.3390/jcm11206026