- Research article
- Open access
- Published:
Effect of aspirin on PET parameters in primary non-small cell lung cancer and its relationship with prognosis
BMC Cancer volumeĀ 20, ArticleĀ number:Ā 510 (2020)
Abstract
Background
18 F-FDG is a glucose analogue whose metabolic index SUV can effectively reflect the metabolic level of tumor microenvironment. Aspirin can affect the uptake of 18F-FDG by cancer cells, reducing the SUVmax value of primary tumors, exerting antitumor effect. This study aimed to evaluate the prognostic value of long-term aspirin and the relationship between aspirin intake and PET parameters value of primary tumor in non-small cell lung cancer (NSCLC).
Methods
Eighty-one NSCLC patients were recruited and divided into two groups: aspirin medication group and control group, who underwent surgery and had pathological diagnosis data between January 2012 and December 2016. Clinical characteristics were retrospective analyzed to evaluate the possibility of clinical prognosis, respectively. Kaplan-Meier curves and a Cox proportional hazard model were applied to evaluate the predictors of prognosis.
Results
The PET/CT SUVmax of the primary tumor in the aspirin group was lower than that in the control group (Pā<ā0.05). Compared with the control group, the SUVmax, SUVmean and TLG of the primary tumor in aspirin group were lower, but the MTV value had no significant difference. Cox regression analysis showed that N stage and TNM stage were predictors of the prognosis. There was a significant difference in the use of aspirin in NSCLC patients.
Conclusion
Aspirin can reduce SUVmax, SUVmean and TLG in primary tumor and aspirin can improve the prognosis of patients with NSCLC.
Background
Aspirin is the most used, longest-lived, non-steroidal anti-inflammatory drug in the world. Epidemiological and clinical experiments have shown that aspirin can prevent and treat various tumors such as lung cancer, colorectal cancer, cholangiocarcinoma, esophageal cancer and gastric cancer, in addition to antipyretic and anti-platelet aggregation [1,2,3,4,5]. A meta-analysis of randomized studies including five assessments of daily aspirin for prevention of cardiovascular events showed aspirin reduced the risk of 35% of fatal adenocarcinomas and 31% of metastatic adenocarcinomas, and reduced the risk of 74% of current and follow-up transitions [6, 7]. However, some studies have concluded that aspirin does not reduce the risk of cancer [8,9,10].
18āF-deoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) effectively combines two images of anatomical structure and metabolic function [11]. As a non-invasive method, it is widely used in clinical staging and efficacy evaluation. 18āF-FDG is a glucose analogue whose metabolic index of maximum standardized uptake value (SUVmax) can effectively reflect the metabolic level of tumor microenvironment. The existing studies have suggested that the SUVmax of primary lung cancer is associated with clinical stage, pathological type, lymph node status, and tumor proliferation rate [12, 13]. Other quantitative parameters of PET / CT can represent the metabolic load of tumor, such as the metabolic volume (MTV) and the total glycolysis (TLG), which also has certain prognostic value. High SUVmax has become one of the poor prognostic factors in patients with NSCLC. Tracer 18F-FDG can be transported into cells mainly through glucose transporters protein (Glut). Animal studies have shown that aspirin can destroy the Glut of tumor cells, and the uptake of 18F-FDG in tumor cells is positive correlated with the expression of Glut [14]. In addition, previous studies have shown that long-term use of aspirin can reduce the SUVmax of primary colorectal cancer. The aim of this study is to investigate the prognostic value of long-term aspirin and the relationship between aspirin intake and SUVmax value of primary tumor on PET/CT SUVmax in primary non-small cell lung cancer (NSCLC), and to provide a reference for further development of treatment strategies and prognosis.
Methods
Patients and population
Eighty-one patients with non-small cell lung cancer patient data from January 2012 to December 2016 were selected.
Entry criteria:
- 1)
Patients underwent baseline evaluation with PET/CT before surgery.
- 2)
Clinical stage was from I to III.
- 3)
No neoadjuvant radiotherapy or chemotherapy before surgery.
- 4)
Completely record information about the patientās use of aspirin, including usage, dosage, and time of use. Meanwhile, five patients were excluded for the early loss of follow-up. According to the application of aspirin or not, it was divided into aspirin medication group and control group. Patients in the aspirin medication group received oral aspirin 75āmg/day for at least 5āyears. The control group did not take or occasionally take aspirin. All patients underwent regular follow-up after surgery (reviewed once every 3āmonths in 2āyears and once every 6 to 8āmonths after 2āyears). The recorded follow-up time was from 1 to 160āmonths after surgery.
Whole body 18āF-FDG PET/CT examination
The scanning device was PHILIPS GEMINI TF64-PET/CT device. The scanning parameters were tube voltage 120KV, tube current 50āmA, layer thickness 5āmm, layer spacing 5āmm. All patients underwent PET/CT before blood glucose control, fasting for 6āh or more, and banned sugary drinks. The synthesized 18F-fluorodeoxyglucose (18F-FDG) was intravenously injected into the patient at a dose of 0.125āmCi/KG. The patients rested for 1āh after injecting the drug, and a whole body scan was performed after urination. The scan ranged from cranial crest to mid-femur. More than two experienced nuclear medicine physicians performed the attenuation correction and iterative reconstruction of the obtained image. With SUVāā„ā2.5 as the threshold, the region of interest (ROI) was set in the radionuclide concentration area. The SUVmax, SUVmean and MTV of the area were calculated by computer software, and TLG: TLGā=āMTVāĆāSUVmean was calculated to obtain TLG of each focus.
Statistical processing and follow-up
Analysis was performed by using SPSS 21.0 statistical software. The surgery day was the initial point of observation, and the metastatic or recurrence day was the end point of observation. This time period was called disease-free survival (DFS). The chi-square test was used for the count data, the t-test was used for the measurement data. The survival rate was calculated by the Kaplan-Meier method, the survival curve was plotted, and the log-rank test was performed. Multivariate survival analysis was performed using a Cox proportional hazards regression model with forward stepwise regression. All statistical analyses were statistically significant at Pā<ā0.05.
Results
Comparison of clinical features between the two groups
Among the 81 cases included in the study, 60 were men and 21 were women, aged 32ā71āyears (median age 56āyears). The pathological types of lung cancer included 32 cases of adenocarcinoma, 37 cases of squamous cell carcinoma, and 12 cases of large cell carcinoma. The level of differentiation was 18 cases with high differentiation, 28 cases with moderate differentiation, and 35 cases with poor differentiation. According to UICC 2017 lung cancer staging criteria, 14 cases of stage I, 58 cases of stage II, and 9 cases of stage III were included, all of which were postoperative staging. There were 23 patients (28.4%) in the aspirin group and 58 patients (71.6%) in the control group. At the end of the follow-up, 2 patients were lost to follow-up, 75 patients had tumor recurrence or metastasis, and 4 patients had no disease progression. The median follow-up time was 52āmonths and there were no significant differences in age, gender, pathological stage, pathological type, and tumor differentiation between the aspirin group and the control group (TableĀ 1).
Effect of aspirin on PET / CT metabolic parameters in primary NSCLC
The PET/CT SUVmax, SUVmean and TLG of primary NSCLC in aspirin group were lower than those in control group, which indicated that long-term aspirin administration could reduce SUVmax, SUVmean and TLG of primary lung cancer (pā<ā0.05). There was no significant difference in MTV between aspirin group and control group (pā>ā0.05). (TableĀ 2).
Survival analysis of the whole group of patients
The median and range of tumor SUVmax, SUVmean, MTV and TLG were 9.7 (2.9ā21.7), 8.5 (2.8ā18.6), 15.65 (2.12ā110.95) cm3 and 110.95 (2.77ā1264.83), respectively. The median was the cut off for grouping. The 2-year disease-free survival rates of aspirin group and control group were 56.5 and 41.4%, respectively, suggesting that long-term oral aspirin can improve the disease-free survival of patients with non-small cell lung cancer (Fig.Ā 1).
Univariate survival analysis
Kaplan Meier method was used for univariate survival analysis. The factors included: age (ā„ 60āyears old, <ā60āyears old), gender, T stage (T1, T2, T3), N stage (N0, N1, N2), pathological type (squamous cell carcinoma, adenocarcinoma and large cell carcinoma), differentiation degree (high differentiation, medium differentiation and low differentiation), aspirin, TNM stage (I, II, III), SUVmax (ā„ 9.7, <ā9.7)ćSUVmean (ā„8.5, <ā8.5)ćMTV (ā„15.65, <ā15.65)ćTLG (ā„110.95, <ā110.95). The results showed that N stage, TNM stage, aspirin history, SUVmax value, SUVmean and TLG were related to the prognosis of patients (Pā<ā0.05). But age, gender, T stage, pathological type, degree of differentiation and MTV had no significant effect on the prognosis (pā>ā0.05). (TableĀ 3).
Multivariate survival analysis
Six variables with statistical significance in the above single factor analysis: N stage, TNM stage, aspirin medication history, SUVmax value, SUVmean, TLG were included in the Cox model analysis of multiple factors forward stepwise regression. The results showed that N stage and TNM stage were risk factors affecting prognosis (TableĀ 4).
Discussion
In recent years, the role of PET/CT in the early diagnosis, clinical staging and prognosis evaluation of malignant solid tumors has been widely recognized [12, 13, 15]. At present, a widely used tracer for PET/CT is 18F-fluorodeoxyglucose, whose biological behavior is similar to glucose in vivo. The maximum normalized uptake value and the average normalized uptake value reflect the uptake level of 18F-FDG by tumor tissues, and can provide metabolic activity information of tumor cells at the molecular level. It has been reported that SUV, a parameter representing tumor metabolic activity, was a prognostic factor of NSCLC, but the correlation was not as significant as that of stage and tumor volume [10]. The metabolic volume parameters, including tumor metabolic volume (MTV) [16] and total glycolysis (TLG) [17], can represent tumor metabolic load, also have the certain prognostic value. Mazzola et al. proved that 18FDG-PET/CT parameters might be the predictive of response after stereotactic ablative radiotherapy (SABR) for lung metastases [18]. However, whether the metabolic parameters of PET / CT are independent prognostic factors for NSCLC is not consistent at present. Liu J et al. used evidence-based meta-analysis to investigate the prognostic value of PET/CT SUVmax values in patients with operable stage I-II NSCLC [19]. The results showed that the SUVmax value was positively correlated with the risk of recurrence and metastasis. The high SUVmax value indicated that patients were more prone to recurrence and metastasis, and more active treatment measures were needed. Cistaro et al. analyzed 49 patients with stage I-II NSCLC who underwent 18F-FDG PET-CT before surgery and found that SUVmax was an independent prognostic factor [20]. With a SUVmax value of 9 as the cut-off point, the 2-year DFS in the high SUVmax group and the primary tumor size >ā3ācm group (37.5%) was significantly lower than the 2-year DFS in the low SUVmax group and the primary tumor size <ā3ācm group (90%). Yoo IeR et al. performed a retrospective analysis of 80 patients with T1N0 or T2N0 NSCLC who underwent 18F-FDG PET before surgery. The results showed that SUVmax (Pā=ā0.004) and lung adenocarcinoma (Pā=ā0.005) were independent prognostic factors for postoperative disease-free survival [21]. Tomita et al. retrospectively analyzed 197 patients with NSCLC who underwent 18F-FDG PET before surgery, suggesting that SUVmax (Pā=ā0.0004) and serum CEA levels (Pā<ā0.0001) were independent prognostic factors for 5-year survival [22]. BillĆØ et al. studied 413 patients with NSCLC who underwent surgical treatment and survival analysis showed that SUVmax (Pā=ā0.006), TNM stage (Pā=ā0.0001) and differentiation (Pā=ā0.04) were independent prognostic factors affecting survival [23]. All of the above studies have shown that SUVmax was an independent prognostic factor for non-small cell lung cancer. However, there were also some studies showing that SUVmax was not an independent prognostic factor. Downey et al. analyzed 487 patients with NSCLC surgery and found that SUVmax has only independent prognostic value for cTNM staging, but no independent prognostic value for pTNM staging [24]. Hoang et al. studied the prognostic significance of SUVmax in 214 patients with advanced non-small cell lung cancer, and grouped them with a boundary of 11.1. No SUVmax was found to have prognostic value [25]. Therefore, the value of SUVmax in the prognosis of patients with NSCLC remains to be confirmed by further large-scale and prospective studies.
Hypoxia is one of the basic characteristics of solid tumors. Under hypoxic microenvironment, hypoxia-inducible factors in cells are the key transcriptional regulators that mediate adaptive responses in cells [26]. In addition, the expression of Glut-1, which is a key vector of glucose metabolism, is mainly regulated by HIF-1Ī± to meet the energy needs of tumor growth. Molecular biology studies have shown that in the hypoxic environment, Glut-1, which is one of the downstream target genes of HIF-1Ī±, will be up-regulated accordingly, providing tumor tissue with abundant glucose for cell activity [27]. The PET/CT tracer 18F-FDG differs from glucose in that the hydroxyl group at the 2nd carbon atom is substituted by 18, but like glucose, 18F-FDG enters the cell mainly through a transporter such as glucose transporter-1. However, after 18F-FDG enters the cell, it is unable to continue to participate in sugar metabolism through the glycolytic pathway after being catalyzed by hexokinase to produce 6-phosphate-18F-FDG, but accumulated in the cells [28]. Therefore, PET / CT metabolic parameters can reflect the hypoxic state of the tumor to some extent [29]. Our results suggested that the SUVmax, SUVmean and TLG were related to the application of aspirin. There was no significant difference in gender, age, tumor type, degree of differentiation, TNM stage, tumor T stage, and tumor N stage between the aspirin group and the control group. Furthermore, the mean SUVmax of the primary lesions of NSCLC in the aspirin group was 7.3āĀ±ā3.34, which was lower than that of the control group 12.10āĀ±ā5.13. The difference was statistically significant (Pā<ā0.05). The SUVmax, SUVmean and TLG value of the aspirin group were lower than that of the control group, suggesting that long-term use of aspirin could reduce the SUVmax value of primary lesions in patients with NSCLC. By performing survival analysis on this group of NSCLC patients, univariate analysis showed that tumor N stage, TNM stage, application of aspirin, and primary SUVmax values, SUVmean and TLG were associated with prognosis. Multivariate analysis suggested that the application of aspirin was not an independent prognostic factor. It only suggested that the tumor N stage, TNM stage were independent prognostic factors. This result was consistent with the findings of SUV in colorectal cancer, and the reason for this result might be related to the small number of cases selected [30]. The 2-year disease-free survival rate of aspirin group was higher than that of the control group, suggesting that long-term oral aspirin can improve the disease-free survival of patients with non-small cell lung cancer. These results suggest that aspirin can improve the prognosis of patients with NSCLC.
Aspirin is a mechanism for affecting the uptake of 18F-FDG by lung cancer cells, reducing the SUVmax value of tumor primary tumors, and thus improving the prognosis of patients. A number of studies have suggested that non-steroidal anti-inflammatory drugs inhibit tumor angiogenesis-related factors [31,32,33]. Tumor angiogenesis and microenvironmental abnormalities are the result of an imbalance between pro-angiogenic factors and angiogenesis inhibitors in the local microenvironment. In the special environment of tumor tissue, pro-angiogenic factors are significantly increased, and vascular endothelial cells and lymphatic endothelial cells continue to proliferate and migrate under the action of these promoting factors. However, the vascular system thus formed is defective in morphology and function, mainly manifested in the fluctuation of blood flow in spatial distribution and temporal distribution, which leads to the formation of tumor hypoxia microenvironment. In this process, Angiogenesis-related factors play an important role [34]. Aspirin, a COX2 inhibitor, may exert an anti-tumor effect by inhibiting tumor neovascularization and improving the tumor hypoxia microenvironment. Hypoxic microenvironment is the initiator of malignant transformation and even metastasis of tumors, and also plays a central role in tumor chemo-radiation resistance [35, 36]. Therefore, if the tumor microenvironment can be improved, it is expected to reduce the malignant biological potential of tumor cells and improve the efficacy of radiotherapy and chemotherapy, thereby improving the prognosis of patients. Based on the clinical phenomenon that aspirin reduces the uptake of 18F-FDG in NSCLC primary tumors, we speculated that aspirin improved the hypoxia of lung cancer cells, thereby improving the clinical prognosis of patients.
Conclusions
This article mainly evaluated the effect of aspirin on PET/CT SUVmax in patients with non-small cell lung cancer and its impact on patient prognosis. The results showed that N-stage, TNM stage were independent risk factors for prognosis. Meanwhile, long-term use of aspirin could reduce the PET/CT SUVmax value, SUVmean and TLG of primary non-small cell lung cancer. These provide a new idea for further exploring the role of aspirin in cancer prevention and treatment and further taking timely and effective interventions. Due to the relatively small number of cases in this study, further sample studies are still needed.
Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- 18āF-FDG:
-
18āF-deoxyglucose
- SUVmax:
-
Maximum standardized uptake value
- PET/CT:
-
Positron emission tomography/computed tomography
- NSCLC:
-
Non-small cell lung cancer
- Glut:
-
Glucose transporters protein
- DFS:
-
Disease-free survival
- MTV:
-
Metabolic volume
- TLG:
-
The total glycolysis
- SUVmean:
-
Mean standardized uptake value
- ROI:
-
The region of interest
References
Hassan C, Rex DK, Cooper GS, Zullo A, Launois R, Benamouzig R. Primary prevention of colorectal cancer with low-dose aspirin in combination with endoscopy: a cost-effectiveness analysis. Gut. 2012;61(8):1172ā9.
Choi J, Ghoz HM, Peeraphatdit T, Baichoo E, Addissie BD, Harmsen WS, Therneau TM, Olson JE, Chaiteerakij R, Roberts LR. Aspirin use and the risk of cholangiocarcinoma. Hepatology. 2016;64(3):785ā96.
Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Curhan GC, Fuchs CS. Long-term use of aspirin and nonsteroidal anti-inflammatory drugs and risk of colorectal cancer. Jama. 2005;294(8):914ā23.
Oh SW, Myung SK, Park JY, Lee CM, Kwon HT. Korean meta-analysis study G: aspirin use and risk for lung cancer: a meta-analysis. Ann Oncol. 2011;22(11):2456ā65.
Spence AD, Busby J, Johnston BT, Baron JA, Hughes CM, Coleman HG, Cardwell CR. Low-dose aspirin use does not increase survival in 2 independent population-based cohorts of patients with esophageal or gastric cancer. Gastroenterology. 2018;154(4):849ā860 e841.
Rothwell PM, Wilson M, Price JF, Belch JF, Meade TW, Mehta Z. Effect of daily aspirin on risk of cancer metastasis: a study of incident cancers during randomised controlled trials. Lancet. 2012;379(9826):1591ā601.
Cuzick J, Thorat MA, Bosetti C, Brown PH, Burn J, Cook NR, Ford LG, Jacobs EJ, Jankowski JA, La Vecchia C, et al. Estimates of benefits and harms of prophylactic use of aspirin in the general population. Ann Oncol. 2015;26(1):47ā57.
Cardwell CR, Kunzmann AT, Cantwell MM, Hughes C, Baron JA, Powe DG, Murray LJ. Low-dose aspirin use after diagnosis of colorectal cancer does not increase survival: a case-control analysis of a population-based cohort. Gastroenterology. 2014;146(3):700ā8 e702.
Ventura L, Miccinesi G, Barchielli A, Manneschi G, Puliti D, Mantellini P, Orso F, Zappa M. Does low-dose aspirin use for cardiovascular disease prevention reduce colorectal cancer deaths? A comparison of two cohorts in the Florence district, Italy. Eur J Cancer Prev. 2018;27(2):134ā9.
McCarthy M. US panel recommends low dose aspirin to prevent cardiovascular disease and colorectal cancer. Bmj. 2016;352:i2061.
Kelloff GJ, Hoffman JM, Johnson B, Scher HI, Siegel BA, Cheng EY, Cheson BD, O'Shaughnessy J, Guyton KZ, Mankoff DA, et al. Progress and promise of FDG-PET imaging for cancer patient management and oncologic drug development. Clin Cancer Res. 2005;11(8):2785ā808.
Na II, Byun BH, Kang HJ, Cheon GJ, Koh JS, Kim CH, Choe DH, Ryoo BY, Lee JC, Lim SM, et al. 18F-fluoro-2-deoxy-glucose uptake predicts clinical outcome in patients with gefitinib-treated non-small cell lung cancer. Clin Cancer Res. 2008;14(7):2036ā41.
Gayed I, Vu T, Iyer R, Johnson M, Macapinlac H, Swanston N, Podoloff D. The role of 18F-FDG PET in staging and early prediction of response to therapy of recurrent gastrointestinal stromal tumors. J Nuclear Med. 2004;45(1):17ā21.
Kumar A, Vishvakarma NK, Tyagi A, Bharti AC, Singh SM. Anti-neoplastic action of aspirin against a T-cell lymphoma involves an alteration in the tumour microenvironment and regulation of tumour cell survival. Biosci Rep. 2012;32(1):91ā104.
Hong D, Lunagomez S, Kim EE, Lee JH, Bresalier RS, Swisher SG, Wu TT, Morris J, Liao Z, Komaki R, et al. Value of baseline positron emission tomography for predicting overall survival in patient with nonmetastatic esophageal or gastroesophageal junction carcinoma. Cancer. 2005;104(8):1620ā6.
Paesmans M, Berghmans T, Dusart M, Garcia C, Hossein-Foucher C, Lafitte JJ, Mascaux C, Meert AP, Roelandts M, Scherpereel A, et al. Primary tumor standardized uptake value measured on fluorodeoxyglucose positron emission tomography is of prognostic value for survival in non-small cell lung cancer: update of a systematic review and meta-analysis by the European Lung Cancer Working Party for the International Association for the Study of Lung Cancer Staging Project. J Thorac Oncol. 2010;5(5):612ā9.
Vesselle H, Freeman JD, Wiens L, Stern J, Nguyen HQ, Hawes SE, Bastian P, Salskov A, Vallieres E, Wood DE. Fluorodeoxyglucose uptake of primary non-small cell lung cancer at positron emission tomography: new contrary data on prognostic role. Clin Cancer Res. 2007;13(11):3255ā63.
Mazzola R, Fiorentino A, Di Paola G, Giaj Levra N, Ricchetti F, Fersino S, Tebano U, Pasetto S, Ruggieri R, Salgarello M, et al. Stereotactic ablative radiation therapy for lung oligometastases: predictive parameters of early response by (18)FDG-PET/CT. J Thorac Oncol. 2017;12(3):547ā55.
Liu J, Dong M, Sun X, Li W, Xing L, Yu J. Prognostic value of 18F-FDG PET/CT in surgical non-small cell lung cancer: a meta-analysis. PLoS One. 2016;11(1):e0146195.
Cistaro A, Quartuccio N, Mojtahedi A, Fania P, Filosso PL, Campenni A, Ficola U, Baldari S. Prediction of 2 years-survival in patients with stage I and II non-small cell lung cancer utilizing (18)F-FDG PET/CT SUV quantification. Radiol Oncol. 2013;47(3):219ā23.
Yoo Ie R, Chung SK, Park HL, Choi WH, Kim YK, Lee KY, Wang YP. Prognostic value of SUVmax and metabolic tumor volume on 18F-FDG PET/CT in early stage non-small cell lung cancer patients without LN metastasis. Biomed Mater Eng. 2014;24(6):3091ā103.
Tomita M, Shimizu T, Ayabe T, Onitsuka T. Maximum SUV on positron emission tomography and serum CEA level as prognostic factors after curative resection for non-small cell lung cancer. Asia-Pac J Clin Oncol. 2012;8(3):244ā7.
Bille A, Okiror L, Skanjeti A, Errico L, Arena V, Penna D, Ardissone F, Pelosi E. The prognostic significance of maximum standardized uptake value of primary tumor in surgically treated non-small-cell lung cancer patients: analysis of 413 cases. Clin Lung Cancer. 2013;14(2):149ā56.
Downey RJ, Akhurst T, Gonen M, Park B, Rusch V. Fluorine-18 fluorodeoxyglucose positron emission tomographic maximal standardized uptake value predicts survival independent of clinical but not pathologic TNM staging of resected non-small cell lung cancer. J Thorac Cardiovasc Surg. 2007;133(6):1419ā27.
Hoang JK, Hoagland LF, Coleman RE, Coan AD, Herndon JE 2nd, Patz EF Jr. Prognostic value of fluorine-18 fluorodeoxyglucose positron emission tomography imaging in patients with advanced-stage non-small-cell lung carcinoma. J Clin Oncol. 2008;26(9):1459ā64.
Hockel M, Vaupel P. Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects. J Natl Cancer Inst. 2001;93(4):266ā76.
Calvert JW, Cahill J, Yamaguchi-Okada M, Zhang JH. Oxygen treatment after experimental hypoxia-ischemia in neonatal rats alters the expression of HIF-1alpha and its downstream target genes. J Appl Physiol. 2006;101(3):853ā65.
Surasi DS, Bhambhvani P, Baldwin JA, Almodovar SE. O'Malley JP: (1)(8)F-FDG PET and PET/CT patient preparation: a review of the literature. J Nuclear Med Technol. 2014;42(1):5ā13.
Dierckx RA, Van de Wiele C. FDG uptake, a surrogate of tumour hypoxia? Eur J Nucl Med Mol Imaging. 2008;35(8):1544ā9.
Su B, Xu B, Wan J. Correlation between long-term aspirin use and F-fluorodeoxyglucose uptake in colorectal cancer measured by PET/CT. PLoS One. 2014;9(10):e109459.
Farooqui M, Li Y, Rogers T, Poonawala T, Griffin RJ, Song CW, Gupta K. COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia. Br J Cancer. 2007;97(11):1523ā31.
Dai X, Yan J, Fu X, Pan Q, Sun D, Xu Y, Wang J, Nie L, Tong L, Shen A, et al. Aspirin inhibits cancer metastasis and angiogenesis via targeting Heparanase. Clin Cancer Res. 2017;23(20):6267ā78.
Zhao Q, Wang Z, Wang Z, Wu L, Zhang W. Aspirin may inhibit angiogenesis and induce autophagy by inhibiting mTOR signaling pathway in murine hepatocarcinoma and sarcoma models. Oncol Lett. 2016;12(4):2804ā10.
Shiao J, Thomas KM, Rahimi AS, Rao R, Yan J, Xie XJ, DaSilva M, Spangler A, Leitch M, Wooldridge R, et al. Aspirin/antiplatelet agent use improves disease-free survival and reduces the risk of distant metastases in stage II and III triple-negative breast cancer patients. Breast Cancer Res Treat. 2017;161(3):463ā71.
Jain RK, Martin JD, Stylianopoulos T. The role of mechanical forces in tumor growth and therapy. Annu Rev Biomed Eng. 2014;16:321ā46.
Cuvillier O, Ader I, Bouquerel P, Brizuela L, Gstalder C, Malavaud B. Hypoxia, therapeutic resistance, and sphingosine 1-phosphate. Adv Cancer Res. 2013;117:117ā41.
Acknowledgements
We thank the individual who participated in this study.
Funding
This study was supported by the Science, Technology & Innovation Commission of Shenzhen Municipality (grants NO. JCYJ20160422144516003). The fund mentioned above was used for designation of this study, the collection, analysis of the data as well as the manuscript writing. The funder of the Science, Technology & Innovation Commission of Shenzhen Municipality (grants No. JCYJ20160422144516003) is from Jinghua Chen who is responsible for performing this study and writing the paper.
Author information
Authors and Affiliations
Contributions
RX conceived and designed the whole project, JC and JX performed the experiments. JH performed statistical analyses and JC wrote the paper. All authors have read and approved the manuscript.
Corresponding author
Ethics declarations
Ethics approval and consent to participate
This is a retrospective study. This study was approved and the permission to access the medical records was granted by the Medical Ethics Committee of the Shenzhen Peopleās Hospital (No. LL-KT201603008).
Consent for publication
Not applicable.
Competing interests
The authors declare that there is no conflict of interests.
Additional information
Publisherās Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
About this article
Cite this article
Chen, J., Xia, J., Huang, J. et al. Effect of aspirin on PET parameters in primary non-small cell lung cancer and its relationship with prognosis. BMC Cancer 20, 510 (2020). https://doi.org/10.1186/s12885-020-06983-2
Received:
Accepted:
Published:
DOI: https://doi.org/10.1186/s12885-020-06983-2