Heart Rate Variability is an Independent Predictor of Lymph Node Metastasis in Patients with Cervical Cancer

References

• Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. doi:10.3322/caac.2159031912902
   PubMed Web of Science ®Google Scholar
• Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin. 2016;66(2):115–132. doi:10.3322/caac.2133826808342
   PubMed Web of Science ®Google Scholar
• Marth C, Landoni F, Mahner S, McCormack M, Gonzalez-Martin A, Colombo N; ESMO Guidelines Committee. Cervical cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017;28(suppl 4):iv72–iv83. doi:10.1093/annonc/mdx22028881916
   PubMed Web of Science ®Google Scholar
• Du R, Li L, Ma S, Tan X, Zhong S, Wu M. Lymph nodes metastasis in cervical cancer: incidences, risk factors, consequences and imaging evaluations. Asia Pac J Clin Oncol. 2018;14(5):e380–e385. doi:10.1111/ajco.1299729855154
   PubMed Web of Science ®Google Scholar
• Gien LT, Covens A. Lymph node assessment in cervical cancer: prognostic and therapeutic implications. J Surg Oncol. 2009;99(4):242–247. doi:10.1002/jso.2119919048600
   PubMed Web of Science ®Google Scholar
• Williams AD, Cousins C, Soutter WP, et al. Detection of pelvic lymph node metastases in gynecologic malignancy: a comparison of CT, MR imaging, and positron emission tomography. AJR Am J Roentgenol. 2001;177(2):343–348. doi:10.2214/ajr.177.2.177034311461859
   PubMed Web of Science ®Google Scholar
• Choi HJ, Ju W, Myung SK, Kim Y. Diagnostic performance of computer tomography, magnetic resonance imaging, and positron emission tomography or positron emission tomography/computer tomography for detection of metastatic lymph nodes in patients with cervical cancer: meta-analysis. Cancer Sci. 2010;101(6):1471–1479. doi:10.1111/j.1349-7006.2010.01532.x20298252
   PubMed Web of Science ®Google Scholar
• Kim TJ, Choi JJ, Kim WY, et al. Gene expression profiling for the prediction of lymph node metastasis in patients with cervical cancer. Cancer Sci. 2008;99(1):31–38. doi:10.1111/j.1349-7006.2007.00652.x17986283
   PubMed Web of Science ®Google Scholar
• Huang L, Lin JX, Yu YH, Zhang MY, Wang HY, Zheng M. Downregulation of six microRNAs is associated with advanced stage, lymph node metastasis and poor prognosis in small cell carcinoma of the cervix. PLoS One. 2012;7(3):e33762. doi:10.1371/journal.pone.003376222438992
   PubMed Web of Science ®Google Scholar
• Liu P, Zhang C, Liao Y, et al. High expression of PTPRM predicts poor prognosis and promotes tumor growth and lymph node metastasis in cervical cancer. Cell Death Dis. 2020;11(8):687. doi:10.1038/s41419-020-02826-x32826853
   PubMed Web of Science ®Google Scholar
• Chen J, Yao D, Li Y, et al. Serum microRNA expression levels can predict lymph node metastasis in patients with early-stage cervical squamous cell carcinoma. Int J Mol Med. 2013;32(3):557–567. doi:10.3892/ijmm.2013.142423799609
   PubMed Web of Science ®Google Scholar
• Wang W, Jia HL, Huang JM, et al. Identification of biomarkers for lymph node metastasis in early-stage cervical cancer by tissue-based proteomics. Br J Cancer. 2014;110(7):1748–1758. doi:10.1038/bjc.2014.9224569473
   PubMed Web of Science ®Google Scholar
• Kotowicz B, Fuksiewicz M, Kowalska M, Jonska-Gmyrek J, Bidzinski M, Kaminska J. The value of tumor marker and cytokine analysis for the assessment of regional lymph node status in cervical cancer patients. Int J Gynecol Cancer. 2008;18(6):1279–1284. doi:10.1111/j.1525-1438.2007.01176.x18217970
   PubMed Web of Science ®Google Scholar
• Zhang LX, Wei ZJ, Xu AM, Zang JH. Can the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio be beneficial in predicting lymph node metastasis and promising prognostic markers of gastric cancer patients? Tumor maker retrospective study. Int J Surg. 2018;56(56):320–327. doi:10.1016/j.ijsu.2018.06.03729969732
   PubMed Web of Science ®Google Scholar
• Takeda M, Sakuragi N, Okamoto K, et al. Preoperative serum SCC, CA125, and CA19-9 levels and lymph node status in squamous cell carcinoma of the uterine cervix. Acta Obstet Gynecol Scand. 2002;81(5):451–457. doi:10.1034/j.1600-0412.2002.810513.x12027820
   PubMed Web of Science ®Google Scholar
• Chen L, Zhang F, Sheng XG, Zhang SQ, Chen YT, Liu BW. Peripheral platelet/lymphocyte ratio predicts lymph node metastasis and acts as a superior prognostic factor for cervical cancer when combined with neutrophil: lymphocyte. Medicine (Baltimore). 2016;95(32):e4381. doi:10.1097/MD.000000000000438127512849
   PubMed Web of Science ®Google Scholar
• Simó M, Navarro X, Yuste VJ, Bruna J. Autonomic nervous system and cancer. Clin Auton Res. 2018;28(3):301–314. doi:10.1007/s10286-018-0523-129594605
   PubMed Web of Science ®Google Scholar
• Bautista M, Krishnan A. The autonomic regulation of tumor growth and the missing links. Front Oncol. 2020;10:744. doi:10.3389/fonc.2020.0074432477953
   PubMed Web of Science ®Google Scholar
• Gidron Y, Perry H, Glennie M. Does the vagus nerve inform the brain about preclinical tumours and modulate them? Lancet Oncol. 2005;6(4):245–248. doi:10.1016/S1470-2045(05)70096-615811620
   PubMed Web of Science ®Google Scholar
• Arab C, Dias DP, Barbosa RT, et al. Heart rate variability measure in breast cancer patients and survivors: a systematic review. Psychoneuroendocrinology. 2016;68(68):57–68. doi:10.1016/j.psyneuen.2016.02.01826943345
   PubMed Web of Science ®Google Scholar
• Zhou X, Ma Z, Zhang L, et al. Heart rate variability in the prediction of survival in patients with cancer: a systematic review and meta-analysis. J Psychosom Res. 2016;89(89):20–25. doi:10.1016/j.jpsychores.2016.08.00427663106
   PubMed Web of Science ®Google Scholar
• Bijoor SN, Subbalakshmi NK, Banerjee S. Influence of cancer and its severity on vagal nerve activity assessed by time domain measures of heart rate variability. Res J Pharmacol Biol Chem Sci. 2016;7(3):1215–1220.
   Google Scholar
• Bettermann H, Kröz M, Girke M, Heckmann C. Heart rate dynamics and cardiorespiratory coordination in diabetic and breast cancer patients. Clin Physiol. 2001;21(4):411–420. doi:10.1046/j.1365-2281.2001.00342.x11442574
   PubMedGoogle Scholar
• Arab C, Vanderlei LCM, da Silva Paiva L, et al. Cardiac autonomic modulation impairments in advanced breast cancer patients. Clin Res Cardiol. 2018;107(10):924–936. doi:10.1007/s00392-018-1264-929721647
   PubMed Web of Science ®Google Scholar
• Hu S, Lou J, Zhang Y, Chen P. Low heart rate variability relates to the progression of gastric cancer. World J Surg Oncol. 2018;16(1):49. doi:10.1186/s12957-018-1348-z29514707
   PubMed Web of Science ®Google Scholar
• Pan J, Tompkins WJ. A real-time QRS detection algorithm. IEEE Trans Biomed Eng. 1985;32(3):230–236. doi:10.1109/TBME.1985.3255323997178
   PubMed Web of Science ®Google Scholar
• Lipponen JA, Tarvainen MP. A robust algorithm for heart rate variability time series artefact correction using novel beat classification. J Med Eng Technol. 2019;43(3):173–181. doi:10.1080/03091902.2019.164030631314618
   PubMedGoogle Scholar
• Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability: standards of measurement, physiological interpretation and clinical use. Circulation. 1996;93(5):1043–1065. doi:10.1161/01.CIR.93.5.10438598068
   PubMed Web of Science ®Google Scholar
• Singh D, Vinod K, Saxena SC. Sampling frequency of the RR interval time series for spectral analysis of heart rate variability. J Med Eng Technol. 2004;28(6):263–272. doi:10.1080/0309190041000166235015513744
   PubMedGoogle Scholar
• Welch P. The use of fast Fourier transform for the estimation of power spectra: a method based on time averaging over short, modified periodograms. IEEE Trans Audio Electroacoust. 1967;15:70–73. doi:10.1109/TAU.1967.1161901
   Google Scholar
• Brennan M, Palaniswami M, Kamen P. Do existing measures of Poincaré plot geometry reflect nonlinear features of heart rate variability? IEEE Trans Biomed Eng. 2001;48(11):1342–1347. doi:10.1109/10.95933011686633
   PubMed Web of Science ®Google Scholar
• Varon C, Lazaro J, Bolea J, et al. Unconstrained estimation of HRV indices after removing respiratory influences from heart rate. IEEE J Biomed Health Inform. 2019;23(6):2386–2397. doi:10.1109/JBHI.2018.288464430507541
   PubMed Web of Science ®Google Scholar
• Moody G, Mark R, Zoccola A, Mantero S. Derivation of respiratory signals from multi-lead ECGs. Comput Cardiol. 1985;12:113–116.
   Google Scholar
• Tarvainen MP, Niskanen JP, Lipponen JA, Ranta-Aho PO, Karjalainen PA. Kubios HRV–heart rate variability analysis software. Comput Methods Programs Biomed. 2014;113(1):210–220. doi:10.1016/j.cmpb.2013.07.02424054542
   PubMed Web of Science ®Google Scholar
• Sullivan GM, Feinn R. Using effect size-or why the P value is not enough. J Grad Med Educ. 2012;4(3):279–282. doi:10.4300/JGME-D-12-00156.123997866
   PubMedGoogle Scholar
• Yanaranop M, Sathapornteera N, Nakrangsee S. Risk factors of pelvic lymph node metastasis in cervical adenocarcinoma following radical hysterectomy and pelvic lymphadenectomy. J Med Assoc Thai. 2014;97(Suppl 11):S87–S95.
   PubMedGoogle Scholar
• Fagotti A, Pedone Anchora L, Conte C, et al. Beyond sentinel node algorithm. Toward a more tailored surgery for cervical cancer patients. Cancer Med. 2016;5(8):1725–1730. doi:10.1002/cam4.72227230108
   PubMed Web of Science ®Google Scholar
• Gulseren V, Kocaer M, Gungorduk O, et al. Preoperative predictors of pelvic and para-aortic lymph node metastases in cervical cancer. J Cancer Res Ther. 2019;15(6):1231–1234. doi:10.4103/jcrt.JCRT_467_1731898653
   PubMed Web of Science ®Google Scholar
• Zhou J, Ran J, He ZY, et al. Tailoring pelvic lymphadenectomy for patients with stage IA2, IB1, and IIA1 uterine cervical cancer. J Cancer. 2015;6(4):377–381. doi:10.7150/jca.1096825767608
   PubMed Web of Science ®Google Scholar
• Nanthamongkolkul K, Hanprasertpong J. Predictive factors of pelvic lymph node metastasis in early-stage cervical cancer. Oncol Res Treat. 2018;41(4):194–198. doi:10.1159/00048584029562222
   PubMed Web of Science ®Google Scholar
• Brennan M, Palaniswami M, Kamen P. Poincaré plot interpretation using a physiological model of HRV based on a network of oscillators. Am J Physiol Heart Circ Physiol. 2002;283(5):H1873–H1886. doi:10.1152/ajpheart.00405.200012384465
   PubMed Web of Science ®Google Scholar
• Shaffer F, Ginsberg JP. An overview of heart rate variability metrics and norms. Front Public Health. 2017;5:258. doi:10.3389/fpubh.2017.0025829034226
   PubMed Web of Science ®Google Scholar
• McCraty R, Shaffer F. Heart rate variability: new perspectives on physiological mechanisms, assessment of self-regulatory capacity, and health risk. Glob Adv Health Med. 2015;4(1):46–61. doi:10.7453/gahmj.2014.073
   PubMedGoogle Scholar
• Fadul N, Strasser F, Palmer JL, et al. The association between autonomic dysfunction and survival in male patients with advanced cancer: a preliminary report. J Pain Symptom Manage. 2010;39(2):283–290. doi:10.1016/j.jpainsymman.2009.06.01420152590
   PubMed Web of Science ®Google Scholar
• Wang YM, Wu HT, Huang EY, Kou YR, Hseu SS. Heart rate variability is associated with survival in patients with brain metastasis: a preliminary report. Biomed Res Int. 2013;2013:503421. doi:10.1155/2013/50342124102056
   PubMed Web of Science ®Google Scholar
• Guo Y, Koshy S, Hui D, et al. Prognostic value of heart rate variability in patients with cancer. J Clin Neurophysiol. 2015;32(6):516–520. doi:10.1097/WNP.000000000000021026629761
   PubMed Web of Science ®Google Scholar
• Cole SW, Nagaraja AS, Lutgendorf SK, Green PA, Sood AK. Sympathetic nervous system regulation of the tumour microenvironment. Nat Rev Cancer. 2015;15(9):563–572. doi:10.1038/nrc397826299593
   PubMed Web of Science ®Google Scholar
• Pagani M, Lombardi F, Guzzetti S, et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympatho-vagal interaction in man and conscious dog. Circ Res. 1986;59(2):178–193. doi:10.1161/01.RES.59.2.1782874900
   PubMed Web of Science ®Google Scholar
• Arai Y, Saul JP, Albrecht P, et al. Modulation of cardiac autonomic activity during and immediately after exercise. Am J Physiol. 1989;256(1 Pt 2):H132–H141. doi:10.1152/ajpheart.1989.256.1.H1322643348
   PubMed Web of Science ®Google Scholar
• Alvarenga ME, Richards JC, Lambert G, Esler MD. Psychophysiological mechanisms in panic disorder: a correlative analysis of noradrenaline spillover, neuronal noradrenaline reuptake, power spectral analysis of heart rate variability, and psychological variables. Psychosom Med. 2006;68(1):8–16. doi:10.1097/01.psy.0000195872.00987.db16449406
   PubMed Web of Science ®Google Scholar
• Moak JP, Goldstein DS, Eldadah BA, et al. Supine low-frequency power of heart rate variability reflects baroreflex function, not cardiac sympathetic innervation. Heart Rhythm. 2007;4(12):1523–1529. doi:10.1016/j.hrthm.2007.07.01917997358
   PubMed Web of Science ®Google Scholar
• Goldstein DS, Bentho O, Park MY, Sharabi Y. Low-frequency power of heart rate variability is not a measure of cardiac sympathetic tone but may be a measure of modulation of cardiac autonomic outflows by baroreflexes. Exp Physiol. 2011;96(12):1255–1261. doi:10.1113/expphysiol.2010.05625921890520
   PubMed Web of Science ®Google Scholar
• de Lartigue G. Putative roles of neuropeptides in vagal afferent signaling. Physiol Behav. 2014;136(136):155–1569. doi:10.1016/j.physbeh.2014.03.01124650553
   PubMed Web of Science ®Google Scholar
• Lin SC, Chen MF. Increased yin-deficient symptoms and aggravated autonomic nervous system function in patients with metastatic cancer. J Altern Complement Med. 2010;16(10):1059–1063. doi:10.1089/acm.2009.048720874442
   PubMed Web of Science ®Google Scholar
• Billman GE. The LF/HF ratio does not accurately measure cardiac sympatho-vagal balance. Front Physiol. 2013;4:26. doi:10.3389/fphys.2013.0002623431279
   PubMed Web of Science ®Google Scholar
• Hayes JD, Dinkova-Kostova AT, Tew KD. Oxidative stress in cancer. Cancer Cell. 2020;38(2):167–197. doi:10.1016/j.ccell.2020.06.00132649885
   PubMed Web of Science ®Google Scholar
• Mantovani A, Allavena P, Sica A, Balkwill F. Cancer-related inflammation. Nature. 2008;454(7203):436–444. doi:10.1038/nature0720518650914
   PubMed Web of Science ®Google Scholar
• Zahalka AH, Frenette PS. Nerves in cancer. Nat Rev Cancer. 2020;20(3):143–157. doi:10.1038/s41568-019-0237-231974491
   PubMed Web of Science ®Google Scholar
• Erin N, Akdas Barkan G, Harms JF, Clawson GA. Vagotomy enhances experimental metastases of 4THMpc breast cancer cells and alters substance P level. Regul Pept. 2008;151(1–3):35–42. doi:10.1016/j.regpep.2008.03.01218499282
   PubMedGoogle Scholar
• Erin N, Duymuş O, Oztürk S, Demir N. Activation of vagus nerve by semapimod alters substance P levels and decreases breast cancer metastasis. Regul Pept. 2012;179(1–3):101–108. doi:10.1016/j.regpep.2012.08.00122982142
   PubMedGoogle Scholar
• Giese-Davis J, Wilhelm FH, Tamagawa R, et al. Higher vagal activity as related to survival in patients with advanced breast cancer: an analysis of autonomic dysregulation. Psychosom Med. 2015;77(4):346–355. doi:10.1097/PSY.000000000000016725886831
   PubMed Web of Science ®Google Scholar
• Shi B, Wang L, Yan C, Chen D, Liu M, Li P. Nonlinear heart rate variability biomarkers for gastric cancer severity: a pilot study. Sci Rep. 2019;9(1):13833. doi:10.1038/s41598-019-50358-y31554856
   PubMed Web of Science ®Google Scholar
• Ciurea AM, Gheonea DI, Schenker M, Mehedințeanu AM, Târtea GC, Vere CC. The prognostic correlation of heart rate variability at diagnosis with survival of patients with hepatocellular carcinoma. Diagnostics (Basel). 2021;11(5):890. doi:10.3390/diagnostics1105089034067711
   PubMedGoogle Scholar
• De Couck M, Gidron Y. Norms of vagal nerve activity, indexed by Heart Rate Variability, in cancer patients. Cancer Epidemiol. 2013;37(5):737–741.23725879
   PubMed Web of Science ®Google Scholar
• Gonzalez H, Hagerling C, Werb Z. Roles of the immune system in cancer: from tumor initiation to metastatic progression. Genes Dev. 2018;32(19–20):1267–1284.30275043
   PubMed Web of Science ®Google Scholar
• Voss A, Schulz S, Schroeder R, Baumert M, Caminal P. Methods derived from nonlinear dynamics for analysing heart rate variability. Philos Trans a Math Phys Eng Sci. 2009;367(1887):277–296. doi:10.1098/rsta.2008.023218977726
   PubMed Web of Science ®Google Scholar
• Voss A, Kurths J, Kleiner HJ, et al. The application of methods of non-linear dynamics for the improved and predictive recognition of patients threatened by sudden cardiac death. Cardiovasc Res. 1996;31(3):419–433. doi:10.1016/S0008-6363(96)00008-98681329
   PubMed Web of Science ®Google Scholar
• Huikuri HV, Perkiömäki JS, Maestri R, Pinna GD. Clinical impact of evaluation of cardiovascular control by novel methods of heart rate dynamics. Philos Trans A Math Phys Eng Sci. 2009;367(1892):1223–1238. doi:10.1098/rsta.2008.029419324705
   PubMed Web of Science ®Google Scholar
• Ward-Hartstonge KA, Kemp RA. Regulatory T-cell heterogeneity and the cancer immune response. Clin Transl Immunol. 2017;6(9):e154. doi:10.1038/cti.2017.43
   PubMed Web of Science ®Google Scholar
• Tracey KJ. Reflex control of immunity. Nat Rev Immunol. 2009;9(6):418–428. doi:10.1038/nri256619461672
   PubMed Web of Science ®Google Scholar
• Wang M, Zhao J, Zhang L, et al. Role of tumor microenvironment in tumorigenesis. J Cancer. 2017;8(5):761–773. doi:10.7150/jca.1764828382138
   PubMed Web of Science ®Google Scholar
• Kessenbrock K, Plaks V, Werb Z. Matrix metalloproteinases: regulators of the tumor microenvironment. Cell. 2010;141(1):52–67. doi:10.1016/j.cell.2010.03.01520371345
   PubMed Web of Science ®Google Scholar
• Qiao G, Chen M, Bucsek MJ, Repasky EA, Hylander BL. Adrenergic signaling: a targetable checkpoint limiting development of the antitumor immune response. Front Immunol. 2018;9:164. doi:10.3389/fimmu.2018.0016429479349
   PubMed Web of Science ®Google Scholar
• Huan HB, Wen XD, Chen XJ, et al. Sympathetic nervous system promotes hepatocarcinogenesis by modulating inflammation through activation of alpha1-adrenergic receptors of Kupffer cells. Brain Behav Immun. 2017;59:118–134. doi:10.1016/j.bbi.2016.08.01627585737
   PubMed Web of Science ®Google Scholar
• Le CP, Nowell CJ, Kim-Fuchs C, et al. Chronic stress in mice remodels lymph vasculature to promote tumour cell dissemination. Nat Commun. 2016;7:10634. doi:10.1038/ncomms1063426925549
   PubMed Web of Science ®Google Scholar
• Sood AK, Bhatty R, Kamat AA, et al. Stress hormone-mediated invasion of ovarian cancer cells. Clin Cancer Res. 2006;12(2):369–375. doi:10.1158/1078-0432.CCR-05-169816428474
   PubMed Web of Science ®Google Scholar
• Karimi K, Bienenstock J, Wang L, Forsythe P. The vagus nerve modulates CD4+ T cell activity. Brain Behav Immun. 2010;24(2):316–323. doi:10.1016/j.bbi.2009.10.01619887104
   PubMed Web of Science ®Google Scholar
• Reijmen E, Vannucci L, De Couck M, De Grève J, Gidron Y. Therapeutic potential of the vagus nerve in cancer. Immunol Lett. 2018;202(202):38–43. doi:10.1016/j.imlet.2018.07.00630077536
   PubMed Web of Science ®Google Scholar
• Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 2007;117(2):289–296. doi:10.1172/JCI3055517273548
   PubMed Web of Science ®Google Scholar
• Brown TE, Beightol LA, Koh J, Eckberg DL. Important influence of respiration on human R-R interval power spectra is largely ignored. J Appl Physiol. 1993;75(5):2310–2317. doi:10.1152/jappl.1993.75.5.23108307890
   PubMed Web of Science ®Google Scholar
• Niederer D, Vogt L, Thiel C, et al. Exercise effects on HRV in cancer patients. Int J Sports Med. 2013;34(1):68–73. doi:10.1055/s-0032-131481622895874
   PubMed Web of Science ®Google Scholar
• Chuang CY, Han WR, Li PC, Young ST. Effects of music therapy on subjective sensations and heart rate variability in treated cancer survivors: a pilot study. Complement Ther Med. 2010;18(5):224–226. doi:10.1016/j.ctim.2010.08.00321056846
   PubMed Web of Science ®Google Scholar
• Hou L, Zhou W, Ren J, et al. Radiomics analysis of multiparametric MRI for the preoperative prediction of lymph node metastasis in cervical cancer. Front Oncol. 2020;10:1393. doi:10.3389/fonc.2020.0139332974143
   PubMed Web of Science ®Google Scholar
• Calabrese A, Santucci D, Landi R, et al. Radiomics MRI for lymph node status prediction in breast cancer patients: the state of art. J Cancer Res Clin Oncol. 2021;147(6):1587–1597. doi:10.1007/s00432-021-03606-633758997
   PubMed Web of Science ®Google Scholar
• Huang YQ, Liang CH, He L, et al. Development and validation of a radiomics nomogram for preoperative prediction of lymph node metastasis in colorectal cancer. J Clin Oncol. 2016;34(18):2157–2164. doi:10.1200/JCO.2015.65.912827138577
   PubMed Web of Science ®Google Scholar