Top

Published in:

01-04-2019 | Original Article

The prognostic and predictive role of hyponatremia in patients with advanced non-small cell lung cancer (NSCLC) with bone metastases

Authors: S. Rinaldi, M. Santoni, G. Leoni, I. Fiordoliva, G. Marcantognini, T. Meletani, G. Armento, D. Santini, T. Newsom-Davis, M. Tiberi, F. Morgese, M. Torniai, M. Bower, Rossana Berardi

Published in: Supportive Care in Cancer | Issue 4/2019

Abstract

Purpose

Hyponatremia and bone metastasis (BMs) are known as negative prognostic factors in patients affected by metastatic non-small cell lung cancer (NSCLC). Hyponatremia is associated with higher risk of osteoporosis and bone fracture, but no data are available about the relationship between hyponatremia and bone metastasis. This study aims to analyze the prognostic impact of hyponatremia in NSCLC patients with bone metastases.

Methods

We retrospectively collected data about advanced NSCLC patients. Survival curves were estimated using Kaplan–Meier method, and comparisons were made using chi-square test.

Results

Six hundred forty-seven patients were enrolled into the study. BMs were present in 264 patients (41%) at diagnosis, while hyponatremia appeared in 237 (37%) patients during the first-line treatment. Patients without BMs had a median overall survival (mOS) of 15.9 months (95% CI 14.1–17.9) versus 11.4 months (95% CI 9.4–13.4) for patients with BMs (p = 0.001). Eunatremic patients had a better outcome (mOS 16.3 months, 95% CI 14.6–18.0 vs 10.3 months, 95% I 7.6–12.8, p = 0.003). Considering the two variables, patients with BMs and hyponatremia had a mOS of 10.1 months (95% CI 4.3–15.9), patients with hyponatremia without BMs 11.9 months (95% CI 11.4–12.4), while mOS was 13.1 months (95% CI 12.0–14.2) for eunatremic patients with BMs versus 17.1 months (95% CI 15.2–19.1) in eunatremic patients without BMs (p = 0.0020). Hyponatremic patients developed metachronous BMs significantly earlier (3.73 vs 5.76 months, p = 0.0187).

Conclusions

Our study showed that hyponatremia is an important prognostic factor and it should be necessarily considered to enhance the management of NSCLC patients with BMs.

Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30. https://doi.org/10.3322/caac.21332 PubMedCrossRef

Novello S, Barlesi F, Califano R, Cufer T, Ekman S, Levra MG, Kerr K, Popat S, Reck M, Senan S, Simo GV, Vansteenkiste J, Peters S, Guidelines Committee ESMO (2016) Metastatic non-small-cell lung cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. AnnOncol 27(suppl 5):v1–v27. https://doi.org/10.1093/annonc/mdw326 CrossRef

Janssen-Heijnen ML, van Erning FN, de Ruysscher DK,Coebergh JW, Groen HJ (2015) Variation in causes of death in patients with non-small cell lung cancer according to stage and time since diagnosis. Ann Oncol 26: 902–907. https://doi.org/10.1093/annonc/mdv061

Mundy G (2002) Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2:584–593. https://doi.org/10.1038/nrc867 PubMedCrossRef

Coleman R (2001) Metastatic bone disease: clinical features, pathophysiology and treatment strategies. Cancer Treat Rev 27:165–176. https://doi.org/10.1053/ctrv.2000.0210 PubMedCrossRef

Sugiura H, Yamada K, Sugiura T, Hida T, Mitsudomi T (2008) Predictors of survival in patients with bone metastasis of lung cancer. Clin Orthop Relat Res 466:729–736. https://doi.org/10.1007/s11999-007-0051-0 PubMedPubMedCentralCrossRef

Berenson J, Rajdev L, Broder M (2006) Managing bone complications of solid tumors. Cancer Biol Ther 5:1086–1089PubMedCrossRef

Botteman M, Foley I, Marfatia A, Brandman J, Langer C (2007) Economic value of zoledronic acid versus placebo in the treatment of skeletal metastasis in patients with lung cancer: the case of the United Kingdom (UK). J ClinOncol 25:6617. https://doi.org/10.1200/jco.2007.25.18_suppl.6617 CrossRef

Saad F, Lipton A, Cook R, Chen Y, Smith M, Coleman R (2007) Pathologic fractures correlate with reduced survival in patients with malignant bone disease. Cancer 110:1860–1867. https://doi.org/10.1002/cncr.22991 PubMedCrossRef

10.

Petereit C, Zaba O, Teber I, Grohé C (2011) Is hyponatremia a prognostic marker of survival for lung cancer? Pneumologie 65:565–571. https://doi.org/10.1055/s-0030-1256668 PubMedCrossRef

11.

Sengupta A, Banerjee SN, Biswas NM, Jash D, Saha K, Maji A, Bandyopadhyaya A, Agarwal S (2013) The incidence of hyponatraemia and its effect on the ECOG performance status among lung cancer patients. J ClinDiagn Res 7:1678–1682. https://doi.org/10.7860/JCDR/2013/5900.3225 CrossRef

12.

Ghali JK (2008) Mechanisms, risks, and new treatment options for hyponatremia. Cardiology 111:147–157. https://doi.org/10.1159/000121596 PubMedCrossRef

13.

Sørensen JB, Andersen MK, Hansen HH (1955) Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) in malignant disease. J Intern Med 238:97–110CrossRef

14.

Kobayashi N, Usui S, Yamaoka M, Suzuki H, Kikuchi S, Goto Y, Sakai M, Sato Y (2014) The influence of serum sodium concentration on prognosis in resected non-small cell lung cancer. ThoracCardiovascSurg 62:338–343. https://doi.org/10.1055/s-0033-1359713 CrossRef

15.

Berardi R, Santoni M, Newsom-Davis T, Caramanti M, Rinaldi S, Tiberi M, Morgese F, Torniai M, Pistelli M, Onofri A, Bower M, Cascinu S (2016) Hyponatremia normalization as an independent prognostic factor in patients with advanced non-small cell lung cancer treated with first-line therapy. Oncotarget 8:13372. https://doi.org/10.18632/oncotarget.13372 CrossRef

16.

Berardi R, Rinaldi S, Caramanti M, Grohè C, Santoni M, Morgese F, Torniai M, Savini A, Fiordoliva I, Cascinu S (2016) A hyponatremia in cancer patients: time for a new approach. Crit Rev Oncol Hematol 102:15–25. https://doi.org/10.1016/j.critrevonc.2016.03.010 PubMedCrossRef

17.

Renneboog B, Musch W, Vandemergel X, Manto MU, Decaux G (2006) Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med 119:71–78. https://doi.org/10.1016/j.amjmed.2005.09.026 PubMedCrossRef

18.

Cumming K, Hoyle GE, Hutchison JD, Soiza RL (2014) Prevalence, incidence and etiology of hyponatremia in elderly patients with fragility fractures. PLoS One 5;9(2):e88272. https://doi.org/10.1371/journal.pone.0088272

19.

Barsony J, Sugimura Y, Verbalis JG (2011) Osteoclast response to low extracellular sodium and the mechanism of hyponatremia-induced bone loss. J Biol Chem 286:10864–10875. https://doi.org/10.1074/jbc.M110.155002 PubMedCrossRef

20.

Verbalis JG, Barsony J, Sugimura Y, Tian Y, Adams DJ, Carter EA, Resnick HE (2010) Hyponatremia-induced osteoporosis. J Bone Miner Res 25:554–563. https://doi.org/10.1359/jbmr.090827 PubMedCrossRef

21.

Gankam KF, Andres C, Sattar L, Melot C, Decaux G (2008) Mild hyponatremia and risk of fracture in the ambulatory elderly. Q J Med 101:583–588. https://doi.org/10.1093/qjmed/hcn061 CrossRef

22.

Eberhardt WE, Mitchell A, Crowley J, Kondo H, Kim YT, Turrisi A 3rd, Goldstraw P, Rami-Porta R (2015) International Association for Study of Lung Cancer Staging and Prognostic Factors Committee, Advisory Board Members, and Participating Institutions. The IASLC Lung Cancer Staging Project: proposals for the revision of the M descriptors in the forthcoming eighth edition of the TNM classification of lung cancer. J Thorac Oncol 10(11):1515–1522. https://doi.org/10.1097/JTO.0000000000000673 PubMedCrossRef

23.

Fagerland MW, Hosmer DW, Bofin AM (2008) Multinomial goodness-of-fit tests for logistic regression models. Stat Med 27:4238–4253. https://doi.org/10.1002/sim.3202 PubMedCrossRef

24.

Mickey RM, Greenland S (1989) The impact of confounder selection criteria on effect estimation. Am J Epidemiol 129:125–137PubMedCrossRef

25.

Pepe MS, Kerr KF, Longton G, Wang Z (2013) Testing for improvement in prediction model performance. Stat Med 32:1467–1482. https://doi.org/10.1002/sim.5727 PubMedPubMedCentralCrossRef

26.

Tsuya A, Kurata T, Tamura K, Fukuoka M (2007) Skeletal metastases in non-small cell lung cancer: a retrospective study. Lung Cancer 57:229–232. https://doi.org/10.1016/j.lungcan.2007.03.013 PubMedCrossRef

27.

Quint LE, Tummala S, Brisson LJ, Francis IR, Krupnick AS, Kazerooni EA, Iannettoni MD, Whyte RI, Orringer MB (1996) Distribution of distant metastases from newly diagnosed non-small cell lung cancer. Ann Thorac Surg 62:246–250PubMedCrossRef

28.

Kuchuk M, Kuchuk I, Sabri E, Hutton B, Clemons M, P W-P (2015) The incidence and clinical impact of bone metastases in non-small cell lung cancer. Lung Cancer 89(2):197–202. https://doi.org/10.1016/j.lungcan.2015.04.007 PubMedCrossRef

29.

Kosteva J, Langer C (2004) Incidence and distribution of skeletal metastases in NSCLC in the era of PET. Lung Cancer 46(Suppl 1):S45

30.

Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. A Cancer J Clin 60:277–300. https://doi.org/10.3322/caac.20073 CrossRef

31.

Santini D, Barni S, Intagliata S, Falcone A, Ferraù F, Galetta D, Moscetti L, La Verde N, Ibrahim T, Petrelli F, Vasile E, Ginocchi L, Ottaviani D, Longo F, Ortega C, Russo A, Badalamenti G, Collovà E, Lanzetta G, Mansueto G, Adamo V, De Marinis F, Satolli MA, Cantile F, Mancuso A, Tanca FM, Addeo R, Russano M, Sterpi M, Pantano F, Vincenzi B, Tonini G (2015) Natural history of non-small-cell lung cancer with bone metastases. Sci Rep 22(5):18670. https://doi.org/10.1038/srep18670 CrossRef

32.

Zhang L, Gong Z (2017) Clinical characteristics and prognostic factors in bone metastases from lung cancer. Med SciMonit 24(23):4087–4094

33.

Palmer BF, Gates JR, Lader M (2003) Causes and management of hyponatremia. Ann Pharmacother 37:1694–1702. https://doi.org/10.1345/aph.1D105 PubMedCrossRef

34.

Castillo JJ, Vincent M, Justice E (2012) Diagnosis and management of hyponatremia in cancer patients. Oncologist 17:756–765. https://doi.org/10.1634/theoncologist.2011-0400 PubMedPubMedCentralCrossRef

35.

Pagani S, Fini M, Giavaresi G, Salamanna F, Borsari V (2015) The active role of osteoporosis in the interaction between osteoblasts and bone metastases. Bone 79:176–182. https://doi.org/10.1016/j.bone.2015.06.002 PubMedCrossRef

36.

Ross MD, Biswas Roy S, Patil PD, Huang JL, Thawani N, Drosten R, Panchabhai TS (2018 Feb 20) Coexistent non-small cell carcinoma and small cell carcinoma in a patient presenting with hyponatremia. Case Rep Pulmonol 2018:1718326–1718324. https://doi.org/10.1155/2018/1718326 PubMedPubMedCentralCrossRef

37.

Penttilä P, Bono P, Peltola K, Donskov F (2018 Jun 4) Hyponatremia associates with poor outcome in metastatic renal cell carcinoma patients treated with everolimus: prognostic impact. Acta Oncol:1–6. https://doi.org/10.1080/0284186X.2018.1477256

38.

Fibbi B, Benvenuti S, Giuliani C, Deledda C, Luciani P, Monici M, Mazzanti B, Ballerini C, Peri A (2016) Low extracellular sodium promotes adipogenic commitment of human mesenchymal stromal cells: a novel mechanism for chronic hyponatremia-induced bone loss. Endocrine 52(1):73–85. https://doi.org/10.1007/s12020-015-0663-1 PubMedCrossRef

39.

Ayus JC, Bellido T, Negri AL (2017) Hyponatremia and fractures: should hyponatremia be further studied as a potential biochemical risk factor to be included in FRAX algorithms? Osteoporos Int 28(5):1543–1548. https://doi.org/10.1007/s00198-017-3907-5 PubMedCrossRef

40.

HansenO SP, Hansen KH (2010) The occurrence of hyponatremia in SCLC and the influence on prognosis. A retrospective study of 453 patients treated in a single institution in a 10-year period. Lung Cancer 68:111–114. https://doi.org/10.1016/j.lungcan.2009.05.015 CrossRef

41.

Jeppesen AN, Jensen HK, Donskov F, Marcussen N, von der Maase H (2010) Hyponatremia as a prognostic and predictive factor in metastatic renal cell carcinoma. Br J Cancer 102:867–872. https://doi.org/10.1038/sj.bjc.6605563 PubMedPubMedCentralCrossRef

42.

Kim HS, Yi SY, Jun HJ, Lee J, Park JO, Park YS, Jang J, Kim HJ, Ko Y, Lim HY, Kang WK (2007) Clinical outcome of gastric cancer patients with bone marrow metastases. Oncology 73(3–4):192–197. https://doi.org/10.1159/000127386 PubMedCrossRef

Title: The prognostic and predictive role of hyponatremia in patients with advanced non-small cell lung cancer (NSCLC) with bone metastases
Authors: S. Rinaldi
M. Santoni
G. Leoni
I. Fiordoliva
G. Marcantognini
T. Meletani
G. Armento
D. Santini
T. Newsom-Davis
M. Tiberi
F. Morgese
M. Torniai
M. Bower
Rossana Berardi
Publication date: 01-04-2019
Publisher: Springer Berlin Heidelberg
Published in: Supportive Care in Cancer / Issue 4/2019
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI: https://doi.org/10.1007/s00520-018-4489-2

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2019

The impact of parental cancer on preadolescent children (0–11 years) in Western Australia: a longitudinal population study

Modeling symptom drivers of oral intake in long-term head and neck cancer survivors

Breast Cancer Collaborative Registry informs understanding of factors predicting sleep quality

Urine cultures at the onset of febrile neutropenia rarely impact antibiotic management in asymptomatic adult cancer patients

Dimensions of sedentary behavior and objective cognitive functioning in breast cancer survivors

Undiagnosed cardiac deficits in non-small cell carcinoma patients in the candidate population for anti-cachexia clinical trials

Keynote webinar | Spotlight on antibody–drug conjugates in cancer