Download PDF
CC BY 4.0 · Brazilian Journal of Oncology 2022; 18: e-20220350
DOI: 10.5935/2526-8732.20220350
Original Article
Clinical Oncology

Is platelet-lymphocyte ratio (PLR) a predictor of thrombosis and together with circulating tumor cells capable to determine recurrence-free survival in patients with gastric cancer?

A razão plaqueta-linfócito (PLR) é um preditor de trombose e, juntamente com as células tumorais circulantes, é capaz de determinar a sobrevida livre de recorrência em pacientes com câncer gástrico?
Bruno Soriano Pignataro
1   Departament of Vascular and Endovascular Surgery, A.C. Camargo Cancer Center, Brazil
,
Emne Ali Abdallah
2   IQVIA, São Paulo, Brazil
,
Celso Abdon Lopes Mello
3   Department of Medical Oncology, A.C. Camargo Cancer Center, São Paulo, Brazil
,
Vinicius Fernando Calsavara
4   Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
,
Kenji Nishinari
1   Departament of Vascular and Endovascular Surgery, A.C. Camargo Cancer Center, Brazil
,
Anna Paula Carreta Ruano 
3   Department of Medical Oncology, A.C. Camargo Cancer Center, São Paulo, Brazil
,
Marcello F Fanelli
5   Oncologia Clínica da Rede São Camilo, São Paulo, Brazil
,
Guilherme Yazbek
1   Departament of Vascular and Endovascular Surgery, A.C. Camargo Cancer Center, Brazil
,
Ludmilla Thomé Domingos Chinen
6   Núcleo de Ensino e Pesquisa da Rede São Camilo, São Paulo, Brazil
› Author Affiliations Financial support: None to declare.
› Further Information
   Permissions and Reprints All articles of this category

ABSTRACT

Introduction: Cancer-associated thrombosis (CAT) is a major cause of morbidity and mortality in oncology patients. There are no accurate risk assessment tools to predict venous thromboembolism (VTE). Circulating tumor cells (CTCs), circulating tumor microemboli (CTM), and high platelet-lymphocyte ratio (PLR) may predispose to VTE.

Objective: To evaluate correlations of CTCs, CTM, and PLR with VTE and recurrence-free survival (RFS) in gastric cancer patients.

Material and Methods: Patients with gastric cancer (localized and metastatic disease) were recruited (March 2016 to April 2017). CTCs were analysed by ISET at two timepoints: before neoadjuvant treatment (CTC1) and after surgery/before adjuvant therapy (CTC2) for patients with localized disease, and before first-line chemotherapy (CTC1) and after 6 months (CTC2) for patients with metastases. VTE incidence was determined retrospectively. RFS was estimated by Kaplan-Meier analysis.

Results: We evaluated 93 patients. According to Khorana scores, 63 (67.7%) patients were at intermediate and 30 (32.3%) were at high risk for VTE. VTE incidence was 20.4% and CTM were found in 39.8%. VTE developed in 7/37 (18.9%) CTM-positive and in 11/50 (22%) CTM-negative patients (p=0.93). When PLR >288, VTE occurred in 7/14 patients (p=0.005). PLR also associated with poor RFS (p<0.0001). CTC2 was associated with poor RFS (p<0.0001). CTC2, PLR and VTE were independent prognostic factors for RFS (p=0.005, 0.043, and <0.0001, respectively).

Conclusion: PLR is a prognostic indicator for VTE and RFS in gastric cancer patients. Neither CTC, nor CTM improved risk stratification for VTE in our studied population. PLR, CTC2, and VTE were independent prognostic factors for RFS.

RESUMO

Introdução: A trombose associada ao câncer (TAC) é uma das principais causas de morbidade e mortalidade em pacientes oncológicos. Não existem ferramentas de avaliação de risco precisas para prever tromboembolismo venoso (TEV). Células tumorais circulantes (CTCs), microêmbolos tumorais circulantes (MTC) e alta relação plaquetas-linfócitos (RPL) podem predispor ao TEV.

Objetivo: Avaliar as correlações de CTCs, MTC e RPL com TEV e sobrevida livre de recorrência (SLR) em pacientes com câncer gástrico.

Material e Métodos: Foram recrutados pacientes com câncer gástrico (doença localizada e metastática) (março de 2016 a abril de 2017). As CTCs foram analisadas pelo ISET em dois momentos: antes do tratamento neoadjuvante (CTC1) e após a cirurgia/antes da terapia adjuvante (CTC2) para pacientes com doença localizada, e antes da quimioterapia de primeira linha (CTC1) e após 6 meses (CTC2) para pacientes com metástases. A incidência de TEV foi determinada retrospectivamente. A SLR foi estimada pela análise de Kaplan-Meier.

Resultados: Avaliamos 93 pacientes. De acordo com os escores de Khorana, 63 (67,7%) pacientes estavam no nível intermediário e 30 (32,3%) estavam em alto risco para TEV. A incidência de TEV foi de 20,4% e MTC foram encontrados em 39,8%. TEV desenvolveu-se em 7/37 (18,9%) pacientes MTC-positivos e em 11/50 (22%) pacientes MTC-negativos (p=0,93). Quando RPL >288, ocorreu TEV em 7/14 pacientes (p=0,005). A RPL também associou-se à baixa SLR (p<0,0001). CTC2 foi associado com SLR ruim (p<0,0001). CTC2, RPL e TEV foram fatores prognósticos independentes para SLR (p=0,005, 0,043 e <0,0001, respectivamente).

Conclusão: RPL é um indicador prognóstico para TEV e SLR em pacientes com câncer gástrico. Nem CTC, nem MTC melhoraram a estratificação de risco para TEV em nossa população estudada. RPL, CTC2 e TEV foram fatores prognósticos independentes para SLR.

Keywords:

Platelet-lymphocyte ratio - Circulating tumor cells - Circulating tumor microemboli - Thrombosis - Gastric cancer

Descritores:

Relação plaqueta-linfócito - Células tumorais circulantes - Microêmbolos tumorais circulantes - Trombose - Câncer de intestino

ETHICAL APPROVAL AND CONSENT TO PARTICIPATE

Approved by the ethics committee: (CEP 2134/15).


AUTHORS' CONTRIBUTIONS

B.S.P: data analysis and interpretation, manuscript writing; E.A.A: data analysis and interpretation, collection and/or assembly of data; C.A.L.M: conception/design, data analysis and interpretation; V.F.C: statistical analysis; K.N.: data analysis and interpretation; A.P.C.R.: collection and/or assembly of data; M.F.F.: interpretation and manuscript writing; G.Y: data analysis and interpretation, final approval of manuscript; L.T.D.C: conception/design, data analysis and interpretation, manuscript writing, final approval of manuscript.


CONFLICTS OF INTEREST

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.




Publication History

Received: 04 May 2022

Accepted: 01 July 2022

Article published online:
25 July 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution 4.0 International License, permitting copying and reproduction so long as the original work is given appropriate credit (https://creativecommons.org/licenses/by/4.0/)

Thieme Revinter Publicações Ltda.
Rua do Matoso 170, Rio de Janeiro, RJ, CEP 20270-135, Brazil

Bibliographical Record
Bruno Soriano Pignataro, Emne Ali Abdallah, Celso Abdon Lopes Mello, Vinicius Fernando Calsavara, Kenji Nishinari, Anna Paula Carreta Ruano, Marcello F Fanelli, Guilherme Yazbek, Ludmilla Thomé Domingos Chinen. Is platelet-lymphocyte ratio (PLR) a predictor of thrombosis and together with circulating tumor cells capable to determine recurrence-free survival in patients with gastric cancer?. Brazilian Journal of Oncology 2022; 18: e-20220350.
DOI: 10.5935/2526-8732.20220350
 

  • REFERENCES

  • 1 Khorana AA, Francis CW, Culakova E, Kuderer NM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 2007; Mar; 5 (03) 632-634
    Search in Google Scholar
  • 2 Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; Mar; 160 (06) 809-815
    Search in Google Scholar
  • 3 Heit JA, Spencer FA, White RH. The epidemiology of venous thromboembolism. J Thromb Thrombolysis 2016; 41 (01) 3-14
    Search in Google Scholar
  • 4 Silverstein MD, Heit JA, Mohr DN, Pettterson TM, O'Falon WM, Melton LJ. Trends in the incidence of deep vein thrombosis and pulmonary embolism. Arch Intern Med 1998; Mar; 158 (06) 585-593
    Search in Google Scholar
  • 5 Khorana AA, Francis CW. Risk prediction of cancer-associated thrombosis: appraising the first decade and developing the future. Thromb Res 2018; Apr; 164 (Suppl 1): S70-S6
    Search in Google Scholar
  • 6 Khorana AA, Kuderer NM, Culakova E, Lyman GH, Francis CW. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood 2008; May; 111 (10) 4902-4907
    Search in Google Scholar
  • 7 Verso M, Agnelli G, Barni S, Gasparini G, LaBianca R. A. modified Khorana risk assessment score for venous thromboembolism in cancer patients receiving chemotherapy: the Protecht score. Intern Emerg Med 2012; Jun; 7 (03) 291-292
    Search in Google Scholar
  • 8 Ay C, Dunkler D, Marosi C, Chiriac AL, Vormittag R, Simanek R. et al. Prediction of venous thromboembolism in cancer patients. Blood 2010; Dec; 116 (24) 5377-5382
    Search in Google Scholar
  • 9 Nichetti F, Ligorio F, Montelatici G, Porcu L, Zattarin E, Provenzano L. et al. Risk assessment of thromboembolic events in hospitalized cancer patients. Sci Rep 2021; Sep; 11: 18200
    Search in Google Scholar
  • 10 Cristofanilli M, Budd GT, Ellis MJ, Stopeck A, Matera J, Miller MC. et al. Circulating tumor cells, disease progression, and survival in metastatic breast cancer. N Engl J Med 2004; Aug; 351 (08) 781-791
    Search in Google Scholar
  • 11 Abdallah EA, Braun AC, Flores BCTCP, Senda L, Urvanegia AC, Calsavara V. et al. The potential clinical implications of circulating tumor cells and circulating tumor microemboli in gastric cancer. Oncologist 2019; Sep; 24 (09) 854-863
    Search in Google Scholar
  • 12 Phillips KG, Lee AM, Tormoen GW, Rigg RA, Kolatkar A, Luttgen M. et al. The thrombotic potential of circulating tumor microemboli: computational modeling of circulating tumor cell-induced coagulation. Am J Physiol Cell Physiol 2015; Feb; 308 (03) C229-C36
    Search in Google Scholar
  • 13 Mego M, De Giorgi U, Broglio K, Dawood S, Valero V, Andreopoulou E. et al. Circulating tumour cells are associated with increased risk of venous thromboembolism in metastatic breast cancer patients. Br J Cancer 2009; Dec; 101 (11) 1813-1816
    Search in Google Scholar
  • 14 Beinse G, Berger F, Cottu P, Dujaric ME, Kriegel I, Guilhaume MN. et al. Circulating tumor cell count and thrombosis in metastatic breast cancer. J Thromb Haemost 2017; Oct; 15 (10) 1981-1988
    Search in Google Scholar
  • 15 Bystricky B, Reuben JM, Mego M. Critical reviews in oncology/hematology circulating tumor cells and coagulation - minireview. Crit Rev Oncol/Hematol 2017; Jun; 114: 33-42
    Search in Google Scholar
  • 16 Tormoen GW, Haley KM, Levine RL, McCarty OJT. Do circulating tumor cells play a role in coagulation and thrombosis?. Front Oncol 2012; Sep; 10 (02) 115
    Search in Google Scholar
  • 17 Yüksel M, Yıldız A, Oylumlu M, Akyüz A, Aydın M, Kaya H. et al. The association between platelet/lymphocyte ratio and coronary artery disease severity. Anatol J Cardiol 2015; Aug; 15 (08) 640-647
    Search in Google Scholar
  • 18 Hudzik B, Szkodzinski J, Gorol J, Niedziela J, Lekston A, Gasior M. et al. Platelet-to-lymphocyte ratio is a marker of poor prognosis in patients with diabetes mellitus and ST-elevation myocardial infarction. Biomark Med 2015; 9 (03) 199-207
    Search in Google Scholar
  • 19 Ferroni P, Riondino S, Formica V, Cereda V, Tosetto L, La Farina F. et al. Venous thromboembolism risk prediction in ambulatory cancer patients: clinical significance of neutrophil/lymphocyte ratio and platelet/lymphocyte ratio. Int J Cancer 2015; Mar; 136 (05) 1234-1240
    Search in Google Scholar
  • 20 Lausen B, Schumacher M. Maximally selected rank statistics. Biometrics 1992; Mar; 48 (01) 73
    Search in Google Scholar
  • 21 Key NS, Khorana AA, Kuderer NM, Bohlke K, Lee AYY, Arcelus JI. et al. Venous thromboembolism prophylaxis and treatment in patients with cancer: ASCO clinical practice guideline update. J Clin Oncol 2020; Feb; 38 (05) 496-520
    Search in Google Scholar
  • 22 Krebs MG, Hou JM, Sloane R, Lancashire L, Priest L, Nonaka D. et al. Analysis of circulating tumor cells in patients with non-small cell lung cancer using epithelial marker-dependent and -independent approaches. J Thorac Oncol 2012; Feb; 7 (02) 306-315
    Search in Google Scholar
  • 23 Lee KW, Bang SM, Kim S, Lee HJ, Shin DY, Koh Y. et al. The incidence, risk factors and prognostic implications of venous thromboembolism in patients with gastric cancer. J Thromb Haemost 2010; Mar; 8 (03) 540-547
    Search in Google Scholar
  • 24 Khorana AA. Simplicity versus complexity: an existential dilemma as risk tools evolve. Lancet Haematol 2018; Jun; 5 (07) e273-e4
    Search in Google Scholar
  • 25 Carrier M, Abou-Nassar K, Mallick R, Tagalakis V, Shivakumar S, Schattner A. et al. Apixaban to prevent venous thromboembolism in patients with cancer. N Engl J Med 2019; Feb; 380 (08) 711-719
    Search in Google Scholar
  • 26 Khorana AA, Soff GA, Kakkar AK, Vadhan-Raj S, Riess H, Wun T. et al. Rivaroxaban for thromboprophylaxis in high-risk ambulatory patients with cancer. N Engl J Med 2019; Feb; 380 (08) 720-728
    Search in Google Scholar
  • 27 Khorana AA, Noble S, Lee AYY, Soff G, Meyer G, O'Connell C. et al. Role of direct oral anticoagulants in the treatment of cancer-associated venous thromboembolism: guidance from the SSC of the ISTH. J Thromb Haemost 2018; Sep; 16 (09) 1891-1894
    Search in Google Scholar
  • 28 Ay C, Pabinger I, Cohen AT. Cancer-associated venous thromboembolism: burden, mechanisms, and management. Thromb Haemost 2017; Jan; 117 (02) 219-230
    Search in Google Scholar