The impact of right ventricular function on prognosis in patients with stage III non-small cell lung cancer after concurrent chemoradiotherapy

  • Lu ChenEmail author
  • Jinjuan Huang
  • Weihua Wu
  • Shengjun Ta
  • Xiaoyi Xie
Original Paper


Right ventricular (RV) impairment after cancer therapy-related cardiotoxicity and its prognostic implications in lung cancer have not been examined. The present research sought to evaluate RV structure, function, and mechanics in stage III non-small-cell lung cancer (NSCLC) before and after concurrent chemoradiotherapy (CCRT), and to explore the associations between RV impairments, radiation dose, and all-cause mortality. This prospective investigation included 128 inoperable NSCLC patients who were scheduled to receive CCRT. Echocardiographic examination and strain evaluation was performed at baseline and 6 months post-CCRT in all participants. Conventional RV dimensions revealed no significant changes post-CCRT. However, a reduction in RV free wall strain (RV-fwLS) was observed at 6 months post-CCRT (− 28.3 ± 4.6% vs. − 25.5 ± 4.8%, P < 0.001). The same was revealed for global RV longitudinal strain (RV-GLS) (− 23.4 ± 2.9% vs. − 20.2 ± 3.4%, P < 0.001). Pearson correlation showed that RV radiation mean dose was related with the percentage change in RV-fwLS (r = 0.303, P = 0.001) and RV-GLS (r = 0.284, P = 0.002). In multivariable analysis, the percentage change in RV-fwLS was an independent predictor of all-cause mortality (HR 1.296, 95% CI 1.202–1.428, P < 0.001). RV longitudinal strain is deteriorated at 6 months post-CCRT. The RV mechanics deterioration was associated with radiation dose and affected the long-term outcome of stage III NSCLC patients treated with CCRT.


Right ventricle Strain Chemoradiotherapy Non-small cell lung cancer 



This work was supported by the Shanghai Charity Cancer Research Center [Grant No. SCCRC17004].

Conflict of interest

All authors declare no conflicts of interest.


  1. 1.
    Auperin A, Le Pechoux C, Rolland E, Curran WJ, Furuse K, Fournel P, Belderbos J, Clamon G, Ulutin HC, Paulus R, Yamanaka T, Bozonnat MC, Uitterhoeve A, Wang XF, Stewart L, Arriagada R, Burdett S, Pignon JP (2010) Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non–small-cell lung cancer. J Clin Oncol 28(13):2181–2190CrossRefGoogle Scholar
  2. 2.
    Aleman BM, van den Belt-Dusebout AW, De Bruin ML, van’t Veer MB, Baaijens MH, de Boer JP, Hart AA, Klokman WJ, Kuenen MA, Ouwens GM, Bartelink H, van Leeuwen FE (2007) Late cardiotoxicity after treatment for Hodgkin lymphoma. Blood 109:1878–1886CrossRefGoogle Scholar
  3. 3.
    Hooning MJ, Botma A, Aleman BM, Baaijens MH, Bartelink H, Klijn JG, Taylor CW, van Leeuwen FE (2007) Long-term risk of cardiovascular disease in 10-year survivors of breast cancer. J Natl Cancer Inst 99:365–375CrossRefGoogle Scholar
  4. 4.
    Wang K, Eblan MJ, Deal AM, Lipner M, Zagar TM, Wang Y, Mavroidis P, Lee CB, Jensen BC, Rosenman JG, Socinski MA, Stinchcombe TE, Marks LB (2017) Cardiac toxicity after radiotherapy for stage III non–small-cell lung cancer: pooled analysis of dose-escalation trials delivering 70 to 90 Gy. J Clin Oncol 35:1387–1394CrossRefGoogle Scholar
  5. 5.
    Wachters FM, Van Der Graaf WT, Groen HJ (2017) Cardiotoxicity in advanced non-small cell lung cancer patients treated with platinum and non-platinum based combinations as first-line treatment. Anticancer Res 24:2079–2083Google Scholar
  6. 6.
    Mor-Avi V, Lang RM, Badano LP, Belohlavek M, Cardim NM, Deru-meaux G, Galderisi M, Marwick T, Nagueh SF, Sengupta PP, Sicari R, Smiseth OA, Smulevitz B, Takeuchi M, Thomas JD, Vannan M, Voigt JU, Zamorano JL (2011) Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indication sendorsed by the Japanese Society of Echocardiography. J Am Soc Echocardiogr 24:277–313CrossRefGoogle Scholar
  7. 7.
    Negishi K, Negishi T, Hare JL, Haluska BA, Plana JC, Marwick TH (2013) Independent and incremental value of deformation indices for prediction of trastuzumab-induced cardiotoxicity. J Am Soc Echocardiogr 26:493–498CrossRefGoogle Scholar
  8. 8.
    Mele D, Malagutti P, Indelli M, Ferrari L, Casadei F, Da Ros L, Pollina A, Fiorencis A, Frassoldati A, Ferrari R (2016) Reversibility of left ventricle longitudinal strain alterations induced by adjuvant therapy in early breast cancer patients. Ultrasound Med Biol 42:125–132CrossRefGoogle Scholar
  9. 9.
    Tanindi A, Demirci U, Tacoy G, Buyukberber S, Alsancak Y, Coskun U, Yalcin R, Benekli M (2011) Assessment of right ventricular functions during cancer chemotherapy. Eur J Echocardiogr 12:834–840CrossRefGoogle Scholar
  10. 10.
    Groarke JD, Nguyen PL, Nohria A, Ferrari R, Cheng S, Moslehi J (2014) Cardiovascular complications of radiation therapy for thoracic malignancies: the role for non-invasive imaging for detection of cardiovascular disease. Eur Heart J 35:612–623CrossRefGoogle Scholar
  11. 11.
    Guendouz S, Rappeneau S, Nahum J, Dubois-Rande J-L, Gueret P, Monin J-L, Lim P, Adnot S, Hittinger L, Damy T (2012) Prognostic significance and normal values of 2D strain to assess right ventricular systolic function in chronic heart failure. Circ J 76:127–136CrossRefGoogle Scholar
  12. 12.
    Iacoviello Iacoviello M, Citarelli G, Antoncecchi V, Romito R, Monitillo F, Leone M, Puzzovivo A, Lattarulo MS, Rizzo C, Caldarola P, Ciccone MM (2016) Right ventricular longitudinal strain measures independently predict chronic heart failure mortality. Echocardiography 33:992–1000CrossRefGoogle Scholar
  13. 13.
    Gulati A, Ismail TF, Jabbour A, Alpendurada F, Guha K, Ismail NA, Raza S, Khwaja J, Brown TDH, Morarji K, Liodakis E, Roughton M, Wage R, Pakrashi TC, Sharma R, Carpenter JP, Cook SA, Cowie MR, Assomull RG, Pennell DJ, Prasad SK (2013) The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy. Circulation 128:1623–1633CrossRefGoogle Scholar
  14. 14.
    Mendis S, Lindholm LH, Mancia G, Whitworth J, Alderman M, Lim S, Heagerty T (2007) World Health Organization (WHO) and International Society of Hypertension (ISH) risk prediction charts: assessment of cardiovascular risk for prevention and control of cardiovascular disease in low and middle-income countries. J Hypertens 25:1578–1582CrossRefGoogle Scholar
  15. 15.
    Bradley JD, Paulus R, Komaki R, Masters G, Blumenschein G, Schild S, Bogart J, Hu C, Forster K, Magliocco A, Kavadi V, Garces YI, Narayan S, Iyengar P, Robinson C, Wynn RB, Koprowski C, Meng J, Beitler J, Gaur R, Curran W Jr, Choy H (2015) Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study. Lancet Oncol 16:187–199CrossRefGoogle Scholar
  16. 16.
    Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, Flachskampf FA, Foster E, Goldstein SA, Kuznetsova T, Lancellotti P, Muraru D, Picard MH, Rietzschel ER, Rudski L, Spencer KT, Tsang W, Voigt JU (2015) Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 16:233–270CrossRefGoogle Scholar
  17. 17.
    Tuohinen SS, Skyttä T, Virtanen V, Virtanen M, Luukkaala T, Kellokumpu-Lehtinen PL, Raatikainen P (2016) Detection of radiotherapy-induced myocardial changes by ultrasound tissue characterisation in patients with breast cancer. Int J Cardiovasc Imaging 32:767–776CrossRefGoogle Scholar
  18. 18.
    Tuohinen SS, Skyttä T, Poutanen T, Huhtala H, Virtanen V, Kellokumpu-Lehtinen PL, Raatikainen P (2017) Radiotherapy-induced global and regional differences in early stage left-sided versus right-sided breast cancer patients: speckle tracking echocardiography study. Int J Cardiovasc Imaging 33:463–472CrossRefGoogle Scholar
  19. 19.
    Christiansen JR, Massey R, Dalen H, Kanellopoulos A, Hamre H, Ruud E, Kiserud CE, Fossa SD, Aakhus S (2016) Right ventricularfunction in long-term adult survivors of childhood lymphomaand acute lymphoblastic leukaemia. Eur Heart J Cardiovasc Imaging 17:735–741CrossRefGoogle Scholar
  20. 20.
    Murbraech K, Holte E, Broch K, Smeland KB, Holte H, Rosner A, Lund MB, Dalen H, Kiserud C, Aakhus S (2016) Impaired right ventricularfunction in long-term lymphoma survivors. J Am Soc Echocar-diogr 29:528–536CrossRefGoogle Scholar
  21. 21.
    Boczar KE, Aseyev O, Sulpher J, Johnson C, Burwash IG, Turek M, Dent S, Dwivedi G (2016) Right heart function deteriorates in breast cancer patients undergoing anthracycline-based chemotherapy. Echo Res Pract 3:79–84CrossRefGoogle Scholar
  22. 22.
    Calleja A, Poulin F, Khorolskym C, Shariat M, Bedard PL, Amir E, Rakowski H, McDonald M, Delgado D, Thavendiranathan P (2015) Right ventricular dysfunction in patients experiencing cardiotoxicity during breast cancer therapy. J Oncol 2015:609194CrossRefGoogle Scholar
  23. 23.
    Chang WT, Shih JK, Feng YH, Chiang CY, Kuo YH, Chen WY, Wu HC, Cheng JT, Wang JJ, Chen ZC (2016) The early predictive value of right ventricular strain in epirubicin-induced cardiotoxicity in patients with breast cancer. Acta Cardiol Sin 32:550–559Google Scholar
  24. 24.
    Ozawa K, Funabashi N, Tanabe N, Tatsumi K, Kobayashi Y (2016) Contribution of myocardial layers of right ventricular free wall to right ventricular function in pulmonary hypertension: analysis using multilayer longitudinal strain by two-dimensional speckle-tracking echocardiography. Int J Cardiol 215:457–462CrossRefGoogle Scholar
  25. 25.
    Kukulski T, H¨ubbert L, Arnold M, Wranne B, Hatle L, Sutherland GR (2000) Normal regional right ventricular function and its change with age: a Doppler myocardial imaging study. J Am Soc Echocardiogr 13:194–204CrossRefGoogle Scholar
  26. 26.
    Torrent-Guasp F, Ballester M, Buckberg GD, Carreras F, Flotats A, Carrió I, Ferreira A, Samuels LE, Narula J (2001) Spatial orientation of the ventricular muscle band: physiologic contribution and surgical implications. J Thorac Cardiovasc Surg 122:389–392CrossRefGoogle Scholar
  27. 27.
    Burger A, Loffler H, Bamberg M, Rodemann HP (1998) Molecular and cellular basis of radiation fibrosis. Int J Radiat Biol 73:401–408CrossRefGoogle Scholar
  28. 28.
    Taunk NK, Haffty BG, Kostis JB, Goyal S (2015) Radiation-induced heart desease: pathologic abnormalities and putative mechanisms. Front Oncol 5:39CrossRefGoogle Scholar
  29. 29.
    Chen Z, Wu Z, Ning W (2019) Advances in molecular mechanisms and treatment of radiation-induced pulmonary fibrosis. Transl Oncol 12:162–169CrossRefGoogle Scholar
  30. 30.
    Abratt RP, Morgan GW, Silvestri G, Willcox P (2004) Pulmonary complications of radiation therapy. Clin Chest Med 25:167–177CrossRefGoogle Scholar
  31. 31.
    Padrão AI, Moreira-Gonçalves D, Oliveira PA, Teixeira C, Faustino-Rocha AI, Helguero L, Vitorino R, Santos LL, Amado F, Duarte JA, Ferreira R (2015) Endurance training prevents TWEAK but not myostatin-dediated cardiac remodelling in cancercachexia. Arch Biochem Biophys 567:13–21CrossRefGoogle Scholar
  32. 32.
    Tadic M, Baudisch A, Haßfeld S, Heinzel F, Cuspidi C, Burkhardt F, Escher F, Philipp A, Pieske B, Genger M (2018) Right ventricular function and mechanics in chemotherapy and radiotherapy-naïve cancer patients. Int J Cardiovasc Imaging 34:1581–1587CrossRefGoogle Scholar
  33. 33.
    Hatakenaka M, Yonezawa M, Nonoshita T, Nakamura K, Yabuuchi H, Shioyama Y, Nagao M, Matsuo Y, Kamitani T, Higo T, Nishikawa K, Setoguchi T, Honda H (2012) Acute cardiac impairment associated with concurrent chemoradiotherapy for esophageal cancer: magnetic resonance evaluation. Int J Radiat Oncol Biol Phys 83:e67–73CrossRefGoogle Scholar
  34. 34.
    Haugnes HS, Wethal T, Aass N, Dahl O, Klepp O, Langberg CW, Wilsgaard T, Bremnes RM, Foss SD (2010) Cardiovascular risk factors and morbidity in long-term survivors of testicular cancer: a 20-year follow-up study. J Clin Oncol 28:4649–4657CrossRefGoogle Scholar
  35. 35.
    Ma H, Jones KR, Guo R, Xu P, Shen Y, Ren J (2010) Cisplatin compromises myocardial contractile function and mitochondrial ultrastructure: role of endoplasmic reticulum stress. Clin Exp Pharmacol Physiol 37:460–465CrossRefGoogle Scholar
  36. 36.
    van Kessel M, Seaton D, Chan J, Yamada A, Kermeen F, Hamilton-Craig C, Butler T, Sabapathy S, Morris N (2017) Erratum to: prognostic value of right ventricular free wall strain in pulmonary hypertension patients with pseudo-normalized tricuspid annular planesystolic excursion values. Int J Cardiovasc Imaging 33:585CrossRefGoogle Scholar
  37. 37.
    Alghamdi MH, Mertens L, Lee W, Yoo SJ, Grosse-Wortmann L (2013) Longitudinal right ventricular function is a better predictor of right ventricular contribution to exercise performance than global or outflow tract ejection fraction in tetralogy of Fallot: a combined echocardiography and magnetic resonance study. Eur Heart J Cardiovasc Imaging 14:235–239CrossRefGoogle Scholar
  38. 38.
    D’Andrea A, Stanziola A, D’Alto M, Di Palma E, Martino M, Scarafile R, Molino A, Rea G, Maglione M, Calabrò R, Russo MG, Bossone E, Saggar R (2016) Right ventricular strain: an independent predictor of survival in idiopathic pulmonary fibrosis. Int J Cardiol 222:908–910CrossRefGoogle Scholar
  39. 39.
    Cavalcante JL, Rijal S, Althouse AD, Delgado-Montero A, Katz WE, Schindler JT, Crock F, Harinstein ME, Navid F, Gleason TG, Lee JS (2016) Right ventricular function and prognosis in patients with low-flow, low-gradient severe aortic stenosis. J Am Soc Echocardiogr 29:325–333CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of UltrasoundShanghai Chest Hospital, Shanghai Jiao Tong UniversityShanghaiChina
  2. 2.Department of CardiologyShanghai Chest Hospital, Shanghai Jiao Tong UniversityShanghaiChina
  3. 3.Department of UltrasoundYan’an People’s HospitalYan’anChina

Personalised recommendations