Skip to main content

Advertisement

SpringerLink
Log in

Early GLS changes detection after chemoradiation in locally advanced non-small cell lung cancer (NSCLC)

  • Diagnostic Imaging in Oncology
  • Published:
La radiologia medica Aims and scope Submit manuscript

Abstract

Purpose

Chemoradiation is the standard treatment in patients with locally advanced non-small-cell lung cancer (LA-NSCLC), and thanks to the recent combination with immunotherapy, median survival has unexpectedly improved. This study aims to evaluate early changes in cardiac function after chemoradiotherapy (CRT) in LA-NSCLC by multimodal use of advanced imaging techniques.

Materials and methods

This is a prospective, observational cohort study. At the beginning of combined treatment, screening tests including blood samples, electrocardiogram (ECG), echocardiographic examination (TTE), and cardiac magnetic resonance were performed in all patients with LA-NSCLC. ECG and cardiac marker assays were performed weekly during treatment. ECG and TTE were performed at month 1 (M1) and month 3 (M3) after the end of CRT.

Results

This preliminary analysis included thirty-four patients with a mean age of 69.5 years. The median follow-up was 27.8 months. 62% of patients were in stage IIIA. Radiation therapy was delivered with a median total dose of 60 Gy with conventional fractionation. All patients were treated with concurrent CRT, and 65% of cases were platinum-based therapy. Global longitudinal strain (GLS) and ejection fraction (EF) progressively decreased from baseline to M1 and M3. There was a strong correlation between GLS and EF reduction (at M1: p = 0.034; at M3: p = 0.018). Cardiac arrhythmias occurred in eight patients (23.5%) at a mean follow-up of 15.8 months after CRT.

Conclusions

Reduction in GLS is an early sign occurring after the end of CRT for LA-NSCLC. Future studies are needed to identify variables that can increase the risk of cardiac events in this patient population to implement adequate damage prevention strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

ASE:

American society of Echocardiography

ASCVD:

Atherosclerotic cardiovascular disease algorithm from AHA/ACC

CRT:

Chemoradiotherapy

CTRCD:

Cancer therapeutics–related cardiac dysfunction

ECG:

Electrocardiographic/electrocardiogram

EDV:

End-diastolic volume

EF:

Ejection fraction

EQD2:

Equivalent dose for a 2 Gy/fraction treatment

ESC:

European society of cardiology

ESV:

End-systolic volume

GLS:

Global longitudinal strain

LA-NSCLC:

Locally advanced NSCLC

LV:

Left ventricular

LVEF:

Left ventricle ejection fraction

NSCLC:

Non-small cell lung cancer

RIHD:

Radiation-induced heart disease

RT:

Radiotherapy

STE:

Speckle tracking echocardiography

2D:

Two-dimensional

2D-STE:

Two-dimensional speckle tracking echocardiography

3D:

Three-dimensional

References

  1. Gray JE, Villegas A, Daniel D et al (2020) Three-year overall survival with durvalumab after chemoradiotherapy in stage III NSCLC—Update from PACIFIC. J Thorac Oncol 15:288–293. https://doi.org/10.1016/j.jtho.2019.10.002

    Article  CAS  Google Scholar 

  2. Bradley JD, Hu C, Komaki RR et al (2020) Long-term results of NRG oncology RTOG 0617: standard- versus high-dose chemoradiotherapy with or without cetuximab for unresectable stage III non–small-cell lung cancer. JCO 38:706–714. https://doi.org/10.1200/JCO.19.01162

    Article  CAS  Google Scholar 

  3. Lancellotti P, Nkomo VT, Badano LP et al (2013) Expert consensus for multi-modality imaging evaluation of cardiovascular complications of radiotherapy in adults: a report from the European association of cardiovascular imaging and the American society of echocardiography. J Am Soc Echocardiogr 26:1013–1032. https://doi.org/10.1016/j.echo.2013.07.005

    Article  Google Scholar 

  4. Degens J, De Ruysscher D, Houben R et al (2020) Are patients with stage III non-small cell lung cancer treated with chemoradiotherapy at risk for cardiac events? Results from a retrospective cohort study. BMJ Open 10:e036492. https://doi.org/10.1136/bmjopen-2019-036492

    Article  Google Scholar 

  5. Evangelista A, Flachskampf F, Lancellotti P et al (2008) European Association of Echocardiography recommendations for standardization of performance, digital storage and reporting of echocardiographic studies. Eur J Echocardiogr 9:438–448. https://doi.org/10.1093/ejechocard/jen174

    Article  Google Scholar 

  6. Erven K, Jurcut R, Weltens C et al (2011) Acute radiation effects on cardiac function detected by strain rate imaging in breast cancer patients. Int J Radiation Oncol Biol Phys 79:1444–1451. https://doi.org/10.1016/j.ijrobp.2010.01.004

    Article  Google Scholar 

  7. Lo Q, Hee L, Batumalai V et al (2015) Subclinical cardiac dysfunction detected by strain imaging during breast irradiation with persistent changes 6 weeks after treatment. Int J Radiation Oncol Biol Phys 92:268–276. https://doi.org/10.1016/j.ijrobp.2014.11.016

    Article  Google Scholar 

  8. Tuohinen SS, Skyttä T, Poutanen T et al (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 33:463–472. https://doi.org/10.1007/s10554-016-1021-y

    Article  Google Scholar 

  9. Al-Kindi SG, Oliveira GH (2016) Incidence and trends of cardiovascular mortality after common cancers in young adults: Analysis of surveillance, epidemiology and end-results program. WJC 8:368. https://doi.org/10.4330/wjc.v8.i6.368

    Article  Google Scholar 

  10. Underberg RWM, Lagerwaard FJ, Slotman BJ et al (2005) Benefit of respiration-gated stereotactic radiotherapy for stage I lung cancer: An analysis of 4DCT datasets. Int J Radiation Oncol Biol Phys 62:554–560. https://doi.org/10.1016/j.ijrobp.2005.01.032

    Article  Google Scholar 

  11. Chen L, Huang J, Wu W et al (2019) The impact of right ventricular function on prognosis in patients with stage III non-small cell lung cancer after concurrent chemoradiotherapy. Int J Cardiovasc Imaging 35:1009–1017. https://doi.org/10.1007/s10554-019-01590-0

    Article  CAS  Google Scholar 

  12. Chen L, Ta S, Wu W et al (2019) Prognostic and added value of echocardiographic strain for prediction of adverse outcomes in patients with locally advanced non-small cell lung cancer after radiotherapy. Ultrasound Med Biol 45:98–107. https://doi.org/10.1016/j.ultrasmedbio.2018.09.012

    Article  Google Scholar 

  13. Gupta A, Lawrence AT, Krishnan K et al (2007) Current concepts in the mechanisms and management of drug-induced QT prolongation and torsade de pointes. Am Heart J 153:891–899. https://doi.org/10.1016/j.ahj.2007.01.040

    Article  Google Scholar 

  14. Wenzel-Seifert K, Wittmann M, Haen E (2011) QTc prolongation by psychotropic drugs and the risk of Torsade de Pointes. Dtsch Arztebl Int 108:687–693. https://doi.org/10.3238/arztebl.2011.0687

    Article  Google Scholar 

  15. Lang RM, Badano LP, Mor-Avi V et al (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 16:233–270. https://doi.org/10.1093/ehjci/jev014

    Article  Google Scholar 

  16. Mor-Avi V, Lang RM, Badano LP et al (2011) Current and evolving echocardiographic techniques for the quantitative evaluation of cardiac mechanics: ASE/EAE consensus statement on methodology and indications endorsed by the Japanese Society of Echocardiography. Eur J Echocardiogr 12:167–205. https://doi.org/10.1093/ejechocard/jer021

    Article  Google Scholar 

  17. Zamorano JL, Lancellotti P, Rodriguez Muñoz D et al (2016) 2016 ESC Position Paper on cancer treatments and cardiovascular toxicity developed under the auspices of the ESC Committee for Practice Guidelines: The Task Force for cancer treatments and cardiovascular toxicity of the European Society of Cardiology (ESC). Eur Heart J 37:2768–2801. https://doi.org/10.1093/eurheartj/ehw211

    Article  Google Scholar 

  18. Plana JC, Galderisi M, Barac A et al (2014) Expert consensus for multimodality imaging evaluation of adult patients during and after cancer therapy: a report from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Eur Heart J Cardiovasc Imaging 15:1063–1093. https://doi.org/10.1093/ehjci/jeu192

    Article  Google Scholar 

  19. Čelutkienė J, Pudil R, López-Fernández T et al (2020) Role of cardiovascular imaging in cancer patients receiving cardiotoxic therapies: a position statement on behalf of the H eart F ailure A ssociation (HFA), the E uropean A ssociation of C ardiovascular I maging (EACVI) and the Cardio-Oncology C ouncil of the E uropean S ociety of C ardiology (ESC). Eur J Heart Fail 22:1504–1524. https://doi.org/10.1002/ejhf.1957

    Article  CAS  Google Scholar 

  20. Goff DC, Lloyd-Jones DM, Bennett G et al (2014) 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association task force on practice guidelines. Circulation. https://doi.org/10.1161/01.cir.0000437741.48606.98

    Article  Google Scholar 

  21. Edvardsen T, Helle-Valle T, Smiseth OA (2006) Systolic dysfunction in heart failure with normal ejection fraction: speckle-tracking echocardiography. Prog Cardiovasc Dis 49:207–214. https://doi.org/10.1016/j.pcad.2006.08.008

    Article  Google Scholar 

  22. Armenian SH, Hudson MM, Mulder RL et al (2015) Recommendations for cardiomyopathy surveillance for survivors of childhood cancer: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Oncol 16:e123–e136. https://doi.org/10.1016/S1470-2045(14)70409-7

    Article  Google Scholar 

  23. Sawaya H, Sebag IA, Plana JC et al (2012) Assessment of echocardiography and biomarkers for the extended prediction of cardiotoxicity in patients treated with anthracyclines, taxanes, and trastuzumab. Circ Cardiovasc Imaging 5:596–603. https://doi.org/10.1161/CIRCIMAGING.112.973321

    Article  Google Scholar 

  24. Negishi K, Negishi T, Hare JL et al (2013) Independent and incremental value of deformation indices for prediction of Trastuzumab-induced cardiotoxicity. J Am Soc Echocardiogr 26:493–498. https://doi.org/10.1016/j.echo.2013.02.008

    Article  Google Scholar 

  25. Thavendiranathan P, Poulin F, Lim K-D et al (2014) Use of myocardial strain imaging by echocardiography for the early detection of cardiotoxicity in patients during and after cancer chemotherapy. J Am Coll Cardiol 63:2751–2768. https://doi.org/10.1016/j.jacc.2014.01.073

    Article  Google Scholar 

  26. Ersbøll M, Valeur N, Mogensen UM et al (2013) Prediction of all-cause mortality and heart failure admissions from global left ventricular longitudinal strain in patients with acute myocardial infarction and preserved left ventricular ejection fraction. J Am Coll Cardiol 61:2365–2373. https://doi.org/10.1016/j.jacc.2013.02.061

    Article  Google Scholar 

  27. Yingchoncharoen T, Gibby C, Rodriguez LL et al (2012) Association of myocardial deformation with outcome in asymptomatic aortic stenosis with normal ejection fraction. Circ Cardiovasc Imag 5:719–725. https://doi.org/10.1161/CIRCIMAGING.112.977348

    Article  Google Scholar 

  28. Nagata Y, Takeuchi M, Wu VC-C et al (2015) Prognostic value of LV deformation parameters using 2D and 3D speckle-tracking echocardiography in asymptomatic patients with severe aortic stenosis and preserved LV ejection fraction. JACC Cardiovasc Imaging 8:235–245. https://doi.org/10.1016/j.jcmg.2014.12.009

    Article  Google Scholar 

  29. Tsai H-R, Gjesdal O, Wethal T et al (2011) Left ventricular function assessed by two-dimensional speckle tracking echocardiography in long-term survivors of Hodgkin’s lymphoma treated by mediastinal radiotherapy with or without anthracycline therapy. Am J Cardiol 107:472–477. https://doi.org/10.1016/j.amjcard.2010.09.048

    Article  Google Scholar 

  30. Jurcut R, Ector J, Erven K et al (2007) Radiotherapy effects on systolic myocardial function detected by strain rate imaging in a left-breast cancer patient. Eur Heart J 28:2966. https://doi.org/10.1093/eurheartj/ehm311

    Article  Google Scholar 

  31. Trivedi SJ, Choudhary P, Lo Q et al (2019) Persistent reduction in global longitudinal strain in the longer term after radiation therapy in patients with breast cancer. Radiother Oncol 132:148–154. https://doi.org/10.1016/j.radonc.2018.10.023

    Article  Google Scholar 

  32. Ghobadi G, van der Veen S, Bartelds B et al (2012) Physiological Interaction of Heart and Lung in Thoracic Irradiation. Int J Radiation Oncol Biol Phys 84:e639–e646. https://doi.org/10.1016/j.ijrobp.2012.07.2362

    Article  Google Scholar 

  33. Heggemann F, Grotz H, Welzel G et al (2015) Cardiac function after multimodal breast cancer therapy assessed with functional magnetic resonance imaging and echocardiography imaging. Int J Radiation Oncol Biol Phys 93:836–844. https://doi.org/10.1016/j.ijrobp.2015.07.2287

    Article  Google Scholar 

  34. Sritharan HP, Delaney GP, Lo Q et al (2017) Evaluation of traditional and novel echocardiographic methods of cardiac diastolic dysfunction post radiotherapy in breast cancer. Int J Cardiol 243:204–208. https://doi.org/10.1016/j.ijcard.2017.05.007

    Article  Google Scholar 

  35. Lo Q, Hee L, Batumalai V et al (2017) Strain imaging detects dose-dependent segmental cardiac dysfunction in the acute phase after breast irradiation. Int J Radiation Oncol Biol Phys 99:182–190. https://doi.org/10.1016/j.ijrobp.2017.05.030

    Article  Google Scholar 

  36. Tuohinen SS, Skytta T, Huhtala H et al (2019) Left ventricular speckle tracking echocardiography changes among early-stage breast cancer patients three years after radiotherapy. Anticancer Res 39:4227–4236. https://doi.org/10.21873/anticanres.13584

    Article  CAS  Google Scholar 

Download references

Acknowledgements

Preliminary data from this work have previously been published in abstract form in two international scientific conferences: 2021 Word Conference on Lung Cancer IASLC (International Association for the Study of Lung Cancer) P29.02 Early GLS Changes Detection After Chemoradiation in Locally Advanced NSCLC. Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 2021; 16(10):S1046-S1047. https://doi.org/10.1016/j.jtho.2021.08.397; European SocieTy for Radiotherapy and Oncology (ESTRO) Congress of 2021PH-0276 Prospective study exploring early cardiac toxicity in radiotherapy for LA-NSCLC: Preliminary Analysis. Radiotherapy and Oncology 2021;161:S185-S186. https://doi.org/10.1016/S0167-8140(21)07291-1

Funding

The authors declare that no funds, Grants, or other support were received during the preparation of this manuscript.

Author information

Authors and Affiliations

  1. Unit of Cardiac Sciences, Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy

    Simona Mega, Myriam Carpenito, Maria Laura Novembre & Francesco Grigioni

  2. Department of Radiation Oncology, Campus Bio-Medico University of Rome, Rome, Italy

    Michele Fiore, Marianna Miele, Luca Eolo Trodella, Edy Ippolito & Sara Ramella

Authors
  1. Simona Mega
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michele Fiore
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Myriam Carpenito
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Laura Novembre
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Marianna Miele
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Luca Eolo Trodella
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Francesco Grigioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Edy Ippolito
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Sara Ramella
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SM, MF, MC, EI, MLN: material preparation, data collection and analysis; EI, MC, MF, SM: review of the literature and writing and editing of the manuscript; FG, SR, MM, LET: critical revision to scientific content; SR, FG: conceptual guidance, critical revision to scientific content, and editing of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Myriam Carpenito.

Ethics declarations

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest or non-financial interest in the subject matter or materials discussed in this manuscript.

Ethics approval

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Campus Bio-Medico University of Rome (12/09/2017- n. 25.2(17)19 OSS ComEt CBM).”

Informed consent

The informed consent was obtained from all individual participants included in the study.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mega, S., Fiore, M., Carpenito, M. et al. Early GLS changes detection after chemoradiation in locally advanced non-small cell lung cancer (NSCLC). Radiol med 127, 1355–1363 (2022). https://doi.org/10.1007/s11547-022-01557-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11547-022-01557-7

Keywords

Search

Navigation