Top

Published in:

Open Access 01-12-2018 | Research

Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer

Authors: L. Torre-Bouscoulet, W. R. Muñoz-Montaño, D. Martínez-Briseño, F. J. Lozano-Ruiz, R. Fernández-Plata, J. A. Beck-Magaña, C. García-Sancho, A. Guzmán-Barragán, E. Vergara, M. Blake-Cerda, L. Gochicoa-Rangel, F. Maldonado, M. Arroyo-Hernández, O. Arrieta

Published in: Respiratory Research | Issue 1/2018

Abstract

Background

Radiation pneumonitis (RP) is a frequent complication of concurrent chemoradiotherapy (CCRT) and is associated with severe symptoms that decrease quality of life and might result in pulmonary fibrosis or death. The aim of this study is to identify whether pulmonary function test (PFT) abnormalities may predict RP in non-small cell lung cancer (NSCLC) patients.

Methods

A prospective multi-institutional study was conducted with locally advanced and oligometastatic NSCLC patients. All participants were evaluated at baseline, end of CCRT, week 6, 12, 24, and 48 post-CCRT. They completed forced spirometry with a bronchodilator, body plethysmography, impulse oscillometry, carbon monoxide diffusing capacity (DLCO), molar mass of CO₂, six-minute walk test and exhaled fraction of nitric oxide (FeNO). Radiation pneumonitis was assessed with RTOG and CTCAE. The protocol was registered in www.clinicaltrials.gov (NCT01580579), registered April 19, 2012.

Results

Fifty-two patients were enrolled; 37 completed one-year follow-up. RP ≥ Grade 2 was present in 11/37 (29%) for RTOG and 15/37 (40%) for CTCAE. Factors associated with RP were age over 60 years and hypofractionated dose. PFT abnormalities at baseline that correlated with the development of RP included lower forced expiratory volume in one second after bronchodilator (p = 0.02), DLCO (p = 0.02) and FeNO (p = 0.04). All PFT results decreased after CCRT and did not return to basal values at follow-up.

Conclusions

FEV₁, DLCO and FeNO prior to CCRT predict the development of RP in NSCLC. This study suggests that all patients under CCRT should be assessed by PFT to identify high-risk patients for close follow-up and early treatment.

Available only for authorised users

Bray F, Ren JS, Masuyer E, Ferlay J. Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer [Internet]. 2013;132:1133–45. Available from: http://globocan.iarc.fr/Pages/burden_sel.aspx CrossRef

Arrieta O, Guzman E, Bouscout LT, Garza JD La, Sancho CG, Lever AP, et al. Cancer de Pulmón de Células No Pequeñas, Clinicas Oncológicas de Iberoamerica, Consenso Nacional de Cancer de Pulmón de México. 2016;

Sause W, Kolesar P, Taylor S, Johnson D, Livingston R, Komaki R, et al. Final results of phase III trial in regionally advanced Unresectable non-small cell lung Cancer: radiation therapy oncology group, eastern cooperative oncology group, and southwest oncology group. Chest. 2000;117:358–64.CrossRefPubMed

Aupérin A, Le Péchoux C, Rolland E, Curran WJ, Furuse K, Fournel P, et al. Meta-analysis of concomitant versus sequential radiochemotherapy in locally advanced non-small-cell lung cancer. J Clin Oncol [Internet]. Centre for Reviews and Dissemination (UK). 2010 [cited 2016 Nov 15];28:2181–2190. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20351327.

Vokes EE, Herndon JE, Kelley MJ, Cicchetti MG, Ramnath N, Neill H, et al. Induction Chemotherapy Followed by Chemoradiotherapy Compared With Chemoradiotherapy Alone for Regionally Advanced Unresectable Stage III Non-Small-Cell Lung Cancer: Cancer and Leukemia Group B. J Clin Oncol [Internet]; 2007 [cited 2016 Sep 19];25:1698–1704. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17404369.

Steuer CE, Behera M, Ernani V, Higgins KA, Saba NF, Shin DM, et al. Comparison of Concurrent Use of Thoracic Radiation With Either Carboplatin-Paclitaxel or Cisplatin-Etoposide for Patients With Stage III Non–Small-Cell Lung Cancer. JAMA Oncol [Internet]. 2016 [cited 2016 Dec 30]; Available from: http://oncology.jamanetwork.com/article.aspx?doi=10.1001/jamaoncol.2016.4280

Villarreal-Garza C, de la Mata D, Zavala DG, Macedo-Perez EO, Arrieta O. Aggressive treatment of primary tumor in patients with non–small-cell lung Cancer and exclusively brain metastases. Clin Lung Cancer. 2013;14:6–13.CrossRefPubMed

Arrieta O, Villarreal-Garza C, Zamora J, Blake-Cerda M, de la Mata MD, Zavala DG, et al. Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation. Radiat Oncol [Internet]. BioMed Central; 2011 [cited 2016 Nov 15];6:166. Available from: http://ro-journal.biomedcentral.com/articles/10.1186/1748-717X-6-166

Gomez DR, Blumenschein GR, Lee JJ, Hernandez M, Ye R, Camidge DR, et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. Lancet Oncol [Internet]. 2016 [cited 2016 Dec 30];17:1672–1682. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1470204516305320

10.

Villarreal-Garza C, de la Mata D, Zavala DG, Macedo-Perez EO, Arrieta O. Aggressive Treatment of Primary Tumor in Patients With Non–Small-Cell Lung Cancer and Exclusively Brain Metastases. Clin Lung Cancer [Internet]. 2013 [cited 2016 Dec 30];14:6–13. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1525730412000848

11.

Arrieta O, Luna Palencia RL, Macedo-Pérez O, Barron F, Corona Cruz JF, Chinchilla Trigos LA, et al. P1.06–007 Radical Treatment of Synchronous Oligometastatic Non-Small Cell Lung Cancer (NSCLC). J Thorac Oncol [Internet]. 2017 [cited 2017 Mar 29];12:S668–S669. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1556086416321128

12.

Rodrigues G, Lock M, D’Souza D, Yu E, Van Dyk J, Armstrong J, et al. Prediction of radiation pneumonitis by dose - volume histogram parameters in lung cancer--a systematic review. Radiother Oncol [Internet]. Elsevier; 2004 [cited 2016 Dec 22];71:127–138. Available from: http://www.ncbi.nlm.nih.gov/pubmed/15110445.

13.

Kim M, Lee J, Ha B, Lee R, Lee K-J, Suh HS. Factors predicting radiation pneumonitis in locally advanced non-small cell lung cancer. Radiat Oncol J [Internet]. Korean Society for Therapeutic Radiology and Oncology; 2011 [cited 2016 Sep 19];29:181–190. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22984669.

14.

Rancati T, Ceresoli GL, Gagliardi G, Schipani S, Cattaneo GM. Factors predicting radiation pneumonitis in lung cancer patients: a retrospective study. Radiother Oncol. 2003;67:275–83.CrossRefPubMed

15.

Bradley JD, Hope A, El Naqa I, Apte A, Lindsay PE, Bosch W, et al. {A figure is presented}A Nomogram to Predict Radiation Pneumonitis, Derived From a Combined Analysis of RTOG 9311 and Institutional Data. Int J Radiat Oncol Biol Phys [Internet]. NIH Public Access; 2007 [cited 2016 Dec 22];69:985–992. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17689035.

16.

Palma DA, Senan S, Tsujino K, Barriger RB, Rengan R, Moreno M, et al. Predicting radiation pneumonitis after Chemoradiation therapy for lung Cancer: an international individual patient data meta-analysis. Int J Radiat Oncol. 2013;85:444–50.CrossRef

17.

Wen J, Liu H, Wang Q, Liu Z, Li Y, Xiong H, et al. Genetic variants of the LIN28B gene predict severe radiation pneumonitis in patients with non-small cell lung cancer treated with definitive radiation therapy. Eur J Cancer [Internet]. 2014 [cited 2016 Dec 30];50:1706–1716. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0959804914002512

18.

Jin H, Tucker SL, Liu HH, Wei X, Yom SS, Wang S, et al. Dose-volume thresholds and smoking status for the risk of treatment-related pneumonitis in inoperable non-small cell lung cancer treated with definitive radiotherapy. Radiother Oncol [Internet]. Elsevier; 2009 [cited 2016 Dec 30];91:427–432. Available from: http://www.ncbi.nlm.nih.gov/pubmed/18937989.

19.

Robnett TJ, Machtay M, Vines EF, McKenna MG, Algazy KM, McKenna WG, et al. Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys [Internet]. Elsevier; 2000 [cited 2016 Dec 30];48:89–94. Available from: http://www.ncbi.nlm.nih.gov/pubmed/10924976.

20.

Kong FM (Spring), Wang S. Nondosimetric Risk Factors for Radiation-Induced Lung Toxicity. Semin Radiat Oncol [Internet]. Elsevier; 2015;25:100–109. Available from: https://doi.org/10.1016/j.semradonc.2014.12.003

21.

Arrieta O, Gallardo-Rincón D, Villarreal-Garza C, Michel RM, Astorga-Ramos AM, Martínez-Barrera L, et al. High Frequency of Radiation Pneumonitis in Patients with Locally Advanced Non-small Cell Lung Cancer Treated with Concurrent Radiotherapy and Gemcitabine after Induction with Gemcitabine and Carboplatin. J Thorac Oncol [Internet]. 2009 [cited 2016 Dec 30];4:845–852. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1556086415324242

22.

Wang D, Zhu J, Sun J, Li B, Wang Z, Wei L, et al. Functional and biologic metrics for predicting radiation pneumonitis in locally advanced non-small cell lung cancer patients treated with chemoradiotherapy. Clin Transl Oncol [Internet]. 2012 [cited 2016 Dec 30];14:943–952. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22855174

23.

Dehing-Oberije C, De Ruysscher D, van Baardwijk A, Yu S, Rao B, Lambin P, et al. The importance of patient characteristics for the prediction of radiation-induced lung toxicity. Radiother Oncol [Internet]. Elsevier; 2009 [cited 2016 Dec 30];91:421–426. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19147245.

24.

Chen S, Zhou S, Zhang J, Yin F-F, Marks LB, Das SK. A neural network model to predict lung radiation-induced pneumonitis. Med Phys [Internet]. 2007 [cited 2016 Dec 30];34:3420–3427. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17926943.

25.

Ferrero C, Badellino S, Filippi AR, Focaraccio L, Levra MG, Levis M, et al. Pulmonary function and quality of life after VMAT-based stereotactic ablative radiotherapy for early stage inoperable NSCLC: a prospective study. Lung Cancer [Internet]. 2015 [cited 2018 Feb 22];89:350–356. Available from: https://www.sciencedirect.com/science/article/pii/S0169500215300039.

26.

Wang J, Cao J, Yuan S, Ji W, Arenberg D, Dai J, et al. Poor baseline pulmonary function may not increase the risk of radiation-induced lung toxicity. Int J Radiat Oncol Biol Phys [Internet]. Elsevier; 2013 [cited 2016 Dec 30];85:798–804. Available from: http://www.ncbi.nlm.nih.gov/pubmed/22836048.

27.

Kong F-M, Hayman JA, Griffith KA, Kalemkerian GP, Arenberg D, Lyons S, et al. Final toxicity results of a radiation-dose escalation study in patients with non-small-cell lung cancer (NSCLC): predictors for radiation pneumonitis and fibrosis. Int J Radiat Oncol Biol Phys [Internet]. Elsevier; 2006 [cited 2016 Dec 30];65:1075–1086. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16647222.

28.

Tsujino K, Hirota S, Endo M, Obayashi K, Kotani Y, Satouchi M, et al. Predictive value of dose-volume histogram parameters for predicting radiation pneumonitis after concurrent chemoradiation for lung cancer. Int J Radiat Oncol [Internet]. Elsevier; 2003 [cited 2016 Dec 30];55:110–115. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0360301602038075

29.

Yamashita H, Kobayashi-Shibata S, Terahara A, Okuma K, Haga A, Wakui R, et al. Prescreening based on the presence of CT-scan abnormalities and biomarkers (KL-6 and SP-D) may reduce severe radiation pneumonitis after stereotactic radiotherapy. Radiat Oncol [Internet]. BioMed Central; 2010 [cited 2016 Sep 19];5:32. Available from: http://www.ncbi.nlm.nih.gov/pubmed/20459699.

30.

Budczies J, Klauschen F, Sinn B V, Zs B, Rffy G˝, Schmitt WD, et al. Cutoff Finder: A Comprehensive and Straightforward Web Application Enabling Rapid Biomarker Cutoff Optimization. PLoS One [Internet]. 2012 [cited 2017 Mar 6];7. Available from: http://molpath.charite.de/cutoff.

31.

Abratt RP, Morgan GW, Silvestri G, Willcox P. Pulmonary complications of radiation therapy. Clin Chest Med. 2004;25:167–77.CrossRefPubMed

32.

Parashar B, Edwards A, Mehta R, Pasmantier M, Wernicke AG, Sabbas A, et al. Chemotherapy Significantly Increases the Risk of Radiation Pneumonitis in Radiation Therapy of Advanced Lung Cancer. Am J Clin Oncol [Internet]. 2010 [cited 2016 Nov 15];1. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20498591.

33.

Salinas F V, Winterbauer RH. Radiation pneumonitis: a mimic of infectious pneumonitis. Semin Respir Infect [Internet]. 1995 [cited 2016 Sep 19];10:143–153. Available from: http://www.ncbi.nlm.nih.gov/pubmed/7481128.

34.

Johansson S, Bjermer L, Franzen L, Henriksson R. Effects of ongoing smoking on the development of radiation-induced pneumonitis in breast cancer and oesophagus cancer patients. Radiother Oncol. 1998;49:41–7.CrossRefPubMed

35.

Hildebrandt MAT, Komaki R, Liao Z, Gu J, Chang JY, Ye Y, et al. Genetic Variants in Inflammation-Related Genes Are Associated with Radiation-Induced Toxicity Following Treatment for Non-Small Cell Lung Cancer. Cordes N, editor. PLoS One [Internet]. Public Library of Science; 2010 [cited 2016 Dec 2];5:e12402. Available from: http://dx.plos.org/10.1371/journal.pone.0012402

36.

Janjigian YY, McDonnell K, Kris MG, Shen R, Sima CS, Bach PB, et al. Pack-years of cigarette smoking as a prognostic factor in patients with stage IIIB/IV nonsmall cell lung cancer. Cancer [Internet]. Wiley Subscription Services, Inc., A Wiley Company; 2010 [cited 2016 Dec 2];116:670–675. Available from: http://doi.wiley.com/10.1002/cncr.24813

37.

Arrieta O, Cardona AF, Martín C, Más-López L, Corrales-Rodríguez L, Bramuglia G, et al. Updated Frequency of EGFR and KRAS Mutations in NonSmall-Cell Lung Cancer in Latin America: The Latin-American Consortium for the Investigation of Lung Cancer (CLICaP). J Thorac Oncol [Internet]. 2015 [cited 2016 Dec 30];10:838–843. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1556086415323984

38.

Arrieta O, Ramírez-Tirado L-A, Báez-Saldaña R, Peña-Curiel O, Soca-Chafre G, Macedo-Perez E-O. Different mutation profiles and clinical characteristics among Hispanic patients with non-small cell lung cancer could explain the “Hispanic paradox”. Lung Cancer [Internet]. 2015 [cited 2016 Dec 30];90:161–166. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0169500215300349

39.

Kong F-M (spring), Ritter T, Quint DJ, Senan S, Gaspar LE, Komaki RU, et al. Consideration of dose limits for organs at risk of thoracic radiotherapy: atlas for lung, proximal bronchial tree, esophagus, spinal cord, ribs, and brachial plexus. Int J Radiat Oncol 2011;81:1442–1457.

40.

Borst GR, Ishikawa M, Nijkamp J, Hauptmann M, Shirato H, Onimaru R, et al. Radiation pneumonitis in patients treated for malignant pulmonary lesions with hypofractionated radiation therapy. Radiother Oncol [Internet]. Elsevier; 2009 [cited 2016 Dec 28];91:307–313. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19321217.

41.

Larici AR, del Ciello A, Maggi F, Santoro SI, Meduri B, Valentini V, et al. Lung abnormalities at multimodality imaging after radiation therapy for non-small cell lung cancer. Radiographics [Internet]. Radiological Society of North America; 2011 [cited 2016 Sep 19];31:771–789. Available from: http://pubs.rsna.org/doi/10.1148/rg.313105096

42.

Giridhar P, Mallick S, Rath GK, Julka PK. Radiation Induced Lung Injury: Prediction, Assessment and Management. Asian Pacific J Cancer Prev [Internet]. 2015 [cited 2016 Dec 22];16:2613–2617. Available from: http://koreascience.or.kr/journal/view.jsp?kj=POCPA9&py=2015&vnc=v16n7&sp=2613

43.

Ojanguren I, Cruz MJ, Villar A, Barrecheguren M, Morell F, Muñoz X. Utility of Exhaled Nitric Oxide Fraction for the Diagnosis of Hypersensitivity Pneumonitis. Lung [Internet]. 2016 [cited 2016 Dec 22];194:75–80. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26566790.

44.

Haccuria A, Michils A, Ebastien Michiels S, Van Muylem A. Exhaled nitric oxide: A biomarker integrating both lung function and airway inflammation changes. J Allergy Clin Immunol. 2014;134:554–9.CrossRefPubMed

45.

Sabatelli L, Seppälä U, Sastre J, Crater G. Cost-effectiveness and budget impact of routine use of fractional exhaled nitric oxide monitoring for the Management of Adult Asthma Patients in Spain running title: cost-effectiveness of routine use of FeNO. J Investig Allergol Clin Immunol. 2017;27(2):89–97.

46.

Beerthuizen T, Voorend-van Bergen S, van den Hout WB, Vaessen-Verberne AA, Brackel HJ, Landstra AM, et al. Cost-effectiveness of FE _NO -based and web-based monitoring in paediatric asthma management: a randomised controlled trial. Thorax [Internet]. 2016 [cited 2016 Dec 22];71:607–613. Available from: http://www.ncbi.nlm.nih.gov/pubmed/27048197.

Title: Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer
Authors: L. Torre-Bouscoulet
W. R. Muñoz-Montaño
D. Martínez-Briseño
F. J. Lozano-Ruiz
R. Fernández-Plata
J. A. Beck-Magaña
C. García-Sancho
A. Guzmán-Barragán
E. Vergara
M. Blake-Cerda
L. Gochicoa-Rangel
F. Maldonado
M. Arroyo-Hernández
O. Arrieta
Publication date: 01-12-2018
Publisher: BioMed Central
Published in: Respiratory Research / Issue 1/2018
Electronic ISSN: 1465-993X
DOI: https://doi.org/10.1186/s12931-018-0775-2

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung Cancer

Abstract

Background

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2018

Clinical variables predicting the risk of a hospital stay for longer than 7 days in patients with severe acute exacerbations of chronic obstructive pulmonary disease: a prospective study

Ciliated conical epithelial cell protrusions point towards a diagnosis of primary ciliary dyskinesia

Roles of mitochondrial ROS and NLRP3 inflammasome in multiple ozone-induced lung inflammation and emphysema

Influence of viral infection on the relationships between airway cytokines and lung function in asthmatic children

Anti-inflammatory duration of action of fluticasone furoate/vilanterol trifenatate in asthma: a cross-over randomised controlled trial

Efficacy and safety of nintedanib in advanced idiopathic pulmonary fibrosis

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page