Pneumonitis after radiotherapy for lung cancer (PARALUC): an interventional study to create a symptom-based scoring system for identification of patients developing radiation pneumonitis

Dirk Rades, Elisa Marie Werner, Esther Glatzel, Marie-Christine Eggert, Denise Olbrich, Soeren Tvilsted, Sabine Bohnet, Dirk Rades, Elisa Marie Werner, Esther Glatzel, Marie-Christine Eggert, Denise Olbrich, Soeren Tvilsted, Sabine Bohnet

Abstract

Background: Pneumonitis is a possible side effect of radiotherapy for lung cancer. Since it can occur up to several months following treatment, symptoms may not be associated with previous radiotherapy, and pneumonitis can become severe before diagnosed. This study aimed to develop a symptom-based scoring system to contribute to earlier detection of radiation pneumonitis requiring medical intervention (grade ≥ 2).

Methods: Patients irradiated for lung cancer complete a paper-based questionnaire (symptom-based score) during and up to 24 weeks following radiotherapy. Patients rate symptoms potentially associated with pneumonitis, and scoring points are assigned to severity of these symptoms. Sum scores are used to identify radiation pneumonitis. If radiation pneumonitis is suspected, patients undergo standard diagnostic procedures. If grade ≥ 2 pneumonitis is confirmed, medical intervention is indicated. The discriminative power of the score will be assessed by calculating the area under the receiver operating characteristic curve (AUC). If statistical significance of the AUC is reached, the optimal sum score to predict radiation pneumonitis will be established, which is defined as a cut-off value with sensitivity ≥90% and specificity ≥80%. Assuming a ratio between patients without and with pneumonitis of 3.63, a sample size of 93 patients is required in the full analysis set to yield statistical significance at the level of 5% with a power of 90% if the AUC under the alternative hypothesis is at least 0.9. Considering potential drop-outs, 98 patients should be recruited. If > 20% of patients are not satisfied with the score, modification is required. If the dissatisfaction rate is > 40%, the score is considered not useful. In 10 patients, functionality of a mobile application will be tested in addition to the paper-based questionnaire.

Discussion: If an optimal cut-off score resulting in sufficiently high sensitivity and specificity can be identified and the development of a symptom-based scoring system is successful, this tool will contribute to better identification of patients experiencing pneumonitis after radiotherapy for lung cancer.

Trial registration: Clinicaltrials.gov ( NCT04335409 ); registered on 2nd of April, 2020.

Keywords: Lung cancer; Prevalence; Radiation pneumonitis; Radiotherapy; Symptom-based score.

Conflict of interest statement

Dirk Rades is member of the editorial board of BMC Cancer. Otherwise, the authors declare that they have no competing interest related to the study presented here.

Figures

Fig. 1
Fig. 1
Schedule of enrolment, interventions and assessments

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30. doi: 10.3322/caac.21590.
    1. Leitlinienprogramm Onkologie (Deutsche Krebsgesellschaft, Deutsche Krebshilfe, AWMF): Prävention, Diagnostik, Therapie und Nachsorge des Lungenkarzinoms, Langversion 1.0,2018, AWMF-Registernummer: 020/007OL, .
    1. Verma V, Simone CB, 2nd, Werner-Wasik M. Acute and late toxicities of concurrent chemoradiotherapy for locally-advanced non-small cell lung cancer. Cancers. 2017;9:E120. doi: 10.3390/cancers9090120.
    1. Rades D, Glatzel E, Werner EM, Bohnet S. Prevalence and characteristics of symptomatic pneumonitis after radiotherapy of patients with locally advanced lung cancer. Anticancer Res. 2019;39:6909–6913. doi: 10.21873/anticanres.13911.
    1. Giridhar P, Mallick S, Rath GK, Julka PK. Radiation induced lung injury: prediction, assessment and management. Asian Pac J Cancer Prev. 2015;16:2613–2617. doi: 10.7314/APJCP.2015.16.7.2613.
    1. National Institutes of Health/National Cancer Institute . Common terminology criteria for adverse events (CTCAE) version 5.0. Bethesda: National Institutes of Health/National Cancer Institute; 2017.
    1. Bentzen SM, Constine LS, Deasy JO, Eisbruch A, Jackson A, Marks LB, Ten Haken RK, Yorke ED. Quantitative analyses of normal tissue effects in the clinic (QUANTEC): an introduction to the scientific issues. Int J Radiat Oncol Biol Phys. 2010;76(3 Suppl):S3–S9. doi: 10.1016/j.ijrobp.2009.09.040.
    1. Dang J, Li G, Ma L, Diao R, Zang S, Han C, Zhang S, Yao L. Predictors of grade ≥2 and grade ≥3 radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with three-dimensional conformal radiotherapy. Acta Oncol. 2013;52:1175–1180. doi: 10.3109/0284186X.2012.747696.
    1. Palma DA, Senan S, Tsujino K, Barriger RB, Rengan R, Moreno M, Bradley JD, Kim TH, Ramella S, Marks LB, De Petris L, Stitt L, Rofrigues G. Predicting radiation pneumonitis after chemoradiation therapy for lung cancer: an international individual patient data meta-analysis. Int J Radiat Oncol Biol Phys. 2013;85:444–450. doi: 10.1016/j.ijrobp.2012.04.043.
    1. Louvel G, Bahleda R, Ammari S, Le Péchoux C, Levy A, Massard C, Le Pavec J, Champiat S, Deutsch E. Immunotherapy and pulmonary toxicities: can concomitant immune-checkpoint inhibitors with radiotherapy increase the risk of radiation pneumonitis? Eur Respir J. 2018;51:1701737. doi: 10.1183/13993003.01737-2017.
    1. Zhang XJ, Sun JG, Sun J, Ming H, Wang XX, Wu L, Chen ZT. Prediction of radiation pneumonitis in lung cancer patients: a systematic review. J Cancer Res Clin Oncol. 2012;138:2103–2116. doi: 10.1007/s00432-012-1284-1.
    1. Nalbantov G, Kietselaer B, Vandecasteele K, Oberije C, Berbee M, Troost E, Dingemans AM, van Baardwijk A, Smits K, Dekker A, Bussink J, De Ruysscher D, Lievens Y, Lambin P. Cardiac comorbidity is an independent risk factor for radiation-induced lung toxicity in lung cancer patients. Radiother Oncol. 2013;109:100–106. doi: 10.1016/j.radonc.2013.08.035.
    1. Li F, Zhou Z, Wu A, Cai Y, Wu H, Chen M, et al. Preexisting radiological interstitial lung abnormalities are a risk factor for severe radiation pneumonitis in patients with small-cell lung cancer after thoracic radiation therapy. Radiat Oncol. 2018;13:82. doi: 10.1186/s13014-018-1030-1.
    1. Torre-Bouscoulet L, Munoz-Montano WR, Martínez-Briseno D, Lozano-Ruiz FJ, Fernandez-Plata R, Beck-Magana JA, Garcia-Sancho C, Guzman-Barragan A, Vergara E, Blake-Cerda M, Gochicoa-Rangel L, Maldonado F, Arroyo-Hernandez M, Arrieta O. Abnormal pulmonary function tests predict the development of radiation-induced pneumonitis in advanced non-small cell lung cancer. Respir Res. 2018;19:72. doi: 10.1186/s12931-018-0775-2.
    1. National Institutes of Health/National Cancer Institute . Common terminology criteria for adverse events (CTCAE) version 3.0. Bethesda: National Institutes of Health/National Cancer Institute; 2006.
    1. Choi YW, Munden RF, Erasmus JJ, Park KJ, Chung WK, Jeon SC, Park CK. Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis. Radiographics. 2004;24:985–997. doi: 10.1148/rg.244035160.
    1. Larici AR, del Ciello A, Maggi F, Santoro SI, Meduri B, Valentini V, Giordano A, Bonomo L. Lung abnormalities at multimodality imaging after radiation therapy for non-small cell lung cancer. Radiographics. 2011;31:771–789. doi: 10.1148/rg.313105096.
    1. Bradley J, Movsas B. Radiation pneumonitis and esophagitis in thoracic irradiation. Cancer Treat Res. 2006;128:43–64. doi: 10.1007/0-387-25354-8_4.
    1. Schrepp M, Hinderks A, Thomaschewski J. Applying the user experience questionnaire (UEQ) in different evaluation scenarios. In: Marcus A, editor. Design, user experience, and usability. Theories, methods, and tools for designing the user experience. Lecture notes in computer science, volume 8517. New York City: Springer International Publishing; 2014. pp. 383–392.
    1. DeLong ER, DeLong DM, Clarke-Pearson DL. Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach. Biometrics. 1988;44:837–845. doi: 10.2307/2531595.
    1. Inoue A, Kunitoh H, Sekine I, Sumi M, Tokuuye K, Saijo N. Radiation pneumonitis in lung cancer patients: a retrospective study of risk factors and the long-term prognosis. Int J Radiat Oncol Biol Phys. 2001;49:649–655. doi: 10.1016/S0360-3016(00)00783-5.
    1. Basch E, Reeve BB, Mitchell SA, Clauser SB, Minasian LM, Dueck AC, et al. Development of the National Cancer Institute’s patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE) J Natl Cancer Inst. 2014;106:dju244. doi: 10.1093/jnci/dju244.
    1. Hagelstein V, Ortland I, Wilmer A, Mitchell SA, Jaehde U. Validation of the German patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE™) Ann Oncol. 2016;27:2294–2299. doi: 10.1093/annonc/mdw422.

Source: PubMed

Sponsorzy i współpracownicy

Warunki medyczne

Interwencje lekowe

3
Subskrybuj