Inhalative steroids as an individual treatment in symptomatic lung cancer patients with radiation pneumonitis grade II after radiotherapy - a single-centre experience

C Henkenberens, S Janssen, M Lavae-Mokhtari, K Leni, A Meyer, H Christiansen, M Bremer, N Dickgreber, C Henkenberens, S Janssen, M Lavae-Mokhtari, K Leni, A Meyer, H Christiansen, M Bremer, N Dickgreber

Abstract

Purpose: To assess efficacy of our single-centre experience with inhalative steroids (IS) in lung cancer patients with symptomatic radiation pneumonitis (RP) grade II.

Material and methods: Between 05/09 and 07/10, 24 patients (female, n = 8; male, n = 16) with lung cancer (non-small cell lung carcinoma [NSCLC]: n = 19; small cell lung cancer [SCLC]: n = 3; unknown histology: n = 2) and good performance status (ECOG ≤1) received definitive radiotherapy to the primary tumour site and involved lymph nodes with concurrent chemotherapy (n = 18), sequential chemotherapy (n = 2) or radiation only (n = 4) and developed symptomatic RP grade II during follow-up. No patient presented with oxygen requiring RP grade III. The mean age at diagnosis was 66 years (range: 50-82 years). Nine patients suffered from chronic obstructive pulmonary disease (COPD) before treatment, and 18 patients had a smoking history (median pack years: 48). The mean lung dose was 15.5 Gy (range: 3.0-23.1 Gy). All patients were treated with IS. If a patient's clinical symptoms did not significantly improve within two weeks of IS therapy initiation, their treatment was switched to oral prednisolone.

Results: All 24 patients were initially treated with a high dose IS (budesonide 800 μg 1-0-1) for 14 days. Of the patients, 18 showed a significant improvement of clinical symptoms and 6 patients did not show significant improvement of clinical symptoms and were classified as non-responders to IS. Their treatment was switched to oral steroids after two weeks (starting with oral prednisolone, 0.5 mg/kg bodyweight; at least 50 mg per day). All of these patients responded to the prednisolone. None of non-responders presented with increased symptoms of RP and required oxygen and / or hospitalization (RP grade III). The median follow-up after IS treatment initiation was 18 months (range: 4-66 months). The median duration of IS treatment and prednisolone treatment was 8.2 months (range: 3.0-48.3 months) and 11.4 months (range: 5.0-44.0 months), respectively. Of the 18 IS treatment responders, 2 (11.1 %) patients with pre-existing grade 2 COPD still required IS (400 μg twice a day) 45.0 and 48.3 months after radiotherapy, respectively. For the remaining 16 responders (88.9 %), IS therapy was stopped after 7.7 months (range: 3.0-18.2 months). None of the patients treated with IS developed any specific IS-related side effects such as oral candidiasis.

Conclusion: This single-centre experience shows that high-dose IS is an individual treatment option for radiation-induced pneumonitis grade II in patients with a good performance status.

Figures

Fig. 1
Fig. 1
Overall survival of all patients (left), and differences (right) between responders (blue curve) and non-responders (green curve)

References

    1. Claude L, Perol D, Ginestet C. A prospective study on radiation pneumonitis following conformal radiation therapy in non-small-cell lung cancer: clinical and dosimetric factors analysis. Radiother Oncol. 2004;71(2):175–181. doi: 10.1016/j.radonc.2004.02.005.
    1. Christodoulou M, Bayman N, McCloskey P,Rowbottom C, Faivre-Finn C. New radiotherapy approaches in locally advanced non-small cell lung cancer. Eur J Cancer. 2014;50(3):525–34.
    1. Dang J, Li G, Lu X, Yao L, Zhang S, Yu Z. Analysis of related factors associated with radiation pneumonitis in patients with locally advanced non-small-cell lung cancer treated with three-dimensional conformal radiotherapy. J Cancer Res Clin Oncol. 2010;136(8):1169–78.
    1. De Vries M, Berendsen AJ, Bosveld HE ,Kerstjens HA, van der Molen T. COPD exacerbations in general practice: variability in oral prednisolone courses. BMC Fam Pract; 2012. doi:10.1186/1471-2296-13-3.
    1. Dörr W, Bertmann S, Herrmann T. Radiation induced lung reactions in breast cancer therapy. Modulating factors and consequential effects. Strahlenther Onkol. 2005;181(9):567–573. doi: 10.1007/s00066-005-1457-9.
    1. Dörr W, Baumann M, Herrmann T. Radiation-induced lung damage: a challenge for radiation biology, experimental and clinical radiotherapy. Int J Radiat Biol. 2000;76(4):443–446. doi: 10.1080/095530000138420.
    1. Enache I, Noel G, Jeung MY, Meyer N, Oswald-Mammosser M, Pistea C, et al. Impact of 3D conformal radiotherapy on lung function of patients with lung cancer: a prospective study. Respiration. 2013;86(2):100–08.
    1. Fay M, Tan A, Fisher R, Mac Manus M, Wirth A, Ball D. Dose-volume histogram analysis as predictor of radiation pneumonitis in primary lung cancer patients treated with radiotherapy. Int J Radiat Oncol Biol Phys. 2005;61(5):1355–63.
    1. Fu XL, Huang H, Bentgel G, Clough R, Jirtle RL, Kong FM, et al. Predicting the risk of symptomatic radiation-induced lung injury using both the physical and biologic parameters V and transforming growth factor ß. Int J Radiat Oncol Biol Phys. 2001;50(4):899–908.
    1. Franzen L, Bjermer L, Hendriksson R, Littbrand B, Nilsson K. Does smoking protect against radiation-induced pneumonitis? Int J Radiat Oncol Biol Phys. 1989;56(5):721–4.
    1. Graham MW, Purdy JA, Emami B, Harms W, Bosch W, Lockett MA et al. Clinical dose-volume histogram analysis for pneumonitis after 3D treatment for non-small cell lung cancer (NSCLC). Int J Radiat Oncol Biol Phys. 1999;45(2):323–9.
    1. Hernando ML, Marks LB, Bentel GC, Zhou SM, Hollis D, Das SK, et al. Radiation-induced pulmonary toxicity: a dose-volume histogram analysis in 201 patients with lung cancer. Int J Radiat Oncol Biol Phys. 2001;51(3):650–9.
    1. Hernberg M, Virkkunen P, Maasilta P, Keyriläinen J, Blomqvist C, Bergh J et al. Pulmonary toxicity after radiotherapy in primary breast cancer patients: results from a randomized chemotherapy study. Int J Radiat Oncol Biol Phy. 2002;52(1):128–36.
    1. Höller U, Feyer P. Management und Prophylaxe von organbezogenen Toxizitäten – Pneumotoxizität unter Strahlentherapie. Im Focus Onkologie. 2007;9:61–67.
    1. Hurkmans CW, Borger JH, Bos LJ, van der Horst A, Pieters BR, Lebesque JV et al. Cardiac and lung complication probabilities after breast cancer irradiation. Radiother Oncol. 2000;55(2):145–51.
    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 long-term prognosis. Int J Radiat Oncol Biol Phys. 2001;49(3):649–55.
    1. Kim S, Park SY, Song JH, Song JH, Seon HJ, Kim YH et al. Corticosteroid therapy against treatment-related pulmonary toxicities in patients with lung cancer. J Thorac Dis. 2014;6(9):1209–17.
    1. Kwa SL, Lebesque JV, Theuws JC, Marks LB, Munley MT, Bentel G et al. Radiation pneumonitis as a function of mean lung dose: an anlysis of pooled data of 540 patients. Int J Radiat Oncol Biol Phy. 1998;42(1):1–9.
    1. Lind P, Marks LB, Hardenberg PH, Clough R, Fan M, Hollis D et al. Technical factors associated with radiation pneumonitis after local +/− regional radiation therapy for breast cancer. Int J Radiat Oncol Biol Phys. 2002;52(1):137–43.
    1. Lingos TI, Recht A, Vicini F, Abner A, Silver B, Harris JR. Radiation pneumonitis in breast cancer patients treated with conservative surgery and radiation therapy. Int J Radiat Oncol Biol Phys. 1991;21(2):355–60.
    1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.
    1. Pagel J, Mohorn M, Kloetzer KH, Fleck M, Wendt TG . Inhalative versus systemische Pneumonitisprophylaxe bei Thoraxbestrahlungen. Strahlenther Onkol. 1998;174(1):25–9.
    1. Marks LB, Yorke ED, Jackson A, Ten Haken RK, Constine LS, Eisbruch A et al. Use of normal tissue complication probability models in the clinic. Int J Radiat Oncol Biol Phys. 2010;76(3):10–9.
    1. McCarty MJ, Lilis P, Vukelja SJ. Azathioprine as a steroid-sparing agent in radiation pneumonitis. Chest. 1996;109(5):1397–400. doi: 10.1378/chest.109.5.1397.
    1. Mao J, Kocak Z, Zhou S, Garst J, Evans ES, Zhang J et al. The impact of induction chemotherapy and the associated tumor response and subsequent radiation-related changes in lung function and tumor response. J Radiat Oncol Biol Phys. 2007;27(5):1360–69.
    1. Monson JM, Stark P, Reilly JJ, Sugarbaker DJ, Strauss GM, Swanson SJ et al. Clinical radiation pneumonitis and radiographic changes after thoracic radiation therapy for lung carcinoma. Cancer. 1998;82(5):842–50.
    1. Müller G, Kiricuta IC, Stieß J, Bohndorf, W. Strahlenpneumonitis und Lungenfibrose nach CT-geplanter Radiotherapie des Bronchialkarzinoms. Strahlenther Onkol. 1994;170(7):400–7.
    1. National Cancer Institute: Common Terminology Criteria for Adverse Events (CTCAE) v.4.0. . Accessed 22/06/2015
    1. Seppenwoolde Y, Lebesque JV, de Jaeger K, Belderbos JS, Boersma LJ, Schilstra C et al. Comparing different NTCP models that predict the incidence of radiation pneumonitis. Normal tissue complication probability. Int J Radiat Oncol Biol Phys. 2003;55(3):724–35.
    1. Robnett TJ, Machtay M, Vines EF, McKenna MG, Algazy KM, McKenna WG. Factors predicting severe radiation pneumonitis in patients receiving definitive chemoradiation for lung cancer. Int J Radiat Oncol Biol Phys. 2000;48(1):89–94.
    1. Sekine I, Sumi M, Ito Y, Nokihara H, Yamamoto N, Kunitoh H et al. Retrospective analysis of steroid therapy for radiation-induced lung injury in lung cancer patients. Radiother Oncol. 2006;80(1):93–7.
    1. Steen NE, Methlie P, Lorentzen S, Hope S, Barrett EA, Larsson S et al. Increased systemic cortisol metabolism in patients with schizophrenia and bipolar disorder: a mechanism for increased stree vulnerability. J Clin Psychiatry. 2011;72(11):1515–21.
    1. S2 guideline “supportive care in radiation oncology” by the DEGRO, Version 1.2, February 2015. . Accessed 22 June 2015
    1. Tsoutsou PG. The interplay between radiation and the immune system in the field of post-radical pneumonitis and fibrosis and why it is important to understand it. Expert Opin Pharmacother. 2014;15(13):1781–83.
    1. 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 Biol Phys. 2003;55(1):110–5.
    1. Wang S, Liao Z, Wei X, Liu HH, Tucker SL, Hu CS et al. Analysis of clinical and dosimetric factors associated with treatment-related pneumonitis (TRP) in patients with non-small-cell lung cancer (NSCLC) treated with concurrent chemotherapy and three-dimensional conformal radiotherapy (3D-CRT). Int J Radiat Oncol Biol Phys. 2006;66(5):1399–407.
    1. Yorke ED, Jackson A, Rosenzweig KE, Braban L, Leibel SA, Ling CC. Correlation of dosimetric factors and radiation pneumonitis for non-small-cell lung cancer patients in a recently completed dose escalation study. Int J Radiat Oncol Biol Phys 2005. 2005;63(3):672–82.
    1. Zhang XJ, Sun JG, Sun J, Ming H, Wang XX, Wu L, et al. Prediction of radiation pneumonitis in lung cancer patients: a systematic review. J Cancer Res Clin Oncol. 2012;138(12):2010–16.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever