[en] BACKGROUND AND PURPOSE: Radiation recall pneumonitis (RRP) is a delayed radiation-induced lung toxicity triggered by systemic agents, typically anticancer drugs. Immune checkpoint inhibitors (ICIs) have recently been identified as potential causal agents of RRP but its real incidence and potential risk factors remain unknown. MATERIALS AND METHODS: Medical records and CTs of patients treated with programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1) inhibitors for advanced lung cancer between 2014 and 2019 at our tertiary center, and who had a previous history of lung irradiation were retrospectively analyzed. We identified RRP as lung CT modifications occurring in the irradiation field >6 months after conventionally fractionated radiotherapy completion and >1 year after stereotactic body radiation therapy. Clinical and dosimetric data were analyzed to identify potential risk factors for RRP. RESULTS: Among 348 patients treated with ICIs, data from 80 eligible patients were analyzed (median age, 69 years [interquartile range, 11]; 45 men). Fifteen patients (18.8%) presented with RRP. Median time between end of radiotherapy and RRP was 450 days (range, 231-1859). No risk factor was significantly associated with RRP. ICI-related pneumonitis was associated with RRP in 33.3% of cases (p = 0.0021), developing either concomitantly or after RRP. Incidence of grade ≥ 3 pneumonitis in the RRP population was 13.3 %. CONCLUSION: We demonstrated a high incidence of RRP (18.8%) in our population of previously irradiated patients treated with ICIs for lung cancer. We identified no risk factors for RRP, but an association was noted between RRP and ICI-related pneumonitis.
Disciplines :
Radiology, nuclear medicine & imaging
Author, co-author :
COUSIN, François ; Centre Hospitalier Universitaire de Liège - CHU > Département de Physique Médicale > Service médical de médecine nucléaire et imagerie onco
DESIR, Colin ; Centre Hospitalier Universitaire de Liège - CHU > Département de Physique Médicale > Service médical de radiodiagnostic
BEN MUSTAPHA, Selma ; Centre Hospitalier Universitaire de Liège - CHU > Département de Physique Médicale > Service médical de radiothérapie
MIEVIS, Carole ; Centre Hospitalier Universitaire de Liège - CHU > Département de Physique Médicale > Service médical de radiothérapie
Coucke, Philippe ; Université de Liège - ULiège > Département des sciences cliniques > Radiothérapie
Hustinx, Roland ; Université de Liège - ULiège > Département des sciences cliniques > Médecine nucléaire
Language :
English
Title :
Incidence, risk factors, and CT characteristics of radiation recall pneumonitis induced by immune checkpoint inhibitor in lung cancer.
Ding, X., Ji, W., Li, J., Zhang, X., Wang, L., Radiation recall pneumonitis induced by chemotherapy after thoracic radiotherapy for lung cancer. Radiat Oncol, 6, 2011, 24.
Shibaki, R., Akamatsu, H., Fujimoto, M., Koh, Y., Yamamoto, N., Nivolumab induced radiation recall pneumonitis after two years of radiotherapy. Ann Oncol 28 (2017), 1404–1405.
Awad, R., Nott, L., Radiation recall pneumonitis induced by erlotinib after palliative thoracic radiotherapy for lung cancer: case report and literature review: post radiation erlotinib induced pneumonitis. Asia Pac J Clin Oncol 12 (2016), 91–95.
McGovern K, Ghaly M, Esposito M, Barnaby K, Seetharamu N. Radiation recall pneumonitis in the setting of immunotherapy and radiation: a focused review. Future Sci OA. 2019;5:FSO378.
Chen, Y., Huang, Z., Xing, L., Meng, X., Yu, J., Radiation recall pneumonitis induced by anti-PD-1 blockade: a case report and review of the literature. Front Oncol, 28, 2020, 561.
Giroux Leprieur, E., Dumenil, C., Julie, C., Giraud, V., Dumoulin, J., Labrune, S., et al. Immunotherapy revolutionises non-small-cell lung cancer therapy: results, perspectives and new challenges. Eur J Cancer 78 (2017), 16–23.
Michot, J.M., Bigenwald, C., Champiat, S., Collins, M., Carbonnel, F., Postel-Vinay, S., et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer 54 (2016), 139–148.
Porcu, M., De Silva, P., Solinas, C., Battaglia, A., Schena, M., Scartozzi, M., et al. Immunotherapy associated pulmonary toxicity: biology behind clinical and radiological features. Cancers, 11, 2019, 305.
Teng, F., Li, M., Yu, J., Radiation recall pneumonitis induced by PD-1/PD-L1 blockades: mechanisms and therapeutic implications. BMC Med, 18, 2020, 275.
Jenkins, P., Welsh, A., Computed tomography appearance of early radiation injury to the lung: correlation with clinical and dosimetric factors. Int J Radiat Oncol 81 (2011), 97–103.
Phernambucq, E.C.J., Palma, D.A., Vincent, A., Smit, E.F., Senan, S., Time and dose-related changes in radiological lung density after concurrent chemoradiotherapy for lung cancer. Lung Cancer 74 (2011), 451–456.
Choi, Y.W., Munden, R.F., Erasmus, J.J., Joo Park, K., Chung, W.K., Jeon, S.C., et al. Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis. RadioGraphics 24 (2004), 985–997.
Larici, A.R., del Ciello, A., Maggi, F., Santoro, S.I., Meduri, B., Valentini, V., et al. Lung abnormalities at multimodality imaging after radiation therapy for non-small cell lung cancer. RadioGraphics 31 (2011), 771–789.
Ikezoe, J., Takashima, S., Morimoto, S., Kadowaki, K., Takeuchi, N., Yamamoto, T., et al. CT appearance of acute radiation-induced injury in the lung. Am J Roentgenol 150 (1988), 765–770.
Wang, S., Liao, Z., Wei, X., Liu, H.H., Tucker, S.L., Hu, C., 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 66 (2006), 1399–1407.
Bernchou, U., Schytte, T., Bertelsen, A., Bentzen, S.M., Hansen, O., Brink, C., Time evolution of regional CT density changes in normal lung after IMRT for NSCLC. Radiother Oncol 109 (2013), 89–94.
Hanania, A.N., Mainwaring, W., Ghebre, Y.T., Hanania, N.A., Ludwig, M., Radiation-induced lung injury. Chest 156 (2019), 150–162.
Guckenberger, M., Heilman, K., Wulf, J., Mueller, G., Beckmann, G., Flentje, M., Pulmonary injury and tumor response after stereotactic body radiotherapy (SBRT): results of a serial follow-up CT study. Radiother Oncol 85 (2007), 435–442.
Yamamoto T, Kadoya N, Morishita Y, Sato Y, Matsushita H, Umezawa R, et al. Assessment and agreement of the CT appearance pattern and its severity grading of radiation-induced lung injury after stereotactic body radiotherapy for lung cancer. Ahmad A, editor. PLOS ONE. 2018;13(10):e0204734.
Trovo, M., Linda, A., El Naqa, I., Javidan-Nejad, C., Bradley, J., Early and late lung radiographic injury following stereotactic body radiation therapy (SBRT). Lung Cancer 69 (2010), 77–85.
Citrin, D.E., Mitchell, J.B., Mechanisms of normal tissue injury from irradiation. Semin Radiat Oncol 27 (2017), 316–324.
Citrin, D.E., Shankavaram, U., Horton, J.A., Shield, W., Zhao, S., Asano, H., et al. Role of type II pneumocyte senescence in radiation-induced lung fibrosis. JNCI J Natl Cancer Inst 105 (2013), 1474–1484.
Demaria, S., Golden, E.B., Formenti, S.C., Role of local radiation therapy in cancer immunotherapy. JAMA Oncol, 1, 2015, 1325.
Kainthola, A., Haritwal, T., Tiwari, M., Gupta, N., Parvez, S., Tiwari, M., et al. Immunological aspect of radiation-induced pneumonitis, current treatment strategies, and future prospects. Front Immunol, 2, 2017, 506.
Sharabi, A.B., Lim, M., DeWeese, T.L., Drake, C.G., Radiation and checkpoint blockade immunotherapy: radiosensitisation and potential mechanisms of synergy. Lancet Oncol 16 (2015), e498–e509.
Voong, K.R., Hazell, S.Z., Fu, W., Hu, C., Lin, C.T., Ding, K., et al. Relationship between prior radiotherapy and checkpoint-inhibitor pneumonitis in patients with advanced non–small-cell lung cancer. Clin Lung Cancer 20 (2019), e470–e479.
Hwang, W.L., Niemierko, A., Hwang, K.L., Hubbeling, H., Schapira, E., Gainor, J.F., et al. Clinical outcomes in patients with metastatic lung cancer treated with PD-1/PD-L1 inhibitors and thoracic radiotherapy. JAMA Oncol, 4, 2018, 253.
Shaverdian, N., Lisberg, A.E., Bornazyan, K., Veruttipong, D., Goldman, J.W., Formenti, S.C., et al. Previous radiotherapy and the clinical activity and toxicity of pembrolizumab in the treatment of non-small-cell lung cancer: a secondary analysis of the KEYNOTE-001 phase 1 trial. Lancet Oncol 18 (2017), 895–903.
Antonia, S.J., Villegas, A., Daniel, D., Vicente, D., Murakami, S., Hui, R., et al. Durvalumab after chemoradiotherapy in Stage III non–small-cell lung cancer. N Engl J Med 377 (2017), 1919–1929.
Cho, J.Y., Kim, J., Lee, J.S., Kim, Y.J., Kim, S.H., Lee, Y.J., et al. Characteristics, incidence, and risk factors of immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer. Lung Cancer 125 (2018), 150–156.
Kalisz, K.R., Ramaiya, N.H., Laukamp, K.R., Gupta, A., Immune checkpoint inhibitor therapy–related pneumonitis: patterns and management. RadioGraphics, 4, 2019, 190036.
Nishino, M., Hatabu, H., Hodi, F.S., Imaging of cancer immunotherapy: current approaches and future directions. Radiology 290 (2019), 9–22.
Pozzessere, C., Bouchaab, H., Jumeau, R., Letovanec, I., Daccord, C., Bourhis, J., et al. Relationship between pneumonitis induced by immune checkpoint inhibitors and the underlying parenchymal status: a retrospective study. ERJ Open Res 6 (2020), 165–2019.