Manage cookies/Do not sell my data we use in the preference centre. The patient’s clinical course and radiologic findings are particularly notable because they illustrate the distinct manifestations of both radiation and ICB-related pneumonitis, as well as the potential interplay between the two processes. The surgical margins were negative. Data and samples were collected on a DF-HCC institutionally review board approved protocol (05–042). Springer Nature. Google Scholar. Cancer immunotherapy-induced rheumatic diseases emerge as new clinical entities. Unfortunately, the pathogenesis of SARS-CoV-2 puts patients with lung cancer at particular risk of infection. Pneumonitis is a rare but serious adverse event caused by cancer immunotherapy. He currently remains asymptomatic with no evidence of recurrent melanoma. However it is notable that this process was limited to the ipsilateral right lung that had received radiation while the left lung remained without evidence of pneumonitis. Anti-PD-1 inhibitor-related pneumonitis in non-small cell lung Cancer. D noted as residual GGO (white arrow, f); however, additional new foci of peripheral consolidation with surrounding GGO are noted both outside of the radiation field (white arrows, e) and within the irradiated lung (black arrows, e, f). Oxaliplatin-induced pulmonary interstitial disease is an increasingly recognized entity. Effort was made to minimize radiation dose to the lung to the extent possible (Fig. Circulating cytokines predict immune-related toxicity in melanoma patients receiving anti-PD-1-based immunotherapy. Burmeister BH, Henderson MA, Ainslie J, Fisher R, Di Iulio J, Smithers BM, et al. Nishino M, Ramaiya NH, Awad MM, Sholl LM, Maattala JA, Taibi M, et al. This virus, ... as has routinely testing all patients with radiologic abnormalities and symptoms consistent with radiation/immunotherapy-induced pneumonitis prior to corticosteroid treatment. Google Scholar. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Circulating biomarker analyses demonstrated increases in CXCR2, IL1ra and IL2ra that coincided with the development of symptomatic pneumonitis. Article  Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. N Engl J Med. 2016;2(12):1607–16. Bang A, Wilhite TJ, Pike LRG, Cagney DN, Aizer AA, Taylor A, et al. Blood was collected prospectively on an institutionally review board approved protocol. Significant morbidity and mortality can result, and severe pneumonitis attributed to ICB precludes continued therapy. The study involved a melanoma patient treated with standard of care therapy who developed a spectrum of toxicity consistent with radiation and ICB-related pneumonitis. Immune checkpoint inhibitors (ICIs) are monoclonal antibodies that target inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death protein 1 (PD-1), or its ligand, programmed cell death protein ligand 1 (PD-L1), and lead to immune activation in the tumor micro-environment. Shibaki R, Akamatsu H, Fujimoto M, Koh Y, Yamamoto N. Nivolumab induced radiation recall pneumonitis after two years of radiotherapy. Can we forecast or predict pulmonary toxicity? Thank you for your interest in spreading the word on European Respiratory Society . These results should be confirmed because the correlation between toxicity and longer survival may be due to a lead-time bias. The CT scan of March 2018 consistent with pneumonitis was performed on 3/12/18. A recent prospective study included 38 patients with advanced NSCLC treated with anti-PD-1. It remains unclear whether higher and/or lower dose radiation parameters will be more or less predictive of pneumonitis in the setting of ICB, although the overall tolerability of combined radiation / ICB will likely make this a difficult question to address. 2006;66(5):1281–93. Significant morbidity and mortality can result, and severe pneumonitis attributed to ICB precludes continued therapy. Immunotherapy-induced endocrinopathies: assessment, management and monitoring Edson Nogueira, Tom Newsom-Davis, and Daniel L. Morganstein Therapeutic Advances in Endocrinology and Metabolism 2019 10.1177/2042018819896182 Although it is important to reemphasize that prospective studies such as the PACIFIC trial [5] have demonstrated that the combination of lung directed radiation and ICB is not a high risk approach, further investigations are needed to elucidate the mechanisms underlying any potential interaction and identify potential clinical, radiologic and molecular predictors such as genetics or some underlying susceptibility, such as comorbidities or baseline inflammatory changes in the lung, that could lead to an increased risk of patients developing radiation induced pneumonitis exacerbated by immunotherapy. Pneumonitis develops in less than 5% of patients treated with PD-1/PD-L1 inhibitor ICB monotherapy. Ther. Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. Endoscopy, including bronchoalveolar lavage and transbronchial lung biopsies can refine a diagnosis by excluding pulmonary infection and showing lymphocytic alveolitis. 2018. Table 1 shows the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE) gradings for immunotherapy-induced diarrhoea and colitis. MRI brain revealed changes thought to be more consistent with small past infarcts, also with no evidence of metastatic disease. It is also likely that additional cytokines and/or immune cell populations such as myeloid or other innate immune cells might play important roles in mediating effects of radiation / ICB. TreaTmenT The patient was started on oseltamivir and intravenous meth-ylprednisolone of 60mg daily and then changed to oral pred-nisone of 40 mg daily which was tapered after 4 weeks. It is reassuring that TNFalpha-inhibition, a more established treatment for ICB-induced toxicity, was clinically effective despite the potential contribution of radiation related lung injury in this case. However, a combination of immunotherapy (pembrolizumab) with chemotherapy was not linked to an increased risk of pneumonitis in lung cancer . 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non-small-cell lung cancer, 1314PAssociation between immune-related adverse events (irAEs) and atezolizumab efficacy in advanced NSCLC: analyses from the phase III study OAK, Correlation between immune-related adverse events and efficacy in non-small cell lung cancer treated with nivolumab. Lung toxicities associated with ICI treatment are not exceptional. Such a collaborative initiative could standardise and facilitate immune-related adverse event management, and this has already been reported in some centres, such as the Gustave Roussy Cancer Center (Villejuif, France) [45]. The goal of this chapter is to instruct readers on the incidence and clinical manifestations of pneumonitis and to offer guidance in the evaluation and treatment of patients with pneumonitis. Objective We sought to investigate the long-term outcomes of patients who develop immune checkpoint inhibitor (ICI)-induced inflammatory arthritis (IA), to define factors associated with IA persistence after ICI cessation, the need for immunosuppressants and the impact of these medications on underlying malignancies. MS and MM collected and performed the correlative blood analyses. Furthermore, manifestations of lung toxicity in this case were suggestive of an interaction between radiation and ICB-mediated toxicity, as the radiation induced pneumonitis developed at a relatively low radiation dose otherwise unlikely to result in symptomatic toxicity, and the ICB-related pneumonitis was limited to the ipsilateral right lung. Reassuringly, both retrospective and prospective data suggest that this combination is, in general, well tolerated [5,6,7]. The incidence of pneumonitis was higher in combination regimens (including nivolumab and ipilimumab, given concurrently or sequentially, or nivolumab plus peptide vaccines) than in monotherapy (6.6%) . All samples were tested in duplicate, according to manufacturer’s protocols. pneumonitis T cell analysis - immunohistochemistry - flow cytometry - clonal analysis - CD8+ PD1+ T cells in the BALF are over-represented compared to what is seen in the peripheral blood > Tumor Infiltrating Lymphocytes might have a role in the pathogenesis of irAE (limit: no pulmonary biopsy available) bronchoalveolar lavage fluid (BALF) However, it is challenging to identify rare idiosyncratic interactions as well as delayed effects. 2f, white arrow). Overall survival favoured patients who received atezolizumab and presented immune-related adverse events versus those who did not (HR 0.79, 95% CI 0.60–1.05) [42]. However, these patients are at risk for both ICB- and radiation- mediated lung toxicity, and differentiating between the two can have important consequences relevant to clinical management such as impact on the decision to continue or restart ICB therapy. Early recognition and prompt initiation of high dose, systemic corticosteroids and supportive care in our patient resulted in resolution of pneumonitis without compromise of the antitumor effect. Chuzi S, Tavora F, Cruz M, Costa R, Chae YK, Carneiro BA, et al. The patient’s symptoms briefly improved, but then worsened again in conjunction with another attempt at corticosteroid taper. Online ISSN: 1600-0617, Copyright © 2021 by the European Respiratory Society. Interstitial pneumonitis with fibrosis occurs after 3–6 months of therapy. (16–18). A study assessed the benefit of atezolizumab (an anti-PD-L1 treatment) in patients with and without immune-related adverse events in the primary efficacy population (n=850). His corticosteroids were increased and his symptoms improved. Awareness of radiological patterns and clinical manifestations of ICI-ILD are necessary to rapidly diagnose and treat these possible serious events. Finally, the subsequent pattern of lung injury that was observed consisting of waxing and waning consolidations in peripheral and lower lung distributions involving both irradiated and non-irradiated lung areas (distinct from the patterns observed initially) that occurred despite ongoing corticosteroid use indicate a more complex process as compared to pneumonitis related to either radiation or ICB alone, suggesting the possibility of effects from both immune-checkpoint blockade and radiation as an underlying mechanism. 2017;28(6):1404–5. Correspondence to Pneumonitis, pleural effusion, sarcoidosis European Journal of Cancer 54 (2016) 139-148. JAMA oncology. Citation Lomax, A.J., McGuire, H.M., McNeil, C. et al. California Privacy Statement, Terms and Conditions, The volume of the total right lung receiving 20 Gy was < 14% (V20 = 13.6%) and volume of the total lung receiving 20 Gy was < 8%. There was significant extracapsular extension noted on pathology. ... various rashes, pneumonitis, hepatitis, encephalopathy, neuropathy, thyroiditis and hypophysitis are some of the wide-ranging adverse effects attributed to ICIs. Rates of radiation pneumonitis vary significantly based on the amount of lung irradiated, as well as the dose of radiation that is delivered [3]. However, in this case, both the maximum dose to the lung and volume of lung irradiated were within parameters that are associated with a relatively low pneumonitis risk. Organ Systems Affected by PD-1/PD-L1 ... Pathogenesis –poorly understood Normal ranges obtained from testing pooled normal serum and the literature: CXCL2 47.8 pg/mL; IL1ra 1.3 pg/mL; IL2ra 1055 pg/mL17; Note: Second blood draw performed on 2/28/18 (at the time the patient developed symptoms consistent with pneumonitis. … https://doi.org/10.1186/s40425-019-0583-3, DOI: https://doi.org/10.1186/s40425-019-0583-3. The patient was briefly hospitalized, and he started treatment with corticosteroids at a dose of 1 mg/kg of IV solumedrol which was transitioned to oral prednisone. to be involved in the pathogenesis of sarcoidosis.14-17 Chronic exposure to environmental or infectious antigens induces up-regulation of negative regulators of T cells such as PD-1.18 Recently, Braun et al19 showed that PD-1 pathway is upregulated in active sarcoidosis. Immunotherapy-induced pneumonitis is a rare complication with incidence estimated around 3%. Article  2a and b). He did not receive any additional treatment at this time. The diagnosis between COVID-19-induced pneumonia and immunotherapy-induced pneumonitis may be challenging in the era of COVID-19 outbreak. A whole-blood RNA transcript-based gene signature is associated with the development of CTLA-4 blockade-related diarrhea in patients with advanced melanoma treated with the checkpoint inhibitor tremelimumab.

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