NSIP pattern should be distinguished from atypical infectious processes, which can often be determined on the basis of clinical parameters. However, suspicion for this entity as a distinct pneumonitis pattern should be raised in the absence of infectious symptoms and be confirmed at imaging by documenting resolution of findings after withholding therapy or after a trial of steroid therapy. Treatment is often effective, although recurrence is possible. Grade 1 immune-related pneumonitis is managed with close observation and consideration of holding immunotherapy. Immune-related pneumonitis presenting as an organising pneumonia pattern in a patient with metastatic lung cancer that occurred after 13 cycles of anti-PD1 therapy. NSIP pattern in a 67-year-old man undergoing pembrolizumab therapy for stage IV lung adenocarcinoma. Figure 6b. Patterns of onset and resolution of immune-related adverse events of special interest with ipilimumab: detailed safety analysis from a phase 3 trial in patients with advanced melanoma, Immune-related adverse events with immune checkpoint blockade: a comprehensive review, Nivolumab plus ipilimumab in advanced melanoma, Pneumonitis in Patients Treated With Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy, Incidence of Programmed Cell Death 1 Inhibitor-Related Pneumonitis in Patients With Advanced Cancer: A Systematic Review and Meta-analysis, Incidence of Pneumonitis With Use of Programmed Death 1 and Programmed Death-Ligand 1 Inhibitors in Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Trials, Toxicities of Immunotherapy for the Practitioner, Immune-checkpoint inhibitors associated with interstitial lung disease in cancer patients, U.S. Department of Health and Human Services. Immune-Related Adverse Event Guideline: Pneumonitis Severe new onset of symptoms limiting ARDS Invest calcium, CRP) antigen Pulmonary irAEs have been observed following treatment with immunotherapy and have occurred after a single dose and after as many as 48 treatments. Correspondence from The New England Journal of Medicine — Anti–PD-1–Related Pneumonitis during Cancer Immunotherapy Furthermore, the use of serum markers for the prediction and monitoring of ICI therapy–related pneumonitis is also an active area of investigation. AIP–ARDS pattern of pneumonitis in a 57-year-old man undergoing nivolumab therapy for stage IV lung adenocarcinoma. INTRODUCTION:There is an increasing usage of immune-checkpoint inhibitors (ICI) including programmed cell death-1 inhibitors for several cancers including melanoma. A bronchiolitis pattern is not a well-described pattern, only evident in one large case series and several case reports (25,36,37). The symptoms improved on discontinuation of atezolizumab and a course of prednisone. A radiological review of all serial CT scans of patients with pneumonitis was performed by an experienced chest radiologist, blinded to the clinical data. (c) Axial chest CT image obtained 1 month later after withholding ICI therapy and administering steroid therapy shows residual, although significantly improved, airspace disease (arrows). Pneumonitis is a potentially lethal side effect of immune checkpoint inhibition, occurring in 1–5% of patients enrolled in trials [2–11]. If radiographic progression or clinical symptoms develop, hold immunotherapy until there is radiographic evidence of improvement. Interlobular septal thickening and a “crazy-paving” pattern may also be present (34). The largest study to date by Delaunay et al (25) includes 64 cases of pneumonitis with the following CT patterns described: (a) OP (23%), (b) hypersensitivity pneumonitis (HP) (16%), (c) nonspecific interstitial pneumonia (NSIP) (8%), and (d) bronchiolitis (6%). This article reviews the mechanism of ICIs and ICI therapy complications, with subsequent management techniques and illustrations of the various radiologic patterns of ICI–therapy related pneumonitis. The results indicated the utility of a radiographic pattern–based approach as a guide for patient treatment and monitoring for immunotherapy-related pneumonitis. Many of these adverse events are unique from those previously observed with conventional chemotherapy regimens. Lucian Beer, Maximilian Hochmair, Helmut Prosch. Infection, including atypical and fungal causes such as invasive aspergillosis, should also be considered and often can be distinguished by clinical and laboratory findings. Histopathologic findings include cellular interstitial pneumonitis, organizing pneumonia (OP), and less commonly diffuse alveolar damage (21). However, a combination of immunotherapy (pembrolizumab) with chemotherapy was not linked to an increased risk of pneumonitis in lung cancer . (2018) memo - Magazine of European Medical Oncology. HP pattern is indistinguishable from that of HP associated with allergen exposure (classically birds), and detailed exposure and occupational histories should be sought. We compared treatment associated pneumonitis (TAP) related to immune checkpoint inhibitors (ICI) or chemotherapies (chemo) in advanced non-small cell lung cancer (aNSCLC) patients (pts) with and without (+/-) past medical history (PMH) of Pn, using data from clinical trials (CT… AIP–ARDS pattern is not a prevalent pattern of ICI therapy–related pneumonitis, although it is associated with the most severe clinical course and extent of lung involvement at imaging, manifesting with median CTCAE grade 3 symptoms (31). (b) Axial chest CT image shows new multifocal ground-glass opacities (black arrows), with interval enlargement of several pulmonary masses (white arrows). In addition, undergoing combination immunotherapy, concurrent radiation therapy, and previous high-dose chemotherapy are also thought to be risk factors (48). ICI therapy–related pneumonitis is an irAE, potentially resulting in significant morbidity with possible discontinuation of therapy and possible mortality. (b) Axial CT image in a 63-year-old woman undergoing gemcitabine therapy for pancreatic cancer shows bilateral subpleural reticular opacities, with background faint ground-glass and interstitial opacities (arrows) that are more pronounced in the left lower lobe. Spectrum of treatment-related pneumonitis among various therapy types. Recurrent pneumonitis pattern, location of involvement, and severity may vary compared with those at initial presentation. Findings of radiation recall pneumonitis include consolidative or ground-glass opacities limited to a prior radiation field (Fig 8). Figure 4c. 1115, © 2021 Radiological Society of North America, Improved survival with ipilimumab in patients with metastatic melanoma, Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents, Mechanisms of action and rationale for the use of checkpoint inhibitors in cancer. (a) Axial CT image in a 65-year-old man undergoing ipilimumab therapy for metastatic melanoma shows large bilateral lower lobe pleural-based consolidative and ground-glass opacities (arrows). In the last decade, the introduction of immunotherapy has revolutionized the management and treatment approaches for a number of malignancies. (a) Baseline axial chest CT image shows a medial left lower lobe lung mass with surrounding ground-glass halo sign (arrow), a finding corresponding to adenocarcinoma. Spectrum of treatment-related pneumonitis among various therapy types. Immunotherapy was subsequently held, and steroid therapy was administered. The lungs and pleural spaces are clear, the mediastinal contours are within the normal limits. (2015) Cancer immunology research. Recipient of a Certificate of Merit award for an education exhibit at the 2018 RSNA Annual Meeting. Because of the greater experience with larger clinical trials involving ICI therapies and emerging toxicity profiles, different patterns with respect to presentation, imaging findings, and management have become apparent between ICI therapy–related and conventional chemotherapy-related pneumonitis. HP pattern in a 52-year-old woman who underwent nivolumab therapy for stage IV lung adenocarcinoma. Some patients were diagnosed with concomitant patterns, and a distinctive pattern was not identified in 36% of cases. GI = gastrointestinal. (b) Axial chest CT image obtained 4 months later after nivolumab therapy shows multifocal peripheral and subpleural mid- and lower-lung airspace consolidations (arrows), a finding consistent with an OP pattern of pneumonitis. In the melanoma cohort, the development of a sarcoidlike reaction has been associated with an eventual therapeutic response (43). Airspace disease can also be migratory, changing location or configuration over time (33). Radiation recall pneumonitis in a 65-year-old woman with metastatic breast cancer. Minimal subpleural ground-glass opacities in the right lower lobe were thought to be dependent atelectasis. 58, No. With ongoing ICI clinical trials, the number of approvals and combinations and complexity of treatment regimens is expected to grow in the foreseeable future. In patients with non–small cell lung carcinoma, the incidence and severity of pneumonitis has been shown to be higher in patients undergoing treatment with PD-1 inhibitors compared with those undergoing treatment with PD-L1 inhibitors (3.6% vs 1.3%, respectively), with a lower incidence in those patients undergoing treatment with CTLA-4 inhibitors (23,24). Currently in its fifth version, the CTCAE categorizes symptoms on a five-point grading scale according to increasing severity (Table 2). 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