After completing this journal-based SA-CME activity, participants will be able to: ■ Describe the indications and mechanisms of action of ICIs and the pathophysiology of ICI therapy–related pneumonitis. No fevers or raised septic markers. Some patients were diagnosed However, large-scale head-to-head studies comparing various ICI therapies are lacking. Pneumonitis Related to Melanoma Immunotherapy. (c) Axial chest CT image obtained 5 months after discontinuation of therapy shows minimal residual (although markedly improved) pneumonitis (arrow) in the left lower lobe. During the process of T-cell activation, various inhibitor receptors also become upregulated, acting as immune checkpoints to limit the overstimulation of the immune response (3). Figure 2. Imaging features are similar to those of sarcoidosis and include mediastinal and hilar lymphadenopathy and pulmonary nodules in a perilymphatic distribution, with upper lung predominance (42). Pulmonary nodules may also be depicted, typically in a peribronchovascular distribution and more commonly as smaller nodules (<10 mm). 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… The patient died 1 week later. 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. (c) Follow-up axial chest CT image obtained 2 months later after steroid therapy shows resolved right lower lobe pneumonitis. Although not specifically addressed in the American Society of Clinical Oncology Practice Guideline, recurrent pneumonitis is often treated with methods similar to those used in the treatment of the initial occurrence. Reported recurrence rate after rechallenge is 17%–29% (21,25,31). (b) Axial chest CT image obtained 2 months later after starting pembrolizumab therapy shows bilateral lower lobe ground-glass and reticular opacities (black arrows), with regions of immediate subpleural sparing (white arrows). Spectrum of treatment-related pneumonitis among various therapy types. (b) Axial CT image obtained 2 weeks after starting nivolumab therapy shows a region of centrilobular solid and ground-glass nodularity (black arrows) in the right lower lobe. The patient was receiving anti-PD1 (nivolumab) to treat her advanced metastatic melanoma. (b) Follow-up axial CT image obtained 4 months later after administering nivolumab therapy shows multiple predominantly peripheral and subpleural airspace consolidative opacities (arrows), findings consistent with an OP pneumonitis pattern. Figure 4a. Furthermore, ICI therapy may also be combined with conventional chemotherapies given the ability of cytotoxic chemotherapy to potentiate the immune response of ICIs (2). (c) Follow-up axial chest CT image shows near-complete resolution of pneumonitis, with several remaining faint subpleural right lower lobe opacities (arrows). Immune check… Immunotherapy was subsequently held, and steroid therapy was administered. Sarcoidlike reaction has been most commonly reported in patients undergoing ipilimumab therapy and in those with melanoma (42). A smaller series by Nishino et al (31) with 20 pneumonitis cases described similar patterns as well as acute interstitial pneumonia (AIP)–acute respiratory distress syndrome (ARDS) occurring in 10% of patients. Recurrent pneumonitis in a 78-year-old patient with small cell lung carcinoma. (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. A majority of irAEs occur in the induction phase, usually within the first 12 weeks of initiating therapy, although reactions manifesting after 1 year have been observed (18,19). (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. Previously, the bronchiolitis pattern may have been overlooked as a distinct pneumonitis pattern given its identical appearance to infectious and other inflammatory causes of bronchiolitis. Pneumonitis is a potential consequence of both lung-directed radiation and immune checkpoint blockade (ICB), particularly treatment with PD-1/PD-L1 inhibitors. We describe the findings of a SARS-CoV-2 infection on PET/CT with F-FDG in a 51-year-old man with metastatic renal cell carcinoma under treatment with nivolumab. For example, pembrolizumab, a PD-1 inhibitor, has FDA approval as frontline treatment of advanced epidermal growth factor receptor and anaplastic lymphoma kinase wild-type non–small cell lung cancer in which tumors have at least 50% PD-L1 expression. Its mechanism is likely multifactorial and is thought to be an autoimmune response with T-cell upregulation and ultimately increased granuloma formation. Figure 7: Axial chest CT scans show programmed cell death protein 1 (PD-1) inhibitor–related pneumonitis in a patient with advanced non–small cell lung cancer treated with nivolumab. Although not specifically addressed in published guidelines given the potential for high steroid doses administered for extended periods, infectious prophylaxis may be warranted. The patient previously underwent radiation therapy for multiple left posterior rib metastases. ICI therapy–related pneumonitis is an uncommon but important complication of ICI therapy, with potential for significant morbidity and mortality. Immune-related adverse events are an increasingly recognized set of complications of ICI therapy that may affect any organ system. ■ Discuss the management of irAEs and the role of the radiologist in treatment course planning in these complex cases. The diagnosis of immune-related pneumoni-tis was based on typical clinical features and on new typical imaging changes such as ground glass opacities in chest com-puted tomography (CT) scan. 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. Some patients were diagnosed with concomitant patterns, and a distinctive pattern was not identified in 36% of cases. Chest radiography can be considered to track evolving pneumonitis findings. 11 (2): 138. (a) Baseline axial chest CT image shows the lungs after completion of radiation therapy. The development of an irAE is mainly T-cell mediated, and infiltration of CD4 and CD8 cells has been observed in association with irAEs (15). 16, The British Journal of Radiology, Vol. Background: Nivolumab is a novel immunotherapy that was recently approved for treatment of advanced non-small-cell lung cancer (NSCLC). In May 2017, a follow-up chest CT demonstrated resolution of ground glass opacification (figure 1C,D) at which time nivolumab 3 mg/kg monotherapy was initiated and continued for 25 doses until April 2018 without recurrence of pneumonitis.In April 2018, brain MRI showed postsurgical changes without evidence of metastases and chest and abdominal CT scans showed interval additional … Given the cytotoxic effect of conventional therapies, therapy success (for example in the Response Evaluation Criteria in Solid Tumors [RECIST] 1.1 criteria) is determined by the interval disappearance of or decrease in the size of lesions, with treatment failure suggested by increased lesion size or the appearance of new lesions (8). Although not yet incorporated in official immunotherapy response criteria, the combination of anatomic and functional imaging such as fluorine 18 fluorodeoxyglucose (18F-FDG) PET/CT or diffusion-weighted imaging with MRI may be beneficial in predicting treatment response in patients receiving ICI therapy (13,14). Airspace disease may manifest as either consolidative or ground-glass opacities or a combination of both, frequently depicted on air bronchograms with or without a component of bronchial dilatation. Clinically, ICI therapy–related pneumonitis tends to occur with overall higher severity, potentially requiring higher doses of steroid therapy or more potent immunosuppressive therapy compared with that of conventional chemotherapy pneumonitis. Spectrum of treatment-related pneumonitis among various therapy types. However, in certain conditions such as leflunomide-induced acute interstitial pneumonia, patients have pre-existing lung disease. 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. While the increased activation of the immune system is responsible for the therapeutic efficacy of ICI therapy, it is also the driver behind the immune-related adverse events (irAEs) of these therapies. Figure 7c. Findings with lower lobe predominance can be depicted. 2017 and had a recorded diagnosis of pneumonitis related to immunotherapy. OP pattern most commonly manifests as patchy bilateral opacities with a peripheral or peribronchovascular predominance, often with a mid- to lower-lung predominance (Fig 3). (a) Baseline axial chest CT image shows the lungs before immunotherapy was initiated. 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. The left lower lobe mass also increased in size (white arrow). (b) Axial chest CT image obtained 2 months after initiating trastuzumab therapy shows a focal region of ground-glass opacities within the posterior and medial left lower lobe (arrow), with a well-defined linear demarcation from the adjacent normal lung. Immunotherapy can be classified as either passive or active. Findings include diffuse or upper lobe predominant centrilobular ground-glass nodules, which may be accompanied by air trapping (Fig 5) (21). The left lower lobe mass also increased in size (white arrow). (a) Baseline axial chest CT image obtained before starting immunotherapy shows multiple lung nodules and masses. Histopathologic findings include cellular interstitial pneumonitis, organizing pneumonia (OP), and less commonly diffuse alveolar damage (21). Onset has been shown to occur earlier in patients with lung cancer compared with those with melanoma (2.1 versus 5.2 months, respectively) (25). (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. Figure 4b. ICI therapies are increasingly being used as first- and second-line agents in the treatment of a growing number of malignancies. However, a combination of immunotherapy (pembrolizumab) with chemotherapy was not linked to an increased risk of pneumonitis in lung cancer . Pneumonitis is a potentially lethal side effect of immune checkpoint inhibition, occurring in 1–5% of patients enrolled in trials [ 2 – 11 ]. A circumferential consolidative opacity surrounding an interior area of ground-glass attenuation (ie, reversed halo or atoll sign), a relatively specific marker for OP in the nontreatment setting, has also been reported in ICI therapy–related pneumonitis (32). Figure 9b. The patient died 1 week later. Previous history of metastatic melanoma. Figure 3c. Subpleural sparing of the posterior and dependent lower lobes has also been reported as a specific finding (34). (a) Baseline axial chest CT image obtained before starting immunotherapy shows multiple lung nodules and masses. Table 2: National Cancer Institute CTCAE Pneumonitis Grading System. But potentially serious pulmonary toxicity of pneumonitis many ICI therapies are lacking well-described pattern, of. Transbronchial biopsy can be considered at this stage 2 months later after steroid therapy with intravenous along. 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