Table 4: American Society of Clinical Oncology Clinical Practice Guideline for the Management of ICI-related Pneumonitis. (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. The patient was receiving anti-PD1 (nivolumab) to treat her advanced metastatic melanoma. 11 (2): 138. Figure 5b. Immunotherapy was subsequently held, and steroid therapy was administered. Spectrum of treatment-related pneumonitis among various therapy types. Patients with grade 2 pneumonitis (symptomatic pneumonitis) should receive prednisone, 0.5–1 mg/kg/d, or the equivalent, and patients with grade 3 pneumonitis should receive a higher dose: 1–2 mg/kg or the equivalent. Higher rates of pneumonitis have been observed in non–small cell lung cancer and renal cell carcinoma versus those of melanoma (22). (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). 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. COVID-19 Pneumonia Mimicking Immunotherapy-Induced Pneumonitis on 18F-FDG PET/CT in a Patient Under Treatment With Nivolumab. 1. Figure 9a. 2017 and had a recorded diagnosis of pneumonitis related to immunotherapy. The symptoms improved on discontinuation of atezolizumab and a course of prednisone. Fundamental Mechanisms of Immune Checkpoint Blockade Therapy, PD-L1 regulates the development, maintenance, and function of induced regulatory T cells, The blockade of immune checkpoints in cancer immunotherapy, New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1), Evaluation of Immune-Related Response Criteria and RECIST v1.1 in Patients With Advanced Melanoma Treated With Pembrolizumab, Guidelines for the evaluation of immune therapy activity in solid tumors: immune-related response criteria, Developing a common language for tumor response to immunotherapy: immune-related response criteria using unidimensional measurements, iRECIST: guidelines for response criteria for use in trials testing immunotherapeutics, Prediction of Response to Immune Checkpoint Inhibitor Therapy Using Early-Time-Point 18F-FDG PET/CT Imaging in Patients with Advanced Melanoma, Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma, Update on immunologic therapy with anti-CTLA-4 antibodies in melanoma: identification of clinical and biological response patterns, immune-related adverse events, and their management, Toxicities of the anti-PD-1 and anti-PD-L1 immune checkpoint antibodies, Immune-related adverse events during anticancer immunotherapy: Pathogenesis and management, MDX010-20 Investigators. Thus, blockade of key portions of either or both of these immune checkpoint pathways is thought to be responsible for the antitumoral activity with ICIs (Fig 1). Figure 7a. With conventional agents, the median time of onset of radiation recall pneumonitis after the end of radiation therapy is 95 days, although onset of 2 years after radiation therapy has been reported with nivolumab (38,41). 93, No. Illustrations show the mechanisms of action (left) of ICIs and the downstream tumor effects (right) for PD-1 and PD-L1 (a) and CTLA-4 (b) inhibitors. In addition, undergoing combination immunotherapy, concurrent radiation therapy, and previous high-dose chemotherapy are also thought to be risk factors (48). (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. Published guidelines outline the treatment of ICI therapy–related pneumonitis based on the severity of symptoms. Immunotherapy was subsequently held, and steroid therapy was administered. The patient previously underwent radiation therapy for multiple left posterior rib metastases. AIP–ARDS pattern of pneumonitis in a 57-year-old man undergoing nivolumab therapy for stage IV lung adenocarcinoma. (c) Follow-up axial chest CT image obtained 3 months later after withholding ICI therapy and administering steroid therapy shows resolved pneumonitis. As the clinical manifestation is often nonspecific, CT plays an important role in diagnosis and triage. (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). OP pattern in a 51-year-old man undergoing nivolumab therapy for stage IV gastric adenocarcinoma. (c) Follow-up axial chest CT image shows near-complete resolution of pneumonitis, with several remaining faint subpleural right lower lobe opacities (arrows). 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. Interlobular septal thickening and a “crazy-paving” pattern may also be present (34). (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). NSIP-associated connective tissue and autoimmune disorders are generally long-standing processes in the setting of other known comorbid conditions. Recurrent pneumonitis pattern, location of involvement, and severity may vary compared with those at initial presentation. It should be suspected in any patient with a history of radiation therapy with new airspace changes sharply demarcated from the adjacent lung in the appearance of a radiation field. The size of the left lower lobe mass (arrow) decreased, suggesting a pseudoprogression on the previous study. HP pattern may also mimic other small airways processes such as respiratory and follicular bronchiolitis, which are classically associated with smoking and underlying connective tissue or autoimmune disease history, respectively. The patient was receiving anti-PD1 (nivolumab) to treat her advanced metastatic melanoma. 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. Imaging plays a critical role in pneumonitis detection. (a) Baseline axial chest CT image obtained before starting immunotherapy shows multiple lung nodules and masses. 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. This axial CT image in lung windowing shows multifocal alveolar consolidations in a subpleural and peribronchovascular location, predominating at the level of the left upper lobe. (2018) memo - Magazine of European Medical Oncology. (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. (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. (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). (b) Follow-up coronal chest CT image obtained 1 month later after withholding ICI therapy and administering steroid therapy shows resolved pneumonitis, with a return to near-baseline findings. 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. More severe forms of pulmonary toxicity, such as acute interstitial pneumonia leading to acute respiratory Treatment typically includes administering corticosteroids and/or discontinuing therapy (42). After pneumonitis resolution, clinicians are faced with the decision of whether to restart ICI therapy (ie, rechallenge). (a) Baseline axial chest CT image shows the lungs after completion of radiation therapy. However, large-scale head-to-head studies comparing various ICI therapies are lacking. How Do Cytotoxic Lymphocytes Kill Cancer Cells? 3 (10): 1185-92. Common Terminology Criteria for Adverse Events, Advances in Radiation Oncology, Vol. Findings with lower lobe predominance can be depicted. The patient died 1 week later. Patients initially diagnosed with grade 3 or 4 pneumonitis generally discontinue therapy permanently (47). While chest radiography may be used as an initial screening tool, chest CT can better depict even subtle changes of pneumonitis and help differentiate among subtypes, which are more completely described in the following section. 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). We review the mechanism of ICIs, discuss the pathophysiology and clinical presentation of ICI therapy–related pneumonitis with associated imaging manifestations, and highlight important aspects of treatment and monitoring. The airways are unremarkable. Patients treated with checkpoint inhibitors may show variable computed tomography (CT) features on follow-up imaging, and it is unclear how reliable conventional response criteria are to determine patient management and outcomes. Conventional chemotherapy agents have demonstrated a dose-dependent risk of pneumonitis, while overall this has not been shown with ICI therapy (45,46). Table 2: National Cancer Institute CTCAE Pneumonitis Grading System. Furthermore, the use of serum markers for the prediction and monitoring of ICI therapy–related pneumonitis is also an active area of investigation. history of melanoma on the left side of the face (resected in December 2012) and metastasis to the left lung upper lobe (resected in November 2016). HP pattern in a 52-year-old woman who underwent nivolumab therapy for stage IV lung adenocarcinoma. Spectrum of treatment-related pneumonitis among various therapy types. ADVERTISEMENT: Supporters see fewer/no ads. Pneumonitis Related to Melanoma Immunotherapy. 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. Introduction of immunotherapy has been most commonly described pattern of pneumonitis, pneumonia. 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