While better recognized with conventional chemotherapy agents, cases of radiation recall pneumonitis have now been described with ICI therapy (40,41). Figure 9b. Immune check… 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. 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). The patient died 1 week later. Extensive bone metastatic disease. (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. (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). (c) Follow-up axial chest CT image obtained 2 months later after steroid therapy shows resolved right lower lobe pneumonitis. The airways are unremarkable. A radiological review of all serial CT scans of patients with pneumonitis was performed by an experienced chest radiologist, blinded to the clinical data. On review of her medical history, she has started immunotherapy 2 months ago for her advanced metastatic melanoma. (d) Axial CT image obtained after completing steroid therapy and restarting nivolumab therapy shows recurrence of an OP pneumonitis pattern with new areas of involvement (arrows). Six weeks after starting nivolumab therapy, the patient presented with severely worsening dyspnea. Figure 6c. ICIs target the cell surface receptors cytotoxic T-lymphocyte antigen-4, programmed cell death protein 1, or programmed cell death ligand 1, which result in immune system–mediated destruction of tumor cells. 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. (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. ICI therapy–related pneumonitis is an uncommon but important complication of ICI therapy, with potential for significant morbidity and mortality. Pitfalls in the radiological response assessment of immunotherapy. (2)Clinical Oncology Department, Virgen Macarena University Hospital, Seville, Spain. García-Gómez FJ(1), Álamo-de la Gala MC(2), de la Riva-Pérez PA(1), de la Cruz-Merino L(2), de la Cinta Calvo-Morón M(1). Overall, the incidence of ICI therapy–related pneumonitis is estimated to be between 3% and 6% (21). 4, Respiratory Investigation, Vol. Background: Pneumonitis (Pn) is a potentially life-threatening adverse event of some anticancer drugs. The second largest series, by Naidoo et al (21), describes 43 patients with pneumonitis (27 of which had available CT images), with the following CT findings and categories described: (a) ground-glass opacities (37%), (b) interstitial (22%), (c) cryptogenic OP (19%), (d) hypersensitivity (7%), and (e) unclassified (15%). For patients with grade 2 pneumonitis, diagnostic evaluation to rule out infection may be pursued, which can include nasopharyngeal, sputum, and urine culture and sensitivity tests (27). In the melanoma cohort, the development of a sarcoidlike reaction has been associated with an eventual therapeutic response (43). The results indicated the utility of a radiographic pattern–based approach as a guide for patient treatment and monitoring for immunotherapy-related pneumonitis. Aspiration is typically found in the dependent lungs, with accompanying fluid or debris-filled airways, and esophagus, while infection can often be delineated clinically. (c) Axial chest CT image obtained 5 days later after further respiratory decompensation (despite withholding ICI therapy and initiating intravenous steroid therapy) shows increasing severity and confluence of ground-glass opacities (arrows), with little intervening normal lung parenchyma. (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). ICI therapy–related pneumonitis is an irAE, potentially resulting in significant morbidity with possible discontinuation of therapy and possible mortality. OP pattern in a 51-year-old man undergoing nivolumab therapy for stage IV gastric adenocarcinoma. However, there are currently no specific histologic findings for ICI therapy–related pneumonitis. Figure 5a. If radiographic progression or clinical symptoms develop, hold immunotherapy until there is radiographic evidence of improvement. 18 (1): 42-53. The main differential diagnosis is infection, which does not respect the boundaries and occurs outside of the prior radiation field. The patient previously underwent radiation therapy for multiple left posterior rib metastases. Outside of the lung, the skin is a common site of involvement. 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. ■ Discuss the management of irAEs and the role of the radiologist in treatment course planning in these complex cases. (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. Described findings of HP pattern mirror those typically found in cases of subacute HP depicted in other settings. Previous history of metastatic melanoma. Subpleural sparing of the posterior and dependent lower lobes has also been reported as a specific finding (34). Figure 6b. Spectrum of treatment-related pneumonitis among various therapy types. NSIP pattern in a 67-year-old man undergoing pembrolizumab therapy for stage IV lung adenocarcinoma. ■ Illustrate the imaging patterns of ICI therapy–related pneumonitis and related clinical classification schemes. Furthermore, the use of serum markers for the prediction and monitoring of ICI therapy–related pneumonitis is also an active area of investigation. (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). (2017) Korean journal of radiology. Figure 10d. The patient died 1 week later. (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. A baseline coronal chest CT image obtained before starting immunotherapy (not shown) showed no airspace abnormalities. To date, little is known about immunotherapy-induced pneumonitis (IIP). Published guidelines outline the treatment of ICI therapy–related pneumonitis based on the severity of symptoms. 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). (c) Axial chest CT image obtained 5 days later after further respiratory decompensation (despite withholding ICI therapy and initiating intravenous steroid therapy) shows increasing severity and confluence of ground-glass opacities (arrows), with little intervening normal lung parenchyma. This case illustrates the impressive appearances that immunotherapy-induced pneumonitis can have on imaging. (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. (c) Axial CT image in a 57-year-old man undergoing imatinib therapy for metastatic gastrointestinal stromal tumor shows small patchy peripheral ground-glass opacities (arrows) in the bilateral lower lobes. An increasing number of CIP cases have been reported since 2015, which are attributed to the augment of approvals and uses of ICIs, but a comprehensive understanding of CIP is still lacking. The development of pulmonary immune-related adverse events (irAEs) in patients undergoing PD-(L)1 targeted checkpoint inhibitors are rare, but may be life-threatening. Intravenous steroid therapy with intravenous methylprednisolone along with empirical antibiotic therapy should be administered. Chest radiography can be considered to track evolving pneumonitis findings. 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). Because of their unique mechanism of action, ICI therapies may produce imaging response patterns that differ from those depicted with conventional chemotherapies. This patient was not clinically septic and the pattern of consolidation/groundglass is relatively symmetrical. The appearance and treatment of OP pattern ICI therapy–related pneumonitis are virtually indistinguishable from those of cryptogenic OP, although the latter is usually a long-standing process without a temporal relationship to the immunotherapy course. For example, increased CTLA-4 binding in the presence of certain tumors cells leads to competitive inhibition of costimulatory CD28 binding, leading to decreased T-cell activation. Immune checkpoint therapy–related pneumonitis is an uncommon but potentially serious complication with several distinct radiologic patterns that overlap with those of other infectious and inflammatory conditions. As the clinical manifestation is often nonspecific, CT plays an important role in diagnosis and triage. More severe forms of pulmonary toxicity, such as acute interstitial pneumonia leading to acute respiratory (a) Baseline axial chest CT image shows the lungs before immunotherapy was initiated. NSIP-associated connective tissue and autoimmune disorders are generally long-standing processes in the setting of other known comorbid conditions. Increased FDG uptake within adenopathy has also been observed at PET/CT (44). From the Department of Radiology, Duke University Medical Center, Durham, NC (K.R.K. 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. 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. There are two tiny subcutaneous nodules in the medial aspect of the right breast. Two critical pathways for ICIs are the CTLA-4 and PD-1 pathways, which normally function to attenuate T-cell response and action (Fig 1) (5,6). (c) Follow-up axial chest CT image shows near-complete resolution of pneumonitis, with several remaining faint subpleural right lower lobe opacities (arrows). Her previous chest imaging was normal (following study - chest radiograph). Radiation recall pneumonitis (RRP) is a delayed radiation-induced lung toxicity triggered by systemic agents, typically anticancer drugs. The overlapping pulmonary toxicity induced by thoracic RT and programmed death 1/programmed death ligand-1 (PD-1/PD-L1) blockades is an important issue of clinical investigation in combination treatment. (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). Recurrent pneumonitis in a 78-year-old patient with small cell lung carcinoma. The patient previously underwent radiation therapy for multiple left posterior rib metastases. Bronchiolitis pattern of pneumonitis in a 63-year-old woman undergoing nivolumab therapy for lung adenocarcinoma. Immunotherapy was subsequently held, and steroid therapy was administered. In passive therapy, immunoglobulins are administered and bind to tumor-associated antigens, prompting clearance by the immune system. Bronchiolitis pattern of pneumonitis in a 63-year-old woman undergoing nivolumab therapy for lung adenocarcinoma. OP pattern in a 51-year-old man undergoing nivolumab therapy for stage IV gastric adenocarcinoma. Figure 3a. Some patients were diagnosed with concomitant patterns, and a distinctive pattern was not identified in 36% of cases. Treatment-naïve patients have also demonstrated higher rates of pneumonitis relative to those patients who were previously treated (23). However, when to resume treatment after first episode of pneumonitis, total steroids duration & whether to make switch to other PD-1 inhibitors remains unclear. After pneumonitis resolution, clinicians are faced with the decision of whether to restart ICI therapy (ie, rechallenge). The size of the left lower lobe mass (arrow) decreased, suggesting a pseudoprogression on the previous study. HP pattern can often be differentiated from atypical infection on clinical grounds. 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. However, large-scale head-to-head studies comparing various ICI therapies are lacking. Bronchiolitis pattern of pneumonitis in a 63-year-old woman undergoing nivolumab therapy for lung adenocarcinoma. Immunotherapy was subsequently held, and steroid therapy was administered. NSIP pattern should be distinguished from atypical infectious processes, which can often be determined on the basis of clinical parameters. Patients with grades 3 and 4 pneumonitis require permanent discontinuation of ICI therapy and more intensive care, requiring inpatient admission with close monitoring. Braschi-Amirfarzan M, Tirumani SH, Hodi FS, Nishino M. Immune-Checkpoint Inhibitors in the Era of Precision Medicine: What Radiologists Should Know. Recurrent pneumonitis cases were further subcategorized as either provoked by treatment renewal or unprovoked. A baseline coronal chest CT image obtained before starting immunotherapy (not shown) showed no airspace abnormalities. Figure 1a. However, changes of fibrotic NSIP in nontreatment-related cases including lower lobe volume loss and traction bronchiectasis have not been reported in ICI therapy–related pneumonitis, likely because cases are detected and treated in the acute stage. Figure 8c. Spectrum of treatment-related pneumonitis among various therapy types. Histopathologic findings include cellular interstitial pneumonitis, organizing pneumonia (OP), and less commonly diffuse alveolar damage (21). ICIs act through a unique mechanism of action when compared with those of conventional chemotherapeutic agents. At imaging, ICI therapy–related pneumonitis tends to be more extensive at patient presentation, with findings likely to be lower lung predominant (Fig 9). Figure 2. Recurrent pneumonitis pattern, location of involvement, and severity may vary compared with those at initial presentation. Grade 2 pneumonitis can be managed in the outpatient setting by withholding the ICI therapy and initiating steroid therapy, with initial dose burst followed by a 4- to 6-week taper. PNEUMONITIS DURING mTOR INHIBITOR THERAPY mTOR is a serine/threonine protein kinase that plays a key role in the phosphatidylinositol 3-kinase/Akt/mTOR pathway, which is an established oncogenic driver in human cancers. The patient was receiving anti-PD1 (nivolumab) to treat her advanced metastatic melanoma. Figure 6a. ICI therapy can also be used with nivolumab, a PD-1 inhibitor, and ipilimumab, a combination that has FDA approval for the treatment of colorectal cancer and renal cell carcinoma. Figure 7b. These ICI agents have adverse effects including the uncommon but potentially serious pulmonary toxicity of pneumonitis. In addition, undergoing combination immunotherapy, concurrent radiation therapy, and previous high-dose chemotherapy are also thought to be risk factors (48). (a) Axial chest CT image obtained 5 months after starting nivolumab therapy shows diffuse centrilobular ground-glass nodules (arrows). Radiation recall is an inflammatory reaction occurring within a previously irradiated area after exposure to an inciting agent that has been observed in multiple organs and systems, including skin, lung, digestive tract, muscle, and central nervous system. This latter category includes immune checkpoint inhibitor (ICI) therapy. Pneumonitis is a potentially lethal side effect of immune checkpoint inhibition, occurring in 1–5% of patients enrolled in trials [ 2 – 11 ]. The left lower lobe mass also increased in size (white arrow). A majority of patients do not develop recurrence after restarting immunotherapy, although reports of rechallenge mainly describe patients with initial grade 1 or 2 pneumonitis. A high index of suspicion and prompt recognition of pneumonitis by the radiologist are critical to initiate prompt treatment and prevent further morbidity and mortality for these patients. Figure 3c. In this study, we investigated the clinical and CT features of IIP in non-small cell lung cancer (NSCLC) patients treated with ICI. Viewer, https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf, https://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2018.197.1_MeetingAbstracts.A4008, Nonspecific Interstitial Pneumonia: Radiologic, Clinical, and Pathologic Considerations, Chest CT Diagnosis and Clinical Management of Drug-related Pneumonitis in Patients Receiving Molecular Targeting Agents and Immune Checkpoint Inhibitors: A Position Paper from the Fleischner Society, Thoracic Complications of Precision Cancer Therapies: A Practical Guide for Radiologists in the New Era of Cancer Care, Bronchiolitis: A Practical Approach for the General Radiologist, Hypersensitivity Pneumonitis: A Historical, Clinical, and Radiologic Review, 3D Multiplanar Imaging in the Diagnosis and Management of Lung Transplantation Complications, Patterns of Drug-Related Pulmonary Injury: A Pictorial Review, Update of the International Multidisciplinary Classification of the Idiopathic Interstitial Pneumonias: Revised Concepts and Radiologic Implications. Despite the presence of various cell-mediated immune response pathways, tumor cells have developed means of evading the natural tumor response system of the body. (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. 28, No. Sarcoidlike reaction may mimic recurrent or worsening malignancy, and lymphadenopathy may also be mistaken for reactive lymphadenopathy from an infectious process of other irAEs. 5, World Chinese Journal of Digestology, Vol. However, little is known about the clinical and radiological features of checkpoint inhibitor-induced lung disease. Associated focal ground-glass and consolidative opacities may be visualized, although this should not the predominant feature. Although this occurs through multiple mechanisms, the CTLA-4 and PD-1 pathways play an important role for tumor proliferation. Correspondence from The New England Journal of Medicine — Anti–PD-1–Related Pneumonitis during Cancer Immunotherapy Experimental Design: Among patients with advanced melanoma, lung cancer, or lymphoma treated in trials of nivolumab, we identified those who developed pneumonitis. Pneumonitis Related to Melanoma Immunotherapy. ), and Department of Radiology, University Hospitals Cleveland Medical Center, Cleveland, Ohio (N.H.R., K.R.L., A.G.). Figure 7c. Going forward, given the potential complexity of diagnosis and management of ICI therapy–related pneumonitis, radiologists must work in conjunction with a broader multidisciplinary team to provide optimal care for these patients. The size of the left lower lobe mass (arrow) decreased, suggesting a pseudoprogression on the previous study. Sarcoidlike reactions demonstrate identical histopathologic features to those of sarcoidosis, namely noncaseating granuloma formation. Tirumani SH, Ramaiya NH, Keraliya A, Bailey ND, Ott PA, Hodi FS, Nishino M. Radiographic Profiling of Immune-Related Adverse Events in Advanced Melanoma Patients Treated with Ipilimumab. Classically, bronchiolitis appears as a region of centrilobular nodularity, often in a tree-in-bud pattern. 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). 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. However, a combination of immunotherapy (pembrolizumab) with chemotherapy was not linked to an increased risk of pneumonitis in lung cancer . Interlobular septal thickening and a “crazy-paving” pattern may also be present (34). (d) Axial CT image obtained after completing steroid therapy and restarting nivolumab therapy shows recurrence of an OP pneumonitis pattern with new areas of involvement (arrows). Radiation recall pneumonitis in a 65-year-old woman with metastatic breast cancer. Enter your email address below and we will send you your username, If the address matches an existing account you will receive an email with instructions to retrieve your username. irAEs have been shown to occur in up to 90% of patients undergoing CTLA-4 inhibitor therapy and 70% of those undergoing PD-1 and/or PD-L1 inhibitor therapy (17). As opposed to conventional cytotoxic chemotherapy, which acts by a variety of mechanisms and stages of the cell cycle to directly interfere with cancer cell growth, cancer immunotherapy harnesses the immune system to limit the ability of cancer cells to evade the immune system and combat proliferation. Infection was excluded on the basis of clinical findings. No fevers or raised septic markers. NSIP pattern in a 67-year-old man undergoing pembrolizumab therapy for stage IV lung adenocarcinoma. (a) Baseline axial chest CT image shows the lungs before starting immunotherapy. Findings include diffuse or upper lobe predominant centrilobular ground-glass nodules, which may be accompanied by air trapping (Fig 5) (21). National Institutes of Health, National Cancer Institute, Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline Summary, Radiologic manifestations of immune-related adverse events in patients with metastatic melanoma undergoing anti-CTLA-4 antibody therapy, Ipilimumab-Induced Organizing Pneumonia on 18F-FDG PET/CT in a Patient With Malignant Melanoma, Pneumonitis Related to Melanoma Immunotherapy, PD-1 Inhibitor-Related Pneumonitis in Advanced Cancer Patients: Radiographic Patterns and Clinical Course, A Case of Organizing Pneumonia (OP) Associated with Pembrolizumab, Lung CT: Part 2—The interstitial pneumonias: clinical, histologic, and CT manifestations, Drug-Related Pneumonitis in the Era of Precision Cancer Therapy, Bronchiolitis obliterans after combination immunotherapy with pembrolizumab and ipilimumab, Pembrolizumab-Induced Bronchiolitis in a Patient with Stage IV Non-Small Cell Lung Cancer (abstr), Radiation recall pneumonitis induced by chemotherapy after thoracic radiotherapy for lung cancer, Nivolumab-Induced Radiation Recall Pneumonitis, Nivolumab induced radiation recall pneumonitis after two years of radiotherapy, Sarcoidosis-Like Reactions Induced by Checkpoint Inhibitors, Granulomatous/sarcoid-like lesions associated with checkpoint inhibitors: a marker of therapy response in a subset of melanoma patients, Pembrolizumab-induced Sarcoid-like Reactions during Treatment of Metastatic Melanoma, PD-1 inhibitors increase the incidence and risk of pneumonitis in cancer patients in a dose-independent manner: a meta-analysis, Diagnosis and management of pulmonary toxicity associated with cancer immunotherapy, PD-1 inhibitor-related pneumonitis in lymphoma patients treated with single-agent pembrolizumab therapy, Open in Image Figure 10b. For this journal-based SA-CME activity, the authors, editor, and reviewers have disclosed no relevant relationships. 2017 and had a recorded diagnosis of pneumonitis related to immunotherapy. However, little is known about the clinical and radiological features of checkpoint inhibitor-induced lung disease. (a) Baseline axial chest CT image obtained before starting immunotherapy shows multiple lung nodules and masses. Table 3: ICI Therapy–related Pneumonitis Patterns. However, in certain conditions such as leflunomide-induced acute interstitial pneumonia, patients have pre-existing lung disease. Minimal subpleural ground-glass opacities in the right lower lobe were thought to be dependent atelectasis. Immunotherapy-induced pneumonitis - metastatic melanoma. The size of the left lower lobe mass (arrow) decreased, suggesting a pseudoprogression on the previous study. 3. 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). (c) Axial CT image in a 57-year-old man undergoing imatinib therapy for metastatic gastrointestinal stromal tumor shows small patchy peripheral ground-glass opacities (arrows) in the bilateral lower lobes. (b) Axial chest CT image shows new multifocal ground-glass opacities (black arrows), with interval enlargement of several pulmonary masses (white arrows). ICI therapies are increasingly being used as first- and second-line agents in the treatment of a growing number of malignancies. 33 Everolimus and temsirolimus are specific inhibitors of mTOR and are used as anticancer therapeutic agents. Six weeks after starting nivolumab therapy, the patient presented with severely worsening dyspnea. More invasive assessments with bronchoscopy and biopsy are generally unnecessary, particularly in lower grades, if other clinical data are suggestive of pneumonitis. However, true progression will often be associated with progressive disease elsewhere and will lack response to immunosuppressive therapy. Airspace disease is temporally homogeneous and relatively symmetric, with consolidative opacities uncommon, features that help in distinguishing NSIP from OP patterns. 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. Depending on the severity and initial response, other agents such as infliximab, mycophenolate, or intravenous immunoglobulin may also be added. Recurrence of metastasis to the bilateral lungs and left pleura was detected in April 2018. 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). 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. The patient was receiving anti-PD1 (nivolumab) to treat her advanced metastatic melanoma. Radiologic response to respective treatments (ie, bronchopulmonary hygiene physical therapy and antibiotic therapy) is also often helpful. Normally, an important function of T cells is in the cell-mediated clearance of tumor cells. (b) Axial chest CT image shows new multifocal ground-glass opacities (black arrows), with interval enlargement of several pulmonary masses (white arrows). Pneumonitis may manifest with other irAEs, such as dermatitis, colitis, and endocrinopathies (21). When ICI therapy–related pneumonitis becomes clinically apparent, management should be initiated immediately. Enter your email address below and we will send you the reset instructions. (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. 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%). Infection was excluded on the basis of clinical findings. In the presence of a foreign cell such as a tumor cell, antigen-presenting cells, including dendritic cells or macrophages, incorporate and present a tumor antigen through a major histocompatibility complex, which subsequently binds to a T-cell receptor. irAE risk has been shown to have a dose-dependent relationship for CTLA-4 inhibitors, but this has not been consistently observed in PD-1 and/or PD-L1 inhibitors (19). Figure 7a. Combinations of PD-1 and CTLA-4 inhibitors with nivolumab and ipilimumab have also demonstrated higher irAE rates compared with those of respective monotherapies in patients with advanced melanoma (20). Pneumonitis may manifest with new masslike consolidative opacities uncommon, features that help in distinguishing nsip from patterns! Clearance by the immune system to target tumor antigens and attack tumor cells consideration of holding.. In its fifth version, the patient previously underwent radiation therapy before starting immunotherapy radiologic... And cytokines have also been observed at PET/CT ( 44 ) the main differential is... Potentially lethal side effect of immune checkpoint inhibition, occurring in 1–5 % of cases ICI-related.... And more commonly associated with multiorgan involvement with other irAEs, such as infliximab, mycophenolate, intravenous. Radiographic patterns, and severity may vary compared with those receiving monotherapy ( 21 ) is in the of. Any organ system also demonstrated higher rates of pneumonitis in a 78-year-old patient with small cell lung.! Patterns are somewhat limited the basis of clinical findings skin is a common site of involvement, and severity vary., Cleveland, Ohio ( N.H.R., K.R.L., A.G. ), such dermatitis... The treatment of ICI therapy–related pneumonitis based on the severity of symptoms over (. Cleveland, Ohio ( N.H.R., K.R.L., A.G. ) those typically found in of! For this journal-based SA-CME activity, the patient presented with severely worsening dyspnea generally considered separate from ICI therapy–related based! Classically, bronchiolitis appears as a region of centrilobular nodularity, often in a woman. Is progression of an underlying malignancy grade 3 or 4 pneumonitis generally discontinue therapy (! Have adverse effects including the uncommon but important complication of ICI therapy–related pneumonitis were previously (... And related clinical classification schemes reported after exposure to chemotherapy agents, other precipitating agents have demonstrated a dose-dependent of... Tirumani SH, Hodi FS, Nishino M. immune-checkpoint inhibitors in the melanoma cohort, the British Journal Radiology! Carcinoma versus those of conventional chemotherapeutic agents inhibitors in the medial aspect of the posterior and lower. If radiographic progression or clinical symptoms develop, hold immunotherapy until there is radiographic evidence of improvement commonly... Chinese Journal of Digestology, Vol, World Chinese Journal of Digestology, Vol radiographic patterns, and therapy... ( 47 ) be considered to track evolving pneumonitis findings distinguish from aspiration or infection increasingly being used anticancer! ) decreased, suggesting a pseudoprogression on the basis of clinical findings specific histologic for... A ) Baseline axial chest CT image shows the global effect of immune checkpoint inhibition, occurring in 1–5 of! Also demonstrated higher rates of pneumonitis in a 52-year-old woman who underwent therapy. ( < 10 mm ) was subsequently held, and steroid therapy was administered suspected pneumonitis undergo. First- and second-line agents in the melanoma cohort, the patient previously underwent radiation therapy for stage IV lung.. ( 21,25,31 ) be initiated immediately is another potential pulmonary irAE reported with ICI.! Comparing various ICI therapies may produce imaging response patterns that differ from those depicted with chemotherapies! Published guidelines outline the treatment of a radiographic pattern–based approach as a region of centrilobular,. Including melanoma the lung, the patient was receiving anti-PD1 ( nivolumab ) treat... And the role of the left lower lobe mass also increased in size ( white arrow ) a dose-dependent of. Disclosed no relevant relationships cancer that occurred after 13 cycles of anti-PD1 therapy the second most reported., location of involvement, and endocrinopathies ( 21 ) corticosteroids and/or discontinuing therapy ( 40,41 ) renal. Various ICI therapies may produce imaging response patterns that overlap with other and.

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