Optimizing Inpatient Care for Lung Cancer Patients with Immune Checkpoint Inhibitor- Related Pneumonitis Using a Clinical Care Pathway Algorithm

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This study aimed to assess the impact of implementing a clinical care pathway algorithm on reducing the time to treatment for ICI-P. Methods Patients with lung cancer and suspected ICI-P were enrolled, and a multi-modal intervention promoting algorithm use was implemented in two phases. Pre- and post-intervention analyses were conducted to evaluate the primary outcome of time from ICI-P diagnosis to treatment initiation. Results Of the 82 patients admitted with suspected ICI-P, 73.17% were confirmed to have ICI-P, predominantly associated with non-small cell lung cancer (91.67%) and stage IV disease (95%). Pembrolizumab was the most commonly used immune checkpoint inhibitor (55%). The mean times to treatment were 2.37 days in the pre-intervention phase and, 3.07 days ( p =0.46), and 1.27 days ( p =0.40) in the post-intervention phases 1 and 2, respectively. Utilization of the immunotoxicity order set significantly increased from 0% to 27.27% (p = 0.04) after phase 2. While there were no significant changes in ICU admissions or inpatient mortality, outpatient pulmonology follow-ups increased statistically significantly, demonstrating enhanced continuity of care. The overall mortality for patients with ICI-P was 22%, underscoring the urgency of optimizing management strategies. Notably, all patients discharged on high-dose corticosteroids received appropriate gastrointestinal prophylaxis and prophylaxis against Pneumocystis jirovecii pneumonia infections at the end of phase 2. Conclusion Implementing a clinical care pathway algorithm for ICI-P management standardizes care practices and enhances patient outcomes, underscoring the importance of structured approaches. Immune checkpoint inhibitor-related pneumonitis clinical care pathway algorithm onco-hospitalist Figures Figure 1 Figure 2 Introduction Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by activating the immune system against tumors and improving outcomes in various malignancies 1-5 . While offering promising long-term responses, ICIs can also trigger inflammatory effects collectively known as immune-related adverse events (irAEs), which are believed to arise from immunologic enhancement and disruption of normal immune-system homeostasis. These adverse events can be severe and affect any organ system, even resulting in hospitalization or fatality 6 ; irAES can occur alone or in combination (multisystem irAEs or overlap syndromes 7 ) and can develop at any time after ICI administration 8 . Managing irAEs involves several key steps including 1) identifying the irAE through a thorough medical history and physical exam; 2) promptly identifying and evaluating competing diagnoses, including disease progression, infections, or comorbidities; 3) grading the irAE on a scale from 1 to 5 (1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, and 5 = causing death) using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0 9 ; 4) consulting an organ specialist, if necessary; 5) initiating immunosuppression, usually through the use of corticosteroids; and 6) modifying the administration of the ICI according to the patient’s needs 10 . Early recognition and intervention are crucial for successful irAE management. Delayed diagnosis and treatment may lead to adverse outcomes, even death, underscoring the importance of maintaining a high suspicion index among clinicians 11 . Pneumonitis, defined as a focal or diffuse inflammation of the lung parenchyma 12 , is a potentially fatal irAE that manifests as interstitial lung disease. Immune checkpoint inhibitor–related pneumonitis (ICI-P) presents in 4 patterns: 1) organizing pneumonia, 2) nonspecific interstitial pneumonia, 3) hypersensitivity pneumonitis, and 4) diffuse alveolar damage; each has distinctive clinical, radiological, and pathological features 13 . The rates of ICI-P vary by the drug class administered and the tumor type. As monotherapies, PD-1, and PD-L1 inhibitors are associated with a higher incidence of any-grade pneumonitis (2.7%-5%) and high-grade pneumonitis (0.8%-2.0%) than CTLA-4 blockers (any-grade pneumonitis, 1.3%; high-grade pneumonitis, 0.3%). Combinations of PD-1 or PDL-1 with a CTLA-4 inhibitor can increase ICI-P rates, which approach 10% in some studies 14 . The mortality rate from ICI-P is around 10% 6 , and patients who develop ICI-P have worse survival outcomes and require more healthcare than those without ICI-P 15 . Inpatient ICI-P management needs improvement. Specific targets include the time from ICI-P diagnosis to treatment initiation; chemoprophylaxis for the complications of corticosteroid-based immunosuppression (e.g., gastrointestinal [GI] bleeding, opportunistic infections like Pneumocystis jirovecii pneumonia [PJP]) for patients on a glucocorticoid dose equivalent to 20 or more mg/day of prednisone for at least 4 weeks; and timely follow up with oncologists and organ-specific specialists (pulmonologists for the purposes of this study). With the increasing incidence of irAEs requiring hospitalization, oncology-hospitalists (physicians specialized in inpatient cancer care) 16 are at the forefront of irAE management. Clinical care pathways rooted in evidence-based knowledge enhance teamwork, standardize practices, streamline care processes, and reduce burnout risk in acute hospital settings 17,18 . While professional oncology organizations offer guidelines for irAE management, none provide a comprehensive care pathway from presentation to follow-up after hospitalization 10,14,19,20 . To address this gap, the Onco-Hospital Medicine (OHM) Service at The University of Texas MD Anderson Cancer Center developed a clinical care pathway algorithm for the inpatient management of ICI-P in lung cancer patients requiring hospitalization, mapping key phases and interventions 21 . The algorithm integrates established guidelines with practical experience, providing information on assessing, grading, and managing ICI-P 22 . It also includes a process for triaging patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as the algorithm was developed during the global coronavirus disease 19 (COVID-19) pandemic 23 . The objectives of this clinical care pathway algorithm were to increase the awareness and recognition of ICI-P, facilitate timely diagnosis and treatment, activate a multidisciplinary team for the care of patients with ICI-P, and ensure adequate follow-up after hospital discharge, ultimately leading to better patient outcomes and reduced variations in patient care 24 . In parallel with the development of the algorithm, the Institutional-led Toxicity Working Group created an inpatient immune-mediated toxicity work-up (immunotoxicity) order set with clinical orders standardizing and expediting the work-up and diagnosis of irAEs, including ICI-P. This order set was integrated into the patients’ electronic health records. The study aimed to improve the care and outcomes for lung cancer patients suspected of having ICI-P by implementing a clinical care pathway algorithm into daily hospital practice and by developing and disseminating educational materials to encourage clinical staff to use the algorithm. METHODS We conducted a retrospective cohort study of patients with lung cancer who were admitted to the OHM service at MD Anderson Cancer Center with suspicion of ICI-P from January 1, 2020, to December 31, 2022. Patients were included in the study if they 1) had at least 1 diagnosis code for neoplasm of the lung/bronchus or bronchial tree/trachea per the International Classification of Diseases, version 10 (ICD-10) 25 ; 2) had received at least 1 ICI (pembrolizumab, nivolumab, ipilimumab, durvalumab, atezolizumab; and 3) were admitted to or discharged from the OHM service during the study period. The patients’ electronic health records were used to obtain information regarding their demographics and treatments. Patients were classified as having suspected ICI-P if healthcare providers had included ICI-P as part of the differential diagnosis for the patients’ clinical presentations. ICI-P was evaluated further through diagnostic testing and/or consultation with a pulmonologist. Patients were classified as having confirmed ICI-P if there was a consensus regarding the diagnosis at the end of the hospitalization period among the patients’ healthcare providers, including oncology-hospitalists, oncologists, and pulmonologists, that the patient’s clinical presentation was ICI-P or if ICI-P therapy was initiated during hospitalization. Since ICI-P is a diagnosis of exclusion, we excluded from the study any patient with a confirmed or suspected competing diagnosis, including those with an active pulmonary infection like COVID-19, lung cancer progression, radiation-induced pneumonitis, or pneumonitis associated with another therapeutic agent such as a tyrosine-kinase inhibitor. We developed a multimodal intervention to promote the use of the clinical care pathway algorithm in the OHM service. Interventions were rolled out in 2 phases: phase 1 included educational sessions, while phase 2 included the distribution of flashcards and notepads that contained information on the clinical presentation of ICI-P and the clinical care pathway algorithm. Additionally, we sent out monthly reminder emails and developed and presented a videoclip animation of the clinical care pathway algorithm (Figures 1 and 2). The primary outcome of our study was the time to the first ICI-P treatment, i.e., the time to treatment before and after implementation of the clinical care pathway. Secondary outcomes included the ICU admission rate, inpatient mortality rate, length of stay, 30-day unplanned readmission rate, use of the immunotoxicity order set, frequency of pulmonology and oncology consultations, time to the first pulmonology and oncology consultations, use of GI and PJP prophylaxis for patients discharged on high doses of corticosteroids (a dose of prednisone or its equivalent of ≥ 20 mg/day), and time to the first post-discharge follow-up with the pulmonary and oncology services. We used descriptive statistics [frequency distribution, mean (± s.d.), and median (range)] to summarize patients’ characteristics. We used the Kruskal-Wallis test to compare the time to treatment between the pre-intervention and post-intervention phases. P-values less than 0.05 were considered statistically significant. All analyses were conducted using SAS (version 9.4, Cary, NC) software. The study was approved by the Quality Improvement Approval Board at MD Anderson. RESULTS Of the 82 patients admitted with a suspicion of ICI-P, 60 (73.17%) had confirmed ICI-P, 64 (78.05%) received an ICI, and the immunotoxicity order set was used in 10 (12.20%). Of those with confirmed ICI-P, 19 (31.67%) patients were included in the pre-intervention group (from January 1, 2020, to January 26, 2021), 30 (50.00%) were included in post-intervention phase 1 (from January 27, 2021, to January 31, 2022), and 11 (18.33%) were included in post-intervention phase 2 (from February 1, 2022, to December 31, 2022). Fifty-five (91.67%) of the patients in our cohort of patients with confirmed ICI-P had NSCLC, and 57 (95.00%) patients had stage IV disease. Thirty-five (58.33%) were men, and 47 (78.33%) were White. The mean age of the patients at admission was 66.55 years (range, 38.03-84.9 years). Pembrolizumab, a PD-1–receptor blocker, was the most-used ICI (33 [55.00%] patients), followed by the combination of ipilimumab + nivolumab (9 [15.00%] patients). Forty-eight (80.00%) patients were on active immunotherapy at the time of admission. Twenty-five (41.67%) patients had received 3 doses or less of an ICI before admission. Fifty-five (91.67%) patients presented with a respiratory complaint (e.g., dyspnea) on admission, and 13 (21.67%) had a concurrent irAE in addition to ICI-P. All patients had severe ICI-P (grade ³3 per the CTCAE, version 5.0). Fifty-nine (98.33%) patients received corticosteroids for the treatment of ICI-P, and 10 (16.67%) also received infliximab for steroid-refractory ICI-P. A pulmonology consultation was requested for 59 (98.33%) patients, and the mean time between the ICI-P diagnosis and the consultation was 2.53 days (range, 0.00-16.0 days) (Table 1). The mean time to treatment was 2.37 days (range, 0-12 days) in the pre-intervention phase, 3.07 days (range, 0-17 days) in post-intervention phase 1 ( p = 0.46 for the pre-intervention phase versus post-intervention phase 1), and 1.27 days (range, 0-6 days) in post-intervention phase 2 ( p = 0.40 for the pre-intervention phase versus post-intervention phase 2). Use of the immunotoxicity order set increased from 0% during the pre-intervention phase to 20% after phase 1 ( p = 0.07) and 27.27% after phase 2 ( p = 0.04). The percentage of patients discharged on high-dose steroids who received prescriptions for PJP prophylaxis increased from 71.43% in the pre-intervention phase to 95.24% in post-intervention phase 1 ( p = 0.13) and 100% in post-intervention phase 2 ( p = 0.13). ICU stays were needed in 42.11% of the patients in the pre-intervention phase, 26.67% of those in post-intervention phase 1 ( p = 0.35), and 27.27% of those in post-intervention phase 2 ( p = 0.47). The inpatient mortality rate was 26.32% in the pre-intervention phase, 16.67% in post-intervention phase 1 ( p = 0.48), and 18.18% in post-intervention phase 2 ( p = 1.00) (Table 2). There were no statistically significant changes in the overall ICU admission or inpatient mortality rates from the pre-intervention phase to the post-intervention phases 1 and 2 ( p = 0.5 and p = 0.6, respectively). Of the 48 patients discharged alive (Table 3), 41 (85.42%) were on a glucocorticoid dose equivalent to ³ 20 mg/day of prednisone; all of these patients were also on GI prophylaxis with a proton-pump inhibitor or a histamine type-2-receptor antagonist, and all were prescribed PJP prophylaxis. Outpatient follow-up with an oncologist was documented in 35 (72.92%) patients, and the median time to first oncology follow-up was 20.0 days. Outpatient follow-up with a pulmonologist increased significantly from 23.1% in the pre-intervention phase to 64% in post-intervention phase 1 ( p = 0.0382) and 100% in post-intervention phase 2 ( p = 0.0031), with an overall p -value of 0.0030. The median time to first follow-up with a pulmonologist was 18.5 days. DISCUSSION To our knowledge, this is the first study to evaluate the effectiveness of a clinical care pathway for managing ICI-P in hospitalized patients with lung cancer. The study shows a reduction in the time to initiate ICI-P treatment in this patient population. Additionally, we have increased the usage of the immunotoxicity order set in the electronic health records. Our comprehensive, multimodal intervention played a vital role in encouraging healthcare providers to use the order set. Although the observed change did not reach statistical significance, we believe this approach is a pioneering and unique effort in the field. In cases where grade 3 or 4 pneumonitis leads to hypoxia or respiratory compromise, hospitalization is required as it can be life-threatening 26-28 . Guidelines for diagnosing and managing irAEs recommend multidisciplinary consultation, high doses of oral or intravenous corticosteroids, and discontinuation of ICI therapy 29-31 . In our study, 91.67% of confirmed ICI-P patients had NSCLC, and 95% had stage IV. Pembrolizumab was the most common ICI (55%). Glucocorticoids were frequently used (98.33%), while second-line immunosuppressants were rare. This could be due to the low incidence of steroid-refractory ICI-P or hesitancy to initiate advanced immunosuppression without a clearly preferred approach to immunosuppressive therapy. Steroid-refractory ICI-P, an often-fatal clinical phenomenon with poorly understood incidence 32,33 , was identified in 10 (16.67%) patients in our cohort, necessitating escalation to infliximab, a tumor necrosis factor-alpha inhibitor that reduces inflammation and alters the immune response. A systematic review of 159 studies involving 33,253 patients showed that using glucocorticoids increased the risk of GI bleeding and perforation 34 . Consequently, best-practice guidelines recommend acid suppression for patients at risk of GI bleeding 35 . Within our patient cohort, those discharged while receiving a glucocorticoid dose equal to or greater than 20 mg/day of prednisone were given GI prophylaxis in either a proton-pump inhibitor or a histamine type-2 receptor antagonist. Similarly, all these patients received PJP prophylaxis. Thus, our study’s interventions helped ensure compliance with the recommended best practices to prevent GI complications and opportunistic infections while on glucocorticoids 36 . We observed no significant changes in ICU admissions or inpatient mortality from the pre-intervention phase to the post-intervention phases 1 and 2 (p = 0.5 and p = 0.6, respectively). The overall mortality rate for patients with ICI-P was 22%, which is higher than the typically reported mortality rate of approximately 10% in the literature 37 . However, our findings are consistent with those of a real-world cohort investigation involving 315 patients with lung cancer who were treated with ICIs in 6 healthcare centers (1 academic center, 1 community referral center, and 4 community centers) within the University of North Carolina network. This study reported an ICI-P incidence rate of 9.5%, with 60% of patients requiring hospitalization for ICI-P management. The risk of mortality within this patient subset was 32% 38 . Therefore, our findings and those of the aforementioned study suggest that ICI-P is more common and severe than previously reported, and it carries an unexpectedly high mortality rate. Our study's interventions resulted in more timely follow-up appointments with the oncology and pulmonology services. It is worth noting that the project and data collection took place during the peak of the COVID-19 pandemic, which posed significant challenges. Clinical presentation and radiological findings of ICI-P and SARS-CoV-2 can be quite similar; patients with respiratory symptoms needed to be isolated until their SARS-CoV-2 tests were available, causing delays in ICI-P diagnosis and treatment. Moreover, the widespread prevalence of COVID-19 pneumonia created a diagnostic bias, as it was the leading differential diagnosis in most patients with respiratory symptoms. The study had a limitation in that it relied on billing codes and other coded data to identify ICI-P. This is because there are no specific ICD-10 codes available for the disease. To identify potential cases of ICI-P for the incidence analysis, broad codes were used intentionally. This was because clinicians often use various codes when faced with an uncertain diagnosis of ICI-P. Bronchoscopy, which is recommended in irAE management guidelines, is infrequently used in severe ICI-P cases because patients may be clinically unstable and unable to undergo an invasive procedure under anesthesia. Unfortunately, none of the patients in our cohort could undergo diagnostic bronchoscopy due to their clinical instability. The primary value of invasive bronchoscopy is identifying alternative etiologies for the patient’s symptoms (e.g., disease progression, infectious pneumonia) 39 . Noninvasive alternatives like diagnostic biomarkers for ICI-P may be preferable but remain elusive. Future studies of ICI-P should focus on describing its clinical features more accurately and optimizing its diagnostic algorithms, given the current lack of a gold standard for diagnosis. CONCLUSION This study provides valuable insights into the management and outcomes of patients with lung cancer who exhibit symptoms of ICI-P (Immune Checkpoint Inhibitor-Related Pneumonitis). It emphasizes the critical role of onco-hospitalists in managing severe cases of ICI-P that require hospitalization. By implementing a clinical care pathway algorithm based on evidence, the variability in the time taken to administer treatment was reduced, and there was a significant increase in the use of the immunotoxicity order set. Consequently, the implementation led to the standardization of clinical care. Importantly, the study underscores the feasibility of implementing best practices in patient care even outside the confines of comprehensive cancer centers, making these practices relevant and applicable to nononcologists and healthcare practitioners in diverse clinical contexts. At our institution, continual educational efforts to bolster adherence to the established care pathway algorithm and enhance patient outcomes will be imperative. STATEMENTS AND DECLARATIONS Acknowledgment of research support : This work was funded by the Division of Internal Medicine Research and Quality Improvement Development Award at the University of Texas MD Anderson Cancer Center. This project is partly supported by the National Institutes of Health/National Cancer Institute under the award number P30CA 016672. ACKNOWLEDGMENTS We thank Laura L. Russell, Scientific Editor of the Research Medical Library at MD Anderson Cancer Center, for editing this article. Funding This work was funded by the Division of Internal Medicine Research and Quality Improvement Development Award at the University of Texas MD Anderson Cancer Center. This project is partly supported by the National Institutes of Health/National Cancer Institute under the award number P30CA 016672. Competing Interests Maggie Lu has the following declarations outside the submitted work: holds stock with Amgen. All other authors have no relevant financial or non-financial interests to disclose. Author Contributions Study concept and design : Joanna-Grace M Manzano MD MPH, Maggie Lu PharmD, Maria Franco-Vega MD, Norman Brito-Dellan MD. Data collection: All authors Statistical analysis and interpretation : Heather Y. Lin Ph.D., Joanna-Grace M Manzano MD MPH, Juan Ignacio Ruiz MD, Norman Brito-Dellan MD, Christine B Peterson Ph.D. Data analysis and interpretation: All authors. Manuscript preparation and final approval: Norman Brito-Dellan, MD, wrote the first draft of the manuscript, and all authors commented on previous versions. All authors read and approved the final manuscript. Ethics approval This is a quality improvement study, which was approved by the Quality Improvement Approval Board (QIAB) at MD Anderson Cancer Center. Ethical approval was not required by the reviewing/approving body. Consent to participate Not applicable. Consent for publication Not applicable. There is no patient-identifiable data in this publication. References Zimmermann S, Peters S, Owinokoko T, Gadgeel SM: Immune checkpoint inhibitors in the management of lung cancer. American Society of Clinical Oncology Educational Book 38:682-695, 2018 Ruffo E, Wu RC, Bruno TC, et al: Lymphocyte-activation gene 3 (LAG3): The next immune checkpoint receptor, Seminars in immunology, Elsevier, 2019, pp 101305 Kroemer G, Zitvogel L: Immune checkpoint inhibitors. Journal of Experimental Medicine 218, 2021 Onoi K, Chihara Y, Uchino J, et al: Immune checkpoint inhibitors for lung cancer treatment: a review. Journal of clinical medicine 9:1362, 2020 Armstrong SA, Liu SV: Immune checkpoint inhibitors in small cell lung cancer: a partially realized potential. Advances in Therapy 36:1826-1832, 2019 Wang DY, Salem J-E, Cohen JV, et al: Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA oncology 4:1721-1728, 2018 Moreira A, Loquai C, Pföhler C, et al: Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors. European Journal of Cancer 106:12-23, 2019 Postow MA, Sidlow R, Hellmann MD: Immune-related adverse events associated with immune checkpoint blockade. New England Journal of Medicine 378:158-168, 2018 Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, 2017. https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf. Accessed May 12, 2023. Thompson JA, Schneider BJ, Brahmer J, et al: Management of Immunotherapy-Related Toxicities, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network 17:255-289, 2019 Porcu M, De Silva P, Solinas C, et al: Immunotherapy associated pulmonary toxicity: biology behind clinical and radiological features. Cancers 11:305, 2019 Disayabutr S, Calfee CS, Collard HR, Wolters PJ: Interstitial lung diseases in the hospitalized patient. BMC medicine 13:245, 2015 Zhong L, Altan M, Shannon VR, Sheshadri A: Immune-Related Adverse Events: Pneumonitis, Immunotherapy, Springer, 2020, pp 255-269 Shannon VR, Anderson R, Blidner A, et al: Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune-related adverse events: pulmonary toxicity. Supportive Care in Cancer 28:6145-6157, 2020 Tiu BC, Zubiri L, Iheke J, et al: Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study. Journal for immunotherapy of cancer 10, 2022 Chen EJ: Being an Oncology Hospitalist. Hospital Medicine Clinics 5:335-346, 2016 Lodewijckx C, Decramer M, Sermeus W, et al: Eight-step method to build the clinical content of an evidence-based care pathway: the case for COPD exacerbation. Trials 13:229, 2012 Deneckere S, Euwema M, Lodewijckx C, et al: Better interprofessional teamwork, higher level of organized care, and lower risk of burnout in acute health care teams using care pathways: a cluster randomized controlled trial. Medical care:99-107, 2013 Brahmer JR, Lacchetti C, Schneider BJ, et al: Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 36:1714, 2018 Haanen J, Carbonnel F, Robert C, et al: Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 28:iv119-iv142, 2017 Rotter T, de Jong RB, Lacko SE, et al: Clinical pathways as a quality strategy. Improving healthcare quality in Europe:309, 2019 Wood LS: Immune-related adverse events from immunotherapy: Incorporating Care Step Pathways to improve management across tumor types. Journal of the advanced practitioner in oncology 10:47, 2019 Naidoo J, Reuss JE, Suresh K, et al: Immune-related (IR)-pneumonitis during the COVID-19 pandemic: multidisciplinary recommendations for diagnosis and management. Journal for immunotherapy of cancer 8, 2020 Middleton S, Barnett J, Reeves DS: What is an integrated care pathway?, Hayward Medical Communications, 2001 World Health Organization. International statistical classification of diseases and related health problems (10th ed.). 2019 Chuzi S, Tavora F, Cruz M, et al: Clinical features, diagnostic challenges, and management strategies in checkpoint inhibitor-related pneumonitis. Cancer management and research 9:207, 2017 Shannon VR: Pneumotoxicity associated with immune checkpoint inhibitor therapies. Current opinion in pulmonary medicine 23:305-316, 2017 Naidoo J, Wang X, Woo KM, et al: Pneumonitis in patients treated with anti–programmed death-1/programmed death ligand 1 therapy. Journal of Clinical Oncology 35:709, 2017 Weber JS, Kähler KC, Hauschild A: Management of immune-related adverse events and kinetics of response with ipilimumab. Journal of Clinical Oncology 30:2691-2697, 2012 Thompson JA, Schneider BJ, Brahmer J, et al: NCCN guidelines insights: management of immunotherapy-related toxicities, version 1.2020: featured updates to the NCCN guidelines. Journal of the National Comprehensive Cancer Network 18:230-241, 2020 Puzanov I, Diab A, Abdallah K, et al: Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. Journal for immunotherapy of cancer 5:1-28, 2017 Camard M, Besse B, Cariou P-L, et al: Prevalence and outcome of steroid-resistant/refractory pneumonitis induced by immune checkpoint inhibitors. Respiratory Medicine and Research 82:100969, 2022 Balaji A, Hsu M, Lin CT, et al: Steroid-refractory PD-(L) 1 pneumonitis: incidence, clinical features, treatment, and outcomes. Journal for immunotherapy of cancer 9, 2021 Narum S, Westergren T, Klemp M: Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ open 4:e004587, 2014 Cook D, Guyatt G: Prophylaxis against upper gastrointestinal bleeding in hospitalized patients. New England Journal of Medicine 378:2506-2516, 2018 Shah NJ, Cook MR, Wu T, et al: The Risk of Opportunistic Infections and the Role of Antibiotic Prophylaxis in Patients on Checkpoint Inhibitors Requiring Steroids. Journal of the National Comprehensive Cancer Network 20:800-807. e1, 2022 Zhai X, Zhang J, Tian Y, et al: The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients. Cancer Biology & Medicine 17:599, 2020 Atchley WT, Alvarez C, Saxena-Beem S, et al: Immune checkpoint inhibitor-related pneumonitis in lung cancer: real-world incidence, risk factors, and management practices across six health care centers in North Carolina. Chest 160:731-742, 2021 Cho JY, Kim J, Lee JS, et al: Characteristics, incidence, and risk factors of immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer. Lung Cancer 125:150-156, 2018 Tables Table 1. Patients’ characteristics. Characteristic Patients with suspected ICI-P n = 82 Patients with confirmed ICI-P n = 60 Age at admission in years, mean (SD) 66.36 (11.28) 66.55 (12.14) Intervention phase, n (%) Pre-intervention 22 (26.83) 19 (31.67) Post-intervention 1 36 (43.90) 30 (50.00) Post-intervention 2 24 (29.27) 11 (18.33) Consensus on ICI-P diagnosis, n (%) 60 (73.17) N/A Sex, n (%) Men 48 (58.54) 35 (58.33) Women 34 (41.46) 25 (41.67) Race, n (%) American Indian * 1 (1.22) 1 (1.67) Asian 5 (6.10) 5 (8.33) Black + 5 (6.10) 3 (5.00) White 66 (80.49) 47 (78.33) Other ^ 5 (6.10) 4 (6.67) Ethnicity, n (%) Hispanic or Latino 10 (12.20) 7 (11.67) Not Hispanic or Latino 71 (86.59) 53 (88.33) Declined to answer 1 (1.22) - Lung cancer type, n (%) NSCLS 73 (89.02) 55 (91.67) SCLC 9 (10.98) 5 (8.33) Cancer stage at admission, n (%) Stage III 10 (12.20) 3 (5.00) Stage IV 72 (87.80) 57 (95.00) Active treatment with ICI, n (%) 64 (78.05) 48 (80.00) Type of ICI, n (%) Atezolizumab 11 (13.41) 7 (11.67) Durvalumab 11 (13.41) 7 (11.67) Durvalumab + tremelimumab 2 (2.44) 1 (1.67) Ipilimumab + nivolumab 15 (18.29) 9 (15.00) Nivolumab 4 (4.88) 3 (5.00) Pembrolizumab 39 (47.56) 33 (55.00) Number of ICI doses received before admission, n (%) ≤ 3 36 (43.90) 25 (41.67) 4-6 21 (25.61) 15 (25.00) 7-9 8 (9.76) 6 (10.00) ≥ 10 17 (20.73) 14 (23.33) First line of ICI therapy, n (%) 66 (80.49) 45 (75.00) Respiratory complaint on admission, n (%) 71 (86.59) 55 (91.67) Use of immunotoxicity order set, n (%) 10 (12.20) 9 (15.00) ICI, immune checkpoint inhibitor; ICI-P, immune checkpoint inhibitor–related pneumonitis; ICU, intensive care unit; N/A, not applicable; NSCLS, non-small cell lung cancer; SCLC, small cell lung cancer; SD, standard deviation. * Including Alaska Natives. + Including African Americans. ^ Including self-reported mixed races and other races not otherwise specified Of the 60 patients with confirmed ICI-P, 59 (98.33%) patients received corticosteroids for the treatment of ICI-P, and 10 (16.67%) also received infliximab for steroid-refractory ICI-P. Pulmonology was consulted in 59 (98.33%) patients, and the mean time between the ICI-P diagnosis and the consultation was 2.53 days (range, 0.00-16.0 days). Oncology was consulted in 37 (61.67%) patients. Table 2. Patient characteristics by intervention phase among patients with confirmed ICI-P (N= 60). Characteristic Pre-intervention phase Post-intervention phase 1 p -value (post-intervention phase 1 versus pre-intervention phase) Post-intervention phase 2 p -value (post-intervention phase 2 versus pre-intervention phase) Time to treatment of ICI-P in days, mean (min-max) 2.37 (0-12) 3.07 (0-17) 0.46 1.27 (0-6) 0.40 Use of immunotoxicity order set (N = 60), n (%) 0/19 (0.00) 6/30 (20.00) 0.07 3/11 (27.27) 0.04 ICU stay (N = 60), n (%) 8/19 (42.11) 8/30 (26.67) 0.35 3/11 (27.27) 0.47 Inpatient mortality (N = 60), n (%) 5/19 (26.32) 5/30 (16.67) 0.48 2/11 (18.18) 1.00 Length of hospital stay in days, mean (min-max) 17.68 (2-41) 12.60 (3-28) 0.0418 13.82 (3-38) 0.2037 Pulmonology consultation, n (%) 18/19 (94.74) 30/30 (100) 0.3878 11/11 (100) 1.00 Primary Oncology consultation, n (%) 10/14 (71.43) 12/25(48.00) 0.1935 3/9 (33.33) 0.1023 Discharged with PPI/H2 blockers if on steroids (N = 45*), n (%) 12/12 (100) 19/23 (82.61) 0.29 9/9 (100) N/A Discharged with PJP prophylaxis if on steroids (≥ 20 mg/day prednisone) (N = 46*), n (%) 10/14 (71.43) 20/21 (95.24) 0.13 9/9 (100) 0.13 Readmission (N = 12 + ), n (%) 5/14 (35.71) 5/23 (21.74) 0.4537 2/8 (25.00) 1.000 30-day mortality (N = 48), n (%) 3/14 (21.43) 7/25 (28.00) 0.7212 1/9(11.11) 1.0000 Follow-up pulmonology appointment arranged if treated for ICI-P, n (%) 7/14 (50.00) 19/25(76.00) 0.1574 8/9 (88.9) 0.0858 Patient received outpatient pulmonology follow-up, n (%) 3/13 (23.10) 16/25 (64.00) 0.0382 6/6 (100) 0.0031 Time to first pulmonology follow-up in days, mean (min-max) 43.44 (4-111) 24.16 (1-99) 0.3757 32.75 (5-110) 0.8097 Time to first oncology follow-up in days, mean (min-max) 43.44 (4-111) 25.00 (1-99) 0.3958 32.75 (5-110) 0.8097 H2, histamine type-2 receptor; ICI-P, immune checkpoint inhibitor–related pneumonitis; ICU, intensive care unit; max, maximum; min, minimum; PJP, Pneumocystis jirovecii pneumonia; PPI, proton-pump inhibitor. *One patient in the pre-intervention phase had missing data on PPI use, and 2 patients (1 in the pre-intervention phase and 1 in the post-intervention phase) had missing data on prednisone use. + Of the 48 patients alive at discharge, 12 (25.00%) patients were readmitted within 30 days (all cause-readmissions). No data were available for 3 (6.25%) of the 48 patients. Table 3. Inpatient mortality and discharge dispositions for patients with confirmed ICI-P (N = 60). Patient outcome n (%) Died as inpatient 12 (20.00) Discharged 48 (80.00) To home without home health or physical therapy services 25 (52.08) To home with home health or physical therapy services 9 (18.75) To skilled nursing facility 7 (14.58) To home with hospice services 4 (8.33) To acute care hospital 1 (2.08) To another health care institution 1 (2.08) To a rehabilitation facility 1 (2.08) ICI-P, immune checkpoint inhibitor–related pneumonitis. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 16 Sep, 2024 Read the published version in Supportive Care in Cancer → Version 1 posted Editorial decision: Revision requested 22 Jun, 2024 Reviews received at journal 17 Jun, 2024 Reviewers agreed at journal 17 Jun, 2024 Reviews received at journal 13 Jun, 2024 Reviewers agreed at journal 01 Jun, 2024 Reviewers agreed at journal 16 May, 2024 Reviewers invited by journal 14 May, 2024 Editor assigned by journal 13 May, 2024 Submission checks completed at journal 08 Apr, 2024 First submitted to journal 02 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4209489","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":288881508,"identity":"cbd4c831-aafc-4f39-8ab9-c15653e4dabf","order_by":0,"name":"Norman Brito-Dellan","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIie3OsQqCQBzH8X8cOElzYPgMF0IiRC/SFEJT1+wkQdBUzUk9hA/Q8JcDXSzXA1tamhoMGhoaEmkLDt0i7jv8p/vwOwCV6hfrACDAoLqd+gRh0pCUr3kDYhvrCy+8bNROjpG4H3zTBhLfHxLi7BOKmOYsSGeus71yy5lr7q4rIVRMAKNlzkKc9g0dcRyibhHZFz/kxMLs1jde6NcmyEJRrgCSirQKGTnHgGnqskDcLGeF3KJcc4lEAM2XpPC8Idtk0554om/SZMFbT5n5rpwgejNS1nRFpVKp/rs3oIda1/FJcx4AAAAASUVORK5CYII=","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":true,"prefix":"","firstName":"Norman","middleName":"","lastName":"Brito-Dellan","suffix":""},{"id":288881511,"identity":"cdcecfd2-4c0d-4920-b95b-1e4209fa8057","order_by":1,"name":"Maria Cecilia Franco-Vega","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Cecilia","lastName":"Franco-Vega","suffix":""},{"id":288881514,"identity":"5e717bfb-01d2-4fb4-b092-10adbd02905d","order_by":2,"name":"Juan Ignacio Ruiz","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Juan","middleName":"Ignacio","lastName":"Ruiz","suffix":""},{"id":288881516,"identity":"54587d4a-c9e6-4d4b-8a6f-220d1a332979","order_by":3,"name":"Maggie Lu","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Maggie","middleName":"","lastName":"Lu","suffix":""},{"id":288881518,"identity":"3bc6bb21-20e4-411d-b37f-4ec151aa5ace","order_by":4,"name":"Hadeel Sahar","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Hadeel","middleName":"","lastName":"Sahar","suffix":""},{"id":288881519,"identity":"f5744243-9fec-45f4-8d7b-bc858b6fbf10","order_by":5,"name":"Pramuditha Rajapakse","email":"","orcid":"","institution":"University of Massachusetts Chan Medical School","correspondingAuthor":false,"prefix":"","firstName":"Pramuditha","middleName":"","lastName":"Rajapakse","suffix":""},{"id":288881520,"identity":"524853c2-e2e7-468d-87fe-ac82d466c2e8","order_by":6,"name":"Heather Y. Lin","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Heather","middleName":"Y.","lastName":"Lin","suffix":""},{"id":288881521,"identity":"4dc28cb9-6c2f-47dc-becf-5ae7814d1acc","order_by":7,"name":"Christine Peterson","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Christine","middleName":"","lastName":"Peterson","suffix":""},{"id":288881522,"identity":"9dc6fae7-2bec-4056-b389-c9290cd90e89","order_by":8,"name":"Daniel Leal Alviarez","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"Leal","lastName":"Alviarez","suffix":""},{"id":288881523,"identity":"3dc62944-eda6-4f8b-95d1-e50805bd461f","order_by":9,"name":"Haider Altay","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Haider","middleName":"","lastName":"Altay","suffix":""},{"id":288881524,"identity":"c963ea0e-92c0-432f-b3eb-1081110adf4a","order_by":10,"name":"Sophy Tomy","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Sophy","middleName":"","lastName":"Tomy","suffix":""},{"id":288881525,"identity":"d148a469-b71c-4abb-9760-cc073f18700d","order_by":11,"name":"Joanna-Grace Mayo Manzano","email":"","orcid":"","institution":"The University of Texas MD Anderson Cancer Center","correspondingAuthor":false,"prefix":"","firstName":"Joanna-Grace","middleName":"Mayo","lastName":"Manzano","suffix":""}],"badges":[],"createdAt":"2024-04-03 02:52:09","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4209489/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4209489/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00520-024-08867-8","type":"published","date":"2024-09-16T15:57:01+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":54596507,"identity":"d495b1c1-5ca0-4bb0-a290-73628a945dfd","added_by":"auto","created_at":"2024-04-12 19:04:48","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":95483,"visible":true,"origin":"","legend":"\u003cp\u003eTimeline of interventions\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-4209489/v1/5c397a0b16584fc69189234e.png"},{"id":54596508,"identity":"78f3ca94-aa28-4230-9370-bed305378ce6","added_by":"auto","created_at":"2024-04-12 19:04:48","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":2087328,"visible":true,"origin":"","legend":"\u003cp\u003eMultimodal interventions\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-4209489/v1/57f61af8a570168516905ec5.png"},{"id":65103896,"identity":"c6895e00-f3fe-48e4-b553-ae140f17527b","added_by":"auto","created_at":"2024-09-23 16:09:10","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2644011,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4209489/v1/6e800631-ab6c-4237-a237-62a8e59df1fa.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Optimizing Inpatient Care for Lung Cancer Patients with Immune Checkpoint Inhibitor- Related Pneumonitis Using a Clinical Care Pathway Algorithm","fulltext":[{"header":"Introduction","content":"\u003cp\u003eImmune checkpoint inhibitors (ICIs) have revolutionized cancer treatment by activating the immune system against tumors and improving outcomes in various malignancies\u0026nbsp;\u003csup\u003e1-5\u003c/sup\u003e. While offering promising long-term responses, ICIs can also trigger inflammatory effects collectively known as immune-related adverse events (irAEs), which are believed to arise from immunologic enhancement and disruption of normal immune-system homeostasis. These adverse events can be severe and affect any organ system, even resulting in hospitalization or fatality\u003csup\u003e6\u003c/sup\u003e; irAES can occur alone or in combination (multisystem irAEs or overlap syndromes\u003csup\u003e7\u003c/sup\u003e) and can develop at any time after ICI administration\u003csup\u003e8\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eManaging irAEs involves several key steps including 1) identifying the irAE through a thorough medical history and physical exam; 2) promptly identifying and evaluating competing diagnoses, including disease progression, infections, or comorbidities; 3) grading the irAE on a scale from 1 to 5 (1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, and 5 = causing death) using the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE), version 5.0\u003csup\u003e9\u003c/sup\u003e; 4) consulting an organ specialist, if necessary; 5) initiating immunosuppression, usually through the use of corticosteroids; and 6) modifying the administration of the ICI according to the patient’s needs\u003csup\u003e10\u003c/sup\u003e. Early recognition and intervention are crucial for successful irAE management. Delayed diagnosis and treatment may lead to adverse outcomes, even death, underscoring the importance of maintaining a high suspicion index among clinicians\u003csup\u003e11\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ePneumonitis, defined as a focal or diffuse inflammation of the lung parenchyma\u003csup\u003e12\u003c/sup\u003e, is a potentially fatal irAE that manifests as interstitial lung disease. Immune checkpoint inhibitor–related pneumonitis (ICI-P) presents in 4 patterns: 1) organizing pneumonia, 2) nonspecific interstitial pneumonia, 3) hypersensitivity pneumonitis, and 4) diffuse alveolar damage; each has distinctive clinical, radiological, and pathological features\u003csup\u003e13\u003c/sup\u003e. \u0026nbsp;The rates of ICI-P vary by the drug class administered and the tumor type. As monotherapies, PD-1, and PD-L1 inhibitors are associated with a higher incidence of any-grade pneumonitis (2.7%-5%) and high-grade pneumonitis (0.8%-2.0%) than CTLA-4 blockers (any-grade pneumonitis, 1.3%; high-grade pneumonitis, 0.3%). Combinations of PD-1 or PDL-1 with a CTLA-4 inhibitor can increase ICI-P rates, which approach 10% in some studies\u003csup\u003e14\u003c/sup\u003e. The mortality rate from ICI-P is around 10%\u003csup\u003e6\u003c/sup\u003e, and patients who develop ICI-P have worse survival outcomes and require more healthcare than those without ICI-P\u003csup\u003e15\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eInpatient ICI-P management needs improvement. Specific targets include the time from ICI-P diagnosis to treatment initiation; chemoprophylaxis for the complications of corticosteroid-based immunosuppression (e.g., gastrointestinal [GI] bleeding, opportunistic infections like \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e pneumonia [PJP]) for patients on a glucocorticoid dose equivalent to 20 or more mg/day of prednisone for at least 4 weeks; and timely follow up with oncologists and organ-specific specialists (pulmonologists for the purposes of this study).\u003c/p\u003e\n\u003cp\u003eWith the increasing incidence of irAEs requiring hospitalization, oncology-hospitalists (physicians specialized in inpatient cancer care)\u003csup\u003e16\u003c/sup\u003e are at the forefront of irAE management. Clinical care pathways rooted in evidence-based knowledge enhance teamwork, standardize practices, streamline care processes, and reduce burnout risk in acute hospital settings\u003csup\u003e17,18\u003c/sup\u003e. While professional oncology organizations offer guidelines for irAE management, none provide a comprehensive care pathway from presentation to follow-up after hospitalization\u003csup\u003e10,14,19,20\u003c/sup\u003e. To address this gap, the Onco-Hospital Medicine (OHM) Service at The University of Texas MD Anderson Cancer Center developed a clinical care pathway algorithm for the inpatient management of ICI-P in lung cancer patients requiring hospitalization,\u0026nbsp;mapping key phases and interventions\u003csup\u003e21\u003c/sup\u003e.\u0026nbsp;The algorithm integrates established guidelines with practical experience, providing information on assessing, grading, and managing ICI-P\u003csup\u003e22\u003c/sup\u003e. It also includes\u0026nbsp;a process for triaging patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as the algorithm was developed during the global coronavirus disease 19 (COVID-19) pandemic\u003csup\u003e23\u003c/sup\u003e. The objectives of this clinical care pathway algorithm were to increase the awareness and recognition of ICI-P, facilitate timely diagnosis and treatment, activate a multidisciplinary team for the care of patients with ICI-P, and ensure adequate follow-up after hospital discharge, ultimately leading to better patient outcomes and reduced variations in patient care\u003csup\u003e24\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eIn parallel with the development of the algorithm, the Institutional-led Toxicity Working Group created an inpatient immune-mediated toxicity work-up (immunotoxicity) order set with clinical orders standardizing and expediting the work-up and diagnosis of irAEs, including ICI-P. This order set was integrated into the patients’ electronic health records.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study aimed to improve the care and outcomes for lung cancer patients suspected of having ICI-P by implementing a clinical care pathway algorithm into daily hospital practice and by developing and disseminating educational materials to encourage clinical staff to use the algorithm.\u003c/p\u003e"},{"header":" METHODS","content":"\u003cp\u003eWe conducted a retrospective cohort study of patients with lung cancer who were admitted to the OHM service at MD Anderson Cancer Center with suspicion of ICI-P from January 1, 2020, to December 31, 2022. Patients were included in the study if they 1) had at least 1 diagnosis code for neoplasm of the lung/bronchus or bronchial tree/trachea per the International Classification of Diseases, version 10 (ICD-10)\u003csup\u003e25\u003c/sup\u003e; 2) had received at least 1 ICI (pembrolizumab, nivolumab, ipilimumab, durvalumab, atezolizumab; and 3) were admitted to or discharged from the OHM service during the study period.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe patients’ electronic health records were used to obtain information regarding their demographics and treatments. Patients were classified as having suspected ICI-P if healthcare providers had included ICI-P as part of the differential diagnosis for the patients’ clinical presentations. ICI-P was evaluated further through diagnostic testing and/or consultation with a pulmonologist. Patients were classified as having confirmed ICI-P if there was a consensus regarding the diagnosis at the end of the hospitalization period among the patients’ healthcare providers, including oncology-hospitalists, oncologists, and pulmonologists, that the patient’s clinical presentation was ICI-P or if ICI-P therapy was initiated during hospitalization. Since ICI-P is a diagnosis of exclusion, we excluded from the study any patient with a confirmed or suspected competing diagnosis, including those with an active pulmonary infection like COVID-19, lung cancer progression, radiation-induced pneumonitis, or pneumonitis associated with another therapeutic agent such as a tyrosine-kinase inhibitor.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe developed a multimodal intervention to promote the use of the clinical care pathway algorithm in the OHM service. Interventions were rolled out in 2 phases: phase 1 included educational sessions, while phase 2 included the distribution of flashcards and notepads that contained information on the clinical presentation of ICI-P and the clinical care pathway algorithm. Additionally, we sent out monthly reminder emails and developed and presented a videoclip animation of the clinical care pathway algorithm (Figures 1 and 2). The primary outcome of our study was the time to the first ICI-P treatment, i.e., the time to treatment before and after implementation of the clinical care pathway. Secondary outcomes included the ICU admission rate, inpatient mortality rate, length of stay, 30-day unplanned readmission rate, use of the immunotoxicity order set, frequency of pulmonology and oncology consultations, time to the first pulmonology and oncology consultations, use of GI and PJP prophylaxis for patients discharged on high doses of corticosteroids (a dose of prednisone or its equivalent of\u0026nbsp;≥\u0026nbsp;20 mg/day), and time to the first post-discharge follow-up with the pulmonary and oncology services.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe used descriptive statistics [frequency distribution, mean (± s.d.), and median (range)] to summarize patients’ characteristics. We used the Kruskal-Wallis test to compare the time to treatment between the pre-intervention and post-intervention phases. P-values less than 0.05 were considered statistically significant. All analyses were conducted using SAS (version 9.4, Cary, NC) software. \u0026nbsp; The study was approved by the Quality Improvement Approval Board at MD Anderson.\u0026nbsp;\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eOf the 82 patients admitted with a suspicion of ICI-P, 60 (73.17%) had confirmed ICI-P, 64 (78.05%) received an ICI, and the immunotoxicity order set was used in 10 (12.20%).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOf those with confirmed ICI-P, 19 (31.67%) patients were included in the pre-intervention group (from January 1, 2020, to January 26, 2021), 30 (50.00%) were included in post-intervention phase 1 (from January 27, 2021, to January 31, 2022), and 11 (18.33%) were included in post-intervention phase 2 (from February 1, 2022, to December 31, 2022). Fifty-five (91.67%) of the patients in our cohort of patients with confirmed ICI-P had NSCLC, and 57 (95.00%) patients had stage IV disease. Thirty-five (58.33%) were men, and 47 (78.33%) were White. The mean age of the patients at admission was 66.55 years (range, 38.03-84.9 years). Pembrolizumab, a PD-1–receptor blocker, was the most-used ICI (33 [55.00%] patients), followed by the combination of ipilimumab + nivolumab (9 [15.00%] patients). Forty-eight (80.00%) patients were on active immunotherapy at the time of admission. Twenty-five (41.67%) patients had received 3 doses or less of an ICI before admission. Fifty-five (91.67%) patients presented with a respiratory complaint (e.g., dyspnea) on admission, and 13 (21.67%) had a concurrent irAE in addition to ICI-P. All patients had severe ICI-P (grade\u0026nbsp;³3 per the CTCAE, version 5.0). Fifty-nine (98.33%) patients received corticosteroids for the treatment of ICI-P, and 10 (16.67%) also received infliximab for steroid-refractory ICI-P. A pulmonology consultation was requested for 59 (98.33%) patients, and the mean time between the ICI-P diagnosis and the consultation was 2.53 days (range, 0.00-16.0 days) (Table 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe mean time to treatment was 2.37 days (range, 0-12 days) in the pre-intervention phase, 3.07 days (range, 0-17 days) in post-intervention phase 1 (\u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.46 for the pre-intervention phase versus post-intervention phase 1), and 1.27 days (range, 0-6 days) in post-intervention phase 2 (\u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.40 for the pre-intervention phase versus post-intervention phase 2). Use of the immunotoxicity order set increased from 0% during the pre-intervention phase to 20% after phase 1 (\u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.07) and 27.27% after phase 2 (\u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.04). The percentage of patients discharged on high-dose steroids who received prescriptions for PJP prophylaxis increased from 71.43% in the pre-intervention phase to 95.24% in post-intervention phase 1 (\u003cem\u003ep\u003c/em\u003e = 0.13) and 100% in post-intervention phase 2 (\u003cem\u003ep\u003c/em\u003e = 0.13). ICU stays were needed in 42.11% of the patients in the pre-intervention phase, 26.67% of those in post-intervention phase 1 (\u003cem\u003ep\u003c/em\u003e = 0.35), and 27.27% of those in post-intervention phase 2 (\u003cem\u003ep\u003c/em\u003e = 0.47). The inpatient mortality rate was 26.32% in the pre-intervention phase, 16.67% in post-intervention phase 1 (\u003cem\u003ep\u003c/em\u003e = 0.48), and 18.18% in post-intervention phase 2 (\u003cem\u003ep\u003c/em\u003e = 1.00) (Table 2). There were no statistically significant changes in the overall ICU admission or inpatient mortality rates from the pre-intervention phase to the post-intervention phases 1 and 2 (\u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.5 and \u003cem\u003ep\u0026nbsp;\u003c/em\u003e= 0.6, respectively).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOf the 48 patients discharged alive (Table 3), 41 (85.42%) were on a glucocorticoid dose equivalent to\u0026nbsp;³\u0026nbsp;20 mg/day of prednisone; all of these patients were also on GI prophylaxis with a proton-pump inhibitor or a histamine type-2-receptor antagonist, and all were prescribed\u0026nbsp;PJP prophylaxis. Outpatient follow-up with an oncologist was documented in 35 (72.92%) patients, and the median time to first oncology follow-up was 20.0 days. Outpatient follow-up with a pulmonologist increased significantly from 23.1% in the pre-intervention phase to 64% in post-intervention phase 1 (\u003cem\u003ep\u003c/em\u003e = 0.0382) and 100% in post-intervention phase 2 (\u003cem\u003ep\u003c/em\u003e = 0.0031), with an overall \u003cem\u003ep\u003c/em\u003e-value of 0.0030. The median time to first follow-up with a pulmonologist was 18.5 days.\u0026nbsp;\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eTo our knowledge, this is the first study to evaluate the effectiveness of a clinical care pathway for managing ICI-P in hospitalized patients with lung cancer. The study shows a reduction in the time to initiate ICI-P treatment in this patient population. Additionally, we have increased the usage of the immunotoxicity order set in the electronic health records. Our comprehensive, multimodal intervention played a vital role in encouraging healthcare providers to use the order set. Although the observed change did not reach statistical significance, we believe this approach is a pioneering and unique effort in the field.\u003c/p\u003e\n\u003cp\u003eIn cases where grade 3 or 4 pneumonitis leads to hypoxia or respiratory compromise, hospitalization is required as it can be life-threatening\u003csup\u003e26-28\u003c/sup\u003e. Guidelines for diagnosing and managing irAEs recommend multidisciplinary consultation, high doses of oral or intravenous corticosteroids, and discontinuation of ICI therapy\u003csup\u003e29-31\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eIn our study, 91.67% of confirmed ICI-P patients had NSCLC, and 95% had stage IV. Pembrolizumab was the most common ICI (55%). Glucocorticoids were frequently used (98.33%), while second-line immunosuppressants were rare. This could be due to the low incidence of steroid-refractory ICI-P or hesitancy to initiate advanced immunosuppression without a clearly preferred approach to immunosuppressive therapy. Steroid-refractory ICI-P, an often-fatal clinical phenomenon with poorly understood incidence\u003csup\u003e32,33\u003c/sup\u003e, was identified in 10 (16.67%) patients in our cohort, necessitating escalation to infliximab, a tumor necrosis factor-alpha inhibitor that reduces inflammation and alters the immune response.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA systematic review of 159 studies involving 33,253 patients showed that using glucocorticoids increased the risk of GI bleeding and perforation\u003csup\u003e34\u003c/sup\u003e. Consequently, best-practice guidelines recommend acid suppression for patients at risk of GI bleeding\u003csup\u003e35\u003c/sup\u003e. Within our patient cohort, those discharged while receiving a glucocorticoid dose equal to or greater than 20 mg/day of prednisone were given GI prophylaxis in either a proton-pump inhibitor or a histamine type-2 receptor antagonist. Similarly, all these patients received PJP prophylaxis. Thus, our study\u0026rsquo;s interventions helped ensure compliance with the recommended best practices to prevent GI complications and opportunistic infections while on glucocorticoids\u003csup\u003e36\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe observed no significant changes in ICU admissions or inpatient mortality from the pre-intervention phase to the post-intervention phases 1 and 2 (p = 0.5 and p = 0.6, respectively). The overall mortality rate for patients with ICI-P was 22%, which is higher than the typically reported mortality rate of approximately 10% in the literature\u003csup\u003e37\u003c/sup\u003e.\u0026nbsp;However, our findings are consistent with those of a real-world cohort investigation\u0026nbsp;involving 315 patients with lung cancer who were treated with ICIs in 6 healthcare centers (1 academic center, 1 community referral center, and 4 community centers) within the University of North Carolina network. This study reported an ICI-P incidence rate of 9.5%, with 60% of patients requiring hospitalization for ICI-P management. The risk of mortality within this patient subset was 32%\u003csup\u003e38\u003c/sup\u003e.\u0026nbsp;Therefore, our findings and those of the aforementioned study suggest that ICI-P is more common and severe than previously reported, and it carries an unexpectedly high mortality rate.\u003c/p\u003e\n\u003cp\u003eOur study\u0026apos;s interventions resulted in more timely follow-up appointments with the oncology and pulmonology services.\u003c/p\u003e\n\u003cp\u003eIt is worth noting that the project and data collection took place during the peak of the COVID-19 pandemic, which posed significant challenges. Clinical presentation and radiological findings of ICI-P and SARS-CoV-2 can be quite similar; patients with respiratory symptoms needed to be isolated until their SARS-CoV-2 tests were available, causing delays in ICI-P diagnosis and treatment. Moreover, the widespread prevalence of COVID-19 pneumonia created a diagnostic bias, as it was the leading differential diagnosis in most patients with respiratory symptoms.\u003c/p\u003e\n\u003cp\u003eThe study had a limitation in that it relied on billing codes and other coded data to identify ICI-P. This is because there are no specific ICD-10 codes available for the disease. To identify potential cases of ICI-P for the incidence analysis, broad codes were used intentionally. This was because clinicians often use various codes when faced with an uncertain diagnosis of ICI-P.\u003c/p\u003e\n\u003cp\u003eBronchoscopy, which is recommended in irAE management guidelines, is infrequently used in severe ICI-P cases because patients may be clinically unstable and unable to undergo an invasive procedure under anesthesia. Unfortunately, none of the patients in our cohort could undergo diagnostic bronchoscopy due to their clinical instability. The primary value of invasive bronchoscopy is identifying alternative etiologies for the patient\u0026rsquo;s symptoms (e.g., disease progression, infectious pneumonia)\u003csup\u003e39\u003c/sup\u003e. Noninvasive alternatives like diagnostic biomarkers for ICI-P may be preferable but remain elusive. Future studies of ICI-P should focus on describing its clinical features more accurately and optimizing its diagnostic algorithms, given the current lack of a gold standard for diagnosis.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eThis study provides valuable insights into the management and outcomes of patients with lung cancer who exhibit symptoms of ICI-P (Immune Checkpoint Inhibitor-Related Pneumonitis). It emphasizes the critical role of onco-hospitalists in managing severe cases of ICI-P that require hospitalization. By implementing a clinical care pathway algorithm based on evidence, the variability in the time taken to administer treatment was reduced, and there was a significant increase in the use of the immunotoxicity order set. Consequently, the implementation led to the standardization of clinical care. Importantly, the study underscores the feasibility of implementing best practices in patient care even outside the confines of comprehensive cancer centers, making these practices relevant and applicable to nononcologists and healthcare practitioners in diverse clinical contexts.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAt our institution, continual educational efforts to bolster adherence to the established care pathway algorithm and enhance patient outcomes will be imperative.\u0026nbsp;\u003c/p\u003e"},{"header":"STATEMENTS AND DECLARATIONS","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgment of research support\u003c/strong\u003e:\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis work was funded by the Division of Internal Medicine Research and Quality Improvement Development Award at the University of Texas MD Anderson Cancer Center.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis project is partly supported by the National Institutes of Health/National Cancer Institute under the award number P30CA 016672.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eACKNOWLEDGMENTS\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Laura L. Russell, Scientific Editor of the Research Medical Library at MD Anderson Cancer Center, for editing this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was funded by the Division of Internal Medicine Research and Quality Improvement Development Award at the University of Texas MD Anderson Cancer Center.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThis project is partly supported by the National Institutes of Health/National Cancer Institute under the award number P30CA 016672.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMaggie Lu has the following declarations outside the submitted work: holds stock with Amgen.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAll other authors\u0026nbsp;have no relevant financial or non-financial interests to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStudy concept and design\u003c/em\u003e: Joanna-Grace M Manzano MD MPH, Maggie Lu PharmD, Maria Franco-Vega MD, Norman Brito-Dellan MD.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eData collection:\u003c/em\u003e All authors\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis and interpretation\u003c/em\u003e: Heather Y. Lin Ph.D., Joanna-Grace M Manzano MD MPH, Juan Ignacio Ruiz MD, Norman Brito-Dellan MD, Christine B Peterson Ph.D.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eData analysis and interpretation:\u003c/em\u003e All authors.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eManuscript preparation and final approval:\u003c/em\u003e Norman Brito-Dellan, MD, wrote the first draft of the manuscript, and\u0026nbsp;all authors commented on previous versions. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis is a quality improvement study, which was approved by the Quality Improvement Approval Board (QIAB) at MD Anderson Cancer Center. Ethical approval was not required by the reviewing/approving body.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable. There is no patient-identifiable data in this publication.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eZimmermann S, Peters S, Owinokoko T, Gadgeel SM: Immune checkpoint inhibitors in the management of lung cancer. American Society of Clinical Oncology Educational Book 38:682-695, 2018\u003c/li\u003e\n \u003cli\u003eRuffo E, Wu RC, Bruno TC, et al: Lymphocyte-activation gene 3 (LAG3): The next immune checkpoint receptor, Seminars in immunology, Elsevier, 2019, pp 101305\u003c/li\u003e\n \u003cli\u003eKroemer G, Zitvogel L: Immune checkpoint inhibitors. Journal of Experimental Medicine 218, 2021\u003c/li\u003e\n \u003cli\u003eOnoi K, Chihara Y, Uchino J, et al: Immune checkpoint inhibitors for lung cancer treatment: a review. Journal of clinical medicine 9:1362, 2020\u003c/li\u003e\n \u003cli\u003eArmstrong SA, Liu SV: Immune checkpoint inhibitors in small cell lung cancer: a partially realized potential. Advances in Therapy 36:1826-1832, 2019\u003c/li\u003e\n \u003cli\u003eWang DY, Salem J-E, Cohen JV, et al: Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA oncology 4:1721-1728, 2018\u003c/li\u003e\n \u003cli\u003eMoreira A, Loquai C, Pf\u0026ouml;hler C, et al: Myositis and neuromuscular side-effects induced by immune checkpoint inhibitors. European Journal of Cancer 106:12-23, 2019\u003c/li\u003e\n \u003cli\u003ePostow MA, Sidlow R, Hellmann MD: Immune-related adverse events associated with immune checkpoint blockade. New England Journal of Medicine 378:158-168, 2018\u003c/li\u003e\n \u003cli\u003eCommon Terminology Criteria for Adverse Events (CTCAE) Version 5.0, 2017.\u003c/li\u003e\n \u003cli\u003ehttps://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcae_v5_quick_reference_5x7.pdf. Accessed May 12, 2023.\u003c/li\u003e\n \u003cli\u003eThompson JA, Schneider BJ, Brahmer J, et al: Management of Immunotherapy-Related Toxicities, Version 1.2019, NCCN Clinical Practice Guidelines in Oncology. Journal of the National Comprehensive Cancer Network 17:255-289, 2019\u003c/li\u003e\n \u003cli\u003ePorcu M, De Silva P, Solinas C, et al: Immunotherapy associated pulmonary toxicity: biology behind clinical and radiological features. Cancers 11:305, 2019\u003c/li\u003e\n \u003cli\u003eDisayabutr S, Calfee CS, Collard HR, Wolters PJ: Interstitial lung diseases in the hospitalized patient. BMC medicine 13:245, 2015\u003c/li\u003e\n \u003cli\u003eZhong L, Altan M, Shannon VR, Sheshadri A: Immune-Related Adverse Events: Pneumonitis, Immunotherapy, Springer, 2020, pp 255-269\u003c/li\u003e\n \u003cli\u003eShannon VR, Anderson R, Blidner A, et al: Multinational Association of Supportive Care in Cancer (MASCC) 2020 clinical practice recommendations for the management of immune-related adverse events: pulmonary toxicity. Supportive Care in Cancer 28:6145-6157, 2020\u003c/li\u003e\n \u003cli\u003eTiu BC, Zubiri L, Iheke J, et al: Real-world incidence and impact of pneumonitis in patients with lung cancer treated with immune checkpoint inhibitors: a multi-institutional cohort study. Journal for immunotherapy of cancer 10, 2022\u003c/li\u003e\n \u003cli\u003eChen EJ: Being an Oncology Hospitalist. Hospital Medicine Clinics 5:335-346, 2016\u003c/li\u003e\n \u003cli\u003eLodewijckx C, Decramer M, Sermeus W, et al: Eight-step method to build the clinical content of an evidence-based care pathway: the case for COPD exacerbation. Trials 13:229, 2012\u003c/li\u003e\n \u003cli\u003eDeneckere S, Euwema M, Lodewijckx C, et al: Better interprofessional teamwork, higher level of organized care, and lower risk of burnout in acute health care teams using care pathways: a cluster randomized controlled trial. Medical care:99-107, 2013\u003c/li\u003e\n \u003cli\u003eBrahmer JR, Lacchetti C, Schneider BJ, et al: Management of immune-related adverse events in patients treated with immune checkpoint inhibitor therapy: American Society of Clinical Oncology Clinical Practice Guideline. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 36:1714, 2018\u003c/li\u003e\n \u003cli\u003eHaanen J, Carbonnel F, Robert C, et al: Management of toxicities from immunotherapy: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 28:iv119-iv142, 2017\u003c/li\u003e\n \u003cli\u003eRotter T, de Jong RB, Lacko SE, et al: Clinical pathways as a quality strategy. Improving healthcare quality in Europe:309, 2019\u003c/li\u003e\n \u003cli\u003eWood LS: Immune-related adverse events from immunotherapy: Incorporating Care Step Pathways to improve management across tumor types. Journal of the advanced practitioner in oncology 10:47, 2019\u003c/li\u003e\n \u003cli\u003eNaidoo J, Reuss JE, Suresh K, et al: Immune-related (IR)-pneumonitis during the COVID-19 pandemic: multidisciplinary recommendations for diagnosis and management. Journal for immunotherapy of cancer 8, 2020\u003c/li\u003e\n \u003cli\u003eMiddleton S, Barnett J, Reeves DS: What is an integrated care pathway?, Hayward Medical Communications, 2001\u003c/li\u003e\n \u003cli\u003eWorld Health Organization. International statistical classification of diseases and related health problems (10th ed.). 2019\u003c/li\u003e\n \u003cli\u003eChuzi S, Tavora F, Cruz M, et al: Clinical features, diagnostic challenges, and management strategies in checkpoint inhibitor-related pneumonitis. Cancer management and research 9:207, 2017\u003c/li\u003e\n \u003cli\u003eShannon VR: Pneumotoxicity associated with immune checkpoint inhibitor therapies. Current opinion in pulmonary medicine 23:305-316, 2017\u003c/li\u003e\n \u003cli\u003eNaidoo J, Wang X, Woo KM, et al: Pneumonitis in patients treated with anti\u0026ndash;programmed death-1/programmed death ligand 1 therapy. Journal of Clinical Oncology 35:709, 2017\u003c/li\u003e\n \u003cli\u003eWeber JS, K\u0026auml;hler KC, Hauschild A: Management of immune-related adverse events and kinetics of response with ipilimumab. Journal of Clinical Oncology 30:2691-2697, 2012\u003c/li\u003e\n \u003cli\u003eThompson JA, Schneider BJ, Brahmer J, et al: NCCN guidelines insights: management of immunotherapy-related toxicities, version 1.2020: featured updates to the NCCN guidelines. Journal of the National Comprehensive Cancer Network 18:230-241, 2020\u003c/li\u003e\n \u003cli\u003ePuzanov I, Diab A, Abdallah K, et al: Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. Journal for immunotherapy of cancer 5:1-28, 2017\u003c/li\u003e\n \u003cli\u003eCamard M, Besse B, Cariou P-L, et al: Prevalence and outcome of steroid-resistant/refractory pneumonitis induced by immune checkpoint inhibitors. Respiratory Medicine and Research 82:100969, 2022\u003c/li\u003e\n \u003cli\u003eBalaji A, Hsu M, Lin CT, et al: Steroid-refractory PD-(L) 1 pneumonitis: incidence, clinical features, treatment, and outcomes. Journal for immunotherapy of cancer 9, 2021\u003c/li\u003e\n \u003cli\u003eNarum S, Westergren T, Klemp M: Corticosteroids and risk of gastrointestinal bleeding: a systematic review and meta-analysis. BMJ open 4:e004587, 2014\u003c/li\u003e\n \u003cli\u003eCook D, Guyatt G: Prophylaxis against upper gastrointestinal bleeding in hospitalized patients. New England Journal of Medicine 378:2506-2516, 2018\u003c/li\u003e\n \u003cli\u003eShah NJ, Cook MR, Wu T, et al: The Risk of Opportunistic Infections and the Role of Antibiotic Prophylaxis in Patients on Checkpoint Inhibitors Requiring Steroids. Journal of the National Comprehensive Cancer Network 20:800-807. e1, 2022\u003c/li\u003e\n \u003cli\u003eZhai X, Zhang J, Tian Y, et al: The mechanism and risk factors for immune checkpoint inhibitor pneumonitis in non-small cell lung cancer patients. Cancer Biology \u0026amp; Medicine 17:599, 2020\u003c/li\u003e\n \u003cli\u003eAtchley WT, Alvarez C, Saxena-Beem S, et al: Immune checkpoint inhibitor-related pneumonitis in lung cancer: real-world incidence, risk factors, and management practices across six health care centers in North Carolina. Chest 160:731-742, 2021\u003c/li\u003e\n \u003cli\u003eCho JY, Kim J, Lee JS, et al: Characteristics, incidence, and risk factors of immune checkpoint inhibitor-related pneumonitis in patients with non-small cell lung cancer. Lung Cancer 125:150-156, 2018\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003eTable 1. Patients\u0026rsquo; characteristics.\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"546\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with\u0026nbsp;\u003c/p\u003e\n \u003cp\u003esuspected ICI-P\u0026nbsp;\u003c/p\u003e\n \u003cp\u003en = 82\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003ePatients with confirmed ICI-P n = 60\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eAge at admission in years, mean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e66.36 (11.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e66.55 (12.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eIntervention phase, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Pre-intervention\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e22 (26.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e19 (31.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Post-intervention 1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e36 (43.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e30 (50.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Post-intervention 2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e24 (29.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e11 (18.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eConsensus on ICI-P diagnosis, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e60 (73.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eSex, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Men\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e48 (58.54)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e35 (58.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Women\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e34 (41.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e25 (41.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eRace, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;American Indian\u003csup\u003e*\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Asian\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e5 (8.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Black\u003csup\u003e+\u003c/sup\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e3 (5.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;White\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e66 (80.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e47 (78.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Other\u003csup\u003e^\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e5 (6.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e4 (6.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eEthnicity, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Hispanic or Latino\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e10 (12.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e7 (11.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Not Hispanic or Latino\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e71 (86.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e53 (88.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Declined to answer\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eLung cancer type, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;NSCLS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e73 (89.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e55 (91.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;SCLC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e9 (10.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e5 (8.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eCancer stage at admission, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Stage III\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e10 (12.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e3 (5.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;Stage IV\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e72 (87.80)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e57 (95.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eActive treatment with ICI, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e64 (78.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e48 (80.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eType of ICI, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Atezolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e11 (13.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e7 (11.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Durvalumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e11 (13.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e7 (11.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Durvalumab + tremelimumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e2 (2.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e1 (1.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Ipilimumab + nivolumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e15 (18.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e9 (15.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Nivolumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e4 (4.88)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e3 (5.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; Pembrolizumab\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e39 (47.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e33 (55.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eNumber of ICI doses received before admission, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026le; 3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e36 (43.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e25 (41.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 4-6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e21 (25.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e15 (25.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp; \u0026nbsp; 7-9\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e8 (9.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e6 (10.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp; \u0026nbsp;\u0026ge; 10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e17 (20.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e14 (23.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eFirst line of ICI therapy, n (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e66 (80.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e45 (75.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eRespiratory complaint on admission, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e71 (86.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e55 (91.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"52.747252747252745%\" valign=\"top\"\u003e\n \u003cp\u003eUse of immunotoxicity order set, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.73992673992674%\" valign=\"top\"\u003e\n \u003cp\u003e10 (12.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20.512820512820515%\" valign=\"top\"\u003e\n \u003cp\u003e9 (15.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eICI, immune checkpoint inhibitor; ICI-P, immune checkpoint inhibitor\u0026ndash;related pneumonitis; ICU, intensive care unit; N/A, not applicable; NSCLS, non-small cell lung cancer; SCLC, small cell lung cancer; SD, standard deviation.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e*\u003c/sup\u003eIncluding Alaska Natives.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e+\u003c/sup\u003eIncluding African Americans.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e^\u003c/sup\u003eIncluding self-reported mixed races and other races not otherwise specified\u003c/p\u003e\n\u003cp\u003eOf the 60 patients with confirmed ICI-P, 59 (98.33%) patients received corticosteroids for the treatment of ICI-P, and 10 (16.67%) also received infliximab for steroid-refractory ICI-P. Pulmonology was consulted in 59 (98.33%) patients, and the mean time between the ICI-P diagnosis and the consultation was 2.53 days (range, 0.00-16.0 days). Oncology was consulted in 37 (61.67%) patients.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTable 2. Patient characteristics by intervention phase among patients with confirmed ICI-P (N= 60).\u003c/p\u003e\n\u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"718\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003eCharacteristic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003ePre-intervention phase\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003ePost-intervention phase 1\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value (post-intervention phase 1 versus pre-intervention phase)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003ePost-intervention phase 2\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value (post-intervention phase 2 versus pre-intervention phase)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003eTime to treatment of ICI-P in days, mean (min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e2.37 (0-12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e3.07 (0-17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e1.27 (0-6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e0.40\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003eUse of immunotoxicity order set (N = 60), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e0/19 (0.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e6/30 (20.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.07\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e3/11 (27.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e0.04\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003eICU stay (N = 60), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e8/19 (42.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e8/30 (26.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e3/11 (27.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e0.47\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003eInpatient mortality (N = 60), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e5/19 (26.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e5/30 (16.67)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e2/11 (18.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003eLength of hospital stay in days, mean (min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e17.68 (2-41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e12.60 (3-28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.0418\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e13.82 (3-38)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e0.2037\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003ePulmonology consultation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e18/19 (94.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e30/30 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.3878\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e11/11 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003ePrimary Oncology consultation, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e10/14 (71.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e12/25(48.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.1935\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e3/9 (33.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e0.1023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003eDischarged with PPI/H2 blockers if on steroids (N = 45*), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e12/12 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e19/23 (82.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e9/9 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003eDischarged with PJP prophylaxis if on steroids (\u0026ge; 20 mg/day prednisone) (N = 46*), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e10/14 (71.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e20/21 (95.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e9/9 (100)\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e0.13\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003eReadmission (N = 12\u003csup\u003e+\u003c/sup\u003e), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e5/14 (35.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e5/23 (21.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.4537\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e2/8 (25.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003e30-day mortality (N = 48), n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e3/14 (21.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e7/25 (28.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.7212\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e1/9(11.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e1.0000\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003eFollow-up pulmonology appointment arranged if treated for ICI-P, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e7/14 (50.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e19/25(76.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.1574\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e8/9 (88.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e0.0858\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003ePatient received outpatient pulmonology follow-up, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e3/13 (23.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e16/25 (64.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.0382\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e6/6 (100)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e0.0031\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003eTime to first pulmonology follow-up in days, mean (min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e43.44 (4-111)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e24.16 (1-99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.3757\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e32.75 (5-110)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e0.8097\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"30.22284122562674%\" valign=\"top\"\u003e\n \u003cp\u003eTime to first oncology follow-up in days, mean (min-max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e43.44 (4-111)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e25.00 (1-99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e0.3958\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.206128133704736%\" valign=\"top\"\u003e\n \u003cp\u003e32.75 (5-110)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.649025069637883%\" valign=\"top\"\u003e\n \u003cp\u003e0.8097\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eH2, histamine type-2 receptor; ICI-P, immune checkpoint inhibitor\u0026ndash;related pneumonitis; ICU, intensive care unit; max, maximum; min, minimum; PJP, \u003cem\u003ePneumocystis jirovecii\u0026nbsp;\u003c/em\u003epneumonia; PPI, proton-pump inhibitor.\u003c/p\u003e\n\u003cp\u003e*One patient in the pre-intervention phase had missing data on PPI use, and 2 patients (1 in the pre-intervention phase and 1 in the post-intervention phase) had missing data on prednisone use.\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e+\u003c/sup\u003eOf the 48 patients alive at discharge, 12 (25.00%) patients were readmitted within 30 days (all cause-readmissions). No data were available for 3 (6.25%) of the 48 patients.\u003c/p\u003e\n\u003cp\u003eTable 3. Inpatient mortality and discharge dispositions for patients with confirmed ICI-P (N = 60).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.36734693877551%\" valign=\"top\"\u003e\n \u003cp\u003ePatient outcome\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.632653061224488%\" valign=\"top\"\u003e\n \u003cp\u003en (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.36734693877551%\" valign=\"top\"\u003e\n \u003cp\u003eDied as inpatient\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.632653061224488%\" valign=\"top\"\u003e\n \u003cp\u003e12 (20.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.36734693877551%\" valign=\"top\"\u003e\n \u003cp\u003eDischarged\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.632653061224488%\" valign=\"top\"\u003e\n \u003cp\u003e48 (80.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.36734693877551%\" valign=\"top\"\u003e\n \u003cp\u003eTo home without home health or physical therapy services\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.632653061224488%\" valign=\"top\"\u003e\n \u003cp\u003e25 (52.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.36734693877551%\" valign=\"top\"\u003e\n \u003cp\u003eTo home with home health or physical therapy services\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.632653061224488%\" valign=\"top\"\u003e\n \u003cp\u003e9 (18.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.36734693877551%\" valign=\"top\"\u003e\n \u003cp\u003eTo skilled nursing facility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.632653061224488%\" valign=\"top\"\u003e\n \u003cp\u003e7 (14.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.36734693877551%\" valign=\"top\"\u003e\n \u003cp\u003eTo home with hospice services\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.632653061224488%\" valign=\"top\"\u003e\n \u003cp\u003e4 (8.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.36734693877551%\" valign=\"top\"\u003e\n \u003cp\u003eTo acute care hospital\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.632653061224488%\" valign=\"top\"\u003e\n \u003cp\u003e1 (2.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.36734693877551%\" valign=\"top\"\u003e\n \u003cp\u003eTo another health care institution\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.632653061224488%\" valign=\"top\"\u003e\n \u003cp\u003e1 (2.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"68.36734693877551%\" valign=\"top\"\u003e\n \u003cp\u003eTo a rehabilitation facility\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"31.632653061224488%\" valign=\"top\"\u003e\n \u003cp\u003e1 (2.08)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eICI-P, immune checkpoint inhibitor\u0026ndash;related pneumonitis.\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Immune checkpoint inhibitor-related pneumonitis, clinical care pathway algorithm, onco-hospitalist","lastPublishedDoi":"10.21203/rs.3.rs-4209489/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4209489/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cu\u003ePurpose\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eImmune checkpoint inhibitor-related pneumonitis (ICI-P) is a condition associated with high mortality, necessitating prompt recognition and treatment initiation. This study aimed to assess the impact of implementing a clinical care pathway algorithm on reducing the time to treatment for ICI-P.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eMethods\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003ePatients with lung cancer and suspected ICI-P were enrolled, and a multi-modal intervention promoting algorithm use was implemented in two phases. Pre- and post-intervention analyses were conducted to evaluate the primary outcome of time from ICI-P diagnosis to treatment initiation.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eResults\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eOf the 82 patients admitted with suspected ICI-P, 73.17% were confirmed to have ICI-P, predominantly associated with non-small cell lung cancer (91.67%) and stage IV disease (95%). Pembrolizumab was the most commonly used immune checkpoint inhibitor (55%). The mean times to treatment were 2.37 days in the pre-intervention phase and, 3.07 days (\u003cem\u003ep\u003c/em\u003e=0.46), and 1.27 days (\u003cem\u003ep\u003c/em\u003e=0.40) in the post-intervention phases 1 and 2, respectively. Utilization of the immunotoxicity order set significantly increased from 0% to 27.27% (p = 0.04) after phase 2. While there were no significant changes in ICU admissions or inpatient mortality, outpatient pulmonology follow-ups increased statistically significantly, demonstrating enhanced continuity of care. The overall mortality for patients with ICI-P was 22%, underscoring the urgency of optimizing management strategies. Notably, all patients discharged on high-dose corticosteroids received appropriate gastrointestinal prophylaxis and prophylaxis against Pneumocystis jirovecii pneumonia infections at the end of phase 2.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConclusion\u003c/u\u003e\u003c/p\u003e\n\u003cp\u003eImplementing a clinical care pathway algorithm for ICI-P management standardizes care practices and enhances patient outcomes, underscoring the importance of structured approaches.\u003c/p\u003e","manuscriptTitle":"Optimizing Inpatient Care for Lung Cancer Patients with Immune Checkpoint Inhibitor- Related Pneumonitis Using a Clinical Care Pathway Algorithm","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-12 19:04:43","doi":"10.21203/rs.3.rs-4209489/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-06-22T11:02:03+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-17T17:35:48+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"31043729276441371942756573503817010908","date":"2024-06-17T15:37:22+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-06-13T09:17:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"220117232309687072102073592422436465351","date":"2024-06-02T02:20:26+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"144848897422838330856093876785524568649","date":"2024-05-16T12:11:01+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-05-14T11:57:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-05-13T20:14:59+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-08T14:13:19+00:00","index":"","fulltext":""},{"type":"submitted","content":"Supportive Care in Cancer","date":"2024-04-03T02:50:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"supportive-care-in-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jscc","sideBox":"Learn more about [Supportive Care in Cancer](https://www.springer.com/journal/520)","snPcode":"520","submissionUrl":"https://submission.nature.com/new-submission/520/3","title":"Supportive Care in Cancer","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"2e12b010-f485-465e-9e4d-4dc00c4b59f4","owner":[],"postedDate":"April 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-23T15:59:27+00:00","versionOfRecord":{"articleIdentity":"rs-4209489","link":"https://doi.org/10.1007/s00520-024-08867-8","journal":{"identity":"supportive-care-in-cancer","isVorOnly":false,"title":"Supportive Care in Cancer"},"publishedOn":"2024-09-16 15:57:01","publishedOnDateReadable":"September 16th, 2024"},"versionCreatedAt":"2024-04-12 19:04:43","video":"","vorDoi":"10.1007/s00520-024-08867-8","vorDoiUrl":"https://doi.org/10.1007/s00520-024-08867-8","workflowStages":[]},"version":"v1","identity":"rs-4209489","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4209489","identity":"rs-4209489","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}