Bacterial pneumonia during successful treatment of metastatic endometrial cancer with dostarlimab- case report and a literature review

Bacterial pneumonia during successful treatment of metastatic endometrial cancer with dostarlimab- case report and a literature review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Bacterial pneumonia during successful treatment of metastatic endometrial cancer with dostarlimab- case report and a literature review Federica Cosso, Maria Cristina Petrella, Martina Izzi, Marco Vangelisti, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4749851/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Endometrial cancer is a frequent female cancer characterized by four molecular subtypes including the microsatellite instable-high (MSI-H) subgroup where use of immune checkpoint inhibitors (ICIs) showed encouraging activity in the metastatic setting. Nonetheless, adverse events during this particular treatment are still new in endometrial cancer and lack of data on ICIs long-term use are currently available. Herein, we report a rare case of MSI-H metastatic endometrial cancer which has developed a bacterial pneumonia that could mimic an immune-related adverse events during a long-term response with dostarlimab. Figures Figure 1 1. Introduction Endometrial cancer (EC) is the seventh most frequent female cancer worldwide and the fourth in Europe, occurring most frequently in women between 65 and 75 years of age. In recent years, the mortality has increased, consequent to an increase of obesity, which is a major risk factor; other important risk factors are hypertension, hyperinsulinemia, prolonged exposure to estrogen, polycystic ovary syndrome, and tamoxifen use. 1,2 The increasing incidence of EC required a better definition of prognostic groups for the use of more appropriate therapies. Therefore, in 2023 the FIGO staging was updated including the molecular measures identified by the Cancer Genome Atlas (TCGA); in particular, it described at least 4 molecular subtypes of EC: polymerase ϵ (POLE)-mutant, microsatellite instable-high (MSI-H), copy number low, and copy number high 3 . Among these, the first subtype has a good outcome, the MSI-H subgroup and the fourth have an intermediate prognosis, and the p53-abn has the worst clinical outcome 4 According to the diagnostic algorithm, immunohistochemical (IHC) staining for p53 and mutations in mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, MSH6) is now recommended as standard practice for molecular classification. 4 The highest incidence of dMMR and MSI-H has been reported in EC (25%-30%) and colorectal cancer (10%-15%) of all stages 5,6 It has been documented that tumors with elevated dMMR and/or MSI (MSI-H) have increased tumor-infiltrating lymphocytes and increased expression of programmed cell death receptor 1 (PD-1) and its ligands (PD-L1 and PD-L2), thus allowing the use of immune checkpoint inhibitors (ICIs) 7,8 Dostarlimab, an anti PD-L1 agent, showed encouraging activity in EC dMMR with progression on or after previous platinum-based therapy 9 The recent introduction of ICIs in metastatic MSI-H EC patients raises the attention to understand the safety profile on the long-term use to help patients to get the most benefit minimizing the onset of adverse events. We report a clinical case of a patient with advanced EC and MSI-H treated with dostarlimab presenting a bacterial pneumonia that could mimic an ICI-interstitial lung disease (ILD) adverse event after a long-term response. 2. Case Presentation A 68-year-old patient, in January 2020, after vaginal bleeding, underwent diagnostic investigation with transvaginal ultrasound and subsequent Computed Tomography (CT) scan finding an endometrial lesion with associated retroperitoneal and pelvic bilateral adenopathies. In June 2020, she underwent robotic hysterectomy and adnexectomy. Histopathological examination diagnosed endometrioid adenocarcinoma of the uterine body, Grading 3 (poorly differentiated tumor) ER +, PR +, p53 -/+. pT3b N0 (sentinel lymph node); FIGO IIIB. The treatment included adjuvant chemotherapy with Carboplatin and Paclitaxel, of which only one administration was performed due to a subsequent hospitalization for ischemic stroke. In December 2020, she performed RT on pelvic excavation, common iliac, internal iliac, external iliac, presacral, obturator, parametrium and vaginal dome for a total dose of 45Gy. Subsequent clinical, instrumental, and biochemical follow up resulted negative until January 2023, when new genital blood loss appeared. Thus, an MRI of the pelvis with contrast was performed, revealing a vaginal dome solid mass, infiltrating the mesorectum with cranio-caudal diameter of 34 mm, antero-posterior of 25 mm and latero-lateral of 33 mm. Bilateral external iliac lymph node enlargements were also found. CT scan performed subsequently also confirmed a picture of peritoneal carcinosis. Polymerase Chain Reaction Real Time (PCR) analysis detected MSI-H (instability of protein BAT25, BAT26, NR21, NR22, NR24, NR27, CAT25, MONO27) and accordingly in February 2023 a first-line immunotherapy with Dostarlimab 500 mg every week for 4 cycles was administered. By multiplex-PCR, Lynch syndrome was also ruled out. At the end of the induction therapy CT scan showed regression of local disease with a dimensional and numerical reduction of peritoneal implants. Hence, the maintenance with dostarlimab 1000 mg every 6 weeks was dispensed. In September 2023, after 4 doses of maintenance therapy, she performed a CT scan that confirmed further dimensional reduction of peritoneal implant. In November 2023 a worsening of postural instability, dizziness and objective fatigue was reported requiring a hospitalization. The CT scan showed extensive " ground-glass" consolidative parenchymal thickenings with crazy-paving aspects and predominantly mantle-like distribution involving the right upper lobe, middle lobe, and LID, to be attributed to pneumonia picture. At the abdominal area, numerical and dimensional reduction of peritoneal implants. Broncho-Alveolar Lavage was positive for Moraxella catarrhalis. Therefore, intravenous corticosteroid therapy and antibiotic therapy with meropenem, linezolid was started with a consequent clinical-instrumental resolution achieved. (Fig. 1 ) Immunotherapy was suspended for three months, and resumed once the pneumonia was solved. Treatment with Dostarlimab is still ongoing and the CT scan performed in May 2025 confirmed a partial response of at least 15 months. 3. Discussion Treatment options have historically been limited for patients with advanced or recurrent EC who have disease progression on or after first-line platinum-based chemotherapy, including those with dMMR/MSI-H tumors, with limited efficacy and no standard of care for second-line therapy. 4 In this setting, ICIs have shown remarkable responses in advanced EC, especially in those harbouring dMMR/MSI alteration. A recent review included 15 clinical trials employing ICIs in advanced EC: anti-PD1 (pembrolizumab, nivolumab, dostarlimab) and anti-PD-L1 agents (avelumab, atezolizumab, durvalumab) that were administered as single agents to evaluate their efficacy. 10 When considering only MSI patients, ORR ranged from 26.7–58%, while in MSS patients the ORR was 3–26.7%. Among MSI groups, mPFS to ICI monotherapy was 8.1 months (range 5.5–13.1 mos) while in all-comers patients the mPFS ranged from 1.7 to 18.9 months. 10 Accordingly, the updated results of the GARNET study reported a 45.5% (95% CI 7.1–54.0) of ORR in 143 patients with dMMR/MSI-H EC, patients with 6.0 (95% CI 4.1–18.0) months of mPFS. 11 Consistent with these previous investigations, the present case exhibited a good response to dostarlimab, with a response maintained for more than 15 months. Nevertheless, ICIs are associated with adverse reactions (AEs) that differ from those of conventional chemotherapy and targeted molecular therapy. A systematic literature review was undertaken in March 2024 using the following keywords ``IMMUNOTHERAPY IN ENDOMETRIAL CANCER '' to assess the tolerability of immunotherapy in metastatic EC. Starting from 48 scientific articles we selected 11 clinical trials in which monoimmunotherapy was performed in patients who reported EC (Table 1); three of them were not included for missing safety data. 12,13 A total of 143 patients with dMMR/MSI-H EC and 156 patients with MMRp/MSS EC were evaluated in the GARNET, a phase I single-arm study of dostarlimab monotherapy. The most frequently occurring treatment-related AEs (TRAEs) were respectively: fatigue (17.8%), diarrhea (14.6%), and nausea (13.7%). The most common irTRAEs were hypothyroidism (8.3%), arthralgia (3.2%), increased ALT (2.5%), and increased AST (2.2%). Pneumonitis occurred in 3 pts 1.0%, of which 2 (1.3%) dMMR/MSI-H and 1 (0.6%) MMRp/MSS. 11 The nonrandomized, open-label, multicohort, phase II KEYNOTE-158 included 90 patients with previously treated MSI-H/dMMR advanced EC receiving pembrolizumab 200 mg once every 3 weeks for 35 cycles. TRAEs occurred in 68 patients (76%) and the most frequently reported were pruritus (24%), fatigue (21%), and diarrhea (16%) while irTRAEs were hypothyroidism (14%), hyperthyroidism (8%), and infusion reactions (4%). Pneumonitis was registered in 1 patient. 14 A single-center, randomized, open-label, phase II study of durvalumab 1500 mg (n = 38) versus durvalumab 1500 mg plus tremelimumab 75 mg every 4 weeks in patients with EC showed that in the first arm the most common grade 3 or higher TRAEs were anemia (n = 3, 8%), hyperglycemia (n = 2, 5%), elevated lipase (n = 2, 5%), diarrhea, elevated alanine transaminase, hyponatremia, and lymphocyte decrease (each n = 1, 3%). No pneumonia was recorded. 15 The phase II trial evaluated the PD-L1 inhibitor avelumab in two cohorts of patients with EC: ( 1 ) dMMR and/or documented mutation in the exonuclease domain of POLE, MMRD/POLE cohort; and ( 2 ) MMRp cohort. Frequent TRAEs of any grade (≥ 10%) were fatigue (n = 11, 35.5%), nausea (n = 5, 16.1%), hypothyroidism (n = 4, 12.9%) and decreased neutrophil count (n = 4, 12.9%). Of 31 patients who initiated avelumab 1 (67%) patient for each cohort had pneumonitis. 16 A multicenter phase II study was performed in women with EC with pMMR tumor or dMMR progressing after one to three lines of chemotherapy. Sixty-nine women received durvalumab 1500 mg given every 4 weeks until progression or unacceptable toxicity. There were 19 irAEs reported, mainly of grades 1 and 2 (n = 18), including hypothyroidism (n = 7), hyperthyroidism (n = 8), pneumonitis (n = 2) and hypoadrenalism (n = 1). 17 The Phase I, multi-center, first-in-human, open-label, dose-escalation/expansion clinical trial investigated single-agent atezolizumab in cohorts of patients with recurrent epithelial ovarian or uterine cancer (UC). The most common any-grade TRAEs in the latter cohort (n = 15) were diarrhea and fatigue, which occurred in 3 (20.0%) and 2 patients (13.3%), respectively; grade 3 TRAEs were diarrhea, colitis and rash (n = 1 each). No differentiation with MSI was performed. 18 The KEYNOTE-028 is a multicohort, open-label, phase Ib basket trial investigating the safety and efficacy of pembrolizumab in 24 patients with PD-L1–positive advanced EC. TRAEs of any grade were experienced by 13 patients (54.2%); those occurring in ≥ 10% of patients included fatigue (n = 5; 20.8%), pruritus (n = 4; 16.7%), pyrexia (n = 3; 12.5%), and decreased appetite (n = 3; 12.5%). 19 The phase II study evaluated the efficacy and safety of nivolumab in 43 patients with advanced/recurrent UC. The 62.8% of patients had AEs and those with an incidence ≥ 10% were: hypertransaminasemia (n = 11, 25.6%), pruritus (n = 6, 13.9%), fatigue (n = 6, 13.9%), hypothyroidism (n = 5, 11.6%). Only 2 patients had MSI -H but no specific AEs was reported. 20 According to this review fatigue diarrhea, nausea, pruritus and hypothyroidism were common TRAEs transversely described across different anti PD-L1/PD-1 in advanced EC. (Table I) Some cases of pneumonitis were registered. In fact, lung toxicities, such as interstitial lung disease (ILD), associated with ICIs are not exceptional. ICI-ILD are usually linked to nonspecific clinical symptoms and occur during the first few months with characteristic radiological signs that include ground-glass opacities, organizing pneumonitis patterns and condensations. Organizing pneumonia is characterized by lymphocytic interstitial inflammation. 21 Both entities occur from a T-helper-1 uncontrolled immune response but usually do not coexist. These results suggest an immune-mediated mechanism of toxicity. 21 In this case report our patient presented worsening aspecific symptoms and imaging that could mimic ICI- ILD. However, after an in-depth analysis a bacterial pneumonia was found which was most likely related to patient’ comorbidities. Accordingly, dostarlimab was well tolerated and it could be resumed once the pneumonia was solved 4. Conclusion In summary, we described ICIs in a patient with advanced EC and MSI-H; TRAEs during this particular treatment are still new in EC and accordingly real-world data on the long-term use are needed to properly manage ICIs. In fact, although a potential pulmonary irTRAE was suspected at first in our case, it was crucial to isolate the bacteria; its resolution allowed to continue dostarlimab and to maintain the response achieved. Declarations This case report complies with the specific requirements of our institution and no ethics approval was needed. Informed consent The participant has consented to the submission of the case report to the journal and an informed consent was obtained. Funding Declaration The author(s) received no financial support for the research, authorship, and/or publication of this article. Author Contribution F.C. and M.I. wrote the main manuscript text. M.V. prepared figures 1C.C. prepared table 1.G.R. contributed to the conception of the workM.C.P made substantial contributions to the design of the work.A.V. Ensured the accuracy or integrity of any part of the work.G.A. approved the version to be published.All authors reviewed and approved the manuscript. Data Availability The datasets generated during the current study are available from the corresponding author on reasonable request. References Concin, N.; Matias-Guiu, X.; Vergote, I.; Cibula, D.; Mirza, M. R.; Marnitz, S.; Ledermann, J.; Bosse, T.; Chargari, C.; Fagotti, A.; Fotopoulou, C.; Gonzalez Martin, A.; Lax, S.; Lorusso, D.; Marth, C.; Morice, P.; Nout, R. A.; O’Donnell, D.; Querleu, D.; Raspollini, M. R.; Sehouli, J.; Sturdza, A.; Taylor, A.; Westermann, A.; Wimberger, P.; Colombo, N.; Planchamp, F.; Creutzberg, C. L. ESGO/ESTRO/ESP Guidelines for the Management of Patients with Endometrial Carcinoma. Int. J. Gynecol. 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Tables Table I Treatment- Related Adverse Events (TRAEs) that occurred in ≥ 10% of patients with endometrial cancer who underwent to monoimmunotherapy in clinical trials. TRAEs Dostarlimab GARNET Pembrolizumab KEYNOTE-158 Pembrolizumab KEYNOTE-028 Avelumab Durvalumab Atezolizumab Nivolumab Fatigue 17.8 21 20.8 35.5 57 13.3 13.9 Diarrhea 14.6 16 20 20 Nausea 13.7 16.1 33 Pruritus 24 16.7 13.9 Hypothyroidism 14 12.9 11.6 Decreased neutrophil count 12.9 Costipation 30 General disorders and administration site conditions 29 Skin and subcutaneous tissue disorders 20 Pain 17 Urinary tract infection 14 Vomiting 14 Anorexia 12.5 13 Dyspnea 13 Gastrointestinal disorders 13 Anemia 12 Hyperthyroidism 12 Rash 12 Hypertransaminasemia 25.6 Additional Declarations No competing interests reported. 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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-4749851","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":341906689,"identity":"7e4e3bbb-5b5e-4e8b-9941-a94b18f9c4d3","order_by":0,"name":"Federica Cosso","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYBAC9gYGAwYQggIbBgZmxgcHkEQwAM8BVC1pQC3MBkBB3Hp40Aw8DMTMIBE8WtibNz6uKLCTZ2A/fPjjj4rzidvZmRkPMBT8wa2F51ix4RmDZMMGnrQ0aZ4ztxN3NjMz4HWYvUSOmWSDwQHGBgkeM2bGttuJGw7zH8DvF/k35j+BWuyBWow//mw7B9RCwBYeoOGMQC2JQC0GErxtB4jQwpNWDHRYcnIbxC/JxmAtCQbGuLWwH974seGPnW0/JMTsZDecP8z84cMfOZxa4IANhZdAWMMoGAWjYBSMAjwAAAuVTrbrN7wmAAAAAElFTkSuQmCC","orcid":"","institution":"Careggi University Hospital","correspondingAuthor":true,"prefix":"","firstName":"Federica","middleName":"","lastName":"Cosso","suffix":""},{"id":341906690,"identity":"a642385c-5204-4800-9d2a-cb9bac9d1ceb","order_by":1,"name":"Maria Cristina Petrella","email":"","orcid":"","institution":"Careggi University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Maria","middleName":"Cristina","lastName":"Petrella","suffix":""},{"id":341906691,"identity":"8c757ee4-aa34-4994-bb44-1d12719dda2a","order_by":2,"name":"Martina Izzi","email":"","orcid":"","institution":"Careggi University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Martina","middleName":"","lastName":"Izzi","suffix":""},{"id":341906692,"identity":"a7bd9e62-7ea0-4c9e-a40b-09c1487e816b","order_by":3,"name":"Marco Vangelisti","email":"","orcid":"","institution":"Careggi University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Marco","middleName":"","lastName":"Vangelisti","suffix":""},{"id":341906695,"identity":"2d77bf19-d993-4970-84ba-c16fc3188aa4","order_by":4,"name":"Cecilia Cerbai","email":"","orcid":"","institution":"Careggi University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Cecilia","middleName":"","lastName":"Cerbai","suffix":""},{"id":341906696,"identity":"9a3c5626-7af4-4a36-bf79-aa92006f6f97","order_by":5,"name":"Gemma Rossi","email":"","orcid":"","institution":"Careggi University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gemma","middleName":"","lastName":"Rossi","suffix":""},{"id":341906699,"identity":"11369468-16c2-4dcb-b2fe-7df9c725e232","order_by":6,"name":"Alessandro Villanucci","email":"","orcid":"","institution":"Careggi University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Alessandro","middleName":"","lastName":"Villanucci","suffix":""},{"id":341906700,"identity":"4111e28f-c4bd-4511-aa82-1b5bcc020244","order_by":7,"name":"Gianni Amunni","email":"","orcid":"","institution":"Careggi University Hospital","correspondingAuthor":false,"prefix":"","firstName":"Gianni","middleName":"","lastName":"Amunni","suffix":""}],"badges":[],"createdAt":"2024-07-16 12:51:35","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4749851/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4749851/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63419118,"identity":"1b7fae3b-3cc8-4337-aa28-2be5fcfe9b84","added_by":"auto","created_at":"2024-08-28 02:26:34","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":1462055,"visible":true,"origin":"","legend":"\u003cp\u003eCT scan imaging from November 2023 (upper) to January 2024 (middle) and May 2024 (lower)\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-4749851/v1/e9e224df097c91631a9c7b38.png"},{"id":63419119,"identity":"d370cba8-a3a3-4e8c-afe2-b2616d874114","added_by":"auto","created_at":"2024-08-28 02:26:39","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2054509,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4749851/v1/e432b914-f8eb-4b23-a767-1071aa90fe54.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Bacterial pneumonia during successful treatment of metastatic endometrial cancer with dostarlimab- case report and a literature review","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eEndometrial cancer (EC) is the seventh most frequent female cancer worldwide and the fourth in Europe, occurring most frequently in women between 65 and 75 years of age. In recent years, the mortality has increased, consequent to an increase of obesity, which is a major risk factor; other important risk factors are hypertension, hyperinsulinemia, prolonged exposure to estrogen, polycystic ovary syndrome, and tamoxifen use. \u003csup\u003e1,2\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe increasing incidence of EC required a better definition of prognostic groups for the use of more appropriate therapies. Therefore, in 2023 the FIGO staging was updated including the molecular measures identified by the Cancer Genome Atlas (TCGA); in particular, it described at least 4 molecular subtypes of EC: polymerase ϵ (POLE)-mutant, microsatellite instable-high (MSI-H), copy number low, and copy number high \u003csup\u003e3\u003c/sup\u003e. Among these, the first subtype has a good outcome, the MSI-H subgroup and the fourth have an intermediate prognosis, and the p53-abn has the worst clinical outcome \u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eAccording to the diagnostic algorithm, immunohistochemical (IHC) staining for p53 and mutations in mismatch repair (MMR) proteins (MLH1, PMS2, MSH2, MSH6) is now recommended as standard practice for molecular classification. \u003csup\u003e4\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe highest incidence of dMMR and MSI-H has been reported in EC (25%-30%) and colorectal cancer (10%-15%) of all stages \u003csup\u003e5,6\u003c/sup\u003e It has been documented that tumors with elevated dMMR and/or MSI (MSI-H) have increased tumor-infiltrating lymphocytes and increased expression of programmed cell death receptor 1 (PD-1) and its ligands (PD-L1 and PD-L2), thus allowing the use of immune checkpoint inhibitors (ICIs) \u003csup\u003e7,8\u003c/sup\u003e Dostarlimab, an anti PD-L1 agent, showed encouraging activity in EC dMMR with progression on or after previous platinum-based therapy \u003csup\u003e9\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe recent introduction of ICIs in metastatic MSI-H EC patients raises the attention to understand the safety profile on the long-term use to help patients to get the most benefit minimizing the onset of adverse events.\u003c/p\u003e \u003cp\u003eWe report a clinical case of a patient with advanced EC and MSI-H treated with dostarlimab presenting a bacterial pneumonia that could mimic an ICI-interstitial lung disease (ILD) adverse event after a long-term response.\u003c/p\u003e"},{"header":"2. Case Presentation","content":"\u003cp\u003eA 68-year-old patient, in January 2020, after vaginal bleeding, underwent diagnostic investigation with transvaginal ultrasound and subsequent Computed Tomography (CT) scan finding an endometrial lesion with associated retroperitoneal and pelvic bilateral adenopathies.\u003c/p\u003e \u003cp\u003eIn June 2020, she underwent robotic hysterectomy and adnexectomy. Histopathological examination diagnosed endometrioid adenocarcinoma of the uterine body, Grading 3 (poorly differentiated tumor) ER +, PR +, p53 -/+. pT3b N0 (sentinel lymph node); FIGO IIIB.\u003c/p\u003e \u003cp\u003eThe treatment included adjuvant chemotherapy with Carboplatin and Paclitaxel, of which only one administration was performed due to a subsequent hospitalization for ischemic stroke. In December 2020, she performed RT on pelvic excavation, common iliac, internal iliac, external iliac, presacral, obturator, parametrium and vaginal dome for a total dose of 45Gy.\u003c/p\u003e \u003cp\u003eSubsequent clinical, instrumental, and biochemical follow up resulted negative until January 2023, when new genital blood loss appeared.\u003c/p\u003e \u003cp\u003eThus, an MRI of the pelvis with contrast was performed, revealing a vaginal dome solid mass, infiltrating the mesorectum with cranio-caudal diameter of 34 mm, antero-posterior of 25 mm and latero-lateral of 33 mm. Bilateral external iliac lymph node enlargements were also found. CT scan performed subsequently also confirmed a picture of peritoneal carcinosis.\u003c/p\u003e \u003cp\u003ePolymerase Chain Reaction Real Time (PCR) analysis detected MSI-H (instability of protein BAT25, BAT26, NR21, NR22, NR24, NR27, CAT25, MONO27) and accordingly in February 2023 a first-line immunotherapy with Dostarlimab 500 mg every week for 4 cycles was administered.\u003c/p\u003e \u003cp\u003eBy multiplex-PCR, Lynch syndrome was also ruled out.\u003c/p\u003e \u003cp\u003eAt the end of the induction therapy CT scan showed regression of local disease with a dimensional and numerical reduction of peritoneal implants. Hence, the maintenance with dostarlimab 1000 mg every 6 weeks was dispensed.\u003c/p\u003e \u003cp\u003eIn September 2023, after 4 doses of maintenance therapy, she performed a CT scan that confirmed further dimensional reduction of peritoneal implant.\u003c/p\u003e \u003cp\u003eIn November 2023 a worsening of postural instability, dizziness and objective fatigue was reported requiring a hospitalization. The CT scan showed extensive \" ground-glass\" consolidative parenchymal thickenings with crazy-paving aspects and predominantly mantle-like distribution involving the right upper lobe, middle lobe, and LID, to be attributed to pneumonia picture. At the abdominal area, numerical and dimensional reduction of peritoneal implants.\u003c/p\u003e \u003cp\u003eBroncho-Alveolar Lavage was positive for Moraxella catarrhalis. Therefore, intravenous corticosteroid therapy and antibiotic therapy with meropenem, linezolid was started with a consequent clinical-instrumental resolution achieved. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) Immunotherapy was suspended for three months, and resumed once the pneumonia was solved. Treatment with Dostarlimab is still ongoing and the CT scan performed in May 2025 confirmed a partial response of at least 15 months.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e "},{"header":"3. Discussion","content":"\u003cp\u003eTreatment options have historically been limited for patients with advanced or recurrent EC who have disease progression on or after first-line platinum-based chemotherapy, including those with dMMR/MSI-H tumors, with limited efficacy and no standard of care for second-line therapy.\u003csup\u003e4\u003c/sup\u003e In this setting, ICIs have shown remarkable responses in advanced EC, especially in those harbouring dMMR/MSI alteration.\u003c/p\u003e\u003cp\u003eA recent review included 15 clinical trials employing ICIs in advanced EC: anti-PD1 (pembrolizumab, nivolumab, dostarlimab) and anti-PD-L1 agents (avelumab, atezolizumab, durvalumab) that were administered as single agents to evaluate their efficacy. \u003csup\u003e10\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eWhen considering only MSI patients, ORR ranged from 26.7–58%, while in MSS patients the ORR was 3–26.7%. Among MSI groups, mPFS to ICI monotherapy was 8.1 months (range 5.5–13.1 mos) while in all-comers patients the mPFS ranged from 1.7 to 18.9 months. \u003csup\u003e10\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAccordingly, the updated results of the GARNET study reported a 45.5% (95% CI 7.1–54.0) of ORR in 143 patients with dMMR/MSI-H EC, patients with 6.0 (95% CI 4.1–18.0) months of mPFS. \u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eConsistent with these previous investigations, the present case exhibited a good response to dostarlimab, with a response maintained for more than 15 months.\u003c/p\u003e\u003cp\u003eNevertheless, ICIs are associated with adverse reactions (AEs) that differ from those of conventional chemotherapy and targeted molecular therapy.\u003c/p\u003e\u003cp\u003eA systematic literature review was undertaken in March 2024 using the following keywords \u003cem\u003e``IMMUNOTHERAPY IN ENDOMETRIAL CANCER\u003c/em\u003e'' to assess the tolerability of immunotherapy in metastatic EC. Starting from 48 scientific articles we selected 11 clinical trials in which monoimmunotherapy was performed in patients who reported EC (Table\u0026nbsp;1); three of them were not included for missing safety data.\u003csup\u003e12,13\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eA total of 143 patients with dMMR/MSI-H EC and 156 patients with MMRp/MSS EC were evaluated in the GARNET, a phase I single-arm study of dostarlimab monotherapy. The most frequently occurring treatment-related AEs (TRAEs) were respectively: fatigue (17.8%), diarrhea (14.6%), and nausea (13.7%). The most common irTRAEs were hypothyroidism (8.3%), arthralgia (3.2%), increased ALT (2.5%), and increased AST (2.2%). Pneumonitis occurred in 3 pts 1.0%, of which 2 (1.3%) dMMR/MSI-H and 1 (0.6%) MMRp/MSS. \u003csup\u003e11\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe nonrandomized, open-label, multicohort, phase II KEYNOTE-158 included 90 patients with previously treated MSI-H/dMMR advanced EC receiving pembrolizumab 200 mg once every 3 weeks for 35 cycles. TRAEs occurred in 68 patients (76%) and the most frequently reported were pruritus (24%), fatigue (21%), and diarrhea (16%) while irTRAEs were hypothyroidism (14%), hyperthyroidism (8%), and infusion reactions (4%). Pneumonitis was registered in 1 patient.\u003csup\u003e14\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eA single-center, randomized, open-label, phase II study of durvalumab 1500 mg (n = 38) versus durvalumab 1500 mg plus tremelimumab 75 mg every 4 weeks in patients with EC showed that in the first arm the most common grade 3 or higher TRAEs were anemia (n = 3, 8%), hyperglycemia (n = 2, 5%), elevated lipase (n = 2, 5%), diarrhea, elevated alanine transaminase, hyponatremia, and lymphocyte decrease (each n = 1, 3%). No pneumonia was recorded. \u003csup\u003e15\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe phase II trial evaluated the PD-L1 inhibitor avelumab in two cohorts of patients with EC: (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) dMMR and/or documented mutation in the exonuclease domain of POLE, MMRD/POLE cohort; and (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) MMRp cohort. Frequent TRAEs of any grade (≥ 10%) were fatigue (n = 11, 35.5%), nausea (n = 5, 16.1%), hypothyroidism (n = 4, 12.9%) and decreased neutrophil count (n = 4, 12.9%).\u003c/p\u003e\u003cp\u003eOf 31 patients who initiated avelumab 1 (67%) patient for each cohort had pneumonitis. \u003csup\u003e16\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eA multicenter phase II study was performed in women with EC with pMMR tumor or dMMR progressing after one to three lines of chemotherapy. Sixty-nine women received durvalumab 1500 mg given every 4 weeks until progression or unacceptable toxicity. There were 19 irAEs reported, mainly of grades 1 and 2 (n = 18), including hypothyroidism (n = 7), hyperthyroidism (n = 8), pneumonitis (n = 2) and hypoadrenalism (n = 1).\u003csup\u003e17\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe Phase I, multi-center, first-in-human, open-label, dose-escalation/expansion clinical trial investigated single-agent atezolizumab in cohorts of patients with recurrent epithelial ovarian or uterine cancer (UC). The most common any-grade TRAEs in the latter cohort (n = 15) were diarrhea and fatigue, which occurred in 3 (20.0%) and 2 patients (13.3%), respectively; grade 3 TRAEs were diarrhea, colitis and rash (n = 1 each). No differentiation with MSI was performed. \u003csup\u003e18\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe KEYNOTE-028 is a multicohort, open-label, phase Ib basket trial investigating the safety and efficacy of pembrolizumab in 24 patients with PD-L1–positive advanced EC. TRAEs of any grade were experienced by 13 patients (54.2%); those occurring in ≥ 10% of patients included fatigue (n = 5; 20.8%), pruritus (n = 4; 16.7%), pyrexia (n = 3; 12.5%), and decreased appetite (n = 3; 12.5%). \u003csup\u003e19\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe phase II study evaluated the efficacy and safety of nivolumab in 43 patients with advanced/recurrent UC. The 62.8% of patients had AEs and those with an incidence ≥ 10% were: hypertransaminasemia (n = 11, 25.6%), pruritus (n = 6, 13.9%), fatigue (n = 6, 13.9%), hypothyroidism (n = 5, 11.6%). Only 2 patients had MSI -H but no specific AEs was reported.\u003csup\u003e20\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eAccording to this review fatigue diarrhea, nausea, pruritus and hypothyroidism were common TRAEs transversely described across different anti PD-L1/PD-1 in advanced EC. (Table I) Some cases of pneumonitis were registered.\u003c/p\u003e\u003cp\u003eIn fact, lung toxicities, such as interstitial lung disease (ILD), associated with ICIs are not exceptional. ICI-ILD are usually linked to nonspecific clinical symptoms and occur during the first few months with characteristic radiological signs that include ground-glass opacities, organizing pneumonitis patterns and condensations. Organizing pneumonia is characterized by lymphocytic interstitial inflammation.\u003csup\u003e21\u003c/sup\u003e Both entities occur from a T-helper-1 uncontrolled immune response but usually do not coexist. These results suggest an immune-mediated mechanism of toxicity.\u003csup\u003e21\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIn this case report our patient presented worsening aspecific symptoms and imaging that could mimic ICI- ILD. However, after an in-depth analysis a bacterial pneumonia was found which was most likely related to patient’ comorbidities. Accordingly, dostarlimab was well tolerated and it could be resumed once the pneumonia was solved\u003c/p\u003e"},{"header":"4. Conclusion","content":"\u003cp\u003eIn summary, we described ICIs in a patient with advanced EC and MSI-H; TRAEs during this particular treatment are still new in EC and accordingly real-world data on the long-term use are needed to properly manage ICIs. In fact, although a potential pulmonary irTRAE was suspected at first in our case, it was crucial to isolate the bacteria; its resolution allowed to continue dostarlimab and to maintain the response achieved.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThis case report complies with the specific requirements of our institution and no ethics approval was needed.\u003c/p\u003e\u003cp\u003e \u003ch2\u003eInformed consent\u003c/h2\u003e \u003cp\u003e The participant has consented to the submission of the case report to the journal and an informed consent was obtained.\u003c/p\u003e \u003ch2\u003eFunding Declaration\u003c/h2\u003e \u003cem\u003eThe author(s) received no financial support for the research, authorship, and/or publication of this article.\u003c/em\u003e\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eF.C. and M.I. wrote the main manuscript text. M.V. prepared figures 1C.C. prepared table 1.G.R. contributed to the conception of the workM.C.P made substantial contributions to the design of the work.A.V. Ensured the accuracy or integrity of any part of the work.G.A. approved the version to be published.All authors reviewed and approved the manuscript.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eConcin, N.; Matias-Guiu, X.; Vergote, I.; Cibula, D.; Mirza, M. R.; Marnitz, S.; Ledermann, J.; Bosse, T.; Chargari, C.; Fagotti, A.; Fotopoulou, C.; Gonzalez Martin, A.; Lax, S.; Lorusso, D.; Marth, C.; Morice, P.; Nout, R. A.; O\u0026rsquo;Donnell, D.; Querleu, D.; Raspollini, M. R.; Sehouli, J.; Sturdza, A.; Taylor, A.; Westermann, A.; Wimberger, P.; Colombo, N.; Planchamp, F.; Creutzberg, C. L. 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Rev. 2019, \u003cem\u003e28\u003c/em\u003e (154). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1183/16000617.0012-2019\u003c/span\u003e\u003cspan address=\"10.1183/16000617.0012-2019\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable I Treatment- Related Adverse Events (TRAEs) that occurred in \u0026ge; 10% of patients with endometrial cancer who underwent to monoimmunotherapy in clinical trials.\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"718\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTRAEs\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDostarlimab\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eGARNET\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePembrolizumab\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eKEYNOTE-158\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003ePembrolizumab\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eKEYNOTE-028\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAvelumab\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDurvalumab\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eAtezolizumab\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eNivolumab\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eFatigue\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e17.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e21\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e20.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e35.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e57\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e13.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eDiarrhea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e14.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eNausea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e13.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e16.1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003ePruritus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e24\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e16.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eHypothyroidism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e12.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e11.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eDecreased neutrophil count\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e12.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eCostipation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eGeneral disorders and administration site conditions\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e29\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eSkin and subcutaneous tissue disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003ePain\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eUrinary tract infection\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eVomiting\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eAnorexia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e12.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eDyspnea\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eGastrointestinal disorders\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eAnemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eHyperthyroidism\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eRash\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"15.73816155988858%\" valign=\"top\"\u003e\n \u003cp\u003eHypertransaminasemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.231197771587743%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.484679665738161%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"9.192200557103064%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"11.838440111420613%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.09192200557103%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.584958217270195%\" valign=\"top\"\u003e\n \u003cp\u003e25.6\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\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":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-4749851/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4749851/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eEndometrial cancer is a frequent female cancer characterized by four molecular subtypes including the microsatellite instable-high (MSI-H) subgroup where use of immune checkpoint inhibitors (ICIs) showed encouraging activity in the metastatic setting. Nonetheless, adverse events during this particular treatment are still new in endometrial cancer and lack of data on ICIs long-term use are currently available.\u003c/p\u003e \u003cp\u003eHerein, we report a rare case of MSI-H metastatic endometrial cancer which has developed a bacterial pneumonia that could mimic an immune-related adverse events during a long-term response with dostarlimab.\u003c/p\u003e","manuscriptTitle":"Bacterial pneumonia during successful treatment of metastatic endometrial cancer with dostarlimab- case report and a literature review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-28 02:26:29","doi":"10.21203/rs.3.rs-4749851/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-19T05:32:47+00:00","index":"","fulltext":""},{"type":"reviewerAgreed","content":"289632979752471558107705893816136883264","date":"2024-08-06T12:01:17+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-04T16:50:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"250779441273846404669327445201436564290","date":"2024-08-04T15:45:07+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-04T05:07:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"101979356321873431179511245687307595833","date":"2024-08-04T05:00:29+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-29T15:54:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-29T15:04:49+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-27T04:18:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Discover Medicine","date":"2024-07-16T12:50:06+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"discover-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Discover Medicine](https://link.springer.com/journal/44337)","snPcode":"44337","submissionUrl":"https://submission.springernature.com/new-submission/44337/3","title":"Discover Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Discover Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"3d4222c9-82ba-46eb-bcd5-e8ad9036d0ca","owner":[],"postedDate":"August 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-12-02T10:39:00+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-28 02:26:29","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4749851","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4749851","identity":"rs-4749851","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}