bluuebunny/crossref_metadata_2025_split huggingface dataset:
Edema and serositis as an adverse event in patients with cancer receiving immune checkpoint blockade: Systematic review to evaluate this immune-related adverse event and associated treatment strategies.
Authors: Elias Evelyn , Rohs Nicholas Cole , Koseki Mako , Chesta Fnu , Takaoka Kensuke , Nishimura Yoshito , Fujiwara Yu 
Published: June 2023

2649 Background: Immune checkpoint blockade (ICB) is a standard therapeutic option for certain patients with solid tumors, often leading to durable responses. Immune-related adverse events (irAEs) can impact treatment duration and patients' quality of life. The mechanism of irAEs is proposed to be an inflammatory response triggered by blocking immune checkpoints, and nonspecific symptoms like edema and fluid accumulation can occur. We performed a systematic review to summarize reported studies evaluating edema and serositis to explore edema and serositis as an irAE and management strategies. Methods: We performed a database search in Medline, Embase, and Web of Science for studies reporting the incidence and outcome of immune-related generalized edema (irGE) including peripheral edema, capillary leak syndrome, serositis, pleural/peritoneal/pericardial effusion, and anasarca as an irAE among patients with solid tumors treated with ICB. Two independent reviewers analyzed the eligibility of each article. Those that did not report outcomes related to irGE were excluded. The number of patients, cancer type, name and type of ICB, type of irGE, treatment of irGE, and treatment outcome for irGE were extracted from each article to summarize the characteristics of irGE. Results: 662 articles were identified, and 80 studies were included (65 case reports/series, 8 cohort studies, 3 phase 1/2 clinical trials) that described clinical characteristics and treatment outcomes for AEs from 196 patients, and 259 irGE incidences reported. The median age was 62 (Interquartile range: 55-68). 35.9% of cases were female (n=28/78). Commonly reported irGEs were pericardial effusion (n=115, 44.4%), pleural effusion (n=58, 22.4%), peripheral edema (n=40, 15.4%), and ascites (n=19, 7.3%). PD-1 blockade was utilized in 75.8% of cases, followed by PD-L1 blockade (14.9%) and dual ICB (CTLA4 and PD-1 blockade, 4.6%). Common cancers where irGE occurred were: lung cancer (63.9%), malignant melanoma (17.0%), and urothelial carcinoma (3.1%). We classified irGEs into primary irGE (n=84, 42.9%), secondary to other irAEs (n=41, 20.9%), secondary to pseudoprogression (n=14, 7.1%), and cancer progression (n=13, 6.6%). Glucocorticoid was used to manage irGEs in 91 patients (46.4%); 48 cases (24.5%) required the prednisone-equivalent dose of > 1 mg/kg/day. ICB discontinuation was confirmed in 96 cases (49.0%) among which 53 (27.0%) permanently stopped ICB use due to irGEs. Conclusions: irGE is an important irAE among patients with solid tumors receiving ICB. Most cases required glucocorticoid therapy along with discontinuation of ICB, which could result in poorer quality of life and potentially impact outcomes. The pathophysiology, incidence and clinical outcomes of irGE need to be accurately described in further studies.
Real-world data: Clinical characteristics and outcomes of patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab in Veteran Health Administration.
Authors: Alkadimi Munaf , Lucero Kana , Boyle Lauren Diaz , Fierro Maria Elena , Franklin Kathleen , Nooruddin Zohra , Mader Michael 
Published: June 2023

2651 Background: Advanced Hepatocellular carcinoma (HCC) is an aggressive tumor, and most patients have a poor prognosis. Recent clinical trials have demonstrated improved survival with molecularly targeted treatment and immunotherapy. Atezolizumab plus Bevacizumab (A+B ) is the recommended first-line treatment for advanced HCC based on the phase 3 IMbrave 150 trial. However, in a real-life setting, many patients do not meet the inclusion criteria of this landmark trial. This study proposes a retrospective review of outcomes of advanced HCC patients receiving A + B in Veterans Health Administration (VHA). Methods: Patients with advanced HCC receiving 1st line systemic therapy with A+ B at the VHA between Dec 1, 2019, to Mar 1, 2022, were selected from the electronic medical records (EMR) using ICD-9 and ICD-10 codes. Abstractors reviewed EMR and followed from their index date of A+ B initiation until death or their last VHA visit, with the study period ending on Jan 31, 2023. The Chi-Squared test was used to compare rates, and the Mann-Whitney test was used to compare medians. Results: A total of 332 patients met the study criteria. The median age was 67 yrs., 99% were males, 63% non-Hispanic White, 26% were Black, 66 % had ECOG ≥ 1, 84% had CPS class A, 16% had CPS class B and C, 62% had grade 2 ALBI score, 56% had viral hepatitis-caused HCC, 80 % had cirrhosis, and 67% had prior local therapies. The outcomes are shown. Conclusions: In our real world, despite having similar PFS as the phase 3 IMbrave 150 trial, our OS at 12 months was lower (52% vs. 67%), given that we had more elderly patients with moderate liver dysfunction and 40% were non-white. This study provides actual outcomes in clinical practice where patients do not match the study population of the pivotal trial. [Table: see text]
Safety and efficacy of immune checkpoint inhibitors (ICIs) in patients (pts) with cardiac metastases (mets) from solid tumors.
Authors: Nassar Amin , Abou Alaiwi Sarah , El Zarif Talal , Denu Ryan Austin , Hayek Salim S. , Goodman Rachel S , Woodford Rachel , Neilan Tomas G. , Haykal Tarek , Kojima Yuji , Trevino Alexandra , Hui Gavin , Tandon Ankita , El-Am Edward , Mittra Arjun , Baena Javier , Choudhary Arrush , Grynberg Shirly , Choueiri Toni K. , Naqash Abdul Rafeh 
Published: June 2023

2653 Background: Given underlying differences in the tumor microenvironment across metastatic sites, ICIs demonstrate variable efficacy depending on sites of met involvement. Data on the safety and outcomes of pts on ICIs with cardiac mets are limited. Methods: In an international multi-center retrospective study, pts with solid tumors and baseline mets to the heart who had received ≥1 cycle of ICIs were included. Immune-related adverse events (irAEs) were graded per CTCAE v5.0. Objective response rates (ORR) were evaluated by RECIST1.1 when available. Median overall survival (mOS) and median progression-free survival (mPFS) were calculated from time of ICI initiation using the Kaplan-Meier method. Results: 110 pts across 20 institutions were identified with a median follow-up of 36 (95% CI 26-51) months. Melanoma (38%, n=42) and non-small cell lung cancer (NSCLC, 24%, n=26) were the most common cancers. Median age at ICI initiation was 65 (IQR: 59-75) years and 29% (n=26) received combination ICI therapy with anti-PD1 and anti-CTLA4. Overall, 62% (n=68) received ICIs as 1st line. The mets were mostly located in the atria (37%, n=41) and ventricles (35%, n=39). At ICI initiation, 21% (n=23) had a cardiac thrombus. Of 78 pts with available echocardiographic data at time of ICI initiation, the mean ejection fraction was 61+/- 7.1%. Cardiology referrals and cardiac MRIs since time of cancer diagnosis were completed on 53% (n=58) and 47% (n=52) of pts, respectively. Overall, 36.4% (n=40) of pts had cardiac complications from the mets, including arrhythmias (13%, n=14), arterial/venous emboli (3.6%, n=4), and cardiac tamponade (2.7%, n=3). For NSCLC, ORR, mPFS (95% CI), and mOS (95% CI) were 23%, 4.4 months (3.0-7.5), and 9.9 months (5.9-14.7), respectively. For melanoma, ORR, mPFS, and mOS were 35.7%, 9.1 months (5.2-20), and 29 months (14-58), respectively. Cardiac met ORRs for NSCLC and melanoma were 27% and 43%, respectively. 74% (N=71/96) of pts with evaluable response data had concordant response in the burden of overall disease and cardiac disease. IrAEs are shown. Conclusions: Although cardiac mets are frequently associated with cardiac complications, ICIs demonstrate meaningful efficacy with no overtly concerning safety signals. Close to three-quarter of pts have concordant response in the overall disease and cardiac disease burden. Multi-disciplinary approach involving cardiologists and oncologists need to be implemented to appropriately manage pts with cardiac mets. [Table: see text]
Pan tumor outcomes to immune checkpoint inhibitors in patients of Native American origin in the United States: The multicenter POINT-US study.
Authors: Phan Minh Duc , El Tomb Paul Antoine , Khreis Tariq , Meissner Tobias , Elsey Rachel , Xu Bing , Arshad Junaid , Rozell Umbreen Arshad , Tjong Elysia , Florou Vaia , Puri Sonam , Khan Arsalan , Rhoades Dorothy , Aljumaily Raid , Ayanambakkam Adanma , Burtman Anthony , Bigbey Mark , Sjoquist Michael , Williams Casey B. , Naqash Abdul Rafeh ,   OUHSC
Published: June 2023

2654 Background: Despite receiving identical standard-of-care therapies, epidemiological data indicate that Native American (NA) patients (pts) with cancer have worse outcomes vs. White pts. ICIs have revolutionized the treatment of certain tumors, however pts from certain racial and ethnic groups, including NA pts, are underrepresented in ICI trials. Methods: This is an ongoing multi-center retrospective study across four U.S. academic cancer centers that serve a high volume of NA pts. We included pts with self-reported race as NA in electronic medical records. We evaluated clinical outcomes and immune-related adverse events (irAEs) of 71 NA pts age ≥18 years with various solid tumors treated with ICI-based therapies between 2015 to 2021. IrAEs were defined based on the Common Terminology Criteria for Adverse Events (version 5.0) or RECIST 1.1. as available, was used to determine objective response rate (ORR). Kaplan Meier log-rank method was used to generate median progression free survival (mPFS) and median overall survival (mOS). Results: Median age (range) at ICI initiation was 62 (24 -81) years; 43 (60%) were males, with 26 (37%) females, 2 pts with missing gender data. 55 (77%) of pts had ECOG performance status 0. The distribution of top six tumor types included (number of pts [%]): non-small cell lung cancer (NSCLC) 22 (31%), renal cell carcinoma (RCC) 16 (23%), melanoma 7 (10%), small cell lung cancer (SCLC) 4 (6%), hepatocellular carcinoma 4(6%); colorectal adenocarcinoma, head and neck squamous cell carcinoma, cervical squamous cell carcinoma each had 3 pts (4%). Most pts (51 [72%]) received single agent ICI, 12 (17%) had dual ICI, 4 (6%) had chemotherapy+ ICI, and remaining had either ICI + tyrosine kinase inhibitor or ICI + study drug (4 [6%]). 55% of pts with NSCLC underwent tumor next-generation sequencing (NGS) while <30% of patients with renal cell carcinoma or melanoma had tumor NGS performed. Among 71 pts, 17 (24%) had any grade (G) irAE, 4 (6%) were reported to be ≥G3. The median time to irAE onset was 18 weeks and 3 (4%) pts discontinued ICI due to irAEs. The mPFS, mOS and ORR for the most frequent tumors (N ≥5) are shown. Conclusions: Although limited by sample size, our emerging data provides new insights into ICI efficacy and irAEs in NA pts that have been unknown to date. To our knowledge, this is the first and only attempt to date evaluating ICI outcomes in NA pts. Updated clinical data and tumor genomics will be presented at the meeting. [Table: see text]
A comprehensive pan-cancer analysis of PD-L1 expression using clone E1L3N in Chinese patients with cancer.
Authors: Lu Huangbin , Huang Zhan , Ge Huijuan , Wang Hongyu , Ruan Li , Zheng Frank 
Published: June 2023

2656 Background: Immune checkpoint inhibitors (ICIs) benefit patients with multiple cancer types, and the expression of programmed death ligand 1 (PD-L1) protein assessed by immunohistochemistry (IHC) has been correlated with response and survival benefit from anti-PD-1/PD-L1 ICI therapies in several cancer types. IHC assay with E1L3N clone is currently approved by the NMPA for PD-L1 detection in non-small cell lung cancer (NSCLC), but its performance in other cancer types needs to be further validated. Thus, we performed this study to examine the prevalence of PD-L1 expression in a wide variety of tumor types in Chinese pan-cancer patients using the E1L3N antibody clone. Methods: From 2019 to 2022, a total of 13,647 patient across multiple tumor types were analyzed. Tumor tissue samples were subjected to IHC. PD-L1 expression was tested using the E1L3N PD-L1 IHC assay (Amoy Diagnostics, Xiamen, China), and scored with the tumor proportion score (TPS) and combined positive score (CPS). PD-L1 expression status was identified as positive and negative according to TPS or CPS. For NSCLC: negative (TPS < 1%), low expression (TPS 1-49%), and high expression (TPS ≥ 50%). For gastric/gastroesophageal junction carcinoma (GC/GJC): negative (CPS < 1), low expression (CPS 1-5), and high expression (CPS ≥ 5). For other cancer: negative (CPS < 1), low expression (CPS 1-10), and high expression (CPS ≥ 10). Results: In total, 14 cancer types were enrolled in the present study, including 68.2% NSCLC, 6.9% colorectal carcinoma (CRC), and 3.8% GC/GJC, and the remaining 21.1% include esophageal cancer (EC), breast cancer, cervical cancer (CC), biliary tract cancer (BTC), pancreatic cancer (PC), ovarian cancer, renal cancer, small cell lung cancer, urothelial carcinoma (UC), bladder cancer, head and neck squamous cell carcinoma (HNSCC), etc. PD-L1 positivity by TPS was observed in 52.5% NSCLC patients, similar to the frequency of PD-L1 expression in Chinese NSCLC patients detected using 22C3 clone. 76.0% and 36.7% of GC/GJC patients with PD-L1-positive tumors at a CPS cutoff of ≥ 1 and ≥ 5, respectively. PD-L1 positive expression frequency was higher than that in western GC/GJC patients detected using 22C3 and 28-8 clone (as reported from previous research: PD-L1 positivity with CPS ≥ 1 was 45.5% using the 22C3 assay and 49.1% using the 28-8 assay). 73.6% and 17.5% of CRC patients with PD-L1-positive tumors at a CPS cutoff of ≥ 1 and ≥ 10, respectively. In addition, 8 tumors (EC, CC, breast cancer, PC, BTC, UC, HNSCC, and bladder cancer) had the prevalence of PD-L1 CPS ≥ 1 greater than 50%. Conclusions: E1L3N can be used as a reliable alternative antibody clone to evaluate PD-L1 expression status not only in NSCLC patients but also in other cancer types.
Factors associated with severe immune checkpoint inhibitor-induced pneumonitis.
Authors: Abu-Sbeih Hamzah , Moodabagil Meghana , Peng Jing , Ma Jianing , Easterling Robert , Viveiros Matthew , Li Mingjia , Secor Austin , Goodyear Evelyn , Kendra Kari Lynn , Otterson Gregory Alan , Presley Carolyn J , Donnelly Edwin , Meara Alexa Simon , Owen Dwight Hall , Ho Kevin 
Published: June 2023

2658 Background: Immune checkpoint inhibitor (ICI) induced pneumonitis (ICIp) can be severe and even fatal, but risk factors for severe ICIp remain poorly characterized. In this abstract, we characterize ICIp and assess factors associated with severe disease. Methods: This is a retrospective study of consecutive patients who received ICI therapy and developed ICIp at the Ohio State University (2013-2020). Patients with ICIp were identified from a pharmacy database using ICD-10 codes followed by chart review to confirm diagnosis. ICIp was graded based on the CTCAE v5.0 criteria. Laboratory values were collected at the onset of ICIp. A thoracic radiologist reviewed chest imaging for pattern and severity. Survival probabilities were estimated with Kaplan-Meier curve and compared with log rank test. Results: Of 2963 patients who received ICI, we identified 119 patients (4%) with ICIp: 75 (63%) were males; 79 (66%) received PD-1 inhibitor monotherapy; and 71 (60%) had lung cancer. ICIp was severe (grade 1-2) in 69 patients (58%) and mild (grade 3-5) in 50 (42%). 74 patients (62%) were hospitalized. 63 patients (53%) needed oxygen supplementation. ICI therapy was held in all patients except one. ICI was rechallenged in 26 patients; 6 of them (23%) had recurrence of ICIp symptoms. All but 2 patients received steroids for the treatment of ICIp. 10 patients received non-steroidal medications (7 IVIG, 2 infliximab, 1 rituximab, 1 abatacept, 1 cyclophosphamide). Steroids were tapered in 6 patients of those who received non-steroidal medications. 3 of the patients who received IVIG had improvement of symptoms. Factors associated with severe ICIp. 21 patients (18%) died while hospitalized for ICIp are shown. Patients with severe ICIp had shorter overall survival than those with mild ICIp (P < 0.001). Conclusions: ICIp is a serious adverse event that limits ICI treatment and can lead to hospitalization and death. Factors associated with severe ICIp in our study include lower lymphocyte and eosinophil counts, lower albumin levels, finding of consolidation or bronchiectasis on imaging, and lower predicted FVC and TLC. Prospective studies are merited to validate our findings and to investigate the appropriate treatment of ICIp. [Table: see text]
Immune-related adrenal insufficiency: A single center retrospective analysis.
Authors: Polshina Natalya , Filonenko Daria , Volkova Ekaterina , Zhukova Lyudmila 
Published: June 2023

2659 Background: Immune checkpoint inhibitors (ICI) became widely used for treatment of various malignancies. They may cause different immune-related adverse events (irAEs), including adrenal insufficiency (irAI). IrAI was reported to be comparatively uncommon but potentially life threatening. We conducted a retrospective single center study to identify and describe the incidence and characteristics of AI associated with ICI. Methods: We reviewed the medical records of patients treated at an oncological department at Loginov Moscow Clinical Scientific Center between Sep’2019 and Jan’2023 with immunotherapy under direct cortisol monitoring every 6-8 weeks. The main criteria for AI was low serum cortisol in the absence of glucocorticoid intake. Results: A total 101 patients (pts) treated by ICI or ICI in combination with chemotherapy or targeted therapy for various malignancies were included in our retrospective analysis. 16 patients (15.8%) were diagnosed with AI: 7 pts with renal cell carcinoma (RCC), 6 pts with melanoma (2 in adjuvant setting), 1 with non-small-cell lung cancer (NSCLC), 1 with small-cell lung cancer (SCLC), 1 with MSI-high colorectal cancer (CRC). Median age was 65 (range 46-79), the majority (10 pts, 62.5%) were male. The median time of irAI onset from ICI start was 5 months (range 2-15). Assessment of serum cortisol was performed every 6-8 weeks routinely and off-schedule in patients who had new onset AI-like symptoms. The most frequent symptoms were unspecific and included fatigue and weakness (100%), loss of appetite/anorexia (69%), hypotension (50%), weight loss (44%), insomnia (38%), chills (31%), nausea/vomiting (31%), muscle pain or cramps (31% and 25% respectively), dizziness (25%), dry mouth (25%), headache (13%), fever (6%). Remarkably, laboratory detected serum cortisol decline preceded any AI symptoms in 7 patients (43.7%). Other 7 patients (43.7%) had concurrent secondary hypothyroidism which suggested panhypopituitarism. Hydrocortisone replacement led to rapid symptoms recovery in 15/16 patients. Additional treatment with fludrocortisone was required for only one patient who had primary/mixed AI due to bilateral metastases of RCC in adrenal glands. All patients resumed immunotherapy after symptoms resolved. Only 1 patient needed treatment modification (ipilimumab cessation). By 12th February 2023 median follow-up from irAI onset is 7 months (range 0.5-37), 12 patients are alive, they all remain on permanent hydrocortisone replacement therapy. Conclusions: Routine cortisol assessment during immunotherapy allowed us to detect irAI in 15.8% of patents that is higher than usually reported. Detection of irAI before clinical presentation let us prevent severe consequences including life threating. We consider that routine cortisol assessment during immunotherapy should be implemented in clinical practice.
Impact of obesity on the risk of immune-related adverse events (irAEs) among patients receiving immune-checkpoint inhibitors (ICI) treatment: A retrospective cohort study.
Authors: Elsaid Mohamed I. , Paskett Electra D. , Shendre Aditi , Manne Ashish , Li Lang 
Published: June 2023

2660 Background: Recent studies suggest that obesity is linked to improved progression-free and overall survivals in patients treated with Immune-Checkpoint Inhibitors (ICI). Studies have also shown that irAEs occurrence following ICI infusion is associated with improved survival. Current evidence on the relationship between obesity and the risk of irAEs has been inconclusive. We aimed to assess the impact of obesity on the risk of irAEs after ICI infusion using data from a large retrospective cohort. Methods: The study included newly diagnosed stage I-VI cancer patients treated with ICIs between 2012 and 2021 at the Ohio State University Comprehensive Cancer Center. Patients’ body mass index (BMI) data at or before ICI infusion were classified into normal <25.0 Kg/M2, 25 to < 30 Kg/M2 overweight and obese ≥ 30 Kg/M2. An incident irAE was defined as any gastrointestinal, pulmonary, dermatological, endocrine or hepatobiliary irAEs following ICI infusion. Cox proportional hazard models were fitted to test the associations between obesity and 1) any irAEs and 2) organ-specific irAEs. We evaluated the dose-response association between BMI and irAEs using a three-knot restricted cubic spline in the adjusted Cox proportional models. Results: A total of 4,761 patients were included in the study with a median age of 62 years, 59.2% males and 89% White non-Hispanics. An estimated 34.7%, 31.5% and 33.8% of patients had normal, overweight, and obese BMIs. The median time to incident irAEs was 4.3 months. An estimated 2,791 (58.6%) experienced an irAE, with 28.8% having gastrointestinal, 17.7% pulmonary, 23.7% dermatological, 21.8% endocrine, and 4.4% hepatobiliary irAEs. BMI was a significant predictor of increased risk of irAEs, adjusted hazard ratio (aHR) 1.08 (95%CI: 0.98 to 1.19) overweight vs. normal BMI and aHR 1.17 (95% CI: 1.06 to 1.28) obese vs. normal BMI. In the organ-specific irAEs models, obese vs. normal BMI patients had higher risks of gastrointestinal aHR 1.23 (95% CI: 1.07 to 1.41), dermatological aHR 1.25 (95% CI: 1.07 to 1.28), and hepatobiliary aHR 1.61 (95% CI: 1.11 to 2.36) irAEs. A dose-response was observed in the relationship between BMI and the risk of irAEs whereby patients with BMIs lower than 22 Kg/M2 (median normal BMI range 18.5-24.9 Kg/M2) had lower risks of irAEs [BMI 18.5 Kg/M2 vs. 22 Kg/M2, aHR 0.93 (95% CI, 0.88 to 0.97)] and those with BMIs higher than 22 Kg/M2 had higher risks of irAEs [BMI 30 Kg/M2 vs. 22 Kg/M2, aHR 1.19 (95%CI, 1.09 to 1.29)] and [BMI 40 Kg/M2 vs. 22 Kg/M2, aHR 1.22 (95% CI, 1.11 to 1.34)]. Conclusions: Among patients treated with ICIs, higher BMI was significantly associated with an increased risk of irAEs. Patients with obesity should be monitored for symptom management following ICIs infusion. Our findings help to explain the previously reported benefits of increased BMI and higher irAEs rates on improved survival.