bluuebunny/crossref_metadata_2025_split huggingface dataset:
Postoperative prognosis in patients with NSCLC with different EGFR mutation sites.
Authors: Dong Chao , Zhang Hushan , Liu Weiqing , Kong Deyu , Chen Xiao , Mo Fei , Deng Jun , Qian Ying 
Published: June 2023

e20528 Background: Lung cancer can be divided into small cell lung cancer and non-small cell lung cancer. At the same time, non-small cell lung cancer can be divided into non-small cell lung cancer with different molecular mutations. Among them, the EGFR mutation accounts for about 50% of the patients with non-small cell lung cancer in China, which is a large group of patients. The EGFR mutation has many sites and many forms of mutational subtypes, including common mutations such as L858R, and rare mutations. Although the proportion of rare mutations is small, it is still different from common mutations in patients with TKI treatment and immunity. Methods: This study collected and analyzed the data from Formalin-Fixed Paraffin-Embedded (FFPE) tissues of 330 NSCLC patients which received surgery and underwent a targeted next-generation sequencing (NGS) assay performed by 3DMed Clinical Laboratory Inc., a College of American Pathologists (CAP) certified and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory of 3D Medicines Inc. between January, 2019 and June, 2022 in China, to obtain a comprehensive molecular profile of EGFR mutations. genomic alterations, tumor mutational burden (TMB) and PD-L1 expression were analyzed. Gene mutation and TMB level were analyzed by NGS, detected PD-L1 expression by using Dako PD-L1 IHC 22C3 pharmDx, Tumor Proportion Score (TPS) was used to determine expression of PD-L1. Finally, the postoperative follow-up data were also collected and analyzed in this study. Results: Therefore, we retrospectively analyzed the tissue samples of patients with non-small cell lung cancer who received surgical treatment, and carried out NGS detection and analysis, as well as postoperative follow-up. Among them, patients with EGFR mutations accounted for 51.2%. We further analyzed the TMB and PD-L1 expression levels of different EGFR mutation subtypes. First, we found that different EGFR mutation sites, whether common mutations such as L859R, 19del or unusual mutations such as S768I, There is no difference in the prognosis after operation, but it is very significant that our results show that there are two or more EGFR mutations at the same time. Conclusions: NSCLC with EGFR mutation is a very large group of patients, which should be further subdivided into different subtypes according to different EGFR mutation sites, and should perform individualized management. This study found that patients with two or more EGFR mutations and patients with EGFR single site mutations are different types of NSCLC, with different postoperative prognosis, and it may be related to the differences in the expression levels of TMB and PD-L1, which is a direction worthy of further exploration in the future.
Association of TP53 mutations with the expression of PD-L1 expression and TMB, and R175H could be the predictor of neoantigen.
Authors: Wang Lucas , Yang Yaxian , Wang Heran , Fan WenTao , Lian Bin , Jin Ying , Luo Weiquan , Long Zhongming , Huang Mingming , Wang Yongsi , Wen Yunjie , Huang Jian 
Published: June 2023

e20530 Background: Lung cancer (LC) is the second leading causes of cancer-related mortality and composed of diverse molecular types. PD-L1 expression and tumor mutation burden (TMB) are important biomarkers of tumor immunotherapy. TP53 mutation is associated with neoantigen productions which is also involved in tumor immunotherapy. The relationship between PD-L1 expression, TMB and TP53 mutations have not yet been fully studied, and the neoantigens derived from TP53 mutations need to be explored. Methods: The total 1932 LC tissue samples (from same number of patients) in formalin fixed and paraffin embedded were collected from Guangzhou Huayin Health Medical Group Co.,Ltd. By targeting next generation sequencing (NGS) of 600 genes, the mutations of TP53 and TMB were obtained. PD-L1 expression was determined according to the tumor proportion score (TPS) evaluated by immunohistonchemistry (the cutoff of PD-L1 is greater than 1% TPS). Neoantigen predictions based on binding affinity data (https://services.healthtech.dtu.dk/service.php?NetMHCcons-1.1). In this data set, mutated peptides of TP53 with a binding affinity of IC50≤50 nM was regarded as candidate neoantigens. Results: Among 1932 samples, 890 (46%) were TP53 mutated. The positive rate of PD-L1 in TP53 mutant type (MT) group was higher than that in TP53 wide type (WT) group(p < 0.01). The WT group had a lower TMB compared with MT group (p = 0.002). The intersection of 49 candidate neoantigens and TP53 high-frequency mutation sites was R175H, which could predicate a neoantigen. Conclusions: This study determined the connection between TP53 mutations and PD-L1 expression and TMB, also made neoantigen prediction of R175H mutation. This study may provide theoretical insights for drug developments of treating lung cancer.
Incidence of additional primary malignancies in patients with malignant peritoneal mesothelioma.
Authors: Pandav Vivek , Patel Jaydeepbhai , Inampudi Jyothik Varun , Li Shenduo , Mahadevia Himil , Koshiya Hiren , Lou Yanyan , Manochakian Rami , Bagaria Sanjay Prakash , Zhao Yujie 
Published: June 2023

e20535 Background: Malignant peritoneal mesothelioma (MPM) is a rare disease with about 600 new cases per million people diagnosed annually in the U.S. High incidence of germline mutations has been reported in MPM patients (pts) without asbestos exposure. However, the incidence rate of developing multiple primary cancers in this population is unknown. The aim of this study is to investigate the frequency of additional malignancies in MPM pts. Methods: Using the Mayo Clinic Cancer Registry, we identified 64 pts who were treated for MPM from January 2002-December 2022 with updated follow-up data until 01/15/2023. Electronic medical records were reviewed. Results: Among the patient cohort, 25 pts were male, and 39 pts were female. 14/64 (22%) pts were found to have at least one additional malignancy, including breast cancer (4/14, 29%), colon cancer (3/14, 21%), lymphoma (3/14, 21%), ovarian cancer (2/14, 14%), melanoma (2/14, 14%), anal squamous cell carcinoma (1/14, 7%), papillary thyroid cancer (1/14, 7%), Chronic lymphocytic leukemia (1/14, 7%), renal cell carcinoma (1/14, 7%), squamous cell carcinoma of tongue (1/14, 7%), hepatocellular carcinoma (1/14, 7%) and pituitary macroadenoma (1/14, 7%). 4/14 (29%) pts had more than one (2-4) non-MPM malignancies. The median age at diagnosis of MPM was 65 years (44-82). The median age at diagnosis of non-MPM malignancies was 66 years (18-81). Most of the patients (11/14) were diagnosed with non-MPM malignancy within 12 months of diagnosis of MPM. Most pts (11/14, 78%) were diagnosed with non-MPM malignancy first, among which 5 pts (45%) were found to have MPM on surveillance scans. Germline mutation information was not available except for 2 pts with known family history (FH) of Lynch syndrome and Li-Fraumeni syndrome. FH was available in 29 pts, out of which 28 pts had FH of cancer identified in first-degree relatives. Among the 14 pts with additional malignancies, 9 pts had FH of cancer in first-degree relatives. Among all pts, 15 (18%) pts had a history of asbestos exposure. Among pts who also had non-MPM malignancies, 3/14 (21%) pts had a history of asbestos exposure. Among the 21 non-MPM cancers, 1/21 (5%), 11/21(52%), 1/21(5%), 3/21(14%), and 5/21(24%) non-MPM malignancies were stage 0, stage I, II, and III, or unknown at the diagnosis respectively. All except 1 pt underwent curative treatment for their non-MPM malignancies, and 12 pts had no evidence of disease at death or the time of last follow-up. Conclusions: The rate of multiple primary malignancies in pts with MPM is high, indicating possible genetic predisposition associated with this disease. Early genetic consultation and evaluation for germline mutations may need to be considered for these pts to improve long-term outcomes.
Impact of BAP1 mutational status on immunotherapy outcomes in advanced malignant pleural mesothelioma: A single institution experience.
Authors: Ogbue Olisaemeka , Unlu Serhan , Sorathia Sharmeen , Nanah Abdel Rahman , Abdeljaleel Fatima , Haddad Abdo S. , Daw Hamed 
Published: June 2023

e20537 Background: Malignant pleural mesothelioma (MPM) is a rare and aggressive tumor of mesothelial cells usually diagnosed at advanced stages with dismal prognosis. Most patients progress after 1st line systemic chemotherapy. In the last decade, single or dual agent immune checkpoint inhibitor (ICI) therapy has emerged as a therapeutic option. BAP1 is a commonly mutated tumor suppressor gene in MPM that has been shown to correlate negatively with survival in other solid tumors. We sought to determine the impact of BAP1 mutation on outcomes with ICIs when used as second line systemic therapy. Methods: We retrospectively reviewed a cohort of MPM patients who received ICIs at the Cleveland Clinic foundation between 2017-2022. Patients must have progressed after 1st line systemic chemotherapy prior to ICI. We then compared oncologic outcomes of ICI therapy based on BAP1 mutational status on Next-Generation Sequencing (NGS). End points of interest were overall response rate (ORR) and progression free survival (PFS) while on ICIs. Results: There were a total of 43 MPM patients who received ICIs following progression on pemetrexed/carboplatin (Median age 74 years, IQR 66-81, range 57-92) with a male predominance (M:F ratio 39:4). Histologies included- 58% epithelioid, 28% sarcomatoid and 14% mixed/biphasic histology. Single agent ICI therapy with nivolumab or pembrolizumab was used in 65%. Median follow up was 3 months. BAP1 mutation on NGS was detected in 16%. Other mutated genes included CDKN2A- 7%, BRAF- 5%, MTAP 2% and PTEN 2%. We compared baseline characteristics and outcomes between BAP1 wild type (WT) and BAP1 mutated (MT) groups. Median age at mesothelioma diagnosis were similar 74 vs 70 years (0.3347) with no significant differences in either asbestos or smoking exposure (Table 1). An analysis of outcomes revealed an ORR to ICI of 33% (36% vs 29% respectively [p = 0.9]). PFS was similar between both groups - 4 months [95% CI, 3-NA] for BAP1 WT vs 4 months [95% CI, 2-18] for BAP1 MT group. Conclusions: BAP1 mutation had no prognostic significance on either response rates or disease progression while on ICI therapy in our cohort of advanced MPM patients. The identification of predictive biomarkers for immunotherapy of MPM is an area of unmet clinical need. [Table: see text]
Trends and survival of malignant mesothelioma across racial groups between 2000-2019: A real-world study.
Authors: Al Armashi Abdul Rahman , Alkrekshi Akram , Al Zubaidi Anas , Hammad Faris , Elantably Dina , Mahmood Omar , Truong Vien , Ngo Tam N.M. , Bruno Debora S. 
Published: June 2023

e20539 Background: Malignant mesothelioma of the pleura (MMP) is a rare and aggressive malignancy and predominantly affects patients of White race in the U.S. Despite treatment advancements, the 5-year survival rate remains between 5% and 10%. Studies assessing racial disparities in MMP are lacking. We conducted a retrospective study to evaluate prevalence, survival and mortality trends among racial groups. Methods: We used the SEER database to determine the racial prevalence of all histological subtypes of MMP between 2000 and 2019. We calculated racial and histological subtype survival Cox proportional hazard ratios while controlling for age, gender, ethnicity, surgery, chemotherapy, and radiation use. Second, we used the CDC WONDER database to identify all mesothelioma deaths for the same period. Age-adjusted mortality (AAM) rates per 100,000 persons were standardized to 2000 US census data and stratified by race. Results: A total of 12791 patients were identified, mostly White (95%), followed by Blacks (%5) and Asians (0.4%). The percentages of patients with epithelioid, sarcomatoid and biphasic histologies were as follows: Whites (67.6%, 19.2%, 13.2%), Blacks (70.4%, 19.4%, 10.1%), and Asians (64.4%, 23.6%, 11.9%). As demonstrated in Table 1, compared to Whites, regardless of stage, survival was worse for Blacks (HR 1.16) and Asians (HR 1.14). As expected, survival was inferior for pts with sarcomatoid MMP followed by biphasic. Epithelioid MMP had the most favorable prognosis. Lastly, using the CDC WONDER database over the same period, there were 47,323 White, 2,068 Black, and 541 Asian MMP deaths. AAM was 0.8, 0.3, and 0.2 per 100,000 persons for White, Black, and Asian patients, respectively. AAM declined from 2000 to 2019 by 22% (0.9 to 0.7) in White, 50% (0.4 to 0.2) in Black, and 33% (0.3 to 0.2) in Asian. Conclusions: This is one of the largest population-based studies analyzing MMP racial disparities and histologic subtypes. Mortality analysis revealed declines across all racial groups, with the greatest decline among Blacks, which is two-fold that of Whites. However, a survival gap between races and histological subtypes persists. Despite no differences in the prevalence of histologic subtypes, mortality was 16% higher for Black patients when compared to Whites. Asian patients also had a higher risk of death of 14%, though the aggressive sarcomatoid subtype was more prevalent in this racial group. Social determinants of health and biological differences, could be responsible. Further studies are needed. [Table: see text]
Survival trends among patients with mesothelioma: Impact of initial therapy at academic centers.
Authors: Mooradian Ariana , Kimbrough ErinMarie , Hochwald Alexander , Sacchi de Camargo Correia Guilherme , Manochakian Rami , Zhao Yujie , Lou Yanyan 
Published: June 2023

e20540 Background: Mesothelioma is an aggressive malignancy with few approved treatment options. Rare malignancies are often seen in higher volume at academic centers which are considered equipped with better expertise. Outcomes of mesothelioma in the novel therapeutic era and impact of initial treatment at academic versus community centers have not been reported. Methods: Mesothelioma cases from 2004-2019 were collected from The National Cancer Database (NCDB). Epidemiologic factors including sex, age, income, education, insurance status and location were assessed as well as overall survival across academic and community centers. Overall survival (OS) was plotted by type of treatment facility, accounting for several factors available in NCDB. Results: A total of 30136 mesothelioma patients were included in the analysis. 13482 (44.7%) were treated in academic centers and 16654 (55.3%) were treated in community practice locations. A higher proportion of patients with comorbidity scores of 2 or higher were seen in the community setting as compared to the academic setting (12.2% vs 7.6%). The distribution of diagnostic stages was similar between academic and community settings (14.1% vs 14.5% Stage I; 28.5% vs 30.7% Stage IV). A higher number of patients received surgery (39.6% vs 21.3%), chemotherapy (59% vs 45.3%), and immunotherapy (5.2% vs 3.5%) when presenting to academic rather than community settings, respectively (p value < 0.001). OS for all patients was 1.093 years (range: 0-16.47 years) for those treated in an academic center and 0.66 years (95% CI: 0-16.690; p < 0.001) for those treated in the community. Conclusions: Data from NCDB database shows that treatment of mesothelioma at academic centers was associated with improved overall survival when compared to receiving treatment in the community despite seeing similar proportions of early and late-stage disease at presentation. Patients were more likely to receive treatment of any kind if presenting to academic centers.
Incidence of immune checkpoint inhibitor induced myocarditis in patients with mesothelioma from a regional tertiary cancer centre covering a patient population of 2.6 million.
Authors: Johnson Alexandra , Chapman Adam , Garbutt Nicholas , Griffiths Richard , Pope Anthony , Olsson-Brown Anna Claire 
Published: June 2023

e20541 Background: As a large regional tertiary cancer centre with an established cardio-oncology service a high incidence immune checkpoint inhibitor (ICI) induced myocarditis was recognised in mesothelioma patients receiving combination ICIs (cICI). A retrospective analysis of myocarditis in patients with mesothelioma was conducted. The utility of baseline cardiac markers as a prospective stratification tool for the development of ICI induced myocarditis in this patient group was investigated. Methods: A retrospective analysis of 118 patients with mesothelioma treated with ICIs over a 5 year period at the Clatterbridge Cancer Centre, Liverpool, UK. Baseline characteristics, treatment regimen, co-morbidities and the presence of malignant pericardial or cardiac disease were recorded. Baseline cardiac markers (high sensitivity Troponin T (hsTT) and pro-BNP) were recorded for patients initiating ICI treatment from July 2022 when regional baseline testing was introduced. A diagnosis of myocarditis was confirmed by cardiac MRI (n = 6) or clinically by the cardio-oncology team when MRI was clinically unfeasible (n = 1). Statistical analysis was undertaken with Fishers Exact test. Results: 33 patients received cICI treatment with Ipilimumab and Nivolumab, 85 patients received monotherapy ICIs (mICI), 5 as a SACT combination. Myocarditis occurred in 12.1% (n = 4) of patients receiving cICIs vs 3.5% (n = 3) of patients receiving mICIs. The median onset was 57 days with cICI and 245 days with mICI treatment. Baseline (b/l) cardiac assessment was undertaken in 22 patients (66.7%) of those treated with cICIs and 8 patients (9.4%) treated with mICI therapy. An abnormal b/l pro-BNP ( > 500 ng/L) was identified in 5 cICI patients and 1 mICI patient. Those with elevated b/l pro-BNP in the cICI setting all had a significant cardiac association; either an increased incidence of myocarditis (n = 3/5) (p = 0.0065) or pericardial/ invasive cardiac disease (n = 2/5) (p = 0.0433). In the cICI population myocarditis was not seen in patients with a b/l pro-BNP < 500ng/L. Of the 8 mICI patients with b/l cardiac assessment, 1 patient had an elevated pro-BNP which was associated with pericardial extension. Regarding baseline hsTT in the cICI group, the incidence of myocarditis was not increased with mild b/l elevations (14-24 ng/L), however, a moderately elevated level ( > 24ng/L) was associated with an increased incidence of myocarditis (p = 0.0026). Conclusions: In this cohort of patients with mesothelioma there was a high incidence of cICI induced myocarditis. As patients treated with cICIs with abnormal b/l cardiac markers had an increased risk of developing ICI induced myocarditis, b/l cardiac markers could potentially be used to help stratify the risk of ICI induced myocarditis and inform treatment discussions. Further studies are now required.
Demographic and racial characteristics, and survival trends in pleural mesothelioma: A population based study.
Authors: Patel Dhaval , Yadukumar Lekha , Dourado Claudia M. , Leighton John Charles 
Published: June 2023

e20543 Background: Mesothelioma is a rare and aggressive type of cancer that originates from the visceral and parietal pleura. Approximately 3,000 people are diagnosed with mesothelioma in the United States each year ( < 0.03% of all cancers). The prognosis is poor, with a 5-year survival rate of only 7 to 10%. With a latency period of 30 to 60 years, mesothelioma is typically diagnosed at an advanced age. Our objective is to investigate the demographic and racial factors that affect prognosis and survival rates in patients with pleural mesothelioma. Methods: We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database. Socioeconomic and racial factors in 13,166 patients diagnosed with mesothelioma from 2000 to 2019 were analyzed using the Pearson chi-square test. Cancer-specific survival outcomes were compared across racial and ethnic factors using the Kaplan-Meier analysis. Results: The patients were predominantly male (78.3%) and White (91.3%). Gender-based differences were narrower among the Asian/Pacific Islander population (74.5% male vs. 25.5% female) and Black population (76.8% male vs. 23.2% female) compared to Whites (78.5% male vs. 21.5% female). In the Asian/Pacific Islander population, 59.7% of patients were diagnosed with mesothelioma after 2010, compared to 40.3% diagnosed before 2010 (p-value < 0.001). Of the 12,029 new mesothelioma diagnoses in the White population, 51.6% occurred before 2010 and 48.4% after 2010. Distant disease was more prevalent in the Black population at 68%, compared to 64% in White patients and 62.3% in Asian/Pacific Islanders. Patients with a household income above $65,000 accounted for 60.8%. 57.9% of Black patients had an income below $65,000, compared to 38.9% of White patients and 23% of Asian/Pacific Islanders. At diagnosis, 51% of Black patients were married, compared to 69.5% of Asian/Pacific Islander patients and 64.5% of White patients. Chemotherapy was administered to 41.7% of patients (p-value < 0.07), followed by surgery (24.5%, p-value < 0.003) and radiation (10.4%, p-value < 0.026). 75.8% of Black individuals did not receive treatment, compared to 71.6% of Asian/Pacific Islanders and 70.1% of White patients (p-value < 0.001). The cumulative incidence of mesothelioma-related death was 70.2%. The 1-year, 3-year, and 5-year survival rates for Black patients were 29%, 5%, and 1% respectively; for White patients, the rates were 33.2%, 6.5%, and 2.1%; and for Asian/Pacific Islander patients, the rates were 31%, 6%, and 2%. Conclusions: Our study highlights the interplay of socioeconomic and racial factors that may impact survival trends. Black patients have a poorer survival rate compared to White and Asian/Pacific Islander populations. This disparity could be attributed to several factors such as later stage diagnosis, lower marital status, household income, and reduced access to treatment options.