tbuckley/cabot-search huggingface dataset:
Shannon index analysis in TCR sequencing for patients with lung adenocarcinoma: The clinical implications.
Authors: Bo Jiang, Yangui Lin, Hongliang Hui, Huaming Li, Yiqian Zhang, Shuxiong Zhou, Xiaoni Zhang, Hui Li, Zhijuan Huang, Yuanyuan Liu, Linfeng Dong
Journal: Journal of Clinical Oncology (2024)

e20053 Background: Immune repertoire (IR) is the collection of functionally diverse T and B cells in an individual's circulatory repertoire at a particular time. The CDR3 is the main variation region of the CDR of T cell receptors (TCRs), which directly determines the antigen specificity of the receptor. The purpose of this study was to investigate the differences in TCRs between tumor patients and healthy people by using NGS sequencing of the CDR3 region of the human TRB. Shannon indices and Simpson indices were used to evaluate the TCR richness and evenness. Methods: From 2018 to 2022, a total of 537 cases of lung adenocarcinoma and 85 cases of healthy individual PBMC in China were collected. We identified 59 V and 14 J genes in the TRB CDR3 region by amplicon sequencing, and analyzed the differences between Shannon_index and simpson index. Results: TCR diversity were significantly higher in healthy people compared to lung adenocarcinoma patients as determined by Shannon index analysis ( P = 0.006), and the uniformity of TCRs in the latter group was lower (Simpson index 0.997 and 0.992 for controls and cases, respectively). For different age groups of lung cancer patients (age 20-44, n = 66; age 45-59, n = 205; age 60-74, n = 221; age 75-90, n = 45), the overall abundance and uniformity of T cells in lung cancer patients decreased with the increase of age (Shannon index: 7.91, 7.63, 7.38, 6.99, respectively. Simpson Index: 0.996, 0.994, 0.991, 0.986 respectively). The downward trend in the Shannon index between healthy individuals and lung adenocarcinoma patients exhibit a high correlation (spearman r = 1, P &lt; 0.01), indicating that age rather than cancer may be the main factor in immune decline in patients with lung adenocarcinoma. In terms of gender, the abundance and uniformity of T cell types in male patients were lower than that in female patients (male: Shannon index = 7.36, Simpson index = 0.991; Female: Shannon index = 7.61, Simpson index = 0.994), suggesting higher levels of immunity in the female patients. Conclusions: The Shannon index (immune diversity) in TCR sequencing was significantly different between lung adenocarcinoma patients and healthy individuals. In patients with lung adenocarcinoma, immunity declines more due to aging than the cancer itself. TCR diversity was lower in male lung adenocarcinoma patients than in female patients. In conclusion, Shannon index (immune diversity) in TCR sequencing can be used as a predictor of lung adenocarcinoma.
Anticoagulation and lung cancer mortality: A National Inpatient Sample analysis 2020.
Authors: Sripada Preetham Kasire, Maneeth Mylavarapu, Karun Neupane
Journal: Journal of Clinical Oncology (2024)

e20003 Background: Cancer can induce a hypercoagulable state, which can lead to clinically apparent venous thromboembolism. Studies have established a relationship between hypercoagulable state and lung cancer. However, the prognosis of lung cancer patients on anticoagulation is not well studied. Furthermore, the effect of anticoagulation has remained ambiguous due to the risk of bleeding, and the decision is made clinically. In this study, we aim to determine the impact of long-term anticoagulation on mortality in patients with lung cancer hospitalizations. Methods: This is a retrospective analysis with data extracted from National Inpatient Sample (NIS) data from 2020. All the hospitalizations with lung cancer using the ICD 10 (International Classification of Diseases tenth revision) codes were included. The study cohort was grouped into those who were on long-term anticoagulants and those who were not. Demographics (age, race, sex, region, and hospital size), co-morbidities, and hospitalization costs were compared between the two groups of patients. As the primary outcome, the odds of mortality were analyzed. A p &lt; 0.05 was considered statistically significant. Results: Out of 378470 patients who were hospitalized with lung cancer in 2020, 51,100 (13.5%) were on long-term anticoagulation therapy. The anticoagulation group was relatively older (median age, 71.64 years vs. 69.15 years), male predominant (54.69% vs 50.69%), and predominantly white (81.39% vs 76.49%). The anticoagulant group had a higher prevalence of prior history of DVT/PE (31.78% vs. 4.31%) and a higher Charleston co-morbidity index score (6.08 vs 5.85). The adjusted odds ratio of mortality in the anticoagulation group was 0.77, 95% CI (0.71-0.84, p &lt; 0.0001). Furthermore, the average length of stay was approximately half a day shorter, and the total cost of hospitalization was $12,539 less in the anticoagulation group. Conclusions: This NIS study showed statistically significant findings, indicating that lung cancer patients who are on anticoagulation experienced lower odds of mortality, shorter length of stay, and lesser costs of hospitalization. However, the anticoagulation group was found to have a higher prevalence of co-morbidities and a higher co-morbidity index. Hence, further research with prospective studies needs to be done to understand the reasons behind these associations.
Exploring the role of pembrolizumab in mesothelioma: A single-arm analysis of available data.
Authors: Syed Mujtaba Ali Naqvi, Nouman Shafique, - Muhibullah, Navneet Kaur, Jawad Ahmed, Sarmad Zain, Digbijay Kunwar, Atta Ur Rehman, Hassan Nawaz, Ali Haider, Abdul Qadeer, Shammas Bajwa, Zainab Javeed, Ali Ghaffar, Sheraz Ahmad Tariq, Muhammad Ihsan Ahmed, Amna Ehsan, Iqra Shafiq, Abdul Ghani Iqbal, Adnan Safi
Journal: Journal of Clinical Oncology (2024)

e20097 Background: Malignant Mesothelioma (MMe) is a neoplasm of mesothelium and has a very poor survival rate. Over half the patients of MMe express programmed death-ligand 1 (PD-L1) which binds to the PD-1 receptor on T-cells which in turn suppresses their ability to kill tumors. Pembrolizumab is a PD-1 inhibitor antibody and it has shown efficacy in combating MMe. Our analysis aims to summarize data related to objective response rates (ORR) and adverse effects of Pembrolizumab therapy in MMe patients. Methods: We conducted an online search through PubMed, Cochrane, and Clinicaltrials.gov databases from their inception till January 25, 2024, to identify studies that reported the use of Pembrolizumab in patients with MMe. Data were extracted and analyzed and proportions with their 95% confidence interval have been reported. Onlinemeta v1.0 was used for all analyses. Results: A total of six studies with 549 patients reported the use of Pembrolizumab in patients with MMe. ORR was observed in 36.2% (32.3% - 40.4%; p &lt; 0.01) of patients receiving Pembrolizumab while 20.4% (17.2%- 24.0%; p &lt; 0.01) of patients experienced adverse effects of the therapy. Median survival ranged from 9.5 to 17.3 months whereas progression-free survival ranged from 2.5 to 7.1 months in patients. Conclusions: Pembrolizumab has an ORR and safety profile comparable to other immunotherapies. Further studies are needed to extensively study the drug and its effects in detail in patients with MMe. [Table: see text]
Understanding the safety and toxicity profile of durvalumab for Black patients with lung cancer.
Authors: Hafsa M Gundroo, Kapil Chandora, Deborah Anthony Jack, Benson Arnett, Sanjay R. Jain
Journal: Journal of Clinical Oncology (2024)

e20051 Background: Constituting 12.2% of all new cancer diagnosis in 2023,Lung cancer continues to be among the most common cancers in the US. According to statistics 1 in 16 black males and1 in 20 black females are likely to develop lung cancer in their lifetime.The results of the PACIFIC trial changed the paradigm of management in non-resectable NonSmall Cell Ca and made Durvalumab the standard of care. The toxicity profile of the drug were extensively studied in the study however, only 2% (n-14) of the study population was Black. More studies are required to understand the tolerability and toxicity profile of the drug in the Black population. Methods: This is a retrospective study. Study population consisted of 55 self-identified African Americans diagnosed with stage 3 Non-small Cell Ca who received Durvalumab for consolidation therapy after chemo radiation at a large safety net hospital between 2018-2023.Their charts were reviewed to study: 1. The development of any grade- known adverse side effects of the drug. 2. The tolerability of the drug- assessed as the lack of severe toxicities resulting in discontinuation of the drug. 3. Appearance of any peculiar adverse effects not previously known. 4. Adverse side effects warranting the use of more healthcare resources, like ED visits and hospital admissions for adverse effects. The results were then compared to the results of the PACIFIC trial. Results: 52.7% (n=29) developed known adverse effects of the drug-any grade.20 % (n=11) developed severe adverse effects leading to discontinuation of therapy.32.7%(n=18) were able to tolerate completion of therapy in-spite of adverse effects. 16.3% ( n=9) required ED visits/ hospital visit due to immunotherapy adverse effects. ADRs leading to discontinuation of therapy-pneumonitis -9%, Debilitating Chest Pain-1.8%, Hyperglycemia- 1.8%, severe fatigue-1.8%, atrial fibrillation-1.8%, Autoimmune hepatitis -1.8% and Pan uveitis -1.8%. Other adverse effects are listed in the table. Conclusions: Based on our results, AA are more likely to develop any grade adverse effects than was estimated in the PACIFIC trial, however, the percentage of the AA population discontinuing therapy due to severe adverse effect was lower. While the occurrence of most common adverse effects including Pneumonitis was comparable to the PACIFIC trial, thyroid dysfunction – both hypo and hyperthyroidism was about 3 times more in the AA population. All the thyroid dysfunctions noted were G1 and G2, and did not require discontinuation of therapy. We therefore, recommend providers to be more watchful for signs and symptoms suggestive of thyroid dysfunction when treating AA patients with Durvalumab. [Table: see text]
Helical tomotherapy was superior to intensity-modulated radiation therapy in hippocampal avoidance prophylactic cranial irradiation in patients with limited-stage small-cell lung cancer.
Authors: Shuangqing Lu, Guanzhong Gong, Haoyu Liu, Yaru Tian, Wanhu Li, Jingrun Zhou, Jiling Niu, Hui Zhu
Journal: Journal of Clinical Oncology (2024)

e20099 Background: Hippocampal avoidance (HA) techniques have been developed to reduce the risk of neurocognitive dysfunction associated with prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC). However, applying different radiotherapy techniques to HA has not yet been further analyzed. This study discussed the dosimetric differences between intensity-modulated radiation therapy (IMRT) and helical tomotherapy (TOMO) in HA-PCI and analyzed the benefit of the dosimetric advantage in the risk of brain metastasis (BM) from a clinical perspective. Methods: We retrospectively evaluated patients who underwent PCI from June 2020 to December 2021 at Shandong Cancer Hospital. They were divided according to hippocampal avoidance and radiotherapy techniques: IMRT without HA (non-HA-IMRT), HA-IMRT, and HA-TOMO. The cumulative incidence of BM, target coverage (TC), homogeneity index (HI), conformity index (CI), and hippocampal doses of these radiotherapy programs were evaluated. Results: One hundred seventy-two patients were included in the analysis: 56, 78, and 38 patients in the non-HA-IMRT, HA-TOMO, and HA-IMRT groups, respectively. The 2-year cumulative incidence of BM was 31.4% in patients with HA (78 patients in the HA-TOMO group and 38 patients in the HA-IMRT group) and 23.2% in patients without HA (hazard ratio [HR]: 0.75, 95% confidence interval [95% CI]: 0.43-1.31; P= 0.340). However, the 2-year cumulative incidence of BM was lower in the HA-TOMO group than in the HA-IMRT group (25.0% vs. 44.7%, HR: 0.51, 95% CI: 0.26-0.99; P= 0.029). Both techniques achieved hippocampal protection, but HA-TOMO accomplished significantly better TC (96.24%±0.65% vs. 93.75%±2.45%, P&lt; 0.001), HI (0.09±0.02 vs. 0.27±0.12, P&lt; 0.001), and CI (0.88±0.02 vs. 0.85±0.04, P&lt; 0.001). Conclusions: HA-PCI did not increase BM risk. Additionally, HA-TOMO could achieve better TC, HI, and CI with respect to the planned tumor in the brain while achieving more rapid dosing in the hippocampal region. The cumulative incidence of BM was lower with HA-TOMO than with HA-IMRT.
Osimertinib related cardiotoxicity in patients with non-small cell lung cancer.
Authors: Samuel Akaakole Mensah, Waleed Alruwaili, Syed Ahmad, Brijesh Patel, Mohammed Almubarak
Journal: Journal of Clinical Oncology (2024)

e20011 Background: There have been cases of cardiotoxicity induced by osimertinib in patients with non-small cell lung cancer (NSCLC). Limited data exists for a comprehensive cardiotoxicity profile analysis for osimertinib in NSCLC patients. Methods: Data was retrospectively collected from electronic medical records for all patients who were started on osimertinib for NSCLC at West Virginia University Health System between 7/2016 and 1/2024. Prevalence of heart failure (HF), atrial fibrillation, and prolonged QT before and after starting osimertinib were calculated. Corrected QT interval was calculated using the Fredericia formula. QT prolongation was defined as a QTc &gt;500 milliseconds (ms). Results: A total of 116 participants with NSCLC on osimertinib were included in the analysis with median age of 52.2 years, 69.8% female, and mean 1.52 years of follow-up. The study population was 93.1% of white race, and significant comorbidities within the overall population included hypertension (70.7%), hyperlipidemia (53.4%), tobacco use (38.8%), coronary artery disease (18.1%) and diabetes mellitus (15.5%) (Table). Out of 85 patients with no specified prior cardiac abnormalities, 29.4% developed new onset cardiac abnormalities (Table). The median QTc increased from 429 ms to 444 ms after starting osimertinib, and 8.8% of patients had QTc &gt;500 ms. Conclusions: Osimertinib is used in NSCLC and appears to be associated with an increase in cardiac abnormalities. A direct causal relationship between osimertinib use and cardiotoxicity has not yet been established. Given the strong association between this medication exposure and the observed cardiac toxicities, use of osimertinib may entail closer cardiac monitoring of electrocardiogram and echocardiographic abnormalities. [Table: see text]
DAREON-8: A phase I, open-label, dose escalation/expansion trial of the DLL3-targeting T-cell engager, BI 764532, combined with first-line (1L) standard of care (platinum, etoposide, and anti-PD-L1 antibody) in patients (pts) with extensive-stage small cell lung carcinoma (ES-SCLC).
Authors: Solange Peters, Stephane Champiat, Tatsuya Yoshida, Nicolas Dorleacq, Yiyuan Ma, Lijiang Geng, Ticiana Leal
Journal: Journal of Clinical Oncology (2024)

TPS8127 Background: Platinum/etoposide chemotherapy in combination with anti-PD-L1 antibodies is the 1L standard of care (SoC) for pts with ES-SCLC. However, most pts relapse and subsequent treatment (Tx) options are limited. Hence, outcomes are poor with a 5-year survival rate of &lt; 7%. Delta-like ligand 3 (DLL3) is a Notch receptor ligand expressed on tumor cells but not on normal cells. BI 764532 is an IgG-like T-cell engager (TcE) that binds simultaneously to CD3 on T-cells and DLL3 on tumor cells, resulting in selective, T-cell mediated tumor cell lysis. An ongoing Phase I trial of BI 764532 (NCT04429087) in pts with pretreated DLL3-positive tumors demonstrated an overall response rate of 28%, a disease control rate of 54%, and a manageable safety profile. Here, we describe DAREON-8 (NCT06077500), a Phase I open-label dose escalation/expansion trial of BI 764532 plus SoC as a 1L Tx for pts with ES-SCLC. Methods: Pts will be recruited from ~20 sites into this two-part trial. In Part A (dose escalation), ~30 pts will receive escalating doses of intravenous BI 764532 (target dose after step-in dosing) plus carboplatin/etoposide + atezolizumab. Dose escalation will be guided by a Bayesian logistic regression model with overdose control. Tx with BI 764532 will continue for 36 months, withdrawal or progressive disease (PD). The primary objective is to determine the maximum tolerated dose (MTD) of BI 764532 and/or the recommended dose for expansion (RDE)/recommended Phase II dose (RP2D) for BI 764532 plus SoC. Safety, efficacy and/or PK assessments will guide the RDE/RP2D. The primary endpoint focuses on the occurrence of dose-limiting toxicities (DLTs) in the MTD evaluation period. In Part B (dose expansion), ~30 pts will receive BI 764532 at the RDE/RP2D determined in Part A for 36 months, withdrawal or PD and platinum/etoposide + either atezolizumab or durvalumab. The primary objective of Part B is to confirm the safety and tolerability of BI 764532 at the RDE/RP2D plus SoC Tx as measured by the occurrence of DLTs during the on-Tx period. Key inclusion criteria include confirmed ES-SCLC; no prior systemic treatment for ES-SCLC; and eligibility to receive platinum/etoposide chemotherapy + anti-PD-L1 antibodies. Key exclusion criteria include previous Tx with DLL3-targeting TcEs; persistent, unresolved toxicity from previous Txs; immunodeficiency, or systemic steroid or other immunosuppressive therapy ≤7 days prior to first dose of BI 764532; and significant cardio/cerebrovascular disease. Clinical trial information: NCT06077500 .
Characterization of DNA damage repair mutations in lung cancer in an underserved urban patient population.
Authors: Jeremy Kao, Mary Pasquinelli, Ryan Huu-Tuan Nguyen, Lawrence Eric Feldman, Frank Weinberg
Journal: Journal of Clinical Oncology (2024)

e20058 Background: DNA-damage repair (DDR) mutations in lung cancer have shown potential for use as therapeutic targets and predictive biomarkers. However, the relationship between DDR mutations and socioeconomic factors remains largely unknown. In this study, we characterize the distribution of DDR gene mutations in lung cancer patients at a single academic medical center serving a unique population consisting of primarily underserved, underinsured patients. Methods: All lung cancer patients seen at the University of Illinois Chicago (UIC) between 11/2/2015 and 9/11/2023 with TEMPUS genetic data available were included in the study (N = 235). DDR mutations of interest were ARID1A, ATM, ATR, ATRX, BAP1, BRCA1, BRCA2, BRIP1, CHEK2, ERCC3, FANCA, FANCC, MLH3, MRE11, MSH6, MUTYH, NBN, PALB2, and RAD50. The population was subdivided into a DDR mutation positive group and a DDR mutation negative group. Each group was compared with respect to lung cancer type, tumor mutational burden (TMB), and socioeconomic factors including sex, race, insurance category, and zip code. Results: The overall frequency of DDR mutations in the population was 28.5% (n = 67). The most common DDR mutations were ARID1A (20.7%), CHEK2 (12.8%), ATM (9.9%), BRCA2 (9.9%), ATRX (7.9%), and MUTYH (7.9%). The histological distribution of the DDR mutation positive group was adenocarcinoma (76.1%), squamous cell carcinoma (4.4%), adenosquamous carcinoma (2.9%), neuroendocrine carcinoma (5.9%), and other (10.4%). The histological distribution of the DDR negative group was adenocarcinoma (60.1%), squamous cell carcinoma (22.0%), adenosquamous carcinoma (1.1%), neuroendocrine carcinoma (4.1%), and other (12.5%). There was a significant effect in TMB, t(55) = 2.97, p = 0.004, with a higher mean TMB in the DDR positive group (M = 14.4, SD = 11.1) compared to the DDR negative group (M = 9.4, SD = 5.1). The most common zip codes in the DDR positive groupwere 60608 (9.0%), 60629 (9.0%), and 60616 (7.5%) compared to 60616 (8.3%), 60609 (5.3%), and 60624 (4.7%) in the DDR negative group. Demographic factors of the two groups are compared below. Conclusions: The frequency and distribution of DDR mutations in lung cancer at UIC appears similar to what has been previously reported in the literature. There is a higher tumor mutational burden in lung cancers with DDR mutations, which may suggest greater susceptibility to immunotherapy. There may be a correlation between the presence of DDR mutations and lung cancer type, insurance category, and patient geographic distribution. Future work will include obtaining further geographic data for the study population such as average income, pollution exposure, and smoking rate by neighborhood. [Table: see text]
Prognostic impact of clinical stage on non-surgical patients with pleural mesothelioma.
Authors: Brendan Knapp, Giordano Fabricio Cittolin Santos, Ningying Wu, Mary Ellen Flanagan, Maun Baral, Feng Gao, Anjali Rohatgi, Jeffrey Ward, Ramaswamy Govindan, Daniel Morgensztern
Journal: Journal of Clinical Oncology (2024)

e20096 Background: Most patients with pleural mesothelioma (PM) are not surgical candidates and receive systemic therapy. Clinical stage is usually not reported in mesothelioma clinical trials. We evaluated the prognostic impact of clinical stage in mesothelioma using a large database with the hypothesis that M1 patients will have worse OS compared to M0 patients. Methods: The Surveillance, Epidemiology and End Results (SEER) Program was used to identify adult patients with PM diagnosed between 2004 and 2020, who received chemotherapy and did not undergo surgery. Patients with unknown stage were excluded. Staging was subdivided into I, II-III and IV for better accuracy. Age, sex, and stage were included in multivariable analyses (MVAs) using a Cox proportional hazard regression model. Unadjusted OS was estimated by the Kaplan-Meier method and compared using log-rank tests. Results: Among the 10,422 patients, 2,644 (25.4%) met the inclusion criteria. Histology classification was not available for 1,120 patients (42.4%), which were reported as malignant mesothelioma. Most patients were male (78.3%) and older than 70 years (54.5%). There were 970 patients (36.7%) with stage I, 893 (33.8%) with stage II-III and 781 (29.5%) with stage IV. The median OS for all patients was 11 months, with 1-year, 3-year and 5-year OS of 43.9%, 10.3% and 4.3% respectively. The median OS for stages I, II-III, and IV was 13 months, 11 months, and 9 months respectively, with 1-year OS of 50.5%, 42.8% and 36.9% respectively and 5-year OS for stages I, II-III, and IV of 5.3%, 3.0% and 4.9% respectively. The median and 1-year OS were 12 months and 46.8% respectively for M0 and 9 months and 36.9% respectively for M1 (p &lt; 0.001). For patient with M0, the median OS for N0, N1 and N2 was 12 months, 11 months, and 11 months, respectively. In MVA, worse OS was observed in patients with age 71 or older compared to &lt; 60 (HR 1.24, 1.09-1.4), and in male patients compared to females (HR 1.27, 1.15.-1.4). Stage IV was associated with worse OS when compared to stage II-III (HR 1.11, 1.001-1.23, p = 0.04) and stage I (HR 1.34, 1.21-1.49, p &lt; 0.001) while stage II-III was associated with worse OS compared to stage I (HR 1.21, 1.1-1.33, p = 0.0001). Conclusions: Clinical stage is a significant predictor for outcomes in patients with unresected pleural mesothelioma treated with chemotherapy, has been underreported, and should be included in clinical trials for a better evaluation of novel treatment strategies.