bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicopathologic characteristics and outcomes for patients with KRAS G12D-mutant non-small cell lung cancer (NSCLC).
Authors: Cooper Alissa Jamie , Muzikansky Alona , Lennerz Jochen K , Mino-Kenudson Mari , Hung Yin P , Piotrowska Zofia , Dagogo-Jack Ibiayi , Sequist Lecia V. , Lin Jessica Jiyeong , Gainor Justin F. , Heist Rebecca Suk 
Published: June 2022

e21024 Background: Co-occurring mutations in KRAS-mutant NSCLC are associated with discrete biological properties and modulate therapeutic susceptibilities. As G12D-specific inhibitors are expected to enter the clinic, we sought to define the clinicopathologic characteristics and outcomes of patients (pts) with KRAS G12D-mutant NSCLC. Methods: This was a retrospective single-institution study. Pts with NSCLC and KRAS G12D mutations detected by the Massachusetts General Hospital SNaPshot next-generation sequencing assay were identified. Clinical and pathologic characteristics, including co-mutation status and survival outcomes, were collected by chart review. Results: Among pts who underwent SNaPshot testing between May 2014 and August 2021, 665 had cancers that were positive for KRAS G12D, of whom 107 (16.1%) had NSCLC. Most common histology was adenocarcinoma (93, 86.9%). PD-L1 level was < 1% in 24 (22.4%), 1-49% in 19 (17.8%), > 50% in 13 (12.2%), and not assessed in 51 (47.7%). Co-occurring mutations were frequent: 17 NSCLCs had co-occurring STK11 mutations (15.9%), 36 (33.6%) TP53 mutations, and 11 (10.3%) SMARCA4 mutations, of which 2 were truncating. Genetic alterations were detected in a variety of other genes including in the RTK/RAS/MAPK (20, 18.7%), PI3K/AKT/mTOR (12, 11.2%), cell-cycle (17, 15.9%), and WNT (11, 10.3%) pathways. Among 58 tumors with KEAP1 mutation testing, 10 (17.2%) were positive. 75 (70.1%) pts had metastatic disease, including 51 pts who had metastatic disease at initial diagnosis. CNS metastases were present in 27 (36.0%) pts, including 14 pts with CNS metastases at initial diagnosis. Among the 57 pts with metastatic disease who received first-line therapy, 28 (49.1%) received platinum-based chemotherapy, 17 (29.8%) immunotherapy alone, and 12 (21.1%) platinum chemotherapy plus immunotherapy. Median PFS in pts treated with first-line therapy was 4.0 months (95% CI 2.1– 5.7) and median OS 14.3 months (95% CI 8.1 – 27.4). When stratified by co-mutation status, pts with STK11 mutations had significantly worse outcomes than STK11-wild-type (median PFS: 1.2 months vs 4.8 months, p = 0.0165; median OS: 4.3 months vs 21.6 months, p = 0.0015), whereas TP53 exerted no influence. Conclusions: Co-occurring mutations were common in pts with KRAS G12D-mutant NSCLC. Outcomes were poorer for KRAS G12D/ STK11 pts, whereas co-occurring TP53 did not impact survival. Clinical trials examining G12D inhibitors should stratify by STK11.
Treatment pattern and outcomes in patients with uncommon or compound EGFR mutations in India: CRSF 2020-03 study.
Authors: Avaronnan Manuprasad , Kothari Rushabh , Talele Avinash , Talreja Vikas , Goyal Gautam , Raut Nirmal Vivek , Karpe Ashay 
Published: June 2022

e21034 Background: Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) resulted in significant improvement in the outcomes of patients with activating EGFR mutations. But the ideal treatment of patients harboring uncommon, or compound mutations is not well defined. This multicentric audit was conducted to study the distribution, treatment pattern, and outcomes of patients with uncommon or compound EGFR mutations. Methods: This was a multicentric retrospective study that included patients with uncommon (mutations other than Exon 19 deletions and Exon 21 L858R) or compound (double or complex) mutations treated during the period of 2017-2020. Statistical analysis was done using SPSS version 20.0. Descriptive statistics were used wherever appropriate. Kaplan Meier Aanlaysis was performed for estimation of PFS and OS. Results: Total 99 patients with uncommon or compound mutations were included in the study. The median age was 55 years (25-82 years). Majority were males (n=65,67%) and 47 (47%) were smokers. Sixty-seven patients (68 %) had a single uncommon mutation and the remaining 32 (32%) had compound mutations. Most common mutations were exon 20 insertion (n=34, 35%) and T790M (N=16,16%). Other frequent mutations observed were exon 18 G719X (n=7,7%) and exon 21 L861Q (n=3,3%). Twenty-three patients (n=23,23%) were eligible only for best supportive care. Thirty-two patients (32%) received first-generation TKI, 30 patients (30%) received palliative chemotherapy and 11 patients (11 %) received Osimertinib. Gefitinib with chemotherapy was used in 2 patients and combination of Gefitinib with Afatinib was used in one patient. Overall response rate and clinical benefit rate with first line treatment was 23% and 35% respectively. Response could not be assessed in 14 patients. Median PFS was 5 months (95% CI 3.4-6.9) and median OS was 8.3 months (95% CI 3.3- 13). In patients who received any form of systemic treatment, median PFS was 6.2 months (95% CI- 3.3-9.1) and OS was 11 months (95% CI -8.9-13.9). Conclusions: The most frequent uncommon mutations in India are exon 20 insertion followed by compound mutations and exon 20 T790M mutation. Outcomes of patients with these rare mutations are dismal in the real world setting with the available treatment options.
The impact of body mass index and serum albumin in patients with advanced-stage non-small cell lung cancer.
Authors: Bello Andreas , Makani Neeharika Srivastava 
Published: June 2022

e21037 Background: Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer diagnoses. Previous literature has evaluated associations between physical factors and outcomes in NSCLC. Throughout these studies, important physical factors that affect overall survival (OS) in NSCLC patients are body mass index (BMI) and serum albumin (SA) levels. In terms of BMI, previous research has come across the “obesity paradox.” That is, presenting an obese BMI serves as a protective role in patient survival. Hypoalbuminemia, defined as SA levels < 3.5 g/dL, has been shown to have a significantly adverse effect on both early and late stage patients’ outcomes. Our study aims to analyze the role of BMI and SA in patients with advanced-stage NSCLC. Methods: This retrospective study includes 112 patients with stage III and stage IV NSCLC identified between January 1st, 2014 through December 31st, 2018. Categorical and continuous analyses (Pearson’s chi-square and Kruskal-Wallis test) were performed to analyze the associations between median OS, BMI, and SA. BMI subgroups are classified according to the Center for Disease Control guidelines. BMI and SA are calculated at time of diagnosis. OS is defined as the date of diagnosis until the date of death. Other notable confounders investigated include treatment modality, histology, and comorbidities. Results: Of the 112 patients, 57% of patients identified as male. The study population mean age was 73 years. The majority (88%) of patients identified as white. The median BMI was 26.1, with 26% of patients presenting as obese. The median SA level of the population was 3.8 g/dL, with 34% of patients presenting as hypoalbuminemic. Study population median OS was 0.734 years. Median OS for the obese BMI subgroup was 1.42 years, compared to 0.70, 0.71, and 0.42 years for overweight, normal, and underweight BMI, respectively. Kruskal-Wallis analyses confirm that patient BMI plays a significant difference in terms of OS, with a significant subgroup difference between patients with obese and underweight BMIs (p = 0.05). Regarding SA, both chi-square and Kruskal-Wallis tests confirm that at the time of diagnosis, patients with normal SA have a longer median OS compared to their hypoalbuminemic counterparts (median OS 1.29 years vs 0.32 years, respectively; OR = 6.72, 95% CI [2.48, 18.22], p < 0.001). Conclusions: Our study reveals that an obese BMI plays a significant protective role regarding OS when evaluating prognostic outcomes between obese and underweight patients. Further, as SA levels are a known biomarker for nutritional status, our study highlights the importance of nutritional and educational optimization among healthcare professionals and patients alike prior to the diagnosis of malignancy. Future large prospective cohort studies are needed to analyze the efficacy of nutritional optimization, and further justify the “obesity paradox” and its underlying framework.
Evaluation of tumor gene expression profile (GEP) in minority patients with stage IV non-small cell lung cancer (NSCLC).
Authors: Villanueva Matthew , Uribe Carlos Carracedo , Brice Kayla , Dumais Katerine , Nano Olger , Rodriguez Mitchelle , Osmon Elizabeth , Raez Luis E. 
Published: June 2022

e21043 Background: Differences in tumor gene expression profile (GEP) may contribute to disparities in lung cancer incidence and survival between racial and ethnic groups. For patients with stage IV NSCLC, tumor biomarker analysis is important for identification of potentially effective targeted therapies. However, despite advancements in biomarker testing and targeted therapy, minority patient enrollment in clinical trials remains low and it has been shown that minority patients are less likely to undergo next-generation sequencing (NGS) compared to Non-Hispanic Whites (NHW). As such, frequencies of tumor biomarkers in minority populations in the United States are not well-defined. This study aimed to determine the extent of tumor GEP diversity in minority patients vs NHW. Methods: This retrospective study included 196 adult patients with stage IV NSCLC that had a baseline NGS of tumor tissue or blood (liquid biopsy) performed between July 1, 2015 and June 30, 2021. Minority populations included Hispanic, African American, and Asian patients. Data collected utilizing the electronic medical record included patient demographics, detection of tumor biomarkers and treatment initiated. Descriptive statistics were calculated for all demographic and clinical variables. Comparisons of actionable epidermal growth factor receptor (EGFR) mutation frequency between NHW and minority patients were done using Chi-squared and Fisher’s exact tests. Results: Of the 196 patients evaluated, baseline characteristics included 46% male, 67% former smokers, 54% NHW, 31% Hispanic, 9% African American, 5% Asian, and 1% other. The median age at diagnosis was 66 ± 12 years. Actionable mutations (EGFR, KRAS, BRAF, ROS-1, ALK, MET, NTRK 1-3) were found in 50% of patients (see Table). The frequency of actionable EGFR mutations was higher in minority patients overall compared to NHW (39.3% vs 21.5%; p < 0.01). The frequency of actionable EGFR mutations was similar between NHW and Hispanic patients (21.5% vs 27.9%; p = 0.35), however differences were observed comparing NHW to African American (21.5% vs 50%; p = 0.02) and Asian (21.5% vs 90%; p < 0.01) patients, respectively. Conclusions: Among patients with stage IV NSCLC, the GEP of minority patients varied from that of NHW. Asian patients had the highest frequency of EGFR mutations, followed by African American and Hispanic patients, respectively. Larger studies are needed to validate these findings.[Table: see text]
Assessing effectiveness of first-line carboplatin, pemetrexed, and pembrolizumab in patients with recurrent/metastatic lung adenocarcinoma.
Authors: Ip Andrew , Gutierrez Martin , Warren Mary E. , Pfister David G. , Brady Owen , Shen Ronglai , Riely Gregory J. 
Published: June 2022

e21045 Background: Randomized clinical trial data support the addition of immune checkpoint inhibitors to standard first-line platinum-doublet in patients with recurrent/metastatic non-small cell lung cancer. In the landmark KN189 Trial in which patients received carboplatin or cisplatin in combination with pemetrexed and pembrolizumab, the updated analysis (Gadgeel et al, JCO 2020) reported a median overall survival of 22 months. To explore the translation of this clinical trial-proven efficacy to clinical effectiveness in routine practice, we sought to explore patient outcomes with the combination of pemetrexed, carboplatin, and pembrolizumab as initial therapy for patients with recurrent or metastatic non-squamous non-small cell lung cancer. Methods: At two large, urban, academic medical centers (Hackensack University Medical Center and Memorial Sloan Kettering Cancer Center), we reviewed patient treatment data to identify all patient all patients with recurrent/metastatic non-squamous non-small cell lung cancer who received carboplatin, pemetrexed, and pembrolizumab as initial therapy for recurrent/metastatic NSCLC from June 2017 to December 2020. Patients with EGFR mutations or ALK gene fusions were excluded. From the medical record, we obtained baseline clinical characteristics, patient treatments and duration, as well as overall survival. Results: We identified 523 patients treated with carboplatin/pemetrexed/pembrolizumab, with 399 events occurring during the observation period. Baseline characteristics: 47% women and median age 66 (Interquartile range 59-72). The median overall survival from start of therapy was 11 months (95% confidence interval 9-12 months). Conclusions: In routine clinical practice, initiation of chemotherapy + immune checkpoint inhibitor as first-line therapy for patients with recurrent/metastatic NSCLC led to shorter median overall survival than reported in clinical trials. To further evaluate this finding, we will explore patient baseline characteristics including performance status, comorbidities, organ function as well as explore outcomes of a historical cohort of patients administered carboplatin and pemetrexed.
Prognostic effect of TP53 mutation combined with EGFR mutation or KRAS mutation on non-small cell lung cancer.
Authors: Li Ying , Jiang Da , Niu Xuhui , Zhou Xinliang , Hong Lei , Cui Yanzhi , Shi Ke , Jin Hui , Zhang Xue , Huang Fang , Song Wenya , Fan Shaoshuang , Deng Ruoying 
Published: June 2022

e21046 Background: To explore the prognostic value of TP53 co-mutation with EGFR or KRAS in advanced non-small cell lung cancer. Methods: 314 patients with advanced non-small cell lung cancer (NSCLC) admitted to the Department of Oncology of the Fourth Hospital of Hebei Medical University from January 2016 to January 2021 were retrospectively analyzed, all with complete genetic information.According to the analysis results, EGFR and KRAS were identified as co-mutated genes.TP53 mutation was used as the experimental group and TP53 wild as the control group.Patients in TP53 mutation group were further classified and discussed according to different exon 4, 5, 6, 7, 8, other mutations and mutations could not be classified.Co-mutation group was studied according to TP53/KRAS mutation status, and according to KRASG12 mutation, Patients were divided into TP53/KRASG12C (wt/wt), TP53/KRASG12C (wt/mut), TP53/KRASG12C (mut/mut) and TP53/KRASG12C (mut/mut) for further grouping.In the study of TP53/EGFR co-mutation, TP53/EGFR mutation status was divided into groups, and subgroup analysis was conducted according to different TP53 exon mutations.SPSS 26.0 software was used to analyze the data, and P < 0.05 indicated statistical difference. Results: The frequency of single gene mutation in 314 patients was analyzed. The most common mutation was TP53 (64.3%), followed by EGFR (49.4%).TP53wt group compared with TP53mut group OS (34.3m vs 28.9m; HR = 1.263, 95% ci: 0.933 1.709;P = 0.131).The OS of Exon4 group was 23 months, Exon8 group was 44.5 months, and TP53wt group was 34.3 months, no statistical significance was observed (P = 0.159).In the TP53/KRAS co-mutation group, the median OS of KRAS/TP53 (mut/mut) group and KRAS/TP53 (wt/wt) group was 29.4m vs 34.3m; HR = 2.482, 95%Cl:1.378-4.471, P = 0.002).In subgroup analysis, the median OS of KRASG12Cmut/TP53mut group and KRASG12Cmut/TP53wt group were (8.9m vs 34.9m; HR = 38.268, 95%CL: 8.359-175.183, P = 0.199), (3.1m vs 34.3m; HR = 2.572, 95%Cl:1.344-4.922,P = 0.004).In the TP53/EGFR co-mutation group, the median OS of EGFRmut/TP53mut, EGFRwt/TP53mut, EGFRmut/TP53wt and EGFRwt/TP53wt were 32.9, 17.9, 42.7 and 31.2 months, respectively (P = 0.004).In subgroup analysis, the median OS of EGFRmut/ TP53Exon4-mut versus EGFRwt/TP53wt group was (25.8m vs 31.1m; HR = 2.909, 95%Cl: 1.438-5.886, P = 0.003). Conclusions: TP53 is a factor of poor prognosis in NSCLC patients, patients with TP53/KRAS co-mutation have poor survival, and kRASG12C-mut /TP53mut subgroup have worse prognosis.Patients with TP53/EGFR co-mutation had a better prognosis, and the EGFRmut/ TP53Exon4-mut subgroup had the worst prognosis.
The rate of venous thromboembolism in patients with non-small cell lung cancer treated with chemotherapy or check point inhibitors.
Authors: Singu Sriharsha , Bakalov Veli , Helfand Alexander M , Kancharla Pragnan , White Richard , Khattab Ahmed , Miller Katherine , Samhouri Yazan , Finley Gene Grant 
Published: June 2022

e21053 Background: Treatment with immune checkpoint inhibitors (CPI) targeting PD-1 or PD-L1 significantly improves progression free survival and overall survival in patients with non-small cell lung cancer (NSCLC). Emerging literature suggests that the proinflammatory state of CPIs may increase the risk of thromboembolism, both venous (VTE) and arterial (ATE), which is of great concern as thromboembolism remains a major cause of mortality in patients with NSCLC. We performed a retrospective cohort study to evaluate thromboembolic outcomes in patients on immunotherapy for NSCLC. Methods: We reviewed the records of all patients diagnosed with stage IV NSCLC between December 2016 and December 2019 and treated with chemotherapy, CPIs, or both in one of the largest integrated academic health systems in Western Pennsylvania. Khorana scores (to predict the risk of future VTE) were calculated for each patient based on available data at the time of diagnosis. Logistic regression analyses were done to evaluate clinical predictors of VTE. Survival outcomes were analyzed using Kaplan-Meier estimates and a log rank test was used to compare survival estimates. Data was analyzed using SPSS v26 (IBM Corp). Results: A total of 110 patients with stage IV NSCLC were identified, 87.1% had ECOG ≤2, 67.0% had adenocarcinoma and 25.7% had squamous cell carcinoma, and 39.1% had PD-L1 staining ≥50%. Immunotherapy related adverse events (IrAE) of any grade were found in 28.2%. Overall, 25.5% received chemotherapy only, 27.7% received CPIs alone, and 45.5% received chemo + CPIs. A Khorana score of ≥2 was found in 43.6% of patients. Prophylactic anticoagulation was used in 0.9% of patients. VTE was detected in 18.3% and ATE in 10.0% of the cohort; therapeutic anticoagulation was given in 14.7% of patients. Median overall survival was 25.5 months (95% CI 18.7-32.3) in patients without VTE versus 13.7 months (95% CI 3.1-24.3) in patients with a VTE diagnosis (HR 1.96, 95% CI 1.11-3.45; p = 0.02). Khorana score of ≥2 was not a significant predictor of VTE in this cohort (univariate OR 1.34, p = 0.53, multivariate OR 1.13, p = 0.81), but was associated with worse survival (HR 2.38, 95% CI 1.48-3.83, p < 0.001). Conclusions: In this retrospective cohort, VTE was associated with decreased overall survival. While no significant association between elevated Khorana score and VTE was identified, elevated Khorana score at the time of diagnosis was an independent predictor of survival in patients with NSCLC. Of note, there was a low rate of prophylactic anticoagulation in this cohort.
Longitudinal sequencing of T cell receptor revealed radiotherapeutic efficacy and prognosis in non-small cell lung cancer patients with brain metastasis.
Authors: Dong Xiaorong , Tong Fan , Zeng Hao 
Published: June 2022

e21056 Background: Liquid biopsy has played a unique role in long-term surveillance of brain metastasis in non-small cell lung cancer (NSCLC), due to the inaccessibility of solid metastatic biopsies. T cell-mediated immunity is critical in the oncogenesis and metastasis of NSCLC, and sequencing in T cell receptor (TCR) provides a robust method to quantify T cell diversity. Therefore, we aimed to explore the alteration of TCR through liquid biopsy before and after radiotherapy of NSCLC brain metastases. Methods: Thirty NSCLC patients with brain metastases receiving brain radiotherapy were enrolled in this study. Cerebrospinal fluid (CSF) and peripheral blood were collected at baseline, 24 hours (T0) and 28 days (T28) after treatment. TCR sequences were identified by high-throughput sequencing in both compartments. Results: At baseline, dimension reduction analysis identified distinct signatures of V and J gene recombination in blood and CSF TCR sequences. Throughout treatment, both compartments experienced a TCR diversity decrease, however, the degradation of low-abundance clones and the expansion of emerging clones might be two separate processes underwent in blood and CSF, respectively. Diversity changes in blood were possibly related to pulmonary responses, while the increase of maximal clone abundance in CSF might indicate a favorable intracranial response. Superior blood TCR diversity at T28 against baseline was associated with longer OS (HR = 5.700, p = 0.039). Patients with increase of maximal clone abundance ≥ 50 in CSF also had a better intracranial PFS (HR = 8.320, p = 0.011). The predictive effects of these markers were independent of other clinical factors in multivariate Cox analysis. Conclusions: CSF and peripheral blood were independent compartments showing disparate TCR signatures. Longitudinal surveillance of both compartments could be a promising method to predict clinical outcomes for NSCLC patients with brain metastases.