bluuebunny/crossref_metadata_2025_split huggingface dataset:
CASTOR1 phosphorylation as a predictor of survival in male patients with KRAS-mutated lung adenocarcinoma.
Authors: Loo Suet Kee , Sica Gabriel , Wang Xian , Li Tingting , Chen Luping , Gaither-Davis Autumn , Huang Yufei , Burns Timothy F. , Stabile Laura P. , Gao Shou-Jiang 
Published: June 2024

e20015 Background: Lung cancer, a leading global cause of cancer-related mortality, necessitates enhanced prognostic markers for improved treatment outcomes. This study focuses on the predictive value of phosphorylated cytosolic arginine sensor for mTORC1 subunit 1 at S14 (pCASTOR1) in lung adenocarcinoma (LUAD) patients, specifically in males with KRAS mutations. Methods: This retrospective study, approved by University of Pittsburgh IRB, utilized formaline-fixed paraffin embedded primary tissues from two independent cohorts of patients who underwent thoracic surgical procedures at the University of Pittsburgh Medical Center (UPMC) from 2002 to 2011. Comprehensive clinical, demographical and pathological information was obtained from UPMC Cancer Registry, with cases lacking incomplete information excluded from analysis. Study endpoints included overall survival (OS) and relapse-free survival (RFS). An antibody targeting pCASTOR1 was employed to analyze LUAD tumor and adjacent non-tumor lung tissues from both cohorts. A pathologist, blinded to patient information and survival outcomes, conducted scoring in 5% increments. Scores were categorized as low or high pCASTOR1 based on second or third quartile. Correlations between pCASTOR1 scores and OS/RFS were examined, stratifying by clinical, pathological, demographic, or genotype data. Univariate OS and RFS analyses were conducted using the Kaplan-Meier method and log-rank test, while multivariate survival significance was assessed via Cox regression analysis. Additionally, unpaired T-tests were utilized to compare pCASTOR1 levels between non-tumor and tumor cells. A significance threshold of p < 0.05 was applied for all analyses. Results: Tumor cells exhibited significantly elevated pCASTOR1 scores compared to non-tumor cells in both cohorts (P < 0.05). High pCASTOR1 scores predicted poor OS (HR = 3.3, P = 0.0008) and RFS (HR = 3.0, P = 0.0035) in male patients with KRAS mutations in Cohort 1. pCASTOR1 remained an independent predictor for OS (HR = 4.1, P = 0.0047) and RFS (HR = 3.5, P = 0.0342) after controlling for other factors. Cohort 2, comprised solely of smokers with incomplete genotype information, validated these findings, with high pCASTOR1 scores correlating with worse OS (HR = 4.8, P = 0.0363). Notably, in early-stage LUAD, elevated pCASTOR1 scores were associated with significantly worse OS (HR = 3.3, P = 0.0176) and RFS (HR = 3.1, P = 0.0277) in male patients with KRAS mutations in Cohort 1, and worse OS (HR = 5.0, P = 0.0069) and RFS (HR = 5.0, P = 0.0069) in Cohort 2, akin to late-stage patients. Conclusions: Elevated pCASTOR1 score serves as a robust biomarker predicting poor OS and RFS in male LUAD patients with KRAS mutations, offering potential clinical utility in optimizing treatment strategies for this subgroup.
Comprehensive germline and somatic DDR genomic profiles of Chinese patients with multiple primary lung cancer.
Authors: Yang Yingshun , Li Mingwei , Wang Shuai , Pei Guotian , Qin Jiayue , Cao Shanbo , Huang Yuqing 
Published: June 2024

e20019 Background: The number of multiple primary lung cancer (MPLC) patients has rapidly increased in recent years. Disruption of the DNA damage repair (DDR) gene is related to cancer risk, progression, and treatment selection. However, the characteristics and significance of DDR alterations remain undefined in MPLC. Methods: A total of 133 Chinese MPLC patients with 308 lesions were enrolled and 784 single-focus lung cancer (SFLC) patients were analyzed as a control in the present study. Genetic testing was performed by utilizing the next-generation sequencing (NGS) of 808 cancer-related genes including 276 DDR genes. The patients were divided into 3 groups: DDR-germline (germline variants, N = 11), DDR-somatic group (somatic variants, N = 98), and the non-DDR group (no DDR variants, N = 24). Results: The overall DDR variants were identified in 82.0% (109/133) of the patients, and a total of 283 variants were found, with almost all being somatic (254/283). The most commonly germline alterations were found in RAD50 (1.5%), WRN (1.5%) and BRCA2 (0.8%), while in the somatic mutations, TP53 (26.3%) showed the highest frequency. DDR-somatic group was more likely to have alterations in TP53, LRP1B, ERBB2 and MYC compared with DDR-germline group. Taken non-DDR group as reference, mutations in TP53 (P<0.05), ALK and PIK3CA were more common in DDR-germline group, but EGFR, RBM10, TP53, LRP1B, TERT and MYC (all P<0.05) in DDR-somatic group. Furthermore, the DDR-somatic group exhibits the highest median tumor mutational burden (6.56) compared with 3.55 (P<0.01) in DDR-germline and 3.69 (P<0.01) in non-DDR group. In addition, the copy number variation (CNV) was statistically different among the three groups (P<0.001). The proportion of copy number gain patients in DDR-somatic group is the highest (28.3%) compared with 12.0% in DDR-germline group and 10.9% in non-DDR group (P<0.01). DDR-somatic MPLC and SFLC patients possessed distinct somatic genomic characteristics, especially with significantly different prevalence in TP53, RBM10, KRAS, BRAF, and ALK (all P<0.05). Moreover, we also found notable differences in the prevalence of TP53 and CNV (both P<0.05) between DDR-germline MPLC and SFLC patients. Conclusions: MPLC patients exhibit a distinctive DDR mutations landscape. The differences in the mutation profile between the DDR-germline and DDR-somatic groups and the distinct actionable genes may indicate the different target-therapy choices for MPLC patients.
Induction immune checkpoint inhibitors and chemotherapy for patients with stage III non-small cell lung cancer: A real-world experience.
Authors: Zheng Shuohan , Sun Ciming , Zhang Hao , Xu Huimin , Dong Baiqiang , Hou Zan , Chen Ming , Li QiWen 
Published: June 2024

e20057 Background: Immune checkpoint inhibitors (ICIs) have become the standard consolidation therapy for stage III unresectable non-small cell lung cancer (NSCLC). Whether induction ICIs combined with chemotherapy can further improve efficacy is controversial. In this study, we used real-world data to explore the possibility of ICIs plus chemotherapy before definitive chemoradiation therapy (CRT). Methods: Patients with stage III NSCLC (including postoperative recurrence), who received definitive CRT from 2016 to 2022, was retrospective reviewed. Survival outcomes and the incidence of pneumonia were calculated and compared between patients with induction ICIs plus chemotherapy or not. Results: A total of 156 patients undergoing definitive RCT were analyzed. Among them, 103 patients received induction ICIs plus chemotherapy, and 53 patients received induction chemotherapy before RCT or concurrent chemoradiotherapy. The 5-year overall survival (OS) rates were 75.0% and 44.4%, respectively. The median OS was not reached (NR) and 36.5 months, indicating a significant improvement of survival with the addition of induction ICIs (P = 0.03). However, there were no significant differences between the two groups in median progression-free survival (PFS) (22.4 vs. 13.6 months; P = 0.09), locoregional recurrence-free survival (LRFS) (38.0 vs. 36.9 months; P = 0.73), and distant metastasis-free survival (DMFS) (37.8 vs. 25.5 months; P = 0.14). Multivariate analysis showed that induction ICIs plus chemotherapy was an independent favorable prognostic factor for OS (HR 2.89; 95% CI, 1.24-6.75; P = 0.01). The incidence of grade 2 or higher pneumonia in the two groups was 37.2% and 29.2%, respectively (P = 0.35). Additionally, we found that patients with consolidation ICIs after induction ICIs had a better OS, with a 4-year OS rate of 90.7% and 65.5% (P = 0.03). Patients undergoing 5-6 cycles of induction ICIs seemed to have a better outcome compared to those with 3-4 cycles or 1-2 cycles (93.8% vs. 77.4% vs. 60.5%). Conclusions: For patients with stage III NSCLC receiving definitive CRT, the combination of induction ICIs and chemotherapy improves OS without a significant increase of pneumonia in real-world practice. This treatment strategy warrants further research.
Effect of intrinsic STING of CD8+T cells on self-metabolic reprogramming and anti-tumor effects.
Authors: Xu Qiuli , Hua Xin , Li Bingbing , Jiang Bei , Xu Ruiqing , Lv Tangfeng , Song Yong 
Published: June 2024

e20062 Background: Many preclinical studies have demonstrated that STING agonists have effective anti-tumor effects, but their adverse effects prevent practical use. Previous research by our team has demonstrated that STING has a more significant anti-tumor role in host immune cells than tumor cells, and the level of STING mRNA is associated with the outcome of immunotherapy in non-small cell lung cancer. Although STING is necessary for CD8+T cells to exert immunological activity, its effect on CD8+T cells is debatable. Therefore, we will concentrate on the particular roles of STING in CD8+T cells. Methods: We used in vitro and in vivo models to confirm the influence of STING on CD8+T cell function. We examined the impact of STING on CD8+T cell metabolic function using RNA-seq, Seahorse, flow, electron microscopy, and other techniques. STING knockout mice were used to study the effect of competitive inhibition of glycolytic products during immunotherapy. In addition, we collected peripheral blood immune cells from 30 immunotherapy patients to examine the correlation between immune cell glycolysis levels and immunotherapy efficacy. Results: RNA-seq showed significant changes in signaling pathways such as glycolysis/glycogen synthesis, oxidative phosphorylation, tricarboxylic acid cycle, and one carbon unit in STING-/- CD8+T cells. In vitro experiments revealed that the inactivation of the STING gene reduced the number of mitochondria, altered the choice of metabolic pathways, and impaired the anti-tumor ability. Flow results showed that the mean fluorescence intensity of mitochondria in STING-/- CD8+T decreased. Seahorse experiment showed that STING-/- CD8+T glycolysis was enhanced, and oxidative phosphorylation was decreased. Meanwhile, the content of lactic acid in the culture supernatant of STING-/- CD8+ T increased dramatically, the high level of lactic acid further inhibited the proliferation of CD8+ T and the secretion of IFN-γ. Competitive inhibition of the glycolysis process or lactic acid formation can save the function of STING-/- CD8+ T cells and the secretion of IFN-γ, save the immunotherapy effect of STING-/- mice. This provides a new therapeutic idea for patients with low STING expression and poor immunotherapy response. In the peripheral blood immune cells of immunotherapy patients, we observed a negative correlation between the mRNA levels of glycolysis-associated molecules and STING. Additionally, we found a correlation between the levels of glycolysis-associated molecules in immune cells and immunotherapy efficacy outcomes. Conclusions: Our study is the first to explore the effect of STING on the metabolic process in CD8+ T cells. Intervening in the metabolic process of STING-deficient CD8+ T can save the efficacy of immunotherapy.
Pulmonary blastoma: An NCDB analysis of demographic and socioeconomic factors.
Authors: Ramos Brianna Eillen , Tade Yanick , Khatib Rawaan , Sadighian Assal , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: June 2024

e20069 Background: Pulmonary blastoma (PB) is a rare sarcomatoid carcinoma classified as a non-small cell lung cancer with a poor prognosis and no standard treatment. This malignancy exhibits glandular proliferation with a morular component resembling embryonic development. Leading PB treatment favors surgical resection with concurrent chemotherapy. However, radiation is recommended for inoperable tumors. Further analysis of diagnostic trends may provide information about the epidemiology of PB. The National Cancer Database (NCDB) was analyzed to establish the demographic factors in diagnosed patients. Methods: A retrospective cohort study from 2004 to 2020 was conducted using the NCDB. 146 patients were identified with a histologically confirmed diagnosis of PB (ICD-O-3 code 8972). Race, gender, Hispanic origin, urban/rural residence, insurance coverage, treatment approaches, and mean survival rates were analyzed via descriptive statistics. Regression analysis was performed to examine incidence trends. Results: 146 patients diagnosed with PB were identified in the NCDB, where the incidence rate of diagnoses strongly declined annually (R² = 0.079). The average age of diagnosis was 50 years (SD = 26, range = 1-90 years), with women (56%) more likely to be affected than men (44%). The majority of patients identified as White (80%) and non-Hispanic (88%), lived in metropolitan counties with a population greater than 1 million (58%), and were privately insured (45%). The top primary sites of diagnoses were the upper (38%) and lower (28%) lobe of the bronchus or lung. For patients who did not receive palliative care (93%), many received surgery (75%) as their primary treatment. Within this group, chemotherapy and radiation therapy were also chosen as treatment options (48% and 27%, respectively). The majority of individuals (66%) had a Charlson-Deyo comorbidity score of 0. The survival rates were 58% at two years, 49% at five years, and 34% at ten years. The mean survival was also found to be 86 months. Conclusions: To the best of our knowledge, this is the first NCDB analysis on pulmonary blastoma and helps provide insight on a previously understudied topic. Results demonstrated that the majority of PB patients are non-Hispanic White females, who were primarily diagnosed at the upper lobe of the bronchus or lung. These findings confirmed similar descriptions from other databases and earlier case reports. This is the first time the socioeconomic factors of PB patients have been described in the literature: PB patients typically do not receive palliative care and choose to undergo surgery as their primary treatment. Further research is indicated to provide a greater insight on the effects of demographic/socioeconomic factors on diagnostic criteria, chosen treatments, and overall survival rates of patients with PB.
The treatment modalities and radiotherapy pattern in patients with primary lung cancer in Japan.
Authors: Hu Qingqing , Huang Titan , Nakajo Ko , Zhang Yongjing , Qiu Hong 
Published: June 2024

e20070 Background: In Japan, lung cancer has high incidence and mortality among all cancers. The study is to understand the existing status of the treatment modalities in Japan, especially for radiotherapy (RT). Methods: This was a retrospective cohort study using the Japan Medical Data Center (JMDC) database. A cohort of adult patients with at least two diagnosis codes of primary lung cancer (ICD-10-CM: C34) during January 1st, 2015-March 31st, 2023, and initiated lung cancer treatment was included in the study. The initial treatment episode was defined as a period with the first single or multiple treatments before a 90-day gap. Patients were followed up until a record of death, or the last enrollment in JMDC. The cohort was stratified into four exclusive groups: Group A: ≥1 record of distant metastasis; Group B-1: ≥1 record of regional metastasis; Group B-2: no record of surgery and no metastasis; Group C: ≥1 record of surgery and no metastasis. The characteristics, initial treatment episode and RT patterns were described across the four groups. Results: A total of 9,373 patients were included, with Group A 1,625 (17.3%), Group B-1 527 (5.6%), Group B-2 2084 (22.2%), and Group C 5137 (54.8%). The median follow-up was 21.2 months of the cohort. The median (IQR) time to initial treatment episode from the initial diagnosis was 27 (27), 35 (40), 34 (47) and 38 (36) days for the four groups, respectively. Most of patients in group A (74.1%), B-1 (70.8%), and B-2 (67.6%) had a >3 months duration of initial treatment, and only 32.7% in group C. For treatment involved in the initial treatment episode, RT was accounted for 59.2%, 29.8%, 43.4%, and 4.7% in four groups respectively. For treatment categories in Groups A, B-1, and B-2, RT only was performed in 15.5%, 2.2% and 6.9% of patients with single treatment; and RT was commonly performed with chemotherapy in multiple treatments, with proportions of 83.6%, 95.3% and 95.6% among no surgery. For RT with chemotherapy group, the median RT fractions are 22, 36 and 42, covering a median duration of 35, 43 and 43 days of RT. Conclusions: In Japan, the initial treatment episode usually starts in 30 days and lasts more than 3 months for metastasis and unresectable primary lung cancer. RT only is not commonly performed, and RT with chemotherapy is commonly performed in initial treatment episode. [Table: see text]
Fetal adenocarcinoma: An NCDB analysis of socioeconomic and demographic factors.
Authors: Han Emily , Moroz Mark , Puvvadi Suraj , Joseph Angel , Silberstein Peter T. , Heise Craig , Hsia Beau 
Published: June 2024

e20076 Background: Fetal adenocarcinoma (FA) is a rare subtype of lung neoplasia whose structure is similar to a developing fetal lung. Chest x-ray is valuable for diagnosis as 25 - 40% of patients with FA are asymptomatic. FA is classified into low-grade and high-grade, predominantly occurring in children and older males with a smoking history. The rarity of FA suggests that evaluating its diagnostic patterns could expand awareness of its epidemiology. Impactful demographic factors of FA were established through analysis of the National Cancer Database (NCDB). Methods: The 2004 - 2020 National Cancer Database (NCDB) was utilized to perform a retrospective analysis of all 120 patients with a histologically confirmed diagnosis of FA (ICD-O-3 Code 8333). Descriptive statistics were employed to examine demographic factors, including sex, age, race, Hispanic ethnicity, urban/rural residence, Charlson-Deyo comorbidity score (CDCS), and treatment facility type. Additionally, regression analysis was utilized to demonstrate incidence trends. Exclusion criteria included missing values. Results: The NCDB identified 120 patients from 2004 - 2020. Over this time period, there was a slightly increasing incidence of patients diagnosed per year (R2 = 0.4461). Represented age at diagnosis featured negative skewness (-0.8), and the mean age was 54.4 years (95% CI = 51.2 - 57.6, SD = 17.6). Most patients were female (57%), White (76%), and non-Hispanic (95%). The vast majority of patients (85%) resided in metropolitan areas, with a slight majority of patients (53%) hailing from areas of 1 million population or more. Regions of the United States were well-represented, with a plurality of patients from the South Atlantic (21%). Most patients were diagnosed at Stage I (56%) and had a CDCS of 0 (61%). The primary tumor site was the upper lung lobes, and most (83%) patients underwent surgery as primary treatment. Multiple facility types were utilized in the care of patients, including research programs (42%), comprehensive community cancer center programs (30%), and integrated network cancer programs (25%). The 30-day mortality rate was 1%, comparable to the 90-day mortality rate of 3%. Five years after diagnosis, 60% of patients were alive. Conclusions: To the best of our knowledge, this is the first NCDB analysis to examine the sociodemographic factors concerning prognosis in patients with FA. Our results are consistent with previous studies finding that patients with low-stage FA tend to have favorable outcomes. Our study is the first documentation of location demographics of patients with FA: Most patients live in metropolitan counties along the Atlantic Coast. Future investigations on the prognostic significance of demographic and socioeconomic factors should be performed to optimize treatment approaches for improved mortality rates of diverse patients with FA.
Long-term survival of single and multifocal stage 1 lung carcinoma using image-guided thermal ablation.
Authors: Jahanshahi Noor J. , Kooraki Soheil , Villegas Bianca , Kim Grace Hyun J. , Goldman Jonathan W. , Genshaft Scott J. , Suh Robert D. , Abtin Fereidoun 
Published: June 2024

e20087 Background: Image-guided thermal ablation (IGTA) is an effective treatment option for patients with non-small cell lung cancers (NSCLC), offering an excellent alternative to invasive surgery. We seek to compare long-term survival metrics between single and multifocal stage IA NSCLC patients who underwent IGTA. Methods: IRB-approved, HIPAA-compliant, retrospective study of patients who underwent IGTA for NSCLC during 2015 and 2016. Patient demographics, clinical and imaging follow-ups, tumor characteristics, and procedural technical outcomes were reviewed. We analyzed technical success, 5-year overall survival (OS), progression-free survival (PFS), cancer-specific survival (CSS), and Kaplan-Meier survival analysis between single and multifocal NSCLC cohorts, as well as different tumor stages. Results: 37 patients (mean ± SD age=71.6±8.8) ablated for single (n=15 (40.5%)) or multifocal (n=22 (59.5%)) NSCLC were identified. Multifocal NSCLC were sub-classified into 2-3 (n=12 (32.4%)) and ≥4 tumors (n=10 (27%)). All ablations were completed successfully. Across 119 IGTA encounters, patients were treated using cryoablation (n=66), microwave ablation (MWA) (n=49), and radiofrequency ablation (RFA) (n=4). At the time of ablation, individual nodules were staged at T1A=46 (38.7%), T1B=54 (45.4%), T1C=16 (13.5%) and T2A=3 (2.5%). Local recurrence was observed in 4/119 (3.3%) tumors; two were reablated once with MWA and cryoablation with no further recurrence, the third was reablated twice with MWA and had no recurrence, and the fourth was reablated once with MWA and subsequently treated with radiotherapy. Multifocal NSCLC patients exhibited significantly better 5-year OS of 85.6% compared to single NSCLC patients at 35.7% (HR=0.14, p=0.003, 95% CI: 0.037, 0.51). PFS and CSS at 5 years were higher for multifocal NSCLC compared to single NSCLC, but only significant for PFS (HR=0.25, p=0.014, 95% CI: 0.084, 0.76). PFS and CSS of subjects with ≥4 tumors were both 100%, 2-3 tumors at 58.7% and 90.9%, and single tumors at 35.7% and 83.1%, respectively. There was no significant difference between tumor T stages for OS and PFS (p=0.48 and p=0.56, respectively; see Table). No patient staged at T1A at the initial IGTA encounter died as a result of cancer, meaning cancer-specific survival was greatest in T1A tumors (see Table). Conclusions: IGTA is an effective treatment for multifocal and early-stage NSCLC. Our results demonstrated consistent trends in improved survival for multifocal NSCLC. The size of tumor up to 3 cm did not have significant impact on overall survival or progression-free survival. [Table: see text]