bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor immune infiltrates and overall survival in non-small cell lung cancer are associated with an unsupervised radiomic signature.
Authors: Oh Jung Hun , Veeraraghavan Harini , Apte Aditya , Tannenbaum Allen , Deasy Joseph O. 
Published: June 2023

e20525 Background: We investigated whether radiomic features derived from computed tomography (CT) scans are predictive of survival and are correlated with immune cell types in non-small cell lung cancer (NSCLC), employing a mathematical network-based approach. Methods: DICOM data of pre-treatment CT scans and associated clinical variables for 116 NSCLC patients were downloaded from The Cancer Imaging Atlas (TCIA). RNA-Seq gene expression profiles for the matched cases were downloaded from the GEO database (GSE103584). CIBERSORT scores that consist of 22 immune cell types were generated using the R library (CIBERSORT) on the RNA-Seq gene expression profiles. From contoured tumors on CT scans, 83 radiomic features including tumor volume were extracted, utilizing the CERR radiomics toolbox. Radiomic networks were constructed with a threshold of Spearman correlation coefficient of 0.85 between each pair of radiomic features. The mathematical network-based k-means clustering method was applied to the largest connected network component that consists of 40 radiomic features, using the Wasserstein distance from optimal mass transport (OMT), to minimize the summed distance between k partitioned centroids and their respective data points. For the sub-groups identified, Kaplan-Meier survival analysis was conducted with log-rank test and CIBERSORT scores and clinical variables were then compared among the sub-groups using Kruskal-Wallis test. Results: The median age was 69 years (range: 46–85 years). Eighty-seven patients (75.0%) were males. Most patients were former (N = 75, 64.7%) or current smokers (N = 24, 20.7%). The median follow-up time (last follow-up or death) was 44 months and 75 patients were alive at last contact. The Wasserstein distance-based k-means method resulted in 3 sub-groups (high: N = 32, medium: N = 45, low-risk: N = 39). Kaplan-Meier analysis on the 3 sub-groups showed a significant difference in overall survival with log-rank p = 0.02. There were no significant differences for the variables mentioned above among the sub-groups. Two immune cell types showed statistically significant differences among the sub-groups: mast cells resting with p = 0.004 and M2 macrophages with p = 0.013 using Kruskal-Wallis test. The values for both immune cell types increased from high < medium < low-risk group. There was a significant volume difference with p < 0.001, but the difference did not fully account for the survival difference; the median volume was 30.8 cc, 2.7 cc, and 12.8 cc for high, medium, and low-risk groups, respectively. Conclusions: A radiomic network analysis, utilizing a mathematical network-based method, resulted in sub-groups with the survival difference in NSCLC patients. Furthermore, these sub-groups had significantly different immune cell types likely associated with the survival.
Perioperative IDO-1 dynamic changes in NSCLC patients.
Authors: Sun Zhijuan , Chen Weiwei , Ye Zhenghao , Wang Sichao , Pang Dazhi , Kong Feng-Ming Spring 
Published: June 2023

e20532 Background: Indoleamine 2,3-dioxygenase (IDO) is an enzyme that is involved in the metabolism of tryptophan, an essential amino acid. It is known to play a role in the regulation of the immune system, and has been linked to perioperative immune status. Specifically, IDO has been shown to be upregulated in the perioperative period, leading to an increased risk of infection and other complications. This is thought to be due to the increased production of kynurenine, a metabolite of tryptophan, which has been associated with immunosuppression. Additionally, IDO has been linked to increased levels of inflammation and oxidative stress, which can further contribute to the risk of complications during surgery. Thus, understanding the role and dynamic changes of IDO in the perioperative period is important for optimizing patient outcomes. Methods: Patients with non-small cell lung cancer (NSCLC) who underwent surgery were enrolled in this study prospectively. Peripheral blood at different time points: preoperative, post anesthesia, post-vascular incision, post-tumor resection, and 3 days after surgery. The serum tryptophan and kynurenine were measured, and the kynurenine to tryptophan (K:T) ratio was used as an indicator of IDO activity. Paired Wilcoxon test was used to identify the significant difference of IDO activity at five different time points. The Kaplan–Meier log-rank test was used to assess the correlation between overall survival (OS), progression-free survival (PFS), and IDO activity. Results: A total of 46 patients were enrolled in this study. The median follow-up time was 24.7 (range: 0.9 – 35.3) months. No patients died during the follow-up time. The PFS at 2 years was 76% (95% CI, 76%-100%). In all patients, IDO activity was not correlated significantly with better PFS. Surgical procedure does not affect levels of plasma IDO at any pathological stage in NSCLC significantly. The level of serum IDO of post-vascular incision was significantly correlated with that of 3 days after surgery (R2 = 0.7, P < 0.05). The level of preoperative level of serum kynurenine was significantly correlated with that of post-vascular incision and post-tumor resection (R2 = 0.7/0.73, P < 0.05). Conclusions: Surgical procedure does not have a significant effect on the serum IDO levels during the perioperative period. The perioperative levels of serum IDO are not correlated with the surgical prognosis of NSCLC, thus alternative markers are needed to better predict the surgical prognosis of NSCLC patients.
Tumor immune microenvironment of different lesions in patients with multiple primary lung cancer.
Authors: Li Yun , Qi Yingxue , Luo Ningning , Li Mengmeng , Sun Tingting , Qi Chuang 
Published: June 2023

e20549 Background: More and more multiple primary lung cancers (MPLCs) are found clinically. The driver genes and clinical differences between different lesions in MPLCs are obvious, which may affect the choice of subsequent treatment options. As a new type of therapy, immunotherapy has improved the survival of lung cancer patients to a certain extent. However, the efficacy of immunotherapy on different lesions of the same patient with MPLCs is not yet clear. Our study explored the similarities and differences of the tumor immune microenvironment in MPLCs lesions and provided a theoretical basis for immunotherapy in MPLCs. Methods: We collected 20 surgical tumor lesion samples from 10 patients with MPLCs for 289-gene panel RNA sequencing using NanoString nCounter. All tumor tumor immune microenvironment (TIME) cell infiltration scores were calculated as arithmetic mean of the constituent genes. Immune infiltration and expression of immune-related genes in different groups were assessed. Results: All 10 patients in our study were lung adenocarcinoma. Firstly, we classified them using an unsupervised consensus clustering based on TIME-signature gene expression used nonnegative matrix factorization of R package. The results revealed the cluster number of two was optimal (TIME Cluster1: n = 6 patients / 12 lesions; TIME Cluster2: n = 4 patients / 8 lesions). It is worth noting that the two lesions of the same patient are divided into the same group, indicating that the immune microenvironment status of the two lesions of the same person is basically similar. In addition, the nertrophils, NK CD56dim cells and GEP score of Cluster1 is significantly higher than that of Cluster2. Then we grouped them according to gender, ipsilateral or heteroside primary lesions, left or right lung, and pathological infiltration or non-infiltration, and found there was no significant difference in the immune microenvironment between the all the two groups. Conclusions: Dual primary samples from the same individual have similar immune microenvironments and may respond similarly to immunotherapy. Prospective immune-related clinical trials can be designed for further verification in MPLCs patients.
Radiomics to predict checkpoint inhibitor pneumonitis based on chest CT scans in patients with advanced cancer.
Authors: Vos Wim , Cousin François , Wendling Mathieu , Freres Pierre , Guiot Julien , Occhipinti Mariaelena , Hustinx Roland 
Published: June 2023

e20550 Background: Checkpoint inhibitor pneumonitis (CIP) is a concerning immune-related adverse event responsible for treatment discontinuation, hospitalization, with acknowledged possible fatal cases. The aim of our study was to assess the potential role of machine learning models, combining pre-treatment CT lung radiomic features with clinical data, to predict the risk of developing CIP. Methods: A cohort of 116 patients with different type advanced malignancies (81% lung cancer, 14% melanoma, 8% other solid tumors) treated with immune checkpoint inhibitors (ICIs) were retrospectively enrolled in this study and divided into a CIP (n = 35) and a control group (n = 81). Each patients had a chest CT scan at baseline and associated clinical covariates. Lungs and lobes were segmented semi-automatically on pre-treatment CT scans. We extracted radiomics features and selected them by the Minimum Redundancy Maximum Relevance (mRMR) method. Clinical-only, radiomics-only, and clinical-radiomics models (both lung- and lobe-based) were built using generalized linear (GLM) and random forest (RF) models to predict the occurrence of CIP. A nested 5-fold cross-validation scheme was used in the training, validation and test sets. Model performances were assessed in terms of Area under the Curve (AUC). Results: The most accurate clinical (RF) and the best radiomic (lobe-based GLM) models achieved AUCs of 0.72 (95%CI:0.51-0.92) and 0.71 (95%CI:0.58-0.84) on the test set, respectively. No statistically significant differences have been found between lung- and lobe-based radiomic models. The RF model combining lung-based radiomic and clinical features showed the best performances overall with an AUC of 0.75 (95%CI:0.62-0.88) on the test set. Conclusions: CT-based lung radiomic, and clinical models alone show moderate to good performances at identifying patients at risk of developing CIP. Nevertheless, we demonstrated the added value of machine learning models built combining clinical and radiomic features to better stratify the risk of developing CIP in patients with advanced malignancies treated with ICIs.
The association of race and curative-intent treatment with mortality outcomes among early-stage NSCLC.
Authors: Liu Qinran , Koru-Sengul Tulay , Lopes Gilberto , Pinheiro Paulo S. 
Published: June 2023

e20563 Background: Racial disparities in early-stage non-small cell lung cancer (NSCLC) survival have persisted between blacks and whites in the past few decades. The role of receipt of curative-intent surgery and/or stereotactic body radiation therapy (SBRT) in this disparity is unclear. We examined the associations of race/ethnicity and curative-intent treatment (surgery and/or SRBT) with mortality outcomes among early-stage NSCLC patients, using population-based data from Florida, the third largest state in the US and the second state in the number of cancer cases diagnosed annually. Methods: Florida Cancer Data System (FCDS) data were used to estimate cancer-specific mortality for all patients diagnosed in the state between 2007 to 2018 for each racial/ethnic group: non-Hispanic black (NHB), Hispanic, and Asian/Pacific Islander (API)) and non-Hispanic whites (NHW). FCDS were further individually linked to population-based discharge data (94% match rate) containing patient-level comorbidities and treatment-specific information. Multivariable Cox proportional hazards regression models were applied to study the association of race/ethnicity and curative-intent treatment with lung cancer-specific mortality (LCSM). Competing risk analysis (deaths by other causes) for LCSM was performed. Results: We identified 63,872 early-stage NSCLC patients; 83.2% NHW, 6.6% NHB, 8.7% Hispanic, 0.77% API, and 0.79% other races; 72.2% of patients received curative-intent treatment (surgery and/or SRBT). The median lung cancer-specific survival time for all patients was 5.43 years (95% CI, 5.30-5.56). After inclusion of all clinical and sociodemographic factors including stage at diagnosis and comorbidities, race/ethnicity (NHB vs NHW: hazard ratio [HR], 1.06; 95% CI, 1.00-1.11) and curative-intent treatment (SBRT vs curative-intent surgery: HR, 1.87; 95% CI, 1.78-1.97;) were both independently associated with LCSM. Nevertheless, after combining the effect of race/ethnicity and curative-intent treatment in the same fully adjusted model, NHB patients who received curative-intent treatment experienced nearly identical survival as their NHW counterparts (HR, 0.95; 95% CI, 0.87-1.03). Similar findings were observed in competing risk analysis (subdistribution hazard ratio [sHR], 0.97; 95% CI: 0.89-1.02). Conclusions: In this racially diverse population, receipt of curative-intent treatment revealed comparable survival between NHB and NHW patients. The results underscore the importance of considering receipt of (specifically) curative-intent treatment rather than receipt of any form of surgery or radiotherapy in racial/ethnic survival disparities. The uptake of curative-intent surgery and SBRT, which currently stands at 56.5% and 9.4% respectively, should be increased to improve survival outcomes for early-stage NSCLC for all.
The role of immunotherapy in stage III large cell neuroendocrine carcinoma of the lung (LCNEC): A retrospective NCDB analysis.
Authors: Findakly Dawood , Shi Runhua , Beedupalli Kavitha 
Published: June 2023

e20568 Background: Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare lung cancer subtype. Despite advances in understanding lung cancer biology, a consensus on the use of consolidation immunotherapy (IO) in patients with LCNEC is still lacking. Methods: Using National Cancer Database (NCDB), we reviewed stage III lung LCNEC cases diagnosed from 2017 through 2019 with a follow-up through 2020. Several variables were incorporated into the multivariate logistic regression analysis, including age, gender, race, Charlson-Deyo comorbidity score (CDCS), insurance status, and IO use. Survival distribution was examined using the Kaplan-Meier analysis and compared by the log-rank test. Results: A total of 956 cases with a male:female ratio of 1.2:1, and a median age (±SD, range) of 66.4 (±9.7, 37–90) years—baseline characteristics are shown in the Table. In the univariate analysis, IO use (n = 184) resulted in a superior median overall survival (mOS; 30.6 vs. 20.3 months, HR 0.76, 95% CI 0.62-0.96, p = 0.02, compared to no IO use). Results from multivariate analysis further demonstrated survival benefit with IO use (HR 0.79, 95% CI 0.63-0.98, p = 0.03, compared to no IO use). Additionally, in the multivariate analysis, the female gender was associated with improved survival (HR 0.84, 95% CI 0.71-0.99, p = 0.04); while notable factors associated with reduced survival were age ≥75 years (HR 1.45, 95% CI 1.08-1.95, p = 0.01, compared to 18-64 years age group), CDCS of ≥1 (HR 1.19, 95% CI 1.004-1.420, p = 0.04, compared to zero), and Medicaid (HR 1.46, 95% CI 1.05-2.05, p = 0.02, compared to private insurance). There was no statistical significance for OS noted with age group 65-74 years (HR 1.09, 95% CI 0.84-1.42, p = 0.49, compared to 18-64 years age group); and race (African American, HR 1.001, 95% CI 0.77-1.29, P = 0.99, compared to White). Conclusions: This study shows that IO improves survival in stage III LCNEC. Despite the inherent limitations of the database, our findings are intriguing and warrant further evaluation through prospective clinical trials in order to assess and optimize the benefit of IO in this patient population. [Table: see text]
Correlation analysis of MRD positivity after non-small cell lung cancer surgery.
Authors: Dong Daling , Jiang Bin , Wei Wei , Wang Chao , Yang Qian , Yan Tingzhi , Zheng Liken , Shao Weikang , Xiong Gang , Zhang Shixin 
Published: June 2023

e20590 Background: To explore the relationship between postoperative molecular residual disease (MRD) status in patients with non-small cell lung cancer (NSCLC) and clinicopathological features, gene mutations, the tumour immune microenvironment and treatment effects. Methods: The clinical data of 90 patients with stage I-IIIA NSCLC who underwent radical resection of lung cancer from January 2021 to March 2022 in our hospital were retrospectively collected, and demographic data, clinicopathological characteristics, genetic test results, MRD status, and treatment effects were analysed. Results: Sex, age, smoking status, pathological type, and gene mutations were not associated with postoperative MRD status. T (tumour diameter > 3 cm) and N (lymph node metastasis) were statistically correlated with MRD positivity ( p values of 0.004 and 0.003, respectively). The higher the proportion of micropapillary and solid pathological subtypes of lung adenocarcinoma, the higher was the MRD-positivity rate after surgery ( p = 0.005). MRD positivity was correlated with vascular invasion ( p = 0.0002). For the expression of programmed cell death ligand 1 (PD-L1), tumour positive score (TPS) ≥ 1% and combined positive score (CPS) ≥ 5 were correlated with postoperative MRD status ( p value distribution was 0.0391 and 0.0153). For ctDNA clearance, among postoperative MRD-positive patients, postoperative adjuvant targeted therapy was superior to chemotherapy for patients without gene mutations. Conclusions: Postoperative ctDNA-MRD status in NSCLC patients is associated with primary tumour size, lymph node metastasis, lung adenocarcinoma pathological subtype, vascular invasion, TPS and CPS for PD-L1 expression; for postoperative MRD-positive patients, clearance of ctDNA by adjuvant EGFR-TKI target treatment is superior to chemotherapy.
Treatment of newly developed metastases after definitive chemoradiotherapy +/- ICI for unresectable stage III NSCLC.
Authors: Taugner Julian , Hofstetter Kerstin , Käsmann Lukas , Kröninger Sophie , Schmidt Sofie , Tufman Amanda , Reinmuth Niels , Duell Thomas , Belka Claus , Eze Chukwuka , Manapov Farkhad 
Published: June 2023

e20603 Background: Assessment of salvage treatment for newly developed metastases in patients previously treated with curative-intent concurrent chemoradiation (cCRT) +/- immune checkpoint inhibition (ICI) for unresectable stage III NSCLC. Methods: We analysed data of 136 patients treated from 2011 to 2020 in as single tertiary cancer centre. Location of first observed distant metastasis (DM) were categorized as brain/intracranial metastasis (BM), organ metastasis (OM) and skeletal metastasis (SM). Treatment with radiotherapy (RT) and systemic therapy (ST); sub-divided into chemo- (CT), immuno (IT) and tyrosine kinase inhibitor therapy (TKI) was assessed. Results: All patients received definitive cCRT ≥ 60 Gy with 2 courses of chemotherapy. Thirty-six (26%) patients received ICI. Median follow-up was 49.7 months, median PFS was 9.9 (95%CI: 7.0-12.7) months, 12- and 24-month PFS-rates were 42% and 29%, respectively. Median OS was 31.2 months (95% CI 16.9 – 45.6), 12- und 24-month-OS-rates were 74% und 53%. Sixty-one patients (45%) developed metastasis: 21 (15%) BM, 20 (15%) OM und 20 (15%) SM. Median OS of patients with BM, OM and SM was 27.4, 25.5 and 17.9 months, respectively (p = 0.821). In total 45/61 patients were initially treated with cCRT and 16 with cCRT+ICI. Median OS was 26.5 (cCRT+ICI) vs. 23.4 (cCRT) months (p = 0.121); 12- and 24- month survival rates were 94% vs. 64% and 63% vs. 47%. Patients with SM survived significantly longer, if the initial treatment included ICI (Median not reached vs. 7.5 months; p = 0.042). Fifty-three (87%) of 61 patients received the following salvage therapy: 28 (53%) RT, 10 (19%) ST and 15 (28%) combined RT + ST. Patients with SM showed a trend towards longer OS after RT-alone (p = 0.069). Thirteen patients with adenocarcinoma received ST: 7 CT and 6 TKI with a significant longer OS (40.1 months TKI vs. 12.1 months CT; p = 0.040). All 21 patients with BM were treated with RT. Patients treated with stereotactic radiosurgery (SRS) showed a significant longer OS of 40.1 months vs. 12.2 months for patients treated with whole brain radiotherapy (WBRT) (p = 0.016). Conclusions: Patients with SM had a significantly longer OS if their initial therapy consisted of cCRT+ICI vs. cCRT alone. Patients with BM as first site of metastasis had a significantly longer OS when treated with SRS vs. WBRT. Salvage treatment with TKI resulted in a significantly longer OS compared to salvage CT in patients with adenocarcinomas.
Incidence of central nervous system metastases (mCNS) and overall survival (OS) in patients with stage III non-small cell lung cancer (NSCLC) treated with definitive chemoradiation followed by durvalumab (Durva).
Authors: Sharp John , Zhao Songzhu , Patel Sandip , Wei Lai , Li Mingjia , Brownstein Jeremy , WELLIVER Meng Xu , Haglund Karl , Palmer Joshua David , Beyer Sasha , Raval Raju R. , Shields Peter G. , He Kai , Kaufman Jacob , Memmott Regan Michelle , Alahmadi Asrar , Carbone David Paul , Otterson Gregory Alan , Presley Carolyn J , Owen Dwight Hall 
Published: June 2023

e20605 Background: In the landmark PACIFIC trial, 6.3% of patients with unresectable stage III NSCLC receiving durva after chemoradiation developed mCNS. Data on incidence of mCNS in non-clinical trial patient populations are needed to evaluate CNS surveillance strategies. Methods: We conducted a retrospective study of patients with unresectable stage III NSCLC treated with durva following chemoradiation from 2018 to 2021 with baseline CNS imaging showing no mCNS. Patient characteristics and outcomes were assessed, including age, tumor histology, stage, mCNS incidence, and survival. OS was calculated from date of initiation of durva to death or censored at last follow-up. Results: Out of 86 patients included in our study, a total of 17 (19.8%) developed mCNS after starting durva. Development of mCNS was not associated with age, sex, histology, T or N staging or PD-L1 expression (Table 1). Three patients (3.5%) had CNS-only metastases whereas 14 (16.3%) had progression outside the CNS. The median time from baseline CNS imaging to first durva was 3.8 months (IQR 3.0 – 4.9) in the cohort. The median time from first durva to development of mCNS was 4.7 months (IQR 2.3 – 8.7). Median OS in patients with mCNS was 15.2 months (95% CI 8.6 – 25.9) compared to 36.9 months (95% CI 27.2 – NR) in patients without mCNS (p = 0.010). Conclusions: Incidence of mCNS among a cohort of patients with stage III NSCLC managed with durva after chemoradiation was 19.8% which is higher than that observed in landmark clinical trials. The OS for patients with mCNS was shorter than those without mCNS. Most mCNS occurred within 6 months of starting durva and were often accompanied by systemic progression. Further research is needed to understand optimal surveillance strategies for mCNS in this patient population. [Table: see text]