bluuebunny/crossref_metadata_2025_split huggingface dataset:
Respiratory toxicities after concurrent chemoradiotherapy and subsequent consolidation immune checkpoint inhibitors in locally advanced non-small cell lung cancer: Infectious and non-infectious subtypes by pathogen NGS testing.
Authors: Qiu Bo , Xiong Mai , Liu FangJie , Zhang PengXin , Zhou Rui , Wang DaQuan , Luo YiFeng , Liu YiMei , Guo JinYu , Chen NaiBin , Li Shiyue , Liu Hui 
Published: June 2023

e20557 Background: Consolidation immune checkpoint inhibitors (ICIs) following concurrent chemoradiotherapy (CCRT) have significantly improved survival in locally advanced non-small cell lung cancer (LA-NSCLC), while the associated respiratory toxicities were of particular concern. We aimed to investigate the > = G2 respiratory toxicities, the characteristics of concomitant infection, and provide detailed information for clinical management. Methods: We reviewed 77 LA-NSCLC patients treated with CCRT and consolidation ICIs. The details of > = G2 respiratory toxicities and concomitant infection were analyzed. Potential risk factors for > = G2 respiratory toxicities were explored by univariable and multivariable analysis. Respiratory toxicities were collected from the start of consolidation ICIs till 6 months after the last infusion of ICIs. Concomitant infection was defined as positive findings from next-generation sequencing (NGS) of bronchoalveolar lavage sampling. Results: Patients were treated with definitive radiotherapy at a median dose of 60 Gy (IQR, 60-64), concurrently with weekly docetaxel and platinum and followed by single-agent ICIs. The median duration of consolidation ICIs was 5.4 months (IQR, 2.3-8.2). Twenty-six patients (33.8%) experienced > = G2 respiratory toxicities by a median of 4.8 months (IQR 1.5-6.6) after initiation of consolidation ICIs. Pneumonitis (14, 18.2%) and tracheobronchitis (13, 16.9%) were the most common > = G2 respiratory disorders. Location of primary tumor (p = 0.027) and the proportion of CD3+ lymphocyte before consolidation ICIs (p = 0.044) were independent risk factors for the occurrence of > = G2 respiratory toxicities. Eleven patients (14.3%) had > = G2 respiratory toxicities and concomitant infection. Identified pathogens included bacteria (n = 9), Aspergillus (n = 5), Pneumocystis (n = 1) and Leptosvirus (n = 1). Concomitant infection was more commonly detected in patients with tracheobronchitis compared with those with pneumonitis ( p= 0.002), was associated with a higher grade of toxicity ( p= 0.050) and relatively poorer outcome after management ( p= 0.002). Conclusions: Respiratory toxicities after CCRT and subsequent consolidation ICIs in LA-NSCLC mainly included pneumonitis and tracheobronchitis, and could be separated into infectious and non-infectious subtypes. Bacteria and Aspergillus were the predominant pathogens. Our findings highlight the importance of the bronchoscopy and pathogen NGS testing to detect airway disease and specific infection. Long-term systemic steroids might adversely affect respiratory toxicities with concomitant opportunistic infection, which should be taken into account at the onset of management.
The association between body mass index and distribution intensity of tumor treating fields (TTFields) in the lungs.
Authors: Mooney Carly , Naveh Ariel , Shapira Nadav , Berger Brian 
Published: June 2023

e20559 Background: Tumor Treating Fields (TTFields) therapy is a first-in-class locoregional and noninvasive cancer treatment modality. TTFields are electric fields that disrupt processes necessary for cancer cell viability and tumor progression. A portable medical device generates TTFields, which are delivered noninvasively to the tumor area via 2 pairs of transducer arrays placed on the skin. TTFields therapy is currently approved for recurrent and newly diagnosed glioblastoma and pleural mesothelioma, with studies underway in other solid tumor types, including non-small cell lung cancer (NSCLC). Preclinical studies have shown that the effectiveness of TTFields depends on several factors, including field intensity. Given that 1 in 3 adults is overweight or obese, it is relevant to determine the effect of body mass index (BMI) on TTFields intensity to the lungs. Simulation-based methods were utilized, with the hypothesis that TTFields could be delivered to regions of interest (ROI) at therapeutic field intensities of > 1 V/cm, irrespective of BMI. Methods: Female computer phantom models with BMIs of 22 (healthy), 26 (overweight), and 30 (obese) were used to simulate TTFields intensity using small (13 disk) and large (20 disk) arrays placed on the thoracic region. The distribution of TTFields in each model was then determined using a computer-generated electric field intensity map. Field intensity values across the entire lungs were analyzed and compared. Results: When TTFields were delivered with large arrays, field intensities were clinically meaningful ( > 1 V/cm) in all lobes of the lungs for all BMI models. When TTFields were delivered with small arrays, meaningful levels of field intensity were achieved in all lung lobes, except for the BMI 30 model, where field intensities were slightly lower than 1 V/cm in the right middle lobe. Conclusions: These results show that TTFields can be delivered at therapeutic field intensities in patients with a BMI up to 30, providing the appropriate TTFields array size is used. Results from this simulation-based study support current clinical studies of TTFields therapy in lung cancer, (LUNAR, NCT02973789) and underscore the importance of appropriate array size selection. Additionally, these results may provide guidance for using TTFields therapy to treat a broad population of patients with lung tumors.
Endostatin in combination with PD-1 antibody plus chemotherapy as first-line regimen for EGFR/ALK-negative, advanced or metastatic non-small cell lung cancer: A real-world study.
Authors: Zhang Jing , Sun Shengjie , Zhao Xiao , Liu Minglu , Qiu Lupeng , Yang Zizhong , Zhang Guoqing 
Published: June 2023

e20564 Background: In recent years, treatment for advanced or metastatic NSCLC has been significantly improved with the emergence of a combination strategy of immunotherapy with antiangiogenic drugs plus chemotherapy. Although endostatin (an antiangiogenic agent) combined with chemotherapy has been approved by the China Food and Drug Administration in treatment-naïve and re-treatment NSCLC patients, the clinical evidence supporting its combination with programmed cell death-1 (PD-1) antibody for advanced or metastatic NSCLC is still insufficient. Therefore, we aimed to evaluate the effectiveness and safety of endostatin combined with PD-1 antibody plus chemotherapy as the first-line treatment for locally advanced or distant metastatic NSCLC with EGFR/ALK-negative. Methods: This was a retrospective, singer-center, real-world study conducted between June 2018 and December 2021. The primary endpoint was progression-free survival (PFS); the secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. Results: Overall, 68 patients were included. The median PFS and OS were 22.0 months (95% confidence interval [CI]: 16.6-27.4 months) and 31.0 months (95% CI: 23.4 months-not reached [NR]), respectively, with a median follow-up of 21.4 months (range, 8.3-44.4 months). At the data cutoff, 33 patients (48.5%) remained progression-free and 24 patients (35.3%) had died. Short-term clinical efficacy was assessed after 2 consecutive treatment cycles, with an ORR of 72.06% (complete response [CR], n = 3; partial response [PR], n = 46) and a DCR of 95.59% (CR, n = 3; PR, n = 46; stable disease, n = 16). Further subgroup analysis determined that a significantly better ORR (89.2% vs. 51.6%), median PFS (23.4 vs. 13.2 months), and median OS (NR vs. 18.0 months) for patients with stage Ⅲ B/Ⅲ C vs. stage Ⅳ NSCLC (all p ≤ 0.001). Besides, the median PFS (8.0 months vs. 22.5 months, p = 0.004) and OS (13.0 vs. 31.0 months, p = 0.027) of patients with brain metastasis were significantly shorter than those without brain metastasis. The ORR in patients who had a PD-L1 tumor proportion score (TPS) of < 1%, 1%-49%, ≥ 50%, and unknown were 50%, 50%, 75.0%, and 86.1%, respectively ( p = 0.025). All patients (100%) experienced treatment-related adverse events (AEs). The majority of AEs were grade 1 or 2 (57/68, 83.82%). Conclusions: In the real-world scenario, endostatin combination with PD-1 antibody plus chemotherapy obtained encouraging efficacy and favorable safety in advanced or metastatic NSCLC. The combination strategy in this study furnished beneficial evidence for the treatment of advanced or metastatic NSCLC and is essential for determining the best treatment option.
A preliminary analysis of integrating thymosin α1 into concurrent chemoradiotherapy and consolidative immunotherapy.
Authors: Liu FangJie , Qiu Bo , Wang DaQuan , Zhou Rui , Zhang PengXin , Zheng ShiYang , Guo JinYu , Luo QiaoTing , Guo SuPing , Liu Hui 
Published: June 2023

e20569 Background: The study aimed to investigate the efficacy of integrating Thymosin into concurrent chemoradiotherapy (CCRT) and consolidative immunotherapy in unresectable locally advanced non-small cell lung cancer (LA-NSCLC). Methods: Ninety-one stage IIIA-IIIC LA-NSCLC patients enrolled from Jan 1, 2020, to Oct 31, 2022 were analyzed retrospectively. All patients received CCRT (total irradiation dose of 60Gy and weekly concurrent docetaxel and cisplatin) and consolidative immunotherapy (Nivolumab/Tislelizumab). Thymosin α1 (1.6 mg) was administered once a week from the start of treatment till 2 months after CCRT or till the last prescription of consolidative immunotherapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints included the overall survival (OS) and toxicity. Results: There were 31 patients who received Thymosin α1 till the last prescription of consolidative immunotherapy, 40 patients received Thymosin α1 till 2 months after CCRT and 20 patients without the administration of Thymosin α1. The median follow-up time was 28.3 months (range 8.2~31.6 months). The median PFS was 26.1 months in Thymosin α1+consolidative immunotherapy group, 15.3 months in Thymosin α1+CCRT group and 12.6 months in control group (P = 0.116). The median OS was not reached in Thymosin α1+consolidative immunotherapy group, 26 months in Thymosin α1+CCRT group and 16.5 months in control group (P = 0.046). The median courses of consolidative immunotherapy were 8 Thymosin α1+consolidative immunotherapy group, 6 in Thymosin α1+CCRT group and 3 in control group (P = 0.060). There were higher ≥grade 3 acute lymphopenia (62.3%) and acute grade 2 pneumonitis (8.0%) in the control group. The long-term use of Thymosin α1 was also found to be related to the lower level of IL-6(P = 0.048), CD 16+NK cells and CD56+NK cells (P = 0.043). Conclusions: The integration of Thymosin α1 into CCRT and consolidative immunotherapy could yield synergistic effect in LA-NSCLC patients. The combination might contribute to prolonged use of consolidative immunotherapy and survival benefit.
Impact of SARS-COV2 infection on the clinical outcomes in patients with lung cancer.
Authors: Swarna Siri Chandana , Deenadayalan Vaishali , Litvin Rafaella , Dasgupta Mona , Kim Junglee , Gupta Shweta 
Published: June 2023

e20572 Background: The outbreak of 2019 Novel coronavirus disease (COVID-19) has led to various deleterious outcomes in cancer patients. Those with lung cancer would be more susceptible to increased morbidity and mortality. We aimed to study the outcomes of COVID infection in patients with lung cancer. Methods: Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database-2020 was queried to identify all admissions with COVID in patients with and without lung cancer. The groups were compared for socio-demographic differences, medical comorbidities, inpatient mortality, length of stay (LOS), and total hospital charges (THC). Secondary outcomes included a diagnosis of thrombocytopenia (TCP), Acute Respiratory Failure (ARF), sepsis, anemia, pancytopenia and shock. Statistics were performed using t-test, univariate and multinomial logistic regression. Results: A total 4,625 COVID admissions occurred in patients with lung cancer. Among them 71% (N = 3,288) were white, 17% (N = 805) were African American (AA) and 6.7% (N = 310) were Hispanic (HISP). Lung cancer patients had higher rates of smoking heart failure, CKD, CAD, COPD and anemia (p < 0.01) and lower rates of DM and obesity (p < 0.01). Lung cancer patients were more likely to have Medicare and less likely to have private insurance and were older (mean age 64.7 vs 71.9, p < 0.01). On multivariate regression, after adjusting for confounders those with lung cancer had higher odds of all-cause mortality (aOR 1.41; 95% CI 1.18-1.70 ,p = < 0.001). Among lung cancer patients, mean LOS was lower by 1 day (95% CI -1.4 to -0.4, p < 0.001) and THC was also lower (-$16,672; 95% CI -22950 to -10393, p < 0.001). Among the secondary outcomes, lung cancer patients had higher rates of pancytopenia (7.46% vs 1.59%, p < 0.001), neutropenia (3.46% vs 0.68%, p < 0.001) and venous thromboembolism (8.97% vs 4.29%, p = 0.006). Conclusions: COVID-19 infection led to increased mortality in lung cancer patients compared to those without lung cancer. This explains the overwhelming impact the pandemic left on lung cancer patients. The LOS and THC was decreased for lung cancer patients which may be explained by early death compared to non-lung cancer cohort. This study highlights the importance of decreasing the risk factors for COVID infection among lung cancer patients, including encouraging vaccination.
Deep learning algorithm for automatic prediction of visceral pleural invasion of lung cancer based on surgical video.
Authors: Xu Hao , Mu Wei , Zou Ruiyang , Cao Caifang , Sun Zewen , Cheng Sida , Guan Tian , Li Hao , Chen Xiuyuan , Jiang Guanchao , Yang Fan , Wang Jun , Tian Jie , Zhou Jian 
Published: June 2023

e20578 Background: Visceral pleural invasion (VPI) is an important prognostic indicator in lung cancer that is difficult to predict. We aimed to develop a deep learning algorithm that predicts VPI using videos of lesions. Methods: We included 346 patients who underwent thoracoscopic surgery at our department from 2015 to 2021, corresponding to 3800 images. The patient data and image data were divided into training set, validation set and testing set. The algorithm was developed based on the ResNet architecture used for image feature extraction and classification. All images were labeled for lesions and processed to fit the algorithm. We recruited two thoracic attendings and one radiologist to identify VPI using intraoperative video and preoperative CT, respectively. The performance of the algorithm was evaluated by comparison with the performance of the attendings and the radiologist. Results: At the patient level, the algorithm had satisfactory AUC values in the training set (0.85), validation set (0.83) and testing set (0.81). The DeLong test showed statistic difference between the algorithm and two attendings and a radiologist in the training set (p < 0.001, p < 0.001, p < 0.001), validation set ( p= 0.006, p= 0.002, p= 0.026) and testing set ( p= 0.008, p= 0.012, p= 0.007). At the image level, the algorithm also outperformed two attendings and a radiologist with significantly great AUC values in the training set (0.83 vs. 0.52 vs. 0.53 vs. 0.65; p< 0.001, p< 0.001, p< 0.001), validation set (0.78 vs. 0.50 vs. 0.54. vs. 0.68; p< 0.001, p< 0.001, p= 0.048) and testing set (0.79 vs. 0.53 vs. 0.60 vs. 0.58; p< 0.001, p< 0.001, p< 0.001). Conclusions: The video-based deep learning algorithm could satisfactorily predict VPI and achieved expert-level performance better than thoracic attending surgeons and the radiologist we recruited.
A 9-gene signature in circulating tumor DNA based on molecular residual disease detection to predict recurrence of resectable non–small-cell lung cancer.
Authors: Lu Di , Wang Zhouyu , Yang Airong , Chen Zhiming , Wang Zhizhi , Li Jing , Li Shaobin , Cai Kaican 
Published: June 2023

e20579 Background: Molecular residual disease (MRD) status is associated with the recurrence of non-small cell lung cancer (NSCLC) after complete resection. In clinical practice, MRD-positive patients are still uncertain of the specific recurrence time, and may even not relapse. Besides, it remains unclear whether the mutational signatures of circulating tumor DNA (ctDNA) based on MRD detection (ctDNA-MRD) may help predict recurrence. Therefore, we performed this analysis to explore whether the ctDNA-MRD mutational signatures could help predict recurrence, especially in MRD-positive population. Methods: Two investigators independently searched public databases for articles related with MRD in lung cancer published up to July 31, 2022. After screening, raw data from two published studies on resectable NSCLC were analyzed. Gene clusters were established based on the clearance of ctDNA after surgery. Kaplan-Meier and multivariate analyses were performed to find genes (Monitor genes) and clinical variables associated with recurrence-free survival (RFS). Lasso method was used to find recurrence-related genes based on perioperative ctDNA (preoperative and longitudinal ctDNA). Monitor genes and recurrence-related genes were defined as 9-gene signature. The mutational status of Monitor genes and 9-gene signature in perioperative ctDNA, as well as clinical variables, were used to establish prognostic models. The power of the models in distinguishing recurrence was shown as the area under the curve (AUC). Results: Data from 168 patients with at least one somatic mutation detected in tumors were included in the analysis. DNMT3A, EGFR, TP53, KEAP1, NAV3 (Monitor genes), and clinical variables (stage, adjuvant therapy) were factors associated with RFS. The AUC of the model based on Monitor gene mutations in perioperative ctDNA was 0.774, and the AUC reached 0.807 when clinical variables were included. The AUC of the models based on clinical variables, 9-gene signature (Monitor genes, KRAS, NTRK3, RPL5, and SOX2) in perioperative ctDNA for predicting the recurrence in the overall population and MRD-positive population were 0.840 and 0.832, respectively. Conclusions: This analysis reveals that perioperative ctDNA mutational signatures are helpful to predict postoperative recurrence, so it is necessary to pay attention to the specific gene mutations in ctDNA-MRD. [Table: see text]
Multi-omics analysis to reveal the change of peripheral blood TCR repertoire and tumor burden during neoadjuvant chemotherapy combined with sequential PD-1 blockade for patients with non-small cell lung cancers: A single-center, single-arm phase 2 trial.
Authors: Yang Bo , Liang Chaoyang , Song Qi , Xiong Qi , Li Jie , Long Yaping , Zhou Wenhao 
Published: June 2023

e20582 Background: Preoperative neoadjuvant chemotherapy combined with immunotherapy has been applied to the treatment of non-small cell lung cancer (NSCLC). However, the optimal dosage of chemotherapy and sequencing for chemotherapy and immunotherapy remains controversial. Methods: In this single-arm phase 2 trial, patients with stage IB to IIIA resectable NSCLC were enrolled and received 2 cycles of dose-limiting platinum-based chemotherapy (albumin-bound paclitaxel or pemetrexed plus cisplatin or carboplatin) on day 1, combined with sintilimab (200mg) on day 5 before undergoing radical surgery. Combination postoperative adjuvant therapy with the same regimen was administered. The primary endpoints were objective response rate (ORR) and major pathological response (MPR). Biopsies and plasma at different timepoint were collected and performed with RNA sequencing, circulating tumor DNA sequencing and T cell receptor (TCR) sequencing. Results: 17 patients were enrolled. After neoadjuvant treatment, patients with completed response, partial responses and stable diseases were 11.8% (2/17), 70.6% (12/17) and 17.6% (3/17), respectively, yielding an ORR of 82.4%. Radiological downstaging was achieved in 82.4% (14/17) of patients. All patients (17/17, 100%) experienced the R0 resection. Pathologic complete response and MPR were identified in 35.2% (6/17) patients and 23.5% (4/17) patients, respectively. Only 1 of the 17 patients (5.9%) experienced grade 3 or greater adverse event. Multi-omics analysis revealed chemotherapy combined with sequential PD-1 blockade results in the increase of dominated TCR clones and the decrease of the tumor burden. Especially during chemotherapy of cycle 1, the dominated TCR clones were significantly increased, and the maxVAF of ctDNA was significantly decreased. The change between the dominated TCR clones and maxVAF of ctDNA was negatively correlated. Conclusions: In patients with stage IB to IIIA resectable NSCLC, the neoadjuvant therapy with dose-limiting platinum-based chemotherapy combined with sequential sintilimab was safer and resulted in significant antitumor activity in patients with resectable NSCLC. The changes in TCR repertoire and ctDNA during treatment were analyzed, which provided evidence for the rationality of neoadjuvant chemotherapy combined with sequential PD-1 blockade. Clinical trial information: ChiCTR2000033092 .
NK cell expansion after primary multimodal treatment to predict progression free survival in inoperable stage III NSCLC.
Authors: Hofer Thomas Philipp , Käsmann Lukas , Nieto Alexander , Pelikan Carolyn , Taugner Julian , Eze Chukwuka , Tufman Amanda , Belka Claus , Manapov Farkhad , Noessner Elfriede 
Published: June 2023

e20584 Background: During multimodal cancer therapy an acute lymphocytopenia occurs, which is associated with poor survival in inoperable stage III NSCLC patients. A prospective analysis of peripheral blood mononuclear cells (PBMCs) during multimodal treatment was performed to assess dynamic changes of leukocyte subpopulations after concurrent chemo-radioimmunotherapy (cCRT) in order to extract biomarkers to predict progression free survival (PFS). Methods: 20 patients (17 male, 3 female), at median age of 65.5 years (range 34 to 79), 11 suffering from adenocarcinoma, 8 squamous cell carcinoma, and 1 undifferentiated NSCLC, were enrolled in the study. They received thoracic radiotherapy (TRT, 2/20, 10%), cCRT (11/20, 55%), or cCRT with checkpoint inhibition (cCRT-ICI, 7/20, 35%), one patient (1/20, 5%) withdrew consent and was excluded from analysis. Patients were grouped into poor ( < 6months), intermediate (≥6 < 12 months), or favorable (≥12 months) PFS. Blood was analyzed via flow cytometry for leukocyte sub-populations at 9 time points. Here, we report on NK cells and focus on the time period starting after end of TRT until 6 months thereafter. The area under curve (AUC) of absolute cell counts for this period was calculated to provide an aggregate measure for the time-course dynamics. Results: NK cell counts were consistently low in all patients at the end of TRT. Patient-individual recovery of cell counts 6 months after RTend (expressed as the AUC) was observed, which was beneficially affected by consolidation ICI (one-tailed t-test, p = 0.031). Retrospective assignment of the AUC values to the PFS groups revealed a positive association of high AUC values with PFS. Patients with longest PFS (≥12 months; 9/19) had higher AUC values compared to patients with intermediate PFS (≥6 < 12 months; 5/19; t-test p = 0.043) or poor PFS ( < 6months; 5/19; p = 0.0018). The difference between AUC values of intermediate and poor PFS groups was also significant (p = 0.039). Conclusions: Patients who responded with early NK cell expansion after TRT, cCRT, or cCRT-ICI had significantly longer PFS compared to those without increase. Longitudinal monitoring of NK cells and calculating the AUC (RTend and 6 months thereafter), which reflects absolute cell counts, is a promising biomarker to predict PFS.