bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors on survival for patients of EGFR mutation advanced lung adenocarcinoma with EGFR-TKIs combined with radiotherapy: Real-world data from single center.
Authors: Wang Yuxiang , Yu Wenjian , Shi Jian , Jiang Nan , Wang Zhoufan , Yang Jie , Jia Zhongfei , Song Meng 
Published: June 2021

e21126 Background: The aim was to retrospectively evaluate survival and prognostic factors for patients of advanced lung adenocarcinoma with EGFR mutation by a real world data. Methods: From Jan, 2015 to Dec, 2020, lung adenocarcinoma with EGFR positive mutation, advanced (clinical stage III-IV), without surgery, received EGFR-TKIs and radiotherapy (RT) were enrolled. OS and PFS were calculated. Results: 238 patients were included, 101 in males and 137 in females; the median ages was 61. The RT was performed at the time of no-PD in 71 and PD in 167 cases. The median dose of RT was 50 Gy. The rate of acute AE during RT was 36.1% in grade 1-2 and 4.8% in grade 3-4. The follow-up ended at 30, Dec, 2020. The 1-, 2-, 3-years OS,PFS1and PFS2 were 84.4%,59.7%, 38.7%, 52.0%,29.4%, 16.3%, 86.6%, 64.6%, 45.6%. mOS, mPFS1and mPFS2 were 30.3, 14.1, 33.6 months, respectively. Multivariate analysis showed the independent factors for OS were ages (median were 34.0 and 24.9 months for ≤65 and > 65) and clinical stage (median were 22.8, 34.8 and 27.4 months for stage III (33), IVA (84) and IVB (121 cases), respectively), chemotherapy (CT) (median were 27.4, 28.1, 32.5, 44.3 months for TKIs alone(120), TKIs concurrent CT (43), TKIs sequential CT (32), CT sequential TKIs (43 cases), respectively) and total response (the medians were 32.5, 27.2, 33.3 months for CR(7)+PR(107), SD(70) and PD(54 cases), respectively); Independent factors: PFS1 was the time of RT at no-PD and PD (the median were 17.8 and13.2 months), chemotherapy, (the median were 16.1, 12.1, 11.0, 13.5 for TKIs alone, TKIs concurrent CT, TKIs sequential CT, CT sequential TKIs), and total response (the medians were 18.8, 11.7, 10.9 months for CR+PR, SD and PD); PFS2 was the total response (the medians were 58.3, 21.6, 20.9 months for CR+PR, SD and PD, respectively). Univariate analysis also showed doses of RT (the median was 12.3 months for < 50 Gy and 15.5 months for ≥ 50 Gy, p = 0.018) was associated with PFS1, the first-line drugs of TKIs (the median were 39.1, 35.0, 25.6 and 38.6 months for Gefitinib (89), Icotinib (109), Erlotinib (29) and others (11 cases), respectively, p = 0.044) and chemotherapy (the medians were 45.6, 30.6, 18.7, 41.4 months for TKIs alone, TKIs concurrent CT, TKIs sequential CT, CT sequential TKIs, respectively, p = 0.007) were related with PFS2; but the type of EGFR mutation (94 in 19 exon, 118 in 21 exon and 26 cases in others) was not related with survival. Conclusions: EGFR-TKIs combined RT was tolerable and efficient for patients of advanced lung adenocarcinoma with EGFR mutation. TKIs add RT at the time of no-PD could improve PFS1. CT sequential TKIs was probably in favour of OS, even PFS. The better total response (CR+PR) was associated with longer OS, PFS1 and PFS2. But the result need to be proved furtherly.
Efficacy and safety of anlotinib in the treatment of lung cancer.
Authors: Zhou Xinliang , Dou Yan , Jiang Da 
Published: June 2021

e21129 Background: Anlotinib was approved by the National Medical Products Administration (NMPA) on 5/8/18 and 8/30/19 for the third-line treatment of patients with advanced NSCLC and SCLC. But in the real world, Anlotinib is also used in the second-line treatment of lung cancer. This study aims to evaluate the efficacy of using Anlotinib in the second-line or further treatment of lung cancer in the real-world. Methods: We conducted a retrospective case-control study of NSCLC/SCLC patients at our center from 1/1/19 to 6/30/20. Patient demographic, clinicopathologic, therapeutic and outcomes data were collected. Kaplan-Meier curve and Cox proportional hazards were utilized. Results: Of 167 patients were enrolled in this study, 106 were in Anlotinib group and 61 were in chemotherapy group. The analysis found that pathological types, ECOG PS, and therapeutic were independent factors affecting PFS and OS in lung cancer patients (P < 0.05- can be a specific value). There was a significant difference in DCR between the anlotinib group and chemotherapy group(P < 0.05), and the anlotinib group was better than chemotherapy group in mPFS (4.1 vs 3.1 months, P = 0.001) and mOS (7.682 vs 6,386 months, P = 0.011). Among the second-line treatment patients, ORR, DCR and PFS were no difference between Anlotinib group and chemotherapy group (P > 0.05). The Anlotinib group was significantly better than Chemotherapy group in mOS (10.083vs6.737 months, P = 0.026). In third-line and further treatment patients, therapeutic and ECOG PS were independent factors of PFS and OS (P < 0.05), and pathological type was an independent factor of OS (P < 0.001). There was a significant difference in DCR between anlotinib group and chemotherapy group (P = 0.011). The mPFS (3.8vs2.5 months, P < 0.001) and mOS (7.407vs5.412 months, P = 0.023) are significantly better than chemotherapy group. In terms of adverse events, the incidence of hypertension (32.80%vs9.84%) and hand-foot syndrome (28.30%vs14.75%) in anlotinib group was higher than that in chemotherapy group, but the incidence of leukopenia (4.72%vs37.7) %), fatigue (14.15%vs34.42%), anorexia (16.04%vs39.34%) and other adverse events was lower than chemotherapy group, and the incidence of III-IV adverse events is low. Conclusions: Compared with using chemotherapy alone, the second-line and further treatment of Anlotinib can significantly elevate the survival of lung cancer patients, and the safety and tolerability are better.
Performance status and activity level of lung cancer patients using wearable devices as passive monitoring: A scoping review.
Authors: Ponce Aix Santiago , Crama Leonardo , Núñez-Benjumea Francisco J. , Sánchez Sergio , Cervera-Torres Sergio , López Mar , Arnáiz Pablo , Fernández-Luque Luis 
Published: June 2021

e21141 Background: Lung Cancer (LC) and particularly non-small cell lung cancer (NSCLC) is considered one of the most lethal types of cancer to date. Suitability and toxicity of treatment, or eligibility of LC patients for clinical trials usually rely on subjective indicators of Performance Status (PS) such as the Eastern Cooperative Oncology Group (ECOG) and Karnofsky indexes. In recent years, however, the use of electronic wearable devices has increasingly come to the fore with the aim of increasing objectivity of PS assessments. These devices are capable of objectively and passively monitor health-related outcomes such as daily physical activity and sleep patterns. Consequently, a comprehensive review of the current state of the art in this matter can provide further insights for future research within oncology areas in general, and lung cancer, in particular. The main goal of this scoping review is to identify and categorize scientific publications that, over the past 10 years, used wearable devices as means of monitoring activity level of LC patients. Methods: The study follows the PRISMA-ScR framework (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). Results: A total of 32 studies were identified as suitable to be included in the review where (n = 22; 68.7%) focused on physical activity and (n = 10; 31%) in sleep or circadian patterns. Approximately half of the studies used a wrist wearable. Device output included step counts, activity counts, metabolic equivalents, time active, time spent in moderate-to-vigorous activity, sedentary time, sleep duration, sleep efficiency, total sleep time/sleep duration, sleep onset latency, wake times, and wrist movement per minute. However, step counts arose as one of the most representative outcomes of physical activity (n = 17; 53%). In general, higher levels of physical activity and circadian organization (day/night activity balance) as measured by actigraphy, are associated with less fatigue, pain, and better quality of life. Conclusions: This review shows that wearable devices, and especially wrist wearables, are increasingly used in oncology settings as a reliable method to monitor physical and sleep activity and to complement PS assessment. Further research is needed, however, to determine the extent to which this methodology can be used to more directly objectivize current PS assessment itself.
Predictors of response in EGFR-mutant metastatic non-small cell lung cancer patients treated with tyrosine kinase inhibitors.
Authors: Aydiner Adnan , Dogan Izzet , Khanmammadov Nijat , Saip Pinar , Vatansever Sezai 
Published: June 2021

e21149 Background: EGFR mutations are detected in 15-62% of patients with non-small cell (NSCLC) lung cancer. We can use tyrosine kinase inhibitors (such as erlotinib, gefitinib, afatinib) to treat patients with EGFR-mutant lung cancer. Tyrosine kinase inhibitors improve the survival outcomes of the patients. This study aimed to assess predictors of overall response rate (complete or partial response) in EGFR-mutant non-small cell lung cancer patients treated with EGFR inhibitors. Methods: Data of the EGFR-mutant lung cancer patients were evaluated retrospectively. Clinical, pathological, radiological, and treatment features of the patients were recorded. SPSS 25 version was used for statistical analysis. Kaplan-Meier and Cox-regression methods were used for survival analysis. Also, predictors of overall response were evaluated with logistic regression analysis. Results: 105 patients were included in the study. The female/male patients ratio was 1.25, and the median age was 61 (range, 33-85) years. Adenocarcinoma (90.4%) was the most common histopathological type. The ratios of Exon 19, exon 21, and other (rare or multiple) mutations were 59%, 25%, and 16%, respectively. 89 (84.9%) patients were de-novo metastatic at diagnosis. Before EGFR inhibitor therapy, the patients had received chemotherapy (22.9%) and palliative radiotherapy (40%). The patients received erlotinib (83.8%) or other EGFR inhibitors (16.2%) for treatment. Median overall survival was 30.8 (range 20.2-41.4) months. Overall response rate (complete or partial response) was 61.9%, stable response 11.4%, and progressive disease 26.7%. In logistic regression analysis, we found that age (p = 0.008), number of metastasis sites (p = 0.037), pathological type (adenocarcinoma or other types) (p = 0.001) were statistically significant for the overall response rate. However, gender (p = 0.98), tumor localizations (left or right lung) (p = 0.39), de-novo metastasis (p = 0.81), EGFR mutations type (p = 0.13), and type of EGFR inhibitör (p = 0.30) were not statistically significant. Conclusions: In this study, we showed real-life outcomes of the patients with EGFR-mutant metastatic non-small cell lung cancer. The data of predictors of overall response for EGFR inhibitors is limited. We detected that age, the number of metastatic organs, and histopathological type of tumor were affected the response of treatment.
PD-1/PD-L1 inhibitors plus chemotherapy versus bevacizumab plus chemotherapy as first-line treatment for advanced nonsquamous non-small cell lung cancer: A Bayesian network meta-analysis of randomized controlled trials.
Authors: Zhang Zhibo , Zhai Jinzhao , Yan Xiang , Zhang Fan , Li Xiaoyan , Zhang Sujie , Yuan Fang , Mu Shuai , Zhi Xiaoyu , Ge Xiangwei , Lu Di , Hu Yi , Wang Jinliang 
Published: June 2021

e21152 Background: Chemotherapy in combination with PD-1/PD-L1 inhibitor or bevacizumab have demonstrated superior efficacy to chemotherapy in the first-line treatment for non-squamous non-small-cell lung cancer (NS-NSCLC). However, there has been no randomized study comparing PD-1/PD-L1 inhibitors plus chemotherapy (immune-chemo) with bevacizumab plus chemotherapy (bev-chemo). Thus, we performed this network meta-analysis (NMA) to evaluate the comparative efficacy and safety of immune-chemo and bev-chemo as first-line treatment for NS-NSCLC. Methods: The randomized controlled trials (RCTs) were identified by searching PubMed, Embase, the Cochrane library, and conference abstracts until Oct 2020. Bayesian NMA with fixed effect consistency model was applied to estimate hazard ratio (HR) and Odds ratio (OR) with their 95% confidence intervals (CIs). The outcomes included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and grade ≥3 treatment-related adverse events (TRAEs). Results: 15 RCTs involving 6541 advanced NS-NSCLC patients were eligible for analysis. For OS, immune-chemo (HR 0.70, 95% CI 0.64-0.79) and bev-chemo (0.87, 0.79-0.95) significantly prolonged survival compared with chemotherapy. For PFS, immune-chemo (0.58, 0.53-0.62) and bev-chemo (0.66, 0.61-0.71) were significantly superior to chemotherapy. For ORR, immune-chemo (2.42, 1.93-3.08) and bev-chemo (2.27, 1.75-2.92) were associated with better benefits than chemotherapy. However, immune-chemo (1.61, 1.08-2.35) and bev-chemo (1.83, 1.08-2.90) increased grade ≥3 TRATEs compared with chemotherapy. The results of Bayesian NMAs shown that immune-chemo (PFS: 0.88[0.80-0.97]; OS: 0.81[0.72-0.92]) was associated with better outcomes than bev-chemo, while there were no significant differences in ORR and the risk of grade ≥3 TRATEs (Table). Conclusions: Immune-chemo and bev-chemo are superior to chemotherapy in first-line treatment of NS-NSCLC. Immune-chemo could significantly improve clinical outcomes compared with bev-chemo without higher severe TRAEs. [Table: see text]
Real-world outcomes of patients with advanced non-small cell lung cancer and driver mutations treated with frontline immunotherapy and/or chemotherapy.
Authors: Muthusamy Bharathi , Pennell Nathan A. , Belli Andrew J. , Hansen Eric , Devincenzo Victoria , Shankaranarayana Shubha , He Ming , Wang Ching-Kun 
Published: June 2021

e21156 Background: The identification of driver mutations and development of targeted therapies have significantly improved outcomes of patients with advanced non-small cell lung cancer (aNSCLC). It has been shown in clinical trials that immunotherapy (IO) has limited effectiveness in patients with aNSCLC and driver mutations, but as there is a lag in the widespread use of targeted agents for newer driver oncogenes it is important to define the efficacy of non-targeted treatments. We sought to explore the real-world treatment patterns and outcomes of patients with aNSCLC and driver mutations treated with first-line (1L) chemotherapy (chemo) as compared to chemo +/- IO. Methods: This retrospective study utilized the COTA real-world database, a de-identified database derived from the electronic health records of healthcare providers in the United States. Patients included in the study had diagnosed aNSCLC and at least one positive test result for BRAF v600, HER2 mutation, EGFR, MET, RET or ROS1 prior to the initiation of 1L therapy. Additionally, patients must have received frontline chemotherapy, IO monotherapy, or IO+chemo combination in the advanced setting. Outcomes to first-line treatment (real-world progression-free survival (rwPFS) and real-world time to next treatment (rwTTNT)) were calculated using the Kaplan-Meier method. Results: A total of 170 qualified patients were identified as having at least one positive mutation and having received frontline chemotherapy (n=119), IO monotherapy (n=28), or chemo+IO combination (n=23). Mean age was 65 yrs and patients were predominantly white (71.2%), treated in the academic setting (74.1%), and denovo metastatic (67.1%). Outcomes to 1L treatment are reported in Table. Patients treated with 1L chemo+IO combination had longer rwPFS and rwTTNT as compared to patients treated with chemo alone or IO monotherapy, though outcomes did not reach statistical significance. Conclusions: Our study showed that in a real-world population of patients with aNSCLC and driver mutations, patients treated with chemo+IO combination had longer rwPFS and rwTTNT as compared to those treated with chemo alone or IO monotherapy. The overall short duration of benefit supports the model of using targeted treatment as optimal first line therapy, and the overall lack of benefit from IO. [Table: see text]
An investigation on biomarkers of hyperprogressive disease after PD-1/PDL-1 therapies in Chinese non-small cell lung cancer patients.
Authors: Song Qingchun , Han Lei , Mao Yulong , Huang Tanxiao 
Published: June 2021

e21173 Background: Immune checkpoint inhibitors (ICIs), such as PD-1/PD-L1 antibodies, are becoming standard of care for lung cancer treatment. However, low response rates to ICI antibodies and even hyperprogressive disease (HPD) have limited the clinical application of ICIs. Considering HPD for patients means shorter survival times and worse prognoses, valid biomarkers are in urgent demand to predict the occurrence of HPD and the efficacy of ICI. Here, we explored the genomic biomarkers of HPD in Chinese non-small cell lung cancer (NSCLC) patients. Methods: 749 NSCLC patients with both genomic information and PD-L1 expression data were screened from HapLab database. HaploX 605-gene panel sequencing, covering 1.31 MB genome, was performed to analyze the genomic data of patients. PDL-1 expression was detected by immunochemistry. Results: 15 genes related to HPD were detected altered in NSCLC patients. Collectively, 511 out of 749 patients (68.22%) had at least one alteration of HPD related genes. The frequent alterations were EGFR mutation (46.86%), ALK fusion (7.49%), MDM2 amplification (6.54%), KEAP1 mutation (5.34%), STK11 mutation (4.27%), FGF3/4 amplification (4.14%), DNMT3A mutation (2.14%) and MDM4 amplification (2.00%). While in EGFR wild-type and ALK-negative patients, the top 5 frequent alterations were KEAP1 mutation (8.96%), FGF3/4 amplification (7.00%), STK11 mutation (6.16%), PTEN mutation (5.32%) and MDM2 amplification (4.20%). Notably, EGFR mutation (49.27%, 68/138), ALK fusion (9.42%, 13/138) and MDM2 amplification (4.35%, 6/138) were also observed in PDL-1 positive (TPS≥1%) patients. Conclusions: It is urgent to identify specific biomarkers that could predict HPD and to develop eﬀective methods to prevent HPD. Our study investigated the genomic alterations associated with HPD in Chinese NSCLC patients.
The comparison of mutation-based biomarkers for early-stage and advanced-stage non-small cell lung caner.
Authors: Yao Jie , Zhang Xiuqin , Pan Liangbin , Wang Yuxuan , Chen Ke , Han Jiajun , Mao Guocai , Zhang Biao , Wang Nan , He Yuange , Gu Dejian , Chen Rongrong , Ma Haitao 
Published: June 2021

e21176 Background: In recent years, immune checkpoint inhibitors have shown promise in the treatment of advanced-stage non-small cell lung cancer (NSCLC), more and more clinical studies have proved this treatment could also be effective for early-stage NSCLC. It’s confirmed that the count of somatic mutations (SM) and tumor mutation burden (TMB) were related to the effect of immunotherapy for advanced stage tumors but this relationship was not proved in early stage tumors, the inherent difference between early stage and advanced stage cancer is unclear. So we compared the SM count and driver mutation frequency for the ES and AS NSCLC cancer. Methods: We retrospectively analyzed the genetic aberrations in 288 patients of Chinese NSCLC patients. All the patients were detected by hybridization capture-based NGS 1021-gene panel sequencing with tumor tissue and peripheral blood control samples. Results: The genetic alterations in 288 patients with NSCLC were analyzed by defined stage categories, the tumors in clinical stage I-IIIa were classified as early-stage (ES) group and stage IIIb-IV were classified as advanced-stage (AS) group. The results showed that the actionable mutation frequency in driver genes such as EGFR/BRAF/MET/ERBB2/KRAS and structural variations called Fusions in ALK/ROS1/RET/NTRK was different in the two groups but was not statistically significant (Table). The average SM count (9.6 versus 6.25, p=0.0001) and the TMB-high (TMB-H) frequency (3.6% versus 13.2%, p=0.002) was significantly higher in AD group (Table). In other words, the driver mutation frequencies has no significant difference between the ES and AS groups but the AS group showed more somatic mutation count and TMB-H frequency, revealing there were more non-driver mutations in AS tumors. The proved relationship between SM count and TMB and the clinical effect of immunotherapy for advanced-stage patients may inapplicable for early-stage tumors, new biomarkers need to be explored for the immunotherapy of early-stage NSCLC patients. Conclusions: There was no significant variation between the early-stage and advanced-stage patients with driver mutations, but more non-driver mutations in advanced-stage patients. The immunotherapy biomarkers such as somatic mutation count and TMB for advanced-stage tumors could be inapplicable for early-stage tumors. The biomarkers for immunotherapy of early-stage NSCLC patients need further research.[Table: see text]
Effectivness of a shortened cycle of monoimmunotherapy in NSCLC.
Authors: Artemeva Elizaveta , Moiseenko Fedor Vladimirovich , Abduloeva Nuriniso , Volkov Nikita , Egorenkov Vitaly , Zhabina Albina , Artemiev Semen , Moiseyenko Vladimir 
Published: June 2021

e21179 Background: Monoimmunotherapy for NSCLC is performed in all patients with a high level of PD-L1 expression ( > 50%) or patients with severe comorbidity and contraindications to therapy with platinum drugs with intermediate level of PD-L1 expression (1-49%).Therapy is carried out up to 2 years, disease progression or intolerable toxicity. An important issue is determining the optimal duration of treatment in order to find a balance between effectiveness, toxicity, cost and burden on the healthcare system. To date, there are no prospective studies with sufficient power devoted to this issue. Methods: The analysis included patients with histologically verified inoperable NSCLC who received the first line of therapy in 2018-2020. 25/230 patients received monoimmunotherapy in the first line (16 men, 9 women; mean age 65.4 years; PD-L1 level > / = 50% - 18 patients (72%), 1-49% - 3/25 ( 12%), 0% - 1/25 (4%), not assessed - 3/25 (12%), adenocarcinoma - 13 (52%), squamous cell - 12 (48%); All patients received pembrolizumab therapy 200 mg 1 once every 21 days. Results: The mean follow-up time was 5.3 months (95% CI 3.4–7.2). The average number of immunotherapy injections (min-max) is 6.4 (1–28). The objective response rate (ORR) in 1 line was 16/23 (64%) (complete regression - 2 patients (8%), partial regression - 3 (12%), stabilization - 11 (44%), progression - 3 (12 %), not assessed - 6 (24%), 2 (8%) patients died after the 1st injection of immunotherapy. Before the progression of the disease or until the end of the planned duration, 16 (64%) of 25 patients interrupted therapy: (10/16 (62%) due to the tightening of the requirements of the epidemiological situation, 6/16 (38%) refused to visit medical institutions. Average follow-up after the end of treatment 7.0 (1.3 - 12.2) months (min-max). 11/16 (68%) are observed without progression 9.3 months (4.0 - 12.1) (min-max PD in 4/16 (25%) after a mean follow-up time of 4.4 months (2.9 - 7.9) (min-max), 1 (6%) patient was lost to follow-up. Conclusions: The obtained data indirectly indicate the absence of a tendency towards a decrease in mPFS and mOS in the group of NSCLC patients who received MIT in the first line of treatment, for whom treatment was discontinued unscheduled, and not continued until 2 years or until the progression of the tumor process was recorded.