bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pooled analysis of clinical activity of immune checkpoint immunotherapy in relapsing/refractory ES-SCLC.
Authors: Vosuri Venkata , McGreevy Joseph , Ghous Ghulam , Doll Donald C. , Tuncer Tolga 
Published: June 2021

e20572 Background: ES-SCLC is an aggressive lung cancer with high rates of relapse following induction regimens. Immune checkpoint immunotherapy (ICI) seems promising in the refractory/relapsing setting based on a smaller number of studies with smaller sample sizes. Here we report a pooled estimate of clinical activity of ICI in above patients based on published phase II/III trials so far. Methods: PubMed, EMBASE, Cochrane review, and clinicaltrials.gov databases were searched for phase II/III randomized controlled trials studying immune checkpoint immunotherapy in second or third line setting for ES-SCLC treatment. Data were extracted based on Reviews and Meta- Analysis guidelines. DerSimonian-Laird (DL) random effects model was used to estimate the pooled proportion of patients achieving objective response rate (ORR), pooled proportion of patients experiencing therapy related adverse events (TRAEs grade ≥ 1), pooled median progression free survival (PFS) and pooled median overall survival (OS), and weights were estimated using inverse variance method. Statistical heterogeneity was calculated using the I2 and chi-squared test. Outcomes were calculated by using ‘Metafor’ and ‘Meta’ packages by R-Studio and “CRAN” project. Results: Five studies with a total of 698 patients who received immune checkpoint immunotherapy were analyzed. Median age of patients who received treatment was 63 yrs. The pooled proportion of patients who achieved ORR was 15% (95% CI 0.11 to 0.20). Pooled Median PFS was about 1.54 (95% CI, 1.34- 1.74) months and median OS was 6.46 (95% CI, 5.13- 7.73) months. The pooled proportion of patients who experienced adverse events during the treatment was 49% (95% CI 0.38 to 0.60). Conclusions: ICI as second or third line treatment choice offers modest improvement in progression free survival and overall survival in ES-SCLC patients who have not received ICI as first line in combination with etoposide and platinum based therapies.
Clinical utility of circulating genetically anormal cells in stage I small-cell lung cancer diagnosis.
Authors: Wang Hui , Wang Ziqi , Zheng Xiaoxuan , Sun Jiayuan , Zhang Xiaoju , Ye Xin , Chen Yanci , Huang Meng , Zhang Juncheng , Yang Xiaozheg , Bai Chunxue 
Published: June 2021

e20581 Background: Small-cell lung cancer (SCLC) is an aggressive disease with rapid progression rate and high metastatic potential that accounts for 15% of all lung cancers. Early-stage SCLC is usually asymptomatic; therefore, the majority of the SCLC patients were diagnosed in advanced stages. Although some radiological features were reported with advanced stages SCLC by CT scans, diagnosis of early stages SCLC from CT images has remained challenging since the radiological features are not distinct. Neuron-specific enolase (NSE) is commonly used in the clinical setting as a biomarker for SCLC, but the sensitivity of the test did not meet the needs. Here, we proposed a study using Circulating Genetically Abnormal Cells (CAC) to improve the diagnosis rate of SCLC in the early stages. Methods: A series of 26 stage I SCLC patients were enrolled from October 2019 to October 2020. All participants were having newly discovered pulmonary nodules ≤ 30mm when enrolled in the study, with no previous cancer history. Before the histopathological examination, 10 ml of peripheral blood were collected from each patient for CAC test, by using a 4 color FISH–based assay to detect the genetic abnormalities of 3p22.1, 3q29, 10q22.3, and CEP10 in the chromosome. Besides, NSE was performed on all participants. Both tests were intended to evaluate the malignant risk of lung nodules. Results: Confirmed by histopathological exam, 69% patients were diagnosed with SCLC located on the central part of the lung, and 31% patients were found to have peripheral-type SCLC. 88% of the patients in the overall cohort were smokers or past smokers, and only 12% participants had a family history of cancer. For Immunohistochemistry tests, the numbers of participants with positive CD56, TTF-1, CgA, CK, Syn and Ki-67 ≥ 60% are 65%, 58%, 12%, 42%, 50% and 69%, respectively. For diagnostic performance, the sensitivity of CAC in the over-all cohort is 73.08% (95%CI: 52.21%-88.43%), compared with 50.00% (95%CI: 29.93%- 70.07%) for NSE. CAC has achieved 77.78% (95%CI: 52.36% - 93.59%) and 62.5% (95%CI：24.49% - 91.48%) sensitivity in the centra and peripheral group. For NSE, the sensitivity of these two groups were 55.56% (95%CI: 30.76% - 78.47%) and 37.5% (95%CI: 8.52% - 75.51%). Conclusions: Compared with NSE, CAC is more sensitive to stage I SCLC, especially for SCLC that arising in central locations. This non-invasive method can be a complementary diagnostic tool with LDCT for smokers aged ≥65 with newly discovered pulmonary nodules. Clinical trial information: ChiCTR1900026233.
Every three weekly irinotecan for refractory/relapsed small cell lung cancer.
Authors: Nutalapati Snigdha , Yan Donglin , Morgan Rachael , Chauhan Aman 
Published: June 2021

e20584 Background: Current NCCN guidelines support weekly irinotecan regimen for refractory/relapsed SCLC (small cell lung cancer). Despite prior studies that used irinotecan for other solid malignancies included both weekly and three weekly regimens, NCCN do not acknowledge three weekly regimen for SCLC due to insufficient data, especially from United States patient population. We aimed to study clinical efficacy, side effect profile and cost analysis of three weekly irinotecan regimens for refractory/relapsed SCLC. Methods: Retrospective analysis of relapsed/refractory SCLC or high-grade neuroendocrine carcinoma (HGNEC) patients treated with every 3 weekly irinotecan (300 mg/m2) regimen between 2010 and 2020 at NCI-designated Markey Cancer Center/University of Kentucky healthcare was performed. Median PFS and adverse events per CTCAE 5.0 were determined. Results: A total of thirty-eight patients were included in our analysis, 32 with SCLC and 6 with HGNEC. Of 6 patients with HGNEC, primary site included bladder (n=1), prostate(n=1), gastroesophageal junction(n=1) and unknown primary (n=3). Mean age at diagnosis was 58 years. Mean prior line of therapies were 1.8 (range=1 to 4) and mean number of irinotecan cycles were 3.5 (range=1 to 12). Median progression free survival was 2.1 months (95% CI-1.6 to 8.1). Grade (G) 2, 3 and 4 adverse events were noted among 20.5%, 33.3% and 7.8% respectively. G3 and G4 neutropenia was seen in 2.6% and 5.3%; neutropenic fever was noted among 5.3%; G2 and G3 diarrhea among 7.9% and 15.8%; ileus among 5.3%; enterocolitis among 2.6%; G2 and G3 nausea and vomiting among 7.9% and 10.5%; G3 transaminitis among 2.6%; G3 and G4 acute kidney injury was seen among 5.1% and 2.6% respectively. Estimated overall costs (including infusion related expenses, cost of pre-medications and irinotecan) to deliver three 100mg/m2 doses with every weekly regimen was $661 compared to only $268 for a single 300mg/m2 dose with every three-weekly regimen. Conclusions: In previously treated patients with refractory/relapsed SCLC, every three weekly irinotecan regimen was found to have comparable efficacy and adverse event profile. Diarrhea, nausea, vomiting and neutropenia are the most common adverse events reported. Moreover, cost effectiveness of every 3 weekly regimen and reduced number of infusions should potentially benefit patients who live far from health care facility as is the case in rural Appalachia and also help reduce financial toxicity.
Short-term efficacy and long-term survival of limited-stage small cell lung cancer treated with large fractionation radiotherapy and conventional fractionation radiotherapy.
Authors: Chen Cheng , Jiang Yingying , Jiang Ning , He Kang , Chen Cheng , Zhao Lijun , Kong Cheng , Song Xue , Wang Xiaohua , He Xia , Zhu Xiangzhi 
Published: June 2021

e20586 Background: Hyperfractionation (1.5Gy per dose twice a day, total dose 45Gy) or conventional fractionation (2Gy per dose once a day, total dose 60-70Gy) is the recommended dose fractionation for LS-SCLC. However, the optimal segmentation mode and dose of radiotherapy have not been determined. In this study, we evaluated the short-term efficacy and toxic and side effects of macrofractionation to explore the feasibility of macrofractionation radiotherapy in the treatment of LS-SCLC patients. Methods: From May 2011 to February 2020, 52 patients with LS-SCLC admitted to Jiangsu Cancer Hospital were retrospectively analyzed. The patients were divided into two groups according to the dose separation mode, including 29 cases in the large division group (3-4Gy per dose once a day, total dose 45-60Gy) and 23 cases (2Gy per dose once a day, total dose 50-68Gy) in the conventional division group. The short-term efficacy, 1-year survival rate and some other aspects of the two groups were compared. Results: The short-term overall response rate of large segmentation group was 79.3%, and there was significant difference compared with 52.2% of conventional segmentation group ( χ2 =4.293, P<0. 05) (Table). The 1-year survival rate of the large segmentation group was similar to that of the conventional segmentation group (82.8% vs．82.6%). The median survival time of large segment group was 30 months,which was not significantly different from the 34 months of conventional segment group (χ2=0.417, P>0.05). In terms of the effect of the two fractionated dose modes on long survival, 31.0% of patients in the large fractionation group survived more than 48 months, compared with only 13% in the conventional fractionation group. In addition, in the subgroup analysis of this study, it was found that compared with conventional fractionation radiotherapy, patients aged 45-65 years with ECOG score of 0-1 and lesions less than 5cm before radiotherapy could obtain more significant survival benefit from large fractionation radiotherapy, with statistically significant difference between the two groups (χ2=4.874, P<0.05). Conclusions: Large segmentation radiotherapy in the treatment of patients with LS-SCLC can improve the therapeutic effect and prolong the survival, especially for patients aged 45-65 years with ECOG score of 0-1 and lesions less than 5cm before radiotherapy , the survival benefit is more significant. In addition, large fractionated radiotherapy showed certain advantages in the long-term survival of patients with LS-SCLC, which is worthy of further clinical application.[Table: see text]
Prevalence [P] of molecular biomarkers [MB] expression [exp] in patients [pts] with metastatic adenocarcinoma lung [MAC]: Illinois CancerCare [ILCC] analysis.
Authors: Kumar Nikhil , Gomez Patrick Leigh , Harper Jamie 
Published: June 2021

e21004 Background: Treatment of MAC is guided by MB. These include Programmed Death Ligand 1 (PDL1), Epidermal Growth Factor Receptor (EGFR), Anaplastic Lymphoma Kinase (ALK) & ROS1. There is little information available on P of MB in US Midwestern population, a largely homogenous Caucasian group. We examined the expression (exp) of the MB in pts with MAC who presented at ILCC in 2018, one of the largest practices in US Midwest. Methods: We conducted a retrospective analysis of all MAC pts who presented at ILCC in 2018. We analyzed the exp of PDL1, EGFR, ALK, and ROS1 in these pts. PDL1 status was defined as high if PDL1 was ≥50%, low if 1- < 50% and -ve if 0- < 1%. High and low groups [all pts with > 1%] were designated +ve. Results: In 2018 there were 125 pts seen at ILCC with MAC. As of 6/2019, 57/125 [46%] pts were alive. Pts: median age 69 yrs [45-89], median PS 1 [0-3], males 62%, current/former smokers 90%, Caucasians 95%. PDL1 results were available in 104/125 pts [83%], EGFR in 95 (76%), ALK in 97 (78%), and ROS1 in 95 (76%). Previously reported papers have described PDL1+ to be as high as 58% in MAC. However, in our study only 53/104 (51%) pts were PDL1+. Though, 26/104 (25%) did have high PDL1 exp [consistent with other reports]. 27/104 (26%) had low PDL1 exp and 51/104 (49%) pts were PDL1-ve. EGFR mutation [M] was found in 11/95 (12%), ALK M was found in 5/97 (5%) pts & ROS1 M was found in 2/95 (2%), the results of these three mutations are consistent with other groups. Conclusions: Our results indicate that exp of PDL1+ pts at ILCC is lower than reported by others, yet the proportion of those with ≥50% PDL1 in our group is similar to others. Exp of EGFR, ALK, and ROS1 in our pts is similar to other studies.[Table: see text]
Platinum-based chemotherapy combined with endostar in the treatment of advanced NSCLC: A real world study.
Authors: Jiang Wei , Sun Wei , Li Wenhui , Gao Jing , Wang Hui , Zhou Wei , Liang Jing , Aa Lixiang , Zhao Changhong , Wang Luhua 
Published: June 2021

e21033 Background: Recombinant human endostatin (endostar), an angiogenesis inhibitor, has been approved for the treatment of NSCLC in combination with chemotherapy in China. This study aims to evaluate real world efficacy and safety of endostar combined with platinum-based chemotherapy in the treatment of advanced NSCLC. Methods: This study retrospectively collected electronic medical record system (EMR) information of NSCLC patients (pts) who received endostar combined with platinum-based chemotherapy regiments from June 2012 to August 2019 in 7 cancer hospitals after obtaining ethical approval. Baseline characteristics, efficacy evaluation and safety data were analyzed. Tumor response was evaluated according to RECIST 1.1. Adverse events (AEs) were graded according to NCI-CTC AE 4.0. The endpoints include objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and safety. Results: 512 advanced NSCLC pts who received endostar combined with platinum-based chemotherapy regiments were analyzed. The median age of pts was 59.2 years. Most pts were male, accounting for 75.2%. 63.3% pts was diagnosed at stage IV. 40.0% pts was adenocarcinoma and 35.4% pts was squamous cell carcinoma. 81.4% pts received endostar combined with chemotherapy as first-line. 292 people were included in the efficacy analysis set. The ORR, DCR and median PFS were 34%, 73% and 8.2 (95% CI 6.0-13.7) months, respectively. There were no significant differences of ORR and DCR among common platinum-based chemotherapy. The most common AEs were gastrointestinal reactions (29%), bone marrow suppression (14%), and liver damage (12%). Conclusions: The real-world data confirmed the superiority of endostar plus platinum-based chemotherapy in Chinese advanced NSCLC pts, with acceptable adverse effects. Clinical trial information: ChiCTR2000035129.
A phase II study of anlotinib plus whole brain radiation therapy (WBRT) for advanced non-small cell lung cancer with multiple brain metastases.
Authors: Zhu Xiangzhi , Tao Hua , Jiang Ming , Shi Meiqi , Kong Cheng , Song Xue , Zhang Nan , Chen Cheng , Jiang Ning , Zhao Lijun , Yan Pengwei , He Xia 
Published: June 2021

e21063 Background: The prognosis of non-small-cell lung cancer (NSCLC) patients(pts) with multiple brain metastases is poor. WBRT is the main treatment for the pts, but QUARTZ study showed that the efficacy of WBRT is unsatisfactory. The synergistic effect of the antiangiogenic therapy with radiation therapy has been well established. Anlotinib, an antiangiogenic multi-target TKI, had significantly improved progression-free survival (PFS) of advanced NSCLC with Brain Metastases. This study aimed to evaluate the efficacy and safety of anlotinib combined with WBRT in pts with brain metastases ( > 3) from advanced NSCLC. Methods: Advanced NSCLC pts with brain metastases ( > 3) who were histologically confirmed to be driver gene wild type or positive and pts who had received two or more previous treatments were eligible. Pts with meningeal metastasis were excluded. All pts were treated with anlotinib (12 mg, QD, day 1 to 14 of a 21-day cycle) combined with WBRT (DT 30Gy/12f), followed by maintenance therapy with anlotinib until disease progression or treatment intolerance. The primary endpoint was intracranial progression-free survival (iPFS). Secondary endpoints were extracranial PFS (ePFS), OS and toxicity. Results: As of 25 Jan 2021, 28 pts were enrolled. The median age was 57.5 years with 46.4% male. 89.3% of pts with adenocarcinoma. 21.4% pts harbored EGFR mutation. A total of 25 pts were included in efficacy analysis. In intracranial evaluation, ORR was 64.0%, DCR was 88.0%, median iPFS was 11.1 months (95% CI 5.9 to 12.1). In extracranial evaluation, ORR was 12.0%, DCR was 84.0%, median ePFS was 6.0months (95% CI 3.2 to 8.8). Most common grade 1-2 adverse events (AEs) were hypertension (67.8%), fatigue (64.2%)，anorexia (46.4%) and hand and foot skin reaction (37.5%). The most common grade 3-4 AEs were hypertension (12.5%), hand and foot skin reaction (10.7%) and fatigue (7.2%). No intracranial hemorrhage occurred during treatment. Dose adjustment due to AE occurred in 21.4% patients. Conclusions: This prospective study shows that the combination of anlotinib and WBRT for patients with multiple brain metastases after standard treatment resistance exhibited an effective therapeutic approach and manageable AEs. For further investigation, large sample and additional clinical trials are warranted. Clinical trial information: ChiCTR1900022093.
A novel combination score based on early serum tumor markers and neutrophil-to-lymphocyte ratio dynamics predicts response to PD-1/PD-L1 inhibitors in advanced non-small cell lung cancer.
Authors: Wang Jun , Tang Yin , Sun Yahong , Yin Beibei , Guan Yaping , Feng Dongfeng 
Published: June 2021

e21095 Background: Serum tumor markers (STM) are viewed as surrogate indicators of tumor burden, and neutrophil-to-lymphocyte ratio (NLR) has been reported to be associated with the systematic inflammation and immunity status of the host. The present study was designed to evaluate early STM and NLR dynamics as combined biomarkers to predict efficacy and prognosis for advanced non-small cell lung cancer (NSCLC) patients who received immunotherapy with PD-1/PD-L1 inhibitors. Methods: We retrospectively reviewed patients with advanced NSCLC who were treated with PD-1/PD-L1 inhibitors. Several STM, including carcinoembryonic antigen (CEA), cytokeratin-19 fragments (CYFRA 21–1), neuron specific enolase (NSE), carbohydrate antigen 19–9 (CA19–9), and carbohydrate antigen 125 (CA125), and NLR were routinely measured or calculated at NSCLC diagnosis. Early leading STM and NLR change were evaluated between immunotherapy initiation and the first subsequent restaging. At least 20% decreases of the leading STM were considered as leading STM decrease after immunotherapy. Both pretreatment and posttreatment NLR < 5 were considered as continuous low NLR. A combination score based on the leading STM and NLR dynamics was calculated. The effects of leading STM change, NLR change, and the combination score on objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were analyzed in a training cohort (n = 79) and confirmed in a validation cohort (n = 35). Results: A total of 120 patients were included in this retrospective cohort study. The median age was 63.0 years and 71.0% was male. Overall, ORR was 20.0%, and median OS and PFS were 6.2 and 4.6 months, respectively. Patients with low combination score had a significantly improved ORR (15/60) compared to those with intermediate (0/11), or high score (0/4) ( P = 0.032). In the training cohort, the combination score was significantly associated with OS ( P < 0.001) and PFS ( P < 0.001) for all patients, as well as for those with stable and progressive disease ( P < 0.001 for OS; P < 0.001 for PFS). This combination score was also further confirmed to stratify patients with different prognosis in terms of OS ( P < 0.001) and PFS ( P < 0.001) in the validation cohort. In a multivariable model, the combination score was an independent indicator for predicting OS ( P < 0.001) and PFS ( P < 0.001). Conclusions: A simple and novel combination score based on early STM and NLR dynamics representing surrogate indicators of tumor burden, and immunity status, respectively, can accurately predict efficacy and prognosis for advanced NSCLC patients with PD-1/PD-L1 blockade.
Anlotinib combined with s-1 in the third-line or later-line treatment of stage IV non-small cell lung cancer: Study for phase II clinical trial.
Authors: Yang Xiyue , Du Xiaobo 
Published: June 2021

e21115 Background: At present, for stage IV non-small-cell lung cancer (NSCLC), after the failure of second-line treatment, the effective rate of third-line treatment is not very well. We designed this study to evaluate the efficacy and safety of anlotinib combined with S-1 as a third-line treatment for patients with stage IV NSCLC. Methods: According to the inclusion and exclusion criteria, 29 patients will be treated with anlotinib plus S-1 based on Simon’s optimal two-stage design.They will undergo computed tomography (CT) every two cycles to assess the therapeutic effect according to RECIST.If the efficacy is assessed as SD, PR, CR after six cycles, anlotinib will be maintained until disease progression or death. Statistical analysis of the data will be conducted using SPSS (version 22.0).The primary endpoint is the objective response rate (ORR). The secondary endpoints are disease control rate(DCR),progression-free survival(PFS), overall survival(OS), and safety. Results: Between Jan 10, 2019, and Oct 31, 2020, a total of 29 patients were enrolled for treatment.At data cutoff (Jan 11, 2021),27(93.1%) patients had discontinued the study, and 2 (6.9%) patients were still receiving treatment. The median follow-up time was 11.2 months (IQR 8.2-20.1). Objective responses were achieved in 11 (37.9%; 95%CI 20.7-57.7) of 29 patients in the intention-to-treat population,which reached this trial’s primary endpoint. Disease control was achieved in 18 patients (62.1%; 95%CI 42.3-79.3);The median overall survival was 16.7months (95%CI 14.9-18.6);the median progression-free survival was 5.8 months (95% CI 2.9-8.7). The most common grade 3 adverse events were Gastrointestinal reactions (3[10.3%]),Fatigue (2[6.9%]), and Hypertension (2 [6.9%]).No grade 4 treatment-related adverse events, or treatment-related deaths occurred. Conclusions: The combination of anlotinib with S-1 in the third-line or later-line treatment of stage IV NSCLC shows promising anti-tumour activity and manageable toxicities in patients with NSCLC, and further study in phase 3 trials will be planned in the future. Clinical trial information: ChiCTR1900020948.