bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spread through air spaces in non-small cell lung cancer: Experience of a tertiary hospital.
Authors: Calvo Virginia , Garitaonaindia Yago , Martinez Cutillas Marta , TRASEIRA CRISTINA , Redondo Isabel , Aguado Ramon , Lorduy Ana Collazo , Campo Cañaveral Jose Luis , Martin Lopez Javier , Ospina Serrano Aylen Vanessa , Blanco Mariola , Crowley Silvana , Romero Roman Alejandra , Gil Barturen Mariana , Parejo Consuelo , Provencio-Pulla Mariano 
Published: June 2023

e20606 Background: Tumor spread through air space (STAS) is a novel pattern of invasion related to poor prognosis in non-small cell cancer (NSCLC). In 2015, Kyuichi Kadota first described spread through air spaces (STAS) as a novel histologic pattern of invasion related to poor prognosis NSCLC. The objective of this study is to describe the incidence of STAS in a surgical series of NSCLC patients resected in Hospital Universitario Puerta de Hierro-Majadahonda and identify the association of STAS with clinicopathological characteristics. Methods: Observational retrospective cohort study was performed from 2015 to 2021. Inclusion criteria were: age more than 18 years, histologically confirmed diagnosis of NSCLC, clinical stage I-IV and radical treatment with surgery. Descriptive analysis was performed. Results: 178 patients were included. 69.1% (123) were male, median age was 68.0 years. In relation to histological subtypes: 65.2% were adenocarcinoma, 22.5% squamous-cell carcinoma and 12.3% other histologies. Patients were classified by pathological stage: 71.9% were in stage I, 11.4% in stage II, 15.6% in stage III and 1.1% in stage IV. STAS was observed in the surgical specimen in 62 cases (34.8%). In Table-1 the association of STAS with clinicopathological characteristics is shown. Conclusions: In our study, we found statistically significant association between STAS and histological subtype and presence of lympho-vascular invasion. STAS were present more frequently in adenocarcinoma and were associated with more incidence of lympho-vascular invasion, as reported in other studies. More analysis are required for further description of this dissemination pattern and its implication in the prognosis of the patients. [Table: see text]
Survival for patients of stage III non-small cell lung cancer after radiotherapy in different periods.
Authors: Wang Zhuofan , Liu Qi , Wang Yuxiang , Qi Zhan , Zhang Zhimen , Shi Jian , Chen Xinyuan , Zhang Jian , Wang Yuan , Jia Zhongfei , Song Meng , Zhao Yan 
Published: June 2023

e20611 Background: Concurrent chemoradiotherapy (CCRT) is the main treatment for patients of unresectable stage Ⅲ non-small cell lung cancer (NSCLC).To retrospectively analyze prognosis and its related factors for patients of unresectable stage III NSCLC after radiotherapy in different periods. Methods: From 2000 to 2010 and from 2015 to 2019, patients of stage III NSCLC which received radiotherapy in the Fourth Hospital of Hebei Medical University were enrolled. Statistical analysis was used with the SPSS 21.0 software.The Kaplan-Meier method, log-rank test and Cox model were used for survival analysis, univariate analysis, and multivariate analysis, respectively. Results: A total of 808 patients of stage III NSCLC were enrolled. There were 674 males and 134 females. The median age was 63 years old( 29-86 years old ) . Radiotherapy (RT) were performed in 474 patients between 2000 to 2010 and in 334 patients between 2015 to 2019. There were 240 cases received with RT alone, 449 cases with sequential chemoradiotherapy (Seq-CRT) and 119 cases with CCRT. 55 were treated with 3-dimensional radiotherapy (2DRT) plus 3-dimensional conformal radiotherapy (3DCRT)，386 with 3DCRT，and 367 with intensity-modulated radiotherapy（IMRT)， respectively. The median doses was 60 Gy (range 36-77Gy). The median overall survival (OS) was 21.0 months (19.4-22.6 months), and the 1-, 3- and 5-year OS rates were 69.8%, 30.7% and 21.3%, respectively. Under univariate analysis, gender, age, radiotherapy technology，period of treatment and whether combined chemotherapy were significantly associated with OS ( P< 0.05). The median OS was 18.0 months in group of 2000-2010 and 26.1 months in group of 2015-2019, respectively. The median OS for groups of2DRT+3DCRT, 3DCRT and IMRT were 10.0, 21.0, 23.4 months, respectively. The median OS for RT alone, Seq-CRT and CCRT was 17.0, 21.0, 30.3 months, respectively. Under multivariate analysis, sex, age, times of RT and combined chemotherapy were independent prognostic factors for OS ( P< 0.05). Conclusions: From 2DRT to 3DCRT or IMRT, the OS in patients of stage Ⅲ NSCLC was gradually increased; the OS was more higher in patients treated between 2015-2019 also. In addition, the OS was significantly longer in patients with CCRT than with Seq-CRT or RT alone.
Surgery with adjuvant chemotherapy versus chemoradiation for early-stage large cell neuroendocrine cancer (LCNEC) of the lung: A SEER plus based analysis.
Authors: Shah Anish , Potluri Lakshmi Bhavani , Budhathoki Pravash , Gaire Suman , Uprety Dipesh 
Published: June 2023

e20616 Background: LCNEC of the lung is a rare and highly aggressive tumor with neuroendocrine differentiation. Given its rare occurrence and lack of data from large randomized trials, treatment recommendations are based on the extrapolation of data, primarily from small-cell lung cancer studies. We conducted this study to evaluate the survival difference among patients with LCNEC with an N1 disease between those who received surgery and adjuvant chemotherapy versus definitive chemotherapy and radiotherapy. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER) plus 18 registries database to identify patients diagnosed with LCNEC with tumor stage of T1, T2, or T3 and nodal stage of N1. The study population included patients, 18 years and above, who underwent surgical resection followed by adjuvant chemotherapy and patients who received definitive chemo-radiotherapy for early stage LCNEC. Kaplan-Meier and log rank test were used to compare overall survival (OS) and Cancer specific survival (CSS). Multivariate survival analysis was done using the cox proportional hazards regression model. Results: A total of 178 patients were included, 57.3% (n = 102) were < 65-year-old, 50.56% (n = 90) were male, mostly Caucasian 87.08% (n = 155) and identified as non-Hispanic 93.26% (n = 166). Out of them, 70.22% (n = 125) underwent surgery plus adjuvant chemotherapy and 29.78% (n = 53) underwent chemoradiation. Patients who underwent surgery with adjuvant chemotherapy had higher overall survival (OS) than chemoradiation (37 vs. 11 months respectively). 3-year (49.9% vs. 15.7%) and 5-year OS rates (36.7% vs. 10.4%) were also higher in the earlier group. On multivariate analysis after adjusting for age, gender, race and origin, patients who received chemoradiation had higher hazards as compared to those who received surgery and adjuvant chemotherapy (Hazard ratio: 2.91, 95% Confidence interval (CI):1.93,4.37, P value < 0.001). When examining the cancer specific survival (CSS), similar results were observed with higher CSS in the surgery with adjuvant chemotherapy group (18 vs. 8 months) reaching a statistical significance of P < 0.001 and higher hazards in chemoradiation group (Hazard ratio: 3.33, 95% Confidence interval (CI):2.09,5.28, P value < 0.001). 3-year survival (26.47% vs. 2.7 %) and 5-year CSS rates (11.76% vs. not reached) were also pronounced in the patients treated with surgery with adjuvant chemotherapy. Conclusions: Our study demonstrates that patients with early stage LCNEC (T1-3 N1) disease treated with surgery and adjuvant chemotherapy had statistically significant overall and cancer specific survival rates compared to those treated with chemoradiation.
Real-world analysis of ICI efficacy in ES-SCLC patients with and without brain metastases: A call for inclusion in clinical trials.
Authors: Cao Yuanzhen , Afzal Muhammad Zubair , Lu Ziyao , Sharma Aditya , Pirruccello Jonathan P. , Shirai Keisuke 
Published: June 2023

e20621 Background: Immune checkpoint inhibitors (ICIs) have proven successful in treating extensive stage small-cell lung cancer (ES-SCLC). Atezolizumab, a PD-L1 inhibitor, is approved as first-line therapy for ES-SCLC in combination with chemotherapy. SCLC has a high incidence to spread to the brain with more than 50% of patients developing brain metastases (BM) during their clinical course. However, patients with BM have frequently been excluded from clinical trials due to their perceived poor prognosis. This study aimed to assess the efficacy of ICI in achieving disease response and managing intracranial disease in patients with ES-SCLC. Methods: We conducted a retrospective study on patients with biopsy-confirmed ES-SCLC treated with at least one cycle of atezolizumab/carboplatin/etoposide combination from 2015 to 2022. Overall survival (OS), progression-free survival (PFS) and radiographic response were noted in patients with and without BM. Intracranial (IC) response was documented in patients with radiographic evidence of BM who had at least one follow-up brain imaging after the start of ICI. Results: A total of 83 patients were included, 39.3% (n = 33) of which had BM. Median follow-up was 8 (95%CI: 4.5-11.6) months. Baseline characteristics were summarized in the table below. Disease progression occurred in 90.9% patients with BM and death in 51.5%. Among 21 patients who fulfilled IC response assessment criteria, one (4.8%) had complete response, four (19.0%) had partial response, two (9.5%) had stable disease and fourteen (66.7%) had disease progression. Median duration of IC response was 5.3 (95%CI: 0.00-20.35) months; IC objective response rate was 23.8%. No difference was found in OS (10 vs. 30 months, P = 0.3) or PFS (6 vs. 7 months, P = 0.18) in patients with and without BM respectively. Patients with > 3 BM (n = 16) had inferior OS (7 vs. 21 months, P = 0.01) and PFS (5 vs. 6 months, P = 0.002) compared to those with ≤3 BM. Conclusions: This study demonstrated that ICI achieved similar outcomes in patients with and without BM and produced meaningful intracranial response in patients with BM. Therefore, further clinical trials on ES-SCLC should encompass patients with BM, especially those with ≤3 BM. Future research on a larger, more diverse patient population is warranted. [Table: see text]
Correlations between overall response rate, progression-free survival and overall survival in refractory small cell lung cancer treated with lurbinectedin.
Authors: Wasifuddin Mustafa , Ilerhunmwuwa Nosakhare Paul , Hakobyan Narek , Tahir Muhammad , Abowali Hesham , Avezbakiyev Boris 
Published: June 2023

e20623 Background: Lurbinectedin is a novel second-line option for refractory small-cell lung cancer. It is a synthetic alkaloid that functions by covalently binding to DNA and generates double-strand breaks, and disrupts DNA-protein interactions and RNA transcription. It is yet to be well established in the literature if the overall response rate (ORR) can predict progression-free survival (PFS) and/or overall survival (OS). This study aims to investigate the correlations between PFS, ORR, and OS in refractory small-cell lung cancer treated with lurbinectedin. Methods: PubMed, Google Scholar, and Clinicaltrials.gov databases were queried for randomized, phase 3 clinical trials, phase 2 trials, phase 1 trials with expansion cohorts, and retrospective and prospective studies. The criteria for eligibility included a clinical diagnosis of treatment-refractory small cell lung cancer, at least one prior line of therapy, articles in English, and lurbinectedin treatment. ORR, OS, and PFS data were extracted manually from the selected studies, and correlation analyses with Spearman’s rank correlation were performed. Results: Seventy-one articles and trials were identified. Seven articles, including 849 patients, met our criteria and were included for further analyses. OS and PFS were strongly correlated (rs = 0.9196, p-value = 0.02), whereas the correlation between OS and ORR was not statistically significant (rs = 0.6696, p-value = 0.20). Also, the correlation between ORR and PFS was not statistically significant (rS = 0.6785, p-value = 0.05419). Conclusions: There was a strong correlation between OS and PFS in studies investigating lurbinectedin use in patients with refractory small-cell lung cancer. There were no significant correlations between ORR and PFS/OS. We propose that PFS can be used as a surrogate for OS in studies involving lurbinectedin-treated refractory small-cell lung cancer, especially when the time to reach OS is protracted.
Outcome of immune checkpoint inhibitors in patients with extensive-stage small-cell lung cancer and brain metastases.
Authors: Wang Chunyu , Jing Fangfang , Zhang Fan , Tao Haitao , Ma Junxun , Hu Yi , Wang Lijie 
Published: June 2023

e20625 Background: Brain metastases (BMs) are common in extensive-stage small-cell lung cancer (SCLC) and are underrepresented in pivotal clinical trials that demonstrate the efficacy of immune checkpoint inhibitors (ICIs). We conducted a retrospective analysis to assess the role of ICIs in BM lesions in less selected patients. Methods: Patients with histologically confirmed extensive-stage SCLC who were treated with ICIs were included in this study. Objective response rates (ORRs) were compared between the with-BM and without-BM groups. Kaplan‒Meier analysis and the log-rank test were used to evaluate and compare progression-free survival (PFS). The intracranial progression rate was estimated using the Fine-Gray competing risks model. Results: A total of 133 patients were included, 45 of whom started ICI treatment with BMs. In the whole cohort, the overall ORR was not significantly different for patients with and without BMs (p = 0.856). The median progression-free survival for patients with and without BMs was 6.43 months (95% CI: 4.70-8.17) and 4.37 months (95% CI: 3.71-5.04), respectively (p = 0.054). In multivariate analysis, BM status was not associated with poorer PFS (p = 0.101). Our data showed that different failure patterns occurred between groups, with 7 patients (8.0%) without BM and 7 patients (15.6%) with BM having intracranial-only failure as the first site progression. The cumulative incidences of brain metastases at 6 and 12 months were 15.0% and 32.9% in the without-BM group and 46.2% and 59.0% in the BM group, respectively (Gray’s p < 0.0001). Conclusions: Although patients with BMs had a higher intracranial progression rate than patients without BMs, the presence of BMs was not significantly associated with a poorer ORR and PFS with ICI treatment in multivariate analysis.
Anlotinib plus irinotecan or docetaxel in small-cell lung cancer (SCLC) relapsed within six months: Updated results from a single-arm, phase Ⅱ study.
Authors: Zhang Minna , Chen Xueqin , Jiang Hong , Wang Jiaoli , Ye Jian , Ma Shenglin , Xia Bing 
Published: June 2023

e20629 Background: There is still no unsatisfactory treatment strategy for patients (pts) with advanced SCLC relapsed within six months after first-line treatment, although chemotherapy alone is the standard treatment. Anlotinib, an oral multitarget tyrosine kinase inhibitor, effectively inhibits angiogenesis and enhances tumor cell response to chemotherapy. In the ALTER 1202 trial, anlotinib had significantly improved progression-free survival (PFS) and overall survival (OS) of advanced SCLC pts who received at least two lines chemotherapy. Therefore, we presented the updated efficacy and safety of anlotinib plus irinotecan or docetaxel in SCLC relapsed within six months after first-line treatment. Methods: Eligible pts with advanced SCLC who have relapsed within six months after first-line platinum-based treatment received anlotinib (12mg, QD from day 1 to 14 of a 21-day cycle, the dose could be adjusted to 10mg or 8mg according to the patient's tolerance) and irinotecan (65mg/m2, day1,8, q3w, up to 4 cycles) or docetaxel (60mg/m2, q3w, up to 4 cycles) until progression or intolerable toxicity. The primary endpoint was the objective response rate (ORR). Secondary endpoints included PFS, the disease control rate (DCR), OS and safety. Results: As of Jan 31, 2023, we recruited 39 pts, among which 36 pts (median age: 63.2 years, male: 86.1%, ECOG PS 1: 80.6%, brain metastasis: 58.3%, liver metastasis: 36.1%) were eligible for efficacy analysis. Median follow-up time was 17.2 months (95% Cl, 8.27 -26.13 ). Of 36 evaluable pts, 1 pts had complete response (CR) , 20 pts reached partial response (PR) and 11 pts had stable disease(SD). The ORR was 58% (21/36) and the DCR was 89% (32/36), respectively. The median PFS was 4.4 months (95%Cl: 3.73- 5.08). The median OS was 7.9 months (95%Cl: 5.28-10.52). The Progression-free survival and overall survival in patients with recurrence > 3 months and ≤ 6 months (PFS 6.5 m and OS 11.9 m) after first-line therapy improved more significantly than in patients with recurrence ≤ 3 months (PFS 4.1 m and OS 5.9 m). Most common grade 1-2 treatment-related adverse events (TRAEs) included weakness(58.3%), anorexia(38.9%), anemia(25%), hypertension (15.6%), Oral mucositis (13.9%) and leucopenia (11.1%). 3 pts (8.3%) suffered from grade 3 AEs, which were thrombocytopenia, leukopenia, and anemia. Conclusions: Anlotinib combined with irinotecan or docetaxel as second-line treatment for non-sensitive recurrent SCLC (i.e., extensive-stage disease time to relapse: 0-6 months) showed superior efficacy and safety compared with standard chemotherapy. It may become a novel therapeutic strategy for the population. Clinical trial information: NCT04757779 .
Racial disparities in the prevalence of extrathoracic metastases in lung cancer patients and survival: A SEER database study (2010–2019).
Authors: Al Armashi Abdul Rahman , Alkrekshi Akram , Al Zubaidi Anas , Hammad Faris , Elantably Dina , Truong Vien , Ngo Tam N.M. , Bruno Debora S. 
Published: June 2023

e20630 Background: Metastatic disease at the time of lung cancer diagnosis influences therapy choice and prognosis. Metastasis to the brain, bones, and liver may lead to higher morbidity. Differences in the prevalence of metastatic sites among patients (pts) of White (W) and Black (B) race and their association with overall survival need further elucidation. Methods: Utilizing the SEER database from 2010-2019, we identified W and B pts with metastatic small cell (SCLC), squamous cell (SQ-NSCLC), and adenocarcinoma (AD-NSCLC). Only pts with bone, brain, or liver metastasis (mets) at diagnosis were included. Metastatic site prevalence rates were determined. Cox proportional hazard ratios for survival were calculated while controlling for gender, ethnicity, other metastatic sites, chemotherapy, and radiation. Results: Total of 338,411 pts, 11.4% of B race. In SCLC, B pts had a higher prevalence of brain mets, while W pts demonstrated a higher prevalence of bone and liver mets. Survival between W and B pts with SCLC was comparable except for modest superior survival in B pts with liver mets. In SQ-NSCLC, metastatic disease for the 3 sites of interest was more prevalent in B pts, most notably in brain. However, survival did not differ. In AD-NSCLC, B pts were more likely to present with brain and liver mets. B pts with bone mets had inferior survival. Conclusions: Significant differences in patterns of mets at the time of lung cancer diagnosis between W and B pts exist. B pts with SCLC and liver mets had longer survival. Interestingly, B pts with bone mets and SQ-NSCLC had better survival while those with AD-NSCLC fared worse. Multiple factors, including socioeconomic, environmental/smoking patterns and access to healthcare, may have contributed. Further studies are needed. [Table: see text]
The changing landscape of small-cell lung cancer.
Authors: Cittolin Santos Giordano Fabricio , Knapp Brendan , Ganesh Bharath , Gao Feng , Stinchcombe Tom , Govindan Ramaswamy , Morgensztern Daniel 
Published: June 2023

e20634 Background: Small-cell lung cancer (SCLC) is an aggressive histologic subtype of lung cancer with distinct biology and clinical course. The aim of this study is to investigate the trends in demographics and outcomes. Methods: We queried the Surveillance, Epidemiology, and End Results (SEER) database to assess the incidence, demographics, and survival for SCLC using SEER 8 (8 registries), which include data from 1975 to 2019. The pattern of metastases was evaluated using SEER 17 from 2010 to 2019. Jointpoint analysis was used to calculate the trends in annual percentage change according to year of diagnosis. Results: There were 530,198 patients with lung cancer, including 73,362 (13.8%) patients with SCLC in the SEER 8. The percentage of SCLC among all lung tumors progressively increased from 13.3% in 1975 to a peak of 17.5% in 1986, followed by steadily decrease since 1990, reaching 11.1% in 2019. The incidence per 100,000 population increased from 9.5 in 1975 to 15.3 in 1986 followed by a gradual decline to 6.5 in 2019. Among patients with SCLC included in SEER 8, demographic changes from 1975-1979 to 2015-2019 included increased median age at diagnosis from 63 years to 69 and increased percentage of women from 31.4% to 51.2%. The percentage of patients with stage IV increased from 56.9% to 63.8% from 1995-1999 to 2000-2004, and to 69.5% in 2010-2014 without further increase. Among the 55,035 patients with SCLC in SEER 17 from 2010 to 2019, the most common sites of metastasis at diagnosis were mediastinal lymph nodes (69.9%) liver (30.5%), bone (22.8%), and brain (15.8%). The median, 1-year, and 5-year overall survival increased from 6 months, 23%, and 3.6% respectively in 1975-1979 to 7 months, 30.8%, and 6.8% respectively in 2010-2019 (P < 001). Conclusions: The incidence of SCLC in the United States reached a peak in 1985 to 1989 followed by a gradual decline. Demographic changes included an increased median age at diagnosis and the percentage of women, which surpassed men in the last study period. There was also an increase in the percentage of stage IV. The improvement in 5-year OS has been statistically significant but clinically modest.
A study on oligo-progression after durvalumab plus platinum-etoposide for ES-SCLC.
Authors: Watanabe Kageaki , Misawa Kazuhito , Uematsu Mao , Hashimoto Kana , Hosomi Yukio 
Published: June 2023

e20642 Background: Chemotherapy plus immune-checkpoint inhibitor(ICI) therapy is the standard of care for untreated extensive-stage small cell lung cancer(ES-SCLC), but the pattern of progression has not been fully investigated. It is known that a certain percentage of patients with ES-SCLC have Oligo-Progression, and ICI treatment can be continued with the addition of local therapy. This is great significance in the current situation where post-treatment is limited. Methods: We performed a retrospective analysis of patients with ES-SCLC treated with durvalumab plus platinum–etoposide regimen from September 2020 to January 2023 in our institution. Results: Forty patients were included, median age was 68 years (range 45-89), 32 (80%) patients were male and 8 (20%) patients were female, ECOG-PS was 0 or 1 in 25 (63%) patients, 2 or 3 in 15 (38%) patients, 38 (95%) patients had a smoking history, 39 (98%) patients were Stage IV, and the regimens were durvalumab plus cisplatin–etoposide in 15 (38%) patients and durvalumab plus carboplatin–etoposide in 25 (63%) patients. The median PFS was 5.9 months (95% CI: 3.8-8.0) and the median OS was 25.4 months (95% CI: 6.0-44.8). 14(35%) patients were still on treatment. Of the 17 (43%) patients with confirmed RECIST-PD, 4 patients had Oligo-Progression. All of them continued ICI treatment with additional radiation therapy. Two patients are continuing ICI treatment. Two patients with second recurrence, and the time from RECIST-PD to second recurrence was 5 months and 18 months, respectively. Conclusions: Among patients with RECIST-PD after durvalumab plus Platinum–Etoposide for ES-SCLC, Oligo-Progression was observed in 24%, and the strategy of continued ICI treatment in addition to local therapy may be promising.