bluuebunny/crossref_metadata_2025_split huggingface dataset:
Promising efficacy of immune-checkpoint inhibitor with chemotherapy for SMARCA4-deficient thoracic sarcomatoid tumors.
Authors: Lin Ying , Zhang Yao , Hu Zhihuang , Wu Xianghua , Wang Jialei , Wang Huijie 
Published: June 2022

e21074 Background: SMARCA4-deficient thoracic sarcomatoid tumors (SD-TSTs) is a rare and highly aggressive disease that lack clear treatment guidelines. This research reports the clinicopathological features of SD-TSTs and the promising efficacy of immune-checkpoint inhibitor with chemotherapy in SD-TSTs. Methods: A total of 16 patients were diagnosed and treated with SD-TSTs in Fudan University Shanghai Cancer Center (FUSCC) from January, 2017 to December, 2021. Clinicopathologic, genomic characteristics and treatment information were obtained and analyzed. Results: SD-TSTs were diagnosed at median age of 64.5 years old, and predominantly affected male (100%) with heavier smoking history (≥20 pack-year). Many patients were diagnosed at advanced stages (Stage I 18.8%, Stage II 25%, Stage III 25% and Stage IV 43.8%). The most often metastatic sites were adrenal gland, lymph nodes, bone and liver, while brain metastasis was not found. For patients underwent radical therapy, median disease-free survival is 4.8 months, indicating a rapid relapse pattern even for early-stage patients. 8 patients with Stage IV SD-TSTs were treated in FUSCC. As for first-line therapy, 3 patients received chemotherapy, whose regimen included gemcitabine plus cisplatin, doxorubicin plus ifosfamide, and vincristine, doxorubicin plus cyclophosphamide alternating with ifosfamine and etoposide. 5 patients received immune-checkpoint inhibitor plus chemotherapy as first-line therapy, including 3 patients treated with pembrolizumab plus nab-paclitaxel and carboplatin, 1 patient treated with tislelizumab plus nab-paclitaxel and carboplatin and 1 patient treated with sintilimab plus paclitaxel and carboplatin. Median progression-free survival (PFS) of first line was 6.53 months for all patients. First-line median PFS was significantly higher for patients with immune-checkpoint inhibitor plus chemotherapy than those treated with only chemotherapy (not reach vs. 2.73 months, p = 0.07). This result suggested that SD-TSTs were irresponsive to chemotherapy, including those used for sarcomas, and better responded to immune-checkpoint inhibitor included regimen. Conclusions: SD-TSTs is a highly aggressive disease. Immune-checkpoint inhibitor combined with chemotherapy showed promising efficacy in metastatic SD-TSTs than traditional chemotherapy. Considering the low incidence of SD-TSTs, our research contains the largest sample size by far to report the efficacy of immune-checkpoint inhibitor plus chemotherapy in this deadly disease.
The prognosis of EGFR complex mutation or co-mutation with tyrosine kinase inhibitor treatment in non-small cell lung cancer.
Authors: Jiang Da , Fu Yuhui , Zhou Xinliang , Li Ying , Cui Yanzhi , Hong Lei , Jin Hui , Shi Ke , Huang Fang , Zhang Xue , Fan Shaoshuang , Song Wenya , Deng Ruoying 
Published: June 2022

e21086 Background: To compare the prognoses of EGFR complex mutation, co-mutation and single mutation with first-line TKI treatment in NSCLC patients. Methods: A retrospective study of 215 patients with EGFR-mutated NSCLC who were admitted to the Department of Medical Oncology, the Fourth Hospital of Hebei Medical University from January 2015 to January 2021, all received first-line EGFR-TKI therapy. According to the type of mutation, they were divided into 48 cases (22.3%) of EGFR single mutation group, 48 cases (22.3%) of complex mutation group, and 142 cases (66.0%) of co-mutation group, of which 23 cases (10.6%) both had complex mutation and co-mutation. The prognoses of the latter two groups were compared with that of the single mutation group respectively. SPSS 26.0 was used to analyze the data, and P < 0.05 indicated the difference was statistically significant. Results: Progression-free survival (PFS): the co-mutation group was shorter than the single mutation group (11.0m vs 13.5m; HR = 1.492, 95%CI: 1.036-2.149; P= 0.030), especially the co-mutation was occurred in TP53 (10.5 m vs 13.0m; HR = 1.665, 95%CI: 1.234-2.248; P= 0.001) or HER family (9.0m vs 12.0m; HR = 2.435, 95%CI: 1.492-3.974; P< 0.001). Overall survival (OS): compared with the single mutation group, complex mutation group (36.5m vs 52.0m; HR = 1.480, 95%CI: 0.821-2.668; P= 0.193), co-mutation group (41.0m vs 52.0m; HR = 1.418, 95%CI: 0.901-2.231; P= 0.131) were not statistically different, but the co-mutation of PTEN pathway significantly reduced OS (24.0m vs 46.0m; HR = 1.884, 95%CI: 1.137 -3.120; P= 0.014). Objective response rate (ORR) and disease control rate (DCR) of first-line EGFR-TKI: single mutation group separately compared with complex mutation group and co-mutation group (ORR: 64.6% vs 6.2% vs 27.4%, P< 0.001; DCR: 100% vs 70.8% vs 91.5%, P < 0.001 and 0.007 respectively). After the first-generation EGFR-TKI treatment and secondary EGFR E20 T790M mutation, the presence or absence of the original sensitive mutation affects the PFS of the first-generation TKI (12.0m vs 11.0m; HR = 1.109, 95%CI:0.739-1.664 ; P= 0.616), PFS of the third-generation TKI (10.0m vs 8.0m; HR = 1.130, 95%CI: 0.717-1.781; P= 0.599) and OS (34.0m vs 44.5m; HR = 0.834, 95%CI: 0.505-1.377; P= 0.478) were not statistically different. Conclusions: EGFR co-mutation is a predictor of poor prognosis in NSCLC patients treated with EGFR-TKI; after first-generation EGFR-TKI resistance, the disappearance of the original sensitive mutation cannot predict the prognosis.
Immunotherapy in Hispanic patients with advanced non-small cell lung cancer: A real-world data.
Authors: Lujan Mauricio , Lema Mauricio , Preciado Beatriz , Lema Camila , Egurrola Jorge , Cardona Zorrilla Andres Felipe , Gonzalez Diego Mauricio , Mantilla William Armando , Pino Luis , Rojas Gustavo , Gomez-Abreo Diego Andres , Munevar Isabel , Manneh Raimundo , Manneh Kopp Ray , Lobaton Jose F. , Calle Esteban , Borras Mariana , Triana Ivan Camilo , Pineda Mateo , Moran Ortio Diego 
Published: June 2022

e21094 Background: Nivolumab is a human programmed death receptor-1 (PD-1) blocking antibody, used as treatment option in patients with advanced non-small cell lung cancer (NSCLC). We assessed the nivolumab efficacy in terms of survival and response to treatment as second- or third-line therapy in patients with advanced NSCLC. Methods: This is a multicentric observational study. Data of patients with advanced NSCLC who received nivolumab as second (2L) or third-line (3L) treatment were analyzed retrospectively. Information regarding patient demographics and clinical backgrounds, treatment patterns from diagnosis to post-nivolumab treatment, effectiveness, and safety of nivolumab treatment were collected. The outcomes evaluated were overall survival (OS), progression-free survival (PFS), and objective reponse rate to treatment (ORR). OS and PFS were estimated with the Kaplan-Meier method. Statistical analysis was carried out using SPSS version 21.0. Results: Eleven centers distributed across the country (Colombia) participated. Data from 178 patients were included. The median follow-up was 26.8 months (IQR 20.3 - 40.4). Women represented 51.7% of the population, and the median age was 63 years (IQR 56-72 years). Nivolumab was commonly used as a 2L treatment. The ORR with nivolumab as 2L treatment was 21.0%. The median PFS and OS were 5.5 months (95%CI: 4.5 – 6.5) and 12.4 months (95%CI: 10.8 – 14.0), respectively. In 3L the ORR with nivolumab was 15.0%. The overall incidence of adverse events was 1.7%. Conclusions: Nivolumab effectiveness and safety in this scenario was consistent with than reported by previous trials and other real world data.
Pan-immune-inflammation value as a predictive biomarker for survival in advanced non-small cell lung cancer patients treated with immunotherapy.
Authors: Sooi Kenneth , Low Jia Li , Miow Qing Hao , Kumarakulasinghe Nesaretnam Barr , Sundar Raghav , Huang Yiqing 
Published: June 2022

e21095 Background: It is well known that chronic inflammation can enable immune escape by suppressing immune surveillance. This promotes cancer growth and development, which forms the basis of immune checkpoint inhibitors use. Pan-Immune-Inflammation Value (PIV), a type of immune-inflammatory biomarker, has shown predictive value in various cancer patient populations (colorectal, melanoma, breast, oesophagus, ALK-positive lung cancer) and patients with ANCA-associated vasculitis. We aimed to evaluate the role of PIV as a predictive biomarker in advanced non-small cell lung cancer (NSCLC), whereby immune checkpoint inhibitor therapy is frequently used. Methods: We conducted a retrospective review of advanced NSCLC patients who received immunotherapy in the National University Hospital, Singapore between January 2015 and January 2022. PIV was calculated as: (neutrophil count × platelet count × monocyte count)/lymphocyte count, with the median value used to distinguish between high and low PIV. Kaplan–Meier method and Cox proportional hazards regression models were used for survival analyses. Results: 203 patients were included in the study. The median age was 63, 70% were males, 76% were Chinese, 83% had ECOG Performance Status ≤1 and 70% had adenocarcinoma histology. The immunotherapy agents used were Pembrolizumab (82%), Nivolumab (13%) and Atezolizumab (5%). Chemotherapy was given in conjunction with immunotherapy in 37% of the population. The median PIV value derived was 790 and patients with a low baseline PIV experienced better progression-free survival (PFS) and overall survival (OS). The median PFS was 249 days in PIV-low vs 145 days in PIV-high cohorts (hazard ratio for progression or death from any cause [HR] 0.58, 95% Confidence Interval [CI] 0.40-0.86, p < 0.01) and the median OS was 794 days in PIV-low vs 420 days in PIV-high cohorts (HR 0.69, 95% CI 0.49-0.96, p = 0.03). Patients who had higher PIV, ECOG performance status ≥2, liver metastases, immunotherapy exposure in 2nd line or later, use of immunotherapy alone without chemotherapy had worse OS in univariate analysis, but only PIV (HR = 1.61, 95% CI 1.08-2.40, p < 0.02) was an independent prognostic factor in multivariate analysis. Amongst the patients with known PD-L1 status (n = 158), univariate analysis showed that PD-L1 ≥1 and PD-L1 ≥50 were not prognostic for OS whereas PIV remained an independent prognostic factor in both univariate and multivariate analyses. Conclusions: PIV appears to be a strong predictor of survival outcomes for patients with advanced NSCLC receiving immunotherapy as part of their cancer treatment. Prospective clinical trials are required to validate the predictive value of PIV in NSCLC patients receiving immunotherapy, as well as evaluating PIV’s performance against PD-L1.
Tumor neutrophil extracellular traps and pretreatment neutrophils in association with progression-free survival in patients with metastatic non-small cell lung cancer receiving pembrolizumab alone or with chemotherapy.
Authors: Petrova Mila , Parvanov Dimiter , Ganeva Rumiana , Metodiev Dimiter , Bachurska Svitlana , Eneva Mariyana , Penkova Polya , Popov Teodor , Nikolov Krasimir , Taushanova Margarita , Kraleva Petya , Ruseva Rossitza Krasteva , Zhelev Kiril , Donev Ivan 
Published: June 2022

e21099 Background: Background: In this multicentric retrospective study, we evaluated the relationship between pre- treatment blood neutrophils and neutrophil extracellular traps (NET) in biopsy samples and their predictive value for progression progression-free survival (PFS) in patients with non-small-cell lung cancer (NSCLC) receiving immunotherapy alone or in combination with chemotherapy as a first-line treatment. Methods: Patients with metastatic NSCLC (n = 100) were retrospectively analyzed between Apr 2018 and Sep 2021; 77.5% of the patients received platinum-containing chemotherapy with Pembrolizumab, and 22.5% – Pembrolizumab only as a first-line treatment. Pre-treatment blood neutrophils were counted. Tissue sections were stained immunohistochemically for Neutrophil elastase (NE) and Histone H3. Both NE and Histone H3 stained tissue areas were calculated manually and determined by Image-J software. We considered the extracellular components that were double-positive for NE and H3 to be NET. Results: In correspondence analysis, patients with low levels (< 33rd percentile) of pre-treatment neutrophils were grouped with low amounts (< 33rd percentile) of NET-positive tumor areas (p = 0.02). The amounts of NET-positive tumor areas were not related to other clinicopathological characteristics of the patients. Patients with an intermediate/high amount of NET-positive areas had significantly shorter mean PFS, 10.7 (95% CI: 9.6–11.8) than those with low NET-positive areas, 14.8 (95% CI: 11.5–18.1) (log-rank test p = 0.003). Moreover, in a multivariate Cox regression model, the presence of an intermediate/high amount of NET-positive areas was an independent predictive factor for shorter PFS, HR 2.1 (95% CI: 1.2–3.7; p = 0.005). Conclusions: Our study suggests that tumor formation of NETs is related to the numbers of pre-treatment neutrophils and may mediate neutrophil-induced antitumor resistance. Excessive NET formation in tumor tissue is a potential negative predictive marker for shorter PFS.
Actionable insights for managing inter-reader variability of RECIST overall response in lung clinical trials: A retrospective analysis.
Authors: Beaumont Hubert , Iannessi Antoine 
Published: June 2022

e21102 Background: To assess drug efficacy in clinical trials with imaging endpoints, the FDA recommends blinded independent central review (BICR) with double reads to ensure robust image interpretation. However, discordance created by double-reading adds burden and costs that stakeholders strive to minimize. Given that selection of tumors at baseline is reported to cause one third of adjudications, we tested a set of risk factors arising from baseline evaluations and trained models likely to predict discrepancies in RECIST responses. Methods: We pooled and retrospectively analyzed data from five lung cancer clinical trials that used RECIST with BICR and double reads including a total of 1720 patients. Firstly, we analyzed the distribution of four kinds of response discrepancies (KoD): progression or date of progression (PD), response or date of response (OR), progression or response (ANY) and best response (BR). We derived discrepancy rates, average time-point of the first occurrence of KoD and the proportion of time-points before KoD out of total time-point number (compared using Marascuilo procedure) as key indicators of the at-risk period of discordance. Secondly, from the baseline evaluations performed by readers, we computed the odds ratios of 32 risk factors for discrepancies including differences in measurements, tumor selection and disease locations. Finally, based on 77 features, we trained a Random Forest (RF) and a deep learning (DL) model to predict KoDs. Results: On average, respectively for PD, OR, ANY and BR, discrepancy rates were 41.5%, 49.1%, 66.3% and 28.7%; number of time-points for first occurrence were 4.6, 2.7, 2.7 and 4.8; and the proportion of time-points before KoD were 30.7%, 24.7%, 33.1% and 23.2% (significantly different). The main risk factors for discrepancies were miss-detection of measurable disease, completely different disease selection, miss-selection of lung tumors and when readers’ difference in sum of diameters was between 10% and 20%. However, associations were weak, with no association when one of the readers selected infrequent diseases (e.g., skin, gastric). DL outperformed RF. Classification performances were generally poor. PD was not predictable. BR performances were positive predictive value: 81.0 [95% CI: 78.8; 83.2], negative predictive value: 73.3 [95% CI: 72.8; 73.8]. Conclusions: The KoDs have different distributions, but all occur in the first third of the patient evaluation defining a risk period. We confirmed the reported association of selection and measurement at baseline with responses' variabilities. However, the associations were weak and did not allow good prediction of the variability in responses. For BICR of lung cancer trials using RECIST, our results support the implementation of a monitoring of variability focusing on the baseline and the beginning of the evaluation of the patients.
Integrated analysis of transcriptome profiles in lung adenocarcinoma with spread through air spaces.
Authors: Pan Bo , Jia Dexin , Geng Jianxiong , Cui Chengwei , Yu Yan 
Published: June 2022

e21103 Background: Spread through air spaces (STAS) is a recently described invasive pattern of lung cancer with a relatively poor prognosis. The current study aims to evaluate and compare the transcriptome patterns and tumor microenvironment (TME) of STAS positive and negative lung adenocarcinoma (LUAD) cases. Methods: Nineteen LUAD patients who underwent radical surgery were enrolled in the current study, of which 11 were STAS-positive and 8 were STAS-negative. We performed RNA sequencing and data analyzes of the patient’s resected primary tumor tissue samples in a College of American Pathologists accredited laboratory (Genecast Biotechnology Co., Ltd, Wuxi). Results: A total of 841 differently expressed genes (DEGs) were identified between STAS positive and negative groups, including 442 up-regulated and 399 down-regulated DEGs in STAS positive tumors. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses indicated that the 841 DEGs were significantly enriched in humoral immune response, cell adhesion molecules, and IL-17 signaling pathways, and so on. Moreover, hypoxia VHL targets up was exceedingly up-regulated in STAS positive tumors through gene set enrichment analysis (GSEA). In addition, the abundance of regulatory T cells (Tregs) showed a borderline significant trend to be higher in STAS positive cases. Conclusions: Our study is the first to report the transcriptome profiles and TME of LUAD patients with STAS. These novel findings may add to further understanding underlying biological mechanisms of STAS occurrence and help developing rationale treatments to deliver more survival benefits for STAS positive LUAD patients.
Neoadjuvant Toripalimab plus chemotherapy in patients with stage IIB-IIIB NSCLC: A single-center, prospective, single-arm, phase 2 trial (Renaissance Study).
Authors: Yan Shi , Chen Jinfeng , Wang Jia , Lv Chao , Bi Jiwang , Yang Xin , Li Shaolei , Wang Yuzhao , Li Xiang , Yang Yue , Wu Nan 
Published: June 2022

e21128 Background: Neoadjuvant treatment of a programmed cell death protein 1 (PD-1) inhibitor plus chemotherapy has been shown to be promising in treating resectable non-small cell lung cancer (NSCLC). The current study aimed to investigate the efficacy and safety of toripalimab plus double platinum-based chemotherapy as neoadjuvant treatment for stage IIB-IIIB NSCLC. Methods: Study eligibility involved stage IIB-IIIB, wildtype EGFR/ALK NSCLC pts with ECOG PS 0-1 status. Pts received 2-4 cycles of toripalimab (240mg, q3w) plus cisplatin-based chemotherapy. All pts were assessed by imaging/surgical indication after the second cycle of treatment. Pts who cannot undergo surgery will be reassessed after another 1-2 cycles of neoadjuvant therapy. Primary endpoints were major pathological response (MPR), complete pathological response (pCR). Secondary endpoints were objective response rate (ORR), R0 resection rate and safety. Results: A total of 52 eligible pts (median age: 62, IQR: 45-76; female: 4, 7.7%) were enrolled and received 2-4 cycles neoadjuvant treatment since Mar 2021. 42 pts had squamous cell carcinoma and 10 pts had non-squamous cell carcinoma. Disease distribution in stage IIB, IIIA and IIIB consisted of 14, 30 and 8 pts, respectively. 15 pts were undergoing preoperative treatment or preparing for surgery, 32 pts underwent resection (median interval between neoadjuvant treatment and surgery: 67 days, IQR 39-113), 5 pts were unsuitable for surgery (1 pt had immune-related pneumonia; 2 pts who had stable disease were considered radical radiotherapy and immunotherapy for maintenance due to the difficulty of surgery induced by tumor location and lymph node metastasis; 2 pts continued toripalimab plus chemotherapy or radiotherapy due to high surgical risk induced by old age and poor performance status). 20 pts (20/32, 62.5%) achieved MPR, including 16 pts (16/32, 50%) with pCR. 6 pts (6/8, 75%), 12 pts (12/18, 66.7%), and 2 pts (2/6, 33.3%) with stage IIB, IIIA and IIIB achieved MPR respectively. R0 resection was achieved for all 32 pts (100%). 23 pts underwent surgery with cN2/N1 at baseline (23/24, 95.8%) achieved nodal downstaging. For pts who finished radiological reassessment (45 pts finished the treatment schedule and only 43 pts finished radiological reassessment), ORR was 83.7% (36/43). Grade 1-2 TRAEs were reported in 33 patients (33/45, 73.3%). Grade 3-4 TRAEs were reported in 6 pts (6/45, 13.3%). Conclusions: Toripalimab plus platinum-based doublet as neoadjuvant treatment yields a high MPR rate, manageable toxicity and feasible surgical resection in stage IIB-IIIB NSCLC. Clinical trial information: NCT04606303.
Insights into the advanced non-small cell lung cancer patient journey: Treatment decision-making, preferences, and quality of life considerations.
Authors: Wheatley-Price Paul , Ferris Andrea Stern , Barros Luciana Holtz De Camargo , Mancera Font Adriana , Ornstein Carly , Saez Daniel , Szmytke Ewelina , Vallone Stefania , May Suepattra Grace , Konidaris Gerasimos , Shaddock Hampton 
Published: June 2022

e21129 Background: Individuals with advanced non-small-cell lung cancer (aNSCLC) who have undergone multiple lines of prior therapy face a poor prognosis and limited treatment options, significantly impacting quality of life (QoL). This exercise explored European, North, and South American patient advocate perspectives on QoL and its relation to treatment decision-making and preferences in aNSCLC. Methods: A global aNSCLC patient advocacy advisory board was convened with organizations from Europe, US, Canada, and Brazil, asking participants about QoL and treatment side effects, and how these relate to subsequent care and treatment decision-making. The discussion was moderated by an oncologist, transcribed, and analyzed using thematic analysis. Results: Preserving one’s independence was highlighted as a key component of QoL, with advocates noting that tumor-related symptoms and treatment toxicities have a substantial negative impact on an individual’s ability to engage in daily activities. Fatigue – both physical and psychological – is especially burdensome, particularly for those who have undergone multiple lines of therapy. Participants also noted the need for more accessible care (e.g., telehealth appointments, oral therapies) that fits into the routines of individuals and caregivers. The importance of palliative care and its ability to improve QoL was noted, showing the need for health systems to better integrate palliative care into treatment regimens. Finally, participants noted that treatment priorities change as individuals undergo subsequent lines of therapy, with participants noting the importance of independence and QoL in later stages of therapy, and thus must be assessed regularly by the care team. Conclusions: Individuals with aNSCLC place importance on consideration of QoL when making treatment decisions, particularly those related to maintaining independence. While there remains a need for additional and more effective therapies, an integrated and accessible care approach, with patient-provider communication focusing on maintaining QoL and independence, should be a priority.