bluuebunny/crossref_metadata_2025_split huggingface dataset:
Why are oncologists not testing all NSCLC patients for biomarkers in the U.S. market?
Authors: Winkelman Daniel F. , Varkhedkar Vaibhav M. , Stellander-Amato Holly , Bailey Lesley , Kachadourian Anise 
Published: June 2021

e21003 Background: NSCLC has the greatest number of biomarkers of any tumor type. If a patient is not biomarker tested, he or she may not receive access to targeted therapies that often offer greater efficacy through personalized therapy. The purpose of this research study is to examine the reasons certain lung cancer patients are not tested in the United States for biomarkers. Methods: This study followed market research best practices. The study was based on a survey of the BrandImpact Oncology panel conducted on patient visits during Q4 2020 at the point-of-prescribing. Results: The baseline measure of NSCLC patients that were being treated but had a biomarker status that was unknown ranges from 9% to 12% of patient visits. The biomarkers examined included ALK, ROS-1, EGFR and PD-L1. The Oncologists who treat NSCLC patients received the following question: When treating patients in your practice with NSCLC cancer what are your top 3 reasons for not conducting biomarker testing? As outlined in the table below which reflects all survey responses, the top four reasons for not conducting biomarker testing are: not enough tumor sample for testing purposes, patient has early stage of disease, patient is not healthy enough and patient cost associated with testing. Conclusions: The overall results indicate the absence of biomarker testing for lung cancer patients is mainly due to two different patient types. The early-stage patient was a key reason for not testing despite advances in early stage indications and diagnostic technology which provide increasing evidence that testing should be done earlier in the treatment journey. The late-stage patient which is seen more often in Academic institutions and who often has more aggressive cancer. The speed of receiving the biomarker test results for these more severe patients likely needs to be addressed. In the Community, setting cost of branded therapies can be an issue and in some cases biomarker testing is not readily available in all practices. It should also be noted that “not enough tumor sample for testing” was the number one reason for not conducting biomarker testing, but this issue can now be addressed through liquid NGS technology.[Table: see text]
Effect of PDL1 expression [exp] on overall survival [OS] in patients [pts] with metastatic adenocarcinoma lung [MAC]: Illinois CancerCare [ILCC] analysis.
Authors: Kumar Nikhil , Gomez Patrick Leigh , Harper Jamie 
Published: June 2021

e21005 Background: Effect of PDL1 on OS in patients with MAC is controversial. This relationship has not been studied systematically in U.S. midwestern population, a largely homogenous Caucasian group. We examined the effect of PDL1 expression on OS in MAC pts at ILCC, one of the largest practices in U.S. Midwest. Methods: We conducted a retrospective analysis of all MAC pts who presented at ILCC in 2018. PDL1 status was defined as high if PDL1 was ≥50%, low if 1≤50% & -ve if 0≤1%. High and low groups together were called +. Statistical analysis was performed using the log rank Kaplan Meier method. Results: Results were available in 104/125 pts [83%]. 68/104 pts [65%] received anti PDL1 antibodies Nivolumab, Pembrolizumab, Durvalumab, & Atezolizumab. 43/68 pts were PDL1+ and 25/68 were -ve. Median OS of PDL1+ high exp was 10.78 months [m] & of low exp was 9.7 m. There was no statistical difference in OS in these groups [p = 0.984778]. We also evaluated this relationship between all PDL1+ pts [high and low expressers together] and PDL1- ve pts. We did not find any difference between these groups either. Median OS of all PDL1+ was 9.77 m & PDL1 -ve was 6.67 m [p = 0.435038]. Conclusions: Our study suggests that OS of MAC in our pt population is not influenced by PDL1 status. The potential influence of patient ethnic, genetic & molecular biomarker traits on OS needs to be explored further.[Table: see text]
Comprehensive cancer genomics-based screening of new therapeutic targets and biomarkers for lung cancer.
Authors: Daigo Yataro , Takano Atsushi , Nakamura Yusuke 
Published: June 2021

e21031 Background: Since the clinical outcome of advanced lung cancer patients is still poor after standard therapies, development of new anti-cancer drugs with minimum risk of adverse effects and cancer biomarkers for precision medicine is urgently required. Methods: We have been screening new therapeutic target molecules and molecular biomarkers for lung cancers as follows; i) To identify overexpressed genes in lung cancers by the gene expression profile analysis, ii) To verify the target genes for their scarce expression in normal tissues, iii) To validate the clinicopathologic importance of their protein expression by tissue microarray covering 263 lung cancers, and iv) To confirm their function for the growth and/or invasive ability of the lung cancer cells by siRNAs and gene transfection assays. Results: We identified dozens of candidate target molecules and selected a gene encoding protein with a GAP domain, LAPG1 (lung cancer-associated protein with Gap domain 1). Immunohistochemical analysis showed that LAPG1 expression was observed in 69.9% of lung cancers. Moreover positivity of LAPG1 expression was associated with poor prognosis of lung cancer patients. Knockdown of LAPG1 expression by siRNAs suppressed growth of lung cancer cells. Introduction of LAPG1 increased the invasive activity of mammalian cells, indicating that LAPG1 could be a prognostic biomarker and therapeutic target for lung cancers. Conclusions: Comprehensive cancer genomics-based screening could be useful for selection of new cancer biomarkers and molecular targets for developing small molecules, antibodies, nucleic acid drugs, and immunotherapies.
Antifungal imidazole: Potential new antineoplastic agent-cytotoxic effects on non-small cell lung cancer cell lines (A549).
Authors: Kahraman Erkan , Goker Erdem 
Published: June 2021

e21037 Background: There are many drugs that can be applied to the treatment of lung cancer. These therapeutics include classical chemotherapeutics, targeted drugs against driver mutations, and immunotherapeutics. However, still, new agents are required to better results and patients outcomes. Recently, imidazole and its compounds, a type of antifungal drugs, were found to have antitumor efficacy in several cancer types. Its effects on non-small-cell lung cancer cells are yet known. This study aimed to detect anti-cancer properties of imidazole on non-small-cell lung cancer cells and suitability for clinical usage as an anti-cancer agent. Methods: We used A549 cell lines that are non-small-cell lung cancer cells in this study. A549 cells were treated with imidazole (molecular grade) at 1, 5, 10, 20, 40, 80 mM doses for 24, 48 and 72 hours. Cytotoxicity and IC50 values (the half-maximal inhibitory concentration) were calculated using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) analysis. Colony formation assay was performed to detect the effect of imidazole on cancer cell colony formation ability. The cellular morphological alterations were observed on bright-field microscopy using Giemsa staining. Cellular migration status of A549 cells was defined with in vitro scratch assay up to 48th hour. Results: Cytotoxicity assay results showed that low-level imidazole induced cell proliferation. However, high-level imidazole treatment decreased the cell viability of A549 cells in a dose and time-dependent manner. The IC50 value was calculated as 60 mM, 28 mM, and 15,9 µM doses respectively at 24, 48, 72 hours in A549 cells. Also, we determined that the number of colonies (number of colonies: 42.7 ± 3.06) formed in A549 cell lines treated with imidazole at IC50 dose was statistically less than the colony number of the control group (number of colonies: 70.7 ± 5.13) (p < 0.01). Interestingly, we observed that colony number increased at a low dose (at 5 mM) imidazole treated group, statistically significant (p < 0.05). Cellular morphology was not affected at low doses; however, at the IC50 dose, A549 cells changed their cellular morphology, lost cell-cell contact, decreased cytoplasmic volume, and differentiated from parental morphology. In addition to these effects, we observed that imidazole treated cells decreased their migration capabilities compared with control group cells (p < 0.05). Conclusions: Our results have shown that antifungal imidazole treatment inhibits cancer cell biological responses such as proliferation, colony formation ability, and motility in non-small lung cancer cell lines in a dose and time-dependent manner. These results suggest that imidazole would be the right candidate for the synergy with other therapeutic options such as immunotherapy. This introductory study allows us further studies exploring the synergy and its mechanism.
Does denosumab offer survival benefits? Our experience with denosumab in metastatic non-small cell lung cancer patients treated with immune-checkpoint inhibitors.
Authors: Cao Yenong , Afzal Muhammad Zubair , Shirai Keisuke 
Published: June 2021

e21039 Background: Lung cancer is the leading cause of cancer-related death in the United States. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of non-small-cell lung cancer (NSCLC). Denosumab is a humanized monoclonal antibody to RANK ligand used to prevent skeletal-related events of bone metastases in solid tumors. In preclinical and some clinical studies, denosumab have shown to have some anti-tumor properties. We are reporting the clinical outcomes in our NSCLC patients who received RANKL inhibitor in combination with ICIs. Methods: This observational study used retrospective data from a tertiary cancer center from 2015-2020. Stage IV non-small cell lung cancer patients who received denosumab within 30 days of ICIs (pembrolizumab, nivolumab, atezolizumab, ipilimumab) were included. Median overall survival (OS), progression free survival (PFS), best radiographic responses were obtained. Univariate, multivariate analyses and logistic regression analyses were done, and Kaplan-Meier curves were obtained for survival analysis. Results: We identified 69 patients and all had skeletal metastasis, and 37.7% had brain metastases. Median duration of concomitant use of denosumab and ICI was 1.5 months. Median OS was 6.3 months and median PFS was 2.8 months. Overall response rate was 18.8% and disease control rate was 40.6%. Median OS in patients with concomitant denosumab and ICIs more than 3 months was 11.5 months, comparing to 3.6 months in patients with < 3 months of concomitant therapy (P=0.0005). OS and PFS did not differ with respect to brain metastases or number of skeletal metastases. However, the duration of ICIs and denosumab overlap was associated with improved OS and PFS. Among the 18.8% of patients who achieved complete response (CR) and partial response (PR), six-month survival rate was 100% and one-year survival rate was 69.2%. Conclusions: Patients receiving combination therapy did not perform poorly despite of poor prognostic features such as brain metastases and numerous skeletal metastases. Although we did notice potential benefit of the longer duration of concomitant use of ICI and denosumab, future prospective clinical trials are needed to evaluate the synergistic effect of RANKL inhibitors/ICI and if duration of RANKL inhibitors matters.
Myocarditis as a rare, yet serious adverse event associated with immune checkpoint inhibitors in patients with non-small cell lung cancer: Case series from a large community-based cancer center.
Authors: Hendawi Mohamed , Peterson Luke , Tadesse Eyob ale , Wolf Frank M. , Brown Thomas D. , Thompson Michael A. 
Published: June 2021

e21047 Background: Patients (pts) with lung cancer and other cancers treated with immune checkpoint inhibitors (ICI) may experience immune related adverse events (irAE). These can present with variable severity and with single- or multi-organ involvement including pneumonitis, colitis, hepatitis, and myocarditis/pericarditis. The incidence of myocarditis has been reported between 0.06% and 2.4% and is associated with a high mortality (25% to 50%). This retrospective review of real-world data (RWD) investigates myocarditis as a high-grade adverse event in pts with lung cancer treated with ICIs. Methods: Pts were identified and characterized using RWD in the Syapse Learning Health Network platform from 2010 to 2020 at Advocate Aurora Health Care. Eligible pts included: ≥18 years old; histologically confirmed NSCLC; and myocarditis diagnosis by ICD codes. Additional chart review was performed to confirm timing of ICI treatment and myocarditis. All pts identification and review were performed after IRB review. Results: 12,686 pts with non-small cell lung cancer were eligible for review. The median age at diagnosis was 70; 54% were female; 86% were White and 12% were Black; 1,975 (15.6%) were treated with an ICI and of those 4 cases (0.2%) of myocarditis were identified. All 4 pts were White females, ages 46, 59, 65, and 74 years. Pathology included lung adenocarcinoma (3) and an undifferentiated lung carcinoma (1). All pts had metastatic disease, and none had a prior history of cardiac disease. ICIs were pembrolizumab (2), durvalumab (1), and nivolumab (1). Median time from initial dose of ICI to diagnosis of myocarditis was 62 days [range: 42-185]. All 4 pts presented with chest pain and elevated troponin T [median 0.07 ng/ml (range: 0.06-0.08)]. All pts had echocardiography at the time of diagnosis, and 2 pts had cardiac MRI that confirmed myocarditis. 3 pts were treated with a prednisone taper. 1 pt died of recurrent congestive heart failure and ventricular tachycardia despite rescue attempt with high dose corticosteroids. 2 pts had additional concomitant irAEs of hypothyroidism/colitis, and thyroiditis/pneumonitis, respectively. Conclusions: Many irAEs are reversible. This RWD analysis confirms that clinically evident myocarditis is a rare but serious adverse event of ICI therapy. Early consideration, diagnosis, and intervention may help prevent poor outcomes. Termination of ICI therapy along with initiation of corticosteroids constitute the current standard of management. Further research is warranted to better identify high risk groups, surveillance measures, and improved management of ICI associated myocarditis.
The relationship between evolving sarcopenia and efficacy of immune checkpoint inhibitor in non-small cell lung cancer patients.
Authors: Makiguchi Tomonori , Tanaka Hisashi , Taima Kageaki , Tatsuo Soichiro , Iida Saya , Kakeda Shingo , Tasaka Sadatomo 
Published: June 2021

e21049 Background: Sarcopenia has been receiving attention due to its association with prognoses in patients with cancer. We investigated the association between evolving sarcopenia assessed with computed tomography (CT) and outcome of non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICIs). Methods: In this retrospective study, 47 NSCLC patients who received ICIs at our Hirosaki University Hospital were enrolled. Skeletal muscle area at the level of the third lumbar vertebra (L3-SMA) was measured from CT images before and 90 days after the ICI treatment. The factor related to the poor efficacy of ICIs was determined by logistic regression analysis. The prognostic cut-off value was estimated by a receiver operating characteristic (ROC) curve. As covariate factors, age, gender, smoking history, histology, performance status (PS), PD-L1 tumor proportion score (TPS), status of driver mutations, body mass index (BMI), serum protein and albumin levels, and lymphocyte count were included. Results: In the univariate analysis, reduction rate of L3-SMA, PS, BMI, serum protein and albumin levels, and lymphocyte count were significantly associated with efficacy. In the multivariate analysis, only reduction rate of L3-SMA was significant. The cut-off value was estimated to be 6%. The study subjects were divided into two groups by the cut-off value. In both of progression free and overall survival analysis, those with more than 6% of reduction had significantly shorter period being free of events than that of the other. Conclusions: Evolving sarcopenia assessed with CT images is promising as a prognostic factor in Japanese NSCLC patients receiving ICIs.
Surrogates of response to treatment of non-small cell lung cancer with immunotherapy: Toxicity and leukocyte ratios—Experience of a center.
Authors: Moratiel Pellitero Alba , Ruiz Moreno Ines , Cruellas Mara , Alonso Marin Natalia , Ocáriz Maitane , Gascon Ruiz Marta , Sesma Goñi Andrea , Zapata-Garcia Maria , Zurera Berjaga Maria , Marti Pi Maria , Goas Gomez Ana , Camacho Fuentes Carlos , Sanchez Cortes Carla , Alvarez Maria , Quilez Elisa , Torres Irene , Lambea- Sorrosal Julio Jose , Isla Dolores , Lastra Rodrigo 
Published: June 2021

e21052 Background: Immunotherapy is proposed as a therapeutic novelty in metastatic non-small cell lung cancer (NSCLC), in many cases already in front line. It presents different adverse effects than traditional schemes, due to the stimulation of the immune system. There is a possible relationship between toxicity and response. Neutrophil-to-lymphocyte ratio (NLR) as a possible predictive factor of response. Objectives: Evaluating the response according to the toxicity degree in NSCLC patients in real clinical practice. Analyze whether pretreatment NLR high patients have a worse prognosis. Methods: Observational, retrospective, analytical, single-center study. HCULB stage IV NSCLC patients with inmunotherapy treatment during 2016-2018. Descriptive and multivariate analysis. Toxicity grade: CTCAE version 4.0. Response assessment: RECIST 2.0 and immunorelated criteria. Toxicity degree and response (global and individualized results according to treatment and histology). Neutrophil-to-lymphocyte ratio and response. Results: N = 43 patients (35 men, 8 women). Average age 64 years. Response: 3 complete response (CR) (toxicity ≥2), 13 partial response (PR) (toxicity ≥1), 13 stable disease (SD), 12 progression (P) (only 4 toxicity and ≤2), 2 not evaluated. Hypothyroidism as the most common irAE. Relationship between toxicity and response: the absence of irAEs conditions worse prognosis p < 0.05. Histology: 25 adenocarcinoma [18 with irAES (1 CR, 7 PR, 8 SD,) and 7 without (1 SD, 5 P, 1 no ev.)]; 17 squamous [13 with irAES (1 CR, 6 PR, 4 SD) and 4 without (3 P, 1 no ev.)]; 1 adenosquamous with irAES and CR. Drug: Atezolizumab N = 8 [6 with irAES (2 PR, 3 SD, 1 P) and 2 without (both P)], Nivolumab N = 16 [9 with irAES (1 CR, 3 PR, 3 SD, 2 P) and 7 without (1 SD, 4 P, 2 no ev.)], Pembrolizumab N = 19 [17 with irAEs (2 CR, 8 PR, 6 SD, 1 P) and 2 without (both P)]. Significant positive correlation between toxicity and response (p < 0.001) R = 0.067, (CI 99% 0.378-0.837), regardless of histology and drug. It is observed a better response in those patients who presented a NRL close to 3 or less at the beginning of treatment. On the contrary, it is observed that subjects with NRL greater than 4 obtained worse results when they were treated with immunotherapy. Conclusions: The appearance of irAES like a response indicator of immune system, seem to conditione better evolution. In contrast, the absence of toxicity predicts a worse prognosis. Further studies with a larger sample are needed to confirm our findings about the predictive value of NLR and optimize therapeutic regimens if necessary.
A real-world study of camrelizumab in the treatment of advanced lung cancer patients.
Authors: Gu Kangsheng , Bi Minghong , Zhao Dong , Cheng Huaidong , Wang Genhe , Qian Hong , Min Xuhong , Xia Xiaoyang , Wang Fan , Hu Zhiqiang 
Published: June 2021

e21056 Background: Camrelizumab, as a humanized antibody against PD-1, has shown high efficiency and survival benefits in clinical studies on lung cancer treatment. This study aims to observe the efficacy and safety of Camrelizumab in the treatment of advanced lung cancer in the real world. Methods: This is a prospective, open, multi-center observational study that includes patients with advanced lung cancer who are older than 18 years of age, regardless of gender, with an ECOG score of 0-2. Results: As of November 18, 2020, a total of 253 patients have been enrolled. Males accounted for 187 cases (74.2%). The ECOG PS score was 0 in 44 cases (17.3%), 1 in 162 cases (64.0%), and 2 in 47 cases (18.6%). There were 181 patients (71.5%) of stage IV, 96 patients (37.9%) of adenocarcinoma, and 98% of patients did not undergo PD-L1 testing. A history of radiotherapy accounted for 31.2%, and a history of surgery on the primary lesion accounted for 20.2%. Camrelizumab accounted for 29.6% of the first-line treatment, 27.2% of the second-line treatment, and 43.1% of the third-line and above. Camrelizumab monotherapy accounted for 20.1%, camrelizumab combined with chemotherapy accounted for 56.3%, combined anti-angiogenesis therapy accounted for 22.1%, and combined anti-angiogenesis + chemotherapy accounted for 1.5%. Among the 199 patients with evaluable efficacy, 4 were CR, 46 were PR, 116 were SD, and 33 were PD. The ORR reached 25.1% and the DCR reached 83.4%. The overall adverse event rate was 33.7%, the major adverse event RCCEP rate was 22.6%, appetite loss was 5%, and fatigue was 3.5%. There were 4 cases (2%) of RCCEP with adverse events greater than or equal to grade 3. Conclusions: In this real-world study of lung cancer, most of the patients enrolled were patients with poor PS score and late stage, but the efficacy and safety of camrelizumab in patients with advanced lung cancer were still confirmed. The dominant population and combination therapy are still under study. Clinical trial information: ChiCTR2000034595.
Association of MUC16 mutations with immunotherapy biomarkers in Chinese non-small cell lung cancer patients.
Authors: Han Tao , Guo Taiyan , You Xia , He Qianru , Zhang Qin , Qi Chuang 
Published: June 2021

e21061 Background: MUC16 is frequently mutated in non-small cell lung cancer (NSCLC). Previous studies showed MUC16 mutation were associated with TMB and prognostic outcome in gastric cancer patients and may benefits for patients with immunotherapy. Herein, we aimed to characterize the association of MUC16 with immunotherapy biomarkers in Chinese and Western NSCLC patients. Methods: Next-generation sequencing data and clinical data were collected from 1053 TCGA NSCLC patients (Western cohort). A 539-gene panel targeted sequencing assay was performed on FFPE tumor samples from 1056 Chinese pan-cancer patients (Chinese cohort). Both MUC16 mutation ratio and TMB were calculated on the two cohorts following the same criteria. Results: In total, 269 (25%) of the 1056 Chinese patients and 494 (47%) of the 1053 Western patients had at least one mutation of MUC16 genes ( MUC16 mutant group). The Chinese cohort had a higher mutation frequency of MUC16 gene than the Western cohort (25% vs. 47%, p＜0.001). In both cohorts, TMB was higher in the MUC16 mutant group compared to non- MUC16 mutant group. In Chinese cohort, PD-L1 positive was not associated with MUC16 mutation. However, patients with MUC16 mutation were not associated with prolonged survival in Western immunotherapy cohort. Conclusions: Our study provided a landscape of MUC16 mutations in a much larger Chinese NSCLC group, which could be a valuable complement to TCGA dataset. Both in Chinese and Western cohorts, the higher TMB in MUC16 mutant patients suggested potential efficacy from immunotherapy of MUC16 mutant group. A larger validation cohort of MUC16 mutant is required to confirm these findings in the further.