bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gaps and factors in patient awareness of biomarker test timing and purpose in non-small cell lung cancer (NSCLC): Baseline assessment for implementation of 4R Oncology model.
Authors: Mohindra Nisha Anjali , Trosman Julia R. , Houseknecht Stefanie , Feliciano Josephine Louella , Sacks Ruth Lauren , Cain Joan E. , Souter Benjamin , Waugh Wendi , Woodyard Jennifer , Martin Jeremiah , Schmidt Laura , Chang Cara , Rediske Anna , Zavala Sonia , Lycan Thomas William , Martin Nikki A. , Boehmer Leigh , Plotkin Elana , Lile Ashley , Weldon Christine B. 
Published: June 2023

e21059 Background: Biomarker testing is necessary for optimal 1st line treatment selection in advanced NSCLC. Patient understanding of timing and purpose of biomarker testing is imperative for patient engagement in care, but is challenging to achieve (Martin Oncol Issues 2022). The 4R Oncology model of patient self-management and timely care delivery has been shown to improve patient knowledge of timing/sequence of care in breast cancer (Trosman JCOOP 2021) but has not been studied in NCLSC in relation to biomarker testing. 4R is being implemented at 5 centers (3 community and 2 academic) in NSCLC. We report baseline assessment of patient awareness of biomarker testing timing and purpose to inform 4R implementation. Methods: Pre-implementation surveys of patients with advanced NSCLC at 5 centers Aug – Dec 2022. Metrics are listed in Table. Results: Survey response rate: 46% (65/142). Respondents were 65% white, 42% high school educated or less, 46% with annual income ≤$30K. While all patients were aware of receiving non-biomarker tests, > 40% were not aware of receiving biomarker testing (Table). About half knew why or how long they needed to wait for results, but only 29% received this information from providers. Of those tested, the majority reported provider discussions of biomarkers or therapy selection and were clear about results or therapy selection. Awareness (eg knowing to wait for results before therapy) was associated with receiving printed NSCLC materials (45% vs 7%, p < .01), education above high school (69% vs 41%, p = .03) and income > $30K (67% vs 32%, p = .01). Willingness to wait for test results was associated with knowing how to prepare for treatment while waiting (89% vs 46%, p < .01). Race did not impact these metrics. Conclusions: Considerable gaps exist in patient awareness of timing and purpose of biomarker testing. We refined the 4R model to emphasize biomarker timing in printed visual material, facilitate patient-provider discussions and engage patients in health maintenance while waiting for results. We revised 4R to a lower literacy level. Results will be reported when available. [Table: see text]
Prognostic effects of TP53 variants co-occuring in patients with HER2-mutated non-small cell lung cancer (NSCLC).
Authors: Feng Jamie , Hueniken Katrina , Fan Zhen (Jason) , Corke Lucy , Leighl Natasha B. , Liu Geoffrey , Bradbury Penelope Ann , Sacher Adrian G. , Eng Lawson , Stockley Tracy , Tsao Ming Sound , Shepherd Frances A. 
Published: June 2023

e21065 Background: TP53 variants are common in NSCLC and have been reported as prognostic of poor outcome. The impact of TP53 variants in ERBB2/HER2-mutated NSCLC is unclear. Methods: A total of 40 patients with HER2-mutated NSCLC at Princess Margaret Cancer Centre were identified retrospectively; next generation sequencing results were reviewed for TP53 variant status. Associations between TP53 status with patient and tumor characteristics, and outcomes (overall survival [OS] and progression-free survival [PFS]), were investigated. Median survival was computed by Kaplan-Meier estimator; differences between groups were assessed via Cox proportional hazards regression. Results: Co-occurring TP53 variants and HER2 mutations were found in 19/40 patients (47.5%). Median age was 64.5 years and most patients were female (65%), never-smokers (74%), and had adenocarcinoma (90%; Table 1). Median OS was 39.3 months (95% CI:31 months – not reached [NR]) in the TP53 wildtype (WT) cohort compared to 20.5 months (95% CI:3.7 months - NR) in the TP53 variant cohort (HR 2.65 (95% CI: 1.09-6.43; p = 0.03). Median PFS was 30.9 months [16.7-59.8] vs 15.9 months [10.2-NR], although not statistically significant (HR 1.86, 95% CI 0.83-4.18; p = 0.13). There was a tendency for presence of brain metastases at any point for those with TP53 variants (38% versus 63%, p = 0.11). Of the 29 de novo stage IV patients, 10 (36%) had first line targeted treatment. The rest had chemoimmunotherapy (29%), chemotherapy (25%) or immunotherapy (11%). Overall response rates were similar to first line palliative treatment (33% vs 38%, p = 1.00). Conclusions: Co-occuring TP53 variants with HER2 mutations are prognostic of shorter OS and PFS in NSCLC, and may be associated with a higher incidence of brain metastases. Our larger validation dataset with ~75 patients will be presented.[Table: see text]
Serum tumor biomarkers as a surrogate for radiographic assessment of non-small cell lung cancer.
Authors: Strum Scott , Vincent Mark David , Gipson Meghan , McArthur Eric , Breadner Daniel Adam 
Published: June 2023

e21076 Background: Conventional tumor markers are positioned to serve as a useful adjunct in lung cancer management. However, most studies in this field have been specific to a particular disease stage or treatment regimen. Thus, the purpose of this research was to assess whether three minimally invasive, low-cost serum tumor markers (CEA, CA19-9, and CA-125) held associations with radiographic and clinical outcomes in non-small cell lung cancer (NSCLC) patients who received systemic therapy in a more comprehensive patient population. Methods: This was a single-center retrospective study of NSCLC patients treated between January 2016 and August 2020. Serum tumor markers were statistically analyzed for differences in patients who responded or progressed (RECIST 1.1 or iRECIST criteria), associations with demographic and clinical characteristics, and all-cause mortality in pre-defined populations. Disease response was assessed radiographically using RECIST 1.1 criteria. Results: From 533 NSCLC patients screened, 165 met inclusion criteria. Of these, 50.9% were male and 49.1% female. 69.7% had stage IV disease at baseline. The proportion of patients with an elevated CEA, CA-125, and CA19-9 at baseline were 58.8%, 50.9%, and 30.3%, respectively. A subset of 92 patients had paired tumor markers and radiographic scans, from which median (IQR) fold-change in tumor markers from nadir to progression was 2.13 (IQR 1.24 - 3.02; p < 0.001) for CEA (n = 47), 1.46 (IQR 1.13 - 2.18; p < 0.001) for CA19-9 (n = 46), and 1.53 (IQR 0.96 - 2.12; p < 0.001) for CA-125 (n = 47). Median (IQR) fold-change in tumor markers from baseline to radiographic response was 0.50 (IQR 0.27, 0.95; p < 0.001) for CEA (n = 39), 1.08 (IQR 0.74, 1.61; p = 0.99) for CA19-9 (n = 35), and 0.47 (IQR 0.18, 1.26; p = 0.008) for CA-125 (n = 35). Lastly, an elevated baseline CEA was not associated with a difference in overall survival (HR 1.05, 95% CI 0.63-1.74, p = 0.84) in patients with stage IV disease within the total population. Conclusions: Serum CEA, CA-125, and CA19-9 levels were significantly different than nadir in patients who progressed. CEA and CA-125 were significantly different than baseline in those who responded. These cost-effective tumor markers may serve as an important adjunct to clinical decision making. Analysis within a controlled clinical trial is warranted.
The impact of cationic amphiphilic antihistamines on patients with lung cancer receiving immunotherapy.
Authors: Chiang Cho Hung , Chiang Cho Han , See Xin Ya , HSIA YUANPING , Peng Chun-Yu , Horng Chuan-Sheng , Chang Yu-Cheng , Wang Shih-Syuan , Chiang Cho Hsien , Peng Cheng-Ming , Shiah Her-Shyong 
Published: June 2023

e21078 Background: H1-antihistamines are long-used medications for the treatment of allergies. In preclinical studies, antihistamines, particularly those with cationic amphiphilic properties, have been found to have anti-tumor effects. In observational studies, H1-antihistamines have been associated with improved survival in patients receiving immune checkpoint inhibitors (ICIs) in pan-cancer association studies. However, the impact of antihistamines on lung cancer is unclear. We aim to evaluate the effect of antihistamines on lung cancer patients receiving ICIs. Methods: We conducted a retrospective cohort study at two tertiary referral centers in Taiwan involving lung cancer patients receiving ICI therapy. Antihistamines were subclassified into cationic amphiphilic and non-cationic amphiphilic antihistamines according to their lipophilic properties. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). Results: We identified 336 lung cancer patients receiving ICIs, of which 294 were antihistamine users (43 cationic amphiphilic and 222 non-cationic amphiphilic) and 42 were non-antihistamine users. Compared with non-antihistamine users, antihistamine users had a longer OS (median 24.4 vs. 6.4 months, p = 0.002) and PFS (median 8.2 versus 4.1 months, p = 0.049). Among antihistamine users, cationic amphiphilic antihistamine users had a longer OS (median 38.0 versus 17.8 months, p = 0.015) and PFS (median 17.5 versus 6.2 months, p < 0.001) than non-cationic amphiphilic antihistamine users. In Cox proportional hazard analysis, antihistamines and particularly cationic amphiphilic antihistamines were associated with a 30-55% lower risk of all-cause mortality and disease progression. Conclusions: The use of antihistamines, particularly those with cationic amphiphilic properties, was associated with improved outcomes among lung cancer patients undergoing immunotherapy.[Table: see text]
Efficacy and safety of dose-escalated alectinib in patients with metastatic ALK-positive NSCLC and CNS relapse on standard dose alectinib.
Authors: Cheung Justin Matthew , Kang Jiyoon , Yeap Beow Y. , Peterson Jenn , Do Andrew , Digumarthy Subba R , Gainor Justin F. , Lin Jessica Jiyeong 
Published: June 2023

e21079 Background: Central nervous system (CNS) metastases represent a common cause of morbidity and mortality in patients (pts) with ALK-positive (ALK+) non-small cell lung cancer (NSCLC), with limited therapeutic options. We previously reported re-induction of CNS responses using dose intensification of alectinib in two pts with metastatic ALK+ NSCLC who had experienced CNS progression on standard dose alectinib. However, this strategy has not been assessed in larger cohorts. Methods: In this retrospective study, pts were eligible if they had advanced ALK+ NSCLC with CNS relapse on standard dose alectinib (600 mg twice daily) and subsequently received dose-escalated alectinib (900 mg twice daily). Medical records and radiographic imaging were reviewed to determine treatment outcomes. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1. Treatment-related adverse events (trAEs) were graded per the CTCAE version 5.0. Results: 27 pts were eligible [male, 67%; median age at diagnosis, 53 (range, 31-69)]. Pts had previously received median 3 lines of systemic therapy (range, 1-12) and median 2 ALK TKIs (range, 1-4); all had received standard dose alectinib with CNS progression. 19 pts (70%) had received prior CNS-directed radiotherapy (RT) [median time from most recent RT to dose-escalated alectinib, 13.9 months (mos) (range, 0.2-52.3)]. The median duration of dose-escalated alectinib therapy in this cohort was 7.7 mos (95% CI, 4.8-10.9), with median overall progression-free survival (PFS) of 7.8 mos (95% CI, 4.9-13.7). Among 25 response-evaluable pts with baseline measurable or non-measurable CNS metastases, the CNS objective response rate (ORR) was 8.0% (95% CI, 1.0-26.0), with 2 pts having intracranial complete responses. CNS disease control rate (DCR) was 92.0% (95% CI, 74.0-99.0), with median CNS duration of response (DoR) of 5.3 mos (95% CI, 3.4-8.3) and median CNS PFS of 7.1 mos (95% CI, 4.4-13.7). Of 3 patients with baseline measurable CNS disease, all 3 had best intracranial response of SD, and median CNS PFS was 6.7 mos (95% CI, 6.2-not reached). Dose-escalated alectinib was well tolerated with no drug discontinuation due to trAE and no grade 3 or higher trAEs. One pt required dose reduction to 750 mg twice daily due to intolerable grade 2 fatigue. 23 pts (85%) experienced grade 1-2 trAEs. Grade 1-2 trAEs that occurred in 10% of pts were anemia (52%), fatigue (37%), constipation (26%), bilirubin increase (15%), alkaline phosphatase increase (15%), and peripheral neuropathy (11%). Conclusions: Dose intensification of alectinib demonstrated meaningful efficacy and tolerability in pts with metastatic ALK+ NSCLC who had experienced CNS disease relapse on standard dose alectinib, and may represent a viable therapeutic option for re-establishing CNS disease control.
Real-world assessment of treatment effectiveness in patients with advanced non-small cell lung cancer (aNSCLC) with MET exon 14 skipping (METex14).
Authors: Furqan Muhammad , Karanth Siddharth , Goyal Ravi K. , Shih Yu-Hsuan , Cai Beilei , Rombi Julien , Davis Keith L. , Caro Nydia , Saliba Teddy Rassem 
Published: June 2023

e21112 Background: Capmatinib is approved for patients (pts) with advanced stage (a)NSCLC harboring METex14. However, there is limited data on capmatinib activity in comparison to other approved therapies. We assessed real-world (rw) clinical outcomes of pts with aNSCLC with METex14 who initiated treatment with capmatinib, immunotherapy (IO), or chemotherapy (CT) regimens. Methods: In a retrospective chart review, data were abstracted by a sample of oncologists invited nation-wide in the US who randomly selected prespecified numbers of charts, with larger sampling targets for capmatinib and IO therapies. Eligible pts were aged ≥18 years, had stage ≥IIIB NSCLC and METex14; received first-line (1L) systemic therapy after 1 January 2017 with follow up of ≥6 months after starting 1L therapy (except death) as of the data abstraction date; and did not receive MET inhibitors other than capmatinib. Clinical outcomes included best overall real world response rate (rwORR), progression-free survival (rwPFS), overall survival (OS), and time to treatment discontinuation (TTD). RwORR was assessed using rw-RECIST guided by RECIST 1.1 criteria or physician documentation. All measures were descriptively analyzed. Time-to-event outcomes were assessed per line of therapy via Kaplan-Meier methods. Results: In total, 287 eligible pts were identified. Median age was 63.3 years, 71% were male, 41% were non-White, and 49.5% were treated in community settings. 15 pts had brain metastasis at diagnosis. Pts who received 1L capmatinib had higher rwORR and longer rwPFS, OS, and TTD than pts who received 1L IO mono or CT alone or in combination (Table 1). Pts treated with second-line (2L) capmatinib had higher rwORR than other treatments but was a smaller pt population. Conclusions: Our analysis suggests that capmatinib in aNSCLC with METex14 yields numerically better clinical outcomes than IO or CT alone or in combination. These findings support use of capmatinib in this setting and may inform clinical decision making in routine practice. [Table: see text]
Comparative proteomic profiling of plasma exosomes in patients with lung cancer with brain metastasis and liver metastasis.
Authors: Li Sini , Qu Yan , Liu Lihui , Bai Hua , Wang Jie 
Published: June 2023

e21123 Background: Brain or liver metastases are the main causes of lung cancer-related death. Predicting liver or brain metastases before having evidence from imaging of the tumors is challenging, but important for early patient intervention. Accumulating evidence has suggested that circulating exosomes in the blood could mediate cancer metastasis by transferring specific proteins to the target cells. Methods: Using liquid chromatography-MS/MS, we analyzed the proteomic profiles of plasma exosomes derived from 42 metastatic lung cancer patients (including 26 solitary brain metastasis (BM) and 16 solitary liver metastasis (LM)), 25 local advanced (LA) lung cancer patients without metastasis, and 5 healthy controls (HC), and explored organ-specific proteomic biomarkers. Results: 120 and 143 differentially expressed exosomal proteins were found to be the dysregulated candidates in BM and LM of lung cancer (BM-DEEPs, LM-DEEPs), as compared to the LA lung cancer samples, respectively. The bioinformatics analyses indicated the homogeneity and heterogeneity in BM-DEEPs and LM-DEEPs. In terms of homogeneity, they were mainly involved in the protein activation cascade, collagen-containing extracellular matrix, and ECM-receptor interaction. In terms of heterogeneity, the BM-DEEPs were significantly enriched in S100 protein and calcium-dependent protein, while the LM-DEEPs were mainly enriched in integrin, lipoprotein, heat shock protein and proteoglycans. Moreover, our study also revealed the heterogeneity in plasma-derived exosome proteomics in patients with non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), which partly explained the different metastatic characteristics of NSCLC and SCLC. Additionally, we found that MUC5B and SELL could be used as a reliable diagnostic marker of BM, while APOH, CD81 and CCT5 could help to diagnose LM in lung cancer patients. Conclusions: For the first time, we revealed the comprehensive and comparative proteomic profiles of plasma-derived exosomes from lung cancer patients with solitary brain and liver metastasis. We further proposed some potential biomarkers and pathological mechanisms, which could serve as excellent resource for further studies investigating lung cancer metastasis.
Analysis of significant weight gain in patients using alectinib for ALK-positive lung cancer.
Authors: Sikkema Barend Joël , de Leeuw Simon , Pruis Melinda , Mohseni Mostafa , Veerman Geerten Dieuwert Marijn , Paats Marthe , Dumoulin Daphne W , Smit Egbert F. , Schols Annemie M.W.J. , Mathijssen Ron H.J. , Van Rossum Elisabeth , Dingemans Anne-Marie C. 
Published: June 2023

e21138 Background: Alectinib is standard of care for metastatic anaplastic lymphoma kinase positive (ALK+) nonsmall cell lung cancer (NSCLC). Weight gain is an unexplored side effect reported in ~10%. To prevent or intervene alectinib-induced weight gain, more insight in its extent and etiology is needed. Methods: Change in body composition was analyzed in a prospective series of 46 patients with ALK+ NSCLC, treated with alectinib. Waist circumference, skeletal muscle (SM), visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were quantified using sliceOmatic software on computed tomography (CT) images at baseline, three months (3M) and one year (1Y). To investigate an exposure-toxicity relationship, alectinib plasma concentrations were quantified. Four patients with > 10 kg weight gain were referred to Erasmus MC Obesity Center for in-depth analysis (dietary habits, metabolic/endocrine assessment). Results: Mean increase in waist circumference was 9 cm (9.7%, p < 0.001) in 1Y with a 40% increase in abdominal obesity (p = 0.014). VAT increased 10.8 cm2 (15.0%, p = 0.003) in 3M and 35.7 cm2 (39.0%, p < 0.001) in 1Y. SAT increased 18.8 cm2 (12.4%, p < 0.001) in 3M and 45.4 cm2 (33.3%, p < 0.001) in 1Y. The incidence of sarcopenic obesity increased from 23.7% to 47.4% during 1Y of treatment. Baseline waist circumference was a positive predictor of increase in VAT (p = 0.037). No exposure-toxicity relationship was found. In-depth analysis showed increased appetite in two patients and metabolic syndrome in all four patients. Conclusions: Alectinib caused significant increased abdominal obesity, sarcopenic obesity, SAT and VAT quickly after initiation. This may lead to serious metabolic disturbances in long-surviving patients.[Table: see text]
PD-L1 expression as a unique negative predictive biomarker in advanced squamous NSCLC when treated with first-line chemotherapy.
Authors: Wong Zhun Hong Nicky , Zhao Joseph J , Zhu Ke Xin , Yap Dominic Wei Ting , Kumarakulasinghe Nesaretnam Barr , Huang Yiqing , Sundar Raghav 
Published: June 2023

e21140 Background: PD-L1 expression has been established as a positive predictive biomarker for immune checkpoint inhibition in advanced non-small cell lung cancer (NSCLC). We hypothesize that PD-L1 serves as a negative predictive biomarker of chemotherapy in squamous NSCLC in contrast to non-squamous NSCLC. Methods: Phase III randomized trials that investigated PD-L1 expression as a biomarker in advanced squamous NSCLC at first-line were identified and included through a systematic search of Embase and PubMed from inception until 24th September, 2022. To investigate the anti-thesis, trials that reported PD-L1 stratified KM plots in non-squamous NSCLC were evaluated too. Only trials that reported PD-L1 stratified KM curves of chemotherapy arms were included. A graphical reconstructive algorithm was used to retrieve survival data from reported Kaplan-Meier (KM) curves. Pooled survival analyses for progression-free and overall survival (PFS, OS) were conducted with Cox proportional hazard models with a shared-frailty term incorporated to account for inter-study differences. Results: Five phase III randomized trials (2 squamous NSCLC and 3 non-squamous NSCLC) reporting PD-L1 stratified KM plots of patients treated with first-line chemotherapy were included. In patients with squamous histology, PD-L1 expression negatively predicted for chemotherapy benefit – patients with higher PD-L1 expression were at a higher risk of tumour progression (PD-L1 ≥50% [n = 187] vs PD-L1 < 1% [n = 247]: HR = 1.474, 95%-CI: 1.171-1.855, p < 0.001; PD-L1 ≥50% [n = 187] vs PD-L1 1-49% [n = 239]: HR = 1.300, 95%-CI: 1.033-1.625, p = 0.025). Conversely, in patients with non-squamous histology, no significant differences in tumour progression was shown between PD-L1 subgroups (PD-L1 ≥50% [n = 137] vs PD-L1 < 1% [n = 242]: HR = 1.238, 95%-CI: 0.919-1.667, p = 0.160; PD-L1 ≥50% [n = 137] vs PD-L1 1-49% [n = 199]: HR = 0.958, 95%-CI: 0.714 -1.285, p = 0.780). No significant difference in OS was found between PD-L1 subgroups dichotomized at 1% & 50% among patients with squamous histology. In contrast, in patients with non-squamous histology, PD-L1 was a positive biomarker for chemotherapy benefit – patients with higher PD-L1 were at a lower risk of mortality (PD-L1 ≥50% [n = 40] vs PD-L1 < 1% [n = 150]: HR = 0.523, 95%-CI: 0.316-0.865, p = 0.012). Conclusions: These findings suggest that PD-L1 expression is uniquely a negative predictor for tumour progression in advanced squamous NSCLC treated with first-line chemotherapy.