bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a serum miRNA panel for detection of early stage non-small cell lung cancer.
Authors: Zhang Echo Xinyu , Su Chang , Cai Songhua , Qu Jiahao , Guo Xiaotong , Cao Yuan , Cao Mengjing 
Published: June 2024

3058 Background: Lung cancer remains the leading cause of cancer deaths, largely due to late-stage diagnosis. Early detection significantly improves survival rates, but current methods like chest X-rays and low-dose CT (LDCT) scans face limitations in sensitivity and specificity. MicroRNAs (miRNAs) are small non-coding RNAs whose dysregulation has been widely observed in different stages of cancer. Evidence suggests that circulating miRNAs could be promising biomarkers for early diagnosis of lung cancer. In this study, we developed and validated a 15-miRNA panel as a blood-based minimally invasive test for early detection of non-small cell lung cancer (NSCLC) using the proprietary multiplex quantitative real-time PCR (qPCR). Methods: 332 serum samples (182 Stage I&II NSCLC, 150 healthy controls) were divided into training (n=266) and validation (n=66) cohorts. Differentially expressed serum miRNAs were screened with Miseq sequencing followed by qPCR validation. The multi-miR panel was developed with a logistic regression model and validated using an independent cohort. Receiver operating characteristic curves were constructed to evaluate the diagnostic accuracy of the panel. A stem-loop quadruplex qPCR assay was invented for concurrent detection of 4 miRs in a single reaction. Results: 15 differentially expressed miRNAs were selected for logistic model construction based on their Ct values (Ct<35) and high diagnostic accuracy of stage I&II NSCLC (AUC>0.7). The 15-miRNA panel model achieved 88.4% sensitivity, 81.7% specificity (AUC = 0.912) in the training cohort (Table), and was validated with 94.4% sensitivity, 73.3% specificity (AUC = 0.892) in the validation cohort. Quantification of 15 miRs and 1 internal control was performed in 4 reactions tubes via quadruplex qPCR assay. Conclusions: The serum 15-miR panel developed and validated in this retrospective study exhibited robust performance for detection of early stage NSCLC. The panel demonstrates potential diagnostic applications and clinical utility to be implemented together with LDCT in current lung cancer screening program as a blood biomarker to reduce false positive results. In addition, the proposed stem-loop quadruplex qPCR system offers an efficient and promising approach for miRNA profiling in future clinical applications. [Table: see text]
A highly sensitive, low input, and automated assay for molecular residual disease detection (MRD) using whole-genome sequencing (WGS).
Authors: Liu Li , Tsai Jeff , Luong Khai , Bilke Sven , Davila Michael , Ding Yuan , Do Manh Vu , Gibson Jacob , Movsesyan Artem , Roessler Kyria , Song Fan , Talia Heather , Taylor Pete , Truong Jacquelyn , Wu Weixin , Zhu Yunjiao , Han James , Pawlowski Traci L. 
Published: June 2024

3060 Background: Molecular residual disease (MRD) detection using cell-free DNA (cfDNA) for solid tumors requires a highly sensitive and specific assay that can overcome the limitation of low abundance circulating-tumor DNA (ctDNA) in a standard blood draw with fast sample-to-answer turn-around time (TAT). Here we describe the development and analytical performance of Illumina’s TruSight Oncology MRD WGS assay (TSO MRD, for research use only), for detecting MRD using tumor-informed whole-genome sequencing (WGS) of cfDNA extracted from plasma samples across multiple cancer types. Methods: The TSO MRD assay was built using Illumina’s best-in-class WGS library preparation, informatics and sequencing technologies. The assay is composed of two major steps, fingerprinting and ctDNA detection. At the fingerprinting step, the DNA from tumor tissue and matched normal samples is analyzed through WGS to generate a sample specific somatic variant list. At the ctDNA detection step, the cfDNA extracted from plasma is analyzed through shallow WGS and the presence of ctDNA is detected using the tumor specific fingerprint as an input in the MRD analysis pipeline. The plasma extraction and WGS library preparation workflows are fully automated for high-throughput sample processing with minimum hands-on time and touch points. Results: Testing of commercial MRD reference materials and ctDNA-positive samples serially diluted into normal cfDNA background demonstrated a limit of detection of down to 0.001% VAF or 10 parts per million (PPM) in multiple cancer types. Testing of a panel of normal plasma samples from healthy individuals assessed against 20 sets of fingerprints from multiple cancer types demonstrated an analytical specificity of 99.7%. Testing of ctDNA samples with multiple operators, instruments and library prep start days demonstrated high reproducibility in MRD detection. The ctDNA testing works at an optimal input amount of 5 ng and a minimum input amount down to 2 ng, which yields a high sample success rate from one standard 10 ml of blood draw. The TAT of the fingerprinting and the ctDNA detection steps is 5-7 days, respectively. Conclusions: The TSO MRD assay demonstrated high analytical sensitivity and specificity in detecting the presence of ctDNA from low input plasma samples with automated workflow and fast TAT. This assay enables a single streamlined solid tumor MRD platform for multiple cancer types.
RNA-based fusion testing in gastrointestinal (GI) carcinomas: A single-institution experience.
Authors: Caughey Bennett Adam , Wang Charlotte , Iafrate A. John , Corcoran Ryan Bruce 
Published: June 2024

3061 Background: Molecular profiling with next-generation sequencing is critical to provide appropriate clinical care in most GI cancers. However, outside of biliary tract cancers (BTCs), the utility of routine comprehensive fusion testing in GI carcinomas is not well established. We evaluated fusion testing of GI carcinomas in routine clinical care at Massachusetts General Hospital Cancer Center (MGHCC). Methods: Patients with confirmed GI carcinomas who underwent RNA-based tissue fusion testing at MGHCC between Jan 2016 and April 2023 were included. Samples with tumor cellularity <20% or not meeting quality controls were excluded. Fusions of known clinical relevance were evaluated for molecular and histopathologic associations. Results: 2300 GI cancers with at least 1 fusion assay were included (see Table). As expected, BTCs had the highest incidence of fusions (13.7%), 80% of which were FGFR2. Fusions were detected in 3.9-7.7% of colorectal (CRC), pancreatic ductal (PDAC), esophagogastric (EGC), and small bowel (SBC) carcinomas. Fusions of BRAF, FGFR1-3, NTRK1/3, RSPO2/3, and NRG1 were rare (excepting FGFR2 in BTCs) but observed in 3 or more cancer types. Consistent with prior studies, the 3 NTRK1 fusions observed in CRC were associated with MLH1 loss and 15 of 21 (71%) PDAC tumors with fusions were KRAS wild-type (WT). RSPO2/3fusions were the second most frequent after FGFR1-3. RSPO3fusions were predominantly seen in CRC and SBC and were associated with poorly differentiated histology (43%), microsatellite stability (100%), APC WT (92.6%), and KRAS (44.4%), BRAF V600E (40%), and BRCA1/2 mutations (29.6%). Of 5 RSPO2fusions, 4 were in EGC and 100% had poorly differentiated histology and TP53 mutations. No fusions were detected in 47 GI neuroendocrine tumors. Conclusions: Although individually rare, in aggregate RNA-based testing identifies clinically relevant fusions in a small but significant fraction of BTC, CRC, PDAC, EGC, and SBC. Molecular selection may identify subpopulations in which fusion testing is higher yield. CRC and SBC harboring RSPO3 fusions have a distinct molecular and pathologic phenotype, including a potentially novel association with BRCA1/2 mutations. Several detected fusions had novel partners that were nonetheless predicted actionable, highlighting the utility of partner-agnostic fusion testing in this population. [Table: see text]
Dabrafenib and trametinib in patients with tumors with BRAF V600E/k mutations: Updated results from NCI-MATCH arm H.
Authors: Salama April K.S. , Wang Victoria , Macrae Erin Renee , Park Jong-In , Chen Helen X. , Gray Robert James , McShane Lisa , Rubinstein Lawrence , Williams P. Mickey , Hamilton Stanley R. , Armstrong Deborah Kay , Tricoli James V. , Conley Barbara A. , Arteaga Carlos L. , Harris Lyndsay , O'Dwyer Peter J. , Chen Alice P. , Flaherty Keith 
Published: June 2024

3110 Background: The NCI-MATCH precision medicine trial assigns patients (pts) with solid tumors, lymphomas or multiple myeloma to a targeted therapy based on genetic alterations identified in pretreatment biopsies. Arm H (EAY131-H) evaluated the combination of the BRAF inhibitor (inh) dabrafenib (DAB), and the MEK inh, trametinib (TRM), in pts with BRAF V600E/K mutations. Thirty-five pts in the primary cohort (PC) were enrolled from Jan 2016-Feb 2018, with 30 patients included in the primary efficacy analysis (1). The trial reactivated for an expansion cohort (EC) in October 2020. Methods: Pts could enroll based on molecular results from approved local CLIA labs; central confirmation was required to be included in primary efficacy analyses. Pts with melanoma, thyroid, or colorectal cancer were excluded. Pts with NSCLC were excluded after the US Food and Drug Administration (FDA) approved DAB/TRM in 2017. Pts received DAB 150 mg po BID and TRM 2 mg PO daily on 28-day cycles until disease progression or intolerable toxicity, with restaging every 2 cycles. The primary endpoint was objective response rate (ORR); secondary endpoints included progression-free survival (PFS), 6-month (mo) PFS, and overall survival (OS). Results: An additional 9 pts were accrued to the EC; 6 pts were eligible, started treatment and molecularly confirmed. One pt never started therapy and 2 pts had inadequate tissue for central molecular confirmation, resulting in a combined cohort (CC) population of 36 pts. The trial closed to accrual in Jan 2023. In the CC, 17 different histologies were represented. In the EC, 38% of pts were female, with a median age of 60; > 50% had received at least 3 lines of prior therapy. In the 6 pts with central assay results, 1 pt with a pilocytic astrocytoma had a CR, with a PFS >18 mo and 1 pt with GBM had a PR, with a PFS of >12 mo. The 2 pts without central assay results had PRs, both were alive and free of progression for >7 mo. Median OS in the EC is 19.8 mo. For the CC, the confirmed ORR is 36.1% (90% CI 22.9-51.2%); the estimated 6 mo PFS is 67.6% (90% CI 54.5-80.8%). Median OS for the CC is 28.6 mo. At the time of data cutoff (Nov 2023) 2 pts in the PC and 1 pt in the EC are still on therapy. Adverse events were comparable to previously reported profiles of DAB/TRM. Conclusions: In this pretreated cohort of BRAFV600 mutated solid tumors, the combination of DAB/TRM showed clinically meaningful activity with durable responses seen in pts across multiple histologies, further supporting the disease agnostic approval by the FDA for this regimen. 1. J Clin Oncol. 2020;38[33]. Clinical trial information: NCT04439292 .
Meta-analysis of the efficacy and safety of anlotinib combined with chemotherapy in the treatment of small cell lung cancer.
Authors: Gao Ting , Zhao Peiwen , Li Juanzhi , Li Yingjie , Li Xinxin , He Xiaopeng 
Published: June 2024

e20101 Background: Immunotherapy combined with chemotherapy(CT) has become the standard treatment for SCLC. For patients who are not eligible for immune checkpoint inhibitors, CT alone has limited efficacy. Anlotinib (AL3818), an oral, small-molecular TKI, has displayed significant anti-angiogenesis and anti-tumor growth effects through the inactivation of the VEGFR, PDGFR, FGFR and c-Kit. Several study indicated that anlotinib could prolong PFS in patients with SCLC. A meta-analysis investigating the efficacy and safety of anlotinib in combination with CT for patients with SCLC is needed. SCLC is urgently demanding novel and effective strategies. Herein, this study was to evaluate the safety and efficacy of anlotinib plus CT for SCLC. This investigation of the efficacy and safety of anlotinib in combination with CT may provide a reference for the treatment selection and management of SCLC. Methods: The studies were searched through PubMed, Embase, Cochrane Library, Web of Science up to July 28, 2023, and China National Knowledge Internet (CNKI), Wanfang, and VIP databases up to July 4, 2023. The outcomes include ORR, DCR, mPFS, OS, VEGF, and AE. Subgroup analysis was performed regarding chemotherapy drug types and the number of previous treatment cycles. Results: A total of 16 studies with 1083 patients were included in the study. Anlotinib plus chemotherapy showed significantly better efficacy in improving ORR, DCR, and mPFS compared with anlotinib therapy alone or CT alone and better PFS, 1-year and 2-year OS, and lower VEGF compared with chemotherapy alone (all P <0.05). The combination of anlotinib with CT had a significantly higher risk of leukopenia (RR: 1.41, 95% CI: 1.09 to 1.82, P =0.008). Based on the subgroup analyses, the anlotinib plus etoposide group and anlotinib plus irinotecan were superior to the etoposide and the irinotecan groups, respectively, in terms of ORR outcome and DCR outcome. The risk of thrombocytopenia and myelosuppression was higher in the anlotinib plus etoposide group than in the etoposide group. For patients receiving one or NA cycle of therapy before, anlotinib plus CT was superior to CT for DCR outcome, and in patients receiving more than 2 cycles of treatment before, there was a higher risk of myelosuppression outcomes in the anlotinib plus CT group than in the anlotinib group. After more than 2 cycles of treatment, a higher risk of gastrointestinal reaction outcomes in the anlotinib plus CT group than anlotinib group. Conclusions: The findings in the present study suggest that the combination of anlotinib with CT could provide improved PFS, ORR, DCR, and OS in patients with SCLC. This meta-analysis may innovate new prospects in the therapy for SCLC.
Real-world burden and treatments of chemotherapy-induced myelosuppression among patients with extensive-stage small-cell lung cancer: A retrospective real-world study in China.
Authors: Fei Kailun , Zhang Yundi , Dong Yiting , Liman Liman , Li Yiqi , Yang Wenjing , Wang Jie , Wang Zhijie 
Published: June 2024

e20102 Background: Chemotherapy-induced myelosuppression (CIM) is the major dose-limiting and severe complication for chemotherapy, particularly etoposide plus platinum-based therapy (EP), in patients with extensive-stage small-cell lung cancer (ES-SCLC). CIM adversely affects patient quality of life and imposes substantial economic burden. In China, there’s a scarcity of related studies, especially in large cohort. This study aims to summarize the burden and treatments of CIM in ES-SCLC patients using a nationally representative real-world database. Methods: Data were derived from 53 hospitals across 28 provinces, as part of the National Cancer Center (NCC) database. ES-SCLC patients receiving EP between 2018.1.1 and 2022.12.31 were included. CIM events, namely chemotherapy induced neutropenia (CIN), thrombocytopenia (CIT), and anemia (CRA) were identified based on laboratory tests and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5. Incidence, treatments and impact on hospitalization cost of CIM were described. Results: 7,505 patients were included, with an average age of 61.2 years (SD = 9.02) and an average of 5.0 chemotherapy cycles (SD = 2.01). The overall incidence of CIM was 91.95%, with grade 3-4 CIM occurring in 25.09% patients. Incidence of CIN, CIT, and CRA, were 44.74%, 39.20%, and 86.48%, respectively, with febrile neutropenia at 0.72%. Among patients with CIN, 90.89% patients used granulocyte colony stimulating factor (G-CSF), and 90.56% used it prophylactically. Among patients with CIT, 17.47% used recombinant human thrombopoietin (rhTPO) and 25.49% used recombinant human interleukin-11 (rhIL-11). Among patients with CRA, 10.26% used erythropoiesis-stimulating agent (ESA). Occurrence of grade 1-2 CIM and grade 3-4 CIM may increase 9.37% and 32.36% hospitalization cost per chemotherapy cycle, respectively (¥23,316.3 vs ¥21,318.2, ¥28,217.0 vs ¥21,318.2), compared to patients without any CIM. Conclusions: Incidence of CIM is notably high among ES-SCLC patients receiving EP, and treatments like G-CSF, rhTPO, rhIL-11 and ESA are widely used. Occurrence of CIM critically escalates hospitalization cost. Innovations to protect bone marrow from chemotherapy-induced damage are promising to alleviate the burden and benefit quality of life for ES-SCLC patients.[Table: see text]
Lurbinectedin versus platinum rechallenge in relapsed extensive stage small cell lung cancer: A retrospective cohort study.
Authors: Libre Michael , Lu Matthew , Lessans Spencer , Wu Jenny , Bhatia Shreya , Iams Wade Thomas 
Published: June 2024

e20110 Background: Outcomes in small cell lung cancer (SCLC) remain exceptionally poor. Although patients typically have an excellent initial response to platinum doublet chemotherapy, relapse occurs quickly. Despite multiple available therapeutic options for patients with relapse after first-line treatment, there remains limited evidence indicating a preferred second-line therapy. We present findings from a retrospective cohort study comparing lurbinectedin with platinum rechallenge in a real-world setting. Methods: Patient records were identified from Vanderbilt Ingram Cancer Center between 2000 and 2023. The study cohort included extensive-stage (ES) SCLC patients treated with second-linelurbinectedin or platinum rechallenge following initial platinum-based chemotherapy.Primary outcomes included overall survival (OS) and progression-free survival (PFS). Secondary outcomes were drug-related adverse events including hospitalization, neutropenic fever, and laboratory abnormalities by CTCAE definitions. Analysis was done in R using Kaplan-Meier estimates and Cox proportional hazards models. Results: 57 patients met inclusion criteria, with 21 receiving lurbinectedin and 36 receiving platinum rechallenge. Cohorts were similar for sex, race, comorbidities, and performance status. The platinum rechallenge group skewed younger with longer chemotherapy-free interval (CTFI) (median 9.71 months vs. 2.59 months for lurbinectedin). Median PFS was 4.37 (1.53, 5.94) vs. 2.63 months (1.68, 4.40) (p = 0.030) and median OS was 8.61 (4.91, 14.26) vs. 4.70 months (2.63, 6.73) (p = 0.001) for platinum rechallenge and lurbinectedin, respectively. In a Cox proportional hazard analysis, OS and PFS hazard ratios for lurbinectedin compared to platinum rechallenge were 4.43 (1.89-10.4, p < 0.001) and 2.03 (0.87-4.8) (p = 0.102) after adjusting for age, sex, race, comorbidities, and CTFI. Notably, the OS and PFS hazard ratios for CTFI alone were 0.96 (0.9-1.0) and 0.99 (0.98-1.0). There was no statistically significant difference in hospitalizations, neutropenic fever, anemia, or transaminitis between groups, although 7 (29%) of platinum rechallenge patients discontinued due to tolerability compared to 0 (0%) with lurbinectedin. Conclusions: This retrospective cohort study suggests that second-line platinum rechallenge in patients with relapsed ES-SCLC may be associated with improved OS and PFS compared to lurbinectedin. While time since last platinum was notably different between cohorts, CTFI alone did not appear to explain the observed difference in outcomes. Drug-related safety events were similar, although tolerability led to greater discontinuation with platinum chemotherapy. Although a small, single-center retrospective study, these results support further research to identify an optimal therapeutic strategy in second-line treatment of ES-SCLC.
Treatment of relapsed small cell lung cancer in the real-world: A comparison of platinum-etoposide rechallenge and cyclophosphamide-doxorubicin-vincristine (CAV) chemotherapy.
Authors: Chowdhury Deepro , McKinnon Mathieu , Wheatley-Price Paul , Moore Sara 
Published: June 2024

e20123 Background: Small-cell lung cancer (SCLC) is an aggressive malignancy, representing 15% of all diagnosed lung cancers. Initial therapy involves platinum-based chemotherapy, with recent evidence supporting the addition of immunotherapy. Despite excellent initial response to treatment, relapses are common and there is little prospective evidence available to guide second-line therapy. Depending on response to the previous regimen, second-line treatment can involve platinum-etoposide (PE) re-challenge or other therapies including CAV (cyclophosphamide-doxorubicin-vincristine), topotecan, taxanes, or immunotherapy. Methods: We reviewed all patients diagnosed with SCLC at the Ottawa Hospital from January 2014 – December 2021, and identified those treated with second-line systemic therapy. Baseline demographics, diagnostic, and treatment information were collected. The primary outcome was overall survival compared between platinum-etoposide re-challenge and CAV. Results: During the study period, 680 patients were diagnosed with SCLC, 521(76%) received first-line systemic therapy, and 161/521 (31%) went on to receive second-line systemic therapy. Baseline characteristics at initial diagnosis of this second-line cohort: median age 64, 93 (58%) female, 156 (97%) former/current smoking history, 156 (97%) extensive-stage. First-line treatment was almost exclusively platinum-based (n = 154, 96%). At the time of second-line therapy: 105 (69%) had ECOG performance status (PS) 0-1, and 103 (64%) had chemosensitive disease with a treatment-free interval (TFI) > 90 days. Second-line regimens included platinum-etoposide (n =64, 43%), CAV (n =67, 41%), platinum-irinotecan (n =3, 2%), docetaxel (n =10, 6%), and other (n =12, 7%). Median overall survival from the start of second line chemotherapy was 5.7 months (95% CI 5.0-6.4). Comparing patients who received PE-re-challenge versus CAV, there were no significant differences in age, sex, smoking history, or stage at diagnosis. Patients receiving CAV were more likely to have a lower performance status (ECOG >2: 40% versus 23%, p = 0.04) have a TFI < 180 days (81% vs 62%, p = 0.002). PE chemotherapy led to higher physician-assessed clinical benefit (83% vs 55%, p < 0.001) and median overall survival (7.3 (95% CI 5.7 – 8.8) versus 4.1 (95% CI 2.8 – 5.4 months), p < 0.001) compared to those receiving CAV. In a sensitivity analysis for patients with TFI < 180 days, PE-re-challenge had a higher mOS than CAV (6.2 (95% CI 5.1-7.2) versus 4.1 (95% CI 3.0 - 5.2), p < 0.003). Conclusions: Patients who receive second-line systemic therapy for relapsed SCLC represent a small subset of the overall SCLC patient population. In this real-world study, platinum-etoposide re-challenge appeared to offer benefit over CAV, even in patients with PFI < 180 days.