EP-1358 SBRT for de novo pulmonary tumors in patients with completely resected early stage NSCLC

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

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A Two-arm (Phase 2) Exploratory Study of Nivolumab Monotherapy or in Combination With Nab-paclitaxel and Carboplatin in Early Stage NSCLC in China

Case Medical Research ◽

10.31525/ct1-nct04015778 ◽

2019 ◽

Author(s):

Keyword(s):

Exploratory Study ◽

Early Stage ◽

Phase 2 ◽

Early Stage Nsclc

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A Study of Toripalimab or Placebo Plus Chemotherapy as Treatment in Early Stage NSCLC

Case Medical Research ◽

10.31525/ct1-nct04158440 ◽

2019 ◽

Author(s):

Keyword(s):

Early Stage ◽

Early Stage Nsclc

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P2.11-10 Discovery of Potential Biomarkers That Discriminate Early Stage NSCLC from Controls by Non-Targeted Metabolomics Profiling

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2019.08.1710 ◽

2019 ◽

Vol 14 (10) ◽

pp. S795-S796

Author(s):

J. Kim ◽

R. Balshaw ◽

C. Trevena ◽

S. Banerji ◽

L. Murphy ◽

...

Keyword(s):

Early Stage ◽

Targeted Metabolomics ◽

Early Stage Nsclc ◽

Potential Biomarkers

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Sequential fate-switches in stem-like cells drive the tumorigenic trajectory from human neural stem cells to malignant glioma

Cell Research ◽

10.1038/s41422-020-00451-z ◽

2021 ◽

Author(s):

Xiaofei Wang ◽

Ran Zhou ◽

Yanzhen Xiong ◽

Lingling Zhou ◽

Xiang Yan ◽

...

Keyword(s):

Malignant Glioma ◽

Single Cell ◽

De Novo ◽

Early Stage ◽

Lineage Tracing ◽

Human Neural Stem Cells ◽

Transcriptional Reprogramming ◽

Neural Stem Progenitor Cells ◽

Human Gbm ◽

End Stage

AbstractGlioblastoma (GBM) is an incurable and highly heterogeneous brain tumor, originating from human neural stem/progenitor cells (hNSCs/hNPCs) years ahead of diagnosis. Despite extensive efforts to characterize hNSCs and end-stage GBM at bulk and single-cell levels, the de novo gliomagenic path from hNSCs is largely unknown due to technical difficulties in early-stage sampling and preclinical modeling. Here, we established two highly penetrant hNSC-derived malignant glioma models, which resemble the histopathology and transcriptional heterogeneity of human GBM. Integrating time-series analyses of whole-exome sequencing, bulk and single-cell RNA-seq, we reconstructed gliomagenic trajectories, and identified a persistent NSC-like population at all stages of tumorigenesis. Through trajectory analyses and lineage tracing, we showed that tumor progression is primarily driven by multi-step transcriptional reprogramming and fate-switches in the NSC-like cells, which sequentially generate malignant heterogeneity and induce tumor phenotype transitions. We further uncovered stage-specific oncogenic cascades, and among the candidate genes we functionally validated C1QL1 as a new glioma-promoting factor. Importantly, the neurogenic-to-gliogenic switch in NSC-like cells marks an early stage characterized by a burst of oncogenic alterations, during which transient AP-1 inhibition is sufficient to inhibit gliomagenesis. Together, our results reveal previously undercharacterized molecular dynamics and fate choices driving de novo gliomagenesis from hNSCs, and provide a blueprint for potential early-stage treatment/diagnosis for GBM.

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PD-0418: Dose on cardiac (sub)structures as predictor for OS in early stage NSCLC patients treated with SBRT

Radiotherapy and Oncology ◽

10.1016/s0167-8140(21)00440-0 ◽

2020 ◽

Vol 152 ◽

pp. S226-S227

Author(s):

M. Duijm ◽

D. Pezzulla ◽

W. Schillemans ◽

J. Nuyttens

Keyword(s):

Early Stage ◽

Early Stage Nsclc ◽

Nsclc Patients

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Smoking Behavior in Patients With Early-Stage NSCLC: A Report From ECOG-ACRIN 1505 Trial

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2020.12.017 ◽

2021 ◽

Author(s):

Conor E. Steuer ◽

Opeyemi A. Jegede ◽

Suzanne E. Dahlberg ◽

Heather A. Wakelee ◽

Steven M. Keller ◽

...

Keyword(s):

Early Stage ◽

Smoking Behavior ◽

Early Stage Nsclc

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Comparison of Oncologic Outcomes between Carbon Ion Radiotherapy and Stereotactic Body Radiotherapy for Early-Stage Non-Small Cell Lung Cancer

Cancers ◽

10.3390/cancers13020176 ◽

2021 ◽

Vol 13 (2) ◽

pp. 176

Author(s):

Yuhei Miyasaka ◽

Shuichiro Komatsu ◽

Takanori Abe ◽

Nobuteru Kubo ◽

Naoko Okano ◽

...

Keyword(s):

Lung Cancer ◽

Propensity Score ◽

Small Cell Lung Cancer ◽

Stereotactic Body Radiotherapy ◽

Early Stage ◽

Small Cell ◽

Oncologic Outcomes ◽

Comparison Study ◽

Small Cell Lung ◽

Early Stage Nsclc

Lung cancer is a leading cause of cancer-related deaths worldwide. Radiotherapy is an essential treatment modality for inoperable non-small cell lung cancer (NSCLC). Stereotactic body radiotherapy (SBRT) is the standard treatment for early-stage NSCLC because of its favorable local control (LC) compared to conventional radiotherapy. Carbon ion radiotherapy (CIRT) is a kind of external beam radiotherapy characterized by a steeper dose distribution and higher biological effectiveness. Several prospective studies have shown favorable outcomes. However, there is no direct comparison study between CIRT and SBRT to determine their benefits in the management of early-stage NSCLC. Thus, we conducted a retrospective, single-institutional, and contemporaneous comparison study, including propensity score-adjusted analyses, to clarify the differences in oncologic outcomes. The 3-year overall survival (OS) was 80.1% in CIRT and 71.6% in SBRT (p = 0.0077). The 3-year LC was 87.7% in the CIRT group and 79.1% in the SBRT group (p = 0.037). Multivariable analyses showed favorable OS and LC in the CIRT group (hazard risk [HR] = 0.41, p = 0.047; HR = 0.30, p = 0.040, respectively). Log-rank tests after propensity score matching and Cox regression analyses using propensity score confirmed these results. These data provided a positive efficacy profile of CIRT for early-stage NSCLC.

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Circulating serum exosomal miR-20b-5p and miR-3187-5p as efficient diagnostic biomarkers for early-stage non-small cell lung cancer

Experimental Biology and Medicine ◽

10.1177/1535370220945987 ◽

2020 ◽

Vol 245 (16) ◽

pp. 1428-1436

Author(s):

Zhi-Jun Zhang ◽

Xing-Guo Song ◽

Li Xie ◽

Kang-Yu Wang ◽

You-Yong Tang ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Early Stage ◽

Small Cell ◽

Small Cell Lung ◽

Diagnostic Biomarkers ◽

Non Invasive ◽

Early Stage Nsclc ◽

Nsclc Patients

Circulating exosomal microRNAs (ExmiRNAs) provide an ideal non-invasive method for cancer diagnosis. In this study, we evaluated two circulating ExmiRNAs in NSCLC patients as a diagnostic tool for early-stage non-small lung cancer (NSCLC). The exosomes were characterized by qNano, transmission electron microscopy, and Western blot, and the ExmiRNA expression was measured by microarrays. The differentially expressed miRNAs were verified by RT-qPCR using peripheral blood specimens from NSCLC patients ( n = 276, 0 and I stage: n = 104) and healthy donors ( n = 282). The diagnostic values were measured by receiver operating characteristic (ROC) analysis. The results show that the expression of both ExmiR-20b-5p and ExmiR-3187-5p was drastically reduced in NSCLC patients. The area under the ROC curve (AUC) was determined to be 0.818 and 0.690 for ExmiR-20b-5p and ExmiR-3187-5p, respectively. When these two ExmiRNAs were combined, the AUC increased to 0.848. When the ExmiRNAs were administered with either carcinoembryonic antigen (CEA) or cytokeratin-19-fragment (CYFRA21-1), the AUC was further improved to 0.905 and 0.894, respectively. Additionally, both ExmiR-20b-5p and ExmiR-3187-5p could be used to distinguish early stages NSCLC (0 and I stage) from the healthy controls. The ROC curves showed that the AUCs were 0.810 and 0.673, respectively. Combination of ExmiR-20b-5p and ExmiR-3187-5p enhanced the AUC to 0.838. When CEA and CYFRA21-1 were administered with the ExmiRNAs, the AUCs were improved to 0.930 and 0.928, respectively. In summary, circulating serum exosomal miR-20b-5p and miR-3187-5p could be used as effective, non-invasive biomarkers for the diagnosis of early-stage NSCLC, and the effects were further improved when the ExmiRNAs were combined. Impact statement The high mortality of non-small cell lung cancer (NSCLC) is mainly because the cancer has progressed to a more advanced stage before diagnosis. If NSCLC can be diagnosed at early stages, especially stage 0 or I, the overall survival rate will be largely improved by definitive treatment such as lobectomy. We herein validated two novel circulating serum ExmiRs as diagnostic biomarkers for early-stage NSCLC to fulfill the unmet medical need. Considering the number of specimens in this study, circulating serum exosomal miR-20b-5p and miR-3187-5p are putative NSCLC biomarkers, which need to be further investigated in a larger randomized controlled clinical trial.

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