Development and validation of a novel EHR-based tumor progression outcome to support biomarker discovery.
Kenneth L. Kehl, MD, MPH

May 28th, 2020 - Background: Obtaining clinical outcomes for analysis has historically been a critical barrier to cancer genomics research. EHRs could constitute an important data source to bridge this gap, but EHRs rarely capture structured outcomes such as cancer progression. Novel, robust methods are needed to capture clinically relevant outcomes from EHRs. Methods: Among patients with lung adenocarcinoma wh...

Cross-site concordance evaluation for the CIMAC-CIDC network to establish QC metrics enabling reliable generation of WES and RNA-seq data.
Ignacio Ivan Wistuba, MD

May 28th, 2020 - Background: Whole-exome sequencing (WES) and RNA-sequencing (RNA-seq) have become key components of cancer genomics, and analysis to provide comprehensive evaluation of spectrum somatic alterations and changes in gene expression present in cancer samples. To test the ability to generate comparable data for these genomic assays across CIMAC-affiliated sequencing centers, the CIDC performed a cro...

RAD51Bme as predictive biomarker for PD-1 blockade response in non-small cell lung cancer.
Inês Maria Guerreiro, MD

May 28th, 2020 - Background: Lung cancer (LC) cells frequently express high levels of programmed death-ligand 1 (PD-L1). Although these levels grossly correlate with likelihood of response to specific checkpoint inhibitors, prediction of response is rather imperfect and, thus, more accurate predictive biomarkers are mandatory. We examined the methylation profile of RAD51B, a DNA-repair gene, as candidate predic...

Interferon gamma resistance in setting of LKB1 loss: Phenotypic characterization and investigation of mechanism.
Jacob Kaufman, MD, PhD

May 28th, 2020 - Background: NSCLC Patients with LKB1 loss respond poorly to immune checkpoint inhibitors (ICI). Determining mechanisms of the underlying immune resistance and strategies to overcome it are urgent and unmet clinical needs. Methods: We re-expressed WT LKB1 into LKB1 mutant NSCLC cell lines and measured effects on immune associated phenotypes in vitro. Specifically, we evaluated response to exogen...

Stereotactic body radiotherapy for early-stage non-small cell lung cancer in patients with subclinical interstitial lung disease.
Min Hu, MD

May 28th, 2020 - Background: Stereotactic body radiotherapy (SBRT) is a highly focused radiation treatment, which is now recommended to treat non-small cell lung cancer (NSCLC) patients with early stage disease. The purpose of this study is to evaluate the efficacy and toxicity of SBRT for early stage NSCLC patients with subclinical interstitial lung disease (ILD). Methods: One hundred and nine patients with ea...

Development and validation of a CT-based radiomic model combined with margin-related radiomic features to distinguish precancerous lesions from early-stage lung adenocarcinoma.
Luyu Huang, MD

May 28th, 2020 - Background: The purpose of this study was to investigate whether the combined radiomic model based on tumor-associated and margin-related (5mm) radiomic features can effectively improve prediction performance of distinguishing precancerous lesions from early stage lung adenocarcinoma. Methods: 264 patients underwent preoperative chest CT in Guangdong Provincial People’s hospital from March 1, 2...

Phase I/II study of vorolanib plus nivolumab in patients with thoracic malignancies: immunotherapy (IO) correlatives to differentiate responders from nonresponders.
Katy Beckermann, MD, PhD

May 28th, 2020 - Background: VEGF inhibition is suggested to enhance innate T cell function, activate dendritic cells, block recruitment of regulatory T cells, and decrease myeloid-derived suppressor cells. Vorolanib is a tyrosine kinase inhibitor that is structurally similar to sunitinib but designed to improve safety without compromising efficacy. Response to checkpoint inhibitors in patients with thoracic tu...

Stereotactic body radiation therapy (SBRT) in a developing country: Patterns of failure and response rates.
Daniel Przybysz, MD

May 28th, 2020 - Background: Surgery remains the treatment of choice for early stage lung cancer. For patients without clinical conditions or those who refuse to this procedure, Stereotactic Body Radiation Therapy (SBRT) is the treatment of choice. It is important to understand the patterns of treatment response and toxicities within this practice. Therefore, we aim to analyze and review our data on lung SBRT f...

The mutation profile of genes related to primary resistance to EGFR-TKI in early NSCLC.
Jiangang Ye

May 28th, 2020 - Background: In targeted therapy for patients with advanced non-small cell lung cancer (NSCLC), approximately 30% of NSCLC patients with EGFR mutations develop primary resistance at the beginning of treatment with TKIs. However, the knowledge of primary resistance in early-stage NSCLC patients with EGFR positve remains poorly understood. Methods: Mutations of nine genes that may be related to pr...

Successful mutational profiling of single circulating epithelial tumor cells (CETCs) from patients with solid cancers for guiding therapy.
Dorothea Schott

May 28th, 2020 - Background: Circulating epithelial tumor cells (CETCs) are an important link between primary tumors and metastases and provide a readily accessible source of tumor material from patients with solid cancer. Therefore, they are representative for primary and metastatic lesions to evaluate treatment response in real-time and to guide therapeutic modifications. Beyond enumeration, information on mu...

Prognostic value of SOX2 and CD8+TIL in limited stage small cell lung cancer.
Jinsoo Lee

May 28th, 2020 - Background: SOX2 is a transcriptional factor that drives embryonic stem cell to neuroendocrine cells in lung development and is highly expressed in SCLC. The serum SOX2 antibody in SCLC has been known to mediate neurologic paraneoplastic syndrome. In this study, we evaluated the expression of SOX2 and CD8+ tumor infiltrating lymphocyte (TIL) in LS-SCLC from clinical tumor tissue and their impac...

Phase II trial of the PARP inhibitor, niraparib, in BAP1 and other DNA damage response (DDR) pathway deficient neoplasms (NCT03207347).
azka ali, MD

May 28th, 2020 - Background: BRCA-associated protein-1 (BAP1) is a ubiquitin ligase associated with regulating cell cycle, cell proliferation, DNA damage pathway, and cell death. It also acts as a tumor suppressor gene as seen in hereditary cancer syndrome associated with germline mutations in BAP1. Preclinical studies have shown that PARP-inhibitor treatment of BAP1 mutant cell lines demonstrated significant s...

Immune checkpoint inhibitors combined with chemotherapy/radiotherapy, for EGFR wild-type lung cancer: Efficacy in real-world study.
Jifeng Feng, Doctor's degree

May 28th, 2020 - Background: The role of immune checkpoint inhibitors (anti-PD-1 antibody, ICI) combined with chemotherapy/radiotherapy for EGFR wild-type lung cancer is controversial, especially in 2nd-line or later treatment. The purpose of this study was to investigate the possible beneficial factors for immunotherapy for EGFR wild-type lung cancer. Methods: A total of 279 patients with EGFR wild-type lung c...

A single institution experience with droplet digital polymerase chain reaction (dd-PCR) liquid biopsy (LB) for therapeutic decision in advanced solid tumors.
Andre Marcio Murad, MD, PhD

May 28th, 2020 - Background: Droplet digital polymerase chain reaction (ddPCR) is a promising method for analyzing minor amounts of cell-free circulating free nucleic acid (DNA and RNA) due to its high sensitivity, low cost, and fast reading, since it dispenses bioinformatics, making it an appropriate alternative to new generation sequencing (NGS) for the detection of biomarkers to guide molecularly targeted ca...

PTPRD/PTPRT mutations as potential positive predictor for response of immune checkpoint inhibitors in non-small cell lung cancer (NSCLC).
Jian Zeng

May 28th, 2020 - Background: Immune checkpoint inhibitors (ICIs) have demonstrated positive results in non-small cell lung cancer (NSCLC) patients, with durable responses and prolonged overall survival (OS). Nevertheless, the response rate to immunotherapy is still limited. It is necessary to identify clinically useful biomarkers that can distinguish patients who can respond to ICIs. PTPRD/PTPRT are the phospha...

Potential utility of methylation levels detected from circulating tumor DNA (ctDNA) in predicting molecular residual disease (MRD) in patients with resected non-small cell lung cancer (NSCLC).
Hong HU, MD

May 28th, 2020 - Background: To improve the prognosis of resected lung cancer patients, growing efforts are being invested in finding the most optimal approach to detect MRD and predict relapse. In our study, we aimed to investigate the utility of ctDNA methylation profiling in detecting MRD from patients with resected early-stage NSCLC. Methods: Surgically-resected tumor tissues were obtained from 65 patients ...

Lung cancer exosome specific protein 1(LESP-1) as a potential factor for diagnosis and treatment of non-small cell lung cancer.
Hyun Koo Kim, MD, PhD

May 28th, 2020 - Background: Exosomes are endosome-derived nano size (30-150 nm) extracellular microvesicles released from many cell types including cancer cells and encapsulated by cell membrane play a key role for cell to cell communication. Use of exosomes as a biomarkers in lung cancer is a rising nanotechnology in a liquid biopsy. We explored a role of an exosome specific marker and the relationship betwee...

Effect of STK11 mutations on efficacy of PD-1 inhibition in non-small cell lung cancer (NSCLC) and dependence on KRAS mutation status.
Biagio Ricciuti, MD

May 28th, 2020 - Background: STK11 mutations (STK11m) have been associated with resistance to ICI in KRAS-mutant (KRASm) NSCLC. Whether STK11m status also impacts clinical outcomes to ICI in KRAS wild-type (wt) NSCLC is unknown. Methods: We analyzed clinical outcomes of patients (pts) with NSCLC treated with ICI according to KRAS and STK11 mutation status in independent discovery (DFCI+MGH) and validation (MSKC...

Concordance of next-generation sequencing between tissue and liquid biopsies in non-small cell lung cancer.
Fahmin Basher, MD, PhD

May 28th, 2020 - Background: While genetic profiling has become standard of care for patients diagnosed with non-small cell lung cancer (NSCLC), next-generation sequencing (NGS) provides a wealth of information about targetable mutations. Advances in genetic testing have led to sequencing platforms that utilize tissue itself or extracellular circulating tumor DNA in the blood, known as a “liquid biopsy.”Methods...

An ultra-sensitive multiplexed enrichment of rare DNA variants via toehold exchange principle.
Yue Pu, Ph.D.

May 28th, 2020 - Background: As a major type of liquid biopsy, circulating tumor DNA (ctDNA) provides important somatic mutation information, but the feature of rare allele frequency of mutation in ctDNA hampers its wide application. Methodology with high sensitivity, cost effectiveness, and multiplexing capability is needed for analyzing ctDNA samples. Methods: We have developed a novel methodology, termed MTE...