ctDNA Concentration, MIKI67 Mutations and Hyper-Progressive Disease Related Gene Mutations Are Prognostic Markers for Camrelizumab and Apatinib Combined Multiline Treatment in Advanced NSCLC

SummaryThe aim of this prospective study is to evaluate the clinical use and real-world efficacy of durvalumab maintenance treatment after chemoradiotherapy (CRT) in unresectable stage, locally advanced non-small cell lung cancer (NSCLC). All consecutive patients with unresectable, locally advanced NSCLC and PD-L1 expression (≥1%) treated after October 2018 were included. Regular follow up, including physical examination, PET/CT and/or contrast-enhanced CT-Thorax/Abdomen were performed every three months after CRT. Descriptive treatment pattern analyses, including reasons of discontinuation and salvage treatment, were undertaken. Statistics were calculated from the last day of thoracic irradiation (TRT). Twenty-six patients were included. Median follow up achieved 20.6 months (range: 1.9–30.6). Durvalumab was initiated after a median of 25 (range: 13–103) days after completion of CRT. In median 14 (range: 2–24) cycles of durvalumab were applied within 6.4 (range 1–12.7) months. Six patients (23%) are still in treatment and seven (27%) have completed treatment with 24 cycles. Maintenance treatment was discontinued in 13 (50%) patients: 4 (15%) patients developed grade 3 pneumonitis according to CTCAE v5 after a median of 3.9 (range: 0.5–11.6) months and 7 (range: 2–17) cycles of durvalumab. Four (15%) patients developed grade 2 skin toxicity. One (4%) patient has discontinued treatment due to incompliance. Six and 12- month progression-free survival (PFS) rates were 82% and 62%, median PFS was not reached. No case of hyperprogression was documented. Eight (31%) patients have relapsed during maintenance treatment after a median of 4.8 (range: 2.2–11.3) months and 11 (range: 6–17) durvalumab cycles. Two patients (9%) developed a local-regional recurrence after 14 and 17 cycles of durvalumab. Extracranial distant metastases and brain metastases as first site of failure were detected in 4 (15%) and 2 (8%) patients, respectively. Three (13%) patients presented with symptomatic relapse. Our prospective study confirmed a favourable safety profile of durvalumab maintenance treatment after completion of CRT in unresectable stage, locally advanced NSCLC in a real-world setting. In a median follow-up time of 20.6 months, durvalumab was discontinued in 27% of all patients due to progressive disease. All patients with progressive disease were eligible for second-line treatment.

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Transcriptional impact of resminostat and other HDAC inhibitors on disease-related gene expression in CTCL

European Journal of Cancer ◽

10.1016/s0959-8049(19)30537-4 ◽

2019 ◽

Vol 119 ◽

pp. S10

Author(s):

A.C. Bretz ◽

G. Streubel ◽

U. Parnitzke ◽

M. Borgmann ◽

S. Hamm

Keyword(s):

Gene Expression ◽

Hdac Inhibitors ◽

Related Gene ◽

Disease Related Gene

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Cryopreservation of microglia enables single-cell RNA sequencing with minimal effects on disease-related gene expression patterns

iScience ◽

10.1016/j.isci.2021.102357 ◽

2021 ◽

Vol 24 (4) ◽

pp. 102357

Author(s):

Brenda Morsey ◽

Meng Niu ◽

Shetty Ravi Dyavar ◽

Courtney V. Fletcher ◽

Benjamin G. Lamberty ◽

...

Keyword(s):

Gene Expression ◽

Single Cell ◽

Rna Sequencing ◽

Expression Patterns ◽

Gene Expression Patterns ◽

Related Gene ◽

Single Cell Rna Sequencing ◽

Disease Related Gene

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Thyroid Hormone Up-Regulates an Alzheimer Disease–Related Gene Seladin-1 at the Transcriptional Level

10.1210/endo-meetings.2011.part4.or2.or30-3 ◽

2011 ◽

pp. OR30-3-OR30-3 ◽

Cited By ~ 1

Author(s):

Emi Ishida ◽

Koshi Hashimoto ◽

Atsushi Ozawa ◽

Nobuyuki Shibusawa ◽

Tetsurou Satoh ◽

...

Keyword(s):

Thyroid Hormone ◽

Alzheimer Disease ◽

Transcriptional Level ◽

Related Gene ◽

Disease Related Gene

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Erratum: Delamanid, Bedaquiline, and Linezolid Minimum Inhibitory Concentration Distributions and Resistance-related Gene Mutations in Multidrug-resistant and Extensively Drug-resistant Tuberculosis in Korea

Annals of Laboratory Medicine ◽

10.3343/alm.2019.39.1.113 ◽

2019 ◽

Vol 39 (1) ◽

pp. 113

Keyword(s):

Minimum Inhibitory Concentration ◽

Inhibitory Concentration ◽

Gene Mutations ◽

Multidrug Resistant ◽

Drug Resistant ◽

Related Gene ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Extensively Drug Resistant

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Association between germline DNA damage repair-related genes mutation and tumor mutational burden in lung cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e21163 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e21163-e21163

Author(s):

Wei Nie ◽

Hua Zhong ◽

Ding Zhang ◽

Shiqing Chen ◽

Baohui Han

Keyword(s):

Dna Damage ◽

Dna Damage Repair ◽

Gene Mutations ◽

Related Gene ◽

Mutational Burden ◽

Damage Repair ◽

Tumor Mutational Burden ◽

Group 3 ◽

Group 2 ◽

Group 1

e21163 Background: Deleterious somatic DNA damage repair (DDR) gene mutations are frequent in non-small cell lung cancer (NSCLC) and are associated with improved clinical outcomes of immunotherapy. DDR gene mutations are associated with higher tumor mutational burden (TMB) in cancer. However, the effect of germline DDR-related genes mutation with different functional annotations on TMB in NSCLC patients is still unclear. Methods: 1671 Chinese patients with NSCLC were enrolled in this study. Genomic profiling was performed on formalin-fixed paraffin-embedded tumor samples or peripheral blood by next generation sequencing (NGS) with 733 cancer-related genes panel. The germline mutation data were obtained. All annotations in clinical significance were according to the 2015 American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) guidelines. Results: 1076 patients (64.39%) had germline DDR-related gene mutations and 595 (35.61%) had no germline DDR-related gene mutations. Among patients with DDR-related gene mutations, 78 (7.25%) patients had the pathogenic (P) mutations or likely pathogenic (LP) mutations and 1056 (98.14%) had variants of unknown significance (VOUS) mutations. In total, the median TMB was 3.91 mutations/MB (range, 0-68.16) and 4.47 mutations/MB (range, 0-51.40) in patients with P, LP or VOUS mutations and no germline DDR-related gene mutations, respectively. To the further analysis, we divided patients with germline DDR-related gene mutations into three groups: only P or LP mutations (Group 1), only VOUS mutations (Group 2) and concurrence with P/LP/VOUS mutations (Group 3). Compare to the DDR-negative group, TMB was significantly lower in Group 2 (P < 0.001). No significant differences in Group 1 and Group 3 were observed. In addition, we found that mutations in different DDR pathway could not affect TMB value significantly. Conclusions: Germline DNA damage repair-related genes mutation may be not associated with TMB.

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