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Article ; Online: CodeBreak 200: study limitations, and future directions.

Alharbi, Malak / Awidi, Muhammad / Dy, Grace K

2024 Volume 13, Issue 1, Page(s) 15–21

Language	English
Publishing date	2024-01-05
Publishing country	China
Document type	Editorial ; Comment
ZDB-ID	2901601-0
ISSN	2219-6803 ; 2218-676X
ISSN (online)	2219-6803
ISSN	2218-676X
DOI	10.21037/tcr-23-1477
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Tumor Characteristics and Treatment Responsiveness in Pembrolizumab-Treated Non-Small Cell Lung Carcinoma.

Li, Haiyan / Shyam Sunder, Sunitha / Jatwani, Karan / Bae, Yongho / Deng, Lei / Liu, Qian / Dy, Grace K / Pokharel, Saraswati

Cancers

2024 Volume 16, Issue 4

Abstract: Pembrolizumab, a widely used immune checkpoint inhibitor (ICI), has revolutionized the treatment of non-small cell lung cancer (NSCLC). Identifying unique tumor characteristics in patients likely to respond to pembrolizumab could help the clinical ... ...

Abstract	Pembrolizumab, a widely used immune checkpoint inhibitor (ICI), has revolutionized the treatment of non-small cell lung cancer (NSCLC). Identifying unique tumor characteristics in patients likely to respond to pembrolizumab could help the clinical adjudication and development of a personalized therapeutic strategy. In this retrospective study, we reviewed the clinical data and pathological features of 84 NSCLC patients treated with pembrolizumab. We examined the correlation between the clinical and demographic characteristics and the tumor histopathologic features obtained before immunotherapy. The response to pembrolizumab therapy was evaluated via the Response Evaluation Criteria in Solid Tumors (RECIST). The clinical data and cancer tissue characteristics were assessed and compared among three groups according to the following RECIST: the responsive group (RG), the stable disease group (SD), and the progressive disease group (PD), where the RG comprised patients with either a complete response (CR) or a partial response (PR). The overall survival rate of the RG group was significantly higher than the SD and PD groups. In addition, the percentage of pre-treatment viable tumor cell content in the RG and SD groups was significantly higher. At the same time, the extracellular stroma proportion was significantly lower than that of the PD group. The number of tumor-infiltrating lymphocytes (TILs) in the RG group was significantly higher than in the PD group. There were no significant differences in tumor necrosis, the stroma composition, PD-L1 expression level (TPS 1-49% vs. ≥50%), and treatment response. In conclusion, our population of NSCLC patients who experienced positive treatment responses to pembrolizumab therapy had a better prognosis compared to patients with either SD or PD. Moreover, the relative proportions of viable tumor cells to tumor-associated lymphocytes were associated with responsiveness to treatment. It is expected that larger prospective clinical studies will further validate these findings.
Language	English
Publishing date	2024-02-10
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers16040744
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Article ; Online: Survival Benefit of Perioperative Systemic Chemotherapy for Patients With N0 to N1 NSCLC Having Synchronous Brain Metastasis.

Vedire, Yeshwanth R / Shin, Sarah / Groman, Adrienne / Hennon, Mark / Dy, Grace K / Yendamuri, Sai

JTO clinical and research reports

2023 Volume 4, Issue 6, Page(s) 100522

Abstract: Introduction: In stage IV NSCLC with solitary or oligometastatic brain metastasis, surgical resection of the primary and definitive management of the brain metastasis is an accepted standard. However, the effect of systemic chemotherapy after surgical ... ...

Abstract	Introduction: In stage IV NSCLC with solitary or oligometastatic brain metastasis, surgical resection of the primary and definitive management of the brain metastasis is an accepted standard. However, the effect of systemic chemotherapy after surgical resection on overall survival is not well-established. Methods: We used the National Cancer Database to retrospectively identify individuals with NSCLC as the primary tumor along with synchronous brain metastases who underwent thoracic resection with or without adjuvant chemotherapy. Chi-square and Wilcoxon rank sum tests were performed to compare categorical and continuous variables, respectively, across the treatment groups. Kaplan-Meier and Cox proportional modeling were done to determine the survival benefit. Results: A total of 310 Conclusions: Perioperative chemotherapy for pN0-1 NSCLC with synchronous brain metastasis is associated with improved OS in this analysis.
Language	English
Publishing date	2023-04-30
Publishing country	United States
Document type	Journal Article
ISSN	2666-3643
ISSN (online)	2666-3643
DOI	10.1016/j.jtocrr.2023.100522
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Article ; Online: Loss of Rb1 Associated With the Onset of Acquired Resistance to Trastuzumab Deruxtecan in TP53-/HER2-Mutated Non-Small-Cell Lung Cancer: Case Series.

Gupta, Ashish / Jatwani, Karan / Gupta, Kush / Qiu, Jingxin / Dy, Grace K

JCO precision oncology

2023 Volume 7, Page(s) e2200476

MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung ; Lung Neoplasms ; Trastuzumab ; Camptothecin ; Tumor Suppressor Protein p53 ; Ubiquitin-Protein Ligases ; Retinoblastoma Binding Proteins
Chemical Substances	trastuzumab deruxtecan (5384HK7574) ; Trastuzumab (P188ANX8CK) ; Camptothecin (XT3Z54Z28A) ; TP53 protein, human ; Tumor Suppressor Protein p53 ; RB1 protein, human ; Ubiquitin-Protein Ligases (EC 2.3.2.27) ; Retinoblastoma Binding Proteins
Language	English
Publishing date	2023-02-21
Publishing country	United States
Document type	Journal Article
ISSN	2473-4284
ISSN (online)	2473-4284
DOI	10.1200/PO.22.00476
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Article ; Online: Risk of Further Progression or Death Among Durable Progression-Free Survivors With Melanoma or Non-Small-Cell Lung Cancer in PD-1 Blockade Trials: Implications for Imaging Surveillance.

Deng, Lei / Jiang, Changchuan / Attwood, Kristopher / Zhao, Joseph J / Perimbeti, Stuthi / Hu, Chen / Puzanov, Igor / Dy, Grace K

JCO oncology practice

2023 Volume 19, Issue 10, Page(s) 871–881

Abstract: Purpose: Durable progression-free survivors (dPFSors) over 2 years have been reported among patients with melanoma or non-small-cell lung cancer (NSCLC) who received PD-(L)1 therapy. However, risk of progression still exists and the optimal imaging ... ...

Abstract	Purpose: Durable progression-free survivors (dPFSors) over 2 years have been reported among patients with melanoma or non-small-cell lung cancer (NSCLC) who received PD-(L)1 therapy. However, risk of progression still exists and the optimal imaging surveillance interval is unknown. Methods: Individual patient data for progression-free survival (PFS) were extracted from PD-1 blockade clinical trials with a follow-up of at least 5 years. Patients with a PFS of at least 2 years were considered as dPFSors. Conditional risks of progression/death (P/D) every 3, 4, 6, and 12 months in each subsequent year were calculated. We prespecified three different levels of risk between scans (10%, 15%, or 20%) to allow clinicians and patients to decide on the scanning interval on the basis of considerations of imaging frequency and risk tolerance. An interval is considered acceptable if the upper bound of the 95% CI of the risk at each scan is lower than a prespecified level. Results: Of 1,495 and 3,752 patients with melanoma and NSCLC, 474 (31.7%) and 586 (15.6%) were dPFSors, respectively. Among them, the PFS probability for an additional 3 years was 76.4% and 48.1%, respectively. Not more than 8% of patients had P/D in any quarter in the 3 years. With a risk threshold of 10%, melanoma dPFSors can be scanned every 6 months during the third year and then every 12 months in years 4 and 5. The interval for NSCLC would be every 3 months in the third year and every 4 months in years 4 and 5. The higher risk tolerance of 15% and 20% would allow for less frequent scans. Conclusion: On the basis of their own risk tolerance level, our findings allow clinicians and dPFSors make data-driven decisions regarding the imaging surveillance schedule beyond every 3 months.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Lung Neoplasms/drug therapy ; Programmed Cell Death 1 Receptor/therapeutic use ; Disease-Free Survival ; Melanoma/drug therapy
Chemical Substances	Programmed Cell Death 1 Receptor
Language	English
Publishing date	2023-09-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	3028198-2
ISSN	2688-1535 ; 2688-1527
ISSN (online)	2688-1535
ISSN	2688-1527
DOI	10.1200/OP.23.00353
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Zs.A 7198: Show issues

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Article ; Online: Fluctuations in Gut Microbiome Composition During Immune Checkpoint Inhibitor Therapy.

Sarkar, Joy / Cortes Gomez, Eduardo / Oba, Takaaki / Chen, Hongbin / Dy, Grace K / Segal, Brahm H / Ernstoff, Marc S / Ito, Fumito

World journal of oncology

2023 Volume 14, Issue 3, Page(s) 178–187

Abstract: Background: Immune checkpoint inhibitors (ICIs) such as programmed cell death protein-1 (PD-1) inhibitors or PD-1 ligand-1 (PD-L1) inhibitors have led to remarkable improvement in outcomes of non-small cell lung cancer (NSCLC). Unfortunately, the ... ...

Abstract	Background: Immune checkpoint inhibitors (ICIs) such as programmed cell death protein-1 (PD-1) inhibitors or PD-1 ligand-1 (PD-L1) inhibitors have led to remarkable improvement in outcomes of non-small cell lung cancer (NSCLC). Unfortunately, the significant benefits of ICI therapy are frequently limited by resistance to treatment and adverse effects, and the predictive value of pre-treatment tumor tissue PD-L1 expression is limited. Development of less invasive biomarkers that could identify responders and non-responders in early on-treatment could markedly improve the treatment regimen. Accumulating evidence suggests that baseline gut microbiota profile is associated with response to PD-1/PD-L1 blockade therapy. However, change in the gut microbiome composition during PD-1/PD-L1 blockade therapy and its relation to response remain unclear. Methods: Here, we analyzed pre- and on-treatment fecal samples from five NSCLC patients receiving anti-PD-1 immunotherapy, alone or in tandem with chemotherapy, and performed 16S rRNA sequencing. Results: The overall alpha diversity of the baseline gut microbiome was similar between three responders and two non-responders. While the gut microbiome composition remained stable overall during treatment (R2 = 0.145), responders showed significant changes in microbiome diversity between pre- and on-treatment samples during anti-PD-1 therapy compared to non-responders (P = 0.0274). Within the diverse microbiota, responders showed decreases in the abundance of genera Conclusions: This pilot study identified a substantial change in gut microbiome diversity between pre- and on-treatment samples in NSCLC patients responding to anti-PD-1 therapy compared to non-responders. Our findings highlight the potential utility of gut microbiota dynamics as a noninvasive biomarker to predict response to PD-1/PD-L1 blockade therapy for a wide variety of malignancies, which sets a path for future investigation in larger prospective studies.
Language	English
Publishing date	2023-06-11
Publishing country	Canada
Document type	Journal Article
ZDB-ID	2548989-6
ISSN	1920-454X ; 1920-454X
ISSN (online)	1920-454X
ISSN	1920-454X
DOI	10.14740/wjon1587
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Article ; Online: The role of focal adhesion kinase in lung cancer.

Dy, Grace K

Anti-cancer agents in medicinal chemistry

2012 Volume 13, Issue 4, Page(s) 581–583

Abstract: Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase implicated in carcinogenesis through its pleitropic effects on cell proliferation, survival and metastasis. This article provides a summary of the existing data implicating FAK in lung cancer. ...

Abstract	Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase implicated in carcinogenesis through its pleitropic effects on cell proliferation, survival and metastasis. This article provides a summary of the existing data implicating FAK in lung cancer.
MeSH term(s)	Animals ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Focal Adhesion Protein-Tyrosine Kinases/antagonists & inhibitors ; Focal Adhesion Protein-Tyrosine Kinases/metabolism ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Protein Kinase Inhibitors/chemistry ; Protein Kinase Inhibitors/pharmacology
Chemical Substances	Antineoplastic Agents ; Protein Kinase Inhibitors ; Focal Adhesion Protein-Tyrosine Kinases (EC 2.7.10.2)
Language	English
Publishing date	2012-05-01
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	2217610-X
ISSN	1875-5992 ; 1871-5206
ISSN (online)	1875-5992
ISSN	1871-5206
DOI	10.2174/1871520611313040007
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Zs.A 5583: Show issues

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Jg. 1995 - 2021: Lesesall (2.OG)
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Article: First-line cytotoxic chemotherapy regimen for non-small cell lung cancer in the elderly population: plus ça change.

Dy, Grace K / Khalil, Maya / Yau, Edwin

Translational lung cancer research

2019 Volume 9, Issue 4, Page(s) 1591–1594

Language	English
Publishing date	2019-12-13
Publishing country	China
Document type	Editorial ; Comment
ZDB-ID	2754335-3
ISSN	2226-4477 ; 2218-6751
ISSN (online)	2226-4477
ISSN	2218-6751
DOI	10.21037/tlcr-2020-15
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Article ; Online: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study Evaluating Nintedanib Versus Placebo as Prophylaxis Against Radiation Pneumonitis in Patients With Unresectable NSCLC Undergoing Chemoradiation Therapy.

Dy, Grace K / Prasad, Dheerendra / Kumar, Prasanna / Attwood, Kristopher / Adjei, Alex A

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2021 Volume 16, Issue 3, Page(s) e19–e20

MeSH term(s)	Carcinoma, Non-Small-Cell Lung/therapy ; Double-Blind Method ; Humans ; Indoles ; Lung Neoplasms/therapy ; Radiation Pneumonitis/etiology ; Radiation Pneumonitis/prevention & control
Chemical Substances	Indoles ; nintedanib (G6HRD2P839)
Language	English
Publishing date	2021-02-25
Publishing country	United States
Document type	Clinical Trial, Phase II ; Letter ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1016/j.jtho.2020.11.019
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Zs.A 6664: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 652: Show issues

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Article ; Online: Survival outcomes of alternate dosing schedule of pemetrexed as maintenance therapy in NSCLC: Single institution experience.

Faber, Mark G / Wang, Chong / Kommi Reddy, Sruthi / Meagher, Alison / Early, Amy / Chen, Hongbin / Dy, Grace K

Lung cancer (Amsterdam, Netherlands)

2022 Volume 165, Page(s) 49–53

Abstract: Background: Maintenance therapy with pemetrexed has shown survival benefit in patients with advanced stage non-small cell lung cancer (NSCLC). The recommended dose schedule is 500 mg/m 2 in 21-day cycles. Prolonged treatment with maintenance pemetrexed ... ...

Abstract	Background: Maintenance therapy with pemetrexed has shown survival benefit in patients with advanced stage non-small cell lung cancer (NSCLC). The recommended dose schedule is 500 mg/m 2 in 21-day cycles. Prolonged treatment with maintenance pemetrexed can result in cumulative toxicities. We sought to compare treatment outcomes in patients receiving an alternate maintenance schedule in realworld practice. Methods: This single-center, retrospective study investigated patients with advanced stage (IIIB and IV) NSCLC receiving at least two doses of maintenance pemetrexed from May 1, 2011 to June 30, 2016. The objective was to compare time on treatment with maintenance pemetrexed therapy initiated at a standard schedule (q3 weeks) versus an alternate schedule (q4 weeks or longer). Also evaluated were progressionfree survival (PFS) and overall survival (OS) differences between the two groups. Results: 129 patients were included, of whom 40 started the alternate schedule no later than cycle 3 of treatment (29 of 40 patients initiated maintenance treatment on the alternate schedule). Average time on maintenance treatment for patients appeared to be longer in the patients who received the alternate schedule regimen (195 vs 263 days, p =0.008). OS trended towards better survival among patients receiving the alternate schedule regimen (11.9 vs 18.1 months, p =0.3). Limiting the analysis to ALK wildtype, the patients showed a similar trend, with median PFS (7.6 vs 11.5 months, p =0.46) and OS (11.9 vs 17.6 months, p =0.38), still favoring the alternate schedule. Conclusions: The alternate dosing schedule of maintenance pemetrexed (q4 weeks or longer) is feasible and not detrimental to OS. Future investigations evaluating the optimal administration schedule of maintenance pemetrexed is warranted.
Language	English
Publishing date	2022-01-22
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	632771-0
ISSN	1872-8332 ; 0169-5002
ISSN (online)	1872-8332
ISSN	0169-5002
DOI	10.1016/j.lungcan.2022.01.010
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Zs.A 2135: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 423: Show issues

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