Publication

Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors

Tamminga, M., de Wit, S., Hiltermann, T. J. N., Timens, W., Schuuring, E., Terstappen, L. W. M. M. & Groen, H. J. M., 10-Jul-2019, In : Journal for immunotherapy of cancer. 7, 1, 9 p., 173.

Research output: Contribution to journalArticleAcademicpeer-review

APA

Tamminga, M., de Wit, S., Hiltermann, T. J. N., Timens, W., Schuuring, E., Terstappen, L. W. M. M., & Groen, H. J. M. (2019). Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors. Journal for immunotherapy of cancer, 7(1), [173]. https://doi.org/10.1186/s40425-019-0649-2

Author

Tamminga, Menno ; de Wit, Sanne ; Hiltermann, T Jeroen N ; Timens, Wim ; Schuuring, Ed ; Terstappen, Leon W M M ; Groen, Harry J M. / Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors. In: Journal for immunotherapy of cancer. 2019 ; Vol. 7, No. 1.

Harvard

Tamminga, M, de Wit, S, Hiltermann, TJN, Timens, W, Schuuring, E, Terstappen, LWMM & Groen, HJM 2019, 'Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors', Journal for immunotherapy of cancer, vol. 7, no. 1, 173. https://doi.org/10.1186/s40425-019-0649-2

Standard

Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors. / Tamminga, Menno; de Wit, Sanne; Hiltermann, T Jeroen N; Timens, Wim; Schuuring, Ed; Terstappen, Leon W M M; Groen, Harry J M.

In: Journal for immunotherapy of cancer, Vol. 7, No. 1, 173, 10.07.2019.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Tamminga M, de Wit S, Hiltermann TJN, Timens W, Schuuring E, Terstappen LWMM et al. Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors. Journal for immunotherapy of cancer. 2019 Jul 10;7(1). 173. https://doi.org/10.1186/s40425-019-0649-2


BibTeX

@article{e8e40b0ef963416eb00d27fa28fe6a40,
title = "Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors",
abstract = "Background: Non-small cell lung cancer (NSCLC) patients treated with checkpoint inhibitors show long lasting responses, but it is hard to predict which patients will profit from this treatment with the currently used marker, programmed death ligand 1 (PD-L1). We hypothesized that circulating tumor cells (CTC) or tumor derived extracellular vesicles (tdEV) are markers of treatment efficacy.Methods: Patients with advanced NSCLC treated with checkpoint inhibitors were included. Blood was drawn at baseline (T0) and at 4 weeks of treatment (T1) for analysis of CTC and tdEV using CellSearch (R). Tumor response was classified as partial or complete response based on the response evaluation criteria in solid tumors (RECISTv1.1) measured 4-6 weeks after start of treatment Durable response was defined as stable disease, partial or complete response without disease progression at 6 months. Analyses were adjusted for covariables including PD-L1 expression.Results: We included 104 patients (30 with a tumor response, 74 non-responders, 2 responses not evaluable due to early death); 63 patients provided T1 samples. All patients were treated with PD-L1 inhibitors. The majority of patients received second (85{\%}) or third line (treatment with nivolumab monotherapy (89{\%}).CTC were present in 33/104 patients at T0 (32{\%}) and 17/63 at T1 (27{\%}), 9/63 patients had CTC (14{\%}) at both time points. The presence of CTC, both at T0 (OR = 0.28, p = 0.02,) and T1 (OR = 0.07, p <0.01), was an independent predictive factor for a lack of durable response and was associated with worse progression free and overall survival. More tdEV were associated with shorter survival but not with response rate.Conclusion: CTC occur in one third of advanced NSCLC patients and their presence is a predictive factor for a worse durable response rate to checkpoint inhibitors. tdEV are associated with shorter survival but not with response.",
keywords = "Circulating tumor cells (CTC), Non-small cell lung cancer (NSCLC), Immunotherapy, Checkpoint inhibitors, Tumor derived extracellular vesicles (tdEV), Durable response, Liquid biopsy, DIAGNOSTIC LEUKAPHERESIS, PROGNOSTIC-SIGNIFICANCE, CHALLENGES, PEMBROLIZUMAB, BLOCKADE, SURVIVAL, SIZE",
author = "Menno Tamminga and {de Wit}, Sanne and Hiltermann, {T Jeroen N} and Wim Timens and Ed Schuuring and Terstappen, {Leon W M M} and Groen, {Harry J M}",
year = "2019",
month = "7",
day = "10",
doi = "10.1186/s40425-019-0649-2",
language = "English",
volume = "7",
journal = "Journal for immunotherapy of cancer",
issn = "2051-1426",
publisher = "BMC",
number = "1",

}

RIS

TY - JOUR

T1 - Circulating tumor cells in advanced non-small cell lung cancer patients are associated with worse tumor response to checkpoint inhibitors

AU - Tamminga, Menno

AU - de Wit, Sanne

AU - Hiltermann, T Jeroen N

AU - Timens, Wim

AU - Schuuring, Ed

AU - Terstappen, Leon W M M

AU - Groen, Harry J M

PY - 2019/7/10

Y1 - 2019/7/10

N2 - Background: Non-small cell lung cancer (NSCLC) patients treated with checkpoint inhibitors show long lasting responses, but it is hard to predict which patients will profit from this treatment with the currently used marker, programmed death ligand 1 (PD-L1). We hypothesized that circulating tumor cells (CTC) or tumor derived extracellular vesicles (tdEV) are markers of treatment efficacy.Methods: Patients with advanced NSCLC treated with checkpoint inhibitors were included. Blood was drawn at baseline (T0) and at 4 weeks of treatment (T1) for analysis of CTC and tdEV using CellSearch (R). Tumor response was classified as partial or complete response based on the response evaluation criteria in solid tumors (RECISTv1.1) measured 4-6 weeks after start of treatment Durable response was defined as stable disease, partial or complete response without disease progression at 6 months. Analyses were adjusted for covariables including PD-L1 expression.Results: We included 104 patients (30 with a tumor response, 74 non-responders, 2 responses not evaluable due to early death); 63 patients provided T1 samples. All patients were treated with PD-L1 inhibitors. The majority of patients received second (85%) or third line (treatment with nivolumab monotherapy (89%).CTC were present in 33/104 patients at T0 (32%) and 17/63 at T1 (27%), 9/63 patients had CTC (14%) at both time points. The presence of CTC, both at T0 (OR = 0.28, p = 0.02,) and T1 (OR = 0.07, p <0.01), was an independent predictive factor for a lack of durable response and was associated with worse progression free and overall survival. More tdEV were associated with shorter survival but not with response rate.Conclusion: CTC occur in one third of advanced NSCLC patients and their presence is a predictive factor for a worse durable response rate to checkpoint inhibitors. tdEV are associated with shorter survival but not with response.

AB - Background: Non-small cell lung cancer (NSCLC) patients treated with checkpoint inhibitors show long lasting responses, but it is hard to predict which patients will profit from this treatment with the currently used marker, programmed death ligand 1 (PD-L1). We hypothesized that circulating tumor cells (CTC) or tumor derived extracellular vesicles (tdEV) are markers of treatment efficacy.Methods: Patients with advanced NSCLC treated with checkpoint inhibitors were included. Blood was drawn at baseline (T0) and at 4 weeks of treatment (T1) for analysis of CTC and tdEV using CellSearch (R). Tumor response was classified as partial or complete response based on the response evaluation criteria in solid tumors (RECISTv1.1) measured 4-6 weeks after start of treatment Durable response was defined as stable disease, partial or complete response without disease progression at 6 months. Analyses were adjusted for covariables including PD-L1 expression.Results: We included 104 patients (30 with a tumor response, 74 non-responders, 2 responses not evaluable due to early death); 63 patients provided T1 samples. All patients were treated with PD-L1 inhibitors. The majority of patients received second (85%) or third line (treatment with nivolumab monotherapy (89%).CTC were present in 33/104 patients at T0 (32%) and 17/63 at T1 (27%), 9/63 patients had CTC (14%) at both time points. The presence of CTC, both at T0 (OR = 0.28, p = 0.02,) and T1 (OR = 0.07, p <0.01), was an independent predictive factor for a lack of durable response and was associated with worse progression free and overall survival. More tdEV were associated with shorter survival but not with response rate.Conclusion: CTC occur in one third of advanced NSCLC patients and their presence is a predictive factor for a worse durable response rate to checkpoint inhibitors. tdEV are associated with shorter survival but not with response.

KW - Circulating tumor cells (CTC)

KW - Non-small cell lung cancer (NSCLC)

KW - Immunotherapy

KW - Checkpoint inhibitors

KW - Tumor derived extracellular vesicles (tdEV)

KW - Durable response

KW - Liquid biopsy

KW - DIAGNOSTIC LEUKAPHERESIS

KW - PROGNOSTIC-SIGNIFICANCE

KW - CHALLENGES

KW - PEMBROLIZUMAB

KW - BLOCKADE

KW - SURVIVAL

KW - SIZE

U2 - 10.1186/s40425-019-0649-2

DO - 10.1186/s40425-019-0649-2

M3 - Article

VL - 7

JO - Journal for immunotherapy of cancer

JF - Journal for immunotherapy of cancer

SN - 2051-1426

IS - 1

M1 - 173

ER -

ID: 90737905