International study on inter-reader variability for circulating tumor cells in breast cancer

M Ignatiadis; S Riethdorf; FC Bidard; I Vaucher; M Khazour; F Roth; J Metallo; G Rouas; RE Payne; RC Coombes; I Teufel; U Andergassen; S Apostolaki; E Politaki; D Mavroudis; S Bessi; M Pestrin; A De Leo; M Campion; M Reinholz; E Perez; M Piccart; E Borgen; B Naume; J Jimenez; CM Aura; L Zorzino; MC Cassatella; MT Sandri; Bianca Mostert; Stefan Sleijfer; Jaco Kraan; W Janni; T Fehm; B Rack; L Terstappen; M Repollet; JY Pierga; C Miller; C Sotiriou; S Michiels; K Pantel

doi:10.1186/bcr3647

International study on inter-reader variability for circulating tumor cells in breast cancer

M Ignatiadis, S Riethdorf, FC Bidard, I Vaucher, M Khazour, F Roth, J Metallo, G Rouas, RE Payne, RC Coombes, I Teufel, U Andergassen, S Apostolaki, E Politaki, D Mavroudis, S Bessi, M Pestrin, A De Leo, M Campion, M ReinholzE Perez, M Piccart, E Borgen, B Naume, J Jimenez, CM Aura, L Zorzino, MC Cassatella, MT Sandri, Bianca Mostert, Stefan Sleijfer, Jaco Kraan, W Janni, T Fehm, B Rack, L Terstappen, M Repollet, JY Pierga, C Miller, C Sotiriou, S Michiels, K Pantel

Medical Oncology

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Introduction: Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch (R) system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement. Methods: CellSearch (R) images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2-vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (.) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test. Results: For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median. of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and < 3CTCs (median 87%, range 66 to 95%) compared to M0 and >= 3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2-vs HER2+), the median agreement was 87% (range 51 to 95%) with a median. of 0.74 (range 0.25 to 0.90). Conclusions: The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required.

Original language	Undefined/Unknown
Journal	Breast Cancer Research
Volume	16
Issue number	2
DOIs	https://doi.org/10.1186/bcr3647
Publication status	Published - 2014

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EMC MM-03-86-01
EMC MM-03-86-08

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Cite this

Ignatiadis, M., Riethdorf, S., Bidard, FC., Vaucher, I., Khazour, M., Roth, F., Metallo, J., Rouas, G., Payne, RE., Coombes, RC., Teufel, I., Andergassen, U., Apostolaki, S., Politaki, E., Mavroudis, D., Bessi, S., Pestrin, M., De Leo, A., Campion, M., ... Pantel, K. (2014). International study on inter-reader variability for circulating tumor cells in breast cancer. Breast Cancer Research, 16(2). https://doi.org/10.1186/bcr3647

@article{444e3a12530b47a7bf6f550b112872e1,

title = "International study on inter-reader variability for circulating tumor cells in breast cancer",

abstract = "Introduction: Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch (R) system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement. Methods: CellSearch (R) images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2-vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (.) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test. Results: For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median. of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and < 3CTCs (median 87%, range 66 to 95%) compared to M0 and >= 3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2-vs HER2+), the median agreement was 87% (range 51 to 95%) with a median. of 0.74 (range 0.25 to 0.90). Conclusions: The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required.",

author = "M Ignatiadis and S Riethdorf and FC Bidard and I Vaucher and M Khazour and F Roth and J Metallo and G Rouas and RE Payne and RC Coombes and I Teufel and U Andergassen and S Apostolaki and E Politaki and D Mavroudis and S Bessi and M Pestrin and {De Leo}, A and M Campion and M Reinholz and E Perez and M Piccart and E Borgen and B Naume and J Jimenez and CM Aura and L Zorzino and MC Cassatella and MT Sandri and Bianca Mostert and Stefan Sleijfer and Jaco Kraan and W Janni and T Fehm and B Rack and L Terstappen and M Repollet and JY Pierga and C Miller and C Sotiriou and S Michiels and K Pantel",

year = "2014",

doi = "10.1186/bcr3647",

language = "Undefined/Unknown",

volume = "16",

journal = "Breast Cancer Research",

issn = "1465-5411",

publisher = "BioMed Central Ltd.",

number = "2",

}

Ignatiadis, M, Riethdorf, S, Bidard, FC, Vaucher, I, Khazour, M, Roth, F, Metallo, J, Rouas, G, Payne, RE, Coombes, RC, Teufel, I, Andergassen, U, Apostolaki, S, Politaki, E, Mavroudis, D, Bessi, S, Pestrin, M, De Leo, A, Campion, M, Reinholz, M, Perez, E, Piccart, M, Borgen, E, Naume, B, Jimenez, J, Aura, CM, Zorzino, L, Cassatella, MC, Sandri, MT, Mostert, B , Sleijfer, S , Kraan, J, Janni, W, Fehm, T, Rack, B, Terstappen, L, Repollet, M, Pierga, JY, Miller, C, Sotiriou, C, Michiels, S & Pantel, K 2014, 'International study on inter-reader variability for circulating tumor cells in breast cancer', Breast Cancer Research, vol. 16, no. 2. https://doi.org/10.1186/bcr3647

TY - JOUR

T1 - International study on inter-reader variability for circulating tumor cells in breast cancer

AU - Ignatiadis, M

AU - Riethdorf, S

AU - Bidard, FC

AU - Vaucher, I

AU - Khazour, M

AU - Roth, F

AU - Metallo, J

AU - Rouas, G

AU - Payne, RE

AU - Coombes, RC

AU - Teufel, I

AU - Andergassen, U

AU - Apostolaki, S

AU - Politaki, E

AU - Mavroudis, D

AU - Bessi, S

AU - Pestrin, M

AU - De Leo, A

AU - Campion, M

AU - Reinholz, M

AU - Perez, E

AU - Piccart, M

AU - Borgen, E

AU - Naume, B

AU - Jimenez, J

AU - Aura, CM

AU - Zorzino, L

AU - Cassatella, MC

AU - Sandri, MT

AU - Mostert, Bianca

AU - Sleijfer, Stefan

AU - Kraan, Jaco

AU - Janni, W

AU - Fehm, T

AU - Rack, B

AU - Terstappen, L

AU - Repollet, M

AU - Pierga, JY

AU - Miller, C

AU - Sotiriou, C

AU - Michiels, S

AU - Pantel, K

PY - 2014

Y1 - 2014

N2 - Introduction: Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch (R) system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement. Methods: CellSearch (R) images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2-vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (.) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test. Results: For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median. of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and < 3CTCs (median 87%, range 66 to 95%) compared to M0 and >= 3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2-vs HER2+), the median agreement was 87% (range 51 to 95%) with a median. of 0.74 (range 0.25 to 0.90). Conclusions: The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required.

AB - Introduction: Circulating tumor cells (CTCs) have been studied in breast cancer with the CellSearch (R) system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement. Methods: CellSearch (R) images (N = 272) of either CTCs or white blood cells or artifacts from 109 non-metastatic (M0) and 22 metastatic (M1) breast cancer patients from reported studies were sent to 22 readers from 15 academic laboratories and 8 readers from two Veridex laboratories. Each image was scored as No CTC vs CTC HER2-vs CTC HER2+. The 8 Veridex readers were summarized to a Veridex Consensus (VC) to compare each academic reader using % agreement and kappa (.) statistics. Agreement was compared according to disease stage and CTC counts using the Wilcoxon signed rank test. Results: For CTC definition (No CTC vs CTC), the median agreement between academic readers and VC was 92% (range 69 to 97%) with a median. of 0.83 (range 0.37 to 0.93). Lower agreement was observed in images from M0 (median 91%, range 70 to 96%) compared to M1 (median 98%, range 64 to 100%) patients (P < 0.001) and from M0 and < 3CTCs (median 87%, range 66 to 95%) compared to M0 and >= 3CTCs samples (median 95%, range 77 to 99%), (P < 0.001). For CTC HER2 expression (HER2-vs HER2+), the median agreement was 87% (range 51 to 95%) with a median. of 0.74 (range 0.25 to 0.90). Conclusions: The inter-reader agreement for CTC definition was high. Reduced agreement was observed in M0 patients with low CTC counts. Continuous training and independent image review are required.

U2 - 10.1186/bcr3647

DO - 10.1186/bcr3647

M3 - Article

C2 - 24758318

SN - 1465-5411

VL - 16

JO - Breast Cancer Research

JF - Breast Cancer Research

IS - 2

ER -