EARLY DETECTION OF INVASIVE CANCERS



The earlier CTC are detected, the faster and more effectively a patient can be treated. This non-invasive approach could lead to efficient screening test for population at risk such as heavy smokers.

CENTRE HOSPITALIER UNIVERSITAIRE DE NICE

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Ilie et al. 2014 Plos One

An independently funded, 6-year-long monocentric study, published in 2014, demonstrated that ISET® was able to make a very early diagnosis of lung cancer.


254 patients including 168 patients with COPD followed by ISET® and low dose CT-scan screening :

  • 5 of 168 presented CCC detected by ISET®.
  • Per 10 mL of blood, 19 to 67 isolated CCC and 1 to 3 CCM, Vimentin expression.

In these 5 patients :

  • CT-scan detected a lung nodule 1 to 4 years after CCC detection by ISET® leading to surgical resection  and early diagnosis of Lung Cancer (stage 1A).
  • Follow up of the 5 patients at 18 months after surgery: no tumor recurrence, no CCC.
  •  
Stapes of growing invasive cancer

NATIONAL INSTITUTE OF INTEGRATIVE MEDICINE

542 individuals tested with ISET®: 277 patients with cancer and  256 individuals at risk of developping cancer :

  • 100% of cancer patients presented CTC.
  • 132 at risk individuals (50%) presented CTC.

10 months follow-up of CTC-positive at risk individuals :

  • 20% of at risk individuals diagnosed with early stage cancers by imaging techniques.

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Ried et al. 2017 Asian Pacific Journal of Cancer Prevention

Logo du National Institute Of Integrative Medicine

Ried et al. 2017 Asian Pacific Journal of Cancer Prevention

542 individuals tested with ISET®: 277 patients with cancer and  256 individuals at risk of developping cancer :

  • 100% of cancer patients presented CTC.
  • 132 at risk individuals (50%) presented CTC.

10 months follow-up of CTC-positive at risk individuals :

  • 20% of at risk individuals diagnosed with early stage cancers by imaging techniques.

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PROGNOSTIC VALUE OF ISET® COLLECTED CTC



The prognostic value of CTC collected by ISET® has been demonstrated by multiple independent publications in the context of multiple cancer types

Prognosis value of CTC in multiple cancers

Curve of Prognostic value

Such as Hepato-Cellular Carcinoma (Vona et al. 2004 Hepatology), Non-Small-Cell Lung Cancer (Hofman et al. 2011 Int J Cancer, Hofman et al. 2011 Clin Cancer Res, Chinen et al. 2013 J Thorac Dis, Pailler et al. 2013 J Clin Oncol, Morrow et al. 2016 Ann Oncol, Pailler et al. 2017 Cancer Res, Kallergi et al. 2018 Ther Adv Med Oncol, Diaz et al. 2018 Appl Cancer Res), Small-Cell Lung Cancer (Williamson et al. 2016 Nat Comm), Uveal Melanoma (Mazzini et al. 2014 Cancers), Colorectal Cancer (Abdallah et al. 2015 Int J Cancer, Buim et al. 2015 Cancer Biol Ther, Abdallah et al. 2016 Int J Cancer, Souza e Silva et al. 2016 Oncotargets Ther, Matikas et al. 2017 Transl Oncol, Messaritakis et al. 2018 Cancer Chemother Pharmacol), Pancreatic Cancer (Poruk et al. 2016 Ann Surg), Cutaneous Melanoma (Long et al. 2016 Cancer Med), Head and Neck Cancer (Fanelli et al. 2017 Head & Neck), Ovarian Cancer (Corassa et al. 2017 Applied Cancer Res) and Soft Tissue Sarcoma (Braun et al. 2018 Cancer Biol Ther). Examples are presented in the images below and on the left.

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CTC FOR NON INVASIVE THERANOSTICS



Theranostics allows tailoring to individual patients new targeted treatments which are selected based on molecular characteristics of cancer cells allowing to predictably obtain the cancer’s response to treatment. Theranostics markers already exist and are used on tissues (primary tumors, metastasis). Targeting theranostic tests to Circulating Cancer Cells and Microemboli isolated by ISET® allows the follow up of invasive cancers and tailoring the treatment based on real time analyses of the evolving tumor cell populations.

CTC and ALK status

Paillet et al. 2013 J Clin Oncol

  • 18 ALK-positive patients
  • 14 ALK-negative patients
  • 100% consistent result (T, CTC)
  • 100% of patients with detectable CTCs by ISET®

Single cell analysis: ALK-rearranged CTCs expressed a mesenchymal phenotype contrasting with heterogenous epithelial and mesenchymal marker expressions in tumors. ALK-rearranged CTCs harbored a unique split pattern, and heterogeneous patterns of splits were present in tumors.

A representative example of vimentin/cytokeratins/ CD45/DAPI fluorescent staining of ALK-rearranged CTCs in an ALK-positive patient.

Targeted population

542 individuals tested with ISET®: 277 patients with cancer and  256 individuals at risk of developping cancer :

  • 100% of cancer patients presented CCC.
  • 132 at risk individuals (50%) presented CCC.

10 months follow-up of CCC-positive at risk individuals :

  • 20% of at risk individuals diagnosed with early stage cancers by imaging techniques.

Ilie et al. 2017 Oncotarget

Ilie et al. 2017 Oncotarget

542 individuals tested with ISET®: 277 patients with cancer and  256 individuals at risk of developping cancer :

  • 100% of cancer patients presented CCC.
  • 132 at risk individuals (50%) presented CCC.

10 months follow-up of CCC-positive at risk individuals :

  • 20% of at risk individuals diagnosed with early stage cancers by imaging techniques.

"ROS1-rearranged tumors"

Pailler et al. 2015 Ann Oncol

  • 8 metastatic non-small-cell lung cancer patients

  • 4 ROS1-rearranged tumors

  • ROS1 rearrangement was detected in CTCs of all 4 patients with ROS1-rearranged primary tumor

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ISET® FOR IMMUNOTHERANOSTICS



The progress of immune surveillance and especially immune evasion in cancer cells are driving promising results for treating cancer with efficacy and low toxicity using immunotherapy. The effect of this treatment could be directly followed and adjusted using non-invasive ISET technology.

Evaluation of PD-L1/PD-1 on circulating tumor cells

Kallergi et al. 2018 Ther Adv Med Oncol

  • 30 metastatic non-small-cell lung cancer patients

  • Cytopathological analysis identified CCC in 28 patients (93,3%)

  • By CK+/CD45- IF, epithelial CTC were detected in 17 patients (56,7%)

  • Median progression-free survival (PFS) was significantly shorter in patients with >3 PD-1(+) CTCs at baseline compared with those with <3 PD-1(+) CTCs (p = 0.022) as well as in patients with >1 Giemsa-positive tumor cells (p = 0.025).

Detection of PD-L1 in circulating tumor cells and white blood cells

  • 106 lung adenocarcinoma patients (stages III-IV)

  • Cytopathological analysis identified CCC in 80 patients (75%)

  • 93% concordance of PD-L1 expression between tissue and CTCs (Sensitivity=55%; Specificity=100%)

Ilie et al. 2017 Ann Oncol

Ilie et al. 2017 Ann Oncol

  • 106 lung adenocarcinoma patients (stages III-IV)

  • Cytopathological analysis identified CCC in 80 patients (75%)

  • 93% concordance of PD-L1 expression between tissue and CTCs (Sensitivity=55%; Specificity=100%)

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