Cross-discipline

Translational Research

Description

Advances in our understanding of cancer’s underlying mechanisms have led to considerable innovation in cancer therapies targeting specific molecular alterations. One of the challenges in bringing these technologies to the clinical setting lies in identifying the subset of patients who might benefit. Translational research seeks to finds ways of getting effective treatments to patients as quickly as possible, by translating findings observed in a laboratory to a clinical setting.

EORTC’s translational research covers a large number of projects in several types of cancer, focusing on

  • Validating biomarkers as prognostic factors
  • Correlating certain gene expressions with response to treatment
  • Evaluating tumour response to targeted agents using advanced imaging techniques

Main Achievements

EORTC research in all fields generates a large amount of translational research data and key findings which help advance our understanding of cancer mechanisms. Among those, some flagship examples include:

The MINDACT study, in partnership with BIG (Breast International Group), showed that women identified as “low-risk” using the 70-gene test could consider foregoing this additional treatment, avoiding its serious side-effects, with no difference in outcome.

The CREATE study aims at assessing the activity and safety of Crizotinib in six independent tumour types, including advanced papillary renal cell carcinoma type 1 (pRCC1). So far, the study has showed pRCC1 patients with MET mutations in exons 16-19 (MET +) have had long-lasting disease control benefits. The CREATE study continues for other rare tumour types and is considered a landmark in the field of oncology for rare tumours.

In low-grade Glioma  exploratory analyses in patients with IDHmt/non-codel tumours suggest that treatment with primary chemotherapy might be deleterious; patients in this subgroup treated with temozolomide had a significantly shorter progression-free survival than those who received radiotherapy. Conversely, progression-free survival was similar between patients treated with radiotherapy and temozolomide in both subgroups of patients with IDHmt/codel and IDHwt tumours. However, the IDHwt subgroup was small (n=49), potentially heterogeneous, as this glioma subtype is molecularly insufficiently defined.

Brain

Temozolomide chemotherapy versus radiotherapy in high-risk low-grade glioma (EORTC 22033-26033): a randomised, open-label, phase 3 intergroup study. 

Breast

Liquid biopsy-based clinical research in early breast cancer: The EORTC 90091-10093 Treat CTC trial. 

Children Leukemia

Different outcome of T cell acute lymphoblastic leukemia with translocation t(11;14) treated in two consecutive children leukemia group EORTC trials.  

CD200/BTLA deletions in pediatric precursor B-cell acute lymphoblastic leukemia treated according to the EORTC-CLG 58951 protocol. 

ETV6-RUNX1 confers specific in vivo sensitivity to treatments in childhood B-cell precursor acute lymphoblastic leukemia: results of the EORTC CLG 58881 and 58951 trials (On going).

Prognostic classifier in childhood T-ALL (On going).

Gastro intestinal

EPOC (40983):

  • Prognostic impact of immune response in resectable colorectal liver metastases treated by surgery alone or surgery with perioperative FOLFOX in the randomized EORTC study 40983. 

PETACC-3:

  • Integrated Analysis of Molecular and Clinical Prognostic Factors in Stage II/III Colon Cancer. 
  • Prognosis of stage II and III colon cancer treated with adjuvant 5-fluorouracil or FOLFIRI in relation to microsatellite status: results of the PETACC-3 trial. 
  • Test of four colon cancer risk-scores in formalin fixed paraffin embedded microarray gene expression data. 

Gynecology

Epidermal Growth Factor Receptor (EGFR) Pathway Biomarkers in the Randomized Phase III Trial of Erlotinib Versus Observation in Ovarian Cancer Patients with No Evidence of Disease Progression after First-Line Platinum-Based Chemotherapy. 

Extreme drug resistance for carboplatin and resistance to first-line therapy in advanced-stage ovarian cancer. 

Head & Neck

RP 1353 – 24971-TR project: Evaluation of the association of tumor HPV and p16 status with progression-free survival among patients with stage III or IV HNSCC. (Paper will be submitted soon)

ERP 456 : Translational research linked to afatinib window trial (EORTC 90111) – UCL. (Lab work ongoing)

ERP 459 – Translational research linked to afatinib window trial (EORTC 90111)- INT. (Lab work ongoing)

Imaging

PET analysis in PALETTE trial.  

Consensus paper for the imaging biomarker roadmap.  

Leukemia

High numbers of mobilized CD34+ cells collected in AML in first remission are associated with high relapse risk irrespective of treatment with autologous peripheral blood SCT or autologous BMT. 

Clinical and biological impact of TET2 mutations and expression in younger adult AML patients treated within the EORTC/GIMEMA AML-12 clinical trial. 

Characterization of acute myeloid leukemia based on levels of global hydroxymethylation. 

Lymphoma

RP 1103 – 20982 – Prognostic tissue biomarkers in classical Hodgkin Lymphoma. (Stat analysis ongoing)

Melanoma

Long term follow up of the EORTC 18952 trial of adjuvant therapy in resected stage IIB-III cutaneous melanoma patients comparing intermediate doses of interferon-alpha-2b (IFN) with observation: Ulceration of primary is key determinant for IFN-sensitivity. 

Cutaneous Lymphoma

Proclipi