Lung Adenocarcinoma
Conditions
Brief summary
Every year in France, 30.000 deaths are due to lung cancer and 39.500 new cases of this disease are diagnosed (INCa 2014). Patients suffering from locally advanced non-small-cell lung cancer (NSCLC), stage IIIa, usually undergo a multimodality treatment including chemotherapy with platinum compounds before surgery (called neoadjuvant chemotherapy or induction chemotherapy). The reason of this combined modality treatment is the really poor prognosis of patients presenting a disease already spread to lymph nodes (classified N2 when the lymph node under the carina is affected). Up till now, the five-year survival of patients who underwent surgical resection of N2 NSCLC does not exceed 15%
Detailed description
Every year in France, 30.000 deaths are due to lung cancer and 39.500 new cases of this disease are diagnosed (INCa 2014). Patients suffering from locally advanced non-small-cell lung cancer (NSCLC), stage IIIa, usually undergo a multimodality treatment including chemotherapy with platinum compounds before surgery (called neoadjuvant chemotherapy or induction chemotherapy). The reason of this combined modality treatment is the really poor prognosis of patients presenting a disease already spread to lymph nodes (classified N2 when the lymph node under the carina is affected). Up till now, the five-year survival of patients who underwent surgical resection of N2 NSCLC does not exceed 15%. NOTCH pathway seems to be implicated in the resistance of tumor to chemotherapy. It is known that NOTCH plays a role in the homeostasis of adult stem cells and of cancer stem cells, including intestine cancer and NSCLC. In breast cancer, it has been demonstrated that NOTCH 1 plays a role in the relapse and adding a treatment by an inhibitor of NOTCH decreases the recurrence rate. An activation of the NOTCH pathway was proven in human lung cancer cell lines (A549 and H460) treated with cisplatin. Furthermore, HES1 (Hairy enhance of split), a downstream gene resulting from NOTCH transcription, was upregulated in patient with relapse comparing resistant versus non-resistant adenocarcinoma NSCLC patients. It was proved, NOTCH pathway is associated with overall survival in NSCLC. Recently, it was showed that an inhibitor of NOTCH combined with chemotherapy strongly potentiates the anti-tumor effects of the systemic therapy. Therefore, one can hypothesize that platinum compound-induced NOTCH activation contributes to the resistance of NSCLC and beyond this point, to tumor progression.
Interventions
OTHERbiopsies
The biopsies of lung tumour samples will be analysed by immunochemistry (IHC), western blotting and qPolymerase Chain Reaction (PCR) approaches in Six with demonstrated down-staging of a KRAS mutant adenocarcinoma, Six with demonstrated no down-staging (persistent tumour cell involving lymph nodes in surgically resected specimens) of a KRAS mutant adenocarcinoma and Six with or without non-staging and triple negative adenocarcinoma
Sponsors
Institut de Recherche en Cancérologie de Montpellier (IRCM)
University Hospital, Montpellier
Study design
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
patients of both sex, aged 75 years or younger, diagnostic specimen demonstrating an adenocarcinoma, KRAS mutation on exon 2 and codon 12 or codon 13 or triple negative, clinical pathological N2, having received a platinum-based regimen as first line therapy, at less three courses of chemotherapy must have been delivered, with only these molecules : cisplatin-vinorelbine, cisplatin-gemcitabine, cisplatin-docetaxel, cisplatin-paclitaxel, having been operated upon and having been surgically resected R0 or R1.
Exclusion criteria
patients having received more than one line of preoperative chemotherapy, having received concurrent chemo-radiotherapy as preoperative treatment, no available diagnostic specimen, patients who underwent R2 resection or no resection, patients affected by adenocarcinoma harbouring either EGFR mutation or EML4-ALK translocation, patients with pathological complete response (yT0yN0).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| analysed by immunochemistry (IHC) | 1 day | The biopsies of lung tumour samples will be analysed by immunochemistry (IHC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| western blotting (WB) | 1 day | The biopsies of lung tumour samples will be analysed by western blotting (WB) |
| qPolymerase Chain Reaction (PCR) | 1 day | The biopsies of lung tumour samples will be analysed by qPolymerase Chain Reaction (PCR) |
Countries
France
Contacts
Primary ContactJean Louis PUJOL, MD, PhD
Backup ContactCamille TRAVERT
Outcome results
None listed