Transcript Diapositiva 1

Stem Cells In Clinical Practice:
STELLA Experience
Manolo D’Arcangelo
Department of Oncology
Ospedale Civile di Livorno
Stem cells in clinical practice: from bench to bedside
• CSCs are thought to be the only cancer cell population able to sustain tumor development
growth and progression.
• Current therapies are largely ineffective against CSCs, explaining the high rate of failure of
standard treatments.
STELLA project: our proposal
STELLA: A feasibility study on cancer STem cELLs sensitivity Assay
Advanced
NSCLC
Tumor tissue/effusion collection
for CSCs chemosensitivity assay
Platinum
doublet
Erlotinib
Docetaxel
?????
Personalized
treatment
STELLA project: CSCs isolation
Enzimatic digestion
Chemosensitivity
assay
Flow cytometric
analysis
Orthotopic
xenograft
CD133+ cells
Culture conditions select for
immature cancer cells
STELLA project: chemosensitivity assay - LAB
Chemotherapeutic/biological agents
up to 96h
Orange acridine
staining
Low sensitivity
Average sensitivity
High sensitivity
STELLA project: chemosensitivity assay - CLINIC
Treatment
choice
STELLA project: Study End-points
Primary:
- To evaluate the feasibility of the project in clinical practice.
Secondary:
- To identify LC, CRC and BC stem cells.
- To investigate the sensitivity to anti-tumor agents in vitro.
- To identify drugs potentially effective for a specific patient
STELLA project: patients selection criteria
Inclusion criteria
- Histologically/cytologically confirmed diagnosis of metastatic LC,
CRC and BC.
- Availability of tumor tissue suitable for CSCs extraction.
- Performance status of 100% according to Karnofsky score.
- Failure of conventional therapies or no therapy of proven efficacy.
- Adequate hematological, renal and liver functions.
- No concomitant comorbidity potentially interfering with the study.
- Informed consent form signature.
Exlcusion criteria
- No possibility to obtain fresh tumor tissue.
- Performance status <100% according to Karnofsky score.
- Patient suitable for standard therapies.
- Important comorbidity interfering with the study.
- Significant alteration of liver, hematological or renal function(s).
- No informed consent form signature.
STELLA Results: Patients Characteristics
Number of patients
Median age (range; years)
23
66 (42-85)
Sex
Male
Female
15 (65%)
8 (35%)
Primary cancer
Lung Cancer
Colorectal Cancer
Breast Cancer
Other
18 (78%)
3 (13%)
0
2 (9%)
Histology
Adenocarcinoma
Squamous cell carcinoma
Small cell carcinoma
Other
18 (78%)
1 (4%)
3 (13%)
1 (4%)
Molecular alteration
EGFR mutation
ALK translocation
K-RAS mutation
Number of tissue/effusion collections
Specimen collection site
Liver biopsy
Lymph node biopsy
Lung nodule excision
Ascitis/pleural/pericardial effusion
4 (17%)
1 (4%)
3 (13%)
24
6 (25%)
3 (12,5%)
2 (8%)
13 (54%)
STELLA Results: CSCs isolation
-15 cases (63%) of the 24 procedures
- Failure main reasons:
-Inadequate material (8)
-Delivery accident (1)
-Failure according to primary
cancer:
- 30% of LC
- 67% of CRC
STELLA Results: Chemosensitivity Assay
-7 assays (29%) performed (preliminary data)
- All patients had LC:
-5 adenocarcinoma
-1 undifferentiated NSCLC
-1 SCLC
-Median time for results: 51 days (range: 37-95)
-Median number of tested drugs: 15 (range: 5-28)
-In 6 of the 7 perfomed assays, no drug or combination showed a CSC
mortality superior to 50%. In one case 4 regimens produced a CSC mortality
>50% and 1 combination gave a mortality of 80%.
-To date, no patient treated.
Our experience: a case report
- 26 yo man
- Squamous cell lung carcinoma with metastases to liver and lungs
- EGFR, KRAS, HER-2 wild type, no ALK rearrangement
- 3 previous treatment lines: CDDP+gemcitabine, CBDCA+paclitaxel, docetaxel
Oxaliplatin 130 mg/mq d1
Paclitaxel 175 mg/mq d1
every 21 days
Our experience: a case report
Basal assessment
After four
two cycles
cycles of
of chemotherapy
chemotherapy
STELLA project: Conclusions
• The procedure is feasible in clinical practice.
• Best results with malignant effusions.
• Sensitivity assay performed in about 1/3 of patients.
• Efficacy data still not available.
Phase II trial: ready to go!
[email protected]
A special thanks to:
Dr. Matilde Todaro
Jessica Salvini
Dr. Elisa Lani