Stem Cells In Clinical Practice: STELLA Experience Manolo D’Arcangelo Department of Oncology...
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tem Cells In Clinical Practice: STELLA Experience Manolo D’Arcangelo Department of Oncology Ospedale Civile di Livorno
Transcript of Stem Cells In Clinical Practice: STELLA Experience Manolo D’Arcangelo Department of Oncology...
Stem Cells In Clinical Practice: STELLA Experience
Manolo D’ArcangeloDepartment of OncologyOspedale 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
Platinum doublet
Erlotinib Docetaxel ?????
AdvancedNSCLC
Personalizedtreatment
Tumor tissue/effusion collectionfor CSCs chemosensitivity assay
STELLA project: CSCs isolation
Enzimatic digestion
CD133+ cells Culture conditions select forimmature cancer cells
Chemosensitivityassay
Flow cytometricanalysis
Orthotopic xenograft
Chemotherapeutic/biological agents up to 96h
Orange acridinestaining
High sensitivityAverage sensitivityLow sensitivity
STELLA project: chemosensitivity assay - LAB
Treatmentchoice
STELLA project: chemosensitivity assay - CLINIC
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 CharacteristicsNumber of patients 23Median age (range; years) 66 (42-85)
SexMaleFemale
15 (65%)8 (35%)
Primary cancerLung CancerColorectal CancerBreast CancerOther
18 (78%)3 (13%)
02 (9%)
HistologyAdenocarcinomaSquamous cell carcinomaSmall cell carcinomaOther
18 (78%)1 (4%)
3 (13%)1 (4%)
Molecular alterationEGFR mutationALK translocationK-RAS mutation
4 (17%)1 (4%)
3 (13%)Number of tissue/effusion collections 24Specimen collection siteLiver biopsyLymph node biopsyLung nodule excisionAscitis/pleural/pericardial effusion
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 d1Paclitaxel 175 mg/mq d1every 21 days
Our experience: a case report
After two cycles of chemotherapyBasal assessment After four cycles of 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!
