Stem Cells In Clinical Practice: STELLA Experience Manolo D’Arcangelo Department of Oncology Ospedale Civile di Livorno.

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!

[email protected] special thanks to:

Dr. Matilde Todaro

Jessica Salvini

Dr. Elisa Lani