Data for: Quality insurance in head and neck cancer multidisciplinary team meetings: a watchful eye on real-life experience.

Head and Neck MDT meeting characteristicsTHIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV

Cristalliser l'histoire : la seconde vie des perles préhistoriques en Thaïlande péninsulaire

La Thaïlande péninsulaire compte peu de vestiges archéologiques à l'exception de perles qui cristallisent des passions dévorantes. Collectées, portées, commercialisées, elles font régulièrement la une des journaux. À partir d'une enquête ethnographique réalisée auprès de la mission archéologique franco-thaïe en péninsule thaïe-malaise, cet article éclaire les pratiques de collecte de ces perles par divers acteurs locaux, et envisage les discours et représentations parfois contradictoires auxquels elles donnent lieu

The Role of Gnrh Analogues in 36-Month Disease-Free Survival in Non-Menopausal Patients with Hormone Receptor-Positive Breast Cancer

BACKGROUND AND OBJECTIVE: The effectiveness of ovarian function suppression therapies in patients with non-menopausal breast cancer has not yet been established. This study was performed to evaluate the role of gonadotropin-releasing hormone agonist (GnRH agonist) receptor in reducing local recurrence or metastasis in non-menopausal women with localized breast cancer. METHODS: This clinical trial was performed on 104 non-menopausal women with localized and advanced localized breast cancer (in stages 2 and 3) with positive hormone receptor (HR+) in the two groups of control and intervention with GnRH analog. The control group received standard treatment at the time of the study, which included tamoxifen. The GnRHa group received 3.75 mg triptorelin subcutaneously per month in addition to the standard treatment. Patients were evaluated for local recurrence and metastasis within 36 months. FINDINGS: The mean age of patients was 39.78±3.99 years. 9 patients in the control group (mean metastasis time of 17±6.65 months) and 6 patients in the GnRHa group (mean metastasis time of 14.33±8.12 months) had metastasis (p=0.498). The 36-month disease-free survival was 83.3% in the control group and 88% in the GnRHa group (p=0.518). 36-month disease-free survival in patients with HER2, 1+ or higher levels was greater in the GnRHa group compared to controls (p=0.049). In patients who received GnRH analogues, patients with HER2/neu 1+ and above had 20.7% less metastasis than patients with HER2 0 (p=0.029). However, this significant difference was not seen in the control group and other variables. CONCLUSION: According to the results of this study, GnRH analogues do not have a significant effect on reducing the rate of metastasis in patients who received it compared to other patients in a short-term period

Physiopathologie et modulation pharmacologique de l’entérite radique

International audienc

Ciblage de la famille HER dans les cancers ORL : efficacité biologique de l’association de cétuximab et de pertuzumab combinée à l’irradiation photonique

International audienceObjectif de l’étudeLes cancers épidermoïdes ORL sont associés à un fort taux de récidive loco-régionale et métastatique. Les cellules souches cancéreuses, sous-population hautement migratoire, semblent être une hypothèse majeure à l’origine de la résistance aux traitements. L’objectif du travail était de comparer l’efficacité du blocage pan-HER par une association cétuximab-pertuzumab associé à l’irradiation photonique dans les processus d’invasion et migration de la lignée SQ20B et sa sous-population souche.Matériel et méthodeLa sous-population de CSCs de la lignée SQ20B a été isolée par double tri selon les critères SQ20B/SP/CD44High. La prolifération des cellules SQ20B et SQ20B/CSCs a été étudiée après traitement par cétuximab 5 nM et/ou pertuzumab 20 μg/mL avec ou sans irradiation photonique à 10 Gy. L’analyse de la migration et de l’invasion a été réalisée par test de blessure avec et sans matrigel (IncuCyte). L’activation de récepteur de l’epidermal growth factor (EGFR) (Tyr1068) et des voies de signalisation intracellulaires (phospho-AKT et phospho-MEK1/2) a été étudiée en réponse aux traitements par western blot (WES).RésultatsLe cétuximab inhibe la prolifération cellulaire des cellules SQ20B et non celle de la sous-population souche. L’association cétuximab-pertuzumab inhibe significativement la prolifération des cellules SQ20B et SQ20B/CSCs. La double association cétuximab-pertuzumab associée à une irradiation de 10 Gy inhibe significativement la migration et l’invasion des deux populations cellulaires. Le double traitement inhibe la phosphorylation d’EGFR dans les deux populations. Les cellules SQ20B expriment fortement phospho-AKT à l’inverse des SQ20B/CSCs qui expriment phospho-MEK1/2. Enfin, l’association cétuximab-pertuzumab-10 Gy inhibe fortement l’expression de phospho-AKT et phospho-MEK1/2.ConclusionLe double traitement par cétuximab-pertuzumab associé à l’irradiation photonique inhibe significativement la prolifération, la migration et l’invasion de la lignée SQ20B et sa sous-population souche

Biomarkers of resistance to radiation therapy: a prospective study in cervical carcinoma

Abstract Background Clinical parameters and proteins have recently been suggested as possible causes of radiotherapy (RT) resistance in cervical carcinoma (CC). The objective of the present study was to validate prognostic biomarkers of radiation resistance. Methods The present prospective study included patients undergoing RT with curative intent for histologically proven locally advanced squamous cell CC. Tissues and blood samples were systematically collected before RT initiation. Immuno-histochemistry was performed (IGF-IR α and β, GAPDH, HIF-1 alpha, Survivin, GLUT1, CAIX, hTERT and HKII). Response to radiation was assessed through tumour response 3 months after RT completion, through overall survival (OS) and through progression-free survival (PFS). Results One hundred forty nine patients with a mean age of 46 years were included, with FIGO IIB (n = 53) and FIGO IIIB (n = 96) CCs. 61 patients were treated with exclusive RT + brachytherapy and 88 underwent chemo-radiotherapy + brachytherapy. Our findings suggest an association between hemoglobin level (Hb) (>11 g/dL) and 3 months complete response (p = 0.02). Hb level < 11 g/dL was associated with decreased PFS (p = 0.05) and OS (p = 0.08). Overexpression of IGF-1R β was correlated with a decreased OS (p = 0.007). Overexpression of GLUT1 was marginally correlated with reduced OS (p = 0.05). PFS and OS were significantly improved in patients undergoing chemoradiation versus exclusive radiotherapy (PFS: p = 0.04; OS: p = 0.01). Conclusions IGF-1R β overexpression and Hb level (≤11 g/dl) were associated with poor prognosis, and thus appear to be possible interesting biomarkers of radiation resistance. Our results corroborate previous pre-clinical studies suggesting IGF-1R and hypoxia to be part of the biological pathways leading to radio-resistance

HER Family Blockade in Head and Neck Squamous Cell Carcinoma: Couple Therapy Efficacy of Cetuximab and Pertuzumab Combined With Photon Irradiation

International audiencePurpose/Objective(s)Head and neck squamous cell carcinoma (HNSCC) is a malignancy still associated with severe mortality, due to loco-regional recurrences or distant metastasis. Head and neck cancer stem cells (CSCs) are highly resistant to treatment and have large migratory abilities. These particular properties could explain treatment resistances in this location. If EGFR is strongly overexpressed in 80-100% of HNSCC, HER2 and HER3 seem to be also expressed in these lines. The aim of the present study was to explore the efficacy of HER1-2-3 blockade through cetuximab-pertuzumab association with or without photon irradiation on the proliferation and migration/invasion capabilities of a HNSCC chemo and radio resistant human cell line (SQ20B) and its corresponding stem cell line (SQ20B/CSCs).Materials/MethodsSQ20B/CSCs subpopulation was isolated through double cell sorting: side population (SP) (Hoechst exclusion) and CD44 staining: SP/CD44High. SQ20B and SQ20B/CSCs proliferation was studied after treatment with cetuximab 5nM + pertuzumab 20mg/mL treatment +/- 10Gy photon irradiation. Invasion and migration were assessed with scratch wound assay with or without matrigel. EGFR, phospho-EGFR (Tyr1068), HER2 and HER3 basal protein expression was studied. Activation or inhibition of RAS/MAPK and AKT-mTOR downstream signaling cascade was studied through phospho-AKT (Ser473), phospho-MEK1/2(Ser217/221) expression exposed to combined treatments.ResultsCetuximab strongly inhibits SQ20B proliferation, migration and invasion when it has a small effect on SQ20B/CSCs. Cetuximab-pertuzumab treatment combined with radiation has a potent significant inhibitory effect on SQ20B and SQ20B/CSCs proliferation, migration and invasion. EGFR is overexpressed in SQ20B, and under-expressed in SQ20B/CSCs, while HER2 and HER3 are expressed equivalently in both populations in basal conditions. Phospho-AKT is strongly expressed in SQ20B, at the opposite of SQ20B/CSCs which express phospho-MEK1/2. Cetuximab-pertuzumab treatment combination with 10Gy photon irradiation switches off both phospho-AKT and phospho-MEK1/2 expression in the two populations.ConclusionCetuximab-pertuzumab couple pan-HER treatment combined with photon irradiation significantly inhibits proliferation, invasion and migration of SQ20B HNSCC cell line and its CSCs subpopulation, through both AKT-mTOR and Ras-MAPK downstream signaling blockade. HER family seems to be a promising therapeutic target in HNSCC

Outcome and Prognosis Factors of Stage IV Cervical Cancer Patients: A Decade Experience

International audiencePurpose/Objective(s)The aim of this study was to identify and compare prognostic factors, management strategies, and outcomes of very locally advanced cervical cancer (CC) (i.e., stages IVA) and metastatic CC (i.e., stages IV).Materials/MethodsA retrospective review was conducted, based on all consecutive patients treated for stage IV CC in a comprehensive cancer care center between 2004 and 2017.ResultsSixty-eight patients were included. Performance status (PS) was ≥ 2 for 35.9%. Median age at diagnosis was 60.5. There were 24 stage IVA CC (35.3%) and 44 stage IVB CC (64.7%). Seventeen patients with stage IVB CC had only para-aortic lymph nodes metastases (38.6%), 13 had only distant metastases (29.5%) and 14 had both (31.8%). Patients with stage IVA CC experienced a radiotherapy with curative intent (n=14, 58.3%) +/- a concomitant chemotherapy, or a palliative treatment (n=10, 41.7%). Twenty-three patients with stage IVB CC received a prior chemotherapy (52.3%), eleven a primary concomitant chemoradiation (25%), and ten a palliative treatment (22.7%). The mean follow-up was 18.0 months. The 5-year overall survival was 5.1% for stages IVA (95%CI=0.7-33.9), and 10.5% for stages IVB (95%CI=3.7-29.7). In multivariate analysis, PS>1 was identified as a poor prognostic factor of disease-specific survival for stage IVA CC. PS>1 and pelvic lymph nodes involvement were identified as poor prognostic factors of overall survival and disease-specific survival for stage IVB CC.ConclusionIn daily clinical practice, outcomes of stages IV CC are poor. Treatment of advanced and metastatic CC remains challenging. New management strategies are needed, as well as efficient preventive strategies

Targeting Cancer Stem Cells in HNSCC: Synergic Effect of Cetuximab and ABT-199 in Combination with Photon Radiation

International audiencePurpose/Objective(s)Concurrent cetuximab based radio-chemotherapy is a validated scheme in head and neck squamous cell carcinoma (HNSCC). Cancer Stem Cells (CSCs) are highly resistant to treatment, have large migratory abilities, and are hypothesized to be responsible for a significant part of recurrences. Apoptotic signaling in CSCs is a major way of treatment escape, through Bcl-2 proteins family. The aim of the present study was to explore the synergic effect between cetuximab and an anti-Bcl-2 antibody (ABT-199), when combined or not with photon radiation.Materials/MethodsHNSCC chemo and radio resistant human cell line (SQ20B) and its corresponding stem cell line (SQ20B/CSCs) were used to test the treatment combinations. HaCaT cell line was used to assess toxicity on healthy cell population. SQ20B/CSCs subpopulation was isolated through double cell sorting: side population (SP) (Hoechst exclusion) and CD44 staining: SP/CD44High. SQ20B and SQ20B/CSCs proliferation, invasion/migration, and apoptosis were studied after an exposition to cetuximab 5nM + ABT-199 10mM treatment +/- 10Gy photon irradiation. Invasion and migration were assessed based on scratch wound assay with or without matrigel. Apoptosis was measured using caspases 3/7. 3D spheroid assay was performed to validate the results in a 3D culture approach. EGFR, phospho-EGFR (Tyr1068), Bcl-2 and Bcl-xl protein expression were studied.ResultsCetuximab strongly inhibited SQ20B proliferation, migration and invasion whereas it had little effect on SQ20B/CSCs. Conversely, ABT-199 significantly inhibited these properties on SQ20B/CSCs, without showing any effect on SQ20B parental cell line. Cetuximab-ABT-199 combined with radiation had a significant inhibitory effect on both SQ20B and SQ20B/CSCs proliferation, migration and invasion. Although exclusive cetuximab had no pro-apoptotic effect, activation of caspases 3/7 was induced by ABT-199 and enhanced by the cetuximab+ABT-199 combination in both populations. Cetuximab was a strong inhibitor of 3D-spheroid proliferation in SQ20B, whereas ABT-199 strongly decreased spheroid size in CSCs. EGFR was overexpressed in SQ20B, and under-expressed in SQ20B/CSCs. Bcl2 was overexpressed in SQ20B/CSCs. Although cetuximab moderately inhibited HaCaT cell proliferation, the drug combination did not significantly enhanced toxicity.ConclusionCetuximab+ABT-199 combined with photon radiation significantly inhibited proliferation, invasion and migration of SQ20B HNSCC cell line and its CSCs subpopulation, with an acceptable toxicity profile on healthy cell lines. Apoptotic cell death was enhanced by this drug combination