Sébastien Salas - Academia.edu (original) (raw)
Papers by Sébastien Salas
F1000 prime reports, May 12, 2015
Leiomyosarcomas are malignant mesenchymal tumours that derive from the smooth muscle lineage. The... more Leiomyosarcomas are malignant mesenchymal tumours that derive from the smooth muscle lineage. They are studied and frequently treated as if they are the same as other soft tissue sarcomas. Recent developments suggest that a different approach may be more appropriate. Their underlying genetic mechanisms remain unclear, and complex. Unbalanced karyotypic defects are the only shared features observed across different leiomyosarcoma subtypes. Unlike other soft tissue sarcomas, leiomyosarcomas are particularly sensitive to the combination of gemcitabine and docetaxel. Furthermore, treatment with trabectedin has shown a good efficacy in leiomyosarcomas, mainly in the form of chronic disease stabilisation.
BMC Cancer, Aug 24, 2016
Background: While hypothyroidism has frequently been reported with the use of TKIs, the thyroid-s... more Background: While hypothyroidism has frequently been reported with the use of TKIs, the thyroid-stimulating hormone (TSH) suppressing effect of TKIs is rare, except for thyroiditis. We describe a case with progressive recurrent chordoma who initially became hyperthyroid in a context of autoimmunity under sorafenib treatment and later under imatinib treatment. Case presentation: A 57-year-old man with lumbar chordoma began daily treatment of 800 mg sorafenib. He did not have any other medication or recent iodinated-contrast exposure and his family history was negative for thyroid and autoimmune disease. There was no history of neck pain, irradiation or trauma, recent fever or viral illness. Pre-treatment TSH was normal. After 18 weeks of treatment, the patient presented hyperthyroidism with positive anti-TSH receptor antibodies. More surprisingly, Graves' disease recurred during treatment with imatinib. Conclusion: The fact that Graves' disease occurred after two different TKIs suggests that it could be a rare but important class effect. Anti-TSH receptor antibodies should be systematically measured when TSH decreases in order to avoid the erroneous diagnosis of transient hyperthyroidism due to thyroiditis.
Journal for ImmunoTherapy of Cancer, Jul 1, 2020
et al. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in advanced squa... more et al. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in advanced squamous cell carcinoma of the head and neck: results from a phase I cohort.
Clinical cancer drugs, Jan 9, 2018
Background-Upfront screening for dihydropyrimidine dehydrogenase (DPD) deficiency in patients sch... more Background-Upfront screening for dihydropyrimidine dehydrogenase (DPD) deficiency in patients scheduled for 5-FU should help reduce the risk of toxicities by preventive adaptive dosing. Our group has developed a simple functional testing categorizing patients upon their DPD status, i.e. extensive metabolizer (EM) or poor metabolizer (PM) patients, using UH2/U ratio measurement in plasma as a surrogate for DPD activity. 5-FU dosing can then be tailored according to DPD deficiency status. Objectives-We present here an observational study of this strategy implemented in routine clinical practice when treating head-and-neck cancer patients. Results-A total of 218 evaluable adult patients were treated with a 5-FU-regimen, with DPDbased adaptive dosing. Among them, 20 (9%) were identified as PM and received subsequently a 20-50% reduced dosing of 5-FU as compared with EM patients (2102 ±254 mg VS. 2577 ±353mg, p<0.001 ttest). Gender (Female) was associated with higher risk for being PM (p=0.01, Pearson's Chi squared test). Overall, early severe toxicities were seen only in 5% of patients, all being EM with standard dosing. Similarly, overall severe toxicities were observed in 12.8% of patients only, both figures being markedly lower than usually reported with standard 5-FU. Despite the average −20% reduction in 5-FU dosing between PM and EM patients, clinical efficacy was not statistically different between the two groups (p = 0.2774, chi-square test).
BMC Cancer, Jul 14, 2023
Background Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC... more Background Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) have a poor prognosis and limited therapeutic options. Immune checkpoint inhibitors (ICIs) are effective in patients with tumor progression < 6 months following first-line, platinum-based chemotherapy (PBC), but data are missing for patients with progression ≥ 6 months after the last platinum dose. Methods Retrospective analysis (six French centers, 2008-2019) of all consecutive R/M-HNSCC patients. treated first-line with PBC and tumor progression ≥ 6 months after the last platinum dose. Primary endpoint: progressionfree survival after second-line therapy (PFS2). Additional endpoints: overall survival from Day 1 of first-line (OS1) and second-line (OS2) therapy. Results R/M-HNSCC patients (n = 144) received cisplatinum (n = 67, 47%) or carboplatinum (n = 77, 53%) first-line.
Cancers, Mar 3, 2020
Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous... more Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous histological subtypes of frequent poor prognosis. Liposarcomas (LPS) are the most frequent type among them, and the aggressiveness and deep localization of dedifferentiated LPS are linked to high levels of recurrence. Current treatments available today lead to five-year overall survival has remained stuck around 60-70% for the past three decades. Here, we highlight a correlation between Aurora kinasa A (AURKA) and AURKB mRNA overexpression and a low metastasis-free survival. AURKA and AURKB expression analysis at genomic and protein level on a 9-STS cell lines panel highlighted STS heterogeneity, especially in LPS subtype. AURKA and AURKB inhibition by RNAi and drug targeting with AMG 900, a pan Aurora Kinase inhibitor, in four LPS cell lines reduces cell survival and clonogenic proliferation, inducing apoptosis and polyploidy. When combined with doxorubicin, the standard treatment in STS, aurora kinases inhibitor can be considered as an enhancer of standard treatment or as an independent drug. Kinome analysis suggested its effect was linked to the inhibition of the MAP-kinase pathway, with differential drug resistance profiles depending on molecular characteristics of the tumor. Aurora Kinase inhibition by AMG 900 could be a promising therapy in STS.
JAMA Oncology, Jun 1, 2023
IMPORTANCE There remains an unmet need to improve clinical outcomes in patients with recurrent or... more IMPORTANCE There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). OBJECTIVE To evaluate clinical benefit of first-line nivolumab plus ipilimumab vs nivolumab alone in patients with R/M SCCHN. DESIGN, SETTING, AND PARTICIPANTS The CheckMate 714, double-blind, phase 2 randomized clinical trial was conducted at 83 sites in 21 countries between October 20, 2016, and January 23, 2019. Eligible participants were aged 18 years or older and had platinum-refractory or platinum-eligible R/M SCCHN and no prior systemic therapy for R/M disease. Data were analyzed from October 20, 2016 (first patient, first visit), to March 8, 2019 (primary database lock), and April 6, 2020 (overall survival database lock). INTERVENTIONS Patients were randomized 2:1 to receive nivolumab (3 mg/kg intravenously [IV] every 2 weeks) plus ipilimumab (1 mg/kg IV every 6 weeks) or nivolumab (3 mg/kg IV every 2 weeks) plus placebo for up to 2 years or until disease progression, unacceptable toxic effects, or consent withdrawal. MAIN OUTCOMES AND MEASURES The primary end points were objective response rate (ORR) and duration of response between treatment arms by blinded independent central review in the population with platinum-refractory R/M SCCHN. Exploratory end points included safety. RESULTS Of 425 included patients, 241 (56.7%; median age, 59 [range, 24-82] years; 194 males [80.5%]) had platinum-refractory disease (nivolumab plus ipilimumab, n = 159; nivolumab, n = 82) and 184 (43.3%; median age, 62 [range, 33-88] years; 152 males [82.6%]) had platinum-eligible disease (nivolumab plus ipilimumab, n = 123; nivolumab, n = 61). At primary database lock, the ORR in the population with platinum-refractory disease was 13.2% (95% CI, 8.4%-19.5%) with nivolumab plus ipilimumab vs 18.3% (95% CI, 10.6%-28.4%) with nivolumab (odds ratio [OR], 0.68; 95.5% CI, 0.33-1.43; P = .29). Median duration of response for nivolumab plus ipilimumab was not reached (NR) (95% CI, 11.0 months to NR) vs 11.1 months (95% CI, 4.1 months to NR) for nivolumab. In the population with platinum-eligible disease, the ORR was 20.3% (95% CI, 13.6%-28.5%) with nivolumab plus ipilimumab vs 29.5% (95% CI, 18.5%-42.6%) with nivolumab. The rates of grade 3 or 4 treatment-related adverse events with nivolumab plus ipilimumab vs nivolumab were 15.8% (25 of 158) vs 14.6% (12 of 82) in the population with platinum-refractory disease and 24.6% (30 of 122) vs 13.1% (8 of 61) in the population with platinum-eligible disease. CONCLUSIONS AND RELEVANCE The CheckMate 714 randomized clinical trial did not meet its primary end point of ORR benefit with first-line nivolumab plus ipilimumab vs nivolumab alone in platinum-refractory R/M SCCHN. Nivolumab plus ipilimumab was associated with an acceptable safety profile. Research to identify patient subpopulations in R/M SCCHN that would benefit from nivolumab plus ipilimumab over nivolumab monotherapy is warranted.
Journal of Clinical Oncology
TPS6110 Background: Elderly patients with locally advanced head and neck squamous cell carcinoma ... more TPS6110 Background: Elderly patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are largely underrepresented in clinical trials (CT). Broad access to CTs in this population is challenging due to an increased prevalence of comorbidities and ageing-related conditions. However, as population-age increases, more and more elderly patients are diagnosed with LA-HNSCC although many are not eligible to receive standard cisplatin-based concurrent chemoradiation (CRT). CRT-related toxicities, treatment burden and compliance are a concern. NBTXR3, a first-in-class radioenhancer, composed of functionalized hafnium oxide nanoparticles, is administered by one-time intratumoral injection and activated by radiotherapy (RT). NBTXR3 is designed to locally amplify the tumor-killing effect of radiotherapy without additional toxicity to surrounding healthy tissue. NBTXR3 has been shown to prime the adaptive immune response in cancer models. NBTXR3 obtained EU marketing approv...
Journal of Geriatric Oncology
Purpose: The COVID-19 vaccination campaign began in December 2020, in France, and primarily targe... more Purpose: The COVID-19 vaccination campaign began in December 2020, in France, and primarily targeted the eldest people. Our study aimed to determine the level of acceptance of vaccination in a population of older patients with cancer. Methods: From January 2021, we offered vaccination with the BNT162b2 COVID-19 vaccine to all patients 70 years and older, addressed to our geriatric oncology center in Marseille University Hospital (AP-HM) for geriatric assessment before initiation of an oncological treatment. Objectives were to evaluate acceptance rate of COVID-19 vaccination, and to assess vaccine safety, reactogenicity, and efficacy two months after the first dose. Results: Between January 18, 2021 and May 7, 2021, 150 older patients with cancer were offered vaccination after a geriatric assessment. The majority were men (61.3%), with a mean age of 81 years. The two most frequent primary tumors were digestive (29.4%) and thoracic (18%). The vaccine acceptance rate was 82.6% and the complete vaccination rate (2 doses) reached 75.3%. Among the vaccinated patients, 15.9% reported mild side effects after the first dose and 23.4% after the second dose, mostly arm pain and fatigue. COVID-19 cases were observed in 5.1% of vaccinated patients compared with 16.7% in unvaccinated patients. Of the 22 vaccinated patients who agreed to have their serum tested, 15 had antibodies against the spike protein at day 21 after the first dose. Conclusion: Our study showed a high acceptance rate of COVID-19 vaccination, with good tolerance in this frail population. These results highlight the benefits of organizing vaccination campaigns at the very beginning of oncological management in older patients. Clinical Trial Registration This study was registered the 23 th May, 2019 in ClinicalTrials.gov (NCT03960593).
Cancers, 2020
Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous... more Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous histological subtypes of frequent poor prognosis. Liposarcomas (LPS) are the most frequent type among them, and the aggressiveness and deep localization of dedifferentiated LPS are linked to high levels of recurrence. Current treatments available today lead to five-year overall survival has remained stuck around 60–70% for the past three decades. Here, we highlight a correlation between Aurora kinasa A (AURKA) and AURKB mRNA overexpression and a low metastasis-free survival. AURKA and AURKB expression analysis at genomic and protein level on a 9-STS cell lines panel highlighted STS heterogeneity, especially in LPS subtype. AURKA and AURKB inhibition by RNAi and drug targeting with AMG 900, a pan Aurora Kinase inhibitor, in four LPS cell lines reduces cell survival and clonogenic proliferation, inducing apoptosis and polyploidy. When combined with doxorubicin, the standard treatment in S...
Journal of Clinical Oncology, 2017
11041 Background: A subset of metastatic GIST exhibit very long-term survival after imatinib (IM)... more 11041 Background: A subset of metastatic GIST exhibit very long-term survival after imatinib (IM) introduction. The aim of this study was to analyse the clinico-biological characteristics of GIST pts alive > 10 years (yrs) after diagnosis (dx) of metastases (mets) and identify possible factors associated with long-term survival. Methods: Pts were identified from 2 sarcoma databases; NetSarc and ConticaGIST. Clinical data prospectively registered in the databases were supplemented with retrospective review of medical records. Results: We identified 141 pts (75 men, 66 women) with median age 54 (17-84) yrs and median ECOG 0 (0-2). Primary tumors (T) were all CD117+, and mainly gastric or intestinal (64 & 45 pts), with median size 10 (2-40) cm, CD34+ (82 pts), mitoses/50 HPF ≤ 5 (n = 36), or > 5 (n = 81). Genotype was documented in 82 (58%) pts with 73 (89%) KIT mutations (in exons 11,9 and 12 of 69, 3, and 1 pts respectively) and 9 WT KIT. 129 (91%) T were resected, 124 upfront,...
Revue de l'infirmiere, 2017
Radiotherapy forms a significant part of cancer treatment. Caregivers support and advise patients... more Radiotherapy forms a significant part of cancer treatment. Caregivers support and advise patients to help them to adapt to the treatment and limit the occurrence of side effects. A nurse and member of a mobile support care and palliative care unit shares her experience of working in a team using sophrology to relieve the anxiety resulting from the wearing of a mask in radiotherapy.
The Lancet Oncology, 2016
Revue de Chirurgie Orthopédique et Réparatrice de l'Appareil Moteur, 2007
de mutation de BRAF à 8 % dans le groupe des GIST non mutées pour KIT ou PDGFRα. La signification... more de mutation de BRAF à 8 % dans le groupe des GIST non mutées pour KIT ou PDGFRα. La signification biologique de la mutation V600E dans les GIST est inconnue mais elle pourrait être associée à la progression de la maladie et à un mauvais pronostic comme cela semble être le cas dans les mélanomes. Cette observation pourrait avoir des conséquences dans le traitement des GIST puisqu'un traitement, le BAY 43-9006 qui cible entre autre la protéine B-raf pourrait être utilisé.
La Revue de Médecine Interne, 1998
Red cell autoantibodies are very rarely observed in pregnant women. We report one case related to... more Red cell autoantibodies are very rarely observed in pregnant women. We report one case related to the presence of a lupus anticoagulant. A 32-year-old woman had a history of two intrauterine deaths that had occurred at weeks 32 and 33, respectively. Due to the presence of a lupus anticoagulant, prednisone (20 mg/day) and subcutaneous calcium heparin were administered during her third pregnancy. The direct antiglobulin test remained positive throughout the pregnancy; however, hemolysis could not be detected. Caesarean section was done in emergency at week 29, due to fetal bradycardia related to severe fetal hemolysis. When autoimmune hemolysis occurs during pregnancy, risks for the fetus increase with the severity of hemolysis in the mother. It is thought that child mortality reflects the existence of anemia, rather than the existence of hemolysis. Our observation suggests that severe fetal hemolysis may occur, despite the absence of hemolysis in the mother.
La Revue de Médecine Interne, 1998
Virchows Archiv, 2008
Sir, Angiosarcomas are rare malignant soft tissue tumors that show differentiation toward endothe... more Sir, Angiosarcomas are rare malignant soft tissue tumors that show differentiation toward endothelial cells occurring in various clinical settings, including lymphedema-associated angiosarcoma, idiopathic angiosarcoma on the head and neck in elderly people, angiosarcoma arising on chronically sundamaged skin and post-irradiation angiosarcoma [4]. Chronic lymphedema secondary to mastectomy and axillary lymphadenectomy for breast cancer, and more rarely to infectious disease, congenital disease and traumatism, is a known predisposing condition for cutaneous and superficial soft tissue angiosarcoma. We report a new case of high-grade abdominal wall angiosarcoma in a chronically lymphedematous abdominal panniculus due to morbid obesity. A 44-year-old morbidly obese man presented with a skin lesion in the periumbilical region. Clinical examination revealed a 10-cm papular lesion on a post-operative abdominal wall hernia. There was a clinical history of Crohn's disease diagnosed 34 years previously. Treatment included many abdominal operations. A contrast-enhanced computed tomography scan of the abdomen revealed extensive heterogeneous thickening of the skin and subcutaneous fat, with infiltration of the abdominal musculature (Fig. 1). In October 2006, a dermolipectomy was performed. Histologically, the tumor involved the whole dermis, subcutaneous fat with an infiltrative pattern and margins. Beside the tumor, many ectatic vessels lined by a normal appearing endothelium were noted (Fig. 2a). Cell proliferation consisted of solid sheets of fusiform cells with Virchows Arch (2008) 453:217–219 DOI 10.1007/s00428-008-0623-8
European Journal of Cancer Care, 2011
A study of 28 flat bone osteosarcomas: prognostic factors and early and long-term outcome Limited... more A study of 28 flat bone osteosarcomas: prognostic factors and early and long-term outcome Limited information is available on clinical management of Flat Bone Osteosarcomas (FBOS). We retrospectively analysed prognostic factors and outcome. Twenty-eight patients were treated in our institution. Survival curves were obtained by the Kaplan-Meier method and compared with the log-rank test. The overall survival (OS) rates at 5 and 10 years were 52.4% and 45.8% respectively. The event-free survival (EFS) rates at 5 and 10 years were 41.5%. The factors influencing EFS in univariate analysis were location, metastatic disease at diagnosis, effect of neoadjuvant chemotherapy, histological response and adequate local tumour control. Location, metastatic disease at diagnosis, effect of neoadjuvant chemotherapy, histological response and local recurrence were statistically correlated with OS. Multivariate analysis retained metastatic disease at diagnosis as prognostic factors of EFS and OS. Our results suggest a more favourable outcome of FBOS as the use of a treatment scheme based on the protocols for long bone osteosarcomas. However, an adequate local treatment is essential to ensure a better outcome.
European Journal of Cancer, 2012
The study objective was to validate a specific quality of life (QoL) questionnaire for caregivers... more The study objective was to validate a specific quality of life (QoL) questionnaire for caregivers of cancer patients, the CareGiver Oncology Quality of Life questionnaire (CarGOQoL), based on the exclusive points of view of the caregivers. Materials and methods: A 75-item questionnaire generated from content analysis of interviews with caregivers was self-completed by 837 caregivers of cancer patients. In addition to sociodemographic data and patient characteristics, self-reported questionnaires assessing QoL, burden, coping and social support were collected. Psychometric properties combined methods relying on both classical test theory and item response theory. Results: The final 29 items selected assessed 10 dimensions: psychological well-being, burden, relationship with health care, administration and finances, coping, physical wellbeing, self-esteem, leisure time, social support and private life; they were isolated from principal component analysis explaining 73% of the total variance. The missing data and the floor effects were low. Some ceiling effects were found for B (34%). Cronbach's alpha coefficients ranged from 0.72 to 0.89, except private life (PL) (0.55). Unidimensionality of the scales was confirmed by Rasch analyses. Correlations with other instruments confirmed the isolated content and significant links were found with respect to patient's characteristics. Reproducibility and sensitivity to change were found satisfactory. Conclusion: The CarGOQoL could provide a reliable and valid measure of caregivers of cancer patients' QoL which are key-actors in the provision of health care.
F1000 prime reports, May 12, 2015
Leiomyosarcomas are malignant mesenchymal tumours that derive from the smooth muscle lineage. The... more Leiomyosarcomas are malignant mesenchymal tumours that derive from the smooth muscle lineage. They are studied and frequently treated as if they are the same as other soft tissue sarcomas. Recent developments suggest that a different approach may be more appropriate. Their underlying genetic mechanisms remain unclear, and complex. Unbalanced karyotypic defects are the only shared features observed across different leiomyosarcoma subtypes. Unlike other soft tissue sarcomas, leiomyosarcomas are particularly sensitive to the combination of gemcitabine and docetaxel. Furthermore, treatment with trabectedin has shown a good efficacy in leiomyosarcomas, mainly in the form of chronic disease stabilisation.
BMC Cancer, Aug 24, 2016
Background: While hypothyroidism has frequently been reported with the use of TKIs, the thyroid-s... more Background: While hypothyroidism has frequently been reported with the use of TKIs, the thyroid-stimulating hormone (TSH) suppressing effect of TKIs is rare, except for thyroiditis. We describe a case with progressive recurrent chordoma who initially became hyperthyroid in a context of autoimmunity under sorafenib treatment and later under imatinib treatment. Case presentation: A 57-year-old man with lumbar chordoma began daily treatment of 800 mg sorafenib. He did not have any other medication or recent iodinated-contrast exposure and his family history was negative for thyroid and autoimmune disease. There was no history of neck pain, irradiation or trauma, recent fever or viral illness. Pre-treatment TSH was normal. After 18 weeks of treatment, the patient presented hyperthyroidism with positive anti-TSH receptor antibodies. More surprisingly, Graves' disease recurred during treatment with imatinib. Conclusion: The fact that Graves' disease occurred after two different TKIs suggests that it could be a rare but important class effect. Anti-TSH receptor antibodies should be systematically measured when TSH decreases in order to avoid the erroneous diagnosis of transient hyperthyroidism due to thyroiditis.
Journal for ImmunoTherapy of Cancer, Jul 1, 2020
et al. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in advanced squa... more et al. Bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in advanced squamous cell carcinoma of the head and neck: results from a phase I cohort.
Clinical cancer drugs, Jan 9, 2018
Background-Upfront screening for dihydropyrimidine dehydrogenase (DPD) deficiency in patients sch... more Background-Upfront screening for dihydropyrimidine dehydrogenase (DPD) deficiency in patients scheduled for 5-FU should help reduce the risk of toxicities by preventive adaptive dosing. Our group has developed a simple functional testing categorizing patients upon their DPD status, i.e. extensive metabolizer (EM) or poor metabolizer (PM) patients, using UH2/U ratio measurement in plasma as a surrogate for DPD activity. 5-FU dosing can then be tailored according to DPD deficiency status. Objectives-We present here an observational study of this strategy implemented in routine clinical practice when treating head-and-neck cancer patients. Results-A total of 218 evaluable adult patients were treated with a 5-FU-regimen, with DPDbased adaptive dosing. Among them, 20 (9%) were identified as PM and received subsequently a 20-50% reduced dosing of 5-FU as compared with EM patients (2102 ±254 mg VS. 2577 ±353mg, p<0.001 ttest). Gender (Female) was associated with higher risk for being PM (p=0.01, Pearson's Chi squared test). Overall, early severe toxicities were seen only in 5% of patients, all being EM with standard dosing. Similarly, overall severe toxicities were observed in 12.8% of patients only, both figures being markedly lower than usually reported with standard 5-FU. Despite the average −20% reduction in 5-FU dosing between PM and EM patients, clinical efficacy was not statistically different between the two groups (p = 0.2774, chi-square test).
BMC Cancer, Jul 14, 2023
Background Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC... more Background Patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M-HNSCC) have a poor prognosis and limited therapeutic options. Immune checkpoint inhibitors (ICIs) are effective in patients with tumor progression < 6 months following first-line, platinum-based chemotherapy (PBC), but data are missing for patients with progression ≥ 6 months after the last platinum dose. Methods Retrospective analysis (six French centers, 2008-2019) of all consecutive R/M-HNSCC patients. treated first-line with PBC and tumor progression ≥ 6 months after the last platinum dose. Primary endpoint: progressionfree survival after second-line therapy (PFS2). Additional endpoints: overall survival from Day 1 of first-line (OS1) and second-line (OS2) therapy. Results R/M-HNSCC patients (n = 144) received cisplatinum (n = 67, 47%) or carboplatinum (n = 77, 53%) first-line.
Cancers, Mar 3, 2020
Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous... more Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous histological subtypes of frequent poor prognosis. Liposarcomas (LPS) are the most frequent type among them, and the aggressiveness and deep localization of dedifferentiated LPS are linked to high levels of recurrence. Current treatments available today lead to five-year overall survival has remained stuck around 60-70% for the past three decades. Here, we highlight a correlation between Aurora kinasa A (AURKA) and AURKB mRNA overexpression and a low metastasis-free survival. AURKA and AURKB expression analysis at genomic and protein level on a 9-STS cell lines panel highlighted STS heterogeneity, especially in LPS subtype. AURKA and AURKB inhibition by RNAi and drug targeting with AMG 900, a pan Aurora Kinase inhibitor, in four LPS cell lines reduces cell survival and clonogenic proliferation, inducing apoptosis and polyploidy. When combined with doxorubicin, the standard treatment in STS, aurora kinases inhibitor can be considered as an enhancer of standard treatment or as an independent drug. Kinome analysis suggested its effect was linked to the inhibition of the MAP-kinase pathway, with differential drug resistance profiles depending on molecular characteristics of the tumor. Aurora Kinase inhibition by AMG 900 could be a promising therapy in STS.
JAMA Oncology, Jun 1, 2023
IMPORTANCE There remains an unmet need to improve clinical outcomes in patients with recurrent or... more IMPORTANCE There remains an unmet need to improve clinical outcomes in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN). OBJECTIVE To evaluate clinical benefit of first-line nivolumab plus ipilimumab vs nivolumab alone in patients with R/M SCCHN. DESIGN, SETTING, AND PARTICIPANTS The CheckMate 714, double-blind, phase 2 randomized clinical trial was conducted at 83 sites in 21 countries between October 20, 2016, and January 23, 2019. Eligible participants were aged 18 years or older and had platinum-refractory or platinum-eligible R/M SCCHN and no prior systemic therapy for R/M disease. Data were analyzed from October 20, 2016 (first patient, first visit), to March 8, 2019 (primary database lock), and April 6, 2020 (overall survival database lock). INTERVENTIONS Patients were randomized 2:1 to receive nivolumab (3 mg/kg intravenously [IV] every 2 weeks) plus ipilimumab (1 mg/kg IV every 6 weeks) or nivolumab (3 mg/kg IV every 2 weeks) plus placebo for up to 2 years or until disease progression, unacceptable toxic effects, or consent withdrawal. MAIN OUTCOMES AND MEASURES The primary end points were objective response rate (ORR) and duration of response between treatment arms by blinded independent central review in the population with platinum-refractory R/M SCCHN. Exploratory end points included safety. RESULTS Of 425 included patients, 241 (56.7%; median age, 59 [range, 24-82] years; 194 males [80.5%]) had platinum-refractory disease (nivolumab plus ipilimumab, n = 159; nivolumab, n = 82) and 184 (43.3%; median age, 62 [range, 33-88] years; 152 males [82.6%]) had platinum-eligible disease (nivolumab plus ipilimumab, n = 123; nivolumab, n = 61). At primary database lock, the ORR in the population with platinum-refractory disease was 13.2% (95% CI, 8.4%-19.5%) with nivolumab plus ipilimumab vs 18.3% (95% CI, 10.6%-28.4%) with nivolumab (odds ratio [OR], 0.68; 95.5% CI, 0.33-1.43; P = .29). Median duration of response for nivolumab plus ipilimumab was not reached (NR) (95% CI, 11.0 months to NR) vs 11.1 months (95% CI, 4.1 months to NR) for nivolumab. In the population with platinum-eligible disease, the ORR was 20.3% (95% CI, 13.6%-28.5%) with nivolumab plus ipilimumab vs 29.5% (95% CI, 18.5%-42.6%) with nivolumab. The rates of grade 3 or 4 treatment-related adverse events with nivolumab plus ipilimumab vs nivolumab were 15.8% (25 of 158) vs 14.6% (12 of 82) in the population with platinum-refractory disease and 24.6% (30 of 122) vs 13.1% (8 of 61) in the population with platinum-eligible disease. CONCLUSIONS AND RELEVANCE The CheckMate 714 randomized clinical trial did not meet its primary end point of ORR benefit with first-line nivolumab plus ipilimumab vs nivolumab alone in platinum-refractory R/M SCCHN. Nivolumab plus ipilimumab was associated with an acceptable safety profile. Research to identify patient subpopulations in R/M SCCHN that would benefit from nivolumab plus ipilimumab over nivolumab monotherapy is warranted.
Journal of Clinical Oncology
TPS6110 Background: Elderly patients with locally advanced head and neck squamous cell carcinoma ... more TPS6110 Background: Elderly patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) are largely underrepresented in clinical trials (CT). Broad access to CTs in this population is challenging due to an increased prevalence of comorbidities and ageing-related conditions. However, as population-age increases, more and more elderly patients are diagnosed with LA-HNSCC although many are not eligible to receive standard cisplatin-based concurrent chemoradiation (CRT). CRT-related toxicities, treatment burden and compliance are a concern. NBTXR3, a first-in-class radioenhancer, composed of functionalized hafnium oxide nanoparticles, is administered by one-time intratumoral injection and activated by radiotherapy (RT). NBTXR3 is designed to locally amplify the tumor-killing effect of radiotherapy without additional toxicity to surrounding healthy tissue. NBTXR3 has been shown to prime the adaptive immune response in cancer models. NBTXR3 obtained EU marketing approv...
Journal of Geriatric Oncology
Purpose: The COVID-19 vaccination campaign began in December 2020, in France, and primarily targe... more Purpose: The COVID-19 vaccination campaign began in December 2020, in France, and primarily targeted the eldest people. Our study aimed to determine the level of acceptance of vaccination in a population of older patients with cancer. Methods: From January 2021, we offered vaccination with the BNT162b2 COVID-19 vaccine to all patients 70 years and older, addressed to our geriatric oncology center in Marseille University Hospital (AP-HM) for geriatric assessment before initiation of an oncological treatment. Objectives were to evaluate acceptance rate of COVID-19 vaccination, and to assess vaccine safety, reactogenicity, and efficacy two months after the first dose. Results: Between January 18, 2021 and May 7, 2021, 150 older patients with cancer were offered vaccination after a geriatric assessment. The majority were men (61.3%), with a mean age of 81 years. The two most frequent primary tumors were digestive (29.4%) and thoracic (18%). The vaccine acceptance rate was 82.6% and the complete vaccination rate (2 doses) reached 75.3%. Among the vaccinated patients, 15.9% reported mild side effects after the first dose and 23.4% after the second dose, mostly arm pain and fatigue. COVID-19 cases were observed in 5.1% of vaccinated patients compared with 16.7% in unvaccinated patients. Of the 22 vaccinated patients who agreed to have their serum tested, 15 had antibodies against the spike protein at day 21 after the first dose. Conclusion: Our study showed a high acceptance rate of COVID-19 vaccination, with good tolerance in this frail population. These results highlight the benefits of organizing vaccination campaigns at the very beginning of oncological management in older patients. Clinical Trial Registration This study was registered the 23 th May, 2019 in ClinicalTrials.gov (NCT03960593).
Cancers, 2020
Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous... more Soft tissue sarcoma (STS) are rare and aggressive tumours. Their classification includes numerous histological subtypes of frequent poor prognosis. Liposarcomas (LPS) are the most frequent type among them, and the aggressiveness and deep localization of dedifferentiated LPS are linked to high levels of recurrence. Current treatments available today lead to five-year overall survival has remained stuck around 60–70% for the past three decades. Here, we highlight a correlation between Aurora kinasa A (AURKA) and AURKB mRNA overexpression and a low metastasis-free survival. AURKA and AURKB expression analysis at genomic and protein level on a 9-STS cell lines panel highlighted STS heterogeneity, especially in LPS subtype. AURKA and AURKB inhibition by RNAi and drug targeting with AMG 900, a pan Aurora Kinase inhibitor, in four LPS cell lines reduces cell survival and clonogenic proliferation, inducing apoptosis and polyploidy. When combined with doxorubicin, the standard treatment in S...
Journal of Clinical Oncology, 2017
11041 Background: A subset of metastatic GIST exhibit very long-term survival after imatinib (IM)... more 11041 Background: A subset of metastatic GIST exhibit very long-term survival after imatinib (IM) introduction. The aim of this study was to analyse the clinico-biological characteristics of GIST pts alive > 10 years (yrs) after diagnosis (dx) of metastases (mets) and identify possible factors associated with long-term survival. Methods: Pts were identified from 2 sarcoma databases; NetSarc and ConticaGIST. Clinical data prospectively registered in the databases were supplemented with retrospective review of medical records. Results: We identified 141 pts (75 men, 66 women) with median age 54 (17-84) yrs and median ECOG 0 (0-2). Primary tumors (T) were all CD117+, and mainly gastric or intestinal (64 & 45 pts), with median size 10 (2-40) cm, CD34+ (82 pts), mitoses/50 HPF ≤ 5 (n = 36), or > 5 (n = 81). Genotype was documented in 82 (58%) pts with 73 (89%) KIT mutations (in exons 11,9 and 12 of 69, 3, and 1 pts respectively) and 9 WT KIT. 129 (91%) T were resected, 124 upfront,...
Revue de l'infirmiere, 2017
Radiotherapy forms a significant part of cancer treatment. Caregivers support and advise patients... more Radiotherapy forms a significant part of cancer treatment. Caregivers support and advise patients to help them to adapt to the treatment and limit the occurrence of side effects. A nurse and member of a mobile support care and palliative care unit shares her experience of working in a team using sophrology to relieve the anxiety resulting from the wearing of a mask in radiotherapy.
The Lancet Oncology, 2016
Revue de Chirurgie Orthopédique et Réparatrice de l'Appareil Moteur, 2007
de mutation de BRAF à 8 % dans le groupe des GIST non mutées pour KIT ou PDGFRα. La signification... more de mutation de BRAF à 8 % dans le groupe des GIST non mutées pour KIT ou PDGFRα. La signification biologique de la mutation V600E dans les GIST est inconnue mais elle pourrait être associée à la progression de la maladie et à un mauvais pronostic comme cela semble être le cas dans les mélanomes. Cette observation pourrait avoir des conséquences dans le traitement des GIST puisqu'un traitement, le BAY 43-9006 qui cible entre autre la protéine B-raf pourrait être utilisé.
La Revue de Médecine Interne, 1998
Red cell autoantibodies are very rarely observed in pregnant women. We report one case related to... more Red cell autoantibodies are very rarely observed in pregnant women. We report one case related to the presence of a lupus anticoagulant. A 32-year-old woman had a history of two intrauterine deaths that had occurred at weeks 32 and 33, respectively. Due to the presence of a lupus anticoagulant, prednisone (20 mg/day) and subcutaneous calcium heparin were administered during her third pregnancy. The direct antiglobulin test remained positive throughout the pregnancy; however, hemolysis could not be detected. Caesarean section was done in emergency at week 29, due to fetal bradycardia related to severe fetal hemolysis. When autoimmune hemolysis occurs during pregnancy, risks for the fetus increase with the severity of hemolysis in the mother. It is thought that child mortality reflects the existence of anemia, rather than the existence of hemolysis. Our observation suggests that severe fetal hemolysis may occur, despite the absence of hemolysis in the mother.
La Revue de Médecine Interne, 1998
Virchows Archiv, 2008
Sir, Angiosarcomas are rare malignant soft tissue tumors that show differentiation toward endothe... more Sir, Angiosarcomas are rare malignant soft tissue tumors that show differentiation toward endothelial cells occurring in various clinical settings, including lymphedema-associated angiosarcoma, idiopathic angiosarcoma on the head and neck in elderly people, angiosarcoma arising on chronically sundamaged skin and post-irradiation angiosarcoma [4]. Chronic lymphedema secondary to mastectomy and axillary lymphadenectomy for breast cancer, and more rarely to infectious disease, congenital disease and traumatism, is a known predisposing condition for cutaneous and superficial soft tissue angiosarcoma. We report a new case of high-grade abdominal wall angiosarcoma in a chronically lymphedematous abdominal panniculus due to morbid obesity. A 44-year-old morbidly obese man presented with a skin lesion in the periumbilical region. Clinical examination revealed a 10-cm papular lesion on a post-operative abdominal wall hernia. There was a clinical history of Crohn's disease diagnosed 34 years previously. Treatment included many abdominal operations. A contrast-enhanced computed tomography scan of the abdomen revealed extensive heterogeneous thickening of the skin and subcutaneous fat, with infiltration of the abdominal musculature (Fig. 1). In October 2006, a dermolipectomy was performed. Histologically, the tumor involved the whole dermis, subcutaneous fat with an infiltrative pattern and margins. Beside the tumor, many ectatic vessels lined by a normal appearing endothelium were noted (Fig. 2a). Cell proliferation consisted of solid sheets of fusiform cells with Virchows Arch (2008) 453:217–219 DOI 10.1007/s00428-008-0623-8
European Journal of Cancer Care, 2011
A study of 28 flat bone osteosarcomas: prognostic factors and early and long-term outcome Limited... more A study of 28 flat bone osteosarcomas: prognostic factors and early and long-term outcome Limited information is available on clinical management of Flat Bone Osteosarcomas (FBOS). We retrospectively analysed prognostic factors and outcome. Twenty-eight patients were treated in our institution. Survival curves were obtained by the Kaplan-Meier method and compared with the log-rank test. The overall survival (OS) rates at 5 and 10 years were 52.4% and 45.8% respectively. The event-free survival (EFS) rates at 5 and 10 years were 41.5%. The factors influencing EFS in univariate analysis were location, metastatic disease at diagnosis, effect of neoadjuvant chemotherapy, histological response and adequate local tumour control. Location, metastatic disease at diagnosis, effect of neoadjuvant chemotherapy, histological response and local recurrence were statistically correlated with OS. Multivariate analysis retained metastatic disease at diagnosis as prognostic factors of EFS and OS. Our results suggest a more favourable outcome of FBOS as the use of a treatment scheme based on the protocols for long bone osteosarcomas. However, an adequate local treatment is essential to ensure a better outcome.
European Journal of Cancer, 2012
The study objective was to validate a specific quality of life (QoL) questionnaire for caregivers... more The study objective was to validate a specific quality of life (QoL) questionnaire for caregivers of cancer patients, the CareGiver Oncology Quality of Life questionnaire (CarGOQoL), based on the exclusive points of view of the caregivers. Materials and methods: A 75-item questionnaire generated from content analysis of interviews with caregivers was self-completed by 837 caregivers of cancer patients. In addition to sociodemographic data and patient characteristics, self-reported questionnaires assessing QoL, burden, coping and social support were collected. Psychometric properties combined methods relying on both classical test theory and item response theory. Results: The final 29 items selected assessed 10 dimensions: psychological well-being, burden, relationship with health care, administration and finances, coping, physical wellbeing, self-esteem, leisure time, social support and private life; they were isolated from principal component analysis explaining 73% of the total variance. The missing data and the floor effects were low. Some ceiling effects were found for B (34%). Cronbach's alpha coefficients ranged from 0.72 to 0.89, except private life (PL) (0.55). Unidimensionality of the scales was confirmed by Rasch analyses. Correlations with other instruments confirmed the isolated content and significant links were found with respect to patient's characteristics. Reproducibility and sensitivity to change were found satisfactory. Conclusion: The CarGOQoL could provide a reliable and valid measure of caregivers of cancer patients' QoL which are key-actors in the provision of health care.