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"Varatharajah, Sharmini"
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Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT): a phase II study (GASPAR)
by
Corbinais, Stéphane
,
Poulain, Laurent
,
Brachet, Pierre-Emmanuel
in
5-Fluorouracil
,
Adenocarcinoma
,
Adjuvant treatment
2022
Background
Perioperative chemotherapy and surgery are a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, the prognosis remains poor for this population. The FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen is considered as the new standard chemotherapy regimen for perioperative strategy, despite associated with a 5-year overall survival rate (OS) amounting 45% following radical surgery.
Immunotherapy with antibodies that inhibit PD-1/ PD-L1 interaction has recently emerged as a new treatment option with promising and encouraging early trial results for patients with advanced or metastatic gastric or GEJ adenocarcinoma. Currently, no trials have investigated the impact of perioperative immunotherapy in combination with chemotherapy for resectable gastric or GEJ adenocarcinoma.
Methods
GASPAR trial is a multicenter open-label, nonrandomized, phase II trial to evaluate the efficacy and safety of Spartalizumab in combination with the FLOT regimen as perioperative treatment for resectable gastric or GEJ adenocarcinoma. The main endpoint is the proportion of patients with pathological complete regression (pCR) in the primary tumour after preoperative treatment.
Systemic treatment will include a pre-operative neoadjuvant and a post-operative adjuvant treatment, during which FLOT regimen will be administered every two weeks for 4 cycles and Spartalizumab every four weeks for 2 cycles.
For patients with confirmed tumor resectability on imaging assessment, surgery will be realized within 4–6 weeks after the last dose of preoperative chemotherapy. Post-operative systemic treatment will then be initiated within 4–10 weeks after surgery.
Using a Simon’s two-stage design, up to 67 patients will be enrolled, including 23 in the first stage.
Discussion
Currently, no trials have investigated the impact of immunotherapy in combination with FLOT chemotherapy as perioperative treatment for resectable gastric or GEJ adenocarcinoma. Some studies have suggested a change in the tumor immune micro-environment following neoadjuvant chemotherapy in this setting, reinforcing the relevance to propose a phase II trial evaluating efficacy and safety of Spartalizumab in combination with perioperative chemotherapy, with the aim of improving treatment efficacy and survival outcomes.
Trial registration
NCT04736485, registered February, 3, 2021.
Journal Article
Determinants of the access to remote specialised services provided by national sarcoma reference centres
by
Tétreau, Raphaël
,
Dalban, Cécile
,
Piperno-Neumann, Sophie
in
Analysis
,
Biomedical and Life Sciences
,
Biomedicine
2021
Background
Spatial inequalities in cancer management have been evidenced by studies reporting lower quality of care or/and lower survival for patients living in remote or socially deprived areas. NETSARC+ is a national reference network implemented to improve the outcome of sarcoma patients in France since 2010, providing remote access to specialized diagnosis and Multidisciplinary Tumour Board (MTB). The IGéAS research program aims to assess the potential of this innovative organization, with remote management of cancers including rare tumours, to go through geographical barriers usually impeding the optimal management of cancer patients.
Methods
Using the nationwide NETSARC+ databases, the individual, clinical and geographical determinants of the access to sarcoma-specialized diagnosis and MTB were analysed. The IGéAS cohort (
n
= 20,590) includes all patients living in France with first sarcoma diagnosis between 2011 and 2014. Early access was defined as specialised review performed before 30 days of sampling and as first sarcoma MTB discussion performed before the first surgery.
Results
Some clinical populations are at highest risk of initial management without access to sarcoma specialized services, such as patients with non-GIST visceral sarcoma for diagnosis [OR 1.96, 95% CI 1.78 to 2.15] and MTB discussion [OR 3.56, 95% CI 3.16 to 4.01]. Social deprivation of the municipality is not associated with early access on NETSARC+ remote services. The quintile of patients furthest away from reference centres have lower chances of early access to specialized diagnosis [OR 1.18, 95% CI 1.06 to 1.31] and MTB discussion [OR 1.24, 95% CI 1.10 to 1.40] but this influence of the distance is slight in comparison with clinical factors and previous studies on the access to cancer-specialized facilities.
Conclusions
In the context of national organization driven by reference network, distance to reference centres slightly alters the early access to sarcoma specialized services and social deprivation has no impact on it. The reference networks’ organization, designed to improve the access to specialized services and the quality of cancer management, can be considered as an interesting device to reduce social and spatial inequalities in cancer management. The potential of this organization must be confirmed by further studies, including survival analysis.
Journal Article
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy to Treat Pseudomyxoma Peritonei of Ovarian Origin: A Retrospective French RENAPE Group Study
by
Omar, Alhadeedi
,
Quenet, François
,
Trecourt, Alexis
in
Appendiceal Neoplasms
,
Chemotherapy
,
Combined Modality Therapy
2024
Background
Ovarian pseudomyxoma peritonei (OPMP) are rare, without well-defined therapeutic guidelines. We aimed to evaluate cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) to treat OPMP.
Methods
Patients from the French National Network for Rare Peritoneal Tumors (RENAPE) database with proven OPMP treated by CRS/HIPEC and with histologically normal appendix and digestive endoscopy were retrospectively included. Clinical and follow-up data were collected. Histopathological and immunohistochemical features were reviewed.
Results
Fifteen patients with a median age of 56 years were included. The median Peritoneal Cancer Index was 16. Following CRS, the completeness of cytoreduction (CC) score was CC-0 for 9/15 (60%) patients, CC-1 for 5/15 (33.3%) patients, and CC-2 for 1/15 (6.7%) patients. The median tumor size was 22.5 cm. After pathological review and immunohistochemical studies, tumors were classified as Group 1 (mucinous ovarian epithelial neoplasms) in 3/15 (20%) patients; Group 2 (mucinous neoplasm in ovarian teratoma) in 4/15 (26.7%) patients; Group 3 (mucinous neoplasm probably arising in ovarian teratoma) in 5/15 (33.3%) patients; and Group 4 (non-specific group) in 3/15 (20%) patients. Peritoneal lesions were OPMP pM1a/acellular, pM1b/grade 1 (hypocellular) and pM1b/grade 3 (signet-ring cells) in 13/15 (86.7%), 1/15 (6.7%) and 1/15 (6.7%) patients, respectively. Disease-free survival analysis showed a difference (
p
= 0.0463) between OPMP with teratoma/likely-teratoma origin (groups 2 and 3; 100% at 1, 5, and 10 years), and other groups (groups 1 and 4; 100%, 66.6%, and 50% at 1, 5, and 10 years, respectively).
Conclusion
These results suggested that a primary therapeutic strategy using complete CRS/HIPEC for patients with OPMP led to favorable long-term outcomes.
Journal Article
Can a Benefit be Expected from Surgical Debulking of Unresectable Pseudomyxoma Peritonei?
by
Dumont, Frédéric
,
Honoré, Charles
,
Varatharajah, Sharmini
in
Adult
,
Aged
,
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
2016
Purpose
This study evaluated the role of surgical debulking in improving pseudomyxoma peritonei (PMP)-related symptoms if complete cytoreductive surgery (CCRS) of huge PMP is unachievable.
Methods
This was a retrospective analysis of a prospective database of all patients in our tertiary care center treated for PMP between 1992 and 2014. All cases of surgical debulking in patients scheduled for CCRS that proved unachievable during the operation were selected for the present study.
Results
Among the 338 patients operated on for PMP, 39 (11.5 %) had undergone surgical debulking because CCRS was unachievable. All of these patients were symptomatic before surgery, and the median PCI was 32 (5–39). More than 80 % of the disease burden was resected in 23 patients (59 %). Mortality and major morbidity rates were 2.5 and 23 %, respectively. After debulking surgery, symptoms gradually subsided over a median time of 23 months and 50 % of the patients no longer experienced PMP-related symptoms after a median follow-up of 24.5 months. After a median follow-up of 46.4 months (range 3–120), median overall (OS) and progression-free (PFS) survival times were 55.5 and 20 months, respectively. Five-year OS and PFS rates were 46 and 11 %, respectively.
Conclusions
Aggressive debulking surgery in case of unachievable CCRS for huge PMP can offer prolonged relief of PMP-related symptoms and long-term survival, in experienced centers that are able to be sufficiently aggressive to resect the major part of the disease, and conservative enough to achieve low mortality and good quality of life.
Journal Article
Perioperative treatment in resectable gastric cancer with spartalizumab in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel
by
Corbinais, Stéphane
,
Poulain, Laurent
,
Brachet, Pierre-Emmanuel
in
Adjuvant treatment
,
Antimitotic agents
,
Antineoplastic agents
2022
Perioperative chemotherapy and surgery are a standard of care for patients with resectable gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, the prognosis remains poor for this population. The FLOT (fluorouracil, leucovorin, oxaliplatin, and docetaxel) regimen is considered as the new standard chemotherapy regimen for perioperative strategy, despite associated with a 5-year overall survival rate (OS) amounting 45% following radical surgery. GASPAR trial is a multicenter open-label, nonrandomized, phase II trial to evaluate the efficacy and safety of Spartalizumab in combination with the FLOT regimen as perioperative treatment for resectable gastric or GEJ adenocarcinoma. The main endpoint is the proportion of patients with pathological complete regression (pCR) in the primary tumour after preoperative treatment. Currently, no trials have investigated the impact of immunotherapy in combination with FLOT chemotherapy as perioperative treatment for resectable gastric or GEJ adenocarcinoma. Some studies have suggested a change in the tumor immune micro-environment following neoadjuvant chemotherapy in this setting, reinforcing the relevance to propose a phase II trial evaluating efficacy and safety of Spartalizumab in combination with perioperative chemotherapy, with the aim of improving treatment efficacy and survival outcomes.
Journal Article
Management and outcomes of adolescent and young adult sarcoma patients: results from the French nationwide database NETSARC
by
Lervat, Cyril
,
Anract, Philippe
,
Penel, Nicolas
in
Adolescent
,
Adolescents and young adults
,
AYAs
2023
Background
The initial management of patients with sarcoma is a critical issue. We used the nationwide
French National Cancer Institute
-funded prospective sarcoma database NETSARC to report the management and oncologic outcomes in adolescents and young adults (AYAs) patients with sarcoma at the national level.
Patients and methods
NETSARC database gathers regularly monitored and updated data from patients with sarcoma. NETSARC was queried for patients (15–30 years) with sarcoma diagnosed from 2010 to 2017 for whom tumor resection had been performed. We reported management, locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) in AYA treated in French reference sarcoma centers (RSC) and outside RSC (non-RSC) and conducted multivariable survival analyses adjusted for classical prognostic factors.
Results
Among 3,227 patients aged 15–30 years with sarcoma diagnosed between 2010 and 2017, the study included 2,227 patients with surgery data available, among whom 1,290 AYAs had been operated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed including pre-treatment biopsy (RSC: 85.9%; non-RSC 48.1%), pre-treatment imaging (RSC: 86.8%; non-RSC: 56.5%) and R0 margins (RSC 57.6%; non-RSC: 20.2%) (
p
< 0.001). 3y-OS rates were 81.1% (95%CI 78.3–83.6) in AYA in RSC and 82.7% (95%CI 79.4–85.5) in AYA in non-RSC, respectively. Whereas no significant differences in OS was observed in AYAs treated in RSC and in non-RSC, LRFS and PFS were improved in AYAs treated in RSC compared to AYAs treated in non-RSC (Hazard Ratios (HR): 0.58 and 0.83, respectively).
Conclusions
This study highlights the importance for AYA patients with sarcoma to be managed in national sarcoma reference centers involving multidisciplinary medical teams with paediatric and adult oncologists.
Journal Article
ASO Visual Abstract: Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy to Treat Pseudomyxoma Peritonei of Ovarian Origin: A Retrospective French RENAPE Group Study
by
Omar, Alhadeedi
,
Quenet, François
,
Trecourt, Alexis
in
ASO Visual Abstract
,
Cancer
,
Chemotherapy
2024
Journal Article
Tertiary lymphoid structures in epithelioid malignant peritoneal mesothelioma are associated with neoadjuvant chemotherapy, but not with prognosis
by
Bonnefoy, Isabelle
,
Piessen Guillaume
,
Mery Eliane
in
Adaptive immunity
,
Chemotherapy
,
Etiology
2021
Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant peritoneal mesothelioma. The relationship between a strong adaptive immune response and a better prognosis in malignant solid tumors is widely known. Due to the low incidence of epithelioid malignant peritoneal mesothelioma (EMPM), very little is known about their immune micro-environment. We encountered several cases of tertiary lymphoid structures in EMPM in a previous study and aimed to investigate in the same series the prevalence, clinicopathological features, and the prognostic impact associated with tertiary lymphoid structures in EMPM (TLS-EMPM). Cases of EMPM, from 1995 to 2018, were retrieved from 7 French institutions from the RENAPE Network. The predictions in terms of overall survival (OS) and progression-free survival (PFS) of TLS-EMPM were analyzed. We report 52 cases of TLS-EMPM among a series of 138 cases of EMPM. TLS-EMPM was significantly associated with neoadjuvant chemotherapy, and was not a prognostic indicator for OS (p = 0.652) and PFS (p = 0.804) in our series. TLS is a component of the host immune response to EMPM significantly associated with neoadjuvant chemotherapy, but was not a predictor of prognosis for overall and progression-free survivals in this series. These findings provide another possible etiology for tertiary lymphoid structures.
Journal Article
Management and outcomes of adolescent and young adult sarcoma patients: results from the French nationwide database NETSARC
2023
Abstract Background The initial management of patients with sarcoma is a critical issue. We used the nationwide French National Cancer Institute -funded prospective sarcoma database NETSARC to report the management and oncologic outcomes in adolescents and young adults (AYAs) patients with sarcoma at the national level. Patients and methods NETSARC database gathers regularly monitored and updated data from patients with sarcoma. NETSARC was queried for patients (15–30 years) with sarcoma diagnosed from 2010 to 2017 for whom tumor resection had been performed. We reported management, locoregional recurrence-free survival (LRFS), progression-free survival (PFS), and overall survival (OS) in AYA treated in French reference sarcoma centers (RSC) and outside RSC (non-RSC) and conducted multivariable survival analyses adjusted for classical prognostic factors. Results Among 3,227 patients aged 15–30 years with sarcoma diagnosed between 2010 and 2017, the study included 2,227 patients with surgery data available, among whom 1,290 AYAs had been operated in RSC, and 937 AYAs in non-RSC. Significant differences in compliance to guidelines were observed including pre-treatment biopsy (RSC: 85.9%; non-RSC 48.1%), pre-treatment imaging (RSC: 86.8%; non-RSC: 56.5%) and R0 margins (RSC 57.6%; non-RSC: 20.2%) ( p < 0.001). 3y-OS rates were 81.1% (95%CI 78.3–83.6) in AYA in RSC and 82.7% (95%CI 79.4–85.5) in AYA in non-RSC, respectively. Whereas no significant differences in OS was observed in AYAs treated in RSC and in non-RSC, LRFS and PFS were improved in AYAs treated in RSC compared to AYAs treated in non-RSC (Hazard Ratios (HR): 0.58 and 0.83, respectively). Conclusions This study highlights the importance for AYA patients with sarcoma to be managed in national sarcoma reference centers involving multidisciplinary medical teams with paediatric and adult oncologists.
Journal Article