21 results on '"L. Polastro"'
Search Results
2. 789 Prognostic impact of mesenteric lymph node metastasis in patients with advanced ovarian cancer
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M Chintinne, CF Pop, Joseph Kerger, Gabriel Liberale, Isabelle Veys, L Polastro, Denis Larsimont, and A El Asmar
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medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Retrospective cohort study ,medicine.disease ,Gastroenterology ,Metastasis ,medicine.anatomical_structure ,Lymphatic system ,Internal medicine ,medicine ,Stage (cooking) ,business ,Ovarian cancer ,Lymph node ,Pathological - Abstract
Introduction/Background* Digestive tract resection is a common procedure performed in bulky advanced-stage ovarian cancer (AOC) to achieve complete cytoreductive surgery (CRS). Very few data are available on the incidence and the prognostic impact of mesenteric lymph node (MLN) involvement. The aim of this study is to determine the incidence of MLN involvement in patients undergoing a digestive tract resection at the time of CRS for AOC and to analyze its prognostic impact. Methodology A retrospective study including patients who underwent CRS for AOC between 2006 and 2017. Patient’s clinico-pathological characteristics were collected, incidence of various LN basin involvement were analyzed focusing on MLN. Overall survival (OS) and disease free survival (DFS) were calculated with the KM method. Result(s)* During the study period 72 of 176 (40.9%) patients with stage III-IVa AOC had a digestive tract resection during CRS with the recto-sigmoid resection being the most frequent (52 patients). There was an involvement of the serosa in 38 (52.8%), sub-serosa in 10 (13.9%), muscularis propria in 10 (13.9%), and mucosa in 5 cases (6.9%), respectively. MLN were found in 37 out of 72 (51.4%) patients with digestive tract resection. 25 patients (67.5%) had MLN involvement with a median of 5 involved nodes (range, 1 to 45). There was a trend in worse 5-year OS (45.8% vs 63.6%, p=0.064) for patients with MLN involvement. Conclusion* Patients with AOC involving the digestive tract is associated with a high incidence of MLN metastasis. Resection of the associated lymphatic tributaries of affected bowel segment and correct pathological examination of the MLN should be performed regularly to improve staging and better evaluate their prognostic impact in case of LN involvement.
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- 2021
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3. 519MO Phase III EMPOWER-Cervical 1/GOG-3016/ENGOT-cx9 trial of cemiplimab in recurrent or metastatic (R/M) cervical cancer: Long-term survival analysis
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A. Oaknin, B.J. Monk, L. Polastro, A. Cristina de Melo, H.S. Kim, Y.M. Kim, A.S. Lisyanskaya, V. Samouëlian, D. Lorusso, F.B. Damian, C-L. Chang, S. Takahashi, D. Ramone, B. Maćkowiak-Matejczyk, J. Li, S. Jamil, M.D. Mathias, M.G. Fury, and K.S. Tewari
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Oncology ,Hematology - Published
- 2022
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4. [Cardiac metastase of a soft tissue sarcoma: a case report and a review of the literature]
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L, Polastro, N, de Saint Aubain, M, Lemort, F, Delhaye, and A, Awada
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Heart Neoplasms ,Fatal Outcome ,Thigh ,Chondrosarcoma ,Buttocks ,Humans ,Female ,Sarcoma ,Middle Aged ,Neoplasms, Connective and Soft Tissue ,Ultrasonography - Abstract
Soft tissue sarcomas represent rare tumors. They recur most often locally and in the lungs. We report the case of a 58-year woman who was treated for awith chemotherapy and then surgery. About a year after the end of the treatment an intracardiac mass was identified during a follow up chest CT-scan. The patient underwent a surgical resection of that mass found to bel myxoid chondrosarcoma metastasis. Only 2 cases of cardiac dissemination of extraskeletal myxoid chondrosarcoma have been described. The differential diagnosis of intracardiac masses is discussed. In some carefully selected cases atrisks of obstructive shock or embolization and unique metastatic location, cardiac surgery should be considered.
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- 2015
5. Assessment of the American College of Surgeons Surgical Risk Calculator (ACS-SRC) for Prediction of Early Postoperative Complications in Patients Undergoing Cytoreductive Surgery for Ovarian Peritoneal Carcinomatosis.
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Kabeya C, Khaled C, Polastro L, Moreau M, Bucella D, Fastrez M, and Liberale G
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- Humans, Female, Middle Aged, Retrospective Studies, Risk Assessment methods, Aged, Adult, Cytoreduction Surgical Procedures methods, Peritoneal Neoplasms surgery, Ovarian Neoplasms surgery, Postoperative Complications
- Abstract
Ovarian cancer (OC) is diagnosed at a locally advanced stage in two-thirds of cases. The first line of treatment consists of cytoreductive surgery (CRS) combined with neoadjuvant and/or adjuvant chemotherapy. However, CRS can be associated with high rates of postoperative complications (POCs), and detection of fragile patients at high risk of POCs is important. The American College of Surgeons Surgical Risk Calculator (ACS-SRC) provides a predictive model for early POCs (30 days) for any given surgical procedure. This study aimed to evaluate the performance of the ACS-SRC in predicting the occurrence of early POCs for patients undergoing CRS for OC. This was a retrospective study that included patients undergoing CRS for advanced OC between January 2010 and December 2022. Early POCs were reviewed, and the rate of POCs was compared with those predicted by the ACS-SRC to evaluate its accuracy (i.e., discrimination and calibration). A total of 218 patients were included, 112 of whom underwent extensive surgery/resection. A total of 94 complications were recorded. This cohort demonstrated correct calibration of the ACS-SRC for the prediction of surgical site infection, readmission, and the need for nursing care post-discharge (NCPD; transfer to revalidation center or need for nursing care at home). Using both the discrimination and calibration methods, the score only predicted NCPD. In this study, the ACS-SRC was shown to be of little value for patients undergoing cytoreductive surgery for ovarian peritoneal carcinomatosis, as it only accurately predicted NCPD.
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- 2024
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6. A Multimodal Patient-Centered Teleprehabilitation Approach for Patients Undergoing Surgery for Breast Cancer: A Clinical Perspective.
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Mostaqim K, Lahousse A, Ubaghs S, Timmermans A, Deliens T, Vanhoeij M, Fontaine C, de Jonge E, Van Hoecke J, Polastro L, Lamotte M, Cuesta-Vargas AI, Huysmans E, and Nijs J
- Abstract
Breast cancer is the most common malignancy among women worldwide, and advances in early detection and treatment have significantly increased survival rates. However, people living beyond breast cancer often suffer from late sequelae, negatively impacting their quality of life. Prehabilitation, focusing on the period prior to surgery, is a unique opportunity to enhance oncology care by preparing patients for the upcoming oncological treatment and rehabilitation. This article provides a clinical perspective on a patient-centered teleprehabilitation program tailored to individuals undergoing primary breast cancer surgery. The proposed multimodal program includes three key components: patient education, stress management, and physical activity promotion. Additionally, motivational interviewing is used to tailor counseling to individual needs. The proposed approach aims to bridge the gap between diagnosis and oncological treatment and provides a holistic preparation for surgery and postoperative rehabilitation in breast cancer patients. The aim of this preparation pertains to improving mental and physical resilience. By integrating current evidence and patient-centered practices, this article highlights the potential for teleprehabilitation to transform clinical care for breast cancer patients, addressing both logistical challenges and holistic well-being.
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- 2024
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7. Implementation of a remote symptom monitoring pathway in oncology care: analysis of real-world experience across 33 cancer centres in France and Belgium.
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Franzoi MA, Ferreira AR, Lemaire A, Rodriguez J, Grosjean J, Ribeiro JM, Polastro L, Grellety T, Artignan X, Le Du K, Pagliuca M, Nouhaud É, Autheman M, André F, Basch E, Metzger O, Ferté C, Di Palma M, Scotté F, and Vaz-Luis I
- Abstract
Background: Remote patient monitoring (RPM) of symptoms using electronic patient reported outcomes (ePROs) has been shown to reduce symptom burden and hospitalizations, increase dose intensity and improve quality of life of patients during systemic therapy being recommended by international guidelines in routine oncology practice. However, implementation in routine care has been slow and faces several challenges. In this study we report on the real-world multi-center implementation of a RPM pathway encompassing weekly patient symptom ePRO reporting with electronic alert notifications triggered to providers for severe or worsening symptoms., Methods: An RPM pathway was implemented in 33 European cancer centers in France and Belgium between November 2021 and August 2023. The implementation process followed a standardized phasic process of Exploration, Preparation, Implementation and Sustainment. Patient-level and system-level implementation metrics were collected and evaluated according to the Reach, Effectiveness, Adoption, Implementation and Maintenance (RE-AIM) framework., Findings: Across the 33 cancer centers, the RPM pathway was implemented for 3015 patients cared for by 168 providers. The RPM pathway enabled effective and timely symptom management with 94.6% of all alerts (10,132/10,711) evolving to an improvement two weeks later, among which 88.4% (9468/10,711) showed ≥2 grades of improvement on the 5-point scale of the Patient-Reported Outcomes Common Terminology (PRO-CTCAE). The median time to alert management by the care team was 13 h 41 min (25th percentile: 1 h 42 min, 75th percentile: 1 day + 19 h 54 min), with 80% (36,269/45,334) of alerts managed by a nurse navigator telephone call. Patient adherence with weekly ePRO reporting was 82% (2472/3015). In an experience survey, 87% (32/38) of providers were satisfied with integrating the solution into their organization and 90% (276/307) of the patients felt that ePRO reporting positively impacted their care. As of March 2024, the pathway has been maintained in all participating centers, with activation of an additional 18 centers following data lock, and reimbursement for this RPM pathway approved in France in October 2023., Interpretation: These findings demonstrate the feasibility of implementing and maintaining an RPM pathway during routine care across a diverse group of cancer centers in the European setting, with high levels of patient and provider engagement, and positive clinical impact., Funding: Part of this work was funded Breast Cancer Research Foundation (Career Development Award to Maria Alice Franzoi) and Resilience (nurse navigation and technology support)., Competing Interests: Maria Alice Franzoi: Research Funding: Resilience Care (Institution). Speaker honoraria: Novartis (Institution). Arlindo Ferreira: Resilience (Employment). Antoine Lemaire: Consultancy or speaker honoraria: Ethypharm, Kyowa Kirin, Baxter, Alfasigma, Mundi Pharma, Accord Healthcare. Joseph Rodriguez: None. Jessica Grosjean: None. Joana M Ribeiro: Travel, Accommodations, Expenses: Gilead, Astra Zeneca, eESO, Exact Sciences, Novartis, Pfizer, Roche and Sanofi, MSD. Laura Polastro: Speaker fees: Resilience; Research Funding: Resilience (institution). Thomas Grellety: Speaker fees: Resilience. Xavier Artignan: None. Katell Le Du: None. Martina Pagliuca: Travel expenses: Gilead. Élodie Nouhaud: Resilience (Employment). Maximilien Autheman: Resilience (Employment). Fabrice André: Research Funding: AstraZeneca (Inst), Novartis (Inst), Pfizer (Inst), Eli Lilly (Inst), Roche (Inst), Daiichi (Inst). Travel, Accommodations, Expenses: Novartis, Roche, GlaxoSmithKline, AstraZeneca. Ad boards or symposium compensated to the hospital: AstraZeneca, Lilly, Novartis, Pfizer, Daiichi-Sankyo, Relay Tx and Roche. Ad board compensated to the author: Lilly. Ethan Basch: Stock and Other Ownership Interests: Vector Science. Consulting or Advisory Role: SIVAN Innovation, Navigating Cancer, AstraZeneca, Resilience Care. Other Relationship: Centers for Medicare and Medicaid Services, National Cancer Institute, American Society of Clinical Oncology, JAMA-Journal of the American Medical Association, Patient-Centered OUtcomes Research Institute (PCORI). Otto Metzger: Dr Metzger reported receiving grant funding from Pfizer Inc and personal fees from Merck & Co and Oncoclinicas outside the submitted work. Charles Ferté: Resilience (Employment). Mario Di Palma: Honoraria: AstraZeneca, Novartis. Consulting or Advisory Role: Sandoz. Speakers' Bureau: Amgen, Kyowa Kirin International, MSD Oncology, Mundipharma, Sandoz, Roche. Research Funding: Bayer, Sandoz (Inst), Pierre Fabre (Inst), Fresenius Kabi, Astellas Pharma (Inst), Janssen Oncology (Inst), Roche (Inst), Sanofi (Inst). Travel, Accommodations, Expenses: Pfizer, Novartis. Florian Scotté: Honoraria: Leo Phar, Viatris, Pharmanovia, Amgen, Gilead Sciences, B. MS GmbH & Co. KG, GlaxoSmithKline. Ines Vaz-Luis: Speaker honoraria from Amgen, AstraZeneca, Pfizer/Edimark, Novartis, Sandoz (Institutional); Writing engagement from Pfizer/Edimark (Institutional); Research funding from Resilience Care (Institutional), Travelling Novartis., (© 2024 The Authors.)
- Published
- 2024
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8. ASO Author Reflections: Mesenteric Lymph Node Involvement in Ovarian Cancer Peritoneal Metastases.
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Channawi A, Pop FC, Khaled C, Polastro L, and Liberale G
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- Humans, Female, Lymph Nodes pathology, Lymph Node Excision, Mesentery pathology, Sentinel Lymph Node Biopsy, Peritoneal Neoplasms secondary, Ovarian Neoplasms pathology, Sentinel Lymph Node pathology
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- 2024
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9. Prognostic Impact of Mesenteric Lymph Node Status on Digestive Resection Specimens During Cytoreductive Surgery for Ovarian Peritoneal Metastases.
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Channawi A, Pop FC, Khaled C, Gomez MG, Moreau M, Polastro L, Veys I, and Liberale G
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- Humans, Female, Prognosis, Peritoneum pathology, Retrospective Studies, Cytoreduction Surgical Procedures, Prospective Studies, Lymph Nodes surgery, Lymph Nodes pathology, Carcinoma, Ovarian Epithelial surgery, Survival Rate, Peritoneal Neoplasms secondary, Ovarian Neoplasms pathology, Hyperthermia, Induced
- Abstract
Background: The most common mode of ovarian cancer (OC) spread is intraperitoneal dissemination, with the peritoneum as the primary site of metastasis. Cytoreductive surgery (CRS) with chemotherapy is the primary treatment. When necessary, a digestive resection can be performed, but the role of mesenteric lymph nodes (MLNs) in advanced OC remains unclear, and its significance in treatment and follow-up evaluation remains to be determined. This study aimed to evaluate the prevalence of MLN involvement in patients who underwent digestive resection for OC peritoneal metastases (PM) and to investigate its potential prognostic value., Methods: This retrospective, descriptive study included patients who underwent CRS with curative intent for OC with PM between 1 January 2007 and 31 December 2020. The study assessed MLN status and other clinicopathologic features to determine their prognostic value in relation to overall survival (OS) and progression-free survival (PFS)., Results: The study enrolled 159 women with advanced OC, 77 (48.4%) of whom had a digestive resection. For 61.1% of the patients who underwent digestive resection, MLNs were examined and found to be positive in 56.8%. No statistically significant associations were found between MLN status and OS (p = 0.497) or PFS ((p = 0.659)., Conclusions: In anatomopathologic studies, MLNs are not systematically investigated but are frequently involved. In the current study, no statistically significant associations were found between MLN status and OS or PFS. Further prospective studies with a systematic and standardized approach should be performed to confirm these findings., (© 2023. The Author(s).)
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- 2024
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10. Deep epigastric lymph nodes implication in patients' recurrence pattern after cytoreductive surgery in ovarian peritoneal metastases.
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El Asmar A, Vouche M, Pop F, Polastro L, Chintinne M, Veys I, Donckier V, and Liberale G
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- Female, Humans, Peritoneum pathology, Cytoreduction Surgical Procedures, Retrospective Studies, Neoplasm Recurrence, Local pathology, Lymph Nodes diagnostic imaging, Lymph Nodes pathology, Combined Modality Therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Peritoneal Neoplasms diagnostic imaging, Peritoneal Neoplasms therapy, Peritoneal Neoplasms pathology, Ovarian Neoplasms diagnostic imaging, Ovarian Neoplasms surgery, Hyperthermia, Induced
- Abstract
Introduction: Although complete cytoreductive surgery (CRS) with or without hyperthermic intraperitoneal chemotherapy (HIPEC) offers a good prognosis in patients with peritoneal metastasis of ovarian cancer (PMOC), recurrences are quite common. These recurrences can be intra-abdominal or systemic in nature. Our objective was to study and illustrate the global recurrence pattern in patients operated for PMOC, shedding light on a previously overlooked lymphatic basin at the level of the epigastric artery, the deep epigastric lymph nodes (DELN) basin., Patients and Methods: This was a retrospective study including patients with PMOC who underwent surgery with curative-intent, from 2012 until 2018, at our cancer center, and who presented with any type of disease recurrence on follow-up. CT-scans, MRIs and PET-scans were reviewed in order to determine solid organs and lymph nodes (LN) recurrences., Results: During the study period, 208 patients underwent CRS ± HIPEC, 115 (55.3%) presented with organ or lymphatic recurrence over a median follow-up of 81 months. Sixty percent of these patients had radiologically enlarged LN involvement. The pelvis/pelvic peritoneum was the most common intra-abdominal organ recurrence site (47%), while the retroperitoneal LN was the most common lymphatic recurrence site (73.9%). Previously overlooked DELN were found in 12 patients, with 17.4% implication in lymphatic basin recurrence patterns., Conclusion: Our study revealed the potential role of the DELN basin, previously overlooked in the systemic dissemination process of PMOC. This study sheds light on a previously unrecognized lymphatic pathway, as an intermediate checkpoint or relay, between the peritoneum, an intra-abdominal organ, and the extra-abdominal compartment., Competing Interests: Declaration of competing interest Authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2023
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11. Prognostic value of peritoneal scar-like tissue in patients with peritoneal metastases of ovarian origin presenting for curative-intent cytoreductive surgery.
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El Asmar A, Pop F, Helou EE, Demetter P, Veys I, Polastro L, Bohlok A, and Liberale G
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- Humans, Cytoreduction Surgical Procedures, Cicatrix, Prognosis, Retrospective Studies, Peritoneal Neoplasms therapy, Percutaneous Coronary Intervention
- Abstract
Background: Complete cytoreductive surgery (CRS), remain the gold standard in the treatment of peritoneal metastases of ovarian cancer (PMOC). Given the increasing rate of neoadjuvant chemotherapy in patients with high PCI, prior abdominal surgeries, inflammation and fibrotic changes, the benefit of removing any "peritoneal scar-like tissues" (PST) during CRS, hasn't been thoroughly investigated. Our objective in this retrospective cohort was to identify the proportion of malignant cells positivity in PST of patients with PMOC, undergoing curative-intent CRS ± HIPEC., Methods: This is a retrospective study, conducted at our comprehensive cancer center, including patients with PMOC, presenting for curative-intent CRS. During CRS, benign-looking peritoneal lesions, lacking the typical hard nodular, aggressive, and invasive morphology, were systematically resected or electro fulgurated. PSTs were analyzed for the presence of tumoral cells by our pathologist. Correlations between the presence of PST and their positivity, and the different patients' variables, were studied., Results: In 51% of patients, PST harbored malignant cells. Those were associated with poorly differentiated serous tumors, a high PCI (> 8) and a worse DFS: 17 months in the positive PST group versus 29 months in the negative PST group (p = 0.05), on univariate analysis. Multivariate analysis revealed that PCI > 8 and poorly differentiated primary tumor histology were correlated with a worse DFS, and that higher PCI and advanced FIGO were correlated with a worse OS., Conclusion: Benign-looking PST harbors malignancy in 51% of cases. The benefit of their systematic resection and their prognostic value should be further investigated in larger cohorts., (© 2023. BioMed Central Ltd., part of Springer Nature.)
- Published
- 2023
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12. PARP inhibitors (PARPi) prolongation after local therapy for oligo-metastatic progression in relapsed ovarian cancer patients.
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Gauduchon T, Kfoury M, Lorusso D, Floquet A, Ventriglia J, Salaun H, Moubarak M, Rivoirard R, Polastro L, Favier L, You B, Berton D, de la Motte Rouge T, Mansi L, Abdeddaim C, Prulhiere K, Lancry Lecomte L, Provansal M, Dalban C, and Ray-Coquard I
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- Humans, Female, Carcinoma, Ovarian Epithelial drug therapy, Retrospective Studies, Neoplasm Recurrence, Local drug therapy, Poly(ADP-ribose) Polymerase Inhibitors, Ovarian Neoplasms drug therapy
- Abstract
Background: PARP inhibitors (PARPi) have revolutionized the management of high-grade epithelial ovarian cancer (HGOC) treatment. However, a significant number of patients relapse or progress under PARPi, leading to the introduction of a new line of systemic therapy such as chemotherapy. In patients with a limited number of metastatic sites at progression, -referred to as an oligometastatic progression- a potential indication for local therapy followed by re-introduction or continuation of PARPi treatment rather than initiating a new line of chemotherapy could be proposed. However, the impact of such strategies on progression free survival (PFS) in these patients remains unknown., Methods: This international multicenter retrospective study evaluated the efficacy of PARPi continuation or re-introduction in patients with HGOC after local treatment for oligometastatic progression. The main objective was to assess PFS under PARPi after local therapy (PFS post-LT). Secondary objectives included safety and overall survival (OS)., Results: 74 patients were identified in 20 centers between April 2020 and November 2021. 65% of patients were BRCA mutated and 92% had received ≥2 lines of prior systemic chemotherapy before the initial introduction of PARPi. Main progression sites were lymph nodes (42%), peritoneum (27%), liver (16%), other visceral (16%) and abdominal wall (4%). Local therapies included radiotherapy (45%), surgery (43%), both (7%), percutaneous thermal ablation (4%) or chemoembolization (1%). Median PFS post-LT was 11.5 months [95% CI 7.4; 17.2]. After a median follow up of 14.8 months, 6 patients (8.1%) discontinued PARPi due to toxicity. The 1-year overall survival rate was 90.7% [95% CI 79.1; 96.0]., Conclusions: With close to one year without progression or introduction of a new line of systemic therapy, this study reports the feasibility and potential benefit of this original strategy in patients with oligometastatic progression under PARPi., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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13. Prognostic value of preoperative serological biomarkers in patients undergoing cytoreductive surgery for ovarian cancer peritoneal metastases.
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Khaled C, El Asmar A, Raisi O, Moreau M, Polastro L, Veys I, Pop FC, Donckier V, and Liberale G
- Abstract
Objectives: Peritoneal metastases of ovarian cancer (PMOC) are common at initial presentation. Cytoreductive surgery (CRS) of curative intent has been proven to be efficient in increasing the overall survival (OS) and the disease-free survival (DFS) of these patients. Nevertheless, CRS is associated with high postoperative morbidity, which makes patient selection a major concern. Appropriate prognostic factors that can predict patient outcomes after surgery are still lacking. Preoperative biomarkers and their ratios have been shown to be predictive of patient prognosis for various solid tumors. We aimed to study their correlation with the prognosis of patients undergoing CRS for PMOC., Methods: This retrospective study included patients with PMOC operated by CRS. Preoperative biomarkers and other clinicopathological characteristics were studied to determine their prognostic value in terms OS and DFS., Results: 216 patients were included. Patients with preoperative hemoglobin (Hb) <11.7 g/dL had a poorer prognosis in terms of OS (p=0.0062) and DFS (p=0.0077). Additionally, increased neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR) >0.32, and platelet-to-lymphocyte ratio (PLR) >214.5 were associated with worse OS (p=0.022, p=0.0028, and p=0.0018, respectively) and worse DFS (p=0.028, p=0.003, and p=0.019, respectively). Multivariate analysis showed that the variables mentioned above were independent predictive factors for OS and DFS., Conclusions: Preoperative Hb level, NLR, MLR, and PLR are prognostic factors for OS and DFS in PMOC patients operated by curative CRS., Competing Interests: Competing interests: Authors state no conflict of interest., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)
- Published
- 2023
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14. Inhibition of RANK signaling in breast cancer induces an anti-tumor immune response orchestrated by CD8+ T cells.
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Gómez-Aleza C, Nguyen B, Yoldi G, Ciscar M, Barranco A, Hernández-Jiménez E, Maetens M, Salgado R, Zafeiroglou M, Pellegrini P, Venet D, Garaud S, Trinidad EM, Benítez S, Vuylsteke P, Polastro L, Wildiers H, Simon P, Lindeman G, Larsimont D, Van den Eynden G, Velghe C, Rothé F, Willard-Gallo K, Michiels S, Muñoz P, Walzer T, Planelles L, Penninger J, Azim HA Jr, Loi S, Piccart M, Sotiriou C, and González-Suárez E
- Subjects
- Adult, Animals, Breast Neoplasms blood, Breast Neoplasms drug therapy, Breast Neoplasms pathology, Cell Line, Tumor, Chemokines metabolism, Denosumab pharmacology, Denosumab therapeutic use, Female, Humans, Immunosuppression Therapy, Immunotherapy, Inflammation Mediators metabolism, Lymphocytes, Tumor-Infiltrating immunology, Mice, Inbred C57BL, Middle Aged, Models, Biological, Myeloid Cells immunology, Neoplasm Staging, Neutrophils immunology, RANK Ligand blood, RANK Ligand metabolism, Breast Neoplasms immunology, CD8-Positive T-Lymphocytes immunology, Immunity, Receptor Activator of Nuclear Factor-kappa B metabolism, Signal Transduction
- Abstract
Most breast cancers exhibit low immune infiltration and are unresponsive to immunotherapy. We hypothesized that inhibition of the receptor activator of nuclear factor-κB (RANK) signaling pathway may enhance immune activation. Here we report that loss of RANK signaling in mouse tumor cells increases leukocytes, lymphocytes, and CD8
+ T cells, and reduces macrophage and neutrophil infiltration. CD8+ T cells mediate the attenuated tumor phenotype observed upon RANK loss, whereas neutrophils, supported by RANK-expressing tumor cells, induce immunosuppression. RANKL inhibition increases the anti-tumor effect of immunotherapies in breast cancer through a tumor cell mediated effect. Comparably, pre-operative single-agent denosumab in premenopausal early-stage breast cancer patients from the Phase-II D-BEYOND clinical trial (NCT01864798) is well tolerated, inhibits RANK pathway and increases tumor infiltrating lymphocytes and CD8+ T cells. Higher RANK signaling activation in tumors and serum RANKL levels at baseline predict these immune-modulatory effects. No changes in tumor cell proliferation (primary endpoint) or other secondary endpoints are observed. Overall, our preclinical and clinical findings reveal that tumor cells exploit RANK pathway as a mechanism to evade immune surveillance and support the use of RANK pathway inhibitors to prime luminal breast cancer for immunotherapy.- Published
- 2020
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15. MOMENTUM: A Phase I Trial Investigating 2 Schedules of Capecitabine With Aflibercept in Patients With Gastrointestinal and Breast Cancer.
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Camera S, Deleporte A, Bregni G, Trevisi E, Pretta A, Telli TA, Polastro L, Gombos A, Kayumba A, Ameye L, Piccart-Gebhart M, Awada A, Sclafani F, and Hendlisz A
- Subjects
- Adult, Aged, Anorexia chemically induced, Anorexia diagnosis, Anorexia epidemiology, Antineoplastic Combined Chemotherapy Protocols adverse effects, Breast Neoplasms pathology, Capecitabine adverse effects, Colorectal Neoplasms pathology, Dose-Response Relationship, Drug, Drug Resistance, Neoplasm, Feasibility Studies, Female, Hand-Foot Syndrome diagnosis, Hand-Foot Syndrome epidemiology, Hand-Foot Syndrome etiology, Humans, Hypertension chemically induced, Hypertension diagnosis, Hypertension epidemiology, Male, Maximum Tolerated Dose, Middle Aged, Recombinant Fusion Proteins adverse effects, Response Evaluation Criteria in Solid Tumors, Severity of Illness Index, Stomach Neoplasms pathology, Antineoplastic Combined Chemotherapy Protocols administration & dosage, Breast Neoplasms drug therapy, Capecitabine administration & dosage, Colorectal Neoplasms drug therapy, Receptors, Vascular Endothelial Growth Factor administration & dosage, Recombinant Fusion Proteins administration & dosage, Stomach Neoplasms drug therapy
- Abstract
Background: Although data from preclinical and clinical studies provide a strong rationale for combining capecitabine with anti-angiogenic agents, clinical development of this fluoropyrimidine in combination with aflibercept has lagged behind other treatments. We conducted a nonrandomized, noncomparative, 2-arm, phase I trial to address this unmet need., Patients and Methods: Patients with chemorefractory gastrointestinal and breast cancer were sequentially recruited into a continuous (Arm A, starting dose 1100 mg/m
2 /day) or intermittent (Arm B, 2 weeks on/1 week off, starting dose 1700 mg/m2 /day) capecitabine dosing arm. Aflibercept was administered at a flat dose of 6 mg/kg every 3 weeks in both arms. A classical 3 + 3, dose-escalation design was used. The primary objective was to establish the maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended dose for phase II trials., Results: Thirty-eight eligible patients were recruited of whom 33 were assessable for DLTs (15 in arm A and 18 in arm B). Fourteen had colorectal cancer, 8 gastric cancer, and 11 breast cancer. DLTs included grade 2 hand-foot syndrome, grade 2 anorexia considered unacceptable by the patient, and grade 3 hypertension. The recommended dose for phase II trials for capecitabine was established at 1300 mg/m2 /day in Arm A and 2500 mg/m2 /day in Arm B with treatment-related grade ≥ 3 adverse events occurring in 47% and 50% of patients, respectively. Among 26 assessable patients, the objective response rate was 15.4% in Arm A and 7.7% in Arm B., Conclusion: Combining capecitabine with aflibercept is feasible and associated with a manageable safety profile and some anti-tumor activity in patients with chemorefractory gastrointestinal and breast cancer., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2020
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16. Immunotherapy in gynecological cancers: where are we?
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Polastro L, Closset C, and Kerger J
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- Antineoplastic Agents, Immunological therapeutic use, B7-H1 Antigen antagonists & inhibitors, B7-H1 Antigen immunology, Female, Genital Neoplasms, Female drug therapy, Genital Neoplasms, Female immunology, Humans, Programmed Cell Death 1 Receptor antagonists & inhibitors, Programmed Cell Death 1 Receptor immunology, Randomized Controlled Trials as Topic, Genital Neoplasms, Female therapy, Immunotherapy methods
- Abstract
Purpose of Review: This manuscript discusses the clinical evidence on immunotherapy for ovarian, endometrial, and cervical cancer. We report here the results of the clinical trials and present the ongoing trial in this area., Recent Findings: Immunotherapy has become a pillar of cancer treatment improving the prognosis of many patients with a broad variety of solid malignancies. Unfortunately, until recently the progress achieved in some other tumors has not been seen in the majority of patients with gynecological cancer. Except for some subgroups of endometrial cancers the immune checkpoint inhibitors in monotherapy have shown unsatisfactory results. However, several combinations of immunotherapy with other drugs are under investigation and are very promising. It is essential, to develop tools to select the patients who will response best to immunotherapy., Summary: Combined immune checkpoint inhibitors with targeted therapies are awaited in gynecological cancers and could provide additional benefit.
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- 2020
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17. A radical approach to achieve complete cytoreductive surgery improve survival of patients with advanced ovarian cancer.
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Liberale G, Pop CF, Polastro L, Kerger J, Moreau M, Chintinne M, Larsimont D, Nogaret JM, and Veys I
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma mortality, Carcinoma pathology, Carcinoma secondary, Conservative Treatment, Female, Humans, Middle Aged, Neoplasm Recurrence, Local epidemiology, Neoplasm Recurrence, Local prevention & control, Neoplasm Staging, Neoplasm, Residual, Ovarian Neoplasms mortality, Ovarian Neoplasms pathology, Peritoneal Neoplasms mortality, Peritoneal Neoplasms secondary, Peritoneal Neoplasms surgery, Postoperative Complications epidemiology, Postoperative Complications prevention & control, Retrospective Studies, Survival Analysis, Treatment Outcome, Carcinoma surgery, Cytoreduction Surgical Procedures methods, Ovarian Neoplasms surgery
- Abstract
Introduction: Cytoreductive surgery of locally advanced ovarian cancer has evolved in the last few years from surgery to remove macroscopic residual disease (<1cm; R2b) to macroscopic complete cytoreductive surgery with no gross residual disease (R1). The aim of this study was to evaluate the impact of the adoption of a maximalist surgical approach on postoperative complications, disease recurrence and survival., Materials and Methods: This was a retrospective study using prospectively collected data on patients who received either conservative approach (CA) or radical approach (RA) surgical treatment for primary ovarian cancer stage IIIc/IVa/IVb between June 2006 and June 2013., Results: Data for 114 patients were included, 33 patients in the CA group and 68 patients in the RA group were consequently analysed. In the RA group, operative time was longer, in relation to more complex surgical procedures; with more blood losses and a higher rate of compete macroscopic resection. Totally, 77% of the patients had postoperative complications, with more grade I/II complications in the RA group but the same rates of grade III/IV complications in the both groups (P=0.14). For all patient study population, the overall and disease-free survivals were improved in case of no macroscopic residual disease. Overall survival was improved in the RA group (P=0.05), with no difference in terms of disease-free survival (P=0.29) CONCLUSION: A radical approach in advanced ovarian cancer allows a higher rate of complete cytoreductive surgery impacting overall survival. However, a non-significant trend for increased mild complications (grade I/II) rate is observed in this group., (Copyright © 2019. Published by Elsevier Masson SAS.)
- Published
- 2020
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18. Pseudoadjuvant chemotherapy in resectable metastatic colorectal cancer.
- Author
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Polastro L, El Hachem G, and Hendlisz A
- Subjects
- Chemotherapy, Adjuvant, Clinical Trials, Phase III as Topic, Colorectal Neoplasms pathology, Humans, Neoplasm Staging, Randomized Controlled Trials as Topic, Colorectal Neoplasms drug therapy, Colorectal Neoplasms surgery
- Abstract
Purpose of Review: In this article, we focus on the potential benefits and risks of chemotherapy administration before (perioperative) or after (pseudoadjuvant) a curative resection of colorectal cancer (CRC) metastases., Recent Findings: In the published evidence, there is a lack of survival benefit from peri or postoperative chemotherapy in the context of resectable metastatic CRC. However, high-risk patients may have a certain benefit when receiving a postoperative cytotoxic treatment. Apart from, according to the published data, the administration of a preoperative chemotherapy has been associated with serious parenchymal liver damage and an increase in the postoperative morbidity-mortality rate., Summary: Surgery is the only potentially curative treatment for metastatic CRC, but the risk of recurrence remains high. The current guidelines recommend the administration of either a perioperative or a pseudoadjuvant chemotherapy in this setting despite the absence of survival benefit. A better selection of patients who may require and gain an advantage from chemotherapy in the setting of resectable metastasis is highly needed. In this view, a prospective trial enrolling patients at high risk of recurrence is ongoing.
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- 2018
- Full Text
- View/download PDF
19. Results of the Belgian expanded access program of eribulin in the treatment of metastatic breast cancer closely mirror those of the pivotal phase III trial.
- Author
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Aftimos P, Polastro L, Ameye L, Jungels C, Vakili J, Paesmans M, van den Eerenbeemt J, Buttice A, Gombos A, de Valeriola D, Gil T, Piccart-Gebhart M, and Awada A
- Subjects
- Adult, Aged, Aged, 80 and over, Breast Neoplasms mortality, Breast Neoplasms pathology, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Humans, Middle Aged, Neoplasm Metastasis, Treatment Outcome, Antineoplastic Agents therapeutic use, Breast Neoplasms drug therapy, Furans therapeutic use, Ketones therapeutic use
- Abstract
Background: Eribulin is a non-taxane microtubule dynamics inhibitor that showed a survival benefit versus treatment of physician's choice in a phase III trial enrolling patients with metastatic breast cancer (MBC)., Methods: The E7389-G000-398 trial was designed to provide eribulin to MBC patients pre-treated with anthracylines, taxanes and capecitabine. Patient characteristics, efficacy and safety data were collected prospectively. Efficacy and survival analyses were performed using retrospectively collected data of patients treated at a single institution., Results: One hundred fifty-four patients were enrolled and the median number of previous lines of chemotherapy was 4. The most frequent adverse events were fatigue/asthenia (74%), alopecia (55%), peripheral neuropathy (46%) and neutropenia (43%). Objective response rate (ORR) was 24% in the evaluable population and 14% in patients pre-treated with both taxanes and vinorelbine. In patients with oestrogen receptor (ER)+/human epidermal growth factor receptor 2 (HER2)- MBC, response rate was 29% and 21% with triple-negative disease. Activity was minimal in HER2+ MBC treated with eribulin monotherapy (14% ORR). Median progression-free survival was 3.2 months. Median overall survival was 11.3 months; 77% of patients were alive at 6 months and 43% at 12 months., Conclusion: Eribulin was active in MBC patients with a high tumour burden and predominant visceral disease. Safety profile was similar to what was reported in the phase III trials. Prophylactic granulocyte colony-stimulating factor administration allowed optimal dose intensity and could have contributed to the recorded response rate. Activity is sustained after treatment with taxanes and vinorelbine. The recently investigated combination of eribulin and trastuzumab should lead to higher activity in HER2-positive MBC., (Copyright © 2016 Elsevier Ltd. All rights reserved.)
- Published
- 2016
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20. [Cardiac metastase of a soft tissue sarcoma: a case report and a review of the literature].
- Author
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Polastro L, de Saint Aubain N, Lemort M, Delhaye F, and Awada A
- Subjects
- Buttocks, Chondrosarcoma diagnostic imaging, Chondrosarcoma surgery, Fatal Outcome, Female, Heart Neoplasms diagnostic imaging, Heart Neoplasms surgery, Humans, Middle Aged, Neoplasms, Connective and Soft Tissue diagnostic imaging, Neoplasms, Connective and Soft Tissue surgery, Sarcoma diagnostic imaging, Sarcoma surgery, Thigh, Ultrasonography, Chondrosarcoma secondary, Heart Neoplasms secondary, Neoplasms, Connective and Soft Tissue secondary, Sarcoma pathology
- Abstract
Soft tissue sarcomas represent rare tumors. They recur most often locally and in the lungs. We report the case of a 58-year woman who was treated for awith chemotherapy and then surgery. About a year after the end of the treatment an intracardiac mass was identified during a follow up chest CT-scan. The patient underwent a surgical resection of that mass found to bel myxoid chondrosarcoma metastasis. Only 2 cases of cardiac dissemination of extraskeletal myxoid chondrosarcoma have been described. The differential diagnosis of intracardiac masses is discussed. In some carefully selected cases atrisks of obstructive shock or embolization and unique metastatic location, cardiac surgery should be considered.
- Published
- 2014
21. Eribulin mesylate in the management of metastatic breast cancer and other solid cancers: a drug review.
- Author
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Polastro L, Aftimos PG, and Awada A
- Subjects
- Alopecia chemically induced, Antineoplastic Agents adverse effects, Antineoplastic Agents pharmacology, Carcinoma drug therapy, Chemotherapy, Adjuvant, Clinical Trials as Topic, Drug Approval, Drug Resistance, Neoplasm, Drugs, Investigational, Ethers, Cyclic pharmacology, Fatigue chemically induced, Female, Furans adverse effects, Furans chemistry, Furans pharmacology, Humans, Ketones adverse effects, Ketones chemistry, Ketones pharmacology, Macrolides pharmacology, Molecular Targeted Therapy, Multicenter Studies as Topic, Neoadjuvant Therapy, Neutropenia chemically induced, Peripheral Nervous System Diseases chemically induced, Tubulin Modulators adverse effects, Tubulin Modulators chemistry, Tubulin Modulators pharmacology, United States, United States Food and Drug Administration, Antineoplastic Agents therapeutic use, Breast Neoplasms drug therapy, Carcinoma secondary, Furans therapeutic use, Ketones therapeutic use, Tubulin Modulators therapeutic use
- Abstract
In the new era of 'precision' cancer medicine, new drug development has shifted from cytotoxic chemotherapy to molecularly targeted agents. Eribulin mesylate, a microtubule-destabilizing agent, is the only 'classical' cytotoxic agent approved for the treatment of breast cancer in the last 7 years. This synthetic analogue of halichondrin B, isolated from the marine sponge 'Halicondria Okaida', was responsible for prolonging overall survival of heavily pretreated metastatic breast cancer patients in a large Phase III trial. Eribulin is now under clinical development in earlier settings such as the neo-adjuvant and adjuvant settings. Furthermore, its unique mechanism of action and the absence of cross-resistance with taxanes have led to the design of clinical trials in multiple indications: bladder cancer, lung cancer, prostate cancer… The main adverse events are neutropenia, fatigue and peripheral neuropathy.
- Published
- 2014
- Full Text
- View/download PDF
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