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Article ; Online: Dostarlimab for the treatment of advanced endometrial cancer.

Redondo, Andres / Gallego, Alejandro / Mendiola, Marta

Expert review of clinical pharmacology

2022 Volume 15, Issue 1, Page(s) 1–9

Abstract: Introduction: Between 20% and 30% of the endometrial cancers (EC) are associated with a deficiency of a mismatch repair (MMRd) protein or high microsatellite instability (MSI-H), characteristics that render the tumor more sensitive to immune checkpoint ... ...

Abstract	Introduction: Between 20% and 30% of the endometrial cancers (EC) are associated with a deficiency of a mismatch repair (MMRd) protein or high microsatellite instability (MSI-H), characteristics that render the tumor more sensitive to immune checkpoint inhibitors. There is no standard treatment for advanced EC after progression to a platinum-containing regimen. Areas covered: The phase I GARNET clinical trial assessed the safety, tolerability, and antitumor activity of anti-PD1 dostarlimab in patients with advanced solid tumors. The A1 cohort of this trial enrolled patients with MMRd or MSI-H recurrent or advanced EC who had previously received a platinum-containing regimen. The results of this cohort showed significant clinical activity, durable responses, and a favorable safety profile, without reducing quality of life. Based on these data, dostarlimab achieved accelerated approval. Expert opinion: Although a randomized study has not yet been conducted, dostarlimab monotherapy should be the treatment of choice for patients with advanced MMRd EC in progression after a platinum-containing regimen. Selecting patients with EC for immune checkpoint inhibitors using the MMRd predictive biomarker could facilitate more efficient and sustainable health systems and avoid the use of more toxic combinations, leading to personalized medicine.
MeSH term(s)	Antibodies, Monoclonal, Humanized/adverse effects ; DNA Mismatch Repair ; Endometrial Neoplasms/chemically induced ; Endometrial Neoplasms/drug therapy ; Female ; Humans ; Immune Checkpoint Inhibitors ; Microsatellite Instability ; Quality of Life
Chemical Substances	Antibodies, Monoclonal, Humanized ; Immune Checkpoint Inhibitors ; dostarlimab
Language	English
Publishing date	2022-02-22
Publishing country	England
Document type	Journal Article
ISSN	1751-2441
ISSN (online)	1751-2441
DOI	10.1080/17512433.2022.2044791
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Article ; Online: Controversies in the treatment of advanced ovarian cancer in the PARP inhibitors era: a Delphi consensus.

Redondo, Andrés / Barretina, Pilar / Pérez-Fidalgo, Alejandro / Rubio, María Jesús / González-Martín, Antonio

Journal of gynecologic oncology

2023 Volume 34, Issue 5, Page(s) e57

Abstract: Objective: Our aim was to reach a consensus on the management of the most controversial issues of advanced ovarian cancer.: Methods: Nominal group and Delphi techniques were used. A steering committee of 5 experts analyzed current management of ... ...

Abstract	Objective: Our aim was to reach a consensus on the management of the most controversial issues of advanced ovarian cancer. Methods: Nominal group and Delphi techniques were used. A steering committee of 5 experts analyzed current management of advanced ovarian cancer, identified controversies, critically analyzed the evidence, and formulated guiding statements for clinicians. Subsequently, a panel of 15 experts was selected to test agreement with the statements through two Delphi rounds. Items were scored on a 4-point Likert scale from 1 (totally disagree) to 4 (totally agree). In the first and second rounds, consensus was considered if ≥70% of answers pertained to category 1 or category 4. Results: Overall, 112 statements were incorporated in the following areas: 1) biomarkers and hereditary ovarian cancer; 2) first-line treatment; 3) recurrent disease when platinum might be the best option; and 4) post-poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors setting. In the first Delphi round, 37 statements reached consensus and did thus not pass to the second round. After the second round, another 18 statements reached consensus. Forty-six of the consensus were with the agreement and 9 with the disagreement. Conclusion: Through the methodology used, a consensus was reached in approximately half of the statements. The results of this work may be useful in addressing the most controversial issues on the management of advanced ovarian cancer.
MeSH term(s)	Humans ; Female ; Poly(ADP-ribose) Polymerase Inhibitors/therapeutic use ; Consensus ; Delphi Technique ; Ovarian Neoplasms/drug therapy
Chemical Substances	Poly(ADP-ribose) Polymerase Inhibitors
Language	English
Publishing date	2023-04-07
Publishing country	Korea (South)
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2478405-9
ISSN	2005-0399 ; 2005-0380
ISSN (online)	2005-0399
ISSN	2005-0380
DOI	10.3802/jgo.2023.34.e57
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Zs.A 6484: Show issues

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Article ; Online: Patient-reported outcomes in the GARNET trial in patients with advanced or recurrent mismatch repair-deficient/microsatellite instability-high endometrial cancer treated with dostarlimab.

Kristeleit, Rebecca / Mathews, Cara / Redondo, Andres / Boklage, Susan / Hanlon, Jennifer / Im, Ellie / Brown, Jubilee

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society

2022

Abstract: Objective: There is an increase in patient-reported outcome assessments to gain information on new drug candidates from the patient's perspective. A data gap remains in patient-reported outcome measurements for anti-programmed death 1 (anti-PD-1) ... ...

Abstract	Objective: There is an increase in patient-reported outcome assessments to gain information on new drug candidates from the patient's perspective. A data gap remains in patient-reported outcome measurements for anti-programmed death 1 (anti-PD-1) therapies in endometrial cancer. We present patient-reported outcome measures collected from patients with mismatch repair-deficient/microsatellite instability-high advanced or recurrent endometrial cancer treated with dostarlimab, an anti-PD-1 monoclonal antibody, in an expansion cohort of the GARNET trial. Methods: GARNET (NCT02715284) is a phase I single-arm study of dostarlimab monotherapy in multiple tumor types. Patients with advanced or recurrent mismatch repair-deficient/microsatellite instability-high endometrial cancer were treated with 500 mg of intravenous dostarlimab once every 3 weeks for four cycles, then 1000 mg of intravenous dostarlimab every 6 weeks. Patient-reported outcome assessments were an exploratory endpoint, measured using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30). Results: At data cut-off, 88 patients with mismatch repair-deficient endometrial cancer were included in the analysis. Patient-reported outcome assessment completion was >95.5% throughout cycle 7 of the trial, with no individual domain completion <90.9%. Quality of life, emotional functioning, and social functioning showed improvement compared with baseline. All symptom scores showed either improvement or stability from baseline through cycle 7. Categorical change in response across all symptom scales and single-item response scores showed stability or improvement for most patients. For patients who saw a worsening of their categorical change in response, ≤7.4% experienced a 2-category worsening and ≤2.5% experienced a 3-category worsening. Conclusions: Most patients remained stable or had improved quality of life while receiving dostarlimab for the treatment of recurrent or advanced mismatch repair-deficient endometrial cancer. Trial registration number: NCT02715284.
Language	English
Publishing date	2022-08-16
Publishing country	England
Document type	Journal Article
ZDB-ID	1070385-8
ISSN	1525-1438 ; 1048-891X
ISSN (online)	1525-1438
ISSN	1048-891X
DOI	10.1136/ijgc-2022-003492
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Zs.A 3198: Show issues

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Article ; Online: Characterisation of new in vitro models and identification of potentially active drugs in angiosarcoma.

Mendiola, Marta / Saarela, Jani / Escudero, Francisco Javier / Heredia-Soto, Victoria / Potdar, Swapnil / Rodriguez-Marrero, Silvia / Miguel, Maria / Pozo-Kreilinger, Jose Juan / Berjon, Alberto / Ortiz-Cruz, Eduardo / Feliu, Jaime / Redondo, Andres

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie

2024 Volume 173, Page(s) 116397

Abstract: Angiosarcoma is a rare soft tissue sarcoma originating from endothelial cells. Given that current treatments for advanced disease have shown limited efficacy, alternative therapies need to be identified. In rare diseases, patient-derived cell models are ... ...

Abstract	Angiosarcoma is a rare soft tissue sarcoma originating from endothelial cells. Given that current treatments for advanced disease have shown limited efficacy, alternative therapies need to be identified. In rare diseases, patient-derived cell models are crucial for screening anti-tumour activity. In this study, cell line models were characterised in 2D and 3D cultures. The cell lines' growth, migration and invasion capabilities were explored, confirming them as useful tools for preclinical angiosarcoma studies. By screening a drug library, we identified potentially effective compounds: 8-amino adenosine impacted cell growth and inhibited migration and invasion at considerably low concentrations as a single agent. No synergistic effect was detected when combining with paclitaxel, gemcitabine or doxorubicin. These results suggest that this compound could be a potentially useful drug in the treatment of AGS.
MeSH term(s)	Humans ; Hemangiosarcoma/drug therapy ; Endothelial Cells/pathology ; Doxorubicin/pharmacology ; Doxorubicin/therapeutic use ; Sarcoma/drug therapy ; Paclitaxel/pharmacology ; Paclitaxel/therapeutic use
Chemical Substances	Doxorubicin (80168379AG) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2024-03-12
Publishing country	France
Document type	Journal Article
ZDB-ID	392415-4
ISSN	1950-6007 ; 0753-3322 ; 0300-0893
ISSN (online)	1950-6007
ISSN	0753-3322 ; 0300-0893
DOI	10.1016/j.biopha.2024.116397
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Ud II Zs.198: Show issues

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Article ; Online: Periosteal Ewing Sarcoma with Distant Metastases: Report of Two Patients and Review of the Literature.

Pena-Burgos, Eva M / Díez-Corral, María C / Ortiz-Cruz, Eduardo J / Bernabéu, Daniel / Tapia-Viñe, Mar / Redondo, Andrés / Pérez-Martínez, Antonio / Peláez, Alberto / Venegas Mascaró, Clara / Escudero López, Adela / Pozo-Kreilinger, Jose J

International journal of surgical pathology

2024 , Page(s) 10668969241246473

Abstract: Periosteal Ewing sarcoma (ES) is an exceedingly rare topographic subtype of the ES. To our knowledge, only 60 patients have been reported in the medical English language literature. It predominantly affects men in the second decade of life and arises in ... ...

Abstract	Periosteal Ewing sarcoma (ES) is an exceedingly rare topographic subtype of the ES. To our knowledge, only 60 patients have been reported in the medical English language literature. It predominantly affects men in the second decade of life and arises in the long tubular bone diaphysis. PES rarely develops distant metastases. We report two patients of this rare ES location that were found on the distal tibial shaft and proximal femoral diaphysis of a 21-year-old man and an 8-year-old boy, respectively. Both patients were treated with neoadjuvant chemotherapy, wide resection, and adjuvant chemotherapy. One of our patients had lung metastases at the time of diagnosis and died 5 years later. The other patient presented intramedullary humeral bone metastasis 19 years after diagnosis. There has been no evidence of disease in the 26 years of follow-up. Close follow-up of periosteal ES is recommended because distant metastases may exceptionally occur, even several years after diagnosis.
Language	English
Publishing date	2024-05-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1336393-1
ISSN	1940-2465 ; 1066-8969
ISSN (online)	1940-2465
ISSN	1066-8969
DOI	10.1177/10668969241246473
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Article ; Online: Long-term response to olaparib in

Gallego, Alejandro / Garrido, Diego / Yébenes, Laura / Mendiola, Marta / Castelo, Beatriz / Redondo, Andres

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society

2021 Volume 31, Issue 9, Page(s) 1292–1296

MeSH term(s)	Antineoplastic Agents/pharmacology ; Antineoplastic Agents/therapeutic use ; BRCA1 Protein ; Brain Neoplasms/drug therapy ; Brain Neoplasms/secondary ; Female ; Humans ; Middle Aged ; Ovarian Neoplasms/complications ; Ovarian Neoplasms/drug therapy ; Phthalazines/pharmacology ; Phthalazines/therapeutic use ; Piperazines/pharmacology ; Piperazines/therapeutic use
Chemical Substances	Antineoplastic Agents ; BRCA1 Protein ; BRCA1 protein, human ; Phthalazines ; Piperazines ; olaparib (WOH1JD9AR8)
Language	English
Publishing date	2021-06-18
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	1070385-8
ISSN	1525-1438 ; 1048-891X
ISSN (online)	1525-1438
ISSN	1048-891X
DOI	10.1136/ijgc-2020-002225
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Article ; Online: Impacto de la primera ola de la pandemia de COVID-19 en la atención a pacientes oncológicos en un hospital terciario.

Cruz-Castellanos, Patricia / Ortiz-Cruz, Eduardo / Sánchez-Méndez, Jose Ignacio / Tapia, Mar / Morera, Rosa / Redondo, Andrés

Revista espanola de patologia : publicacion oficial de la Sociedad Espanola de Anatomia Patologica y de la Sociedad Espanola de Citologia

2022 Volume 55, Issue 2, Page(s) 77–84

Abstract: Blackground: The COVID-19 pandemic has over-burdened the Spanish health service and, as a result, affected the treatment and management of oncological patients. The aim of this study is to make a descriptive analysis of the management of oncological ... ...

Title translation	The impact of the first wave of the COVID-19 pandemic on oncological patients in a tertiary hospital.
Abstract	Blackground: The COVID-19 pandemic has over-burdened the Spanish health service and, as a result, affected the treatment and management of oncological patients. The aim of this study is to make a descriptive analysis of the management of oncological patients and the functioning of the tumour committees in the University Hospital La Paz (Madrid) during the first wave of the pandemic. Materials and methods: A descriptive analysis was made, based on the results of a questionnaire given to all 18 adult tumour committees and 3 paediatric tumour committees in the University Hospital La Paz. Further information was obtained from all the hospital services involved in the diagnosis and treatment of oncological patients. Results: During the first wave of the pandemic, there was a significant decrease in diagnostic tests. For many weeks, the majority of oncological surgical procedures were delayed or referred to other hospitals. Highly beneficial systemic and radiotherapeutic treatments were maintained and preoperative treatment was increased. The diagnosis and treatment of paediatric tumours was unaltered. Tumour committees were affected but each one adjusted in a different way. All the departments involved in the diagnosis and treatment of oncological patients made contingency plans to minimalize the effect on patients. Conclusion: This study shows how the management of oncological patients and the functioning of tumour committees was affected during the COVID-19 pandemic.
MeSH term(s)	Adult ; COVID-19 ; Child ; Humans ; Neoplasms/epidemiology ; Neoplasms/therapy ; Pandemics ; Surveys and Questionnaires ; Tertiary Care Centers
Language	Spanish
Publishing date	2022-01-19
Publishing country	Spain
Document type	Journal Article
ZDB-ID	2463888-2
ISSN	1988-561X ; 1988-561X
ISSN (online)	1988-561X
ISSN	1988-561X
DOI	10.1016/j.patol.2021.12.001
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Article: Design of Ionic Liquids for Fluorinated Gas Absorption: COSMO-RS Selection and Solubility Experiments

Sosa, Julio E. / Santiago, Rubén / Redondo, Andres E. / Avila, Jocasta / Lepre, Luiz F. / Gomes, Margarida Costa / Araújo, João M. M. / Palomar, José / Pereiro, Ana B.

Environmental science & technology. 2022 Apr. 18, v. 56, no. 9

2022

Abstract: In recent years, the fight against climate change and the mitigation of the impact of fluorinated gases (F-gases) on the atmosphere is a global concern. Development of technologies that help to efficiently separate and recycle hydrofluorocarbons (HFCs) ... ...

Abstract	In recent years, the fight against climate change and the mitigation of the impact of fluorinated gases (F-gases) on the atmosphere is a global concern. Development of technologies that help to efficiently separate and recycle hydrofluorocarbons (HFCs) at the end of the refrigeration and air conditioning equipment life is a priority. The technological development is important to stimulate the F-gas capture, specifically difluoromethane (R-32) and 1,1,1,2-tetrafluoroethane (R-134a), due to their high global warming potential. In this work, the COSMO-RS method is used to analyze the solute–solvent interactions and to determine Henry’s constants of R-32 and R-134a in more than 600 ionic liquids. The three most performant ionic liquids were selected on the basis of COSMO-RS calculations, and F-gas absorption equilibrium isotherms were measured using gravimetric and volumetric methods. Experimental results are in good agreement with COSMO-RS predictions, with the ionic liquid tributyl(ethyl)phosphonium diethyl phosphate, [P₂₄₄₄][C₂C₂PO₄], being the salt presenting the highest absorption capacities in molar and mass units compared to salts previously tested. The other two ionic liquids selected, trihexyltetradecylphosphonium glycinate, [P₆₆₆₁₄][C₂NO₂], and trihexyl(tetradecyl)phosphonium 2-cyano-pyrrole, [P₆₆₆₁₄][CNPyr], may be competitive as far as their absorption capacities are concerned. Future works will be guided on evaluating the performance of these ionic liquids at an industrial scale by means of process simulations, in order to elucidate the role in process efficiency of other relevant absorbent properties such as viscosity, molar weight, or specific heat.
Keywords	absorbents ; absorption ; air ; climate change ; equipment ; hydrofluorocarbons ; ionic liquids ; phosphates ; refrigeration ; solubility ; specific heat ; viscosity
Language	English
Dates of publication	2022-0418
Size	p. 5898-5909.
Publishing place	American Chemical Society
Document type	Article
ISSN	1520-5851
DOI	10.1021/acs.est.2c00051
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Are antiangiogenics a good 'partner' for immunotherapy in ovarian cancer?

García-Martínez, Elena / Redondo, Andres / Piulats, Josep Maria / Rodríguez, Analía / Casado, Antonio

Angiogenesis

2020 Volume 23, Issue 4, Page(s) 543–557

Abstract: Ovarian cancer (OC) is associated with poor survival because there are a limited number of effective therapies. Two processes key to OC progression, angiogenesis and immune evasion, act synergistically to promote tumor progression. Tumor-associated ... ...

Abstract	Ovarian cancer (OC) is associated with poor survival because there are a limited number of effective therapies. Two processes key to OC progression, angiogenesis and immune evasion, act synergistically to promote tumor progression. Tumor-associated angiogenesis promotes immune evasion, and tumor-related immune responses in the peritoneal cavity and tumor microenvironment (TME) affect neovascular formation. Therefore, suppressing the angiogenic pathways could facilitate the arrival of immune effector cells and reduce the presence of myeloid cells involved in immune suppression. To date, clinical studies have shown significant benefits with antiangiogenic therapy as first-line therapy in OC, as well as in recurrent disease, and the vascular endothelial growth factor (VEGF) inhibitor bevacizumab is now an established therapy. Clinical data with immunomodulators in OC are more limited, but suggest that they could benefit some patients with recurrent disease. The preliminary results of two phase III trials have shown that the addition of immunomodulators to chemotherapy does not improve progression-free survival. For this reason, it could be interesting to look for synergistic effects between immunomodulators and other active drugs in OC. Since bevacizumab is approved for use in OC, and is tolerable when used in combination with immunotherapy in other indications, a number of clinical studies are underway to investigate the use of bevacizumab in combination with immunotherapeutic agents in OC. This strategy seeks to normalize the TME via the anti-VEGF actions of bevacizumab, while simultaneously stimulating the immune response via the immunotherapy. Results of these studies are awaited with interest.
MeSH term(s)	Angiogenesis Inhibitors/immunology ; Combined Modality Therapy ; Female ; Humans ; Immune System/pathology ; Immunotherapy ; Neovascularization, Pathologic/drug therapy ; Ovarian Neoplasms/drug therapy ; Ovarian Neoplasms/immunology
Chemical Substances	Angiogenesis Inhibitors
Language	English
Publishing date	2020-07-20
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1484717-6
ISSN	1573-7209 ; 0969-6970
ISSN (online)	1573-7209
ISSN	0969-6970
DOI	10.1007/s10456-020-09734-w
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Article ; Online: Comparison of Methods for Testing Mismatch Repair Status in Endometrial Cancer.

Mendiola, Marta / Heredia-Soto, Victoria / Ruz-Caracuel, Ignacio / Baillo, Amparo / Ramon-Patino, Jorge Luis / Escudero, Francisco Javier / Miguel, Maria / Pelaez-Garcia, Alberto / Hernandez, Alicia / Feliu, Jaime / Hardisson, David / Redondo, Andres

International journal of molecular sciences

2023 Volume 24, Issue 19

Abstract: Approximately 20-30% of endometrial carcinomas (EC) are characterized by mismatch repair (MMR) deficiency (dMMR) or microsatellite instability (MSI), and their testing has become part of the routine diagnosis. The aim of this study was to establish and ... ...

Abstract	Approximately 20-30% of endometrial carcinomas (EC) are characterized by mismatch repair (MMR) deficiency (dMMR) or microsatellite instability (MSI), and their testing has become part of the routine diagnosis. The aim of this study was to establish and compare the MMR status using various approaches. Immunohistochemistry (IHC), PCR-based MSI, and the detection of defects in the four key MMR genes (MLH1, PMS2, MSH2, and MSH6) via methylation-specific multiplex ligation-dependent probe amplification (MLPA) and targeted next-generation sequencing (NGS) were performed. MSH3 expression was also evaluated. A set of 126 early-stage EC samples were analyzed, 53.2% of which were dMMR and 46.8% of which were proficient MMR (pMMR) as determined using IHC, whereas 69.3% were classified as microsatellite stable, while 8.8% and 21.9% were classified MSI-low (MSI-L) and MSI-high (MSI-H), respectively. In total, 44.3% of the samples showed genetic or epigenetic alterations in one or more genes; MLH1 promoter methylation was the most common event. Although acceptable concordance was observed, there were overall discrepancies between the three testing approaches, mainly associated with the dMMR group. IHC had a better correlation with MMR genomic status than the MSI status determined using PCR. Further studies are needed to establish solid conclusions regarding the best MMR assessment technique for EC.
MeSH term(s)	Female ; Humans ; DNA Mismatch Repair/genetics ; Endometrial Neoplasms/diagnosis ; Endometrial Neoplasms/genetics ; Endometrial Neoplasms/pathology ; Colorectal Neoplasms/diagnosis ; Neoplastic Syndromes, Hereditary/diagnosis ; Microsatellite Instability
Language	English
Publishing date	2023-09-23
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms241914468
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