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Article ; Online: Successful treatment with selpercatinib after pralsetinib-related pneumonitis and intracranial failure in a patient with RET-rearranged nonsmall cell lung cancer.

Cognigni, Valeria / Giudice, Giulia Claire / Bozzetti, Francesca / Milanese, Gianluca / Moschini, Ilaria / Casali, Miriam / Mazzaschi, Giulia / Tiseo, Marcello

Anti-cancer drugs

2024

Abstract: Pralsetinib and selpercatinib are two highly potent and selective rearranged during transfection (RET) inhibitors that substantially improved the clinical outcome of patients with RET-rearranged non-small cell lung cancer. Treatment with one RET ... ...

Abstract	Pralsetinib and selpercatinib are two highly potent and selective rearranged during transfection (RET) inhibitors that substantially improved the clinical outcome of patients with RET-rearranged non-small cell lung cancer. Treatment with one RET inhibitor after failure of the other is generally not recommended because of cross-resistance mechanisms. We report the case of a patient affected by metastatic RET-rearranged non-small cell lung cancer who experienced long-lasting disease control with pralsetinib. After 13 months from treatment start, the patient developed recurrent drug-related pneumonitis, requiring temporary interruptions and dose reductions and eventually failing to control the disease. Selpercatinib was then started as an off-label treatment, allowing both clinical and radiological intracranial disease control. Selpercatinib was well-tolerated at full dosage, and no pulmonary event occurred. In our case report, after pralsetinib dose reduction due to pulmonary toxicity, the therapeutic switch to selpercatinib allowed the patient to receive a full-dose treatment, eventually restoring disease control. Our case report and a few literature data suggest that switching from pralsetinib to selpercatinib may represent a therapeutic opportunity, especially for patients with brain metastases.
Language	English
Publishing date	2024-03-08
Publishing country	England
Document type	Journal Article
ZDB-ID	1065301-6
ISSN	1473-5741 ; 0959-4973
ISSN (online)	1473-5741
ISSN	0959-4973
DOI	10.1097/CAD.0000000000001590
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Article ; Online: Potential benefit of β-glucans as adjuvant therapy in immuno-oncology: a review.

Cognigni, Valeria / Ranallo, Nicoletta / Tronconi, Francesca / Morgese, Francesca / Berardi, Rossana

Exploration of targeted anti-tumor therapy

2021 Volume 2, Issue 2, Page(s) 122–138

Abstract: Fungal compounds have long been used for centuries as food supplements. β-glucans have been identified as the most interesting molecules with beneficial effects in several chronic diseases. ...

Abstract	Fungal compounds have long been used for centuries as food supplements. β-glucans have been identified as the most interesting molecules with beneficial effects in several chronic diseases.
Language	English
Publishing date	2021-04-30
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2692-3114
ISSN (online)	2692-3114
DOI	10.37349/etat.2021.00036
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Article: The Landscape of ALK-Rearranged Non-Small Cell Lung Cancer: A Comprehensive Review of Clinicopathologic, Genomic Characteristics, and Therapeutic Perspectives.

Cognigni, Valeria / Pecci, Federica / Lupi, Alessio / Pinterpe, Giada / De Filippis, Chiara / Felicetti, Cristiano / Cantini, Luca / Berardi, Rossana

Cancers

2022 Volume 14, Issue 19

Abstract: During the last decade, the identification of oncogenic driver mutations and the introduction of tyrosine kinase inhibitors (TKIs) in daily clinical practice have substantially revamped the therapeutic approach of oncogene-addicted, non-small cell lung ... ...

Abstract	During the last decade, the identification of oncogenic driver mutations and the introduction of tyrosine kinase inhibitors (TKIs) in daily clinical practice have substantially revamped the therapeutic approach of oncogene-addicted, non-small cell lung cancer (NSCLC). Rearrangements in the anaplastic lymphoma kinase (ALK) gene are detected in around 3-5% of all NSCLC patients. Following the promising results of Crizotinib, a first-generation ALK inhibitor (ALK-i), other second-generation and more recently third-generation TKIs have been developed and are currently a landmark in NSCLC treatment, leading to a significant improvement in patients prognosis. As clinical trials have already demonstrated high efficacy of each ALK-i, both in terms of systemic and intracranial disease control, comparative studies between second and third generation ALK-i are still lacking, and primary or secondary ALK-i resistance inevitably limit their efficacy. Resistance to ALK-i can be due to ALK-dependent or ALK-independent mechanisms, including the activation of bypass signaling pathways and histological transformation: these findings may play an important role in the future to select patients' subsequent therapy. This review aims to provide an overview of underlying molecular alterations of ALK-i resistance and point out promising role of liquid biopsy in predicting tumor response and monitoring resistance mutations. The purpose of this review is also to summarize current approval for ALK-rearranged NSCLC patients, to help clinicians in making decisions on therapeutic sequence, and to deepen the role of clinicopathological and genomic characteristics influencing patients' prognosis during treatment with ALK-i.
Language	English
Publishing date	2022-09-29
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14194765
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Article ; Online: A case report of metastatic giant sarcomatoid melanoma with BRAF V600E mutation: a complete response to targeted therapy.

Torresetti, Matteo / Brancorsini, Donatella / Morgese, Francesca / Cognigni, Valeria / Scalise, Alessandro / Berardi, Rossana / Di Benedetto, Giovanni

Oncotarget

2020 Volume 11, Issue 34, Page(s) 3256–3262

Abstract: Sarcomatoid melanoma is an extremely rare pattern of malignant melanoma, and only few cases have been described throughout the literature. We herein report a case of a patient with newly diagnosed, metastatic giant sarcomatoid melanoma of the arm. The ... ...

Abstract	Sarcomatoid melanoma is an extremely rare pattern of malignant melanoma, and only few cases have been described throughout the literature. We herein report a case of a patient with newly diagnosed, metastatic giant sarcomatoid melanoma of the arm. The patient underwent surgical removal of the huge mass, and NGS sequencing demonstrated BRAF V600E mutation. In view of histological, immunohistochemical and molecular findings, a combined BRAF/MEK inhibitor (BRAF/MEK-i) therapy was prescribed as first line treatment. A complete response (over one year) to targeted therapy was obtained, and no adverse events have been reported. The patient maintained a full range of shoulder and elbow movements, and she is able to live independently and resume her daily activities. We therefore recommend that all patients with undifferentiated melanomas, sarcomatoid cutaneous malignancies or other mesenchymal tumours, should undergo BRAFV600E mutation testing.
Language	English
Publishing date	2020-08-25
Publishing country	United States
Document type	Case Reports
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.27701
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Article ; Online: Tumor burden as possible biomarker of outcome in advanced NSCLC patients treated with immunotherapy: a single center, retrospective, real-world analysis.

Lenci, Edoardo / Marcantognini, Giulia / Cognigni, Valeria / Lupi, Alessio / Rinaldi, Silvia / Cantini, Luca / Fiordoliva, Ilaria / Carloni, Anna Lisa / Rocchi, Marco / Zuccatosta, Lina / Gasparini, Stefano / Berardi, Rossana

Exploration of targeted anti-tumor therapy

2021 Volume 2, Issue 3, Page(s) 227–239

Abstract: Aim: The role of tumor burden (TB) for patients with non-small cell lung cancer (NSCLC) receiving immunotherapy is still unknown. The aim of this analysis was to analyze the prognostic value of TB in a real-world sample of advanced NSCLC patients.: ... ...

Abstract	Aim: The role of tumor burden (TB) for patients with non-small cell lung cancer (NSCLC) receiving immunotherapy is still unknown. The aim of this analysis was to analyze the prognostic value of TB in a real-world sample of advanced NSCLC patients. Methods: Sixty-five consecutive patients with advanced NSCLC treated with immunotherapy as first or second line therapy were retrospectively analyzed between August 2015 and February 2018. TB was recorded at baseline considering sites and number of metastases, thoracic Results: Median age was 70 years and most patients (86.2%) had a good performance status (PS-Eastern Cooperative Oncology Group < 2). No significant difference in OS was noted between subgroups of patients according to TB. Bone metastases (BM) had a negative prognostic impact [median OS (mOS), 13.8 Conclusions: This study underlines the negative prognostic impact of specific metastatic sites, presence of NMD and extrathoracic disease in advanced NSCLC patients treated with immunotherapy. However, TB does not appear to affect the outcome of these patients.
Language	English
Publishing date	2021-06-28
Publishing country	United States
Document type	Journal Article
ISSN	2692-3114
ISSN (online)	2692-3114
DOI	10.37349/etat.2021.00043
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Article ; Online: Prognostic Impact of Blood Lipid Profile in Patients With Advanced Solid Tumors Treated With Immune Checkpoint Inhibitors: A Multicenter Cohort Study.

Pecci, Federica / Cantini, Luca / Cognigni, Valeria / Perrone, Fabiana / Mazzaschi, Giulia / Agostinelli, Veronica / Mentrasti, Giulia / Favari, Elda / Maffezzoli, Michele / Cortellini, Alessio / Rossi, Francesca / Chiariotti, Rebecca / Venanzi, Francesco Maria / Lo Russo, Giuseppe / Galli, Giulia / Proto, Claudia / Ganzinelli, Monica / Tronconi, Francesca / Morgese, Francesca /

Campolucci, Carla / Moretti, Marco / Vignini, Arianna / Tiseo, Marcello / Minari, Roberta / Rocchi, Marco Luigi Bruno / Buti, Sebastiano / Berardi, Rossana

The oncologist

2023 Volume 29, Issue 3, Page(s) e372–e381

Abstract: Background: Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed.: Materials and ...

Abstract	Background: Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed. Materials and methods: We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes. Results: At a median follow-up of 32.9 months, among 430 enrolled patients, those with TC ≥ 200 mg/dl showed longer median progression-free survival (mPFS; 6.6 vs. 4.7 months, P = .4), although not reaching statistical significance, and significantly longer median overall survival (mOS; 19.4 vs. 10.8 months, P = .02) compared to those with TC < 200 mg/dl. Conversely, patients with TG ≥150 mg/dl displayed shorter PFS (3.4 vs. 5.1 months, P = .02) and OS (7.1 vs. 12.9 months, P = .009) compared to those with TG <150 mg/dl. TC and TG were then combined in a "LIPID score" identifying three subgroups: good-risk (GR) (TC ≥200 mg/dl and TG <150 mg/dl), intermediate-risk (IR) (TC <200 mg/dl and TG <150 mg/dl or TC ≥200 mg/dl and TG ≥150 mg/dl) and poor-risk (PR) (TC <200 mg/dl and TG ≥150 mg/dl). The mPFS of GR, IR, and PR groups was 7.8, 4.3, and 2.5 months, respectively (P = .005); mOS of GR, IR, and PR was 20.4, 12.4, and 5.3 months, respectively (P < .001). At multivariable analysis, the PR profile represented an independent poor prognostic factor for both PFS and OS. Conclusions: We developed a lipid score that defined subgroups of patients with cancer who differently benefit from ICIs. Further mechanistic insights are warranted to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs.
MeSH term(s)	Humans ; Immune Checkpoint Inhibitors ; Retrospective Studies ; Prognosis ; Lipids ; Triglycerides ; Neoplasms/drug therapy
Chemical Substances	Immune Checkpoint Inhibitors ; Lipids ; Triglycerides
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Multicenter Study ; Journal Article
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1093/oncolo/oyad273
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Zs.A 4845: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: BRCA-associated protein 1 (BAP1) and miR-31 combination predicts outcomes in epithelioid malignant pleural mesothelioma.

Murrone, Albero / Cantini, Luca / Pecci, Federica / Cognigni, Valeria / Copparoni, Cecilia / Rinaldi, Silvia / Fiordoliva, Ilaria / Monaco, Federica / Rubini, Corrado / Barbisan, Francesca / Cimadamore, Alessia / Giampieri, Riccardo / Bianchi, Francesca / Tomasetti, Marco / Amati, Monica / Santarelli, Lory / Berardi, Rossana

Journal of thoracic disease

2021 Volume 13, Issue 10, Page(s) 5741–5751

Abstract: Background: Malignant pleural mesothelioma (MPM) is an aggressive disease, with few available treatment options. Identification of novel prognostic and predictive biomarkers is a priority. In MPM patients, BRCA-associated protein 1 (BAP1) alterations ... ...

Abstract	Background: Malignant pleural mesothelioma (MPM) is an aggressive disease, with few available treatment options. Identification of novel prognostic and predictive biomarkers is a priority. In MPM patients, BRCA-associated protein 1 (BAP1) alterations are detected in about 60% of cases and miR-31 seems to be involved in BAP1 regulation at post-transcriptional level. The aim of this study was to evaluate the interaction between BAP1 and miR-31 in MPM and their prognostic role in MPM. Methods: The expression of BAP1 and miR-31 was analyzed in tissues of 55 MPM patients treated with first-line chemotherapy. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier method and Log-rank test was used to investigate differences among subgroups. Multivariate Cox regression analysis was used to evaluate independent predictors of survival. Results: In the whole cohort, loss of BAP1 was associated with a significant improvement in OS, but not in PFS. Lower miR-31 levels were detected in epithelioid MPM (e-MPM) compared to the non-epithelioid subtypes and resulted associated with BAP1 loss. By looking at the e-MPM subgroup, loss of BAP1 was not able to predict clinical outcome. Conversely, miR-31 levels were significantly associated with PFS (P=0.028), but not with OS (P=0.059). By combining the two biomarkers, e-MPM patients with BAP1 loss/low miR-31 levels showed a better prognosis compared to the ones with BAP1 retained/high miR-31 levels (median OS 22.6 Conclusions: In this preliminary study, we found that the prognostic stratification of e-MPM patients may be improved by simultaneously assessing of BAP1 status and miR-31 levels. The two-biomarker score is useful to identify a subgroup of e-MPM tumors characterized by BAP1 retained and high miR-31 levels with worse clinical outcome.
Language	English
Publishing date	2021-11-03
Publishing country	China
Document type	Journal Article
ZDB-ID	2573571-8
ISSN	2077-6624 ; 2072-1439
ISSN (online)	2077-6624
ISSN	2072-1439
DOI	10.21037/jtd-21-555
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Article ; Online: Lynch syndrome-associated lung cancer: pitfalls of an immunotherapy-based treatment strategy in an unusual tumor type.

Maccaroni, Elena / Lenci, Edoardo / Agostinelli, Veronica / Cognigni, Valeria / Giampieri, Riccardo / Mazzanti, Paola / Di Pietro Paolo, Marzia / Bianchi, Francesca / Brugiati, Cristiana / Belvederesi, Laura / Pagliaretta, Silvia / Mandolesi, Alessandra / Scarpelli, Marina / Murrone, Alberto / Morgese, Francesca / Ballatore, Zelmira / Berardi, Rossana

Exploration of targeted anti-tumor therapy

2021 Volume 2, Issue 3, Page(s) 240–248

Abstract: Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline alterations in mismatch repair (MMR) genes leading to increased risk of colon cancer as well as other cancer types. Non-small cell lung cancer (NSCLC) is not among typical ... ...

Abstract	Lynch syndrome is a hereditary cancer predisposition syndrome caused by germline alterations in mismatch repair (MMR) genes leading to increased risk of colon cancer as well as other cancer types. Non-small cell lung cancer (NSCLC) is not among typical Lynch syndrome-associated tumors: pembrolizumab, an immune checkpoint inhibitor, is actually approved for the treatment of NSCLC patients and represents a promising treatment option for patients with advanced metastatic MMR-deficient cancer, regardless of tumor origin. This case report describes the clinical presentation and management of a 74-year-old female with a history of rectal adenocarcinoma and ovarian cancer, who has a documented frameshift pathogenic variant in the exon 8 of
Language	English
Publishing date	2021-06-28
Publishing country	United States
Document type	Case Reports
ISSN	2692-3114
ISSN (online)	2692-3114
DOI	10.37349/etat.2021.00044
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Article ; Online: Alarming Drop in Early Stage Colorectal Cancer Diagnoses After COVID-19 Outbreak: A Real-World Analysis from the Italian COVID-DELAY Study.

Mentrasti, Giulia / Cantini, Luca / Zichi, Clizia / D'Ostilio, Nicola / Gelsomino, Fabio / Martinelli, Erika / Chiari, Rita / La Verde, Nicla / Bisonni, Renato / Cognigni, Valeria / Pinterpe, Giada / Pecci, Federica / Migliore, Antonella / Aimar, Giacomo / De Vita, Francesca / Traisci, Donatella / Spallanzani, Andrea / Martini, Giulia / Nicolardi, Linda /

Cona, Maria Silvia / Baleani, Maria Giuditta / Rocchi, Marco Luigi Bruno / Berardi, Rossana

The oncologist

2022 Volume 27, Issue 9, Page(s) e723–e730

Abstract: Background: Coronavirus disease 2019 (COVID-19) has triggered the disruption of health care on a global scale. With Italy tangled up in the pandemic response, oncology care has been largely diverted and cancer screenings suspended. Our multicenter ... ...

Abstract	Background: Coronavirus disease 2019 (COVID-19) has triggered the disruption of health care on a global scale. With Italy tangled up in the pandemic response, oncology care has been largely diverted and cancer screenings suspended. Our multicenter Italian study aimed to evaluate whether COVID-19 has impacted access to diagnosis, staging, and treatment for patients newly diagnosed with colorectal cancer (CRC), compared with pre-pandemic time. Methods: All consecutive new CRC patients referred to 8 Italian oncology institutions between March and December 2020 were included. Access rate and temporal intervals between date of symptoms onset, radiological and cytohistological diagnosis, treatment start and first radiological evaluation were analyzed and compared with the same months of 2019. Results: A reduction (29%) in newly diagnosed CRC cases was seen when compared with 2019 (360 vs 506). New CRC patients in 2020 were less likely to be diagnosed with early stage (stages I-II-III) CRC (63% vs 78%, P < .01). Gender and sidedness were similar regardless of the year. The percentage of tumors with any mutation among BRAF, NRAS, and KRAS genes were significantly different between the 2 years (61% in 2020 vs 50% in 2019, P = .04). Timing of access to cancer diagnosis, staging, and treatment for patients with CRC has not been negatively affected by the pandemic. Significantly shorter temporal intervals were observed between symptom onset and first oncological appointment (69 vs 79 days, P = .01) and between histological diagnosis and first oncological appointment (34 vs 42 days, P < .01) during 2020 compared with 2019. Fewer CRC cases were discussed in multidisciplinary meetings during 2020 (38% vs 50%, P = .01). Conclusions: Our data highlight a significant drop in CRC diagnosis after COVID-19, especially for early stage disease. The study also reveals a remarkable setback in the multidisciplinary management of patients with CRC. Despite this, Italian oncologists were able to ensure diagnostic-therapeutic pathways proper operation after March 2020.
MeSH term(s)	COVID-19/epidemiology ; Colorectal Neoplasms/diagnosis ; Colorectal Neoplasms/epidemiology ; Colorectal Neoplasms/genetics ; Early Detection of Cancer ; Humans ; Italy/epidemiology ; Pandemics
Language	English
Publishing date	2022-07-18
Publishing country	England
Document type	Journal Article ; Multicenter Study
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1093/oncolo/oyac129
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Zs.A 4845: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 494: Show issues

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Article: The Gustave Roussy Immune (GRIm)-Score Variation Is an Early-on-Treatment Biomarker of Outcome in Advanced Non-Small Cell Lung Cancer (NSCLC) Patients Treated with First-Line Pembrolizumab.

Journal of clinical medicine

2021 Volume 10, Issue 5

Abstract: Background: The Gustave Roussy Immune (GRIm)-Score takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check- ... ...

Abstract	Background: The Gustave Roussy Immune (GRIm)-Score takes into account neutrophil-to-lymphocyte ratio (NLR), serum albumin concentration and lactate dehydrogenase (LDH) and its prognostic value has been investigated in patients treated with immune check-point inhibitors (ICIs). To further assess the prognostic and predictive value of baseline GRIm-Score (GRImT0) in advanced non-small cell lung cancer (aNSCLC) patients, we separately investigated two cohorts of patients treated with first-line pembrolizumab or chemotherapy. We also investigated whether GRIm-Score at 45 days since treatment initiation (GRImT1) and GRIm-Score difference between the two timepoints may better predict clinical outcomes (GRImΔ = GRImT0 - GRImT1). Methods: We retrospectively evaluated 222 aNSCLC patients: 135 treated with pembrolizumab and 87 treated with chemotherapy as the first-line regimen. NLR, serum albumin and LDH concentrations were assessed at T0 and at T1. According to the GRIm-Score, patients were assigned 1 point if they had NLR > 6, LDH > upper limit normal or albumin < 3.5 g/dL. Patients with a GRIm-Score < 2 were considered as having a low Score. Results: In both cohorts, no difference in terms of overall survival (OS) between patients with low and high GRImT0 was found. Otherwise, median OS and progression free survival (PFS) of the low GRImT1 group were significantly longer than those of the high GRImT1 group in pembrolizumab-treated patients, but not in the CHT cohort (pembrolizumab cohort: low vs. high; median OS not reached vs. 9.2 months, Conclusion: Our data shown that GRImT1 and GRImΔ are more reliable peripheral blood biomarkers of outcome compared to GRImT0 in aNSCLC patients treated with pembrolizumab and might represent useful biomarkers to drive clinical decisions in this setting.
Language	English
Publishing date	2021-03-02
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2662592-1
ISSN	2077-0383
ISSN	2077-0383
DOI	10.3390/jcm10051005
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