Publications by authors named "Molina-Cerrillo J"

While the role of cancer stem cells (CSCs) in tumorigenesis, chemoresistance, metastasis, and relapse has been extensively studied in solid tumors, such as adenocarcinomas or sarcomas, the same cannot be said for neuroendocrine neoplasms (NENs). While lagging, CSCs have been described in numerous NENs, including gastrointestinal and pancreatic NENs (PanNENs), and they have been found to play critical roles in tumor initiation, progression, and treatment resistance. However, it seems that there is still skepticism regarding the role of CSCs in NENs, even in light of studies that support the CSC model in these tumors and the therapeutic benefits of targeting them.

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Introduction: Renal cell carcinoma (RCC) is one of the most common types of urogenital cancer. The introduction of immune-based combinations, including dual immune-checkpoint inhibitors (ICI) or ICI plus tyrosine kinase inhibitors (TKIs), has radically changed the treatment landscape for metastatic RCC, showing varying efficacy across different prognostic groups based on the International Metastatic RCC Database Consortium (IMDC) criteria.

Materials And Methods: This retrospective multicenter study, part of the ARON-1 project, aimed to evaluate the outcomes of favorable-risk metastatic RCC patients treated with immune-based combinations or sunitinib.

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Introduction: The COVID-19 pandemic is a great burden worldwide, but its impact on patients with genitourinary cancer (GUC) is poorly characterized. This study aimed to characterize the clinical features and evolution of GUC patients affected by COVID-19 in Spain.

Patients And Methods: SOGUG-COVID-19 was an observational ambispective non-interventional study that recruited patients with SARS-CoV-2 infection who had been treated for GUC in 32 Spanish hospitals.

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Article Synopsis
  • - Enfortumab vedotin (EV) is effective for patients with advanced urothelial carcinoma who have previously received platinum chemotherapy and immune therapy, despite lacking research on those treated with avelumab maintenance.
  • - A study of 182 patients showed a median overall survival of 12.7 months and a progression-free survival of 7.9 months, with 39% achieving a positive response to EV after avelumab treatment.
  • - The study confirms EV's effectiveness, suggesting it can be a viable option for patients previously treated with avelumab, with manageable side effects like grade ≥ 3 neuropathy and skin rash occurring in a minority of cases.
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  • Advances in immuno-oncology have improved treatment for renal cell carcinoma, but patients with "primary refractory" disease have poor outcomes; our study found a 19% prevalence of this group among 1,709 metastatic clear cell patients across 72 centers in 22 countries.
  • The highest primary refractory rate was 27% with nivolumab/ipilimumab, while pembrolizumab/lenvatinib had the lowest at 10%; those classified as primary refractory only had a median survival of 7.6 months compared to 55.7 months for non-primary refractory patients.
  • Significant predictors of survival for primary refractory patients included factors like prior nephrectomy and presence of bone/brain metastases, highlighting the complex
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  • A study compared the combination treatment of tivozanib and nivolumab against tivozanib alone for patients with advanced renal cell carcinoma who progressed after one or two prior therapies, focusing on the post-immune checkpoint inhibitor (ICI) setting.
  • The TiNivo-2 trial included 343 patients from 190 sites across multiple continents, with the primary goal of evaluating progression-free survival (PFS) as the main outcome.
  • Results showed that the median PFS was 5.7 months for the combination therapy and 7.4 months for tivozanib monotherapy, indicating no significant advantage for the combination treatment based on the hazard ratio.
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  • - Metastatic renal cell carcinoma (mRCC) with sarcomatoid features (sRCC) is aggressive and has a poor prognosis; this study aimed to investigate its clinical features and outcomes compared to non-sarcomatoid patients.
  • - The study analyzed data from 1362 mRCC patients, finding that the median overall survival for sRCC patients was 26.8 months, significantly lower than the 35.3 months for non-sRCC patients.
  • - Both first-line treatment strategies, immunotherapy combined with immunotherapy (IO + IO) and immunotherapy with a tyrosine kinase inhibitor (IO + TKI), showed similar survival outcomes, confirming that
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  • The study focuses on the effectiveness of pembrolizumab, an immune checkpoint inhibitor, for advanced urothelial carcinoma (UC) patients with poor performance status (ECOG-PS 2).
  • Among 1,040 patients, those with ECOG-PS 2 had significantly lower median overall survival (3.7 months) compared to those with ECOG-PS 0-1 (18.2 months), highlighting the challenges faced by this group.
  • Key factors affecting outcomes included the presence of liver metastases and disease progression during first-line therapy, indicating a need for careful evaluation of these patients' conditions.
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  • - Medullary thyroid carcinoma (MTC) is a rare cancer originating from the thyroid's neuroendocrine C-cells, and a new two-tier grading system based on tumor characteristics like proliferation and necrosis has been established to help predict patient outcomes.
  • - A transcriptomic analysis of 21 MTC samples revealed a significant upregulation of various genes in high-grade tumors, suggesting distinct molecular pathways involved in tumor aggressiveness, such as DNA damage repair and apoptosis.
  • - The study found that DLL3 expression is correlated with poorer survival rates in MTC patients, particularly when DLL3 is overexpressed in at least 50% of tumor cells, indicating its potential as a biomarker for aggressive disease. *
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Upper tract urothelial carcinoma (UTUC) accounts for the 5-10% of all urothelial carcinomas (UCs). In this analysis, we reported the real-world data from the ARON-2 study (NCT05290038) on the efficacy of pembrolizumab in patients with UTUC who recurred or progressed after platinum-based chemotherapy. Medical records of patients with metastatic UTUC treated with pembrolizumab as second-line therapy were reviewed from 34 institutions in 14 countries.

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  • There is ongoing debate about whether sex influences the effectiveness of immune checkpoint inhibitors in cancer treatment, specifically for metastatic renal cell carcinoma (mRCC).
  • A study involving 1,827 mRCC patients from multiple countries found that overall median overall survival (OS) was similar for both sexes, but males performed better in specific subgroups, particularly younger patients and those with certain cancer histologies.
  • Interestingly, female sex was identified as a negative prognostic factor in patients with sarcomatoid differentiation, suggesting that despite women having stronger immune responses, their outcomes in these cases were worse than those of men.
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Background: About 20% of patients with renal cell carcinoma present with non-clear cell histology (nccRCC), encompassing various histological types. While surgery remains pivotal for localized-stage nccRCC, the role of cytoreductive nephrectomy (CN) in metastatic nccRCC is contentious. Limited data exist on the role of CN in metastatic nccRCC under current standard of care.

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Article Synopsis
  • - The ARON-2 study investigated the real-world effectiveness of pembrolizumab, an immune checkpoint inhibitor, in patients with advanced urothelial carcinoma who had progression after platinum-based chemotherapy, utilizing data from 836 patients across 88 institutions in 23 countries.
  • - Results showed median overall survival (OS) of 10.5 months and overall response rate (ORR) of 31%; those who progressed after initial chemotherapy (cohort A) had lower OS (9.1 months) compared to those who recurred within a year post-chemotherapy (cohort B) with 14.6 months OS.
  • - Multivariate analysis identified several prognostic factors affecting OS and progression-free survival (PFS),
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Background And Objective: Papillary renal cell carcinoma (pRCC) is the most frequent histological subtype of non-clear cell RCC (nccRCC). Owing to the heterogeneity of nccRCC, patients are often excluded from large phase 3 trials focused on clear cell RCC, so treatment options for nccRCC remain limited. Our aim was to investigate the efficacy of first-line treatment with tyrosine kinase inhibitors (TKIs) or immuno-oncology (IO)-based combinations in patients with pRCC.

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Background: Systemic treatment with immune combinations is the gold standard for metastatic renal cell carcinoma (mRCC) worldwide. The systemic immune-inflammation index (SII) is a prognostic marker for several types of malignant neoplasms, including mRCC, in the era of tyrosine kinase inhibitor (TKI) treatment. Data regarding the prognostic value of the SII in patients with mRCC treated with immunotherapy are scarce and controversial.

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The ARON-2 study (NCT05290038) aimed to assess the real-world efficacy of pembrolizumab in patients recurred or progressed after platinum-based chemotherapy. This retrospective analysis reports the outcomes of urothelial carcinoma (UC) patients with bone metastases (BM). Medical records of patients with documented metastatic UC treated by pembrolizumab as second-line therapy were reviewed from60 institutions in 20 countries.

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Background: Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab.

Methods: We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries.

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Background: The upfront treatment of metastatic renal cell carcinoma (mRCC) has been revolutionized by the introduction of immune-based combinations. The role of cytoreductive nephrectomy (CN) in these patients is still debated. The ARON-1 study (NCT05287464) was designed to globally analyze real-world data of mRCC patients receiving first-line immuno-oncology combinations.

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Background: Renal c carcinoma (RCC) is one of the most common urinary cancers worldwide, with a predicted increase in incidence in the coming years. Immunotherapy, as a single agent, in doublets, or in combination with anti-vascular endothelial growth factor receptor tyrosine kinase inhibitors (TKIs), has rapidly become a cornerstone of the RCC therapeutic scenario, but no head-to-head comparisons have been made. In this setting, real-world evidence emerges as a cornerstone to guide clinical decisions.

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Background: Immuno-oncology combinations have achieved survival benefits in patients with metastatic renal cell carcinoma (mRCC).

Objective: The ARON-1 study (NCT05287464) was designed to globally collect real-world data on the use of immuno-combinations as first-line therapy for mRCC patients.

Patients And Methods: Patients aged ≥ 18 years with a cytologically and/or histologically confirmed diagnosis of mRCC treated with first-line immuno-combination therapies were retrospectively included from 47 International Institutions from 16 countries.

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Background: The advent of immune-checkpoint inhibitors has challenged previous treatment paradigms for advanced urothelial carcinoma (UC) in the post-platinum setting as well as in the first-line setting for cisplatin-ineligible patients. In this study, we investigated the effectiveness of pembrolizumab as first-line treatment for cisplatin-ineligible UC.

Methods: Data from patients aged ≥ 18 years with cisplatin-ineligible UC and receiving first-line pembrolizumab from January 1st 2017 to September 1st 2022 were collected.

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Purpose: To describe our current protocol for surgical and postsurgical management of abdominal paragangliomas (PGLs) and pheochromocytomas, with a special focus on multidisciplinary management in centres with experience.

Methods: The physicians involved in the management of patients with abdominal PGLs and pheochromocytomas of our hospital reviewed systematically current knowledge on the surgical management of abdominal PGLs and pheochromocytomas.

Results: Currently, surgery is considered the treatment of choice for abdominal PGLs and pheochromocytomas.

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Background: Obesity has been associated with improved response to immunotherapy in cancer patients. We investigated the role of body mass index (BMI) in patients from the ARON-1 study (NCT05287464) treated by dual immuno-oncology agents (IO+IO) or a combination of immuno-oncology drug and a tyrosine kinase inhibitors (TKI) as first-line therapy for metastatic renal cell carcinoma (mRCC).

Patients And Methods: Medical records of patients with documented mRCC treated by immuno-oncology combinations were reviewed at 47 institutions from 16 countries.

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Circadian rhythm regulates cellular differentiation and physiology and shapes the immune response. Altered expression of clock genes might lead to the onset of common malignant cancers, including Renal Cell Carcinoma (RCC). Data from Cancer Genome Atlas (TCGA) indicate that clock genes , , , and are overexpressed in RCC tissues and correlate with patients' prognosis.

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Background: Immunotherapy has determined unprecedented long-term responses in several hematological and solid tumors. In the MOUSEION-03 study, we conducted a meta-analysis to determine the possibility of achieving complete remissions (CR) with immunotherapy or immuno-oncology combinations in cancer patients.

Methods: The primary endpoint was to assess the incidence of CR in cancer patients receiving immune checkpoint inhibitors (ICIs) alone or in combination with other agents versus control treatments.

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