Publications by authors named "Marco Brugia"

Globally, more than 1 million new cases of gastric cancer were estimated in 2020, ranking fourth in cancer mortality. Currently although in resectable gastric cancer and esophagogastric junction (EGJ) adenocarcinoma a perioperative triplet chemotherapy regimen including a fluoropyrimidine, a platinum compound and docetaxel (FLOT) demonstrated a better overall survival, the survival rate is still very low, and a massive effort is still required to improve clinical prognosis. High microsatellite instability (MSI-H) status in gastric cancer is a favorable prognostic factor but poor data are available on its predictive role for perioperative FLOT chemotherapy in resectable gastric cancer.

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To investigate the impact of natremia in metastatic colorectal cancer (mCRC) patients treated with aflibercept plus folinic acid, 5-fluorouracil, oxaliplatin and irinotecan (FOLFIRI). A total of 84 mCRC patients receiving aflibercept plus FOLFIRI as second-line treatment were enrolled and divided into two groups based on their median sodium value. Progression-free survival and overall survival were analyzed.

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R-CHOP standard chemotherapy is successful in about 60% of diffuse large B-cell lymphoma (DLBCL) patients. Unresponsive patients have a poor prognosis, and predictive biomarkers of response to R-CHOP are lacking. We conducted the first prospective GWAS study aimed at exploring constitutional biomarkers predictive of R-CHOP efficacy and toxicity.

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Article Synopsis
  • Management of metastatic colorectal cancer (mCRC) involves a continuum of care, primarily utilizing options like trifluridine/tipiracil and regorafenib after patients progress on standard therapies.
  • Fruquintinib, a selective inhibitor for VEGFR-1, -2, and -3, has shown significant anti-tumor effects and was approved for treatment in China based on the successful phase III FRESCO trial.
  • The subsequent FRESCO-2 trial validated these findings in various regions, showing fruquintinib improves overall survival in a heavily pretreated population and highlighting the need for identifying patients who may benefit most from this therapy.
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Resectable gastric or gastroesophageal (G/GEJ) cancer is a heterogeneous disease with no defined molecularly based treatment strategy. Unfortunately, nearly half of patients experience disease recurrence despite standard treatments (neoadjuvant and/or adjuvant chemotherapy/chemoradiotherapy and surgery). In this review, we summarize the evidence of potential tailored approaches in perioperative treatment of G/GEJ cancer, with a special focus on patients with human epidermal growth factor receptor-2(HER2)-positive and microsatellite instability-high (MSI-H) tumors.

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Colorectal cancer (CRC) is the third most common cancer worldwide, with approximately 1.9 million new diagnoses and 935 000 deaths annually. Overall, there is accumulating evidence that receiving all available treatments leads to a survival advantage and, although tailored treatments might be appropriate for selected patients, the one-size-fits-all approach is still widely used in chemo-refractory patients.

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Article Synopsis
  • About half of metastatic colorectal cancers have RAS mutations, which are important for understanding prognosis and developing targeted therapies, particularly focusing on KRAS hotspot mutations.
  • A study examined the association of KRAS mutations with patient characteristics, prognosis, and response to antiangiogenic treatments using data from 183 patients with advanced CRC.
  • Results showed specific KRAS mutations linked to certain metastatic patterns and demographics, with KRAS exon 4 mutations associated with significantly longer overall survival compared to other mutations.
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Purpose: To verify whether the intensification of the upfront chemotherapy backbone with a modified schedule of modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) increases the activity of fluorouracil, leucovorin, and oxaliplatin when both regimens are combined with panitumumab as initial treatment for and wild-type (wt) metastatic colorectal cancer (mCRC).

Methods: TRIPLETE was a prospective, open-label, phase III trial in which previously untreated patients with unresectable and wt mCRC were randomly assigned 1:1 to modified FOLFOX/panitumumab (control group) or mFOLFOXIRI/panitumumab (experimental group) up to 12 cycles, followed by fluorouracil/-leucovorin/panitumumab until disease progression. The primary end point was objective response rate (ORR) according to RECIST 1.

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Background: Immune-related adverse events (irAEs) are inflammatory side effects, which can occur during immune-checkpoint(s) inhibitors (ICIs) therapy. Steroids are the first-line agents to manage irAEs because of their immunosuppressive properties. However, it is still debated whether or when steroids can be administered without abrogating the therapeutic efforts of immunotherapy.

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Article Synopsis
  • Perioperative FLOT has emerged as the preferred treatment for patients with operable gastric or gastroesophageal adenocarcinoma, achieving a 5-year overall survival rate of 45%, compared to only 23% for surgery alone.
  • The RealFLOT study, an observational trial in Italy, aimed to assess the feasibility and safety of FLOT, as well as surgical outcomes and response rates in a real-world patient population, finding that safety profiles were consistent with existing literature.
  • The results showed a modest pathological complete response rate (7.3%), but significant improvements in disease-free and overall survival for patients achieving pCR, indicating its promising role as a predictor for better outcomes.
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The addition of aflibercept to FOLFIRI has been demonstrated to improve survival in patients with metastatic colorectal cancer (mCRC) who progressed after receiving a standard oxaliplatin-based regimen. In this retrospective, single-institution, observational study we collected clinical data from mCRC patients who received aflibercept in combination with FOLFIRI in routine clinical practice from October 2012 to March 2021 to describe feasibility and efficacy of this regimen in a real-world population. Forty-nine patients receiving aflibercept-FOLFIRI as second-line treatment were identified, 40.

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Purpose: Immune checkpoint inhibitors have opened a new scenario in the treatment of cancer. These agents can elicit adverse events, which may affect different systems and organs, including the endocrine system. The aims of this study were to evaluate the impact of the anti-PD-1 molecules nivolumab and pembrolizumab on endocrine toxicity and on patient outcome.

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Background: Within the OMITERC prospective study (OMIcs application from solid to liquid biopsy for a personalised ThERapy of Cancer), we explored the prognostic role of liquid biopsy encompassing cell-free DNA (cfDNA) and circulating tumour cells (CTCs) in KRAS mutated metastatic colorectal cancer (mCRC).

Methods: We defined a workflow including pre-analytical and analytical procedures collecting blood before therapy and every 3 months until disease progression (PD). CTCs were counted by CellSearch® and isolated by DEPArray™.

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The potent, RET-selective tyrosine kinase inhibitors (TKIs) pralsetinib and selpercatinib, are effective against the RET V804L/M gatekeeper mutants, however, adaptive mutations that cause resistance at the solvent front RET G810 residue have been found, pointing to the need for the development of the next-generation of RET-specific TKIs. Also, as seen in EGFR- and ALK-driven NSCLC, the rising of the co-occurring amplifications of KRAS and MET could represent other escaping mechanisms from direct inhibition. In this review, we summarize actual knowledge on RET fusions, focusing on those involved in NSCLC, the results of main clinical trials of approved RET-inhibition drugs, with particular attention on recent published results of selective TKIs, and finally, pre-clinical evidence regarding resistance mechanisms and suggestion on hypothetical and feasible drugs combinations and strategies viable in the near future.

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Somatostatine analogs (SSAs) are currently indicated in the treatment of acromegaly and neuroendocrine tumors (NETs). Actually, pregnancy in patients with acromegaly and NETs does not represent an exceptional event because reproductive behavior has changed in the last decades and patients with NETs show more frequently long-term survival. The safety profile of SSAs during pregnancy is still controversial.

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Five-year overall survival of stage III colorectal cancer (CRC) patients treated with standard adjuvant chemotherapy (ACHT) is highly variable. Genomic biomarkers and/or transcriptomic profiles identified lack of adequate validation. Aim of our study was to identify and validate molecular biomarkers predictive of ACHT response in stage III CRC patients by a transcriptomic approach.

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Background: Merkel cell carcinoma (MCC) is a rare neuroendocrine malignancy of the skin characterized by high aggressiveness. Four main factors are implicated in its development: immunosuppression, ultraviolet radiation, age and the Merkel cell polyomavirus (MCPyV). In recent years, immune checkpoint inhibitors have shown clinical activity in MCC treatment.

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Background: Surgical treatment is the cornerstone in the management of colorectal cancer (CRC) liver metastases. The aim of this study is to identify clinicopathological factors affecting disease-free (DFS) and overall survival (OS) in patients undergoing potentially curative liver resection for CRC metastasis.

Methods: All consecutive patients undergoing liver resection for first recurrence of CRC from February 2006 to February 2018 were included.

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Osteonecrosis of the jaw (ONJ) is a rare treatment related side effect that was firstly described in 2002 through a case report in metastatic bone cancer patient treated with bisphosphonates (BPs) therapy. ONJ is defined as an eight weeks or longer clinical finding of exposed bone in the oral cavity without response to appropriate therapy. The diagnosis is mainly clinical but often requires a radiological confirmation with an orthopantomography.

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Colorectal cancer is the third leading cause of cancer-related deaths in the western world. Despite therapeutic advances, the prognosis of metastatic colorectal cancer patients remains poor due to intrinsic or acquired tumor drug resistance. The main mechanisms of tumor drug resistance are represented by genetic and epigenetic alterations.

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About 60% of patients with diffuse large B-cell lymphoma (DLBCL) may be cured by primary chemotherapy with an R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) regimen. Most of the rest will die of the disease, mainly due to the occurrence of tumor drug resistance. Many efforts have been made to explain the molecular mechanisms of drug resistance in patients with cancer, including those with DLBCL.

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Objectives: Sunitinib is the standard care for first-line treatment of metastatic renal cell carcinoma. The aim of this study was to determine whether a sunitinib regimen of 50 mg/day 2-weeks on/1-week off could maintain the same dose-intensity as the standard 4-weeks on/2-weeks off schedule, and provide the same efficacy in terms of objective response, progression-free survival and overall survival, while reducing drug-related toxicity.

Methods: A total of 31 patients with metastatic renal cell carcinoma received sunitinib orally at the dose of 50 mg/day in a 2-weeks on/1-week off regimen until disease progression or intolerable toxicities occurred.

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