Publications by authors named "Giovanni Luca Frassineti"

Article Synopsis
  • Primary squamous cell carcinoma (SCC) can arise in various body parts, with primary gastric squamous cell carcinoma (GSCC) being particularly rare, exemplified by a case of a 72-year-old woman diagnosed with it.
  • Diagnostic imaging, including CT scans and ultrasound-endoscopy, revealed a significant mass at the celiac tripod, leading to further tests confirming poorly differentiated carcinoma with squamous differentiation.
  • The study emphasizes the need for well-defined diagnostic criteria for GSCC due to the lack of consensus in current classifications, suggesting that a standardized diagnostic panel might improve accuracy.
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Post-neoadjuvant therapy (post-NAT) and post-surgical circulating tumor DNA (ctDNA) risk stratification may enhance the management of patients with locally advanced rectal cancer (LARC). In this study, we assessed the prognostic value of ctDNA-based MRD detection in LARC patients using a personalized, tumor-informed ctDNA assay. Plasma samples from LARC patients (N = 30) were analyzed retrospectively using the Signatera™ assay.

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Article Synopsis
  • * Patients taking metformin had significantly shorter OS (HR 1.9) and PFS (HR 1.6) compared to those not using the medication, while no such differences were found in the Lenvatinib cohort.
  • * The findings suggest a negative impact of metformin usage on patient outcomes specifically in the context of Atezolizumab plus Bevacizumab treatment for HCC, highlighting the need for
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Background: Serum biomarkers have been investigated as predictive risk factors for cancer-related cardiovascular (CV) risk, but their analysis is limited to their baseline level rather than their overtime change. Besides historically validated causal factors, inflammatory and oxidative stress (OS) related markers seem to be correlated to CV events but this association needs to be further explored. We conducted an observational study to determine the predictive role of the longitudinal changes of commonly used and OS-related biomarkers during the cancer treatment period.

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Background: Peritoneal carcinomatosis significantly worsens the prognosis of patients with gastric cancer. Cytoreduction + hyperthermic intraperitoneal chemotherapy (HIPEC) has shown promising results in the prevention and treatment of peritoneal carcinomatosis in advanced gastric cancer (AGC); however, its application remains controversial owing to the variability of the approaches used to perform it and the lack of high-quality evidence. This systematic review and meta-analysis aimed to investigate the role of surgery and HIPEC in the prevention and treatment of peritoneal carcinomatosis of gastric origin.

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Article Synopsis
  • This study explored how initial and ongoing levels of the neutrophil-to-lymphocyte ratio (NLR) affect the survival rates of patients with metastatic colorectal cancer undergoing chemotherapy with or without bevacizumab.
  • Researchers analyzed data from a phase III trial involving 239 patients to assess how these inflammation markers influenced progression-free survival (PFS).
  • Results indicated that while baseline NLR impacted PFS mainly in the bevacizumab group, the overall treatment effect varied significantly based on initial NLR levels, highlighting the need for further research to identify underlying factors influencing treatment outcomes.
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Background: Validated predictors of sensitivity or resistance to Bevacizumab (Bev) are not available, and Inflammatory Indexes (IIs) has been reported to be useful prognostic factors in various malignant solid tumours, including metastatic colorectal cancer (mCRC).

Objectives: To explore the prognostic value of IIs in mCRC patients treated with first-line chemotherapy plus Bev.

Design: One hundred and eighty-two patients diagnosed with mCRC and treated with first line chemotherapy plus Bev were considered for this prospective non-pharmacological study.

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Background: Upfront anti-EGFR therapy represents the standard of care for patients with left-sided, MSS/pMMR, RAS and BRAF wild-type mCRC. Molecular 'hyperselection' may optimize EGFR inhibition by detecting additional resistance alterations.

Materials And Methods: We used comprehensive genomic profiling on archival samples of elderly patients enrolled in the PANDA trial to detect: HER2 amplification/mutations; MET amplification; NTRK/ROS1/ALK/RET rearrangements; PIK3CA exon 20 mutations; PTEN alterations; AKT1 mutations; MAP2K1 mutations.

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Purpose: Plasma circulating tumor DNA (ctDNA) is a valuable resource for tumor characterization and for monitoring of residual disease during treatment; however, it is not yet introduced in metastatic colorectal cancer (mCRC) routine clinical practice. In this retrospective exploratory study, we evaluated the role of ctDNA in patients with mCRC treated with chemotherapy plus bevacizumab.

Materials And Methods: Fifty-three patients were characterized for and status on tumor tissue before the start of treatment.

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Background And Aims: Perioperative treatment is currently the gold standard approach in Europe for locally advanced gastric cancer (GC). Unfortunately, the phenomenon of patients dropping out of treatment has been frequently observed. The primary aims of this study were to verify if routine blood parameters, inflammatory response markers, sarcopenia, and the depletion of adipose tissues were associated with compliance to neoadjuvant/perioperative chemotherapy.

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Bevacizumab (Bev) plus chemotherapy is a standard first-line treatment in metastatic colorectal cancer (mCRC), however to date no predictive factors of response have been identified. Results of our previous analysis on patients enrolled in a randomized prospective phase III multicenter study (ITACa study) showed a predictive value of Vascular Endothelial Growth Factor (VEGF) polymorphism (VEGF + 936), a 27-nucleotide variable number tandem repeat (VNTR) of the endothelial nitric oxide synthase (eNOS) gene and eNOS + 894 polymorphism. mCRC patients, treated with Bev plus chemotherapy, were included in this prospective validation trial.

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Purpose: To verify whether both doublet chemotherapy with a modified schedule of fluorouracil, leucovorin, and oxaliplatin (mFOLFOX) and monochemotherapy with fluorouracil plus leucovorin (5-FU + LV) achieve satisfactory efficacy when both regimens are combined with panitumumab (PAN) as initial treatment of elderly patients with / wild-type metastatic colorectal cancer (mCRC).

Patients And Methods: PANDA (ClinicalTrials.gov identifier: NCT02904031) was an open-label, randomized phase II noncomparative trial in previously untreated patients age 70 years and older with unresectable / wild-type mCRC.

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The identification of predictive factors for treatment of pancreatic cancer (PC) is an unmet clinical need. In the present work, we analyzed blood-derived extracellular vesicles (EVs) from patients with advanced PC in order to find a molecular signature predictive of response to therapy. We analyzed samples from 21 patients with advanced PC, all receiving first-line treatment with gemcitabine + nab-paclitaxel.

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Article Synopsis
  • PVs and LPVs in genes are linked to a higher risk of breast and ovarian cancers, especially in hereditary cases like HBOC; recent studies also connect these variants to pancreatic cancer.
  • Inherited genetic factors account for 10% to 20% of pancreatic cancer cases, with variation in germline alterations among different ethnic groups, particularly in Italian HBOC families.
  • The study focuses on a specific group of HBOC patients from the eastern coast of Emilia Romagna, aiming to determine the prevalence of a particular variant and its implications for cancer risk, which is important for genetic counseling and monitoring.
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Hemophagocytic lymphohistiocytosis (HLH) is a rare and life-threatening condition characterized by uncontrolled activation of the immune system. HLH is a reactive mononuclear phagocytic response that occurs in association with a constellation of conditions such as malignancies and infections. The clinical diagnosis of HLH remains challenging because HLH can present with symptoms that significantly overlap with other causes of cytopenia, such as sepsis, autoimmune diseases, hematological cancers, and multiorgan failure.

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A second-line standard of treatment has not yet been identified in patients with soft tissue sarcomas (STS), so identifying predictive markers could be a valuable tool. Recent studies have shown that the intratumoral and inflammatory systems significantly influence tumor aggressiveness. We aimed to investigate prognostic values of pre-therapy neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), systemic inflammatory index (SII), progression-free survival (PFS), and overall survival (OS) of STS patients receiving second-line treatment.

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Purpose: This randomized, open-label trial compared the efficacy and safety of adjuvant -paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430).

Methods: We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to -paclitaxel (125 mg/m) + gemcitabine (1,000 mg/m) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles.

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Purpose: To investigate the safety and efficacy of nivolumab plus cabozantinib with or without ipilimumab in patients with advanced hepatocellular carcinoma.

Methods: In cohort 6 of the multicohort, open-label, phase I/II CheckMate 040 study, patients who were treatment-naive, sorafenib-intolerant, or had progressed on sorafenib were randomly assigned 1:1 to nivolumab 240 mg once every 2 weeks plus cabozantinib 40 mg once daily (doublet arm); or nivolumab 3 mg/kg every 2 weeks plus cabozantinib 40 mg once daily with ipilimumab 1 mg/kg once every 6 weeks (triplet arm). Primary objectives were safety and tolerability, objective response rate, and duration of response by investigator assessment per RECIST v1.

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Neuroendocrine tumors (NETs) are rare neoplasms frequently characterized by an upregulation of the mammalian rapamycin targeting (mTOR) pathway resulting in uncontrolled cell proliferation. The mTOR pathway is also involved in skeletal muscle protein synthesis and in adipose tissue metabolism. Everolimus inhibits the mTOR pathway, resulting in blockade of cell growth and tumor progression.

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Isocitrate dehydrogenase (IDH)1/2 mutations are the most frequent druggable alterations in intrahepatic cholangiocarcinoma (iCCA), reported in ~20% of cases. Preclinical evidence indicates that these mutations are associated with homologous recombination deficiency (HRD), which could be exploited as a target for platinum chemotherapy (ChT) and PARP inhibitors. However, the role of IDH1/2 mutations as surrogate biomarkers for platinum efficacy is unknown.

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Spontaneous pneumothorax (PNX) is an infrequent manifestation of primary lung cancer, soft tissue sarcoma and metastasis. There are no easily accessible data in the literature regarding the correlation between PNX and antibiotics, whereas cases of PNX following chemotherapy have been observed. Only 1-10% of treatment-related adverse events are estimated to be reported to the Food and Drug Administration.

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Takotsubo syndrome (TTS) is an uncommon cardiovascular condition also known as stress-induced cardiomyopathy or broken heart disease. The syndrome, characterized by acute non-coronary segmental ventricular dysfunction, commonly occurs as a reaction to severe emotional or physical stress and can cause significant problems. Several classes of chemotherapeutic agents that are known to be cardiotoxic have been shown to be associated with TTS in cancer patients.

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Background: After the REGATTA trial, patients with stage IV gastric cancer could only benefit from chemotherapy (CHT). However, some of these patients may respond extraordinarily to palliative chemotherapy, converting their disease to a radically operable stage. We present a single centre experience in treating peritoneal carcinomatosis from gastric cancer.

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Analysis of plasma-derived cell-free DNA (cfDNA) might allow for the early identification of resistance in metastatic colorectal carcinoma (mCRC) patients receiving anti-EGFR monoclonal antibodies. We tested plasma samples from the Erbitux Metastatic Colorectal Cancer Strategy (ERMES) phase III trial of FOLFIRI+Cetuximab in first-line treatment of RAS/BRAF wild-type mCRC. Samples were collected at baseline ( = 37), at 8 weeks of treatment ( = 32), progressive disease (PD; = 36) and 3 months after PD ( = 21).

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Pancreatic ductal adenocarcinoma (PDAC) has one of the most dismal prognoses of all cancers due to its late manifestation and resistance to current therapies. Accumulating evidence has suggested that the malignant behavior of this cancer is mainly influenced by the associated strongly immunosuppressive, desmoplastic microenvironment and by the relatively low mutational burden. PDAC develops and progresses through a multi-step process.

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