Floriana Nappo's research while affiliated with Istituto Oncologico Veneto and other places
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Publications (31)
727
Background: In order to identify targetable mutations, the Comprehensive Genomic Profiling (CGP) is an important tool. Technologies like extensive genomic NGS panels analyze multiple genes and biomarkers in a single assay. With multi-omics analysis, clinicians could increase the possibility to provide a tailored therapy. In literature, evidence...
Background:
Reliability of mismatch repair proteins and microsatellite instability assessment is essential in order to define treatment strategy and identify candidates to immune checkpoint inhibitors in locally advanced gastroesophageal carcinoma. We evaluated the concordance of deficient mismatch repair (dMMR) and microsatellite instability-high...
Signet-ring cell/poorly cohesive cell (SRC) carcinoma is an aggressive variant of pancreatic ductal adenocarcinoma (PDAC). This study aimed to clarify its clinicopathological and molecular profiles based on a multi-institutional cohort of 20 cases. The molecular profiles were investigated using DNA and RNA sequencing. The clinicopathological parame...
Background
FLOT regimen is the standard perioperative treatment in Western countries for patients with locally advanced gastric (GC) or gastroesophageal junction cancer (GEJC). High microsatellite instability (MSI-H) and Mismatch Repair deficient (dMMR) demonstrated a favorable prognostic role and a concomitant negative predictive impact on the ben...
358
Background: In resectable GAC/GEJAC, MSI status is associated with better survival and potential lack of benefit from chemotherapy. Given the high responsiveness of MSI tumors to immunotherapy, neoadjuvant or definitive dual CTLA-4/PD(L)-1 inhibition may allow omission of chemotherapy or surgery. Methods: INFINITY is a multicentre, single-arm,...
Background
Colorectal cancer (CRC) is one of the most common cancers; ∼20% of patients have metastases at diagnosis, and 50%-60% subsequently develop metachronous metastases. Bone involvement, despite being rare, is usually associated with higher disease burden, worse prognosis, impaired quality of life, and significant health-related cost. In the...
Gastroesophageal adenocarcinoma is a challenging disease due to its poor prognosis and the presence of few therapeutic options. For these reasons, it is mandatory to identify the subgroup of patients who are at high risk for relapse after curative-intention surgery. In the last years, liquid biopsy has aroused great interest in cancer treatment for...
Background
Early activation of palliative care for patients with advanced cancer is central in the treatment trajectory. At the Veneto Institute of Oncology, a simultaneous-care outpatient clinic (SCOC) has been active since 2014, where patients are evaluated by an oncologist together with a palliative care team. Recently, we reported on consecutiv...
Background
Approximately 50% of colorectal cancers occur in older patients. International societies recommend geriatric tools to optimize treatment of older patients. Comprehensive Geriatric Assessment (CGA) is a multidimensional assessment used to classify patients as fit, vulnerable, or frail. The CGA-based oncological multidimensional prognostic...
Undifferentiated sarcomatoid carcinoma (USC) of the pancreas is a rare but especially aggressive variant of pancreatic ductal adenocarcinoma (PDAC), composed of at least 80% of sarcomatoid cells. This study aimed to elucidate its clinicopathological and molecular features.
The study cohort included 10 patients with pancreatic USC. Clinicopathologic...
e15571
Background: Currently, no validated biomarkers are available for second-line anti-angiogenic treatment in RAS wild type (wt) metastatic colorectal cancer (mCRC) patients (pts) progressing after first-line anti-EGFR. Here, we present the results of a pre-planned interim analysis of the DISTINCTIVE trial (NCT04252456) on prognostic groups iden...
Background and aims:
Biliary tract cancers are rare malignancies with a poor prognosis and scarce therapeutic strategies. The significance of BRCAness in this setting is already unknown.
Method:
Tissue specimens of BTC patients treated with platinum-based chemotherapy have been analyzed through the FOUNDATIONPne assay.
Results:
72/150 (48%) BR...
e16068
Background: The FLOT4-AIO phase II/III trial established perioperative FLOT regimen as the new standard in Western countries for patients (pts) with locally advanced resectable gastric (GC) or gastroesophageal junction cancer (GEJC). Microsatellite instability (MSI-H) showed a favorable prognostic role and a concomitant negative predictive i...
PARP inhibitors are largely recognized as active drugs in BRCA-mutated breast and ovarian malignancies. In pancreatic ductal adenocarcinoma, the PARP inhibitor olaparib has recently been approved as maintenance treatment in patients with germline BRCA mutations reaching disease control after a platinum-based first line chemotherapy, proving signifi...
Background
We report the first case of a patient affected by peritoneal metastases from colon cancer, arising in the context of Lynch syndrome with pathological complete response. The patient was treated with immunotherapy and cytoreductive surgery. This paper discusses the implications of these novel therapies for the management of PM.
Case prese...
Background
The improved immunological understanding revealed the tumor microenvironment as an appealing driver to restore the immune response against cancer cells resulting in a paradigm shift in the oncology field. However, the complexity of the tumor milieu suggests a role of several pathways linking in immunomodulation mechanisms. Pancreatic can...
The tight junction protein claudin-18 (CLDN18), is often expressed in various cancer types including gastric (GC) and gastroesophageal adenocarcinomas (GECs). In the last years, the isoform CLDN18.2 emerged as a potential drug target in metastatic GCs, leading to the development of monoclonal antibodies against this protein. CLDN18.2 is the dominan...
Background
The efficacy of immune checkpoint inhibitors (ICIs) in patients with microsatellite instability (MSI)-high metastatic colorectal cancer (mCRC) is unprecedented. A relevant proportion of subjects achieving durable disease control may be considered potentially ‘cured’, as opposed to patients experiencing primary ICI refractoriness or short...
Background
Regorafenib is a key agent in metastatic colorectal cancer (mCRC), but no validated factors predicting longer survival are available.
Patients and Methods
REALITY was a retrospective multicenter trial in regorafenib-treated mCRC patients with overall survival (OS) ≥ 6 months. We aimed to assess the association between clinical parameter...
SBA classification is still based on the location of the primary tumor, without genetic information. in the current study, an extensive genetic profile of SBA, was performed in order to identify and quantify targetable alterations for a future precision medicine in SBA. Clinical-pathological information for 24 patients affected by SBA were retrospe...
4548
Background: The treatment strategy for patients with resectable gastric cancer changed in the last few years with perioperative treatments. FLOT regimen (fluorouracil, oxaliplatin, docetaxel) turned out to be feasible and effective, offering significant improvement in survival outcomes. However, the safety profile of triplet therapies for elde...
Background
KRAS G12C mutation occurs in about 4% of colorectal cancers (CRCs). Recently, KRAS G12C was identified to be potentially druggable and predictor of response to the novel on AMG510 target treatment. The present work aims to describe clinical-pathological features and prognosis of KRAS G12C mutated metastatic CRCs, compared to other KRAS m...
660
Background: In the NAPOLI I phase III trial, Nanoliposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) showed better outcome compared to 5FU/LV in patients with metastatic Pancreatic Cancer (MPC) progressed to 1st- line gemcitabine-based therapy. Aim of this study is to explore the real-world efficacy and safety of 5FU/LV-nal-...
Gastric cancer (GC) represents a leading cause of cancer related morbidity and mortality worldwide accounting for more than 1 million of newly diagnosed cases and thousands of deaths every year. In the last decade, the development of targeted therapies and the optimization of already available chemotherapeutic drugs has expanded the available treat...
Citations
... Under normal conditions in gastric tissue, splice variant 2 of CLDN18 is located within tight junction complexes between gastric mucosal cells, and CLD18.2 epitopes have limited exposure to circulating antibodies. However, during the transition to a malignant state, loss of cellular polarity causes the CLDN 18.2 epitope to become exposed, making it more readily recognizable by antibodies [29]. The claudin 18.2 isoform represents a promising target for new experimental drugs such as zolbetuximab (IMAB362), currently under investigation in several clinical trials for advanced gastrointestinal tumors [29]. ...
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... A recent study analyzing 3723 gastric cancer patients reported heterogenous MMR staining in 12 cases (0.32%), of which six (0.16%) had clonal MMRd status [12]. Another study analyzing a smaller cohort of 66 gastroesophageal patients reported two cases showing clonal MMRd status (3.0%) [13]. ...
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... However, pathologists should report any carcinoma components that are not conventional PDAC on small biopsies because these findings may be useful for the differential diagnosis and clinical management of patients. 25 ...
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... In addition, a subset of patients in the ITACA-S trial received taxane therapy in the form of cisplatin and docetaxel, but this still does not directly address the impact of MSI-H on outcomes with peri-operative FLOT [58]. The retrospective PROSECCO study attempted to address this question by examining outcomes among patients with MSS and MSI-H gastroesophageal cancer who received peri-operative FLOT [63]. Patients with MSI-H tumors had better DFS and OS compared to patients with MSS tumors who received FLOT [63]. ...
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... The latter one, the INFINITY trial, is an ongoing phase II study of durvalumab + tremelimumab in radically resectable MSI-H EGC. 54 The therapy is administered either as NAT (cohort 1) or as definitive treatment (cohort 2). Preliminary results from cohort 1 have recently been published and reported a pCR rate of 60% and an MPR rate of 80%. ...
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... In the "real-world" PROSECCO study of FLOT (fluorouracil/ leucovorin/oxaliplatin/docetaxel), median overall survival was not reached among the MSI-H/dMMR cohort, but it was 34 months in the MSS group. 2 The improved survival of patients with MSI-H/dMMR metastatic disease who received pembrolizumab in KEYNOTE-059, KEYNOTE-010, and KEYNOTE-062-where median overall survival was not reached 3 -also attests to the more favorable natural history of this subset and to their robust responses to immunotherapy, as many studies have shown. 4 "This was something we never saw in the clinic before the dawn of immunotherapy. ...
... 86 At present, some RCT studies are still exploring whether the combination of standard first-line chemotherapy and bevacizumab-based immunotherapy is effective. [87][88][89] Fruquintinib is a new, oral, highly selective targeting drug for VEGFR. It can inhibit the formation of tumor neovascularization by inhibiting VEGFR phosphorylation and downstream signals on the surface of vascular endothelial cells and play a role in inhibiting tumor growth and metastasis. ...
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... Utilizing ctDNA features, such as methylation patterns, mutations, copy number variation (CNV), and plasma/serum concentration, has shown promising results as a marker for detecting early-stage GC as well as MRD and recurrence [5,96,97]. Yoong Woo et al. demonstrated that postoperative analysis of ctDNA rearrangement by WGS can detect GC recurrence four months earlier than clinical diagnosis, on average. However, the minority of ctDNA-positive cases among post-operative patients remained challenging for ctDNA follow-up reliability [98]. ...
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... The first step is to ensure that the caregiver, together with the patient, understands the patient's state of health: diagnosis and prognosis, both in the sense of limited life expectancy and as well in the direction of the expected progression. In this path, palliative management must also be well understood according to the modern definition of Simultaneous Care from diagnosis to the "end stage" with "remodulation of care" for the well-being of the patient [53]. ...
... In the specific case of individuals with CRC, on whom this review focuses, the prevalence of frailty in the published series ranges from 20 to 43%; in all series, this population group has poorer survival and a greater number of severe complications after surgery [10,11]. These results have also been described in a systematic review by Boakye et al. [12] and in a meta-analysis by Chen et al. [13], both in CRC. ...
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