Publications by authors named "Erica Quaquarini"

22 Publications

  • Page 1 of 1

Poorly Cohesive Carcinoma of the Nonampullary Small Intestine: A Distinct Histologic Subtype With Prognostic Significance.

Am J Surg Pathol 2021 Oct 11. Epub 2021 Oct 11.

Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia Anatomic Pathology, Fondazione IRCCS San Matteo Hospital Clinical Epidemiology & Biometry Unit, Fondazione IRCCS San Matteo Hospital Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital Medical Oncology Unit, ICS Maugeri-IRCCS SpA SB, Pavia Pathology Unit, Department of Surgical and Diagnostic Sciences (DISC), University of Genoa and Ospedale Policlinico San Martino IRCCS, Genoa Surgical Pathology Unit, Department of Medicine (DIMED), University of Padua Veneto Institute of Oncology, IOV-IRCCS, Padua Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori," Meldola Pathology Unit, Department of Medicine and Surgery, University of Insubria, Varese Gatroenterology Unit, ASST Fatebenefratelli-Sacco, L. Sacco University Hospital Department of Biochemical and Clinical Sciences, University of Milan, Milan Division of General and HPB Surgery, ASST Rhodense, Rho Gatroenterology Unit, Department of Systems Medicine, University of Rome "Tor Vergata," Rome, Italy Department of Pathology, Koç University Hospital and Koç University Research Center for Translational Medicine (KUTTAM), Istanbul, Turkey.

Poorly cohesive carcinomas (PCCs) are neoplasms characterized by a dyshesive cell invasion pattern featuring single-cell or cord-like stromal infiltration. Although they have been extensively studied in the stomach and other digestive system organs, limited data regarding nonampullary small bowel poorly cohesive carcinomas (SB-PCCs) are hitherto available. The aims of our study were to analyze the clinicopathologic and immunophenotypical features of SB-PCCs (PCC pattern accounting for >50% of the neoplasm) and to compare them with small bowel adenocarcinomas (SBAs), not otherwise specified (SBAs-NOS) and with cancers with a histologically distinct PCC component accounting for 10% to 50% of the neoplasm (mixed-poorly-cohesive-glandular-SBAs). Fifteen SB-PCCs were identified and compared with 95 SBAs-NOS and 27 mixed-poorly-cohesive-glandular-SBAs. Most SB-PCCs (67%) were composed of <10% of signet-ring cells, and all but 1 SB-PCCs exhibited loss of membranous expression of E-cadherin. Compared with SBAs-NOS, SB-PCCs showed a significantly younger patient age at diagnosis, and a stronger association with Crohn disease, and both SB-PCCs and mixed-poorly-cohesive-glandular-SBAs featured a higher rate of lymphovascular and perineural invasion and a lower percentage of mismatch repair-deficient cases. Importantly, the cancer-specific survival of SB-PCC (hazard ratio: 3.81; 95% confidence interval: 1.90-7.64; P<0.001) and mixed-poorly-cohesive-glandular-SBA (4.12; 2.20-7.71; P<0.001) patients was significantly worse compared with SBAs-NOS cases. This study provides objective evidence to the World Health Organization (WHO) 2019 introduction of SB-PCC as a distinctive subtype of nonampullary SBA, by virtue of its unique clinical and histologic features, and suggests that both SB-PCCs and mixed-poorly-cohesive-glandular-SBAs should be separated from SBAs-NOS.
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http://dx.doi.org/10.1097/PAS.0000000000001821DOI Listing
October 2021

Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study.

Ther Adv Med Oncol 2021 10;13:1758835920987651. Epub 2021 Mar 10.

Medical Oncology Unit, IRCCS ICS Maugeri, Via Maugeri 10, Pavia, 27100, Italy.

Background: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials.

Patients And Methods: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B).

Results: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47-79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6-32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively.

Conclusions: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2- MBC, also suggesting a better performance of the combinations in earlier treatment lines.
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http://dx.doi.org/10.1177/1758835920987651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970542PMC
March 2021

Small Bowel Adenocarcinomas Featuring Special AT-Rich Sequence-Binding Protein 2 (SATB2) Expression and a Colorectal Cancer-Like Immunophenotype: A Potential Diagnostic Pitfall.

Cancers (Basel) 2020 Nov 19;12(11). Epub 2020 Nov 19.

Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia and Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Lombardy, Italy.

Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor expressed by colonic cryptic epithelium and epithelial neoplasms of the lower gastrointestinal (GI) tract, as well as by small bowel adenocarcinomas (SBAs), though at a lower rate. Nevertheless, up to now, only small SBA series, often including a very limited number of Crohn's disease-associated SBAs (CrD-SBAs) and celiac disease-associated SBAs (CD-SBA), have been investigated for SATB2 expression. We evaluated the expression of SATB2 and other GI phenotypic markers (cytokeratin (CK) 7 and CK20, caudal type homeobox 2 (CDX2) and alpha-methylacyl-CoA racemase (AMACR)), as well as mismatch repair (MMR) proteins, in 100 SBAs, encompassing 34 CrD-SBAs, 28 CD-SBAs and 38 sporadic cases (Spo-SBAs). Any mutual association and correlation with other clinico-pathologic features, including patient prognosis, were searched. Twenty (20%) SATB2-positive SBAs (4 CrD-SBAs, 7 CD-SBAs and 9 Spo-SBAs) were identified. The prevalence of SATB2 positivity was lower in CrD-SBA (12%) in comparison with both CD-SBAs (25%) and Spo-SBAs (24%). Interestingly, six SBAs (two CD-SBAs and four Spo-SBAs) displayed a full colorectal carcinoma (CRC)-like immunoprofile (CK7-/CK20+/CDX2+/AMACR+/SATB2+); none of them was a CrD-SBA. No association between SATB2 expression and MMR status was observed. Although SATB2-positive SBA patients showed a more favorable outcome in comparison with SATB2-negative ones, the difference did not reach statistical significance. When cancers were stratified according to CK7/CK20 expression patterns, we found that CK7-/CK20- SBAs were enriched with MMR-deficient cases (71%) and patients with CK7-/CK20- or CK7-/CK20+ SBAs had a significantly better survival rate compared to those with CK7+/CK20- or CK7+/CK20+ cancers ( = 0.002). To conclude, we identified a small (6%) subset of SBAs featuring a full CRC-like immunoprofile, representing a potential diagnostic pitfall in attempts to identify the site of origin of neoplasms of unknown primary site. In contrast with data on colorectal carcinoma, SATB2 expression is not associated with MMR status in SBAs. CK patterns influence patient survival, as CK7-/CK20- cancers show better prognosis, a behavior possibly due to the high rate of MMR-deficient SBAs within this subgroup.
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http://dx.doi.org/10.3390/cancers12113441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7699330PMC
November 2020

Impact of COVID-19 Outbreak on Cancer Patient Care and Treatment: Data from an Outpatient Oncology Clinic in Lombardy (Italy).

Cancers (Basel) 2020 Oct 12;12(10). Epub 2020 Oct 12.

Medical Oncology Unit, ICS Maugeri-IRCCS SpA SB, 27100 Pavia, Italy.

Lombardy was the first area in Italy to have an outbreak of coronavirus disease 19 (COVID-19) at the beginning of 2020. In this context, cancer has been reported as a major risk factor for adverse outcomes and death, so oncology societies have quickly released guidelines on cancer care during the pandemic. The aim of this study was to investigate the management of cancer patients and oncological treatments during the COVID-19 pandemic and to describe the containment measures performed in our outpatient clinic at Pavia (Lombardy). A comparison with the same period of the four previous years (2019, 2018, 2017, and 2016) was also performed. Using our electronic databases, we evaluated the number and characteristics of patients accessing the hospital for anticancer drug infusion from 24 February, 2020 to 30 April, 2020 and the number of radiological exams performed. Although a significant reduction in access for therapy was seen when compared with 2019 (2590 versus 2974, access rate ratio (ARR) = 0.85, < 0.001), no significant differences in access numbers and ARR was evident between 2020 and 2018, 2017, or 2016 (2590 versus 2626 (ARR = 0.07), 2660 (ARR = 0.99), and 2694 (ARR = 0.96), respectively, > 0.05). In 2020, 63 patients delayed treatment: 38% for "pandemic fear", 18% for travel restrictions, 13% for quarantine, 18% for flu syndrome other than COVID-19, and 13% for worsening of clinical conditions and death. Only 7/469 patients developed COVID-19. A significant reduction in radiological exams was found in 2020 versus all the other years considered (211 versus 360, 355, 385, 390 for the years 2020, 2019, 2018, 2017, and 2016, respectively, < 0.001). The low incidence of COVID-19 among our cancer patients, along with the hospital policy to control infection, enabled safe cancer treatment and a continuum of care in most patients, while a small fraction of patients experienced a therapeutic delay due to patient-related reasons.
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http://dx.doi.org/10.3390/cancers12102941DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601200PMC
October 2020

Role of androgen receptor expression in early stage ER+/PgR-/HER2- breast cancer.

Ther Adv Med Oncol 2020 17;12:1758835920958355. Epub 2020 Sep 17.

Medical Oncology Unit, ICS Maugeri-IRCCS SpA SB, Pavia, Italy.

Background: Progesterone receptor (PgR) negative breast cancer (BC) is an aggressive subtype with poor prognosis and reduced response to endocrine treatments. Several studies have suggested that androgen receptor (AR) expression is associated with a favorable tumor biology, longer recurrence free survival (RFS), and overall survival. In the literature no data exist regarding the role of AR expression in early stage estrogen receptor (ER)+/PgR- BCs. The aim of this study was to evaluate the prognostic role of AR expression in this setting.

Patients And Methods: This is a monocentric retrospective study in which 208 patients who underwent surgical intervention for ER+/PgR-/Human Epidermal growth factor Receptor 2 (HER2)- BC were included. The primary objective was to analyze the relationship between AR expression and RFS.

Results: At a median follow-up of 77 months, 75 patients (36%) had a disease relapse (all sites included). AR expression was significantly higher in patients who did not relapse compared with those who relapsed with an impact on RFS (hazard ratio [HR] = 0.99,  = 0.025). Patients with AR expression ⩾80% had a lower risk of relapse compared with those with AR <80% (HR = 0.53,  = 0.008). In addition, breast tumors with higher AR expression had good biological features (low ki67 and nuclear grade) compared with BCs with lower AR expression, at least partly explaining the different outcome.

Conclusions: The results of this study support the potential prognostic role of AR in patients with ER+/PgR- BCs and may contribute to the identification of subgroups of high-risk patients.
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http://dx.doi.org/10.1177/1758835920958355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502860PMC
September 2020

Renal and Cardiovascular Toxicities by New Systemic Treatments for Prostate Cancer.

Cancers (Basel) 2020 Jul 1;12(7). Epub 2020 Jul 1.

Operative Unit of Medical Oncology, IRCCS Istituti Clinici Scientifici Maugeri, 27100 Pavia, Italy.

Prostate cancer (PC) is the most common male cancer in Western Countries. In recent years, the treatment of relapsed or metastatic disease had benefited by the introduction of a variety of new different drugs. In consideration of the relative long survival of PC patients, side effects of these drugs must be considered and monitored. In this review, we analyzed the newly developed therapies for PC treatment, describing the mechanism of action, the metabolism and latest clinical trials that led to the approval of these drugs in clinical practice. We then evaluated the cardiovascular and renal side effects from pivotal phase III and II studies and meta-analyses. Cardiovascular side effects are the most frequent, in particular hypertension, while renal toxicity is rarer and not well described in literature. Therefore, there is a need to better define the effects of these therapies, in order to personalize patient treatment on the basis of their comorbidities and preferences, in addition to their symptoms and disease load.
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http://dx.doi.org/10.3390/cancers12071750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407336PMC
July 2020

Bilateral Breast Metastases from Epstein-Barr Virus-Associated Gastric Cancer during Pregnancy: Is There a Method to Its Madness?

J Gastric Cancer 2020 Mar 11;20(1):106-114. Epub 2019 Sep 11.

Anatomic Pathology Unit, Department of Molecular Medicine, University of Pavia, Pavia, Italy.

Breast metastases of extramammary malignant neoplasms are rare, with an incidence of 0.3%-2.7% among all malignant mammary tumors. Breast metastases from gastric carcinoma are very rare (<0.1%), and this event is even rarer during pregnancy. Herein, we describe a 39-year-old Caucasian woman with a history of an Epstein-Barr virus-associated gastric carcinoma (EBVaGC) that was characterized by prominent tumor infiltrating lymphocytes. Three years after undergoing radical surgery, the patient developed bilateral breast nodules during her pregnancy. A breast biopsy was performed, and histology confirmed a diagnosis of EBVaGC; tumor cells showed positivity for cytokeratin 8/18 and E-cadherin, and negativity for cytokeratin 7, cytokeratin 20, cytokeratin 5/6, caudal type homebox 2, androgen receptor, mammaglobin, gross cystic disease fluid protein-15, and estrogen and progesterone receptors. We also discuss the main diagnostic pitfalls. To our knowledge, this is the first report of an EBVaGC with lymphoid stroma that developed breast metastases during pregnancy.
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http://dx.doi.org/10.5230/jgc.2020.20.e1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105417PMC
March 2020

PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability.

Mod Pathol 2020 07 17;33(7):1398-1409. Epub 2020 Feb 17.

Department of Internal Medicine, University of Pavia and Fondazione IRCCS San Matteo Hospital, Pavia, Italy.

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn's disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1 immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1 cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1 microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.
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http://dx.doi.org/10.1038/s41379-020-0497-0DOI Listing
July 2020

The PI3K/AKT/mTOR and CDK4/6 Pathways in Endocrine Resistant HR+/HER2- Metastatic Breast Cancer: Biological Mechanisms and New Treatments.

Cancers (Basel) 2019 Aug 24;11(9). Epub 2019 Aug 24.

Medical Oncology Unit, IRCCS ICS Maugeri SpA SB, 27100 Pavia, Italy.

Endocrine-based treatments are the normal standard-of-care in women with hormone receptor-positive/Human Epidermal growth factor Receptor 2-negative metastatic breast cancer. Despite the well-known efficacy of these drugs as first-line therapies, about 50% of women develop endocrine resistance and disease progression. The treatment of these patients has represented one of the most important research fields in the last few years, with several multicenter phase II/III trials published or still ongoing. Novel therapies, such as cyclin-dependent kinase (CDK)4/6 and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) inhibitors, have significantly changed the prognosis of patients progressing to a previous endocrine treatment, allowing a great benefit in terms of progression-free survival and, in some cases, of overall survival. However, identifying response predictors is essential for the rational use of these drugs to avoid unnecessary toxicity and costs, and to ensure the optimal therapeutic sequence is used. In this review, we analyze the PI3K/AKT/mTOR and CDK4/6 pathways and their roles in endocrine resistant metastatic breast cancer. We then focus on the new treatments developed and the roles of these drugs in overcoming endocrine resistance, describing the latest clinical trials that led to the approval of the drugs in clinical practice.
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http://dx.doi.org/10.3390/cancers11091242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6770492PMC
August 2019

Palbociclib in metastatic breast cancer: current evidence and real-life data.

Drugs Context 2019 16;8:212579. Epub 2019 Jul 16.

Operative Unit of Medical Oncology IRCCS-ICS Maugeri, Pavia, Italy.

The purpose of this review is to summarize the background and latest evidence for the use of palbociclib, an oral, first-in-class, highly selective cyclin-dependent kinase 4/6 inhibitor, in advanced breast cancer, with a focus on some of the unanswered questions about the performance of this agent in clinical practice. The available clinical data from both controlled clinical trials and real-life experiences concerning palbociclib-based combinations in patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic disease, including patient-reported outcomes and subgroup analyses, have been reviewed and discussed. Palbociclib significantly improved progression-free survival and clinical benefit rates when added to letrozole in postmenopausal women as initial endocrine-based therapy, and it prolonged progression-free survival and overall survival when added to fulvestrant in women who progressed on previous endocrine therapy in randomized clinical trials. Tolerability profile was manageable, with neutropenia occurring most commonly, without detrimental impact on quality of life. Available data from real-life experiences confirm the good performance of palbociclib in unselected, heavily pretreated populations. Palbociclib in combination with endocrine therapy is a valuable emerging option for patients with HR+/HER2- advanced or metastatic breast cancer. Further investigation is needed to provide solutions for palbociclib resistance and to identify the best sequence to use for the best patient benefit with a minimal toxicity.
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http://dx.doi.org/10.7573/dic.212579DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6668507PMC
July 2019

Patterns of treatment and outcome with 500-mg fulvestrant in postmenopausal women with hormone receptor-positive/HER2-negative metastatic breast cancer: a real-life multicenter Italian experience.

Ther Adv Med Oncol 2019 4;11:1758835919833864. Epub 2019 Jun 4.

Medical Oncology Unit, IRCCS-ICS Maugeri, Pavia, Italy.

Background: Fulvestrant 500 mg (F500) is the most active endocrine single agent in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC). Few data are available regarding the effectiveness of the drug in a real-world setting.

Patients And Methods: This prospective, multicenter cohort study aimed to describe the patterns of treatment and performance of F500 in a large population of unselected women with MBC, focusing on potential prognostic or predictive factors for disease outcome and response. The primary endpoints were progression-free survival (PFS) and clinical benefit rate.

Results: From January 2011 to December 2015, 490 consecutive patients treated with F500 were enrolled. Overall, three different cohorts were identified and analyzed: the first received F500 after progression from previous chemotherapy (CT) or endocrine therapy; the second received the drug for metastatic disease; and the third was treated as maintenance following disease stabilization or a response from a previous CT line. Median overall survival (OS) in the whole population was 26.8 months, ranging from 32.4 in first line to 22.0 and 13.7 months in second line and subsequent lines, respectively. Both the presence of liver metastasis and the treatment line were significantly associated with a worse PFS, while only the presence of liver metastasis maintained its predictive role for OS in multivariate analysis.

Conclusions: The effectiveness of F500 was detected in patients treated both upon disease progression and as maintenance. The relevant endocrine sensitivity of 80% of patients included in the study could probably explain the good results observed in terms of outcome.
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http://dx.doi.org/10.1177/1758835919833864DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6552357PMC
June 2019

Non-traumatic splenic rupture in amyloidosis as a rare evolution of multiple myeloma.

Clin Pract 2019 May 7;9(2):1146. Epub 2019 May 7.

Department of Oncology, Maugeri Clinical and Scientific Institutes (IRCCS), Pavia.

We report the case of a 64-year-old man with a diagnosis of IgG lambda multiple myeloma (MM) symptomatic for bone lesions for which he received autologous stem cell transplant after induction treatment and high-dose melphalan, thalidomide and lenalidomide therapy. Twelve years after the diagnosis, he had an unexpected and acute onset of abdominal pain with signs of hypovolemic shock. A computed tomography scan was immediately performed and demonstrated a splenic rupture. A splenectomy was performed but, a week after, the patient developed an acute respiratory distress syndrome and died. After histological exam of the spleen, non-traumatic spleen rupture due to amyloidosis was our final diagnosis. This event is potentially fatal and rare in patients with MM; clinicians should be aware of this potential course of the disease and monitor patients also for amyloid induced organ damages.
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http://dx.doi.org/10.4081/cp.2019.1146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536836PMC
May 2019

Multicenter, single arm, phase II trial on the efficacy of ortataxel in recurrent glioblastoma.

J Neurooncol 2019 May 6;142(3):455-462. Epub 2019 Feb 6.

Istituto di Ricerche Farmacologiche Mario Negri, IRCCS, Milan, Italy.

Background And Purpose: Glioblastoma (GBM) is the most aggressive and frequent subtype of all malignant gliomas. At the time of recurrence, therapeutic options are lacking. Ortataxel, a second-generation taxane was reported to be effective in pre-clinical and phase I clinical studies. The aim of this study was to evaluate a potential therapeutic activity of ortataxel in patients with GBM recurring after surgery and first line treatment.

Methods: In this phase II study, according to a two stage design, adult patients with histologically confirmed GBM in recurrence after surgery or biopsy, standard radiotherapy and chemotherapy with temozolomide were considered eligible. Patients included were treated with ortataxel 75 mg/m i.v. every 3 weeks until disease progression. The primary objective of the study was to evaluate the activity of ortataxel in terms of progression free survival (PFS) at 6 months after the enrollment. PFS, overall survival at 9 months after the enrollment, objective response rate, compliance and safety were evaluated as secondary endpoints.

Results: Between Nov 26, 2013 and Dec 12, 2015, 40 patients were recruited across six centres. The number of patients alive and free from progression at 6 months after the enrollment, observed in the first stage was four (11.4%), out of 35 patients included in the analysis, below the minimum number of events (7 out of 33) required to continue the study with the second stage The most important toxicities were neutropenia and hepatotoxicity that occurred in 13.2% of patients and leukopenia that occurred in 15.8% of patients.

Conclusion: Overall ortataxel treatment fail to demonstrate a significant activity in recurrent GBM patients. However in a limited number of patients the drug produced a benefit that lasted for a long time.

Trial Registration: This study is registered with ClinicalTrials.gov, number NCT01989884.
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http://dx.doi.org/10.1007/s11060-019-03116-zDOI Listing
May 2019

Nivolumab Induced Thyroid Dysfunction: Unusual Clinical Presentation and Challenging Diagnosis.

Front Endocrinol (Lausanne) 2018 17;9:813. Epub 2019 Jan 17.

Unit of Internal Medicine and Endocrinology, ICS Maugeri IRCCS, University of Pavia, Pavia, Italy.

In recent years, immune checkpoint inhibitors (ICIs) had a great impact in cancer therapy. ICIs display a peculiar toxicity profile, which is characterized by autoimmune-like manifestations against multiple organs, including endocrine glands. We hereby report the case history of two patients who experienced nivolumab-induced endocrine immuno-related adverse events (irAEs). Thyroid dysfunction in both patients presented with a low serum level of TSH. However, endocrine evaluation showed a completely different etiology and clinical evolution. The two patients' histories indicate that nivolumab can cause a large spectrum of thyroid and endocrine dysfunctions resulting in cumbersome diagnostic problems. In these peculiar patients the evaluation of endocrine experts is warranted.
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http://dx.doi.org/10.3389/fendo.2018.00813DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345097PMC
January 2019

Eribulin Treatment in Patients with Liver Metastatic Breast Cancer: Eight Italian Case Reports.

Oncology 2018 24;94 Suppl 1:34-44. Epub 2018 Jul 24.

Oncologia Medica dell'Ospedale S. Vicenzo di Taormina, Taormina, Italy.

Liver metastases are very common in metastatic breast cancer (MBC); current treatments for these lesions are based on systemic chemotherapy, endocrine- or human epidermal growth factor receptor 2 (HER2)-targeted therapy, and palliative therapy. However, no standard approach has been clearly identified for second and further chemotherapy lines in MBC patients. In the phase III clinical trial EMBRACE, eribulin was particularly effective in reducing liver lesions and improving both overall survival and progression-free survival in liver MBC patients. In this series, we collected 8 case reports of Italian clinical practice in which eribulin has shown significant efficacy in reducing liver metastases in MBC patients: complete response was reported in 2 patients, and 4 patients achieved partial response. The treatment was well tolerated, thus confirming that eribulin is a suitable therapeutic option for elderly patients and for those who have metastatic HER2-negative disease. In the setting of MBC, the sequencing of therapeutic agents should consider expected response, side effects, tumor characteristics, and patient's preferences, in order to successfully tailor the most appropriate therapy beyond earlier lines.
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http://dx.doi.org/10.1159/000489067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193749PMC
July 2018

Lower motor neuron syndrome in a patient with HER2-positive metastatic breast cancer: A case report and review of the literature.

Clin Neurol Neurosurg 2018 09 6;172:141-142. Epub 2018 Jul 6.

IRCCS "C. Mondino" Foundation, National Neurological Institute, Pavia, Italy.

Paraneoplastic neurological syndromes are very rare and often associated to breast, ovarian and small cells lung cancers. Paraneoplastic motor neuron diseases (MNDs) are even rarer, and frequently described in patients with breast cancer. We presented the first case of patient affected by HER2-positive breast tumor and possible paraneoplastic lower motor neuron disease. In literature, few cases are reported but no one highlights the tumor receptors' profile. Instead, HER2-positive breast cancers are prone to be related to anti-Yo-associated paraneoplastic cerebellar disorders. Anti-onconeural antibodies positivity can be rarely found, confirming that paraneoplastic MND have no specific biomarkers. The presence of CSF oligoclonal bands (OBs) suggests the presence of immune-mediated mechanism, in absence of other possible OBs causes.
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http://dx.doi.org/10.1016/j.clineuro.2018.06.038DOI Listing
September 2018

Vinflunine in Advanced Transitional Cell Cancer of the Urothelial Tract: A Potential Option for Maintenance Therapy? A Case Series.

Oncol Res Treat 2018 22;41(1-2):8-13. Epub 2018 Jan 22.

Istituti Clinici Scientifici Maugeri, Pavia, Italy.

Introduction: Vinflunine is a microtubule inhibitor approved in Europe as second-line treatment of advanced transitional cell cancer of the urothelium (TCCU). The inability to continue with a first-line platinum-based regimen beyond 6 cycles suggested investigating the use of vinflunine as switch maintenance therapy in patients with response or stable disease after first-line therapy.

Methods: Patients with advanced TCCU and documented disease control after 3-6 cycles of first-line platinum-based chemotherapy received vinflunine maintenance therapy within 6 weeks of the last cycle. Our analysis aimed to examine the performance of vinflunine in terms of activity and safety in such a patient population.

Results: 28 consecutive patients were studied. After a median follow-up of 25 months, vinflunine was associated with a median progression-free survival of 9 months (range 4 to > 16 months) and a disease control rate of 64%; median overall survival was not reached. Treatment was well tolerated, with no unexpected safety events. The most common adverse events of grade ≥ 3 were neutropenia (21%) and constipation (14%); no toxicity-related death occurred.

Conclusions: Our results suggest that vinflunine may be a suitable maintenance treatment option for TCCU patients who received a maximum of 6 cycles of platinum-based chemotherapy commonly used as first-line treatment.
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http://dx.doi.org/10.1159/000481098DOI Listing
August 2019

Eribulin across multiple lines of chemotherapy: a retrospective study on quality of life and efficacy in metastatic breast cancer patients.

Future Oncol 2017 Apr;13(11s):11-23

Operative Unit of Medical Oncology, Fondazione Maugeri-IRCCS, Via Maugeri 10, 27100 Pavia, Italy.

This study evaluates efficacy, tolerability and health-related quality of life of eribulin in patients with metastatic breast cancer. Predictive and/or prognostic factors of outcome were also analyzed. Among 44 women receiving eribulin mesylate, one patient had a complete response, 22.7% a partial response and 25% a stable disease. Median overall survival and median progression-free survival were 11.8 and 4.5 months, respectively. Treatment was well tolerated; the most frequent adverse events were neutropenia (52%), leukopenia (50%), fatigue (38%) and alopecia (40%). No significant reductions of health-related quality of life parameters were observed. Disease control during previous chemotherapy lines was related with better outcome with eribulin. In conclusion, eribulin treatment should be considered in a multiple chemotherapy lines strategy in metastatic breast cancer.
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http://dx.doi.org/10.2217/fon-2016-0517DOI Listing
April 2017

Uncommon dihydropyrimidine dehydrogenase mutations and toxicity by fluoropyrimidines: a lethal case with a new variant.

Pharmacogenomics 2016 14;17(1):5-9. Epub 2015 Dec 14.

Departmental Unit of Medical Oncology, IRCCS Fondazione Maugeri, 4, Via Salvatore Maugeri, I-27100 Pavia, Italy.

DPD is the rate-limiting enzyme involved in the metabolism of 5-fluorouracil and its prodrugs, capecitabine and tegafur. Many cases of severe toxicities by fluoropyrimidines are reported in the literature, sometimes with lethal outcome, due to a poor or null metabolizer phenotype. The exon 14-skipping mutation IVS14+1G>A and the c.2846A>T are the most common deficient variants. However, many additional variants of the DPYD gene with unclear functional significance have been reported. We describe a patient with metastatic breast cancer who received capecitabine and trastuzumab at standard doses. Six days after beginning capecitabine, the patient developed fever, leucopenia and neutropenia, mucositis, hand-foot syndrome, multiple organ dysfunction and eventually died. Since the toxicity profile was compatible with capecitabine administration, complete exon sequencing of DPYD was carried out and the patient was found to be compound heterozygous for the rare mutation c.257C>T in exon 4, c.496A>G in exon 6, the new variant c.1850C>T in exon 14 and c.2194G>A in exon 18. Given the marginal role of c.496A>G and c.2194G>A in DPD deficiency, the cause of death was suggested to be dependent on the novel c.1850C>T in combination with c.257C>T. The complexity of DPD pharmacogenetics suggests the need to develop cost-effective screening approaches to identify patients at risk of severe toxicities.
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http://dx.doi.org/10.2217/pgs.15.146DOI Listing
September 2016

Which patients with metastatic breast cancer benefit from subsequent lines of treatment? An update for clinicians.

Ther Adv Med Oncol 2013 Nov;5(6):334-50

Departmental Operative Unit of Medical Oncology, Fondazione Maugeri-IRCCS, Via Maugeri, 10 27100 Pavia, Italy.

The outcome of patients with metastatic breast cancer (MBC) has clearly improved over the past decades and the proportion of women living with their disease for several years is increasing. However, the usefulness of multiple lines of treatment is still debated and under evaluation. The available data from both randomized trials and large retrospective series are reviewed and discussed in order to analyze management practices, with emphasis on potential prognostic and predictive factors for clinical outcome. At present, evidence-based medicine provides some support for the use of second-line and to a lesser degree and in selected cases, third-line chemotherapy in human epidermal growth factor receptor 2 (HER2) negative MBC. Beyond third-line treatment, messages from recently reported retrospective studies also suggest a clear potential gain for women receiving further therapies after disease progression, since each line can contribute to a longer survival. In HER2-positive disease, the data from observational and retrospective studies support a clinical benefit from the use of trastuzumab beyond disease progression and emerging evidences from randomized controlled trials are leading to the introduction of newer HER2-targeted therapies in multiple lines. The question 'How many lines of treatment should we give patients?' clearly needs further research through prospective, high-quality clinical trials, aiming for a better definition of factors with prognostic and predictive role. In the meantime, the 'optimal' treatment strategy should probably be to use as many therapeutic options as possible, either in sequence or combination, to keep the best efficacy/toxicity balance, considering MBC as a chronic disease.
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http://dx.doi.org/10.1177/1758834013508197DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3799296PMC
November 2013

Serum pharmacokinetics in patients treated with transarterial chemoembolization (TACE) using two types of epirubicin-loaded microspheres.

Anticancer Res 2012 May;32(5):1769-74

Laboratory for Environmental and Toxicological Testing, IRCCS Fondazione S. Maugeri, Istituto Scientifico di Pavia, Pavia, Italy.

Aim: The purpose of this study was the pharmacokinetic (PK) profile assessment in the serum of patients affected by hepatocellular carcinoma (HCC) treated with transarterial chemoembolization (TACE) with drug-eluting beads.

Patients And Methods: This study included 20 patients, 12 treated with DC Bead® and 8 with HepaSphere Microsphere®, preloaded with epirubicin. No patient randomization was used for the inclusion in one group or in the other. Peripheral blood samples were obtained from all patients after the treatment, until 24 hours past the procedure.

Results: The pharmacokinetic study showed low peak serum epirubicin concentrations with greater drug exposure for the DC Bead® group (p<0.05). The highest drug concentration after microsphere injection was observed at 5 minutes in all 20 patients. In the time interval between 1 and 24 hours after TACE, persisting levels of epirubicin were detected in peripheral blood samples.

Conclusion: A persistent and sustained drug elution for both types of microparticles was found.
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May 2012
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