Publications by authors named "A Laffi"

14 Publications

Should temozolomide be used on the basis of O-methylguanine DNA methyltransferase status in patients with advanced neuroendocrine tumors? A systematic review and meta-analysis.

Cancer Treat Rev 2021 Sep 22;99:102261. Epub 2021 Jul 22.

IEO, European Institute of Oncology, IRCCS, Milan, Italy. Electronic address:

Background: Temozolomide (TEM) is an active treatment in metastatic neuroendocrine tumors (NETs). Patients affected by glioblastoma multiforme or advanced melanoma treated with TEM who have deficiency of O-methylguanine DNA methyltransferase (MGMT) have a better responses and survival. However, the predictive role of MGMT in patients with NETs treated with TEM is still debated.

Methods: We conducted a systematic review of the literature and meta-analysis, based on PRISMA methodology, searching in the main databases (PubMed, Embase, Scopus, Web of Science, Cochrane Library and clinical trial.gov) and the proceedings of the main international congresses, until April 26, 2021.

Results: Twelve out of 616 articles were selected for our analysis, regarding a total of 858 NET patients treated with TEM-based chemotherapy. The status of MGMT had been tested in 513 (60%) patients, using various methods. The pooled overall response rate (ORR) was higher in MGMT-deficient compared with MGMT-proficient NETs, with a risk difference of 0.31 (95% confidence interval, CI: 0.13-0.50; p < 0.001; I: 73%) and risk ratio of 2.29 (95% CI: 1.34-3.91; p < 0.001; I: 55%). The pooled progression free survival (PFS) (hazard ratio, HR = 0.56; 95% CI: 0.43-0.74; p < 0.001) and overall survival (OS) (HR = 0.41; 95% CI: 0.20-0.62; p = 0.011) were longer in MGMT-deficient versus MGMT-proficient NETs.

Conclusions: Our meta-analysis suggested that MGMT status may be predictive of TEM efficacy. However, due to the high heterogeneity of the evaluated studies the risk of biases should be considered. On this hypothesis future homogeneous prospective studies are warranted.
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http://dx.doi.org/10.1016/j.ctrv.2021.102261DOI Listing
September 2021

Coronavirus disease 2019 in patients with neuroendocrine neoplasms: Preliminary results of the INTENSIVE study.

Eur J Cancer 2021 09 30;154:246-252. Epub 2021 Jun 30.

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO) IRCCS, Milan, Italy.

Background: Specific data regarding coronavirus disease 2019 (COVID-19) in patients with neuroendocrine neoplasms (NENs) are lacking. The aim of this study is to describe the characteristics of patients with NENs who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive.

Material And Methods: This is a worldwide study collecting cases of patients with NENs along with a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between June 1, 2020, and March 31, 2021. Centres treating patients with NENs were directly contacted by the principal investigator. Patients with NENs of any primary site, grade and stage were included, excluding small-cell lung carcinoma and mixed adenoneuroendocrine carcinoma.

Results: Among 81 centres directly contacted, 88.8% responded and 48.6% of them declined due to lack of cases or interest. On March 31, 2021, eight recruiting centres enrolled 89 patients. The median age was 64 years at the time of COVID-19 diagnosis. Most patients had metastatic, non-functioning, low-/intermediate-grade gastroenteropancreatic NENs on treatment with somatostatin analogues and radioligand therapy. Most of them had comorbidities. Only 8% of patients had high-grade NENs and 12% were receiving chemotherapy. Most patients had symptoms or signs of COVID-19, mainly fever and cough. Only 3 patients underwent sub-intensive treatment, whereas most of them received medical therapies, mostly antibiotics. In two third of cases, no changes occurred for the anti-NEN therapy. More than 80% of patients completely recovered without sequelae, whereas 7.8% patients died due to COVID-19.

Conclusions: Patients included in this study reflect the typical NEN population regardless of SARS-CoV-2. In most cases, they overcome COVID-19 without need of intensive care, short-term sequelae and discontinuation of systemic oncological therapy.
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http://dx.doi.org/10.1016/j.ejca.2021.06.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241688PMC
September 2021

Gastroenteropancreatic grade 3 neuroendocrine tumors: a single entity or a heterogeneous group? A retrospective analysis.

J Endocrinol Invest 2021 Jul 19. Epub 2021 Jul 19.

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO), IRCCS, Via Ripamonti 435, 20141, Milan, Italy.

Purpose: Grade 3 neuroendocrine tumor (NET G3) is a novel pathologic category within gastro-entero-pancreatic (GEP) neuroendocrine neoplasms (NENs) but its clinical behavior and therapeutic management still remain challenging. Prognostic and predictive factors aiding NET G3 management are needed.

Patients And Methods: We performed a retrospective analysis from 2015 to 2020 of all patients with > 20% Ki-67, well-differentiated NETs evaluated within our NEN-dedicated multidisciplinary team. We divided the sample according the timing of NET G3 diagnosis, the radiotracers distribution and Ki-67. We analyzed the correlation between these NET G3 features and clinical outcomes.

Results: Among 3238 multidisciplinary discussion reports, we selected 55 patients, 48 from GEP and 7 from an occult GEP origin. In 45 patients, NET G3 diagnosis occurred at the beginning of clinical history (upfront-NET G3), whereas in 10, during the NET G1-G2 clinical history (late-NET G3). Patients with ≤ 30% (34/55) vs. > 30% Ki-67 (21/55) had a better overall survival (OS) (p = 0.042); patients with a homogeneous vs. inhomogeneous/negative Gallium(Ga)-DOTA-Peptide Positron Emission Tomography (PET)/computed tomography (CT) showed a trend to a better OS, and a significant better progression-free survival (PFS) (p = 0.033). A better OS was observed for negative/inhomogeneous vs. homogeneous 18-fluorodeoxyglucose (FDG)-PET/CT (p = 0.027). A trend to a better OS was reported in late- vs. upfront-NET G3, while the latter showed a significantly better response rate (RR) (p = 0.048).

Conclusion: Our findings suggested that Ki-67 cutoff, functional imaging and the timing to NET G3 diagnosis may help clinicians in more accurate selection of NET G3 management. Prospective studies are needed.
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http://dx.doi.org/10.1007/s40618-021-01642-0DOI Listing
July 2021

Irinotecan-based chemotherapy in extrapulmonary neuroendocrine carcinomas: survival and safety data from a multicentric Italian experience.

Endocrine 2021 Jul 6. Epub 2021 Jul 6.

Division of Oncology, Department of Oncology and Hematology, University Hospital of Modena, Modena, Italy.

Purpose: Neuroendocrine carcinomas (NECs) are a rare subgroup of neuroendocrine neoplasms that occasionally originate from gastro-entero-pancreatic (GEP) tract. Evidence of the effectiveness of chemotherapy is scarce. Platinum plus Etoposide regimens are currently the standard treatment in first-line, while little data are available on second-line treatments. The aim of this study is to evaluate the efficacy and safety of irinotecan (IRI)-based chemotherapy in a series of extrapulmonary NECs.

Methods: Patients with NEC diagnosis treated at University Hospitals of Modena, Florence, Pisa, and European Institute of Oncology of Milan with an IRI-based regimen (FOLFIRI or XELIRI) after progression to a first-line platinum-based therapy were enrolled. Objective responses were assessed according to RECIST criteria. Progression-free survival (PFS) and overall survival (OS) were calculated.

Results: Thirty-four patients, 16 males, and 18 females, median age of 59 years (range 32-77), with metastatic NEC were included. Twenty-seven patients had Ki-67 ≥ 55% and four patients Ki-67 of <55% (for three patients data were not available). The median number of treatment cycles of the IRI-based regimen was 7.5 (range 1-16). Six partial responses (17.6%) and 9 stable diseases (26.5%) were observed, with a disease control rate of 44.1%. Median PFS and OS were 4.4 and 5.9 months, respectively. Neutropenia, anemia, and nausea were the only G3-G4 toxicities reported.

Conclusions: Despite the relatively small sample size, IRI-based therapy demonstrated to be a valid option for patients with pretreated extrapulmonary NEC.
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http://dx.doi.org/10.1007/s12020-021-02813-yDOI Listing
July 2021

Carcinoid Syndrome and Hyperinsulinemic Hypoglycemia Associated with Neuroendocrine Neoplasms: A Critical Review on Clinical and Pharmacological Management.

Pharmaceuticals (Basel) 2021 Jun 4;14(6). Epub 2021 Jun 4.

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology (IEO) IRCCS, via G. Ripamonti 435, 20141 Milano, Italy.

The carcinoid syndrome (CS) and hyperinsulinemic hypoglycemia (HH) represent two of the most common clinical syndromes associated with neuroendocrine neoplasms (NENs). The former is mainly related to the serotonin secretion by a small bowel NEN, whereas the latter depends on an insulin hypersecretion by a pancreatic insulinoma. Both syndromes/conditions can affect prognosis and quality of life of patients with NENs. They are often diagnosed late when patients become strongly symptomatic. Therefore, their early detection and management are a critical step in the clinical management of NEN patients. A dedicated and experienced multidisciplinary team with appropriate therapeutic strategies is needed and should be encouraged to optimize clinical outcomes. This review aims to critically analyze clinical features, evidence and treatment options of CS and HH and therefore to improve their management.
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http://dx.doi.org/10.3390/ph14060539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228616PMC
June 2021
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