Publications by authors named "E Pisa"

74 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

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

Prognostic features of gastro-entero-pancreatic neuroendocrine neoplasms in primary and metastatic sites: Grade, mesenteric tumour deposits and emerging novelties.

J Neuroendocrinol 2021 Aug 16;33(8):e13000. Epub 2021 Jul 16.

1st Pathology Division, Department of Pathology and Laboratory Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.

Updates in classification of gastro-entero-pancreatic neuroendocrine neoplasms better reflect the biological characteristics of these tumours. In the present study, we analysed the characteristics of neuroendocrine tumours that could aid in a more precise stratification of risk groups. In addition, we have highlighted the importance of grade (re)assessment based on investigation of secondary tumour lesions. Two hundred and sixty-four cases of neuroendocrine tumours of gastro-entero-pancreatic origin from three centres were included in the study. Tumour morphology, mitotic count and Ki67 labelling index were evaluated in specimens of primary tumours, lymph node metastases and distant metastases. These variables were correlated with overall survival (OS) and relapse-free survival (RFS). Tumour stage, number of affected lymph nodes, presence of tumour deposits and synchronous/metachronous metastases were tested as possible prognostic features. Mitotic count, Ki-67 labelling index, primary tumour site, tumour stage, presence of tumour deposits and two or more affected lymph nodes were significant predictors of OS and RFS. At the same time, mitotic count and Ki-67 labelling index can be addressed as continuous variables determining prognosis. We observed a very high correlation between the measures of proliferative activity in primary and secondary tumour foci. The presence of isolated tumour deposits was identified as an important determinant of both RFS and OS for pancreatic (hazard ratio [HR] = 7.61, 95% confidence interval [CI] = 3.96-14.6, P < 0.0001 for RFS; HR = 3.28, 95% CI = 1.56-6.87, P = 0.0017 for OS) and ileal/jejunal neuroendocrine tumours (HR = 1.98, 95% CI = 1.25-3.13, P = 0.0036 for RFS and HR 2.59, 95% CI = 1.27-5.26, P = 0.009 for OS). The present study identifies the presence of mesenterial tumour deposits as an important prognostic factor for gastro-entero-pancreatic neuroendocrine tumours, provides evidence that proliferative parameters need to be treated as continuous variables and further supports the importance of grade determination in all available tumour foci.
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http://dx.doi.org/10.1111/jne.13000DOI Listing
August 2021

Cerebral cortical thickness and gyrification changes in first-episode psychoses and multi-episode schizophrenia.

Arch Ital Biol 2021 Mar;159(1):3-20

Department of Dynamic and Clinical Psychology, and Health Studies, Faculty of Medicine and Psychology, Sapienza University, Rome; Unit of Psychiatry, 'Sant'Andrea' University Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy - Email:

Cortical thickness (CT) and local gyrification index (LGI) in psychotic disorders may show modifications that relate to clinical course. This observational study aimed to analyse such variables in patients with schizophrenia, compared to healthy controls (HCs). We compared CT and LGI of 18 patients with first-episode psychosis with that of 21 with multi-episode schizophrenia and 16 HCs. CT corrected for false-positive cases (Family-Wise Error Rate) showed a reduction in the multi-episode group compared to HCs in left temporal and parietal, and right temporal, parietal, occipital, and hippocampal cortices. Family-wise corrected LGI was increased in the left inferior and middle frontal cortices, and in the right fusiform gyrus, cingulate, lingual, and parahippocampal gyri in first onset patients compared to HCs. Increased LGI was absent from later stages of psychosis, suggesting that specific CT and LGI alterations may underlie different stages of illness.
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http://dx.doi.org/10.12871/00039829202111DOI Listing
March 2021

Cerebral cortical thickness and gyrification changes in first-episode psychoses and multi-episode schizophrenia.

Arch Ital Biol 2021 Mar;159(1):3-20

Department of Dynamic and Clinical Psychology, and Health Studies, Faculty of Medicine and Psychology, Sapienza University, Rome; Unit of Psychiatry, 'Sant'Andrea' University Hospital, Via di Grottarossa 1035-1039, 00189 Rome, Italy - Email:

Cortical thickness (CT) and local gyrification index (LGI) in psychotic disorders may show modifications that relate to clinical course. This observational study aimed to analyse such variables in patients with schizophrenia, compared to healthy controls (HCs). We compared CT and LGI of 18 patients with first-episode psychosis with that of 21 with multi-episode schizophrenia and 16 HCs. CT corrected for false-positive cases (Family-Wise Error Rate) showed a reduction in the multi-episode group compared to HCs in left temporal and parietal, and right temporal, parietal, occipital, and hippocampal cortices. Family-wise corrected LGI was increased in the left inferior and middle frontal cortices, and in the right fusiform gyrus, cingulate, lingual, and parahippocampal gyri in first onset patients compared to HCs. Increased LGI was absent from later stages of psychosis, suggesting that specific CT and LGI alterations may underlie different stages of illness.
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http://dx.doi.org/10.12871/00039829202111DOI Listing
March 2021
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