Publications by authors named "Nicola Fazio"

176 Publications

Adjuvant Chemotherapy for Stage I Pancreatic Ductal Adenocarcinoma-Is It Based on Evidence or Clinical Wisdom?

JAMA Oncol 2021 Oct 7. Epub 2021 Oct 7.

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

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http://dx.doi.org/10.1001/jamaoncol.2021.3603DOI Listing
October 2021

Compulsory Vaccination for Healthcare Workers in Italy for the Prevention of SARS-CoV-2 Infection.

Vaccines (Basel) 2021 Aug 29;9(9). Epub 2021 Aug 29.

Department of Anatomical, Histological, Forensic and Orthopaedical Sciences, Sapienza University of Rome, P. le del Verano 40, 00161 Rome, Italy.

The European Convention on Human Rights (ECHR) judgement no. 116(2021) of 8 April 2021 establishes the principle of mandatory vaccination, indicating the criteria that national legislation must comply with, following the principle of non-interference in the private life of the individual. Vaccination for the prevention of SARS-CoV-2 infection appears to be an essential requirement for providing healthcare assistance. The European experience with compulsory vaccinations, offers a composite panorama, as the strategy of some European countries is to make vaccinations compulsory, including financial penalties for non-compliance. As in other countries, there is a clear need for Italy to impose compulsory vaccination for healthcare workers, in response to a pressing social need to protect individual and public health, and above all as a defense for vulnerable subjects or patients, for whom health workers have a specific position of guarantee and trust. The Italian Republic provided for mandatory vaccinations for health professionals by Decree-Law of 1 April 2021 no. 44, to guarantee public health and adequate safety conditions. As stated by ECHR, the Italian State, despite having initially opted for recommendation as regards to SARS-CoV-2 vaccination, had to adopt the mandatory system to achieve the highest possible degree of vaccination coverage among health professionals to guarantee the safety of treatments and protection of patients' health. We present the Italian situation on vaccine hesitation in healthcare workers, with updated epidemiological data as well as the doctrinaire, social, and political debate that is raging in Italy and Europe.
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http://dx.doi.org/10.3390/vaccines9090966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8473178PMC
August 2021

Defensive Medicine in the Management of Cesarean Delivery: A Survey among Italian Physicians.

Healthcare (Basel) 2021 Aug 25;9(9). Epub 2021 Aug 25.

Department of Anatomical, Histological, Forensic and Orthopaedical Sciences, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy.

Background And Objectives: This study aims to contribute to the definition of the defensive medicine phenomenon between obstetricians and gynecologists, as well as to possible effects on the frequency of deliveries performed by cesarean sections (CS).

Materials And Methods: a digital questionnaire was administered through a mail-list including 600 gynecological specialists (of these 168 doctors completed the test), both in public and private settings. It was made of twenty multiple choice questions, concerning their awareness about the practice of defensive medicine and the planning and execution of CS. All doctors involved received clear and complete information about the purpose of this study and about the organizations that received their answers. Analyses of variance and regression were performed to describe differences between groups and to estimate the relationships between variables. The value of < 0.5 was considered statistically relevant.

Results: our analysis revealed that most respondents are confident with the defensive medicine definition and characteristics. This survey confirmed that gynecologists fear legal actions promoted by their patients and therefore modulate their choices by implementing professional behaviors of so-called "defensive medicine". This relates to a greater number of medical liability judgements, which more often concern omission or delayed execution of cesarean section, rather than unskillful surgical procedures.

Conclusions: there are few data to support a relation between the high rate of CS and defensive medicine. Numerous scientific studies associated this CS rate with the phenomenon of defensive medicine. This practice is constantly growing in all medical areas, especially in high-risk specialties such as obstetrics and gynecology. Our study highlights physicians' awareness of adopting defensive medicine behaviors in their clinical practice, affecting the choice of the type of delivery to be performed.
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http://dx.doi.org/10.3390/healthcare9091097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8472348PMC
August 2021

Reply to comments on 'COVID-19 in patients with neuroendocrine neoplasms: Preliminary results of a worldwide survey (The INTENSIVE study)'.

Eur J Cancer 2021 Aug 23. Epub 2021 Aug 23.

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

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http://dx.doi.org/10.1016/j.ejca.2021.08.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8380486PMC
August 2021

Biomarker evaluation in radically resectable locally advanced gastric cancer treated with neoadjuvant chemotherapy: an evidence reappraisal.

Ther Adv Med Oncol 2021 1;13:17588359211029559. Epub 2021 Sep 1.

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, via Ripamonti 435, Milan, Lombardia 20141, Italy.

Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced resectable gastric cancer but, despite important progresses, relapse-related death remains a major challenge. Therefore, it appears crucial to understand which patients will benefit from peri-operative treatment. Biomarkers such as human epidermal growth factor receptor-2 (HER2), microsatellite instability (MSI), and Epstein-Barr Virus (EBV) have been widely studied; however, they do not yet guide the choice of perioperative treatment in clinical practice. We performed a narrative review, including 23 studies, addressing the value of tissue- or blood-based biomarkers in the neoadjuvant setting. Ten studies (43.5%) were prospective, and more than half were conducted in East-Asia. Biomarkers were evaluated only post-NAC (on surgical samples or blood) in seven studies (30.4%), only pre-NAC (on endoscopic specimens or blood) in 10 studies (43.5%), and both pre- and post-NAC (26.1%) in six studies. Among the high variety of investigated biomarkers, some of these including MSI-H or enzymatic profile (as TS, UGT1A1, MTHFR, ERCC or XRCC) showed promising results and deserve to be assessed in methodologically sound clinical trials. The identification of molecular biomarkers in patients treated with NAC for locally advanced resectable gastric or EGJ cancer remains crucial.
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http://dx.doi.org/10.1177/17588359211029559DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8414610PMC
September 2021

Evaluation of Physical Risk during Necropsy and Morgue Activities as Risk Management Strategy.

Int J Environ Res Public Health 2021 08 4;18(16). Epub 2021 Aug 4.

Department of Anatomical, Histological, Forensic and Orthopaedic Science, Sapienza University of Rome, Viale Regina Elena 336, 00161 Rome, Italy.

Physical risk assessments allow us to understand work-related critical issues, thus representing a useful tool in risk management strategies. In particular, our study focuses on the identification of already known and emerging physical risks related to necropsy and morgue activities, as well as crime scene investigations. The aim of our study is, therefore, to identify objective elements in order to quantify exposure to such risk factors among healthcare professionals and working personnel. For the research of potentially at-risk activities, data from the Morgue of Policlinico Umberto I Hospital in Rome were used. The scientific literature has been reviewed in order to assess the risks associated with morgue activity. Measurements were performed on previously scheduled days, in collaboration with the activities of different research units. The identified areas of risk were: microclimate; exposure to noise and vibrations; postural and biomechanical aspects of necropsy activities. The obtained results make it possible to detect interindividual variability in exposure to many of the aforementioned risk factors. In particular, the assessment of microclimate did not show significant results. On the contrary, exposure to vibrations and biomechanical aspects of load handling have shown potential risk profiles. For this reason, both profiles have been identified as possible action targets for risk management strategies.
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http://dx.doi.org/10.3390/ijerph18168266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393537PMC
August 2021

Avelumab expanded access program in metastatic Merkel cell carcinoma: Efficacy and safety findings from patients in Europe and the Middle East.

Int J Cancer 2021 Dec 3;149(11):1926-1934. Epub 2021 Aug 3.

Division of Cancer Sciences, University of Manchester and the Christie NHS Foundation Trust, Manchester, UK.

Incidence rates of Merkel cell carcinoma (MCC), an uncommon skin cancer with an aggressive disease course, have increased in recent decades. Limited treatment options are available for patients with metastatic MCC (mMCC). Avelumab, an anti-programmed cell death-ligand 1 monoclonal antibody, became the first approved treatment for mMCC after the results of the phase 2 JAVELIN Merkel 200 study. Prior to its regulatory approval, an expanded access program (EAP) enabled compassionate use of avelumab in patients with mMCC. Here we report findings from patients enrolled in the EAP in Europe and the Middle East. Efficacy and safety data were provided at the discretion of treating physicians. Between March 2, 2016, and December 22, 2018, 403 requests for avelumab were received from 21 countries, and avelumab was supplied to 335 patients. Most patients (96.7%) received avelumab as second-line or later treatment. In 150 patients for whom response data were available, the objective response rate was 48.0%, and in responding patients, median duration of treatment was 7.4 months (range, 1.0-41.7 months). The most common treatment-related adverse events were infusion-related reaction (2.4%) and pyrexia (2.1%), and no new safety signals were observed. Overall, results from European and Middle Eastern patients enrolled in this EAP confirm the efficacy and safety of avelumab treatment observed in previous studies in patients with mMCC.
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http://dx.doi.org/10.1002/ijc.33746DOI Listing
December 2021

First-line avelumab in a cohort of 116 patients with metastatic Merkel cell carcinoma (JAVELIN Merkel 200): primary and biomarker analyses of a phase II study.

J Immunother Cancer 2021 07;9(7)

Division of Dermatology, University of Washington Medical Center at South Lake Union, Seattle, Washington, USA.

Background: Avelumab (anti-programmed death ligand 1 (PD-L1)) is approved in multiple countries for the treatment of metastatic Merkel cell carcinoma (mMCC), a rare and aggressive skin cancer. We report efficacy and safety data and exploratory biomarker analyses from a cohort of patients with mMCC treated with first-line avelumab in a phase II trial.

Methods: Patients with treatment-naive mMCC received avelumab 10 mg/kg intravenously every 2 weeks. The primary endpoint was durable response, defined as objective response (complete or partial response; assessed by independent review) lasting ≥6 months. Additional assessments included progression-free survival (PFS), overall survival (OS), safety, and biomarker analyses.

Results: In 116 patients treated with avelumab, median follow-up was 21.2 months (range: 14.9-36.6). Thirty-five patients had a response lasting ≥6 months, giving a durable response rate of 30.2% (95% CI: 22.0% to 39.4%). The objective response rate was 39.7% (95% CI: 30.7% to 49.2%). Median PFS was 4.1 months (95% CI: 1.4 to 6.1) and median OS was 20.3 months (95% CI: 12.4 to not estimable). Response rates were numerically higher in patients with PD-L1+ tumors, Merkel cell polyomavirus (MCPyV)-negative tumors, and tumors with increased intratumoral CD8 T-cell density. Exploratory analyses did not identify a biomarker that could reliably predict a response to first-line treatment with avelumab; however, a novel gene expression signature to identify the presence of MCPyV+ tumors was derived. Treatment-related adverse events (any grade) occurred in 94 (81.0%) patients, including grade 3/4 events in 21 (18.1%) patients; no treatment-related deaths occurred.

Conclusion: In patients with mMCC, first-line treatment with avelumab led to responses in 40% and durable responses in 30%, and was associated with a low rate of grade 3/4 treatment-related adverse events.
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http://dx.doi.org/10.1136/jitc-2021-002646DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311489PMC
July 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

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

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

Looking for the right TNM staging system for pancreatic neuroendocrine tumors.

Hepatobiliary Surg Nutr 2021 Jun;10(3):382-384

Division of Digestive Surgery, European Institute of Oncology, IEO, IRCCS, Milan, Italy.

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http://dx.doi.org/10.21037/hbsn-2021-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188133PMC
June 2021

Sex-Based Differences in Prognosis of Patients With Gastroenteropancreatic-Neuroendocrine Neoplasms: A Population-Based Study.

Pancreas 2021 May-Jun 01;50(5):727-731

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

Objectives: The aim of this study was to assess sex-based differences in prognosis of a contemporary cohort of gastroenteropancreatic-neuroendocrine neoplasm (GEP-NEN) patients.

Methods: Surveillance, Epidemiology, and End Results database was accessed, and cases with GEP-NENs were selected. Rates of GEP-NEN diagnosis from 1975 to 2016 for both male patients and female patients were reviewed. Survival outcomes of GEP-NEN patients diagnosed from 2010 to 2014 were determined through Kaplan-Meier estimates and multivariable Cox regression analysis. Overall survival analyses were stratified by stage and histology.

Results: A total of 20,836 GEP-NEN patients were diagnosed from 2010 to 2014, and they were included in the current analysis. These include 10,336 male patients and 10,500 female patients. Annual percent change for the age-adjusted rate for GEP-NENs in the United States (1975-2016) is 5.0 (95% confidence interval [CI], 4.8-5.2). When stratified by sex, annual percent change for male patients was 4.8 (95% CI, 4.6-5.1), whereas for female patients, it was 5.0 (95% CI, 4.8-5.3). Female patients have better overall survival compared with male patients among all substrata of patients (according to stage, histology, and differentiation) (P for all comparisons <0.01).

Conclusions: Female sex seems to be associated with better overall survival among patients with GEP-NENs. It is unclear if this is the result of differences in noncancer mortality or is the result of inherent biological differences.
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http://dx.doi.org/10.1097/MPA.0000000000001821DOI Listing
May 2021

Outcome of Patients With Metastatic Lung Neuroendocrine Tumors Submitted to First Line Monotherapy With Somatostatin Analogs.

Front Endocrinol (Lausanne) 2021 27;12:669484. Epub 2021 Apr 27.

Medical Oncology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health University of Brescia, ASST-Spedali Civili, Brescia, Italy.

Objective: Antiproliferative activity of somatostatin analogs (SSAs) has been demonstrated in digestive neuroendocrine tumors (NETs), but few data have been published in patients with pulmonary NETs. We therefore conducted a retrospective study to provide additional data on the outcome of patients with metastatic lung NETs submitted to front line SSAs.

Research Design And Methods: Patients with metastatic lung NET treated with first line SSA-monotherapy (octreotide or lanreotide) in two different reference Institutions were reviewed. Outcome measures were progression-free survival (PFS) overall survival (OS), overall response rate and safety. We also explored prognostic factors associated with PFS.

Methods: The outcome of consecutive patients (pts) with metastatic lung NETs, who underwent first-line treatment with SSAs, recruited from 2014 on 2019 in two Italian reference Institutions, was retrospectively evaluated.

Results: Thirty-one patients entered the study: 14 (45.2%) with typical and 17 (54.8%) atypical carcinoid. Six patients (19.4%) had a carcinoid syndrome. 60.0% of patients had Ki-67 ≤ 10%. Two (6.5%) patients obtained a partial response, 24 (77.4%) disease stabilization while 5 (16.1%) had progressive disease. Median progression free survival (PFS) was 28.6 months, median overall survival (OS) was not attained. Ki-67 ≤ 10%, typical carcinoid histotype and non-functioning disease, were associated with a non-significant PFS prolongation. PFS in patients with atypical carcinoids and in those with Ki-67 >10% was greater than 19 months.

Conclusions: The long PFS and OS obtained in this case series suggest that SSAs could be effective as first line approach in the management of patients with progressive, metastatic pulmonary NET.
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http://dx.doi.org/10.3389/fendo.2021.669484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8111295PMC
April 2021

Alpelisib in combination with everolimus ± exemestane in solid tumours: Phase Ib randomised, open-label, multicentre study.

Eur J Cancer 2021 Jul 5;151:49-62. Epub 2021 May 5.

Institut Gustave Roussy, Villejuif, France.

Background And Purpose: Combined mTORC1 inhibition with everolimus (EVE) and phosphatidylinositol 3-kinase catalytic subunit p110α blockade with alpelisib (ALP) has demonstrated synergistic efficacy in preclinical models and supports testing the combination of ALP and EVE in the clinical setting. The primary objective was to determine the maximum tolerated dose (MTD)/recommended dose for expansion (RDE) of ALP in combination with EVE and in combination with EVE and exemestane (EXE) and subsequently assess safety, preliminary efficacy and effect of ALP on the pharmacokinetics of EVE and determine the magnitude of the drug-drug interaction.

Patients And Methods: Dose escalation phases were conducted in patients with advanced solid tumours and in postmenopausal women with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). The dose expansion phase was conducted in patients with pancreatic neuroendocrine tumour and renal cell carcinoma (RCC) (both mechanistic target of rapamycin inhibitor [mTORi]-naive), in patients with mTORi-pretreated solid tumours and in postmenopausal women with HR+, HER2- ABC.

Results: During the doublet escalation phase, dose-limiting toxicities (DLTs) were reported in 5 of 10 (50%) patients: one patient had grade (Gr) 2 hyperglycemia and one patient had Gr 3 diarrhoea in the 300 mg dose group, one patient had Gr 2 hyperglycemia and one patient had Gr 4 hypocalcaemia in the 250 mg dose group, and one patient in the 200 mg dose group had Gr 3 diarrhoea and Gr 3 stomatitis. The combination of ALP 250 mg + EVE 2.5 mg was declared as the MTD/RDE in subjects with advanced solid tumours. In the triplet escalation phase, one patient who received ALP 200 mg + EVE 2.5 mg + EXE 25 mg had a DLT of Gr 3 acute kidney injury. This dose combination was declared as the MTD and RDE in subjects with advanced HR-positive HER2-negative BC. The common adverse events (≥30% patients), occurring across all phases, were hyperglycaemia, stomatitis, diarrhoea, nausea, asthenia, decreased appetite and fatigue. The sixteen-week progression-free survival rate was 52.4% (90% confidence interval [CI]: 32.8, 71.4) in the RCC cohort, 35.3% (90% CI: 16.6, 58.0) in the prior pNET cohort and 30.0% (90% CI: 8.7, 60.7) in the prior mTORi cohort. The pharmacokinetics of 2.5 mg of EVE was largely unchanged in the presence of ALP, independent of the dose (250 mg or 300 mg). There were no clinically relevant drug-drug interactions observed between ALP and EVE.

Conclusion: The overall safety profile of ALP with EVE and EXE is manageable and reversible; no unexpected safety signals were noted compared with the individual safety profiles. Pharmacokinetics of ALP, EVE and EXE was largely unchanged in combination with each other.
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http://dx.doi.org/10.1016/j.ejca.2021.03.042DOI Listing
July 2021

Lenvatinib in Patients With Advanced Grade 1/2 Pancreatic and Gastrointestinal Neuroendocrine Tumors: Results of the Phase II TALENT Trial (GETNE1509).

J Clin Oncol 2021 Jul 4;39(20):2304-2312. Epub 2021 May 4.

Osteoncology and Rare Tumours Center, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.

Purpose: Approved systemic therapies for advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have shown limited capacity to reduce tumor burden and no antitumor activity after progression to targeted agents (TAs). We investigated the efficacy and safety of lenvatinib in patients with previously treated advanced GEP-NETs.

Patients And Methods: This was a multicenter, single-arm, open-label, phase II trial with two parallel cohorts (ClinicalTrials.gov identifier: NCT02678780) involving 21 institutions in 4 European countries. Eligible patients had histologically confirmed advanced grade 1-2 pancreatic (panNET) or GI (GI-NET) NETs with documented tumor progression after treatment with a TA (panNET) or somatostatin analogs (GI-NET). Patients were treated with lenvatinib 24 mg once daily until disease progression or treatment intolerance. The primary end point was overall response rate by central radiology review. Secondary end points included progression-free survival, overall survival, duration of response, and safety.

Results: Between September 2015 and March 2017, a total of 111 patients were enrolled, with 55 (panNET) and 56 (GI-NET) patients in each cohort. The median follow-up was 23 months. The overall response rate was 29.9% (95% CI, 21.6 to 39.6): 44.2% (panNET) and 16.4% (GI-NET). The median (range) duration of response was 19.9 (8.4-30.8) and 33.9 (10.6-38.3) months in the panNET and GI-NET groups, respectively. The median progression-free survival was 15.7 months (95% CI, 14.1 to 19.5). The most common adverse events were fatigue, hypertension, and diarrhea; 93.7% of patients required dose reductions or interruptions.

Conclusion: We report the highest centrally confirmed response reported to date with a multikinase inhibitor in advanced GEP-NETs, with a particularly strong response in the panNET cohort. This study provides novel evidence for the efficacy of lenvatinib in patients with disease progression following treatment with other TAs, suggesting the potential value of lenvatinib in the treatment of advanced GEP-NETs.
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http://dx.doi.org/10.1200/JCO.20.03368DOI Listing
July 2021

A Machine Learning Decision Support System (DSS) for Neuroendocrine Tumor Patients Treated with Somatostatin Analog (SSA) Therapy.

Diagnostics (Basel) 2021 Apr 28;11(5). Epub 2021 Apr 28.

Medical Oncology Unit, Careggi University Hospital, Largo Brambilla 4, 50134 Florence, Italy.

The application of machine learning (ML) techniques could facilitate the identification of predictive biomarkers of somatostatin analog (SSA) efficacy in patients with neuroendocrine tumors (NETs). We collected data from 74 patients with a pancreatic or gastrointestinal NET who received SSA as first-line therapy. We developed three classification models to predict whether the patient would experience a progressive disease (PD) after 12 or 18 months based on clinic-pathological factors at the baseline. The dataset included 70 samples and 15 features. We initially developed three classification models with accuracy ranging from 55% to 70%. We then compared ten different ML algorithms. In all but one case, the performance of the Multinomial Naïve Bayes algorithm (80%) was the highest. The support vector machine classifier (SVC) had a higher performance for the recall metric of the progression-free outcome (97% vs. 94%). Overall, for the first time, we documented that the factors that mainly influenced progression-free survival (PFS) included age, the number of metastatic sites and the primary site. In addition, the following factors were also isolated as important: adverse events G3-G4, sex, Ki67, metastatic site (liver), functioning NET, the primary site and the stage. In patients with advanced NETs, ML provides a predictive model that could potentially be used to differentiate prognostic groups and to identify patients for whom SSA therapy as a single agent may not be sufficient to achieve a long-lasting PFS.
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http://dx.doi.org/10.3390/diagnostics11050804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145352PMC
April 2021

Outcomes of small-cell versus large-cell gastroenteropancreatic neuroendocrine carcinomas: A population-based study.

J Neuroendocrinol 2021 May 19;33(5):e12971. Epub 2021 Apr 19.

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

The recent World Health Organization classification for gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) classified poorly differentiated GEP-NENs into small cell and large cell categories. The present study aimed to assess the differences in outcomes between patients with both histological categories. The Surveillance, Epidemiology and End Results (SEER) database (1975-2016) was accessed and patients with small cell and large cell GEP-neuroendocrine carcinomas (NECs) were extracted. Differences in survival outcomes were explored through Kaplan-Meier survival estimates and multivariable Cox regression models. In total, 2204 patients with GEP-NEC were identified in the survival cohort, including 1698 patients with small cell NEC (77%) and 506 patients with large cell NEC (23%). Using Kaplan-Meier analysis/log-rank testing, large cell GEP-NEC was associated with better overall survival compared to small cell NEC (P < 0.01). Using multivariable Cox regression analysis, large cell GEP-NEC was associated with better overall survival (large cell GEP-NEC versus small cell GEP-NEC, hazard ratio = 0.77; 95% confidence interval = 0.68-0.86) and cancer-specific survival (large cell GEP-NEC versus small cell GEP-NEC, hazard ratio = 0.79; 95% 95% confidence interval = 0.69-0.91). Patients with small cell GEP-NEC have worse survival outcomes compared to those with large cell GEP-NEC. Further efforts are needed to identify biological differences and treatment sensitivities between both histological categories.
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http://dx.doi.org/10.1111/jne.12971DOI Listing
May 2021

Relationship between metabolic toxicity and efficacy of everolimus in patients with neuroendocrine tumors: A pooled analysis from the randomized, phase 3 RADIANT-3 and RADIANT-4 trials.

Cancer 2021 Aug 15;127(15):2674-2682. Epub 2021 Apr 15.

The University of Texas MD Anderson Cancer Center, Houston, Texas.

Background: Hyperglycemia and hypercholesterolemia are class effects of mammalian target of rapamycin inhibitors such as everolimus. This post hoc pooled analysis assessed the potential impact of these events on the efficacy of everolimus.

Methods: Patients with advanced, low- or intermediate-grade pancreatic, gastrointestinal, or lung neuroendocrine tumors received either oral everolimus at 10 mg/d or a placebo in the RAD001 in Advanced Neuroendocrine Tumors 3 (RADIANT-3) and RAD001 in Advanced Neuroendocrine Tumors 4 (RADIANT-4) trials. A landmark progression-free survival (PFS) analysis by central review was performed for patients treated for at least 16 weeks (n = 308) and according to the occurrence of any-grade adverse events (AEs) within this treatment period.

Results: The overall PFS with everolimus from the pooled analysis was 11.4 months (95% confidence interval, 11.01-13.93 months), which was consistent with the findings of RADIANT-3 and RADIANT-4. Overall, 19.1% and 9.8% of patients in RADIANT-3 and 11.9% and 6.4% of patients in RADIANT-4 developed any-grade hyperglycemia and hypercholesterolemia, respectively (regardless of the study drug). The duration of everolimus exposure was longer in patients who developed these AEs versus patients without these AEs. Overall, 308 patients were exposed to treatment for at least 16 weeks (hyperglycemia, 39 of 269 patients; hypercholesterolemia, 20 of 288 patients). No association was observed between the development of these AEs and PFS (18.8 and 14.1 months with and without hyperglycemia, respectively, and 14.1 and 14.8 months with and without hypercholesterolemia, respectively).

Conclusions: Although limitations apply because of the small number of AEs observed, there was no significant impact of these AEs on PFS; this suggests similar efficacy in the presence or absence of these events.
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http://dx.doi.org/10.1002/cncr.33540DOI Listing
August 2021

Knowns and unknowns of bone metastases in patients with neuroendocrine neoplasms: A systematic review and meta-analysis.

Cancer Treat Rev 2021 Mar 19;94:102168. Epub 2021 Feb 19.

Department of Medical Oncology, ENETS Centre of Excellence, The Christie NHS Foundation Trust, Division of Cancer Sciences, University of Manchester, Manchester, United Kingdom. Electronic address:

Objective: This systematic review and meta-analysis aimed to develop an evidence-based summary of current knowledge of bone metastases (BMs) in neuroendocrine neoplasms (NENs), inform diagnosis and treatment and standardise management between institutions.

Methods: PubMed, Medline, EMBASE and meeting proceedings were searched for eligible studies reporting data on patients with BMs and NENs of any grade of differentiation and site; poorly-differentiated large/small cell lung cancer were excluded. Data were extracted and analysed using STATA v.12. Meta-analysis of proportions for calculation of estimated pooled prevalence of BM and calculation of weighted pooled frequency and weighted pooled mean for other variables of interest was performed .

Results: A total of 149 studies met the eligibility criteria. Pooled prevalence of BMs was 18.4% (95% CI 15.4-21.5). BMs were mainly metachronous with initial diagnosis of NEN (61.2%) and predominantly osteoblastic; around 61% were multifocal, with a predisposition in axial skeleton. PET/CT seemed to provide (together with MRI) the highest sensitivity and specificity for BM detection. Almost half of patients (46.4%) reported BM-related symptoms: pain (66%) and skeletal-related events (SREs, fracture/spinal cord compression) (26.2%; weightedweighted mean time-to-SRE 9.9 months). Management of BMs was multimodal [bisphosphonates and bone-modifying agents (45.2%), external beam radiotherapy (34.9%), surgery (14.8%)] and supported by little evidence. Overall survival (OS) from the time of diagnosis of BMs was long [weighted mean 50.9 months (95% CI 40.0-61.9)]. Patients with BMs had shorter OS [48.8 months (95% CI 37.9-59.6)] compared to patients without BMs [87.4 months (95% CI 74.9-100.0); p = 0.001]. Poor performance status and BM-related symptoms were also associated with worse OS.

Conclusions: BMs in patients with NENs remain underdiagnosed and undertreated. Recommendations for management of BMs derived from current knowledge are provided. Prospective studies to inform management are required.
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http://dx.doi.org/10.1016/j.ctrv.2021.102168DOI Listing
March 2021

First Results of β-Radioguided Surgery in Small Intestine Neuroendocrine Tumors with Y-DOTATOC.

Cancer Biother Radiopharm 2021 Jun 18;36(5):397-406. Epub 2021 Feb 18.

Division of Nuclear Medicine, Istituto Europeo di Oncologia, IRCCS, Milano, Italy.

In neuroendocrine tumor (NET), complete surgery could better the prognosis. Radioguided surgery (RGS) with β-radioisotopes is a novel approach focused on developing a new probe that, detecting electrons and operating with low background, provides a clearer delineation of the lesions with low radiation exposition for surgeons. As a first step to validate this procedure, specimens of tumors expressing somatostatin receptors, as small intestine neuroendocrine tumor (SI-NET), were tested. SI-NET presents a high uptake of a beta-emitting radiotracer, Y-DOTATOC. Five SI-NET patients were enrolled after performing a Ga-DOTATOC positron emission tomography/computed tomography (CT) and a CT enterography; 24 h before surgery, they received 5 mCi of Y-DOTATOC. Surgery was performed as routine. Tumors and surrounding tissue were sectioned in different samples and examined with the beta-detecting probe. All the tumor samples showed high counts of radioactivity that was up to a factor of 18 times higher than the corresponding cutoff value, with a sensitivity of 96% and a specificity of 100%. These first RGS tests showed that this probe can discriminate very effectively between tumor and healthy tissues by the administration of low activities of Y-DOTATOC, allowing more precise surgery.
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http://dx.doi.org/10.1089/cbr.2020.4487DOI Listing
June 2021

Avelumab treatment in Italian patients with metastatic Merkel cell carcinoma: experience from an expanded access program.

J Transl Med 2021 02 15;19(1):70. Epub 2021 Feb 15.

Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Naples, Italy.

Background: The incidence of Merkel cell carcinoma (MCC), a rare form of skin cancer with a poor prognosis, has increased in Italy in recent decades. Avelumab, an anti-programmed death ligand 1 monoclonal antibody, is approved for the treatment of metastatic MCC (mMCC) based on the results of the phase 2 JAVELIN Merkel 200 trial. The global avelumab expanded access program (EAP) was designed to provide compassionate use of avelumab prior to approval for patients with mMCC who had limited treatment options. We report findings from a subgroup of Italian patients enrolled in the avelumab EAP.

Methods: Eligible patients had mMCC and progressive disease following ≥ 1 prior line of chemotherapy or were ineligible for chemotherapy or clinical trial participation. Patients received avelumab 10 mg/kg intravenously every 2 weeks. Treating physicians were provided with an initial 3-month supply of avelumab; resupply was permitted if the patient achieved a complete response, partial response, stable disease, or other clinical benefit per physician assessment. Safety and efficacy data for the EAP were reported at the treating physician's discretion.

Results: Between April 1, 2016, and September 14, 2018, 109 requests for avelumab were received from Italy, and 102 were approved. All but 1 of the approved patients had received ≥ 1 prior line of therapy. At data cutoff (March 22, 2019), 95 patients had been supplied with avelumab and response data were available for 55 patients. The objective response rate in response-evaluable patients was 29.1%, including 6 patients (10.9%) who achieved a complete response and 10 patients (18.2%) who achieved a partial response; in the total population supplied with avelumab (n = 95), the proportion who had an objective response was 16.8%. The median duration of treatment in responding patients was 9.7 months (range, 3.5-41.7 months). The most frequently reported treatment-related adverse events were infusion-related reaction (single preferred term; n = 3 [3.2%]) and pyrexia (n = 2 [2.1%]).

Conclusions: Results from Italian patients enrolled in the avelumab EAP are consistent with the findings of the JAVELIN Merkel 200 trial and confirm the efficacy and safety of avelumab treatment in this population.
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http://dx.doi.org/10.1186/s12967-021-02730-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885451PMC
February 2021

Immunotherapy in Neuroendocrine Neoplasms: Where Are We Now?

Curr Treat Options Oncol 2021 02 8;22(3):19. Epub 2021 Feb 8.

Department of Oncology, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada.

Opinion Statement: Immune checkpoint inhibitors (ICIs) represent a breakthrough in the management of many hard-to-treat cancers over the past decade with demonstrable improvement in survival outcomes. We reviewed the state of the art of ICIs in neuroendocrine neoplasms (NENs). While ICIs have become part of the standard of care for the management of small cell lung cancer (SCLC), their role is still unclear in the management of extra-pulmonary (EP) poorly differentiated neuroendocrine carcinomas (NECs) as well as in the management of well-differentiated neuroendocrine tumors (NETs). Conflicting results derived from the various studies in NETs and EP NECs therefore for specific settings, such as the lung NETs, or therapeutic regimen, e.g., combo vs single agent, for ICIs benefit. Therefore, at the moment, no ICIs approach is justified for NETs and EP NECs in clinical practice. Future investigations should be designed with the aim to overcome the several limitations of the current trials, e.g., lacking of a central pathology review or heterogeneity of the cohorts, in order to reduce the risk of biases. Future trials combining ICIs with other biological agents are welcome. This review aims to provide a comprehensive overview of the biological rationale and evolving clinical applications of the use of ICIs in the management of NENs (both well-differentiated and poorly differentiated groups).
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http://dx.doi.org/10.1007/s11864-021-00817-4DOI Listing
February 2021

Spartalizumab in metastatic, well/poorly-differentiated neuroendocrine neoplasms.

Endocr Relat Cancer 2021 Jan 1. Epub 2021 Jan 1.

S Singh, Medical Oncologist, Sunnybrook Health Sciences Centre, Toronto, Canada.

Spartalizumab, a humanized anti-programmed death protein 1 (PD-1) monoclonal antibody, was evaluated in patients with well-differentiated metastatic grade 1/2 neuroendocrine tumors (NET) and poorly-differentiated gastroenteropancreatic neuroendocrine carcinomas (GEP-NEC). In this phase II, multicenter, single-arm study, patients received spartalizumab 400 mg every 4 weeks until confirmed disease progression or unacceptable toxicity. The primary endpoint was confirmed overall response rate (ORR) according to blinded independent review committee using response evaluation criteria in solid tumors 1.1. The study enrolled 95 patients in the NET group (30, 32 and 33 in the thoracic, gastrointestinal, and pancreatic cohorts, respectively), and 21 patients in the GEP-NEC group. The ORR was 7.4% (95% confidence interval [CI]: 3.0, 14.6) in the NET group (thoracic, 16.7%; gastrointestinal, 3.1%; pancreatic, 3.0%), which was below the predefined success criterion of ≥10%, and 4.8% (95% CI: 0.1, 23.8) in the GEP-NEC group. In the NET and GEP-NEC groups, the 12-month progression-free survival was 19.5% and 0%, respectively, and the 12-month overall survival was 73.5% and 19.1%, respectively. The ORR was higher in patients with ≥1% PD-L1 expression in immune/tumor cells or ≥1% CD8+ cells at baseline. The most common adverse events considered as spartalizumab-related included fatigue (29.5%) and nausea (10.5%) in the NET group, and increased aspartate and alanine aminotransferases (each 14.3%) in the GEP-NEC group. The efficacy of spartalizumab was limited in this heterogeneous and heavily pre-treated population; however, the results in the thoracic cohort is encouraging and warrants further investigation. Adverse events were manageable and consistent with previous experience.
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http://dx.doi.org/10.1530/ERC-20-0382DOI Listing
January 2021

Updated Efficacy and Safety Outcomes for Patients with Well-Differentiated Pancreatic Neuroendocrine Tumors Treated with Sunitinib.

Target Oncol 2021 01 7;16(1):27-35. Epub 2021 Jan 7.

Department of Medical Oncology, Paris Saint-Joseph Hospital Group, Paris, France.

Background: Sunitinib prolonged progression-free survival (PFS) versus placebo in patients with metastatic pancreatic neuroendocrine tumors (panNETs) in a phase III trial. The efficacy and safety of sunitinib in patients with panNETs were confirmed in an open-label phase IV trial.

Objective: To assess the clinical benefit with sunitinib using the combined data from these trials.

Patients And Methods: An updated overall survival (OS) in patients with panNETs for the phase IV trial was provided, and an analysis of results from the sunitinib-treated combined cohort from the phase III and IV trials (combined cohort) was conducted to assess PFS, OS, and objective response rate (ORR).

Results: The updated median OS for the phase IV trial was 54.1 months (95% CI 37.9-not reached). Investigator-assessed median PFS for the combined cohort (n = 102) was 12.9 months (95% CI 7.4-16.7) with a significant benefit versus placebo in the phase III trial (n = 35) (HR 0.429; 95% CI 0.245-0.752; p = 0.001). Median OS could not be calculated for the combined cohort or placebo group due to the high number of patients censored; however, the estimated HR of 0.303 (CI 0.100-0.921; p = 0.013) favored sunitinib. ORR for the combined cohort was 16.7% (95% CI 10.0-25.3). Sunitinib was well tolerated in both trials with a safety profile similar to previously seen in other studies.

Conclusions: The combined analysis of these studies confirms the objective tumor responses and improvements in PFS observed in the initial phase III trial, providing further support for the clinical benefit of sunitinib in patients with advanced panNETs. CLINICALTRIALS.

Gov Identifiers: NCT00428597 and NCT01525550.
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http://dx.doi.org/10.1007/s11523-020-00784-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810649PMC
January 2021

The rare entity of bilateral and unilateral neuroendocrine metastases to the breast: a case series and literature review.

Ecancermedicalscience 2020 15;14:1123. Epub 2020 Oct 15.

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumours, European Institute of Oncology, IEO, IRCCS, Milan 20132, Italy.

Introduction: Primary neuroendocrine neoplasms (NENs) in the breast are very rare. Until 2011, the prevalence was 0.1% of all breast lesions and 1% of all NENs, whereas metastatic breast NENs represent 1%-2% of all breast tumours. However, it seems that over the last 5 years the diagnostic frequency of breast NENs has increased, probably for more alert specialists and advanced diagnostic tools, leading to a prevalence of 2%-5% of diagnosed breast cancers, mostly in the elderly population. Breast metastases from extramammary malignancies are uncommon and bilateral ones are even more uncommon, with few reported in the literature. We describe four clinical settings of breast metastases from different NENs and the multidisciplinary approach for diagnosis and treatment.

Methods: Four patients were found to have NEN primaries metastasised to the breast. A literature review was conducted to identify similar cases and characterise breast metastases from neuroendocrinal tumors (NETs).

Results: Two patients presented with bilateral breast metastases (one with well-differentiated panNET and another with atypical lung carcinoid) and two had unilateral (one with moderately differentiated lung NET and one with atypical lung carcinoid). There are about 13 cases of NEN breast metastases reported in the English literature. The ileum is the most common primary site, followed by the appendix, duodenum, pancreas and lung.

Conclusion: Breast lesions from extramammary primary often pose a diagnostic challenge, since a breast nodule can be the first and often the only presentation of the disease. However, differentiating between primary and secondary NEN breast lesions is essential, owing to different clinical management and prognosis.
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http://dx.doi.org/10.3332/ecancer.2020.1123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652541PMC
October 2020

Discussing motherhood when the oncological prognosis is dire: ethical considerations for physicians.

ESMO Open 2020 11;5(6):e000956

Department of Gynaecologic Oncology, European Institute of Oncology IRCCS, Milano, Italy. Electronic address:

Physicians are increasingly open to discussing and supporting pregnancy after cancer treatment. However, counselling patients who are seeking pregnancy despite advanced oncological disease and/or uncertain prognosis is still challenging. Two paradigmatic cases are presented and analysed to illustrate the ethical uneasiness faced by treating physicians when seriously ill patients seek fertility preservation and/or pregnancy. Review of ethical issues is built around the four principles of biomedical ethics. Respect for patients autonomy in relation to managing realistic expectations and avoiding giving patients false hopes opens the analysis. It is followed by considering fair allocation of resources and meaningful distinction between protecting patients from harm and contributing to their welfare. Responsibilities towards the unborn child are discussed in a light of maternal and fetal interdependency. Respecting personal autonomy requires abstaining from controlling inferences to the individual patient's choices, but it does not mean that patients should be left on their own to pick and choose their disease management approaches without advice and guidance from healthcare professionals. Physicians should reason evaluating the potential harms and checking if benefits will outweigh the risks and if costs will produce the best overall results. Responsibilities towards the unborn child can be managed by balancing the respect for maternal autonomy and beneficence for pregnant woman and her fetus. The oncologist cannot determine how patients should view their disease but with empathy and compassion can help them understand the logical rationale behind clinical advice.
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http://dx.doi.org/10.1136/esmoopen-2020-000956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7656910PMC
November 2020

Results of Surgical Resection of Locally Advanced Pulmonary Neuroendocrine Tumors.

Ann Thorac Surg 2021 08 29;112(2):405-414. Epub 2020 Oct 29.

Division of Thoracic Surgery, European Institute of Oncology (IEO), IRCCS, Milan, Italy; Department of Oncology and Hematology-Oncology, University of Milan, Milan, Italy. Electronic address:

Background: Pulmonary neuroendocrine tumors include well-differentiated and poorly differentiated histology for which cell type has proved to be a determinant of survival in many studies. In patients diagnosed with bronchial carcinoid and large cell neuroendocrine carcinoma (LCNEC), surgery is the treatment of choice even in the case of locally advanced disease with lymph node involvement.

Methods: We retrospectively analyzed patients undergoing anatomic lung resection for bronchial carcinoid or LCNEC with lymph node involvement (N1/N2) at the final pathologic examination (pN+). Characteristics of patients and differences in overall survival and disease-free survival are presented according to tumor type. Overall survival of distinct histologic groups was compared with survival in our institutional experience in stage I patients, without nodal involvement (pN0).

Results: In all, 325 patients underwent surgical resection for neuroendocrine tumors; 89 patients had nodal involvement. Five-year survival was 89% in pN+ bronchial carcinoid both for typical carcinoid and atypical carcinoid but worse for pN+ LCNEC (47%). Cell type did not influence the prognosis in N0 disease, and no differences in survival were evident between N0 and N+ in the bronchial carcinoid group. In the group of LCNEC, 5-year overall survival was much worse for pN+ LCNEC (47%) compared with pN0 LCNEC (91%).

Conclusions: Bronchial carcinoids have the best prognosis, and surgery remains the treatment of choice for both early and locally advanced disease. On the contrary, aggressive forms (LCNEC) with lymph nodal metastasis have a poor prognosis, and they need to be treated with an aggressive multidisciplinary approach.
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http://dx.doi.org/10.1016/j.athoracsur.2020.09.021DOI Listing
August 2021

Personalizing Multimodal Treatment in Patients With Pancreatic Neuroendocrine Tumors.

Authors:
Nicola Fazio

JCO Oncol Pract 2020 11 21;16(11):729-730. Epub 2020 Oct 21.

Division of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, European Institute of Oncology, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy.

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http://dx.doi.org/10.1200/OP.20.00749DOI Listing
November 2020
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