Tumori Journal Abstract Book - October 2020 - 133

G - Neuroendocrine Tumours and Sarcomas	

G05
Immunogenetic and
immunophenotypic
characterization of Merkel Cell
Carcinoma
De Summa S.1, Strippoli S.2, Fucci L.1, Mangia A.1, Armenio A.1,
Figliuolo F.1, Pinto R.1, Lorusso C.1, Quaresimini D.1, Catacchio I.1,
Saponaro C.1, Zambetti M.1, De Risi I.1, Palermo L.1, Ruggieri E.1,
Tommasi S.1, Guida M.1
1

IRCCS Istituto Tumori Giovanni Paolo II, Bari; 2Barletta Hospital, Barletta

Background: Merkel Cell Carcinoma (MCC) is a rare and
aggressive malignancy, commonly occurring in elderly
white men mostly over 50 years and in sun-exposed areas.
MCC seems to be associated to exposure to ultraviolet
radiation and polyomavirus (MCPyV) infection. To date,
the major peculiarity in the MCC genomic patterns have
been described in relation to the presence or not of the viral
infection. Brisk response and high CD8+ lymphocytic
infiltration together with tumor PD-L1 expression have
been found associated to a better outcome. The approval of
immune-checkpoint inhibitors (ICIs) has been a fundamental step forward in the management of MCC, which
historically was treated with chemotherapy. ICI treatment
displayed improved overall survival and durable response
irrespectively of virus infection.
In the present study, we aimed to focus on immune-related
genes, both at DNA and expression levels, integrating
microenvironment data to better elucidate the immunological setting of MCC.
Material and methods: A cohort of 25 MCC patients,
50% presenting MCPyV infection, underwent mutational
analysis through a custom-designed NGS targeted amplicon-based panel related to 41 genes involved in immune
checkpoint/response and inflammation. iCD4+, pCD4+,
iCD8+and pCD8+ lymphocytic infiltration and PDL-1
have also been analyzed by IIC.
Results: Unsupervised analysis showed two groups of
patients: one characterized by 30% with sun-exposed
lesions, 50% of MCPyV-positivity and 80% PD-L1 positive cases; the other was associated to the predominant
presence of CD276, immuboglobulin family gene alteration, (73%), is mostly enriched in MCPyV-positive and
subject with sun-exposed lesions. Moreover, 53% of
MCCs expressed PD-L1 and 60% showed low iCD4+
lymphocytic infiltration. Expression study identified a
cluster characterized by 71% of MCPyV-positive subjects,
71% of Ki-67 low expression, 85.71% of PD-L1 expressing cases and iCD8+ lymphocytic infiltration. Integrated
analysis highlighted a cluster with the presence of CD276
mutation, low TMB, negative expression of PD-L1, low
levels of iCD4+ andiCD8+ lymphocytic expression.
Conclusions: To fully benefit from the survival advantage
of ICI treatment, a multilayer approach, including somatic

133
alterations, microenvironment and gene expression could
be the best one, also to eventually test combination therapies (e.g., targeted therapy and ICI)

G06
First-line fluoropyrimidine and
oxaliplatin chemotherapy
in gastro-entero-pancreatic
grade 3 well-differentiated
neuroendocrine tumors (NET G3)
Lamberti G.1, Pusceddu S.2, Ibrahim T.3, Bongiovanni A.3, Berardi R.4,
Torniai M.4, Prinzi N.2, Manuzzi L.1, Campana D.1
1
NET Team Bologna Centro di Eccellenza ENETS - Università di Bologna,
Bologna; 2IRCCS Fondazione Istituto Nazionale dei Tumori, Milano; 3IRCCS
Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori, Meldola
(FC); 4AOU Ospedali Riuniti, Ancona

Background: The 2019 World Health Organization
(WHO) classification of neuroendocrine neoplasia (NEN)
introduced the new category of well-differentiated NEN
with Ki67 proliferation index ⩾20% (NET G3).
Fluoropyrimidine-based regimens with oxaliplatin
(FOLFOX/XELOX) were a treatment option in neuroendocrine carcinomas with low Ki67, but their efficacy in the
newly defined NET G3 category is unknown. Objective of
this study was to describe FOLFOX/XELOX efficacy in
NET G3 and identify factors associated with outcome.
Patients and methods: We retrospectively collected consecutive gastro-entero-pancreatic NET G3 patients who
received a FOLFOX/XELOX as first-line treatment at 4
NEN-dedicated Italian Centers. Concomitant somatostatin
analog (SSA) treatment was allowed. Factors associated
with response by RECIST, progression-free survival
(PFS), and overall survival (OS) were analyzed.
Results: Thirty-four NET G3 patients (median age 55
years) were identified. Twenty-two patients (65%) had a
pancreatic NET, while 12 (35%) had a gastrointestinal primary. Median Ki67 was 30% (range 20-50). Treatment
was FOLFOX in 17 (50%) and XELOX in 17 patients
(50%), while 16 (47%) received also concomitant SSA.
After a median follow-up of 21.9 months, median PFS was
7.9 months (95%CI: 6.8-11.4) and median OS was 30.0
months (95%CI: 13.8-NA). The 13 patients whose tumor
responded to FOLFOX/XELOX (38% [95%CI 22-56])
had longer PFS (21.9 vs 7.3 months; p<0.001) and OS
(78.9 vs 10.0 months; p=0.01) compared with those who
did not respond. After correcting for potential confounding
factors with multivariate analysis, objective disease
response to FOLFOX/XELOX was associated with a
reduced risk for progression (HR: 0.20 [95%CI: 0.070.58]; p=0.003) and death (HR: 0.26 [95%CI: 0.07-0.98];
p=0.046) while higher Ki67 was associated with an
increased risk for progression (HR: 1.09 [95%CI: 1.02-



Tumori Journal Abstract Book - October 2020

Table of Contents for the Digital Edition of Tumori Journal Abstract Book - October 2020

Contents
Tumori Journal Abstract Book - October 2020 - Cover1
Tumori Journal Abstract Book - October 2020 - Cover2
Tumori Journal Abstract Book - October 2020 - I
Tumori Journal Abstract Book - October 2020 - II
Tumori Journal Abstract Book - October 2020 - Contents
Tumori Journal Abstract Book - October 2020 - IV
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