Tumori Journal Abstract Book - October 2020 - 60

60	
Ospedaliero - Universitaria Policlinico di Modena, Modena, Italy, Modena;
6
Department of Public Health, University of Naples Federico II, Napoli

Background: Mitochondria (Mi) are fundamentally implicated in cancer biology, including initiation, growth, metastasis, relapse, and acquired drug resistance. Mi are considered
as the target organelles for therapeutic strategies of several
cancers including CCA. The project aims to dissect the novel
MiPa, to identify all molecular players, to functional characterize their role in CCA, to identify novel targeted therapies,
to develop a gene signature exhibiting consistent prognostic
power and predictive value as potential biomarker.
Methods: HTS has been performed by using Prestwick
Chemical Library (Prestwick) and siGENOME DruggableGenome-Library (Dharmacon). CASP9 activity has measured
using the ApoAlert CASP9 assay (Clontech). Cell viability
was monitored by CellTiter-Blue assay (Promega). The patient
cohort consists of 100 patients retrospectively identified by
Univeristy of Modena, IT. Lentiviral-based shRNA and
CRISPR/Cas9 systems were utilized to establish stable gene
knockdown and knockout model. FFPE-RNA extraction,
RNAseq, WES and bioinformatic analyses will beperformed
using protocols and pipeline available at TIGEM (2).
Results: Molecular players of the novel MiPa, which triggers APAF1-independent CASP-9 activation have been
identified using a proteomic approach combined to siRNA
library screening. HTS allowed to identify compounds targeting the novel MiPa. Two compounds were found to inhibit
tumour growth in vitro and their anti-tumour efficacy has
been assessed. Experiments in HuCCT-1, KMCH, CCLP,
SW1, EGI, TFK1 cell lines revealed their effect on autophagy
inhibition and apoptosis and correlated the MiPa pathway
with drug treatment response and drug resistance. Wholegenome analysis is ongoing to profile the novel MiPa gene
signature in cell lines treated and not with standard therapeutic approach and in a cohort of 100 CCA patients.
Conclusions: A novel MiPa has been identified regulating
the apoptosis in CCA. Implication of the novel MiPa in
drug resistance and sensitivity to classical therapeutic
treatment has been assessed. Whole-transcriptome and
exome analysis are ongoing to evaluate the clinical value
of the MiPa gene signature in CCA patients.
1.Indrieri, A., et al., EMBO Mol Med, 2013.
2.Cacchiarelli D, et al., Cell. 2015.

C28
Immune-inflammatory indexes
and BMI as predictors of outcome
and treatment response in
advanced gastric cancer receiving
ramucirumab-containing second-line
Riccò B.1, Salati M.1, Bocconi A.1, Rimini M.1, Santini C.1, Caputo F.1,
Rovesti G.1, Canino F.1, Riggi M.L.1, Bardasi C.1, Benatti S.1, Casadei
Gardini A.1, Gelsomino F.1, Dominici M.1, Luppi G.1, Spallanzani A.1
1

Università degli Studi di Modena e Reggio Emilia, Modena

Tumori Journal 106(2S)
Background: The efficacy of Ramucirumab in the treatment of advanced gastric cancer was demonstrated in the
two pivotal study REGARD and RAINBOW, which both
demonstrated significant improvements in Overall
Survival (OS) and Progression-Free Survival (PFS).
However, data on validated clinical and biochemical predictive factors in a real-life setting are still lacking.
Matherial and methods Retrospective analysis of medical
records of patients with advanced gastric cancers treated
with ramucirumab or ramucirumab/paclitaxel from April
2015 to April 2020 at Modena Cancer Center was conducted. Clinicopathological and biochemical parameters
deemed of interest were collected. The cut-off value for continuous variables was assessed at 75° percentile. Treatment
effects were evaluated by univariate and multivariate Cox
proportional hazards regression models for OS and logistic
regression analysis.
Results: During the study period, 49 patients with advanced
gastric cancers were treated with ramucirumab alone (6.1%)
or in combination with paclitaxel (93.9%) as second line
therapy. At the multivariate, only CEA showed to impact on
the second-line PFS with statistical significance (p=0.013,
95% Confidence Interval [CI] 1.08-6.4). By performing a
logistic regression analysis, Absolute Neutrophil Count
(ANC), Neutrophil Lymphocyte Ratio (NLR), Systemic
Inflammatory Index (SII), CEA, Body Mass Index (BMI),
ECOG Performance Status and Clinical Benefit (defined as
complete response, partial response and stable disease versus disease progression) showed to be correlate with a PFS
of more than 6 months. ECOG 0 and BMI>25 were the
main predictive factors associated with Clinical Benefit
(p=0.018 and p= 0.0006, respectively).
Conclusions: Favorable inflammatory indexes, CEA,
BMI and ECOG confer a better second-line PFS. ECOG
and BMI seem to be strictly related to Clinical Benefit,
thus making these two parameters predictive of response
to Ramucirumab. In the future, it will be mandatory a validation of our results on a larger population by the use of
more specific parameters for the sarcopenia assessment.

C29
Retrospective assessment of the
prognostic value of the neutrophil/
lymphocyte ratio (NLR) in advanced
pancreatic cancer (APC) patients
undergoing palliative chemotherapy.
Interdisciplinary Group
Intercompany Care (GIC) of biliopancreatic cancers, Alessandria-Asti,
Rete Oncologica del Piemonte e della
Valle d'Aosta, Italy
Traverso E.S.1, Alessio M.2, Gabelli V.3, Bellotti G.4, Fusco V.4,
Amisano M.5, Nada E.5, Silvestri S.5, Novi M.L.6, Gemme C.6,
Barbero S.7, Segreto A.L.8, Pastorino A.7, Varese P.9, Erra S.10,
Mariani N.11, Feyles E.12, Muni A.13, Numico G.4



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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