Tumori Journal Abstract Book - October 2020 - 44

44	
Background: Genetic polymorphism of genes encoding
drug-metabolizing enzymes constitutes individual's susceptibility to drugs. UDP-glucuronosyltransferase (UGT)
is an enzyme encoded by polymorphic UGT1A and
UGT2B genes. The incidence of genetic polymorphisms
and associated altered gene functions results in interindividual variability in metabolic clearance and elimination of drugs. Mutations in the UGT1A1 gene are very
common in the south of Italy and have been implicated in
Gilbert syndrome and a more aggressive childhood subtype Crigler-Najjar syndrome. Based on the high incidence in our region of subclinical Gilbert syndrome we
have decided to look for the presence of UGT polymorphism in patients with heavily pretreated metastatic colon
cancer (mCRC) and to administer lower dose of irinotecan as a single-agent for patients known to be homozygous for the UGT1A1*28 allele. Our strategy was
designed to investigate the relationship between UGT1A1
polymorphisms and the incidence of adverse events or
the therapeutic effect in mCRC patients who received
irinotecan.
Material (patients) and methods: In our center three of
ten mCRC patients tested for UGT1A polymorphism were
homozygous carriers of the UGT1A1*28 allele. In base of
FDA recommendations these patients could be treated by
reduced dosage of irinotecan based chemotherapy. We
started with 70% of the standard dose of be-weekly irinotecan. If the patient didn't tolerate this initial dose, the dose
could be decreased.
Results: From November 2017 to January 2019 three patients
received lower doses of single agent irinotecan treatment. The
median PFS was 14 months. The best radiological response
evaluated by CT scan was partial response and the all patients
reported great clinical benefit. The incidence rates of typical
side effects of irinotecan regimes were very low. The main
side effect of asinthomatic neutropenia (grade ⩾ 3) and sporadic diarrhea occurred in two of these patients were resolved
by exclusive support care without hospitalization.
Conclusions: Although the presence of variants of UGT
increase hypothetical risk of irinotecan toxicity, we observed
in our clinical practice magnificent clinical benefit and minimal side effects in patients with heavily pretreated metastatic colon cancer receiving a low dose of be-weekly
irinotecan regimen. This therapy appears to be effective and
seems to be a reasonable option for this setting of patients.

B28
KRAS and BRAF concomitant
mutations in patients
with Metastatic Colon
Adenocarcinoma
Pisconti S.1, Cito P.2, Friscini A.3, Luccarelli G.4, Lazzari G.5, Modoni
G.4, Russo F.4, Fanelli F.4, Nenna C.4, D'alessandro A.R.4, Pastore C.4,

Tumori Journal 106(2S)
Galeano T.4, Broussard C.4, Nisi C.4, Bruno M.4, Silvano G.5, Leone
M.F.6, Brunetti A.E.2, Lasigna M.B.2, Cafiero C.7
1

Struttura Complessa di Oncologia ASL TA, Ospedale S.G. Moscati, Taranto;
Struttura Semplice Terapie Oncologiche ASL TA, Ospedale San Pio,
Castellaneta; Taranto; 3Struttura Complessa di Oncologia ASL TA, Ospedale
S.G. Moscati, Taranto; 4Struttura Complessa di Oncologia ASL TA, Ospedale
S.G. Moscati, Taranto; 5Struttura Complessa di Radioterapia Oncologica ASL
TA, Ospedale S.G. Moscati, Taranto; 6Direzione Medica Presidio Centrale
ASL TA, Ospedale S.S. Annunziata, Taranto; 7Struttura Complessa di
Oncoematologia ASL TA, Ospedale S.G. Moscati, Taranto
2

Background: Colorectal cancer (CRC) is characterized
by several critical genes mutation and altered signaling
pathways (e.s WNT, RAS, MAPK, PI3K) important in
the initiation and tumor progression. The most frequent
mutations in CRC are missense with gain of function in
KRAS and BRAF. Of note, about 50-60% of colorectal
cancers are mutated in the KRAS gene, indicating that
up to 40% of patients with colorectal cancer (CRC)
could respond to antibody therapy with the anti-epidermal growth factor receptor (EGFR). However, 40% of
patients with wild-type KRAS primary tumors do not
respond to this therapy. In these patients, data suggest
that the mutated BRAF gene, occur in 5-10% of tumors,
may influences responsiveness to the therapy. Herein we
investigated the presence of BRAF mutation in addition
to KRAS analysis.
Materials and Methods: We describe three cases of metastatic colorectal cancer (mCRC) with rapid progression of
disease: patients (1M/2F, age range 60-70 years old) were
admitted to the " S.G. Moscati Hospital" of Taranto. After
obtaining informed consent, patients were subjected to
liver biopsy. The EGFR immunohistochemical expression
was investigated by immunohistochemistry (anti-EGFR
monoclonal antibody) and by molecular analysis of KRAS
and BRAF mutations.
Results: Hematoxylin and eosin slides were reviewed by
the pathologist to confirm the diagnosis (mCRC) and
select the best representative area of tumor for DNA
extraction. The molecular analysis showed the coexistence
of KRAS and BRAF mutations in hepatic metastases and
the presence of the BRAF V600E mutation alone in the
primary tumor of our patients.
Conclusions: Patients affected by mCRC, as considered
for therapy with anti-EGFR antibodies, should be tested
for the presence of KRAS mutation prior to therapy. It is
unclear whether the lack of response in wild-type KRAS
CRC is due to BRAF mutations, but the data suggest that
mutated BRAF confers resistance to anti-EGFR therapy
administered beyond first-line treatment. In our patients
the BRAF mutation in primary tumor turned out to be a
negative prognostic factor. Additional studies are required
to determine the clinical-pathological effect of KRAS and
BRAF simultaneous mutations on the CRC disease course
and treatment outcome, and for better management of
these patients.



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
Tumori Journal Abstract Book - October 2020 - V
Tumori Journal Abstract Book - October 2020 - 1
Tumori Journal Abstract Book - October 2020 - 2
Tumori Journal Abstract Book - October 2020 - 3
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Tumori Journal Abstract Book - October 2020 - Cover3
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