Download before the 2 nd cycle

XXVIII Riunione Nazionale MITO
“Il lato oscuro di Venere”
Mesagne (Brindisi), 19-20 Gennaio 2017
Studio retrospettivo sulla correlazione tra fattori biologici
immunologici e outcome nelle pazienti con tumori
ginecologici (MITO24): PROGRESS REPORT
Sara Testoni, Ugo De Giorgi
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (I.R.S.T.)
IRCCS Meldola
Systemic immune-inflammation index (SII),
Platelet/lymphocyte ratio (PLR) and
Title of the project
Neutrophyls/lymphocyte ratio (NLR) as
prognostic/predictive factors in gynecological
cancers.
Research line
Prognostic factors in gynecological cancers
Principal Investigator
Ugo De Giorgi
Medical Oncology , IRST-IRCCS
Address and e-mail
Via P. Maroncelli 47014 Meldola
[email protected]
Participating centres
Centres from MITO group
Cancer and inflammation
Cancer and inflammation are strictly linked and cancer patients present local and systemic
modifications in inflammatory parameters as the Neutrophyl/Lymphocyte ratio (NLR), in erythrocyte
sedimentation rate, in the level of serum inflammatory cytokines, and acute-phase proteins, as well
as observed in infectious or inflammatory diseases.1-3
 Platelets can induce circulating tumor cell epithelial-mesenchymal transition and promote
extravasation to metastatic sites. 4,5
 Neutrophyls can promote adhesion and seeding of distant organ sites through secretion of
circulating growth factors such as VEGF and proteases. 6,7
 Lymphocytes play a crucial role in tumor defense by inducing cytotoxic cell death and inhibiting
tumor cell proliferation and migration, thereby dictating the host immune response to malignancy.8
 Inflammation induces cancer microenvironment and systemic changes that are favorable for
cancer progression.
References
1.
2.
3.
4.
5.
6.
7.
8.
Balkwill F, Mantovani A. Cancer and inflammation: implications for pharmacology and therapeutics. Clin Pharmacol Ther. 2010 Apr;87(4):401-6
Gabay C, Acute-phase proteins and other systemic responses to inflammation. New Engl J Medi1999;340(6):448–54
Guthrie GJ, Charlesb KA, Roxburgha CS, Horgana PG, McMillana DC, Clarkec SJ. The systemic inflammation-based neutrophil–lymphocyte ratio: Experience in patients with cancer. Crit Rev Oncol Hematol. 2013 ;88(1):218-30
Labelle M, Begum S, Hynes RO. Direct signaling btween platelets and cancer cells induces epithelial-mesenchymal-like transition and promote metastasis. Cancer Cell 2011; 20:576-590.
Schumacher D, Strilic B, Sivaraj KK, et al. Platelet-derived nucleotides promote tumor-cell transendothelial migration and metastasis via P2Y2 receptor. Cancer Cell 2013;24:130-137.
Cools-Lartigue J, Spicer J, McDonald B, et al. Neutrophyl extracellular traps sequester circulating tumor cells and promote metastasis. J Clin Invest 2013; 123:3446-58.
Rossi L, Santoni M, Crabb SJ, Scarpi E, Burattini L, Chau C, Bianchi E, Savini A, Burgio SL, Conti A, Conteduca V, Cascinu S, De Giorgi. U. High Neutrophil-to-lymphocyte Ratio Persistent During First-line Chemotherapy Predicts Poor Clinical Outcome in
Patients with Advanced Urothelial Cancer. Ann Surg Oncol. 2014 Sep 19. [Epub ahead of print]
De Giorgi U, Mego M, Scarpi E, Giuliano M, Giordano A, Reuben JM, Valero V, Ueno NT, Hortobagyi GN, Cristofanilli M. Relationship between lymphocytopenia and circulating tumor cells as prognostic factors for overall survival in metastatic breast
cancer. Clin Breast Cancer 2012;12(4):264-9.
Background
Background
Objectives
To evaluate prognostic and predictive implications of SII, PLR, NLR levels and changes
associated and establish a novel risk stratification model in patients with advanced GC
receiving chemotherapy +/- other agents.
Primary objective: correlations with OS
Secondary objective: correlations with PFS, ORR, safety, histotypes, CA125.
Study design and study population
Review retrospectively medical charts of patients with advanced gynaecological cancers (GC) treated with 1st line
CT (+/- bevacizumab for ovarian cancer ) or subsequent therapies from 1st January 2007 to 30th June 2015.
Databases will be separated according to the primary tumors and clinical setting:
 1st line Cervical Cancer (CC)
 1st line Endometrial cancer (EC)
 1st line Ovarian Cancer (OC)
A specific sub-study on SII, PLR and NLR in OC treated with or without bevacizumab in 1st line setting will be performed focusing on patients with
stage III-IV.
 2nd line OC (sharing between patients with platinum sensitive/refractory disease)
The optimal cut-off values of SII, PLR and NLR will be evaluated in every disease and setting at baseline (C1D1
pre-therapy) and before the 2nd cycle (C2D1 pre-therapy).
Exclusion criteria will include:
 <1month from treatment use of steroids or other systemic antineoplastic therapy
 <1 month from treatment or during the 1st cycle of CT onset of infection
 G-CSF use within 1 week from the 2nd cycle
Database (1st line Ovarian Cancer)
Family history
Date of of breast or
stage III
ASCITES
Center Pt number
Histology
Grading
birth
ovarian
or IV
YES/NO
cancer (Y/N)
Baseline Baseline
Baseline
Baseline
platelet neutrofil lymphocite
PS (ECOG)
ca125 value
count
count
count
Weight
(kg)
before
before before 2nd
nd
2 cycle 2nd cycle
cycle
platelet neutrofil lymphocite
count
count
count
Best
1st line
Date of
date
dose
Interval
response
regimen (eg number
last
start 1st
reducti surgery,
RECIST
carbo-taxof
cycle
line
on
yes or
criteria
beva) with
cycles
of 1st
chemo
yes/not
not
(CR, PR,
doses
line CT
SD, PD)
Height
(cm)
Metastatic sites before 1° line
(PE=peritoneum, LI=liver, LU=lung,
BO=bone, PL=pleura; SP=spleen,
MN=mediastinal nodes, RN=retroperitoneal
nodes, others…specify)
before 2nd
before 2nd
cycle (precycle ca125
2nd cycle)
value
NLR value
During
following
cycles Ca125
lower value
and cycle
neutropenia G-CSF use
Reason for CT
grade 4 in the in the first
(and/or beva) Grade 3-4 toxicities
first cycle (yes cycles (yes
interruption)
or not
or not)
Date of progression Progression
Number of further Date of death or
(or date of last
score (0=no,
CT regimens
last follow-up
follow-up if no PD)
1=yes)
Status at last
follow-up score
0=alive 1=dead
comments/
further information
Participating centres
No. Pazienti
segnalati/inseriti
178
Numero tot
di casi ricevuti
149
Casi trattati con
carbo-tax+BEVA
33
33
1 (3%)
Oncologia Ospedale Infermi
0
0
0
Oncologia Medica Seconda
Università di Napoli (SUN)
22
22
8 (36%)
Ospedale Legnago
11
43
6 (14%)
U.O.Medicina Oncologica
di Carpi, AUSL di Modena
34
34
8 (24%)
6
0
-
6
6
0
Istituto Tumori “Pascale”
10
0
-
Giorgia Mangili
HSRaffaele
62
62
Giovanni Scambia
Ginecologia OncologicaPoliclinico Gemelli
8 (12%)
-
-
-
No. centro
Città
PI
Istituto
01
Meldola
Ugo De Giorgi
02
Ravenna
Claudia Casanova
IRST IRCCS
Oncologia Ospedale
S.M. delle Croci
03
Rimini
Valentina Arcangeli
04
Napoli
Michele Orditura
05
Legnago
06
Carpi
Lucia Longo
07
Reggio Emilia
Alessandra Bologna
08
Biella
09
Napoli
Sandro Pignata
10
Milano
11
Roma
Oncologia, Osp. S.Maria
Nuova
Ospedale Biella
TOT. Ricevuti:
349
24 (17%)
55 (16%)
Sara Testoni
[email protected]
IRCCS IRST – Via P. Maroncelli 40
47014 Meldola (FC)
Background
x-tile 3.6.1 software (Yale University, New Haven, CT)
internet – free
http://medicine.yale.edu/lab/rimm/research/software.aspx