Background: Neuroendocrine carcinomas (NECs) of the digestive tract are rare and aggressive tumours. In localised disease the treatment is surgery. Based on expert consensus, international guidelines recommend the administration of adjuvant chemotherapy combining etoposide and platinum derivatives, justified by the high risk of metastatic relapse. However, no clinical study has proven the benefit of neoadjuvant or adjuvant chemotherapy. Objectives: We aimed to evaluate the effect of neoadjuvant +/– adjuvant and adjuvant therapy in this indication. Methods: We performed a retrospective observational French study to evaluate overall survival (OS) and disease-free survival (DFS), prognostic factors for survival, and chemotherapy toxicity. Results: Seventy-three patients had surgical resection of a localised digestive NEC between January 1, 2000 and December 31, 2016. The majority of patients presented colorectal (35%) tumours and the median Ki-67 value was 70%. Forty-three patients received chemotherapy, either perioperative (neoadjuvant +/– adjuvant) or adjuvant. The median OS and DFS for the whole population was 24 and 9 months, respectively. The median OS and DFS for patients receiving chemotherapy was 62 and 13 months, respectively. Positive postoperative node status and Ki-67 ≥80% had a negative prognostic impact on OS and DFS. Administration of chemotherapy had a positive prognostic impact on OS and DFS. Sixteen grade 3/4 toxicities were reported without toxic death. Conclusions: Our results suggest a positive effect on survival of chemotherapy in resected digestive NECs, but further studies are needed to confirm these results.

1.
Yao
JC
,
Hassan
M
,
Phan
A
,
Dagohoy
C
,
Leary
C
,
Mares
JE
, et al.
One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States
.
J Clin Oncol
.
2008
Jun
;
26
(
18
):
3063
72
.
[PubMed]
0732-183X
2.
Korse
CM
,
Taal
BG
,
van Velthuysen
ML
,
Visser
O
.
Incidence and survival of neuroendocrine tumours in the Netherlands according to histological grade: experience of two decades of cancer registry
.
Eur J Cancer
.
2013
May
;
49
(
8
):
1975
83
.
[PubMed]
0959-8049
3.
T. Walter J-YS C Lepage
.
Epidemiology of digestive neuroendocrine tumors with focus on French data
.
Hepato-Gastro
.
2013
;
2013
(
20
):
160
6
.
4.
Rindi
G
,
Inzani
F
,
Solcia
E
.
Pathology of gastrointestinal disorders
.
Endocrinol Metab Clin North Am
.
2010
Dec
;
39
(
4
):
713
27
.
[PubMed]
0889-8529
5.
Basturk
O
,
Yang
Z
,
Tang
LH
,
Hruban
RH
,
Adsay
V
,
McCall
CM
, et al.
The high-grade (WHO G3) pancreatic neuroendocrine tumor category is morphologically and biologically heterogenous and includes both well differentiated and poorly differentiated neoplasms
.
Am J Surg Pathol
.
2015
May
;
39
(
5
):
683
90
.
[PubMed]
0147-5185
6.
Coriat
R
,
Walter
T
,
Terris
B
,
Couvelard
A
,
Ruszniewski
P
.
Gastroenteropancreatic Well-Differentiated Grade 3 Neuroendocrine Tumors: Review and Position Statement
.
Oncologist
.
2016
Oct
;
21
(
10
):
1191
9
.
[PubMed]
1083-7159
7.
Perren
A
,
Couvelard
A
,
Scoazec
JY
,
Costa
F
,
Borbath
I
,
Delle Fave
G
, et al.;
Antibes Consensus Conference participants
.
ENETS Consensus Guidelines for the Standards of Care in Neuroendocrine Tumors: Pathology: Diagnosis and Prognostic Stratification
.
Neuroendocrinology
.
2017
;
105
(
3
):
196
200
.
[PubMed]
0028-3835
8.
Klöppel
G
.
Neuroendocrine Neoplasms: Dichotomy, Origin and Classifications
.
Visc Med
.
2017
Oct
;
33
(
5
):
324
30
.
[PubMed]
2297-4725
9.
Scoazec
JY
,
Couvelard
A
,
Monges
G
,
Guyétant
S
,
Bisot-Locard
S
,
Parot
X
, et al.;
PRONET Study Group
.
Professional Practices and Diagnostic Issues in Neuroendocrine Tumour Pathology: Results of a Prospective One-Year Survey among French Pathologists (the PRONET Study)
.
Neuroendocrinology
.
2017
;
105
(
1
):
67
76
.
[PubMed]
0028-3835
10.
Dasari
A
,
Mehta
K
,
Byers
LA
,
Sorbye
H
,
Yao
JC
.
Comparative study of lung and extrapulmonary poorly differentiated neuroendocrine carcinomas: A SEER database analysis of 162,983 cases
.
Cancer
.
2017
;
•••
:
[PubMed]
0008-543X
11.
Sorbye
H
,
Strosberg
J
,
Baudin
E
,
Klimstra
DS
,
Yao
JC
.
Gastroenteropancreatic high-grade neuroendocrine carcinoma
.
Cancer
.
2014
Sep
;
120
(
18
):
2814
23
.
[PubMed]
0008-543X
12.
Sorbye
H
,
Welin
S
,
Langer
SW
,
Vestermark
LW
,
Holt
N
,
Osterlund
P
, et al.
Predictive and prognostic factors for treatment and survival in 305 patients with advanced gastrointestinal neuroendocrine carcinoma (WHO G3): the NORDIC NEC study
.
Ann Oncol
.
2013
Jan
;
24
(
1
):
152
60
.
[PubMed]
0923-7534
13.
Pellat
A
,
Wislez
M
,
Svrcek
M
,
Hammel
P
,
Afchain
P
,
André
T
.
[Therapeutic management of poorly differentiated neuroendocrine lung tumors and neuroendocrine carcinomas of the digestive system]
.
Bull Cancer
.
2016
Oct
;
103
(
10
):
880
95
.
[PubMed]
0007-4551
14.
Garcia-Carbonero
R
,
Sorbye
H
,
Baudin
E
,
Raymond
E
,
Wiedenmann
B
,
Niederle
B
, et al.;
Vienna Consensus Conference participants
.
ENETS Consensus Guidelines for High-Grade Gastroenteropancreatic Neuroendocrine Tumors and Neuroendocrine Carcinomas
.
Neuroendocrinology
.
2016
;
103
(
2
):
186
94
.
[PubMed]
0028-3835
15.
Cicin
I
,
Karagol
H
,
Uzunoglu
S
,
Uygun
K
,
Usta
U
,
Kocak
Z
, et al.
Extrapulmonary small-cell carcinoma compared with small-cell lung carcinoma: a retrospective single-center study
.
Cancer
.
2007
Sep
;
110
(
5
):
1068
76
.
[PubMed]
0008-543X
16.
Strosberg
JR
,
Cheema
A
,
Weber
J
,
Han
G
,
Coppola
D
,
Kvols
LK
.
Prognostic validity of a novel American Joint Committee on Cancer Staging Classification for pancreatic neuroendocrine tumors
.
J Clin Oncol
.
2011
Aug
;
29
(
22
):
3044
9
.
[PubMed]
0732-183X
17.
Coriat
R
,
Terris
B
,
Walter
T
.
In Reply
.
Oncologist
.
2017
Mar
;
22
(
3
):
359
60
.
[PubMed]
1083-7159
18.
Smith
JD
,
Reidy
DL
,
Goodman
KA
,
Shia
J
,
Nash
GM
.
A retrospective review of 126 high-grade neuroendocrine carcinomas of the colon and rectum
.
Ann Surg Oncol
.
2014
Sep
;
21
(
9
):
2956
62
.
[PubMed]
1068-9265
19.
Shafqat
H
,
Ali
S
,
Salhab
M
,
Olszewski
AJ
.
Survival of patients with neuroendocrine carcinoma of the colon and rectum: a population-based analysis
.
Dis Colon Rectum
.
2015
Mar
;
58
(
3
):
294
303
.
[PubMed]
0012-3706
20.
Lara
PN
 Jr
,
Natale
R
,
Crowley
J
,
Lenz
HJ
,
Redman
MW
,
Carleton
JE
, et al.
Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124
.
J Clin Oncol
.
2009
May
;
27
(
15
):
2530
5
.
[PubMed]
0732-183X
21.
Moertel
CG
,
Kvols
LK
,
O’Connell
MJ
,
Rubin
J
.
Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms
.
Cancer
.
1991
Jul
;
68
(
2
):
227
32
.
[PubMed]
0008-543X
22.
Mitry
E
,
Baudin
E
,
Ducreux
M
,
Sabourin
JC
,
Rufié
P
,
Aparicio
T
, et al.
Treatment of poorly differentiated neuroendocrine tumours with etoposide and cisplatin
.
Br J Cancer
.
1999
Dec
;
81
(
8
):
1351
5
.
[PubMed]
0007-0920
23.
Walter
T
,
Tougeron
D
,
Baudin
E
,
Le Malicot
K
,
Lecomte
T
,
Malka
D
, et al.
: Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort. Eur J Cancer Oxf Engl 1990
2017
;79:158–165.
24.
Casas
F
,
Ferrer
F
,
Farrús
B
,
Casals
J
,
Biete
A
.
Primary small cell carcinoma of the esophagus: a review of the literature with emphasis on therapy and prognosis
.
Cancer
.
1997
Oct
;
80
(
8
):
1366
72
.
[PubMed]
0008-543X
25.
Haugvik
SP
,
Janson
ET
,
Österlund
P
,
Langer
SW
,
Falk
RS
,
Labori
KJ
, et al.
Surgical Treatment as a Principle for Patients with High-Grade Pancreatic Neuroendocrine Carcinoma: A Nordic Multicenter Comparative Study
.
Ann Surg Oncol
.
2016
May
;
23
(
5
):
1721
8
.
[PubMed]
1068-9265
26.
Jesinghaus
M
,
Konukiewitz
B
,
Keller
G
,
Kloor
M
,
Steiger
K
,
Reiche
M
, et al.
Colorectal mixed adenoneuroendocrine carcinomas and neuroendocrine carcinomas are genetically closely related to colorectal adenocarcinomas
.
Mod Pathol
.
2017
Apr
;
30
(
4
):
610
9
.
[PubMed]
0893-3952
27.
Takizawa
N
,
Ohishi
Y
,
Hirahashi
M
,
Takahashi
S
,
Nakamura
K
,
Tanaka
M
, et al.
Molecular characteristics of colorectal neuroendocrine carcinoma; similarities with adenocarcinoma rather than neuroendocrine tumor
.
Hum Pathol
.
2015
Dec
;
46
(
12
):
1890
900
.
[PubMed]
0046-8177
28.
Brieau
B
,
Lepère
C
,
Walter
T
,
Lecomte
T
,
Guimbaud
R
,
Manfredi
S
, et al.
Radiochemotherapy Versus Surgery in Nonmetastatic Anorectal Neuroendocrine Carcinoma: A Multicenter Study by the Association des Gastro-Entérologues Oncologues
.
Medicine (Baltimore)
.
2015
Oct
;
94
(
42
):
e1864
.
[PubMed]
0025-7974
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