clinical practice guidelines Annals of Oncology 24 (Supplement 6): vi57–vi63, 2013

doi:10.1093/annonc/mdt344

Gastric cancer†: ESMO–ESSO–ESTRO Clinical Practice

Guidelines for diagnosis, treatment and follow-up
T. Waddell1, M. Verheij2, W. Allum3, D. Cunningham4, A. Cervantes5 & D. Arnold6*
1
GI Clinical Trials Unit, Royal Marsden Hospital, Sutton, UK; 2Department of Radiation Oncology and Division of Biological Stress Response, The Netherlands Cancer
Institute, Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands; 3Department of Surgery, Royal Marsden Hospital, London; 4Department of Medicine, Royal
Marsden Hospital, Sutton, UK; 5Department of Hematology and Medical Oncology, INCLIVA, University of Valencia, Valencia, Spain; 6Department of Medical Oncology,
Tumor Biology Center, Freiburg, Germany

These Guidelines were developed by the European Society for Medical Oncology (ESMO), the
European Society of Surgical Oncology (ESSO) and the European Society of Radiotherapy and
Oncology (ESTRO) and are published jointly in the Annals of Oncology, the European Journal of
Surgical Oncology and Radiotherapy & Oncology. The three societies nominated authors to write
the guidelines as well as reviewers to comment on them.

These Clinical Practice Guidelines are endorsed by the Japanese Society of Medical Oncology (JSMO)

incidence and epidemiology diagnosis and pathology

clinical practice
In 2012, there were ∼140 000 new cases of gastric cancer Screening for gastric cancer is routine in Japan and Korea,

guidelines
diagnosed across all European countries, making it the sixth where the incidence is much higher than in Western countries.
commonest cancer diagnosis. Perhaps more importantly, it In symptomatic patients, the presenting features commonly
remains the fourth commonest cause of cancer-related death, include weight loss, dysphagia, dyspepsia, vomiting, early satiety
being responsible for ∼107 000 deaths annually [1]. Despite a and/or iron-deficiency anaemia.
gradual decline in the worldwide incidence of gastric cancer, Diagnosis should be made from a gastroscopic or surgical
there has been a relative increase in the incidence of tumours biopsy reviewed by an experienced pathologist, and histology
of the oesophago-gastric junction (OGJ) and gastric cardia. should be reported according to the World Health Organisation
The peak incidence is in the seventh decade, and the disease criteria [IV, C].
is approximately twice as common in men as in women. Ninety percent of gastric cancers are adenocarcinomas, and
There is a marked geographic variation, with the highest rates these are sub-divided according to histological appearances into
reported in East Asia, South America and Eastern Europe diffuse (undifferentiated) and intestinal (well differentiated)
and the lowest rates in the United States and Western types (Lauren classification). These Clinical Practice Guidelines
Europe [2]. do not apply to rarer gastric malignancies, such as
The risk factors for gastric cancer include male gender, gastrointestinal stromal tumours (GIST), lymphomas and
cigarette smoking, Helicobacter pylori infection, atrophic neuroendocrine tumours.
gastritis, partial gastrectomy and Ménétrier’s disease. A small
number of patients may have a genetic predisposition staging and risk assessment
syndrome, including hereditary non-polyposis colorectal Initial investigations include physical examination, blood count
cancer, familial adenomatous polyposis, hereditary diffuse and differential, liver and renal function tests, endoscopy and
gastric cancer and Peutz Jeghers syndrome. If this is suspected contrast-enhanced computed tomography (CT) scan of the thorax
based upon family history, then patients should be referred to a and abdomen ± pelvis. Positron emission tomography (PET)
genetics specialist for assessment as per International Gastric imaging, if available, may improve staging through an increased
Cancer Linkage Consortium guidelines [3] [V, B]. detection of involved lymph nodes/metastatic disease. However, it
may be uninformative in some patients, especially those with
mucinous tumours [III, B] (Table 1).
Endoscopic ultrasound (EUS) is helpful in determining the
*Correspondence to: ESMO Guidelines Working Group, ESMO Head Office, Via L. Taddei 4, proximal and distal extent of the tumour and provides further
CH-6962 Viganello-Lugano, Switzerland. assessment of the T and N stages, although it is less useful in
E-mail: [email protected] antral tumours [III, B]. Laparoscopy ± peritoneal washings for
†
These guidelines do not refer to the separate entity of OGJ tumours. malignant cells is recommended in all stage IB–III stomach

© The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: [email protected].
clinical practice guidelines Annals of Oncology

Table 1. Diagnostic and staging investigations in gastric cancer

Procedure Purpose
Routine blood tests Check for evidence of iron-deficiency anaemia.
Check hepatic and renal function to determine appropriate therapeutic options.
Endoscopy + biopsy Obtain tissue for diagnosis, histological classification and molecular biomarkers, e.g. HER-2 status.
CT thorax + abdomen ± pelvis Staging of tumour—particularly to detect local/distant lymphadenopathy and metastatic disease sites.
Endoscopic ultrasound (EUS) Accurate assessment of T and N stage in potentially operable tumours.
Determine proximal and distal extent of the tumour.
Laparoscopy + washings To exclude occult metastatic disease involving the diaphragm/peritoneum.
Positron emission tomography (PET, if available) May improve detection of occult metastatic disease in some cases.

Table 2. TNM staging of gastric cancer (7th Edition of AJCC/UICC Guidelines) [6, 7]

Primary tumour (T) Regional lymph nodes (N) Distant metastasis (M)
TX Primary tumour cannot be assessed NX Regional lymph node(s) cannot be MX Distant metastasis cannot be assessed
assessed
T0 No evidence of primary tumour N0 No regional lymph node metastasis M0 No distant metastasis
Tis Carcinoma in situ: intraepithelial tumour N1 Metastasis in one to two regional M1 Distant metastasis or positive peritoneal
without invasion of the lamina propria lymph nodes cytology
T1a Tumour invades lamina propria or N2 Metastasis in three to six regional
muscularis mucosae lymph nodes
T1b Tumour invades submucosa N3 Metastasis in seven or more regional
lymph nodes
T2 Tumour invades muscularis propria
T3 Tumour penetrates subserosal connective
tissue without invasion of visceral
peritoneum or adjacent structuresa
T4a Tumour invades serosa (visceral peritoneum)
T4b Tumour invades adjacent structuresb
a
T3 tumours also include those extending into the gastrocolic or gastrohepatic ligaments, or into the greater or lesser omentum, without perforation of the
visceral peritoneum covering these structures.
b
Adjacent structures include the spleen, transverse colon, liver, diaphragm, pancreas, abdominal wall, adrenal gland, kidney, small intestine and retro-
peritoneum.
Edge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging Handbook, 7th ed. New York, NY.: Springer, 2010. Used with the permission of the American
Joint Committee on Cancer (AJCC), Chicago, Illinois. The original source for this material is the AJCC Cancer Staging Handbook, Seventh Edition (2010)
published by Springer Science and Business Media LLC, www.springer.com.

cancers considered to be potentially resectable to exclude occult management of local/locoregional

metastatic disease [4, 5] [III, B]. disease
The TNM classification should be recorded and the
corresponding stage determined according to the seventh surgery
edition of the Union for International Cancer Control (UICC) Surgical resection is the only treatment modality that is
[6]/American Joint Cancer Committee (AJCC) [7] guidelines potentially curative, though the majority of patients still relapse
and staging manual (Tables 2 and 3). A careful tumour staging following resection and therefore combined modality
is fundamental to ensuring that patients are appropriately approaches are standard for ≥stage 1B disease. The extent of
selected for treatment interventions. resection is determined by the preoperative stage. Early gastric
cancers (T1a) may be amenable to endoscopic resection if they
are well-differentiated, ≤2 cm, confined to the mucosa and not
treatment planning ulcerated [8] [III, B]. The associated lymph node metastatic risk
Multi-disciplinary treatment planning is mandatory. The core is virtually zero for this group. Guidelines from the National
membership of the multi-disciplinary team should include Cancer Centre in Tokyo have expanded these criteria in patients
surgeons, medical and radiation oncologists, gastroenterologists, with intestinal-type histology and no evidence of lympho-
radiologists and pathologists, as well as dieticians and nurse vascular invasion to include: intramucosal cancers without
specialists if available [IV, C]. ulceration regardless of tumour size; intra-mucosal cancers

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Annals of Oncology clinical practice guidelines
Table 3. AJCC/UICC stage grouping (7th Edition) [6, 7] In the West, a Dutch [10] and a UK Medical Research Council
(MRC) trial [11] failed to demonstrate any initial survival
Stage grouping T stage N stage M stage advantage with D2 resection. However, the 15-year follow-up
Stage 0 Tis N0 M0 results from the Dutch trial [12] demonstrated fewer
Stage IA T1 N0 M0 locoregional recurrences and gastric cancer-related deaths with
Stage IB T1 N1 M0 D2 resection, though this was slightly offset by an increase in
T2 N0 M0 postoperative mortality and morbidity. A recent meta-analysis
Stage IIA T1 N2 M0 of 12 randomised, controlled trials (RCTs) confirmed no overall
T2 N1 M0 survival (OS) benefit for D2 lymphadenectomy, although a
T3 N0 M0 benefit was seen among patients who had resection without a
Stage IIB T1 N3 M0 splenectomy and/or pancreatectomy [13]. The current
T2 N2 M0 consensus view in the West is that, for patients deemed to be
T3 N1 M0 medically fit, D2 dissection should be the standard procedure
T4a N0 M0 carried out in specialised, high-volume centres with appropriate
Stage IIIA T2 N3 M0 surgical expertise and postoperative care [14] [I, B].
T3 N2 M0
Laparoscopic surgery has been evaluated as an alternative to
T4a N1 M0
open surgery with the potential benefits of decreased operative
Stage IIIB T3 N3 M0
morbidity and reduced recovery times. Meta-analyses confirm
T4a N2 M0
these benefits in distal gastrectomy, though some concerns
T4b N0-1 M1
remain regarding long-term outcomes and the possibility for
Stage IIIC T4a N3 M0
T4b N2-3 M0
reduced nodal harvest with a laparoscopic approach [15, 16]
Stage IV Any T Any N M1 [I, A]. In addition, operative morbidity is greater particularly in
total gastrectomy and there remains a lack of consensus on the
Edge SB, Byrd DR, Compton CC, eds. AJCC Cancer Staging Handbook, 7th preferred approach to the technique of anastomosis following a
ed. New York, NY.: Springer, 2010. Used with the permission of the laparoscopic total gastrectomy. Trials are currently ongoing in
American Joint Committee on Cancer (AJCC), Chicago, Illinois. The Japan (JCOG-0912), Korea (KLASS and KLASS-02) and China
original source for this material is the AJCC Cancer Staging Handbook, to compare an open versus laparoscopic surgery in early gastric
Seventh Edition (2010) published by Springer Science and Business Media cancer, and these should provide further evidence regarding the
LLC, www.springer.com. role of laparoscopic surgery.

<3 cm with ulceration or cancers with early invasion into the perioperative chemotherapy
sub-mucosa (sm1) measuring <3 cm. In this expanded group,
The UK MRC MAGIC trial was the first trial to evaluate the role
the risk of lymph node metastases also remains low, provided
of perioperative chemotherapy with six cycles of ECF
that an endoscopic submucosal en bloc resection is undertaken
[epirubicin 50 mg/m2 D1, cisplatin 60 mg/m2 D1 and 5-
to permit precise histological assessment [9] [III, B].
fluorouracil (5-FU) 200 mg/m2/day D1-21 Q21] compared with
T1 tumours which do not meet the criteria for endoscopic
surgery alone in patients with resectable stage II and III gastric
therapy will require surgery, though the extent is less than for
cancers [17]. The results demonstrated that chemotherapy
other gastric cancers (see below). In particular, the lymph node
improved the 5-year survival rate from 23% to 36%, with
dissection can be limited to perigastric nodes and include local
manageable toxic effects. A subsequent FNCLCC (Féderation
N2 nodes, referred to as D1 alpha and D1 beta according to the
Nationale des Centres de Lutte Contre le Cancer) and FFCD
position of primary tumour. Sentinel node mapping may
(Fédération Francophone de la Cancérologie Digestive) trial has
further modify these approaches.
reported similar results with the use of a 28-day regimen of
Radical gastrectomy is indicated for resectable stage IB–III
perioperative cisplatin (100 mg/m2 D1) and 5-FU (800 mg/m2/
disease. Sub-total gastrectomy may be carried out if a
day D1-5) [18]. Perioperative chemotherapy has therefore been
macroscopic proximal margin of 5 cm can be achieved between
widely adopted as the standard of care throughout most of the
the tumour and the OGJ. A margin of 8 cm has been advocated
UK and Europe [I, A]. Since capecitabine avoids the need for an
for diffuse type cancers. Otherwise, a total gastrectomy is
indwelling central venous access device, and is non-inferior to
indicated [III, A]. Perioperative therapies should be considered
5-FU in the advanced disease setting [19], many centres use
in these patients (see below).
ECX (epirubicin, cisplatin, capecitabine) perioperatively in
The extent of nodal dissection accompanying radical
preference to ECF [IV, C]. Other platinum / fluoropyrimidine
gastrectomy has been extensively debated (D1: removal of
doublets may be considered in patients with specific drug
perigastric lymph nodes versus D2: removal of perigastric
contraindications.
lymph nodes plus those along the left gastric, common hepatic
and splenic arteries and coeliac axis). The current UICC/AJCC
TNM classification recommendations (7th edition) include adjuvant chemoradiotherapy
excision of a minimum of 15 lymph nodes to allow reliable For patients who undergo surgery for ≥stage IB oesophago-
staging [6, 7]. Experience from both observational and gastric cancer without administration of preoperative
randomised trials in Asian countries has demonstrated that D2 chemotherapy, the treatment options include either
dissection leads to superior outcomes compared with D1 [II, B]. chemoradiotherapy or chemotherapy delivered in the adjuvant

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clinical practice guidelines Annals of Oncology

setting (see below). Evidence is currently lacking to inform the In current postoperative chemoradiation regimens,
choice between these two treatment modalities in the adjuvant radiotherapy may be given to a total dose of 45 Gy in 25
setting. Further data on these options are awaited from the fractions of 1.8 Gy, 5 fractions/week by 3D-conformal or
ongoing randomised, phase III CRITICS trial, in which patients intensity-modulated radiation therapy techniques. The clinical
receive three cycles of pre-operative chemotherapy followed by target volume encompasses the gastric bed (with stomach
surgery and are then randomised between adjuvant remnant when present), anastomoses and draining regional
chemotherapy and chemoradiotherapy. lymph nodes (for delineation manual: www.critics.nl).
The North American Intergroup-0116 trial demonstrated
that adjuvant therapy with five cycles of 5-FU/leucovorin (Q28) adjuvant chemotherapy
plus concomitant radiotherapy (45 Gy in 25 fractions over 5
A large, individual patient-level meta-analysis of adjuvant
weeks) during cycles 2 and 3 resulted in improved OS at 5 years
chemotherapy in gastric cancer has confirmed a 6% absolute
compared with surgery alone. After 10 years of follow-up, this
benefit for 5-FU-based chemotherapy compared with surgery
result remains significant with a hazard ratio for OS of 1.32 in
alone (HR 0.82, 95% CI 0.76–0.90; P < 0.001) in all subgroups
favour of adjuvant chemoradiotherapy [20] [I, A]. This
tested [25] [I, A]. However, historically a greater benefit has been
treatment approach is considered standard therapy in the
noted with this approach in Asian studies compared with those
United States, though it has not gained wide acceptance in
in Western populations and uptake of this approach in Europe
Europe due to concerns about potential late toxic effects and the
remains limited due to a perceived lack of benefit and routine use
quality of surgery within the trial. Fifty-four percent of patients
of perioperative chemotherapy. In Asian populations, an OS
underwent less than a D1 lymphadenectomy, suggesting that
benefit following adjuvant chemotherapy was confirmed
postoperative chemoradiation may be compensating for sub-
following D2 resection in the ACTS-GC trial evaluating adjuvant
optimal surgery [II, B]. This is supported by retrospective data
S-1 [26] [I, A]. The CLASSIC trial evaluated an adjuvant
from the Dutch D1D2 trial, demonstrating that
capecitabine–oxaliplatin doublet and has reported significantly
chemoradiotherapy reduces local recurrence rates following D1
improved overall and disease-free survival [27]. See Figure 1.
resection, but provides no benefit in patients who have
undergone D2 resection [21] [IV, B]. However, other
randomised and non-randomised data suggest potential benefits management of advanced/metastatic
from postoperative chemoradiation even after optimal D2 disease
dissection [22–24] [I, B], and this is the subject of ongoing
randomised trials. A retrospective comparison of the Dutch palliative chemotherapy and radiotherapy
D1D2 trial has also confirmed significant improvements in OS Patients with stage IV disease should be considered for palliative
and local recurrence rates with the use of chemoradiotherapy chemotherapy, which improves survival compared with best
after a microscopically incomplete (R1) resection [21] [IV, B]. supportive care alone [28] [I, A]. However, co-morbidities,

Figure 1. Algorithm for the management of gastric cancer.

vi | Waddell et al. Volume 24 | Supplement 6 | October 2013

Annals of Oncology clinical practice guidelines
organ function and performance status must always be taken notably, gastric cancers are frequently found to harbour copy
into consideration [II, B]. Although resection of the primary number alterations in key oncogenes and tumour suppressor
tumour is not generally recommended in the palliative setting, a genes [39]. These findings have potentially important
small number of advanced disease patients may be deemed to be therapeutic implications as oncologists attempt to target the key
operable following a good response to systemic therapy. pathways driving the tumour in each individual patient.
Response to systemic treatments should normally be assessed In HER-2 positive gastric cancer (10%–15% of cases), the
with interval CT imaging of chest, abdomen and pelvis. phase III ToGA trial demonstrated clinically and statistically
Alternative imaging techniques may be used if required to significant improvements in response rate, progression-free
monitor known sites of disease (e.g. magnetic resonance survival (PFS) and OS with the addition of trastuzumab to a
imaging for bone lesions). cisplatin–fluoropyrimidine doublet (median OS 13.8 versus
Combination regimens based upon a platinum– 11.1 months, HR 0.74, 95% CI, 0.60–0.91; P = 0.0048) [40].
fluoropyrimidine doublet are generally used, and there remains The benefits of trastuzumab were even more marked in the
controversy regarding the need for triplet regimens. However, a traditionally defined HER-2 positive subgroup with IHC 2+/
meta-analysis has demonstrated significant benefit from adding FISH-positive tumours or IHC 3+ tumours. In these patients,
an anthracycline to a platinum and fluoropyrimidine doublet the median OS was improved from 11.8 months to 16.0 months
[28] [I, A]. The UK REAL-2 trial demonstrated (HR 0.65). Following the ToGA trial results, trastuzumab was
non-inferiority between ECF, ECX, EOF (epirubicin, licensed in Europe for use in HER-2 positive disease (IHC3+ or
oxaliplatin, 5-FU) and EOX (epirubicin, oxaliplatin, 2+/FISH-positive) in combination with capecitabine or 5-
capecitabine) [19]. The EOX regimen was associated with fluorouracil and cisplatin. This regimen now represents the
numerically longer median OS (11.2 versus 9.9 months, HR standard of care for these patients [I, A].
0.80, 95% CI, 0.66–0.97; P = 0.02) than ECF without the need The AVAGAST trial evaluating bevacizumab in combination
for an indwelling catheter and with reduced rates of with first-line chemotherapy failed to demonstrate any
thromboembolism [29]. Additionally, a meta-analysis has improvement in OS, though both PFS and response rate were
demonstrated that capecitabine is associated with improved OS significantly improved [41] [I, C]. A second anti-angiogenic
compared with infused 5-FU within doublet and triplet regimes agent, ramucirumab, has recently been confirmed to have
[30] [I, A]. single-agent activity in the second-line setting with a modest
Alternative first-line chemotherapy options include taxane- 1.4-month improvement in OS compared with best supportive
based regimens or irinotecan plus 5-FU [31]. The addition of care [42] [I, B]. Neither agent is currently in routine clinical use.
3-weekly docetaxel to 5-FU/cisplatin (DCF) is associated with Anti-EGFR therapies have failed to improve outcomes with
increased activity, but also adds toxic effects including increased recently reported negative phase III results when cetuximab [43]
rates of febrile neutropaenia [32] [I, C]. Modified DCF regimens or panitumumab [44] was added to first-line chemotherapy,
therefore continue to be explored in an attempt to maintain and a negative phase III trial of single-agent gefitinib compared
activity while mitigating against excessive toxic effects. with best supportive care in the second-line [45] [I, D].
In patients of adequate performance status, second-line Other molecular targets which are currently showing promise
chemotherapy is associated with proven improvements in OS in the advanced disease setting include:
and quality of life compared with best supportive care, with
treatment options including irinotecan, docetaxel or paclitaxel • Overexpression or amplification of the MET receptor – MET
[33–37] [I, A]. A randomised, phase III trial directly comparing targeted therapies are currently entering phase III trials in this
weekly paclitaxel with irinotecan has demonstrated similar population.
efficacy for both the regimens, with the median OS of 8 to 9 • Amplification of FGFR – anti-FGFR therapy is currently
months in a Japanese population [37] [I, A]. Additionally, undergoing evaluation.
consideration should always be given to inclusion in any
appropriate clinical trials [V, B]. Alternatively, in patients with
disease progression >3 months following first-line follow-up and long-term implications
chemotherapy, it may be appropriate to consider a re-challenge In the setting of operable gastric cancer, the complexity of
with the same drug combination [IV, C]. treatment frequently induces symptoms which adversely affect
In patients with symptomatic locally advanced or recurrent health-related quality of life. A regular follow-up may allow
disease, hypofractionated radiotherapy is an effective and well- investigation and treatment of symptoms, psychological support
tolerated treatment modality which may palliate bleeding, and early detection of recurrence, though there is no evidence
obstructive symptoms or pain [38] [III, B]. See Figure 1. that it improves survival outcomes [46–48] [III, B].
New strategies for patient follow-up are currently undergoing
evaluation, including patient-led self-referral and services led by
personalised medicine clinical nurse specialists.
As in other solid organ tumours, the biological abnormalities In the advanced disease setting, identification of patients for
underpinning the development and progression of gastric second-line chemotherapy and clinical trials requires regular
cancer are being increasingly elucidated through ongoing follow-up to detect symptoms of disease progression before
international research. These tumours are now known to be significant clinical deterioration [IV, B].
highly molecularly diverse and may be driven by a number of If relapse/disease progression is suspected then a clinical
different genetic and epigenetic abnormalities. Perhaps most history, physical examination and directed blood tests should be

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clinical practice guidelines Annals of Oncology

Table 4. Levels of evidence and grades of recommendation (adapted from references

the Infectious Diseases Society of America-United States Public Health
Service Grading Systema) 1. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J et al. Cancer incidence and
mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer
2013; 49: 1374–1403.
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I Evidence from at least one large randomised, controlled trial of of environmental risk factors. Best Pract Res Clin Gastroenterol 2006; 20:
good methodological quality (low potential for bias) or meta- 633–649.
analyses of well-conducted, randomised trials without 3. Fitzgerald RC, Hardwick R, Huntsman D et al. Hereditary diffuse gastric cancer:
heterogeneity updated consensus guidelines for clinical management and directions for future
II Small randomised trials or large randomised trials with a research. J Med Genet 2010; 47: 436–444.
suspicion of bias (lower methodological quality) or meta- 4. Nath J, Moorthy K, Taniere P et al. Peritoneal lavage cytology in patients with
analyses of such trials or of trials with demonstrated oesophagogastric adenocarcinoma. Br J Surg 2008; 95: 721–726.
heterogeneity 5. de Graaf GW, Ayantunde AA, Parsons SL et al. The role of staging laparoscopy in
oesophagogastric cancers. Eur J Surg Oncol 2007; 33: 988–992.
III Prospective cohort studies
6. Sobin L, Gospodarowicz M, Wittekind C. TNM Classification of Malignant Tumours,
IV Retrospective cohort studies or case–control studies
7th edition. Oxford: Wiley-Blackwell 2009.
V Studies without control group, case reports, experts opinions
7. Edge S, Byrd D, Compton C et al. AJCC Cancer Staging Manual. 7th edition.
Grades of recommendation
New York, NY: Springer 2010.
A Strong evidence for efficacy with a substantial clinical benefit,
8. Tada M, Tanaka Y, Matsuo N et al. Mucosectomy for gastric cancer: current status
strongly recommended in Japan. J Gastroenterol Hepatol 2000; 15(Suppl): D98–102.
B Strong or moderate evidence for efficacy but with a limited clinical 9. Gotoda T, Iwasaki M, Kusano C et al. Endoscopic resection of early gastric cancer
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C Insufficient evidence for efficacy or benefit does not outweigh the 2010; 97: 868–871.
risk or the disadvantages (adverse events, costs, …), optional 10. Bonenkamp JJ, Hermans J, Sasako M et al. Extended lymph-node dissection for
D Moderate evidence against efficacy or for adverse outcome, gastric cancer. N Engl J Med 1999; 340: 908–914.
generally not recommended 11. Cuschieri A, Fayers P, Fielding J et al. Postoperative morbidity and mortality after
E Strong evidence against efficacy or for adverse outcome, never D1 and D2 resections for gastric cancer: preliminary results of the MRC
recommended randomised controlled surgical trial. The Surgical Cooperative Group. Lancet 1996;
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Dykewicz CA. Summary of the guidelines for preventing opportunistic 12. Songun I, Putter H, Kranenbarg EM et al. Surgical treatment of gastric cancer:
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13. Jiang L, Yang KH, Guan QL et al. Survival and recurrence free benefits with
different lymphadenectomy for resectable gastric cancer: a meta-analysis. J Surg
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patients who are candidates for further chemo- or radiotherapy 14. Dikken JL, van Sandick JW, Allum WH et al. Differences in outcomes of oesophageal
[IV, B]. and gastric cancer surgery across Europe. Br J Surg 2013; 100: 83–94.
The aggressive nature of gastric cancer, and historically poor 15. Memon MA, Khan S, Yunus RM et al. Meta-analysis of laparoscopic and open
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16. Haverkamp L, Weijs TJ, van der Sluis PC et al. Laparoscopic total gastrectomy
concept of survivorship is only now beginning to evolve. Long- versus open total gastrectomy for cancer: a systematic review and meta-analysis.
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the experts and the ESMO faculty.
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observation after curative gastric cancer resection. J Clin Oncol 2012; 30:
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conflict of interest 21. Dikken JL, Jansen EP, Cats A et al. Impact of the extent of surgery and
Dr Allum has received speaker’s honoraria for conferences and postoperative chemoradiotherapy on recurrence patterns in gastric cancer. J Clin
workshops from Lilly, Nestle and Astellas Oncology. Prof. Oncol 2010; 28: 2430–2436.
22. Kim S, Lim DH, Lee J et al. An observational study suggesting clinical benefit for
Cunningham has reported advisory board of Amgen and Roche
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Pharmaceuticals; research funding from Amgen, Celgene, gastric resection with D2 nodal dissection for adenocarcinoma of the stomach. Int
Novartis, Roche and Sanofi. Prof. Arnold has reported research J Radiat Oncol Biol Phys 2005; 63: 1279–1285.
grants from Roche and Sanofi. The other authors have reported 23. Lee J, Lim do H, Kim S et al. Phase III trial comparing capecitabine plus cisplatin
no potential conflicts of interest. versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in

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Annals of Oncology clinical practice guidelines
completely resected gastric cancer with D2 lymph node dissection: the ARTIST 36. Roy AC, Park SR, Cunningham D et al. A randomized phase II study of PEP02
trial. J Clin Oncol 2012; 30: 268–273. (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally
24. Zhu WG, Xua DF, Pu J et al. A randomized, controlled, multicenter study advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma.
comparing intensity-modulated radiotherapy plus concurrent chemotherapy with Ann Oncol 2013; 24: 1567–1573.
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Volume 24 | Supplement 6 | October 2013 doi:10.1093/annonc/mdt344 | vi