CES202002 - 09 - Cáncer de esófago y estómago

Cáncer de esófago y estómago

Temario
• Cáncer de esófago
• Cáncer de estómago

Objetivo
• Obtener un conocimiento GENERAL del manejo USUAL de pacientes
con las patologías a discutir desde la sospecha diagnóstica, hasta el
las pautas de seguimiento post-tratamiento, pasando por los aspectos
más relevantes de tratamientos con intención curativa.

Cancer New cases (World) Deaths (World) New cases (Colombia) Deaths (Colombia)
Breast 2’088.849 (2) 626.679 (5) 13.380 (1) 3.702 (4)
Prostate 1’276.106 (4) 358.989 (8) 12.712 (2) 3.166 (5)
Lung 2’093.876 (1) 1’761.007 (1) 5.856 (5) 5.236 (2)
Stomach 1’033.701 (5) 782.685 (3) 7.419 (4) 5.505 (1)
Colon & rectum 1’849.518 (3) 880.792 (2) 9.140 (3) 4.489 (3)
Lymphoma (NH) 509.990 (10) 248.724 (11) 4.170 (6) 1.676 (10)
Uterine cérvix 569.847 (8) 311.365 (9) 3.853 (7) 1.775 (9)
Leukemia 437.003 (12) 309.006 (10) 3.126 (8) 2.192 (7)
Ovarian 295.414 (17) 184.799 (14) 2.414 (9) 1.252 (11)
Pancreas 458.918 (11) 402.232 (7) 2.311 (10) 2.142 (8)
Liver 841.080 (6) 781.636 (4) 2.279 (11) 2.216 (6)
Multiple mieloma 159.885 (21) 106.105 1323 (14) 806 (14)
Esophagus 572.034 (7) 508.585 (6) 922 (15) 710 (15)
Hodgkin 79.999 (25) 26.167 743 (16) 216
Brain 296.851 (16) 241.037 (12) 1884 (12) 1.176 (12)
Gallbladder 219.420 (19) 165.087 (17) 1657 (13) 1.104 (13)
All 18’078.957 9’555.027 101.893 46.057
http://gco.iarc.fr/today/

http://bit.ly/2v8zXA3
Tipo Mundo Estados Unidos Colombia
Incidencia Mortalidad Incidencia Mortalidad Incidencia Mortalidad
Todo 197 101 351 91 178 79
Mama 46.3 13.0 84.0 12.6 44.0 11.9
Colo-rectal 19.7 8.9 25.9 8.3 15.8 7.6
Pulmón 22.6 18.6 34.8 22.2 10.1 9.0
Próstata 29.3 7.6 74.6 7.7 49.8 12.0
Esófago 6.3 5.5 3.3 2.5 1.6 1.2
Estómago 11.1 8.2 4.1 1.8 12.8 9.4
Cérvix 13.1 6.9 6.5 1.9 12.7 5.7
Endometrio 8.4 1.8 20.3 3.0 5.2 1.1
Ovario 6.6 3.9 8.5 4.1 8.0 4.1
Hígado 9.3 8.5 6.7 4.9 3.9 3.8
Páncreas 4.8 4.4 7.6 6.5 4.0 3.7
Incidencia y mortalidad por cáncer en el Mundo, Estados
Unidos y Colombia
GLOBOCAN - 2018
/100.000 habitantes-año

Esophageal and Gastro-
esophageal cancer

Lagergren J, Lancet, 2017https://www.thelancet.com/clinical/diseases/oesophageal-carcinoma

Mundo Estados Unidos Colombia
6.3 5.5 3.3 2.5 1.6 1.2
Incidencia y mortalidad por cáncer en el Mundo, Estados Unidos y
Colombia –
Tipo: Esófago
GLOBOCAN - 2018
Incidencia (USA/Colombia): 2x
Mortalidad (USA/Colombia): 2x

Esophageal and gastro-esophageal junction carcinomas
Domper Arnal MJ, W J Gastroenterol, 2015; https://www.nccn.org
Genetic susceptibility Recommendations Gene
Tylosis and non-epidermolytic palmo-plantar keratosis
and Howel Evans Syndrome
UGI endoscopy begining at age 20 RHBDF2
Familial Barrett’s esophagus UGI endoscopy Unknown
Bloom syndrome UGI endoscopy begining at age 20 BLM/RECQL3
Fanconi syndrome Screening UGI endoscopy FANCD1, BRCA2, FANCN (PALB2)
Risk factors Squamous Adenocarcinoma
Geography Southeastern Africa, Asia, Iran,
South america
Western Europe, USA, Australia
Race Black White
Gender Male (6:1) Male (3:1)
Alcohol ++++ -
Tobacco ++++ ++
Obesity - +++
GERD - ++++
Diet: low fruits and vegetables ++ +
Socioeconomic conditions ++ -
Genetic aspects ++ +

Workup Comment 1 Comment 2
H&P
Upper GI endoscopy and biopsy
Chest/abdominal CT
Pelvic CT with contrast If clinically indicated
FDG PET-CT If no evidence of M1 disease
CBC and Chemistry
Endoscopic ultrasound If no evidence of M1
MSI-H/dMMR If metastatic disease suspected or documented
Her2 / PD-L1 If metastatatic disease suspected or documented Only in adenocarcinoma
Bronchoscopy If tumor above the carina with no evidence of M1
Assign Siewert category GEJ tumors (lower esoph, cardial – true GEJ, subcardial 5 cm to 1 cm, above; +1 to -2 cm; and -2 to -5 cm
Smoking cessation counseling
Nutritional assessment
Screen for family history
https://www.nccn.org

+5 cm
+1 cm
-2 cm
-5 cm
S1
S2
S3

Adenocarcinoma

Clinical suspicion
Mechanic dysphagia
GERD Barrett’s esophagus
UGI endoscopy /
Biopsy
Weight-loss

Clinical suspicion
Mechanic dysphagia
GERD Barrett’s esophagus
UGI endoscopy /
Biopsy
TNM/Stage
Very-early
(Tis/T1a)
Early (pT1b)
Locally advanced 1
pT2-T4a N0 or N+
Locally advanced 2
T4b N0/N+
Metastatic
Weight-loss

Very-early
(Tis/T1a)
Early (pT1b)
Locally advanced 1
pT1b-T4a N0 or N+
Locally advanced 2
T4b N0/N+
Metastatic
Endoscopic
resection
Esophagectomy
Pre-operative chemo-
radiotherapy
Definitive chemo-
radiotherapy
Palliative
chemotherapy
CROSS: Paclitaxel + Carbo + RT (41 GyI Ox/Cis-platin + FU + RT (50 Gy)
Squamous-cell esophageal carcinoma
N0 N1 N2 N3 M1
Tis/T1a 0/I I III IVa IVb
T1b I I III IVa IVb
T2 II II III IVa IVb
T3 II III III IVa IVb
T4a IVa IVa IVa IVa IVb
T4b Iva IVa IVa IVa IVb

Esophageal carcinoma (including GEJ)
CROSS: ChemoRT – followed by surgery vs Surgery
RT (41.3 Gy)
Carboplatin AUC 2 qW x5
Paclitaxel 50 mg/m2 qW x5
4-6 weeks
Surgery
Van Hagen, NEJM, 2012
T1N1 or T2-3N0-1 and no clinical evidence of metastatic spread (M0)
SCC: Squamous-cell carcinoma
AC: Adenocarcinoma

Very-early
(Tis/T1a)
Early (pT1b)
Locally advanced 1
pT1b-T4a N0 or N+
Locally advanced 2
T4b N0/N+
Metastatic
Endoscopic
resection
Surgery
Peri-operative
chemotherapy
Peri-operative
chemotherapy
Palliative
chemotherapy
FLOT4: Docetaxel + Oxaliplatin + FU FLOT4: Docetaxel + Oxaliatin + FU
Adenocarcinoma esophageal carcinoma
N0 N1 N2 N3 M1
T1b I I III IVa IVb

Gastric adenocarcinoma (including GEJ)
FLOT4: Perioperative chemotherapy in gastric cancer
FLOT4
- Fluoruracil + Folinate
- Oxaliplatin
- Docetaxel
Surgery
Al-Batran, Lancet, 2019
cT2 or higher or nodal positive stage (cN+), or both, resectable tumours, with no evidence of distant
metastases
FLOT4
- Fluoruracil + Folinate
- Oxaliplatin
- Docetaxel
Median OS: 50 months

Very-early
(Tis/T1a)
Early (pT1b)
Locally advanced 1
pT1b-T4a N0 or N+
Locally advanced 2
T4b N0/N+
Metastatic
Endoscopic
resection
Esophagectomy
Pre-operative chemo-
radiotherapy
Definitive chemo-
radiotherapy
Palliative
chemotherapy
CROSS: Paclitaxel + Carbo + RT (41 GyI Ox/Cis-platin + FU + RT (50 Gy)
Squamous-cell esophageal carcinoma
Very-early
(Tis/T1a)
Early (pT1b)
Locally advanced 1
pT1b-T4a N0 or N+
Locally advanced 2
T4b N0/N+
Metastatic
Endoscopic
resection
Surgery
Peri-operative
chemotherapy
Peri-operative
chemotherapy
Palliative
chemotherapy
FLOT4: Docetaxel + Oxaliplatin + FU FLOT4: Docetaxel + Oxaliatin + FU
Adenocarcinoma esophageal carcinoma

TNM/Stage Preferred initial therapy Alternative
cTis-cT1a cN0 cM0 Endoscopic resection Esophagectomy
pT1b cN0 cM0 Esophagectomy
cT1b/T2 cN0 – Low-Risk, <2 cm, Well- differentiated Esophagectomy Preoperative chemo-RT
cT1b-cT4a cN0-N+ Preoperative chemo-RT* Definitive chemo-RT**
cT4b cN0-N+ Definitive chemo-RT
Metastatic disease Palliative chemotherapy
Squamous-cell carcinoma of the esophagus (non-cervical, including Siewert I GEJ carcinoma)
*Carboplatin + Paclitaxel; **Cisplatin + Fluorouracil
cTis-cT1a cN0 cM0 Endoscopic resection Esophagectomy
pT1b cN0 cM0 Surgery
cT2-cT4a cN0-N+ Perioperative Chemo* Preoperative chemo-RT**
cT4b cN0-N+ Perioperative Chemo* Preoperative chemo-RT**
Adenocarcinoma of the esophagus (GEJ carcinoma)
*FLOT: Docetaxel + Oxaliplatin + FU; **Carboplatin + Paclitaxel

Sequelae Comment 1 Comment 2
Malnutrition Malabsorption Weight monitoring/ profesional counseling Measure vitamins B and D, folic and Calcium
Delayed gastric emptying Small portions (5 small meals/day) Avoid high fat and fiber
Dumping syndrome Small portions (5 small meals/day) Consume high fiber/protein, low in simple carbs/sweets
Reflux symptoms Avoid lying flat / avoid full prone position Consider PPI
Dysphagia Evaluate anatomic stricture
Follow-up Usual care Comments
Surveillance strategy q3-6 mo x1-2 yr; q6-12 mo for 3-5 yr, then q1-yr
Imaging and UGI endoscopy as clinically indicated
Duration of follow-up: 5 years

Prognosis 5-yr
Overall survival (All) 19.2%
Early 45%
Locally-advanced 23%
Metastatic 4%

Mundo Estados Unidos Colombia
11.1 8.2 4.1 1.8 12.8 9.4
Incidencia y mortalidad por cáncer en el Mundo, Estados Unidos y
Colombia –
Tipo: Estómago
GLOBOCAN - 2018
Incidencia (USA/Colombia): 0.3x
Mortalidad (USA/Colombia): 0.2x

Workup Comment 1 Comment 2
H&P
Upper GI endoscopy and biopsy
Chest/abdominal CT
Pelvic CT with contrast If clinically indicated
FDG PET-CT If no evidence of M1 disease
CBC and Chemistry
Endoscopic ultrasound If no evidence of M1
MSI-H/dMMR If metastatic disease suspected or documented
Her2 / PD-L1 If metastatatic disease suspected or documented
Bronchoscopy If tumor above the carina with no evidence of M1
Assign Siewert category GEJ tumors (lower esoph, cardial – true GEJ, subcardial 5 cm to 1 cm, above; +1 to -2 cm; and -2 to -5 cm
Smoking cessation counseling
Nutritional assessment
Screen for family history
Stomach cancer

Clinical suspicion
Dyspepsia
Hematemesis Melena
UGI endoscopy /
Biopsy
TNM/Stage
Very-early
(Tis/T1a)
Locally advanced
(cM0)
Metastatic
(cM1)
Weight-loss

Muestra: 33 últimos pacientes
-Corte: 01/2020
Distribución por estadíos y subtipo a la presentación en
pacientes con cáncer gástrico
MLM
Estadío N %
Intestinal 16 48
Difuso 15 46
N/A 2 6
Estadío N %
I 2 6
II 4 12
III 14 42
IV 13 40

Very-early
(Tis/T1a)
Locally advanced
(cM0)
Metastatic
(cM1)
Endoscopic
resection/surgery
Perioperative
chemotherapy
Palliative
chemotherapy
FLOT4: Docetaxel + Oxaliplatin + FU
N0 N1 N2 N3 M1
T1b I I III IVa IVb

cTis-cT1a cN0 cM0 Endoscopic resection Surgery
cT1b-cT4b cN0-N+ Perioperative Chemo* Surgery followed by chemo** or chemo-RT***
*FLOT: Docetaxel + Oxaliplatin + FU; **XELOX: Capecitabine + Oxaliplatin; *** Fluorouracil / Folinic acid
Stomach carcinoma

Gastric cancer
Follow-up Usual care Comments
Surveillance strategy q3-6 mo x1-2 yr; q6-12 mo for 3-5 yr, then q1-yr
Imaging and UGI endoscopy as clinically indicated
Duration of follow-up: 5 years
Locally-advanced Chest/Abdomen and pelvic CT q6-12mo for 2-years, then every
year until year 5
Monitor B12 and Iron deficiency Gastrectomy

Stomach cancer
Prognosis 5-yr
Overall survival (All) 31%
Early 68%
Locally-advanced 30%
Metastatic 5.2%

Medicamentos para cáncer
gastrointestinal

Drug MOA Included in Main toxicities
Fluorouracil
+/- Folinic acid
Antimetabolite (inhibition of
thymidilate synthase)
Chemo-RT for esophageal, gastric and rectal cancer
Adjuvant therapy for colon and rectal cancer
FOLFOX-based regimens (for GEJ, gastric, colon and rectal cancer)
FOLFIRI-based regimens (for metastatic colorectal cancer)
Diarrhea
Mucositis
Myelosuppression
Capecitabine Pro-drug converted to FU inside
tumor cells
Chemo-RT for rectal cancer. Adjuvant therapy for GEJ, gastric, colon and
rectal cancer
XELOX-based regimens
Diarrhea
Hand-foot skin syndrome
Myelosuppression
Mucositis
Oxalipatin Similar to alkylating agents (anti
DNA agent)
FOLFOX
XELOX
Sensory-neuropathy
Myelosuppression
Nausea/vomiting
Irinotecan Topoisomerase I inhibitor (anti DNA
agent)
FOLFIRI-based regimens, especially in metastatic colorectal cancer Diarrhea,
Myelosuppression
Alopecia
Bevacizumab Anti VEGF monoclonal antibody Metastatic colon cancer in combination with chemotherapy Hypertension
Bleed
Delayed wound healing
Proteiunria
Cetuximab Anti EGFR monoclonal antibody Metastatic colon cancer alone, or in combination with chemotherapy
(requires RAS wild type)
Skin rash
Diarrhea
Hypomagnesemia
Ramucirumab Anti VEGFR monoclonal antibody Metastatic gastric cancer in 2nd-line, with paclitaxel Hypertension
Bleed
Delayed wound healing…
Trastuzumab Anti HER2 monoclonal antibody Metastatic Her2+ gastric adenocarcinoma Cardiotoxicity

CES202002 - 09 - Cáncer de esófago y estómago

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