CES2019-02: Cáncer gastrointestinal III - Visión del oncólogo

CES2019-02 – Cáncer gastrointestinal III – Visión
del oncólogo
Mauricio Lema Medina MD
@Onconerd

Topics
• Esophageal and gastroesophageal carcinomas
• Gastric cancer
• Colorectal cancer

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/

Esophageal and Gastro-
esophageal cancer

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

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

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%

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

Very-early
(Tis/T1a)
Locally advanced
(cM0)
Metastatic
(cM1)
Endoscopic
resection/surgery
Perioperative
chemotherapy
Palliative
chemotherapy
FLOT4: Docetaxel + Oxaliplatin + FU

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
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%
Metastatic 5.2%

Clinical suspicion
Hematochezia
Anemia Obstruction/perforation
LGI endoscopy /
Biopsy
TNM/Stage
Weight-loss

Workup Comment 1
H&P
Lower GI endoscopy and biopsy
Consider abdomino/pelvic MRI
CEA
Chest/abdomen/pelvic CT
CBC and Chemistry
Enterostomy planning
PET-CT NOT indicated
MSI/dMMR Especially in stages II and IV
RAS/BRAF genotyping Form stage IV disease
Colon cancer

Clinical suspicion
Hematochezia
Anemia Obstruction/perforation
LGI endoscopy /
Biopsy
TNM/Stage
Stage I and
low-risk II
High-risk
stage II
Stage III
Resectable stage IV
(M1a)
Unresectable
stage IV
Weight-loss
High risk stage II is defined by:
Less than 12 LN resected
Bowel obstruction
Bowel perforation
Grade 3 (in MSS)
Perineural, ymphatic or vascular involvement
Positive or close surgical margins

Stage I and
low-risk II
High-risk
stage II
Stage III
Resectable stage IV
(M1a)
Unresectable
stage IV
Surgery
Adjuvant
chemotherapy
Adjuvant
chemotherapy
Surgery, followed by
adj. chemotherapy
Palliative
chemotherapy
Chemotherapy regimens for non-metastatic disease
FOLFOX: Fluorouracil + Folinic acid + Oxaliplatin
XELOX: Capecitabine + Oxaliplatin
FULV: Fluorouracil + Folinic acid
In general, Oxaliplatin-based chemotherapy is preferred.
Exceptions: older and frail patients
Colon cancer

Stage I and
low-risk II
High-risk
stage II
Stage III
Resectable stage IV
(M1a)
Unresectable
stage IV
Surgery
Adjuvant
chemotherapy
Adjuvant
chemotherapy
Surgery, followed by
adj. chemotherapy
Palliative
chemotherapy
Chemotherapy regimens for metastatic disease
FOLFOX + (Bevacizumab or Cetuximab or Panitumumab)
FOLFIRI (Fluouracil + Folinate + Irinotecan) + (Bevacizumab or Cetuximab or Panitumumab)
XELOX + Bevacizumab
FULV + Bevacizumab: Fluorouracil + Folinic acid
Anti EGFR agents (Cetuximab and
Panitumumab) only active in RAS wild-type,
especially in left-sided colorectal cancer
Colon cancer

Workup Comment 1
H&P
Lower GI endoscopy and biopsy
Consider rigid proctoscopy
Pelvic MRI
CEA
Chest/abdomen CT
Endorectal ultrasound If MRI contraindicated
CBC and Chemistry
Enterostomy planning
PET-CT NOT indicated
MSI/dMMR Especially in stages II and IV
RAS/BRAF genotyping Form stage IV disease
Rectal cancer

T1 No T1-2 N0
T3, N any with clear
circumferental margin
(CRM) by MRI
T3 with involved CRM, T4,
unresectable (M0)
Unresectable
stage IV
Transanal
local excision
Transabdominal
resection
Pre-operative Chemo-RT, adjuvant Chemo (if Clear
CRM after re-staging)
Palliative
chemotherapy
Rectal cancer
Chemo-RT (with Capecitabine or
Fluorouracil-based chemo)
Surgery (at
week 7 post RT)
4-6 months of adjuvant chemotherapy with
Oxaliplatin-based chemo (FOLFOX/XELOX)
Typical course of a stage T3/T4 or N+ rectal cancer
Preoperative Chemo-RT decreases
Local recurrence decreases from 12% to 6% (compared to post-Op Chemo-RT)

Colorectal cancer
Stage I Colonoscopy at 1 y, repeat at 1 yr if advanced adenoma or 3 yr if
not; then, every 5 yr
Stage II / III H&P every 3-6 mo for 2 yr, then every 6 mo for a total of 5 y
CEA with every visit
Chest/abdomen/pelvic CT every 6-12 mo for a total of 5 yr
Colonoscopy (as stage I)
PET-CT is not indicated
Resected stage IV H&P every 3-6 mo for 2 yr, then every 6 mo for a total of 5 y
CEA with every visit
Chest/abdomen/pelvic CT every 6-12 mo for a total of 5 yr
Colonoscopy (as stage I)
Gastrectomy
Sequelae Main recommendations Comments
QoL Distress/pain, neuropathy, fatigue, sexual
dysfunction
Measure vitamins B and D, folic and Calcium
Chronic diarrhea/incontinence Antidiarrheal, bulk-forming agents Diet manipulation, protective undergarments
Management of an ostomy Small portions (5 small meals/day) Consume high fiber/protein, low in simple carbs/sweets
Reflux symptoms Support group Ostomy clinic
Oxaliplatin neuropathy Consider duloxetine (if painful, only) Heat, ice, acupuncture…

When to test for hereditary
colo-rectal cancer

Colorectal cancer
Prognosis 5-yr
Overall survival (All) 64%
Early 89%
Metastatic 13%

Chemotherapy agents
commonly used in
gastrointestinal oncology

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

CES2019-02: Cáncer gastrointestinal III - Visión del oncólogo

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