The most frequent gastrointestinal
malignant tumors
R. Němeček
J. Tomášek, I.Kocáková, I.Kiss,
R. Obermannová, Š. Tuček
Masaryk Memorial Cancer
Institute
CLINIC OF COMPREHENSIVE CANCER CARE
LF MU, Brno
The most frequent cancers
- men
Dusek L. et al. Klin. Onkol 2014; 27 (Suppl 2): 2S19-2S39
The most frequent cancers
- women
Dusek L. et al. Klin. Onkol 2014; 27 (Suppl 2): 2S19-2S39
CRC: The 3rd most common malignancy worldwide I: 1 850 000/year, M: 880 000 / year
CRC:
Gastric
cancer:
5th most common malignancy worldwide.
3rd most common cause of death from malignancy worldwide
4th most common cause of death from malignancy worldwidePancreatic
cancer
Gastrointestinal malignancies
clinical symptoms
Colon:
• blood in the stool, episodes of rectal bleeding
(more common in right sided bowel cancers)
- asymptomatic patients - screening – faecal occult blood test
• changing of bowel habits - worsening constipation,
alternation of constipation and diarrhea
(more common in left sided bowel cancers)
Rectal cancer
• tenesmus
General symptoms:
• fatigue, weakness, anemia, loss of appetite, unintended
weight loss, cramping or abdominal pain …
CRC:
• often asymptomatic / nonspecific symptoms
• upper abdominal pain, nausea, heartburn, vomiting
• sense of fullness in the upper abdomen after the
eating of a small portion of meal
• loss of apetite (meat disgust)
• weight loss, fatigue…
• bleeding → haematemesis, melena
• anemia → fatigue, weakness, dyspnea…
Gastric cancer:
• NO SYMPTOMS in early stages
• typically diagnosed in advanced stage !!!
• pain in the upper abdomen or back
• obstructive jaundice
– skin, pale stool, dark urine
• fatigue, weakness
• unexplained weight loss
• nausea, vomitting ….(duodenal obstruction)
• diabetes mellitus …
Pancreatic cancer:
Difference?
12months
vs.
7 years
Pancreatic cancer (Ductal adenocarcinoma)
Pancreatic neuroendocrine
tumors
(3-5% pancreatic malignancies)
Diagnostic methods
Colonoscopy, sigmoideoscopy
(rectoscopy)
biopsy histology
Staging (extent of disease): TNM
• abdomninal and pelvic CT
• chest CT or chest X-ray
• preoperative staging of rectal cancer
– pelvic MRI and/or endoscopic ultrasound
• tumor markers: CEA, CA 19-9
Medical history, physical examination
Blood count, biochemistry, urinalysis
CRC:
• Gastroscopy
biopsy histology
Staging: TNM
• abdomninal and pelvic CT
• chest CT or chest X-ray
• tumor markers: CEA, CA 72-4
• History, physical examination
• Lab. tests: CBC , Blood Chemistry, Urinalysis
Gastric cancer:
• endoscopic ultrasound (EUS)
Fine Needle Aspiration Biopsy (cytology)
• ERCP – individual cases
Staging: TNM
• abdomninal and pelvic CT
• chest CT or chest X-ray
• tumor markers: CEA, CA 19-9
• History, physical examination
• Lab. tests: CBC , Blood Chemistry, Urinalysis
Pancreatic cancer
TNM classification:
Stadium I = small tumor, mostly N0, always M0
Stadium IV = M1
Stadium II a III = inbetween
e.g. CRC:
• St. II – T3,T4 a N0
• St. III –any T , N+
Histology
ADENOCACINOMA
= neoplasia of epithelial tissue (glandular origin)
CRC
- intestinal, mucinous …
- testing : MSI (early stages) / RAS status (metastatic)
Gastric cancer – Lauren classification:
- intestinal type (better prognosis)
- diffuse type (worse prognosis)
- testing: HER2 in advanced stages
Pancreatic cancer
- ductal adenocarcinoma (mostly)
GRADING = degree of differentiation = aggressiveness
G1- well differentiated x G3 - poorly differentiated
Treatment: Surgery
- complete surgical removal with adequate margins, mesocolon
dissection (minimal count of dissected lymph nodes = 12)
Colon: immediately
- hemicolectomy
– right
– left
Rectum: following neoadjuvant chemotherapy
- LAR = low anterior resection
- Abdominoperineal amputation (Miles) … permanent colostomy,
higher rate of sexual and urinary dysfunction
Primarily metastatic patients without symptoms of intestinal obstruction:
no surgery but systemic treatment immediately!
CRC - resection :
Right Left
- R0 resection = histologically negative margins
D1 lymphadenectomy includes only nodes adjacent to the stomach
D2 lymphadenectomy (hepatic, left gastric, celiac, and splenic arteries,
as well as those in the splenic hilum)
• Diffuse type – total gastrectomy
• Intestinal type - subtotal (partial) gastrectomy
(min 5cm proximal and distal)
Gastric cancer :
Resectability ˂ 20% cases
Head of the pancreas :
- Whipple surgery (hemipancreatoduodenectomy)
= remove part of the pancreas, part of the small
intestine and the gallbladder.
Body of the pancreas:
- total pancreatectomy
Tail of the pancreas:
- distal pancreatectomy
Pancreatic cancer :
Oncological therapy
- localized stage
Colon cancer:
- adjuvant chemotherapy (CHT) for 6 months in stage III
and in high risk patients with stage II CRC (low risk st. II only 3 months or no CHT)
- CHT : continuous administration of 5-FU more effective than bolus –FU
- Capecitabine = oral prodrug of 5-FU
- Addint oxaliplatine (FOLFOX4) demonstrated a significant improvement of
prognosis in stage III colon cancer patients
- No radiotherapy !!!
Rectal cancer:
- neoadjuvant concomitant chemo-radiotheraty (CH-RT) in risk patients
T3, T4 and/or N+ (EUS or MRI)
RT 50Gy throughout 5 weeks + capecitabine
- Surgery should be performed 6 to 8 weeks
after completion of chemoradiation
- adjuvant chemotherapy
CRC:
Neoadjuvant (preoperative) radiation
therapy in rectal cancer
Preoperative radiation therapy advantages:
– tumor down-staging
– increase chance of resectability
(possibly permitting the use of a sphincter-sparing
procedure)
– decrease the risk of local recurrence
– preoperative radiation therapy works better in
well-oxygenated tissues prior to surgery
Neoadjuvant chemotherapy :
– downstaging of the disease to increase the chance of resectability
– decrease micrometastatic disease burden prior to surgery
– reduce the rate of local and distant recurrences
– improve survival
Perioperative chemotherapy:
FLOT regimen (5-FU + LV + oxaliplatine + docetaxel)
FLOT…FLOT…FLOT… FLOT… surgery… FLOT… FLOT…FLOT…FLOT
(or FOLFOX – in case of frailty patients)
Adjuvant radiotherapy was associated with improvements in both
overall and relapse-free survival and reduction in locoregional
failure, but significant toxicity. Today – CHT = preffered option!
Gastric cancer: various treatment options
• adjuvant CHT (gemcitabine) …. total duration 5-6months
• since 2018 – adjuvant CHT FOLFIRINOX
(FU + oxaliplatin + irinotecan)
• adjuvant chemoradiotherapy – 5-FU based
(recently used only rarely)
• Risk of relapse …. up to 80-100% !!
Pancreatic
cancer :
Oncological treatment
of
advanced /metastatic disease
• Metastasis: liver, lung, peritoneal …. local relapse
• Metastatic disease regimens: 5-FU or capecitabine
– in combination with irinotecan (FOLFIRI regimen)
– in combination with oxaliplatin (FOLFOX / XELOX regimen)
Terms:
• „palliative“ x „curative“ therapy x „best supportive care “
• „cycle o chemotherapy“ x line of therapy“ („1st, 2nd, 3rd…“)
• Targeted therapy:
- anti EGFR – cetuximab, panitumumab
- anti VEGF – bevacizumab, aflibercept, ramucirumab
- multitargeted tyrosine kinase inhibitor : regorafenib
• Rectal cancer : palliative radiotherapy
Metastatic CRC:
MOÚ, Brno
Epidermal growth factor receptor (EGFR):
Monoclonal antibodies cetuximab and panitumumab
Vascular endothelial growth factor (VEGF):
bevacizumab, aflibercept, ramucirumab
Small tumor (1–2mm)
• avascular
Larger tumor
• vascular
• potential to metastasize
VEGF
angiogenic
switch
MOÚ, Brno
Effect of neoadjuvant chemotherapy/targeted anti-EGFR therapy
in patients with initially unresectable colorectal liver metastases.
Curative-intent resections of liver metastases have significantly
improved long-term survival, with acceptable postoperative
morbidity, including older patients.
MOÚ, Brno
Effect of neoadjuvant chemotherapy/targeted anti-EGFR therapy
in patients with initially unresectable colorectal liver metastases.
Curative-intent resections of liver metastases have significantly
improved long-term survival, with acceptable postoperative
morbidity, including older patients.
Chance to cure
Liver metastases treatment
• Surgery - the only potentially curative treatment
• Local ablative techniques:
- Radiofrequency ablation (RFA)
- Microwave ablation (MWA)
- Cryosurgery
- Percutaneous ethanol injection (PEI)
• chemoembolization (TACE)
• intra-arterial chemotherapy
infusion (liver)
• stereotactic radiotherapy (SBRT)
Liver ablation methods
• Radiofrequency ablation (RFA)
• Microwave ablation (MWA)
• Cryosurgery
• Percutaneous ethanol injection (PEI)
• Surgical procedures with palliative intent: wide local excision, partial
gastrectomy, total gastrectomy, gastrointestinal anastomosis, and bypass
• palliative CHT : 5-FU, cisplatin or oxaliplatin based (DDP/FU/FA or FOLFOX )
epirubicin, docetaxel
• Second line : taxans (paklitaxel / docetaxel) or irinotekan
• Targeted therapy:
- anti HER2 – trastuzumab (Herceptin) (1st line)
(HER2 positive – cca 20% patients)
- anti VEGF – ramucirumab (2nd line)
Gastric cancer - advanced
unresectable /metastatic:
1. 5-FU +oxaliplatine + irinotecan (FOLFIRINOX regimen)
2. Gemcitabine + nab-paclitaxel albumin-bound nanoparticle formulation
3. Gemcitabin monotherapy (worse PS, less toxicity)
• Targeted therapy:
- anti-EGFR: erlotinib ….. minimal benefit … not used !!
• Radiotherapy - palliative , locally advanced tumor
• Best Supportive Care (BSC) ….. optimal therapy in many patients
• very poor prognosis
Pancreatic cancer - advanced
unrecectable /metastatic :
The prognosis of metastatic disease
24 – 30 months
8- 16 months
6- 12 months
Median overall survival
(otherwise in good condition, best treatment)
Thank you for
your attention