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Flashcards in Upper GI cancers Deck (49)
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1

Incidence & mortality rates of cancers in 2019

Incidence: 

  1. breast 
  2. prostate
  3. colorectal
  4. melanoma
  5. lung
  6. lymphoma
  7. head & neck with lip
  8. leukaemia
  9. kidney
  10. thyroid
  11. pancreas
  12. bladder
  13. uterine
  14. unknown primary
  15. liver
  16. stomach
  17. multiple myeloma
  18. brain
  19. oesophagus
  20. myelodysplastic syndrome
  21. ovarian
  22. non-melanoma of skin
  23. gallbladder
  24. cervical
  25. mesothelioma

Mortality

  1. lung
  2. colorectal
  3. prostate
  4. breast
  5. pancreas
  6. unknown primary
  7. liver
  8. leukaemia
  9. melanoma
  10. lymphoma
  11. brain
  12. oesophagus
  13. stomach
  14. bladder
  15. head & neck
  16. multiple myeloma
  17. ovarian
  18. kidney
  19. mesothelioma
  20. non-melanoma of skin
  21. uterine
  22. myelodysplastic syndrome
  23. other soft tissue
  24. gallbladder
  25. cervical 

2

incidence of pancreatic cancer

incidence is rising of unclear reason

 

By 2030, PDAC is predicted to be the 2nd leading cause of cancer related death

3

Functions of pancreas

 

  • Exocrine functions
    • Amylase
    • Lipase
    • Protease
  • Endocrine functions
    • Insulin 
    • Glucagon
    • Somatostatin
    • Pancreatic polypeptide

4

Types of pancreatic cancer

 

  • Adenocarcinoma (PDAC) 90%
  • Neuroendocrine (PanNET)
  • Lymphoma
  • Sarcoma

5

Px of pancreatic cancer

 

  • Predominantly adenocarcinoma
    • 60-70% originate from head of pancreas
    • Obstructive jaundice
  • Other symptoms can be non-specific:
    • Epigastric/ back pain
    • Fatigue
    • Anorexia
    • Weight loss
    • Malabsorption

Often presents late 

6

Why is prognosis of pancreatic cancer so poor?

vague symptoms -> late presentation

Aggressive biology

Desmoplastic stroma

Low immunogenicity

7

Ix of pancreatic cancer

 

  • Imaging
    • CT/MRI
    • MRCP
  • Tissue biopsy
    • Endoscopic ultrasound
    • CT guided biopsy
    • ERCP: cytology from scrapings of bile duct tract. diagnostic yield not high.  
  • Bloods
    • LFTs
    • Ca19-9

8

Mx of pancreatic adenocarcinoma

Depends if localised (40%) or metastatic (60%)

1. localised: 

  • resectable -> surgery + adjuvant chemo
  • borderline resectable -> neo-adjuvant therapy
  • unresectable -> unclear optimum strategy. Any role for downsizing, surgery, RFA, RT etc.

2. metastatic: 

  • oligometastatic disease: unclear optimum strategy. Any role for downsizing, surgery, RFA, RT etc.
  • disseminated disease: palliative chemotherapy 

9

Surgical mx of pancreatic cancer

Surgical goal = R0 resection 

1. Whipple's procedure

2. Pylorus-preserving pancreaticoduodenectomy (PPPD)

  • Similar to Whipple’s
  • Avoids removal of stomach or pylorus
  • Tail of pancreas joined onto small bowel or stomach

3. Distal pancreatectomy

 

adjuvant chemotherapy post surgical mx. 

10

Mx of advanced pancreatic disease

holistic care is important

  • biliary obstruction: stent, PTC
  • duodenal obstructoin: stent, palliative bypass
  • nutrition: dietitian input, creon
  • pain: analgesic ladder, coeliac plexus nerve block
  • hyperglycaemia/diabetes
  • nausea
  • psychological support; Male patients with pancreatic cancer have 11-fold increased risk of committing suicide vs. general population
  • advanced care planning; future admission, ceiling of care, preferred place of death. 
  • palliative care

11

SE of Nab-paclitaxel/gemcitabine in pancreatic cancer

increased overall survival compared to gemcitabine on its own

paclitaxel; a taxane. 

SE: Neutropenia, Fatigue, Nausea, Diarrhoea, Sensory neuropathy

gemcitabine usually well tolerated on its own

12

FOLFIRINOX use in pancreatic cancer

Improved OS & PFS with FOLFIRINOX compared to gemcitabine 

More grade 3-4 haematotoxicity, diarrhoea, neuropathy

13

Use of PARP inhibitors in pancreatic cancer

pancreatic cancer can be a/w BRCA1 or 2 mutations

In metastatic pancreatic cancer with BRCA1/2 mutations, who had 16 weeks of first line platinum chemotherapy with no limit to duration and without progression, PARP inhibitor (olaparib) improved PFS, but not OS. 

14

Px of hepatocellular carcinoma

 

  • Often detected at screening for management for cirrhosis
  • Non-specific symptoms
    • Weight loss
    • Fatigue
    • RUQ pain
    • Liver failure
    • Jaundice

15

Risk factors of hepatocellular carcinoma

 

  • Chronic liver disease
    • Viral hepatitis
    • EtOH
    • Autoimmune
  • Hepatitis B infection –non-cirrhotic
  • Obesity
  • Type II diabetes
  • NASH

16

Dx of hepatocellular carcinoma

  • History: risk factors, symptoms/signs for CLD including portal HTN. 
  • Bloods: aetiology of liver disease (hepB/C etc), liver function (PT, albumin, bilirubin), FBC (platelets), AFP
  • All liver cirrhotic patients
    • Ultrasound liver
    • Alpha-fetoprotein levels
  • Multiphasic CT/MRI
    • Non-contrast
    • Arterial phase
    • Washout in portal venous phase (2-5min post contrast)
  • CT CAP to rule out extrahepatic spread 
  • Biopsy?
  • Primary vs. metastatic cancer
  • Benign nodule?

17

Scoring system for cirrhosis

Child Pugh class

depends on encephlopathy, ascites, bilirubin, albumin, PT

18

Barcelona clinic liver cancer staging system

combines tumour stage + ECOG performance status

Stage A/0: singel tumour of any size or up to 3 nodules <3cm, preserved liver function, ECOG PS 0

Stage B: multinodular, preserved liver function, ECOG PS 0

Stage C: portal invasion, extrahepatic spread, preserved liver function, ECOG PS 1-2

Stage D: end stage liver function, ECOG 3-4. 

19

Loco-regional therapies for hepatocellular carcinoma

 

  • Ablation:  Radiofrequency, EtOH, microwave
  • Transarterial (chemotherapy) embolisation (TACE or TAE)
  • Stereotactic radiosurgery
  • Brachytherapy
  • SIRT (selective internal radiotherapy)
  • Surgical resection
  • Orthotopic liver transplantation

20

Principles of mx of hepatocellular carcinoma based on Barcelona clinic liver cancer (BCLC) staging

BCLC A: resection, ablation

BCLC B: LTx resection, TACE. If failed, systemic therapy

BCLC C: sorafenib, lenvatinib. Nivolumab. 

BCLC D: BSC

 

21

Sorafenib in hepatocellular carcinoma

- indication

- clinical significance

- SE

 

Multiple kinase inhibitors. 

  • 1st systemic therapy to demonstrate survival benefit
  • Child Pugh A 
  • Advanced HCC
  • improved OS
  • Most common toxicities
    • Diarrhoea
    • Hand-foot syndrome
    • Hypertension
  • Lenvatinib is non-inferior to sorafenib 

22

Immunotherapy in hepatocellular carcinoma

 

Atezolizumab (anti PD-L1 antibody) + bevacizumab (anti-VEGF antibody)

higher overall response rates with combination therapy

23

Molecular characteristics of gastric cancer

influenced by primary tumour location

 

Upper esophagus: ESCC

mid oesophagus: EBV

higher prevalence of tumours related to microsatellite instabilty lower in oesophagus & stomach, which responds to immunotherapy

body of stomach: diffuse histology. 

24

Px of gastric cancer

 

Dysphagia

Weight loss

Loss of appetite

Abdominal pain

Iron deficiency

25

Risk factors of gastric cancer

- environmental

- host

 

  • Environmental
    • Obesity
    • H. pylori infection
    • Salt intake
    • Epstein Barr virus infection
    • Cigarette smoking
  • Host factors
    • Barretts
    • CDH1 mutation (Hereditary diffuse gastric cancer)
    • Lynch syndrome (due to impaired DNA mismatch repair)
    • Polyposis syndromes –FAP, Peutz-Jeugers

26

Dx of gastric cancer

 

  • Endoscopy –often used to make primary diagnosis
  • EUS –can be useful in determining T-staging (depth) prior to surgery
  • CT chest abdomen pelvis –to assess for distant spread, quite poor for T-staging
  • PET/CT
  • Laparoscopy –rule out peritoneal disease, if considering resection

27

Prognosis for gastric cancer

 

- outcomes for metastatic gastric cancer is poor

- Surgery offers only realistic chance of cure

28

Surgical mx of gastric cancer

 

  • Surgery determined by location and extent of tumour
  • D2 lymphadenectomy resections
  • Common procedure in East Asia –more modern standard
  • Perioperative chemotherapy indicated Europe/Aus
  • Global variation in treatment strategy

FLOT4 (triplet chemotherapy) neoadjuvant & adjuvant therapy in gastric cancer/adenocarcinoma of gastro-oesophageal junction, non metastatic disease -> better overall survival & disease free survival but higher rates of diarrhoea, neutropaenia, peripheral neuropathy compared to ECF/ECX chemotherapy 

29

Palliative chemotherapy in gastric cancer

 

  • 1st line chemotherapy
    • Platinum/fluoropyrimidine doublet
      • Cisplatin + 5FU/capecitabine
      • FOLFOX (5FU/capecitabine + oxaliplatin)
    • +/- trastuzumab (HER2 overexpressing)
  • 2nd line chemotherapy
    • Irinotecan
    • Paclitaxel +/- ramucirumab (anti-VEGFR2)
  • 3rd line chemotherapy
    • Immunotherapy?
    • Trifluradine/tipiracil? 
    • Regorafenib?

30

Mx of HER2 positive gastric cancer

 

HER2 (IHC or FISH +ve) gastric cancer

Chemotherapy or Chemo + Trastuzumab

Improved median overall survival with addition of trantuzumab