GIST FRCR CO2A Flashcards
(92 cards)
1
Q
MC site for GIST
A
stomach
small intestine
2
Q
origin of GIST
A
interstitial cells of Cajal (responsible for gut motility)
3
Q
RFs for GIST
A
- Sporadic
- familial GIST , inherited mutation in KIT
4
Q
Syndromes a/w GIST
A
- Carney Triad
- Carney Stratakis Syndrome
- Type I NF
- Von Reclinghausen
5
Q
carney Triad
A
young females
Triad of
1. gastric GIST
2. Paraganglioma
3. Pulmonary Chondroma
6
Q
mutations in GIST
A
KIT (CD 117) 75 to 80%
s/times KIT - PDGFRA +
s/times no detectable mutations (syndromes)
7
Q
histological feature of GIST
A
submucosal
grow endophytically
well circumscribed, whorled, fibroid like
larger lesions: cystic degeneration
8
Q
CD117 + tumors
A
Melanoma
Angiosarcoma
Seminoma
9
Q
who should not be Rx with Imatinib
A
PDGFRA mutated GIST
10
Q
How does GIST spread?
A
local spread
rarely through LNs
mets: Liver, lung peritoneum bone etc
11
Q
presentation of GIST
A
emergency with intestinal H’ge or obstruction
Bleeding (50%)
Pain (25 %)
GI obstruction ( 10 to 30 %)
Asymptomatic in 25 to 30%
12
Q
Investigations for staging
A
CT Thorax Abdomen and pelvis
13
Q
is percutaneous Bx advised for GIST?
A
No, risk of necrotic tumor leakage from the biopsy site
14
Q
Staging for GIST
A
localized and metastatic
LN +: metastatic
15
Q
Risk Stratificaiton for GIST
A
Tumor Size and Mitotic Rate
16
Q
when is adjuvant therapy with Imatinib started
A
High risk of recc, as per stratification
17
Q
SOC for inoperable or if residual/metastatic disease GIST
A
Imatinib
18
Q
WHat’s the primary aim of Sx in GIST?
A
complete resection while avoiding tumor rupture
19
Q
Margin for Tumor > 2cm
A
WLE with margin of 1 to 2 cm
20
Q
Lymphadenectomy in GIST?
A
Not required
21
Q
Small tumors <2 cm
A
controversial management
Resection, if not, re imaged at 6 and 12 months with a CT or EUS
22
Q
Duration of Imatinib in adjuvant setting?
A
3 yrs (scandinavian German Study)
23
Q
Indications of Imatinib in GIST
A
CD 117 (KIT) +
inoperable recurrent or metastatic
24
Q
Baseline Investigations b4 Imatinib
A
FBC
LFT
RFT
avoid pregnancy and breast feeding
look for drug interaction via p450 system
25
how to take imatinib
400 mg PO OD Continuously
taken with a large glass of water (to avoid gastric irritation)
Avoid Caffeine and grapefruit for 1 hr b4 and after receiving the dose
avoid lying down for 1 hr afterward
26
Monitoring of pt on imatinib
2 wks post starting
LFT/CBC, assess toxicity and weight
repeat at 4 to 6 weeks
27
when is response assessment done after starting imatinib
@ 3 months with PET CT
28
Why should weight of pt on imatinib be monitored
to assess fluid retention
29
S/Es of Imatinib
1. Nausea and Vomiting
2. Fluid Retention
3. Diarrhoea and dyspepsia
30
How is fluid retention treated?
Diuretic therapy
if severe, stop imatinib
31
when altered LFT requires imatinib termination?
Bil > 3 x ULN
ALT/AST > 5 x ULN
32
should gi bleeding stop imatinib
it occurs often due to response and tumor regression
33
2nd L post imatinib
Sunitinib
34
reason for resistance to imatinib
secondary mutations
35
Dose of sunitinib
50 mg D1 to D 28, gap of 2 weeks
36
Dose reduction of sunitinib
if intolerant, 37.5 mg every day
37
TOXICITIES OF SUNITINIB
1. fatigue, diarrhoea, nausea and skin discoloration
2. Thyroid dysfunction, HTN, mucositis, PPE, hepatic and cardiac toxicities including cardiomyopathy and arrhytmias
38
monitoring of pts on sunitinib
Regular blood tests
Regular BP
Thyroid Function
39
other Rx options in GIST, advanced
dose escalation of imatinib upto 800 mg daily
40
imaging for response assessment
CT Scan
41
R1 resection
re-resection if not possible, adjuvant imatinib
42
NA imatinib?
not standard
may have a role in borderline resectable cases
43
F/U imaging frequency
1. all pts should have a CT scan at 3 months post Surgery
Very Low Risk : no further CT, annual review
Low Risk: CT @ 12 months, thereafter if clinically indicated
Intermediate RISK: CT @ 9 months and then annual for 5 yrs
High RISK: Adjuvant therapy and CT every 6 months for 3 yrs then annual for 5 yrs, Clinical review every 6 months
44
What does GIST stand for?
Gastrointestinal stromal tumour
## Footnote
GISTs are a specific type of tumour found in the gastrointestinal tract.
45
What type of cancer do GISTs belong to?
Soft tissue sarcomas
## Footnote
GISTs are classified as a rare subgroup within soft tissue sarcomas.
46
Where can GISTs occur?
Anywhere in the gastrointestinal tract
## Footnote
GISTs can be found throughout the entire gastrointestinal system.
47
What genetic mutation is associated with familial GIST syndrome?
Germ-line mutations in the KIT gene
## Footnote
Familial GIST syndrome features genetic alterations that can be inherited.
48
How do rare pediatric cases of GISTs typically differ from adult cases?
They are usually wild type with no KIT mutation
## Footnote
Pediatric GISTs may present differently and often have a less aggressive nature.
49
What is the typical clinical course of pediatric GISTs?
More indolent course
## Footnote
Pediatric GISTs generally progress more slowly compared to other types.
50
Large gastric GIST (shown by arrows) arising from the
greater curvature of the stomach.
51
What is the most common site for GISTs?
Stomach (50%)
## Footnote
Other common sites include small bowel (25%), colon (10%), and other sites.
52
What are common presentations of GISTs?
Anaemia or abdominal mass
## Footnote
Abdominal pain can occur with larger tumours.
53
What is the most common pattern of spread for GISTs?
Liver metastases
## Footnote
Other patterns include peritoneal metastases, with bone and lung metastases being rare.
54
What is the morphology of GISTs?
Spindle cell (70%), epithelioid (20%), mixed type (10%)
## Footnote
95% of GISTs express c-KIT or the CD117 antigen.
55
In what percentage of GIST cases do mutations in the KIT gene occur?
Over 90%
## Footnote
Mutations involve exon 11 (66%), 9 (13%), 13 (1.2%), and 17 (0.6%).
56
What is the association of PDGFRA gene mutations in GISTs?
Occurs in 7% of cases, more frequently associated with epithelioid morphology
## Footnote
Usually occurs in the stomach and tends to be indolent.
57
What factors relate to the malignant potential of GISTs?
Size of the tumour, mitotic rate, location of the primary
## Footnote
Described in the NIH consensus criteria.
58
What is the definitive curative treatment for GISTs?
Resection of the primary tumour in the absence of metastases
## Footnote
High risk (and intermediate risk) tumours are at risk of relapse after a clear resection.
59
What is imatinib?
An oral tyrosine kinase inhibitor (TKI)
## Footnote
Blocks signalling via KIT by binding to the ATP-binding pocket essential for phosphorylation and activation of the c-KIT receptor.
60
What is the initial treatment for patients with metastatic disease?
Imatinib 400 mg per day
## Footnote
Patients with inoperable primary tumours without metastases may become operable with imatinib.
61
What is the median time to progression for metastatic disease on imatinib?
2 years
## Footnote
Treatment should be continued without a break until progression, except for toxicity.
62
True or False: Interrupting imatinib treatment is associated with progression of GIST.
True
## Footnote
It has been shown that interrupting treatment leads to progression.
63
GIST Risk Stratification
64
65
Which primary sites of GISTs are more aggressive?
Duodenal and small bowel GISTs are more aggressive than those arising in the stomach.
66
Which exon mutations are associated with a more aggressive course in GISTs?
Mutations in Exon 9 are associated with a more aggressive course than Exon 11.
67
What codon mutations are linked to a higher risk of metastases?
Mutations within codons 562–579 and 557–558 are associated with a higher risk of metastases.
68
What is the correlation between c-KIT or PDGFR mutation location and response to TKIs?
There is a correlation between mutation location and response to imatinib or sunitinib.
69
What is the response rate to imatinib for patients with an exon 11 mutation?
67–84% response rate.
70
What is the response rate to imatinib for patients with an exon 9 mutation?
40–48% response rate.
71
What is the response rate to imatinib for patients without a c-KIT mutation?
0–39% response rate.
72
What is the average duration of response to imatinib for exon 11 mutations?
576 days.
73
What is the average duration of response to imatinib for exon 9 mutations?
308 days.
74
What is the average duration of response to imatinib for patients without a mutation?
251 days.
75
What dose of imatinib has shown greater benefit for patients with exon 9 mutations?
800 mg per day.
76
What is the most common PDGFRA mutation that is resistant to imatinib?
D842V.
77
Which treatment has been shown to be more effective against exon 9 mutant GIST?
Sunitinib.
78
True or False: Secondary mutations that confer resistance to imatinib occur more commonly after prolonged exposure.
True.
79
What is a significant benefit of sunitinib compared to standard dose imatinib?
More effective against exon 9 mutant GIST.
80
Fill in the blank: Patients with exon 11 mutations have a greater chance of response to imatinib at a dose of _______.
400 mg per day.
81
What percentage of cases may achieve temporary control of disease with a progression dose escalation to 800 mg per day?
30–35%
82
What is the median time to progression when escalating the dose to 800 mg per day?
4 months
83
What treatment options may be considered for patients with isolated liver metastasis who have responded to imatinib?
* Local hepatic resection
* Radiofrequency ablation
84
What type of inhibitor is sunitinib malate?
Multi targeted TKI
85
What is the median progression-free survival for patients on sunitinib who have progressed on imatinib?
6 months
86
What percentage of patients achieved a partial response or stable disease on sunitinib?
68%
87
What imaging technique is commonly used to assess response in GIST?
CT scan
88
What alternative imaging technique can detect reduction in tumor activity within days of commencing imatinib?
FDG-PET
89
What is a limitation of RECIST criteria in assessing response in GIST tumors?
May not be the only measure of response
90
Who described alternative criteria to evaluate GIST response?
Choi
91
What percentage reduction in tumor density or unidimensional reduction in tumor size is a better predictor of response than RECIST?
* 15% reduction in tumor density
* 10% unidimensional reduction in tumor size
92
What do Choi's alternative criteria correlate better with compared to RECIST?
Survival
