GIST FRCR CO2A Flashcards
MC site for GIST
stomach
small intestine
origin of GIST
interstitial cells of Cajal (responsible for gut motility)
RFs for GIST
- Sporadic
- familial GIST , inherited mutation in KIT
Syndromes a/w GIST
- Carney Triad
- Carney Stratakis Syndrome
- Type I NF
- Von Reclinghausen
carney Triad
young females
Triad of
1. gastric GIST
2. Paraganglioma
3. Pulmonary Chondroma
mutations in GIST
KIT (CD 117) 75 to 80%
s/times KIT - PDGFRA +
s/times no detectable mutations (syndromes)
histological feature of GIST
submucosal
grow endophytically
well circumscribed, whorled, fibroid like
larger lesions: cystic degeneration
CD117 + tumors
Melanoma
Angiosarcoma
Seminoma
who should not be Rx with Imatinib
PDGFRA mutated GIST
How does GIST spread?
local spread
rarely through LNs
mets: Liver, lung peritoneum bone etc
presentation of GIST
emergency with intestinal H’ge or obstruction
Bleeding (50%)
Pain (25 %)
GI obstruction ( 10 to 30 %)
Asymptomatic in 25 to 30%
Investigations for staging
CT Thorax Abdomen and pelvis
is percutaneous Bx advised for GIST?
No, risk of necrotic tumor leakage from the biopsy site
Staging for GIST
localized and metastatic
LN +: metastatic
Risk Stratificaiton for GIST
Tumor Size and Mitotic Rate
when is adjuvant therapy with Imatinib started
High risk of recc, as per stratification
SOC for inoperable or if residual/metastatic disease GIST
Imatinib
WHat’s the primary aim of Sx in GIST?
complete resection while avoiding tumor rupture
Margin for Tumor > 2cm
WLE with margin of 1 to 2 cm
Lymphadenectomy in GIST?
Not required
Small tumors <2 cm
controversial management
Resection, if not, re imaged at 6 and 12 months with a CT or EUS
Duration of Imatinib in adjuvant setting?
3 yrs (scandinavian German Study)
Indications of Imatinib in GIST
CD 117 (KIT) +
inoperable recurrent or metastatic
Baseline Investigations b4 Imatinib
FBC
LFT
RFT
avoid pregnancy and breast feeding
look for drug interaction via p450 system
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
Monitoring of pt on imatinib
2 wks post starting
LFT/CBC, assess toxicity and weight
repeat at 4 to 6 weeks
when is response assessment done after starting imatinib
@ 3 months with PET CT
Why should weight of pt on imatinib be monitored
to assess fluid retention
S/Es of Imatinib
- Nausea and Vomiting
- Fluid Retention
- Diarrhoea and dyspepsia
How is fluid retention treated?
Diuretic therapy
if severe, stop imatinib
when altered LFT requires imatinib termination?
Bil > 3 x ULN
ALT/AST > 5 x ULN
should gi bleeding stop imatinib
it occurs often due to response and tumor regression
2nd L post imatinib
Sunitinib
reason for resistance to imatinib
secondary mutations
Dose of sunitinib
50 mg D1 to D 28, gap of 2 weeks
Dose reduction of sunitinib
if intolerant, 37.5 mg every day
TOXICITIES OF SUNITINIB
- fatigue, diarrhoea, nausea and skin discoloration
- Thyroid dysfunction, HTN, mucositis, PPE, hepatic and cardiac toxicities including cardiomyopathy and arrhytmias
monitoring of pts on sunitinib
Regular blood tests
Regular BP
Thyroid Function
other Rx options in GIST, advanced
dose escalation of imatinib upto 800 mg daily
imaging for response assessment
CT Scan
R1 resection
re-resection if not possible, adjuvant imatinib
NA imatinib?
not standard
may have a role in borderline resectable cases
F/U imaging frequency
- 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
