current management of gastrointestinal stromal tumor (gist) joint hospital surgical grand round dr....
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Current Management of Gastrointestinal Stromal Tumor (GIST)
Joint Hospital Surgical Grand Round
Dr. Tony Cheung
PYNEH
Gastrointestinal Stromal Tumor Neoplasm of interstitial Cajal cells 3000-6000 cases/ year in the US Equal prevalence in male and female
Site of origin of GIST
3%2%
5%
30%
60%
StomachSmall intestineRectumEsophagusOther abdominal locations
Landmark discovery
1998 Majority of GIST have oncogenic gain-of-function
mutations of the KIT receptor tyrosine kinaseHirota S et al. Science 1998;279:577–580.
2001 Imatinib (Gleevec)
KIT tyrosine kinase inhibitor (TKI)
Joensuu et al. N Engl J Med 2001;1052:1052–1056.
CXR
OGD
EUS
CT
PET
Investigations CXR OGD EUS
look for size, irregular borders, echogenic foci, cystic spaces
Gastrointest Endosc 2003;57: 469–474. Med Clin North Am 2005;89:139–158, viii.
Contrast CT for size and anatomical location determine features of GIST – well vascularized, necrotic ce
ntre, heterogeneous appearance PET
identify metastatic disease monitor response to medical tx
Risk Stratification of GIST Miettinen et al. Am J Surg Pathol 2005;29:52–68.
Classification Size Mitotic rate (/50 HPF)
Prognosis
Benign ≤ 2cm ≤ 5 No tumor related mortality
Very low malignant potential
2-10cm < 5 < 3% recurrence
Uncertain or low malignant potential
≤ 2cm > 5 No reported recurrence
Low to moderate malignant potential
> 10cm
or
2-5cm
≤ 5
or
> 5
12-15%
High malignant potential > 5cm > 5 49-86%
Management
Primary GIST
Advanced / Metastatic GIST
Localized GIST
Goal of operation Complete macroscopic resection with an intact ps
eudocapsule Negative microscopic margin (R0 resection)
If tumor rupture associated with high risk of intraabdominal dissemination of tumor cells and recurrence
However, no additional benefit of wide resection of gastric GIST to obtain generous negative resection margin
Laparotomy
OR
Laparoscopy
Laparotomy
R0 resection options Wedge resection, segmental resection Extensive resection En bloc contiguous visceral resection
Method of choice for all non-gastric GISTs
Laparoscopy
< 5cm tumor for stomach GIST Laparoscopic wedge resections of stomach G
IST Otani et al. Surgery 2006;139(4):484–492.
No series on long term outcome with laparoscopy for non-stomach GIST
adapted from Otani et al. Surgery 2006;139(4):484–492.
But… 5-year overall survival despite negative re
section margin 42-52%Crosby et al. Ann Surg Oncol 2001;8(1):50–59.
Neoadjuvant or adjuvant Neoadjuvant or adjuvant use of tyrosine kinase inuse of tyrosine kinase inhibitorshibitors
Advanced / Metastatic GIST
1. Imatinib alone
2. Imatinib + Cytoreductive surgery
Nature of GIST
Metastatic spread peritoneal cavity liver uncommonly regional lymph nodes
Large GISTs tend to displace rather than invade adjacent organsMiettinen et al. Am J Surg Pathol 2005;29:52–68.
Imatinib alone
Outcome1. Response
2. Primary resistance
3. Secondary resistance
Treatment response of Imatinib for Advanced unresectable GIST
Trial Phase Dose Objective response (PR + CR, %)
Tumor control (PR + CR, %)
EORTC I 400-800mg 63 90
EORTC II 400mg BD 71 89
EORTC III 400mg daily 50 82
EORTC III 400mg BD 54 86
US-Finnish II 400mg daily 66 83
US-Finnish II 600mg daily 66 83
US-Canadian
III 400mg daily 48 75
US-Canadian
III 400mg BD 48 74
Time response to Imatinib Verweij et al. Lancet 2004;364(9440):1127–1134.
Overall survival using Imatinib Verweij et al. Lancet 2004;364(9440):1127–1134.
Response
Overall disease control in 70-85% of patient
Median progression-free survival is 20-24 months
Overall survival time following imatinib therapy > 36 months
Primary resistance / Secondary resistance
Do not achieve stable disease
Progress within 6 months of initial objective response
Develop one or more sites of disease progression after 6 months of measurable benefit
Imatinib then surgery
Recommended timing: 1. when maximal response to TKI observed
2. after at least 6 months of TKI treatment
• Optimal time interval from start of TKI to surgery is unclear
• Minimal tumor shrinkage noted after 9 months of imatinibDeMatteo et al. Ann Surg 2007;245(3):347–352.
Resection rates during surgery for advanced GIST after TKI therapy
High rate of R0/ R1 after TKI therapy
• Surgical candidates• ongoing response • limited disease progression• evolving necrosis or impending emergency
• Non surgical candidates• generalized progression
Surveillance
Surveillance CT thorax/ abdomen/ pelvis q3-6months for 1st 5 years, then annually
PET not routinely needed
Chandrajit et al. J Gastrointest Surg (2008) 12:1592–1599
NCCN guideline Feb 2008
Thank you!