Current Management of Gastrointestinal Stromal Tumor (GIST) Joint Hospital Surgical Grand Round Dr. Tony Cheung PYNEH.

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!