Recent advances in the management of gastrointestinal stromal tumor

Table 1 National Institute Health gastrointestinal stromal tumor consensus criteria

Risk category	Tumor size (cm)	Mitotic count per 50 HPF
Very low risk	< 2	< 5
Low risk	2-5	< 5
Intermediate risk	< 5	6–10
	5-10	< 5
High risk	>5	> 5
	> 10	Any mitotic rate
	Any size	> 10

HPF: High power field.

Table 2 Joensuu criteria for gastrointestinal stromal tumor risk assessment

Risk category	Tumor size (cm)	Mitotic index (per 50 HPF)	Primary tumor site
Very low	< 2	≤ 5	Any
Low	2.1-5	≤ 5	Any
Intermediate	2.1–5	> 5	Gastric
	< 5	6–10	Any
	5.1-10	≤ 5	Gastric
High	Any	Any	Tumor rupture
	> 10	Any	Any
	Any	> 10	Any
	> 5	> 5	Any
	2.1–5	> 5	Non-gastric
	5.1-10	≤ 5	Non-gastric

HPF: High power field.

Table 3 American Joint Committee on Cancer tumor node metastasis system for gastric and omental gastrointestinal stromal tumor

Stage	TNM	Mitotic rate	Stage description
IA	T1 or T2; N0; M0	Low (G1): mitotic rate 5/50 per HPF or less	T1: Tumor ≤ 2 cm; T2: Tumor > 2 cm but ≤ 5 cm; N0: no regional lymph node metastasis; M0: No distant metastasis
IB	T3; N0; M0	Low (G1)	T3: Tumor > 5 cm but ≤ 10 cm; N0: no regional lymph node metastasis; M0: No distant metastasis
II	T1; N0; M0 or T2; N0; M0 or T4; N0; M0	High (G2): mitotic rate > 5/50 HPF; High (G2); or Low (G1)	T1: Tumor ≤ 2 cm; T2: Tumor > 2 cm but ≤ 5 cm; T4: Tumor > 10 cm in greatest dimension; N0: no regional lymph node metastasis; M0: No distant metastasis
IIIA	T3; N0; M0	High (G2)	T3: Tumor > 5 cm but ≤ 10 cm; N0: no regional lymph node metastasis; M0: No distant metastasis
IIIB	T4; N0; M0	High (G2)	T4: Tumor > 10 cm in greatest dimension; N0: no regional lymph node metastasis; M0: No distant metastasis
IV	Any T; N1; M0 or Any T; Any N; M1	Any rate or Any rate	N1: Regional lymph node metastasis; M1: Distant metastasis

TNM: Tumor node metastasis; HPF: High power field.

Table 4 American Joint Committee on Cancer tumor node metastasis system for small intestine, esophagus, colon, rectum, or peritoneum

Stage	TNM	Mitotic rate	Stage description
I	T1 or T2; N0; M0	Low (G1): mitotic rate 5/50 per HPF or less	T1: Tumor ≤ 2 cm; T2: Tumor > 2 cm but ≤ 5 cm; N0: no regional lymph node metastasis; M0: No distant metastasis
II	T3; N0; M0	Low (G1)	T3: Tumor > 5 cm but ≤ 10 cm; N0: no regional lymph node metastasis; M0: No distant metastasis
IIIA	T1; N0; M0 or T4; N0; M0	High (G2): mitotic rate > 5/50 HPF; or Low (G1)	T1: Tumor ≤ 2 cm; T4: Tumor > 10 cm in greatest dimension; N0: no regional lymph node metastasis; M0: No distant metastasis
IIIB	T2; N0; M0 or T3; N0; M0 or T4; N0; M0	High (G2); or High (G2); or High (G2)	T2: Tumor > 2 cm but ≤ 5 cm; T3: Tumor > 5 cm but ≤ 10 cm; T4: Tumor > 10 cm in greatest dimension; N0: no regional lymph node metastasis; M0: No distant metastasis
IV	Any T; N1; M0 or Any T; Any N; M1	Any rate or Any rate	N1: Regional lymph node metastasis; M1: Distant metastasis

TNM: Tumor node metastasis; HPF: High power field.

Table 5 Treatment options of resectable gastrointestinal stromal tumors

Resectable GISTs with minimum morbidity

Resectable GISTs with significant morbidity

Resection followed by risk stratification on pathology: (1) Very low or low risk category – no TKI; and (2) Intermediate or high risk category - TKI.

Preoperative TKI: (1) If patient responds to TKI: continue TKI and proceed with surgery; and (2) If patient does not respond to TKI: surgery if feasible. If surgery not feasible: (a) For limited progression -options include radiofrequency ablation, embolization, chemoembolization, and palliative radiation; and (b) For widespread progression – increase the dose of imatinib as tolerated, If that fails – sunitinib followed by regorafinib followed by avapritinib should be tried. If GIST continues to progress despite TKIs, other options include clinical trials, systemic agents against GIST and best supportive care.

GIST: Gastrointestinal stromal tumor; TKI: Tyrosine kinase inhibitor.