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Table 8. Tumor Characteristics Predictive of Disease Response or Survival

Characteristic

Prognostic Factor

Studies Indicating an Association and Quality

Strength of Association with Tumor Response

Strength of Association with Survival

c-kit mutation

c-kit mutation present vs. absent

Debiec-Rychter, et al., 2004
(quality = 6/6)59

TTP:  patients with C kit mutations less likely to progress (p = 0.03)

patients with c-kit mutations with longer OS (p = 0.015)

Exon 11 mutation

Debiec-Rychter, et al., 2004
(quality = 6/6)59

Heinrich, et al., 2003
(quality = 6/6)47

EFS:  c-kit exon 11 mutation with median EFS 849d; all other mutations EFS 327d

HR 0.17 (0.10-0.29)  p < 0.0001a

HR 0.04 (0.01-0.12)
p < 0.0001a

Exon 9 mutation

Heinrich, et al., 2003
(quality = 6/6)47

 

HR 0.31(0.11-0.89)
p = 0.0289a

Other genes

Gene SPRY4 (found to be downregulated by imatinib in in vitro pre-clinical studies)

Frolov, et al., 2003
(quality = 1/6)60

SPRY4 was "dramatically" decreased in 4/5 patients with PR, expressed at high levels in the 2/2 non-responders, and initially decreased then returned to high levels in the 1/5 PR patient who had an early relapse

 

Gene MAFbx (found to be upregulated by imatinib in in vitro pre-clinical studies)

Frolov, et al., 2003
(quality = 1/6)60

Variable responses (2/5 PR patients had included levels of MAFbx; initially increased and then returned to pre-treatment levels in the patient with PR but early relapse; not changed at all in the one PD patient)

 

Pathology

GIST vs. other STS

Verweij, et al., 2003
(quality = 6/6)48

GIST with 73% DFS at 1yr

Median TTP STS = 58d

 

Abbreviations:  TTP = time to progression; OS = overall survival;  EFS = event free survival; HR = hazard ratio; STS = soft tissue sarcomas; DFS = disease-free survival.

Note:
a. In this study hazard rations greater than one are predictive of poorer prognosis.

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