Case Presentation: GIST 9 th Annual Clinical Cancer Update Conference Squaw Creek, North Lake Tahoe January 2010 Anne Espinoza, M.D. Hematology/Oncology Fellow University of California, San Francisco Initial Presentation 73 y/o previously healthy F with 3 month history of abdominal pain radiating to left shoulder associated symptoms: early satiety, bloating eating well, no weight loss, denies n/v no evidence of GI bleed Patient evaluated by her PMD: labs, abdomen/pelvis CT ordered Initial Work-Up Labs normal CBC, Cr, LFTs Abdominal/Pelvis CT 16.4 x 9.2 cm mass in LUQ located on anterolateral surface of gastric body central necrosis no evidence of metastatic disease
Abdomen/Pelvis CT CT-guided biopsy moderately cellular proliferation of fusiform spindle cells in whorls and short intersecting fascicles estimated mitotic activity 10mf/50hpf immunohistochemical stains CD 117 POSITIVE CD 34 POSITIVE negative: S-100, muscle specific actin, desmin, keratin, EMA, mucin DIAGNOSIS: GASTROINTESTINAL STROMAL TUMOR (GIST) Additional Work-Up Endoscopic Ultrasound 18 x 8 cm gastric mass, subepithelial arising from proximal inferior stomach location: 4cm distal to GE jxn with direct invasion of stomach over 12 x 7 cm area no evidence of associated lymphadenopathy
Additional Work-Up PET/CT LUQ mass markedly FDG-avid (SUV 14.7) hypermetabolic lesion in liver not seen on previous CT scan QUESTION #1 What would you recommend as the first step in management? 1. surgical resection 2. neoadjuvant imatinib with plan for future resection 3. imatinib with no plans for resection Initial Treatment Decision made to start cytoreductive treatment with imatinib given the extent of operation that would be necessary.
QUESTION #2 Would you perform a mutational analysis prior to starting imatinib? 1. YES 2. NO Initial Treatment Patient started on imatinib 400 mg daily After initiation of imatinib, patient developed significant skin toxicity (diffuse macular papular rash) imatinib held briefly, then dose reduced to 200 mg daily skin toxicity resolved follow-up imaging showed no response to treatment QUESTION #3 What would you do now, given lack of response with low-dose imatinib? 1. no further therapy 2. increase imatinib back to 400 mg daily 3. change to sunitinib 4. start chemotherapy 5. proceed to surgical resection
Continued Therapy Imatinib increased back to 400 mg daily no recurrent skin toxicity Follow-up PET/CT scan showed significant response to therapy: decreased size of primary and liver lesion decreased metabolic activity of both lesions Imaging: baseline & post-imatinib BASELINE CT CT post-imatinib Imaging: baseline & post-imatinib BASELINE PET/CT PET/CT post-imatinib
Continued Therapy Patient continued on imatinib at 400 mg daily for approximately six months At six months, imaging showed plateau in response QUESTION #4 What would you do now that patient has had a plateau in response? 1. continue current dose imatinib 2. increase imatinib to 800 mg daily 3. change to sunitinib 4. attempt surgical resection of primary lesion with hepatic metastasectomy or RFA to liver lesion Surgical Resection Patient taken to OR she underwent: subtotal gastrectomy partial hepatectomy
Pathologic Findings 15.5 x 5.9 x 6.9 cm mass arising from gastric wall with internal cystic degeneration Pathologic Findings 20X 200X specimens from liver resection showing significant necrosis (imatinib treatment effect) Pathologic Findings area of viable GIST CD 117 stain
QUESTION #5 What would your plan be for postresection treatment/surveillance? 1. surveillance imaging (PET/CT or CT), no further therapy unless recurrent disease 2. adjuvant imatinib therapy QUESTION #6 How long of a treatment course with adjuvant imatinib would you recommend? 1. six months 2. one year 3. two years 4. indefinite therapy THANK YOU!