Recurrent GIST Research Articles

A Case of Recurrent Gastrointestinal Stromal Tumor with Chondroid Differentiation

Abstract Introduction/Objective Gastrointestinal stromal tumors (GIST) comprise 0.1% to 3% of gastrointestinal neoplasms but are the most common mesenchymal tumors in the gastrointestinal tract. They originate from the interstitial cells of Cajal and most frequently arise in the stomach. However, chondroid differentiation of GIST is extremely rare with less than ten cases reported in the literature. We present a case of a 58-year-old female with recurrent GIST post-imatinib therapy. Methods/Case Report The patient was originally diagnosed with GIST seven years prior when she visited the Emergency Department after a syncopal episode and was incidentally found to have a 11 x 8.5 x 7 cm gastric mass based on abdominal CT scan. She underwent biopsy that showed spindle cell lesion staining positively for DOG1 and CD117 and negatively for desmin, consistent with GIST. She subsequently underwent partial gastrectomy with pathology showing high grade spindle cell type GIST with focal bizarre epithelioid cells and necrosis. Molecular testing identified the tumor to have a c-KIT mutation. Based on large tumor size and risk of recurrence, she was treated with imatinib for three years. Two years after completion of imatinib therapy, her surveillance imaging showed a mass compatible with recurrence measuring 11.8 x 11.7 x 6.7 cm. Additionally, imaging identified a mass in her mid abdomen that was biopsied and showed metastatic GIST supported by immunophenotype. The patient undewent a second partial gastrectomy and the mass on gross examination showed a heterogeneous cut surface displaying some solid and necrotic areas that appears to have invaded adjacent adipose tissue. Histomorphological features showed a spindle component with necrosis and a focus of chondroid differentiation. Tumor cells were immunopositive for DOG1 and CD117. The chondroid component did not stain for either marker. Results (if a Case Study enter NA) NA Conclusion There have been few reported cases of GIST with chondroid differentiation. Moreover, a previous study found three of 35 patients who showed phenotypic alteration post-imatinib therapy with changes ranging from tubulopapillary to epithelioid morphology. However, there has been no case with chondroid differentiation after imatinib therapy reported. This case illustrates the variable response of GIST to imatinib and its possible transformation because of the therapy. To better understand the prognosis of GIST with chondroid differentiation, more cases should be identified, reported, and monitored closely.

Ripretinib therapy in treating advanced gastrointestinal stromal tumors: A single-center analysis in a real-world setting.

e23514 Background: Ripretinib has been proven effective in inhibiting various primary and secondary mutants of KIT/PDGFRA but with limited clinical data. This study is aimed to investigate the efficacy and safety of ripretinib and prognostic predictors based on the current treatment pattern in Chinese patients in a single center. Methods: This retrospective cohort study was based on the prospectively registered database of the First Affiliated Hospital, Sun Yat-sen University. Patients with confirmed recurrent and/or metastatic GIST who received ripretinib as ≥ 2nd line therapy between June 1, 2020, and January 1, 2023 were enrolled. Results: Forty patients receiving ripretinib were enrolled. The median age of the patients was 58.0 years, and the most common primary site of tumor was the small intestine (75.0%). KIT exon 11 (65.0%) was the most common primary mutation, followed by exon 9 (20.0%). Ripretinib was administered as 2nd- and 3rd-line therapy in 17.5% of patients, respectively; as 4th-line therapy in 45% of patients, and as 5th- or later-line therapy in 20% of patients. Thirty patients who received ripretinib as > = 3rd-line therapy were eligible for efficacy evaluation. There was no complete remission. Two patients (6.7%) were partial response, and 20 (66.7%) patients were disease stable for at least 8 weeks. The median follow-up time was 18.0 months. The median progression free survival (PFS) (95% confidence interval [CI]) was 5.9 (2.0, 9.7) months, and the median overall survival (OS) was 13.8 (11.5, 16.0) months. In the univariate analysis, patients with a primary mutation in KIT exon 11 (P = 0.002), better ECOG performance status (P = 0.041), and lower tumor burden, including the number (P = 0.016) and cumulative size (P＜0.001) of tumors, had longer PFS. Patients with a primary mutation in KIT exon 11 (P = 0.019), better ECOG performance status (P＜0.001), fewer tumors (P = 0.014), and a younger age (P = 0.039) had longer OS. In the multivariate analysis, the primary mutation (P = 0.004) and the number and cumulative size of tumors (P = 0.024, P = 0.015, respectively) were independent predictors of PFS. The primary mutation (P = 0.025), the number of tumors (P = 0.002), and ECOG performance status (P = 0.002) were independent factors of OS. Ripretinib was generally well tolerated, and no unexpected toxicities were observed. The most common AEs were anemia (45%), alopecia (28%), constipation (25%), and hypoalbuminemia (25%). Grade 3/4 AEs were reported in 25% of patients, and the most common ones were hand-foot syndrome (8%), anemia (5%), and increased aspartate aminotransferase (5%). Conclusions: Ripretinib was safe and effective in Chinese patients with imatinib-resistant GISTs in a real-world setting. Primary KIT exon 11 mutation, lower tumor burden and better performance status were associated with better survival benefit.

Selected Articles from This Issue

Relapse to MAp. pathway inhibitors (such as BRAF, MEK, and KRAS inhibitors) is common due to the reactivation of ERK and MAPK signaling. In this First Disclosure, Wallis, Munck, and colleagues outline the ERK inhibitor ASTX029. ASTX029 inhibits both the phosphorylation of ERK by MEK as well as its catalytic activity and, therefore, is categorized as a dual-mechanism inhibitor by the authors. The dual-mechanism ERK inhibitor demonstrated anti-tumor activity to MAPK inhibitor-resistant cancers in vitro and in vivo. Their work supports the continued clinical development of ASTX029 in advanced solid tumors.The specific DNA damage O6-methylguanine induced by temozolomide was quantified and set in relation to double-strand breaks, apoptosis and senescence. The findings challenged the model of DNA damage thresholding as O6-methylguanine induced these endpoints in glioblastoma cells without a no-effect threshold. Interestingly, senescence appears to occur at a much lower number of O6-methylguanine molecules than cell death, indicating that low dose temozolomide impedes cytotoxicity by increasing the quiescent population. The data indicate a) need of inhibiting selectively senescence in order to ameliorate the killing effects and b) quantification of O6-methylguanine could serve as a potential biomarker of temozolomide intratumoral dose.Although imatinib can target KIT mutations in gastrointestinal stomach tumor, 40% of localized tumors recur within 5 years. In this study, Sicklick and colleagues report a population of CD34+KITlow GIST cells with a cancer stem cell-like expression profile and were enriched by imatinib treatment. Tumors with low KIT expression had activated Gas6/AXL and NF-κB pathways which could be targeted by bemcentinib (AXL inhibitor) or bardoxolone (NF-κB inhibitor) alone or in combination with imatinib. Their findings present a new population of resistant cells that can be overcome in recurrent GIST disease.Despite advances in experimental therapeutics for refractory acute myeloid leukemia (AML), it remains incurable. The success of CD19 CAR T cells in hematologic malignancies has led to their development in expanding indications. In this manuscript, Rennert and colleagues describe the preclinical development of a CD19-anti-CLEC12A bridge-protein secreting CAR T cell targeting CLEC12A in AML. The CAR19 cells secrete the biparatopic bridging protein to increase the cytotoxicity against CLEC12A-positive AML cells in vitro and in vivo. The efficacy of these cells demonstrates a means to thwart resistance by enhancing CD19-based CAR T cells.

Itʼs Not Recurrence?

Case presentation A 53-year-old man was evaluated for nausea, fatigue and progressive weakness. He had a history of a 20cm (figure A) stage IIIb gastric high-grade, predominantly epithelioid, GIST (figure B, note the epithelioid appearing GIST within the black arrows, the oxyntic mucosa within the blue arrows and the muscularis separating the two areas) extirpated by partial gastrectomy and Billroth II ˜18 months prior. A 3cm LUQ mass was found on surveillance imaging 12 months later while being treated with adjuvant tyrosine-kinase inhibitors. Repeat imaging demonstrated an enlarging 6.7x7.0cm mass within the abdominal mesentery anterior to the left kidney. He was referred for laparoscopic partial small bowel resection and excision of a 10 cm mesenteric mass at the level of the efferent jejunal limb, a 3cm nodule at the level of the proximal ileum and 6 smaller nodules within the small bowel mesentery. Histopathology of the resected masses demonstrated a vimentin positive, uniform, spindled cell lesion with minimal inflammation and a rare mitotic figure. The lack of inflammation, storiform spindled pattern, mucin and obliterative vasculitis, helped exclude inflammatory myofibroblastic tumor and IgG4 disease. CD117 (c-kit) and CD34 were negative, excluding residual or recurrent GIST. However, the spindled cell did demonstrate nuclear and cytoplasmic positivity for beta-catenin, supporting the diagnosis of intra-abdominal mesenteric fibromatosis (figure C). Discussion Mesenteric fibromatosis or desmoid tumor is group of rare benign tumors that can be locally aggressive but do not metastasize. They develop in ˜20% of patients with FAP but can appear spontaneously, with tissue trauma and radiation exposure as reported risk factors. To date, there are about 30 reported cases of mesenteric fibromatosis following GIST resection. Co-existence of mesenteric fibromatosis with GIST has been reported as well. Distinguishing mesenteric fibromatosis from recurrent GIST may be difficult given common similarities in radiologic appearance and c-kit expression. Accurate diagnosis can only be made after surgical removal and histopathologic examination. Unfortunately, surgery for mesenteric fibromatosis is not always curative and high rates of recurrence are common. Watchful waiting should be considered after resection, especially in patients with minimal symptoms.2701_A Figure 1. CT of the abdomen2701_B Figure 2. Epithelioid GIST, 10X2701_C Figure 3. Jejunal mesenteric mass, desmin stain, 20x

Peritoneal dissemination of recurrent small intestine primary GIST, successfully diagnosed by diffusion-weighted imaging

Peritoneal dissemination of recurrent small intestine primary GIST, successfully diagnosed by diffusion-weighted imaging

Crossing-over to imatinib 800 mg in a patient with GIST, after progression with standard dosage: a case report

A 69-years-old patient underwent radical surgery to remove a lesion of small bowel with histological diagnosis of malignant primary stromal cancer of the gastro-intestinal wall (GIST). After a disease-free survival of 25 months instrumental evidence of loco-regional recurrence was detected with subsequent resection of the ileum: histology confirmed recurrent high risk GIST. After 34 months, TC scan showed peritoneal and hepatic progression of disease. Treatment with imatinib was started with standard dose of 400 mg/day, obtaining partial response on peritoneum and liver radiological complete response, after 5 months of therapy. Patient continued treatment with the same dose for 20 months. When radiological progression was detected we decided to increase imatinib to 800 mg/day based on the results of two principal phase III studies. Radiological partial response was reached after three months of therapy. Actually patient is still in treatment with imatinib showing stable disease with good tolerance.

An NGS assay strategy with FFPE and cfDNA to determine primary and secondary mutations across the initial diagnosis and subsequent recurrence/progression of patients with localized, recurrent and metastatic GIST.

10519 Background: Primary and secondary mutations in GIST affect prognosis and treatment response and impacts treatment decision making. A single driver mutation (primary) is found amongst exons of...

Phase 2 Trial to Evaluate the Efficacy and Safety of Dovitinib in Patients (Pts) with Gastrointestinal Stromal Tumor (Gist) Refractory and/or Intolerant to Imatinib (Im)

ABSTRACT Aim: Sunitinib is approved for advanced GIST resistant/refractory to IM; however, disease control rate (DCR) at 12 wk was only ≈ 40%. Thus, novel therapeutic second-line strategies are needed to improve outcomes. Dovitinib inhibits several tyrosine kinases (eg, FGFR, VEGFR, PDGFRb, KIT). DOVIGIST (NCT01478373) is a multicenter, single-arm study to evaluate the efficacy and safety of second-line dovitinib in GIST. Methods: Eligible pts (≥ 18 y) had histologically confirmed GIST; pts had advanced/metastatic GIST refractory/intolerant to IM ≥ 400 mg/day or recurrent GIST after adjuvant IM. All pts had ≥ 1 measurable lesion at baseline. Prior tyrosine kinase inhibitors other than IM were not allowed. Pts received dovitinib 500 mg/day (5 days on/2 days off) until progressive disease (PD), unacceptable toxicity, death, or discontinuation. The primary endpoint was DCR (per RECIST 1.1) at 12 wk. Based on prior trials, DCR ≥45% was deemed clinically meaningful. Key secondary endpoints were progression-free survival (PFS), overall response rate (ORR), and safety. Results: Of 39 pts who received ≥1 dose of dovitinib, 1 had unconfirmed GIST histology; thus, the efficacy analysis included 38 pts (median age, 60 y). The median time from diagnosis to first dose of dovitinib was 46.3 mo; 81.6% had PD on IM, 13.2% discontinued IM due to intolerance, and 5.2% had intolerance and PD. The most common grade 3/4 dovitinib-related adverse events (AEs) were fatigue (12.8%), diarrhea, vomiting, and hypertriglyceridemia (7.7% each); 21.1% discontinued due to AEs. One pt died of a heart attack (suspected drug related). The median PFS was 20.1 wk (90% CI, 12.3-32.1). DCR at 12 wk was 52.6% (Table). Conclusions: DOVIGIST met its primary endpoint. The DCR of 52.6% compares favorably with that of other second-line treatments. Dovitinib had promising efficacy and a manageable safety profile, warranting further studies in GIST. Best Response at 12 Wk, n = 38 n % 90% CI Partial response (PR) 1 2.6 Stable disease (SD) 19 50.0 PD 5 13.2 Unknowna 13 34.2 ORR (≥ PR) 1 2.6 0.1-11.9 DCR (≥ SD) 20 52.6 38.2-66.7 a Not all baseline lesions evaluated during follow-up; no PD detected ≤12 wk on dovitinib. Disclosure: H. Joensuu: The Clinical Research Institute of Helsinki University Hospital has received financial support from Novartis and Bayer AG because HJ participated in advisory group meetings or speaking events; J-Y. Blay: Received research support and honoraria from Novartis, GSK, Roche, Pharmamar, Bayer, MSD, JNJ; E. Fumagalli: Founds for studies and research activities: Amgen Dompe, Bayer, Glaxo SK, Merck SD, Novartis, Pfizer, PharmaMar, Sanofi-Aventis, ImClone, Infinity, Janssen Cilag, Lilly, Molmed, Merck SD, Schering Plough Travel for medical meetings: Novartis; G.E. Grignani: Received travel reimbursement from PharmaMar. Expert opinion for Bayer and Glaxo-Welcome; O. Bouche: Received research support and honoraria from Novartis; S. Bauer: received honoraria by Novartis, Pfizer, Bayer and have received a research grant by Novartis (for a clinical trial). Advisory board for Pfizer; C. Barone: Received honoraria as a speaker and chairman; C. Weiss, S. Crippa, M. Camozzi and R. Castellana: Novartis employee; A. Le Cesne: Received honoraria from GSK, Novartis, Pharmamar and Pfizer for advisory board. All other authors have declared no conflicts of interest.

Germline SDHC mutation presenting as recurrent SDH deficient GIST and renal carcinoma

Germline SDHC mutation presenting as recurrent SDH deficient GIST and renal carcinoma

The role of surgical resection following imatinib treatment in patients with metastatic or recurrent GIST.

10550 Background: Several retrospective studies have suggested that surgical resection of residual lesions could be beneficial if resection was done after disease control (partial response or stable disease) with imatinib in patients with metastatic or recurrent GIST. However, the benefit of surgical resection has not been proven yet compared to imatinib alone. Therefore, we compared the outcomes of surgical resection of residual lesions after imatinib (SI group) with those of imatinib alone (IM group) in patients with metastatic or recurrent GIST controlled with imatinib treatment. Methods: A total of 134 patients with metastatic or recurrent GIST who showed at least 6 months of disease stabilization or response to imatinib were included in this retrospective analysis. Patients were categorized into SI (n=42) or IM (n=92) group. To reduce the selection bias, propensity scores and inverse-probability-weighting (IPTW) adjustment were used in the outcome analysis. Results: Patient and tumor characteristics were statistically similar between SI and IM groups, except median age (51 in SI, 58 in IM, p=0.002), and metastases to peritoneum (12 in SI, 56 in IM, p=0.001). The patients in SI group underwent surgery of residual disease after a median 19.1 months of imatinib treatment (range, 7.2-87.0). With a median follow-up of 58.9 months (range, 15.4-129.1), progression-free survival (PFS) and overall survival (OS) were significantly longer in SI group than in IM group (PFS, 87.7 vs 42.8 months, p=0,001; OS, not reached vs 88.8 months, p=0.001). Multivariate analysis revealed SI group as well as female sex, KIT exon 11 mutation, and low initial tumor burden were associated with longer PFS, and SI group and low initial tumor burden were associated with longer OS. Even after applying IPTW adjustment, SI group showed significantly better outcome in terms of PFS (hazard ratio [HR], 2.326; 95% CI, 1.034-5.236; p=0.0412) and OS (HR, 5.464; 95% CI, 1.460-20.408; p=0.0117). Conclusions: This study strongly suggests that surgical resection of the residual lesions after disease control with imatinib may be beneficial in patients with metastatic or recurrent GIST.

The role of surgical resection following imatinib treatment in patients with metastatic or recurrent GIST.

62 Background: Several retrospective studies have suggested that surgical resection of residual lesions could be beneficial if resection was done after disease control (partial response or stable disease) with imatinib in patients with metastatic or recurrent GIST. However, the benefit of surgical resection has not been proven yet compared to imatinib alone. Therefore, we compared the outcomes of surgical resection of residual lesions after imatinib (SI group) with those of imatinib alone (IM group) in patients with metastatic or recurrent GIST controlled with imatinib treatment. Methods: A total of 134 patients with metastatic or recurrent GIST who showed at least 6 months of disease stabilization or response to imatinib were included in this retrospective analysis. Patients were categorized into SI (n=42) or IM (n=92) group. To reduce the selection bias, propensity scores and inverse-probability-weighting (IPTW) adjustment were used in the outcome analysis. Results: Patient and tumor characteristics were statistically similar between SI and IM groups, except median age (51 in SI, 58 in IM, p=0.002), and metastases to peritoneum (12 in SI, 56 in IM, p=0.001). The patients in SI group underwent surgery of residual disease after a median 19.1 months of imatinib treatment (range, 7.2-87.0). With a median follow-up of 58.9 months (range, 15.4-129.1), progression-free survival (PFS) and overall survival (OS) were significantly longer in SI group than in IM group (PFS, 87.7 vs 42.8 months, p=0,001; OS, not reached vs 88.8 months, p=0.001). Multivariate analysis revealed SI group as well as female sex, KIT exon 11 mutation, and low initial tumor burden were associated with longer PFS, and SI group and low initial tumor burden were associated with longer OS. Even after applying IPTW adjustment, SI group showed significantly better outcome in terms of PFS (hazard ratio [HR], 2.326; 95% CI, 1.034-5.236; p=0.0412) and OS (HR, 5.464; 95% CI, 1.460-20.408; p=0.0117). Conclusions: This study strongly suggests that surgical resection of the residual lesions after disease control with imatinib may be beneficial in patients with metastatic or recurrent GIST.

707P - A Cost-Effectiveness Analysis of Three Years of Adjuvant Imatinib in Kit+ Gastrointestinal Stromal Tumors (GIST) in Greece

ABSTRACT Background and objective Clinical studies have demonstrated the clinical benefit of adjuvant imatinib for patients who undergo complete gross resection for KIT+ GIST both in terms of overall and recurrence-free survival. The aim of this study is to assess the cost-effectiveness of the following treatment options a) 3 yr adjuvant imatinib (IM) vs 1yr IM, b) 3yr IM vs. surgical resection only c) lifetime IM vs. 1 yr IM as adjuvant therapy in patients with KIT GIST, from the perspective of the Greek National Health Service (NHS). Methods A Markov transition state model was developed and populated with data from published literature and expert opinion. All patients enter the model free of recurrence and over subsequent cycles, a patient may remain free of GIST, may enter a state of recurrent GIST or may die of GIST or other causes. The mean starting patient age was 58 years old and the discount rate 3% per year. Resource utilization reflects Greek disease management. Pharmaceutical and adverse events cost was based on 2012 prices. Extensive sensitivity analysis was also undertaken. Results Mean total cost per patient was estimated at €72,899 for 1 yr of adjuvant IM versus €112,910 for 3yr IM. Effectiveness was estimated to be 10.80 and 12.76 life-years and 7.63 and 9.19 QALYs respectively for 1yr vs. 3yr. The incremental cost-effectiveness was thus €20,387 per life-year gained and €25,700 per QALY gained over a patient's lifetime. These results were most sensitive to the rate of GIST recurrence beyond 5 years. The incremental cost of 3 years of IM versus surgical resection alone was €14,649 per life-year gained and €18,448 per QALY gained and €65,943 per life-year gained and €82,851 per QALY gained over a patient's lifetime for lifetime IM treatment versus 1 year of imatinib. These results were most sensitive to the monthly cost of IM. Conclusions This analysis has shown that 3yr adjuvant IM therapy is considered highly cost-effective for the Greek NHS when compared to either 1yr adjuvant IM or surgical resection alone. Lifetime vs. 1y adjuvant IM is associated with a moderate incremental cost-effectiveness ratio that is far below the acceptable threshold of €100.000 for life-threatening diseases. Disclosure M. Raikou: This study was sponsored by Novartis Hellas S.A. All other authors have declared no conflicts of interest.

Preliminary data of nilotinib in the first-line treatment of patients with metastatic or unresectable gastrointestinal stromal tumors (GIST).

TPS332^ Background: Nilotinib (N) is a novel tyrosine kinase inhibitor (TKI) of KIT, PDGFRA, and BCR-AbL that has been shown to inhibit the proliferation of imatinib (I)-resistant GIST cell lines. Preliminary studies with N have shown that it can provide clinical activity in patients (pts) who have failed first- and second-line therapies and is safe in pts with advanced GIST. This Phase II study was conducted to investigate the efficacy of N as first-line treatment. Methods: The multicenter, single-arm trial evaluated the efficacy of N in newly diagnosed pts with unresectable or metastatic GIST or with recurrent GIST post adjuvant treatment. Pts were given N 400 mg bid until disease progression, unacceptable toxicity, or discontinuation for another reason. Primary endpoint was PFS at 6 months determined by RECIST; secondary endpoints included objective tumor response (RECIST), time to overall response, duration of response, progression-free survival, overall survival, and safety. Results: As of December 2...

The GOLD reGISTry: A global observational registry collecting longitudinal data on patients with advanced GIST—Second annual summary.

10092 Background: The GOLD reGISTry is a web-based, prospective, 5-year observational study capturing global/regional diagnosis and disease characteristics, treatment modalities, efficacy parameters, and outcome for patients (pts) with advanced GIST. Methods: Eligible pts had locally advanced, metastatic, or recurrent GIST diagnosed no more than 15 months prior to reGISTry entry. Detailed pt and center information are captured and summarized annually. Data are summarized as of July 2009. Results: The most common eligible diagnoses were recurrence with metastasis (35%) and initial diagnosis of metastatic GIST (30%). 1065 pts enrolled at 156 sites in 34 countries across 5 regions: Latin America (LA, 12%), EU West/Canada (EUW/C, 28%), EU East (EUE, 20%), Asia (A, 39%), and the Middle East (ME, 1%). Most sites are referral centers (89%) that see between 5 and 25 pts with localized (50%) and advanced disease (50%) annually. Mean age of pts was lower in A and LA (56 yrs) than in EUE (60 yrs) and EUW/C (62 yrs)....

ACRIN 6665/RTOG 0132 phase II trial of neoadjuvant imatinib mesylate (IM) for primary and recurrent operable malignant GIST: Imaging findings and correlation with genotype and GLUT4 expression

10552 Background: IM has improved the treatment of GIST patients (pts), but few achieve objective response despite significant clinical benefit. Imaging of tumor metabolism may provide earlier assessment of therapeutic response. In this study, FDG-PET metabolic response (MR) was compared with RECIST, GLUT4 expression, and KIT/PDGFRA mutation status. Methods: FDG-PET was done at baseline, 1–7 days, and 4 or 8 weeks (wk) after IM initiation. Best objective response was defined by RECIST. Immunohistochemical (IHC) tumor GLUT4 expression and mutation analyses were done at baseline and/or surgery. Background-subtracted SUVmax was measured in all lesions and summed; MR based on EORTC criteria was compared to RECIST, GLUT4 expression, and KIT/PDGFRA mutation status. Results: FDG-PET showed high tumor glycolytic activity at baseline (mean SUVmax = 14.2, range: 1.3–53.2), decreasing after 1 wk of IM (5.5, range: 0.5–47.7, p < 0.001, n = 44), and again prior to surgery (3.0, range: 0.5–36.1, p < 0.001, n = 40). FDG-PET response at wk 1 was 3 complete MR (CMR), 33 partial MR (PMR), 6 stable metabolic disease (SMD), and 2 progressive metabolic disease (PMD). Prior to surgery, FDG-PET response was 3 CMR, 33 PMR, 4 SMD, and no PMD. For 39 pts, RECIST best response was 2 PR, 36 SD, and 1 PD. GLUT4 expression decreased in 19 pts with PMR, and 3 with SMD. Among 12 pts with exon 11 mutation, 11 had PMR, 1 SMD; among 5 pts with wild-type genotype, 4 had PMR, and 1 SMD. Conclusions: After IM initiation, MR by FDG-PET was documented earlier (1–7 days), and was of much greater magnitude (36/40) than that documented by RECIST (2/39). IHC data suggest that: (1) GLUT4 plays a role in FDG uptake in GIST; (2) GLUT4 decreases in most pts with PMR; and, (3) the biologic action of IM interacts with glycolysis and GLUT4 expression. No difference in PMR was seen in pts with exon 11 vs. wild type mutations. [Table: see text]

Coexistence of gastrointestinal stromal tumor (GIST) and colorectal adenocarcinoma: A case report

BackgroundGastrointestinal stromal tumors (GIST) represent the most common mesenchymal tumors of the digestive tract. Over the last ten years the management of GISTs has dramatically altered but their coexistence with other gasrointesinal tumors of different histogenesis presents a special interest. The coexistence of GISTs with other primaries is usually discovered incidentally during GI surgery for carcinomas.Case presentationWe present here, a case of a 66-year-old patient with intestinal GIST and a synchronous colorectal adenocarcinoma discovered incidentally during surgical treatment of the recurrent GIST. Immunohistochemical examination revealed the concurrence of histologically proved GIST (strongly positive staining for c-kit, vimentin, SMA, and focal positive in S-100, while CD-34 was negative) and Dukes Stage C, (T3, N3, M0 according the TNM staging classification of colorectal cancer).ConclusionThe coexistence of GIST with either synchronous or metachronous colorectal cancer represents a phenomenon with increasing number of relative reports in the literature the last 5 years. In any case of GIST the surgeon should be alert to recognize a possible coexistent tumor with different histological origin and to perform a thorough preoperative and intraoperative control. The correct diagnosis before and at the time of the surgical procedure is the cornerstone that secures the patients' best prognosis.

Clinico-pathologic pattern of gastrointestinal stromal tumors (GIST) in southern India: A single-institution experience

20531 Background: There have been major advances in understanding the behavioral pattern, pharmacological intervention, and clinical response of GIST; yet Indian data in this regard is sparse. This study analyses the clinico-pathologic features in 36 patients (21 male, 15 female) of GIST seen at our institution. Methods: GIST was defined as a mesenchymal spindle or epithelioid cell lesion arising in the GI tract with CD117 immuno-reactivity. Retrospective data from January 03 to March 06 was analyzed for age, tumor site, morphology, immuno- reactivity, prognostic factors, response to treatment (by RECIST), and recurrence or metastasis. All patients had surgery; those with residual, recurrent, or metastatic disease got imatinib till tumor progression. Results: GIST presented at a mean age of 48.2 yrs (SD 6.4, range 34–65). The mean tumor size was 13.9 cm (range 2–42). The most common site was the small intestine (ileum 8, jejunum 7, duodenum 4). 24 patients (66.7%) had localized disease at baseline. Of these, 14 had local recurrence after surgery, and were given imatinib. 5 of them are in complete remission, 4 had partial response (PR), 3 patients died, and 2 had stable disease. Most patients with recurrent GIST had a mitotic rate of >10/50hpf. 8 patients developed metastasis, and received imatinib. Of these, 2 got a PR, 3 had progressive disease and died, and 3 had stable disease. 12 patients (33.3%) had metastasis at baseline (to liver and abdominal cavity), and underwent debulking. Of these, 6 patients with stable disease are on treatment with imatinib, 3 died and 3 were lost to follow-up. Conclusions: Average age of presentation was less than in Western reports. The commonest site was the small intestine as opposed to stomach in western literature. Mitotic rate was a better prognostic factor than gross tumor size. GIST with a mixed cell morphology showed aggressive behavior. Imatinib mesylate is useful in the post-operative management of GIST. [Table: see text] No significant financial relationships to disclose.

Metastatic duodenal GIST: role of surgery combined with imatinib mesylate

BackgroundThe best possible treatment of metastatic high grade large duodenal GIST is controversial. Surgery (with or without segmental organ resection) remains the principal treatment for primary and recurrent GIST. However, patients with advanced duodenal GIST have a high risk of early tumour recurrence and short life expectancy.MethodWe present a case of a young man treated with a combined modality of surgery and imatinib for an advanced duodenal GIST.ResultsHe remains asymptomatic and disease free 42 months following this combined approach.ConclusionTreatment with imatinib has dramatically improved the outlook for patients with advanced, unresectable and/or metastatic disease.

Audit of a series of 40 gastrointestinal stromal tumour cases

Aims To analyze prognostic factors influencing survival and tumour recurrence after resection of gastrointestinal stromal tumours. Methods Forty patients who underwent surgery for a GIST at our institution were reviewed. Patients were classified on the basis of tumour size, mitotic rate and CD117 positivity. The overall survival and disease free survival were calculated using Kaplan–Meier method considering the extent of surgery comparing local tumour excisions with segmental organ resections. Results Tumours were localized in the oesophagus, stomach, duodenum, small bowel and large bowel and rectum. Sixty-five percent of the patients had an intermediate or high risk GIST according to tumour size and mitotic count. In 26/40 patients tumour resection was performed using segmental organ resection, in all other patients local tumour excision was carried out. The mean overall survival was 73 months. Disease free survival was significantly better after local tumour excision compared to segmental organ resection (73 months versus 53 months; p = 0.05). Large tumour size ( p = 0.07) and high mitotic count ( p = 0.14) were negative prognostic factors for disease free survival, although statistical significance was not reached yet. Conclusion Primary surgery remains the cornerstone in the treatment of primary and recurrent GIST. Risk adapted surgery is the most important factor to avoid early tumour recurrence. In case of small tumour size segmental organ resections can be avoided favouring local tumour excisions with a low risk of tumour recurrence.

STI571 for gastrointestinal stromal tumors

Since the effectiveness of STI571 for GIST was reported, therapy for GIST has changed markedly, and the disease has attracted attention. We have treated 19 patients with GIST since 2000 by 19 resections (local resection in 14 patients, total gastrectomy in 2 patients, distal gastrectomy in 2 patients, and hepatectomy in 1 patient), and administered STI571 to 5 patients with unresectable or recurrent GIST. Of these 5 patients, 2, 1, 1, and 1 had PR, SD, PD, and inevaluable disease, respectively, with a response rate of 50%. The disease was controllable in 80% of the patients. All patients had palpebral and crural edema as side effects, which were not severe, suggesting the safety of the drug. It is important to tailor therapy (STI571 or surgery) to the patient.