Adjuvant Imatinib Therapy Research Articles

Efficacy observation on imatinib adjuvant therapy with longer duration in patients with gastrointestinal stromal at intermediate or high risk of recurrence

To evaluate the recurrence-free survival (RFS) and safety of imatinib adjuvant therapy with longer treatment duration in patients undergoing complete resection of localized primary gastrointestinal stromal tumor (GIST). Clinical and follow-up data of 101 GIST patients between March 2004 and May 2009 with intermediate or high recurrence risk receiving imatinib adjuvant treatment and more than 3 years follow-up time in Peking University Cancer Hospital were retrospectively analyzed. Imatinib adjuvant treatment: 3 patients discontinued less than 1 year imatinib treatment because of adverse events; 24, 21 and 18 patients discontinued imatinib after 1 year, 2 years, and 3 years treatment; 8 patients received 3 years adjuvant treatment and were ongoing; 27 patients received more than 4 years imatinib adjuvant treatment. The median follow-up time was 60 months (95%CI:57.9-62.1). Nineteen patients had GIST recurrence, of whom recurrence happened during imatinib adjuvant therapy in 5 patients and after imatinib treatment in 14 patients. The median period from imatinib stopping to recurrence was 12.0 months (95%CI:9.6-14.4). Patients with recurrent GIST achieved tumor control after imatinib resumption. RFS of patients (n=53) with ≥3 years imatinib treatment duration was higher than that of patients (n=48) with <3 years imatinib duration (93.9% vs. 68.0%, P<0.01). In addition, prolonged adjuvant imatinib duration did not significantly increase the adverse events related to treatment (P>0.05). Prolonged adjuvant imatinib duration may further improve RFS rate further in patients with intermediate or high risk of recurrence after complete tumor resection without increased adverse events.

Clinical cases and prognosis analysis of primary gastrointestinal stromal tumors

Objective To analyze the clinical characters,therapeutic effect of gastrointestinal stromal tumors (GIST),the effects of surgical approach and imatinib adjuvant therapy on it.Methods From January 2004 to April 2010,the clinical data of 214 patients with primary GIST were retrospectively analyzed.The effects of surgical approach and imatinib on the survival of the GIST patients were compared.Count data were analyzed by chi-square test,and the survival rates were analyzed with the life table method and Kaplan-Meier curve.Results A total of 214 GIST patients'survival rates of 1-year,3-year,5-year were 93.0％,87.0％ and 80.0％.According to the risk classification of National Institutes of Health,the differences of overall survival rates after surgery were statistically significant (x2 =22.058,P＜0.05).The differences of survival rate among different nuclear division number were statistically significant (x2=26.599,P＜0.05).The survival rate of pathological nuclear division number over 10/50 high power field (HPF) was the lowest.The overall survival rate of patients with gastrointestinal GIST was higher than patients with extragastrointestinal GIST,and the difference was statistically significant (x2 =68.139,P ＜ 0.05).After complete resection of the tumor,the survival rate of patients with local recurrence was higher than those with widely recurrence,and the difference was statistically significant (x2 =4.409,P＜ 0.05).After complete resection of the tumor,the survival rate of patients taking imatinib was higher than that of patients not taking imatinib.Conclusions The surgical treatment was the main therapy for GIST.Complete resection of the tumor and taking imatinib after surgery could improve the prognosis and the survival rate of the GIST patients. Key words: Mesothelioma; Gastrointestinal neoplasms; Surgical procedures, operative; Protein-tyrosine kinases; Prognosis

Prognosis analysis of 247 cases of gastrointestinal stromal tumor

To study the clinicopathologic features and prognostic factors of gastrointestinal stromal tumor (GIST). Clinicopathologic data of 247 patients with GIST from January 2003 to November 2012 in the Affiliated Hospital of Qingdao University Medical College, and the prognostic factors were evaluated retrospectively by univariate and multivariate analysis with Log-rank test and Cox proportional hazard model. Patients were followed up with a median time of 26 months (1 to 113 months). Twenty-six patients developed recurrence or metastasis, and 18 died of GIST. The 1-, 3-, 5-year survival rates were 94%, 91% and 83% respectively. Univariate analysis showed that age, tumor location, tumor size, mitotic count and tumor rupture were predictive factors of survival after resection of primary GIST (all P<0.01). For patients at intermediate and high risk to relapse, imatinib group had a higher 5-year overall survival rate than non-imatinib group (85.7% vs. 81.0%, P<0.05). Multivariate analysis revealed that tumor size (RR=2.248, 95%CI:1.081-4.677, P=0.030), mitotic count (RR=2.220, 95%CI:1.032-4.776, P=0.041) and tumor rupture (RR=5.183, 95%CI:1.677-16.017, P=0.004) were independent prognostic factors. Tumor size, mitotic count and tumor rupture affect the prognosis after resection of primary GIST independently. Imatinib adjuvant therapy can improve overall survival of patients at intermediate and high risk to relapse after surgery.

New prospective on adjuvant treatment for gastrointestinal stromal tumors

Gastrointestinal stromal tumor (GIST) represents the most common mesenchymal tumor of the gastrointestinal tract. With decades of development, surgical excision combined with molecular targeted agents is becoming the mode for the GIST treatment. Imatinib mesylate (IM) is the first-line therapy medicine for GIST adjuvant treatment, and it significantly reduces recurrence or metastasis and increases survival. According to the recently results of SSGXVIII/AIO study, imatinib adjuvant therapy should be administered for at least 3 years for the GIST patients with a high estimated risk of recurrence and metastasis after surgery. Nevertheless, the optimal duration of the adjuvant therapy or the follow-up policy remains unclear, and we look forward to standard assessment criteria for individualized treatment.

Local excision with adjuvant imatinib therapy for anorectal gastrointestinal stromal tumors

Rectal gastrointestinal stromal tumors (GISTs) are uncommon, and the role of local excision versus a more extensive resection after the advent of effective targeted chemotherapy with imatinib is not known. Our aim is to present two cases of large anorectal GIST treated with local excision through a new anterolateral trans-sphincteric approach followed by adjuvant therapy with imatinib. Two patients (both males, 68 and 63 years old) presented at our institution with anorectal GIST in the period October-November 2010. Their medical records, pathology results, and imaging studies were retrospectively reviewed. Both patients presented with an anterior perianal mass. Imaging studies were characteristic of GIST originating in the lower rectum, circumscribed by a pseudocapsule, and protruding into the ischiorectal fossa. Both patients underwent local excision via an anterolateral trans-sphincteric approach. Both tumors were removed intact, with microscopically negative margins. The maximum tumor diameter was 8 and 9 cm, and the diagnosis of GIST was confirmed by positive CD117 and CD34 staining in both cases. Both tumors had a high (>5/50HPF) mitotic index. The patients had an uneventful postoperative course and were discharged on days 5 and 6. Both patients were started on imatinib 400 mg bid postoperatively. Postoperative magnetic resonance imaging and positron emission tomography computed tomography were carried out at 12 months and did not reveal any signs of recurrence. The patients are currently disease-free at 24 and 23 months of follow-up. In selected cases, complete excision of rectal GIST with negative margins is feasible via a trans-sphincteric approach. With the use of adjuvant therapy, which is currently advocated in all high-risk cases, it is possible that local excision with its reduced morbidity may become a viable alternative, especially in patients who would otherwise require abdominoperineal excision such as the two presented here. Prospective studies with longer follow-up are needed to confirm adequate oncologic results.

Comparison of the Long-Term Risk of Recurrence and Other Clinical Outcomes in GIST Patients Receiving Imatinib as Adjuvant Therapy—A Retrospective Chart Extract-Based Approach

PurposeTo compare characteristics of patients, the risk of recurrence, and mortality among adult patients with primary resectable gastrointestinal stromal tumor (GIST) receiving short-term (6–12 months) versus long-term (≥ 24 months) imatinib therapy.MethodsDetailed information on primary resectable KIT-positive GIST patients initiated on imatinib adjuvant therapy was retrospectively collected for short- and long-term imatinib patients from 318 US oncologists using an online data collection form. Patient characteristics were compared using Wilcoxon and Chi-square tests. Disease recurrence and mortality rates were compared using multivariate Cox proportional hazard models.ResultsAmong the 406 short-term and 406 long-term imatinib patients, the median follow-up was 916 and 970 days, respectively. While patients generally had similar demographic characteristics, the short-term group had a higher prevalence of cardiovascular and ischemic heart diseases and patients in the long-term group had a higher pre-surgery risk profile. This finding was consistent with the main reason reported by oncologists for prescribing adjuvant imatinib over longer duration, i.e., patient risk profile. Disease recurrence [5.9 versus 1.2 %, (p < .001)] and mortality rates [7.1 % versus 2.0 %, (p < .001)] were higher in short- versus long-term patients. The adjusted risk of recurrence was 5.30 times (p < .001) higher, and mortality risk was 4.02 times (p < .001) higher in short- versus long-term patients.ConclusionsPatient risk profile is an important factor in oncologists’ decisions to prescribe adjuvant imatinib. Despite the higher risk profile observed in long-term patients, the long-term use of imatinib was associated with a reduction in long-term risk of disease recurrence and mortality.

Clinicopathological study of 113 gastrointestinal stromal tumors

Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract. A retrospective study was done to evaluate the clinical and pathological features and the effect of adjuvant treatment with imatinib. The case records of 113 GIST patients were retrospectively reviewed and the clinicopathological features, treatments, and outcomes were recorded. There were 82 males and 31 females, with a median age of 51years. All patients were symptomatic (mean duration 4months) and abdominal pain was the most common symptom. The primary sites of GIST were small intestine (38), stomach (36), and others (39). The tumor diameter on imaging varied from 1 to 26 (mean 10.9) cm. Thirty percent of patients presented with metastasis. There was no association between tumor size and presence of metastasis (p = 0.9). Most common histology was spindle cell morphology followed by mixed spindle cell and epithelioid morphology. Seventy percent patients had high risk (HR) category as per Fletcher risk score. Fifty-three percent had curative resection, after which 34% had adjuvant imatinib therapy. Recurrence rates were significantly lower in patients receiving adjuvant imatinib therapy (p = 0.003). No statistically significant association was noted between HR Fletcher score, Mib score >10, tumor size >10cm, and the risk of recurrence (p = 0.29, 0.07, and 0.87, respectively). Liver was the most common site of metastasis. Side effects were tolerable and edema and fluid retention were the commonest. Sites of GIST in Indian patients were different from those in western studies. Adjuvant imatinib therapy significantly reduced the risk of recurrence.

Investigation of gastrointestinal stromal tumor (GIST) care management in GIST patients (pts) receiving short-term versus long-term imatinib (IM) adjuvant therapy: A chart review analysis.

195 Background: Although optimal duration of adjuvant IM therapy in Kit+ GIST pts is unknown, the NCCN guidelines recommend treatment for ≥36 months in high-risk pts based on clinical trials showing reduced risk of recurrence and mortality in pts receiving long-term adjuvant IM. The objective of this study was to investigate clinicians’ recurrence risk assessment and GIST management in patients receiving adjuvant IM for short- (6-12 months) vs. long-term (≥24 months) in community practice. Methods: GIST-related and treatment characteristic information on adult pts with primary resectable Kit+ GIST initiating IM ≤84 days after surgery (short-term: 411 pts; long-term: 408 pts) was collected from 320 U.S. oncologists using an online data collection form. In addition, physician prescribing patterns and perception of risk assessment and IM duration were collected. Results: Indicators of risk (tumor size, mitotic count, and tumor location) were significantly associated with IM treatment duration. Tumor rupture status did not impact IM duration, except when unknown, in which case pts had longer IM duration. About 50% of pts had not been tested for Kit mutation; 31% of physicians reported that it would not have changed therapy/management or were not aware of how results should have impacted GIST management. Among short-term pts for whom physicians reported a reason for IM discontinuation, main reasons included non-severe adverse events, completion of the 1-year treatment scheduled, economic constraint/health plan coverage change, and pts’ preference. Overall, 77.8% of surveyed physicians reported that pt risk profile drove their decision of continuing IM over an extended period of time. However, in practice 39.9% of the short-term pts and 48.8% of the long-term pts had a high risk profile as assessed by Fletcher classification; suggesting a lack of consistency between treatment related opinions and practice. Conclusions: These observed discrepancies highlight the need for standardization of risk assessment practices and education among community oncologists and pts.

Gastrointestinal stromal tumor: Our experience

Gastrointestinal stromal tumor: Our experience

706P - Cost-Effectiveness Analysis of Three Year versus One Year Imatinib for the Treatment of Patients at High Risk of Disease Recurrence Following Surgical Resection of Kit (CD117) Positive Gastrointestinal Stromal Tumours (GIST)

ABSTRACT Background Imatinib is licensed for the adjuvant treatment of adult patients who are at significant risk of disease recurrence following resection of KIT (CD117) positive GIST. The SSG Phase III trial has shown significant survival benefits for patients who received three years of treatment with Glivec® (imatinib) after surgery to remove KIT (CD117)-positive GIST (KIT+ GIST) compared to one year of treatment. Aim: To evaluate the cost-effectiveness of three years' imatinib adjuvant therapy in comparison with one year therapy for adult patients at high risk of disease recurrence following surgical resection of KIT (CD117) positive GIST in Scotland. Methods The economic model predicts long-term survival for patients on three years of adjuvant imatinib compared with those on one year of therapy. A Markov state-transition model was used to simulate patient pathways over a lifetime horizon. Patients were grouped into three primary health states: (1) free of recurrent GIST; (2) recurrent GIST; and (3) death (from GIST or other causes). Efficacy data were derived from a retrospective review of the SSG study to identify high risk patients, as defined by the Miettinen risk criteria. Costs (drug costs, hospital appointments for administration and monitoring, and treatment for adverse events) and health related quality of life values were assigned to each health state. Cost-effectiveness was expressed in terms of incremental cost per quality-adjusted life-years (QALYs) gained. Results Three years of adjuvant imatinib therapy for patients at high risk of recurrence was predicted to achieve an additional 1.58 QALYS compared with one year of treatment. These health benefits are gained at an estimated incremental cost per QALY of £14,108. These results were robust to changes in key model parameters. Conclusions The analysis suggests that, for patients at high risk of recurrence following surgical resection of localised GIST, three years of adjuvant imatinib treatment leads to improved long term quality-adjusted survival compared with one year's therapy. Extended adjuvant treatment with imatinib represents good value for money according to currently accepted standards of cost-effectiveness in Scotland. Disclosure L. Gray: I am an employee of Novartis Pharmaceuticals UK Ltd, manufacturer of imatinib. All other authors have declared no conflicts of interest.

704P - Cost-Effectiveness of Three-Years of Adjuvant Imatinib in Gastrointestinal Stromal Tumors (GIST) in Canada

ABSTRACT Background Recent clinical trial data have demonstrated that 3 years (yrs) of adjuvant imatinib therapy for patients with surgically resected GIST leads to a significant improvement in recurrence free survival & overall survival vs. 1 yr of therapy. The objective of this study is to assess cost-effectiveness of treating with 3 yrs vs. 1 yr of adjuvant imatinib in Canada from a payer's perspective. Methods A Markov model was developed to predict GIST recurrence, treatment (txt) costs, & quality-adjusted survival over a lifetime horizon. Patients transitioned between 3 health states: free of GIST recurrence, GIST recurrence, & death. Monthly recurrence & mortality rates for 3 yr & 1 yr imatinib were derived from SSGXVIII/AIO clinical trial. The 5 yr recurrence rate observed in the trial was extrapolated for the remaining duration of the model horizon. First recurrence after active txt was treated with imatinib 400 mg daily and recurrence during active txt was treated with 800mg daily. For subsequent disease progression, patients were treated with imatinib 800mg, sunitinib or best supportive care. After 5 years, txt specific mortality rate was applied for patients with recurrence. Costs & utilities were derived from published literature. Expected costs & quality-adjusted life years (QALYs) were estimated for each txt strategy. Costs & QALYs were discounted at 5% per yr. Extensive sensitivity analyses were conducted. Results Patients on 3 yrs of imatinib had higher QALYs (7.70 vs 6.54) vs. 1yr of imatinib. Total lifetime cost per patient was $182,000 with 3 yrs vs. $134,500 for 1 yr of imatinib therapy. Incremental cost effectiveness ratio of 3 yrs of imatinib vs 1 yr of imatinib was $40,877/QALY. Model results were sensitive to rate of GIST recurrence beyond 5 yrs. At a threshold of $100,000 or $50,000/QALY, 3yr imatinib therapy was cost-effective in 100% of simulations vs. 1 yr of imatinib. Conclusions Model results suggest that treating patients with 3 yrs of imatinib is cost-effective vs. 1 yr of imatinib below the commonly used threshold in Canada. Both clinical & economic results suggest treating surgically resected GIST patients with 3 yrs of imatinib would result in improved quality-adjusted & overall survival. Disclosure A. Parthan: Study was sponsored by Novartis and I have consulting relationship with Novartis. M. Sanon: The study was sponsored by Novartis and I had consultancy relationship with Novartis at the time of the study. J. Coombs: Employed at Novartis and holds Stock for Novartis. K. El Ouagari: employed at Novartis and owns stocks for Novartis

1489P - Final Results of a French Sarcoma Group (FSG) Retrospective Review of 110 Patients with Primary Localized Gastrointestinal Stromal Tumors (GIST) of the Duodenum

ABSTRACT Background Duodenal GISTs represent 3-5% of all GISTs, with limited understanding of patient outcomes from small series. We conducted a retrospective analysis of localized duodenal GISTs over the past 18 years. Methods Patients (pts) were identified in 2 ways: a group of 101 pts reported via survey from 20 FSG centers, and a group of 9 pts included in the BFR14 trial. Results Pts were: 55 females, 55 males, with a median age of 57 years (30-84), and median ECOG 0 (0-3). Abdominal pain, anemia, and overt GI bleeding were the most common symptoms. Tumors (T) originated mainly in D2 (41%), or D3 (27%), with a median size of 5 cm (1.5-30). All pts except four had resection of the primary T. Surgical procedures were: local resection (LR) [segmental duodenectomy (n = 31), wedge local resection (n = 31), local excision (n = 6)], and duodenopancreatectomy (DP, n = 20). Resections were R0 in 84 pts (79%), R1 in 6 pts (6%). T characteristics included: KIT+ (n = 100), CD34 + (n= 54), mitoses/50 HPF ≤ 5 (n= 70), or > 5 (n = 24), Miettinen low-risk (n = 37), and high-risk (n = 19), necrosis (n = 29), spindle cell (n = 84). Genotype was evaluated in 36 cases: KIT exon 11 mutant (n = 30), no mutation (n = 4), and KIT exon 9 mutant (n = 2). 12 pts received neoadjuvant imatinib (IM) therapy resulting in 6 PR, 3 SD, 1 PD. 17 pts received adjuvant IM therapy. With a median FU of 32 months (1-250), 95 pts (86%) are alive. Twenty-eight (26%) pts relapsed: 6 LR, and 26 metastases. The 4-year OS and EFS rates were 89.5% and 68.2 %. The 6-year OS and EFS rates were 89.5% and 36.5%. Univariate analysis showed that: age and ECOG PS have an impact on OS (p= 0.008, p Conclusions Pts with resected duodenal GIST have a reasonably favourable prognosis. LR rather than DP should be pursued if possible to preserve optimal pancreas function. Neoadjuvant IM may potentially allow a proportion of patients requiring DP to undergo LR. Adjuvant IM should be systematically discussed with a patient based on his individual-risk of relapse. Disclosure All authors have declared no conflicts of interest.

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.

Management of Gastrointestinal Stromal Tumors: Looking Beyond the Knife. An Update on the Role of Adjuvant and Neoadjuvant Imatinib Therapy

Gastrointestinal stromal tumors (GISTs) have traditionally been treated with surgical resection alone resulting in high rates of recurrence. However, the discovery of imatinib efficacy in GIST has revolutionized its management. Imatinib may be used as neoadjuvant therapy with the goal of reducing tumor size, minimizing surgical morbidity and, in some cases, rendering inoperable cases operable. In addition, imatinib use in the adjuvant setting to eradicate micrometastases and prevent recurrence has shown promising results in reducing relapse rates. Appropriate patient selection and optimal dose and duration of imatinib therapy remain undecided and require further investigation. We present a literature review and a case report of our patient with a symptomatic gastric GIST managed successfully utilizing neoadjuvant imatinib therapy, laparoscopic limited resection, and adjuvant imatinib therapy.

Cost-effectiveness of 3-years of adjuvant imatinib in gastrointestinal stromal tumors (GIST) in the United States

Background:Recent clinical trial data have demonstrated that 3 years vs 1 year of adjuvant imatinib therapy for patients with surgically resected Kit+ Gastrointestinal Stromal Tumors (GIST) leads to a significant improvement in recurrence-free survival and overall survival. This study assesses the cost-effectiveness of treating patients with 3 years vs 1 year of imatinib from a US payer’s perspective.Methods:A Markov model was developed to predict GIST recurrence and treatment costs. Patients enter the model after surgery and transition among three health states: free of recurrence, recurrence, and death. Recurrence, mortality, costs, and utilities were derived from clinical trial and published literature. Expected costs and quality-adjusted life years (QALYs) were estimated and discounted at 3%/year. Deterministic and probabilistic sensitivity analyses were conducted.Results:Patients receiving 3 years of imatinib had higher QALYs (8.53 vs 7.18) than those receiving 1 year of imatinib. Total lifetime per-patient cost was $302,100 for 3 years vs $217,800 for 1 year of imatinib. Incremental cost effectiveness ratio of 3 years vs 1 year of imatinib was $62,600/QALY. Model results were sensitive to long-term rate of GIST recurrence (beyond 5 years) and cost of imatinib. At a threshold of $100,000/QALY, 3 years vs 1 year of imatinib was cost-effective in 100% of simulations.Limitations:The model is a simplified representation of disease natural history and may not account for all possible health states and complications associated with disease. Resource utilization on treatment was estimated using the resource use data from previous trials, therefore calculated medical costs might be over-estimated compared to the real-world setting.Conclusions:Model results suggest that treatment with 3 years vs 1 year of imatinib is cost-effective at a $100,000/QALY threshold. Clinical and economic results suggest treating surgically resected Kit+ GIST patients with 3 years of imatinib would result in improved quality-adjusted survival.

Length of adjuvant imatinib therapy in GIST: Weighing benefits, side effects and costs

A recent large randomized clinical trial showed a survival advantage with 36 vs 12 months of adjuvant imatinib in patients with resected gastrointestinal stromal tumors (GISTs). However, there was a higher therapy discontinuation rate with the longer duration of treatment. Preferences of individual GIST patients and the imatinib risk/benefit ratio should always be sought before employing this agent in adjuvant setting for longer than 12 months. A shorter duration of therapy may be preferred in patients with a limited life expectancy, serious cardiovascular co-morbidities, diminished compliance or poor adherence to oral therapy. Further study of underlying economic, psychosocial, and physical barriers of longer vs shorter duration of adjuvant therapy in this patient population is probably warranted.

Diagnosis and initial evaluation of patients with gastrointestinal stromal tumor (GIST): An observational study of 1,226 patients.

10088 Background: The GIST registry (reGISTry) is an observational database designed to determine diagnostic method and evaluation of GIST patients outside of clinical trials. We previously described differences in treatment of patients in community versus academic centers (Pisters, Ann Oncol 2011;22:2523-9). Herein we present distinct differences in the diagnosis and initial evaluation of patients with GIST. Methods: The analysis cutoff date was May 2010. Patient demographics, presenting symptoms, diagnostic methodology, and KIT and PDFGRA mutations were described. For localized tumors, size and mitotic index (MI) were collected. Results: 1226 patients were included in this analysis. Initial diagnosis was most commonly made by surgeons (54.6%) and gastroenterologists (15.7%). Primary management decisions were made at time of diagnosis by medical oncologists (53%) and surgeons (53%) (sum &gt;100% due to ≥1 responses/site). 84% were symptomatic at diagnosis, while 16% were diagnosed incidentally. Diagnostic procedure was performed during surgery (75%) and/or by endoscopy (22%) or interventional radiology (11%) using percutaneous core biopsy or fine needle aspirate. Initial diagnostic imaging was by CT scan (76%), endoscopy (25%), ultrasound (12%), or a combination. Most primary GISTs were located in the stomach (55%) or small intestine (28%). At diagnosis, localized and metastatic disease was seen in 83% and 17% of patients, respectively, with metastases mainly in the liver (62%) and/or peritoneum (36%). KIT immunostaining was performed in 93% of patients, with 98% positive. Mutation analysis was carried out in 8% of cases (57% KIT exon 11 and 12% exon 9 mutations). Of localized primary tumors, 52% were &gt;5 cm in size and 23% had &gt;5 mitoses per 50 high-power fields. Conclusions: We found that initial diagnosis is made by several different modalities. The majority of GIST patients are managed by medical and surgical oncologists. Most patients with localized tumor were at intermediate risk of recurrence and would be considered for adjuvant imatinib therapy.

Risk of disease recurrence and mortality in gastrointestinal stromal tumor (GIST) patients receiving short-term versus long-term imatinib adjuvant therapy: A chart review analysis.

e20511 Background: The benefits of long-term (36 months) use of adjuvant imatinib (IM) in high risk GIST patients (pts) have been demonstrated in a recent multicenter, prospective clinical trial that compared efficacy and safety of 3 years vs 1 year IM treatment. However, in clinical practice, there is no consensus on the optimal IM treatment duration after surgery. The objective of this retrospective observational study was to compare the risk of recurrence and survival among primary resectable Kit positive GIST pts treated with adjuvant IM for a short vs an extended period of time in a real-world setting. Methods: Information on adult pts with primary resectable Kit positive GIST initiating imatinib ≤84 days after surgery was collected from 248 U.S. oncologists using an online data collection form. Detailed pt information following first GIST diagnosis, including demographic, GIST-related characteristics (e.g., risk profile), comorbidity profile, IM treatment characteristics, disease recurrence and mortality was collected for pts with short-term (6-12 months) and long-term IM use (≥24 months). Disease recurrence and mortality rates were estimated from the 1st surgery date to the 1st evidence of recurrence, mortality, or end of observation period. Multivariate Cox proportional hazard models were used to compare recurrence and mortality rates between short vs long term IM use pts. Results: Among the 246 short-term and 395 long-term IM pts, the median follow up was 884 and 963 days, respectively. The average age was similar [59.0 (10.4) vs 58.1 (9.5); p=.23] but short-term pts had less males [57.7% vs 69.6% (p&lt;.01)] and a lower Miettinen risk score [0.3 vs 0.4, p&lt; .01)] than long-term pts. Disease recurrence [7.3 vs 1.8%, (p&lt; .01)] and mortality rates [6.9% vs 2.3%, (p &lt; .01)] were also higher in short- vs long-term pts. The adjusted risk of recurrence was 4.77 times [95% CI: 1.98 – 11.48, (p&lt;.01)] higher and mortality risk was 3.44 times [CI: 1.53 – 7.75, (p&lt;.01)] higher in short- vs long-term pts. Conclusions: Use of IM over an extended period of time is associated with a reduction in long-term risk of disease recurrence and mortality.

Primary localized gastrointestinal stromal tumors (GIST) of the duodenum: Final results of a French Sarcoma Group (FSG) retrospective review of 110 patients (pts).

10078 Background: Duodenal GISTs represent 3-5% of all GISTs with limited understanding of patient outcomes from small series. We conducted a retrospective analysis of primary localized duodenal GISTs over the past 18 years. Methods: Pts were identified in two ways: a group of 101 pts reported via survey from 20 FSG centers, and a group of 9 pts enrolled in the BFR14 trial. Results: Pts were:55 females, 55 males, with a median age of 57 years (30-84), and median ECOG 0 (0-3). Abdominal pain, anemia, and GI bleeding were the most common symptoms. Tumors (T) originated mainly in D2 (41%), or D3 (27%), with a median size of 5 cm (1.5-30). All pts except four had resection of the primary T. Surgical procedures were: local resection (LR) [segmental duodenectomy (n=31), wedge local resection (n=31), local excision (n=6)], and duodenopancreatectomy (DP, n=20). Resections were R0 in 84 pts (79%), R1 in 6 pts (6%). T characteristics included: KIT+ (n=100), CD34 + (n= 54), mitoses/50 HPF ≤ 5 (n= 70), or &gt; 5 (n=24), Miettinen low-risk (n=37), and high-risk (n=19), necrosis (n=29), spindle cell (n=84). Genotype was evaluated in 36 cases: KIT exon 11 mutant (n=30), no mutation (n=4), and KIT exon 9 mutant (n=2). 12 pts received neoadjuvant imatinib (IM) therapy resulting in 6 PR, 3 SD, 1 PD. 17 pts received adjuvant IM therapy. With a median FU of 32 months (1-250), 95 pts (86%) are alive. Twenty-eight (26%) pts relapsed: 6 LR, and 26 metastases. The 4-year OS and EFS rates were 89.5% and 68.2 %. The 6-year OS and EFS rates were 89.5% and 36.5%. Univariate analysis showed that: age and ECOG PS have an impact on OS (p= 0.008, p &lt;0.001), necrosis, spindle-cell type, T size, mitoses/50 HPF, and Miettinen risk were predictive of relapse (p&lt; 0.001). In multivariate analysis tumor size and mitoses/ 50 HPF only were predictive of relapse (p&lt; 0.001). Conclusions: Pts with resected duodenal GIST have a reasonably favourable prognosis. LR rather than DP should be pursued if possible to preserve optimal pancreas function. Neoadjuvant IM may potentially allow a proportion of patients requiring DP to undergo LR. Adjuvant IM should be systematically discussed with a patient based on the individual-risk of recurrence.

Le traitement médical des GIST : du palliatif au curatif

Since the discovery of the remarkable efficacy of Imatinib in metastatic GIST at the end of the last century, dozens of studies have further advanced the management of this disease. Considerable progress has been made in the last dozen years thanks to this tyrosine kinase inhibitor, not only in terms of the definition and classification of these tumors, but also in our knowledge of their molecular mechanisms and in the therapeutic management of patients with this rare disease. Treatment of GIST now serves as a model--or even the model--for targeted therapy in oncology. Over 90% of relapsing patients benefit from first-line Imatinib therapy, with a median survival time of 60 months compared to only 18 months before the Imatinib era. This revolution has transformed the outlook of patients with metastatic disease. It has also led to a review of medical and surgical attitudes and prolonged the management of these patients, most of whom will live normally with dormant residual disease. Imatinib should not be interrupted but continued until the tumor progresses or intolerable adverse effects occur. Early studies showed that adjuvant Imatinib therapy given for one year after resection of localized GIST reduced the recurrence rate by 70% in patients with a significant risk of relapse. Administered for three consecutive years, Imatinib even had a significant impact on survival. Despite these results, the optimal duration of Imatinib therapy in the adjuvant setting remains to be defined, as patients who relapse after Imatinib discontinuation remain remarkably sensitive to the same drug In addition to Imatinib (and sunitinib, that has also proven effective in metastatic disease), several other tyrosine kinase inhibitors are in the pipeline. Coupling of these drugs with the GIST molecular profile opens up promising perspectives for the future. Successive advances in GIST therapy have created significant opportunities for the treatment of other tumors.