Surgical Resection of Gastrointestinal Stromal Tumors After Treatment with Imatinib (original) (raw)
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Annals of Surgery, 2007
Objective: To explore the role of surgery of residual disease following a period of therapy with imatinib mesylate in advanced gastrointestinal stromal tumors (GIST). Methods: From January 2001 to June 2005, 159 patients with advanced/metastatic GIST were treated with imatinib mesylate at a single institution. As of June 2002, 38 patients were selected for surgery following a variable period of imatinib therapy. Twentyseven patients were operated on while they were in response, 8 in progression, 3 for localized disease. Clinical, pathologic, and molecular features were assessed and are reported. Results: Postsurgery PFS was 96% at 12 months and 69% at 24 months for responding patients, while it was nil at 12 months for progressing ones. Disease-specific survival at 12 months was 100% for responding patients and 60% for progressing ones. In responding cases, secondary progression was mainly related to postsurgical imatinib discontinuation, irrespective of pathologic or molecular variables. In progressing patients, secondary resistance was mainly related to acquired mutations. Conclusion: In advanced GIST patients who are responding to imatinib mesylate, the role of surgery is not formally demonstrated at the moment, but this option may well be considered investigational, or suitable for an individualized decision-making in the lack of evidence. In our series, patients progressing on imatinib mesylate did not seem to have any major benefit from surgery, although their number is low.
Yonsei Medical Journal, 2009
For patients with primary, localized gastrointestinal stromal tumors (GIST), surgery with complete excision is the treatment of choice. 1 However, more than half of patients experience tumor recurrence during the course of their disease, 2 and complete resection can be achieved only in less than half of these patients who had recurrence of the tumors. Recently, imatinib has been applied in the treatment of unresectable or recurrent GISTs, resulting in improved patient survival. However, long-term results of imatinib in metastatic GIST as well as its complete response during treatment are very rare. 3-6 Moreover, the results of cytoreductive surgery in patients with far advanced or metastatic GISTs who are treated with imatinib are also rare. Herein, we report two patients who have experienced long-term survival with recurrent GIST after receiving cytoreductive surgery with imatinib therapy.
European Journal of Surgical Oncology (EJSO), 2014
Background: Long-term complete remissions remain a rare exception in patients with metastatic gastrointestinal stromal tumors (GIST) treated with IM (imatinib). To date the therapeutic relevance of surgical resection of metastatic disease remains unknown except for the use in palliative intent. Patients and methods: We analyzed overall survival (OS) and progression-free survival (PFS) in consecutive patients with metastatic GIST who underwent metastasectomy and received IM therapy (n ¼ 239). Results: Complete resection (R0þR1) was achieved in 177 patients. Median OS was 8.7 y for R0/R1 and 5.3 y in pts with R2 resection (p ¼ 0.0001). In the group who were in remission at time of resection median OS was not reached in the R0/R1 surgery and 5.1 y in the R2surgery (p ¼ 0.0001). Median time to relapse/progression after resection of residual disease was not reached in the R0/R1 and 1.9 years in the R2 group of patients, who were resected in response. No difference in mPFS was seen in patients progressing at time of surgery. Conclusions: Our analysis implicates possible long-term survival in patients in whom surgical complete remission can be achieved. Incomplete resection, including debulking surgery does not seem to prolong survival. Despite the retrospective character and likely selection bias, this analysis may help in decision making for surgical approaches in metastatic GIST.
Update on management of GIST and postsurgical use of imatinib
Open Access Surgery, 2010
The advent of imatinib is a milestone in the treatment for locally advanced and metastatic gastrointestinal stromal tumor (GIST) at a dose of 400 mg/day. A higher starting dose of 800 mg/day is recommended only for patients harboring the KIT exon 9 mutation. Studies of imatinib plasma levels are presently ongoing, possibly leading to dose adjustments in the single patient. In localized GIST, complete surgical excision (R0) is considered the standard treatment. Imatinib pretreatment is recommended if R0 surgery is not feasible, or if less mutilating surgery might be achieved by cytoreduction. Whenever surgical morbidity is expected to be an issue, imatinib should be considered even for resectable primary disease in the preoperative setting. Patients with completely resected primary GIST at significant risk of recurrence (based on tumor mitotic rate, size, and location) can be considered for adjuvant imatinib. Dose adjustments could be considered for exon 9 mutant GIST. Imatinib is well tolerated, and its side effects including nonhematologic (periorbital edema, fatigue, nausea, diarrhea, myalgia, skin rash, headache, and abdominal and chest pain) and hematologic (anemia, granulocytopenia, and particularly neutropenia) toxicities are usually mild, although the severity of adverse events increases with dose. While treatment should be continued indefinitely in advanced/metastatic patients, because its interruption is generally followed by relatively rapid tumor progression, the optimal duration of postoperative imatinib therapy is presently not known, even if it is likely that longer disease control will be obtained with longer treatment duration. Patients should be aware that it is not possible thus far to predict the impact of adjuvant therapy on survival. However, the impact on disease control has been dramatic, and imatinib represents a major step forward in the treatment of this rare disease.
Surgical Oncology, 2005
Surgical resection is the treatment of choice for the gastrointestinal stromal tumors (GISTs). In the literature, the 5-year patient survival after surgical resection, ranged from 48 to 80%, before the era of imatinib mesylate and the exploration of the prognostication criteria. Imatinib mesylate targets an intracellular signaling molecule of the natural history and malignant development of GISTs, and increased the 5-year survival rate, after the resection of primary low-risk GISTs, to similar values to the normal population. For high-risk GISTs, current knowledge which is still under expansion, show major improvement at the 1-year survival rate of more than 90% versus less than 50% before imatinib era. After surgical resection, for both low and high malignant potential GISTs, a closed control directed to the early identification of confined resectable recurrences, is required. This paper assesses the current knowledge of GIST management, motivated by a case of patient with intermediate risk GIST. r
International Journal of Surgery, 2005
Gastrointestinal stromal tumours (GISTs) are defined as a group of C-KIT positive mesenchymal tumours of the gastrointestinal tract. Although they may arise throughout the gut, the commonest sites are stomach and small intestine. Over 80% of metastases are to the liver and omentum. Targeted therapy (imatinib) can inhibit C-KIT and thereby aberrant tumoural proliferation. Imatinib may induce shrinkage of lesions and cystic change. Such physical changes often correspond with reduced metabolic activity demonstrated by 18-FDG PET scans. These changes may enable metastatectomy reducing tumour pain and the risk of haemorrhage and rupture in the short term. In the long term, resection may lessen the risk of recurrence by removing potentially resistant clones. The precise role of palliative resection for GIST metastases on imatinib remains unclear. Imatinib has changed the natural history of metastatic GISTs, with increased survival times. Surgery remains an important management strategy in the metastatic setting because complete pathological responses are rare with imatinib. Surgery is likely to provide the best palliation, greatest reduction in tumour burden and eliminate resistant clones. A multidisciplinary team approach with expertise concentrated in a few centres specialising in the management of these rare tumours is vital to the successful outcome. Future issues regarding the management of differential response of the metastases to imatinib are highlighted. With the emergence of techniques enabling identification of the precise mutational status of the C-KIT
Journal of Gastrointestinal Cancer, 2012
Purpose To 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. Methods Detailed information on primary resectable KITpositive 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. Results Among 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 presurgery 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. Conclusions Patient 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. Keywords Gastrointestinal stromal tumors. GIST. KIT. KIT inhibitors. Imatinib. Soft tissue sarcomas. Sarcomas Background A gastrointestinal stromal tumor (GIST) is a type of softtissue sarcoma that usually develops in cells within the wall of the stomach or intestines. GISTs may result from the over-expression or activation of mutation in KIT (CD117) protein or platelet-derived growth factor receptor alpha which provides a stimulus for tumor cell proliferation [1, 2]. The incidence of a GIST is estimated to be approximately 3,000-6,000 cases per year in the US [3, 4]. Most common GISTs sites are stomach (60 %), jejunum and ileum (30 %), duodenum (5 %), and colorectum (<5 %) [5, 6]. Approximately 20 % to 25 % of gastric GISTs and 40 % to
Management of gastrointestinal stromal tumours in the Imatinib era: a surgeon's perspective
World Journal of Surgical Oncology, 2008
Background: Surgical resection has remained the mainstay of treatment of GIST with a 5-yearsurvival of 28-35%. Tyrosine kinase inhibitor (Imatinib) has revolutionised the treatment of these tumours. The current research is directed towards expanding the role of this drug in the treatment of GIST. We present our experience of managing GIST in this institute.