[Clinical diagnosis and treatment of gastrointestinal stromal tumor: matching technological breakthrough with patient care].

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the digestive tract. Although GIST has only been recognized as a separate entity for several decades, management strategies for GIST have changed dramatically over time. Advances in treatment have yielded dramatic successes in improving prognosis of patients with GIST. However, the meaningful progress also brings escalating social and economic burdens. There is a long distance between technological breakthroughs and its real benefits of society. Due to the rapid development in a short period, successful experience in disease diagnosis and treatment and the accompanying problems have appeared in a more concentrated and obvious manner. Any medical science exploration and practice initially aim to have the essence of humanism. As practitioners of medical technology, doctors should treat patients as a whole "human" in the process of diagnosis and treatment instead of just focusing on the technology itself. Moreover, doctors should comprehensively consider patients' physical, psychological and social attributes, pay attention to their physical, mental and social needs, find and try to solve problems, so as to promote the developement of medical science in the correct direction.

[Updates and interpretations of the NCCN Clinical Practice Guidelines (2019 6th version) on gastrointestinal stromal tumor].

The diagnosis and treatment of gastrointestinal stromal tumor (GIST) is getting more and more standardized. In the last two decades, due to the elucidation of molecular mechanism of tumorigenesis, as well as the effectiveness of tyrosine kinase inhibitors, GIST has become well-known as one of the most classical models of targeted therapy on solid tumors in the precision medicine era. The National Comprehensive Cancer Network (NCCN) issued the latest version of clinical practice guideline on soft tissue sarcoma in February 2020. Compared with previous versions, the new version of the guideline highlighted the treatment recommendations of avapritinib, which further promoted the precise targeted treatment of GIST.

Imaging surveillance of gastrointestinal stromal tumour: current recommendation by National Comprehensive Cancer Network and European Society of Medical Oncology-European Reference Network for rare adult solid cancers.

Imaging plays an active role in the surveillance of gastrointestinal stromal tumours (GISTs). Risk stratification schemes, based on size, mitotic count, and anatomical site of origin of the GIST, help in planning preoperative and postoperative imaging strategies especially in determining the frequency and duration of surveillance; however, there is no clear consensus on the optimal imaging strategies in patients with GISTs who are completely cured by surgery and patients who are at risk of recurrence. In addition, current surveillance protocols depend on the resectability of the primary tumour and presence of metastatic disease. The objective of this article is to provide a comprehensive review of the role of the different imaging methods for surveillance of GISTs, focusing on the guidelines recommended by National Comprehensive Cancer Network and European Society of Medical Oncology - European Network for Rare adult solid Cancers, and to propose practical guidelines for surveillance of GISTs for various risk categories.

Combination of arginine, glutamine, and omega-3 fatty acid supplements for perioperative enteral nutrition in surgical patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST): A prospective, randomized, double-blind study.

Background: Perioperative enteral nutrition (EN) enriched with immune-modulating substrates is preferable for patients undergoing major abdominal cancer surgery. In this study, perioperative EN enriched with immune-modulating nutrients such as arginine, glutamine, and omega-3 fatty acids was evaluated for its anti-inflammatory efficacy in patients with gastric adenocarcinoma or gastrointestinal stromal tumor (GIST) receiving curative surgery. Materials and Methods: This prospective, randomized, double-blind study recruited 34 patients with gastric adenocarcinoma or gastric GIST undergoing elective curative surgery. These patients were randomly assigned to the study group, receiving immune-modulating nutrient-enriched EN, or the control group, receiving standard EN from 3 days before surgery (preoperative day 3) to up to postoperative day 14 or discharge. Laboratory and inflammatory parameters were assessed on preoperative day 3 and postoperative day 14 or at discharge. Adverse events (AEs) and clinical outcomes were documented daily and compared between groups. Results: No significant differences were observed between the two groups in selected laboratory and inflammatory parameters, or in their net change, before and after treatment. AEs and clinical outcomes, including infectious complications, overall complications, time to first bowel action, and length of hospital stay after surgery, were comparable between treatment groups (all P > 0.05). Conclusion: Immune-modulating nutrient-enriched EN had no prominent immunomodulation effect compared with that of standard EN.

A Novel Theranostic Combination of Near-infrared Fluorescence Imaging and Laser Irradiation Targeting c-KIT for Gastrointestinal Stromal Tumors.

It is difficult to distinguish gastrointestinal stromal tumors (GISTs) from other types of submucosal tumors under conventional gastrointestinal endoscopy. We aimed to detect GISTs by molecular fluorescence imaging using a near-infrared (NIR) photosensitizer (IR700)-conjugated anti-c-KIT antibody and to treat GISTs by photoimmunotherapy with NIR irradiation as a non-invasive theranostic procedure. We also investigated the therapeutic mechanisms. Methods: Human GIST cell lines GIST-T1 and GIST-882M were incubated with IR700-conjugated anti-c-KIT antibody, IR700-12A8, and observed by confocal laser microscopy. Mice with GIST-T1 xenografts or rats with orthotopic xenografts were injected with IR700-12A8 or AF488-conjugated antibody, and observed under IVIS or autofluorescence imaging (AFI) endoscopy. GIST cells were treated with IR700-12A8 and NIR light in vitro and vivo, and cell viability, histology and apoptosis were evaluated. Results: Strong red fluorescence of IR700-12A8 was observed on the cell membrane of GIST cells and was gradually internalized into the cytoplasm. Tumor-specific accumulation of IR700-12A8 was observed in GIST-T1 xenografts in mice. Under AFI endoscopy, a strong fluorescence signal was observed in orthotopic GIST xenografts in rats through the normal mucosa covering the tumor. The percentage of dead cells significantly increased in a light-dose-dependent manner and both acute necrotic and late apoptotic cell death was observed with annexin/PI staining. Cleaved PARP expression was significantly increased after IR700-12A8-mediated NIR irradiation, which was almost completely reversed by NaN3. All xenograft tumors (7/7) immediately regressed and 4/7 tumors completely disappeared after IR700-12A8-mediated NIR irradiation. Histologic assessment and TUNEL staining revealed apoptosis in the tumors. Conclusion: NIR fluorescence imaging using IR700-12A8 and subsequent NIR irradiation could be a very effective theranostic technology for GIST, the underlying mechanism of which appears to involve acute necrosis and supposedly late apoptosis induced by singlet oxygen.

Asian Consensus Guidelines for the Diagnosis and Management of Gastrointestinal Stromal Tumor.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors originating in the gastrointestinal tract. With the introduction of molecular-targeted therapy for GISTs which has yielded remarkable outcomes, these tumors have become a model of multidisciplinary oncological treatment. Although Western clinical guidelines are available for GISTs, such as those published by the National Comprehensive Cancer Network (NCCN) and the European Society of Medical Oncology (ESMO), the clinical situations in Asian countries are different from those in Western countries in terms of diagnostic methods, surgical approach, and availability of new targeted agents. Accordingly, we have reviewed current versions of several GIST guidelines published by Asian countries (Japan, Korea, China, and Taiwan) and the NCCN and ESMO and discussed the areas of dissensus. We here present the first version of the Asian GIST consensus guidelines that were prepared through a series of meetings involving multidisciplinary experts in the four countries. These guidelines provide an optimal approach to the diagnosis and management of GIST patients in Asian countries.

Molecular cytology genotyping of primary and metastatic GI stromal tumors by using a custom two-gene targeted next-generation sequencing panel with therapeutic intent.

BACKGROUND AND AIMS: In an era of precision medicine, customized genotyping of GI stromal tumors by screening for driver mutations will become the standard of care. The fidelity of genotype concordance between paired cytology smears and surgical pathology specimens is unknown. In patients with either primary or metastatic sporadic disease, we sought to determine the frequency of KIT and PDGFRA pathogenic alterations within such specimens, imatinib sensitivity, and the concordance of pathogenic alterations between paired specimens. METHODS: DNA obtained from cytology smears from 36 patients, 24 of whom had paired surgical pathology specimens, underwent targeted next-generation sequencing by using a custom panel to evaluate somatic mutations within KIT (exon 2, 9, 10, 11, 13, 14, 15, 17, 18) and PDGFRA (exon 12, 14, 15, 18) genes. Patients with KIT and PDGRFA wild-type genes completed the Qiagen Human Comprehensive Cancer GeneRead DNAseq Targeted Array V2. RESULTS: Genotyping revealed KIT and PDGFRA mutations in 68% and 15% of patients. The wild-type population did not harbor mutations in BRAF, RAS family, SDHB, SETD2, or NF1. Imatinib sensitivity based on the oncogenic kinase mutation prevalence was estimated to be 68%. Mutational concordance between paired cytology and surgical pathology specimens was 96%. CONCLUSIONS: Our data have demonstrated the ability to stratify either primary or metastatic gastrointestinal stromal tumors by mutational subtype using a targeted next-generation sequencing 2 gene mutation panel. We highlight the ability to use cytology specimens obtained via minimally invasive techniques as a surrogate to surgical specimens given the high mutational landscape concordance between paired specimens.

The standard diagnosis, treatment, and follow-up of gastrointestinal stromal tumors based on guidelines.

Although gastrointestinal stromal tumors (GISTs) are a rare type of cancer, they are the commonest sarcoma in the gastrointestinal tract. Molecularly targeted therapy, such as imatinib therapy, has revolutionized the treatment of advanced GIST and facilitates scientific research on GIST. Nevertheless, surgery remains a mainstay of treatment to obtain a permanent cure for GIST even in the era of targeted therapy. Many GIST guidelines have been published to guide the diagnosis and treatment of the disease. We review current versions of GIST guidelines published by the National Comprehensive Cancer Network, by the European Society for Medical Oncology, and in Japan. All clinical practice guidelines for GIST include recommendations based on evidence as well as on expert consensus. Most of the content is very similar, as represented by the following examples: GIST is a heterogeneous disease that may have mutations in KIT, PDGFRA, HRAS, NRAS, BRAF, NF1, or the succinate dehydrogenase complex, and these subsets of tumors have several distinctive features. Although there are some minor differences among the guidelines--for example, in the dose of imatinib recommended for exon 9-mutated GIST or the efficacy of antigen retrieval via immunohistochemistry--their common objectives regarding diagnosis and treatment are not only to improve the diagnosis of GIST and the prognosis of patients but also to control medical costs. This review describes the current standard diagnosis, treatment, and follow-up of GISTs based on the recommendations of several guidelines and expert consensus.

Clinical Observations on Treatment for Chinese Patients with Gastrointestinal Stromal Tumors.

BACKGROUND: To investigate the diagnostic and treatment methods for Chinese patients with gastrointestinal stromal tumor (GIST). MATERIALS AND METHODS: From January 2004 to June 2014, patients diagnosed with primary GIST and treated by a single medical team in the Department of Digestive Disease of XuYi Hospital of Traditional Chinese Medicine were retrospectively recruited. Re-examination and follow-up was conducted regularly and abdominal enhanced CT, blood biochemistry and responses to surgery or imatinib were recorded. RESULTS: A total of 15 patients were enrolled, including 9 male and 6 female patients, with an average age of 54 years (ranging from 32-81 years). The primary symptoms were abdominal uncomfortable in 5 patients, abdominal pain in 6 patients as well as nausea and vomiting in 4 patients. One patient was diagnosed with bowl obstruction at the first visit. All patients were treated with surgery, and tumor site was confirmed 1 esophagus, 6 stomach, 4 small bowel, and 4 colorectal and all patients were pathologically diagnosed with GIST. Immunochemical test positive for CD 117 was found 12 patients, and positive for CD 34 in7 patients. The median follow-up time was 24 months (range of 3-63). Three metastasis were confirmed 1.5, 2 and 2.6 years postoperatively. Three patients were treatment by imatinib postoperatively. CONCLUSIONS: Surgery remains the main treatment method for Chinese patients with GIST and imatinib could be feasible and safe for treating Chinese patients with GIST.

Underreporting of Gastrointestinal Stromal Tumors: Is the True Incidence Being Captured?

BACKGROUND: Hospital cancer registries are only required to report gastrointestinal stromal tumors (GISTs) if labeled malignant or metastatic, leading to potential loss of cases in national cancer registries. Our objective was to determine whether GISTs are underreported in the US. METHODS: Retrospective review of pathology reports between 2010 and 2013 with diagnosis of GIST was performed at two academic medical centers. Recurrent GISTs were excluded. Pathology reports were cross-referenced to cases reported by each cancer registry. Risk for metastasis/death was determined according to National Comprehensive Cancer Network (NCCN) guidelines. RESULTS: Forty-nine cases of non-recurrent GIST were identified. Only 19/49 (38.8%) cases were reported. None of the 30 non-reported cases were labeled malignant/metastatic on final pathology. To illustrate malignant potential, these tumors were risk stratified. Most (60%) of the non-reported cases were low risk, but there were 4 (13.3%) cases each in the intermediate, high, and unknown risk groups. Additionally, 7/30 (23.0%) cases were treated with tyrosine kinase inhibitors, highlighting clinical concern of malignant GIST. CONCLUSIONS: Our results show that nearly two thirds of GIST cases have been underreported, suggesting that current reporting practices underestimate its true incidence. Revision of reporting guidelines may result in a more accurate estimation of the US disease burden of GIST.

Adherence to Guidelines for Adjuvant Imatinib Therapy for GIST: A Multi-institutional Analysis.

BACKGROUND: Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Adjuvant imatinib therapy improves recurrence-free and overall survival following surgery for patients with high-risk GIST; however, the factors associated with use of adjuvant imatinib therapy are unclear, and adherence to adjuvant imatinib has not been investigated. We sought to determine the clinicopathologic predictors of therapy with adjuvant imatinib following surgical resection for GIST and to determine the utilization of adjuvant imatinib in patients who underwent surgical resection of primary GIST in 2009 or later as recommended by National Comprehensive Cancer network (NCCN) guidelines. METHODS: A multi-institutional cohort including 171 patients who underwent surgery for primary GIST at seven high-volume cancer centers in the USA and Canada between January 2009-December 2012 was used in this study. Receipt of adjuvant imatinib therapy was ascertained, and factors associated with imatinib therapy were analyzed. RESULTS: Following surgery for primary GIST, tumor size (<5.0 cm: ref; 5.0-9.9 cm: odds ratio (OR) 2.36, 95 % confidence interval (CI) 0.74-7.55; >10.0 cm: OR 9.15, 95 % CI 2.28-36.75; p = 0.007), mitotic rate (≤5/50 mitoses per 50 high powered field [HPF]: ref; 6-10/50 HPF: OR 24.91, 95 % CI 3.64-170.35; >10/50 HPF: OR 5.80, 95 % CI 3.64-170.35; p < 0.001), and neoadjuvant therapy (OR 9.52; 95 % CI 2.51-36.14; p = 0.001) were associated with receipt of adjuvant imatinib therapy. Overall, 75 % of patients received appropriate treatment, 23 % of patients were undertreated, and 2 % of patients were overtreated as compared to NCCN guidelines. Adjuvant imatinib therapy was administered in only 53 % of patients for which the NCCN guidelines recommended adjuvant therapy. CONCLUSION: The clinicopathologic factors associated with use of adjuvant imatinib therapy in patients following resection of primary GIST are consistent with established risk factors for recurrence. Adjuvant imatinib therapy remains underutilized in patients with intermediate and high-risk GIST and in patients who receive neoadjuvant therapy. Barriers to adjuvant imatinib therapy in this group of patients needs to be further explored.

Gastrointestinal autonomic nerve tumors: a clinical review.

PURPOSE: Gastrointestinal autonomic nerve tumors (GANTs) are believed to be rare accounting for 1 % of all malignant gastrointestinal tumors. Many gastrointestinal surgeons and gastroenterologists are unaware of this entity. This review aims to highlight the salient clinical features and prognosis of GANTs. METHODS: Using the common search engines and manual cross-referencing, a search of the English literature was conducted for "gastrointestinal autonomic nerve tumor." RESULTS: All of the published literature on GANTs is either case reports or small case series. From 49 retrieved articles, a total of 107 GANT cases were collected with a mean age of 54 years and equal male to female preponderance. The most commonly affected site was small bowel followed by stomach. Esophageal and colorectal GANTs were less frequent. Clinical presentation was variable ranging from non-specific symptoms, abdominal pain, weight loss, iron-deficiency anemia, to obstruction and gastrointestinal bleeding. Acute presentation due to free rupture or perforation with subsequent peritonitis was extremely rare. Endoscopic and radiological investigations were valuable in tumor localization and determination of distant spread. Thirteen patients were lost to or had no follow-up, leaving 94 patients for long-term outcome analysis. All patients were treated by radical surgical resection of the involved organ as this offered the only hope of cure. Local recurrence, metastases, or both developed in 40 % of cases despite radical surgical resection. Resection for local recurrences and hepatic metastases was feasible in some selected cases. Response to adjuvant chemoradiation was poor and imatinib mesilate was effective in cases of metastatic or inoperable CD117-positive GANTs. CONCLUSION: Radical surgical resection of GANTs is the mainstay of treatment. The aggressive behavior after radical resection coined with the poor response to adjuvant chemotherapy call for the urgent need to develop new adjuvant therapies.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in sarcomatosis from gastrointestinal stromal tumor.

The role of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) procedures in the management of patients with gastrointestinal stromal tumor (GIST)-induced sarcomatosis that is refractory to tyrosine kinase inhibitors (TKI) is not well defined. A retrospective analysis of a prospective database of 1070 CRS/HIPEC procedures was performed. Demographics, Eastern Cooperative Oncology Group performance status, resection status, morbidity, mortality, perioperative use of targeted therapies, and overall survival were analyzed. Since 1992, 18 CRS/HIPEC procedures were performed for peritoneal dissemination of GIST. Fifty per cent of these cases were performed before the introduction of TKIs. R0/1 resection was achieved in 72 per cent, whereas 63 per cent of patients were treated with neoadjuvant and/or adjuvant targeted therapy. Thirty-day morbidity and mortality were 33.3 and 5.6 per cent, respectively. Median overall survival after CRS/HIPEC was 3.33 years with 3-year survival of 56 per cent. Median survival in those who did not receive targeted therapy was 1.04 versus 7.9 years for those treated with TKI and cytoreduction. Median postsurgical survival for those treated preoperatively with progression on TKI treatment was 1.35 years versus not reached in those on TKI therapy without progression. Primary therapy for patients with disseminated GIST should be TKI therapy. However, in patients with sarcomatosis from GIST, cytoreduction should be considered before developing TKI resistance. Progression on TKI is associated with poor outcomes even after complete cytoreduction.

Prognostic value of KIT/PDGFRA mutations in gastrointestinal stromal tumors: a meta-analysis.

BACKGROUND: The postulated relationship between KIT/PDGFRA mutations and their prognostic value in gastrointestinal stromal tumors (GISTs) has generated intense attention during the past decade, despite the fact that a great deal of studies have been conducted on this subject. To provide a strong quantitative estimate of this postulated relationship, we carried out a meta-analysis which combined, compared, and summarized the results of existing relevant studies. METHODS: Studies were identified by searching databases and reviewing citations in relevant articles. Of 48 potentially relevant studies, we combined individual patient data from 18 studies which involved 1,487 patients with GISTs, by which we made a comparison between the positive KIT mutation subgroup and the negative KIT mutation subgroup (PDGFRA mutation and wild type). We tabulated and analyzed the patient characteristics from each study, including general information such as age and gender, histopathological parameters, and clinical follow-up outcomes. RESULTS: KIT mutations, compared with PDGFRA mutations and wild type, showed a marked increased risk not only for tumor size (>5 cm) but also for higher mitotic activity (>5), suggesting that KIT mutations significantly correlated with the National Comprehensive Cancer Network (NCCN) high risk or National Institutes of Health (NIH) high risk (1.74 (95% CI, 1.20 to 2.53) and 2.00 (95% CI, 1.08 to 3.68), respectively). Moreover, higher recurrence and metastasis was observed in GISTs with KIT mutations, revealing its closer correlation with clinical malignant risk (P<0.001 for each, with odds ratio (OR) of 2.06 (95%, 1.37 to 3.11) and 2.77 (95%, 1.64 to 4.67), respectively). High risk or malignant GISTs with KIT mutations had a significantly poorer prognosis, as measured by 3-year overall survival, compared to those with PDGFRA mutations and wild type (0.47 (95% CI, 0.25 to 0.90)). CONCLUSIONS: KIT mutations, compared with PDGFRA mutations and wild type, represent a poorer prognostic marker in high risk or malignant GISTs.

Aggressive locoregional management of recurrent peritoneal sarcomatosis.

BACKGROUND AND OBJECTIVES: Peritoneal sarcomatosis responds poorly to systemic chemotherapy and demonstrates high rates of recurrence after resection. We sought to determine perioperative and oncologic outcomes after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) for recurrent sarcomatosis. METHODS: We reviewed 15 patients undergoing 17 CRS/HIPEC for recurrent sarcomatosis from a prospective database. RESULTS: There were four synovial cell sarcomas, five liposarcomas, three leiomyosarcomas, two gastrointestinal stromal tumors (GIST), and three other sarcomas. Adequate cytoreduction (CC-0/1) was achieved in all patients, with a median intra-operative Simplified Peritoneal Carcinomatosis Index of 6 (range: 3-9). Median blood loss and operative time were 1 L (range: 450-5,200) and 402 min (range: 324-680), respectively. Chemoperfusion drug was mitomycin C, cisplatin, or doxorubicin. Significant post-operative complications (Clavien-Dindo III/IV) occurred in four (24%) patients, with no 60-day mortalities and three (18%) 60-day re-admissions. Median intra-abdominal disease-free and overall survival after CRS/HIPEC was 17.2 (95% CI: 2.4-19.7 months) and 22.6 months (95% CI: 6.1-62.6 months), respectively. There was a trend towards delayed recurrence after combined CRS/HIPEC than after prior CRS alone (17.2 months vs. 10.7 months, respectively; P = 0.52). CONCLUSION: Cytoreduction combined with HIPEC may improve loco-regional disease control in patients with recurrent sarcomatosis.

Proteomic approach toward personalized sarcoma treatment: lessons from prognostic biomarker discovery in gastrointestinal stromal tumor.

Sarcomas range from curable tumors to those causing death via metastasis and recurrence. Thus, there is an urgent need for biomarker identification in order to assess the degree of malignancy, predict prognosis, and evaluate possible therapies. Various proteomic approaches and different clinical materials have been used to this end, and candidate biomarkers have been reported for the different types of sarcomas. However, the sample size used in these biomarker studies was generally insufficient, and thus far, no biomarker has been proved useful in clinics. Given that sarcomas are rare, biomarker validation in this setting is more challenging than in other malignancies. In gastrointestinal stromal tumor, adjuvant therapy has proven to be effective. However, only 40% patients experience metastasis after curative surgery alone, and the rest of the patients may not need adjuvant therapy. Using a proteomic approach, we identified pfetin (potassium channel tetramerization domain containing 12, KCTD 12) as a novel prognostic biomarker for sarcoma, and immunohistochemically confirmed its clinical usefulness by a multiinstitutional validation study. Here, we describe our experience and discuss the critical points in the discovery of this biomarker.

Transcatheter arterial chemoembolization for gastrointestinal stromal tumors with liver metastases.

AIM: To evaluate the efficacy and safety of transcatheter arterial chemoembolization (TACE) for gastrointestinal stromal tumor (GIST) with liver metastases after the failure of tyrosine kinase inhibitors (TKIs). METHODS: Patients with histologically confirmed CD117-positive GIST with liver metastases who were resistant and/or intolerant to prior imatinib and/or sunitinib and who received TACE for at least one treatment cycle or only best supportive care and TKI reintroduction were eligible for the study. The patients were divided into two groups: those in TACE group received TACE treatment containing 5-20 mL iodized oil and 40-80 mg doxorubicin hydrochloride and TKI reintroduction or best supportive care, those in control group only received TKI reintroduction or best supportive care. The primary end-point was overall survival and the secondary end-points were, progression-free survival (PFS), response rates, and safety. RESULTS: Sixty patients admitted between June 2008 and October 2011 were eligible for this study, including 22 in TACE group and 38 in control group. In the TACE group, 12 (54.5%) achieved liver partial response, 5 (22.7%) had stable disease, and 5 (22.7%) had liver progressive disease. Disease control rate of liver metastases was 77.3% in the TACE group and 39.5% in the control group. The median liver PFS in TACE group was 47.1 wk (95% CI: 23.9-70.3). The median PFS in TACE group was longer than in control group (30.0 wk, 95% CI: 20.1-39.9 vs 12.9 wk, 95% CI: 11.9-13.9) (P = 0.0001). The median overall survival in TACE group was also longer than in control group (68.5 wk, 95% CI: 57.4-79.6 vs 25.7 wk, 95% CI: 23.2-28.2) (P = 0.0001). TACE treatment significantly reduced the risk of death (hazard ratio: 0.109). Patients without extrahepatic metastases treated with TACE had significantly better prognosis. Most of the adverse events were of grade 1 or 2 and tolerable. CONCLUSION: TACE is effective and well tolerated in GIST patients with liver metastases after TKI failure, and it may be an optional treatment for this disease.

Gastrointestinal stromal tumor surgery and adjuvant therapy.

Gastrointestinal stromal tumors (GIST) are a unique class of mesenchymal tumors identified within the past decade. Intense molecular and genetic study has been used to characterize these tumors and develop treatment strategies. Although the mainstay of treatment remains surgical resection, therapy targeted at inhibiting tyrosine kinases has had dramatic results. Because of the rapid accumulation of information about the diagnosis and treatment of these tumors, the National Comprehensive Cancer Network convened a GIST task force to provide updated recommendations in 2010. As understanding of these tumors advances, rapid changes in recommendations will continue and should warrant regular updates in tumor management.

[Multimodality therapy concepts for soft tissue sarcomas]. / Multimodale Therapiekonzepte bei Weichteilsarkomen.

Despite the fact that soft tissue sarcomas are representing a rare tumor entity with a low incidence rate of about 2-4 per 100,000 per year, they highly require a multimodality therapeutic approach. Based on a reference pathology a complete surgical resection is the first treatment goal. After accomplished R0 resection the local relapse rate can be further decreased by an adjuvant radiotherapy. For primarily irresectable or only partially respectable tumors a neoadjuvant chemotherapy combined with regional hyperthermia should be considered. Patients with metastasized soft tissue sarcomas should receive an anthracyclin-based chemotherapy in a palliative intention. Prognostically more favorable are gastrointestinal stroma tumor, also in advanced stages with metastases, since the tyrosine kinase inhibitors imatinib and sunitinib can induce durable remissions.

Perspective on updated treatment guidelines for patients with gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract and present predominantly in middle-aged and older individuals. Historically, the outlook for patients with GISTs was very poor because of the general lack of efficacy of conventional chemotherapy and the often limited surgical options. However, the recognition of the role of mutations of the v-kit Hardy/Zuckerman 4 feline sarcoma viral oncogene homolog KIT and the platelet derived growth factor receptor alpha gene PDGFRα in the development of GISTs led to the evaluation of potential antitumor effects of the tyrosine kinase inhibitors imatinib and, more recently, sunitinib. Consequently, these molecularly targeted therapies were introduced into clinical practice, and the outcome for patients with GISTs improved considerably. In the last few years, the European Society of Medical Oncology, the National Comprehensive Cancer Network, and the Canadian Advisory Committee on GIST each published a major set of guidelines or practice recommendations for the management of patients with GIST. In the current review, the latest recommendations from each organization are summarized in terms of diagnosis and risk assessment, tumor staging, surgical and/or drug treatment of primary resectable and recurrent metastatic disease, and patient follow-up and assessment. In addition, areas of consensus and points of divergence among the guidelines are highlighted along with any unresolved issues.