Time to Definitive Failure to the First Tyrosine Kinase Inhibitor in Localized GI Stromal Tumors Treated With Imatinib As an Adjuvant: A European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Intergroup Randomized Trial in Collaboration With the Australasian Gastro-Intestinal Trials Group, UNICANCER, French Sarcoma Group, Italian Sarcoma Group, and Spanish Group for Research on Sarcomas

Casali, Paolo G.; Cesne, Axel Le; Velasco, A. Poveda; Kotasek, Dusan; Rutkowski, Piotr; Hohenberger, Peter; Fumagalli, Elena; Judson, Ian; Italiano, Antoîne; Gelderblom, Hans; Adenis, Antoine; Hartmann, Jörg T.; Duffaud, Florence; Goldstein, David; Broto, Javier Martín; Gronchi, Alessandro; Tos, Angelo Paolo Dei; Marréaud, Sandrine; Graaf, Winette T.A. van der; Zalcberg, John; Litière, Saskia; Blay, Jean‐Yves

doi:10.1200/jco.2015.62.4304

Cited by 155 publications

(129 citation statements)

References 18 publications

(2 reference statements)

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“…Most GISTs have a gain-offunction mutation of the c-kit or platelet-derived growth factor receptor alpha (PDGFRA) genes in ICC, which results in ligand-independent activation of the receptors and consequential tumor progression (3)(4)(5). Although surgery is the most effective treatment for resectable primary GISTs without metastasis, post-operative recurrence or metastasis occurs in nearly 30% of patients within 3 years after complete resection in the absence of adjuvant therapy, and those metastatic GISTs are difficult to cure with surgery alone (6)(7)(8)). …”

Section: Introductionmentioning

confidence: 99%

Surgery for metastatic gastrointestinal stromal tumor: to whom and how to?

Kikuchi¹,

Hiramatsu²,

Kamiya³

et al. 2018

Transl. Gastroenterol. Hepatol.

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Although imatinib is a standard treatment for metastatic or recurrent gastrointestinal stromal tumors (GISTs), acquired c-kit mutations reportedly cause secondary resistance to imatinib. Sunitinib is a tyrosine kinase inhibitor (TKI) that can be used as second-line therapy in imatinib-resistant or -intolerant GISTs. For sunitinib-resistant or -intolerant GISTs, regorafenib is a standard third-line treatment. Although TKI therapies have revolutionized the treatment of recurrent or metastatic GISTs, they cannot cure GISTs.Therefore, in the era of TKIs, role of cytoreductive surgery for recurrent or metastatic GISTs has been discussed. Retrospective studies of treatment strategies with front-line surgery prior to imatinib have shown that initial cytoreduction confers no benefit in cases of advanced or recurrent GIST, and administering imatinib is the principle treatment. Most retrospective studies report cytoreductive surgery to be feasible in patients with metastatic GIST whose disease is stable or responsive to imatinib. Cytoreductive surgery may be indicated in limited disease progression refractory to imatinib when complete resection is possible, but case selection is critical. Cytoreductive surgery for metastatic GIST treated with sunitinib seems less feasible because of high rates of incomplete resections and complications. The role of cytoreductive surgery for metastatic GISTs would be difficult to establish in a prospective study; individualized treatments need to be carefully designed based on c-kit and platelet-derived growth factor receptor alpha (PDGFRA) mutations and other factors.

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Section: Introductionmentioning

confidence: 99%

Surgery for metastatic gastrointestinal stromal tumor: to whom and how to?

Kikuchi¹,

Hiramatsu²,

Kamiya³

et al. 2018

Transl. Gastroenterol. Hepatol.

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“…Second, only 8.7% of patients were administered adjuvant therapy in this study, even though 67.0% of the patients were categorized as high-risk. Some studies have shown that 1 or 2 years of adjuvant imatinib significantly improved recurrence-free survival (RFS) after complete resection compared to placebo [23,24]. Additionally, 3 years of adjuvant imatinib therapy has been shown to improve RFS significantly better than just 1 year of the therapy in high-risk GIST patients, and its administration is now recommended in high-risk patients [25,26].…”

Section: Discussionmentioning

confidence: 99%

Appropriate Follow-Up Strategies for Gastrointestinal Stromal Tumor Patients Based on the Analysis of Recurrent Interval and Patterns

et al. 2017

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Background/Aims: Previous studies have proposed risk classifications for patients with gastrointestinal stromal tumor (GIST) after resection and have contributed to the prediction of its prognosis. However, optimal postoperative surveillance has not yet been established. Methods: We retrospectively analyzed data from 115 GIST patients who experienced recurrence after complete resection. The relationships between clinicopathological characteristics and the first recurrence sites, or time to recurrence (TTR), were investigated. We also compared the characteristics between 2 subgroups based on a TTR of ≤5 or >5 years. Results: The first recurrence occurred in the abdomen in 114 of 115 patients (99.1%); one case of esophageal GIST recurred in the lung. Gastric and small intestinal GISTs recurred most frequently in the liver or peritoneum, while the most common recurrences of colorectal GISTs were found to be local. Fourteen patients (12.2%) experienced recurrence after >5 years. Smaller tumors and those categorized as lower risk were significantly more frequent in the TTR >5 years group than in the TTR ≤5 years group. In the TTR >5 years group, local recurrence was the most frequent type of recurrence (42.9%). Conclusion: Based on abdominal examination, postoperative surveillance after complete resection for primary GISTs may be recommended for >5 years.

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“…Das progressionsfreie Überleben in den einzelnen Studien ist sehr lang. Allerdings ist die Interpretation dieser Ergebnisse im Vergleich zu Serien mit primär operierten Patienten schwierig, da die Indikation zur zusätzli-chen postoperativen Imatinib-Therapie, die einen erheblichen Einfluss auf das Auftreten eines Rezidives hat [16,17], in den einzelnen Studien heterogen gestellt wurde.…”

Section: Nicht Metastasierte Gist -Primäre Resektion Vs Neoadjuvanteunclassified