Surgical removal of residual disease during imatinib treatment may allow for complete remission in selected GIST patients after response to therapy, theoretically prolonging durable remission, but it is necessary to continue imatinib for its maintenance.
BACKGROUND:The objectives of the current study were to assess the reliability of the new revision of the American Joint Committee on Cancer (AJCC) staging system for gastrointestinal stromal tumors (GISTs) based on the National Comprehensive Cancer Network-Armed Forces Institute of Pathology risk classification and to analyze the factors that influence after resection for primary GISTs in 2 AJCC groups: patients with GISTs originating from the stomach and omentum (G-GISTs) and patients with other primary GISTs located mainly in the small bowel (nongastric GISTs [NG-GISTs]). METHODS: The authors prospectively analyzed a group of 640 patients with primary, CD117-positive GISTs who underwent surgery with curative intention (R0/R1 resection), including 340 G-GISTs (55.5%) and 300 NGGISTs (44.5%). Factors were explored that had an effect on disease-free survival time (DFS), which was calculated from the date of radical operation to the date of recurrence or last follow-up. The median follow-up was 39 months. RESULTS: Compared with NG-GISTs, G-GISTs were characterized by a significantly lower median size (5.3 cm and 8.5 cm, respectively; P < .0001) and lower mitotic activity (median, 3 in 50 high-power fields [HPF] vs 5 in 50 HPF; P < .0001), and they were diagnosed in older patients (median age, 62 years vs 57 years; P ¼ .002). The most commonly detected mutations in G-GIST were those located in KIT exon 11 (60.5%) and platelet-derived growth factor receptor alpha (PDGFRA) exon 18 (19%) versus KIT exons 11 and 9 in NG-GISTs (72% and 17.4%, respectively). The prognosis of patients who had G-GISTs was significantly better compared that of patients who had NG-GISTs, with 5-year DFS rates of 69% (median, 83 months) versus 43% (median, 33 months), respectively (P < .00001). The most significant prognostic factors that correlated with shorter DFS in both G-GISTs and NG-GISTs were primary tumor size >5 cm and >10 cm (P < .0001) and mitotic index >5 in 50 HPF and >10 in 50 HPF (P < .0001). The 5-year DFS rates in G-GISTs according to AJCC stage categories were as follows: 96% for stage IA tumors, 92% for stage IB tumors, 51% for II tumors, 22% for stage IIIA tumors, and 22% for stage IIIB tumors (P < .0001). The 5-year DFS rates in NG-GISTs according to AJCC categories were as follows: 92% for stage I tumors, 66% for stage II tumors, 28% for IIIA tumors, and 16% for IIIB tumors (P < .0001). The high prognostic significance of the AJCC classification also was confirmed for overall survival data, including the impact of therapy with tyrosine kinase inhibitors. CONCLUSIONS: The reliability of AJCC risk classification after resection of primary GIST was confirmed for DFS and overall survival. Patients with primary G-GISTs had a better prognosis than patients with NG-GISTs. In both groups, primary tumor size and mitotic activity were the most important prognostic factors in terms of DFS. Cancer 2011;117:4916-
The scheduled combined treatment (surgery plus IOBRT) was possible to perform in 66% of RSTS cases that received surgical treatment. The complication rate was high, but we consider it acceptable because of the necessity for extensive aggressive surgical treatment in regionally advanced RSTS. EBRT seems to be an indispensable part of treatment that provides better local control.
The aim of the present study was to evaluate the frequency and type of oncogenic v-raf murine sarcoma viral oncogene homolog B1 (BRAF)/neuroblastoma RAS viral (v-ras) oncogene homolog (NRAS) mutations in cutaneous melanoma with clinically detected nodal metastases (stage IIIB and C) in relation to clinicopathological features and outcome. The clinicopathological data of 250 patients following therapeutic lymphadenectomy (LND) between 1995 and 2010, as well as BRAF/NRAS mutational status in corresponding nodal metastases, were analyzed. The median follow-up time was 53 months. BRAF mutations were detected in 154 (62%) cases (141 p.V600E, nine p.V600K and four others) and mutually exclusive NRAS mutations were detected in 42 (17%) cases. The presence of a BRAF mutation was found to correlate with patients of a younger age. The five-year overall survival (OS) rate was 33 and 43% for LND and primary tumor excision, respectively, and the five-year disease-free survival (DFS) rate for LND was 25%. No correlation was identified between BRAF/NRAS mutational status and RFS or OS (calculated from the date of the LND and primary tumor excision); for BRAF- and NRAS-mutated melanoma, the prognosis was the same for patients with wild-type (WT) melanoma. The important factors which had a negative impact on OS and DFS were as follows: Male gender, >1 metastatic lymph node and extracapsular extension of nodal metastases. The interval between the diagnosis of the initial melanoma to regional nodal metastasis (median, 10 months) was not significantly different between BRAF-mutant and -WT patients. Our largest comprehensive molecular analysis of clinical stage III melanoma revealed that BRAF and NRAS mutational status is not a prognostic marker in stage III melanoma patients with macroscopic nodal involvement, but may have implications for potential adjuvant therapy.
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