The Prognostic Value of Plasma Small Extracellular Vesicles' Phenotype in Patients With Gastrointestinal Stromal Tumor.

BACKGROUND/AIM: For patients with local gastrointestinal stromal tumor (GIST), risk stratification is used to assess the prognosis and identify patients to offer adjuvant treatment. For patients with advanced or metastatic GIST, no such risk stratification exists. This study aimed to investigate the prognostic value of 31 different plasma small extracellular vesicles' (SEVs) surface proteins in GIST patients. MATERIALS AND METHODS: GIST patients from the two sarcoma centers in Denmark were included. Patients were divided into three groups; group 1: patients undergoing radical surgery; group 2: patients with local, locally advanced, or metastatic GIST; and group 3: patients without evidence of disease after radical surgery. Protein microarray technology was used for the analysis of plasma SEVs. The median plasma SEV marker level was used when comparing groups of patients. The primary endpoint was the progression of GIST. Iterative statistical modeling was used to identify a SEV marker profile/model with a prognostic value. RESULTS: A total of 157 patients were included, with a median follow-up time of 2.05 years. In group 2, a high level of carcinoembryonic antigen (CEA) and a low level of glucose transporter 1 (GLUT-1) were found to be poor prognostic factors [univariate analysis; GLUT-1: hazard ratio (HR)=0.47, 95% confidence interval (CI)=0.22-0.98; CEA: HR=2.12, 95%CI=1.02-4.44]. Composing a model consisting of CEA and GLUT-1 adjusted for age at inclusion was found to have a prognostic value (HR=4.93, 95%CI=2.30-10.57, p<0.0001). CONCLUSION: Plasma SEVs in GIST showed that CEA and GLUT-1 might be of prognostic value. However, external validation is needed.

Risk of recurrence in patients with colon cancer stage II and III: a systematic review and meta-analysis of recent literature.

BACKGROUND: Adjuvant chemotherapy is established routine therapy for colon cancer (CC) patients with radically resected stage III and 'high-risk' stage II disease. The decision on recommending adjuvant chemotherapy, however, is based on data from older patient cohorts not reflecting improvements in pre-operative staging, surgery, and pathological examination. The aim is to review the current risk of recurrence in stage II and III patients and second, to estimate the relative importance of routinely assessed clinico-pathological variables. METHODS: The PubMed/MEDLINE and the Cochrane databases were systematically searched for randomized controlled studies and observational studies published after 1 January 2005 with patients included after January 1995 on prognosis in surgically treated stage II and III CC patients. RESULTS: Of 2596 studies identified, 37 met the inclusion criteria and 25 provided data for meta-analysis. The total patient sample size in the 25 studies reporting either disease-free (DFS) or recurrence-free survival was 15 559 in stage II and 18 425 in stage III. Five-year DFS for stage II patients operated without subsequent adjuvant chemotherapy was 81.4% [95% confidence interval (CI) 75.4-87.4; in studies with good/very good quality of reporting 82.7%, (95% CI 80.8-84.6)]. For stage II patients treated with adjuvant chemotherapy, the five-year DFS was 79.3% (95% CI 75.6-83.1). For stage III patients without chemotherapy, five-year DFS was 49.0% (95% CI 23.2-74.8) and for those treated with adjuvant chemotherapy, 63.6% (95% CI 59.3-67.9). The prognostic impact of commonly investigated clinico-pathological parameters, (pT-stage, pN-stage, differentiation, number of lymph nodes studied, MMR-status, and emergency surgery) were confirmed. CONCLUSIONS: In this meta-analysis, studies with good quality of reporting show a five-year DFS of 82.7% for stage II CC without adjuvant chemotherapy, whereas the five-year DFS is 63.8% for stage III CC with adjuvant chemotherapy. Due to insufficient reporting on treatment quality the presented DFS is likely an under-estimation of what is achieved at high-quality centers today.

Positron emission tomography/computed tomography and biomarkers for early treatment response evaluation in metastatic colon cancer.

BACKGROUND: Treatment options for metastatic colon cancer (mCC) are widening. We prospectively evaluated serial 2-deoxy-2-[18F]fluoro-d-glucose positron-emission tomography/computed tomography (PET/CT) and measurements of tissue inhibitor of metalloproteinases-1 (TIMP-1), carcinoembryonic antigen (CEA), and liberated domain I of urokinase plasminogen activator receptor (uPAR(I)) for early assessment of treatment response in mCC patients. METHODS: Thirty-three mCC patients scheduled for first-line chemotherapy with capecitabine and oxaliplatin (CAPOX) and bevacizumab participated; 27 were evaluated by PET/CT before treatment, after one and four treatment series. Morphological and metabolic response was independently assessed according to Response Evaluation Criteria in Solid Tumors and European Organization for Research and Treatment of Cancer PET criteria. Plasma TIMP-1, plasma uPAR(I), and serum CEA were determined. RESULTS: Metabolic response after one treatment course predicted the ability of CAPOX and bevacizumab to induce morphological response after four treatment series with a sensitivity of 80%, specificity of 69%, and odds ratio of 13.9 (95% confidence interval [CI] 1.9; 182). Early metabolically stable or progressive disease was associated with shorter progression-free survival (hazard ratio [HR] = 3.2 [CI 1.3; 7.8]). Biomarker levels at early evaluation were associated with shorter OS (TIMP-1 per unit increase on a log-2-transformed ng/mL scale: HR = 2.6 [CI 1.4; 4.9]; uPAR(I) per 25 fmol/mL increase: HR = 1.5 [CI 1.1; 2.1]). CONCLUSION: This monocentric study demonstrated predictive value of early metabolic PET response and prognostic value of TIMP-1 and uPAR(I) levels in mCC treated with CAPOX and bevacizumab. Results support investigation of PET/CT, TIMP-1, and uPAR(I) guided early treatment adaptation in mCC.