Umut Kefeli

The role of 18F-FDG PET/CT in the assessment of suspected recurrent gastric cancer after initial surgical resection: can the results of FDG PET/CT influence patients’ treatment decision making?

Purpose18F-fluorodeoxyglucose (FDG) PET/CT has been widely used for staging, re-staging and for monitoring therapy-induced changes and response to therapy in patients with various types of cancer, but its utilization for gastric cancer has been limited. The purpose of this study was to evaluate the clinical role of FDG PET/CT in the detection of gastric cancer recurrence as compared with diagnostic CT and to assess the impact of FDG PET/CT results on patients’ treatment planning.MethodsThirty-four patients with suspected recurrent gastric cancer, who had previously undergone curative gastrectomy and lymph node dissection, were retrospectively analysed. The diagnostic CT and FDG PET/CT imaging were performed for all patients as clinically indicated. The results of FDG PET/CT were compared with the findings of the diagnostic CT. The changes in the clinical management of patients according to the results of FDG PET/CT were also evaluated.ResultsFDG PET/CT was performed in 19 patients (55.9%) due to the suspicion of distant metastasis at diagnostic CT. The remaining 15 patients were suspected to have local recurrence at diagnostic CT (n = 4) or gastroscopy (n = 1) and due to an increase in tumour markers or clinical manifestations (n = 10). The FDG PET/CT result was positive in 23 patients (67.6%) and negative in 11 patients (32.4%). In total, 24 (70.6%) of the 34 patients had documented recurrent disease by histopathology in 7 (29.1%) and by clinical follow-up in 17 (70.9%), while 11 patients had no evidence of recurrent disease. FDG PET/CT correctly confirmed recurrent disease in 23 of the patients with recurrence and it was classified as true-positive in these patients. However, FDG PET/CT was false-negative in one patient but recurrent disease was confirmed by histopathology. The overall sensitivity, specificity, accuracy, positive and negative predictive values of FDG PET/CT were significantly superior to those of diagnostic CT (95.8 vs 62.5%, 100 vs 10%, 97 vs 47%, 100 vs 62.5% and 90.9 vs 10%, respectively, p = 0.012) in the detection of recurrent gastric cancer after initial surgery. The FDG PET/CT results changed the patients’ management in 18 (52.9%) cases by leading to the use of previously unplanned treatment procedures in 9 (50%) patients and the avoidance of previously planned therapeutic procedures in 9 (50%) patients.ConclusionFDG PET/CT is a superior post-therapy surveillance modality for the diagnosis of recurrent gastric cancer compared with diagnostic CT imaging after initial surgery. In addition, integrated FDG PET/CT was specifically helpful in optimizing the treatment plan and it might play an important role in treatment stratification in the future.

The importance of multifocal/multicentric tumor on the disease-free survival of breast cancer patients: single center experience.

Objectives:Multifocal/multicentric breast cancers have been comprehensively studied and their outcomes have been compared with unifocal tumors. We evaluated the impact of multifocality and multicentricity on the disease-free survival (DFS) and overall survival of breast cancer patients and tried to analyze the correlation between multifocality/multicentricity (M/M) and other prognostic factors. Material and Methods:Between 1994 and 2009, we analyzed retrospectively 697 breast cancer patients. Multicentric and multifocal breast cancer were defined as the presence of 2 or more invasive tumor foci within the different quadrants of the same breast or within a same quadrant of the breast, respectively. M/M and other prognostic factors were evaluated using univariate and multivariate analyses. Results:Multifocal/multicentric tumors were seen in 107 (15.4%) of the 697 breast cancer patients. pT and pN stage were related with the presence of multifocal/multicentric tumors. As tumor size increased and the number of axillary lymph nodes metastasis increased, the incidence of M/M increased significantly (P=0.003 vs. P=0.02, respectively). Overall, the median DFS time of patients with multifocal/multicentric tumors was significantly worse than that of the unifocal tumors (55 vs. 137 mo, P<0.001). Multivariate analysis showed that the presence of M/M was the most important prognostic factor for DFS (P=0.001, hazard ratio (HR): 0.33; 95% confidence interval (CI), 0.18-0.58), as were pN stage and extracapsular extension of the tumor (P=0.01, HR: 1.74; 95% CI, 1.13-2.69) (P=0.03, HR: 1.9; 95% CI, 1.04-3.47, respectively). M/M were not also statistically significant prognostic factors in breast cancer for overall survival (P=0.06). Conclusions:M/M imparts an unfavorable prognosis on the DFS of breast cancer patients in comparison to unifocal tumors and the presence of multifocal/multicentric tumors were associated with advanced pT and pN stages.

Is Metastatic Lymph Node Ratio Superior to the Number of Metastatic Lymph Nodes to Assess Outcome and Survival of Gastric Cancer

Background: The aim of this study was to determine the prognostic value of metastatic lymph node ratio (n ratio). Patients and Methods: We retrospectively analyzed 202 patients who had undergone curative gastrectomy. The prognostic factors including UICC/AJCC TNM classification and n ratio were evaluated by univariate and multivariate analysis. Results: The n ratio was significantly higher in patients with gastric tumors with undifferentiated histology, greater size, lymphatic vessel, blood vessel and perineural invasion (PNI), and advanced stage. Multivariate analysis indicated that n ratio and pN classification were independent prognostic factors, as were age, tumor size, Borrmann classification, PNI, and tumor differentiation. The receiver operating characteristics (ROC) analysis showed that the sensitivity and the specificity of the presence of lymph node metastasis with 16 lymph nodes resected – which was required to assess the presence of lymph node involvement – were 67.1 and 66.6%, respectively. Three-year overall survival (OS) rates and the median OS time were lower in patients with <16 lymph nodes resected compared to the patients who had >16 lymph nodes resected (p = 0.04). Conclusions: Our results showed that n ratio and pN classification were independent prognostic indicators for OS of patients with radically resected gastric cancer, but the superiority of n ratio to pN stage could not be proved.

Does the Metastatic Lymph Node Ratio Influence the Disease-Free Survival of Patients with Breast Cancer: Single-Center Experiences

Background: Axillary lymph nodes (ALNs) are the most important prognostic factor for survival in breast cancer. Pathological evaluation can affect the number of involved lymph nodes. In the current study, we evaluated whether the metastatic lymph node ratio (n ratio) is important in predicting disease-free survival (DFS) for breast cancer patients. Material and Methods: From 802 breast cancer cases, 427 patients with ALN metastasis were analyzed retrospectively. The n ratio was categorized as n ratio 1 (1–10%), n ratio 2 (10.01–50%) and n ratio 3 (>50%). DFS was established according to the Kaplan-Meier method. Predicting risk factors for relapse were analyzed using the Cox proportional hazards model. Results: The n ratio was significantly higher in breast cancer patients with advanced pathologic pT, pN and clinical stage, undifferentiated histology, lymphovascular and extracapsular invasion, more resected ALNs and positive progesterone receptor. In the univariate analysis, multicentricity, necrosis, grade, pN stage, estrogen receptor and progesterone receptor positivity, trastuzumab and neoadjuvant chemotherapy usage, the presence of inflammatory breast cancer and n ratio were found to be important factors in predicting DFS. Multivariate analysis indicated that multicentricity, neoadjuvant chemotherapy, trastuzumab usage and n ratio were significantly associated with prognosis. Conclusions: The n ratio is inexpensive, easily available and a simple prognostic factor for breast cancer patients with positive ALNs.

Netrin-1 concentrations in patients with advanced gastric cancer and its relation with treatment

Context: Netrin-1 is found to be elevated and usable as a diagnostic biomarker in many human cancers. Objectives: We evaluated serum Netrin-1 concentrations in patients with advanced gastric cancer compared with those in a healthy group. Material and methods: Thirty patients with advanced gastric cancer and thirty healthy people were included in the study. Serum netrin-1 concentrations were measured by quantitative ELISA method in both groups. Results: The mean serum Netrin-1 concentrations were found to be significantly higher in patients with gastric cancer than in healthy controls. The mean serum Netrin-1 concentrations were found to be significantly higher in patients with gastric cancer before the beginning of chemotherapy when compared after the completion of third cycle. Discussion and conclusion: Our results indicated that netrin-1 concentrations elevated in advanced gastric cancer compared to a healthy control group and netrin-1 concentrations decreased with chemotherapy.

Is there any role of thrombin activatable fibrinolysis inhibitor in the development of a hypercoagulable state in gastric cancer

BackgroundThe purpose of this study was to investigate plasma levels of thrombin activatable fibrinolysis inhibitor (TAFI) and TAFI’s relationship with coagulation markers (prothrombin fragment 1 + 2) in gastric cancer patients.MethodsThirty-three patients with gastric adenocarcinoma and 29 healthy control subjects were prospectively enrolled in the study. Patients who had a history of secondary malignancy, thrombosis related disease, oral contraceptive use, diabetes mellitus, chronic renal failure or similar chronic metabolic disease were excluded from the study. A fasting blood sample was drawn from patients to determine the plasma levels of TAFI and Prothrombin Fragment 1 + 2 (F 1 + 2). In addition, data on patient age, sex, body mass index (BMI) and stage of disease were recorded. The same parameters, except stage of disease, were also recorded for the control group. Subsequently, we assessed the difference in the levels of TAFI and F 1 + 2 between the patient and control groups. Moreover, we investigated the relation of TAFI and F 1 + 2 levels with age, sex, BMI and stage of disease in the gastric cancer group.ResultsThere were no statistical differences in any demographic variables (age, gender and BMI) between the groups (Table 1). The mean plasma TAFI levels of the gastric cancer group (69.4 ± 33.1) and control group (73.3 ± 27.5) were statistically similar (P = 0.62). The mean plasma F 1 + 2 level in the gastric cancer group was significantly higher than for those in the control group (549.7 ± 325.3 vs 151.9 ± 67.1, respectively; P < 0.001). In the gastric cancer group, none of the demographic variables (age, gender and BMI) were correlated with either TAFI or F 1 + 2 levels. Also, no significant associations were found between the stage of the cancer and either TAFI or F 1 + 2 levels.ConclusionIn our study, TAFI levels of gastric cancer patients were similar to healthy subjects. The results of our study suggest that TAFI does not play a role in pathogenesis of the hypercoagulable state in gastric cancer patients.

The value of plasma netrin-1 in non-small cell lung cancer patients as diagnostic and prognostic biomarker

Netrin-1 is found to be elevated and purposive as a diagnostic biomarker in many human cancers. We evaluated serum netrin-1 concentrations in patients with advanced non-small cell lung cancer compared with those in a healthy group. Thirty patients with advanced non-small cell lung cancer and 30 healthy people were included in the study. Serum netrin-1 concentrations were measured by quantitative ELISA method in both groups. The mean serum netrin-1 concentrations were found to be significantly higher in patients with non-small cell lung cancer than in healthy controls. The mean serum netrin-1 concentrations were found to be significantly higher in patients with non-small cell lung cancer before the beginning of chemotherapy when compared after the completion of the third cycle. Our results represented that netrin-1 concentrations elevated in advanced non-small cell lung cancer compared to a healthy control group, and netrin-1 concentrations decreased with chemotherapy.

Efficacy of sorafenib in patients with gastrointestinal stromal tumors in the third‑ or fourth‑line treatment: A retrospective multicenter experience

Sorafenib is a multi-targeted tyrosine kinase receptor inhibitor used to treat patients with advanced gastrointestinal stromal tumors (GISTs). The present study evaluated the efficacy and tolerability of sorafenib therapy for patients with GISTs. Between January 2001 and November 2012, 25 patients, from multiple centers, who had received sorafenib as the third- or fourth-line treatment for GISTs were investigated retrospectively. In total, 17 patients were male and eight were female. The median age was 54.0 years (range, 16–82 years). From the patients, 21 received imatinib for longer than six months and four received it for less than six months. The clinical benefit rate of sorafenib was 40.0%. Treatment-related adverse events were reported in 72% of patients. These adverse events were generally mild to moderate in intensity. The median progression-free survival (PFS) and overall survival (OS) times of the patients who received sorafenib were 7.2 and 15.2 months, respectively. The duration of imatinib usage was an independent prognostic factor for PFS and OS. Sorafenib is an effective treatment in patients with GISTs showing a clinical benefit rate of 40.0% and an acceptable tolerability.

Paclitaxel plus Doxorubicin Chemotherapy as Second-Line Therapy in Patients with Advanced Urothelial Carcinoma Pretreated with Platinum plus Gemcitabine Chemotherapy

Background: We retrospectively evaluated the efficacy and toxicity of paclitaxel plus doxorubicin as a second-line treatment in patients with urothelial carcinoma, who had not responded to a prior platinum plus gemcitabine combination. Patients and Methods: All patients received intravenous infusions of paclitaxel (175 mg/m2/h) and doxorubicin (50 mg/m2/30 min) on day 1. Chemotherapy courses were repeated every 21 days. Results: The median followup duration was 13.5 months (range 2.8–22.4 months). Complete and partial responses were observed in 2 (5.6%) and 10 (27.8%) patients, respectively. Median overall survival was 8.9 months (95% confidence interval (CI): 6.2–11.6). Median time to progression was 3.8 months (95% CI: 2.7–4.8). The most common hematologic toxicities were neutropenia (n = 21, 58.3%), thrombocytopenia (n = 10, 27.8%), and anemia (n = 9, 25%). The most common nonhematologic toxicities consisted of fatigue (n = 15, 41.7%), nausea/vomiting (n = 13, 36.1%), peripheral neuropathy (n = 11, 30.6%), and mucositis (n = 6, 16.7%). Dose reductions by 25–35% were performed in 6 (16.7%) patients because of grade 3/4 toxicity. Anthracycline-related heart failure did not occur. Conclusion: 3-weekly courses of cyclic paclitaxel plus doxorubicin were found to be effective and tolerable in patients with urothelial carcinoma, who had not responded to prior platinum- and gemcitabine-based chemotherapy.

Netrin-1 in cancer: Potential biomarker and therapeutic target?:

Netrin-1, a laminin-related protein, is known to be involved in the nervous system development. Recently, Netrin-1’s involvement in other processes such as cell adhesion, motility, proliferation, and differentiation that are important for the development of epithelial tissues has been described. In addition, Netrin-1 and its receptors, deleted in colorectal cancer and uncoordinated-5 homolog, have been linked to apoptosis and angiogenesis. Since these properties are essential for tumor development, Netrin-1 and its receptors have been reported to promote tumorigenesis in many types of cancers. Here, we review the Netrin-1 mediated regulation of cancer, its potential use as a biomarker, and the targeting of the Netrin-1 pathway to treat cancers.