Ahmet Bilici

Treatment options in patients with metastatic gastric cancer: current status and future perspectives.

Despite advances in the treatment of gastric cancer, it remains the worlds second highest cause of cancer death. As gastric cancer is often diagnosed at an advanced stage, systemic chemotherapy is the mainstay of treatment for these patients. However, no standard palliative chemotherapy regimen has been accepted for patients with metastatic gastric cancer. Palliative chemotherapy including fluoropyrimidine, platin compounds, docetaxel and epirubicin prolongs survival, and improves a high quality of life to a greater extent than best supportive care. The number of clinical investigations associated with targeted agents has recently increased. Agents targeting the epidermal growth factor receptor 1 and human epidermal growth factor receptor 2 (HER2) have been widely tested. Trastuzumab was the first target drug developed, and pivotal phase III trials showed improved survival when trastuzumab was integrated into cisplatin/fluoropyrimidine-based chemotherapy in patients with metastatic gastric cancer. Trastuzumab in combination with chemotherapy was thus approved to be a new standard of care for patients with HER2-positive advanced esophagogastric adenocarcinoma. Thus, the evaluation of HER2 status in all patients with metastatic gastroesophageal adenocarcinoma should be considered. Other agents targeting vascular endothelial growth factor, mammalian target of rapamycin, and other biological pathways have also been investigated in clinical trials, but showed little impact on the survival of patients. In this review, systemic chemotherapy and targeted therapies for metastatic gastric cancer in the first- and second-line setting are summarized in the light of recent advances.

Reactivation of hepatitis B virus infection with cytotoxic therapy in non-Hodgkin’s lymphoma

In patients with non-Hodgkin’s lymphoma (NHL), there are some well-known tumor-related adverse prognostic factors that may increase the mortality rate. However, secondary factors such as viral hepatitis carriers that may decrease the cure rates are usually ignored. Reactivation of hepatitis B virus (HBV) infection in patients undergoing cytotoxic treatment for NHL is a well-known complication. Charts of 112 patients with NHL were retrospectively analyzed regarding their hepatitis serology, the indirect effects of seropositivity on disease outcome, and the precautions undertaken in these seropositive patients with NHL. Twelve patients (11%) with HBsAg positivity and two patients (1.7%) with antibody to hepatitis C virus positivity were detected. Eight out of 12 patients (67%) with HBsAg positivity and two patients (50%) with anti-HCV positivity showed reactivation of hepatitis during treatment of NHL. No reactivation was detected in four patients seropositive for HBV, who were given lamivudine prophylaxis before the initiation of chemotherapy schedules. Among patients with hepatitis reactivation, two were treated with lamivudine resulting in dramatic improvement and clinical remission of the disease. The remaining six patients with reactivation were left untreated, resulting in four deaths (67%) due to liver failure secondary to HBV and two deaths secondary to delayed treatment of NHL. One patient seropositive for anti-HCV also developed chronic hepatitis C. Determination of hepatitis serology in all patients with NHL before any chemotherapy administration is crucial, but insufficient, if not taken into consideration. In seropositive patients, HBV DNA should be determined and antiviral prophylaxis with lamivudine should be initiated before any treatment.

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.

Clinical value of FDG PET/CT in the diagnosis of suspected recurrent ovarian cancer: is there an impact of FDG PET/CT on patient management?

PurposeThe aim of this study was to evaluate the clinical value of FDG PET/CT in patients with suspected ovarian cancer recurrence as compared with diagnostic CT, and to assess the impact of the results of FDG PET/CT on treatment planning.MethodsIncluded in this retrospective study were 60 patients with suspected recurrent ovarian cancer who had previously undergone primary debulking surgery and had been treated with adjuvant chemotherapy. Diagnostic CT and FDG PET/CT imaging were performed for all patients as clinically indicated. The changes in the clinical management of patients according to the results of FDG PET/CT were also analysed.ResultsFDG PET/CT was performed in 21 patients with a previously negative or indeterminate diagnostic CT scan, but an elevated CA-125 level, and provided a sensitivity of 95% in the detection of recurrent disease. FDG PET/CT revealed recurrent disease in 19 patients. In 17 of 60 patients, the indication for FDG PET/CT was an elevated CA-125 level and an abnormal diagnostic CT scan to localize accurately the extent of disease. FDG PET/CT scans correctly identified recurrent disease in 16 of the 17 patients, a sensitivity of 94.1%. Moreover, FDG PET/CT was performed in 18 patients with clinical symptoms of ovarian cancer recurrence, an abnormal diagnostic CT scan, but a normal CA-125 level. In this setting, FDG PET/CT correctly confirmed recurrent disease in seven patients providing a sensitivity of 100% in determining recurrence. In four patients, FDG PET/CT was carried out for the assessment of treatment response. Three of four scans were classified as true-negative indicating a complete response. In the other patient, FDG PET/CT identified progression of disease. In total, 45 (75%) of the 60 patients had recurrent disease, in 14 (31.1%) documented by histopathology and in 31 (68.9%) on clinical follow-up, while 15 (25%) had no evidence of recurrent disease. The overall sensitivity, specificity, accuracy, and positive and negative predictive value of FDG PET/CT were significantly superior to those of diagnostic CT (95.5% vs. 55.5%, 93.3% vs. 66.6%, 95% vs. 58.3%, 97.7% vs. 83.3%, 87.7% vs. 33.3%, respectively; p = 0.02) in the detection of recurrent ovarian cancer. FDG PET/CT changed the management in 31 patients (51.6%). It led to the use of previously unplanned treatment procedures in 19 patients (61.2%) and the avoidance of previously planned therapeutic procedures in 12 patients (38.8%).ConclusionOur results confirm that FDG PET/CT is a superior posttherapy surveillance modality for the detection of recurrent ovarian cancer than diagnostic CT imaging. Furthermore, integrated FDG PET/CT was useful specifically in optimizing the treatment plan and it might play an important role in treatment stratification in the future.

Prognostic factors related with survival in patients with pancreatic adenocarcinoma.

The prognosis in patients with pancreatic cancer is poor and this cancer is the fourth leading cause of cancer-related death worldwide. Although surgical resection is the only curative treatment of choice for pancreatic cancer, the majority of patients are diagnosed at an advanced stage, thus only 10%-15% of them are suitable for curative resection and the overall survival is less than 5%. Chemotherapy for metastatic disease is to palliate symptoms of patients and to improve survival. Therefore, prognostic factors are important and a correct definition of poor prognostic factors may help to guide more aggressive adjuvant or aggressive treatment protocols in patients with pancreatic cancer. This article reviews the prognostic factors affecting survival of patients with pancreatic cancer in the light of recent advances in the literature.

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.

Role of human papillomavirus in the development of urothelial carcinoma

It has been estimated that almost 10% of the worldwide cancer burden is linked to human papillomavirus (HPV) infection. Although the association between HPV and bladder carcinoma has been extensively investigated, data on the role of HPV in bladder carcinogenesis are controversial. The aim of the study was to assess the possible role of human papillomavirus in the development of urothelial bladder carcinomas. Formalin-fixed and paraffin-embedded archival tissue samples were used for DNA extraction. Seventy urothelial bladder carcinoma tissues were screened by nested-polymerase chain reaction (PCR) for HPV DNA with a control group of total 18 cervical tissues with invasive cervical carcinoma and cervical intraepithelial neoplasia III (CIN III). In the study group, we did not find HPV DNA positivity in any of the urothelial carcinomas. In the control group, 15 out of 18 (83.3%) samples were positive for the HPV DNA. These results indicated that there was no association between HPV infection and urothelial carcinomas.

Efficiency and Side Effects of Sorafenib Therapy for Advanced Hepatocellular Carcinoma: A Retrospective Study by the Anatolian Society of Medical Oncology

BACKGROUND Inoperable and metastatic hepatocellular carcinoma (HCC) is associated with a poor prognosis and low chemotherapeutic efficiency. Sorafenib is an oral multi-kinase inhibitor exerting its effects via the RAF/ MEK/ERK pathway, vascular endothelial growth factor receptor (VEGFR) and platelet derived growth factor receptor beta (PDGFR-β) tyrosine kinases. Randomized studies have shown a significant contribution of sorafenib to life expectancy and quality of life of cancer patients. The aim of the present study is to evaluate the efficacy and side effects of sorafenib therapy in Turkey. MATERIALS AND METHODS Data for 103 patients (82 males, 21 females) receiving sorafenib therapy in 13 centers from February 2008 to December 2012 were evaluated. Median age was 61 years and median ECOG performance status was 1 (range: 0-2). 60 patients (58%) had hepatitis B, 15 patients (15%) had hepatitis C infection and 12 patients (12%) had a history of alcohol consumption. All of the patients had Child scores meeting the utilization permit of the drug in our country (Child A). RESULTS A total of 571 cycles of sorafenib therapy were administered with a median of four per patient. Among the evaluable cases, there was partial response in 15 (15%), stable disease in 52 (50%), and progressive disease in 36 (35%). Median progression-free survival was 18 weeks and median overall survival was 48 weeks. The dose was reduced only in 6 patients and discontinued in 2 patients due to grade 3-4 toxicity, 18 patients (17%) suffering hand-foot syndrome, 7 (7%) diarrhea, and 2 (2%) vomiting. CONCLUSIONS This retrospective study demonstrated better efficacy of sorafenib therapy in patients with advanced HCC compared to the literature while progression-free survival and overall survival findings were comparable. The side effect rates indicate that the drug was tolerated well. In conclusion, among the available treatment options, sorafenib is an efficient and tolerable agent in patients with inoperable or metastatic HCC.

Factors that Affect Patients' Decision-Making about Mastectomy or Breast Conserving Surgery, and the Psychological Effect of this Choice on Breast Cancer Patients

Background: Breast cancer is the most common cancer in women. Primary treatment is surgery, with breast conserving surgery (BCS) being widely used for early-stage disease. Due to changes in body image, depressive symptoms can occur after surgery. Here, we evaluate factors that affect patients’ decision on surgery, and investigate differences in the level of depression after mastectomy or BCS in a population of Turkish patients. Patients and Methods: One hundred breast cancer patients who had undergone mastectomy or BCS and were followed up at our institution between 2007 and 2008 were included. Patients were questioned about their involvement in surgical decision-making. Depression was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-III) criteria via a Structural Clinical Interview for DSM (SCID). Severity of depression was evaluated by using the Beck Depression Inventory (BDI). Results: Patients who were older than 50 years, had more than 1 child, a history of lactation, and a positive family history of breast cancer mostly preferred mastectomy. However, patients who sought a second opinion and further information on BCS preferred BCS (p < 0.005). There was no statistical correlation between marital status, first childbearing age, and educational status and the decision on surgery type (p > 0.005). Mastectomy patients were prone to depression, but this was not statistically significant (p = 0.099). Conclusion: Age, parenthood, lactation, and positive familial history, as well as thorough information about the type of surgery were important factors for the patients’ decision. After breast cancer surgery, patients might experience depression affecting treatment and quality of life. Therefore, adequate information and communication are essential.

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.