Ahmet Ozet

Discordances in HER2 status between primary gastric cancer and corresponding metastatic sites

OBJECTIVE Determination of human epidermal growth factor receptor-2 status in advanced gastric cancer is important in clinical decision making. In the trastuzumab for GC trial, trastuzumab-based therapy demonstrated a significant overall survival benefit in patients with human epidermal growth factor receptor-2-positive advanced gastric cancer. Human epidermal growth factor receptor-2 discordance in gastric cancer primary and its metastases has been long debated. The aim of the study was to evaluate the rate of human epidermal growth factor receptor-2 discordance and its effect on treatment decisions in advanced gastric cancer. METHODS A total of 74 patients with advanced gastric cancer were included in the study. Both immunohistochemical staining and dual-color silver in situ hybridization were performed in all patients to evaluate the human epidermal growth factor receptor-2 status of the primary lesion and paired metastasis. RESULTS The assessment of human epidermal growth factor receptor-2 status with the immunohistochemical staining method and dual-color silver in situ hybridization revealed a discordance rate of 9.5 and 16.2%, respectively. However, this discordance was clinically meaningful in only one patient leading to a change in treatment decision. While this patient had a human epidermal growth factor receptor-2-negative status in primary tumor (immunohistochemical = 0, dual-color silver in situ hybridization = negative), the human epidermal growth factor receptor-2 status was positive for liver metastasis (immunohistochemical = 2+, dual-color silver in situ hybridization = positive). Trastuzumab was added to the chemotherapy regimen. CONCLUSIONS In this study, we found a higher rate of human epidermal growth factor receptor-2 discordance between primary gastric tumor and metastatic lesions compared with the rates reported in previous studies. Detection of a human epidermal growth factor receptor-2-positive metastasis with a human epidermal growth factor receptor-2-negative primary tumor suggests that investigation of human epidermal growth factor receptor-2 is also required for the metastatic lesion and that trastuzumab could be administered in the case of a positive result.

Prognostic importance of markers for inflammation, angiogenesis and apoptosis in high grade glial tumors during temozolomide and radiotherapy

INTRODUCTION Angiogenesis, inflammation and apoptosis have an important place in the carcinogenesis of high-grade gliomas (HGG). We evaluated the postoperative levels and the prognostic importance of tumor necrosis factor-alpha (TNFα), interleukin 6 (IL6), endoglin (CD105), vascular endothelial growth factor (VEGF), M65 and M30 as markers of inflammation, angiogenesis and apoptosis in patients with HGG. METHODS AND RESULTS Postoperative pretreatment sera were collected from 44 newly diagnosed patients with HGG. The control group was also consisted of 44 healthy people. The median age of all patients with HGG was 59 (range: 30-80). Temozolomide concurrent with radiotherapy was given to 37 patients. Thereafter 24 patients received consolidation temozolomide monotherapy. Mean chemotherapy cycle was 4.2. Progression free survival and overall survival were 6 (95% CI; 5.16-6.83) and 16 months (95% CI; 13.07-18.93) respectively in patients treated with concurrent chemoradiotherapy and consolidation chemotherapy. Relative to the control cohort endoglin (p = 0.000) and TNFα (p = 0.000) levels were significantly lower; however VEGF (p = 0.030) levels were higher in the patient group. In contrast, there were no significant change in IL-6 levels and the plasma apoptotic markers M65 (p = 0.085) and M30 (p = 0.292). In separate log rank tests, these biological markers did not correlate with survival. DISCUSSION AND CONCLUSION In HGG, a significant decrease in endoglin and TNFα levels was observed, while VEGF levels were significantly increased postoperatively. However, with the power from this patient population, no correlation with survival was observed.

Management of brain metastases from non-small cell lung cancer.

PURPOSE The purpose of the following study is to evaluate the treatment modalities, clinical status and prognostic factors affecting survival rates in patients with newly diagnosed brain metastasis from non-small cell lung cancer (NSCLC). PATIENTS AND METHODS NSCLC patients with a new diagnosis of one to four brain metastasis evaluated retrospectively for the effects of treatment regimens on local failure-relapse-free survival (LRFS) and overall survival (OS). The relationship between age, gender, performance status, recursive partitioning analysis (RPA) classification, the primary tumor under control, number of metastatic tumors in the brain and total volume of brain metastasis and prognosis is analyzed. RESULTS Out of a total of 138 (121 male and 17 female) patients, nearly 44.2% received only gamma-knife (GK); 24.6% were received both GK and whole brain radiotherapy (WBRT), 2.9% had GK and surgery, 3.6% received GK, surgery and WBRT, 10.9% had surgery and WBRT and 12.3% received only WBRT for treatment. Median LRFS of surgery plus WBRT group was significantly higher when compared with WBRT group (P<0.0001). The OS was significantly longer for surgery plus WBRT group than the other treatment groups (P=0.037). When median survival of WBRT-only group compared with surgery plus WBRT, it was significantly higher (29.6 months vs. 16.7 months, P=0.006). Median OS of surgery plus WBRT group was significantly higher than GK plus WBRT group (29.6 months vs. 9.3 months, P=0.007). CONCLUSION WBRT is still the most effective treatment method following surgery in selected patients according to their age, performance status and spread of the primary disease with NSCLC had limited number brain metastasis. Adding WBRT treatment after surgery significantly improved OS and LRFS.

Carbonic anhydrase IX is a prognostic biomarker in glioblastoma multiforme: Carbonic anhydrase IX and glioblastoma multiforme

The identification of prognostic factors in patients with glioblastoma multiforme (GBM) represents an area of increasing interest. Carbonic anhydrase IX (CA‐IX), a hypoxia marker, correlates with tumor progression in a variety of human cancers. However, the role of CA‐IX in GBM remains largely unknown. In the present study, we evaluated the prognostic role of CA‐IX in GBM patients. In total, 66 consecutive patients with GBM who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and all patients received temozolomide chemotherapy for at least 3 months. Kaplan–Meier curves and log‐rank tests were used for analysis of progression‐free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on survival. The median OS was longer in patients with low levels of CA‐IX expression (18 months) compared to patients overexpressing CA‐IX (9 months) (P = 0.004). There was not a statistically significant difference in median PFS (3.5 vs. 8 months, P = 0.054) between patients with high or low levels of CA‐IX expression. In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (KPS) (hazard ratio (HR), 3.703; P = 0.001), CA‐IX overexpression (HR, 1.967; P = 0.019), and incomplete adjuvant temozolomide treatment (HR, 2.241; P = 0.003) and gross‐total resection (HR, 1.956; P = 0.034). Our findings indicated that CA‐IX may be a potential prognostic biomarker in the treatment of GBM.

Small cell neuroendocrine carcinoma of the posterior tongue.

In the head and neck mucosa, neuroendocrine carcinomas of the oral cavity is rare. Herein, we present the first report of a small cell neuroendocrine carcinoma in a 54-year-old man on the right lateral posterior tongue. It is important to remember that although neuroendocrine small cell carcinomas (SCCs) are most commonly seen in the lung, they rarely may arise in the extrapulmonary sites, including salivary glands, as well. As there is not any standard therapeutic regimen already existing, it is important to be aware of and to know how to deal with such rare cases.

A Case of Cutaneous Diffuse Large B-cell Lymphoma.

Received/Gelis tarihi : June 10, 2013 Accepted/Kabul tarihi : September 4, 2013 To the Editor, We report the clinical findings of a 55-year-old woman who presented with purple-reddish nodules on her face diagnosed as primary cutaneous diffuse large B-cell lymphoma (PCLBCL), which is very rarely seen in this area. A 55-year-old woman applied to our oncology department after a brief episode of fever, general weakness, and erythematous patches and plaques in the facial area (Figure 1). Other associated symptoms and signs were general malaise and weight loss of 5 kg in 1 month. She had previously been well. A diagnostic biopsy showed an infiltration of large lymphoid cells staining positively for CD20, BCL-6, BCL-2, and PAX5, suggesting a diagnosis of diffuse large B-cell lymphoma (Figure 2). The cells were negative for CD5 and CD10. Renal and liver functions were normal. Bone marrow aspiration and biopsy showed no evidence of lymphoma. There was no other systemic organ involvement. The patient began receiving systemic chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone. After 3 cycles of treatment, the large tumor showed no gradual improvement; this was suggestive of a lack of response. Rituximab plus ifosfamide, carboplatin, and etoposide chemotherapy (R-ICE) were therefore initiated. The patient was treated with 3 cycles of R-ICE chemotherapy. The patient declined additional treatment because her condition remained progressive despite the treatment, and she died soon after. Infomed consent was obtained. PCLBCL is a rare primary cutaneous lymphoma characterized by a diffuse proliferation of large B cells consisting of centroblasts and immunoblasts, occurring most commonly on the legs [1]. PCLBCL affects elderly population with a female predominance. This type of lymphomas tend to develop on the lower limbs, predominantly as large dermal nodules or tumors, which are either solitary or multifocal and rapidly enlarging [1]. PCLBCL can also rarely occur at other cutaneous sites [2]. The prognosis of PCLBCL is poor, with a 5-year survival of 41%-58%

Managing Synchronous Liver Metastases in Colorectal Cancer

The most common site of blood-borne metastases from colorectal cancers (CRC) is the liver. Resection of (liver) metastases is a part of standard treatment of metastatic colorectal cancer. Hepatic resection is the first-line treatment of liver metastases, with 5-year survival rates between 25 and 58%. The enhanced efficacy of systemic chemotherapeutic regimens has increased tumor response rates and improved the progression-free and overall survival of patients with these malignancies. In approximately 20% of patients with initially unresectable liver metastases, the metastases may become resectable after administration of neoadjuvant chemotherapy. Unresectable liver metastases can be managed with systemic therapy and/or a variety of liver-directed techniques such as radiofrequency ablation, hepatic artery infusion, or yttrium-90 radioembolization. Our examination of the literature led us to propose a new patient-oriented algorithm to guide clinicians’ decisions on the best choice of upfront therapy for CRC and synchronous liver metastases. The need for multidisciplinary consensus has become especially important for metastatic CRC.

BRAF Inhibitors for BRAF V600E Mutant Colorectal Cancers: Literature Survey and Case Report

The main method of fighting against colon cancer is targeted treatment. BRAF inhibitors, which are accepted as standard treatment for V600E mutant malign melanomas, are the newest approach for targeted treatment of V600E mutant colorectal cancers. In this case report, we share our experience about the use of BRAF inhibitor vemurafenib on a V600E mutant metastatic right colon adenocarcinoma patient. A 59-year-old male with only lung multiple metastatic V600E mutant right colon cancer presented to our clinic. The patient was evaluated and FOLFOX + bevacizumab treatment was initiated, which was then continued with vemurafenib. A remarkable response was achieved with vemurafenib treatment in which the drug resistance occurred approximately in the sixth month. Even though the patient benefited majorly from vemurafenib, he died on the 20th month of the diagnosis. The expected overall survival for metastatic V600E mutant colon adenocarcinoma patients is 4.7 months. BRAF inhibitors provide new treatment alternatives for V600E mutant colorectal cancers, with prolonged overall survival. BRAF inhibitors in combination with MEK inhibitors are reported as feasible treatment to overcome BRAF inhibitor drug resistance on which phase studies are still in progress. To conclude, BRAF inhibitors alone or in combination with other drugs provide a chance for curing BRAF V600E mutant colorectal cancer patients.

A case of membranous glomerulopathy associated with lung cancer and review of the literature

Membraneous nephropathy (MN) is the most commonly occurring nephrotic syndrome in adults as well as the most common paraneoplastic nephropathy associated with solid tumors, and it is mostly associated with gastrointestinal system and lung carcinomas. Accurate diagnosis is important as the treatment of paraneoplastic glomerulonephritis is very varied from that of idiopathic ones. In the current report, a case of a patient that was referred with proteinuria and edema and was diagnosed with lung cancer, and responded markedly to treatment of malignancy, with improvement of MN, is presented. Active cancer is present in all patients with paraneoplastic MN. In numerous patients, the paraneoplastic MN and cancer diagnoses are made within one year of each other. The treatment of paraneoplastic syndromes is usually associated with the treatment of primary malignancy. There are conflicting data on which treatment modality is more suitable. In conclusion, further studies are required in order to determine the actual incidence of cancer in patients with nephropathy, explain the physiopathological association between cancer and nephropathy and to determine the most suitable treatment approaches.

Liver metastases from adenocarcinomas of unknown primary site: management and prognosis in 68 consecutive patients.

SummaryBackgroundIn this retrospective study, we aimed to evaluate the clinicopathological characteristics of the patients presenting with liver metastases from unknown primary site besides survival rates, treatment outcomes, and prognostic factors.MethodsIn all, 68 patients followed-up at our center with adenocarcinoma of unknown primary (ACUP) metastatic to the liver between 2005 and 2013 were enrolled. All of the liver metastases were proven by liver biopsy and all yielded diagnosis of adenocarcinoma.ResultsMedian age was 61 years (29–90) and most of the patients were male (male/female: 43/25). The liver was the only metastatic site in 2 (3 %) patients whilst 66 patients (97 %) had extrahepatic metastases. The most common extrahepatic metastatic sites were lymph nodes (89.7 %), lungs (32.4 %), bones (25 %), peritoneum (11.8 %), brain (4.4 %), and adrenal glands (2.9 %). Of all 68 patients, 39 (57.4 %) were treated with chemotherapy. Median overall survival (OS) was significantly higher in ACUP patients treated with chemotherapy [12.5 months (95 % CI 8.3–16.7) vs. 4 months (95 % CI 1.2–6.8), (p = 0.026), respectively]. In multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status (p = 0.009), chemotherapy (p = 0.024), serum albumin (p = 0.012), and serum CA 19-9 level (p = 0.026) at initial diagnosis were identified as independent prognostic factors influencing survival for the patients with liver metastases from ACUP.ConclusionPatients with liver metastases from ACUP have poor prognosis and chemotherapy improves survival. Decreased serum albumin level, increased CA 19-9 level and poor performance status are independent poor prognostic factors.