Alper Can

Prognostic and Predictive Value of Hematologic Parameters in Patients with Metastatic Renal Cell Carcinoma: Second Line Sunitinib Treatment Following IFN-alpha

BACKGROUND Long-term survival is a problem with locally advanced and metastatic renal cell carcinomas. Sunitinib malate is an oral multitargeted tyrosine kinase inhibitor, but data on sunitinib use as a second line treatment in metastatic renal cell carcinoma (mRCC) are limited. Prognostic and predictive value of peripheral blood markers has been shown for many cancers. MATERIALS AND METHODS Efficacy and safety profiles of sunitinib after interferon alpha were evaluated based on retrospective data for 23 patients with mRCC. Hematological parameters (neutrophils, lymphocytes, platelets, mean platelet volume, neutrophil/lymphocyte ratio, platelet/lymphocyte ratio) were recorded at the time of metastasis. It was evaluated whether hematological parameters were prognostic and predictive factors. RESULTS Median progression-free survival (PFS) time was 16.5 months (95%CI: 0-34.5). Median overall survival (OS) time was 25.7 months (95%CI: 10.8-40.0). Most common side effects were neutropenia (52.2%), stomatitis (26.1%) and hand-food syndrome (26.1%). PFS was found 3.13 vs 17.1 months in patients with neutrophil / lymphocyte ratio (NLR)>3 vs NLR≤3 (p:0.012). Median OS was 6.96 vs 27.1 months in patients with NLR>3 vs NLR≤3 (p:0.001).While 75% of patients who responded to sunitinib had NLR≤3, in 72% of patients with no response to sunitinib NLR>3 was detected (p:0.036). The association between the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria and NLR was statistically significant (p:0.022). CONCLUSIONS Data on second line sunitinib treatment following cytokine in mRCC are limited. In our study, we observed second line sunitinib treatment following IFN-alpha to be effective and tolerable. NLR appeared to have prognostic and predictive value.

The effects of hematological parameters and tumor-infiltrating lymphocytes on prognosis in patients with gastric cancer

BACKGROUND It is well known that tumor-infiltrating lymphocytes (TIL) and, to a lesser extent, peripheral hematologic parameters from patients with cancer have to effect on prognosis. The aim of this study was to evaluate the effect of hematologic parameters and TIL on prognosis of patients with gastric cancer. METHODS 236 patients who had diagnosed as gastric adenocarcinoma. All hematologic parameters were noted at the time of diagnosis. The number of lymphocyte aggregates as well as the number of lymphocytes within these agregat was counted.The prognostic significance and correlations of high neutrophil-lymphocyte ratio (NLR) together with TIL, was evaluated by multivaried analysis. RESULTS The cut-off values of NLR and derived NLR (dNLR) were 3.8 and 2. The NLR was independently associated with survival (P < 0.001). dNLR was not independently associated with overall survival. No significant advantages for overall survival were found for the high TIL (p: 0.372). It was not determined correlation between TIL - NLR and TIL-lymphoid aggregate density (respectivly, P: 0.104; P: 0.246). CONCLUSIONS The results suggest that the elevated NLR predicts poor overall survival following at the time diagnosis for all stage gastric cancer. dNLR was not independently associated with overall survival. There is insufficient evidence to the assesment of TIL by a nonspesific method. Therefore further studies is required, to confirm our hypothesis in larger patient cohorts.

Cisplatin Plus Gemcitabine for Treatment of Breast Cancer Patients with Brain Metastases: a Preferential Option for Triple Negative Patients?

BACKGROUND To assess the efficacy and tolerability of Cisplatin plus Gemcitabine combination in patients with brain metastases (BM) from breast cancer (BC). MATERIALS AND METHODS Eighteen BC patients with BM who were treated with Cisplatin plus Gemcitabine regimen between 2003-2011 were evaluated. RESULTS A median of 6 cycles of this regimen were received, in fifteen patients (83.3%) as first-line chemotherapy, in 2 as second- line and in 1 as third-line after diagnosis of BM. Dose reduction was performed in 11 (61.1%) patients; major reasons were neutropenia and leukopenia. Grade III neutropenia and Grade II trombocytopenia rates were 33.3% and 16.7% respectively. Overall response rate (ORR; complete+partial response rate) was 33.4% (n=6) for the entire study population; triple negative patients achieved an 66.6% ORR while hormone receptor (HR) positive patients had 25% and HER2 positive patients 12.5%. Median progression-free survival was 5.6 months (2.4-8.8 months, 95%CI) and longer in patients with triple negative breast cancer (TNBC) (median 7.4 months, 95%CI, 2.4-12.3 months) than the patients with other subtypes (median 5 months for HER2 positive and 3.6 months for HR positive patients). Median PFS of the patients with TNBC who received this regimen as first-line was 9.2 months (5.2-13.2 months, 95%CI). CONCLUSIONS Cisplatin plus Gemcitabine may be a treatment option for patients with BM from breast cancer. Longer PFS and higher response rates are results that support the usage of this regimen especially for the triple negative subtype. However, further prospective and randomized trials are clearly required to provide more exact information.

Treatment of metastatic colorectal cancer with or without bevacizumab: can the neutrophil/lymphocyte ratio predict the efficiency of bevacizumab?

BACKGROUND The purpose of this study was to analyze the predictive value of neutrophil/lymphocyte ratio (NLR) to better clarify which patient groups will benefit the most from particular treatments like bevacizumab. MATERIALS AND METHODS A total of 245 treatment-naive metastatic colorectal cancern (mCRC) patients were retrospectively enrolled and divided into 2 groups: 145 group A patients were treated with chemotherapy in combination with bevacizumab, and 100 group B patients were treated as above without bevacizumab. RESULTS Group A patients had better median overall survival (OS) and progression-free survival (PFS) (24.0 and 9.0 months) than group B patients (20 and 6.0 months) (p=0.033; p=0.015). In patients with low NLR, OS and PFS were significantly longer in group A patients (27 vs 18 months, p=0.001; 11 vs 7 months, p=0.017). CONCLUSIONS We conclude that NLR, a basal cancer related inflammation marker, is associated with the resistance to bevacizumab- based treatments in mCRC patients.

Does Immunohistochemistry Provide Additional Prognostic Data in Gastrointestinal Stromal Tumors

BACKGROUND To investigate the predictive and prognostic effects of clinicopathologic and immunohistochemical (IHC) features in patients with gastrointestinal stromal tumours (GISTs). MATERIALS AND METHODS Fifty-six patients who were diagnosed with GIST between 2002 and 2012 were retrospectively evaluated. Relationships between clinicopathologic/immunohistochemical factors and prognosis were investigated. RESULTS Median overall survival (OS) of the whole study group was 74.9 months (42.8-107.1 months), while it was 95.2 months in resectable and 44.7 months in metastatic patients respectively (p=0.007). Epitheliolid tumor morphology was significantly associated with shortened OS as compared to other histologies (p=0.001). SMA(+) tumours were significantly correlated with low (<10/50HPF) mitotic activity (p=0.034). Moreover, SMA(+) patients tended to survive longer and had significantly longer disease-free survival (DFS) times than SMA (-) patients (37.7 months vs 15.9 months; p=0.002). High Ki-67 level (≥30%) was significantly associated with shorter OS (34 vs 95.2 months; 95%CI; p=0.001). CD34 (-) tumours were significantly associated with low proliferative tumours (Ki-67<%10) (p=0.026). Median PFS (progression-free survival) of the patients who received imatinib was 36 months (27.7-44.2 months). CD34 (-) patients had significantly longer PFS times than that of negative tumours; (50.8 vs 29.8 months; p=0.045). S100 and desmin expression did not play any role in predicting the prognosis of GISTs. Multivariate analysis demonstrated that ≥10/50HPF mitotic activity/HPF was the only independent factor for risk of death in GIST patients. CONCLUSIONS Despite the negative prognostic and predictive effect of high Ki-67 and CD34 expression, mitotic activity remains the strongest prognostic factor in GIST patients. SMA positivity seems to affect GIST prognosis positively. However, large-scale, multicenter studies are required to provide supportive data for these findings.

Metastases of renal cell carcinoma to the larynx and thyroid: Two case reports on metastasis developing years after nephrectomy

Renal cell carcinoma (RCC) has a high metastatic potential due to its hematogen and vascular features. It metastasizes frequently to the lungs, the bones, the liver, the lymph nodes and the brain. Metastasis of RCC to the head and neck region is quite rare. In this case report, two RCC patients with head and neck metastases are presented: one occurring after 5 years and the other occurring 17 years after diagnosis.

Multicenter epidemiologic study on hepatocellular carcinoma in Turkey.

BACKGROUND Hepatocellular cancer (HCC) is one of the important health problems in Turkey, being very common and highly lethal. The aim of this study was to determine clinical, demographic features and risk factors. MATERIALS AND METHODS Nine hundred and sixth-three patients with HCC from 13 cities in Turkey were included in this study. RESULTS Only 205 (21%) of the 963 patients were women, with a male:female predominance of 4.8:1 and a median age of 61 years. The etiologic risk factors for HCC were hepatitis B in 555 patients (57.6%), 453 (81%) in men, and 102 (19%) in women, again with male predominance, hepatitis C in 159 (16.5%), (14.9% and 22.4%, with a higher incidence in women), and chronic alcohol abuse (more than ten years) in 137 (14.2%) (16.8% and 4.9%, higher in males). The Child-Pugh score paralleled with advanced disease stage amd also a high level of AFP. CONCLUSIONS According to our findings the viral etiology (hepatitis B and hepatitis C infections) in the Turkish population was the most important factor in HCC development, with alcohol abuse as the third risk factor. The Child-Pugh classification and AFP levels were determined to be important prognostic factors in HCC patients.

Second-Line Irinotecan after Cisplatin, Fluoropyrimidin and Docetaxel for Chemotherapy of Metastatic Gastric Cancer

AIM Tumors of upper gastrointestinal tract are among the cancers that have a quite lethal course. Cytotoxic chemotherapy is the most efficient therapeutic modality for metastatic gastric cancer. In patients who do not respond to first-line treatment, the response rate to second-line therapies is generally low and the toxicity rates high. This study concerned the efficacy and the side effect profile of second-line therapy with irinotecan in the patients who were being followed-up with the diagnosis of metastatic gastric cancer in Izmir, Turkey. MATERIALS AND METHODS We retrospectively evaluated the efficacy and toxicity in 31 patients with metastatic gastric adenocarcinoma who presented to the polyclinic of Medical Oncology of Izmir Ataturk Education and Research Hospital between May 2008 and July 2011. All received chemotherapy regimens containing cisplatin, fluoropyrimidine (5-FU) and docetaxel as the first-line therapy for late stage disease. Irinotecan as a single agent was given at a dose of 210 mg/m(2) on each 21 days. Irinotecan (180 mg/m(2) on day 1), 5-FU (500 mg/m(2) on days 1-2) and leucovorin (LV; 60 mg/m(2) on days 1-2) as a combined regimen were given over a 14 day period. RESULTS Median age was 54 (range, 31-70). Irinotecan was given as a combined regimen for median 6 cycles (range, 3-12) and as a single agent for median 3 cycles (range, 1-10). Metastases were detected in one site in six patients (19%), in two different sites in 17 patients (55%) and in three or more sites in eight patients (26%). Four patients (12.9%) showed partial response and six patients (19.3%) showed stable disease. Progression- free survival (PFS) was found to be 3.26 months (95% CI, 2.3-4.2). Median overall survival (OS) was found to be 8.76 months (95% CI, 4.5-12.9). The most commonly seen grade 3/4 side effect was neutropenia but the the therapy was generally well-tolerated. CONCLUSIONS In this study, it was demonstrated that second-line therapy with irinotecan given following the first-line therapy with cisplatin, fluoropyrimidine (5-FU) and docetaxel was efficient and safe. Further studies are needed for confirmation.

The impact of cell proliferation markers and p53 mutation status on prognosis of non-metastatic colon cancer

We aimed to evaluate the prognostic value of cell cycle proteins and p53 together with clinicopathologic features in non‐metastatic resected colon cancer.

Prognostic Evaluation of Breast Cancer Patients with Evident Bone Marrow Metastasis

In this study, we aimed to evaluate the clinicopathologic characteristics and prognosis of breast cancer (BC) patients with symptomatic bone marrow metastasis (BMM). Fifty‐four BC patients, including patients with and without BMM, were evaluated retrospectively. In particular, the clinicopathologic features and survival of the patients with BMM (n = 27) were assessed and compared with the patients without BMM. All of the patients with BMM also had osseous metastases, and bone was the first site for distant recurrence in the majority of patients in the study group. Anemia was the most frequent symptom at presentation. The median time to BMM was 36.1 months (range 1.6–70.5 months, 95% CI). HER2(+) patients developed BMM earlier than HER2(−) patients (3.2 versus 38.3 months, 95% CI; p = 0.05). Patients with advanced disease at the time of initial BC diagnosis developed BMM earlier than patients with early disease (p = 0.04). Time to development of BMM was significantly shorter in tumors with perinodal infiltration (p = 0.001) and multicentric focus (p = 0.025). Median survival time after the diagnosis of apparent BMM was 6.43 months. Survival after BMM diagnosis in patients with grade III tumors was significantly shorter than in patients with grade I–II tumors (1.43 versus 5.36 months, 95% CI; p < 0.001). Systemic therapy after BMM diagnosis significantly prolonged survival (17.3 versus 0.93 months, 95% CI; p < 0.001). Hormone receptor‐positive, high‐grade, advanced‐stage tumors at the time of initial BC diagnosis were more common in patients with BMM. Invasive lobular histology was also more frequent in patients with BMM. In conclusion, the presence of hormone receptor‐positive, multicentric, grade III, advanced‐stage tumors may be important risk factors for the development of evident BMM in BC patients. Systemic single‐agent chemotherapy can prolong survival in these patients. However, multicenter analyses are required to verify these findings.