To evaluate radiological and clinical features in metastatic anaplastic lymphoma kinase+ non-small cell lung cancer patients and crizotinib efficacy in different lines. This national, non-interventional, multicenter, retrospective archive screening study evaluated demographic, clinical, and radiological imaging features, and treatment approaches in patients treated between 2013-2017. Totally 367 patients (54.8% males, median age at diagnosis 54 years) were included. Of them, 45.4% were smokers, and 8.7% had a family history of lung cancer. On radiological findings, 55.9% of the tumors were located peripherally, 7.7% of the patients had cavitary lesions, and 42.9% presented with pleural effusion. Pleural effusion was higher in nonsmokers than in smokers (37.3% vs. 25.3%, P = .018). About 47.4% of cases developed distant metastases during treatment, most frequently to the brain (26.2%). Chemotherapy was the first line treatment in 55.0%. Objective response rate was 61.9% (complete response: 7.6%; partial response: 54.2%). The highest complete and partial response rates were observed in patients who received crizotinib as the 2nd line treatment. The median progression-free survival was 14 months (standard error: 1.4, 95% confidence interval: 11.2-16.8 months). Crizotinib treatment lines yielded similar progression-free survival (P = .078). The most frequent treatment-related adverse event was fatigue (14.7%). Adrenal gland metastasis was significantly higher in males and smokers, and pleural involvement and effusion were significantly higher in nonsmokers-a novel finding that has not been reported previously. The radiological and histological characteristics were consistent with the literature data, but several differences in clinical characteristics might be related to population characteristics.
Description of patient characteristics, effectiveness and safety in Turkish patients treated with pazopanib for metastatic soft tissue sarcoma (STS). This multicenter study is based on retrospective review of hospital medical records of patients (≥ 18 years) treated with pazopanib for non-adipocytic metastatic STS at 37 Oncology clinics across Turkey. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated with further analysis of data on the three most common histological subtypes (leiomyosarcoma [LMS], undifferentiated pleomorphic sarcoma [UPS], synovial sarcoma [SS]) in the cohort. Data of 552 adults (57.6
The prognostic role of pre-treatment serum alkaline phosphatase (SAP) in patients with osteosarcoma has been investigated in previous studies, but the results are inconsistent. The purpose of this study was to evaluate prognostic factors, especially pre-treatment SAP level, in adolescent and adult patients with localized extremity osteosarcoma. In this retrospective study, 153 patients with high-grade, localized extremity osteosarcoma, treated from 1995 to 2011 were analyzed. Pre-treatment SAP and lactate dehydrogenase (LDH) levels and other clinicopathological data were recorded. Arbitrarily, the group of patients with high SAP was further divided into 3 subgroups: up to 2 times of upper limit normal level; from 2 times to 4 times; higher than 4 times of upper limit normal level. The median age was 19 years (range 13-68), 99 patients (64.7%) were male. The most common primary site was femur (89 patients, 58.2%). The most common histological subtype was osteoblastic (56 patients, 47.0 %), 42.5 % of patients had high pre-treatment SAP levels, 43.1 % of patients had high LDH levels. Median follow-up time was 36 months (4-213). Disease-free survival (DFS) at 5 and 10 years were 42.5 % and 37.1 %, respectively, (median DFS: 36 months); overall survival (OS) at 5 and 10 years were 59.6 % and 50.6 %, respectively, (median OS: 146 months. Univariate analysis for OS showed that male gender (p=0.019), high LDH level (p=0.015), high SAP levels (p=0.011) , presence of tumor positive margins after primary surgery (p=0.004) and tumor necrosis rate (p=0.06) were associated with poor survival. In multivariate analysis, only SAP level higher than 4 times of upper limit normal level (p<0.001) and poor tumor necrosis after preoperative chemotherapy (p=0.026) were found to be significantly associated with poor OS. Pre-treatment SAP level higher than 4 times of upper limit normal level has poor prognostic role in adolescent and adult patients with localized extremity osteosarcoma. Further studies with larger number of patients are needed to determine the most accurate threshold point of high SAP levels as prognostic factor.
Background: Colorectal cancer (CRC) is a rare disease amongst children and adolescents. Previous studies have reported a number of differences between children/adolescents, young adults, and adult patients with CRC. However, none of these studies compared these age groups according to their clinicopathologic and prognostic characteristics. In the current study, we compare these three age groups. Methods:A total of 173 (1.1% of 15,654 patients) young CRC patients (≤25 years) were included in the study. As a control group, 237 adult CRC patients (>25 years) were also included. Patients were divided into three age groups: child/adolescent (10–19 years), young adult (20–25 years), and adult (>25 years). Results: Statistical differences amongst the three groups in terms of gender (p = 0.446), family history (p = 0.578), symptoms of presentation (p = 0.306), and interval between initiation of symptoms and diagnosis (p = 0.710) could not be demonstrated. Whilst abdominal pain (p < 0.001) and vomiting (p = 0.002) were less common in young adults than in other groups, rectal bleeding and changes in bowel habits were relatively less common in adolescents than in other groups. Rectal localisation (p = 0.035), mucinous adenocarcinoma (p < 0.001), and a poorly differentiated histologic subtype (p < 0.001) were less common in the adult group than in other groups. The percentage of patients with metastasis and sites of metastasis (e.g., peritoneum and lung) differed between groups. The median overall survival was 32.6 months in the adolescent group, 57.8 months in the young adult group and was not reached in the adult group (p = 0.022). The median event-free survival of the adolescent, young adult, and adult groups was 29.0, 29.9, and 61.6 months, respectively (p = 0.003). Conclusions: CRC patients of different age groups present different clinicopathologic and prognostic characteristics. Clinicians should be aware of and manage the disease according to these differences.
Purpose: Almost half of all patients diagnosed with non-small cell lung cancer (NSCLC) have distant metastases at presentation. One-third of patients with NSCLC will have brain metastases. Without effective treatment, the median survival is only 1 month. However, it is difficult to treat brain metastases with systemic chemotherapy since the agents have difficulty crossing the blood-brain barrier. Therefore, it is important to estimate the patient's survival prognosis. The aim of this study was to analyze prognostic factors for survival in Turkish patients who received chemotherapy after cranial irradiation for NSCLC with brain metastases. Methods: We retrospectively reviewed 698 patients with brain metastases resulting from NSCLC. Ten potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with overall survival (OS). Results: Among the 10 variables for univariate analysis, six were identified to have prognostic significance; these included sex, smoking history, histology, number of brain metastases, extracranial metastases, and neurosurgical resection. Multivariate analysis by the Cox proportional hazard model showed that a smoking history, extracranial metastases, and neurosurgical resection were independent negative prognostic factors for OS. Conclusion: Smoking history, extracranial metastases, and neurosurgical resection were considered independent negative prognostic factors for OS. These findings may facilitate pretreatment prediction of survival and can be used for selecting patients for more appropriate treatment options.
Introduction Mammalian target of rapamycin is a pathway to block apoptosis. Recent studies showed that the activity of mammalian target of rapamycin pathway increases in endometriotic lesions. Aim of the present study was to study the effect of everolimus agent, a rapamycin analog, in an experimental endometriosis model.Materials and Methods Endometriosis established by the autotransplantation of uterine tissue in the peritoneal cavity was confirmed in 24 rats. The animals were then randomly divided into three groups to receive either everolimus (1.5mg/kg/day, p.o.), anastrozole (0.004mg/day, p.o.), or normal saline (0.1mL, i.p.) for 14 days. Endometriotic foci were excised, stained with hematoxylin and eosin, and endometriosis was scored semiquantitatively. In addition, immunohistochemical examination were performed using primary antibodies of vascular endothelial growth factor, CD117, and Bax.Results Both anastrozole and everolimus lowered endometriosis scores. Significant decreases in ovarian follicles were observed following anastrozole treatment but not everolimus treatment.Conclusion Through its apoptosis-promoting effect, everolimus suppressed endometriotic foci without negatively affecting ovarian reserve. These findings support the hypothesis that everolimus merits further study on the way to developing a new endometriosis drug.
Objective: Lung cancer is the leading cause of cancer-related deaths worldwide.Despite advancement in diagnostic tools and treatment options with technological developments, overall mortality rates in lung cancer patients remains high.Survival rates in lung cancer patients is low especially in advanced diseased inoperable patients in spite of new treatment options like immunotherapy.p53 is mutated in 60-70% of cancer patients and for this reason has been extensively studied recent researches suggest that serum anti-p53Ab can be considered as biomarkers to detect many types of cancers; as ovarian cancer, esophageal cancer, breast cancer and lung cancer.In this study we aimed that are there any diagnostic and prognostic importance of serum anti-p53Ab levels in lung cancer patients.Method: Patients were included who were referred to our department with the purpose of 18 F-FDG-PET/CT imaging for staging due to lung cancer diagnosis (LC) and patients who were performed 18 F-FDG-PET/CT for diagnosis in the cause of the suspected pulmonary nodule in thorax CT but not detected pathologic FDG accumulation (NAPN=pulmonary nodule with non-avid-FDG) and healthy volunteers.Serum anti-p53Ab levels were measured with ELISA method in the all patients.Mean follow up time of patients were 13 months.Results: A total of 65 LC patients (58M/7F), 47 patients with NAPN (20M/27F), and a total of 34 healthy volunteers (26M/8F) were included in this study.Median serum anti-p53Ab levels are 3.4ng/mL in LC patients, 3.77ng/mL in NAPN patients, 3.07ng/mL in healthy volunteers.There is no statistically significant difference for serum anti-p53Ab level between LC patients and NAPN patients (p=0.678).Moreover there is no statistically significant difference for serum anti-p53Ab level between patients and healthy volunteers (p=0.377).Two-year median survival of patients was 14 month.It has been found that there is no effect of serum anti-p53Ab level whether >3.4 or ≤3.4 on the patient survival rate (p=0.652).Conclusions: Even though anti-p53Ab is very important in carcinogenesis, we think that serum anti-p53Ab level by itself is not important in lung cancer diagnosis and survival rates.There are multiple factors in carcinogenesis and this may be the reason of this situation.There is no known cut off value of serum anti-p53 Ab levels for diagnosis of lung cancer patients.Therefore we think that this antibody is not tumor spesific and serum anti-p53 Ab level measurement is not appropriate for lung cancer screening.
PURPOSE:To evaluate the efficacy and adverse events with cetuximab plus FOLFOX administered as second- and third-line therapy in metastatic colorectal cancer (mCRC) patients.METHODS:IPatients were administered cetuximab plus FOLFOX as second- and third-line therapy from January 2010 through October 2015. mCRC patients with wild type KRAS were alsï given irinïtecan and/ïr ïxaliplatin cïmbined with fluorïpyrimidine±bevacizumab. Tumor respïnse and survival were evaluated using RECIST and Kaplan-Meier methïd respectively.RESULTS:Sixty patients were included this study. Cetuximab plus FOLFOX was administered to 40 (66.7%) patients as second-line and to 20 (33.3%) as third-line therapy. The majority of the patients had a good ECOG performance status (PS) (0 or 1). Clinical benefit was partial plus stable disease and it was 75.0% for both of these two lines. The median progression free survival (PFS) was 7.1 months (95% CI=3.2-10.9) and 6.0 months (95% CI=2.4-9.6), in the second-and third-line (p=0.484). The median ïverall survival (ÏS) was 14.3 and 9.2 mïnths in secïnd-and third-line therapy respectively (p=0.071). The common toxicities were haematologic and gastrointestinal, mostly grade 1 and 2.CONCLUSION:The addition of cetuximab to FOLFOX was well-tolerated and had antitumor activity both in second- and third-line therapy in patients with mCRC.
Amac: Akciger kanseri dunya genelinde kansere bagli olumlerin onde gelen nedenidir. Tanisal cihazlar ve teknolojik gelismelere bagli tedavi seceneklerinde ilerlemeye ragmen, akciger kanseri hastalarinda genel mortalite orani hala yuksektir. Akciger kanseri hastalarinda sagkalim oranlari, ozellikle ilerlemis inoperabl hastalikta, immunoterapi gibi yeni tedavi seceneklerine ragmen dusuktur. p53, kanser hastalarinin %60-70’inde mutasyona ugramaktadir ve bu nedenle son zamanlarda yapilan calismalar gostermektedir ki, serum anti-p53 antikorunun, over, ozefagus, meme ve akciger kanseri gibi bazi kanser turlerinin dedekte edilmesinde biyobelirtec olarak dikkate alinabilir. Bu calismada, akciger kanseri hastalarinda, serum anti-p53antikor duzeylerinin tanisal ve prognostik onemini arastirmayi amacladik. Yontem: Calismaya akciger kanseri (AK) tanisi nedeniyle evreleme icin 18F-FDG-PET / BT goruntuleme amaci ile bolumumuze sevk edilen hastalar, toraks BT’sinde supheli pulmoner nodul olup, patolojik FDG birikimi gostermeyen hastalar (NAPN= Non-avid FDG gosteren pulmoner nodul) ve saglikli gonulluler dahil edildi. Serum anti-p53antikor duzeyleri tum hastalarda ELISA yontemi ile olculdu. Hastalarin ortalama takip suresi 13 ay idi. Bulgular: Calismaya toplam 65 AK hastasi (58E/7K), 47 NAPN hastasi (20E/27K) ve 34 saglikli gonullu (26E /8K) dahil edildi. Ortalama serum anti-p53antikor seviyeleri AK hastalarinda 3.4ng/mL, NAPN hastalarinda 3.77ng /mL, saglikli gonullulerde 3.07 ng/ mL idi. AK hastalari ile NAPN hastalari arasinda serum anti-p53antikor duzeyi icin istatistiksel olarak anlamli fark yoktu (p = 0.678). Hatta, hastalar ve saglikli gonulluler arasinda serum anti-p53Ab duzeyi icin istatistiksel olarak anlamli fark yoktu (p = 0.377). Hastalarin iki yillik medyan sagkalimi 14 aydi. Hastalarin sagkalim hizinda, serum anti-p53Ab duzeyinin u003e 3.4 ng/ mL veya ≤3.4 ng/ mL olmasinin herhangi bir etkisinin olmadigi bulundu (p = 0.652). Sonuc : Anti-p53antikoru, karsinogeneziste cok onemli olmasina ragmen, serum anti-p53antikor duzeyinin akciger kanseri tanisinda ve sagkalim oranlarinda tek basina onemli olmadigini dusunuyoruz. Karsinogeneziste birden fazla faktor vardir ve bu durumun nedeni olabilir. Akciger kanseri hastalarinin teshisi icin serum anti-p53antikor duzeylerinin bilinen bir katof degeri yoktur. Bu nedenle, bu antikorun tumor spesifikligi olmadigini ve serum anti-p53antikor duzeyinin akciger kanseri taramasi icin uygun olmadigini dusunuyoruz.
BACKGROUND:Currently, it is accepted that risk assessment of clinical stage I (CS I) nonseminomatous germ cell tumors (NSGCT) patient is mainly dependent on the presence of lymphovascular invasion (LVI). Initial active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection (RPLND) are acceptable treatment options for these patients, but there is no uniform consensus. The purpose of this study was to compare outcomes of active surveillance with adjuvant chemotherapy. METHODS:A total of 201 patients with CS I NSGCT after orchiectomy were included. Outcomes of active surveillance and adjuvant chemotherapy were retrospectively analyzed. The prognostic significance of risk factors for survival and relapse was evaluated. RESULTS:Of the 201 patients, 110 (54.7%) received adjuvant chemotherapy, while the remaining 91 patients (45.3%) underwent surveillance. Relapses were significantly higher for patients underwent surveillance compared to adjuvant chemotherapy group (18.3 vs. 1.2%, p < 0.001). The 5-year relapse-free survival (RFS) rate for patients who were treated with adjuvant chemotherapy was significantly better than those of patients underwent surveillance (97.6 vs. 80.8%, respectively; p < 0.001). Univariate analysis showed that the presence of LVI (p = 0.01) and treatment option (p < 0.001) were prognostic factors for RFS and pT stage (p = 0.004) and invasion of rete testis (p = 0.004) and the presence of relapse (p < 0.001) were significant prognostic factors for OS. Multivariate analysis revealed that the treatment strategy was an independent prognostic factor for RFS (p < 0.001, HR 0.54). A logistic regression analysis demonstrated that treatment options (p = 0.031), embryonal carcinoma (EC) >50% (p = 0.013) and tumor diameter (p = 0.016) were found to be independent factors for predicting relapse. CONCLUSIONS:Our results indicate that adjuvant chemotherapy is associated with improved RFS compared with surveillance for CS I NSGCT patients. Moreover, the treatment strategy is an important prognostic indicator for RFS and a predictive factor for relapse. Although adjuvant chemotherapy seems to be a suitable treatment for patients with risk factors for relapse, surveillance is still preferred management option.
Background/Aims: This study aimed to examine whether UHRF-1 and p53 overexpression is a prognostic marker for gastric cancer. Patients and Methods: Sixty-four patients with gastric cancer (study group) and 23 patients with gastritis (control group) were evaluated. Immunohistochemistry was used to examine expression of UHRF-1 and p53 in gastric cancers and a control group diagnosed with gastritis. Results: The median age was 63 years (18-83 years) in the study group. UHRF-1 was positive in 15 (23%) patients with gastric cancer and fi ve (21.7%) patients with gastritis (P = 0.559). UHRF1 expression level in gastric cancer is more powerful than in gastritis (P = 0.046). Thirty-seven (61%) patients with gastric cancer and only one patient with gastritis were p53 positive (P < 0.001). After a median follow-up of 12 months (1-110), the 2-year overall survival rates were 55% and 30% in negative and positive p53, respectively (P = 0.084). Also, the 2-year overall survival rates were 45% and 53% in negative and positive UHRF-1, respectively (P = 0.132). Conclusion: According to this study, UHRF-1and p53 were not prognostic factors for gastric cancer, whereas they may have a diagnostic value for differantiating between gastric cancer and gastritis.
Objective: Mutations in the p53 gene are the most commonly observed genetic abnormalities in malignancies.The purpose of this study was to assess the diagnostic value of serum anti-p53 antibody (Ab) along with the correlation between serum anti-p53 Ab level and quantitative positron emission tomography (PET) parameters such as maximum standardized uptake value (SUV max ), SUV ave , metabolic tumor volume, total lesion glycolysis (TLG) and tumor size.Methods: Serum anti-p53 Ab level was studied in three groups.Patients who underwent 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) imaging for staging of previously diagnosed lung cancer constituted the first group, while patients who underwent 18 F-FDG PET/CT imaging for evaluation of suspicious pulmonary nodules detected on thorax CT and did not show pathologic FDG accumulation (NAPN=pulmonary nodule with non avid-FDG) were enrolled in the second group.The third group consisted of healthy volunteers.Results: Twenty-eight patients with lung cancer (median age: 62.5, range: 39-77years), 28 patients with NAPN (median age: 65, range: 33-79 years), and 24 healthy volunteers (median age: 62, range: 44-74 years) were enrolled in the study.The serum anti-p53 Ab level was low in healthy volunteers while it was higher in both lung cancer patients and NAPN patients (p<0.05).When serum anti-p53 Ab level and PET parameters were evaluated, there was no significant correlation between serum anti-p53 Ab level and SUV max , SUV ave , TLG, tumor volume and tumor size of patients with lung cancer (p>0.05).Besides, there was no significant difference between serum anti-p53 Ab level and lesion size of NAPN patients (p>0.05). Conclusion:It was determined that serum anti-p53 Ab levels are not significantly correlated with PET parameters, and that serum anti-p53 Ab levels increase in any benign or malignant lung parenchyma pathology as compared to healthy volunteers.These results indicate that this Ab cannot be used as a predictor of malignancy in a lung lesion.
Systemic activation of coagulation and fibrinolysis is frequently observed in cancer patients without thrombosis. Recent studies have showed the association between D-Dimer (DD) and metastatic spread and prognosis of cancer. We aimed to investigate the prognostic value of DD in patients with non metestatic breast cancer (nMBC) and evaluated the DD levels and other variables for overall survival (OS) using univariate and multivariate analyses in 448 patients. The median follow-up time was 50 months (3-151 months). There was only significant relationship between DD and distant metastases (p= 0.052). Performance status (PS) (p< 0.001 and < 0.001), stage (p< 0.001 and < 0.001) , CEA (p< 0.001 and < 0.001), CA 15-3 (p< 0.001 and < 0.001) and DD (p< 0.001 and 0.034) were determined as prognostic factors for OS in univariate analysis. In multivariate analysis, PS (ECOG 0 vs ECOG 1, p= 0.022; ECOG 0 vs ECOG ≥2, (p< 0.001), stage (stage I vs stage II, p= 0.566; stage I vs stage III, p= 0.033), the CA 15-3 (p= 0.048) and DD levels (p= 0.015) were determined as independent prognostic factors for OS . In conclusion, pretreatment high DD level is an important prognostic factor in patients with non metastatic breast cancer and high DD levels were associated with poor outcome.
e14657 Background: CRC is one of the most common tumors in adults, also can occur rarely in children and young adults. Although we know there are some differences between young and adults CRC patients, there is no study demonstrating these differences by comparative studies. The aim of the study to determine these differences by comparing young and adult patients. Methods: Between 2003 to 2014, 119 young CRC patients ( ≤ 25 years) were included in the study from referral center. As a control group, 135 adult patients ( > 25 years) were included in the study from Dicle University medical records. The medical records studied to analyze age, sex, presenting symptoms, presentation, family history, presence of polyps, histological features, localization, stage, and survival outcomes. Results: Median age for young and adult CRC group was 23 (10-25) and 52 (26-94), respectively. There were no statistical differences between two groups in terms of gender (male gender was 51.3% vs. 54.8%, p = 0.571), family history (24.2% vs. 24.6%, p = 0.517), presence of polyps (6.6% vs. 12.1%, p = 0.152), and acute presentation (20.7% vs. 18.8%, p = 0.707). While abdominal pain more common in adult group (55.3% vs. 72.0%, p = 0.008), rectal bleeding (35.9% vs. 37.1%, p = 0.850), change in bowel habit (34.0% vs. 24.2%, p = 0.101), nausea/vomiting (13.6% vs. 7.6%, p = 0.131), and weight loss (17.5% vs. 18.2%, p = 0.889) were similar between two groups. Mucinous histology (44.8% vs. 5.9%, p < 0.001), poorly differentiated tumor (34.7% vs. 10.5%, p < 0.001), rectal localization (40.2% vs. 25.4%, p = 0.021), and presence of metastasis at the time of diagnosis (25.4% vs. 10.4%, p = 0.002) were more common in young group than adults. In adult patients, overall survival was longer (numerically but not statistically) compared with young patients (67.7 months vs. 57.8 months, p = 0.141). Conclusions: This study supports our previous knowledge about differences between young and adult CRC patients.
BACKGROUND:Acute kidney injury is an important issue in chemotherapy receiving patients an neutrophil gelatinase-associated lipocalin has been proposed as a novel marker. We here aimed to assess the role of urinary levels for assessment after platin exposure.MATERIALS AND METHODS:Patients who had treated with cisplatin or carboplatin or oxaliplatin containg regimens were included in this study. Baseline and postchemotherapy serum urea, creatinine, urine neutrophil gelatinase-associated lipocalin and urine creatinine levels were determined. To avoid the effects of hydration during chemotherapy infusion the urinary neutrophil gelatinase-associated lipocalin/urine creatinine ratio was used to determine acute kidney injury.RESULTS:Of a total of 42 patients receiving platin compounds,14 (33.3%) received cisplatin containing regimens, 14 (33.3%) received carboplatin and 14 (33.3%) oxaliplatin. The median age was 60 (37-76) years. Nineteen of the patients (45.2%) had lung cancer, 12 (28.6%) colorectal cancer and 11 (26.2%) others. The median pre and post chemotherapy urine neutrophil gelatinase-associated lipocalin/urine creatinin ratio was 15.6 ng/mg and 35.8 ng/mg (p=0.041) in the cisplatin group, 32.5 ng/mg and 86.3 ng/mg (p=0.004) in the carboplatin group and 40.9 ng/mg and 62.3 ng/ mg (p=0.243) in the oxaliplatin group.CONCLUSIONS:Nephrotoxicity is a serious side effect of chemotherapeutic agentslike cisplatin and carbopaltin, but only to a lower extent oxaliplatin. All platin compounds must be used carefully and urine neutrophil gelatinase-associated lipocalin measurement seems to be promising in detecting acute kidney injury earlier than with creatinine.
Cancer is one of the most common causes of deaths worldwide (Brawley, 2011; Jemal et al., 2011; Siegel et al., 2011). With the developments in the treatment modalities and newly developed chemotherapeutic agents, both the survival rates of the patients and the side effects have increased (Berry et al., 2005; Smith et al., 2009). Nephrotoxicity is a common and important side effect of the chemotherapeutic agents. Cisplatin, carboplatin, gemcitabine, cyclophosphamide, ifosfamide, bevacizumab, and sunitinib are commonly used agents that cause nephrotoxicity via different mechanisms (Launay-Vacher et al., 2007; Lichtman et al., 2007). Nowadays, the diagnosis of renal insufficiency is based on serum creatinine level and glomerular filtration rate. But serum creatinine is not an ideal marker for many reasons (Devarajan, 2008; Nickolas et al., 2008; Parikh and Devarajan, 2008). First, serum creatinine is influenced by
OBJECTIVE: Typically, bone metastasis causes osteolytic and osteoblastic lesions resulting from the interactions of tumor cells with osteoclasts and osteoblasts. In addition to these interactions, tumor tissues may grow inside bones and cause mass lesions. In the present study, we aimed to demonstrate the negative impact of a tumor mass in a large cohort of patients with bone metastatic cancer.METHODS: Data from 335 patients with bone metastases were retrospectively reviewed. For the analysis, all patients were divided into three subgroups with respect to the type of bone metastasis: osteolytic, osteoblastic, or mixed. The patients were subsequently categorized as having bone metastasis with or without a tumor mass, and statistically significant differences in median survival and 2-year overall survival were observed between these patients (the median survival and 2-year overall survival were respectively 3 months and 16% in patients with a tumor mass and 11 months and 26% in patients without a tumor mass; p<0.001).RESULTS: According to multivariate analysis, the presence of bone metastasis with a tumor mass was found to be an independent prognostic factor (p=0.011, hazard ratio: 1.62, 95% confidence interval: 1.11-1.76). Bone metastasis with a tumor mass was more strongly associated with osteolytic lesions, other primary diseases (except for primary breast and prostate cancers), and spinal cord compression.CONCLUSION: Bone metastasis with a tumor mass is a strong and independent negative prognostic factor for survival in cancer patients.
e16094 Background: We evaluated the efficiency and safety of AA in patients with MCRPC after docetaxel chemotherapy. Methods: Between April 2011 and January 2014, we retrospectively evaluated survival outcomes and toxicities of 103 patients with MCRPC after docetaxel chemotherapy who were treated with AA (1000 mg, orally once daily) plus prednisone (5 mg, orally twice daily). Results: Median age was 67 (45-85) and 46% of the patients had at least one comorbid diseases. Median initial diagnosis of PSA was 61.7 ng/dl (3-3,000) and 86.4% of the patients had more than Gleason score 6. Radical prostatectomy and definitive radiotherapy were performed 19.4% and 32% of the patients, respectively. Secondary hormonal manipulation was performed 25.2% of the patients. The 77.7% of the patients progressed while on treatment of the docetaxel. Before the AA, median docetaxel cycles and dose were 7 (1-40) and 900 mg (75-5,400 mg), respectively. Initial of the AA, ECOG performance status 2 and 3 were in 35 patients (34%) and median PSA was 100 ng/dl (0-5371 ng/dl). Metastatic sites were as follow; only bone (n= 52, 50.5%), bone and soft tissue/ lymph node (n= 6, 5.8%) and visceral metastases (n=45, 43.7%). Toxic deaths were in five (4.9%) and dose reduction was applied in 12.6% of the patients. Clinical benefit was 44.6%, median progression free survival and overall survival were 211.86 day (169.23-260.48) and 486.67 day (380.12-593.21), respectively. Most common adverse events were anemia (31.1%), nausea and vomiting (20.4%), elevation of transaminases (12.7%). Conclusions: AA is the effective agent with tolerable safety profile in patients with MRCPC.
BACKGROUND:Breast cancer evolution and tumor progression are controlled by complex interactions between steroid receptors and growth factor receptor signaling. Aberrant growth factor receptor signaling can augment or suppress estrogen receptor function in hormone-dependent breast cancer cells. Thus, we aimed to investigate antitumor effects of sorafenib and lapatinib alone and in combination on MCF-7 breast cancer cells.MATERIALS AND METHODS:Cytotoxicity of the sorafenib and lapatinib was tested in MCF-7 cells by XTT assays. 50, 25, 12.5 and 6.25μM concentrations of sorafenib and 200, 100, 50 and 25μM concentrations of lapatinib were administered alone and in combination. Results were evaluated as absorbance at 450nM and IC50 values are calculated according to the absorbance dataRESULTS:Both sorafenib and lapatinib showed concentration dependent cytotoxic effects on MCF-7 cells. Sorafenib exerted cytotoxic effects with an IC50 value of 32.0μM; in contrast with lapatinib the IC50 was 136.6μM. When sorafenib and lapatinib combined, lapatinib increased cytotoxic effects of sorafenib at its ineffective concentrations. Also at the concentrations where both drugs had cytotoxic effects, combination show strong anticancer effects and killed approximately 70 percent of breast cancer cells.CONCLUSIONS:Combinations of tyrosine kinase inhibitors and cytotoxic agents or molecular targeted therapy has been successful for many types of cancer. The present study shows that both sorafenib and lapatinib alone are effective in the treatment of breast cancer. Also a combination of these two agents may be a promising therapeutic option in treatment of breast cancer.
e15082 Background: Gastric cancer is the second leading cause of cancer death for both sexes worldwide. Ubiquitin-like with PHD and ring-finger domains-1 (UHRF- 1) is essential for cellular proliferation and is overexpressed in various cancers. P53 is a well known tumor suppressor gene and many human cancers are found to have a mutant p53 gene. We aimed to examine whether UHRF-1 and p53 over expression could be diagnostic and prognostic markers of gastric cancer. Methods: Immunohistochemistry was used to examine expression of UHRF-1 and p53 in gastric cancers and a control group diagnosed with gastritis. Results: In total, 64 patients with gastric cancer (study group) and 23 patients with gastritis (control group) were evaluated. The median age was 63 years (18–83) in the study group. UHRF-1 was positive in 15 (23%) patients with gastric cancer and 5 (21.7%) patients with gastritis (p=0.559). Thirty-seven (61%) patients with gastric cancer and only one patient with gastritis were p53 positive (p<0.001). After a mean follow-up of 22 months (±2.8), the 2 year overall survival rates were 55% and 30% in negative and positive p53, respectively (p=0.084). Also, the 2 year overall survival rates were 45% and 53% in negative and positive UHRF-1, respectively (p=0.132). Conclusions: This trial demonstrated that UHRF-1 is not a diagnostic and prognostic factor, wherase p53 could be a diagnostic but not a prognostic factor for gastric cancer.