Publications by authors named "Ahmet Bilici"

115 Publications

The real-life efficacy and safety of osimertinib in pretreated advanced non-small cell lung cancer patients with T790M mutation: a Turkish Oncology Group Study.

J Cancer Res Clin Oncol 2021 Jul 31. Epub 2021 Jul 31.

Department of Medical Oncology, Medipol University, Faculty of Medicine, Istanbul, Turkey.

Introduction: Osimertinib, an irreversible third-generation EGFR-TKI, is the standard of care for second-line treatment of T790M-mutant advanced NSCLC patients whose disease progressed after first-line EGFR-TKI therapy. In this multicenter study, we aimed to determine the real-life efficacy and safety of Osimertinib in pretreated advanced NSCLC patients with T790M mutation.

Materials And Methods: This retrospective trial included advanced T790M-mutant pretreated NSCLC patients who received Osimertinib from 24 different centers in Turkey. Primary endpoint was time-to-treatment discontinuation (TTD). Secondary endpoints were objective response rate (ORR), overall survival (OS), and safety.

Results: Of 163 patients, 68.7% had EGFR exon 19 deletion and 22.7% had exon 21 L858R mutation. Osimertinib was given as second-line treatment in 96 patients (58.9%) and third-line in 48 patients (29.4%). After median of 13-month follow-up, median TTD was 21.6 months with an 82.2% ORR. Estimated median OS was 32.1 months. Grade 3-4 adverse events were seen in 11.7% of the patients.

Conclusion: Osimertinib is a highly effective option in second- or third-line treatment of NSCLC patients with T790M mutation, with a favorable safety profile.
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http://dx.doi.org/10.1007/s00432-021-03748-7DOI Listing
July 2021

Cetuximab-induced rash is associated with overall survival in patients with recurrent/metastatic squamous cell carcinoma of head and neck.

Cancer Chemother Pharmacol 2021 Jul 26. Epub 2021 Jul 26.

Medical Oncology, Faculty of Medicine, Akdeniz University, Dumlupınar Bulvarı, Kampus, 07070, Antalya, Turkey.

Purpose: In this study, we looked for whether treatment-induced rash predicts treatment efficacy in patients with recurrent/metastatic HNSCC treated with Cetuximab and chemotherapy.

Methods: Patients who were treated with platinum-based chemotherapy and cetuximab for the first line treatment of recurrent/metastatic HNSCC were recruited. Presence of rash, hypomagnesemia, hypopotassemia, anemia, neutropenia, thrombocytopenia during treatment and treatment response, date of progression, date of last visit and death were recorded.

Results: A total of 138 patients' data were available for analysis. Any grade of rash was detected in 57 (44.5%) of the patients. The incidence of rash was significantly higher in patients with objective response than in patients with disease progression (%56.8 vs %14.3, p < 0.001). Progression free survival was 7.06 months (4.98-9.15) in patients treated with cetuximab and chemotherapy as first line treatment. In the multivariate analysis; rash was significantly correlated with longer PFS (HR 2.136; 95% CI 1.067-4.278; p = 0.032). Progression free survival was 9.65 months in patients who experienced rash, and 6.02 months in patients without rash, (p = 0.019, log-rank test). Overall survival was 11.24 months (9.65-12.82). In multivariate analysis, the survival of patients with rash was significantly longer than patients without rash (HR 1.954; 95% CI 1.162-3.285; p = 0.012). Overall survival was 15.08 months in patients who experienced rash, and 8.61 months in patients without rash (p = 0.05, log-rank test).

Conclusion: Cetuximab-induced rash is associated with better ORR and longer PFS and OS in patients with recurrent/metastatic HNSCC treated with Cetuximab and platinum-based chemotherapy.
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http://dx.doi.org/10.1007/s00280-021-04328-9DOI Listing
July 2021

The Effect of Primary Surgery in Patients with De Novo Stage IV Breast Cancer with Bone Metastasis Only (Protocol BOMET MF 14-01): A Multi-Center, Prospective Registry Study.

Ann Surg Oncol 2021 Sep 2;28(9):5048-5057. Epub 2021 Feb 2.

Department of Surgery, School of Medicine, Yuzuncuyıl University, Van, Turkey.

Background: More evidence shows that primary surgery for de novo metastatic breast cancer (BC) prolongs overall survival (OS) in selected cases. The aim of this study was to evaluate the role of locoregional treatment (LRT) in BC patients with de novo stage IV bone only metastasis (BOM).

Methods: The prospective, multicenter registry study BOMET MF14-01 was initiated in May 2014. Patients with de novo stage IV BOM BC were divided into two groups: those receiving systemic treatment (ST group) and those receiving LRT (LRT group). Patients who received LRT were further divided into two groups: ST after LRT (LRT + ST group) and ST before LRT (ST + LRT group).

Results: We included 505 patients in this study; 240 (47.5%) patients in the ST group and 265 (52.5%) in the LRT group. One hundred and thirteen patients (26.3%) died in the 34-month median follow-up, 85 (35.4%) in the ST group and 28 (10.5%) in LRT group. Local progression was observed in 39 (16.2%) of the patients in the ST group and 18 (6.7%) in the LRT group (p = 0.001). Hazard of death was 60% lower in the LRT group compared with the ST group (HR 0.40, 95% CI 0.30-0.54, p < 0.0001).

Conclusion: In this prospectively maintained registry study, we found that LRT prolonged survival and decreased locoregional recurrence in the median 3-year follow-up. Timing of primary breast surgery either at diagnosis or after ST provided a survival benefit similar to ST alone in de novo stage IV BOM BC patients.
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http://dx.doi.org/10.1245/s10434-021-09621-8DOI Listing
September 2021

The potential prognostic role of peritumoral eosinophils within whole tumor-associated inflammatory cells and stromal histological characteristics in colorectal cancer.

Pol J Pathol 2020 ;71(3):207-220

Department of General Surgery, Istanbul Medipol University Hospital, Istanbul, Turkey.

We aimed to determine the prognostic role of whole tumor-associated inflammatory cells, especially eosinophils, and stromal histological characteristics in relation to other prognostic parameters in patients with colorectal carcinoma (CRC). A total of 122 patients who underwent an operation for CRC were included in this retrospective study. Conventional (tumor grade, TNM stage and venous invasion [VI]) and other histopathological (intratumoral/peritumoral budding [ITB/PTB], desmoplasia) tumor parameters were recorded and classified by density, as were the tumor-associated inflammatory parameters (intratumoral/peritumoral lymphocytes [ITL/PTL], eosinophils [IE/PTE], overall inflammation [ITI/PTI], Crohn-like inflammation [CLI]). Cancer-specific survival data were analyzed with respect to all tumor parameters. High ITB and PTB were significantly correlated with a higher rate of pT4, VI and desmoplasia (p < 0.05). An association of moderate ITL and extensive PTL with lesser likelihood of VI and metastasis; an association of extensive CLI with a significantly lower rate of metastasis and TNM stage IV; and minimal PTE with a significantly higher rate of pT4 stage, metastasis and ITB were detected (p < 0.05 for each). Our findings revealed that low score tumoral budding and an increase in tumor-related inflammation were associated with lesser likelihood of poor prognostic tumor parameters. Nonetheless, given the association of an increase in PTE with lesser likelihood of ITB, pT4, metastasis, and with non-significantly for better survival rates, our findings emphasize the potential role of peritumoral eosinophils as an additional prognostic parameter in CRC.
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http://dx.doi.org/10.5114/pjp.2020.99787DOI Listing
January 2021

Efficacy of regorafenib in the second-and third-line setting for patients with advanced hepatocellular carcinoma: A real life data of multicenter study from Turkey.

J BUON 2020 Jul-Aug;25(4):1897-1903

Department of Medical Oncology, Trakya University, Medicine Faculty, Edirne, Turkey.

Purpose: After failure of the first-line sorafenib treatment in advanced or metastatic stage hepatocellular carcinoma (HCC), regorafenib is one of the newly-approved targeted agents. We aimed to evaluate the efficacy of regorafenib in patients with advanced HCC treated in the second- or third-line setting.

Methods: In this retrospective and multicenter study, advanced HCC patients not eligible for local therapies, who received a second- or third-line regorafenib therapy after progression on the first-line sorafenib or sequential therapy with chemotherapy (CT) followed by sorafenib, were included.

Results: In the first-line setting, 28 (28.9%) patients received CT and 69 (71.1%) patients received sorafenib. There were 24 (24.7%) patients who were intolerant to sorafenib. Disease control rate (DCR) was 53.6% for all patients treated with regorafenib, 62.3% in patients who received regorafenib in the second-line, and 32.1% for those receiving regorafenib in the third-line (p=0.007). Median progression-free survival (PFS) and overall survival (OS) were 5.6 (range; 4.3-6.9) and 8.8 (range, 6.3-11.3) months for all patients treated with regorafenib vs. 7.1 months and 10.3 months for patients who received regorafenib in the second-line vs. 5.1 and 8.7 months for patients who received regorafenib in the third-line, respectively; however, there was no statistically significant difference (pPFS=0.22 and pOS=0.85).

Conclusion: Although receiving CT as a first-line therapy in advanced HCC patients did not affect the survival rates of subsequent regorafenib therapy, it might diminish the DCR of regorafenib.
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July 2021

The conversion of RAS status in metastatic colorectal cancer patients after first-line biological agent treatment.

Colorectal Dis 2021 Jan 20;23(1):206-212. Epub 2020 Oct 20.

Department of Medical Oncology, Faculty of Medicine, Medipol University, Istanbul, Turkey.

Aim: The aim was to investigate the RAS discordance between initial and recurrent metastasectomy specimens in metastatic colorectal cancer (mCRC) patients treated with chemotherapy (CT) plus biological agents in a first-line setting.

Methods: Patients who had been treated with CT plus bevacizumab or cetuximab or panitumumab followed by R0 resection for potentially resectable colorectal cancer liver metastases were scanned. Among these, patients who developed resectable new metastases after a disease-free interval longer than 6 months were included in the study. We compared the RAS mutation status between the first biopsy and the second metastasectomy specimen.

Results: A total of 82 mCRC patients treated with CT plus biological agents in a first-line setting were included in the study. The first biopsy assessment showed wild-type RAS tumours in 39 (47.6%) patients and mutant RAS tumours in 43 (52.4%) patients. The mean time for new operable liver metastasis after R0 resection was 15.5 months. In the second metastasectomy specimens, the numbers of wild-type and mutant RAS tumours were 30 (36.6%) and 52 (63.4%), respectively. The comparison with the first biopsy specimens showed RAS status conversions in 17 (20.7%) patients. Univariate comparison between patients with and without RAS status conversion revealed that grade, pathological T stage, wild-type RAS tumour and longer biological agent use time in the first-line treatment were significant factors for RAS conversion.

Conclusion: Our results suggest that re-biopsy is needed for an optimal second-line treatment decision in mCRC patients regardless of backbone biological agent, especially in patients with wild-type RAS mCRC.
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http://dx.doi.org/10.1111/codi.15389DOI Listing
January 2021

Does primary tumor localization has prognostic importance in seminoma patients?: Turkish Oncology Group Study.

J BUON 2020 Mar-Apr;25(2):1130-1135

Health Sciences University, Gülhane Training and Research Hospital, Department of Medical Oncology, Ankara, Turkey.

Purpose: The purpose of this study was to determine whether primary tumor localization may be a risk factor for relapse and survival in seminomatous germ cell tumors (GCT) patients.

Methods: In our study, 612 seminomatous GCT patients diagnosed in 22 centers between 01.01.1989 and 03.02.2019 were retrospectively evaluated. Patient interview information, patient files and electronic system data were used for the study.

Results: The primary tumor was localized in the right testis in 305 (49.9%) patients and in 307 (50.1%) in the left testis. Mean age of the patients was 36 years (range 16-85±10.4). The median follow-up period was 47 months (1-298). Recurrence was observed in 78 (12.7%) patients and 29 (4.7%) died during the follow-up period. Four-year overall survival (OS) was 95.4% and 4-year progression-free survival (PFS) was 84.5%. The relationship between localization and relapse was significant in 197 patients with stage 2 and stage 3 (p=0.003). In this patient group, 41 (20.8%) relapses were observed. Thirty (73.2%) of the relapses were in the right testis and 11 (26.8%) in the left testis. Four-year OS was 92.1% in patients with right tumor; and 98.7% in patients with left tumor (p=0.007). When 612 patients were evaluated with a mean follow-up of 4 years, there was a 6.6% survival advantage in patients with left testicular tumor and this difference was significant (p=0.007).

Conclusion: Survival rates of patients with primary right testicular localization were worse compared with left testicular localization, and relapse rates were higher in stage 2 and 3 patients with right testicular localization.
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February 2021

Comparison of skeletal muscle mass loss in patients with metastatic colorectal cancer treated with regorafenib or TAS-102.

J BUON 2019 Sep-Oct;24(5):2198-2204

Department of Medical Oncology, Trakya University Faculty of Medicine, Edirne, Turkey.

Purpose: To assess whether regorafenib and TAS-102 treatments are associated with a change in Skeletal Muscle Area (SMA) as well as to compare Skeletal Muscle Mass (SMM) loss levels between regorafenib and TAS-102 treatments and prognostic significance in the patients with metastatic colorectal cancer (mCRC).

Methods: A total of 36 mCRC patients, who received regorafenib or TAS-102 in the third-line and subsequent settings were assessed in the analysis. SMM changes were assessed with CT scans findings, and they were categorized into two groups as SMM-loss (SMM decrease ≥2%) and SMM-stable (SMM change <2%).

Results: The SMM change after regorafenib therapy was significantly worse compared with TAS-102 therapy (p=0.001). The median overall survival (OS) was longer in SMM-stable group than in SMM-loss group (12.8 months; 95%CI:9.8-15.7) vs. 6.4 months; 95%CI:5.2-7.7, respectively;p=0.04). Cox regression analysis showed that SMM loss was independent prognostic indicator for OS (HR, 2.87; 95%CI: 1.07-7.42, p=0.03).

Conclusion: Although patients who received regorafenib had more SMM loss than those who received TAS-102, there was no difference in OS between drugs.
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April 2020

Elevation in serum uric acid levels predicts favourable response to erlotinib treatment in patients with metastatic non-small-cell lung cancer.

J Clin Pharm Ther 2020 Apr 28;45(2):303-308. Epub 2019 Nov 28.

Department of Nephrology, Faculty of Medicine, Koc University, Istanbul, Turkey.

What Is Known And Objective: Erlotinib is a small molecule tyrosine kinase inhibitor which blocks the activation of epidermal growth factor receptor (EGFR), a transmembrane receptor that is upregulated in many cancer types. Inhibition of angiogenesis with consequent impairments in intratumoral microcirculation is one of the mechanisms through which EGFR inhibition halts the progression of cancer. A consequence of impaired microcirculation is intratumoral hypoxia, which results in increases in serum uric acid levels. The goal of this study was to investigate the relationship between serum uric acid levels and response to erlotinib in metastatic non-small-cell lung cancer (NSCLC).

Methods: A total of 56 patients with metastatic non-small-cell lung cancer who received erlotinib for a duration of at least 3 months were included in this retrospective cohort study. Demographic characteristics, progression status, baseline serum uric levels and 3-month serum uric acid levels were recorded and analysed.

Results And Discussion: Of the study population, 21 (37.5%) were female and 35 (62.5%) were male patients. No significant difference in above demographic characteristics was observed among exitus, survivor with progression and survivor without progression groups. Patients who responded favourably to erlotinib with no progression of their disease had significantly increased uric acid levels at 3-month follow-up (P = .01). Such a correlation was not observed if the patient was exitus (P = .47) or had progressed on erlotinib therapy (P = .19).

What Is New And Conclusion: In conclusion, this study is the first to demonstrate significant increases in serum uric acid levels in patients with metastatic NSCLC who responded favourably to erlotinib and had no progression under erlotinib therapy. Further studies are required to confirm and characterize serum uric acid as a novel biomarker in predicting the outcome in those with metastatic NSCLC.
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http://dx.doi.org/10.1111/jcpt.13071DOI Listing
April 2020

The relationship between positron emission tomography-computed tomography imaging and histopathological features of thyroid incidentalomas detected during follow-up for primary malignancy.

J Cancer Res Ther 2019 Jul-Sep;15(3):589-595

Department of Pathology, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey.

Aim Of The Study: While the rate of thyroid incidentaloma detected on positron emission tomography (PET) was reported as 4%, the malignancy rate was 14%-50%. We evaluated the thyroid nodules which were detected by PET-computerized tomography (CT) in cancer patients and analyzed the pathological results of those thyroid nodules diagnosed by fine needle aspiration biopsy (FNAB) and their correlation with the maximum standardized uptake (SUV) value and PET imaging features.

Materials And Methods: FNAB were performed for 40 thyroid incidentalomas. We analyzed the relationship between the histopathological findings and radiological features by Pearson's correlations and Chi-square-Fisher's exact tests to evaluate the factors associated with SUV.

Results: The median SUV values were 5.4 for thyroid nodules. Totally, 14 malignancies were detected by FNAB (35%).The sensitivity and specificity of SUV value for diagnosis of malignancy were 87.5% and 52%, respectively. Positive and negative predictive values were 36.8% and 92.8%. The most common malignant and benign pathologies were classic variant papillary carcinoma and benign colloidal nodule. The median SUV was the higher in colon cancer thyroid metastasis and oncocytic neoplasia (SUV 14.5 and 13.6, respectively). Histopathological type was not related with nodule size but positively associated with categorical SUV(r = 0.318, P = 0.04) and negatively correlated with both the density of the thyroid nodule in PET-CT (r = -0.0042, P = 0.01) and density of nodule in ultrasound (USG) (r = -0.305, P = 0.05). Margin of the thyroid nodule in USG (P = 0.007) and internal component of the nodule in PET (P = 0.03) were found to be important factors to differentiate benign or malignant lesion.

Conclusion: If the thyroid nodule is detected with flouro-2-deoxy-D-glucose uptake, to differentiate benign nodule from malignant, cytological examination is noteworthy to diagnose the more aggressive type of thyroid nodule and also thyroid metastasis from primary cancer.
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http://dx.doi.org/10.4103/jcrt.JCRT_889_16DOI Listing
November 2019

Prognostic Significance of Metastatic Lymph Node Ratio in Patients with pN3 Gastric Cancer Who Underwent Curative Gastrectomy.

Oncol Res Treat 2019 14;42(4):209-216. Epub 2019 Mar 14.

Medipol University, Medical Faculty, Department of Surgical Oncology, Istanbul, Turkey.

Background: Lymph node involvement is an important prognostic factor in patients with gastric cancer. The aim of this study was to determine the prognostic significance of metastatic lymph node ratio (MLNR) and compare it to the number of lymph node metastasis in pN3 gastric cancer.

Methods: We retrospectively analyzed 207 patients with pN3 gastric cancer who had undergone radical gastrectomy. Prognostic factors and MLNR were evaluated by univariate and multivariate analysis.

Results: An MLNR of 0.75 was found to be the best cut-off value to determine the prognosis of patients with pN3 gastric cancer (p = 0.001). The MLNR was significantly higher in patients with large-sized and undifferentiated tumors, vascular, lymphatic and perineural invasion, and total gastrectomy. In multivariate analysis, MLNR (p = 0.041), tumor differentiation (p = 0.046), and vascular invasion (p = 0.012) were found to be independent prognostic factors for disease-free survival, while both MLNR (p < 0.001) and pN stage (p = 0.002) were independent prognostic indicators, as was tumor size, for overall survival. There was significant difference with respect to the recurrence patterns between MLNR groups. Lymph node and peritoneal recurrences were significantly higher in patients with MLNR > 0.75 compared to the MLNR < 0.75 group (p < 0.05). However, recurrence patterns were similar between pN3a and pN3b.

Conclusion: Our results showed that MLNR was a useful indicator to determine the prognosis and recurrence patterns of patients with radically resected gastric cancer. Moreover, MLNR is a beneficial and reliable technique for evaluating lymph node metastasis.
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http://dx.doi.org/10.1159/000496746DOI Listing
September 2019

Capecitabine-cisplatin versus 5-fluorouracil/leucovorin in combination with radiotherapy for adjuvant therapy of lymph node positive locally advanced gastric cancer.

J Cancer Res Ther 2018 Sep;14(Supplement):S736-S741

Department of Radiation Oncology,, Haydarpasa Numune Education and Research Hospital, Istanbul, Turkey.

Aim Of The Study: Although surgery is considered to be curative treatment, recurrence rates are high in gastric cancer. Adjuvant 5-fluorouracil (5-FU) based chemoradiotherapy has been shown to improve the prognosis. We compared tolerability and efficacy of the two different chemotherapy regimens; 5-FU/leucovorin (LV) versus cisplatin with capecitabine (XP) combined with radiotherapy (RT) in the adjuvant therapy of the lymph node positive locally advanced gastric cancer.

Materials And Methods: Totally, 104 patients who underwent curative surgery with lymph node resection were evaluated, respectively. Patients were stratified two group based on the adjuvant chemoradiotherapy regimen. Group 1 (n = 46) received XP followed capecitabine with RT (XRT) then XP. Group 2 (n = 58) received 5-FU/LV combined with RT postoperatively. Two groups were compared based on clinicopathological parameters. Factors related with disease-free survival (DFS) and overall survival (OS) were analyzed.

Results: Totally, 32 patients had recurrent disease, and there was no difference between two groups. While peritoneal metastasis was more common in XP arm, distant metastasis was commonly seen in 5-FU/LV arm. There was no significant difference between two groups in regard of Grade 3/4 toxicitis; hematologic toxicities were more in 5-FU/LV group than XP arm. In addition, dose modification because of toxicities were more frequent in 5-FU/LV arm (P = 0.003). For all groups, lymph node dissection type was related with DFS, surgical margin and recurrence were important for OS.

Conclusion: XP-XRT regimen is well tolerated with lower toxicity compared the standard 5-FU/LV-RT. Although there is no difference with respect to outcome, patients with XP arm without the necessity of intravenous catheter admitted hospital less frequent than bolus5-FU/LV arm.
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http://dx.doi.org/10.4103/0973-1482.183548DOI Listing
September 2018

Anti-Ri-associated paraneoplastic neurological syndrome: Initial symptom of breast cancer with HER2 overexpression and treatment by dual HER2 blockade.

J Oncol Pharm Pract 2019 Sep 19;25(6):1526-1530. Epub 2018 Aug 19.

2 Deparment of Internal Medicine, Faculty of Medicine, Istanbul Medipol University, Istanbul, Turkey.

Paraneoplastic neurological syndrome is associated with anti-Ri antibodies, which are typically present with opsoclonus-myoclonus-ataxia. Human epidermal growth factor receptor 2 (HER2) overexpression is present in 15%-25% of breast cancer and is associated with poor prognosis. There are a few reports of paraneoplastic neurological syndrome associated with HER2-positive breast cancer in the literature, of which most are anti-Yo-associated paraneoplastic neurological syndrome. We present herein the case of a female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus-myoclonus paraneoplastic neurological syndrome. Following the diagnosis of paraneoplastic syndrome, chemotherapy with dual HER2 blockade and immunomodulating treatment including intravenous immunoglobulin and oral prednisolone were administered. Although the patient was negative for serum anti-Ri antibodies, there was partial clinical improvement and her neurological deficit persisted. To our knowledge, this is the first case report of female patient with HER2-positive breast cancer who had atypical anti-Ri antibody associated with opsoclonus-myoclonus paraneoplastic neurological syndrome and treated with dual HER2 blockade.
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http://dx.doi.org/10.1177/1078155218792672DOI Listing
September 2019

Role of Urotensin-2 in 5-Fluorouracil-Related Arterial Vasoconstriction in Cancer Patients.

Oncol Res Treat 2018 20;41(9):545-549. Epub 2018 Aug 20.

Background: The aim of this study was to identify the possible relationship of 5-fluorouracil (5-FU)-related arterial vasoconstriction with urotensin-2 (UT-2), which has a high potential as an endogenic vasoconstrictor.

Methods: We assigned the patients to 1 of 3 groups. Patients in group 1 received a bolus of 5-FU, those in group 2 a continuous infusion (CI) of 5-FU, and those in group 3 no 5-FU, which was also a control group. Pre- and post-treatment UT-2 levels and brachial arterial diameters were measured and recorded in all patients.

Results: 132 patients were included in the study. Pre- and post-treatment brachial artery diameters were similar in all groups: in group 1 (3.28 ± 0.52 vs. 3.25 ± 0.44 mm, p = 0.740), in group 2 (3.57 ± 0.47 vs. 3.46 ± 0.45 mm, p = 0.441) and in the control group (3.51 ± 0.52 vs. 3.25 ± 0.44 mm, p = 0.818). Pre- and post-treatment UT-2 levels were significantly different in each group: in group 1 (39.5 ± 30.9 vs. 56.7 ± 27.1 ng/ml, p = 0.0001), in group 2 (37.7 ± 33.7 vs. 62.5 ± 37.7 ng/ml, p = 0.0001) and in the control group (52.9 ± 40.2 vs. 60.8 ± 40.7 ng/ml, p = 0.006).

Conclusion: Our findings suggest that UT-2 has a high potential as a vasoconstrictor agent in our bodies and its level increases through a bolus or CI 5-FU. Increased UT-2 levels are likely to play a role in 5-FU-related cardiac toxicity pathogenesis.
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http://dx.doi.org/10.1159/000490120DOI Listing
September 2019

Prognostic Factors for Operated Gallbladder Cancer.

J Gastrointest Cancer 2019 Sep;50(3):451-457

Medical Oncology, Haydarpasa Numune Education and Research Hospital, Selimiye Mah, Şair Nesimi sok, Kardeşler Apt. No: 1, Daire:4, 34668, Uskudar, Istanbul, Turkey.

Purpose: The prognosis of gallbladder cancer is poor. Lymph node metastasis and the stage are known to be the strongest prognostic factors for survival. The aim of this study was to determine the importance of complementary surgery and other prognostic factors for survival of operated gallbladder cancer.

Material And Method: We retrospectively analyzed 62 localized gallbladder cancers. The prognostic factors for survival were evaluated by univariate and multivariate analysis.

Results: The 3-year overall survival (OS) and disease-free survival (DFS) rates were 52.8 and 43.5%, respectively. Totally, 37 patients (59.6%) were diagnosed incidentally during simple cholecystectomy which was performed for benign causes but only 56.4% of them underwent complementary surgery. 51.6% of the recurrence was detected during 18.4 months of follow-up time. R0 resection, T stage, and pathological stage were found to be related with both OS and DFS by univariate analysis. Grade, lymph node metastasis, and adjuvant chemotherapy were also related with DFS. Presence of recurrence, recurrence side, performance score (PS), and perineural invasion (PNI) were related with OS. Peritoneal metastasis, advanced stage disease, and lymph node metastasis were more common among patients who did not undergo complementary surgery. Adjuvant chemotherapy was given more frequently to patients who undergone complementary surgery group. The multivariate analysis indicated that grade, lymph node metastasis, stage, recurrence site, PS, and adjuvant chemotherapy stage were independent prognostic factors for DFS on the other and only stage was a prognostic factor for OS.

Conclusion: Our results showed that incidental diagnosis or complementary surgery was not related with DFS or OS but stage was only an independent prognostic factor for both OS and DFS in resected gallbladder cancer.
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http://dx.doi.org/10.1007/s12029-018-0099-yDOI Listing
September 2019

Prognostic factors for survival in metastatic renal cell carcinoma patients with brain metastases receiving targeted therapy.

Tumori 2018 Dec 9;104(6):444-450. Epub 2018 May 9.

17 Department of Medical Oncology, Institute of Oncology, Istanbul University, Istanbul - Turkey.

Background: The primary objective of our study was to examine the clinical outcomes and prognosis of patients with metastatic renal cell carcinoma (mRCC) with brain metastases (BMs) receiving targeted therapy.

Patients And Methods: Fifty-eight patients from 16 oncology centers for whom complete clinical data were available were retrospectively reviewed.

Results: The median age was 57 years (range 30-80). Most patients underwent a nephrectomy (n = 41; 70.7%), were male (n = 42; 72.4%) and had clear-cell (CC) RCC (n = 51; 87.9%). Patients were treated with first-line suni-tinib (n = 45; 77.6%) or pazopanib (n = 13; 22.4%). The median time from the initial RCC diagnosis to the diagnosis of BMs was 9 months. The median time from the first occurrence of metastasis to the development of BMs was 7 months. The median overall survival (OS) of mRCC patients with BMs was 13 months. Time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months; p = 0.001), histological subtype (non-CC; p<0.05) and number of BMs (>2; p<0.05) were significantly associated with OS in multivariate analysis. There were no cases of toxic death. One mRCC patient with BMs (1.7%) experienced treatment-related cerebral necrosis. All other toxicities included those commonly observed with VEGF-TKI therapy.

Conclusions: The time from the initial diagnosis of systemic metastasis to the development of BMs (<12 months), a non-CC histological subtype, and a greater number of BMs (>2) were independent risk factors for a poor prognosis.
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http://dx.doi.org/10.5301/tj.5000635DOI Listing
December 2018

The clinicopathologic characteristics and prognostic factors of gastroesophageal junction tumors according to Siewert classification.

Turk J Surg 2017 1;33(1):18-24. Epub 2017 Mar 1.

Department of Medical Oncology, Kartal Training and Research Hospital, İstanbul, Turkey.

Objective: The treatment of gastroesophageal junction tumors remains controversial due to confusion on whether they should be considered as primary esophageal or as gastric tumors. The incidence of these tumors with poor prognosis has increased, thus creating scientific interest on gastroesophageal cancers. Esophagogastric cancers are classified according to their location by Siewert, and the treatment of each type varies. We evaluated the prognostic factors and differences in clinicopathologic factors of patients with gastroesophageal junction tumor, who have been treated and followed-up in our clinics.

Material And Methods: We retrospectively analyzed 187 patients with gastroesophageal junction tumors who have been operated and treated in the Oncology Department between 2005 and 2014. The chi-square test was used to evaluate differences in clinicopathologic factors among Siewert groups I, II and III. Prognostic factors were analyzed by univariate and multivariate analysis.

Results: The median age of our patients was 62 years, and approximately 70% was male. Nineteen patients (10.2%) had Siewert I tumors, 40 (21.4%) II, and the remaining 128 (64.4%) had Siewert III tumors. Siewert III tumors were at more advanced pathologic and T stages. Preoperative chemoradiotherapy was mostly applied to Siewert group I patients. There was no difference between the 3 groups in terms of recurrence. While the median overall survival and 2-year overall survival rate were 26.6 months and 39.6%, the median disease free survival and disease free survival rates were 16.5 months and 30.1%, respectively. The N stage, pathologic stage, vascular invasion, lymphatic invasion, perineural invasion, surgical margin, and grade were associated with both overall survival and disease free survival, while pathologic stage and presence of recurrence were significant factors for overall survival. The median disease free survival for Siewert III tumors was 20 months, 11.3 month for Siewert I tumors, and 14 months for Siewert II tumors, but the finding was not statistically significant (p=0.08).

Conclusion: Although gastroesophageal junction tumors were grouped according to their location and they exerted different clinicopathologic properties, their prognosis was similar.
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http://dx.doi.org/10.5152/UCD.2017.3379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5448566PMC
March 2017

Correlation of Caveolin-1 Expression with Prognosis in Patients with Gastric Cancer after Gastrectomy.

Oncol Res Treat 2017 3;40(4):185-190. Epub 2017 Mar 3.

Background: Upregulation of caveolin-1 (Cav-1) expression is correlated with histopathological grade and poor prognosis in several human cancers. However, in gastric cancer, its clinical utility as a useful prognostic molecular marker remains unclear.

Methods: The prognostic importance of Cav-1 expression was retrospectively analyzed by immunohistochemistry in 148 patients with gastric cancer who had undergone radical gastrectomy.

Results: Cav-1 expression was positive in 23 (15.5%) patients and negative in 125 (84.5%) patients. Tumor location, tumor grade, lymph node involvement, pT stage, pTNM stage, and the presence of recurrence were found to be significantly associated with Cav-1 expression. The median disease-free survival (DFS) of patients with negative Cav-1 expression was significantly better than that of patients with positive Cav-1 expression (not reached vs. 10.2 months, p < 0.001). Moreover, patients with positive Cav-1 expression had a worse median overall survival (OS) compared to patients with negative Cav-1 expression (14.2 vs. 40.3 months, p = 0.004). In the multivariate analysis, Cav-1 expression (positive vs. negative) was an independent prognostic factor for DFS (p < 0.001, hazard ratio (HR) 2.58) and OS (p = 0.031, HR 1.87), as was lymph node metastasis.

Conclusion: Our results suggest that positive Cav-1 expression is associated with progression and poor prognosis in gastric cancer patients after radical gastrectomy. Targeting Cav-1 would be a potential option for future gastric cancer treatment.
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http://dx.doi.org/10.1159/000456620DOI Listing
November 2017

Is Change in Hemoglobin Level a Predictive Biomarker of Tyrosine Kinase Efficacy in Metastatic Renal Cell Carcinoma? A Turkish Oncology Group Study.

Cancer Invest 2017 Apr 23;35(4):248-255. Epub 2017 Mar 23.

a Department of Internal Medicine and Medical Oncology , Sakarya University School of Medicine , Sakarya , Turkey.

Background: There are insufficient predictive markers for renal cell carcinoma (RCC).

Methods: A total of 308 metastatic RCC patients were analyzed retrospectively.

Results: The increased hemoglobin (Hb) group had significantly higher progression-free survival and overall survival (OS) compared with the decreased Hb group at 11.5 versus 6.35 months (p < .001) and 21.0 versus 11.36 months (p < .001) respectively. The 1- and 3-year OS rates were higher in the Hb increased group, i.e., 84% versus 64% and 52% versus 35% respectively.

Conclusions: The present study showed that increased Hb levels after tyrosine kinase inhibitor therapy could be a predictive marker of RCC.
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http://dx.doi.org/10.1080/07357907.2017.1292518DOI Listing
April 2017

Evaluation of prognostic factors and treatment in advanced small bowel adenocarcinoma: report of a multi-institutional experience of Anatolian Society of Medical Oncology (ASMO).

J BUON 2016 Sept-Oct;21(5):1242-1249

Department of Medical Oncology, Dr. Lutfi Kirdar Kartal Education and Research Hospital, Istanbul, Turkey.

Purpose: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Since these are rarely encountered tumors, there are limited numbers of studies investigating systemic treatment in advanced SBA. The purpose of this study was to evaluate the prognostic factors and systemic treatments in patients with advance SBA.

Methods: Seventy-one patients from 18 Centers with advanced SBA were included in the study. Fifty-six patients received one of the four different chemotherapy regimens as first-line therapy and 15 patients were treated with best supportive care (BSC).

Results: Of the 71 patients, 42 (59%) were male and 29 (41%) female with a median age of 56 years. Median follow- up duration was 14.3 months. The median progression free survival (PFS) and overall survival (OS) were 7 and 13 months, respectively (N=71). In patients treated with FOLFOX (N=18), FOLFIRI (N=11), cisplatin-5-fluorouracil/ 5-FU (N=17) and gemcitabine alone (N=10), median PFS was 7, 8, 8 and 5 months, respectively, while median OS was 15, 16, 15 and 11 months, respectively. No significant differences between chemotherapy groups were noticed in terms of PFS and OS. Univariate analysis revealed that chemotherapy administration, de novo metastatic disease, ECOG PS 0 and 1, and overall response to therapy were significantly related to improved outcome. Only overall response to treatment was found to be significantly prognostic in multivariate analysis (p=0.001).

Conclusions: In this study, overall response to chemotherapy emerged as the single significant prognostic factor for advanced SBAs. Platin and irinotecan based regimens achieved similar survival outcomes in advanced SBA patients.
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June 2017

Outcomes of surveillance versus adjuvant chemotherapy for patients with stage IA and IB nonseminomatous testicular germ cell tumors.

World J Urol 2017 Jul 3;35(7):1103-1110. Epub 2016 Nov 3.

Department of Medical Oncology, Medical Faculty, Gaziantep University, Gaziantep, Turkey.

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.
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http://dx.doi.org/10.1007/s00345-016-1964-6DOI Listing
July 2017

Evaluation of Prognostic Factors and Adjuvant Chemotherapy in Patients With Small Bowel Adenocarcinoma Who Underwent Curative Resection.

Clin Colorectal Cancer 2017 09 30;16(3):220-227. Epub 2016 Aug 30.

Department of Medical Oncology, Faculty of Medicine, Bezmialem University, İstanbul, Turkey.

Background: Small bowel adenocarcinoma (SBA) is a rare tumor of the gastrointestinal system with poor prognosis. Because these are rarely encountered tumors, the aim of this multicenter study was evaluation of prognostic factors and adjuvant chemotherapy in patients with curatively resected SBA.

Materials And Methods: A total of 78 patients diagnosed with curatively resected SBA were involved in the retrospective study. Forty-eight patients received 1 of 3 different chemotherapy regimens, whereas 30 patients did not receive any adjuvant treatment. No adjuvant and adjuvant chemotherapy cohorts were matched (1:1) by propensity scores based on the likelihood of receiving chemotherapy or the survival hazard from Cox modeling. Overall survival (OS) was compared with Kaplan-Meier estimates.

Results: Median age of 78 patients with curatively resected SBA was 58, and 59% of these were men. According to TNM classification, 8 (10%) of the patients were at stage I, 26 (34%) were at stage II, and 44 (56%) were at stage III. Median follow-up duration was 29 months. Three-year median disease-free survival (DFS) and OS were 62.5% and 67.0%, respectively. In univariate analysis, presence of vascular invasion, perineural invasion, lymph node involvement, and presence of positive surgical margin were significant predictors of poor survival. Multivariate analysis showed that the only adverse prognostic factor independently related with OS was the presence of positive surgical margin (hazard ratio, 0.37; 95% confidence interval, 0.11-1.26; P = .01). Neither DFS nor OS was found to be significantly improved by the adjuvant chemotherapy in both matched and unmatched cohorts.

Conclusions: Only status of surgical margin was determined to be an independent prognostic factor in patients with SBA who underwent curative resection.
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http://dx.doi.org/10.1016/j.clcc.2016.08.002DOI Listing
September 2017

Multicenter experience of adult medulloblastoma: A study of Anatolian Society of Medical Oncology (ASMO).

J BUON 2016 Mar-Apr;21(2):456-60

Department of Medical Oncology, Ankara Oncology Training and Research Hospital,Ankara, Turkey.

Purpose: Medulloblastoma (MB) is rarely seen in adults. For adjuvant therapy in adults the same therapy protocols used in pediatric cases are used. The present study retrospectively evaluated the data of MB patients who were treated in different Oncology Centers in Turkey.

Methods: The data of 60 adult patients with MB from 8 Oncology Centers diagnosed between 2005 and 2012 were retrospectively analyzed.

Results: The median patient age was 28.8 years (range 16-54). The administered chemotherapy included procarbazine+lomustin+vincristine (group A, N=31) and cyclophosphamide/ifosfamide+vincristine+cisplatin (group B, N=13). Median chemotherapy courses were 4 (range 1-8). Median progression free survival (PFS) was 76 months and median overall survival (OS) has not been reached in both groups. In young female patients and in those who received adjuvant chemotherapy, median PFS and OS were longer but without statistical significance. Mean PFS and OS were 65.9 months and 101.2 months in group A and 113.6 months and 141.6 months in group B, respectively.

Conclusion: Improved survival results were obtained in women, in patients aged below 25 years, in those who underwent gross total excision (GTE) and in those who received adjuvant therapy with cyclophosphamide/ifosphamide.
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July 2016

Risk factors for skeletal-related events (SREs) and factors affecting SRE-free survival for nonsmall cell lung cancer patients with bone metastases.

Tumour Biol 2016 Jan 15;37(1):1131-40. Epub 2015 Aug 15.

Department of Medical Oncology, Ankara Oncology Teaching and Research Hospital, Ankara, Turkey.

Skeletal-related events (SREs) for nonsmall cell lung cancer (NSCLC) patients with bone metastasis lead to serious morbidity. The aim of this study was to determine risk factors for SREs in NSCLC patients with bone metastasis and the factors influencing SRE-free survival and overall survival (OS). From 2000 to 2012, we evaluated retrospectively 835 NSCLC patients. Three hundred and thirty-five of them with bone metastasis were included in the study. SREs and the other prognostic factors were evaluated by univariate and multivariate analysis for SRE-free survival and OS. SREs were detected in 244 patients (72.8 %). The most common SREs were the need for radiotherapy (43.2 %) and malignant hypercalcemia (17.6 %). The median time to first SRE was 3.5 months at the median follow-up of 17 months. A multivariate analysis showed that the presence of bone metastasis at diagnosis (p < 0.001), the number of bone metastasis (p = 0.001), baseline hypercalcemia (p = 0.004), and the presence of palliative radiotherapy (p = 0.04) were independent prognostic factors for SRE-free survival. A logistic regression analysis identified that the presence of bone metastasis at diagnosis [odds ratio (OR), 12.6], number of bone metastasis (OR, 3.05), and baseline hypercalcemia (OR, 0.33) were found to be predictive factors in the developing of SRE. The median OS time for patients with SRE was worse than that for patients without SRE (7 vs 12 months, respectively). For OS, male gender, ECOG performance status (PS), high lactate dehydrogenase (LDH) level, hypoalbuminemia, the presence of bone metastasis at diagnosis, the number of bone metastasis, the presence of SREs, the presence of bisphosphonate therapy, and palliative radiotherapy were independent prognostic indicators for OS by the multivariate analysis. Our results indicated that the frequency of SREs was high and the presence of bone metastasis at the time of diagnosis, baseline hypercalcemia, and multiple bone metastases were significant factors predicting the occurrence of SREs. If bone metastases diagnose earlier, treatments for the prevention of SREs may be initiated earlier; thus, the deterioration of quality of life may be preserved.
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http://dx.doi.org/10.1007/s13277-015-3907-zDOI Listing
January 2016

Prognostic markers for metastatic colon cancer patients undergoing multiple metastasectomies.

Turk J Gastroenterol 2015 Sep 24;26(5):386-91. Epub 2015 Jul 24.

Department of Medical Oncology, Haydarpaşa Numune Training and Research Hospital, İstanbul, Turkey.

Background/aims: Following metastasis resection, 5-year survival rate has been reported as approximately 40%. There is no consensus regarding prognostic factors related to progression-free survival after repeated metastasectomies.

Materials And Methods: A total of 21 patients with metastatic colorectal cancer who underwent repeated metastasectomies were retrospectively analyzed. The periods between the first and second metastasectomies and that between the second metastasectomy and progression were defined as metastasis-free survival 1 (MFS1) and metastasis-free survival 2 (MFS2), respectively. Univariate analysis was used to analyze factors related to MFS1 and MFS2.

Results: Approximately two-thirds of the patients had synchronous metastasis, which were localized mostly in the liver (90%). During a 49-months follow-up, MFS1 was 15.7 (8.4-23) months and MFS2 was 26.3 (12.3-40.4) months. Systemic chemotherapy followed the first metastasectomy (p=0.01), and the recurrence site (p=0.03) was found to be related to MFS1. Furthermore, the number of metastases during the first metastasectomy (p=0.02), the type of the chemotherapy regimen administered following the first metastasectomy (p=0.04), and the number of metastases before the second metastasectomy (p=0.03) were significantly related to MFS2.

Conclusion: Surgical resection is currently the most effective and curative form of therapy for colorectal metastasis, whenever possible. Repeated metastasectomies can be achieved safely in experienced centers; thus, the operability of the patients should be evaluated by a multidisciplinary approach during treatment.
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http://dx.doi.org/10.5152/tjg.2015.0169DOI Listing
September 2015

Evaluation of 37,438 consecutive cervical smear results in the Turkish population.

Arch Med Sci 2015 Apr 23;11(2):402-5. Epub 2015 Apr 23.

Department of Pathology, Education and Research Hospital, Erzurum, Turkey.

Introduction: Retrospective evaluation of cervical smear results of women who attended our gynecology policlinics with various symptoms and discussion of the results in the light of the literature.

Material And Methods: We performed a retrospective investigation on 37,438 Pap smear results of women who attended our hospital between January 2011 and December 2012 with a variety of symptoms.

Results: Average patient age was 43 (18-83) years. Of the Pap smear results analyzed, in 21,503 (57.4%) findings were within normal limits, while 153 (0.41%) showed epithelial cell abnormalities and 15,358 (41%) showed inflammation. Four hundred and twenty-four (1.1%) cases were reported to have inadequate Pap smear samples for evaluation. Of the epithelial cell abnormalities, 136 (88.8%) were squamous cell abnormalities and 17 (11.1%) were glandular cell abnormalities. Atypical squamous cells of unknown significance (ASCUS) were reported for 117 (0.3%) Pap smears, while other epithelial abnormalities included atypical glandular cells of unknown significance (AGUS) in 17 (0.05%) cases, low-grade squamous intraepithelial lesion (LSIL) in 8 (0.02%) cases, atypical squamous cells with possible high grade lesion (ASC-H) in 8 (0.02%) cases and high-grade squamous intraepithelial lesion (HSIL) in 3 (0.008%) cases.

Conclusions: Public awareness should be raised on the importance of Pap smear testing repeated at appropriate intervals in the prevention and early diagnosis of cervical cancer. Health education should become more widespread, and the importance of screening programs and regular check-ups should be emphasized more often on this issue in the media.
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http://dx.doi.org/10.5114/aoms.2013.38814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4424238PMC
April 2015

Advances in the management of unresectable or metastatic pancreatic neuroendocrine tumors: chemotherapy, targeted therapy, hormonal treatment, and future directions.

Authors:
Ahmet Bilici

Asian Pac J Cancer Prev 2015 ;16(6):2151-9

Department of Medical Oncology, Istanbul Medipol University, Medical Faculty, Istanbul, Turkey E-mail :

Pancreatic neuroendocrine tumors (pNETs) are rare and heterogenous tumors and surgery to remove the primary tumor is the mainstay of treatment for resectable disease. However, curative surgery is often not feasible, because half of patients with pNET have metastases at the time of diagnosis. Palliative dubulking surgery and liver-directed therapies are appropriate options for these patients. Streptozocin-based regimens are standard, although temozolamide-based treatments are rapidly gaining wide clinical application. Somatostatin analogs are mainly indicated in hormonally active tumors to ameliorate symptoms. In addition, anti-tumoral activity has been proven in well-differentiated NETs. Recently, there has been tremendous progress in the molecular biology of pNETs; thereby, the efficacy of sunitinib and everolimus in the treatment of patients with metastatic pNETs has been proven by large placebo-controlled phase III trials. Currently, there are no definitively proven predictive biomarkers to evaluate response to medical therapies in patients with pNET. Therefore, further studies are needed to individualize and optimize their management. This article reviews systemic chemotherapy, targeted therapies, and anti-secretory treatments for the management of patients with unresectable or metastatic pNETs, summarized in the light of recent advances.
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http://dx.doi.org/10.7314/apjcp.2015.16.6.2151DOI Listing
January 2016

Medication errors in chemotherapy preparation and administration: a survey conducted among oncology nurses in Turkey.

Asian Pac J Cancer Prev 2015 ;16(5):1699-705

Department of Medical Oncology, Ankara Ataturk Training and Research Hospital, Ankara, Turkey E-mail :

Background: Medication errors in oncology may cause severe clinical problems due to low therapeutic indices and high toxicity of chemotherapeutic agents. We aimed to investigate unintentional medication errors and underlying factors during chemotherapy preparation and administration based on a systematic survey conducted to reflect oncology nurses experience.

Materials And Methods: This study was conducted in 18 adult chemotherapy units with volunteer participation of 206 nurses. A survey developed by primary investigators and medication errors (MAEs) defined preventable errors during prescription of medication, ordering, preparation or administration. The survey consisted of 4 parts: demographic features of nurses; workload of chemotherapy units; errors and their estimated monthly number during chemotherapy preparation and administration; and evaluation of the possible factors responsible from ME. The survey was conducted by face to face interview and data analyses were performed with descriptive statistics. Chi-square or Fisher exact tests were used for a comparative analysis of categorical data.

Results: Some 83.4% of the 210 nurses reported one or more than one error during chemotherapy preparation and administration. Prescribing or ordering wrong doses by physicians (65.7%) and noncompliance with administration sequences during chemotherapy administration (50.5%) were the most common errors. The most common estimated average monthly error was not following the administration sequence of the chemotherapeutic agents (4.1 times/month, range 1-20). The most important underlying reasons for medication errors were heavy workload (49.7%) and insufficient number of staff (36.5%).

Conclusions: Our findings suggest that the probability of medication error is very high during chemotherapy preparation and administration, the most common involving prescribing and ordering errors. Further studies must address the strategies to minimize medication error in chemotherapy receiving patients, determine sufficient protective measures and establishing multistep control mechanisms.
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http://dx.doi.org/10.7314/apjcp.2015.16.5.1699DOI Listing
January 2016

Prognostic significance of the recurrence pattern and risk factors for recurrence in patients with proximal gastric cancer who underwent curative gastrectomy.

Tumour Biol 2015 Aug 12;36(8):6191-9. Epub 2015 Mar 12.

Department of Medical Oncology, Medical Faculty, Istanbul Medipol University, Istanbul, Turkey,

Proximal gastric cancer has a high propensity of early recurrence after curative resection due to high incidence of lymph node involvement. In the present study, we aimed to investigate the pattern and time of recurrence and to evaluate the risk factors for recurrence of patients with proximal gastric cancer. Between 2005 and 2013, 99 patients with recurrent proximal gastric cancer who underwent radical gastrectomy were retrospectively analyzed. The prognostic significance of the pattern and the time of recurrence and the relationship between the pattern of recurrence and the other clinicopathological factors were evaluated. The median time to recurrence was 24 months; 45.5 % of patients relapsed within 2 years. Forty-three (43.4 %) patients indicated hematogenous recurrence and 41 (41.4 %) patients revealed peritoneal recurrence with the most predominant patterns. The median progression-free survival (PFS) time for patients with locoregional recurrence was significantly better than that of patients with peritoneal recurrences, hematogenous recurrences, and distant lymph nodes (32.2 vs. 18.9 vs. 18.2 vs. 9.7 months, p = 0.005, respectively). Moreover, the median overall survival (OS) interval for patients with distant lymph nodes recurrence was significantly worse than that of patients with locoregional, peritoneal, and hematogenous recurrences (13.5 vs. 48.5 vs. 31.4 vs. 29.9 months, p = 0.006, respectively). The presence of lymph node metastasis (p = 0.004) and surgery type (p = 0.04) for PFS and the time of recurrence (p = 0.033), lymph node metastasis (p = 0.03), and surgery type (p = 0.04) for OS were found to be independent prognostic factors by multivariate analysis. Logistic regression analysis indicated that the presence of lymph node metastasis and surgery type were independent risk factors for predicting the occurrence of early recurrence (p = 0.001, OR 0.48 and p = 0.028, OR 0.41, respectively). The median OS time of early recurrence patients was significantly shorter than that of patients with late recurrence (16.6 vs. 55.2 months, p < 0.001). Furthermore, proximal gastrectomy, poorly differentiated histology, advanced pT stage, and lymph node metastasis were significantly associated with early recurrence. Our results showed that lymph node metastasis and surgery type were independent risk factors for prediction of early recurrence in proximal gastric cancer. Thus, total gastrectomy with regional lymph node dissection may be a suitable treatment option for proximal gastric cancer patients with tumors that have high risk features for recurrence.
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http://dx.doi.org/10.1007/s13277-015-3304-7DOI Listing
August 2015
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