Publications by authors named "Esra Kaytan Saglam"

28 Publications

  • Page 1 of 1

Outcomes of patients with anal cancer treated with volumetric-modulated arc therapy or intensity-modulated radiotherapy and concurrent chemotherapy.

J Cancer Res Ther 2021 Jan-Mar;17(1):51-55

Department of Radiation Oncology, Istanbul University Medical Faculty, Istanbul, Turkey.

Aims: To evaluate the results of chemoradiation with intensity-modulated radiation therapy (IMRT) or volumetric-modulated arc therapy (VMAT) for the treatment of anal canal cancer patients at three institutions that had advanced devices.

Materials And Methods: A retrospective analysis was performed for patients treated with 5-fluorouracil and mitomycin-based chemotherapy and IMRT or VMAT for anal cancer from 2011 to 2013. Complete response (CR) rates, colostomy-free survival (CFS), disease-free survival (DFS), overall survival (OS), and toxicities were investigated. Toxicities were evaluated with the Common Terminology Criteria for Adverse Events, Version 3.0.

Results: Fifteen patients were included in the analysis. The majority of patients had T2 (53.3%) and N0 (40%) disease according to the staging system that was developed by the American Joint Committee on Cancer. CR was observed in 14 patients (93%), and the median follow-up was 26 months (13-42 months). The 3-year CFS, DFS, and OS were 86%, 86%, and 88%, respectively. Acute Grade 3 toxicities were observed as 6% of hematological, 26% of gastrointestinal, and 26% of dermatological.

Conclusion: Early results confirm that IMRT or VMAT for anal cancer treatment reduces acute toxicities while maintaining high control rates.
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http://dx.doi.org/10.4103/jcrt.JCRT_774_16DOI Listing
March 2021

Prognostic factors in medically inoperable early stage lung cancer patients treated with stereotactic ablative radiation therapy (SABR): Turkish Radiation Oncology Society Multicentric Study.

Clin Respir J 2020 Nov 17;14(11):1050-1059. Epub 2020 Aug 17.

Faculty of Medicine, Radiation Oncology Department, Ankara University, Ankara, Turkey.

Objective: We identified factors influencing outcomes in patients with medically inoperable early stage lung cancer (MIESLC) treated with stereotactic ablative radiation therapy (SABR) at 14 centers in Turkey.

Materials And Methods: We retrospectively analyzed 431 patients with stage I-II MIESLC treated with SABR from 2009 through 2017. Age; sex; performance score; imaging technique; tumor histology and size; disease stage radiation dose, fraction and biologically effective dose with an α/β ratio of 10 (BED ); tumor location and treatment center were evaluated for associations with overall survival (OS), local control (LC) and toxicity.

Results: Median follow-up time was 27 months (range 1-115); median SABR dose was 54 Gy (range 30-70) given in a median three fractions (range 1-10); median BED was 151 Gy (range 48-180). Tumors were peripheral in 285 patients (66.1%), central in 69 (16%) and <1 cm from mediastinal structures in 77 (17.9%). Response was evaluated with PET/CT in most cases at a median 3 months after SABR. Response rates were: 48% complete, 36.7% partial, 7.9% stable and 7.4% progression. LC rates were 97.1% at 1 year, 92.6% at 2 years and 91.2% at 3 years; corresponding OS rates were 92.6%, 80.6% and 72.7%. On multivariate analysis, BED > 100 Gy (P = .011), adenocarcinoma (P = .025) and complete response on first evaluation (P = .007) predicted favorable LC. BED > 120 Gy (hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.1-3.2, P = .019) and tumor size (<2 cm HR 1.9, 95% CI 1.3-3, P = .003) predicted favorable OS. No grade 4-5 acute side effects were observed; late effects were grade ≤3 pneumonitis (18 [4.2%]), chest wall pain (11 [2.5%]) and rib fracture (1 [0.2%]).

Conclusion: SABR produced encouraging results, with satisfactory LC and OS and minimal toxicity. BED > 120 Gy was needed for better LC and OS for large, non-adenocarcinoma tumors.
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http://dx.doi.org/10.1111/crj.13240DOI Listing
November 2020

Prognostic significance of early complete response in patients with locally advanced rectal cancer undergoing preoperative chemoradiotherapy: Multicentric study of Turkish Society for Radiation Oncology Group (TROD).

Turk J Gastroenterol 2020 05;31(5):368-377

Department of Radiation Oncology, Ege University Institute of Oncology, İzmir, Turkey.

Background/aims: To assess the effect of various parameters on the oncologic outcomes, including the time interval between therapy and surgery (S) in locally advanced rectal cancer (LARC) patients receiving preoperative chemoradiotherapy (CRT).

Materials And Methods: The data of 914 LARC patients who received preoperative CRT between 1994 and 2015 were collected retrospectively. Patients received 45-50.4 Gy RT with 5FU based chemotherapy (CT). They all underwent radical resection followed by maintenance CT. Clinical and pathologic variables were compared between the pCR and no-pCR groups. Survival was estimated by the Kaplan-Meier method and Cox proportional hazard model was used in multivariate analysis.

Results: After median follow-up of 60.5 (range=12-297.6) months, median overall survival (OS) was 58.75 months and disease-free survival (DFS) 53.32 months. pCR was observed in 18.9% of all cases. pCR, lymphovascular invasion and metastatic lymph node ratio (mLNR) were significantly associated with OS and DFS on multivariate analysis. The 5-year OS and DFS rates were better in pCR group (95.3% vs 80.7% for OS, p<0.0001 and 87.4% vs 71% for DFS, p<0.0001). pCR patients with 4-8 weeks interval had lower rates of distant metastasis (9% vs 20%, p=0.01) and any recurrences (13.6% vs 29.6%, p=0.001) than the remaining. Both OS and DFS were better in favor of pCR achieved at 4-8 week interval time (p<0.0001 for each).

Conclusion: pCR after preoperative CRT in LARC correlated with better oncologic outcome. The best OS and DFS durations were achieved in patients who experienced pCR after 4-8-weeks interval before surgery.
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http://dx.doi.org/10.5152/tjg.2020.19225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7289170PMC
May 2020

The Impact of Primary Tumor and Locoregional Metastatic Lymph Node SUV on Predicting Survival in Patients with Rectal Cancer.

Mol Imaging Radionucl Ther 2020 Apr;29(2):65-71

University of Health and Sciences, İstanbul Training and Research Hospital, Clinic of Nuclear Medicine, İstanbul, Turkey.

Objectives: The aim of this study was to evaluate the impact of maximum standard uptake value (SUV) of the primary tumor and locoregional metastatic lymph node in predicting survival in patients with the preoperative rectal adenocarcinoma.

Methods: One hundred and fifteen patients [mean age ± standard deviation (SD): 58.7±11.4 years] with biopsy-proven rectal adenocarcinoma underwent F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) imaging for the staging were included in this study. All patients were followed-up for a minimum of 12 months (mean ± SD: 29.7±13.5 months). Tumor-node-metastasis 2017 clinical staging, SUV of the primary rectal tumor and locoregional lymph nodes on the PET/CT studies were evaluated.

Results: All patients had increased FDG activity of the primary tumor. The mean ± SD SUV of the primary tumor and locoregional metastatic lymph node were 21.0±9.1 and 4.6±2.8, respectively. Primary tumor SUV did not have an effect on predicting survival (p=0.525) however locoregional metastatic lymph node SUV had an effect (p<0.05) on predicting survival. Clinical stage of the disease was a factor predicting survival (p<0.001).

Conclusion: F-FDG PET/CT is an effective imaging modality for detecting primary tumors and metastases in rectal adenocarcinoma and clinical stage assessment with PET/CT had an effect on predicting survival. Furthermore, in our study locoregional lymph node SUV was defined as a factor in predicting survival.
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http://dx.doi.org/10.4274/mirt.galenos.2020.40316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201433PMC
April 2020

Prognostic significance of carbonic anhydrase IX overexpression in stage III non-small cell lung cancer patients after neoadjuvant treatment.

Pathol Res Pract 2018 Sep 11;214(9):1291-1296. Epub 2018 Jul 11.

Department of Medical Oncology, Istanbul Haseki Egitim Arastirma Hospital, Istanbul, Turkey.

Background: To assess the prognostic importance of carbonic anhydrase IX (CA IX), a hypoxic biomarker, after neoadjuvant treatment in Stage III non-small cell lung cancer (NSCLC) patients.

Methods: Tissue CA IX expression was examined after surgical resection in 77 patients who had undergone neoadjuvant treatment. The effects of CA IX overexpression and other clinical factors on disease-free survival and overall survival were investigated.

Results: In multivariate analysis, number of neoadjuvant chemotherapy (CT) courses and gender emerged as significant independent predictors for disease-free survival, where administration of 2-3 courses of neoadjuvant chemotherapy (CT) (HR, 3.2 [95% CI 1.3-7.6], p = 0.009) and female gender were associated with poor survival (HR, 3.2 [95% CI 1.3-7.7], p = 0.009). The only significant independent predictor for overall survival was recurrence (HR, 5.6 [95% CI 2.4-12.8], p < 0.001). On the other hand, CA IX overexpression was not associated with disease free survival (p = 0.560) or overall survival (p = 0.799).

Discussion: Our results do not suggest a prognostic role for CA IX overexpression in stage III NSCLC patients who received neoadjuvant treatment.
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http://dx.doi.org/10.1016/j.prp.2018.07.010DOI Listing
September 2018

Neoadjuvant hyperfractionated accelerated radiotherapy plus concomitant 5-fluorouracil infusion in locally advanced rectal cancer: A phase II study.

World J Gastrointest Oncol 2018 Jan;10(1):40-47

Department of Radiation Oncology, Istanbul Medical Faculty, Istanbul University, Istanbul 34093, Turkey.

Aim: To evaluate the efficacy and tolerability of neoadjuvant hyperfractionated accelerated radiotherapy (HART) and concurrent chemotherapy in patients with locally advanced infraperitoneal rectal cancer.

Methods: A total of 30 patients with histopathologically confirmed T2-3/N0+ infraperitoneal adenocarcinoma of rectum cancer patients received preoperative 42 Gy/1.5 Gy/18 days/bid radiotherapy and continuous infusion of 5-fluorouracil (325 mg/m). All patients were operated 4-8 wk after neoadjuvant concomitant therapy.

Results: In the early phase of treatment, 6 patients had grade III-IV gastrointestinal toxicity, 2 patients had grade III-IV hematologic toxicity, and 1 patient had grade V toxicity due to postoperative sepsis during chemotherapy. Only 1 patient had radiotherapy-related late side effects, ., grade IV tenesmus. Complete pathological response was achieved in 6 patients (21%), while near-complete pathological response was obtained in 9 (31%). After a median follow-up period of 60 mo, the local tumor control rate was 96.6%. In 13 patients, distant metastasis occurred. Disease-free survival rates at 2 and 5 years were 63.3% and 53%, and corresponding overall survival rates were 70% and 53.1%, respectively.

Conclusion: Although it has excellent local control and complete pathological response rates, neoadjuvant HART concurrent chemotherapy appears to not be a feasible treatment regimen in locally advanced rectal cancer, having high perioperative complication and intolerable side effects. Effects of reduced 5-fluorouracil dose or omission of chemotherapy with the aim of reducing toxicity may be examined in further studies.
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http://dx.doi.org/10.4251/wjgo.v10.i1.40DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5767792PMC
January 2018

Neoadjuvant volumetric modulated arc therapy in rectal cancer and the correlation of pathological response with diffusion-weighted MRI and apoptotic markers.

Tumori 2018 Aug 8;104(4):266-272. Epub 2018 May 8.

1 Department of Radiation Oncology, Institute of Oncology, Istanbul University, Istanbul - Turkey.

Purpose: In this prospective observational study, we aimed to report the applicability and tolerability of neoadjuvant volumetric modulated arc therapy with simultaneous integrated boost (SIB-VMAT) and concurrent chemotherapy in patients with locally advanced rectal cancer (LARC), and to evaluate the correlation of pathological response with apparent diffusion coefficient (ADC) measurements on diffusion-weighted magnetic resonance imaging (DW-MRI) and apoptotic markers.

Methods: The study enrolled 30 patients with T3 to T4 and/or N+ rectal cancer who preoperatively received SIB-VMAT and concurrent chemotherapy. Before and after the neoadjuvant treatment, apoptotic markers including the nucleosomes and cell-free DNA fragments in the serum samples were examined; DNA integrity was assessed by amplifying the ACTB gene; and the ADC measurements on the DW-MRI were analyzed.

Results: No patients had acute or chronic grade III-IV toxicity. Pathologic complete response (pCR) was achieved in 8 patients (27%), while in 10 patients (33%) near-complete pathological response was obtained. Posttreatment ADC was significantly higher in patients with pCR compared with the others (1.28 vs. 1.10, p = 0.017). ROC curve analysis showed that posttreatment ADC values had a sensitivity of 75% and a specificity of 77.3% for distinguishing the patients with pCR from other responders. On the other hand, posttreatment DNA integrity values were revealed lower than the pretreatment values (p = 0.36). Also, the results revealed an insignificant increase in the posttreatment serum level of nucleosomes (p = 0.72).

Conclusions: Neoadjuvant SIB-VMAT with concurrent chemotherapy was proved to be a feasible treatment regimen in LARC with tolerable side effects, and improved local control rate and pCR rate.
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http://dx.doi.org/10.5301/tj.5000702DOI Listing
August 2018

Association of Three Single Nucleotide Polymorphisms in MTR and MTRR Genes with Lung Cancer in a Turkish Population.

Genet Test Mol Biomarkers 2017 Jul 24;21(7):428-432. Epub 2017 May 24.

3 Department of Radiation Oncology, Institute of Oncology, Istanbul University , Istanbul, Turkey .

Aims: Folate metabolism plays a critical role in DNA methylation and synthesis. Polymorphisms in folate metabolism may affect enzyme activities and thereby affect the cancer risk. Methionine synthase (MTR) and methionine synthase reductase (MTRR) are critical enzymes for the folate cycle. In this study, possible associations between genetic variabilities in MTR and MTRR and susceptibility to lung cancer (LC) were investigated in a Turkish population.

Methods: A case-control study with 193 LC cases and 199 noncancerous controls was conducted. DNA was extracted from leukocytes using the high pure polymerase chain reaction (PCR) template preparation kit. The MTR 2756 A>G (rs1805087), MTRR 524 C > T (rs1532268), and MTRR 66 A>G (rs1801394) genotypes were determined using PCR-restriction fragment length polymorphism (PCR-RFLP) assays. The genotype and haplotype analyses of these polymorphisms were performed using SPSS 21 and Haploview 4.2, respectively.

Results: An association between the MTRR A66G polymorphism and LC (p = 0.042) was found. In addition, this allele was observed more frequently in smokers compared to nonsmokers (p = 0.030). In contrast, the distribution of the MTR 2756 A>G and the MTRR 524 C > T allele frequencies were similar in the subject cases and controls.

Conclusions: In conclusion, the present study suggests an association between the MTRR 66 A>G gene polymorphisms and LC risk in a Turkish population.
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http://dx.doi.org/10.1089/gtmb.2017.0062DOI Listing
July 2017

Delayed versus immediate surgery following short-course neoadjuvant radiotherapy in resectable (T3N0/N+) rectal cancer.

J Cancer Res Clin Oncol 2017 Aug 3;143(8):1597-1603. Epub 2017 Apr 3.

Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Purpose: Preoperative short-course radiotherapy (SCRT) followed by surgery has shown advantage over surgery alone in patients with resectable rectal carcinoma (RC); however, the importance of the timing of surgery after SCRT has not been well defined. This study aimed to investigate the effect of this duration on treatment outcomes.

Methods: Patients who underwent surgery after SCRT (25 Gy/500 cGy/daily/5fr, monday-friday) for resectable and infraperitoneal rectal adenocarcinoma (T3N0/(+)) were included into the study. Patients were divided into two groups in terms of the timing of surgery: delayed surgery (>4 weeks) or immediate surgery (<4 weeks).

Results: A hundred and thirty-six patients were included in the study. Median time between RT and surgery was 4 ± 5.7 (1-58) weeks, where 68% (n = 93) patients underwent delayed surgery (≥4 weeks). The two groups did not differ in terms of surgical margin positivity, pathological tumor regression, N downstaging, or T downstaging (p > 0.05 for all). However, the number of positive lymph nodes was higher in the immediate surgery group [median 3 (0-18) vs. 1 (0-17), p = 0.009]. Median follow-up time was 36 ± 9 (6-93) months. Delayed surgery group had significantly longer mean overall survival (p = 0.038); however, the two groups did not differ in terms of local recurrence, mean time to local recurrence, or mean disease-free survival.

Conclusions: Our findings seem to support the benefit of a longer time interval between radiotherapy and surgery after short-course neoadjuvant radiotherapy in resectable rectal cancer in terms of overall survival. However, there is a need to better define patient characteristics that might benefit from delayed surgery.
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http://dx.doi.org/10.1007/s00432-017-2406-6DOI Listing
August 2017

Effects of Boron-Based Gel on Radiation-Induced Dermatitis in Breast Cancer: A Double-Blind, Placebo-Controlled Trial.

J Invest Surg 2017 Jun 4;30(3):187-192. Epub 2016 Oct 4.

c Department of Radiation Oncology , Bezmialem Vakif University , Istanbul , Turkey.

Aim: This study is aimed to evaluate the effects of boron on radiation-induced skin reactions (RISR) in breast cancer patients.

Material And Methods: After 47 patients with invasive ductal carcinoma underwent radiotherapy, 23 (49%) received a boron-based gel, and 24 (51%) received placebo. Assessments were performed according to the Radiation Therapy Oncology Group (RTOG) skin scale and a Five-Point Horizontal Scale (FPHS).

Results: At the end of the fifth week of radiotherapy, the RTOG scores in the boron group were significantly lower than those in the placebo group (p = .024). The FPHS score was higher in the placebo group than in the boron group, and this difference was not statistically significant (p = .079).

Conclusion: Using the RTOG scoring system, we revealed that the application of a boron-based gel diminished RISR. The mechanism of action is unclear but may be related to antioxidant, wound healing, and thermal degradation effects of boron.
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http://dx.doi.org/10.1080/08941939.2016.1232449DOI Listing
June 2017

Does Metastatic Lymph Node SUVmax Predict Survival in Patients with Esophageal Cancer?

Mol Imaging Radionucl Ther 2015 Oct;24(3):120-7

İstanbul University Cerrahpaşa Faculty of Medicine, Department of Nuclear Medicine, İstanbul, Turkey Phone: +90 212 414 20 00 E-mail:

Objective: We aimed to investigate the SUVmax of primary tumor and metastatic lymph node in predicting survival in patients with esophageal cancer.

Methods: We retrospectively analyzed patients with esophageal cancer between 2009 and 2011 who had FDG positron-emission tomography (PET)/computed tomography (CT). All patients were followed-up to 2013. Clinical staging, SUVmax of primary tumor and metastatic lymph node were evaluated.

Results: One hundred seven patients were included in the study. All patients were followed-up between 2 and 49 months. The mean SUVmax of primary tumor and metastatic lymph node were 19.3±8.8 and 10.4±9.1, respectively. Metastatic lymph node SUVmax had an effect in predicting survival whereas primary tumor SUVmax did not have an effect (p=0.014 and p=0.262, respectively). Multivariate Cox regression analysis showed that clinical stage of the disease was the only independent factor predicting survival (p=0.001).

Conclusion: Among patients with esophageal cancer, the value of primary tumor SUVmax did not have an effect on survival. Clinical stage assessed with FDG PET/CT imaging was found to predict survival in esophageal carcinoma. Additionally, lymph node SUVmax was identified as a new parameter in predicting survival in the present study.
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http://dx.doi.org/10.4274/mirt.36744DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4745404PMC
October 2015

Concomitant etoposide and cisplatin provided improved survival compared with docetaxel and cisplatin in patients with locally advanced non-small cell lung cancer treated with chemoradiotherapy.

Medicine (Baltimore) 2016 Jul;95(30):e4280

Department of Medical Oncology, Institute of Oncology Department of Radiation Oncology Department of Thoracic Surgery Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.

Presently, there is no consensus regarding which chemotherapy regimen is best to administer with radiotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). Herein, our aim was to compare the outcome of patients treated with either etoposide-cisplatin (EP) or docetaxel-cisplatin (DP) in this curative setting.Patients treated with either EP or DP and concurrent radiotherapy from 2004 to2012 were identified and their detailed medical records and follow-up information were obtained for analysis in this retrospective study. Survival rates were compared using Cox proportional hazards regression models with adjustments for confounding parameters provided by propensity score methods.A total of 105 patients were treated with concurrent chemoradiotherapy for LA-NSCLC (stage IIB-IIIA-IIIB). The median ages were 54 years (range, 32-70 years) and 55 years (range, 37-73 years) in the EP (n = 50) and DP (n = 55) groups, respectively. The median follow-up time was 27 months (range, 1-132 months) in the EP group and 19 months (range, 1-96 months) in DP group. There was no significant difference in baseline clinicopathologic features including age, sex, performance status, histologic subtype, and clinical TNM stages between groups. In the univariate analysis, the median overall survival of patients treated with EP was higher than that of patients treated with DP (41 vs. 20 months, P = 0.003). Multivariate analysis further revealed a survival advantage with EP compared with DP (hazard ratio [HR], 0.46; 95% confidence interval: 0.25-0.83; P = 0.009). The toxicity profile of the 2treatment groups was similar except that pulmonary toxicity was higher in the DP group (grade 3-4: 0% vs. 6%, P = 0.024).Concurrent chemoradiotherapy with EP may provide more favorable outcomes than DP and with an acceptable safety profile.
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http://dx.doi.org/10.1097/MD.0000000000004280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5265838PMC
July 2016

Chronomodulated oxaliplatin plus Capecitabine (XELOX) as a first line chemotherapy in metastatic colorectal cancer: A Phase II Brunch regimen study.

Cancer Chemother Pharmacol 2016 Jul 6;78(1):143-50. Epub 2016 Jun 6.

Institute of Oncology, Department of Radiation Oncology, Istanbul University, Istanbul, Turkey.

Purpose: The aim of this study was to evaluate safety and toxicity of chronomodulated capecitabine administered in the morning and at noon according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of first-line XELOX chemotherapy in patients with metastatic colorectal cancer.

Methods: A total of 30 treatment-naïve colorectal cancer patients with metastatic disease were included. Oxaliplatin 130 mg/m(2) on day 1 plus chronomodulated oral capecitabine 2000 mg/m(2) per day were administered (50 % dose at 8:00 a.m. and 50 % dose at 12:00 noon on days 1-14, every 21 days). All adverse events, treatment responses and survival were evaluated. In addition, pharmacokinetic profile of capecitabine was examined in a subset of 5 patients.

Results: Median age was 57.1 years (range 32-77 years). Median follow-up was 19 months (range 3-36 months). Three patients (10 %) had complete response, 13 patients (43.3 %) had partial response and 4 patients (13.3 %) had stabile disease. Ten patients had progressive disease at their first evaluation (33.3 %). The median progression-free survival (PFS) was 10 months (range 2-36 months). There were no grade 4 toxicities. One patient (3.3 %) had grade 3 neutropenia. Hand-foot syndrome developed in three patients (10 %): 6.6 %, grade 1 and 3.3 %, grade 2.

Conclusions: Chronomodulated XELOX seems to represent a promising therapeutic option in the first-line treatment of metastatic colorectal carcinoma due to good tumor control and favorable toxicity profile. Phase III randomized trials are required to assess the actual clinical efficacy and side effect profile of this regimen.
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http://dx.doi.org/10.1007/s00280-016-3067-xDOI Listing
July 2016

LGALS3 and AXIN1 gene variants playing role in the Wnt/ β-catenin signaling pathway are associated with mucinous component and tumor size in colorectal cancer.

Bosn J Basic Med Sci 2016 Feb 4;16(2):108-13. Epub 2016 Feb 4.

Department of Molecular Medicine, Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey..

The Wnt pathway alterations have been identified in colorectal and many other cancer types. It has been reported that galectin-3 (which is encoded by the LGALS3 gene) alters the signaling mechanism in the Wnt/ β-catenin pathway by binding to β-catenin in colon and other cancers. AXIN1 is mainly responsible for the assembly of the β-catenin destruction complex in the Wnt pathway. This study investigated the relationship of rs4644 and rs4652 variants of the LGALS3 gene and rs214250 variants of the AXIN1 gene to histopathological and clinical properties. Our study included a total of 236 patients, of whom 119 had colorectal cancer (42 women, 77 men) and 117 were healthy controls. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and allele-specific oligonucleotide (ASO) PCR methods were used. In addition, the serum galectin-3 level was studied with the enzyme-linked immunosorbent assay (ELISA) method. For the rs4644 variant of the LGALS3 gene, the CC genotype a mucinous component was significantly more common than those without a mucinous component (p=0.026). C allele frequency of the rs214250 variant of the AXIN1 gene was significantly correlated to tumor size in the advanced tumor stage (p=0.022). The CCAACT haplotype was more common in colorectal cancer patients (p=0.022). Serum galectin-3 level was higher in the patient group compared to the control group (5.9± 0.69 ng/ml vs. 0.79±0.01 ng/ml; p<0.001). In conclusion, variants of LGALS3 and AXIN1 genes affect tumor sizes and the mucinous component via Wnt/ β-catenin pathway in the pathogenesis of colorectal cancer.
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http://dx.doi.org/10.17305/bjbms.2016.721DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852991PMC
February 2016

The effect of neoadjuvant therapy on the size, number, and distribution of mesorectal lymph nodes.

Ann Diagn Pathol 2016 Feb 29;20:29-35. Epub 2015 Oct 29.

Istanbul University Istanbul Faculty of Medicine, Department of Pathology, Istanbul, Turkey. Electronic address:

The current therapeutic approach to patients with locally advanced rectal cancer is neoadjuvant radiotherapy or chemoradiotherapy followed by total mesorectal excision. We aimed to investigate the number, size, and distribution of metastatic and nonmetastatic lymph nodes within the mesorectum; whether neoadjuvant therapy has any impact on the number and size of the lymph nodes; and the impact of metastatic lymph node localization on overall and disease-free survival. Specimens from 50 consecutive patients with stage II/III rectal cancer receiving either neoadjuvant radiotherapy or chemoradiotherapy were investigated. Lymph node dissection was carried out by careful visual inspection and palpation. The localization of the each lymph node within the mesorectum and the relation with the tumor site were noted. The size and the number of lymph nodes retrieved decreased significantly with neoadjuvant therapy. Majority of the metastatic and nonmetastatic lymph nodes were located at or proximally to the tumor level and posterior side of the mesorectum. No relation was observed between the overall and disease-free survival, and the localization of the metastatic lymph nodes. Presence of lymph node metastases proximal to the tumor level has no impact on survival compared with the presence of lymph node metastasis only in the peritumoral region of the mesorectum. Although neoadjuvant therapy decreases the size and the number of lymph nodes, reaching an ideal number of lymph nodes for accurate staging is still possible with careful naked eye examination and dissection of perirectal fat. As the majority of metastatic and nonmetastatic lymph nodes are located in peritumoral and proximal compartment, and posterior side of the mesorectum, these regions should be the major interest of dissection.
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http://dx.doi.org/10.1016/j.anndiagpath.2015.10.008DOI Listing
February 2016

Cutaneous melanoma in Turkey: analysis of 1157 patients in the Melanoma Turkish Study.

J BUON 2015 Jul-Aug;20(4):1137-41

Acibadem University School of Medicine, Department of Medical Oncology, Istanbul, Turkey.

Purpose: To develop a large Turkish National Melanoma registry in order to define demographic and clinicopathologic characteristics of patients with melanoma.

Methods: The data was collected from 1635 patients with melanoma through a web-based registry system in 22 centers. Herein we present the results of 1157 patients with cutaneous melanoma.

Results: The patient median age was 56.4 years and 646 (55.8%) were males. The commonest subtype was superficial spreading type (357, 30.9%). The commonest primary site was the lower extremities (N=353, 30.5%). The most common Breslow thickness was 1-2 mm (361 patients, 43.5%). Only 104 (12.5%) patients had a thickness <1mm. Among 694 patients with available data, 136 (19.6%) presented with stage 4 disease while the most frequent stage was stage 3, encountered in 393 (56.6% patients).

Conclusion: Our melanoma registry is the largest in our country providing a snapshot view of cutaneous melanoma and its care. Our patients presented with more advanced stages and they had worse prognosis compared to SEER database.
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November 2015

Adjuvant chemoradiotherapy after D2 resection in gastric cancer: a single-center observational study.

J Cancer Res Clin Oncol 2015 Feb 5;141(2):361-7. Epub 2014 Sep 5.

Department of Radiation Oncology, Institute of Oncology, Istanbul University, Istanbul, Turkey.

Purpose: Previous studies demonstrated survival benefits in association with the addition of chemoradiotherapy after surgery in gastric cancer. This study aimed to examine the efficacy in terms of loco-regional control and survival and safety of 5-FU-based adjuvant chemoradiotherapy after D2 curative surgery.

Methods: This study included 228 patients (81 female, 147 male) treated for gastric cancer with curative surgery plus adjuvant chemoradiotherapy. Majority of the patients underwent at least D2 lymph node resection. Median three cycles of fluorouracil chemotherapy were administered, and 45-Gy radiotherapy was delivered at 1.8 Gy/fraction concomitantly during the second cycle of chemotherapy. Local control, regional control, distant metastasis and overall survival rates were estimated.

Results: The median age of the patients was 54 years (range 25-74 years). The most common grade III toxicities were nausea (10%) and neutropenia (9%). During radiotherapy, grade IV local skin reaction occurred in one patient. Median duration of follow-up was 47 months. Local, regional and distant recurrence developed in 9 (4%), 41 (18%) and 45 (20%) patients, respectively. Overall 5-year survival rate was 57.2%, and disease-free 5-year survival rate was 53.8%. Multivariate analysis identified less than 15 lymph node involvement as an independent predictor of better survival (p < 0.001).

Conclusions: Concomitant 5-FU-based chemoradiotherapy seems to be an effective and tolerable adjuvant regimen on local control and survival in curatively resected node-positive stomach cancer, particularly when combined with D2 resection.
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http://dx.doi.org/10.1007/s00432-014-1816-yDOI Listing
February 2015

The clinical and pathological features of 133 colorectal cancer patients with brain metastasis: a multicenter retrospective analysis of the Gastrointestinal Tumors Working Committee of the Turkish Oncology Group (TOG).

Med Oncol 2014 Sep 10;31(9):152. Epub 2014 Aug 10.

Department of Medical Oncology, Faculty of Medicine, Medical School of Sitki Kocman University, Mugla, 48000, Turkey,

Brain metastasis in colorectal cancer is highly rare. In the present study, we aimed to determine the frequency of brain metastasis in colorectal cancer patients and to establish prognostic characteristics of colorectal cancer patients with brain metastasis. In this cross-sectional study, the medical files of colorectal cancer patients with brain metastases who were definitely diagnosed by histopathologically were retrospectively reviewed. Brain metastasis was detected in 2.7 % (n = 133) of 4,864 colorectal cancer patients. The majority of cases were male (53 %), older than 65 years (59 %), with rectum cancer (56 %), a poorly differentiated tumor (70 %); had adenocarcinoma histology (97 %), and metachronous metastasis (86 %); received chemotherapy at least once for metastatic disease before brain metastasis developed (72 %), had progression with lung metastasis before (51 %), and 26 % (n = 31) of patients with extracranial disease at time the diagnosis of brain metastasis had both lung and bone metastases. The mean follow-up duration was 51 months (range 5-92), and the mean survival was 25.8 months (95 % CI 20.4-29.3). Overall survival rates were 81 % in the first year, 42.3 % in the third year, and 15.7 % in the fifth year. In multiple variable analysis, the most important independent risk factor for overall survival was determined as the presence of lung metastasis (HR 1.43, 95 % CI 1.27-4.14; P = 0.012). Brain metastasis develops late in the period of colorectal cancer and prognosis in these patients is poor. However, early screening of brain metastases in patients with lung metastasis may improve survival outcomes with new treatment modalities.
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http://dx.doi.org/10.1007/s12032-014-0152-zDOI Listing
September 2014

Neoadjuvant chronomodulated capecitabine with radiotherapy in rectal cancer: a phase II brunch regimen study.

Cancer Chemother Pharmacol 2014 Oct 8;74(4):751-6. Epub 2014 Aug 8.

Department of Radiation Oncology, Faculty of Medicine, Bezmialem Vakif University, Istanbul, Turkey.

Purpose: The aim of this study was to evaluate efficacy and safety of chronomodulated capecitabine administered according to a specific time schedule (Brunch Regimen: Breakfast and Lunch) as a part of neoadjuvant chemoradiation therapy in patients with locally advanced rectal cancer.

Methods: Eighty-five patients with stage II and III rectal cancer were included. Patients received capecitabine (1,650 mg/m(2) per day; 60% dose at 8:00 AM and 40% dose at 12:00 noon) administered during pelvic radiation (total 50.4 Gy in 28 fractions, 1.8 Gy daily dose between 2:00 p.m. and 4:00 p.m.). After chemoradiotherapy, patients underwent surgery. The primary endpoints were pathological complete response (pCR) rate and toxicity.

Results: In 17 patients (20%), total tumor regression was achieved according to Dworak pathological grading system. Grade III diarrhea occurred in nine patients (10.5%), while only one patient had grade 3 thrombocytopenia. Grade II or III proctitis were seen in nine (10.5%) subjects, and grade I or II cystitis in six (6.9%). Only three patients (3.3%) developed hand and foot syndrome (both grade I-II). There were no grade IV toxicities.

Conclusions: Brunch Regimen for locally advanced rectal cancer consisting of neoadjuvant chronomodulated capecitabine and concurrent radiation therapy is effective and well tolerated with good safety profile, particularly with regard to the occurrence of hand and foot syndrome, in patients with locally advanced rectal cancer.
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http://dx.doi.org/10.1007/s00280-014-2558-xDOI Listing
October 2014

Neoadjuvant hyperfractionated-accelerated radiotherapy with concomitant chemotherapy in esophageal cancer: phase II study.

J Gastrointest Oncol 2013 Dec;4(4):380-7

Istanbul Bilim University Medical Faculty, Department of Medical Oncology, Istanbul, Turkey;

Purpose: Concomitant use of chemotherapy and a radiation dose schedule that is more efficient compared to conventional radiotherapy may provide better outcomes in patients with esophageal cancer. This study aimed to assess the efficacy and tolerability of neoadjuvant cisplatin-based chemotherapy and hyperfractionated accelerated radiotherapy regimen in this group of patients.

Methods And Materials: A total of 20 newly diagnosed treatment-naïve esophageal cancer patients were included in the study. Neoadjuvant cisplatin and 5-FU were given with 28-day intervals in a total of three courses. Along with the third course of chemotherapy, hyperfractionated accelerated radiotherapy (HART) was given with the following dose schedule: 5760 cGy/36 fr/16 day.

Results: All patients could receive the planned RT dose of 5760 cGy. Odynophagia was the most frequent grade III acute toxicity (50%). None of the acute toxicity reactions required treatment discontinuation. Grade III or higher subacute/late toxicity occurred in 10 patients (75%) including 5 deaths, mostly esophageal. Radiologically, 8 patients (40%) had complete response, 8 (40%) had partial response, and 3 (15%) had stable disease, with only 1 patient (5%) having progressive disease. Seven patients underwent surgery. Overall, 8 patients (40%) had local control. The 5 years overall survival rate was 38.1%.

Conclusions: Neoadjuvant hyperfractionated accelerated radiotherapy plus chemotherapy may help to target local disease control and increase survival in patients with esophageal cancer. Further studies to improve neoadjuvant and radical chemoradiotherapy dose schedules are warranted for maximum tumor control rates with minimal toxicity.
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http://dx.doi.org/10.3978/j.issn.2078-6891.2013.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3819777PMC
December 2013

Successful treatment of triple primary tumor.

Int J Surg Case Rep 2013 27;4(11):1013-6. Epub 2013 Aug 27.

Istanbul University, School of Medicine, Department of Plastic and Reconstructive Surgery, Istanbul, Turkey.

Introduction: The occurrence of multiple primary tumors is rare. Only limited number of cases with triple malignancy have been reported. We report here a rare case of a woman presented synchronous triple tumors, in her lung, breast, skin.

Presentation Of Case: A 56-year-old woman presented with invasive ductal carcinoma of breast, non-small cell lung cancer and malignant melanoma. The patient undergone mastectomy and malignant melanoma tumor excision on-site. After operation stereotactic radiotherapy was given to her lung tumor. Six course of chemotherapy was given to her. She is alive with no progression.

Discussion: The patient was diagnosed with melanoma and staging by FDG/PET. There is not any study about routine using PET/CT in the melanoma staging.

Conclusion: This is a very rare synchronous triple tumor case.
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http://dx.doi.org/10.1016/j.ijscr.2013.08.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3825933PMC
November 2013

Do CDKN2 p16 540 C>G, CDKN2 p16 580 C>T, and MDM2 SNP309 T>G gene variants act on colorectal cancer development or progression?

DNA Cell Biol 2013 Jul 18;32(7):400-8. Epub 2013 Jun 18.

Department of Molecular Medicine, The Institute of Experimental Medicine, Istanbul University, Istanbul, Turkey.

CDNK2 p16 plays a pivotal role in G1/S transition by regulating the p53 pathway, which was regulated by a nuclear oncoprotein, mouse double minute 2 (MDM2). Overexpression of the MDM2 gene has been shown in a number of tumor types, its gene amplification is found to associate with accelerated tumor development and failure to treatment in both hereditary and sporadic cancers. Although genetic association studies have revealed the relationship between certain genetic polymorphisms and genes that play important roles in the development and progression of colorectal cancer (CRC), it is still unknown. Therefore, the polymorphisms of p16 540 C>G, 580 C>T, and MDM2 SNP309 T>G designed to investigate the risk of CRC development and progression in a Turkish population. We enrolled 87 patients with CRC and 75 healthy controls into the study. Genotypings were determined using polymerase chain reaction-restriction fragment length polymorphism techniques. Genotype distributions of p16 540 C>G and 580 C>T were found in agreement with the Hardy-Weinberg equilibrium in patients and controls. MDM2 SNP309 T>G was found in agreement with the Hardy-Weinberg equilibrium in controls, but not in patients. The results of our study, the G allele of p16 540 C>G and GG genotype of MDM2 SNP309 T>G were found significantly lower in patients compared with controls (p<0.001, p<0.05, respectively). Haplotype analyses have shown that the C allele of both the CDKN2 p16 540 C>G and 580 C>T variants together indicate a risk haplotype for the patient group; besides, carrying the G allele of p16 540 and G allele of MDM2 also seems a risk haplotype for the patient group. Our study is the first study that investigates the relationship among variants of CDKN2 p16 540 C>G, 580 C>T, and MDM2 SNP309 T>G risk of CRC and the development and progression in the Turkish population.
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http://dx.doi.org/10.1089/dna.2012.1933DOI Listing
July 2013

Association of clinical and pathological variables with survival in thymoma.

Med Oncol 2012 Sep 6;29(3):2221-8. Epub 2011 Nov 6.

Department of Medical Oncology, Institute of Oncology, Istanbul University, Capa, Istanbul 34093, Turkey.

Our aim was to evaluate clinical and pathological features in prognosis of thymoma patients with particular emphasis on patients with myasthenia gravis (MG). From 1995 to 2010, 140 thymoma patients (women/men: 63/77) with a median age of 46 years (11-80 years) were admitted to our institution. According to World Health Organization (WHO), there were 23 (17%) type A, 12 (9%) type AB, 24 (17%) type B1, 42 (31%) type B2 and 36 (26%) type B3. The distribution of Masaoka stages I, II, III and IV was 24 (17%), 71 (51%), 18 (13%) and 27 (19%), respectively. MG coexisted in 61% of patients. After a mean follow-up of 34 months (1-158 months), 102 (73%) patients are alive and well while 14 (10%) are alive with disease. Twenty-three patients (16%) have died, only 9 died of thymoma. In univariate analyses, completeness of resection (P < .001), WHO histology (P = .008), Masaoka stage (P < .001) and MG (P = .002) were significant prognostic factors for progression-free survival (PFS). Young age (P = .008); Masaoka stages 1 and 2 (P = .039); WHO types A, AB and B1 (P = .031); complete resection (P = .024) and presence of MG (P = .05) significantly correlated with overall survival (OS). In multivariate analysis, Masaoka stages 1 and 2 (P = .038) and presence of MG (P = .01) were significantly correlated with a longer PFS; MG (P = .021) and WHO subtype (P = .022) were found to be significant prognostic factors for OS. Adjuvant radiotherapy improved neither OS nor PFS in completely resected stage 2 thymoma. Masaoka staging, WHO and MG are major determinants of prognosis in Turkish thymoma patients. Additionally, radiotherapy did not provide survival advantage to stage 2 patients with complete resection.
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http://dx.doi.org/10.1007/s12032-011-0101-zDOI Listing
September 2012

Paraoxonase-1 192/55 polymorphisms and the risk of lung cancer in a Turkish population.

Anticancer Res 2011 Jun;31(6):2225-9

Department of Biochemistry, Pharmacy Faculty, Istanbul University, 34116, Istanbul, Turkey.

Aim: The purpose of the present study was to investigate the possible association of paraoxonase-1 (PON1) 192/55 polymorphisms with lung cancer (LC) risk in a Turkish population.

Materials And Methods: A population-based, case-control study was carried out, including 223 patients with LC and 234 controls. The frequencies of PON1 192/55 genotypes were compared in patient and control groups using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

Results: Distribution of PON1 192 R (+) genotype was found to be significantly higher in patients with LC compared to the controls (odds ratio: 1.497, 95% confidence interval: 1.034-2.166). This difference was especially noteworthy in patients with small cell carcinoma and squamous cell carcinoma.

Conclusion: This is the first case-control study on the association between PON1 polymorphisms and LC susceptibility in a Turkish population. Our results suggest that PON1 192 polymorphsim is associated with an increased risk of LC in the Turkish population and may be a useful genetic marker for small cell and squamous cell carcinoma.
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June 2011

Induction chemotherapy with triweekly docetaxel and cisplatin followed by concomitant chemoradiotherapy with or without surgery in stage III non-small-cell lung cancer: a phase II study.

Clin Lung Cancer 2011 Sep 8;12(5):286-92. Epub 2011 May 8.

Institute of Oncology, Istanbul University, Turkey.

Background: The main goal of this study was to evaluate the feasibility and effectivity of triweekly docetaxel/cisplatin followed by weekly docetaxel/cisplatin concomitantly with radiotherapy with or without surgery in locally advanced non-small-cell lung cancer (NSCLC) patients.

Materials And Methods: Thirty five patients with locally advanced NSCLC were enrolled. Combination chemotherapy with triweekly docetaxel/cisplatin (75 mg/m(2)) was administered as induction regimen. After induction chemotherapy, patients were evaluated for surgery if their disease subsequently downstaged. Six cycles of weekly docetaxel/cisplatin (20 mg/m(2)) concurrently with radiotherapy up to a 60 Gy were administered after induction chemotherapy with or without surgery. Response, toxicity, time-to-progression and overall survival were evaluated.

Results: Twelve patients with stage IIIA-N2 and 23 patients with stage IIIB-T4N0-2 were evaluated (median age, 54 years). After 94 cycles of induction chemotherapy, partial response was achieved in 20 patients, 9 patients had stable disease and six had progressive disease. After overall treatment, 6 patients achieved complete response, 19 patients had partial response, 8 patients had progressive disease, and 2 patients had stable disease. Two patients experienced grade 3-4 pulmonary toxicity and 1 patient experienced grade 3 esophageal toxicity. Six patients underwent surgery. Median overall survival for all patients was 15 months and time-to-progression was 13 months with a median follow-up of 22 months.

Conclusion: Triweekly docetaxel plus cisplatin followed by weekly docetaxel plus cisplatin concomitantly with radiotherapy is effective and feasible and seems to be an alternative option for patients who have locally advanced NSCLC. Surgery may provide additional benefit for patients whose disease adequately downstaged after induction chemotherapy.
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http://dx.doi.org/10.1016/j.cllc.2011.03.030DOI Listing
September 2011

Weekly docetaxel and cisplatin with concomitant radiotherapy in addition to surgery and/or consolidation chemotherapy in stage III non-small cell lung cancer.

Cancer Chemother Pharmacol 2011 Dec 17;68(6):1497-505. Epub 2011 Apr 17.

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

Purpose: The aim of this study was to evaluate efficacy and feasibility of a combination of weekly docetaxel and cisplatin administered concomitantly with radiotherapy followed by surgery in addition to consolidation chemotherapy with docetaxel and cisplatin administered every 3 weeks in stage III non-small cell lung cancer (NSCLC).

Methods: A total of 31 histologically proven, locally advanced (stage IIIA-N2 = 9, stage IIIB-T4N0-2 = 22) NSCLC patients were investigated. After administration of 4-6 cycles of weekly docetaxel (20 mg/m(2)) and weekly cisplatin (20 mg/m(2)) concurrently with radiotherapy, patients underwent operation if their disease was appropriately downstaged. Combination chemotherapy with docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks was administered as a consolidation regimen. The treatment response, toxicity, time to progression (TTP) and overall survival (OS) were evaluated.

Results: After concomitant chemoradiotherapy, complete response and partial response occurred in 16.1 and 67.7% of patients, respectively. Thirteen percentage of patients progressed on treatment, and 3.2% had stable disease. Grade 3-4 hematologic and skin toxicities did not occur, whereas 17.9% of them experienced grade 3-4 oesophageal toxicity. Grade 3 pulmonary toxicity and grade 3-4 emesis developed in 9.7 and 6.4% of patients, respectively. Thirteen responsive patients (41.9%) underwent surgery. The toxicity of consolidation chemotherapy was tolerable. Median OS and TTP were 22 ± 5 (range 13-31) and 12 ± 3 (range 7-17) months, respectively. Median follow-up was 22 (range 2-57) months.

Conclusions: Weekly administration of docetaxel and cisplatin concurrently with radiotherapy followed by consolidation chemotherapy is an effective treatment with acceptable toxicity for patients with locally advanced NSCLC especially in combination with surgery.
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http://dx.doi.org/10.1007/s00280-011-1642-8DOI Listing
December 2011

Association between CDKN1A Ser31Arg and C20T gene polymorphisms and colorectal cancer risk and prognosis.

In Vivo 2010 Mar-Apr;24(2):179-83

Institute of Experimental Medicine, Istanbul, Turkey.

Background: CDKN1A (p21(WAF1/CIP1)) plays an important role in cell cycle regulation. Somatic alterations in genes which regulate cell division have been shown to be related to different types of cancer prognosis and survival. The purpose of this study was to investigate the effect of the CDKN1A Ser31Arg and C20T gene polymorphisms in Turkish patients with colorectal cancer.

Patients And Methods: CDKN1A Ser/Arg and C20T polymorphisms were studied in 53 patients with colorectal cancer and 64 healthy controls. Genomic DNA was amplified by polymerase chain reaction (PCR) and genotypes were determinated by the restriction fragment length polymorphism (RFLP) method.

Results: There were statistically significant differences in the distribution of CDKN1A Ser/Arg genotypes and allele frequencies between colorectal cancer patients and healthy controls (p=0.040 and p=0.01, respectively). CDKN1A C20T genotype frequency did not show any significant differences between patients and controls. We combined the results for C20T and Ser31Arg polymorphisms and observed that a lower risk of colorectal cancer was associated with CT/SerArg combined genotypes compared to controls and this difference was statistically significant (p=0.024; odds ratio (OR)=0.322, 95% confidence interval (CI)=0.114-0.912). C20T C allele and SerSer genotypes significantly increased risk compared to other combined genotypes (p=0.034; OR=1.265, 95% CI=1.020-1.569).

Conclusion: The results of present study demonstrated that, potentially, CDKN1A functional polymorphisms may contribute to the risk of colorectal cancer in Turkish.
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May 2010