Publications by authors named "Sule Karaman"

13 Publications

  • Page 1 of 1

Investigation of approaches for internal target volume definition using 4-dimensional computed tomography in stereotactic body radiotherapy of lung cancer.

Med Dosim 2021 Summer;46(2):136-142. Epub 2020 Oct 27.

Division of Medical Physics, Istanbul University Oncology Institute, Istanbul, Turkey.

The present study was undertaken to investigate the suitability of alternative internal target volume (ITV) delineation strategies based on maximum intensity projection (MIP), average intensity projection (AIP), 2 extreme phases and 4 phases images relative to the ITV in stereotactic body radiation therapy (SBRT) for lung cancer. The 4-dimensional computed tomography (4DCT) data of 15 lung cancer patients treated with SBRT in our clinic were used. Five different ITVs were generated as follows: merging GTVs from 10 phases (ITV); merging GTVs from 2 extreme phases (0%, 50%) (ITV); merging GTVs from 4 phases (0%, 20%, 50%, and 70%) (ITV); delineating GTV on MIP (ITV), and delineating GTV on AIP (ITV). PTV, PTV, PTV, PTV, and PTV were generated by adding a 5-mm margin around the related ITV. Volumetric analyses were performed for 4 ITVs and PTVs relative to ITV and PTV. SBRT plans made for all PTVs were evaluated for dosimetric effect of alternative ITV delineation strategies. The mean percentage overlap volume (POV) for PTV PTV, PTV, and PTV relative to PTV were 84.2 ± 5.4%, 92.0 ± 2.9%, 82.2 ± 5.7%, and 73.8 ± 9.3%, for lower-lobe tumors, respectively. The mean POV for PTV PTV, PTV, and PTV relative to PTV were 93.2 ± 2.5%, 95.9 ± 1.0%, 87.5 ± 6.7%, and 83.3 ± 6.8% for upper-lobe, respectively. For lower-lobe tumors the mean differences in V20 and MLD for plans based on PTV and PTV were <0.5% and <10 cGy, compared with a plan based on PTV. The use of PTV based on 4 respiratory phases and a 5-mm margin is a safe approach to reduce the workload of target delineation for tumors located in both lower and upper lobes.
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http://dx.doi.org/10.1016/j.meddos.2020.10.004DOI Listing
October 2020

Does nutritional status affect treatment tolarability, response and survival in metastatic colorectal cancer patients? Results of a prospective multicenter study.

J Oncol Pharm Pract 2020 Sep 22:1078155220959427. Epub 2020 Sep 22.

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

Background: The efficacy and tolerability of modern cytotoxic chemotherapy regimens used in malnourished metastatic colorectal cancer (mCRC) patients is uncertain. The aim of this study was to investigate the effect of malnutrition on efficacy and tolerability of cytotoxic chemotherapy and overall survival in mCRC patients.

Methods: In this multicenter study, demographic, oncologic and nutritional data were collected prospectively from mCRC patients. Nutritional status of the patients were evaluated on the basis of NRI (Nutritional Risk Assessment), BMI (Body Mass Index) and WL (Weight Loss) before the first chemotherapy, after the first and second chemotherapy during 2 cycles of chemotherapy every 15 days. To determine the inter-treatment weight loss toxicity assessment was included to theese parameters after each chemotherapy. NRI calculation was performed as [1.51xserum albumin level (g/L)+41.7xcurrent weight/basic weight]. NRIs were examined in 3 categories as 'no malnutrition' (NRI >97.5), 'moderate malnutrition' (97.5 ≥NRI ≥83.5) or 'severe malnutrition' (NRI <83.5). Response to treatment and drug-induced toxicities were assessed based on Criteria in Solid Tumors (RECIST) 1.1 and National Cancer Institute CTCAE version 4.0 respectively.

Results: One-hundred and thirty-seven mCRC patients were prospectively included. Median age was 48 (range 18-83). Primary location was colon in 66% of patients and 84% of their primary source was left colon. Malnutrition was detected in 39% of the cases. Response rate to treatment was twenty four percent. While there was no significant relationship between chemotherapy response and moderate/severe malnutrition (p = 0.24), moderate/severe malnutrition was associated with multipl site of metastases, WHO PS (World Health Organization Performance Status) of 1, over the median value of CEA/CA 19-9 (carcinoembryonic antigen/carbohydate antigen 19-9) levels (p = 0.003, p = 0.03, p < 0.001, and p = 0.02; respectively). Hypoalbuminemia and moderate/severe malnutrition were associated with all types of toxicity (p < 0.001 and p < 0.001). Moderate/severe malnutrition was associated with thrombocytopenia, and diarrhea following chemotherapy predominately, (p = 0.02 and p = 0.04; respectively). In moderate/severe malnutrition group median overall survival was prominently shorter than those with no malnutrition [6.6 moths (95%CI, 5.6-7.6) vs 11.9 moths (95% CI, 11.1-12.7) respectively, p < 0.001].

Conclusions: Our study showed that moderate/severe malnutrition in mCRC patients was associated with decreased overall survival and increased chemotherapy toxicity.
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http://dx.doi.org/10.1177/1078155220959427DOI Listing
September 2020

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

Serum nectin-2 and nectin-4 are diagnostic in lung cancer: which is superior?

Wien Klin Wochenschr 2019 Sep 22;131(17-18):419-426. Epub 2019 Aug 22.

Institute of Oncology, Istanbul University, Capa, 34093, Fatih, Istanbul, Turkey.

Nectins are immunoglobulin-like molecules that are involved in cell to cell adhesion by forming tight junctions and homophilic/heterophilic interactions. This study aimed to analyze serum nectin‑2 and nectin‑4 levels in lung cancer patients and to evaluate the prognostic, diagnostic and predictive strengths. Data from 74 lung cancer patients were retrospectively examined and enzyme-linked immunosorbent assays (ELISA) were used to measure serum nectin‑2 and nectin‑4 concentrations. A total number of 40 age and sex-adjusted healthy controls were also enrolled in the study. The median serum nectin‑2 and nectin‑4 levels of the patients were significantly higher than those of controls (p < 0.001); however, neither biomarker was found to be associated with clinicopathological parameters, (p > 0.05), and furthermore they were found not to be correlated with either overall survival or progression-free survival (p > 0.05). Even though both markers showed high diagnostic values, serum nectin‑2 was found superior to both serum nectin‑4 and serum nectin-2 + nectin‑4 combinations in the diagnosis of lung cancer according to higher sensitivity, specificity and predictive values. Serum nectin‑2 and nectin‑4 might be used in lung cancer diagnosis but the diagnostic importance of nectin‑2 is higher. The prognostic and predictive strengths in cancer are controversial. Furthermore, the interactions with tumor microenvironments and the potentials as therapeutic targets for malignancies have yet to be elucidated.
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http://dx.doi.org/10.1007/s00508-019-01537-4DOI Listing
September 2019

Detection of serum protein and circulating mRNA of cMET, HGF EGF and EGFR levels in lung cancer patients to guide individualized therapy.

Cancer Biomark 2019 ;25(2):177-184

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

Background: Reseptor tyrosine kinases (cMET and EGFR) are important in lung cancer targeted therapy. We believe if we can use them as markers for clinicians to help decide the diagnosis of lung cancer. This parameter will be important in serum samples of patients with lung cancer diagnosis and treatment. The aim of this study is aimed to evaluate the clinical utility of serum protein and circulating mRNA of cMET and HGF in lung cancer patients. We also analyzed the correlation of mRNA expression with clinicopathologic parameters.

Methods: We performed enzyme-linked immunosorbent assay (ELISA) to measure and compare serum protein and circulating mRNA of cMET and HGF levels in peripheral blood from 60 lung cancer patients and 40 healthy control group.

Results: We found that both protein and gene expression levels of serum c-MET, HGF and EGFR were significantly higher in patients with lung cancer than control group. There was no association between HGF, cMET, EGF, EGFR (both protein and gene) expression levels with age, gender, smoking habit, COPD, pathological types or tumor size, stage, metastatic-non metastatic adenocarcinoma-squamous carcinoma, SCLC-NSCLC. As a result of ROC analysis, serum cMET (AUC: 0.892) and HGF protein (AUC: 0.784) were diagnosed in lung cancer patients (Fig. 1). The AUC values of serum EGF and EGFR proteins were calculated to be 0.631 and 0.692, respectively.

Conclusion: To our knowledge this is the first study comparing the levels of protein and mRNA in the serum material of HGF, c-MET, EGF and EGFR parameters in lung cancer patients' blood samples. Further prospective studies with more participants for better understanding of mechanism and effect for HGF and c-MET inhibitors in lung cancer will help us to identify of these biomarkers role for guiding us to sellect individualized itargeted therapies.
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http://dx.doi.org/10.3233/CBM-182231DOI Listing
December 2019

Abscopal Effect of Radiotherapy in the Immunotherapy Era: Systematic Review of Reported Cases.

Cureus 2019 Feb 20;11(2):e4103. Epub 2019 Feb 20.

Radiation Oncology, Istanbul University Faculty of Medicine, Istanbul, TUR.

Mounting evidence suggests that radiation stimulates the immune system and this contributes to the abscopal effect, which is defined as "response at a distance from the irradiated volume." Though identified more than 50 years ago, the abscopal effect is revisited today. One rationale is that the abscopal effect is often observed with efficient immunotherapy. Here, we give an overview of the clinical data on the abscopal effect, generated by a combination of immunotherapy and radiotherapy (RT). Only papers that included RT in combination with immunotherapy were evaluated according to four main categories including RT parameters, sequencing of therapies, the definition of the abscopal effect, and patient selection. Twenty-four cases in 15 reports were reviewed. The results varied. Patient ages ranged from 24 to 74. RT dose (median total dose 18-58 Gy) varied. Biologically effective dose (BED) 10 was calculated to be a median 49.65 Gy (28-151 Gy). The time to a documented abscopal response ranged from less than a month to 12 months. The large variation concerning fractionation and sequencing of therapies indicates that these conflicting points need to be resolved, to generate for the abscopal effect to be clinically significant.
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http://dx.doi.org/10.7759/cureus.4103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6476623PMC
February 2019

Serum leptin levels may have diagnostic and predictive roles in patients with pancreatic adenocarcinoma treated with gemcitabine-based chemotherapy.

J BUON 2016 Jul-Aug;21(4):895-902

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

Purpose: Leptin is a highly pleiotropic adipokine. Pancreatic adenocarcinoma (PA) and leptin relationship is important. Our aim was to investigate the serum levels of leptin in patients with PA, the relationship of leptin with tumor progression and known prognostic parameters and its diagnostic, predictive and prognostic role.

Methods: Thirty-three patients with PA were investigated. Serum samples were obtained on first admission before treatment and follow-up. Both serum leptin levels were determined using enzyme-linked immunosorbent assay (ELISA). Age, sex, and body mass index (BMI) matched to 20 healthy controls were included in the analysis.

Results: The median patient age at diagnosis was 59 years (range 32-84) and 20 (61%) patients were men. The tumor was located in the head of pancreas in 21 (63%) patients. The most common metastatic site was liver in 23 patients with metastasis (N=19; 83%). The median follow-up time was 26.0 weeks (range 1.0-184.0). At the end of the observation period, 32 patients (97%) had died. The baseline serum leptin levels were significantly higher in patients with PA than in the control group (p=0.02). Thirty-nine percent of 23 metastatic patients who received palliative gemcitabine-based chemotherapy (gCTx) were gCTx-responsive. Serum leptin levels were significantly higher in the gCTx-unresponsive patients compared with gCTx -responsive (median 5.32 vs 1.16 ng/mL, p=0.004). Conversely, serum leptin concentration was found to have no prognostic role on survival (p=0.20).

Conclusion: Serum leptin levels may be a good diagnostic and predictive tool on the response to gCTx in PA patients.
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March 2017

Definitive radiotherapy in locally advanced non-small cell lung cancer: dose and fractionation.

Balkan Med J 2014 Dec 1;31(4):278-85. Epub 2014 Dec 1.

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

Definitive radiotherapy plays a major role in the treatment of locally advanced non-small cell lung cancer (LA NSCLC). After the impact of RT dose for lung cancer was established, a number of trials were structured with the aim of better local control and overall survival by either dose escalation or shortening the total treatment time through conventional/altered fractionation, even in combination with chemotherapy (CT) and other targeted agents. In spite of the increased number of these studies, the optimal dose or fractionation still remains to be determined. Another aspect questioned is the incorporation of these higher doses and shorter treatment times with chemotherapy or targeted agents. This review summarises the results of significant trials on dose and altered fractionation in the treatment of LA-NSCLC with an emphasis on possible future perspectives.
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http://dx.doi.org/10.5152/balkanmedj.2014.14496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4318397PMC
December 2014

Thirteen week rodent feeding study with grain from molecular stacked trait lepidopteran and coleopteran protected (DP-ØØ4114-3) maize.

Food Chem Toxicol 2013 Mar;53:417-27

Pioneer Hi-Bred International, Inc., Johnston, IA, USA.

The results from a subchronic feeding study conducted in Sprague–Dawley rats fed with diets containing grain from 4114 (OECD unique identifier: DP-ØØ4114-3) maize that was untreated (4114) or sprayed in field with glufosinate ammonium (4114GLU) in a design similar to previous studies are reported. The test material, 4114 maize, is a hybrid maize produced by transformation with a DNA construct encoding 4 different transgenic proteins for resistance to lepidopteran pests, coleopteran pests, and tolerance to the herbicidal active ingredient glufosinate ammonium. There were a total of 144 rats divided into 12 groups of 12 rats/sex/group. All experimental diets were formulated by Purina Mills, LLC (St. Louis, MO) in accordance with the standards of Purina Mills Labdiet® Certified Rodent LabDiet® 5002. The incorporation rate of maize grain in all diets was 32% (wt/wt). No biologically significant, treatment related differences in body weight, food consumption, clinical pathology parameters (hematology, blood chemistry, urinalysis, or organ weight) were observed in rats consuming the diets containing 4114 maize grain compared with rats fed conventional maize diets. A number of histologic observations were noted in this study but were background lesions and representative of what would be expected for rats of this age and strain. An independent panel of experts determined certain observations to be spontaneous and not related to the test diet. Accordingly, these results support the conclusion that 4114 maize grain is as safe and nutritious as conventional maize grain.
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http://dx.doi.org/10.1016/j.fct.2012.12.002DOI Listing
March 2013

Two-generation reproductive and developmental toxicity assessment of dietary N-acetyl-L-aspartic acid in rats.

Food Chem Toxicol 2011 Dec 6;49(12):3192-205. Epub 2011 Sep 6.

Pioneer Hi-Bred, International, Inc., Ankeny, IA 50021-7102, USA.

N-acetyl-l-aspartic acid (NAA) is a component of the mammalian central nervous system (CNS) that has also been identified in a number of foods. This paper reports the outcome of a reproductive toxicology study conducted with NAA in Sprague-Dawley rats. NAA was added to diets at target doses of 100, 250 and 500 mg/kg of body weight/day and administered for two consecutive generations. A carrier control group was administered diet with no added NAA and a comparative control group was given aspartate (ASP), the constituent amino acid of NAA, at a target dose of 500 mg/kg of body weight/day. The study evaluated OECD 416 reproductive performance variables and additional segments to assess potential developmental effects, neurobehavioural and ophthalmologic function, and the concentrations of NAA or ASP in brain and plasma. No biologically significant differences were observed in any reproductive response variables, neurobehavioural tests, ophthalmologic examinations, body weights, feed consumption, or organ weights. Further, no test substance related mortalities or adverse clinical, neurohistopathologic or histopathologic findings were observed. Under the conditions of this study, the highest target dose of NAA, 500 mg/kg of body weight/day, represents the no-observed-adverse-effect-level (NOAEL) for reproductive and systemic toxicity, and neurotoxicity for Sprague-Dawley rats.
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http://dx.doi.org/10.1016/j.fct.2011.08.025DOI Listing
December 2011

Subchronic oral toxicity assessment of N-acetyl-L-aspartic acid in rats.

Food Chem Toxicol 2011 Jan 12;49(1):155-65. Epub 2010 Oct 12.

Pioneer Hi-Bred International, Inc., Ankeny, Iowa 50021-7102, USA.

We investigated the systemic effects of subchronic dietary exposure to NAA in Sprague Dawley® rats. NAA was added to the diet at different concentrations to deliver target doses of 100, 250 and 500 mg/kg of body weight/day and was administered for 90 consecutive days. All rats (10/sex/group) survived until scheduled sacrifice. No diet-related differences in body weights, feed consumption and efficiency, clinical signs, or ophthalmologic findings were observed. No biologically significant differences or adverse effects were observed in functional observation battery (FOB) and motor activity evaluations, hematology, coagulation, clinical chemistry, urinalysis, organ weights, or gross pathology evaluations that were attributable to dietary exposure to NAA. Treatment-related increased incidence and degree of acinar cell hypertrophy in salivary glands was observed in both male and female rats in the high dose group. Because there was no evidence of injury or cytotoxicity to the salivary glands, this finding was not considered to be an adverse effect. Based on these results and the actual average doses consumed, the no-observed-adverse-effect-levels (NOAEL) for systemic toxicity from subchronic dietary exposure to NAA were 451.6 and 490.8 mg/kg of body weight/day for male and female Sprague Dawley® rats, respectively.
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http://dx.doi.org/10.1016/j.fct.2010.10.011DOI Listing
January 2011

Mutagenicity studies with N-acetyl-L-aspartic acid.

Food Chem Toxicol 2009 Aug 13;47(8):1936-40. Epub 2009 May 13.

DuPont Company, Toxicology, 2450 SE Oak Tree Ct., Ankeny, IA 50021, USA.

Analytical studies have reported that N-acetyl-L-aspartic acid (NAA) is present at low concentrations in many foods. The current studies were conducted to assess the mutagenicity of NAA using standard OECD guideline in vitro bacterial and in vivo mammalian mutagenicity studies. For comparison and control data, mutagenicity studies were also conducted with its constituent amino acid L-aspartate (ASP) because NAA is metabolized to ASP. The combination of an in vitro method for assessing point mutations in bacteria and an in vivo method to assess clastogenicity in an animal model provided adequate evidence for mutagenicity hazard assessment of NAA. No evidence of mutagenicity was observed in either test system with either NAA or ASP. The results from the current studies demonstrate that the presence of NAA in foods is not likely to represent a risk for mutagenicity.
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http://dx.doi.org/10.1016/j.fct.2009.05.005DOI Listing
August 2009

Analysis of immune response in young and aged mice vaccinated with corn-derived antigen against Escherichia coli heat-labile enterotoxin.

Mol Biotechnol 2006 Jan;32(1):31-42

Plant Transformation Facility, Department of Agronomy, Iowa State University, Ames, IA 50011, USA.

Enterotoxigenic strains of Escherichia coli produce a heat-labile holotoxin (LT), which causes diarrhea. We engineered corn seeds to produce LT-B, the nontoxic subunit of LT, to serve as a plant-derived vaccine to traveler's diarrhea and as an adjuvant for co-administered proteins. We previously demonstrated that a strong mucosal and systemic antibody response is elicited in young mice with oral administration of corn-derived LT-B. The present study examined systemic and mucosal antibody responses to LT-B in young and aged mice, and recall responses to oral administration and injection of LT-B in aged mice. Specific IgA and IgG antibodies were detectable during an 11-mo period, although the concentration of antigen-specific antibodies declined gradually. Booster by feeding or injection dramatically increased the concentration of specific IgA from that seen in young mice. Specific IgG levels were boosted to concentrations similar to those in young mice. This effect may be age-dependent and related to prior immunization exposure. Analysis of the antibody response of naïve aged mice against corn-derived LT-B demonstrated an age-related suppression in specific IgG production, but not specific IgA. These results may provide important information for edible vaccine strategies for young and aged individuals.
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http://dx.doi.org/10.1385/MB:32:1:031DOI Listing
January 2006