Browsing by Author "Sezer, Ahmet"

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Association of Microrna 211 Expression with Prognosis in Colorectal Cancer: A Case-Control Study
(2014) Sumbul, Ahmet Taner; Gogebakan, Bulent; Oztuzcu, Serdar; Yengil, Erhan; Sezer, Ahmet; Aball, Huseyin
Baseline Low Prognostic Nutritional Index Predicts Poor Survival in Locally Advanced Nasopharyngeal Carcinomas Treated With Radical Concurrent Chemoradiotherapy
(2019) Topkan, Erkan; Yucel Ekici, Nur; Ozdemir, Yurday; Besen, Ali Ayberk; Mertsoylu, Huseyin; Sezer, Ahmet; Selek, Ugur; 31184210
Background: To retrospectively assess the impact of prognostic nutritional index (PNI) on survival outcomes of patients with locoregionally advanced nasopharyngeal carcinoma (LA-NPC) treated with concurrent chemoradiotherapy (CCRT). Methods: This study incorporated 154 patients with LA-NPC who received exclusive cisplatinum-based CCRT. Receiver operating characteristic (ROC) curve analysis was utilized for accessibility of pretreatment PNI cutoffs influencing survival results. The primary end point was the interaction between the overall survival (OS) and PNI values, while cancer-specific survival (CSS) locoregional progression-free survival (LR-PFS), distant metastasis-free survival (DMFS), and PFS were the secondary end points. Results: A rounded PNI cutoff value of 51 was identified in ROC curve analyses to exhibit significant link with CSS, OS, DMFS, and PFS outcomes, but not LR-PFS. Patients grouping per PNI value (>= 51 [N = 95] vs <51 [N = 49]) revealed that PNI < 51 group had significantly shorter median CSS (P< .001), OS (P< .001), DMFS (P< .001), and PFS (P< .001) times than the PNI >= 51 group, and the multivariate results confirmed the PNI < 51 as an independent predictor of poor outcomes for each end point (P< .05 for each). The unfavorable impact of the low PNI was also continued at 10-year time point with survival rates of 77.9% versus 42.4%, 73.6% versus 33.9%, 57.9% versus 27.1%, and 52.6% versus 23.7% for CSS, OS, DMFS, and PFS, respectively. Additionally, we found that PNI < 51 was significantly associated with higher rates of weight loss >5% over past 6 months (49.2% versus 11.6%;P= .002) compared to PNI < 51 group. Conclusion: Low pre-CCRT PNI levels were independently associated with significantly reduced CSS, OS, DMFS, and PFS outcomes in patients with LA-NPC treated with definitive CCRT.
Being A Medical Oncologist Near the War Area
(2014) Sumbul, Ahmet Taner; Sezer, Ahmet; Tonyali, Onder; Ozturk, Mehmet Akif; Abali, Huseyin; Ozyilkan, Ozgur; https://orcid.org/0000-0002-6445-1439; https://orcid.org/0000-0001-5596-0920; https://orcid.org/0000-0001-8825-4918; 24965429; AAD-2667-2020; D-7660-2016; AAD-2817-2021
Bintrafusp Alfa With CCRT Followed by Bintrafusp Alfa Versus Placebo With CCRT Followed by Durvalumab in Patients With Unresectable Stage III NSCLC: A Phase 2 Randomized Study
(Başkent Üniversitesi, 2024-03-06) Vokes, Everett E.; Mornex, Francoise; Sezer, Ahmet; Cheng, Ying; Fang, Jian; Baz, David Vicente; Cil, Timucin; Adjei, Alex A.; Ahn, Myung-Ju; Barlesi, Fabrice; Felip, Enriqueta; Garon, Edward B.; Audhuy, Francois; Ito, Rena; Sato, Masashi; Eggleton, S. Peter; Martin, Claudio Marcelo; Reck, Martin; Robinson, Clifford G; Paz-Ares, Luis
Introduction: Preclinical evaluation of bintrafusp alfa (BA) combined with radiotherapy revealed greater antitumor effects than BA or radiotherapy alone. In a phase 1 study, BA exhibited encouraging clinical activity in patients with stage IIIB or IV NSCLC who had received previous treatment. Methods: This multicenter, double-blind, controlled phase 2 study (NCT03840902) evaluated the safety and efficacy of BA with concurrent chemoradiotherapy (cCRT) followed by BA (BA group) versus placebo with cCRT followed by durvalumab (durvalumab group) in patients with unresectable stage III NSCLC. The primary end point was progression -free survival according to Response Evaluation Criteria in Solid Tumors version 1.1 as assessed by the investigator. On the basis of the recommendation of an independent data monitoring committee, the study was discontinued before the maturity of overall survival data (secondary end point). Results: A total of 153 patients were randomized to either BA (n = 75) or durvalumab groups (n = 78). The median progression -free survival was 12.8 months versus 14.6 months (stratified hazard ratio = 1.48 [95% confidence interval: 0.69-3.17]), in the BA and durvalumab groups, respectively. Trends for overall response rate (29.3% versus 32.1%) and disease control rate (66.7% versus 70.5%) were similar between the two groups. Any -grade treatment -emergent adverse events occurred in 94.6% versus 96.1% of patients in the BA versus durvalumab groups, respectively. Bleeding events in the BA group were mostly grade 1 (21.6%) or 2 (9.5%). Conclusions: BA with cCRT followed by BA exhibited no efficacy benefit over placebo with cCRT followed by durvalumab in patients with stage III unresectable NSCLC. (c) 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc. This is an open access article under the CC BY -NC -ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Can Low Molecular Weight Heparins Circumvent the Problem of Coumadine and Chemotherapy Interaction in Cancer Patients with Prosthetic Heart Valves?
(2014) Sezer, Ahmet; Sumbul, Ahmet Taner; Abali, Gulcan; Sumbul, Zehra; Mualloglu, Sadik; Abali, Huseyin
Can serial monitoring of serum Vascular Endothelial Growth Factor (VEGF), Nitric Oxide (NO), and Angiotensin II (ANGII) levels have predictive role during Bevacizumab treatment?
(2014) Sumbul, Ahmet Taner; Disel, Umut; Sezgin, Nurzen; Sezer, Ahmet; Kose, Fatih; Besen, Ali Ayberk; Sumbul, Zehra; Abali, Huseyin; Ozyilkan, Ozgur
Background: Standard treatment of colorectal cancer includes both cytostatic chemotherapy and targeted therapies. Bevacizumab, targeting the VEGF receptor, is one of the primary targeted therapies that achieve better response rate and survival rate as compared to combination chemotherapy. To the best of our knowledge, there is no established single marker that can be used as a predictive marker in bevacizumab therapy. Material/Methods: We enrolled 24 patients with the diagnosis of metastatic colorectal cancer in our study. During the study, 2 blood samples were drawn from patients before the first cycle and after the sixth cycle of bevacizumab therapy. Serum levels of VEGF, ANG II, and NO were recorded. Results: While the change across VEGF levels was found to be a statistically significant decreasing trend (p=0.009), this decrease was not found to be correlated with treatment response and hypertension development. Additionally, no statistically significant difference was found in terms of NO and ANG II levels. Conclusions: This study showed a significant decrease in serum VEGF, but failed to show a significant change in NO and ANG II levels during bevacizumab treatment. Although no significant correlation was found between the presence of hypertension and markers, most patients (83%) had an increase in their blood pressure. Our results suggest that dynamic monitoring of NO and ANG II, along with VEGF, may not be useful as predictive markers for bevacizumab treatment in colorectal cancer.
Cardiotoxicity of Trastuzumab Emtansine (T-DM1): A Single-center Experience
(2021) Acibuca, Aynur; Sezer, Ahmet; Yilmaz, Mustafa; Sumbul, Ahmet Taner; Demircan, Senol; Muderrisoglu, Ibrahim Haldun; Ozyilkan, Ozgur; 0000-0002-3444-8845; 34898302; ABG-4047-2020
Objective New anti-cancer drugs promise to increased survival benefits and reduce adverse events. Trastuzumab emtansine (T-DM1) is a novel anti-human epidermal growth factor receptor 2 agent that has shown minimal cardiotoxicity in clinical trials. However, data on real-life outcomes are required. Methods A retrospective review of our center's medical records was performed, including female patients aged >= 18 years with a diagnosis of metastatic breast cancer who were treated with T-DM1. Descriptive statistics were used to investigate clinical features that could increase the risk of cardiotoxicity. Cardiotoxicity was determined by comparing pre and post-T-DM1 echocardiogram results and was defined as a decrease in the left ventricular ejection fraction (LVEF) >10% to below 55%. Results Data from 41 female patients with a mean age of 52 +/- 11.5 years were evaluated. A significant LVEF decrease (from 59% to 33%) was observed in one patient during T-DM1 treatment. Further investigation showed that this decrease was due to underlying coronary artery disease, and LVEF recovered to the baseline value after coronary revascularization. Conclusion T-DM1 seems to be safe in terms of cardiotoxicity. Real-life data with a larger sample size are still needed to confirm the cardiac safety of T-DM1.
Cemiplimab monotherapy as first-line (1L) treatment of patients with brain metastases from advanced non-small cell lung cancer (NSCLC) with programmed cell death-ligand 1 (PD-L1) >= 50%: EMPOWER-Lung 1 subgroup analysis.
(2021) Sezer, Ahmet
Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial
(2021) Sezer, Ahmet; Kilickap, Saadettin; Gumus, Mahmut; Bondarenko, Igor; Ozguroglu, Mustafa; Gogishvili, Miranda; Turk, Haci M.; Cicin, Irfan; Bentsion, Dmitry; Gladkov, Oleg; Clingan, Philip; Sriuranpong, Virote; Rizvi, Naiyer; Gao, Bo; Li, Siyu; Lee, Sue; McGuire, Kristina; Chen, Chieh I; Makharadze, Tamta; Paydas, Semra; Nechaeva, Marina; Seebach, Frank; Weinreich, David M.; Yancopoulos, George D.; Gullo, Giuseppe; Lowy, Israel; Rietschel, Petra; 33581821
Background We aimed to examine cemiplimab, a programmed cell death 1 inhibitor, in the first-line treatment of advanced non-small-cell lung cancer with programmed cell death ligand 1 (PD-L1) of at least 50%. Methods In EMPOWER-Lung 1, a multicentre, open-label, global, phase 3 study, eligible patients recruited in 138 clinics from 24 countries (aged >= 18 years with histologically or cytologically confirmed advanced non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0-1; never-smokers were ineligible) were randomly assigned (1:1) to cemiplimab 350 mg every 3 weeks or platinum-doublet chemotherapy. Crossover from chemotherapy to cemiplimab was allowed following disease progression. Primary endpoints were overall survival and progression-free survival per masked independent review committee. Primary endpoints were assessed in the intention-to-treat population and in a prespecified PD-L1 of at least 50% population (per US Food and Drug Administration request to the sponsor), which consisted of patients with PD-L1 of at least 50% per 22C3 assay done according to instructions for use. Adverse events were assessed in all patients who received at least one dose of the assigned treatment. This study is registered with ClinicalTrials.gov, NCT03088540 and is ongoing. Findings Between June 27, 2017 and Feb 27, 2020, 710 patients were randomly assigned (intention-to-treat population). In the PD-L1 of at least 50% population, which consisted of 563 patients, median overall survival was not reached (95% CI 17.9-not evaluable) with cemiplimab (n=283) versus 14.2 months (11.2-17.5) with chemotherapy (n=280; hazard ratio [HR] 0.57 [0.42-0.77]; p=0.0002). Median progression-free survival was 8.2 months (6.1-8.8) with cemiplimab versus 5.7 months (4.5-6.2) with chemotherapy (HR 0.54 [0.43-0.68]; p<0.0001). Significant improvements in overall survival and progression-free survival were also observed with cemiplimab in the intention-to-treat population despite a high crossover rate (74%). Grade 3-4 treatment-emergent adverse events occurred in 98 (28%) of 355 patients treated with cemiplimab and 135 (39%) of 342 patients treated with chemotherapy. Interpretation Cemiplimab monotherapy significantly improved overall survival and progression-free survival compared with chemotherapy in patients with advanced non-small-cell lung cancer with PD-L1 of at least 50%, providing a potential new treatment option for this patient population. Copyright (C) 2021 Elsevier Ltd. All rights reserved.
Clinicohistopathological Features and Treatment Outcomes in Testicular Lymphomas: A Single Center Experience
(2018) Sedef, Ali Murat; Kocer, Nazim Emrah; Besen, Ali Ayberk; Mertsoylu, Huseyin; Sezer, Ahmet; Sumbul, Ahmet Taner; Kose, Fatih; Ozyilkan, Ozgur; https://orcid.org/0000-0002-5943-9283; https://orcid.org/0000-0001-8825-4918; AAM-5436-2021; AAD-2817-2021
Clinicohistopathological features and treatment outcomes of neuroendocrine tumors: a single center experience
(2018) Kose, Fatih; Sedef, Ali Murat; Sumbul, Ahmet Taner; Mertsoylu, Huseyin; Besen, Ali Ayberk; Sezer, Ahmet; Ozyilkan, Ozgur; Abali, Huseyin; D-4793-2014
Purpose: Tumor and patient characteristics of neuroendocrine tumors (NET) significantly change between geographical locations that probably induced by environmental and genetic factors throughout the world. Therefore, reporting single center experience may help clarifying epidemiological view and improving decision-making process. Materials and Methods: We performed retrospective analysis of 115 patients of NETs those who followed by Baskent University, department of Medical Oncology and department of General Surgery to record patients and tumors characteristics, treatment modalities, survival rates, and prognostic factors. Results: Median overall survival (OS) time for all group and localized NETs were 44 and 24 months, respectively. Most common primary site was found as gastrointestinal system and then pancreatic region. Curative surgical resection rate was 46% and 8.5% of patients presented with carcinoid syndrome. Liver metastasis was far the most common metastatic site compared to lung, bone, and lymph node metastasis. Over 70 percent of patients were treated with chemotherapy and somatostatin analogs. Conclusion: Patients with higher grade, male gender, and advanced age (>65 years old) had poor survival rate. However, relatively low number of patients and less usage of (<10%) of new treatment modalities created limitations for producing future directions from our study.
The Clinicopathological and Survival Differences Between Never and Ever Smokers with Non-Small Cell Lung Cancer
(2014) Muallaoglu, Sadik; Karadeniz, Cemile; Mertsoylu, Huseyin; Besen, Ali Ayberk; Sezer, Ahmet; Sedef, Ali Murat; Kose, Fatih; Ozyilkan, Ozgur; https://orcid.org/0000-0002-6242-2802; https://orcid.org/0000-0002-1932-9784; https://orcid.org/0000-0002-6445-1439; https://orcid.org/0000-0002-0156-5973; https://orcid.org/0000-0001-8825-4918; 24965406; IVU-7523-2023; M-9530-2014; AAD-2667-2020; G-4827-2016; AAD-2817-2021
Purpose: Cigarette smoking was regarded as the most important carcinogenic factor of lung cancer, yet in recent years lung cancer in never-smokers is an increasingly prominent public health issue. The aim of this study was to assess the epidemiological and clinicopathological characteristics of never-smoker patients with non small cell lung cancer (NSCLC), focusing on clinical risk factors and survival. Methods: We retrospectively analyzed 290 NSCLC patients who presented between 2006 and 2011. Differences in clinical features and survival between never- and ever-smoker patients were analyzed. Student's t-test and Mann-Whitney U-test were used to assess the significance of the variables between the groups. Survival curves were calculated using Kaplan-Meier method. Hazard ratio (HR) for death and its 95% confidence interval (CI) were calculated by Cox regression analysis. Results: There were 243 (83.8%) ever-smokers and 47 (16.2%) never-smokers. In never-smokers females predominated (80.9%) as well as patients with adenocarcinomas (78.7%). At the time of analysis 143 (49.3%) patients had died. The 5-year overall survival (OS) rates were not significantly different between never- and ever-smokers (p=0.410). The median OS of all patients was 26 months (95% CI: 16.8-35.2). The median OS was 23 months (95% CI: 11.8-34.2)for never-smokers and 30 months (95% CI: 19.7-40.3) forever-smokers (p=0.410). Never-smokers tended to present with more advanced disease than ever-smokers (p<0.004) and also with more advanced age (p<0.001). The HR for death increased with poorer Eastern Cooperative Oncology Group (ECOG) performance status (PS) (ECOG 2-3), advanced stage (stage 3-4) and untreated patients. Slightly lower risk for death was registered in patients with adenocarcinoma vs those with squamous cell carcinoma (S CC). Conclusion: Although no difference in survival was seen, definite epidemiologic differences do exist between never-smokers and ever-smokers patients with NSCLC. Future efforts should focus on the underlying biological differences, and on identifying potential non-tobacco related risk factors in order to improve treatment strategies for these two groups of NSCLC patients.
Comparison of Gemcitabine Monotherapy with Gemcitabine and Cisplatin Combination in Metastatic Pancreatic Cancer: A Retrospective Analysis
(2018) Ergun, Yakup; Ozdemir, Nuriye Yildirim; Guner, Ebru Karci; Esin, Ece; Sendur, Mehmet Ali; Koksoy, Elif Berna; Demirci, Nebi Serkan; Eren, Tulay; Dede, Isa; Sezer, Ahmet; Engin, Huseyin; Oksuzoglu, Berna; Yalcin, Bulent; Utkan, Gungor; Zengin, Nurullah; Urun, Yuksel; 30722120
Purpose: Gemcitabine is among the standard first-line agents for the treatment of metastatic pancreatic cancer. However, as the median survival with gemcitabine monotherapy is 6 months, different combinations are being studied for better, prolonged survival. In this multicenter study, we aimed to compare the results of gemcitabine monotherapy with those of gemcitabine and cisplatin combination therapy as first-line treatments for metastatic pancreatic cancer. Methods: Data of 664 patients diagnosed with metastatic pancreatic cancer between January 2007 and December 2016 from seven oncology centers in Turkey were retrospectively evaluated, and 319 patients with gemcitabine alone (n=138) or gemcitabine and cisplatin combination (n=181) as first-line treatment were included. Results: The median patient age was 62 years (range 42-79), being 60 years (42-75) in the gemcitabine/cisplatin arm and 67 years (52-79) in gemcitabine alone arm. no complete response was observed in either arm, whereas partial response rates were 30.1% in gemcitabine/cisplatin arm and 15.3% in gemcitabine alone arm (p=0.001). median overall survival was 8 months (95% CI:7.7-10.2) and was significantly longer in the gemcitabine/cisplatin arm than in the gemcitabine alone arm (10 vs. 6 months, p=0.004). Conclusion: The cemcitabine and cisplatin combination therapy as first-line treatment of metastatic pancreatic cancer yields significantly prolonged survival over gemcitabine monotherapy. In patients with favorable performance conditions, the combination therapy should be preferred.
Comparison of Involved Field Radiotherapy versus Elective Nodal Irradiation in Stage IIIB/C Non-Small-Cell Lung Carcinoma Patients Treated with Concurrent Chemoradiotherapy: A Propensity Score Matching Study
(2020) Topkan, Erkan; Ozdemir, Yurday; Guler, Ozan Cem; Kucuk, Ahmet; Besen, Ali Ayberk; Mertsoylu, Huseyin; Sezen, Duygu; Akdemir, Eyub Yasar; Sezer, Ahmet; Bolukbasi, Yasemin; Pehlivan, Berrin; Selek, Ugur; 0000-0002-1932-9784; 0000-0001-6908-3412; 0000-0002-2218-2074; 0000-0002-6445-1439; 0000-0001-8120-7123; 0000-0002-7862-0192; 32952557; M-9530-2014; AAC-5654-2020; AAG-5629-2021; AAD-2667-2020; AAG-2213-2021; AAD-6910-2021
Background. We retrospectively compared the incidence of isolated elective nodal failure (IENF) and toxicity rates and survival outcomes after elective nodal irradiation (ENI) versus involved-field RT (IFRT) by employing the propensity score matching (PSM) methodology in stage IIIB/C inoperable non-small-cell lung cancer (NSCLC) patients treated with definitive concurrent chemoradiotherapy (C-CRT).Methods. Our PSM examination included 1048 stage IIIB/C NSCLC patients treated with C-CRT from January 2007 to December 2016: a total dose of 66 Gy (2 Gy/fraction) radiotherapy and 1-3 cycles of platinum-based doublet chemotherapy concurrently. The primary and secondary endpoints were the IENF and toxicity rates and survival outcomes after ENI versus IFRT, respectively. Propensity scores were calculated for each group to adjust for confounding variables and facilitate well-balanced comparability by creating 1 : 1 matched study groups.Results. The median follow-up was 26.4 months for the whole study accomplice. The PSM analysis unveiled 1 : 1 matched 646 patients for the ENI (N = 323) and IFRT (N = 323) cohorts. Intergroup comparisons discovered that the 5-year isolated ENF incidence rates (3.4% versus 4.3%;P=0.52) and median overall survival (25.2 versus 24.6 months;P=0.69), locoregional progression-free survival (15.3 versus 15.1 months;P=0.52), and progression-free survival (11.7 versus 11.2 months;P=0.57) durations were similar between the ENI and IFRT cohorts, separately. However, acute grade 3-4 leukopenia (P=0.0012), grade 3 nausea-vomiting (P=0.006), esophagitis (P=0.003), pneumonitis (P=0.002), late grade 3-4 esophageal toxicity (P=0.038), and the need for hospitalization (P<0.001) were all significantly higher in the ENI than in the IFRT group, respectively.Conclusion. Results of the present large-scale PSM cohort established the absence of meaningful IENF or survival differences between the IFRT and ENI cohorts and, consequently, counseled the IFRT as the elected RT technique for such patients since ENI increased the toxicity rates.
Concurrent Chemoradiotherapy with Vinorelbine plus Split-Dose Cisplatin may be an Option in Inoperable Stage III Non-Small Cell Lung Cancer: A Single-Center Experience
(2015) Mertsoylu, Huseyin; Kose, Fatih; Sumbul, Ahmet Taner; Sedef, Ali Murat; Dogan, Ozlem; Besen, Ali Ayberk; Parlak, Cem; Findikcioglu, Alper; Muallaoglu, Sadik; Sezer, Ahmet; Sakalli, Hakan; Ozyilkan, Ozgur; 25731741
Background: Concurrent chemoradiotherapy is the current standard treatment for inoperable stage III non-small cell lung cancer (NSCLC). In this study we aimed to investigate the efficacy and toxicity of CCRT with split dose of cisplatin (30 mg/m(2)) and vinorelbine (20 mg/m(2)) in patients with inoperable stage III NSCLC followed in our oncology clinic. Material/Methods: Medical records of 97 patients with inoperable stage III NSCLC treated with concurrent chemoradiotherapy with cisplatin-vinorelbine were retrospectively analyzed. Cisplatin (30 mg/m(2)) and vinorelbine (20 mg/m(2)) were administered on days 1, 8, 22, and 29 during radiotherapy. Two cycles of consolidation chemotherapy were given. All patient data, including pathological, clinical, radiological, biochemical, and hematological data, were assessed retrospectively using our database system. Results: Our study included 97 unresectable stage III NSCLC patients who were treated with CCRT. Median age was 58 years old (range 39-75) and 87 (89.7%) of the patients were men. ECOG performance score was 0-1 in 93 patients (95.9%). Squamous histology, the most common histology, was diagnosed in 46 patients (47.4%). Median follow-up time was 23.8 months. Median progression-free survival (PFS) and median overall survival time (OS) were 10.3 months and 17.8 months, respectively. Objective response rate and clinical benefit rate were 75.3% and 83.5%, respectively. Distant and local relapse rate were 57.1% and 42.9%, respectively. Hematological and non-hematological grade 3-4 toxicities were seen in 13 (13.4%) and 16 (16.5%) patients, respectively. Six (6.1%) patients died due to toxicity. Conclusions: The results of this study suggest that split-dose cisplatin may offer fewer grade III-IV toxicities without sacrificing efficacy and could be an option in patients with inoperable stage III NSCLC during CCRT. Similar to past studies, despite high response rate during CCRT, distant relapse is the major parameter that influences patient survival in long-term in NSCLC.
Concurrent versus sandwich treatment in adjuvant treatment in high risk operated gastric cancer: A single center experience
(2020) Sezer, Ahmet; Akkus, Berna; Guler, Ozan Cem; Onal, Huseyin Cem; Sumbul, Ahmet Taner; 0000-0001-6908-3412; 0000-0002-2742-9021; 33277854; AAC-5654-2020; D-5195-2014
Purpose: In this study we compared postoperative early vs sandwich chemoradiotherapy in operated stage IIA-IIIC gastric cancer patients in terms of effectiveness and outcome. Methods: The data of 201 gastric cancer patients treated in the same center between December 2006 and June 2017 were retrospectively evaluated. One hundred forty nine patients who were eligible for the study criteria were divided into two groups according to the postoperative treatment modality. The first group included 85 patients who were given chemoradiotherapy simultaneously (ETG) and the second group icluded 64 patients who received sandwich (chemotherapychemoradiotherapy-chemotherapy) (STG) treatment. Overall survival (OS) and disease-free survival (DFS) were evaluated as primary endpoints. Results: The median follow-up time for all patient groups was 26.7 months (1.3-136.5 months). Adjuvant chemotherapy and radiotherapy were initiated concurrently in patients receiving concomitant therapy. Half of the planned chemotherapy, then chemoradiotherapy and then the remaining chemotherapy treatments were given to the sandwich treatment group. A total of 50.4 Gy radiotherapy was given to the concurrent chemoradiotherapy group and a total of 45 Gy radiotherapy to the group receiving the sandwich treatment. OS was 30.6 months (23.7-37.5) in all groups, 30.4 months (23.7-35.0) in concurrent therapy (ETG) and 35.6 months (26.3-45) in sandwich therapy (STG) (p=0.73). DFS was 26.6 months (21.3-32.0) in all groups and 24.5 months (18.1-31.0) in the group receiving ETG, 32.5 months (22.242.8) in STG. (p=0.46). The most common grade 3 and above toxicities were; acute upper gastrointestinal toxicity (19.1% in ETG vs. 9.0% in STG, p=0.01) and hematological toxicity (31.8% in ETG vs. 13.9% in STG; p=0.002). Early cessation of treatment was similar in both groups. In multivariate analysis, female gender (p=0.01), stage III disease, grade III disease were seen as negative predictive factors for overall survival. In DFS multivariate analysis, there was no difference between the groups in terms of gender, T stage, N stage, and AJCC stage. Conclusion: In this study, superiority of sandwich treatment over concurrent treatment was observed in patients with operated stage IIB-IIIC gastric cancer, but the difference was not statistically significant. If this study is performed in larger patient series, the difference of sandwich treatment may become meaningful.
Crizotinib Efficacy and Safety in Patients with Advanced NSCLC Harboring MET Alterations: A Real-Life Data of Turkish Oncology Group
(2022) Gurbuz, Mustafa; Kilickap, Saadettin; Bilici, Ahmet; Karadurmus, Nuri; Sezer, Ahmet; Sendur, Mehmet Ali Nahit; Paydas, Semra; Artac, Mehmet; Fulden Yumuk, Perran; Gursoy, Pinar; Uysal, Mukremin; Senol Coskun, Hasan; Tatli, Ali Murat; Selcukbiricik, Fatih; Disel, Umut; Koksoy, Elif Berna; Guven, Deniz Can; Ugrakli, Muzaffer; Akkus, Erman; Yucel, Sebnem; Erol, Cihan; Karakaya, Serdar; Sakalar, Teoman; Khanmammadov, Nijat; Paksoy, Nail; Demirkazik, Ahmet; 36550824
Crizotinib is a multikinase inhibitor, effective in non-small cell lung cancer (NSCLC) harboring mesenchymal-epidermal transition (MET) alterations. Although small prospective studies showed efficacy and safety of crizotinib in NSCLC with MET alterations, there is limited real-life data. Aim of this study is to investigate real-life efficacy and safety of crizotinib in patients with advanced NSCLC harboring MET alterations. This was a retrospective, multicenter (17 centers) study of Turkish Oncology Group. Patients' demographic, histological data, treatment, response rates, survival outcomes, and toxicity data were collected. Outcomes were presented for the study population and compared between MET alteration types. Total of 62 patients were included with a median age of 58.5 (range, 26-78). Major histological type was adenocarcinoma, and 3 patients (4.8%) had sarcomatoid component. The most common MET analyzing method was next generation sequencing (90.3%). MET amplification and mutation frequencies were 53.2% (n = 33) and 46.8% (n = 29), respectively. Overall response rate and disease control rate were 56.5% and 74.2% in whole study population, respectively. Median progression free survival (PFS) was 7.2 months (95% confidence interval [CI]: 3.8-10.5), and median overall survival (OS) was 18.7 months (95% CI: 13.7-23.7), regardless of treatment line. Median PFS was 6.1 months (95% CI: 5.6-6.4) for patients with MET amplification, whereas 14.3 months (95% CI: 6.7-21.7) for patients with MET mutation (P = .217). Median PFS was significantly longer in patients who have never smoked (P = .040), have good performance score (P < .001), and responded to the treatment (P < .001). OS was significantly longer in patients with MET mutation (25.6 months, 95% CI: 15.9-35.3) compared to the patients with MET amplification (11.0 months; 95% CI: 5.2-16.8) (P = .049). In never-smokers, median OS was longer than smoker patients (25.6 months [95% CI: 11.8-39.3] vs 16.5 months [95% CI: 9.3-23.6]; P = .049). The most common adverse effects were fatigue (50%), peripheral edema (21%), nausea (29%) and diarrhea (19.4%). Grade 3 or 4 adverse effects were observed in 6.5% of the patients. This real-life data confirms efficacy and safety of crizotinib in the treatment of advanced NSCLC harboring MET alteration.
Cutaneous Melanoma in Turkey: Analysis of 1157 Patients in the Melanoma Turkish Study
(2015) Abali, Huseyin; Celik, Ismail; Karaca, Burcak; Turna, Hande; Saglam, Esra Kaytan; Akman, Tulay; Oztop, Ilhan; Coskun, Hasan Senol; Turhal, Nazim Serdar; Sezer, Ahmet; Nayir, Erdinc; Demir, Gokhan; Budakoglu, Burcin; Issikdogan, Abdurrahman; Engin, Huseyin; Kilickap, Saadettin; Coskun, Ugur; Oyan, Basak; Harputluoglu, Hakan; Er, Ozlem; Kavgaci, Halil; Elkiran, Tamer; 26416068
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.
First-Line Cemiplimab Monotherapy and Continued Cemiplimab Beyond Progression Plus Chemotherapy for Advanced Non-Small-Cell Lung Cancer With PD-L1 50% Or More (EMPOWER-Lung 1): 35-Month Follow-Up From A Multicentre, Open-Label, Randomised, Phase 3 Trial
(2023) Ozguroglu, Mustafa; Kilickap, Saadettin; Sezer, Ahmet; Gumus, Mahmut; Bondarenko, Igor; Gogishvili, Miranda; Nechaeva, Marina; Schenker, Michael; Cicin, Irfan; Ho, Gwo Fuang; Kulyaba, Yaroslav; Zyuhal, Kasimova; Scheusan, Roxana-Ioana; Garassino, Marina Chiara; He, Xuanyao; Kaul, Manika; Okoye, Emmanuel; Li, Yuntong; Li, Siyu; Pouliot, Jean-Francois; Seebach, Frank; Lowy, Israel; Gullo, Giuseppe; Rietschel, Petra; 37591293
Background: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression.Methods: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged >= 18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540.Findings: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 261 months (95% CI 221-318; 149 [52%] of 284 died) versus 133 months (105-162; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 057, 95% CI 046-071; p<00001), median progression-free survival was 81 months (95% CI 62-88; 214 events occurred) in the cemiplimab group versus 53 months (43-61; 236 events occurred) in the chemotherapy group (HR 051, 95% CI 042-062; p<00001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 66 months (61-93) and overall survival of 151 months (113-187). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signalsINTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer.Copyright (c) 2023 Elsevier Ltd. All rights reserved.
GLASS: Global Lorlatinib for ALK(+) and ROS1(+) retrospective Study: real world data of 123 NSCLC patients
(2020) Sezer, Ahmet; Ozyilkan, Ozgur; 0000-0002-6445-1439; 0000-0001-8825-4918; 32799090; AAD-2667-2020; AAD-2817-2021
Lorlatinib is a third-generation tyrosine-kinases inhibitor (TKI) targeting ALK/ROS1 fusions. The FDA has approved lorlatinib for TKI-pretreated ALK(+) NSCLC, while its approval for ROS1( + ) is still pending. Here we present the largest real-world data of NSCLC patients harboring ALK/ROS1 rearrangements treated with lorlatinib. Methods: 123 patients were enrolled retrospectively (data cut-off 1/1/2019). Lorlatinib was administered through an early access program for patients with no other available therapy. Outcome and response were defined by each investigator upon RECIST 1.1 criteria. Results: 106 ALK(+) and 17 ROS1(+) patients recruited from 8 different countries. The ALK( + ) cohort included 50 % males, 73 % never-smokers and 68 % with brain metastases. Extracranial (EC) and intracranial (IC) response rates (RR) were 60 % and 62 %, with disease control rates (DCR) of 91 % and 88 % respectively. Mean duration of therapy (DoT) was 23.9 +/- 1.6 months and median overall survival (mOS) was 89.1 +/- 19.6 months. ROS1 cohort enrolled 53 % males, 65 % never-smokers and 65 % had brain metastases. EC and IC RR were 62 % and 67 % with DCR of 92 % and 78 % respectively. Median DoT was 18.1 +/- 2.5 months and mOS of 90.3 +/- 24.4 months. OS and DoT in both cohorts were not significantly correlated with line of therapy nor other parameters. The most common adverse events of any grade were peripheral edema (48 %), hyperlipidemia (47 %), weight gain (25 %) and fatigue (30 %). CNS adverse events such as cognitive effect of grade 1-2 were reported in 18 % of patients. Conclusion: Lorlatinib shows outstanding EC/IC efficacy in ALK/ROS1(+) NSCLC. The observed mOS of 89 +/- 19 months in ALK(+) NSCLC supports previous reports, while mOS from of 90 +/- 24 months is unprecedented for ROS1( + ) NSCLC.