Tıp Fakültesi / Faculty of Medicine

Permanent URI for this collectionhttps://hdl.handle.net/11727/1403

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    National Multi-Center Observational Retrospective Study to Understand Treatment Patterns and Outcomes for Stage III Non-Small Cell Lung Cancer Patients in Turkey: Turkish Society for Radiation Oncology Study, STONE Trial
    (2022) Onal, Cem; Demiral, Ayse Nur; Atalar, Banu; Yalman, Deniz; Dagoglu, Nergiz; Hurmuz, Pervin; Erpolat, Petek; Akyurek, Serap; Gul, Sute Karabulut; Berber, Tanju; Guler, Ozan Cem; Umay, Cenk; Sert, Fatma; Karahacioglu, Eray; Birgi, Sumerya Duru; Yaprak, Gokhan; Saglam, Esra Kaytan
    This study investigated treatment patterns and outcomes in patients with inoperable stage III non-small cell lung cancer (NSCLC) treated with radiotherapy (RT) in Turkey. We included 492 patients with stage III NSCLC in this multi-center retrospective study. Pa-tient demographics, clinical characteristics, and clinical treatment patterns from the time of the initial diagnosis to disease progression were recorded. Additionally, the prognostic factors predicting overall survival (OS) and progression-free survival (PFS) were analyzed. For the initial treatment, 429 patients (89.2%) received chemotherapy and RT, whereas 53 patients (10.8%) were treated only with RT. The first disease progression occurred in 288 patients (58.4%) at 9.3 months (median) after the initial treatment, and 64.6% re-ceived treatment after first progression. The second disease progression occurred in 30 patients, and 20 patients (66.7%) received treatment. Median OS and PFS were 27.0 months and 13.4 months, respectively. Age (p< 0.001), stage (p= 0.04), poor performance score (PS) (p= 0.03) and RT doses (p= 0.002) were independent predictors for OS and PFS in our multivariate analysis. Additional significant predictors for OS in the multivariate analysis were gender (p= 0.004), treatment period (0.02), and irradiation technique (p= 0.02). Disease progression occurred in nearly 58% of the patients, and one-third of these patients remained untreated during the disease progression. These findings indicate a need for additional treatment options in patients with unresectable stage III NSCLC with high-risk features, namely older age, stage IIIB disease, poor PS, and lower RT doses.
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    Small Cell Lung Cancer Stem Cells Display Mesenchymal Properties And Exploit Immune Checkpoint Pathways In Activated Cytotoxic T Lymphocytes
    (2021) Kursunel, M. Alper; Taskiran, Ekim Z.; Tavukcuoglu, Ece; Yanik, Hamdullah; Demirag, Funda; Karaosmanoglu, Beren; Ozbay, Feyza Gul; Uner, Aysegul; Esendagli, Dorina; 0000-0002-6619-2952; 34228218; ABF-9398-2020
    Small cell lung cancer (SCLC) is an aggressive tumor type with early dissemination and distant metastasis capacity. Even though optimal chemotherapy responses are observed initially in many patients, therapy resistance is almost inevitable. Accordingly, SCLC has been regarded as an archetype for cancer stem cell (CSC) dynamics. To determine the immune-modulatory influence of CSC in SCLC, this study focused on the characterization of CD44(+)CD90(+) CSC-like subpopulations in SCLC. These cells displayed mesenchymal properties, differentiated into different lineages and further contributed to CD8(+) cytotoxic T lymphocytes (CTL) responses. The interaction between CD44(+)CD90(+) CSC-like cells and T cells led to the upregulation of checkpoint molecules PD-1, CTLA-4, TIM-3, and LAG3. In the patient-derived lymph nodes, CD44(+) SCLC metastases were also observed with T cells expressing PD-1, TIM-3, or LAG3. Proliferation and IFN-gamma expression capacity of TIM-3 and LAG3 co-expressing CTLs are adversely affected over long-time co-culture with CD44(+)CD90(+) CSC-like cells. Moreover, especially through IFN-gamma secreted by the T cells, the CSC-like SCLC cells highly expressed PD-L1 and PD-L2. Upon a second encounter with immune-experienced, IFN-gamma-stimulated CSC-like SCLC cells, both cytotoxic and proliferation capacities of T cells were hampered. In conclusion, our data provide evidence for the superior potential of the SCLC cells with stem-like and mesenchymal properties to gain immune regulatory capacities and cope with cytotoxic T cell responses. With their high metastatic and immune-modulatory assets, the CSC subpopulation in SCLC may serve as a preferential target for checkpoint blockade immunotherapy .
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    Real-World Treatment Patterns and Clinical Outcomes in Patients With Stage III NSCLC: Results of KINDLE, a Multicountry Observational Study
    (2021) Jazieh, Abdul Rahman; Onal, Huseyin Cem; Tan, Daniel Shao Weng; Soo, Ross A.; Prabhash, Kumar; Kumar, Amit; Huggenberger, Reto; Robb, Stephen; Cho, Byoung-Chul; 34051381
    Introduction: Stage III NSCLC is a heterogeneous disease requiring a multimodal management approach. We conducted a real-world, global study to characterize patients, treatment patterns, and their associated clinical outcomes for stage III NSCLC. Methods: KINDLE was a retrospective study in patients with stage III NSCLC (American Joint Committee on Cancer, seventh edition) diagnosed between January 2013 and December 2017, with at least 9 months of documented follow-up since index diagnosis. In addition to descriptive statistics, Kaplan-Meier methodology evaluated survival estimates; two-sided 95% confidence interval was computed. Cox proportional hazards model was used for univariate and multivariate analyses. Results: A total of 3151 patients from more than 100 centers across 19 countries from Asia, Middle East, Africa, and Latin America were enrolled. Median age was 63.0 years (range: 21.0-92.0); 76.5% were males, 69.2% had a smoking history, 53.7% had adenocarcinoma, and 21.4% underwent curative resection. Of greater than 25 treatment regimens, concurrent chemoradiotherapy was the most common (29.4%). The overall median progression-free survival (95% confidence interval) and median overall survival (mOS) were 12.5 months (12.06-13.14) and 34.9 months (32.00-38.01), respectively. Significant associations (p < 0.05) were observed for median progression-free survival and mOS with respect to sex, region, smoking status, stage, histology, and Eastern Cooperative Oncology Group status. In univariate and multivariate analyses, younger age, stage IIIA, better Eastern Cooperative Oncology Group status, concurrent chemoradiotherapy, and surgery as initial therapy predicted better mOS. Conclusions: KINDLE reveals the diversity in treatment practices and outcomes in stage III NSCLC in a real-world setting in the preimmuno-oncology era. There is a high unmet medical need, necessitating novel approaches to optimize outcomes. (C) 2021 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
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    Laparoscopic gastrostomy under awake thoracic epidural anesthesia: A successful experience
    (2018) Pinar, Huseyin Ulas; Karaca, Omer; Duman, Enes; Dogan, Rafi; 30028480
    General anesthesia is the first choice as an anesthesia method particularly for abdominal operations. However, because neuromuscular blockade induced during general anesthesia will increase atelectasis in a patient with pulmonary disease, it will also increase postoperative ventilator dependence, which will be even more apparent in cases of chronic obstructive pulmonary disease (COPD) that pose a risk, particularly for postoperative complications. Herein, thoracic epidural anesthesia (TEA) was found to be a better option for our patient with severe COPD and stage IV lung cancer, as it provided sufficient anesthesia and better postoperative care for laparoscopic gastrostomy.