Publications by authors named "Umut Disel"

Introduction: Tislelizumab plus investigator-chosen chemotherapy (ICC) demonstrated a statistically significant improvement in overall survival (OS) versus placebo plus ICC in RATIONALE-305 in patients with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric cancer/gastroesophageal junction cancer (GC/GEJC) in the intent-to-treat population and in patients with programmed death-ligand 1 (PD-L1) Tumor Area Positivity (TAP) score ≥ 5%. The United States Food and Drug Administration Oncologic Drugs Advisory Committee voted (September 2024) against first-line treatment with programmed cell death protein-1 inhibitors in this setting in patients with a PD-L1 combined positive score < 1 or TAP score < 1%, due to an unfavorable benefit-risk profile. Thus, we retrospectively analyzed data from RATIONALE-305 in patients with a PD-L1 TAP score ≥ 1%.

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Based on the CheckMate 649 trial, nivolumab plus chemotherapy is the recommended first-line treatment for HER2-negative unresectable advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma. This nationwide, multicenter, retrospective study evaluated the real-world effectiveness of this regimen in Turkish patients and identified subgroups that may experience superior outcomes. Conducted across 16 oncology centers in Turkey, this study retrospectively reviewed the clinical charts of adult patients diagnosed with HER2-negative unresectable advanced or metastatic gastric, GEJ, or esophageal adenocarcinoma from 2016 to 2023.

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Article Synopsis
  • The study aimed to assess the effectiveness and safety of tislelizumab combined with chemotherapy for advanced gastric cancer compared to a placebo with chemotherapy.
  • Conducted from December 2018 to February 2023 across multiple continents, it involved 1,657 adult patients with specific cancer types who had not previously undergone systemic treatment.
  • Results indicated that patients receiving tislelizumab plus chemotherapy experienced significant improvements in overall survival compared to those on placebo and chemotherapy.
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Genomic profiling and other new technologies have increased the volume and complexity of information available for guiding clinical decision-making in precision oncology. Consequently, there is a need for multidisciplinary expert teams, in the form of molecular tumor boards (MTBs), who can translate this information into a therapeutic plan, including matching patients to suitable clinical trials. Virtual MTBs (vMTBs) can help to overcome many of the challenges associated with in-person MTBs, such as limited time availability, access to appropriate experts or datasets, or interactions between institutions.

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Introduction: The advances in immune checkpoint inhibitors (ICIs) were relatively slow in rare tumors. Therefore, we conducted a multi-center study evaluating the efficacy of ICI monotherapy and the combination of ICIs with chemotherapy (CT) in patients with advanced rare tumors.

Methods: In this retrospective cohort study, we included 93 patients treated with ICIs for NCI-defined rare tumors from the 12 cancer centers in Turkey.

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Article Synopsis
  • The study explored how MUTYH gene alterations relate to various cancers and their potential treatable biomarkers, analyzing a large dataset of solid tumors from clinical genomic profiling.
  • It found that 2.8% of tumors had MUTYH alterations, notably with a higher prevalence in colorectal cancers, and these altered tumors had a higher tumor mutational burden and more specific KRAS alterations.
  • The results suggest that MUTYH mutations could be targetable with certain drugs, such as sotorasib for KRAS G12C, and highlight the need for research into treatments that leverage the increased immunogenicity of these cancers.
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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.

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Article Synopsis
  • - The phase 3 RATIONALE-303 trial compared the effectiveness and safety of tislelizumab to docetaxel in patients with advanced non-small cell lung cancer (NSCLC) who had already undergone treatment, involving 805 participants.
  • - The trial showed that patients taking tislelizumab experienced a significant improvement in overall survival (OS) compared to those on docetaxel, with median OS of 17.2 months versus 11.9 months, respectively, and consistent results across various patient groups, especially those with high PD-L1 expression.
  • - Additionally, exploratory analyses suggested that certain genetic mutations (NOTCH1-4) may predict better responses to tislelizumab, while overall
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Purpose: Subset analyses from phase III evaluation of epidermal growth factor receptor inhibition (EGFRi) suggest improved outcomes in patients with amplified gastroesophageal adenocarcinoma (GEA), but large-scale analyses are lacking. This multi-institutional analysis sought to determine the role of EGFRi in the largest cohort of patients with amplified GEA to date.

Patients And Methods: A total of 60 patients from 15 tertiary cancer centers in six countries met the inclusion criteria.

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Purpose: Amplifications of receptor tyrosine kinases (RTKS) are therapeutic targets in multiple tumor types (e.g. HER2 in breast cancer), and amplification of the chromosome 4 segment harboring the three RTKs KIT, PDGFRA, and KDR (4q12amp) may be similarly targetable.

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Somatic ERBB2 amplification or activating mutations occur in approximately 2-5% of metastatic colorectal adenocarcinomas and are presumed to be oncogenic drivers, but limited evidence exists to suggest these lesions are sensitive to targeted monotherapy in patients. Here we present the case of a patient with advanced CRC with pulmonary metastases, who had progressed on both standard of care cytotoxic chemotherapy and anti-EGFR targeted therapy. Comprehensive genomic profiling (FoundationOne(®)) identified amplification of ERBB2 and a TP53 mutation in the metastatic lesion.

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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.

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Background: Patients with advanced cancer may present with obstructive jaundice. Biliary stenting is the treatment of choice. However, which patients benefit most is not well-defined, yet.

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The relationship between thyroid disease and cancer (and cancer therapies) has been under investigation for years. Factors that increase the risk for thyroid disease include iodine deficiency, autoimmune disorders, old age, and pregnancy. The screening policy for thyroid disease in the healthy population is not precisely defined, and the frequency of thyroid dysfunction in untreated cancer patients has not been investigated in any great detail.

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Chronic myeloid leukemia (CML) is a clonal stem cell disorder, and imatinib is a small molecule inhibitor of Bcr-Abl tyrosine kinase (TK) used in cases with CML. Immediate and short-term side effects of this tyrosine kinase inhibitor (TKI) are well known, but the long-term side effects have not yet been clearly identified. Although an increased risk of secondary cancer in cases treated by imatinib was not found in two large series, secondary malignancies have been reported in some cases using TKIs, and this issue is important in daily clinical practice for clinicians.

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Background: The majority of patients with head and neck cancer are treated with concurrent chemoradiotherapy. However, toxicity is substantial so that alternate schedules of cisplatin have been tried to overcome this problem. No formal comparison, however, has been reported between alternate schedules and reference regimen.

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Purpose: Patients with advanced cholangiocarcinoma present with high rate of local complications. The primary aim of this study is to report clinical course of advanced cholangiocarcinoma patients those who were presented with biliary obstruction and treated with percutaneous biliary stenting.

Material And Methods: Patients with unresectable locally advanced or metastatic cholangiocarcinoma followed by our center for a period of 4 years were analyzed.

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Advanced thymic carcinoma (TC) is a very aggressive disease. To date there are no established treatment options for the refractory and recurrent disease and only a few prospective trials have been conducted in patients with TC. Here we present a case of a relapsed TC patient, who, by using combination chemotherapy, showed a positive response to sorafenib with C-KIT exon 11 mutation.

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Background: Hand-foot syndrome (HFS), the most common toxicity of capecitabine, is characterized by tingling, numbness, pain, erythema, dryness, rash, swelling, increased pigmentation, and/or pruritus of the palmar and/or plantar surfaces of the hands and/or feet. HFS is usually seen in both the hands and the feet, with varying severity. We have previously published a case report of dihydropyrimidine dehydrogenase (DPD) deficiency that manifested a variant of HFS.

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Background: The management of the patients with carcinoma of an unknown primary represents a difficult challenge in oncology. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) has provided new insights in the diagnosis, staging, and follow-up of oncological patients.

Aim: This study aimed to investigate the value of FDG PET/CT in clarifying the primary site in our patients with histologically proven tumor metastasis (HPM) or with a high clinical suspicion of malignancy, and the clinical impact of this technique on the management of these patients.

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